title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Biosurfactant synthesis by Pseudomonas aeruginosa LBI isolated from a hydrocarbon-contaminated site. | Pseudomonas aeruginosa LBI (Industrial Biotechnology Laboratory) was isolated from hydrocarbon-contaminated soil as a potential producer of biosurfactant and evaluated for hydrocarbon biodegradation. The emulsifying power and stability of the product was assessed in the laboratory, simulating water contamination with benzene, toluene, kerosene, diesel oil and crude oil at various concentrations. Bacteria were grown at 30 degrees C and shaken at 200 rpm for 168 h, with three repetitions. Surface tension, pH and biosurfactant stability were observed in the cell-free broth after 168 h of incubation. The strain was able to produce biosurfactant and grow in all the carbon sources under study, except benzene and toluene. When cultivated in 30% (w/v) diesel oil, the strain produced the highest quantities (9.9 g l(-1)) of biosurfactant. The biosurfactant was capable of emulsifying all the hydrocarbons tested. The results from the present study demonstrate that Ps. aeruginosa LBI can grow in diesel oil, kerosene, crude oil and oil sludge and the biosurfactant produced has potential applications in the bioremediation of hydrocarbon-contaminated sites. Pseudomonas aeruginosa LBI or the biosurfactant it produces can be used in the bioremediation of environmental pollution induced by industrial discharge or accidental hydrocarbon spills. | 18,795,978 |
RNA extraction from cheese for analysis of in situ gene expression of Lactococcus lactis. | The isolation of high-quality RNA from cheese is a prerequisite for analysis of in situ gene expression of dairy micro-organisms. A method for rapid isolation of bacterial cells from cheese using cold citrate buffer followed by mechanical cell disruption was developed. RNA was extracted from experimental ultrafiltration (UF) cheeses (at 2, 8, 24 h, 7 and 14 days) and from Cheddar cheese (from 1 day to 1 year). The quantity and quality of the extracted RNA was assessed. The transcript abundance of seven genes (tuf, gapB, purM, cysK, ldh, cit and gyrA) was estimated by reverse transcription real-time PCR. In UF cheeses, the quantity of RNA extracted increased from 0.2 to 24 microg g(-1), with an RNA Integrity Number (RIN) above 9. In the experimental Cheddar cheeses, the RNA extraction yield decreased from 67.7 microg g(-1) after 1 day to 23.7 microg g(-1) after 6 months, with RIN value above 9 during the first month. The transcript abundance of the seven genes demonstrated metabolic activity of lactococci after several weeks of ripening in both cheeses. The method described produced large quantities of high-quality RNA for future whole genome expression studies in cheese. | 18,795,980 |
Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn's disease. | Bacterial flagellin is considered an important antigen in Crohn's disease (CD) as it activates innate immunity through Toll-Like Receptor 5 (TLR5) engagement and induces an elevated adaptive immune response. Little is known about the presence of an autoimmune process in CD. We aimed to identify pathogenically relevant autoantigen targets in CD. We screened a random peptide library with pooled sera of patients with active CD. Transepithelial flux of [3H] mannitol in T84 human intestinal epithelial cell line was used to study the epithelial barrier function. Monocyte activation was evaluated by surface expression of activation markers and by production of pro-inflammatory cytokines. Gene modulation of T84 cells exposed to antipeptide antibodies was analysed by gene array. We identified a peptide that shares homology with Salmonella typhimurium flagellin and with self-antigens such as TLR5 and cell junction protein, Pals 1-associated tight junction protein. The affinity-purified antipeptide antibodies recognized the self-antigens and induced increased intestinal epithelial cell permeability. Moreover, the antibodies induced monocyte activation upon binding TLR5. Finally, in cultured intestinal cells (T84) the purified antibodies induced the modulation of clusters of proinflammatory genes similar to the one induced by the engagement of TLR5 by its natural ligand flagellin. Antibodies directed against an immunodominant peptide of flagellin recognize self-antigens and are functionally active suggesting the presence of an autoimmune process that can both facilitate loss of tolerance to intestinal microflora by increasing cell permeability and amplify the innate immunity involvement through a novel mechanism of TLR5 activation. | 18,796,002 |
A food-derived synergist of NGF signaling: identification of protein tyrosine phosphatase 1B as a key regulator of NGF receptor-initiated signal transduction. | Neurotrophins, such as the nerve growth factor (NGF), play an essential role in the growth, development, survival and functional maintenance of neurons in the central and peripheral systems. They also prevent neuronal cell death under various stressful conditions, such as ischemia and neurodegenerative disorders. NGF induces cell differentiation and neurite outgrowth by binding with and activating the NGF receptor tyrosine kinase followed by activation of a variety of signaling cascades. We have investigated the NGF-dependent neuritogenesis enhancer potential of a food-derived small molecule contained in Brassica vegetables and identified the protein tyrosine phosphatase (PTP) 1B as a key regulator of the NGF receptor-initiated signal transduction. Based on an extensive screening of Brassica vegetable extracts for the neuritogenic-promoting activity in the rat pheochromocytoma cell line PC12, we found the Japanese horseradish, wasabi (Wasabia japonica, syn. Eutrema wasabi), as the richest source and identified 6-methylsulfinylhexyl isothiocyanate (6-HITC), an analogue of sulforaphane isolated from broccoli, as one of the major neuritogenic enhancers in the wasabi. 6-HITC strongly enhanced the neurite outgrowth and neurofilament expression elicited by a low-concentration of NGF that alone was insufficient to induce neuronal differentiation. 6-HITC also facilitated the sustained-phosphorylation of the extracellular signal-regulated kinase and the autophosphorylation of the NGF receptor TrkA. It was found that PTP1B act as a phosphatase capable of dephosphorylating Tyr-490 of TrkA and was inactivated by 6-HITC in a redox-dependent manner. The identification of PTP1B as a regulator of NGF signaling may provide new clues about the chemoprotective potential of food components, such as isothiocyanates. | 18,796,006 |
Endovascular management of life-threatening retroperitoneal bleeding. | The aim of this study was to evaluate efficiency of embolotherapy in management of retroperitoneal bleedings. A total of 16 patients with retroperitoneal bleeding who underwent angiography followed by transcatheter embolization within a 4-year period in a single centre were reviewed retrospectively. Electronic charts as well as procedural reports were reviewed to assess immediate angiographic findings and results of embolization. Computed tomography was carried out in eight patients. All computed tomography scans showed retroperitoneal haematoma. In addition, contrast material extravasation consistent with active bleeding was seen in two patients and pseudoaneurysm in one. In the remaining eight patients, diagnosis of retroperitoneal bleeding was established based on combined ultrasound and clinical findings. The technical success rate for selective embolotherapy was 100%. Five of these 16 patients (three women and 13 men) had lumbar artery injury; 10 patients were associated with renal artery injury and one had bilateral internal iliac artery injury. Angiography showed active extravasation, pseudoaneurysm and arteriovenous fistula. For embolization, coils were used in six patients and N-butyl-2-cyanoacrylate in the remaining 10 patients. Four patients died within 1 month of embolotherapy. Transcatheter embolotherapy appears to be a life-saving, safe and effective treatment for retroperitoneal bleedings that may be carried out in emergency situations in haemodynamically unstable patients. | 18,796,028 |
Towards quality control in rectal cancer surgery: a preliminary Greek experience. | The purpose of this study was to evaluate the effect of the introduction of a colorectal unit on provided services for patients with rectal cancer. The colorectal unit in our department was initiated in January 2004. A dedicated database was used to retrieve data from 127 consecutive patients who were operated on electively from March 1995 to December 2005. Treatment parameters were compared for patients before (n = 90) and after (n = 37) the introduction of the colorectal unit. In the entire group of patients, 50.3% presented with locally advanced disease (stage III) and 40.9% with tumours located in the lower third of the rectum. A higher preoperative versus postoperative radiotherapy ratio (P < 0.0001), a higher local excision rate (P = 0.04) and a higher low anterior resection to abdominoperineal resection ratio (P = 0.0011) were noted after the initiation of the colorectal unit. In this small series, although parameters like the number of examined lymph nodes, anastomotic leakage rate and distal resection margin improved, they did not reach statistical significance. The establishment of a colorectal unit seems to have resulted in improved quality of rectal cancer treatment by a dedicated multidisciplinary approach, even after only 2 years of service. | 18,796,031 |
In-hospital mortality of ruptured abdominal aortic aneurysm. | New Zealand, like Australia, has a widely dispersed population in towns at long distances from the main centres. We set out to estimate the in-hospital mortality rate for ruptured abdominal aortic aneurysms in New Zealand and identify factors associated with mortality. Data were gathered prospectively as part of the Vascular Society of New Zealand's continuous audit programme of all member surgeons. Data collection was validated by random record audit. In-hospital mortality of ruptured abdominal aortic aneurysms, defined as death during hospital admission irrespective of cause, was determined for the period 1993-2005. Along with other performance indicators, differences in outcomes were assessed to take into account the trend over the time period, hospital size and number of non-operative admissions. Of the 740 patients admitted with a mean age of 73.9 +/- 8.5 years, 78% were men and 17.8% were declined an operation. The in-hospital mortality was 48.3% and the operative mortality was 37.8%. With univariate analysis increasing patient age, American Society of Anesthesiology score, hospital size and female sex were predictors of in-hospital mortality. Only age and American Society of Anesthesiology score were independent predictors of operative mortality. Women were less likely to have surgery. Over the past 13 years in-hospital mortality of ruptured abdominal aortic aneurysms in New Zealand remained unchanged. In provincial hospitals the operative outcomes were satisfactory, but the reported number not offered surgery was higher. | 18,796,032 |
Transition to adult care: experiences and expectations of adolescents with a chronic illness. | Effective means of transitioning adolescent patients with chronic illness from paediatric to adult medical care are poorly documented and supported by limited evidence. The purpose of this study is to describe expectations and concerns of adolescents with chronic illness regarding transition from subspecialty paediatric to adult-centred care during the transition process in order guide effective programme design and implementation. Qualitative content and thematic analysis of semi-structured individual interviews with 22 adolescents with chronic illness, including cystic fibrosis, sickle cell disease, juvenile rheumatoid arthritis, and inflammatory bowel disease. Interviews took place at 1-3 time points over an 18-month study period. Transition topics included: timing of transfer to adult care, the transition process, attitudes about transition, and factors that might aid transition. During the study period, one-third of participants made the transition to adult-oriented health care. All participants who had transitioned to adult-oriented care reported participating in a structured transition programme. Concerns of those who had not initiated the transition process centred on re-establishing relationships and bringing a new team 'up to speed'. Most adolescents anticipating transfer to adult care identified only downsides and felt unprepared to transition at the time of the interview. Subjects who had transitioned noted benefits of the adult-oriented system, even if they had been ambivalent prior to transfer of care. Participants suggested that earlier discussions about transition, opportunities to meet new healthcare teams and visits to adult-oriented venues prior to transition might aid in the transition process. Subspecialty paediatric providers should anticipate common fears and concerns of adolescents and discuss the benefits of transfer to adult-oriented care. Further evaluation of existing transition programmes is an area for future study and is necessary for improvement of the continuum of care for adolescents with chronic medical conditions. | 18,796,047 |
Parenting interventions and the prevention of unintentional injuries in childhood: systematic review and meta-analysis. | To evaluate the effectiveness of parenting interventions in preventing unintentional injury and increasing parental safety practices. A range of medical and social science electronic databases were searched. Abstracts from the first to seventh World conferences on injury prevention and control and the journal Injury Prevention were hand searched. Randomized controlled trials (RCTs), non-randomized controlled trials (non-RCTs) and controlled before and after studies, providing parenting interventions to parents of children aged 0-18 years and reporting injuries, safety equipment or safety practices were included. Studies were selected, data extracted and quality appraised independently by two reviewers. Pooled relative risks were estimated using random effect models. Fifteen studies (11 RCTs) were included, 11 of which were home visiting programmes and two of which were paediatric practice-based interventions. Thirteen studies recruited families at risk of adverse child health outcomes. Intervention arm families had a significantly lower risk of injury (RR 0.82, 95% CI 0.71-0.95), as measured by self-report of medically or non-medically attended injury. Several studies found fewer home hazards, a home environment more conducive to child safety, or a greater number of safety practices in intervention arm families. Parenting interventions, most commonly provided within the home, using multi-faceted interventions appear to be effective in reducing unintentional child injury. Further research is required to explore the mechanisms by which parenting interventions reduce injury, the features of interventions that are necessary to reduce injury, and their generalizability to different population groups. | 18,796,060 |
The level of Internet access and ICT training for health information professionals in sub-Saharan Africa. | Information and Communication Technologies (ICTs) are important tools for development. Despite its significant growth on a global scale, Internet access is limited in sub-Saharan Africa (SSA). Few studies have explored Internet access, use of electronic resources and ICT training among health information professionals in Africa. The study assessed Internet access, use of electronic resources and ICT training among health information professionals in SSA. A 26-item self-administered questionnaire in English and French was used for data collection. The questionnaire was completed by health information professionals from five Listservs and delegates at the 10th biannual Congress of the Association of Health Information and Libraries in Africa (AHILA). A total of 121 respondents participated in the study and, of those, 68% lived in their countries' capital. The majority (85.1%) had Internet access at work and 40.8% used cybercafes as alternative access points. Slightly less than two-thirds (61.2%) first learned to use ICT through self-teaching, whilst 70.2% had not received any formal training in the previous year. Eighty-eight per cent of respondents required further ICT training. In SSA, freely available digital information resources are underutilized by health information professionals. ICT training is recommended to optimize use of digital resources. To harness these resources, intergovernmental and non-governmental organizations must play a key role. | 18,796,078 |
Incidence and prevalence of inflammatory bowel disease in a Northern California managed care organization, 1996-2002. | There are few estimates of the incidence and prevalence of inflammatory bowel disease in North American communities. We sought to estimate the incidence and prevalence of inflammatory bowel disease (IBD), including Crohn's disease (CD), and ulcerative colitis (UC), among 3.2 million members of Kaiser Permanente, Northern California, for the period 1996-2002. All health plan members who had one or more diagnoses of CD (ICD-9 code 555) or UC (ICD-9 code 556) on computerized records during the period 1996-2002 and with at least 12 months of membership were identified as possible IBD cases (N = 12,059). We randomly sampled 24% of these for chart review to confirm the diagnosis and obtain the initial diagnosis date. Incidence rates and the point prevalence on December 31, 2002 were standardized to the 2000 U. S. Census. The annual incidence rate per 100,000 persons was 6.3 for CD (95% confidence interval [CI], 5.6-7.0) and 12.0 for UC (CI, 11.0-13.0). The point prevalence per 100,000 on December 31, 2002 was 96.3 for CD (95% CI, 89.6-103.0) and 155.8 for UC (95% CI, 146.6-164.9), increasing to 100.3 and 205.8 per 100,000, respectively, when hospital discharge data from 1985 to 1995 were included. The age-specific incidence of CD was bimodal, while UC incidence rose in early adulthood and remained elevated with advancing age. The incidence we estimated for CD was similar to the previous U. S. estimate. Our incidence estimate for UC was much higher than the previous U.S. estimate, but similar to that of recent Canadian and European studies. The prevalence we estimated for CD was somewhat lower than previous estimates. | 18,796,097 |
A new picture of cell wall protein dynamics in elongating cells of Arabidopsis thaliana: confirmed actors and newcomers. | Cell elongation in plants requires addition and re-arrangements of cell wall components. Even if some protein families have been shown to play roles in these events, a global picture of proteins present in cell walls of elongating cells is still missing. A proteomic study was performed on etiolated hypocotyls of Arabidopsis used as model of cells undergoing elongation followed by growth arrest within a short time. Two developmental stages (active growth and after growth arrest) were compared. A new strategy consisting of high performance cation exchange chromatography and mono-dimensional electrophoresis was established for separation of cell wall proteins. This work allowed identification of 137 predicted secreted proteins, among which 51 had not been identified previously. Apart from expected proteins known to be involved in cell wall extension such as xyloglucan endotransglucosylase-hydrolases, expansins, polygalacturonases, pectin methylesterases and peroxidases, new proteins were identified such as proteases, proteins related to lipid metabolism and proteins of unknown function. This work highlights the CWP dynamics that takes place between the two developmental stages. The presence of proteins known to be related to cell wall extension after growth arrest showed that these proteins may play other roles in cell walls. Finally, putative regulatory mechanisms of protein biological activity are discussed from this global view of cell wall proteins. | 18,796,151 |
Biliary peritonitis caused by a leaking T-tube fistula disconnected at the point of contact with the anterior abdominal wall: a case report. | Operations on the common bile duct may lead to potentially serious complications such as biliary peritonitis. T-tube insertion is performed to reduce the risk of this occurring postoperatively. Biliary leakage at the point of insertion into the common bile duct, or along the fistula, can sometimes occur after T-tube removal and this has been reported extensively in the literature. We report a case where the site at which the T-tube fistula leaked proved to be the point of contact between the fistula and the anterior abdominal wall, a previously unreported complication. A 36-year-old sub-Saharan African woman presented with gallstone-induced pancreatitis and, once her symptoms settled, laparoscopic cholecystectomy was performed, common bile duct stones were removed and a T-tube was inserted. Three weeks later, T-tube removal led to biliary peritonitis due to the disconnection of the T-tube fistula which was recannulated laparoscopically using a Latex drain. This case highlights a previously unreported mechanism for bile leak following T-tube removal caused by detachment of a fistula tract at its contact point with the anterior abdominal wall. Hepatobiliary surgeons should be aware of this mechanism of biliary leakage and the use of laparoscopy to recannulate the fistula. | 18,796,154 |
Risk factors for and influence of bloodstream infections on mortality: a 1-year prospective study in a Greek intensive-care unit. | To determine the incidence, risk factors for, and the influence of bloodstream infections (BSIs) on mortality of patients in intensive-care units (ICUs), prospectively collected data from all patients with a stay in an ICU >48 h, during a 1-year period, were analysed. Of 572 patients, 148 developed a total of 232 BSI episodes (incidence 16.3 episodes/1000 patient-days). Gram-negative organisms with high level of resistance to antibiotics were the most frequently isolated pathogens (157 strains, 67.8%). The severity of illness on admission, as estimated by APACHE II score (OR 1.07, 95% CI 1.04-1.1, P<0.001), the presence of acute respiratory distress syndrome (OR 3.57, 95% CI 1.92-6.64, P<0.001), and a history of diabetes mellitus (OR 2.37, 95% CI 1.36-4.11, P=0.002) were risk factors for the occurrence of BSI whereas the development of an ICU-acquired BSI was an independent risk factor for death (OR 1.76, 95% CI 1.11-2.78, P=0.015). Finally, the severity of organ dysfunction on the day of the first BSI episode, as estimated by SOFA score, and the level of serum albumin, independently affected the outcome (OR 1.44, 95% CI 1.22-1.7, P<0.001 and OR 0.47, 95% CI 0.23-0.97, P=0.04 respectively). | 18,796,170 |
Development of cavernous haemangioma following radical chemo-radiotherapy for nasopharyngeal carcinoma. | We report an adult case of nasopharyngeal carcinoma treated with radical chemo-radiotherapy, with subsequent development of a histologically proved temporal cavernous haemangioma within the radiation field. Case report and review of the current literature concerning radiation-induced, secondary, space-occupying lesions. The increasing role of radiotherapy in nasopharyngeal carcinoma treatment, together with improved patient survival, is likely to lead to radiation-induced, secondary, space-occupying lesions being encountered more frequently. We emphasise the need to be vigilant for this important but relatively rare complication, which has significant associated morbidity. | 18,796,183 |
LC-APCI-MS-MS method for the tissue distribution of viaminate after oral administrations to rats. | Fast and sensitive liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method for the specific determination of viaminate in 14 kinds of rat tissues pre-treated with simple procedure was developed and validated. Biological samples were prepared by direct precipitation to skin, stomach, intestine, and liver and extracted by liquid-liquid extraction to lung, kidney, muscle, spleen, brain, fat, testes (male and female), eye, and heart. After addition of menaquinon as internal standard to tissue homogenate, the supernatant was injected into the isocratic chromatographic system using a Waters Symmetry C8 column and methanol-water-formic acid (93:7:0.1) as the eluent. The eluate was completely led into an APCI interface with selected ion monitoring mode and the analytes were quantified using triple quadrupole MS. The assays were successfully validated in the ranges 0.02-20 ng/mL for lung, 0.02-10 ng/mL for kidney, spleen, muscle, brain, fat, eye, and heart, 0.05-10 ng/mL for testicle, 0.4-100 ng/mL for liver, skin and intestine, and 1.0-200 ng/mL for stomach. The accurate and precise studies showed good reproducibility with coefficients of variation below 8.5% and the recoveries range from 90 to 109%. The analytes were chemically stable under all relevant conditions and the assays were applied in tissue distribution study. The results showed that the viaminate concentration was high in skin, low in kidney, and almost undetectable in eye and brain. | 18,796,226 |
A simple high-performance liquid chromatographic method for the estimation of boswellic acids from the market formulations containing Boswellia serrata extract. | A simple, rapid, and reproducible reverse-phase high-performance liquid chromatographic method is developed for the estimation of boswellic acids, the active constituents in Boswellia serrata oleo-gum resin. The chromatographic separation is performed using a mobile phase consisting of acetonitrile-water (90:10, % v/v) adjusted to pH 4 with glacial acetic acid on a Kromasil 100 C18 analytical column with flow rate of 2.0 mL/min and detection at 260 nm. The elution times are 4.30 and 7.11 min for 11-keto beta-boswellic acid (11-KBA) and 3-acetyl 11-keto beta-boswellic acid (A-11-KBA), respectively. The calibration curve is linear in the 11.66-58.30 microg/mL and 6.50-32.50 microg/mL range for 11-KBA and A-11-KBA, respectively. The limits of detection are 2.33 microg/mL and 1.30 microg/mL for 11-KBA and A-11-KBA, respectively. The mean recoveries are 98.24% to 104.17% and 94.12% to 105.92% for 11-KBA and A-11-KBA, respectively. The inter- and intra-day variation coefficients are less than 5%. The present method is successfully applied for the estimation of boswellic acids from the market formulations containing Boswellia serrata extract. | 18,796,232 |
Determination of metolcarb and diethofencarb in apples and apple juice by solid-phase microextraction-high performance liquid chromatography. | A method for the determination of metolcarb and diethofencarb in apples and apple juice is developed using solid-phase microextraction (SPME) coupled with high-performance liquid chromatography (HPLC). The experimental conditions of SPME, such as the kind of extraction fiber, extraction time, stirring rate, pH of the extracting solution, and desorption conditions are optimized. The SPME is performed on a 60 microm polydimethylsiloxane/divinylbenzene fiber for 40 min at room temperature with the solution being stirred at 1100 rpm. The extracted pesticides on the SPME fiber are desorbed in the mobile phase into SPME-HPLC interface for HPLC analysis. Separations are carried out on a Baseline C18 column (4.6 i.d. x 250 mm, 5.0 microm) with acetonitrile-water (55/45, v/v) as the mobile phase at a flow rate of 1.0 mL/min, and photodiode-array detection at 210 nm. For apple samples, the method is linear for both metolcarb and diethofencarb in the range of 0.05-1.0 mg/kg (r > 0.99), with a detection limit (S/N = 3 ) of 15 and 5 microg/kg, respectively. For apple juice, the method is linear for both metholcarb and diethofencarb over the range of 0.05-1.0 mg/L (r > 0.99) with the detection limit (S/N = 3 ) of 15 and 3 microg/L, respectively. Excellent recovery and reproducibility values are achieved. The proposed method is shown to be simple, sensitive, and organic solvent-free, and is suitable for the determination of the two pesticides in apples and apple juice. | 18,796,236 |
The influence of pH on the inhibition of DNA cleavages induced by pyrogallol. | Induction of DNA damage by pyrogallol has been shown at physiological pH, but mutagenesis data also suggest there is inhibition in acidic media. In the present work, the plasmid pBSK was incubated with pyrogallol, under aerobic conditions at 37 degrees C, at pH 7.4, 4.5 or 3.5, for 1, 3 or 5 h, in the absence or presence of Cu(2+). Cleavage of the supercoiled DNA form was analyzed through topology modifications by agarose gel electrophoresis and quantified by densitometry. Independently of the presence of Cu(2+), DNA cleavage at pH 7.4 was significantly (P < 0.001) induced and occurred extensively after 1-h incubation. At pH 4.5, the cleavage was significantly (P < 0.05) induced only after 5 h incubation in the absence of Cu(2+), but was extensive (P < 0.001) after 1-h incubation when the metal ion was present. At pH 3.5, DNA cleavage was inhibited (P > 0.05), after 5-h incubation, even in the presence of Cu(2+). Our results provide evidence that DNA cleavage by pyrogallol is pH-dependent, catalyzed by Cu(2+) , and extensively decreased in acidic pH. Due to the abundant presence of the pyrogallate ion in physiological media, we suggest that this conjugate base form is responsible for DNA cleavage. | 18,796,239 |
The effectiveness and cost-effectiveness of minimal access surgery amongst people with gastro-oesophageal reflux disease - a UK collaborative study. The REFLUX trial. | To evaluate the clinical effectiveness, cost-effectiveness and safety of a policy of relatively early laparoscopic surgery compared with continued medical management amongst people with gastro-oesophageal reflux disease (GORD) judged suitable for both policies. Relative clinical effectiveness was assessed by a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. The economic evaluation compared the cost-effectiveness of the two management policies in order to identify the most efficient provision of future care and describe the resource impact that various policies for fundoplication would have on the NHS. A total of 21 hospitals throughout the UK with a local partnership between surgeon(s) and gastroenterologist(s) who shared the secondary care of patients with GORD. The 810 participants, who were identified retrospectively or prospectively via their participating clinicians, had both documented evidence of GORD (endoscopy and/or manometry/24-hour pH monitoring) and symptoms for longer than 12 months. In addition, the recruiting clinician(s) was clinically uncertain about which management policy was best. Of the 810 eligible patients who consented to participate, 357 were recruited to the randomised arm of the trial (178 allocated to surgical management, 179 allocated to continued, but optimised, medical management) and 453 recruited to the parallel non-randomised preference arm (261 chose surgical management, 192 chose to continue with best medical management). The type of fundoplication was left to the discretion of the surgeon. Participants completed a baseline REFLUX questionnaire, developed specifically for this study, containing a disease-specific outcome measure, the Short Form with 36 Items (SF-36), the EuroQol-5 Dimensions (EQ-5D) and the Beliefs about Medicines and Surgery questionnaires (BMQ/BSQ). Postal questionnaires were completed at participant-specific time intervals after joining the trial (equivalent to approximately 3 and 12 months after surgery). Intraoperative data were recorded by the surgeons and all other in-hospital data were collected by the research nurse. At the end of the study period, participants completed a discrete choice experiment questionnaire. The randomised groups were well balanced at entry. Participants had been taking GORD medication for a median of 32 months; the mean age of participants was 46 years and 66% were men. Of 178 randomised to surgery, 111 (62%) actually had fundoplication. There was a mixture of clinical and personal reasons why some patients did not have surgery, sometimes related to long waiting times. A total or partial wrap procedure was performed depending on surgeon preference. Complications were uncommon and there were no deaths associated with surgery. By the equivalent of 12 months after surgery, 38% in the randomised surgical group (14% amongst those who had surgery) were taking reflux medication compared with 90% in the randomised medical group. There were substantial differences (one-third to one-half standard deviation) favouring the randomised surgical group across the health status measures, the size depending on assumptions about the proportion that actually had fundoplication. These differences were the same or somewhat smaller than differences observed at 3 months. The lower the REFLUX score, the worse the symptoms at trial entry and the larger the benefit observed after surgery. The preference surgical group had the lowest REFLUX scores at baseline. These scores improved substantially after surgery, and by 12 months they were better than those in the preference medical group. The BMQ/BSQ and discrete choice experiment did distinguish the preference groups from each other and from the randomised groups. The latter indicated that the risk of serious complications was the most important single attribute of a treatment option. A within-trial cost-effectiveness analysis suggested that the surgery policy was more costly (mean 2049 pounds) but also more effective [+0.088 quality-adjusted life-years (QALYs)]. The estimated incremental cost per QALY was 19,000-23,000 pounds, with a probability between 46% (when 62% received surgery) and 19% (when all received surgery) of cost-effectiveness at a threshold of 20,000 pounds per QALY. Modelling plausible longer-term scenarios (such as lifetime benefit after surgery) indicated a greater likelihood (74%) of cost-effectiveness at a threshold of 20,000 pounds, but applying a range of alternative scenarios indicated wide uncertainty. The expected value of perfect information was greatest for longer-term quality of life and proportions of surgical patients requiring medication. Amongst patients requiring long-term medication to control symptoms of GORD, surgical management significantly increases general and reflux-specific health-related quality of life measures, at least up to 12 months after surgery. Complications of surgery were rare. A surgical policy is, however, more costly than continued medical management. At a threshold of 20,000 pounds per QALY it may well be cost-effective, especially when putative longer-term benefits are taken into account, but this is uncertain. The more troublesome the symptoms, the greater the potential benefit from surgery. Uncertainty about cost-effectiveness would be greatly reduced by more reliable information about relative longer-term costs and benefits of surgical and medical policies. This could be through extended follow-up of the REFLUX trial cohorts or of other cohorts of fundoplication patients. Current Controlled Trials ISRCTN15517081. | 18,796,263 |
Status of immune mediators in fibromyalgia. | Fibromyalgia (FM) is a form of nonarticular rheumatism characterized by long-term (> 3 months) and widespread musculoskeletal pain. However, the biophysiology of FM has remained elusive, and the treatment remains mainly empirical. There are numerous hypotheses about the pathophysiology of chronic widespread pain and FM; one includes a possible role of cytokines. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress, and aching. Cytokines related to acute or repetitive tissue injuries may be responsible for long-term activation of spinal cord glia and dorsal horn neurons, thus resulting in central sensitization. Pain, stiffness, and depression in FM could be associated with some signs of inflammatory response system activation. Illumination of the pathophysiologic secrets of FM will result in more effective treatment regimens. We review the role of immune mediators in the pathophysiology of FM. | 18,796,266 |
[Smoking--a risk factor for rheumatoid arthritis development]. | Rheumatoid arthritis (RA) is a chronic disabling inflammatory joint disease of unknown aetiology. Genetic and environmental factors are implicated in its pathogenesis. We performed a literature search on MEDLINE, the Cochrane database and EMBASE on the interaction between smoking and RA. It is concluded that previous and current smoking constitute a risk factor for RA development. Smoking acts synergistically with other RA risk factors, including IgM-rheumatoid factor, anti-CCP and shared epitopes. The effect of smoking on the course of RA has not been described in sufficient detail. | 18,796,279 |
Proteomic analysis of proteins associated with tt-DDE induced toxicity in BEAS-2B cells. | Trans, trans-2,4-decadienal (tt-DDE), a specific type of dienaldehyde, is abundant in heated oils or cooking oil fumes. Ingestion of heated oils and exposure to cooking oil fumes has been suggested to have a great health impact in a variety of organs, including the lungs. Previous studies have demonstrated that acute exposures to high doses of tt-DDE have induced oxidative stress, genotoxicity, and cytotoxicity in human lung cells. The objective in utilizing proteomic techniques of this study was to identify protein biomarkers associated with tt-DDE-induced oxidative stress and cytotoxicity in human bronchial epithelial cells BEAS-2B. Experimental results suggested that DJ-1 and cofilin proteins were protein biomarkers for tt-DDE-induced cytotoxicity and oxidative stress in lung cells. DJ-1 was especially an early biomarker for tt-DDE exposure. | 18,796,293 |
Polymorphisms in advanced glycosylation end product-specific receptor (AGER) gene, insulin resistance, and type 2 diabetes mellitus. | Variants in the advanced glycosylation end product-specific receptor (AGER) gene have been associated with diabetic vasculopathy, however their role in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) are uncertain. We investigated the relationship of 3 polymorphisms (rs1800625, rs1800624 and rs2070600) in the AGER gene and their haplotypes with T2DM as well as insulin resistance. A case-control study from community-based population sample of the Boston metropolitan area was performed in 637 diabetic patients and 596 controls (non-diabetic). The relationships between genotypes and T2DM were evaluated by linear and logistic regression models. Associations with insulin resistance [using corrected insulin response (CIR-30), insulin sensitivity index (ISI-120) and oral glucose tolerance test] were also examined among controls. We found no consistent association between prevalent type 2 diabetes mellitus, and "insulin indices" (CIR-30, ISI-120 and oral glucose tolerance test) and the AGER polymorphisms. The A allele in the rs1800624 was modestly associated with a progressive decrease in CIR-30 levels only among Black controls (p=0.03). A suggestive association between the A allele in the rs1800624 and CIR-30 levels was found. Further large and multiethnic studies should be performed to clarify these relationships. | 18,796,298 |
Antidepressant-like effects of the glucocorticoid receptor antagonist RU-43044 are associated with changes in prefrontal dopamine in mouse models of depression. | Chronic corticosterone and isolation rearing paradigms may provide reliable mouse models of depression. Using these models, the present study examined if the specific glucocorticoid receptor antagonist, RU-43044, has an antidepressant-like effect, and studied the possible role of prefrontal neurotransmission on the behavioral effects. Chronic administration of corticosterone and isolation rearing increased the immobility time in the forced swim and tail suspension tests. Subchronic treatment with RU-43044 decreased the immobility time in the forced swim test in chronic corticosterone-treated and isolation-reared mice, but not the control mice. Chronic corticosterone decreased the levels of cortical glucocorticoid receptors and stress-induced increases in plasma corticosterone levels, and blocked the response of plasma corticosterone to dexamethasone, while isolation rearing did not cause any changes in the glucocorticoid receptor system. Both chronic corticosterone and isolation rearing markedly increased high K+ -induced dopamine release, but not serotonin release, in the prefrontal cortex. Subchronic RU-43044 reversed the enhanced release of dopamine in the prefrontal cortex of chronic corticosterone-treated and isolation-reared mice. These results suggest that chronic corticosterone and isolation rearing increase the depressive-like behavior in glucocorticoid receptor-dependent and independent manners, respectively, and that RU-43044 shows an antidepressant-like effect, probably via an inhibition of enhanced prefrontal dopaminergic neurotransmission in these mouse models. | 18,796,307 |
Tf-lipoplexes for neuronal siRNA delivery: a promising system to mediate gene silencing in the CNS. | Although RNAi-based gene silencing holds a great potential for treatment of neurological disorders, its application to the CNS has been restricted by low levels of tissue distribution and cellular uptake. In this work we report that cationic lipid-based vectors can enhance siRNA delivery to neurons both in vitro and in vivo. DOTAP:Chol liposomes associated with transferrin (Tf) and complexed with siRNAs (Tf-lipoplexes) were delivered to primary cultures of luciferase-expressing cortical neurons. Confocal microscopy studies revealed efficient cellular uptake of Cy3-labelled siRNAs after Tf-lipoplex delivery, which was reduced but not completely inhibited by blocking the Tf-receptor with excess Tf. Gene silencing was also evaluated after delivery of anti-luciferase or anti-c-Jun siRNAs. Our results demonstrate that Tf-lipoplexes achieve up to 50% luciferase and c-Jun knockdown, 48 h after transfection, without significant cytotoxicity. Similar results were observed in vivo, where a 40% reduction of luciferase activity was found in the striatum of luciferase mice. In addition, fluorescence microscopy studies showed extensive local distribution and internalization of Tf-lipoplex-associated Cy3-siRNAs without tissue toxicity. Overall, our results demonstrate that Tf-lipoplexes can mediate efficient gene silencing in neuronal cells, both in vitro an in vivo, which may prove useful in therapeutic approaches to neuronal protection and repair. | 18,796,321 |
Pharmacokinetics of olanzapine in Chinese male schizophrenic patients with various smoking behaviors. | Tobacco consumption has been recognized as a factor mediating the interindividual variations in olanzapine's pharmacokinetics and pharmacodynamics. The primary objective of this study was to describe the dose effect of smoking on the dose-plasma concentration relationship and the pharmacokinetics of oral olanzapine in male schizophrenic patients using high-performance liquid chromatography coupled with electrochemical detector. Twenty-seven male schizophrenic inpatients were recruited and were stratified into the following groups according to smoking behaviors: non-smokers (n=9), light-smokers (1-4 cigarettes per day; n=9), and heavy-smokers (>or=5 cigarettes per day; n=9). Plasma olanzapine concentrations were determined up to 120 h following a single oral dose of 10 mg olanzapine. The pharmacokinetic parameters were calculated by the non-compartment method using WinNonlin software. Results show that there was a significant correlation among non-smokers (n=9; 0.79; p=0.01) or combined with light-smokers (n=18; 0.62; p<0.01) between peak plasma olanzapine concentrations (Cmax) and their individual dose-corrected by body weight, but this correlation did not appear in heavy-smokers. There were no significant differences between non-smokers and light-smokers except for significant decreased AUC0-->120 by 45.1% in light-smokers. The mean C(max) and the mean area under the plasma concentration-time curve from time zero to 120 h (AUC0-->120) of the heavy-smoking patients was 9.3+/-4.3 ng/ml (65.2% reduction compared to the non-smokers) and 302.4+/-167.8 h ng/ml (67.6% reduction compared to the non-smokers), respectively. In summary, a daily consumption of 5 cigarettes is probably sufficient for induction of olanzapine metabolism. Smoking cessation is recommended for olanzapine therapy to have better prediction for therapeutic dosages particularly in heavy-smokers. Compared to non-smokers, heavy-smokers therefore require a 50-100% increase in olanzapine doses. Therapeutic drug monitoring will need to be considered when schizophrenic patients change their smoking behaviors. | 18,796,323 |
Effect of antioxidant phytochemicals on the hepatic tumor promoting activity of 3,3',4,4'-tetrachlorobiphenyl (PCB-77). | Polychlorinated biphenyls (PCBs) have promoting activity in the liver, which may be brought about in part by the induction of oxidative stress. In this study we examined the effects of several antioxidant phytochemicals on the tumor promoting activity of 3,3',4'4-tetrachlorobiphenyl (PCB-77). Female Sprague Dawley rats were first injected with diethylnitrosamine (DEN, 150 mg/kg) and one week later the rats were fed an AIN-93 based purified diet or the same diet containing ellagic acid (0.4%), beta-carotene (0.5%), curcumin (0.5%), N-acetyl cysteine (NAC, 1.0%), coenzyme CoQ10 (CoQ10, 0.4%), resveratrol (0.005%), lycopene (10% as Lycovit, which contains 10% lycopene), or a tea extract (1%, containing 16.5% epigallocatechin-3-gallate [EGCG] and 33.4% total catechins). Rats were fed the diets for the remainder of the study. After three weeks, 2/3 of the control rats and all of the antioxidant diet-fed rats were injected i.p. with PCB-77 (300 micromol/kg) every other week for four injections. All rats were euthanized ten days after the last PCB injection. The rats that received PCB-77 alone showed an increase in the number and size of placental glutathione S-transferase (PGST)-positive foci in the liver. Lycopene significantly decreased the number of foci, while curcumin and CoQ10 decreased the size of the foci. In contrast, ellagic acid increased the number but decreased the size of the foci. All of the other phytochemicals showed only slight or no effects. Compared with the PCB-77 group, CoQ10 increased cell proliferation in normal hepatocytes, whereas the other antioxidants had no effect in either normal or PGST-positive hepatocytes. These findings show that none of the antioxidant phytochemicals produced a clear decrease in the promoting activity of PCB-77. | 18,796,325 |
RANKL-induced schlafen2 is a positive regulator of osteoclastogenesis. | Osteoclasts are hematopoietic lineage derived-multinucleated cells that resorb bone. Their activity in balance with that of osteoblast is essential for bone homeostasis. Receptor activator of NF-kappaB ligand (RANKL) is known as an essential cytokine for the osteoclastogenesis, and c-Jun signaling in cooperation with NFAT family is crucial for RANKL-regulated osteoclastogenesis. We show here that schlafen2 (Slfn2), a member of a new family of growth regulatory genes involved in thymocyte development, is critical for osteoclastogenesis. RANKL selectively induces Slfn2 expression in osteoclast precursors via Rac1 signaling pathway. Targeted inhibition of Slfn2 by small interfering RNAs (siRNAs) markedly inhibits the formation of osteoclasts by diminishing the activation of c-Jun and the expression of c-Jun and NFATc1. In contrast, the overexpression of Slfn2 markedly increased phosphorylation and transactivation of c-Jun by RANKL. Together, these results indicate that Slfn2 has an essential role in osteoclastogenesis, functioning upstream of c-Jun and NFATc1. | 18,796,328 |
Methane production potential of leachate generated from Korean food waste recycling facilities: a lab-scale study. | This paper examines the applicability of food waste leachate (FWL) in bioreactor landfills or anaerobic digesters to produce methane as a sustainable solution to the persisting leachate management problem in Korea. Taking into account the climatic conditions in Korea and FWL characteristics, the effect of key parameters, viz., temperature, alkalinity and salinity on methane yield was investigated. The monthly average moisture content and the ratio of volatile solids to total solids of the FWL were found to be 84% and 91%, respectively. The biochemical methane potential experiment under standard digestion conditions showed the methane yield of FWL to be 358 and 478 ml/g VS after 10 and 28 days of digestion, respectively, with an average methane content of 70%. Elemental analysis showed the chemical composition of FWL to be C(13.02)H(23.01)O(5.93)N(1). The highest methane yield of 403 ml/g VS was obtained at 35 degrees C due to the adaptation of seed microorganisms to mesophilic atmosphere, while methane yields at 25, 45 and 55 degrees C were 370, 351 and 275 ml/g VS, respectively, at the end of 20 days. Addition of alkalinity had a favorable effect on the methane yield. Dilution of FWL with salinity of 2g/l NaCl resulted in 561 ml CH(4)/g VS at the end of 30 days. Considering its high biodegradability (82.6%) and methane production potential, anaerobic digestion of FWL in bioreactor landfills or anaerobic digesters with a preferred control of alkalinity and salinity can be considered as a sustainable solution to the present emergent problem. | 18,796,348 |
Effects of streptococcal pyrogenic exotoxin B on pathogenesis of Streptococcus pyogenes. | Streptococcus pyogenes (group A streptococcus, GAS) is a ubiquitous and important human bacterial pathogen. This organism possesses several virulence factors to establish infection. One of these, the streptococcal pyrogenic exotoxin B (SpeB), is the predominant secreted cysteine protease of GAS. SpeB cleaves or degrades host serum proteins such as human extracellular matrix, immunoglobulins, complement components, and even GAS surface and secreted proteins. Destruction of both host and bacterial proteins makes SpeB the key virulence factor in GAS pathogenesis. Although several lines of evidence have shown that SpeB is an important virulence factor of GAS, its role in streptococcal infection remains controversial. Here, we review several publications and describe our current understanding of SpeB in GAS pathogenesis. | 18,796,357 |
Indocyanine green-assisted phacoemulsification in cases of complicated or simple advanced cataracts. | During phacoemulsification for advanced cataracts, particularly when complicated by anterior segment abnormalities, capsulorhexis is very difficult and carries a high risk of complications. This study investigated the efficacy and safety of indocyanine green (ICG)-assisted phacoemulsification in complicated or simple advanced cataracts. Thirty-two patients (35 eyes) underwent phacoemulsification for complicated advanced cataracts (group 1) or simple advanced (mature/hypermature) cataracts (group 2). Anterior segment abnormalities (corneal opacity, small pupil, or glaucoma) in group 1 complicated phacoemulsification. In both groups, 0.5% ICG was used for capsulorhexis, and subsequent procedures were performed in the same routine manner. Group 1 included 15 patients (17 eyes) with a mean age of 60.0 years. Group 2 included 17 patients (18 eyes) with a mean age of 69.4 years (p<0.05). Continuous curvilinear capsulorhexis was completed in all eyes in group 2, but radial tears occurred in four (23.5%) eyes in group 1 (p<0.05). Phacoemulsification was performed uneventfully in all eyes in both groups. Postoperative complications (corneal edema, vitreous prolapse, posterior capsule opacity, elevated intraocular pressure) were seen in five (27.8%) eyes in group 1 and four (23.5%) eyes in group 2 (p>0.05). None of these were attributed to the use of ICG. Visual acuity improved in all eyes in group 2, but in only 11 (64.7%) in group 1 (p<0.01). ICG-assisted phacoemulsification is safe and helpful for complicated or simple advanced cataracts. Differences between the two groups in patient age, intraoperative complications, and visual outcome could be explained by differences in the cause(s) of advanced cataracts. | 18,796,361 |
Prevalence of lower urinary tract symptoms in male aborigines and non-aborigines in eastern Taiwan. | Lower urinary tract symptoms (LUTS) are highly prevalent in men. The relationship of LUTS with socioeconomic level has not been investigated in Asian people. This study investigated the prevalence of LUTS in men and between aborigines and non-aborigines in eastern Taiwan, and their association with demographic, socioeconomic and behavioral characteristics. A survey of LUTS in adult male community residents of Hualien district was conducted in 2006. LUTS were assessed using questionnaires for the International Prostate Symptom Score (IPSS) and Quality of Life Index (QoL-I). The prevalence of each bothersome LUTS, moderate LUTS (IPSS>8) and impaired QoL (QoL-I>4) were compared between aborigines and non-aborigines. The association between the prevalence of LUTS and socioeconomic status was also compared between the two groups. There were 196 aborigines (32%) and 419 non-aborigines (68%) who completed the questionnaires. Nocturia was the most common LUTS in aboriginal and non-aboriginal men. The prevalence of moderate LUTS increased with age (p<0.001) in men overall. Significantly higher prevalence rates of frequency (11.7% vs. 7.2%, p=0.044) and nocturia (31.1% vs. 19.8%, p=0.002) were found in aborigines than non-aborigines. However, there was no significant difference in the prevalence of moderate LUTS (12.8% vs. 8.8%, p=0.220) or impaired QoL (24.3% vs. 19.9%, p=0.088) between aborigines and non-aborigines. The higher prevalence of frequency and nocturia in aborigines was associated with significantly lower educational and economic levels, which were also associated with a higher prevalence of alcohol drinking, betel quid chewing and cigarette smoking. Nocturia was the most common LUTS in community dwelling aboriginal and non-aboriginal adult males. A low socioeconomic level was associated with a higher prevalence rate of moderate LUTS and impaired QoL, especially in aborigines. | 18,796,363 |
Adjuvant chemotherapy for early-stage non-small-cell lung cancer. Single-centre experience and literature review. | In recent years platinum-based chemotherapy has become the standard of care for patients with good performance status after complete resection in stages IB-IIIA non-small-cell lung cancer (NSCLC), although the benefit is mainly in stages II and IIIA. In a retrospective trial we evaluate the clinical efficacy and toxicity profile of a platinum- and taxanes-based adjuvant chemotherapy in completely resected IB-IIIA NSCLC. The primary end point was relapse- free survival (RFS); principal secondary end points were overall survival (OS) and safety of the regimen. Potential predictive factors of efficacy and clinical patterns of relapse were also analysed. From January 2003 to December 2006, 41 patients met the inclusion criteria and were evaluable. Median age at diagnosis was 68.1 years (CI 95% 54-72; range 45-78). Most patients were males (87.7%) and had an Eastern Cooperative Oncology Group performance status score (PS) of 0-1 (87.8%), and 53.6% had adenocarcinomas. Pathological stages were as follow: 48.7% stage IB, 24.3% stage II and 26.8% stage IIIA. 75.6% of patients underwent a lobectomy and mediastinal lymphadenectomy and were treated with a combination of carboplatin AUC6 and paclitaxel 200 mg/m2 (85.36%) for 3 or 4 cycles. With a median follow-up of 18.2 months (range 5.1-46.5), 26 patients (63%) were free of disease and 32 of them were alive (78%). Median RFS was 12.1 months (CI 95% 9.8-14.9) and median OS had not been reached at the time of analysis. Patients with PS< or =1 at diagnosis had a higher RFS [p=0.051 (CI 95% 0.90-0.96)]. Toxicity was generally mild and haematologic events were the most frequent. Non-haematologic toxic effects of chemotherapy were asthenia/ anorexia (12.2%), nausea/vomiting (12.2%) and peripheral neuropathy (17%), but severe toxic effects (grade 3 or greater) were uncommon (<10%). We did not observe treatment-related deaths. Platinum-taxane-based adjuvant chemotherapy in IB-IIIA NSCLC following complete resection is feasible, well tolerated and can be delivered in most patients in the adjuvant setting. Ongoing molecular studies may have value in determining which patients will benefit from adjuvant chemotherapy. | 18,796,373 |
Several deep-sea mussels and their associated symbionts are able to live both on wood and on whale falls. | Bathymodiolin mussels occur at hydrothermal vents and cold seeps, where they thrive thanks to symbiotic associations with chemotrophic bacteria. Closely related genera Idas and Adipicola are associated with organic falls, ecosystems that have been suggested as potential evolutionary 'stepping stones' in the colonization of deeper and more sulphide-rich environments. Such a scenario should result from specializations to given environments from species with larger ecological niches. This study provides molecular-based evidence for the existence of two mussel species found both on sunken wood and bones. Each species specifically harbours one bacterial phylotype corresponding to thioautotrophic bacteria related to other bathymodiolin symbionts. Phylogenetic patterns between hosts and symbionts are partially congruent. However, active endocytosis and occurrences of minor symbiont lineages within species which are not their usual host suggest an environmental or horizontal rather than strictly vertical transmission of symbionts. Although the bacteria are close relatives, their localization is intracellular in one mussel species and extracellular in the other, suggesting that habitat choice is independent of the symbiont localization. The variation of bacterial densities in host tissues is related to the substrate on which specimens were sampled and could explain the abilities of host species to adapt to various substrates. | 18,796,394 |
Genetic inactivation of NPC1L1 protects against sitosterolemia in mice lacking ABCG5/ABCG8. | Mice lacking Niemann-Pick C1-Like 1 (NPC1L1) (NPC1L1(-/-)mice) exhibit a defect in intestinal absorption of cholesterol and phytosterols. However, wild-type (WT) mice do not efficiently absorb and accumulate phytosterols either. Cell-based studies show that NPC1L1 is a much weaker transporter for phytosterols than cholesterol. In this study, we examined the role of NPC1L1 in phytosterol and cholesterol trafficking in mice lacking ATP-binding cassette (ABC) transporters G5 and G8 (G5/G8(-/-) mice). G5/G8(-/-) mice develop sitosterolemia, a genetic disorder characterized by the accumulation of phytosterols in blood and tissues. We found that mice lacking ABCG5/G8 and NPC1L1 [triple knockout (TKO) mice] did not accumulate phytosterols in plasma and the liver. TKO mice, like G5/G8(-/-) mice, still had a defect in hepatobiliary cholesterol secretion, which was consistent with TKO versus NPC1L1(-/-) mice exhibiting a 52% reduction in fecal cholesterol excretion. Because fractional cholesterol absorption was reduced similarly in NPC1L1(-/-) and TKO mice, by subtracting fecal cholesterol excretion in TKO mice from NPC1L1(-/-) mice, we estimated that a 25g NPC1L1(-/-) mouse may secrete about 4 mumol of cholesterol daily via the G5/G8 pathway. In conclusion, NPC1L1 is essential for phytosterols to enter the body in mice. | 18,796,403 |
Differential roles of the COOH termini of AAA subunits of PA700 (19 S regulator) in asymmetric assembly and activation of the 26 S proteasome. | The 26 S proteasome is an energy-dependent protease that degrades proteins modified with polyubiquitin chains. It is assembled from two multi-protein subcomplexes: a protease (20 S proteasome) and an ATPase regulatory complex (PA700 or 19 S regulatory particle) that contains six different AAA family subunits (Rpt1 to -6). Here we show that binding of PA700 to the 20 S proteasome is mediated by the COOH termini of two (Rpt2 and Rpt5) of the six Rpt subunits that constitute the interaction surface between the subcomplexes. COOH-terminal peptides of either Rpt2 or Rpt5 bind to the 20 S proteasome and activate hydrolysis of short peptide substrates. Simultaneous binding of both COOH-terminal peptides had additive effects on peptide substrate hydrolysis, suggesting that they bind to distinct sites on the proteasome. In contrast, only the Rpt5 peptide activated hydrolysis of protein substrates. Nevertheless, the COOH-terminal peptide of Rpt2 greatly enhanced this effect, suggesting that proteasome activation is a multistate process. Rpt2 and Rpt5 COOH-terminal peptides cross-linked to different but specific subunits of the 20 S proteasome. These results reveal critical roles of COOH termini of Rpt subunits of PA700 in the assembly and activation of eukaryotic 26 S proteasome. Moreover, they support a model in which Rpt subunits bind to dedicated sites on the proteasome and play specific, nonequivalent roles in the asymmetric assembly and activation of the 26 S proteasome. | 18,796,432 |
Balancing paediatric anaesthesia: preclinical insights into analgesia, hypnosis, neuroprotection, and neurotoxicity. | Logistical and ethical reasons make conducting clinical research in paediatric practice difficult, and therefore safe and efficacious advances are dependent on good preclinical research. For example, notable advances have been made in preclinical studies of pain processing that correlate well with patient data. Other areas of paediatric anaesthetic research remain in their infancy including mechanisms of anaesthesia and anaesthetic neuroprotection and neurotoxicity. Animal data have identified the potential 'double-edged' sword of administering anaesthetic agents in the young; although these agents can be neuroprotective in certain circumstances, they can be neurotoxic in others. The potential for this toxicity must be balanced against the importance of providing adequate anaesthesia for which there can be no compromise. We review the current state of preclinical research in paediatric anaesthesia and identify areas which require further exploration in order to provide the foundations for well-conducted clinical trials. | 18,796,440 |
Ocular vascular thrombotic events: a diagnostic window to familial thrombophilia (compound factor V Leiden and prothrombin gene heterozygosity) and thrombosis. | In a 12-member, 3-generation kindred with conjoint inheritance of G1691A factor V Leiden (FVL) and G20210A prothrombin gene (PTG) mutations, identified through a proband with amaurosis fugax and his father with nonarteritic ischemic optic neuropathy (NAION), the authors' hypothesis was that ocular thrombosis was a diagnostic window to familial thrombophilia-thrombosis. The authors used polymerase chain reaction (PCR) measures for thrombophilia (FVL, PTG, C677T-A1298C methylenetetrahydrofolate reductase [MTHFR], platelet glycoprotein PLA1A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). The 39-year-old white male proband, with amaurosis fugax and transient ischemic attacks (TIA), was found to be a compound heterozygote for FVL and PTG mutations. His symptoms resolved only after coumadin. His 44-year-old brother (deep venous thrombosis [DVT]) and 46-year-old sister (DVT, pulmonary embolus [PE]) were compound FVL-PTG gene heterozygotes. Of 4 asymptomatic children born to these 3 siblings, 2 were FVL heterozygotes and 2 PTG heterozygotes. The proband's 69-year-old father, with NAION and ischemic stroke, had PTG heterozygosity, familial high factor VIII, and compound MTHFR C677T-A1298C mutation with homocysteinemia. The proband's 61-year-old aunt had PTG heterozygosity, recurrent DVT, and mesenteric artery thrombosis. The proband's 67-year-old mother, free of thrombotic events, was a FVL heterozygote, had high factor VIII, and PAI-1 4G4G homozygosity. In this extended kindred, ocular thrombotic events (amaurosis fugax, NAION) were associated with variegated thrombotic events, including TIA, ischemic stroke, DVT, PE, and mesenteric artery thrombosis, and opened a diagnostic window to family screening and treatment for complex thrombophilias, which had previously been undiagnosed. | 18,796,459 |
Sport therapy for hypertension: why, how, and how much? | Exercise may prevent or reduce the effects of metabolic and cardiovascular diseases, including arterial hypertension. Both acute and chronic exercise, alone or combined with lifestyle modifications, decrease blood pressure and avoid or reduce the need for pharmacologic therapy in patients with hypertension. The hypotensive effect of exercise is observed in a large percentage of subjects, with differences due to age, sex, race, health conditions, parental history, and genetic factors. Exercise regulates autonomic nervous system activity, increases shear stress, improves nitric oxide production in endothelial cells and its bioavailability for vascular smooth muscle, up-regulates antioxidant enzymes. Endurance training is primarily effective, and resistance training can be combined with it. Low-to-moderate intensity training in sedentary patients with hypertension is necessary, and tailored programs make exercise safe and effective also in special populations. Supervised or home-based exercise programs allow a nonpharmacological reduction of hypertension and reduce risk factors, with possible beneficial effects on cardiovascular morbidity. | 18,796,453 |
MonkeySNP: a web portal for non-human primate single nucleotide polymorphisms. | MonkeySNP is a web-based resource created by the Genetic Resource and Informatics Program at the Oregon National Primate Research Center to facilitate access to non-human primate (NHP) single nucleotide polymorphisms (SNP) data. MonkeySNP is a mirror of the NCBI dbSNP database and contains additional NHP subpopulation genotype data and visual genotype displays to support SNP review and selection. http://monkeysnp.ohsu.edu/snp/ Supplementary data are available at Bioinformatics online. | 18,796,476 |
Perceived control moderated the self-efficacy-enhancing effects of a chronic illness self-management intervention. | Identifying moderators of the effects of self-efficacy-enhancing interventions could improve their efficiency. We examined the effects of a home-based variant of the Chronic Disease Self-Management Program on self-efficacy, and explored the moderating effects of perceived control over self-management (PCSM). In a randomized controlled trial, patients (N= 415) aged>40 years with various chronic conditions plus basic activity impairment and/or significant depressive symptoms were randomized to one of three groups: intervention provided in homes or by telephone, v. usual care control. We used mixed effects linear models for repeated measures to examine effects on self-management self-efficacy at 6-month follow-up and explore moderation by PCSM. Only the home intervention had a significant self-efficacy-enhancing effect (Wald test, chi( 2) = 13.8, p = 0.008; effect size = 0.3). The effect was moderated by PCSM, considered as a continuous [effective in subjects with lower PCSM (Wald test, chi(2) = 13.4, p = 0.009)] or categorical (effective only for subjects in the lowest tercile) variable. People with lower PCSM appear more likely to experience enhanced self-efficacy from chronic illness self-management training than those with higher PCSM. These findings, although preliminary, suggest that office-based measurement of PCSM might identify those chronically ill patients likely to benefit most from self-management training. | 18,796,506 |
Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. | Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain. We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy. The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses. Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers. After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups. After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women. | 18,796,517 |
Association of the Kir6.2 E23K variant with reduced acute insulin response in African-Americans. | ATP-sensitive potassium channels are composed of pore-forming (Kir6.x) and regulatory sulfonylurea receptor (SURx) subunits and have been implicated in the maintenance of glucose homeostasis. Kir6.2 and SUR1 are expressed in a broad range of tissues, and no contemporary studies have addressed the physiological impact of variants in Hispanic-Americans and African-Americans carefully phenotyped for components of glucose homeostasis. The objective of this study was to evaluate two nonsynonymous variants in Kir6.2 (E23K) and SUR1 (A1369S) and determine their role in vivo. The Insulin Resistance Atherosclerosis Family Study (IRAS-FS) is a community-based study of Hispanic-Americans (San Antonio, TX, and San Luis Valley, CO) and African-Americans (Los Angeles, CA). A total of 1,040 Hispanic-Americans and 500 African-American individuals formed the basis of this study. The primary glucose homeostasis phenotypes of interest in this study were derived from the frequently sampled iv glucose tolerance test and included insulin sensitivity (S(I)), acute insulin response, and disposition index. In African-Americans, both variants were associated with a significant reduction in insulin secretion in glucose-tolerant carriers of the minor alleles (additive P = 0.00053). S(I), a measure of insulin sensitivity, was not associated. In Hispanic-Americans, there was no association with measures of glucose homeostasis. We conclude that variation marked by the Kir6.2 E23K and SUR1 A1369S mutations is associated with alterations in glucose-stimulated insulin secretion but not with other measures of glucose homeostasis in an African-American population. | 18,796,522 |
Dynamic changes of the renin-angiotensin and associated systems in the rat after pharmacological and dietary interventions in vivo. | To address the multiplicity of the renin-angiotensin system (RAS) with particular interest in its local, synergistic regulation, we investigate dynamic changes of the RAS and associated systems in response to external stimuli in the rat. We tested influences of the RAS blockade (candesartan and enalapril), diuretics (hydrochlorothiazide), high lipid diet, and salt loading on tissue mRNA level of 12 principal genes. Under the hemodynamic conditions appropriately predetermined, we quantitatively evaluated mRNA level changes with and without each intervention in five organs-the brain, heart, kidney, liver, and adipose tissues-of male rats (n = 5 each). A total of 250 tissues were examined by real-time PCR. Significant changes in mRNA level (P < 0.05) were found in a drug-, diet- and tissue-specific manner. For instance, 29% of genes (14 out of 48 tissues showing detectable mRNA levels) were differentially regulated by candesartan and enalapril, although both drugs reduced blood pressure to similar extents. When the overall interactions among 12 genes were compared between interventions, the RAS and associated systems appeared to change in the opposite direction between candesartan and high lipid diet in the adipose tissue and between candesartan and salt loading in the heart. Enalapril, however, induced unique patterns of perturbation in the local RAS under the corresponding conditions. Thus, this study provides a fundamental picture of gene expression profile in vivo in the RAS and associated systems. In particular, our data highlight differential regulation between candesartan and enalapril, which may reflect the individual pharmacological properties regarding clinical implications. | 18,796,534 |
Role of lysosomal acid lipase in the intracellular metabolism of LDL-transported dehydroepiandrosterone-fatty acyl esters. | Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) belong to a unique family of naturally occurring hydrophobic steroid hormone derivatives that are transported in circulating lipoproteins and may act as a source of dehydroepiendrosterone (DHEA) and other biologically active steroid hormones in cells. Here, we studied the metabolic fate of low-density lipoprotein-associated [(3)H]DHEA-FAE ([(3)H]DHEA-FAE-LDL) and the possible role of lysosomal acid lipase (LAL) in the hydrolysis of DHEA-FAE in cultured human cells. When HeLa cells were incubated with [(3)H]DHEA-FAE-LDL, the accumulation of label in the cellular fraction increased with incubation time and could be inhibited by excess unlabeled LDL, suggesting LDL receptor or LDL receptor-related receptor-dependent uptake. During 48 h of chase, decreasing amounts of [(3)H]DHEA-FAE were found in the cellular fraction, while in the medium increasing amounts of unesterified [(3)H]DHEA and its two metabolites, [(3)H]-5alpha-androstanedione (5alpha-adione) and [(3)H]androstenedione (4-adione), appeared. As LDL-cholesteryl ester hydrolysis is dependent on LAL activity, we depleted LAL from HeLa cells using small interfering RNAs and compared the hydrolysis of [(3)H]DHEA-FAE-LDL and [(3)H]cholesteryl-FAE-LDL. The results demonstrated a more modest but significant reducing effect on the hydrolysis of [(3)H]DHEA-FAE compared with [(3)H]cholesteryl-FAE. Moreover, experiments in LAL-deficient human fibroblasts (Wolman disease patient cells) showed that [(3)H]DHEA-FAE hydrolysis was not completely dependent on LAL activity. In summary, LDL-transported [(3)H]DHEA-FAE entered cells via LDL receptor or LDL receptor-related receptor-mediated uptake, followed by intracellular hydrolysis and further metabolism into 5alpha-adione and 4-adione that were excreted from cells. Although LAL contributed to the deesterification of DHEA-FAE, it was not solely responsible for the hydrolysis. | 18,796,546 |
Radiological classification of optic pathway gliomas: experience of a modified functional classification system. | Optic pathway gliomas (OPGs) in childhood are associated with neurofibromatosis type 1 (NF1) and since 1958 have been classified anatomically using the Dodge classification (DC). MR scanning permits a more detailed anatomical description than can be classified by this historical system. A modified Dodge classification (MDC) has been applied to MRI scans from a cohort of 72 patients (36.1% NF1-positive) from 4 centres participating in an international clinical trial. The MDC was feasible, applicable and more detailed than the original DC. NF1-positive cases more commonly involved both optic nerves (p = 0.021) and other multiple locations (p = 0.001). NF1-negative tumours more commonly involved the central chiasm (p = 0.005) and hypothalamus (p = 0.003). Fewer hypothalamus-positive tumours were associated with optic nerve involvement (p = 0.009), whereas more were associated with central chiasm involvement (p<0.001). From diagnosis to follow-up, there was concordance between DC and MDC in 51/72 cases (70.8%). The MDC is therefore proposed for use in clinical trials of new treatments for OPGs. | 18,796,556 |
Minimal length requirement for proteasomal degradation of ubiquitin-dependent substrates. | An erroneous transcriptional process, known as molecular misreading, gives rise to an alternative transcript of the ubiquitin B (UBB) gene. This transcript encodes the protein UBB(+1), which comprises a ubiquitin moiety and a 19-aa C-terminal extension. UBB(+1) is found in affected neurons in neurodegenerative diseases and behaves as an atypical ubiquitin fusion degradation (UFD) proteasome substrate that is poorly degraded and impedes the ubiquitin/proteasome system. Here, we show that the limited length of UBB(+1) is responsible for its inefficient degradation and inhibitory activity. Designed UFD substrates with an equally short 19-aa or a 20-aa C-terminal extension were also poorly degraded and had a general inhibitory activity on the ubiquitin/proteasome system in two unrelated cell lines. Extending the polypeptide to 25 aa sufficed to convert the protein into an efficiently degraded proteasome substrate that lacked inhibitory activity. A similar length dependency was found for degradation of two UFD substrates in Saccharomyces cerevisiae, which suggests that the mechanisms underlying this length constraint are highly conserved. Extending UBB(+1) also converted this protein into an efficient substrate of the proteasome. These observations provide an explanation for the accumulation of UBB(+1) in neurodegenerative disorders and offers new insights into the physical constraints determining proteasomal degradation. | 18,796,559 |
Weakness on the intensive care unit. | Patients who are recovering from critical illness may be weak and difficult to wean from ventilatory support as a complication of their underlying disorder, intercurrent events or treatment given during prolonged intensive care. These patients are difficult to assess because of the severity of their weakness and any accompanying encephalopathy. It is essential to undertake a meticulous review, including assessment of any septic, hypoxic or metabolic derangements and a detailed look at the dosage and duration of medication including antibiotics, neuromuscular junction blocking agents and sedation. If a primary underlying neurological cause or an intercurrent event have been excluded, the likeliest cause of weakness is one of the neuromuscular complications of critical care such as: critical care polyneuropathy, an acute axonal neuropathy which develops in patients with preceding sepsis or multi-organ failure; the use of neuromuscular junction blocking agents or steroids; and critical illness myopathy, which is the most common cause of critical care related weakness. | 18,796,583 |
TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia. | TAR DNA binding protein-43 (TDP-43) is found in ubiquitinated inclusions (UBIs) in some frontotemporal dementias (FTD-U). One form of FTD-U, due to mutations in the valosin containing protein (VCP) gene, occurs with an inclusion body myopathy (IBMPFD). Since IBMPFD brain has TDP-43 in UBIs, we looked for TDP-43 inclusions in IBMPFD muscle. In normal muscle, TDP-43 is present in nuclei. In IBMPFD muscle, TDP-43 is additionally present as large inclusions within UBIs in muscle cytoplasm. TDP-43 inclusions were also found in 78% of sporadic inclusion body myositis (sIBM) muscles. In IBMPFD and sIBM muscle, TDP-43 migrated with an additional band on immunoblot similar to that reported in FTD-U brains. This study adds sIBM and hereditary inclusion body myopathies to the growing list of TDP-43 positive inclusion diseases. | 18,796,596 |
Direct characterization of amyloidogenic oligomers by single-molecule fluorescence. | A key issue in understanding the pathogenic conditions associated with the aberrant aggregation of misfolded proteins is the identification and characterization of species formed during the aggregation process. Probing the nature of such species has, however, proved to be extremely challenging to conventional techniques because of their transient and heterogeneous character. We describe here the application of a two-color single-molecule fluorescence technique to examine the assembly of oligomeric species formed during the aggregation of the SH3 domain of PI3 kinase. The single-molecule experiments show that the species formed at the stage of the reaction where aggregates have previously been found to be maximally cytotoxic are a heterogeneous ensemble of oligomers with a median size of 38 +/- 10 molecules. This number is remarkably similar to estimates from bulk measurements of the critical size of species observed to seed ordered fibril formation and of the most infective form of prion particles. Moreover, although the size distribution of the SH3 oligomers remains virtually constant as the time of aggregation increases, their stability increases substantially. These findings together provide direct evidence for a general mechanism of amyloid aggregation in which the stable cross-beta structure emerges via internal reorganization of disordered oligomers formed during the lag phase of the self-assembly reaction. | 18,796,612 |
Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. | The calcium activated K(+) channel KCa3.1 plays an important role in T lymphocyte Ca(2+) signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca(2+) influx. We previously showed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, is required for KCa3.1 channel activation in human CD4 T lymphocytes. We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1. Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. Decreased expression of PHPT-1 by siRNA in human CD4 T cells resulted in an increase in KCa3.1 channel activity and increased Ca(2+) influx and proliferation after T cell receptor (TCR) activation, indicating that endogenous PHPT-1 functions to negatively regulate CD4 T cells. Our findings provide a previously unrecognized example of a mammalian histidine phosphatase negatively regulating TCR signaling and are one of the few examples of histidine phosphorylation/dephosphorylation influencing a biological process in mammals. | 18,796,614 |
Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation. | Various human disorders are associated with misdistribution of iron within or across cells. Friedreich ataxia (FRDA), a deficiency in the mitochondrial iron-chaperone frataxin, results in defective use of iron and its misdistribution between mitochondria and cytosol. We assessed the possibility of functionally correcting the cellular properties affected by frataxin deficiency with a siderophore capable of relocating iron and facilitating its metabolic use. Adding the chelator deferiprone at clinical concentrations to inducibly frataxin-deficient HEK-293 cells resulted in chelation of mitochondrial labile iron involved in oxidative stress and in reactivation of iron-depleted aconitase. These led to (1) restoration of impaired mitochondrial membrane and redox potentials, (2) increased adenosine triphosphate production and oxygen consumption, and (3) attenuation of mitochondrial DNA damage and reversal of hypersensitivity to staurosporine-induced apoptosis. Permeant chelators of higher affinity than deferiprone were not as efficient in restoring affected functions. Thus, although iron chelation might protect cells from iron toxicity, rendering the chelated iron bioavailable might underlie the capacity of deferiprone to restore cell functions affected by frataxin deficiency, as also observed in FRDA patients. The siderophore-like properties of deferiprone provide a rational basis for treating diseases of iron misdistribution, such as FRDA, anemia of chronic disease, and X-linked sideroblastic anemia with ataxia. | 18,796,625 |
Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. | Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS. | 18,796,626 |
Diffusion-weighted and conventional MR imaging in neonatal hypoxic ischemia: two-year follow-up study. | To establish the supplemental value of diffusion-weighted (DW) magnetic resonance (MR) imaging beyond conventional MR to predict clinical outcome after neonatal hypoxic ischemia (HI) at 2 years of age. Forty-six infants with neonatal HI were enrolled in this prospective study, after approval by the local ethical committee and informed consent of the parents. Neonatal MR imaging ranged from 1 to 45 days after birth. Apparent diffusion coefficient (ADC) was measured in 14 brain regions. DW and conventional images were qualitatively scored for abnormalities, resulting in cumulative scores and patterns of damage. Surviving infants were scored for motor outcome at the age of 2 years, and outcome was classified as poor if the motor score was less than 70 or in case of death. Analyses were performed for the whole group, with additional analyses for the early (0-4 days after birth) and late (>4 days after birth) imaging groups. Twenty-five infants had a good outcome and 21 had a poor outcome. Only in the early imaging group, the infants with poor outcome had significantly lowered ADC values in several brain areas, with the posterior limb of the internal capsule being the most predictive (Wald score = 5.7; P = .017). Cumulative scores of DW imaging were the best predictor of poor motor outcome at the age of 2 years (Wald score = 7.2, P < .01). The basal ganglia and central cortex and the diffuse pattern of brain damage were highly associated with poor outcome (Fisher exact test = 29.8; P < .001). In neonatal HI, DW imaging is a useful additional MR technique to predict the motor outcome at 2 years. Local ADC values had a limited value. Recognition of the patterns of brain damage with DW and conventional MR imaging can be used as a diagnostic tool in neonatal HI. | 18,796,656 |
Direct MR galactography: feasibility study. | To compare T1- and T2-weighted direct magnetic resonance (MR) galactography, indirect MR galactography, and conventional galactography in women with pathologic nipple discharge. The study was approved by the institutional review board. Written informed consent was obtained from all patients. Twenty-three women (age range, 30-85 years) with pathologic nipple discharge and pathologic conventional galactographic findings underwent physical examination, ultrasonography, and MR imaging before surgery. A T2-weighted sequence of the affected breast was performed before (indirect MR galactography), and T1- and T2-weighted sequences were performed after (direct MR galactography), gadopentetate dimeglumine was injected into the discharging duct. MR galactographic findings were analyzed and compared with conventional galactographic findings. Sequences used were T2-weighted three-dimensional constructive interference in steady state (CISS), T1-weighted volumetric interpolated breath-hold examination (VIBE), and T1-weighted fast low-angle shot (FLASH). The 23 patients had a total of 57 findings at conventional galactography. Indirect MR galactography with CISS showed pathologic findings in eight (42%) of 19 patients and showed 15 (33%) of 46 of all findings. Direct MR galactography with CISS showed pathologic findings in 23 (100%) of 23 patients and 47 (82%) of 57 of all findings, that with VIBE showed pathologic findings in 19 (83%) of 23 patients and 38 (67%) of 57 of all findings, and that with FLASH showed pathologic findings in 16 (100%) of 16 patients and 31 (80%) of 39 of all findings. There was a significant (P < .01) difference between indirect MR galactography and all direct MR galactography sequences in the detection of ductal disease. Eight (35%) of 23 women showed additional findings at direct MR galactography in comparison with standard MR imaging sequences. MR galactography has the potential to be used in the diagnostic work-up of pathologic nipple discharge. Direct MR galactography shows more disease than does indirect MR galactography. The highest detection rate for ductal disease compared with that at conventional galactography was found with the direct MR galactography CISS and FLASH sequences. | 18,796,667 |
In vivo 3D high-spatial-resolution MR imaging of intraplaque hemorrhage. | To apply magnetic resonance (MR) imaging of intraplaque hemorrhage (IPH), as compared with histologic analysis as the reference standard, to detect T1 hyperintense intraplaque signal and to test the hypothesis that T1 hyperintense material represents blood products (methemoglobin). Institutional review board approval and patient informed consent were obtained. Eleven patients undergoing carotid endarterectomy were examined with MR imaging of IPH, and MR images were assessed for T1 hyperintense intraplaque signal. A total of 160 images per patient were available for coregistration with corresponding histologic slices. Because of endarterectomy specimen size and degradation and processing artifacts, only 97 images were coregistered to corresponding histologic slices. A grid that consisted of 16 segments was overlaid on images for correlation of MR images and histologic slices. Only one of 16 segments was chosen randomly per slide and used in the analysis. Agreement between MR images and histologic slices was measured with the Cohen kappa statistic. Strong agreement was seen between MR images and histologic slices, with T1-weighted high signal intensity corresponding to hemorrhagic material (kappa = 0.7-0.8). There was a low 2% false-negative rate for the detection of hemorrhage on the basis of T1-weighted hyperintensity (two of 97 measured segments). The results of diagnostic tests for T1 hyperintense detection of hemorrhage were as follows: sensitivity of 100%, specificity of 80%, positive predictive value of 70%, and negative predictive value of 100% for reader 1 and sensitivity of 94%, specificity of 88%, positive predictive value of 78%, and negative predictive value of 97% for reader 2. With its high spatial resolution, MR imaging of IPH permits detection of plaque hemorrhage location, resulting in strong agreement between imaging and histologic findings. | 18,796,681 |
Analysis of herpes simplex virus type 1 restriction fragment length polymorphism variants associated with herpes gladiatorum and Kaposi's varicelliform eruption in sumo wrestlers. | The geographical distribution of herpes simplex virus type 1 (HSV-1) restriction fragment length polymorphism (RFLP) variants BgK(L) and BgO(L) and the high relative frequency (RF) of BgK(L) in orolabial lesions has led to a dispersion-replacement hypothesis for these variants. The pathogenic properties of HSV-1 variants in mice and professional sumo wrestlers were examined here. The wrestlers herpes gladiatorum (HG) was caused by primary and non-primary HSV-1 infections and recurred in many wrestlers. HSV-1 neutralizing antibody titres in sera from wrestlers who did not develop HG were relatively high. HG was caused by distinct HSV-1 variants and strains from wrestlers living in the same sumo stable. The BgK(L) RF was significantly higher in HG cases, particularly in those with Kaposi's varicelliform eruption. These data indicated that reactivation and transmission of latent HSV-1 infections, especially BgK(L), occurred frequently among wrestlers and was caused by severe skin damage. These results support the BgK(L) dispersion hypothesis. | 18,796,708 |
Integration of the reticuloendotheliosis virus envelope gene into the poultry fowlpox virus genome is not universal. | Fowlpox virus (FWPV) is found worldwide in poultry and wild birds. FWPV is a natural example of recombination between viruses, as reticuloendotheliosis virus (REV) fragments have been found in all poultry FWPVs and these are implicated in virulence alteration. We aimed to determine the commonality of this phenomenon and analysed FWPVs collected from 128 poultry flocks and birds over the last 10 years. Various fragments of both viruses were amplified and sequenced at the FWPV integration site, located between FWPV open reading frames 201 and 203. Seven isolates were found to contain no REV insertions, including fragments of the REV env, gag and 5' REV-long terminal repeat (LTR). We demonstrate here for the first time, the existence of poultry FWPVs without REV inserts (two from chickens, one from turkey FWPV and four from wild birds). The REV inserts were heterogeneous in size. In addition to poultry and wild bird isolates, three FWPV vaccine virus strains were examined and found to contain only remnant REV-LTR and no REV envelope gene fragments. | 18,796,713 |
RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses. | Recombinant pestivirus envelope glycoprotein E(rns) has been shown to interfere with dsRNA-induced interferon (IFN-alpha/beta) synthesis. This study demonstrated that authentic, enzymically active E(rns) produced in mammalian cells prevented a dsRNA-induced IFN response when present in the supernatant of bovine cells. Strikingly, IFN synthesis of cells expressing E(rns) was eliminated after extracellular addition, but not transfection, of dsRNA. Importantly, the same applied to cells infected with bovine viral diarrhea virus (BVDV) expressing E(rns) but lacking the N-terminal protease N(pro). Free E(rns) concentrations circulating in the blood of animals persistently infected with BVDV were determined to be approximately 50 ng ml(-1), i.e. at a similar order of magnitude as that displaying an effect on dsRNA-induced IFN expression in vitro. Whilst N(pro) blocks interferon regulatory factor-3-dependent IFN induction in infected cells, E(rns) may prevent constant IFN induction in uninfected cells by dsRNA that could originate from pestivirus-infected cells. This probably contributes to the survival of persistently BVDV-infected animals and maintains viral persistence in the host population. | 18,796,719 |
Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes. | CD8(+) cytotoxic T-lymphocyte (CTL) responses have been shown to be important in the control of human and simian immunodeficiency virus infections. Infection of sheep with visna/maedi virus (VISNA), a related lentivirus, induces specific CD8(+) CTL in vivo, but the specific viral proteins recognized are not known. To determine which VISNA antigens were recognized by sheep CTL, we used recombinant vaccinia viruses expressing the different genes of VISNA: in six sheep (Finnish LandracexDorset crosses, Friesland and Lleyn breeds) all VISNA proteins were recognized except TAT. Two sheep, shown to share major histocompatibility complex (MHC) class I alleles, recognized POL and were used to map the epitope. The pol gene is 3267 bp long encoding 1088 aa. By using recombinant vaccinia viruses a central portion (nt 1609-2176, aa 537-725) was found to contain the CTL epitope and this was mapped with synthetic peptides to a 25 aa region (aa 612-636). When smaller peptides were used, a cluster of epitopes was detected: at least three epitopes were present, at positions 612-623: DSRYAFEFMIRN; 620-631: MIRNWDEEVIKN; and 625-635: EEVIKNPIQAR. A DNA-prime-modified vaccinia virus Ankara (MVA)-boost strategy was employed to immunize four sheep shown to share MHC class I allele(s) with the sheep above. Specific CTL activity developed in all the immunized sheep within 3 weeks of the final MVA boost although half the sheep showed evidence of specific reactivity after the DNA-prime immunizations. This is the first report, to our knowledge, of induction of CTL by a DNA-prime-boost method in VISNA infection. | 18,796,728 |
Exploring the potential of group II introns to inactivate human immunodeficiency virus type 1. | This study examined whether insertion of a mobile group II intron into infectious human immunodeficiency virus type 1 (HIV-1) provirus DNA could inhibit virus replication. Introns targeted against two sites within the integrase-coding region were used. The intron-inserted HIV-1 provirus DNA clones were isolated and tested for virus replication. Similar amounts of HIV-1 RNA, Gag protein and progeny virus were produced from HIV-1 provirus DNA and intron-inserted HIV-1 provirus DNA. However, when the progeny virus was tested for its infectivity, although the group II intron-inserted HIV-1 RNA was packaged and reverse-transcribed, the dsDNA failed to integrate, as expected in the absence of a functional integrase, and virus replication was aborted. These results demonstrate that group II introns can confer 'complete' inhibition of HIV-1 replication at the intended step and should be further exploited for HIV-1 gene therapy and other targeted genetic repairs. | 18,796,730 |
Effects of muscle group and placement site on reliability of hand-held dynamometry strength measurements. | Studies of measuring muscle strength with hand-held dynamometers have produced a variety of results. The purpose of this research was to further investigate the effect of muscle group and placement site on reliability. The purpose of Part I of this study was to examine reliabilities of force measurements generated by four specific muscle groups using a hand-held dynamometer (HHD). Part II's purpose was to determine the effects of HHD placement site on the variability of HHD force measurements. In Part I, two testers obtained measurements of right shoulder abductor, wrist extensor, hip flexor, and ankle dorsiflexor forces in 20 subjects. Two-way analysis of variance indicated a main effect due to tester, but no tester by session interaction and no main effect due to session (p < 0.5). Intraclass correlation coefficients ranged from .76-.93 for within-session, intratester reliabilities, .67-.84, for between-session intratester reliabilities, and .30-.83 for within-session, intertester reliabilities. Reliability tended to be higher when HHD placement sites were farther from joint centers. Part II explored the hypothesis that HHD forces would be less variable if measured distally. One tester measured shoulder abductor forces for 30 subjects at three sites on the upper extremity. Bartlett's Test for homogeneity of variance indicated a lower variability at the distal placement site (p < 0.05). J Orthop Sports Phys Ther 1992;15(5):236-242. | 18,796,778 |
Automated percutaneous discectomy: the role of the physical therapist. | A number of surgical techniques are used in the treatment of herniated intervertebral discs. The purpose of this report was to introduce the technique of automated percutaneous discectomy and suggest a postoperative physical therapy program. Automated percutaneous discectomy (APD) is a new innovative surgical technique used for the treatment of herniated lumbar discs. The procedure is performed under local anaesthesia on an outpatient basis and takes approximately one hour. The success of this procedure depends upon proper patient selection based on physical examination and differential diagnosis. The role of the physical therapist in postoperative care for the APD patient is discussed. The rationale for the suggested protocol is based on the McKenzie approach to the treatment of mechanical low back pain, emphasizing patient education and prophylaxis. The concept of spinal stabilization training is also introduced to facilitate return to daily activities. J Orthop Sports Phys Ther 1992;15(1):2-9. | 18,796,796 |
Medical screening examination: not optional for physical therapists. | This paper was submitted in response to the clinical commentary entitled "Diagnoses Enhances, Not Impedes, Boundaries of Physical Therapy Practice" (JOSPT 13(5):218-219). We have read with interest and respect the clinical commentary by Behr et al (1) regarding boundaries of physical therapy practice. Their review of "Pathological Origins of Trunk and Neck Pain-Parts I (2), II (3), III (4)" reflects some philosophical similarities and differences regarding the physical therapist's role in the differential diagnosis process.We believe that physical therapists should include a medical screening component in their examinations. This screening is a necessary adjunct to history and physical examination components, which are designed to identify mechanical dysfunction(s) related to patients' symptoms and/or functional limitations. The Review of Systems Checklists (Tables 5-10, Part I) (2) present items designed to screen a body system (i.e. gastrointestinal system) for general pathology. The checklists are NOT designed for screening specific diseases-such as peptic ulcer, cholecystitis, pancreatic cancer, or hepatitis. "Yes" responses should prompt therapists to refer their patient to a physician. This is clearly stated in the forward (5) and the subsequent articles (2-4). J Orthop Sports Phys Ther 1991;14(6):241-242. | 18,796,806 |
Rehabilitation of patellofemoral dysfunction: a review of literature. | A large variety of treatment methods have been suggested for patellofemoral dysfunction (PFD). The purpose of this paper was to present a review of the literature on PFD rehabilitation. Current trends in PFD rehabilitation are summarized. Recommendations for clinical application are: evaluate the patient's pattern of symptoms, enhance control of dynamic patellar stability with specific exercises and education, use taping and bracing to improve patellar tracking, intervene to control symptoms through the rehabilitation process, consider the entire lower limb when attempting to reduce abnormal patellofemoral stress, and educate the patient about the multiple factors involved. More research is needed to determine the most effective treatment methods. J Orthop Sports Phys Ther 1991;14(6):243-249. | 18,796,807 |
Intraexaminer, interexaminer, and interdevice comparability of leg length measurements obtained with measuring tape and metrecom. | Leg length inequalities result from a variety of clinical abnormalities. The purpose of this study was to compare repeated leg length measurements taken by two examiners with two devices during a single session. The two devices that were used were a standard tape measure and a Metrecom. Since reliability coefficients do not fully describe the comparability of measurements, ANOVAs were used to describe differences, and Pearson correlations were used to describe relationships between measurements of leg length obtained by the two examiners using the two instruments. Results of the study showed that although reliability and correlation coefficients are high between testers and devices, significant differences in measurements exist between both testers and devices. The measures found to be most comparable were those taken by one examiner using one device. The authors concluded that for clinical purposes, the tape measure may be the more practical device based on its price. It was theorized, however, that in cases of asymmetry or orthopaedic deformity, the accuracy of the Metrecom may be superior. J Orthop Sports Phys Ther 1991;14(6):263-268. | 18,796,809 |
Rehabilitation following ulnar collateral ligament reconstruction of athletes. | All authors of this article are affiliated with the Kerlan-Jobe Orthopaedic Clinic, 501 E. Hardy Street, Suite 200, Inglewood. CA 90301, (213) 674-5200. Athletes involved in throwing activities often subject their elbows to repeated valgus forces. The ulnar collateral ligament (UCL) may become torn and reconstructive surgery may be required. The purpose of this paper is to review the anatomy and biomechanics of the elbow joint and present a rehabilitation program that can be used following UCL reconstruction of the elbow, with an emphasis on a return to throwing activities. J Orthop Sports Phys Ther 1991;14(3):100-105. | 18,796,819 |
Radial tunnel syndrome: an etiology of chronic lateral elbow pain. | Lateral elbow pain is common in athletic and nonathletic populations. Radial tunnel syndrome (RTS) is an infrequent condition that may produce symptoms similar to tennis elbow. However, RTS is distinguished from tennis elbow in that the symptoms are present more than six months and resistant to conservative treatment. Furthermore, three pathognomomic signs indicate RTS: 1) tenderness when palpating the radial tunnel anterior to the neck of the radius, 2) reproduction of symptoms with resisted supination, and 3) resisted extension of the middle finger. The purpose of this article is to review the literature regarding the symptomatology, pathophysiology, and treatment of RTS so clinicians can distinguish RJS from tennis elbow. Both conditions present similar symptoms; however, clinicians should be able to distinguish between them in order to achieve successful pain relief from lateral elbow pain. J Orthop Sports Phys Ther 1991;14(1):14-17. | 18,796,828 |
The effect of eccentric strength training at various speeds on concentric strength of the quadriceps and hamstring muscles. | This study investigated the effect of eccentric training on concentric strength of the quadriceps and hamstring muscles. The dominant legs of 43 college-age males were pretested concentrically using the KIN-COM(R) at speeds of 60 and 180 degrees /sec. Twenty-eight treatment subjects trained eccentrically at one of the testing speeds for a period of eight weeks; the remainder served as the control group. Prior to each training session, the subjects gave a subjective evaluation of muscle soreness. Delayed muscle soreness did not affect the subjects' ability to train eccentrically. A concentric posttest was taken to determine any treatment effects. The quadriceps muscle did not show any significant change after eccentric training. Eccentric training at 60 and 180 degrees /sec significantly increased the concentric strength of the hamstrings. Eccentric training does appear to be effective in developing concentric strength in the hamstrings. The speed of eccentric training was not a factor in concentric conditioning. J Orthop Sports Phys Ther 1991;13(5):226-230. | 18,796,836 |
Effect of mental practice on isometric muscular strength. | This study was conducted in the Department of Physical Therapy, Louisiana State University Medical Center, New Orleans, LA 70112. The purpose of this study was to see if mental practice (MP) would increase voluntary isometric muscle strength in normal individuals. Twenty-four female subjects were randomly assigned to either a control group or a MP group. The study was conducted over a four-day period using a pretest, posttest, and control group design. The MP group participated in four, 30-minute covert practice sessions. During these sessions, subjects were instructed to cognitively practice isometric contractions of their right quadriceps muscle. Surface electromyography was applied during each practice session to ensure that subjects were not physically contracting their muscles. The data were analyzed using a two-way analysis of variance with repeated measures on one of the factors. The results of this study showed that the MP group significantly (p < .05) increased (12.6%) their quadriceps muscle strength compared to the control group. J Orthop Sports Phys Ther 1991;13(5):231-234. | 18,796,837 |
Field comparison of body composition techniques: hydrostatic weighing, skinfold thickness, and bioelectric impedance. | Body composition and appropriate playing weight are frequently requested by coaches. Numerous methods for estimating these figures are available, and each has its own limitation, be it technical or biological. A comparison of three common methods was made-underwater weighting (H2O, the criterion), skinfold thicknesses (SF), and commercial bioelectrical impedance analysis (BIA). Subjects were 29 professional football players measured by each of the three methods after an overnight fast. Data was collected 10 weeks preceding the players' formal training camp. There was no difference for percentage of weight as fat between SF (15.8%) and H2O (14.2%). Bioelectrical impedance analysis significantly (p < .05) overestimated percent fat (19.2%) compared to H20. Error rates when regressing SF on H2O were favorable, whether expressed for the whole sample (3.04%) or by race (1.78% or 3.56% for whites and blacks, respectively). Regression of BIA on H2O showed an elevated, overall error rate (14.12%) and elevated error rates for whites (11.57%) and blacks (13.81%). Of the two estimates of body composition on a racially mixed sample of males, SF provided the best estimate with the least amount of error. J Orthop Sports Phys Ther 1991;13(5):235-239. | 18,796,839 |
Patella fracture: review of the literature and five case presentations. | Patella fractures comprise one percent of all fractures treated in the hospital. They are classified as: 1) transverse, 2) pole, 3) comminuted, and 4) vertical or longitudinal. The principal cause of such fractures is the direct force involved in a fall, an industrial accident, or a motor vehicle accident. Patients who have experienced such fractures are mostly middle-aged and actively employed. In 50 to 66 percent of the cases, surgical treatment is not required. Physical therapy treatment for patella fractures in the medical literature is reviewed. Case studies of five patients ranging in age from 57 to 71 are presented. In these cases the fracture was due to a fall. Two of the five patients had been treated surgically. At the time of discharge from physical therapy, there were persisting problems. These included: knee pain, difficulty with stair climbing, need for assistive devices on uneven surfaces, and weakness of quadriceps and/or hamstrings muscles. J Orthop Sports Phys Ther 1991;13(4):177-183. | 18,796,843 |
The sacroiliac joint: review of anatomy, mechanics, and function. | The purpose of this paper is to review the anatomy and function of the pelvis in order to enhance the clinical understanding of this closed chain kinematic complex. The relevant bony and soft tissue anatomy is discussed with an emphasis on the complex and unique features of the related parts of the pelvis. Osteokinematics of the pelvis and the sacroiliac joints are discussed relevant to functional movements of the spine and lower extremities. Intrapelvic joint surface motion is presented in light of past and more recent experimental work. Questions regarding the validity of clinical sacroiliac models and future research are posed. J Orthop Sports Phys Ther 1991;13(2):71-84. | 18,796,854 |
Relationship between Peak Torque and Angle-specific Torques in an Isokinetic Contraction of Normal and Laterally Unstable Knees. | This study assessed the relationship between the isokinetic peak torque (PT) (speed of movement, 60 degrees /sec and 180 degrees /sec) and the angle-specific torques (ASTs) at 15 and 75 degrees of knee flexion in multiple contractions of the quadriceps and hamstrings in 21 subjects having a chronic lateral collateral ligament (LCL) insufficiency in one knee. At every test speed, the Pearson product moment (r) correlation coefficients between the PT and ASTs were highly significant (p < 0.001) in the uninjured (r = 0.66-0.92) as well as in the LCL insufficient (r = 0.78-0.88) knees. In both extremities, the majority of the correlation coefficients exceeded 0.80, which was the threshold set before the study for the coefficients to be exceeded before the relationship could be considered clinically important. Using regression analysis, both extremities showed completely nonsystematic distribution of the residuals. In conclusion, concerning healthy or LCL-insufficient knees, the correlations between PT and ASTs were high and consistent. Therefore, AST analyses may offer little additional information about thigh muscle function to that obtained through a simpler and more commonly used measurement, the PT analysis. J Orthop Sports Phys Ther 1991;13(2):89-94. | 18,796,855 |
The pathology of shin splints. | The purpose of this review is to critically evaluate experimental evidence describing the pathology associated with shin splints. Shin splints are defined as medial or posteromedial leg pain which is brought about by walking, running, or related activities and which decreases with rest. The evidence indicates that shin splints may be due to pathology of the posteromedial tibial cortex, the periosteum of the posteromedial tibia, or the crural fascia of the deep posterior compartment of the leg. Research is needed to determine if increased pressure in the deep posterior compartment of the leg or pathology of the muscles, tendons, or interosseous membrane of the leg are associated with shin splints. J Orthop Sports Phys Ther 1990;12(3):115-121. | 18,796,881 |
Effects of varying electrode site placements on the torque output of an electrically stimulated involuntary quadriceps femoris muscle contraction. | The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. At the time this study was performed, LTs Ferguson, Blackley, Knight, and Sutlive were students in the US. Army-Baylor University Graduate Program in Physical Therapy. This research was performed in partial fulfillment of their requirements for the Master of Physical Therapy Degrees.The purpose of this study was to evaluate the effects of varying electrode placement on the torque output of an electrically stimulated involuntary quadriceps femoris muscle contraction. Twenty-two volunteer subjects (18 men, 4 women) with a mean age of 21.7 years received electrical stimulation according to a randomized treatment order which included: Femoral nerve and 1) vastus medialis (VM), 2) rectus femoris (RF), 3) vastus lateralis (VL), 4) opposite quadriceps (OQ), and 5) the ipsilateral vastus medialis and vastus lateralis (VM/VL). The subject's knee was placed in 60 degrees of flexion, and the isokinetic dynamometer set at 0 degrees /sec. The peak torque produced by the involuntary quadriceps contraction was measured as a percentage of maximum voluntary isometric contraction (MVIC). An analysis of variance with repeated measures was used to examine the data. The results indicated the mean percentages of MVIC produced by stimulating the VM, VL, and RF sites were significantly greater (p </= 0.05) than the means of the OQ and VM/VL sites. Post hoc testing did not reveal a significant difference in the mean percent MVIC between the VM, VL, and RF sites. The VM, VL, or RF distal electrode site placement may be used clinically in conjunction with ipsilateral femoral nerve stimulation to produce a maximum involuntary isometric contraction of the quadriceps femoris muscle when stimulated electrically. J Orthop Sports Phys Ther 1989;11(1):24-29. | 18,796,931 |
Effectiveness of 10% trolamine salicylate cream on muscular soreness induced by a reproducible program of weight training. | This research was conducted at Miami-Dade Community College/North Campus, and was funded by Thompson Medical Company, New York, NY 10022. The purpose of this study was to evaluate the effectiveness of an over-the-counter topical analgesic cream on soreness elicited by weight training. Soreness was rated four times each day by 34 untrained college students who exercised on 5 consecutive days (arm curls: three sets of up to 20 repetitions using 80% of 7-repetition maximum). Subjects applied either the analgesic or an identical placebo cream over the involved muscles, 4 times per day (double-blind). Elevated plasma creatine kinase (+438%, p < 0.01) in both groups was evidence of muscle damage. Meaningful levels of soreness (>/= 3.0 on a 0-to-10 scale) were reported sooner, and persisted longer, in the placebo group. Whenever soreness was present, levels were lower (p < 0.05) in the analgesic group. It is concluded that a topical 70% trolamine salicylate cream is effective in reducing the duration and severity of muscular soreness caused by exercise. J Orthop Sports Phys Ther 1989;11(1):19-23. | 18,796,932 |
Percent Decline in Peak Torque Production during Repeated Concentric and Eccentric Contractions of the Quadriceps Femoris Muscle. | The purpose of this study was to document the difference between eccentric and concentric fatigue of the quadriceps femoris muscle during a maximal effort 40 repetition bout at 180 degrees /sec. Sixteen female volunteers aged 22 to 32 years were tested twice, at least 7 days apart. The left lower extremity of each subject was used during testing on the Kin-Com(R) dynamometer. Subjects were tested through a range of motion of 0 to 90 degrees of knee flexion while seated. Percent decline in peak torque production was then calculated. The results demonstrated that peak torque production during the 40 repetition bout decreased an average of 0.3% for the eccentric trial and an average of 47.7% for the concentric trial. A significant difference in percent decline in peak torque production between concentric and eccentric trials was found to exist (p < 0.0001). The findings of this study indicate that eccentric training may require the performance of many more repetitions than concentric training in order to obtain muscle fatigue. J Orthop Sports Phys Ther 1989;10(8):309-314. | 18,796,952 |
Medical needs at high school football games in milwaukee. | To help clarify the medical needs at high school football games, injury and treatment data were recorded during medical coverage of 67 varsity games. Injury evaluations were performed on 11 1 athletes for 139 injuries. Sixty-four injuries resulted in the athlete not returning to complete the game and 8 injuries resulted in the athlete being unable to return to play for over 1 week. Contusions (26.6%), sprains (21.6%), strains (8.6%), and suspected fractures (8.6%) accounted for most of the injuries. The most common sites of injuries were the knee (14.4%), lower leg (13.7%), and ankle (1 1.5Oh). Icing and taping were the most common treatments provided. The frequency of injuries verifies the importance of qualified medical coverage at high school football games. The nature of most injuries indicates that besides having skills in basic emergency medicine, the medical personnel should be skilled in the management of acute soft tissue injuries.J Orthop Sports Phys Ther 1988;10(5):167-171. | 18,796,961 |
The Treatment of Soft Tissue Hemorrhages in a Severe Classical Hemophiliac with an Unusual Antibody to Factor VIII. | A known severe classical hemophiliac patient presented with a large hemorrhage into his left shin and complained of paresthesia in his toes. Large doses of factor VIII had failed to halt the expanding shin hematoma. Laboratory investigations revealed an antibody titer of 5 Bethesda units. In vitro and in vivo testing showed swift neutralization of factor VIII to a level of 20% and thereafter degradation of factor VIII in accordance to the half-life expectancy. The patient was successfully treated with a continuous infusion of small doses of cryoprecipitate. The Bethesda method of antibody measurement does not distinguish between low and high affinity antibodies and thus in vitro testing should be carried out before a decision is made on the use of expensive activated prothrombin complex. The initial approach of the physical therapist is to aid in attempting to limit the swelling and enhance hematoma reabsorption. Once the bleeding has been controlled, a long-term physical therapy program is necessary to regain dorsiflexion of the ankle joint.J Orthop Sports Phys Ther 1988;10(4):138-141. | 18,796,965 |
Isokinetic characteristics of the knee in female, professional and university, ballet and modern dancers*. | *Study conducted as part of thesis submitted by R.D.C. in partial fulfillment of the requirements for the degree of Master of Science. The purpose of this investigation was to evaluate isokinetic characteristics of the knee in female, ballet and modern, professional and university dancers in order to evaluate possible differences among the groups. A total of 37 dancers with a mean age of 24.9 years was tested using a Cybex II dynamometer. A multiple analysis of variance (MANOVA) indicated that the ballet dancers had significantly higher H/Q ratios than modern dancers at three speeds (p < 0.024). Post hoc procedures indicated that the professional ballet dancers (PB) had significantly higher H/Q ratios than all other groups at 180 degrees /sec (p < 0.05). Also, although most of these dancers demonstrated normal peak torque/body weight values for knee extension and flexion, specific weaknesses were observed in the force decay rate of the quadriceps curves. It was concluded that these theatrical dancers were not a homogeneous group in terms of certain isokinetic characteristics.J Orthop Sports Phys Ther 1988;9(12):410-418. | 18,796,983 |
Measurement of "regional" lumbar sagittal mobility. | Lumbar sagittal mobility is generally recorded as the overall movement occurring throughout the lumbar spine, in flexion and extension. However, increased information concerning mechanical function will be afforded if the mobility is expressed as the range separately available in the upper and lower regions of the lumbar spine. A simple, noninvasive and reliable technique is described which measures sagittal mobility available from T12 to L4, and from L4 to S1. It uses a modified draftsmans flexicurve and is suitable for use in clinical and field environments. J Orthop Sports Phys Ther 1987;9(4):166-169. | 18,797,006 |
Intra-abdominal pressure as a quantitative measure for spinal stresses. | The purpose of this study was to measure the effects of lifting, placing, and removing different magnitudes of loads on the spinal stress. Eight male volunteers were measured for spinal stress utilizing intra-abdominal pressure (IAP). The loads used in the lifting tasks to different vertical and horizontal levels, varied from 5 kg up to 15 kg and were placed in a random order. The ANOVA analysis revealed significant individual variation (p < 0.001) both when placing and removing the loads. The effect of increase in load magnitude on the mean peak IAP values was highly significant (p < 0.001) when both placing and removing the loads. It is suggested that the area of activity falls within the limits of low truncal stress. The low truncal stress limits are large enough for most loading or unloading activities. Such requirements should also apply to physical therapists using passive movements and transfer activities allowing the therapist to carry out the required treatment or transfer within the safe limits of low truncal stress. J Orthop Sports Phys Ther 1987;9(2):70-76. | 18,797,016 |
Back pain revisited. | The rationale for the judicious use of rotational exercises as well as concepts of exercise progression and modification in back rehabilitation are presented. Several rotational exercises that address both strength and flexibility are described. Other commonly used exercises in back rehabilitation are presented with the focus on detail in positioning and execution aimed at increasing the efficiency of the particular exercise. J Orthop Sports Phys Ther 1987;8(12):556-566. | 18,797,020 |
The Association of Anthropometric Measurements of Thigh Size and B-mode Ultrasound Scanning of Muscle Thickness. | The purpose of this investigation was to determine the association between anthropometric measurements of thigh size and direct measurements of thigh muscle thickness using B-mode ultrasound scanning. Thirty-four male subjects with different exercise habits were tested. Their physical description was as follows: age 28.0 * 6.7 years, height 177.0 + 6.4 cm, weight 75.5 + 12.5 kg, lean body mass 65.6 * 8.4 kg, body fat 13.6 + 5.1%. Anthropometric measurements included skinfolds, girths, and segment volumes of th'e thigh. B-mode ultrasound scanning was performed on the one-third subischial(33% of the distance between the gluteal fold and the popliteal crease) anterior and posterior thigh. Anthropometric variables were more strongly correlated to the anterior versus posterior thigh musculature. The net (corrected for skinfold thickness) one-third subischial girth explained 77.7 and 52.6% of the variance in the muscle thickness of the anterior and posterior thigh, respectively. The results of this study indicate that net girth measurements of the thigh may be useful for estimating thigh muscle thickness. Adding other variables to the net one-third subischial girth with multiple correlation only increased R2 by less than 0.05. J Orthop Sports Phys Ther 1987;8(9):462-468. | 18,797,032 |
Accuracy of the unassisted pain drawings by patients with chronic pain. | This investigation was conducted to test the accuracy of unassisted pain maps drawn by patients with chronic pain. Three aspects of accuracy were investigated, the accuracy of the area of pain reported, whether all existing pains were reported, and whether related symptoms were reported. Thirty-six successive new admissions to a chronic pain rehabilitation center were used as subjects. Each patient filled out the pain map prior to meeting any professional staff. During their examination the investigators completed a new pain map without seeing the patient's map. Thirty-one pairs of pain maps were compared and scored, with most maps showing several pain areas. Area of pain was accurately represented 43% of the time. Of 139 distinct pains found during examination, only 58% were reported in the pain maps. Thirtyfour percent of related symptoms were reported. It appears that unassisted pain maps are sufficiently flawed to discourage their use as an indicator of the patients symptom location J Orthop Sports Phys Ther 1987;8(8):391-396. | 18,797,035 |
Natural rubber latex allergy. | Natural rubber latex (NRL) is a ubiquitous allergen as it is a component of > 40,000 products in everyday life. Latex allergy might be attributed to skin contact or inhalation of latex particles. Latex allergy is an IgE-mediated hypersensitivity to NRL, presenting a wide range of clinical symptoms such as angioedema, swelling, cough, asthma, and anaphylactic reactions. Until 1979, latex allergy appeared only as type IV delayed hypersensitivity; subsequently, the proportion of different allergy types drifted towards type IV contact allergy reactions. Several risk factors for sensitization to NRL are already known and well documented. Some authors have established a positive correlation between a history of multiple surgical interventions, atopy, spina bifida malformation, and latex allergy incidence. We suspect an increase in latex allergy incidence in association with increased atopy and sensitivity to environmental allergens in the industrial population. It is often postulated in literature that the groups of workers at risk for this allergy are essentially workers in the latex industry and healthcare professionals. In this population, direct internal and mucosal contact with NRL medical devices may be the route of sensitization as factors such as the number of procedures and use of NRL materials (catheters and tubes) were associated with increased risk of latex sensitization and allergy. | 18,797,048 |
An open labeled, comparative clinical study on efficacy and tolerability of oral minipulse of steroid (OMP) alone, OMP with PUVA and broad / narrow band UVB phototherapy in progressive vitiligo. | Several modalities of treatment have been tried in vitiligo with varied results; however, Indian data on comparative studies of two or more therapies are limited. We compared different phototherapy methods with an oral steroid as an adjunct to determine the method with the best tolerability and efficacy. Eighty-six patients with progressive vitiligo were randomly assigned to different study groups according to a continuous selection method over a period of one year. Group 1 was given OMP + PUVA, group 2 OMP + UVB (NB), group 3 OMP + UVB (BB) and group 4 was given OMP alone. Each patient was followed up for six months and then released from treatment. Clinical evaluation was made at the end of three and six months. In group 1 (OMP + PUVA), marked improvement was seen in 18.51% while moderate improvement was seen in 66.66% of the patients. Marked improvement was seen in 37.03% in group 2 (OMP + NB-UVB) while 44.44% had moderate improvement. In group 3 (OMP + BB UVB), 8.33% showed marked improvement while moderate improvement was seen in 25% of the patients. Marked and moderate improvement was seen in 5 and 10% of group 4 (OMP) patients, respectively. Our study compared four treatment modalities in vitiligo patients, out of which oral minipulse of steroids (OMP) only had an adjunct value and was not very effective by itself. Narrow band UVB has a definite edge over broad band UVB and should be preferred when both options are available. NB-UVB and PUVA showed comparable efficacy. | 18,797,057 |
U. B. Narayan Rao and the origins of the IJDVL. | Dr. U. B. Narayan Rao L.C.P.S (Bom) (born 23 rd November 1895, died 14 th June 1960) had a busy general practice in Bombay. He adopted dermatology and venereology as his specialty in the 1930's and started the Indian Journal of Venereal Diseases in 1935, the first of its kind in the subcontinent. This journal went on to become the official mouthpiece of the Indian Association of Dermatologists and Venereologists in 1955 and was then known as the Indian Journal of Dermatology and Venereology. Dr. Narayan Rao also played an important role as a founder member of the Bombay Association of Dermato-Venereologists as well as the Indian Association of Dermatologists and Venereologists. Activist, indefatigable worker dedicated to the cause, nationalist, and patriot, generous, dynamic and aggressive, with a flare for arguing; negotiating and convincing, and winning friends in the process, were some of the attributes that may be mentioned of this remarkable person who contributed so much to our specialty. | 18,797,085 |
Self-assessed and clinically diagnosed periodontal health status among patients visiting the outpatient department of a dental school in Bangalore, India. | The purpose of the present cross-sectional study was to assess the extent of agreement between clinical and self-assessed periodontal health status among patients visiting the outpatient department of M.S. Ramaiah Dental College, Bangalore, India. The study population included 216 patients aged between 20 and 44 years who attended the outpatient department of the M.S. Ramaiah Dental College, Bangalore. The study population was subjected to a self-administered questionnaire (questions regarding bleeding gums, deposits on teeth, receding gums, swelling of gums, loose teeth), which was followed by periodontal examination. The clinical examination included an assessment of the periodontal condition, using the criteria of Loe and Silness Gingival Index, the Community Periodontal Index, and Mobility, respectively. The present study showed that the perceived periodontal health status was low and the discrepancy between the subjectively and objectively assessed needs was very distinct. The awareness of the periodontal problems has been reported to increase with increasing severity of the disease due to the destructive changes that set in. | 18,797,102 |
Clinical and radiographic comparison of primary molars after formocresol and electrosurgical pulpotomy: a randomized clinical trial. | Vital pulpotomy is a single-stage procedure defined as the surgical amputation of the coronal portion of exposed vital pulp, usually as a means of preserving the vitality and function of the remaining radicular portion. The aim of this study was to compare the clinical and radiographic success rates for electrosurgical vs formocresol pulpotomy in human primary molar teeth. This was a prospective, randomized clinical trial. In this randomized clinical trial, pulpotomies were performed on 70 primary molars in children aged 5-10 years. The teeth were treated using either a conventional formocresol (35 teeth) or electrosurgical technique (35 teeth). Following the pulpotomy procedure, the teeth were evaluated for clinical and radiographic success for three, six and nine months. The teeth were evaluated for the presence of pain, abscess, fistula, mobility, internal and external resorption, and radiolucency. The data were assessed with Fishers' Exact test. After nine months of follow-up, the clinical and radiographic success rates were 96 and 84% respectively in the electrosurgical group and 100 and 96.8% respectively in the formocresol group. There was no statistically significant difference between the success rates in the two groups ( P > 0.05). Our results showed the failure rates for electrosurgical pulpotomy to be equal to those for formocresol pulpotomy. Although electrosurgical pulpotomy is a nonpharmacological technique giving favorable results, it is still a preservative technique. Further studies using larger samples and longer evaluation periods are recommended. | 18,797,098 |
Reflux esophagitis and Helicobacter pylori infection in patients with scleroderma. | This study aimed to evaluate the possible effects of Helicobacter pylori (H. pylori) infection in reflux esophagitis with scleroderma. There were a total of 138 patients with scleroderma in our hospital between October 1998 and June 2005. Among these patients, 64 consecutive patients of scleroderma, who did not receive medication for gastrointestinal diseases, underwent endoscopy after informed consent. H. pylori was examined using an H. pylori IgG ELISA. The endoscopists graded esophageal mucosal breaks according to the Los Angeles Classification of Esophagitis. Among the 64 patients, 37 patients (57.8%) were positive for H. pylori infection. Reflux esophagitis was observed in 10 of 37 H. pylori-positive patients and in 19 of 27 H. pylori-negative patients. Significantly fewer H. pylori-infected patients had reflux esophagitis than H. pylori-negative patients (p<0.01). The odds ratio for H. pylori infection and reflux esophagitis was 0.16 (95%CI; 0.052-0.47). These findings suggest an important role for H. pylori infection in reflux esophagitis with scleroderma. | 18,797,112 |
Obscure gastrointestinal bleeding caused by small bowel lipoma. | Obscure gastrointestinal bleeding is a very rare entity which accounts for less than 5% of all gastrointestinal bleeding cases. Small bowel tumors are rare but a serious source of obscure gastrointestinal bleeding. Lipomas are the second most common benign tumors in the small bowel and can produce many complications, including gastrointestinal bleeding. Herein, we describe a case of obscure gastrointestinal bleeding caused by a small bowel tumor which was detected by capsule endoscopy and double-balloon enteroscopy preoperatively. Finally, the tumor was surgically confirmed to be a lipoma. | 18,797,119 |
Recurrent takotsubo cardiomyopathy within a short span of time in a patient with hereditary motor and sensory neuropathy. | A 53-year-old woman with hereditary motor and sensory neuropathy was admitted to our hospital with congestive heart failure, followed by cardiogenic shock and acute renal failure. The patient's neuropathy was a rare entity documented first in a local area of Okinawa, Japan. Intensive supportive therapy was performed and the patient recovered within 4 weeks. Echocardiography revealed takotsubo-type left ventricular wall motion abnormality at onset. During hospitalization, restoration and recurrence of apical ballooning were observed at shorter intervals of days. The unique left ventricular wall motion abnormality of takotsubo cardiomyopathy is possibly a dynamically repetitive phenomenon. Serial echocardiographic studies are necessary so as not to miss recurrences within short intervals. | 18,797,121 |
Identification of ultraviolet B-sensitive genes in human peripheral blood cells. | Ultraviolet B (UVB) is a serious irritant for the skin and increases a risk for skin cancer. To identify UVB-sensitive genes in peripheral blood, 11 healthy male volunteers were exposed to 0.3 J/cm(2) of narrow-band (NB)-UVB, about half of minimal erythema dose (MED) in Japanese, and gene expression in blood was analyzed at 4 h, 24 h, 4 d and 7 d after the irradiation using microarray carrying oligonucleotide probes for 2,000 stress-responsive genes. RNA prepared before the irradiation was used as a reference control. Microarray analysis identified 21 genes as UVB-responsive genes with a peak at 24 h in 6 subjects, and real-time PCR validated the significant down-regulation of 9 (ABCB10, ATF1, ABCD3, TANK, FAS, SLC30A9, CHUK, CASP1, and ABCE1) out of the 21 genes in 11 subjects. Considering sensitive and characteristic features of 9 marker genes, they may be useful indicators for monitoring systemic response to UVB irradiation. | 18,797,132 |
BMP2-induced gene profiling in dental epithelial cell line. | Tooth development is regulated by epithelial-mesenchymal interactions and their reciprocal molecular signaling. Bone morphogenetic protein 2 (BMP2) is known as one of the inducers for tooth development. To analyze the molecular mechanisms of BMP2 on ameloblast differentiation (amelogenesis), we performed microarray analyses using rat dental epithelial cell line, HAT-7. After confirming that BMP2 could activate the canonical BMP-Smads signaling in HAT-7 cells, we analyzed the effects of BMP2 on 14,815 gene expressions and profiled them. Seventy-three genes were up-regulated and 28 genes were down-regulated by BMP2 treatment for 24 hours in HAT-7 cells. Functional classification revealed that 18% of up-regulated genes were ECM/adhesion molecules present in the enamel organ. Furthermore, we examined the expression of several differentiation markers in dental epithelial four cell-lineages including inner enamel epithelium (ameloblasts), stratum intermedium, stratum reticulum, and outer enamel epithelium. The results indicated that BMP2 might induce at least two different cell-lineage markers including a BMP antagonist expressed in HAT-7 cells, suggesting that BMP2 could accelerate amelogenesis via BMP signaling. | 18,797,134 |
Clinical training stress and autonomic nervous function in female medical technology students: analysis of heart rate variability and 1/f fluctuation. | To evaluate the level of stress induced by clinical training, ambulatory electrocardiograms from 12 healthy female medical technology students were recorded and the spectral components of heart rate variability (HRV) were analyzed as an index of autonomic nervous function. The HF power reflecting parasympathetic tone was significantly decreased at awakening, compared with that before clinical training (p<0.01). The LF/HF ratio reflecting sympathetic activity also significantly increased during, compared with before clinical training (p<0.01). The slope of the spectral density also changed before and during the clinical training from -1.20+/-0.04 to -1.09+/-0.03 (p<0.05). The 1/f fluctuation of HRV appeared comfortable, and tension was apparently adequate while undergoing clinical training. None of these HRV indices statistically changed while asleep. Thus, the students perceived the stress as a comfortable level of tension and analyzing spectral components and 1/f fluctuation of HRV might be a useful method for evaluating study stress. | 18,797,135 |
The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain. | In this study, we investigated methamphetamine (METH)- induced peroxidative DNA damage in various regions of the rat brain. We injected METH to rats following 2 protocols. For the single administration experiment (group I), 50 mg/kg (i. p.) of METH was administered to observe the acute influence of METH. For the repeated administration experiment (group II), 10 mg/kg/day (i. p.) of METH was injected for 5 days. Immunohistochemically, peroxidative damage DNA, 8-hydroxy-2'- deoxyguanosine (8-OH-dG) was observed, and in situ apoptosis was also observed. In group I, immunoreactivity of 8-OH-dG was only enhanced in neurons of the nucleus accumben of METH-treated rats. On in situ apoptosis detection, positive findings were also enhanced in all examined parts compared to those in the control, though there were no significant increases in 8-OH-dG-immunopositive neurons except in the nucleus accumben. In group II, the nucleus accumben also showed enhanced 8-OH-dG immunopositivity compared to that in the control. There was no significant difference in apoptosis between the control and METH groups. Based on our observations, it is considered that METH induces oxidative DNA damage in the brain, especially in the nucleus accumben. However, those DNA damage might be caused differently between acute and chronic administration. | 18,797,138 |
PPAR alpha and PPAR delta transactivity and p300 binding activity induced by arachidonic acid in colorectal cancer cell line Caco-2. | It is reported that arachidonic acid strongly induces the conformational change in vitro and transactivity of PPAR alpha in colorectal cancer cell line Caco-2. In this study, we demonstrated that the induction of conformational change and transactivity of PPAR delta by arachidonic acid, as well as other polyunsaturated fatty acids, was considerably lower than that of PPAR alpha. Mammalian two-hybrid assay showed that arachidonic acid enhanced binding of one of the coactivators, p300, to PPAR alpha but not to PPAR delta. Additionally, arachidonic acid induced in vitro binding of both PPAR alpha-RXR alpha and PPAR delta-RXR alpha heterodimers to several PPREs on CRBPII, L-FABP and ACO genes. Our results suggest that the lower transactivity of PPAR delta for arachidonic acid in Caco-2 cells, compared with PPAR alpha, is associated with the binding activity of p300 to the receptor. | 18,797,151 |
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