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A new class of irreversible muscarinic antagonists: beta-haloethylamine furoates.
|
The synthesis of a class of ultra-long acting muscarinic antagonists is described. Furthermore, it is noted that the stability of the, in situ, aziridinium ion is sufficiently great so that these agents can be used to study the effect of temperature upon the conformation of the muscarinic cholinoceptor. The inactivation kinetics of these receptors as well as the dissociation constants, Kd, for all probes are presented.
| 10,393
|
Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man.
|
Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg-1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a "simplex" non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (W1) attributed to individual data points. The plasma half-life of paracetamol varied by up to a seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors.
| 10,395
|
Liquid chromatography in pharmaceutical analysis V: determination of an isoniazid-pyridoxine hydrochloride mixture.
|
Operating parameters are described for the qualitative and quantitative analysis of an isoniazid-pyridoxine hydrochloride mixture by high-pressure liquid chromatography. Each compound was chromatographed on an octadecyl column, using absolute methanol-water (60:40) (pH 2.5) containing 0.01 M dioctyl sodium sulfosuccinate. The flow rate was 2.0 ml/min (2500 psig), and the peaks were detected at 293 nm. The analysis was accomplished using ion-pair formation for effecting chromatographic separation. The time required for separation of the drug mixture is approximately 12 min with an accuracy of 1.17-0.30%.
| 10,409
|
Loperamide binding to opiate receptor sites of brain and myenteric plexus.
|
Loperamide, a new antidiarrheal agent, was tested to determine whether its biological activity involves binding to opiate receptor sites. Loperamide and morphine competitively inhibited 3H-naloxone binding to homogenates a guinea-pig brain and myenteric plexus. The Kp values obtain in the presence of Na+ were: morphine, 9.60-10(-9) M (brain), 1.66-10(-7) M (myenteric plexus); loperamide, 7.20-10(-9) M (brain), 1.33-10(-7) M (myenteric plexus); naloxone, 4.78-10(-10) M (brain), 1.27-10(-9) M (myenteric plexus. In the absence of Na+, binding a loperamide and morphine to brain homogenate was enhanced while the binding of naloxone was reduced. Morphine (IC50 = 7.5-10(-8) M) and loperamide (IC50 = 6.9-10(-9) M) inhibited the electrically induced contractions of longitudinal muscle from guinea-pig ileum, and naloxone competitively antagonized these effects. The Kd value calculated for the interaction of naloxone with binding sites associated with the contracting muscle was between 0.98-10(-9) M and 1.85-10(-9) M. In the mouse hot plate test, subcutaneous administration of morphine (minimal effective dose = 6.6 mugmol/kg) and loperamide (minimal effective dose = 78 mugmol/kg) delayed the response to heat stimuli and this effect was completely blocked by prior administration of naloxone. In the anesthetixed dog, intravenous administration of morphine (100 mug/kg) and loperamide (100 mug/kg) enhanced the contractile activity of circular muscle in proximal and distal duodenum, distal ileum and proximal colon but duodenal longitudinal muscle was relaxed; these effects were completely reversed by subsequent administration of naloxone. It is concluded that loperamide binds to opiate receptor sites and possesses opiate agonist activity both in vivo and in vitro.
| 10,422
|
Exonuclease associated with bacteriophage T5-Induced DNA polymerase.
|
T-5-induced DNA polymerase has been shown to possess a 3' leads to 5'-exonucleolytic activity. The exonuclease acts on both native and denatured DNA, but the apparent rate of degradation of denatured DNA is about five times faster than that for native DNA. The enzyme appears to act only on 3'-OH ends and produces mainly 5'-dNMP's. Like polymerase activity, exonuclease activity shows a pH optimum around 8.6. Mg2+, dithiothreitol, and N-ethylmaleimide had identical effects on both the activities. Nicked DNA was almost totally protected from exonuclease action under synthetic conditions, i.e., in the presence of 4dNTP's. Denatured DNA was partly degraded in the early phase of incubation with 4dNTP's, presumably due to unhybridized tails at the 3'-OH primer ends. However, the exonuclease activity was operative in both cases under synthetic conditions, as evidenced by template-dependent conversion of [3H]dTTP to [3H]dTMP.
| 10,451
|
Structural proteins of polyoma virus: proteolytic degradation of virion proteins by exogenous and by virion-associated proteases.
|
A model has previously been proposed for the genetic relatedness of the structural proteins of polyoma virus, based upon similarities in the peptide maps of the major capsid protein VP1 with the virion proteins VP2 and VP3. Newer evidence suggests that this model is incorrect, and that protein VP1 is a product of one viral gene and that the multiple components of VP2 and VP3 are products of a second viral gene. Two-dimensional peptide maps of several preparations of polyoma purified separately from four separate infected-cell lysates has shown a variable content of VP1 peptides in proteins VP2 and VP3, with some preparations being free of detectable VP1 material in VP2 and VP3. An alternative explanation for the presence of VP1 peptides in the regions of VP2 and VP3 of some polyoma preparations involves the cleavage of proteins of polyoma virions during exposure to proteolytic enzymes in lysates of infected cells or to endogenous proteolytic activity of virions. Prolonged incubation of infected-cell lysates at 37 degrees C leads to an increase in the amount of 86,000-dalton dimer of VP1, a decrease in the relative amount of VP1, a decrease in or a loss of the lower band of VP2, and the appearance of a new major protein band of approximately 29,000 daltons. Two-dimensional peptide maps of the new 29,000-dalton protein show that it contains some VP1 peptides, indicating that this protein is derived from proteolytic cleavage of VP1. In addition, extensively purified polyoma virus contains a proteolytic activity that can be activated during disruption of the virus with 0.2 M Na2CO3-NaHCO3 (pH 10.6) in the presence of 5 X 10(-3) M dithiothreitol.
| 10,452
|
A new analgesic testing method using ultrasonic stimulation. I. Effects of narcotic and nonnarcotic analgesics.
|
A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in mice has been designed. The method had the advantage of precision, simplicity of technique, rapidity of measurement, and the fact that the stimuli is innocuous upon repeated application. The nature of the senstaions induced by ultrasonic stimulus is somewhat like that felt with a prick type of pain. Pentazocine (30, 100, 150 mg/kg i.p.) aminopyrine (15,50, 100, 150 mg/kg i.p.), phenacetin (100,150, 200, 250 mg/kg i.p.) sodium salicylate (150, 200, 250 mg/kg i.p.) and other antipyretic analgesics were active in a wide range of doses indicating that this technique is sensitive to the narcotic antagonist and to the weak analgesics as well as to the narcotic analgesics as well as to the narcotic analgesics such as morphine (2.5, 5, 10, 15 mg/kg i.p.), codeine (10, 20, 25, 30, 50 mg/kg i.p.) and pethidine (5,10, 15, 20, 25 mg/kg i.p.). The ultrasonic method is, therefore, applicable in screening procedures when attempting to evaluate the analgesic potency of a wide variety of chemical agents.
| 10,456
|
HLA antigens in arterial occlusive diseases in Japan.
|
Using a NIH standard lymphocytotoxicity test, a possible Japanese specific HLA antigen, HLA-BJW 22.2 was identified in 17 out of 48 patients with thromboangiitis obliterans (35.4 per cent), in 5 out of 15 patients with Takayasu's arteritis (33.3 per cent) and in 11 out of 113 normal controls (9.7 per cent). On the other hand, HLA-CWl was found in 4 out of 47 patients with arteriosclerosis obliterans (8.5 per cent) and in 41 out of 113 normal controls (36.3 per cent).
| 10,460
|
[Hypoxia and polytrauma].
|
The importance of polytrauma and hypoxia, resp., is discussed by the authors with regard to the mortality and the common effect of these is analysed. It was found that in the mortality of the patients suffered polytraumatism the first place (59,4%) is taken by such lesions, in which simultaneous lesion of the skull and the thorax occurs. The values of the blood gas and the acid-base balance of the patients who had suffered polytraumatism, were examined in the 12th--24th hours proceding the death. It was found that whereas--using the possibilities of the intensive therapy--the values of pH, paCO2 and BE could be kept in a part of the cases between the physiological limits--the paO2 value was under the normal value in all cases--moreover 2/3 of the values fell into the domain between 40--60 mmHg--signifying severe hypoxia. On the basis of the analysis it may be presumed that in the process leading to death of the patients who had suffered polytraumatism the anoxic hypoxy plays considerable role. This is supported also by the earlier data published by the institute, according to which the mortality in itself high--33.8%--of polytraumatism increases to 71.4%, if it is associated hypoxy. Consequently the aim of the therapy must be to exert the greatest activity in order to prevent or to combat, resp., the anoxic hypoxy.
| 10,478
|
[Classification and diagnosis of ankle injuries].
|
A new method for the classification of the injuries of the ankle is recommended by the author. The main types according to his classifixation are the following: pronation-flexion, pronation-extension, supination-extension, supination-flexion and supination-extension types. His classification is compared with Lauge-Hansen's and Weber's classification. Critical analysis of these two last classifications is given. The aim of the author's classification is to render help to the doctors for their every-days' curative work. The characteristic symptoms of the pronation and supination, resp., injuries are described. Attention is drawn to "Weber's lace"--this denomination is proposed by the author, since the first description is due to Weber. On the basis of the author's examinations described in his candidate's dissertation "syndesmolysis trigonum"--pathognostic for syndesmolysis--is dealt with. The "reclined" roentgenograms are dealt with. The so-called pronation reclined roentgenogram visualize the rupture of the deltoid ligament and the syndesmolysis in the same time. The sagittal reclined roentgenogram is dealth with separately, by means of which the "table-drawer" symptom may be produced.
| 10,479
|
Triacetylated insulin: biologic activity and resistance to degradation.
|
Tritiated N-hydroxysuccinimide acetate was prepared with specific activities up to 5 Ci/mmole and utilized to prepare tritiated triacetyl insulin. Binding of triacetyl insulin to liver plasma membranes was measured by its capacity to displace 125I-monoiodoinsulin. At low concentrations, less than 10 ng/ml triacetyl insulin appears to be as effective as native insulin in reducing the binding of 125I-monoiodoinsulin to plasma membranes. At concentrations of 20 ng/ml and higher, triacetyl insulin is significantly less effective than native insulin in displacing binding of 125I-monoiodoinsulin to plasma membranes. The properties of triacetyl insulin in this system are not ascribable to deacetylation and conversion of the substituted product to native insulin. Biologic activity of triacetylated insulin was studied in two other in vitro systmes. A comparison was made of the capacity of native beef insulin and its triacetyl derivative to stimulate glucose oxidation by epididymal fat pads. At all three concentrations tested (2, 6, and 18 ng/ml), triacetyl insulin exerted considerable activity, although its potency was significantly less than that of native insulin. Similar effects were observed when biologic activity was measured by induction of tyrosine-alpha-ketoglutarate transaminase in a cultured liver cell system where significant activity of triacetyl insulin was found at concentrations of 10(-9)-10(-7) M. In all systems tested, the activity of triacetylated insulin could not be accounted for by deacetylation and conversion to native insulin. In all systems studied, triacetyl insulin was more resistant to degradation than was monoiodoinsulin.
| 10,504
|
Effect of hydrogen ion buffers on photosynthetic oxygen evolution in the blue-green alga, Agmenellum quadruplicatum.
|
The photosynthetic oxygen evolution capacity of Agmenelium quadruplication suspended in four hydrogen ion buffers (pH 7.4, 0.05 M) and its synthetic marine growth medium was measured with an oxygen electrode. High rates of oxygen evolution were obtained in the growth medium and N-tris(hydroxymethyl)-methylglycine (Tricine) buffer. Compared to oxygen evolution in the growth medium, rates in phosphate buffer and N-tris(hydroxymethyl)-2-aminoethanesulphonic acid (TES) buffer were sometimes reduced by up to 30% and rates in tris (hydroxymethyl) amino-methane (Tris) were consistently reduced by 50%. An incubation-rinsing procedure caused inhibition of oxygen evolution in TES, phosphate, and Tris by 50 to 100%. Oxygen evolution could be restored to cells rinsed in TES or phosphate by resuspension in growth medium or in buffer plus magnesium and calcium ions. Bezoquinone-supported oxygen evolution was not affected by rinsing with any buffer tested except Tris. Ferricyanide was photoreduced at a low rate by cells rinsed in Tes but at a high rate in TES plus magnesium and calcium ions. We interpreted our results to mean that, in Agmenellum quadruplicatum, inhibition of photosynthetic oxygen evolution by Tris occurs at the level of photosystem 2 while the effects of TES and phosphate are on electron-transport occurring after the rate-limiting reaction.
| 10,506
|
Biochemical properties of the prostaglandin/thromboxane synthetase of human blood platelets and comparison with the synthetase of bovine seminal vesicles.
|
The enzyme system which synthesizes prostaglandins and thromboxanes in extracts of washed human platelets has been characterized with respect to kinetic parameters, pH and cofactor dependence, and inhibitor potencies. Arachidonate and dihomo-gamma-linolenate were shown to be mutually competitive substrates, thus providing biochemical support for the assumption that both substrates are metabolized by the same cyclooxygenase, although they are ultimately metabolized to different patterns of products. Products of the synthetase of human leucocytes qualitatively resemble those obtained with human platelets. The prostaglandin synthetase of bovine seminal vesicles was studied under similar conditions, and kinetic parameters and inhibitor potencies were compared with those of platelet extracts.
| 10,602
|
[The Göttinger minipig as a laboratory animal (author's transl)].
|
Blood pictures, serumelectrolytes, acid-base- and bloodgas-values of the arterial blood were determined from two juvenile and one adulte collectives of minipigs (Gottingen strain), which were kept under SPF-conditions. The results were compared with the corresponding values of human blood and should be regarded as base- or orienting values for further investigations.
| 10,610
|
Carbonic anhydrase inhibitor in trout plasma.
|
A manometric assay has been constructed such that carbonic anhydrase dehydration activity can be determined utilizing intact erythrocytes. It was found that unwashed whole trout blood lacks any dehydration activity quite in contrast to whole rat blood. Removal of the plasma and replacement with physiological saline results in pronounced dehydration activity with inhibition restored by replacing the saline with the original plasma. An inhibitor residing in the plasma (probably a protein but not yet fully characterized) is capable of limiting in vivo dehydration activity. The inhibitor could work at the level of the enzyme per se or by inhibiting erythrocytic HCO3 influx, or both. The lack of erythrocytic dehydration activity presumably would alter CO2 excretion patterns; possible implications are discussed.
| 10,613
|
Structural studies on des-pentapeptide (B26-30)-insulin. V. High resolution NMR studies.
|
Preliminary studies have been made of the 250 MHz nuclear magnetic resonance spectra of both insulin and DPI. Differences have been found between DPI and insulin spectra, which indicate that the splitting off of the B-chain C-terminal pentapeptide from insulin has brought about local changes in the conformation of the protein molecule in solution. It seems that these conformational changes have little effect on the biological activity of the hormone. Many studies have revealed that for insulin molecules in solution, an equilibrium exists between aggregation and dissociation, their state of aggregation bearing a close relationship to the concentration as well as pH of the insulin solution. Changes in the concentration and pH value of DPI solutions do not significantly affect the NMR spectra. But as the concentration and pH of the solution are increased, the methyl regions for valine, leucine, and isoleucine and aromatic regions of the insulin spectra are broadened. All these show that zinc-free DPI molecules probably exist as monomers in solution.
| 10,624
|
[Hydrogen ion activity in the cell].
|
Literature data and results of our experiments evidence for a heterogenous hydrogen distribution in cells. Intracellular pH should be regarded as a mean activity of hydrogen ions which is the sum of activities in different phases of a cell. Intracellular pH value does not depend on the transmembrane action potential difference, and is resistant to respiratory and metabolic disorders of acid-base equilibrium in the body. It also slightly changes with changing the electrolyte composition and pH of the medium and is not influenced by metabolic inhibitors. A low hydrogen activity in the cell has a certain functional significance. The pH stability is ensured by a number of regulatory mechanism: the buffer properties of the protoplasm itself, and the active hydrogen transport into the medium. Hydrogen released from cells is supposed to be connected with functioning of a specific respiratory chain of superficial protoplasmic membranes.
| 10,657
|
[Activity and variability of aminopeptidases and gamma-glutamyl transpeptidase of the cutaneous mucous membrane in the cow's rumen].
|
The authors studied the activity, chromatographic and electrophoretic distribution of leucylarylamidase, cystinamino peptidase, and gamma-glutamyl transpeptidase of the cytoplasmatic fraction of cow's rumen mucous membrane homogenate. The results of comparative analysis draw attention to the existence of a certain number of the molecular forms of the enzymes studied, to the activation of leucylarylamidase by Co2+, cystinamino peptidase by Co2+ and Ca2+. The possible functions of the amino peptidases and transpeptidase of glutamic acid in the metabolism of nitrogen compounds of the type of peptides, amino acids, and their amides, are discussed in the study.
| 10,665
|
[Cleavage of alpha-L-arabinofuranoside, beta-D-glucopyranoside and beta-cellobioside of 4-nitrophenol by enzymes of various fungi - a contribution to increase the selectivity of tumor therapy].
|
To carry out long-term experiments as part of a therapy concept of malignant tumours using inactive transport forms of cancerostatic substances and their specific cleavage in the acidic pH region of the tumours by application of extraneous enzymes, we require enzymes with similar catalytic and pharmacokinetic properties which differ from each other in immunological respect. In the search for such enzymes, the alpha-L-arabinofuranosidases from 12 different fungi, among them 9 basidiomycetes, were studied. The enzymes mentioned were demonstrable in all fungi. Optimum pH values ranged between 2.5 and 5.5. The Km values for the cleavage of alpha-L-arabinofuranoside were, in most cases, 0.5 to 1.8 moles-liter-1-10(-3). With regard to pH dependence, the alpha-L-arabinofuranosidases of most of the fungi investigated proved adequate for the long-term trials envisaged. 4-nitrophenyl-beta-D-glucopyranoside and -beta-cellobioside were also cleaved by enzyme preparations of all the 11 fungi investigated. The beta-D-glucopyranosidases showed a less favourable pH dependence than the alpha-L-arabinofuranosidases. The cleavage of 4-nitrophenyl-beta-cellobioside, on the contrary, showed mostly a comparatively favourable pH dependence. On the basis of the coinciding optimal pH values and the occurrence of 4-nitrophenyl-beta-D-glucopyranoside as an intermediate product in the cleavage of the corresponding cellobioside, we assume that both substrates are cleaved by beta-glucosidase. Because the occurrence of the glucoside during the cleavage of cellobioside is undesirable for the therapeutic trial, a method is proposed for selection of an appropriate cellobioside splitting enzyme basing on the present studies and the relevant literature.
| 10,689
|
[Different deoxyribonuclease-activities in bull seminal plasma (author's transl)].
|
By means of the in situ assay of deoxyribonucleases in DNA-containing polyacrylamide gels after separation by micro-disc-electrophoresis different deoxyribonucleases are detectable in bull seminal plasma. There are two groups of acid deoxyribonuclease-activities with a pH optimum at pH 5.0, one with a pH optimum at pH 7.4 and an additional one with a pH optimum at pH 8.5.
| 10,693
|
[Etiopathogenesis of necrotizing arteritis (leukocytoclastic vasculitis)].
|
The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Schönlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarcón-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Schónlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Schónlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found...
| 10,721
|
Controlled trial of fetal intensive care.
|
A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified.
| 10,731
|
[Anaphylactic shock to pentothal induction].
|
In a patient who had been anaesthetised twice with penthiobarbitone, who had contracted a localised then a generalised eczema, collapse appeared during a third anaesthetic induction, 30 minutes after the injection of penthiobarbitone which was revealed by Shelley's test to be the most positive product.
| 10,761
|
[Allergy and anesthesia: environment and psychological factors].
|
The assessment of so-called risk "carriers" is difficult from the standpoint of true allergy and consideration must be given to the following:- the psychology and environment of the patient to be anaesthesia, with regard to any warning signs. -also, though, the psychology and environment of the anaesthetist; himself alerted in the presence of a presumptive allergy. Such an attitude will lead to more rapid assessment of the true nature of the complication occurring. In most instances, acquired presumptions can only lead to widened prevention. A formal anaesthetic consultation, including a careful history, will aid in the detection of problems. It is also of significant value from a legal standpoint, at the same time ensuring application by the anaesthetist of appropriate therapy as early as possible.
| 10,766
|
[Determination of serum IgE].
|
After recalling the properties of IgE antibodies responsible for allergic reactions, the author looks at the methods of assay by the techniques of radial immunodiffusion and radio-immunology. The total serum IgE of 13 subjects who had had an anaphylactic accident during anaesthesia, were assayed according to the latter technique. Elevated values were found in patient with an atopic background. The assay of IgE could be of value in the assessment of the allergic risk in anaesthesia.
| 10,770
|
[Does anesthesia have an immunosuppressive effect?].
|
Immune depression occurs after general anaesthesia. It is related to depression of serum factors after anesthesia with ether or chloroform, or secondary to depression of antibody-producing cells after anaesthesia with halothane, nitrous oxyde or Pentothal. This immune depression augments proneness to bacterial and viral infection and to malignant disease.
| 10,775
|
[Antigenicity of drugs used in anesthesiology].
|
The authors studies the factors involved in the antigenicity of the principal medications used in anaesthetics, including general anaesthesia, local anaesthetics and muscle relaxants. Any attempt at establishing a correlation between the chemical properties of these medications and their haptenic power would seem difficult by virtue of the fact that the complications seen in clinical practice are characterised by their rarity. The latter may be explained either on the basis of a low haptenic power of the substances or by the fact of their administration which is rarely repeated after a short time interval. Finally, the difficulties of this correlation are even further increased by the fact that the haptenic power is not always due to the medication itself, but sometimes to one of its metabolites.
| 10,785
|
[Plasma level of the thiocyanate ion in sodium nitroprusside perfusion].
|
24 subjects were selected at random out of a group of 80 patients undergoing surgery under a hypotensive anaesthetic technique by means of nitroprusside perfusion; the variation of one of the metabolites, the thiocyanide ion, were assayed. Hypotension was of 30 to 380 minutes duration and mean dosage of 12,44 mg (1,99 mug/kg/min). SCN- assays were performed by means of an original technique, which is described in this publication, before any perfusion of nitroprusside, every 30 minutes during perfusion and 30 and 60 minutes after ending the perfusion. Results show that SCN- concentration is increasing during perfusion but not as much as compared with the toxic concentration. Major increase takes place 30 minutes after starting the perfusion (1,27 10(-4) M/l). Increase slows down then and remains on a plateau level until the end of the perfusion where it decreases. Those results allow to reject a toxicity risk related to an increase of SCN- during nitroprusside perfusion. However, the accidents reported after high dosage of NPS and probably related to cyanogenic ion accumulation combined with lactic acidosis as shown in this publication, led the authors to advise a dosage not over 10 mug/kg/min in a maximum of 2 hours time.
| 10,791
|
[Problems presented by closed laryngeal-tracheal injuries].
|
The authors consider the problems raised by severe closed laryngotracheal trauma and report 4 cases. -the immediate tisk to life is due to direct involvement of the respiratory tract requiring emergency measures including cardiorespiratory resuscitation in cases of acute asphyxia. -the origin of the initial respiratory distress, if not obvious from the start, may be suspected in view of the difficulties or impossibility of tracheal intubation, which is also liable to aggravate lesions due to trauma. It is one of these rare cases of resuscitation where emergency tracheotomy is essential. It permits also early, precise surgical exploration. -in cases of fracture of the larynx, a wound of the trachea or rupture and separation of the trachea, the reconstruction must be constructiononstruction must be considered within the first 48 hours. Provision of food and resting of the larynx may be conciliated by installing an esophageal catheter or performing a gastrostomy. Benign trauma, such as contusion or laryngeal commotion, requires close supervision association with medical treatment designed to prevent the onset of lesional oedema.
| 10,813
|
[Personal experience with anesthesia of ambulatory patients operated on in odontostomatological offices].
|
The authors report their experience of anaesthesia of ambulatory patients operated on in dental surgeries; the authors review safety factors, specially, choice of material, drugs and techniques which seem to them essential. They expose in detail their personal techniques, in particular, nasotracheal intubation and open circuit, association of a powerful analgesic drug with a short duration of activity and a mild antiemetic neuroleptic drug completed by inhalation of a mixture of Ethrane and oxygen. The various problems which may occur are considered together with their solutions.
| 10,817
|
Effects of lithium and rubidium on antinociception and behaviour in mice. I. Studies on narcotic analgesics and antagonists.
|
The effects of acute and chronic LiCl and RbCl treatments on the antinociception caused by morphine, pethidine, methadone, pentazocine, nalorphine or naloxone were studied in mice using the hot plate and phenylquinone writhing tests. In both tests morphine, pethidine, and methadone caused significant antinociception whereas the antagonistic drugs were almost inactive. In the hot plate test both the 21 day administration of LiCl and the 5 and 21 day administration of RbCl decreased the antinociceptive effect of morphine. The 5 day administration of LiCl increased the antinociceptive effect of pethidine whereas the acute and 5 day administrations of RbCl abolished it. There were no significant or consistent interactions of the ions with the antinociceptive effect of methadone or the antagonistic drugs. In the phenylquinone writhing test the effects of the ions were inconsistent. Especially in the acute experiments where LiCl and RbCl had some effects on the behaviour of the mice treated with the analgesics, LiCl mostly impaired motor coordination and motor activity whereas RbCl was inactive or had opposite effects. LiCl enhanced the decrease in rectal temperature whereas RbCl was mostly inactive.
| 10,866
|
Evaluation of intrinsic sympathomimetic activity of beta-adrenoceptor blocking drugs in the treatment of patients with angina pectoris.
|
Beta-adrenoceptor blocking drugs with intrinsic sympathomimetic activity (ISA) may be less effective in the treatment of patients with angina pectoris than some others that lack this property. A review of 14 trials comparing beta-adrenoceptor blocking drug with ISA and those without ISA in angina pectoris has been made. The overall picture emerges from both acute and chronic studies using subjective and objective endpoints, that there is no striking difference in effectiveness between the two kinds of beta-adrenoceptor blocking drugs. The one exception is pindolol (a drug with ISA) which, at higher doses, has been shown to be consistently worse than propranolol (a drug without ISA). The reasons for the similarity between propranolol and other bets-blocking drugs with ISA in the trials cited are either that the trial design was defective (the trials were mainly fixed dose comparisons) or that the stimulant effects of those drugs with ISA is not of sufficient magnitude to make a difference. It is suggested that further carefully constructed clinical trials should be carried out before the second reason can be accepted.
| 10,882
|
Characterization of hemoglobin Burke [beta 107 (G9) Gly replaced by Arg].
|
Hb Burke [beta 107 (G9) Gly replaced by Arg] was discovered in a young woman with hemolytic anemia. A substitution in this position has not been previously reported either in the human beta-chain or in any of the animal beta-chains so far sequenced. The abnormal hemoglobin shows heat instability and a lowered oxygen affinity. The substitution of a large charged arginine residue for the small glycine residue in the G helix next to a heme contact (Leu-106) may be responsible for these effects. Hb Burke is compared with five other hemoglobins having Gly-Arg substitutions in other parts of the molecule.
| 10,883
|
Identification and properties of the covalently bound flavin of beta-cyclopiazonate oxidocyclase.
|
Beta-Cyclopiazonate oxidocyclase from Penicillium cyclopium has been previously shown to contain flavin dinucleotide in covalent linkage to the protein. In the present study, a pure flavin mononucleotide peptide was isolated from the enzyme by tryptic-chymotryptic digestion, chromatography on Florisil and on diethylaminoethylcellulose, and hydrolysis with nucleotide pyrophosphatase. The flavin peptide contains 9 amino acids, including histidine in linkage to the flavin, and Asx as the N-terminal residue. The fluorescence of the flavin in the FMN peptide is profoundly quenched even at pH 3.2, where protonation of the imidazole prevents queching of the flavin fluorescence by histidine. This quenching appears to be due to interaction of the flavin with a tryptophan residue, as the quenching is abolished by oxidation of the tryptophan with performic acid. Similarly, the fluorescence of the tryptophan in the peptide is quenched, presumably by the flavin. The flavin of beta-cyclopiazonate oxidocylcase is attached, by the way of the 8alpha-methylene group, to the imidazole ring of a histidine. The aminoacylflavin isolated from the enzyme is identical in the pKa of its imidazole group, in reduction by NaBH4, and in other properties with synthetic 8alpha-(N1-histidyl)riboflavin. The pKa of the histidylriboflavin component of the oxidocyclase is 5.2 before and 5.0 after acid modification of the ribityl chain, as is found in the synthetic derivative. It is concluded that the enzyme contains the N1 isomer of histidylriboflavin and that acid hydrolysis of flavin peptides isolated from the oxidocyclase, while liberating histidylriboflavin, also causes acid modification of the ribityl chain of the flavin moiety.
| 10,963
|
A simple, quantitative approach to the coupling of photophosphorylation to electron flow in terms of proton fluxes.
|
A simple relationship between observed phosphorylation efficiencies (P/e ratios) and internal proton concentration in spinach chloroplast thylakoids has been derived. P/e ratios, varked by either changing the light intensity or by adding the energy transfer inhibitor, 4'-deoxyphlorizin, were found to change with internal proton concentration in accordance with this relationship. A quantitative prediction of the effect of uncouplers on the P/e ratio can probably also be made. By extrapolation of plots of observed P/e ratios against internal proton concentration divided by the overall rate of electron flow, a maximum intrinsic P/e of about 0.66 is obtained. Assuming that two protons appear inside thylakoids per electron transferred, a P/e ratio of 0.66 suggests that three internal protons are consumed for each ATP formed. Internal protons may be considered to be substrates for the phosphorylation reaction. Hill plots of phosphorylation rate vs. internal proton concentration also indicate that three protons are consumed for each ATP synthesized. Thus, the H+ concentration gradient behaves quantitatively, as well as qualitatively, as if it is the connecting link between electron flow and phosphorylation in illuminated thylakoids.
| 10,966
|
Properties and subcellular distribution of guanylate cyclase activity in rat renal medulla: correlation with tissue content of guanosine 3',5'-monophosphate.
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The properties of the guanylate cyclase systems of outer and inner medulla of rat kidney were examined and compared with those of the renal cortex. A gradation in steady-state cyclic guanosine 3',5'-monophosphate (cGMP) levels was observed in incubated slices of these tissues (inner medula greater than outer medulla greater than cortex). This correlated with the proportion of total guanyl cyclase activity in the 100 000 g particulate fraction of each tissue, but was discordant with the relative activities of guanylate cyclase (highest in cortex) and of cGMP-phosphodiesterase (lowest in cortex) in whole tissue homogenates. Soluble guanylate cyclase of cortex and inner medulla exhibited typical Michaelis-Menten kinetics with an apparent Km for MnGTP of 0.11 mM, while the particulate enzyme from inner medulla exhibited apparent positive cooperative behavior and a decreased dependence on Mn2+. Thus, the particulate enzyme could play a key role in regulating cGMP levels inthe intact cell where Mn2+ concentrations are low. The soluble and particulate enzymes from inner medulla were further distinguished by their responses to several test agents. The soluble enzyme was activated by Ca2+, NaN3, NaNo2 and phenylhydrazine, whereas particulate activity was inhibited by Ca2+ and was unresponsive to the latter agents. In the presence of NaNo2, Mn2+ requirement of the soluble enzyme was reduced and equivalent to that of the particulate preparation. Moreover, relative responsiveness of the sollble enzyme to NaNO2 was potentiated when Mg2+ replaced Mn2+ as the sole divalent cation. These changes in metal requirements may be involved in the action of NaNO2 to increase cGMP in intact kidney. Soluble guanylate cyclase of cortex was clearly more responsive to stimulation by NaN3, Nano2, and phenylhydrazine that was soluble activity from either medullary tissue. The effectiveness of the agonists on soluble activity from outer and inner medulla cound also be distinguished. Accordingly, regulation and properties of soluble guanylate cyclase, as well as subcellular enzyme distribution, and distinct in the three regions of the kidney.
| 10,967
|
Properties and subcellular localization of CMP-N-acetylneuraminic acid hydrolase of calf kidney.
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The properties and subcellular distribution of CMP-N-acetylneuraminic acid (CMP-NAcNeu) hydrolase were studied in the cortex of calf kidney. The pH optimum was 9.0 in both Tris - HCl and glycine/NaOH buffer. The apparent Km was 0.47 mM and the apparent V 15.3 mumol/h/g wet wt of calf kidney cortex. A stimulation by divalent metal ions (Ca2+ and Mg2+) was demonstrated for the hydrolase. In the presence of Triton X-100 an increase in enzyme activity was observed. CMP-NAcNeu hydrolase was inhibited by EDTA, beta-mercaptoethanol, nucleoside phosphates and nucleotide-sugars. The inhibition was more pronounced when a sub-optimal CMP-NAcNeu concentration was used. The enzyme appeared to be localized in the plasma membranes. In the plasma membrane preparation of calf kidney cortex, which was derived mainly from the proximal tubule cells, the yield of CMP-NAcNeu hydrolase (13%) and its increase in specific activity (9-fold) was as high as for the plasma membrane marker enzymes. From subcellular distribution studies it appeared that the enzyme was localized mainly at the bursh border side of the plasma membrane of the proximal tubule cell.
| 10,974
|
Studies on aspartase. III. Alteration of enzymatic properties upon trypsin-mediated activation.
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Highly purified aspartase (L-aspartate ammonia-lyase, EC 4.3.1.1) from Escherichia coli, already of full activity, is further activated 3.3-fold by limited treatment with trypsin. The activation requires a few minutes to attain maximum level, and hereafter the activity gradually decreases to complete inactivation. Prior or intermediate addition of soybean trypsin inhibitor results in an immediate cessation of any further change in the enzyme activity. Upon trypsin-mediated activation no appreciable change is detected in the molecular weight of the enzyme subunits as judged from sodium dodecyl sulfate polyacrylamide gel electrophoresis, nor in the pH vs. activity profile in the presence of added metal ions. However, S0.5 and hill coefficient for L-aspartate considerably increase upon activation. As the trypsin-mediated activation proceeds, a marked absorbance difference spectrum of the trypsin-treated aspartase vs. untreated aspartase appears with negative absorbance maxima at 278 and 285 nm. When the trypsin-activated enzyme is denatured in 4 M guanidine-HCl, followed by removal of the denaturant by dilution, the enzyme activity is readily restored to as much as 1.5 times that of the native enzyme, indicating that the trypsin-activated enzyme is rather a stable molecule.
| 10,995
|
Heterogeneity of histidine transport in the Ehrlich cell.
|
We have reexamined the heterogeneity shown by histidine in its uptake by the Ehrlich ascites tumor cell, in the face of a contradiction of our earlier interpretation. We again find the fraction of histidine uptake at neutral pH inhibitable by the model substrate for System A, 2-(methylamino)-isobutyric acid, to be fully dependent on the presence of Na+ or Li+. The small Na+ -independent component not attributable to System L can be identified with System Ly+ through its inhibitability by homoarginine. This component increases as the pH is lowered with an apparent pK' a of 6.1. The simultaneous decrease in the uptake by the neutral systems could be identified, for System L, with the same titration of histidine to its cationic form, but for System A the sharp decrease is identified with the protonation of a structure on the membrane rather than one on the substrate. The action of H+ in the latter case proved approximately non-competitive with Na+ when tested with ordinary substrates.
| 11,000
|
[Effect of cocaine on the tyrosine hydroxylase of rat hypothalamus].
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The influence of cocaine on tyrosine hydroxilase of rat brain hypothalamus was investigated in vivo (0.5 mg/kg) and in vitro (10(--6)--10(--5)M). Cocaine was used as a substance with a known adrenergic type of action. It was shown that under standard conditions cocaine in vitro increased the enzyme activity and decreased the Km for DMPH4 cofactor without changing Vmax of the reaction analyzed by the membrane enzyme. Cocaine in vitro decreased the tyrosine hydroxylase activity, especially that of the membrane enzyme. In this case there occurred a decrease of Km for DMPH4 and a decrease of Vmax of the reaction. The decrease of Vmax is considered to be the result of the secondary effect of cocaine.
| 11,011
|
Differences in the altered energy metabolism of hemorrhagic shock and hypoxemia.
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The effect of hemorrhagic shock, hypoxemia, and anoxia on the levels of adenine and pyridine nucleotides of liver and kidney was assessed. ATP levels in liver and kidney of animals in shock or animals subjected to 7 min of anoxia decreased by 85 and 73%, respectively. Under hypoxic conditions (arterial PO2 AT 18 MMHg), the decrease was only 62 and 48% in liver and kidney, respectively. Tissue NAD levels decreased and NADH levels increased during shock but were found to be essentially unaltered during experimental hypoxemia. Thus, shock produced greater alterations in adenine and pyridine nucleotides than did hypoxemia alone, indicating that stagnant hypoxemia due to shock is more deleterious to energy metabolism than is severe hypoxemia with an otherwise normal circulation. The results also suggest that if an anterial PO2 OF 18 MMHg represents the initial stages of tissue hypoxia, then tissue ATP levels are a more sensitive indicator of this than NAD levels.
| 11,040
|
Microdose mammography.
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Tens of thousands of mammograms are performed daily in the United States. Accumulated radiation biologic data suggest that approximately 90-rad is the level of radition to the breast above which the incidence of cancer may be increase. A microdose system of roentgenography is described that provides better images at one-third to one-fifth the exposure of the commonly used low-dose system and about one-eight to one-tenth the dose of Xeromammography. This system should allow for repeated x-ray study in a patient as required, without exceeding the critical level.
| 11,043
|
Group desensitization of dissimilar anxieties.
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Group desensitization is an effective, efficient anxiety-reduction therapy that, nonetheless, is not applicable in most mental health settings. This paper outlines several procedural modifications that make possible the desensitization of diverse anxieties within a single group and thus make group desensitization a more practical strategy.
| 11,056
|
Effect of ascorbic acid on arylsulfatase A and B activities in human chondrocyte cultures.
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Cultured normal human articular cartilage chondrocytes exhibited decreasing levels of arylsulfatase A and B activities when grown in the presence of increasing levels of ascorbic acid (0 to 90 mug/ml) in the media. That this was not a general effect on all lysosomal enzymes was supported by the increase in acid phosphatase activity and no change in beta-glucuronidase activity observed with increasing levels of vitamin C under identical culture conditions. No decrease in either arylsulfatase activity was observed when ascorbic acid was replaced by ascorbate-2-sulfate. Ascorbic acid did not inhibit either arylsulfatase activity when added directly to the assay mixture. These data, combined with results of mixing experiments, suggest that the effect of vitamin C is mediated through cellular factors produced in response to its inclusion in the growth media.
| 11,078
|
Ferredoxin from a red alga, Porphyra umbilicalis.
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A plant-algal type ferredoxin was isolated from the red alga, Porphyra umbilicalis. In its oxidised form the ferredoxin had absorption maxima at 277, (281), 323, 420 and 462 nm. Two atoms each of non-haem iron and labile sulphur were present per molecule protein. The midpoint potential of the protein was -400 mV and it effectively mediated electron transport in the NADP-photoreduction system of barley. The amino acid composition of Porphyra umbilicalis ferredoxin was determined as (Lys4, His2, Arg1, Asx10, Thr8, Ser7, Glx16-17, Pro3, Gly7, Ala8, Cys5, Val6, Met1, Ile5, Leu8, Tyr5, Phe2). The minimum molecular weight of approximately 11000 was confirmed by sedimentation-equilibrium studies in the analytical ultracentrifuge. Approaching half of the total amino acid sequence was determined by means of an automatic sequencer.
| 11,097
|
Mechanisms by which hapten conjugates of pneumococcal polysaccharide interfere with the challenge of anti-hapten memory cells.
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Incubation of trinitrophenylated hemocyanin (TNP-KLH)-primed spleen cells with microgram amounts of 2,4-dinitrophenyl (DNP) or 2,4,6-trinitrophenyl (TNP) conjugates of pneumococcal polysaccharide type 3 (SIII) for as little as 5 min at 4 degrees C results in a specific "block" of the 19 S and 7 S adoptive memory response to TNP-KLH. This hapten-SIII-induced block of anti-hapten memory B cell responsiveness seems to be an example of specific receptor blockade. The block is specific and can be prevented by simultaneous incubation of the primed cells with hapten-protein conjugates which presumably compete with the hapten-polysaccharide for attachment to the B cell surface via anti-hapten Ig receptors. Removal via capping of these Ig receptors by exposure of TNP-KLH-primed memory cells to rabbit anti-mouse Fab serum for 45 min at 37 degrees C renders these cells refractory to the blocking effect of hapten-SIII. Once the hapten-SIII has attached to the memory cells, these blocked cells can be "rescued" (i.e. returned to a state of responsiveness) by incubating these cells with either mouse anti-SIII at 37 degrees C or rabbit anti-DNP serum at 4 degrees C. Since a papain digest of the IgG fraction of rabbit anti-DNP did not rescue the cells while the intact IgG did, a capping off of the TNP-SIII was proposed as the mechanims for this return to responsiveness of the hitherto blocked cells. A rescue was not seen by treatment of recipient mice with such B cell mitogens as dextran sulfate, endotoxin or purified protein derivative of tuberculin.
| 11,101
|
Suprression of local graft-versus-host reactions by mouse fetal and newborn spleen cells.
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Fetal splenic but not thymic lymphocytes significantly reduce the ability of parenteral adult spleen cells to elicit local graft-versus-host reactions in F1 recipients. This suppressive activity wanes early after birth. There is no requirement for histo compatibility between reacting and suppressor cells.
| 11,102
|
Antiarrhythmic action of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), compared with that of propranolol.
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The antiarrhythmic activity of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), was compared with that of propranolol. KF-577 antagonized ouabain-induced arrhythmias in normal and bilaterally vagotomized guinea pigs; its antagonistic activity was equal to that of propranolol. Reserpinization greatly reduced ouabain intoxication and neither of the two beta-blockers produced further reduction. Aconitine-induced arrhythmias in rats were not antagonized by the two agents. In intact guinea pigs, the reduction of ouabain intoxication by both beta-blockers could not exceed that produced by simulataneous infusion of KCl, and vice versa. In isolated guinea pig atria, propranolol was about 10 times more effective than KF-577 in reducing the ouabain intoxication. The antiaarhythmic activity of KF-577 paralleled its beta-blocking activity in the isolated preparations but not in the intact animals.
| 11,105
|
Relationship between the prevention of rat gastric erosions and the inhibition of acid secretion by prostaglandins.
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The formation of gastric mucosal erosions induced by indomethacin in the rat was inhibited in a time- and dose-dependent manner by antisecretory prostaglandins, the methyl analogues of PGE2 being 400 times as active as the parent prostaglandin. PGA2, a methyl analogue of PGF2alpha and the H2-receptor antagonist metiamide, also inhibited erosion formation. There was a variable relationship between the doses required to inhibit erosions and to inhibit gastric acid secretion. In the anaesthetised rat, the low incidence of erosions with indomethacin was markedly increased by concurrent gastric perfusion with acid saline and taurocholate. This mucosal damage was inhibited by the methyl analogues of PGE2, suggesting protective actions on the mucosa other than inhibition of acid secretion.
| 11,107
|
Centrally induced reduction in sympathetic tone-a postsynaptic alpha-adrenoceptor-stimulating action of imidazolines.
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Naphazoline or oxymetazoline (both 30 mug/kg) were injected into the cisterna magna of anaesthetized cats and reduced blood pressure, heart rate and the electrical discharge rate of small fibre bundles of the preganglionic sympathetic splanchnic nerve. Cats were depleted of endogenous noradrenaline by pretreatment with reserpine (5 mg/kg, 18 h) and alpha-methyl-p-tyrosine (twice 300 mg/kg, 18 and 2 h). In these animals, intracisternal injection of 30 mug/kg oxymetazoline exerted a decrease of sympathetic discharges similar to that described for non-pretreated animals. In noradrenaline-depleted cats intracisternal injection of 1 mug/kg clonidine also decreased the sympathetic discharges. It is concluded that these imidazolines exert their sympathoinhibitory and cardiovascular effects by stimulation of postsynaptic alpha-adrenoceptors in the CNS.
| 11,108
|
Lower esophageal sphincter response to oral administration of cimetidine in normal subjects.
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Anithistamines that specifically block the gastric and secretory action of histamine have recently been developed. One of these H2-receptor blockers, metiamide, has been found to increase lower esophageal sphincter (LES) pressure in the opossum. Because of reported agranulocytosis with metiamide, another H2-receptor blocking agent, cimetidine, was developed. To determine its effect on LES pressure, 8 normal volunteers received placebo or oral doses of cimetidine (50, 100, 200, and 400 mg) in a random, blinded manner. Indicative of adequate absorption, significant serum levels were achieved with all doses of cimetidine (50 mg = 0.17 mug per ml; 100 mg = 0.33 mug per ml; 200 mg = 0.76 mug per ml; and 400 mg = 1.61 mug per ml). Although these serum levels have been found to produce marked inhibition of gastric acid secretion, no discernible effect was found on LES pressure when compared to placebo. Thus cimetidine does not increase LES pressure. It does not decrease sphincter pressure either and is therefore not contraindicated in patients with reflux esophagitis.
| 11,144
|
[Characteristics of two new mutant forms of erythrocyte glucose-6-phosphate dehydrogenase: "Kirovograd" G6PD and "Zhitomir" G6PD].
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The paper comprises the description of properties of three mutant forms of glucoso-6-phosphate dehydrogenase characterized according the WHO program. Preparations of the enzymes were isolated from erythrocytes of patients with G6PD deficiency from three unrelated to one another Ashkenasi families coming from the Ukraine and from Byelorussia. Two new variants of G6PD hitherto never described in the literature were discovered. These variants were designated as "Kirovograd" and "Zhitomir" after the towns the probands came from. The properties of purified enzymes revealed by the methods of the WHO program were as follows: the variant "Kirovograd" has a normal electrophoretic mobility in tris and TEB buffers and 98% of the normal in phosphate buffer. KM for G6P is 6,54; KM for NADP--2,19. It is characterized by a reduced thermostability and by an acute peak of activity at pH 8,5. The variant "Zhitomir" has 90-98% of the normal electrophoretic mobility in TEB buffer and 78-84% in phosphate buffer. KM for G6P is 5,4-8,3. KM for NADP is 1,4-3,1; with deoxyG6P is 50% and with deaminoNADP is 35%. It is also characterized with a reduced thermostability, while the curve of the dependence of its activity on pH has two peaks. Both variants are perfectly inactive with erythrocytes and thus should be assigned to the second group of the mutants variants of G6PD. The comparison of these variants to other variants encountered in the same national group revealed that they resemble certain quantitative variations.
| 11,150
|
Extrinsic signals for monitoring the association reaction of proteins as introduced by fluorescent and non-fluorescent labels.
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Two known dansyl labels (I, II) and 5-[2-(iodoacetamido)ethylamino]-1-naphthalene-sulfonic acid (III) and three new azo-dyes (IV - VI) were covalently attached to alpha-chymotrypsin and to basic pancreatic trypsin inhibitor by four different reactive groups. In order to protect the contact region of the proteins the complex of the two proteins was labeled. Advantage was taken of the fact that a group which is buried in the complex reacts about (see article) times slower than a group which is always exposed (K = dissociation equilibrium constant, [C] = concentration of the complex). The complex was dissociated at pH 3 and the labeled proteins were isolated by column chromatography. They were fully active. The dansyl label was immobilized when introduced by dansyl chloride but highly mobile when attached via the longer imidoester group (II). Changes of absorption and of fluorescence which occur when differently labeled reaction partners recombine were studied. Changes in absorption (up to 18%) were mainly due to interactions of the label of one protein with the other protein. Fluorescence changes of up to 480% could be obtained. They were interpreted in terms of a Förster type energy transfer between donor and acceptor labels and changes of absorption and quantum yield due to interactions of the labels with the proteins. The kinetic constants of complex formation are not seriously altered by the labels (Bösterling, B & Engel, J. (1976) this J. 357, 1297-1307, succeeding). It is concluded that the labeling technique may be of general value for kinetic and equilibrium studies of protein associations.
| 11,168
|
The distribution of hepatitis B surface antigen in Africa and the tropics: report of a population study in Nigeria.
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This preliminary study was designed to examine the distribution of hepatitis B surface antigen (HBsAg) in two contrasting groups in an urban area situated in the tropical forest belt. The sample from the traditional area represents a population of low socio-economic status, living in the central slum areas of the city, and the sample from the peripheral area represents a population of high socio-economic status living in clean modern estates. The prevalence rate of HBsAg by complement fixation (CF) was 12-6 per cent in both areas. There was no statistically significant difference between the two groups with respect to prevalence of the antigen. When both groups were combined, no significant relationship was found between the presence of the antigen and sex, age, marital status, level of education, occupation, income, and a presumed exposure to the antigen from injections, dental treatment, blood tests, surgical operations, blood donations, tribal, (medicinal), tattoo and cosmetic marking, insanitary disposal of faeces, doubtful sources of water supply, and exposure to mosquitoes. No association with genotype was found.
| 11,191
|
Rapid microspectrofluorometric studies in EL2 cells following intracellular accumulation of dibenzocarbazoles.
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Microspectrofluorometric observations were carried out in EL2 ascites cancer cells and dibenzo(a,e)fluoranthene (diB(a,e)F)-grown EL2 cells, following treatment (5 min) with three dibenzocarbazoles (1,2,7,8; 1,2,5,6 and 3,4,5,6). After microinjection of glucose-6-P leading to reduction of NAD(P), a sequence of difference spectra (after substrate minus before) is recorded. In dibenzocarbazole-untreated cells, maximum (NAD(P) reduction (emission maximum at 465-475 nm) is attained within 5 s, followed by a gradual return to initial fluorescence within 20 to 200 s (faster in the diB(a,e)F-grown). In dibenzocarbazole-treated cells there is a rather regular increase in the intensity of the difference spectrum up to approximately 300-500 s. Initially the increase is more predominant in the region around 460-470 nm, but it gains later prominence in the shorter wavelength region (420-430 nm) characteristic of the hydrocarbon (higher and steadier increase in the 3,4,5,6, dibenzocarbazole-treated diB(a,e)F-grown). Subsequently there is a gradual decrease of fluorescence which may or may or not return to initial level. The observed increase spectra require evaluation in terms of possible components (e.g. a mixture of NAD(P)H and hydrocarbon, binding changes, succession of fluorescent metabolites).
| 11,198
|
pH-dependent binding of immunoglobulins to intestinal cells of the neonatal rat.
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Rat and rabbit IgG immunoglobulins conjugated to horseradiah peroxidase as a histochemical marker bind at 0 degrees C to the luminal surface of absorptive cells in isolated segments of jejunum from 10-12-day old rats. Binding is observed at pH 6.0, near the normal luminal pH of the duodenum and jejunum at this age, but not at pH 7.4. Furthermore, no binding occurs when cells are exposed at pH 6.0 to either free peroxidase or peroxidase conjugated to chicken or sheep IgG immunoglobulins or bovine serum albumin. The sensitivity of binding to pH suggests a means whereby immunoglobulins which are selectively absorbed by the cells can be released efficiently at the abluminal surface.
| 11,223
|
Interaction of erythrocytes with human serum proteins. I. Analysis of the effect of pH and ionic strength of the medium.
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The effect of ionic parameters of the medium (pH and ionic strength) on the processes of interaction of tannin-treated erythrocytes and the protein fractions of human serum (macroglobulins, microbulins and albumin) was studied in factorial experiments. Complex effect of these parametres on the processes under investigation and optimum conditions of erythrocyte sensitization were established. Subsequent fixation of antibodies by the erythrocyte diagnostic and their agglutinating activity are manifested in different mannera depending on the conditions of preceding sensitization. Important peculairities were discovered in the mechanism of interaction between the erythrocytes and various serum proteins. The obtained results should be taken into account in the production of erythrocyte antigen and antibody diagnosticums.
| 11,260
|
The coordinate roles of branchial nerve activity and potassium in the stimulation of ciliary activity in Mytilus edulis: observations with phenoxybenzamine, bromolysergic acid and fluorescence histochemistry.
|
Potassium concentrations in excess of 30 mM increase the rate of beating of lateral cilia on the gill of Mytilus edulis. Cilioexcitation produced by low frequency (5 beats/s) electrical stimulation was potentiated with potassium but blocked with bromolysergic acid (a serotonergic inhibitor). Cilioinhibition produced by high frequency (50 beats/s) stimulation was decreased with potassium and phenoxybenzamine (a dopaminergic inhibitor). Phenoxybenzamine enhanced the cilioexcitation produced by potassium. Potassium doses incapable of maintaining a basal rate of beating (less than 30 mM) could increase ciliary activity if phenoxybenzamine was also added. After transection of the branchial nerve, the yellow-fluorophore (serotonergic storage) and cilioexcitatory effect of potassium gradually decrease. This study shows that the potassium effect on ciliary activity (a) increase with low frequency nerve stimulation, presumably through the release of serotonin and (b) decreases with high frequency nerve stimulation, presumably through the release of dopamine.
| 11,265
|
An unusual bilateral pathological fracture.
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An unusual case of a bilateral pathological fracture of the mandible has been presented. The fracture of the right side of the mandible was through an area of bacteroides osteomyelitis and the fracture of the left side of the mandible was through a large cementifying fibroma, which had replaced the left body of the mandible.
| 11,280
|
The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method.
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A method is described for the rapid determination of phenothiazine drugs in a wide variety of pharmaceutical preparations. The drugs are determined by a difference spectrophotometric technique based upon the absorbance of the sulphoxide derivative of the drug relative to the absorbance of a solution of the underivatized drug. The sulphoxide derivatives are formed rapidly and quantitatively at room temperature by the addition of a solution of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid on standing. The difference absorbance of the solutions is proportional to the concentration of the phenothiazine drug in the preparation and is specific for the intact drug in the presence of oxidative and photochemical decomposition products, colouring and flavouring agents, excipients and most co-formulated drugs.
| 11,285
|
A comparison of the effects of morphine and pethidine upon body temperature and the reversal of reserpine's effects upon body temperature in the mouse.
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The effects of morphine and pethidine upon body temperature and upon the reversal of reserpine hypothermia in the mouse were investigated. Both morphine and pethidine produced a dose-dependent fall in body temperature, that of morphine being totally antagonized by nalorphine and partially by naloxone, while that of pethidine was antagonised by naloxone and enhanced by nalorphine. Both drugs reversed reserpine-induced hypothermia. The reversal by morphine, but not by pethidine, was partially antagonized by naloxone. Adrenalectomy prevented the reversal of reserpine hypothermia by pethidine but morphine produced a partial reversal. Ganglion blockade and alpha-and beta-blockade all prevented reversal of reserpine hypothermia by both drugs. The results are discussed with regard to differences between pethidine and morphine and possible involvement of opiate receptors.
| 11,291
|
Enhancement of ethonol-induced withdrawal convulsions by blockade of 5-hydroxytryptamine receptors.
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Male Swiss-Webster mice were made physically dependent on ethanol using the ethanol vapour inhalation technique. Animals pretreated with methysergide, a known 5-hydroxytryptamine receptor blocking agent, had significantly greater alcohol-induced withdrawal convulsions than saline pretreated controls. These findings suggest that the reduction of 5-HT at receptor sites may result in the augmentation of the withdrawal convulsions.
| 11,292
|
Effects of animal maturity on smooth muscle and blood pressure responses to prostaglandins E2 and F2alpha.
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The effects of prostaglandins E2 (PGE2) and F2alpha (PGF2-alpha) on muscle strips from mature and immature rats and guinea-pigs and on rat blood pressure were investigated in the presence of atropine. The colon and stomach strips from immature rats were equally responsive to PGE 2 and PGF2alpha where mature colons were significantly more sensitive to PGF2ALPHA AND MATURE STOMACH STRIPS SIGNIFICANTLY MORE SENSITIVE TO PGE2. On the ileum from immature guinea-pigs the maximum responses to PGE2 and PGF2alpha were 16 and 8% of the histamine maximum respectively. The corresponding figures on the mature ileum were 86 and 75%. Whereas PGE2 was only twice as active as PGF2alpha on immature ilea, it was ten times more active than PGF2alpha on mature muscles. On blood pressure PGF2alpha and PGE2 were both hypotensive in immature rats whereas PGE2 was hypotensive and PGF2alpha hypertensive in mature rats. The results suggest that as the animal gets older, receptors for prostaglandins became increasingly differentiated.
| 11,308
|
Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol.
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Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17 beta-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism.
| 11,314
|
Heat treatment of laser-welded gold alloys.
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(1) Three alloys, G-3, SMG-2, and Ceramco-0, showed no ductility in the aswelded condition. (2) The Ney G-3 as-welded samples had no ductility, but heat treating greatly increased their yield stress. (3) The simulated ceramic firing cycle created a small amount of ductility in SMG-2, but the lowering of the yield stress in Ceramco-0 renders the welds dangerously weak even with improved ductility. (4) The Jelenko F as-welded specimens were acceptable. Heat treatment improved the joints slightly, but this is not considered necessary. (5) The Ney B-2 as-welded specimens produced satisfactory joints which did not benefit from heat treatment. The large loss in ductility with heat treatment is considered undesirable. (6) The unpredictable behavior of Ceramco-0 in this study suggests the need to evaluate each alloy individually before clinical application.
| 11,343
|
Pharmacological activity of nitroxide analogues of dichloroisoproterenol and propranolol.
|
Spin-labeled analogues of dichloroisoproterenol and propranolol were synthesized. It was found that the KD's of both probes for the beta-adrenergic receptors of frog erythrocytes were about 30-fold higher than the KD's previously reported for the parent antagonists. Thus the introduction of a bulky nitroxide moiety in place of the isopropyl group on the amino nitrogen is associated with a decrease in affinity for the beta-adrenergic receptors. Nonetheless, the affinity of the spin-labeled propranolol would appear to be within a range compatible with EPR measurements.
| 11,346
|
Benzodiazepines and withdrawal psychosis. Report of three cases.
|
Three cases of acute psychotic illness following sudden withdrawal from high daily doses of benzodiazepines were associated with agitation and confusion. Disorientation was prominent in two of the patients. None of the patients had had previous psychotic episodes. The condition of all patients was reversed dramatically with hypnotic drugs. Gradual withdrawal was successfully accomplished without relapse, with a follow-up of as much as one year. To our knowledge, this is the first such series in the literature.
| 11,358
|
Effect of glucose and sucrose on the survival in batch culture of Streptococcus mutans C67-1 and a non-cariogenic mutant C67-25. Morphological studies.
|
This study comprised an ultrastructural examination of a cariogenic strain of Streptococcus mutans, C67-1, and a non-cariogenic mutant of that strain, C67-25. The aim of the work was to define more clearly the relationship between S. mutans and dental caries and, more specifically, to elicit ultrastructural evidence for the conclusion from a previous investigation that the greater survival of the parent strain in sucrose broth at uncontrolled pH was related partly to the production in this medium of abundant extracellular polysaccharide (EPS). The strains were grown as previously in 5% (w/v) glucose or sucrose broths, the pH being either allowed to fall or maintained above 6.0, and processed by the thiosemicarbazide technique for election microscopy. It was confirmed that EPS was most abundant in the sucrose broth culture of the parent strain at uncontrolled pH. While the presence of abundant EPS relates to the greater survival of the parent strain in sucrose broth at uncontrolled pH, this organism possesses at least one other mechanism of survival in acid media, possibly dependent on cell wall properties, in view of its greater cell wall thickness and increased survival in pH-uncontrolled glucose broth in the absence of detectable EPS production. It is postulated that intracellular and extracellular polysaccharide formation, cell wall thickening and reduced viability were indicators of unfavourable growth conditions in the test media. Cariogenic strains of S. mutans appear to be able to survive better under such conditions and hence the prevalence of this and other polysaccharide-producing organisms in stagnant sites in natural dental plaques.
| 11,393
|
[The problem of dissecting aneurysm of the aorta and its benign course].
|
On the basis of a personal case, the clinical, diagnostic and therapeutic problems of variants of dissecting aneurysm of the aorta with benign course are discussed. The usefulness of cardio-aortic angioscintigraphy in the interests of early diagnosis of aneurysm and aortography by catheterism for specifying its location and extent, is pointed out. Spontaneous benign development would seem to be tied up with the affected area of the aorta, the modalities of dissection, and above all with the establishment of a distal return breach for blood flow into the aortic lumen. The predominant role of cystic medionecrosis in determining dissection is stressed and the usefulness of intensive pharmacological therapy based essentially on hypotensive and beta-blocking substances confirmed.
| 11,426
|
[Preparative isolation of terrilytin components and study of their enzymatic properties].
|
By ion-exchange chromatography the composition of the fibrinolytic enzyme from Aspergillus terricola-terrilytine-was studied. The preparation contained five components that differed in their substrate specificity. Three of the components and proteolytic and fibrinolytic activities. The isolated fractions were examined with respect to their pH stability, pH optima (casein, hemoglobin and fibrin used as substrates), fibrinolytic and fibrinohenolytic activities.
| 11,462
|
[Autogenic training within the therapeutic scope of schizophrenic patients].
|
The author calls the reader's attention to the rather strange fact that autogenic training, in spite of worldwide recognition and extensive uses of the method in various disciplines of medicine and spheres of live, has not so far been finding wide application in the medical specialty dealing with mental disorders. After discussing some possible causes of this situation and commenting on first signs of a necessary change in attitude toward autogenic training, he reports his own experience in the treatment of schizophrenic patients with this psychotherapeutic method, emphasizing the need for including psychotherapy in a complex concept of the treatment of psychoses.
| 11,518
|
Effects of drugs on the uptake of acetylcholine by human term placenta fragments.
|
An active concentrative component of the ACh accumulation in fragments of human term placenta followed kinetics predicted by the Michaelis-Menten equation (Km greater than 15 mM). This process was competitively inhibited by choline or hemicholinium-3, suggesting the possibility that a common carrier existed. Morphine reduced the 3 H-ACh uptake competitively. Imipramine, desmethylimipramine, haloperidol and chlorpromazine decreased the concentration ratios. This effect was uncompetitive with respect to chlorpromazine. Compared to drug actions on the ACh uptake in innervated tissue drug effects in the placenta were much less predictable for various classes of compounds.
| 11,531
|
Relationship of plasma motilin response to lower esophageal sphincter pressure in man.
|
The effect of intraduodenal instillation of 0.1 N hydrochloric acid or 0.9% saline (control) on lower esophageal sphincter pressure (LESP) and plasma motilin concentrations was studied in five normal volunteers. After acid, LESP and plasma motilin rose concomitantly exceeding basal by about 80% (p less than 0.025) and 90% (p less than 0.05), respectively, at 3 to 4 minutes. Control values did not significantly differ throughout the test period from the mean basal level. These results are compatible with the view that the increase in LESP after duodenal acidification may be mediated by endogenously released motilin.
| 11,547
|
Fetal thymus transplantations in severe combined immunodeficiency.
|
Two brothers with severe combined immunodeficiency were treated with repeated transplantations of fetal thymus tissue. The first patient was not treated until he was critically ill, and the intramuscular transplants had no effect. He died at 11 months of age of overwhelming pneumonia. At postmortem examination a transplanted thymus seemed viable. In the second patient an intramuscular transplant had no effect, but three subsequent intraperitoneal transplants led to transient increase in circulating T lymphocytes with a concomitant fall in B lymphocytes. The results suggested an additive effect of each transplant. However, delayed hypersensitivity skin tests and in vitro mitogen responses were not influenced. Initially, transfer factor was given, and fetal liver was administered intraperitoneally together with the last thymic transplant. Neither of these measures had any observed effect, and this patient, similarly, died of pneumonia at nearly 12 months of age.
| 11,548
|
Cytotoxicity in graft-versus-host reaction. II. Lysis of target cells of parental genotyppe by F1 hybrid macrophages.
|
Graft-versus-host (GVH) reactions were induced in adult F1 hybrid mice with the i.p. injection of parental strain spleen cells. Peritoneal exudate and spleen cells of the F1 hybrids taken 8 days after the induction of GVH reaction had a nonspecific in vitro cytotoxic effect which was measured by using 51Cr-labeled target cells of parental genotype. The cytotoxic cells in the peritoneal exudates were shown to be macrophages which adhered to plastic surfaces and were sensitive to the toxic action of crystalline silica particles. Moreover, the injection of partially purified syngeneic macrophages into the F1 hybrids undergoing GVH reactions increased the cytotoxic activity of the peritoneal exudate cells obtained from these animals. These results suggest that during GVH reaction host macrophages are activated into a state of nonspecific cytotoxicity.
| 11,578
|
Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells.
|
(1)Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. (2) Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. (3) Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. (4) The findings suggest that Tcells, at an early stage of differentiation, are more susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. (5) It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstituting and cellular engineering without producing GVHD.
| 11,582
|
Enzyme histochemical study on fat-storing cells (so-called Ito's cell) of liver.
|
Inorder to gain a foothold in clarifying the functional significance of fatstoring cells, an enzyme histochemical study on these cells was carried out. Fat-storing cells showed no alkaline phosphatase, acid phosphatase or esterase activity but demonstrated a marked gamma-glutamyl transpeptidase activity suggesting the possibility of its participation in the synthesis of fiber protein. This possibility was further heightened by its remarkable activity noted at the site of progressive fibrosis. Fat-storing cells under a normal condition partake in the formation of fibers supporting the sinusoidal wall, and under an abnormal condition gradually change their shape with loss of fat droplets and then transform into fibroblast-like cells closely related to the progress of fibrosis.
| 11,635
|
Some physicochemical properties of human leucocyte migration inhibitory factor (LIF).
|
Leucocyte migration inhibitory factor (LIF) obtained from human lymphocytes stimulated with concanavalin A was consistently and irreversibly blocked by the serine-esterase inhibitor phenyl-methyl sulphonylfuoride (PMSF). This effect was not due to fluoride ions, hydrolysis products of PMSF or to impurities. PMSF pulse treatment of human buffy coat cells did not affect cell migration under agarose. LIF was also irreversibly destroyed by treatment with L-cysteine and 2-mercapto-ethanol, suggesting that the molecule contains disulphide linkage groups decisive for its configuration and biological activity. Di-sodium EDTA completely inhibited LIF activity but only if present during the entire migration period. Removal of EDTA before LIF assay restored LIF activity. Leucotye migration was neighter influenced by L-cysteine nor by EDTA. LIF activity was slightly diminished after treatment at 56 degrees C for 1 h and completely lost at 80 degrees C for 1/2 h. Furthermore, LIF appeared rather stable when treated at pH values between 4 and 11. These findings suggest, but do not prove, an esterase or a protease nature of human LIF.
| 11,637
|
[Distribution and ecology of Ixodes trianguliceps (Birula, 1895) (Acarina, Ixodoidea) in France, particularly in the South-East].
|
Ixodes trianguliceps, parasite of insectivores and rodent mammals seems to be distributed throughout France, except in the mediterranean low altitude areas. This tick which does not manifest any parasitic specificty, has meanwhile preferred hosts (Clethrionomys glareolus, especially). At low altitudes, it likes forests, hedge-rows and heaths and at higher altitudes (Subalpine and alpine), opened area may be densely inhabited. The authors study the numerous concerned vegetal associations and precise the tick's phenology, particularly in the Bas-Dauphiné. They also discuss the many hypothesis concerning the still unknown ecology of I. trianguliceps free instars.
| 11,660
|
Buoyant density of some togaviruses in sucrose density gradient and capacity of their haemagglutinin fractions to interact with antibody.
|
The buoyant densities of Western equine encephalomyelitis virus (an Alphavirus) and tick-borne encephalitis (TBE) virus (a Flavivirus) antigens prepared by different methods were studied. Sucrose density centrifugation revealed a heterogeneity in the density of the virions. The sedimentation pattern and height of peaks of the haemagglutinating activities and infectivity, other conditions being equal, depended both on the virus species and properties of its strains and on the mode of preparation and treatment of the virus-containing material. Different haemagglutinating antigen fractions differed in their capacity to interact with specific antibody. It was suggested that the kinetics of a serological reaction and its result depend on the functional activity of the antigen preparation and, in particular, on the proportion in the reaction mixture of virus particles with a dissimilar antigenic structure.
| 11,662
|
Some immunological mechanisms of the influenza virus antitumour effect.
|
Vaccine strains of influenza A virus inhibited the growth of ascitic tumour cells and outbred rats or inbred mice. The infected tumour bearers had an enhanced immune response to viral and specific tumour antigens. These phenomena are apparently due to the formation of complexes of both antigens on cell membranes and increased immunogenicity of such complexes.
| 11,666
|
Stable erythrocyte diagnostic preparation for passive haemagglutination test with herpes simplex virus antigen.
|
A method for the preparation of stable suspensions of erythrocytes sensitized with herpes simplex virus (HSV) antigen and for their use in the passive haemagglutination test (PHAT) was developed. Formolized sheep erythrocytes were treated with tannin and sensitized with HSV antigen prepared from infected chick embryo cell culture by ultrasonication and virus extraction with alkaline glycine buffer. Antibody titres determined in the PHAT were higher than titres of neutralizing antibody. The specificity of the results was checked by the passive haemagglutination-inhibition test (PHAIT). The sensitized erythrocytes retained their activity for 5 months (the observation period) and gave reproducible results. The availability of stable erythrocyte diagnostic preparations simplifies the detection of herpesvirus antibody and makes the method widely applicable.
| 11,670
|
Present state of alpha and beta adrenergic drugs. II. The adrenergic blocking agents.
|
There are selective blocking agents (antagonists) for alpha receptors and beta receptors. These blocking agents prevent the response to injected agonists and neurogenically released norepinephrine. The principal cardiovascular response to alpha blockade is postural hypotension with reflexly induced cardiac stimulation. If neurogenic vasoconstriction is present, this will be removed. The principal cardiovascular response to beta blockade is bradycardia. If fast arrhythmias are present, these will be slowed. Beta blockade tends to increase peripheral resistance. Unless circulation is previously impaired this vasoconstrictive effect is insignificant.
| 11,680
|
Pharmacology and therapeutic use of antihistamines.
|
The classes of antihistaminic agents, their pharmacology and therapeutic uses, adverse effects, drug interactions, toxic overdoses and abuse are reviewed. It is concluded that antihistamines are valuable drugs for treating a number of conditions and diseases (e.g. allergic rhinitis, motion sickness and parkinsonism), but proof of efficacy has not been established for the treatment of cardiac arrhythmias, peptic ulcers, insomnia and headaches. Because responses to antihistamines may vary, titration of each patient's dose is recommended.
| 11,685
|
Effect of virus infection on the inflammatory response. Depression of macrophage accumulation in influenza-infected mice.
|
To better define the mechanisms by which viruses depress immune function, the effect of influenza infection on the ability of macrophages to accumulate at sites of inflammation was determined. Mice were inoculated with virus, and their inflammatory response measured in vivo by counting the number of leukocytes which accumulated in the peritoneal cavity 2 days after an intraperitoneal injection of phytohemagglutinin. Mice infected with influenza had a 57% and 65% depression of total leukocyte and macrophage accumulation, respectively, as compared to the response of uninfected mice. In contrast, bacterial pneumonia did not produce a decrease in the macrophage response. This indicated that the depression was produced by the virus infection rather than being a nonspecific phenomenon accompanying any inflammatory focus in the lung. The in vitro chemotactic responsiveness of normal peritoneal macrophages incubated with infectious influenza virus was 53% of normal. These experiments suggest that influenza infection may depress a host's ability to mobilize macrophages to inflammatory sites in vivo by inhibiting their chemotactic responsiveness.
| 11,695
|
Formation of slow-reacting substance by guinea pig immunoglobulins.
|
The capacity of guinea pig antibodies to mediate the antigen-induced release of slow-reacting substance (SRS) in the rat peritoneal cavity is restricted to IgG2 and, to a lesser extent, to IgG1 populations of immunoglobulin. IgM and homocytotropic antibody of the reaginic type lacked this activity. The process was partially blocked by previous decomplementation of the rats, was not affected by previous reduction of the circulating leukocytes, and was partially suppressed by previous depletion of circulating platelets with an antiserum to rat platelets.
| 11,696
|
Fluctuation in activity of the molecular forms of cellular DNA polymerase during infection by SV40.
|
Infection of BSC-1 cells by SV40 brings about an increase of 7--11-fold in DNA polymerase activity, found in the nuclei and cytoplasm, respectively. The overall ratio between activites of DNA polymerase beta (3.1S) and DNA polymerase alpha (5.5S) remains fairly constant throughout infection. However,there is a large increase in DNA polymerase alpha2 (7.1S) in the cytoplasm, and its appearance in the nuclei late in infection. The addition of 1 M NaCl to infected cytoplasm,causes an aggregation of DNA polymerase alpha into a higher sedimenting form (9.8S), termed DNA polymerase alpha3. DNA polymerase alpha1, alpha2 and alpha3 are different molecular forms of the same enzyme, as can be seen by their similar inhibition by N-ethyl-maleimide, heparin and NaCl. However, this new activity, alpha3, is stimulated by dithiothreitol to a greater extent at pH 9.30 than at pH 7.94. The conformational changes induced in DNA polymerase and its increase in activity during infection with SV40 are discussed.
| 11,762
|
Thiol-protein disulphide oxidoreductases. Assay of microsomal membrane-bound glutathione-insulin transhydrogenase and comparison with protein disulphide-isomerase.
|
1. Inhibition of endogenous microsomal NADPH oxidase by CO enables membrane-bound glutathione-insulin transhydrogenase (EC 1.8.4.2) to be assayed conveniently by a linked assay involving NADPH and glutathione reductase (EC 1.6.4.2). 2. The specific activity of the enzyme in rat liver microsomal preparations is of the order of 1 nmol of oxidized glutathione formed/min per mg of membrane protein. 3. The specific activity of the enzyme is comparable in rough and smooth microsomal fractions, and the activity is not affected by treatment with EDTA and the removal of ribosomes from rough microsomal fractions. 4. Membrane-bound glutathione-insulin transhydrogenase is not affected by concentrations of deoxycholate up to 0.5%, whereas protein disulphide-isomerase (EC 5.3.4.1) is drastically inhibited. 5. On these grounds it is concluded that, in rat liver microsomal fractions, glutathione-insulin transhydrogenase and protein disulphide-isomerase activities are not both catalysed by a single enzyme species.
| 11,783
|
The action of psychotropic drugs on DOPA induced behavioural responses in mice.
|
The "DOPA potentiation" test in mice was investigated for its usefulness in the detection of compounds with antidepressant properties. It was found that the anti-depressant drugs imipramine, amitriptyline, 5-methylamino-acetyl-6-methyl-5,6-dihydro-phenanthridine-HCl (Org OI77) and 1,2,3,4,10,14b-hexahydro-2-methyl-dibenzo[c,f]pyrazino[1,2-a]azepine-HCl (mianserin, Org GB 94) potentiated the behavioural effect of DOPA in groups of mice which had been treated 17 h previously with the monoamine oxidase inhibitor (MAOI) iproniazid. However, the DOPA response was also potentiated by a variety of centrally acting drugs which do not have antidepressant properties (atropine, methysergide, chlordiazepoxide, apomorphine). The peptide hormones ACTH4-10 and desglycinamide lysine vasopressin had equivocal effects while melanocyte stimulating hormone release-inhibiting factor (MIF) had no effect on the DOPA response. The DOPA response was inhibited by the neuroleptics chlorpromazine and haloperidol. There appeared to be no correlation between the effects of the drugs on the behavioural responses elicited by DOPA and the changes found in the brain concentration of noradrenaline, dopamine, serotonin, gamma-aminobutyric acid, tryptophan and tyrosine. It is concluded that the "DOPA potentiation" test cannot be considered as a reliable test in the detection of anti-depressant compounds.
| 11,809
|
Fluorine-containing analogues of intermediates in the Shikimate pathway.
|
The phosphoenolpyruvate analogue (Z)-phosphoenol-3-fluoropyruvate is a substrate for phenylalanine-inhibitable 3-deoxy-D-arabino-heptulosonic acid-7-phosphate synthase from Escherichia coli. In the presence of excess erythrose 4-phosphate, apparent KM values of 65 and 38 muM were observed for phosphoenol-3-fluoropyruvate and phosphoenolpyruvate, respectively. Because the apparent Vmax for phosphoenol-3-fluoropyruvate is only 1.17% of that for phosphoenolpyruvate, one can study the former as an inhibitor of 3-deoxy-arabino-heptulosonic acid-7-phosphate synthase. Kinetic experiments showed phosphoenol-3-fluoropyruvate to be competitive with respect to phosphoenolpyruvate. Two distinguishable Ki values of 8 and 48 muM were obtained. The product (3S)-3-deoxy--3-fluoro-arabino-heptulosonic acid 7-phosphate was purified, characterized, and shown to act as a substrate for 5-dehydroquinate synthase. 3-Deoxy-3-fluoro-arabino-heptulosonic acid 7-phosphate, in contrast to 3-deoxy-arabino-heptulosonic acid 7-phosphate reacts slowly or not at all with reagents specific for 2-keto-3-deoxy sugars and is relatively resistant to oxidative cleavage by sodium periodate. The expected product of periodate oxidation, 3-fluoro-3-formylpyruvate, cannot be detected. This observation was clarified by studies with model compounds.
| 11,811
|
Studies on the ferrochelatase activity of isolated rat liver mitochondria with special reference to the effect of oxidizable substrates and oxygen concentration.
|
The mitochondrial ferrochelatase activity has been studied in coupled rat liver mitochondria using deuteroporphyrin IX (incorporated into liposomes of lecithin) and Fe(III) or Co(II) as the substrates. 1. It was found that respiring mitochondria catalyze the insertion of Fe(II) and Co(II) into deuteroporphyrin. When Fe(III) was used as the metal donor, the reaction revealed an absolute requirement for a supply of reducing equivalents supported by the respiratory chain. 2. A close correlation was found between the disappearance of porphyrin and the formation of heme which allows an accurate estimate of the extinction coefficient for the porphyrin to heme conversion. The value deltae (mM-1 - cm-1) = 3.5 for the wavelength pair 498 509 nm, is considerably lower than previously reported. 3. The maximal rate of deuteroheme synthesis was found to be approx. 1 nM - min-1 - mg-1 of protein at 37 degrees C, PH 7.4 and optimal substrate concentrations, i.e. 75 muM Fe(III) and 50 muM deuteroporphyrin. 4. Provided the mitochondria are supplemented with an oxidizable substrate, the presence of oxygen has no effect on the rate of deuteroheme synthesis.
| 11,817
|
Fluorescence properties of 2' (or 3')-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate and its use in the study of binding to heavy meromyosin ATPase.
|
2' (or 3')-O-(2,4,6-Trinitrophenyl) adenosine 5'-triphosphate (N3ph-ATP), which contains a Meisenheimer complex moiety, is one of the class of compounds which do not fluoresce in water but fluoresce both in low polarity solvents and when bound to the protein molecule. Fluorescence intensity of N3ph-ATP in the range of 540 nm, when excited at 410 nm, decreased with increasing the solvent polarity accompanying the increment of the wavelength of maximum emission. When bound to heavy meromyosin ATPase, the fluorescence properties of N3ph-ADP were almost the same as those of N3ph-ATP in a low polarity solvent, suggesting that N3ph-ADP was bound to hydrophobic area on heavy meromyosin ATPase.
| 11,824
|
Excretion and metabolism of nikethamide in the horse.
|
It is well known that nikethamide (N,N-diethylnicotinamide, CoramineR) is metabolized very rapidly to nicotinamide. Hence, there is difficulty in proving that nikethamide has been used as a doping substance because nicotinamide is a normal physiological metabolite in the organism as well as a vitamin preparation. However, an intermediate metabolite (N-ethylnicotinamide) was found by us in the urine of horses treated with CoramineR. This was characterized by gas chromatography/mass spectrometry, and synthesized and identified as being N-ethylnicotinamide. The excretion and metabolism of nikethamide after intramuscular injection in the horse was followed using quantitative gas chromatography of urine extracts over a period of several hours and the results of these experiments are reported. Changes in urinary pH had no significant effect upon either the metabolism or rate of excretion of the drug.
| 11,864
|
Studies on the multiple forms of gamma-glutamyltransferase.
|
In sera of 53 patients with highly raised gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) activity, the gamma-GT was separated by column chromatography on Sephadex DEAE A-50 into two fractions. In 35 sera only one gamma-GT fraction was found at a conductivity of 2.0--2.5 mS and in 18 sera two gamma-GT fractions were found at a conductivity of 0.2 mS and again at 2.0--2.5 mS. There was no opvious correlation to the underlying disease. In 20 sera the additional parameters, protein, protein electrophoresis, free and esterified cholesterol, bilirubin, triglycerides, lipoprotein pattern and lipoprotein X were examined. We recognized, that the two forms of the gamma-GT are not true isoenzymes but that the separation of the gamma-GT into two fractions is caused by a different distribution of the cholesterol containing lipoprotei,s.
| 11,908
|
Lorazepam in the treatment of neurosis.
|
An open study was carried out in 40 ambulatory neurotic patients with classical symptoms of anxiety to assess which of their symptoms responded most readily and favourably to treatment with lorazepam. Doses ranged from 2 mg to 15 mg daily and were adjusted to individual patient needs. The study period lasted 4 weeks and patients' individual symptoms were assessed weekly on a 4-point severity rating scale. The results showed a statistically significant and marked improvement during the first week for the majority of the 16 symptoms assessed, particularly emotional tension, irritability and apprehension. Symptoms with a cognitive element of anxiety were controlled to a lesser extent and were slower to respond. The few side-effects which were reported, mainly somnolence, appeared to be dose related and usually occurred during the first few days of treatment.
| 11,961
|
Immediate hypersensitivity to tuberculin. In vivo and in vitro studies.
|
Immediate responses of hypersensitivity to skin testing with purified derivative of tuberculin (PPD) were observed in 2.3 percent of 3,248 patients seen in an allergy clinic, and the relationship to delayed responses was questioned. Immediate cutaneous reactions to testing with PPD appeared in all age groups and occurred in nonatopic patients but were more common in atopic patients (p less than 0.005). Delayed cutaneous reactions to testing with PPD occurred in only three out of 76 patients with immediate reactivity. Antihistaminic suppression of immediate reactivity was not followed by evidence of delayed cutaneous reactivity. In vitro tests of lymphocytic stimulation revealed indices of stimulation with PPD to be similar both in patients with immediate and delayed cutaneous reactivity. Failure to manifest delayed cutaneous reactivity following immediate cutaneous reactions alone may be explained by antigen-antibody binding and phagocytosis, by suppressor T-lymphocytes, or by impaired release or lack of response to T-lymphocytic mediators. Adverse reactions to administration of BCG vaccine in patients with immediate cutaneous reactivity might be anticipated.
| 11,970
|
Plasma testosterone in prepubertal cryptorchid boys under long-term HCG therapy.
|
Plasma testosterone concentrations were determined before and after 6 weeks of human chorionic gonadotropin treatment in 36 prepubertal boys with bilateral or unilateral cryptorchidism. Mean +/- SD basal and post-treatment values (ng/100 ml) in the bilateral group were: treatment successful (n = 14): 32 +/- 19 and 302 +/- 49, treatment unsuccessful (n = 12): 20 +/- 15 and 176 +/- 73. The figures for the unilateral group were: treatment successful (n = 6): 23 +/- 9 and 244 +/- 41, treatment unsuccessful (n = 5): 22 +/- 11 and 264 +/- 102. In the bilateral group significant differences in the T response emerged when successfully treated boys were compared to unsuccessfully treated ones. It is concluded that Leydig cell function may be impaired in some cases of cryptorchidism.
| 12,073
|
Completed pregnancy following vascularized heterotopic autotransplantation of the Fallopian tube in the ewe.
|
Transplantation of the Fallopian tube is a technically feasible operation. Previous authors have reported pregnancies following turbo-ovarian transplants, but there appears to be no record of gestation following transplantation of the isolated oviduct. This communication illustrates the method that we have used to perform Fallopian tube transplants in the ewe and documents our first full-term pregnancy following this operation. It provides further evidence of the technical feasibility of Fallopian tube transplants.
| 12,117
|
Blastoid transformation of lymphocytes in response to spermatozoa.
|
Microlymphocyte transformation tests were done on 33 female rabbits immunized with different components of rabbit ejaculate. In rabbits injected with total ejaculate or washed spermatozoa a specific stimulation of lymphocytes could be demonstrated by exposure to washed spermatozoa. It is shown that it is necessary to notice the length of time for cultivation, the antigen concentration and especially the time-interval after the last immunization.
| 12,120
|
Reduced red cell membrane potential and acidification of the plasma in response to contrast materials. Time course of the alteration in plasma pH.
|
Radiographic contrast materials added to blood reduce the red cell membrane potential by balancing the internal impenetrable anions, hemoglobin and organic phosphates. In so doing, a redistribution of protons occurs such that plasma is acidified. The time course of acidification of plasma is measured in seconds, with a nadir of pH occurring 12 to 15 seconds after addition of Hypaque (1.5 to 3.0 ml/10 ml blood) and a half-time of acidification requiring about 6 seconds. The acidification process is slowed in part by an initial alkalosis due to Hypaque. The acidification of blood is more rapid after addition of Renografin (1.5 to 3.0 ml/10 ml blood) than after addition of Hypaque since the former solution is slightly acidic. The time course of plasma acidification indicates that a maximal reduction in blood pH may not occur in the capillaries of a regional circulation following injection of contrast materials into its afferent vessel, since the transit time of the contrast material may be less than the time required for maximal acidification of plasma.
| 12,127
|
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