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Local control following therapeutic nodal dissection for melanoma.
Regional recurrence of melanoma is usually treated with surgical resection alone. Unfortunately sites of failure following surgical resection are poorly documented. Little information exists regarding local failure following surgery. In order to define local control, a retrospective analysis was performed of all patients undergoing a potentially curative lymph node dissection for metastatic melanoma. From 1978 to 1988, 48 patients underwent lymph node dissection with removal of all known disease (15 axillary, 25 groin and 8 radical neck dissections). Seven patients had stage II disease with simultaneous resection of the primary lesion and nodal dissection. The remaining 41 patients had stage I disease with dissection delayed until nodal metastasis became apparent. Of these 48 patients, 25 experienced local failure for an overall local control rate of 48%. Univariate and multivariate analysis showed only age to be a statistically significant prognostic indicator of local failure with a rate of 31% for patients < 50 years of age vs. 66% for patients > 50 years of age (P = 0.02). Nodal size, number of nodes involved, extracapsular extension, initial stage, location, or sex did not influence prognosis. Although not statistically significant, time to recurrence was much shorter in patients with extracapsular extension, 5 months vs. 16 months. With an overall local failure rate of 52% following a potentially curable therapeutic nodal dissection further local treatment should be considered.
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{
"pile_set_name": "PubMed Abstracts"
}
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Two components of GABA-induced currents in catfish retinal horizontal cells.
In cone-driven horizontal cells dissociated from the catfish retina, we recorded GABA-induced currents by using a whole-cell voltage-clamp technique. The current consisted of two components. The major component was blocked by picrotoxin, but not by bicuculline, and was identified as a current flowing through the GABAC receptor channel. The second minor component was identified as a current carried by an electrogenic GABA transporter.
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{
"pile_set_name": "PubMed Abstracts"
}
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Tracheal morphology in patients with tracheomalacia: prevalence of inspiratory lunate and expiratory "frown" shapes.
To identify the spectrum of tracheal morphologies in patients with tracheomalacia, and to determine the prevalence of specific inspiratory (lunate) and expiratory (frown) shapes that have been associated with this condition. A retrospective review was performed of a consecutive series of patients with bronchoscopically-proven tracheomalacia who were imaged with inspiratory and dynamic-expiratory computed tomography (CT). The CT images of each patient were reviewed in a blinded, randomized fashion by an experienced thoracic radiologist. For each case, the shape of the trachea at end-inspiration and dynamic expiration was classified using specific tracheal morphologies described in the literature. The study population included 17 patients, with a mean age of 54 years. At inspiration, 16 (94%) of 17 subjects demonstrated a normal tracheal configuration (round, oval, horseshoe, or inverted-pear shape), and 1 (6%) of 17 subjects demonstrated an abnormal "lunate" tracheal configuration (coronal: sagittal ratio >1). At expiration, 9 (53%) of 17 subjects demonstrated a crescenteric, "frown" shape; 1 (6%) subject demonstrated complete collapse; and 7 (41%) subjects demonstrated other morphologies. Inspiratory tracheal morphology is almost always normal in patients with tracheomalacia, with a lunate configuration only rarely observed. In contrast, an expiratory "frown sign" is observed in approximately half of patients with this condition. This sign has the potential to aid the detection of tracheomalacia when patients inadvertently breathe during routine CT scans.
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{
"pile_set_name": "PubMed Abstracts"
}
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Morphological characteristics of styloid process evaluated by computerized axial tomography.
Morphological characteristics of styloid process and ossified stylohyoid ligament and their overall relationships to age and sex were studied by using computerized axial tomography images. The styloid process and ossified stylohyoid ligaments were classified into seven groups according to their shapes and lengths. The styloid process of a length of 25-40 mm, was the most frequently encountered. The elongated styloid process was mostly seen in males. There was no overall correlation between the types of SP and sex. The progressive increase in length with age was not seen in our study.
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{
"pile_set_name": "PubMed Abstracts"
}
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Observational study of job satisfaction in hospital pharmacy technicians.
Intrinsic and extrinsic factors contributing to job satisfaction of pharmacy technicians in two community hospitals were studied. A pharmacy student employed part-time as a pharmacy technician by one of the hospitals observed fellow technicians in a wide range of job activities for 22 months. In a second hospital, the same student conducted similar observations during one summer while posing as a social researcher. Both hospitals had technician training programs providing classroom instruction and on-the-job training. Data were gathered primarily from informal conversations with technicians and pharmacists and by recording activities through notetaking. Formal training programs, praise from pharmacists, opportunities to train other technicians, diversity of job activities, and autonomy in coordinating work with time demands were identified as factors contributing to job satisfaction of technicians. Negative aspects of the job that employers attempted to circumvent or clarify were the unchallenging nature of the work and the limited opportunities for advancement. Technicians' and pharmacists' attitudes toward job enrichment for technicians are discussed, and suggestions for improving technicians' intrinsic and extrinsic job satisfaction are provided. A reliable cadre of pharmacy technicians is necessary for further expansion of clinical pharmacy services under current hospital budgetary restraints. In addition to modifying job activities to promote technicians' intrinsic job satisfaction, pharmacy managers can improve extrinsic satisfaction by providing adequate salaries, job security, and flexible work schedules.
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{
"pile_set_name": "PubMed Abstracts"
}
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Cloning and expression of cynomolgus monkey and baboon zona pellucida proteins.
Partial clones for the three cynomolgus monkey (Macaca fasicularis) zona pellucida genes (cmZPA, cmZPB, and cmZPC) have previously been isolated. These partial clones contained the sequences for the C-terminal portion of each rcmZP protein. To obtain full-length clones for each cmZP, a fresh cynomolgus monkey ovarian cDNA library was constructed. PCR methodology was employed to speed the isolation of full-length clones for each cmZP cDNA. The 3' primers were designed based on sequence information from the previously identified clones; the 5' primers were designed using the human ZP sequences. The PCR technique yielded full-length clones of cmZPA and cmZPC, but not of cmZPB. Therefore, a genomic clone of cmZPB was isolated and the sequence determined. The exon/intron structure is nearly identical to the human ZPB exon/intron structure. New PCR primers were designed based on the cynomolgus monkey ZPB genomic sequence, and a full-length cmZPB cDNA was obtained. The same primers that were used to generate the cmZPB were also used to generate a baboon (Papio cynocephalus) ZPB (bZPB) cDNA. As was done previously for the human zona pellucida (hZP) cDNAs, the cmZP, and bZPB cDNAs were transferred to shuttle vectors for transfection into Chinese Hamster Ovary (CHO) cells. Stable cell lines for producing each ZP protein were isolated. Each cell line secreted the desired recombinant zona pellucida (rZP) protein into the culture medium, and each protein was purified using an established protocol. In terms of size and purity, the purified recombinant cmZP (rcmZP) and rbZPB proteins resemble the rhZP proteins.
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{
"pile_set_name": "PubMed Abstracts"
}
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Association between angiotensin-converting enzyme gene polymorphisms and QT duration in a multiethnic population in Hawaii.
Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii. Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms. The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001). The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Metabolic activity of Krebs cycle in the liver during experimental burns].
Metabolic capacity of the Krebs cycle was limited in liver tissue of rats with experimental thermic burns of the IIIa-IIIb grade, involving 25-30% of a body surface; the phenomenon was primarily manifested in a decrease in the citrate synthesis, which occurred due to a decrease in content of citric acid and to decrease in the rate of 2-14C-pyruvate and 2-14C-acetate incorporation into citric acid. At the same time, impairment of alpha-ketoglutaric acid metabolism was found: specific radioactivity of the substance, after incorporation of 2-14C-pyruvate, was decreased and amount of the metabolite--increased. Simultaneously, activity of isocitrate- and malate dehydrogenases was decreased in liver mitochondria. In burns these impairments might be important for decrease of glucose energy potential in liver tissue and for alteration of other metabolic reactions.
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{
"pile_set_name": "PubMed Abstracts"
}
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Monoclonal antibody-based fluorescence polarization immunoassay for sulfamethoxypyridazine and sulfachloropyridazine.
In this paper, a new monoclonal antibody (Mab) against sulfamethoxypyridazine (SMP) was produced, and a fluorescence polarization immunoassay (FPIA) based on the produced Mab was developed and optimized for the qualitative screening analysis of SMP. The Mab was raised from mice immunized with SMP linked to bovine serum albumin (BSA) by carbodiimide activated ester formation, using a succinic anhydride spacer molecule between SMP and BSA. Fluorescein labeled sulfachloropyridazine (SCP) and SMP (tracer) were synthesized and purified by thin layer chromatography (TLC). The developed screening FPIA method can tolerate up to 20% methanol, and satisfactory assay sensitivity can be obtained between pH 4 and pH 8 and at lower salt concentration. The anti-SMP Mab exhibited a high cross-reactivity with SCP. The effect of the tracer structure on the analytical characteristic of the determination and on antigen-antibody binding constants was studied. The limits of detection (LOD) were 0.7 ng/mL for SMP and 0.25 ng/mL for SCP in buffer, respectively, whereas negligible cross-reactivities were exhibited by related sulfonamides. Analysis of SMP and SCP-fortified milk samples by the FPIA showed average recoveries from 60 to 145%.
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{
"pile_set_name": "PubMed Abstracts"
}
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SEM examination of human erythrocytes in uncoated bloodstains on stone: use of conventional as environmental-like SEM in a soft biological tissue (and hard inorganic material).
Although nowadays the so-called environmental scanning electron microscopes (ESEMs) allow the observation of the samples without metal or carbon coating, many conventional scanning electron microscopes (SEMs) are still in use. On the other hand, the presence of erythrocytes (red blood cells, RBCs) in a smear is considered a blood confirmation. Such a presence has been previously reported even in Lower Stone Age implements. In previous works, I have reported several studies dealing with cytomorphology of RBCs in bloodstains using scanning electron microscopy with standard specimen preparation procedures, i.e. via coating the samples before SEM analysis. In order to explore the potential of conventional SEM as environmental-like SEM in haemotaphonomical studies, two alkaline (limestone) and two acid (flint) rock fragments were smeared with human blood from a male and a female. The bloodstains obtained in this way were then air dried indoors and stored into a non-hermetic plastic box. Afterwards, the smears and their rock substrates were examined directly without coating, via secondary electrons, using a JEOL JSM-6400 scanning electron microscope. Satisfactory results reveal the capability of a conventional SEM to work in secondary-electron mode as an environmental-like SEM on these kinds of biological and inorganic materials, and probably in many other biological and non-biological samples.
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{
"pile_set_name": "PubMed Abstracts"
}
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Dose-intensified chemoradiation is associated with altered patterns of failure and favorable survival in patients with newly diagnosed glioblastoma.
We evaluated whether dose-intensified chemoradiation alters patterns of failure and is associated with favorable survival in the temozolomide era. Between 2003 and 2015, 82 patients with newly diagnosed glioblastoma were treated with 66-81 Gy in 30 fractions using conventional magnetic resonance imaging. Progression-free (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods. Factors associated with improved PFS, OS, and time to progression were assessed using multivariate Cox model and linear regression. Median follow-up was 23 months (95% CI 4-124 months). Sixty-one percent of patients underwent subtotal resection or biopsy, and 38% (10/26) of patients with available data had MGMT promoter methylation. Median PFS was 8.4 months (95% CI 7.3-11.0) and OS was 18.7 months (95% CI 13.1-25.3). Only 30 patients (44%) experienced central recurrence, 6 (9%) in-field, 16 (23.5%) marginal and 16 (23.5%) distant. On multivariate analysis, younger age (HR 0.95, 95% CI 0.93-0.97, p = 0.0001), higher performance status (HR 0.39, 95% CI 0.16-0.95, p = 0.04), gross total resection (GTR) versus biopsy (HR 0.37, 95% CI 0.16-0.85, p = 0.02) and MGMT methylation (HR 0.25, 95% CI 0.09-0.71, p = 0.009) were associated with improved OS. Only distant versus central recurrence (p = 0.03) and GTR (p = 0.02) were associated with longer time to progression. Late grade 3 neurologic toxicity was rare (6%) in patients experiencing long-term survival. Dose-escalated chemoRT resulted in lower rates of central recurrence and prolonged time to progression compared to historical controls, although a significant number of central recurrences were still observed. Advanced imaging and correlative molecular studies may enable targeted treatment advances that reduce rates of in- and out-of-field progression.
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{
"pile_set_name": "PubMed Abstracts"
}
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Surgical correction of severe hammer digit syndrome: a case report.
Survivors of a stroke are forever in a battle for complete recovery. Signs and symptoms of the initial stroke may remain. Patients who has had a stroke may retain some of their initial manifestations, e.g., hemiparesis. Limbs that were initially paralyzed will usually retain signs of upper motor neuron damage. This patient demonstrated such a situation, and we felt that the proper treatment in this case of severe hammer digit syndrome was modified Lambrinudi fusions.
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{
"pile_set_name": "PubMed Abstracts"
}
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The bone-anchor sub-urethral sling for the treatment of iatrogenic male incontinence: subjective and objective assessment after 41 months of mean follow-up.
To evaluate retrospectively the objective and subjective parameters in 42 male patients who underwent bone anchored sub-urethral sling positioning (BAUS) for SUI (stress urinary incontinence) due to ISD (intrinsic sphincter deficiency). Patients with SUI due to radical retropubic prostatectomy (36 patients), transurethral resection of prostate (5 patients) and open simple prostatectomy (1 patient) underwent BAUS positioning between July 1999 and September 2005 (mean FU = 41 months). Before and after surgery, the patients were evaluated by physical examination, urethrocystoscopy, urodynamics, 1 h pad test and QoL questionnaire. Surgical technique involved perineal implantation to the pubic rami using four anchors of a sub-urethral sling made of synthetic (26 patients), biological (4 patients) or mixed (12 patients) material. Patients were stratified into three groups: (1) Cured: dry patients at stress test, pad weight 0-1 g. (2) Improved: patients with mild-moderate incontinence, pad weight 2-50 g. (3) Failed: unchanged patients, pad weight > 50 g. At the final follow-up visit cured, improved and failed patients were 26 (62%), 4 (8%) and 12 (30%), respectively. Mean pad weight significantly decreased from 104.6 to 47.3 g (55%) and mean total questionnaire score significantly increased to 50.7 (66%). Mean ALPP significantly increased to 50.4 cmH2O (44.8%). Better results were seen with synthetic slings. Main complications were perineal pain (76%), detrusor overactivity (12%) and sling infection (4.8%). BAUS implantation is a safe, effective, minimally invasive option for iatrogenic male incontinence due to ISD. It compares favourably with AUS.
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{
"pile_set_name": "PubMed Abstracts"
}
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Hemodynamic tolerance and pharmacokinetics of nicorandil in experimental heart failure.
We tested whether nicorandil (NCR), a nitrovasodilator which also possesses K+ channel action, will produce in vivo hemodynamic tolerance commonly observed with other nitrovasodilators such as nitroglycerin (NTG). NCR was infused at 50 micrograms/kg/min for 10 h through a femoral cannula into conscious rats (n = 5) with congestive heart failure (CHF). Left ventricular end-diastolic pressure (LVEDP), LV peak-systolic pressure (LVPSP), and heart rate (HR) were measured periodically through an implanted catheter. Under these conditions, NCR produced a 40% reduction (p < 0.05) in LVEDP from baseline at 40 min after the start of the infusion. This reduction lasted approximately 6 h, followed by a slow return to baseline between 6 and 10 h. LVPSP was reduced (p < 0.05) from 2 h and leveled at approximately 8 h. HR increased by 12% from baseline at 40 min (p < 0.05). Plasma NCR concentrations were identical at 5 h (pretolerant state) and at 10 h (tolerant state) in these animals, suggesting that plasma pharmacokinetics were unrelated to NCR pharmacodynamics. NCR kinetics were not changed by the presence of CHF. Thus, in this animal model, tolerance to NCR developed in LVEDP but not LVPSP, and the K+ channel action of NCR apparently could not prevent tolerance development to venodilation arising from nitrate action.
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{
"pile_set_name": "PubMed Abstracts"
}
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Thalassemia-like phenotype in a novel complex hemoglobinopathy with α, β, δ globin chain abnormalities.
The occurrence of multiple abnormalities of α, β, δ, and γ globin genes may lead to unusual and complex phenotypes when they arise simultaneously in the same individual. Here, we report the findings of an African American boy who coinherited 3 heterozygous globin gene abnormalities: the unstable β-globin chain variant; hemoglobin (Hb) Showa-Yakushiji [β110(G12) Leu→Pro], the δ-globin chain variant; HbB2 [δ16(A13) Gly→Arg] and α-thalassemia (α-thal); (α-/αα). Hb Showa-Yakushiji had been previously described in Japanese, Indian, and European populations. We report its first occurrence in a child of African ancestry who presented with anemia not responsive to iron and an incomplete β-thalassemia minor phenotype. Although the clinical and laboratory features of Hb Showa-Yakushiji mimic those of a β-thalassemia, the coinheritance of the δ-globin chain variant Hb B2 suppressed the relative increase in Hb A2 usually observed in heterozygotes for the Hb Showa-Yakushiji mutation. Protein-based methods detected only a trace amount of HbB2 and failed to reveal presence of Hb Showa-Yakushiji and α-thal. The latter were only identified through DNA analyses. The diagnostic difficulties, molecular characteristics, and genotype/phenotype correlations of this novel complex hemoglobinopathy syndrome are reviewed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Dietary Iron Modulates Glucose and Lipid Homeostasis in Diabetic Mice.
Imbalance of iron homeostasis has been involved in clinical courses of metabolic diseases such as type 2 diabetes mellitus, obesity, and nonalcoholic fatty liver, through mechanisms not yet fully elucidated. Herein, we evaluated the effect of dietary iron on the development of diabetic syndromes in genetically obese db/db mice. Mice (aged 7 weeks) were fed with high-iron (HI) diets (1000 mg/kg chow) or low-iron (LI) diets (12 mg/kg) for 9 weeks. HI diets increased hepatic iron threefold and led to fourfold higher mRNA levels of hepcidin. HI also induced a 60% increase in fasting glucose due to insulin resistance, as confirmed by decreased hepatic glycogen deposition eightfold and a 21% decrease of serum adiponectin level. HI-fed mice had lower visceral adipose tissue mass estimated by epididymal and inguinal fat pad, associated with iron accumulation and smaller size of adipocytes. Gene expression analysis of liver showed that HI diet upregulated gluconeogenesis and downregulated lipogenesis. These results suggested that excess dietary iron leads to reduced mass, increased fasting glucose, decreased adiponectin level, and enhancement of insulin resistance, which indicated a multifactorial role of excess iron in the development of diabetes in the setting of obesity.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Rare cases of prostatitis caused by invasion of Trichomonas vaginalis with Candida albicans].
Three cases of prostatitis caused by the invasion of T. vaginalis and C. albicans which has been found in different biological materials were described. After per rectum examination perineum biopsy of prostata was performed in all patients; in histopathological preparations pointing at the inflammation reaction of that gland the fungi were detected. Also, the same microorganisms were proved in sexual partners of those patients but multifocal invasion of C. albicans--including genital and urinary organs, mouth and alimentary tract--also in members of their family.
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{
"pile_set_name": "PubMed Abstracts"
}
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Computerised tomography localisation of intrarenal calculi prior to nephrolithotomy.
The use of the EMI CT 5005 scanner in patients with renal calculus disease is described. This investigation was found to be a useful aid in the accurate localisation of calculi within the renal collecting system prior to surgery.
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{
"pile_set_name": "PubMed Abstracts"
}
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Duration of homologous porcine reproductive and respiratory syndrome virus immunity in pregnant swine.
The duration of porcine reproductive and respiratory syndrome virus (PRRSV) homologous immunity was tested in this study and found to last for at least 604 days post experimental exposure to field PRRSV. Eleven gilts (group A) received a primary exposure to field PRRSV by either an oronasal (n = 6) or an intrauterine (n = 5) route. The gilts were naturally bred at selected times (143 to 514 days) after primary virus exposure. They were oronasally exposed a second time to the same strain of virus on or about gestation day 90. Ten age-matched control sows free of PRRSV-specific antibody from the same source farm (group B) were naturally bred and were oronasally exposed to aliquots of the homologous challenge virus on or about gestation day 90. Nine of the 11 gilts in group A and all animals in group B became pregnant following one breeding cycle. The two nonpregnant gilts in group A were each naturally bred during four additional estrus cycles and neither became pregnant. They were exposed to homologous challenge virus 562 and 604 days post primary exposure, respectively. All animals were necropsied 21 days post homologous challenge. Sera and alveolar macrophages from each dam, and sera from each fetus were tested for virus. Transplacental infection was detected in 0/9 and 8/10 litters in groups A and B, respectively. Virus was detected in 0/11 and 10/10 of the alveolar macrophage samples collected in groups A and B, respectively. Serum was harvested at selected times throughout the experiment and tested for PRRSV-specific antibody by indirect immunofluorescence microscopy. All gilts in group A were seropositive for the duration of the experiment, and all animals in group B seroconverted following exposure to field PRRSV. This study shows that adult swine can produce a homologous protective immunity after PRRSV exposure that may persist for the production life of the animal.
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{
"pile_set_name": "PubMed Abstracts"
}
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Nuclear import of cellular retinoic acid-binding protein type I in mouse embryonic cells.
Using confocal microscopy we show that cellular retinoic acid-binding protein type I (CRABP I), expressed in several embryonic cell types, displays a compartmentalized subcellular distribution. The protein was excluded from the nucleus in some cells, while in others it accumulated in the nucleus. In the rat cerebellar cell line ST15A, which expresses CRABP I, the protein was found in the cytoplasm with a prominent nuclear exclusion. Addition of retinoic acid to embryos in vivo and to ST15 A cells in vitro did not affect the localization of the protein. Localization of CRABP I and CRABP I fused to a nuclear localization signal expressed in transfected cells, suggested that cell-specific factors may regulate nuclear import of CRABP I. The potential role of a CRABP I-controlled nuclear import of retinoic acid is discussed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Collective oscillations in the classical nonlinear response of a chaotic system.
We establish a general semiquantitative phase-space picture of the classical nonlinear response in a strongly chaotic system. As opposed to the case of stable dynamics, the response functions decay exponentially at long times. Damped oscillations in response functions are attributed to collective resonances which do not correspond to any periodic classical motions. We calculate analytically the second-order response in a simple chaotic system and demonstrate the relevance of the concept for the interpretation of spectroscopic data.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effect of diet restriction on some biochemical parameters related to aging in mice.
The effects of chronic diet restriction in mice on some biochemical parameters related to aging have been investigated. Restriction of food intake to about one-half of the ad libitum consumption resulted in a significantly decreased growth rate immediately after weaning. In the experimental mice killed after different periods on a restricted diet up to 12 months, in vitro lipoperoxidation, the percent free activities of lysosomal enzymes and the accumulation of lipofuscins in tissues such as brain and heart were lower in comparison to those of the control animals. The superoxide dismutase activity in liver and brain did not show any consistent variations due to diet restrictions. These beneficial influences of decreased food intake on some free radical-mediated cellular damage may underlie its reported effects on longevity, in conformity with the free radical theory of aging.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Evidence-based pharmacotherapy and other somatic treatment approaches for obsessive-compulsive disorder: state of the art].
Meta-analyses of the randomized controlled trials (RCT) in obsessive-compulsive disorder (OCD) have clearly demonstrated that selective serotonin reuptake inhibitors (SSRIs) are the medication treatment of choice, while cognitive behavioural therapy (CBT) with exposure and response prevention is the psychotherapy of choice in OCD. Several guidelines emphasized that SSRIs are the first choice of medication in OCD. It has been noted that these agents may need to be given at a higher dose, and for a longer duration, than is usually the case in disorders such as depression. In the management of refractory patients, medication history should be carefully reviewed and adherence to the recommendations of the guideline established. Antipsychotics (risperidone, quetiapine, haloperidol) are currently the pharmacotherapy augmentation strategy of choice. In those OCD patients who fail to respond to a range of SSRIs and augmentation strategies combined with CBT, more unusual interventions (including deep brain stimulation) can be considered.
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{
"pile_set_name": "PubMed Abstracts"
}
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Abdominal wall hernia repair in cirrhotic patients: outcomes seen at a tertiary care hospital in a developing country.
The outcome of hernia repair in patients with cirrhosis remains poor when compared to non-cirrhotics. The aim of our study was to evaluate the outcome of hernia repair in cirrhotic patients at our tertiary care hospital located in a developing country. A total of 61 patients with cirrhosis underwent hernia repair from January 2001 to December 2007 at our hospital. The mean age of the patients was 52 years and there were 30 males. Early postoperative complications were noted in 20 (33%) patients including two mortalities. The incidence of early complications was higher (71%) in patients with Child class C cirrhosis as compared to patients with either Child class A or B cirrhosis (21%), and the difference was statistically significant (P < 0.001). Except in emergency circumstances, surgery in Child class C patients may either be delayed until the patient is medically optimized or performed early before liver disease progresses to severe decompensation.
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{
"pile_set_name": "PubMed Abstracts"
}
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Is medically assisted death a special obligation?
Several distinct arguments conclude that terminally ill patients have a right to a medically assisted death; two are especially influential: the autonomy argument and the non-harm argument. Both have proven convincing to many, but not to those who view the duty not to kill as an (almost) absolute constraint. Some philosophers see the source of such a constraint in general (deontological) moral principles, other in the nature of the medical profession. My aim in this paper is not to add one further argument in favour of medically assisted death. Rather, I want to shed light on a kind of reason that, to my mind, has not been previously highlighted or defended, and that might shake the principled conviction that doctors are never allowed to actively assist their patients to die. Specifically, my purpose is to show that doctors (as members of the medical profession) have a special duty to provide medically assisted death to consenting terminally ill patients, because (and insofar as) they have been participants in the process leading to the situation in which a patient can reasonably ask to die. In some specific ways (to be explained), they are involved in the tragic fate of those patients and, therefore, are not morally allowed to straightforwardly refuse to assist them to die.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Spanish study of quality of life in migraine (I). Profile of the patient with migraine attending neurology clinics].
Migraine is the main reason for neurological consultation. To analyse the profile of the patient with migraine attending the Neurological Services of our country. Neurologists from 7 hospitals in different spanish regions interviewed 305 patients (at least 40 per hospital) who met migraine diagnostic criteria. They used an ad hoc questionnaire in which detailed demographic and migraine clinical data were included. Patients with transformed migraine or tension-type headache more than two days per week were excluded. The majority (82%), were women, with no other diseases, with an average social (88%) and cultural (41%) level. The mean age at consultation was 38 +/- 11 years, while the mean duration of migraine history was 18 +/- 13 years; 78% met criteria of migraine without aura, 15% of migraine with aura and the remaining (8%) both migraine with and without aura criteria. Main subjective precipitating factors were: stress (80%), foods (68%), drugs (34%), alcohol (20%) and menstruation (8%). Migraine pain was referred to as mild by 4% of cases, as moderate by 59% and as severe in the remaining 37%. The usual duration of migraine attacks ranged from 12 to 24 h in 35% of cases, from 24 to 48 h in 25%, from 4 to 12 h in 23% and was longer than 48 h in the remaining 17%. More than half (53%) had more than 3 attacks per month. The pain was unilateral in 70% of cases, and more than half had vomiting (57%) and sono and/or photophobia (97%). The typical profile of the migraine patient attending the Neurology Services in Spain is that of a woman aged from 20-50, with a long personal history of migraine, otherwise healthy and with an average socioeconomic and cultural level. Our data confirm that migraine attacks are incapacitating in a relevant number of these patients.
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{
"pile_set_name": "PubMed Abstracts"
}
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Local therapy of corneal allograft rejection with cyclosporine.
We evaluated the therapeutic effect of 0.5% topical cyclosporine on human corneal allograft rejection. Sixteen patients (16 eyes) with corneal allograft rejection, refractory to the conventional treatments, were recruited and treated with 0.5% cyclosporine eyedrops in this study. Of 16 eyes with corneal graft rejection after penetrating keratoplasty treated with 0.5% cyclosporine eyedrops, nine eyes were completely cured, six eyes improved markedly, and treatment was ineffective in one eye. A follow-up of 12 to 24 months (three eyes for 12 months, five eyes for 18 months, and eight eyes for 24 months) disclosed that rejection recurred in three of the nine cured eyes--two eyes after suspension of cyclosporine and one eye after removal of the sutures. The recurrence of rejection resolved by resumption of the cyclosporine eyedrops. This study demonstrated that treatment of corneal graft rejection with 0.5% topical cyclosporine yielded good results in eyes with satisfactory preoperative corneal transplantation beds and beneficial effects in eyes with poor preoperative corneal transplantation beds.
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{
"pile_set_name": "PubMed Abstracts"
}
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Purification, crystallization, and preliminary x-ray diffraction studies of the flavoenzyme mercuric ion reductase from Bacillus sp. strain RC607.
The flavoenzyme mercuric ion reductase from Bacillus sp. strain RC607 was purified by dye-ligand affinity chromatography. The protein was crystallized from solutions of high ionic strength, and one of the two crystal forms obtained has proven suitable for x-ray diffraction studies. Preliminary analysis showed that these crystals belong to the tetragonal space group 1422. The unit cell dimensions are a = b = 180.7 A; c = 127.9 A. The diffraction pattern extends to better than 3 A resolution. Crystal density measurements are consistent with one enzyme dimer of 2 x 69,000 Da comprising the asymmetric unit. Trypsin treatment of the native enzyme resulted in the removal of 157 amino acids at the N terminus. After purification, the remaining fragment (amino acids 158-631), which is still fully active in vitro, could be crystallized under the same conditions as native enzyme. Twinning problems, however, did not allow complete analysis of these crystals.
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{
"pile_set_name": "PubMed Abstracts"
}
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Radiation-induced bilateral coronary ostial stenosis in a 17-year-old patient.
Mediastinal irradiation can induce coronary artery disease characterized by the localization of lesions at the proximal segment of the arteries. We report the case of a 17-year-old patient who underwent a mediastinal irradiation for pulmonary sarcoma and developed 15 years later an asymptomatic ischemic cardiopathy. Bilateral coronary ostial stenosis was discovered by a transthoracic echography and coronary angiography showed isolated bilateral ostial stenosis. Coronary bypass grafting was performed with internal thoracic arteries. We recommend testing exercise and echocardiography during follow-up of patients who have received more than 30 Gy of mediastinal radiation. Surgery is the treatment of choice in bilateral ostial stenosis using internal thoracic arteries in young patients if preoperative assessment shows patency.
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{
"pile_set_name": "PubMed Abstracts"
}
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Mycoplasma genitalium, a stealth female reproductive tract.
Mycoplasma genitalium was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. It is a sexually transmitted bacterium associated with a number of urogenital conditions in women like cervicitis, endometritis, pelvic inflammatory disease, infertility, and susceptibility to human immunodeficiency virus (HIV). However, M. genitalium may also act like a stealth pathogen at female reproductive tract, giving no symptoms. Its prevalence varies between different groups, with the average being 0.5-10% in the general population and 20-40% in women with sexually transmitted infections. The recommended treatment of this infection is azithromycin as a single 1-g dose. However, in recent years, macrolide resistance has increased which is significantly lowering the cure rate, being less than 50% in some studies. New treatment regimens need to be investigated due to increasing drug resistance. The discussion and suggestion of an algorithm for management of this infection is the highlight of this paper.
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{
"pile_set_name": "PubMed Abstracts"
}
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The Lewis-Y carbohydrate antigen is expressed by many human tumors and can serve as a target for genetically redirected T cells despite the presence of soluble antigen in serum.
In this study we aimed to determine the suitability of the Lewis-Y carbohydrate antigen as a target for immunotherapy using genetically redirected T cells. Using the 3S193 monoclonal antibody and immunohistochemistry, Lewis-Y was found to be expressed on a range of tumors including 42% squamous cell lung carcinoma, 80% lung adenocarcinoma, 25% ovarian carcinoma, and 25% colorectal adenocarcinoma. Expression levels varied from low to intense on between 1% and 90% of tumor cells. Lewis- was also found in soluble form in sera from both normal donors and cancer patients using a newly developed enzyme-linked immunosorbent assay. Serum levels in patients was often less than 1 ng/mL, similar to normal donors, but approximately 30% of patients had soluble Lewis-Y levels exceeding 1 ng/mL and up to 9 ng/mL. Lewis-Y-specific human T cells were generated by genetic modification with a chimeric receptor encoding a single-chain humanized antibody linked to the T-cell signaling molecules, T-cell receptor-zeta, and CD28. T cells responded against the Lewis-Y antigen by cytokine secretion and cytolysis in response to tumor cells. Importantly, the T-cell response was not inhibited by patient serum containing soluble Lewis-Y. This study demonstrates that Lewis-Y is expressed on a large number of tumors and Lewis-Y-specific T cells can retain antitumor function in the presence of patient serum, indicating that this antigen is a suitable target for this form of therapy.
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{
"pile_set_name": "PubMed Abstracts"
}
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Familial fatal fetal cardiomyopathy with isolated myocardial calcifications: a new syndrome?
We describe three male sib fetuses with isolated myocardial calcifications resulting in intrauterine fetal death (IUFD) as early as the second trimester. No evidence for an underlying mitochondrial cytopathy, dystrophinopathy or myopathy was found. There were no signs of inflammation or a metabolic disorder, and the mother had no prenatal exposure of teratogenic drugs. Furthermore, no mutation in the Barth syndrome gene (G4.5) could be detected. Because isolated calcification of the heart and IUFD are not typical of any previously described inherited cardiomyopathy, it may represent a new familial fetal cardiomyopathy.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Stent graft for rapidly growing thoracic mycotic aneurysm in a patient with advanced lung cancer].
We report a compromised patient with mycotic aneurysm, who was successfully treated by urgent placement of a stent graft. A man in his seventies was admitted to our hospital with relapsing high fever and back pain during chemotherapy for advanced squamous cell carcinoma of the lung. Contrast CT demonstrated a saccular aneurysm of the thoracic aorta and left pleural effusion. Blood cultures were positive for Escherichia coli producing extended spectrum beta-lactamase (ESBL). Therefore, thoracic mycotic aneurysm was diagnosed. Because of rapid growth on consecutive examinations, absolute bed rest was required. Therefore, we performed antibiotic therapy combined with stent graft placement, which achieved complete exclusion of the aneurysm. He was discharged in an ambulatory state, and his quality of life remained good at home until just before death from terminal state of the cancer.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Intertrochanteric flexion osteotomy in aseptic osteonecrosis of the femoral head in adults. Apropos of 52 cases].
Fifty-two intertrochanteric osteotomies were performed in 42 cases of idiopathic avascular necrosis of the femoral head of which 10 were bilateral. By flexion at the osteotomy site, the operation aims to place the superior pole of the femoral head during weight bearing towards the superior part of the acetabulum. The use of a specially angled nail-plate makes the procedure safe and simple. The results were analysed with an average follow-up of 46 months and a minimum follow-up for 2 years. The overall results were good in 72 p. 100 of cases, with better results for pain and mobility than for stability and gait. The results were better when the necrosis did not reach the centre of the head and when there was true relief from weight-bearing pressure. The indication were the best in grade II necrosis in patients less than 55 years old.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Roles of p53 in chemotherapy of glioblastoma].
LN382, a glioblastoma cell line, has a temperature-sensitive mutant p53. At the permissive temperature (34 degrees C), arrest of cell growth at the G1 phase occurred with recovered p53's transcriptional activity, and restored p53 protein turnover. In order to understand the influence of the functional status of p53 on the sensitivity to anticancer agents in glioblastoma cells, I analyzed responses of LN382 cells and U251MG cells with a mutant p53 as a control at 34 degrees C and 37 degrees C to etoposide, paclitaxel, and cisplatin, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). Restoration of p53 protein function in LN382 cells at 34 degrees C reduced the cytotoxicity of etoposide and paclitaxel, whereas that of cisplatin and ACNU was not affected. In contrast, the temperature shift to 34 degrees C did not alter the cytotoxicity of etoposide, paclitaxel, cisplatin, or ACNU in U251MG cells. Transduction of wild-type p53 in LN382 cells also reduced the sensitivity of the cells to etoposide. Cell cycle analysis using flow cytometry revealed that this decrease in sensitivity was associated with an impaired transition to the G2M phase subsequent to the addition of etoposide or paclitaxel. These results indicate that cell cycle arrest induced by wild-type p53 function may abrogate the cytotoxic effects of etoposide and paclitaxel, which are dependent on G2M-associated apoptosis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Computed tomography of intracranial lymphoma.
The appearances on computed tomography (CT) of 17 patients with histologically proven intracranial lymphoma have been analysed and abnormalities detected in 16. Four of the patients had systemic lymphoma. Multiple lesions were seen in eight patients (47%), in six of whom the multiple lesions in each patient were of similar appearance. There was good macroscopic correlation between the CT and post-mortem appearances in the eight patients who subsequently died, although in five, histological examination showed more extensive infiltration. Meningeal involvement was seen more commonly in the cases of systemic lymphoma than in the purely cerebral lymphomas, but parenchymal lesions were equally common in both. Grey matter lesions tended to be clearly demarcated, of increased density with little oedema or displacement; homogeneous density enhancement was produced by the intravenous injection of contrast medium. White matter lesions were usually poorly demarcated, of variable density with marked oedema and displacement, and with heterogeneous enhancement.
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{
"pile_set_name": "PubMed Abstracts"
}
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Formation of ascochitine by plant pathogens of the genus Ascochyta.
Strains of fungi isolated from pulse crops: pea (Pisum sativum) and faba beans (Vicia faba) plants with symptoms of Ascochyta blight, footrot and stems lesions have been examined under laboratory conditions for their ability to produce ascochitine and metabolites toxic toArtemia salina. BothAscochyta pisi Lib and Ascochyta fabae LK Jones isolates formed ascochitine in yields of 20-480mg/kg. The highest yield of ascochitine was produced on rice and the lowest on maize grain.Ascochyta pinodes andPhoma medicaginis varpinodella (LK Jones) Boerema (formerlyAscochyta pinodella LK Jones) did not produce ascochitine.Crystalline ascochitine was found to be of moderate toxicity toArtemia salina larvae (LC50 = 85μg/cm(3)BSM*). Extracts ofPhoma medicaginis var,pinodella cultures were found to be highly toxic toArtemia salina.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effects of fixation method on image cytometric measurement of DNA content and distribution in cells stained for fluorescence with propidium iodide.
We performed image cytometric measurements of DNA content and distribution on cycling human HCT-8 cells stained for fluorescence with propidium iodide (PI). Seven different fixation protocols were evaluated for stoichiometry of PI staining and for their ability to preserve in vivo chromatin structure. Bimodal integrated optical intensity (IOI) histograms were obtained with all fixation protocols. Increased accessibility of DNA to the dye was evident in increased values of the IOI at the GI peak. The fixatives studied, in order of increasing accessibility to DNA, were Regaud's Boehm-Sprenger, Carnoy's, air-drying, methanol, ethanol, and acetone/methanol. In general, the coefficient of variation of the IOI within the G1 peak was higher for fixatives where DNA is less accessible. Features describing the spatial distribution of stain exhibited dramatic changes for Boehm-Sprenger fixation, which were consistent with the observation that in vivo conformation of chromatin is best preserved with this method.
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{
"pile_set_name": "PubMed Abstracts"
}
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Experimental observations of the threshold-like onset of mode instabilities in high power fiber amplifiers.
We report on the observation and experimental characterization of a threshold-like onset of mode instabilities, i.e. an apparently random relative power content change of different transverse modes, occurring in originally single-mode high-power fiber amplifiers. Although the physical origin of this effect is not yet fully understood, we discuss possible explanations. Accordingly, several solutions are proposed in this paper to raise the threshold of this effect.
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{
"pile_set_name": "PubMed Abstracts"
}
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True histiocytic lymphoma with multiple skin nodules.
A 73-year-old white woman developed multiple cutaneous nodules that fluctuated in size and occasionally regressed. The tumor cells infiltrating the dermis were histiocytic by light microscopy, marker studies, and electron microscopy. Similar cells were present in a bone marrow biopsy specimen. A diagnosis of true histiocytic lymphoma was made. The case illustrates some of the problems that may arise in evaluation of clinical and pathologic findings in a patient with a proliferative disorder of histiocytes and demonstrates the contribution that electron microscopy can provide in establishing the diagnosis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Transport of pyruvate by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule.
The characteristics of renal transport of pyruvate by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule were studied. It was found that the uptake of pyruvate in these vesicle preparations occurred by means of multiple transport systems. An electrogenic and Na+-requiring system confined to pars convoluta, exists for transport of pyruvate with an intermediate affinity, KA = 0.71 +/- 0.08 mM. In vesicles from pars recta, the uptake of pyruvate was mediated by a dual transport system with a high (KA1 = 0.30 +/- 0.05 mM) and low affinity (KA2 = 5.75 +/- 0.82 mM). The relation of these three pyruvate transport systems to the transport of other monocarboxylates and dicarboxylates was determined by examination of the inhibitory effect of L-lactate, beta-hydroxybutyrate and L-malate on the renal uptake of pyruvate. It was found that L-malate efficiently reduced the uptake of pyruvate by vesicles from pars convoluta, while addition of monocarboxylates (L-lactate, beta-hydroxybutyrate) has no effect on the transport of pyruvate in this region of proximal tubule. Furthermore, it was observed that Na+-dependent uptake of L-malate was specifically inhibited to about the same extent by 1 mM pyruvate. These findings strongly suggest that pyruvate and L-malate are taken up by the same transport system in vesicles from pars convoluta, which is different from that of L-lactate and beta-hydroxybutyrate. Experiments designed to investigate the substrate specificity for the high and low affinity system for pyruvate in pars recta, revealed that monocarboxylates (L-lactate, beta-hydroxybutyrate) substantially inhibit pyruvate transport at the low, but not the high substrate concentration, indicating that all monocarboxylates compete for the same high-affinity transport system. By contrast, L-malate at low concentrations preferentially inhibited the low-affinity system for pyruvate. This observation led us to suggest that L-malate and pyruvate share a common transport system in pars recta with low affinity for pyruvate and high affinity for L-malate.
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{
"pile_set_name": "PubMed Abstracts"
}
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Mutagenicity of expectorate from workers in a coke plant.
Methanol extracts of hydrolyzed expectorate samples from workers in a coke plant were tested with the Salmonella reversion assay. The expectorates from exposed smokers (but also to a certain extent from exposed non-smokers) were mutagenic; however, the control samples from both smokers and non-smokers were not. The positive results produced by the expectorate samples from exposed smokers suggest a synergistic relationship between exposure to air pollution in the working atmosphere and smoking.
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{
"pile_set_name": "PubMed Abstracts"
}
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Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter.
Global dust storms on Mars are rare1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars4. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes5,6, as well as a decrease in the water column at low latitudes7,8. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H2O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals3. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.
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{
"pile_set_name": "PubMed Abstracts"
}
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[A case of membranous nephropathy with ANCA-associated necrotizing glomerulonephritis during oral administration of PTU for Graves' disease].
We experienced a coincidental case of two types of glomerulopathy associated with Graves' disease. A 64-year-old man, who had been treated with propylthiouracil(PTU) for Graves' disease for 15 years, was admitted to our hospital for macroscopic hematuria and rapidly progressive deterioration of renal function. Although his thyroid function had been within the normal range during treatment, the level of thyrotropin receptor antibody(TRAb) gradually increased from a year before admission. Serological tests revealed that he was positive for myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA). The renal biopsy specimen showed necrotizing and crescentic glomerulonephritis(GN) superimposed on membranous nephropathy(MN). This is a rare case of MN complicated with ANCA associated crescentic GN in a Graves' disease patient. Association of these two renal alterations was not clearly defined. MN involved with Graves' disease also has been rarely reported. Some reports demonstrated deposition of thyroglobulin and other thyroid related antigens in the glomeruli. In the present case, long-term impairment of Graves' disease and elevation of TRAb might have been responsible for the formation and deposition of thyroid-associated immune complex in the glomeruli. As for crescentic GN, PTU might have induced ANCA-associated GN independently of MN. This case is instructive for considering the relation between Graves' disease and renal injury.
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{
"pile_set_name": "PubMed Abstracts"
}
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[The antihypertensive activity of benazepril in the long-term treatment of hypertension patients and its effect on adrenal cortical function].
Changes in arterial hypertension, heart rate and adrenocortical hormones (11-OCS, aldosteron, progestins) in the blood and 24-h urine were followed up in the course of 24-week use of angiotensin-converting enzyme inhibitor benazepril (10-20 mg once a day) in 24 patients with mild and moderate essential hypertension (EH) included in a placebo-controlled randomized study. A 2 and 24-week antihypertensive response was achieved in 75 and 71% of patients, respectively. 24-h urinary excretion of corticosteroids before the treatment was increased. After the treatment benazepril reduced excretion of 11-OCS by 42%, but not of aldosteron the levels of which decreased only within the first 2 weeks of treatment. The above trends in changes of gluco- and mineralocorticoid activity should be taken into consideration in long-term treatment of EH with inhibitors of angiotensin-converting enzyme.
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{
"pile_set_name": "PubMed Abstracts"
}
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Use of complexing agents for effective ion-exchange separation of Co(II)/Ni(II) from aqueous solutions.
Cation-exchange separation of Co(2+)/Ni(2+) from aqueous solutions using water-soluble complexing agents of ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), iminodiacetic acid (IDA), and citrate was experimentally studied at 298 K. Experiments were carried out as a function of initial aqueous pH (1.0-6.0), concentration of total metals (1.5-45.0 mol/m(3)), the concentration ratio of two metals (0.1-10) and of complexing agent to the total metals (0-1). It was shown that the exchange selectivity strongly depended on solution pH and was not completely related to the affinity of any metal with the complexing agents. When a certain level of complexing agent was present, highly effective separation could be achieved at an appropriate pH range (for an equimolar metal solution, e.g., pH 2-3 with EDTA and NTA as well as pH>3 with IDA and citrate). The application potential of this method was highlighted for the separation of Co(2+) from binary mixtures in the presence of trace amount of Ni(2+) due to its high selectivity and the smaller amount of the complexing agents needed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Caspase-3 is involved in IFN-γ- and TNF-α-mediated MIN6 cells apoptosis via NF-κB/Bcl-2 pathway.
TNF-α and IFN-γ are the major pro-inflammatory cytokines in the β-cell destruction. However, the underlying mechanism remains unclear. The present study used a murine insulinoma cell line MIN6 for further investigation of the effect of Caspase-3 on the cytokines-induced pancreatic β-cell apoptosis and analyzed the mechanisms involved in the activation of Caspase-3. It was showed that the combination of IFN-γ and TNF-α significantly reduced the viability of MIN6 cells and the observed cells growth inhibition was due to cell apoptosis as judged by the morphological changes under a confocal laser scanning microscopy and FACS assay of Annexin-V/7-AAD double staining. Accompanying with NF-κB activation and Bcl-2 downregulation, both the cleaved Caspase-3 and PARP, a known substrate of Caspase-3 in vivo, were observed at 24 and 12 h, respectively, after cells exposure to IFN-γ and TNF-α treatment. Pretreatment of Caspase-3 inhibitors remarkably attenuated IFN-γ- and TNF-α-induced cells apoptosis. Inhibition of NF-κB activation led to the increase in Bcl-2 expression, a significant attenuation in Caspase-3 activity, and an obvious amelioration in cells viability in IFN-γ- and TNF-α-treated MIN6 cells. Taken together, our results indicate that Caspase-3 is critical for the induction of MIN6 cells apoptosis and it's activation is further confirmed to be related to the NF-κB-mediated Bcl-2 downregulation, which may be the underlying mechanism of IFN-γ- and TNF-α-mediated MIN6 cells apoptosis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Determination of ester carbonyl 18O/16O ratios in phospholipids by gas chromatography-mass spectrometry.
A method is described for the quantitation of 18O enrichment in phospholipid acyl groups. Methyl esters are prepared by transesterification with sodium hydroxide in methanol and are hydrogenated prior to gas chromatography-mass spectrometry (GC-MS). Estimation of 18O content of the resulting esters is made using the m/z 74 and m/z 76 fragments, which contain both the ester oxygens. The accuracy of the method is demonstrated with synthetic methyl esters and phosphatidylcholines containing a known amount of 18O.
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{
"pile_set_name": "PubMed Abstracts"
}
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Microcrystalline Zinc Coordination Polymers as Single-site Heterogeneous Catalysts for the Selective Synthesis of Mono-oxazolines from Amino Alcohol and Dinitriles.
In our effort to develop coordination polymers (CPs)-based single-site catalysts for the selective synthesis of mono-oxazolines, two Zn-based CPs, [{Zn6 (idbt)4 (phen)4 } ⋅3 H2 O]n (1) and [{Zn3 (idbt)2 (H2 O)4 }⋅2 H2 O]n (2) (H3 idbt= 5,5'-(1H-imidazole-4,5-diyl)-bis-(2H-tetrazole), phen=1,10-phenanthroline) have been synthesized. They exhibit two-dimensional structure and contain isolated and accessible catalytically active sites, mimicking the site isolation of many catalytic enzymes. Micro CPs 1 and 2 are obtained by using surfactant-mediated hydrothermal methods, and an investigation is conducted to explore how different surfactants affect their morphologies and particle sizes. Furthermore, micro 1 and 2 have shown to be effective heterogeneous catalysts for the reaction of amino alcohols and aromatic dinitriles, and exerted a significant influence on the selectivity of the catalytic reactions, yielding mono-oxazolines as the major reaction product.
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{
"pile_set_name": "PubMed Abstracts"
}
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Fabrication of novel magnetic graphene oxide nanocomposites for selective adsorption of mercury from aqueous solutions.
In this work, a novel functionalized graphene oxide (GO) was used as an effective and selective adsorbent for removal of mercury (Hg2+). The magnetic nanocomposite adsorbent (MNA) based on GO was prepared through surface reversible addition-fragmentation chain transfer copolymerization of acrylic monomers and then the formation of Fe3O4 nanoparticles. The structure of MNAs was characterized by using FTIR, SEM, TEM, VSM, XRD, and nitrogen adsorption/desorption isotherms. The results of ion adsorption of MNAs demonstrated high selectivity and adsorption efficiency for Hg2+ in the presence of competing ions. Furthermore, the removal of Hg2+ obeyed a pseudo-second-order model and fitted well to the Langmuir isotherm model with the maximum Hg2+ uptake of 389 mg g-1. The MNA was also confirmed as good materials for re-use and maintained 86% of its initial adsorption capacity for mercury after the fifth regeneration cycles. Finally, the experimental results demonstrated that the solution pH, ion concentration, and temperature had a major impact on Hg(II) adsorption capacity. The results indicate that the MNAs with high adsorption abilities could be very promising adsorbents for the selective recovery of ions in wastewater treatment process. Graphical abstract.
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{
"pile_set_name": "PubMed Abstracts"
}
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Computational insights into the molecular interactions of environmental xenoestrogens 4-tert-octylphenol, 4-nonylphenol, bisphenol A (BPA), and BPA metabolite, 4-methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene (MBP) with human sex hormone-binding globulin.
Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), 4-tert-octylphenol (OP), and 4-nonylphenol (NP) are three high volume production EDCs that are widely used for industrial purposes and are present ubiquitously in the environment. Bisphenol A is metabolized in the human body to a more potent compound (MBP: 4-Methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene). Epidemiological and experimental studies have shown the three EDCs to be associated with adverse effects on reproductive system in human and animals. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The current study was done in order to understand the binding mechanism of OP, BPA, NP, and MBP with human SHBG using in silico approaches. All four compounds showed high binding affinity with SHBG, however, the binding affinity values were higher (more negative) for MBP and NP than for OP and BPA. The four ligands interacted with 19-23 residues of SHBG and a consistent overlapping of the interacting residues for the four ligands with the residues for the natural ligand, dihydrotestosterone (DHT; 82-91% commonality) was shown. The overlapping SHBG interacting residues among DHT and the four endocrine disruptors suggested that these compounds have potential for interference and disruption in the steroid binding function.
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{
"pile_set_name": "PubMed Abstracts"
}
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INCAP studies of vegetable proteins for human consumption.
This article describes the efforts of the Institute of Nutrition of Central America and Panama (INCAP) to develop a relatively low-cost vegetable protein mixture suitable as a complementary food for infants and young children. As it turned out, the resulting product became popular with older children and adults, and its superior nutritional benefits were widely recognized by the population. This effort led to broader studies by INCAP of the nutritional quality of vegetable protein mixtures, including raw materials, processing to convert them into human-grade products, product formulation, and commercialization.
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{
"pile_set_name": "PubMed Abstracts"
}
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Neonatal exposure to methyl chloroform in tape remover.
Methyl chloroform (MC) is commonly used solvent found in some adhesive tape remover products used in intensive care nurseries. Since volatile substances can accumulate inside an infant incubator, we measured levels of MC following simulated use of 2 commercially available adhesive tape remover pads. Readily detectable levels of MC could be found in incubator air for several minutes. Although adult occupational neurotoxic thresholds are higher, increased toxic susceptibility of the neonate CNS indicates caution should be observed.
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{
"pile_set_name": "PubMed Abstracts"
}
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FZD8, a target of p53, promotes bone metastasis in prostate cancer by activating canonical Wnt/β-catenin signaling.
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men and exhibits a high propensity to metastasize to bone. Currently, bone metastasis remains incurable, and therapies are limited. A better understanding of the molecular mechanisms involved in PCa bone metastasis is needed to develop more effective therapeutics for this disease. Herein, we reported that among the FZD family, FZD8 was robustly upregulated in bone-metastastic PCa cell lines and tissues. High levels of FZD8 expression were significantly positively associated with clinical tumor progression and bone metastasis. Furthermore, we found that overexpressing FZD8 promoted, whereas silencing FZD8 suppressed, PCa cell migration, invasion and stem cell-like phenotypes in vitro, through the activation of canonical Wnt/β-catenin signaling. Importantly, downregulation of FZD8 greatly suppressed the incidence of PCa bone metastasis in vivo. Moreover, wild-type p53 transcriptionally repressed FZD8 by directly interacting with the FZD8 promoter. Taken together, these findings uncover a novel mechanism for PCa bone metastasis, and indicate that FZD8 might represent a potential therapeutic target for PCa bone metastasis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Protein kinase C pathway potentiates androgen-mediated gene expression of the mouse vas deferens specific aldose reductase-like protein (MVDP).
Transcription of the mouse vas deferens protein (MVDP) gene, a member of the aldo-keto reductase superfamily, is stimulated by androgens via the androgen responsive element (ARE) located in the proximal promoter (-111 to -97). We investigated interaction between androgens and the protein kinase C (PKC) signalling pathway. Transcriptional regulation was determined by analysis of chloramphenicol acetyltransferase (CAT). T47D cells were transiently transfected with 5' flanking MVDP DNA promoter sequences (-1804 to +41; -510 to +41 and -121 to +41) fused to the reporter (CAT) gene. Androgen-induced transcriptional activity can be enhanced from 6 (1.8 and 0.5 kb MVDP-CAT constructs) to 18 fold (0.16 kb MVDP-CAT construct), in a time and dose-dependent manner, by the PKC activator 12-o-tetradecanoylphorbol-13 acetate (TPA). A mutation in the proximal ARE abolished both androgen and TPA-dependent gene enhancement. TPA influenced minimally MMTV promoter in T47D cells and MVDP promoter in CV1 cells suggesting that the effects of the PKC activator are probably promoter and cell-specific. In contrast, activation of protein kinase A (PKA) via addition of dibutyryl-cAMP (db-cAMP) reduced androgen induction of the MVDP gene.
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{
"pile_set_name": "PubMed Abstracts"
}
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A comparative study of two antimicrobial/anti-inflammatory formulations in the treatment of canine otitis externa.
The efficacy and tolerability of a marbofloxacin-clotrimazole-dexamethasone otic suspension (MCD) was compared with a standard topical treatment using a phase III clinical trial protocol. In a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion to identify the causative pathogen; a further sample was collected in the event of failure or relapse, and from dogs (at day 14) for which Pseudomonas species had been isolated at inclusion. One group received MCD (10 drops per affected ear) once daily and a second received Surolan (containing polymyxin B, miconazole and prednisolone) (5 drops per affected ear), twice daily. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Efficacy and tolerability were evaluated on days 7, 14 and, if necessary, 28 for dogs treated for 14 days. The trial demonstrated equivalence of both treatments in terms of efficacy, with a cure rate of 58.3% for MCD and 41.2% for Surolan. Both medications were equally well tolerated by dogs, but MCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14.
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{
"pile_set_name": "PubMed Abstracts"
}
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Video-assisted thoracic surgery for fibropurulent thoracic empyema: a bridge to open thoracic surgery.
Thoracic empyema remains a serious problem. We evaluated the feasibility and efficacy of video-assisted thoracic surgery (VATS) for fibropurulent thoracic empyema. Twenty-six consecutive patients with thoracic empyema resistant to medical therapy were treated by VATS from 1997 to 2006. The presence of pleural adhesion was not a contraindication. Patients with destroyed lung, bronchopleural fistula, or excessively thickened pleura were excluded. Twenty-two were males and 4 were females with a mean age of 59 years (range 14 to 85). The length of preoperative period was 39.3 +/- 25.3 days, and the length of preoperative treatment was 11.2 +/- 14.3 days. The operating time was 127.6 +/- 45.1 minutes and intraoperative bleeding was 353.8 +/- 438.4 g. Postoperative complications were observed in two cases (8.0%). There were no hospital deaths. Twenty-two cases (84.6%) were cured with a postoperative drainage time of 12.5 +/- 8.2 days. Four cases required an additional operation. However, the VATS procedure was not required to perform additional thoracoplasty using pedicled chest wall muscles. VATS for fibropurulent thoracic empyema is effective and less invasive, and it may be important as a bridge between minimally invasive and conventional open thoracic surgical management.
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{
"pile_set_name": "PubMed Abstracts"
}
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Synthesis and structures of Co bis-trifluoromethylpyrazolate complexes.
Reactions of Co(PMe3)3Cl or CoCl2 with 3,5-(CF3)2-PzNa in hexane give Co(PMe3)3(3,5-(CF3)2-Pz) (1) and Co(PMe3)3(3,5-(CF3)2-Pz)2 (2) respectively (3,5-(CF3)2-PzNa = sodium bis-trifluoromethylpyrazolate). Reaction of (3,5-(CF3)2-PzH) with Co(PMe3)4 produces the unusual complex [cis-Co(PMe3)4H2][Co(PMe3)(3,5-(CF3)2-Pz)3] (3) which formally contains a [Co(III)](+)[Co(II)](-) complex ion pair. Reaction of 3,5-(CF3)2-PzLi with an oxygenated suspension of CoCl2 and 3 equivalents of PMe3 gives (3,5-(CF3)2-Pz)2Co(μ-3,5-(CF3)2-Pz)(μ-OPMe3)Li(OPMe3)2 (4), while 2 reacts with LiOH to give [(PMe3)Co(μ-3,5-(CF3)2-Pz)2(μ(3)-OH)Li]2 (5). Both 2 and 3 react with O2 in toluene solution to give Co(OPMe3)2(3,5-(CF3)2-Pz)2 (6). All compounds have been characterized spectroscopically and by single crystal X-ray diffraction studies.
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{
"pile_set_name": "PubMed Abstracts"
}
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Development and validation of an arthropod maceration protocol for zoonotic pathogen detection in mosquitoes and fleas.
Arthropod-borne diseases remain a pressing international public health concern. While progress has been made in the rapid detection of arthropod-borne pathogens via quantitative real-time (qPCR), or even hand-held detection devices, a simple and robust maceration and nucleic acid extraction method is necessary to implement biosurveillance capabilities. In this study, a comparison of maceration techniques using five types of beads followed by nucleic acid extraction and detection were tested using two morphologically disparate arthropods, the Aedes aegypti mosquito and Xenopsylla spp. flea, to detect the zoonotic diseases dengue virus serotype-1 and Yersinia pestis. Post-maceration nucleic acid extraction was carried out using the 1-2-3 Platinum-Path-Sample-Purification (PPSP) kit followed by qPCR detection using the Joint Biological Agent Identification and Diagnostic System (JBAIDS). We found that the 5mm stainless steel beads added to the beads provided in the PPSP kit were successful in macerating the exoskeleton for both Ae. aegypti and Xenopsylla spp. Replicates in the maceration/extraction/detection protocol were increased in a stepwise fashion until a final 128 replicates were obtained. For dengue virus detection there was a 99% positivity rate and for Y. pestis detection there was a 95% positive detection rate. In the examination of both pathogens, there were no significant differences between qPCR instruments, days ran, time of day ran, or operators.
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{
"pile_set_name": "PubMed Abstracts"
}
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Serial decline of kidney function as a novel biomarker for the progression of atherothrombotic disease.
Impaired kidney function is associated with cardiovascular disease. However, from the available data it cannot be discerned which of the two entities presents first and entails the other. If renal dysfunction is first, a dynamic decline in the estimated glomerular filtration rate (eGFR) should predict vascular events and prove a useful biomarker for atherothrombotic disease. We therefore tested the hypothesis that a decrease in kidney function predicts future vascular events in a high-risk population of angiographically characterized coronary patients. We calculated the eGFR by the Mayo clinic quadratic equation at baseline and after two years in a high-risk population of 400 consecutive men undergoing coronary angiography, of whom 355 had coronary artery disease (CAD). Vascular events were recorded over six years. A serial decrease in kidney function from baseline to the follow-up visit two years later significantly predicted vascular events in the subsequent four years independently from the baseline eGFR with a standardized adjusted hazard ratio (HR) of 1.41 (1.13-1.76); p=0.003. This result proved robust after adjustment for age, BMI, hypertension, diabetes, LDL-C, HDL-C, smoking, and high-sensitivity C-reactive protein (HR=1.41 [1.12-1.78]; p=0.004). The predictive power of eGFR loss was confirmed even after further adjustment for the presence of CAD at baseline (HR=1.43 [1.12-1.81]; p=0.004). In this fully adjusted model a 10 ml/min/1.73 m2 decrease in eGFR independently conferred a 31% increase in cardiovascular event risk (p=0.004). A decline of eGFR over two years strongly, significantly, and independently predicts vascular events over the subsequent four years. Declining eGFR is a readily obtainable and inexpensive candidate new biomarker for the progression of atherothrombotic disease.
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{
"pile_set_name": "PubMed Abstracts"
}
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Sunspots and the recency theory of schizophrenia.
Schizophrenia, a disorder with a high, fairly uniform, global distribution, can occur with or without an accompanying family history of mental disorder. Given the preponderance of sporadic cases and the low fertility of genetic cases, this combination suggests that the disorder might be caused by a globally active teratogen. It has recently been shown that some factor associated with high sunspot activity acts transgenerationally to reduce lifespan. The following article discusses the relevance of that finding to changes in the incidence of schizophrenia and suggests that schizophrenia is caused by some factor associated with sunspots.
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{
"pile_set_name": "PubMed Abstracts"
}
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Four disruptive strategies for removing drug discovery bottlenecks.
Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating a translational gap. Although there have been collaborative public-private partnerships in Europe to share pharmaceutical data, the USA has seemingly lagged behind and this may hold it back. Sharing precompetitive data and models may accelerate discovery across the board, while finding the best collaborators, mining social media and mobile approaches to open drug discovery should be evaluated in our efforts to remove drug discovery bottlenecks. We describe four strategies to rectify the current unsustainable situation.
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{
"pile_set_name": "PubMed Abstracts"
}
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Opioid and Cannabis Co-Use among Adults With Chronic Pain: Relations to Substance Misuse, Mental Health, and Pain Experience.
Opioid misuse constitutes a significant public health problem and is associated with a host of negative outcomes. Despite efforts to curb this increasing epidemic, opioids remain the most widely prescribed class of medications. Prescription opioids are often used to treat chronic pain despite the risks associated with use, and chronic pain remains an important factor in understanding this epidemic. Cannabis is another substance that has recently garnered attention in the chronic pain literature, as increasing numbers of individuals use cannabis to manage chronic pain. Importantly, the co-use of substances generally is associated with poorer outcomes than single substance use, yet little work has examined the impact of opioid-cannabis co-use. The current study examined the use of opioids alone, compared to use of opioid and cannabis co-use, among adults (n = 450) with chronic pain on mental health, pain, and substance use outcomes. Results suggest that, compared to opioid use alone, opioid and cannabis co-use was associated with elevated anxiety and depression symptoms, as well as tobacco, alcohol, cocaine, and sedative use problems, but not pain experience. These findings highlight a vulnerable population of polysubstance users with chronic pain, and indicates the need for more comprehensive assessment and treatment of chronic pain.
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{
"pile_set_name": "PubMed Abstracts"
}
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Difference in the dynamic properties of chiral and racemic crystals of serine studied by Raman spectroscopy at 3-295 K.
Single-crystal polarized Raman spectra (60-4000 cm(-1) at 3 < or = T < or = 295 K) were measured for chiral L- and racemic DL-serine, alpha-amino-beta-hydroxypropionic acid, (NH3)+CH(CH2OH)(COO)-. The Raman spectra of dl-serine do not show any striking changes with temperature or on storage. In contrast to that, the dynamical properties of L-serine change at about 140 K. These changes can be interpreted as the reorientation of the side chain -CH2OH fragments of the zwitterions with respect to the backbone C-C bonds, resulting in the positional disorder of the O-H...O intermolecular H-bonds. The redistribution in the intensities of the Raman spectra of the crystals of L-serine stored for a long time (about a year) indicates the changes in the orientation of the molecular fragments in the direction normal to the axes of the head-to-tail chains. The difference in the thermodynamic functions of L- and DL-serine reported previously [Drebushchak, V. A.; Kovalevskaya, Yu. A.; Paukov, I. E.; Boldyreva, E. V. J. Therm. Anal. Calorim. 2007, 89 (2), 649-654] is explained by the difference in the spectra of external vibrations of the crystals.
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{
"pile_set_name": "PubMed Abstracts"
}
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BAY 11-7082, a nuclear factor-κB inhibitor, reduces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model.
Despite development of therapeutic modalities, myocardial ischemia-reperfusion (I/R) injury remains an important cause of cardiac dysfunction. Multiple strategies exist experimentally, but few are clinically available. Nuclear factor kappa-B (NF-κB) is a key transcription factor in the inflammatory response and is implicated in I/R injury. We hypothesized that the NFκB inhibitor BAY 11-7082 (BAY) would decrease the extent of injury after myocardial I/R. Hypoxia-reoxygenation (H/R) was induced in rat neonatal cardiomyocytes with or without BAY pretreatment. NF-κB activation, vascular cell adhesion molecule (VCAM)-1, and monocyte chemoattractant protein (MCP)-1 were assayed by immunocytochemistry, Western blot or reverse transcriptase-polymerase chain reaction (RT-PCR). Sprague-Dawley rats (n = 7) were administered BAY (130 µg/kg) and I/R was induced by ligation of the left anterior descending artery (LAD) for 30 minutes followed by reperfusion. Infarct size was analyzed after 24 hours. At 2 weeks, echocardiography was performed to evaluate ventricular function and hearts were analyzed for fibrosis and apoptosis. BAY treatment inhibited NF-κB p65 activation, as well as VCAM-1 and MCP-1 expression induced by H/R in cardiomyocytes. Compared with control rats, BAY pretreated rats showed reduced infarct size. Echocardiograms demonstrated preserved systolic function as a fractional shortening in the BAY+I/R group (P < 0.05). Fibrosis was reduced in the BAY+I/R group (P < 0.05) and apoptosis was also reduced in the BAY+I/R group (P < 0.05).In the rat myocardial I/R injury model, BAY significantly reduced the infarct size, and preserved myocardial function. These data demonstrate that a currently available and well-tolerated inhibitor of NF-κB can decrease the risk of myocardial injury associated with I/R.
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{
"pile_set_name": "PubMed Abstracts"
}
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MERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients.
The MER receptor tyrosine kinase (MERTK) gene is critical for the efficient clearance of apoptotic cells and has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the genetic polymorphisms in MERTK to evaluate it as a potential candidate gene for a host genetic study of SLE and clinical manifestations in patients with SLE. By resequencing the coding and flanking regions of the MERTK gene in 24 unrelated Koreans, 37 polymorphisms were identified. Based on gene position, minor allele frequency and inter-single-nucleotide polymorphism (SNP) linkage disequilibrium, six of these polymorphisms were selected for subsequent genotyping and association analysis with the risk of SLE and haematological disorders in 350 Korean SLE patients and 330 controls. Although no significant associations with the risk of SLE were found, logistic regression analyses revealed that variants +465C > G (P = 0.05) and +130215insdelT (P = 0.0005) were significantly associated with decreased risk of leucopenia in SLE patients. Further, +465C > G, +95616G > A, +123157A > G and the haplotype ht1 also showed significant associations (P = 0.006-0.05) with a decreased risk of lymphopenia in SLE patients. Our findings suggest that polymorphisms in MERTK might be one of the genetic risk factors for presenting leucopenia and lymphopenia in SLE patients.
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{
"pile_set_name": "PubMed Abstracts"
}
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Neurobiological substrates of antisocial and borderline personality disorder: preliminary results of a functional fMRI study.
Neuropsychological and imaging studies of patients with antisocial (ASPD) and borderline personality disorder (BPD) are suggestive of frontal lobe dysfunction in these individuals. In normal subjects functional brain imaging has been used to investigate the neuroanatomy of impulse control. There are no such imaging studies in personality-disordered populations. This study aimed to investigate which neuronal networks are involved in response inhibition in Cluster B personality disorders and whether these are different from healthy subjects. We hypothesized that the personality-disordered sample would have attenuated orbitofrontal cortex responses during performance of a Go/NoGo task compared with healthy controls. Eight inpatients with a DSM-IV diagnosis of borderline or antisocial personality disorder and eight healthy controls were scanned using fMRI while performing a Go/NoGo task. Impulsivity was assessed using the Barratt Impulsivity Scale (BIS) and the Impulsiveness-Venturesomeness-Empathy (IVE) inventory. In the control group the main focus of activation during response inhibition was in the prefrontal cortex, specifically the right dorsolateral and the left orbitofrontal cortex. Active regions in the patient group showed a more bilateral and extended pattern of activation across the medial, superior and inferior frontal gyri extending to the anterior cingulate. fMRI is a useful tool to detect brain activation during response inhibition. ASPD and BPD patients activate different neural networks to successfully inhibit pre-potent responses.
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{
"pile_set_name": "PubMed Abstracts"
}
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The role of miR-17-92 cluster in the expression of tumor suppressor genes in unrestricted somatic stem cells.
The miR-17-92 cluster consisted of seven miRNAs (mir-17-5p, -17-3p, -18a, -19a, -20a, -19b-1, and -92a-1). Previous studies have shown this cluster has been over-expressed in several cancers. The aim of this study was to evaluate the over-expression impacts of miR-17-92 on stem cells. In the current work, the effect of miR-17-92 cluster which was cloned in Lentiviral vector has been investigated on unrestricted somatic stem cells (USSCs). Tumor suppressor genes (p53, p15, RBL1, SMAD2, SMAD4, and MAPK-1) expression, especially p53, was considerably reduced. These data show the potential of miR-17-92 for oncogenesis regulation in stem cells. In conclusion, the role of miR-17-92 in USSCs may provide a better understanding of its function in tumorigenesis and for the possible use in cell therapy of the anti-mir-17-92 cluster.
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{
"pile_set_name": "PubMed Abstracts"
}
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Role of climate in the spread of shiga toxin-producing Escherichia coli infection among children.
Haemolytic-uraemic syndrome (HUS) is a rare disease mainly affecting children that develops as a complication of shiga toxin-producing Escherichia coli (STEC) infection. It is characterised by acute kidney injury, platelet consumption and mechanical destruction of red blood cells (haemolysis). In order to test the working hypothesis that the spread of the infection is influenced by specific climatic conditions, we analysed all of the identified cases of infection occurring between June 2010 and December 2013 in four provinces of Lombardy, Italy (Milano, Monza Brianza, Varese and Brescia), in which a STEC surveillance system has been developed as part of a preventive programme. In the selected provinces, we recorded in few days a great number of cases and clusters which are unrelated for spatially distant or for the disease are caused by different STEC serotypes. In order to investigate a common factor that favoured the onset of infection, we have analysed in detail the weather conditions of the areas. The daily series of temperature, rain and relative humidity were studied to show the common climate peculiarities whilst the correlation coefficient and the principal component analysis (PCA) were used to point out the meteorological variable, maximum temperature, as the principal climate element in the onset of the infection. The use of distributed lag non-linear models (DLNM) and the climate indices characterising heat waves (HWs) has allowed to identify the weather conditions associated with STEC infection. The study highlighted a close temporal correlation between STEC infection in children and the number, duration and frequency of heat waves. In particular, if the maximum temperature is greater than 90th percentile, days classified as very hot, for 3 or more consecutive days, the risk of infection is increasing.
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{
"pile_set_name": "PubMed Abstracts"
}
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A long-term study of doxazosin in the treatment of mild or moderate essential hypertension in general medical practice.
This study assessed the long-term (54 weeks) antihypertensive efficacy and safety of doxazosin in the treatment of mild or moderate essential hypertension, defined as sitting and standing diastolic blood pressure of 95 to 114 mm Hg. Of the 153 patients who successfully completed an initial 14-week trial, 61 continued uninterrupted into a 40-week extension study. Optimal antihypertensive efficacy was achieved by week 12 and maintained in all patients for the duration of 1 year. The final mean sitting blood pressure was 148/84 mm Hg and was reduced from a mean baseline level of 173/102 mm Hg. Occasional decreases in heart rate were observed, but these were not considered to be clinically relevant (1 to 3 beats/min). The mean final dose of doxazosin for patients evaluable for efficacy was 2.4 mg/day; 91.7% of patients were taking less than or equal to 4 mg/day. No increase in daily maintenance dose was observed from the initial phase to the long-term extension study. After 1 year of treatment, 93.3% of patients were considered a therapeutic success (sitting diastolic blood pressure greater than or equal to 10 mm Hg reduction from baseline or less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction). In no patients was there a worsening in the severity category of the hypertension. Total serum cholesterol concentrations were reduced significantly (6.6% p = 0.03) at the end of week 14. Reductions in total serum cholesterol levels persisted throughout the extension study, with a final reduction of 5.4%.(ABSTRACT TRUNCATED AT 250 WORDS)
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{
"pile_set_name": "PubMed Abstracts"
}
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Nondestructive optical measurements of a single electron spin in a quantum dot.
Kerr rotation measurements on a single electron spin confined in a charge-tunable semiconductor quantum dot demonstrate a means to directly probe the spin off-resonance, thus minimally disturbing the system. Energy-resolved magneto-optical spectra reveal information about the optically oriented spin polarization and the transverse spin lifetime of the electron as a function of the charging of the dot. These results represent progress toward the manipulation and coupling of single spins and photons for quantum information processing.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Uncertain if physicians' shift work causes patient harm].
The role of physicians' shift work in adverse events causing patient harm is not clear. However, extended shifts reduce psychomotor performance and cognition in daytime after a 24-hour shift. The incidence and preventability of adverse events in Denmark are comparable to other Western countries, despite the fact that Danish physicians do not work extended hours. The role of physicians' shift work in adverse events causing patient harm remains controversial and further research is needed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Reverse perfusion-metabolism mismatch predicts good prognosis in patients undergoing cardiac resynchronization therapy: a pilot study.
Cardiac resynchronization therapy (CRT) improves glucose metabolism in the septum of patients with heart failure, so in the present study the predictive value of combined fluorodeoxyglucose (FDG)-positron emission tomography (PET) and metoxy-isobutyl isonitrile (MIBI)-single photon emission computed tomography (SPECT) for the prognosis of patients undergoing CRT was investigated. Fourteen patients (70.3+/-8.2 years) who underwent FDG-PET and MIBI-SPECT before implantation of a biventricular pacemaker were enrolled. The total number of matches, mismatches, reverse mismatches, summed difference score (SDS: sum total of FDG - MIBI scores) and SDS per segment (%SDS) in each of 5 areas of myocardium (septum, anterior, lateral, inferior area, apex) was calculated and compared between the survival groups (all survival: survival group; survival without ischemic heart disease (IHD): non-IHD survival group) and non-survival group. Both the number of reverse mismatch segments and the %SDS in the septum in the non-IHD survival group were significantly greater than in the non-survival group (3.2+/-1.6 vs 0.5+/-0.6, p<0.05; 0.62+/-0.61 vs -0.11+/-0.19, p<0.05). The receiver-operating characteristics curves for prognosis showed that the area under the curve for the number of reverse mismatch segments in the septum (0.93; confidence interval 0.61-0.98) was significantly greater. A reverse mismatch pattern in the septum can predict a good prognosis for patients treated with CRT.
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{
"pile_set_name": "PubMed Abstracts"
}
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Subtrochanteric fractures of the femur.
A consecutive series of 103 patients with a subtrochanteric fracture were prospectively studied. Ten patients were treated non-operatively, whilst the other 93 had operative treatment. The overall fixation failure rate was 12 per cent with a re-operation rate of 6 per cent by 1 year. There were six (8 per cent) failures of fixation for the 74 fractures treated with the sliding hip screw. No method of fracture classification was demonstrated to be of value in predicting either the choice of treatment or the risk of fracture healing complications. Either intramedullary nailing or extramedullary fixation with a dynamic hip screw appear to give the best results for subtrochanteric fractures.
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{
"pile_set_name": "PubMed Abstracts"
}
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Investigation of excipient and processing on solid phase transformation and dissolution of ciprofloxacin.
Ciprofloxacin, a very slightly soluble antibiotics, is known to exist as both anhydrous and hydrous forms. This study was carried out to investigate the solid phase transformation of ciprofloxacin during conventional formulation processing that impacts the performance of solid dosage forms. In addition, alternative processing and formulation options were also evaluated to circumvent phase transformation. Anhydrate and hydrate of ciprofloxacin were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and powder dissolution. As expected, the anhydrate exhibited significantly higher dissolution rate than the hydrate. However, it rapidly converted to the hydrate upon exposure to aqueous medium. Interestingly, premixing the anhydrate with HPMC in the presence of water or ethanol was found to inhibit the processing-induced phase transition. Further studies demonstrated that wet granulation could be an option for preparing tablets with high loading of ciprofloxacin anhydrate through proper selection of excipients and control of processing conditions. Dissolution study of ciprofloxacin in HPMC based extended release matrix tablets indicated different dissolution rates between tablets containing the anhydrate and hydrate, suggesting transformation to the hydrate was significantly inhibited by HPMC in the gel layer of the hydrated tablets.
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{
"pile_set_name": "PubMed Abstracts"
}
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Mibefradil, a T-type Ca2+ channel blocker, protects against mesenteric ischemia-reperfusion-induced oxidative injury and histologic alterations in intestinal mucosa in rats.
The purpose of the present study was to investigate whether mibefradil can reduce oxidative stress and histologic damage in the rat small bowel subjected to mesenteric ischemia and reperfusion injury. Thirty Sprague-Dawley rats weighing between 210 and 220 g were divided into three groups, each containing 10 rats: group 1, sham operation; group 2, untreated ischemia-reperfusion; and group 3, ischemia-reperfusion plus mibefradil treatment group. Intestinal ischemia for 45 min and reperfusion for 60 min were applied. Ileal specimens were obtained to determine the tissue levels of MDA, CAT, SOD, and GSH-Px and histologic changes. In group 2, MDA values were significantly increased compared to those in groups 1 and 3. In addition, SOD, CAT, and GSH-Px values decreased significantly in group 2 compared to groups 1 and 3. The intestinal injury score increased significantly in group 2 and 3 rats compared to group 1 rats. However, this increase was reduced in group 3 rats compared to group 2. Histopathologically, the rats in group 1 had essentially normal testicular architecture. In group 2 rats, the lesions varied between grade 3 and grade 5. In contrast, most of the specimens in the mibefradil-treated group 3 showed grade 1 injury. Mibefradil plays a role in attenuating reperfusion injury of the small intestine by depressing free radical production and mucosal injury score and regulating postischemic intestinal perfusion while restoring intestinal microcirculatory blood flow and encountered histologic injury.
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{
"pile_set_name": "PubMed Abstracts"
}
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Negative synergism of rainfall patterns and predators affects frog egg survival.
1. The importance of rainfall is recognized in arid habitats, but has rarely been explored in ecosystems not viewed as rainfall limited. In addition, most attempts to study how rainfall affects organismal survival have focused on long-term rainfall metrics (e.g. monthly or seasonal patterns) instead of short-term measures. For organisms that are short lived or are sensitive to desiccation, short-term patterns of rainfall may provide insight to understanding what determines survival in particular habitats. 2. We monitored daily rainfall and survival of arboreal eggs of the treefrog Dendropsophus ebraccatus at two ponds during the rainy season in central Panama. Desiccation and predation were the primary sources of egg mortality and their effects were not independent. Rainfall directly reduced desiccation mortality by hydrating and thickening the jelly surrounding eggs. In addition, rainfall reduced predation on egg clutches. 3. To elucidate the mechanism by which rainfall alters predation, we exposed experimentally hydrated and dehydrated egg clutches to the two D. ebraccatus egg predators most common at our site, ants and social wasps. Ants and wasps preferentially preyed on dehydrated clutches and ants consumed dehydrated eggs three times faster than hydrated eggs. 4. Rainfall patterns are expected to change and the responses of organisms that use rainfall as a reliable cue to reproduce may prove maladaptive. If rainfall becomes more sporadic, as is predicted to happen during this century, it may have negative consequences for desiccation-sensitive organisms.
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{
"pile_set_name": "PubMed Abstracts"
}
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Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats.
Diabetes is associated with an increased risk of fracture, although type 2 diabetes is often characterized by normal bone mineral density (BMD). Enzymatic and glycation-induced non-enzymatic cross-links play important roles in the expression of bone strength. The serum vitamin B6 concentration is lower in patients with diabetes than in healthy controls. The aim our study was to see if spontaneously diabetic WBN/Kob rats in the pre- and post-onset of diabetes would serve as a suitable model for studying the pathogenesis of the susceptibility to fracture in diabetes without the reduction of bone mineral density. Seventy male WBN/Kob rats were obtained at the ages of 1 to 18 months. Seventy normal male Wistar rats were used as the non-diabetic, age-matched control. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline and deoxypyridinoline) and non-enzymatic cross-links (pentosidine) were determined in femoral bone. We also analyzed the serum concentration of vitamin B6 (pyridoxal and pyridoxamine), femoral BMD and a three-point bending test of the femur. A low level of serum vitamin B6 was associated with a decrease in enzymatic crosslinking in bone during the subclinical diabetes stage. After the onset of diabetes, there was a steady decrease in enzymatic cross-links and a steep increase in pentosidine. Furthermore, impaired bone mechanical properties in the WBN/Kob rats despite the lack of reduction in BMD coincided with impaired enzymatic cross-link formation and increases in glycation-induced pentosidine. These results indicate that the alteration of enzymatic and non-enzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes.
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{
"pile_set_name": "PubMed Abstracts"
}
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TB Alliance regimen development for multidrug-resistant tuberculosis.
The recent approval of new tuberculosis (TB) drugs raises hope for new and more effective anti-tuberculosis treatment regimens. The Global Alliance for TB Drug Development (TB Alliance) is committed to ensuring that new anti-tuberculosis drugs fulfill the needs of patients, their families and the local health services that serve the communities. Here we present highlights of the TB Alliance's pipeline of regimen development, with novel regimens for patients with drug-susceptible, multidrug-resistant and extensively drug-resistant TB. The ongoing clinical trials (STAND, NC-005, Nix-TB and LIN-CL001) are outlined and their rationale and goals presented.
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{
"pile_set_name": "PubMed Abstracts"
}
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Rational theophylline use in older asthmatics.
In the sick adult, the variability of clearance from patient to patient may be greater than 50%. A given dose of theophylline that is predicted to result in a serum concentration of 15 micrograms/ml may result in an actual range of serum concentrations from 6.6 to 33 micrograms/ml. Respiratory infections, both acute and chronic, seem to have an adverse effect on theophylline clearance. Studies in adults with acute viral upper respiratory infections, pneumonia, and chronic obstructive pulmonary disease show a significant decrease in clearance.
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{
"pile_set_name": "PubMed Abstracts"
}
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Interference of xenoestrogen o,p'-DDT on the action of endogenous estrogens at environmentally realistic concentrations.
Estrogenic effects of individual chemicals and mixtures of 17β-estradiol (E2) and o,p'-DDT were examined using pS2 and PR gene expressions in MCF-7 cells. Interactions between E2 and o,p'-DDT were evaluated by a statistical method based on factorial design. At levels close to environmentally realistic concentrations, no significant interactions between E2 and o,p'-DDT were observed, suggesting that the xenoestrogen (o,p'-DDT) could act in an additive way with the endogenous estrogen (E2). These results demonstrated the utility of this statistical method in a mixture study, and highlight the potential interference and health risk of low-level xenoestrogens, such as o,p'-DDT.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effects of the capsaicin analogue resiniferatoxin on spinal nociceptive mechanisms in the rat: behavioral, electrophysiological and in situ hybridization studies.
The effect of a single subcutaneous (s.c.) injection of the ultrapotent capsaicin analogue resiniferatoxin (RTX) on responses of adult rats to noxious thermal and mechanical stimulation was examined. The effects of RTX treatment on the nociceptive flexor reflex and activity-dependent increase in spinal excitability after conditioning C-fiber stimulation (CS) were also assessed. Finally, the expression of galanin message associated peptide (GMAP) mRNA in dorsal root ganglion (DRG) cells and the effects of the high affinity galanin receptor antagonist M35 on the flexor reflex in RTX-treated rats were evaluated. RTX, but not vehicle, produced marked thermal hypoalgesia on the hot plate test with partial recovery in about 50% of animals after about 2 weeks and no recovery in the remaining rats after 4 weeks. In all animals there was only a transient and moderate increase in paw withdrawal threshold to mechanical pressure. The flexor reflex in response to a C-fiber CS train was recorded 15-35 days after RTX or vehicle treatment. There was no difference between RTX and vehicle treated rats on baseline response, but RTX treatment lead to less wind-up during the CS and reduced hyperexcitability. This was particularly the case for rats which did not recover from RTX-induced hypoalgesia. The C-fiber mediated hyperexcitability was potentiated by the galanin receptor antagonist M35, more so in the non-recovered rats than in the partially recovered rats. The number of DRG cells expressing GMAP mRNA was significantly higher in non-recovered than in partially recovered rats. Thus, RTX produced marked and prolonged impairment of capsaicin-sensitive afferents and upregulation of the inhibitory neuropeptides GMAP and galanin in DRG neurons, which may underlie the prolonged effect of RTX.
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{
"pile_set_name": "PubMed Abstracts"
}
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Wafer-Scale and Wrinkle-Free Epitaxial Growth of Single-Orientated Multilayer Hexagonal Boron Nitride on Sapphire.
Large-scale growth of high-quality hexagonal boron nitride has been a challenge in two-dimensional-material-based electronics. Herein, we present wafer-scale and wrinkle-free epitaxial growth of multilayer hexagonal boron nitride on a sapphire substrate by using high-temperature and low-pressure chemical vapor deposition. Microscopic and spectroscopic investigations and theoretical calculations reveal that synthesized hexagonal boron nitride has a single rotational orientation with AA' stacking order. A facile method for transferring hexagonal boron nitride onto other target substrates was developed, which provides the opportunity for using hexagonal boron nitride as a substrate in practical electronic circuits. A graphene field effect transistor fabricated on our hexagonal boron nitride sheets shows clear quantum oscillation and highly improved carrier mobility because the ultraflatness of the hexagonal boron nitride surface can reduce the substrate-induced degradation of the carrier mobility of two-dimensional materials.
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{
"pile_set_name": "PubMed Abstracts"
}
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Small-molecule fluorophores and fluorescent probes for bioimaging.
Fluorescent compounds based on synthetic small molecules are powerful tools to visualize biological events in living cells and organisms. Ever since the discovery of organic fluorescent compounds in the late nineteenth century, efforts have been made to "see" the behaviors of specific biomolecules in living systems by using these dyes as labels. Also, following the development of fluorescent Ca(2+) indicators in the 1980s, many fluorescent probes or biosensors, which are defined as molecules that show a change in fluorescence properties in the presence of their target molecule, have been reported and applied in biological research. Today, a variety of probes are available that target metal ions, pH, enzyme activities, and signaling molecules. In this review, we first consider the history of organic fluorescent molecules and discuss their utility for labeling biomolecules and staining cells. Then, we review recent progress in small-molecule fluorescent probes for metal ions and reactive oxygen species, focusing on representative work in each category. Finally, we briefly discuss attempts to create novel kinds of probes, including hybrids of small molecules and genetically encoded proteins, with the potential to overcome some of the limitations of current probes.
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{
"pile_set_name": "PubMed Abstracts"
}
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The tragedy of Tauccamarca: a human rights perspective on the pesticide poisoning deaths of 4 children in the Peruvian Andes.
The pesticide poisoning deaths of 24 children in an isolated Peruvian village make a compelling case that corporate accountability for pesticide poisonings in the developing south should be examined from a human rights perspective. Highly toxic pesticides cannot be used safely under prevailing socioeconomic conditions. The industry asserts that the deaths of these children were accidental, blaming misuse. Tragedies such as these poisonings are not accidents, but foreseeable, and therefore preventable. Sales of highly toxic pesticides that cause repeated and predictable poisonings violate the fundamental human rights to life, health, and security of person. The Tauccamarca tragedy is a clear example of the urgency of applying a precautionary, human rights approach to pesticide issues in the developing south.
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{
"pile_set_name": "PubMed Abstracts"
}
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Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage.
Common sage (Salvia officinalis L., Lamiaceae) is an aromatic and medicinal plant well known for its antioxidant properties. Some in vivo studies have shown the biological antioxidant effects of sage. However, the intracellular antioxidant mechanisms of action are still poorly understood. In this study, we evaluated the cytoprotective effects of two sage extracts (a water and a methanolic extract) against tert-butyl hydroperoxide (t-BHP)-induced toxicity in HepG2 cells. The most abundant phenolic compounds present in the extracts were rosmarinic acid and luteolin-7-glucoside. Both extracts, when co-incubated with the toxicant, protected significantly HepG2 cells against cell death. The methanolic extract, with a higher content of phenolic compounds than the water extract, conferred better protection in this in vitro model of oxidative stress with liver cells. Both extracts, tested in a concentration that protects 80% against cell death (IC(80)), significantly prevented t-BHP-induced lipid peroxidation and GSH depletion, but not DNA damage assessed by the comet assay. The ability of sage extracts to reduce t-BHP-induced GSH depletion by 62% was probably the most relevant contributor to the observed cytoprotection. A good correlation between the above cellular effects of sage and the effects of their main phenolic compounds was found. When incubated alone for 5h, sage extracts induced an increase in basal GSH levels of HepG2 cells, which indicates an improvement of the antioxidant potential of the cells. Compounds present in sage extracts other than phenolics may also contribute to this latter effect. Based in these results, it would be of interest to investigate whether sage has protective effects in suitable in vivo models of liver diseases, where it is known that oxidative stress is involved.
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{
"pile_set_name": "PubMed Abstracts"
}
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[The initial stage of disease].
The many-year experience of comparing the clinical picture of human disease with its pathological picture indicates that man begins to be aware of the pathological process typical of a given disease in many cases after some, not infrequently long period after its initiation and against the background of already developed morphological changes of organs and tissues. This difference in the time between morphologically initial and clinically early manifestation of disease may be explained by the existence in the body of a strong system of compensatory-adaptive reactions directed to the preservation of homeostasis. When these reactions are disturbed, homeostasis is broken and the disease becomes clinically manifest. A disease may be diagnosed early only when it is recognized in this "latent" period. It is in this period that the damage ("break" according to Pavlov) of the regulating systems frequently far from the target organ occurs. Thus, hypertension arises when the centers regulating the constant level of arterial pressure are damaged, while the entire pathology of hypertension is the effect of this damage. Mammary cancer is the effect of dyshormonal damages occurring in endocrine glands. Many diseases of the stomach are associated with primary involvement of various parts of the central and vegetative nervous system. Damages of the immunocompetent system and disturbances of immunological homeostasis are primary in diseases of the connective tissue with immune disorders and determine their clinical pattern and morphology. The results of morphological investigations performed by modern methods indicate that there are no functional diseases and that each disease has its material substrate determined at all levels of organization beginning from molecular and subcellular and ending with systemic. The material substrate of disease is formed from alterations at the site of the initial lesion and alterations in the target organ in which this lesion is manifested externally. The task of the current medicine is to recognize the morphological and clinical essence of the initial period of disease as an entity which is very important for early diagnosis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Influence of tertiary structure domain properties on the functionality of apolipoprotein A-I.
The tertiary structure of apolipoprotein (apo) A-I and the contributions of structural domains to the properties of the protein molecule are not well defined. We used a series of engineered human and mouse apoA-I molecules in a range of physical-biochemical measurements to address this issue. Circular dichroism measurements of alpha-helix thermal unfolding and fluorescence spectroscopy measurements of 8-anilino-1-napthalenesulfonic acid binding indicate that removal of the C-terminal 54 amino acid residues from human and mouse apoA-I has similar effects; the molecules are only slightly destabilized, and there is a decrease in hydrophobic surface exposure. These results are consistent with both human and mouse apoA-I adopting a two-domain tertiary structure, comprising an N-terminal antiparallel helix bundle domain and a separate less ordered C-terminal domain. Mouse apoA-I is significantly less resistant than human apoA-I to thermal and chemical denaturation; the midpoint of thermal unfolding of mouse apoA-I at 45 degrees C is 15 degrees C lower and the midpoint of guanidine hydrochloride denaturation (D1/2) occurs at 0.5 M as compared to 1.0 M for human apoA-I. These differences reflect the overall greater stability of the helix bundle formed by residues 1-189 in human apoA-I. Measurements of the heats of binding to egg phosphatidylcholine (PC) small unilamellar vesicles and the kinetics of solubilization of dimyristoyl PC multilamellar vesicles indicate that the more stable human helix bundle interacts poorly with lipids as compared to the equivalent mouse N-terminal domain. The C-terminal domain of human apoA-I is much more hydrophobic than that of mouse apoA-I; in the lipid-free state the human C-terminal domain (residues 190-243) is partially alpha-helical and undergoes cooperative unfolding (D1/2 = 0.3 M) whereas the isolated mouse C-terminal domain (residues 187-240) is disordered in dilute solution. The human C-terminal domain binds to lipid surfaces much more avidly than the equivalent mouse domain. Human and mouse apoA-I have very different tertiary structure domain contributions for achieving functionality. It is clear that the stability of the N-terminal helix bundle, and the hydrophobicity and alpha-helix content of the C-terminal domain, are critical factors in determining the overall properties of the apoA-I molecule.
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{
"pile_set_name": "PubMed Abstracts"
}
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Early detection of damage to nerves in leprosy.
Methods of examining and diagnosing damage to nerves commonly involved in leprosy are described. The equipment used is inexpensive, gives reliable and repeatable results and is useful in making objective assessments in terms of function in everyday living.
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{
"pile_set_name": "PubMed Abstracts"
}
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Methodologies for the care, maintenance, and breeding of tropical poison frogs.
The Biodiversity Laboratories at Saint Joseph's University house more than 100 exotic and endangered animal species-including insects, fish, amphibians, and reptiles. Research in the laboratories is devoted, primarily, to understanding the genetic and ecological bases of animal behavior. In addition, a common theme of the work is the development of techniques for the successful care of exotic animals within a laboratory setting. Such techniques may be critical to studies aimed at understanding the life histories of endangered species and saving them from extinction. Current projects to study the biology of tropical poison frogs have methodologies to improve captive care, maintenance, and breeding. In this article, I present these methodologies and their impact on the welfare of captive poison frogs.
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{
"pile_set_name": "PubMed Abstracts"
}
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Evaluation of a protease assay based on a natural protein for heavy metals inhibition of activated sludge.
An enzymatic assay employing 2,4,6-trinitrobenzenesulfonic acid to follow the hydrolysis reaction of peptide bonds of a natural protein by activated sludge was evaluated for assessing the inhibition caused by heavy metals on biological treatment processes. The individual and joint effects up to 20 mg/l of Cu(II) and Zn(II) on activated sludge of different ages (6, 10 and 14 days) between a pH range from 6 to 7 was investigated by means of a 2(4) factorial experimental design. From statistical results, it has been concluded that not only the four main effects of these variables have an important influence on protease activity of activated sludge but also some interactions among them. Experimental data showed that Zn(II) was less inhibitory towards proteases than Cu(II) and that their joint effects acted neither synergistically or antagonistically. Sludge age was the variable that more strongly affected the protease activity of activated sludge.
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{
"pile_set_name": "PubMed Abstracts"
}
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Two cases with severe lethal course of Costello syndrome associated with HRAS p.G12C and p.G12D.
Costello syndrome (CS) is a rare congenital disorder characterized by severe failure to thrive, coarse facial appearance, cardiac and skin abnormalities, developmental delay, intellectual disability, and predisposition to malignancies. Heterozygous de novo germline mutations in the proto-oncogene HRAS cause CS. About 80% of patients share the same mutation resulting in the amino acid change p.G12S and present a relatively homogeneous phenotype. Other less common lesions in HRAS can induce a milder phenotype on the one hand and a more severe phenotype on the other broadening the spectrum of clinical manifestations in CS-affected individuals. We report two new patients with the HRAS p.G12C and p.G12D substitutions and a severe neonatal manifestation causing death at the age of three months and 13 days, respectively. Both patients had particularly severe heart involvement with hypertrophic cardiomyopathy and tachyarrhythmia, generalized edema, and respiratory distress. In one case, hypertrophic cardiomyopathy was already noted prenatally. These cases together with other individuals harboring the rare HRAS mutations p.G12C, p.G12V, p.G12D, and p.G12E provide further evidence for a genotype-phenotype correlation that could be of importance for counseling and medical management.
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{
"pile_set_name": "PubMed Abstracts"
}
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The impact of three-dimensional tumor volume on cancer-specific survival for patients with pT1 clear-cell renal cell carcinoma.
To evaluate the impact of three-dimensional tumor volume on cancer-specific survival for patients with pT1 clear-cell renal cell carcinoma (ccRCC). We reviewed a prospectively maintained database of 917 patients who underwent radical nephrectomy or nephron-sparing surgery for unilateral, pT1 ccRCC, including 654 pT1a and 263 pT1b patients, between April 1997 and December 2010. Three-dimensional tumor volume was measured using specialized volumetric software on cross-sectional computed tomography images of a preoperative venous phase. Kaplan-Meier and Cox regression analyses were carried out. The median age was 54 years with a follow-up of 60.8 months. Median tumor size and volume were 3.2 cm and 17.4 cm(3), respectively. Of 917 patients, 54 (5.9 %) had died, including 32 patients with ccRCC (9 patients in pT1a and 23 patients in pT1b). On multivariate analysis, tumor size >3.2 cm and tumor volume >17.4 cm(3) were associated with cancer-specific death in pT1 ccRCC patients. When stratified by pT1a/pT1b status and analyzed on median splits, tumor size >2.5 cm was associated with cancer-specific death but not tumor volume >9.5 cm(3) in pT1a patients. However, in pT1b patients, tumor volume >62.1 cm(3) (P = 0.036, HR 2.91, 95 % CI 1.02-7.77) was highly associated with cancer-specific death but not tumor size >5.0 cm (P = 0.159, HR 1.91, 95 % CI 0.78-4.70). In addition to tumor size, tumor volume is associated with cancer-specific death in pT1 ccRCC patients, particularly in pT1b ccRCC but not in pT1a ccRCC.
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{
"pile_set_name": "PubMed Abstracts"
}
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An operative repair of acromioclavicular separation.
Sixteen patients underwent an open reduction for complete acromioclavicular separation with a loop of woven Dacron arterial graft. This technique of internal fixation permits an early range of shoulder motion and eliminates the need for a second procedure to remove wire or pins. Experience in vascular reconstruction suggests that fibroblastic ingrowth might occur to substitute for the disrupted ligament complex. All but two of the 16 patients showed excellent results: full restoration of shoulder function, satisfactory cosmesis, and complete relief of pain. One required reoperation for an improperly placed loop, and one had definite over-reduction of the clavicle on the acromion but remained asymptomatic. In several, X-rays showed evidence of pressure resorption and periosteal new-bone formation along the clavicle at the site of the loop, but no loss of fixation. This approach was used successfully in acute trauma and as late as one year following injury.
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{
"pile_set_name": "PubMed Abstracts"
}
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Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit.
Previous physiological studies indicate that the olfactory region serves as a major pathway for cerebrospinal fluid (CSF) drainage into the lymphatic system. The present study was undertaken to determine the ultrastructural characteristics of this egress route. New Zealand White rabbits received a single bolus injection of the tracer ferritin (MW 400,000) into both lateral ventricles in such a manner as not to raise the intraventricular pressure above the normal level. The animals were sacrificed via intracardiac perfusion of fixative between less than 12 minutes and 4 hours following injection. The cribriform region was removed en bloc, decalcified, sectioned coronally, and prepared for light and electron microscopic examination. The arachnoid, dura, and periosteum surrounding the fila olfactoria passing through the cribriform plate merge together and form the perineurium, which consists of multiple layers of loosely overlapping cells with widely separated junctions and few vesicles. The perineurium surrounding the olfactory filaments at the superficial submucosal level is only one cell thick. The subarachnoid space freely communicates with the perineural space surrounding each filament. No morphological barrier between the perineural space and the loose submucosal connective tissue was identified. Whether or not the perineurium was multi- or single-layered, ferritin was noted in abundance between the loosely overlapping perineural cells and in the submucosal connective tissue. The distribution of ferritin at 12 minutes was similar to that at 4 hours; however, the quantity of ferritin was increased at 4 hours. These results indicate that no significant barrier to CSF drainage is present at the rabbit cribriform region and that CSF reaches the submucosal region rapidly via open pathways.
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{
"pile_set_name": "PubMed Abstracts"
}
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Difficult clinical challenges in haemophilia: international experiential perspectives.
Haemostasis management in people with haemophilia can present a range of challenges to physicians. Specific challenges that may be encountered relate to regimens for immune tolerance induction, use of central venous access devices, optimizing care of paediatric patients with inhibitors and improving outcomes in acquired haemophilia. There are also challenges related to performing surgery, and the establishment of specialist centres is valuable with regard to this. These challenges are considered in the light of available data, and with perspectives gained from the experience of experts treating patients around the world. Sharing this knowledge may help to improve patient management.
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{
"pile_set_name": "PubMed Abstracts"
}
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[The role of host cells in the genetic regulation of plasmid transfer in Escherichia coli].
The role of serologically typed and nontyped E. coli cells in the expression of genetic regulation systems activity for repressed plasmids transfer (types fin OP, fin U, fin V) was studied. It is shown that the inhibiting action of such plasmids on the tra-genes functions of derepressed plasmids is more expressed in the cells of serologically nontyped E. coli (K-12 strains) than in the cells of serologically typed ones (serogroups O106, O128, O147).
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{
"pile_set_name": "PubMed Abstracts"
}
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Intrauterine devices: present and future.
Although the mortality associated with the use of intrauterine contraception is low, its morbidity is probably higher than that associated with oral contraception. Much anxiety has been generated and whole programs prejudiced by lack of attention to detail during counseling, the fitting of intrauterine devices and follow-up. This paper draws attention to the shared etiology of many of the important adverse effects of the method, the fact that several become increasingly rare with increasing age of the user, and other factors that can assist in choosing the right device for the right woman. Likely future trends are also predicted.
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{
"pile_set_name": "PubMed Abstracts"
}
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K-CL co-transport plays an important role in normal and beta thalassemic erythropoiesis.
Cell volume changes are hallmarks of both cell maturation and apoptosis, and are paralleled by modulation of membrane ion transport pathways. We evaluated the possible role of K-Cl co-transport (KCC) in both normal and beta-thalassemic erythropoiesis in vitro. We studied the effects of the KCC inhibitor, DIOA, on cell proliferation and differentiation, on expression of KCC mRNA and polypeptides, and on expression of cell cycle and apoptosis genes in in vitro liquid-cultures of CD34(+) cells from normal and beta-thalassemic subjects. beta-thalassemic erythroid precursors showed increased abundance of KCC1-3 mRNA and of KCC polypeptides in late erythropoiesis. DIOA markedly modified the composition of normal erythroid precursors, promoting differentiation and arrest at the polychromatic erythroblast stage and resulting in a precursor distribution profile similar to that of untreated beta-thalassemic cells. DIOA up-regulated cyclin-D mRNA levels in late erythropoiesis in both cell models, paralleling changes in the percentage of S-phase-cells. Caspase-3 activity in late erythropoiesis declined to similar degrees in both cell models. DIOA did not modify caspase-3 or -8 mRNA levels. Ineffective erythropoiesis of in vitro cultured beta-thalassemic cells is likely related to impaired cell maturation. KCC activity appears to contribute to erythroid cell growth during late erythropoiesis.
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{
"pile_set_name": "PubMed Abstracts"
}
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High-resolution mapping of the optical near-field components at a triangular nano-aperture.
A triangular nano-aperture in an aluminum film was used as a probe in a scanning near-field optical microscope (SNOM) to image single fluorescent molecules with an optical resolution down to 30 nm. The differently oriented molecules were employed as point detectors to map the vectorial components of the electric field distribution at the illuminated triangular aperture. The good agreement of the experimental results with numerical simulations enabled us to determine both the field map at a triangular aperture and the exact orientations of the probing molecules.
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{
"pile_set_name": "PubMed Abstracts"
}
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