Biomedical subjects
V Williams
Publications and source records attributed to V Williams.
Purification and properties of a procoagulant from peninsula tiger snake (Notechis ater niger) venom.
The procoagulant from Notechis ater niger was purified by gel filtration and anion exchange chromatography. It is a protein with an approximate mol.wt of 58,000 and in the presence of B mercaptoethanol is reduced to two chains with mol.wts of 37,000 and 23,000. The procoagulant has a pI of 7.3. The whole venom requires factor V to be present to bring about coagulation while Ca2+ and phospholipid are not essential, but when present stimulate this process. Normal prothrombin, but not decarboxyprothrombin, is converted by the venom. The activity of the procoagulant from Notechis species has been equated with factor Xa and in this study the similarity is noted, while ecarin-like characteristics in not requiring Ca2+ and phospholipid and an ability to clot heparinised plasma were also noted.
Clinical evaluation of a benzofuroquinolizine alpha 2-adrenoceptor antagonist.
The pharmacodynamics of MK-912, a benzofuroquinolizine alpha-adrenoceptor antagonist, were evaluated in healthy male volunteers. Eight subjects were treated with single oral doses of 0.1, 1.0, and 2.0 mg MK-912 and with a placebo in a four-period, double-blind, balanced, crossover study. Hemodynamic effects were observed with the 2.0 mg dose of MK-912 (peak increase from baseline in systolic and diastolic blood pressure +/- SEM, 14.8/9.2 +/- 2.9/2.1 mm Hg; peak increase in heart rate, 6.3 +/- 2.1 beats/min; p less than 0.05 versus placebo). Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG, a catecholamine metabolite) were increased 29% +/- 7% and 40% +/- 10% above baseline 2 hours after administration of 1.0 and 2.0 mg MK-912, respectively (p less than 0.01 compared with placebo). A modest dose-dependent reduction (5% to 10%) in fasting plasma glucose concentration was observed 1/2 to 1 hour after administration of 1.0 and 2.0 mg MK-912 (p less than 0.05 compared with placebo), without significant change in plasma insulin values. MK-912 was well tolerated, although it did have a mild anxiogenic effect. MK-912 is a potent, orally active agent with a pharmacologic profile consistent with alpha 2-adrenoceptor antagonism.
Severe envenomation with convulsion following multiple bites by a common brown snake, Pseudonaja textilis.
A case report of envenomation by a common brown snake, Pseudonaja textilis, in a 3.3 year old boy is presented. He suffered a brief grand mal convulsion 10 min after the bite which was shortly after removal of a compression bandage. A severe coagulopathy of the defibrination type required administration of five ampoules of brown snake monovalent antivenom (CSL). The association of envenomation by snakes and convulsions is discussed, as is the management of severe defibrination due to envenomation.
Development and characterization of a monoclonal antibody against the tube precipitin antigen of Coccidioides immitis.
Primary infection with Coccidioides immitis is commonly accompanied by the production of an immunoglobulin M precipitin antibody which is detected by the tube precipitin (TP) assay or by the immunodiffusion assay for TP antibody (IDTP assay). In the present investigation, spleen cells from spherulin-immunized BALB/c mice were fused with SP2/O Ag14 myeloma cells, and the resulting hybridomas were screened for antibody to the IDTP antigen by using an enzyme-linked immunosorbent assay. Positive hybridomas were cloned by limiting dilution and injected into pristane-primed mice for ascites production. Characterization of antibody reactivity was accomplished with the IDTP assay, two-dimensional immunoelectrophoresis, and immunoblotting. An immunoglobulin G1 monoclonal antibody which reacts with the IDTP antigen of C. immitis is described. The epitope that is recognized by the monoclonal antibody is also present, but to a lesser extent, on a second coccidioidal antigen which has been designated antigen 2. The monoclonal antibody was not reactive in immunoblots of histoplasmin or blastomycin, indicating that the epitope recognized by this antibody may be specific for C. immitis.
Variation in venom proteins from isolated populations of tiger snakes (Notechis ater niger, N. scutatus) in South Australia.
Pooled venom of peninsula tiger snakes (Notechis ater niger) from 11 insular populations and one mainland area, and from a single population of the mainland tiger snake (N. scutatus) were subjected to SDS-PAGE and gel filtration chromatography. At least 20 proteins were resolved in the SDS-PAGE, some of which were common to all populations, but many others were highly variable. Elution profiles produced through gel filtration showed a clustering of some populations with like profiles, while others had distinctive patterns. Similarities and dissimilarities between each population venom profile were appraised. Variation in the venom patterns was independent of prey type or local ecology. Statistical analysis of the SDS-PAGE banding patterns suggests that grouping of populations was dependent on their relative geographic position and the time of isolation of each population from one another and the mainland population.
Variation in venom constituents within a single isolated population of peninsula tiger snake (Notechis ater niger).
Venom from seven individuals in a homogeneous isolated population of Notechis ater niger on Roxby Island, off the South Australia coast, was subjected to gel filtration liquid chromatography and polyacrylamide gel electrophoresis to determine the extent of homogeneity of the venom constituent profile. The gel filtration chromatograms from six of the specimens were easily equated, while the seventh showed a slight variation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the venoms in a native and reduced state showed no detectable difference between six of the seven individuals, the remaining individual showing minor changes only in the native venom.
Epinephrine-containing test doses--don't throw the baby out with the bath water.
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Parkinson's disease: autotransplantation of adrenal medulla to caudate nucleus of the brain.
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Swivel walkers in Duchenne muscular dystrophy.
Swivel walkers were used to provide low energy ambulation in 11 boys with Duchenne muscular dystrophy in schools for the physically handicapped in South Glamorgan. Our preliminary experience suggests that these walkers improve the quality of life and provide a useful part of the physical treatment of the condition.
The effect of halothane general anaesthesia on platelet function.
Major craniofacial surgery has the potential for very large blood loss, frequently greater than one blood volume. In order that an assessment could be made of any deficiencies of platelet function or coagulation, tests were performed at intervals during the operation. None of the coagulation parameters showed variation below normal limits during the operation, but in vitro platelet aggregation showed significant decreases to several agonists.
Localization of chlorotetracycline fluorescence in human polymorphonuclear neutrophils.
Chlorotetracycline (CTC) has been used in many cells as a probe for membranous calcium. In polymorphonuclear neutrophils (PMN), the changes in CTC fluorescence upon stimulation are considered to monitor an early event in the activation process. Using quantitative video-enhanced microscopy, we report that in resting cells about 80% of the CTC signal emanates from the perinuclear region of the cell, indicating that internal structures are labeled with CTC. Approximately 20% of the total CTC fluorescence is taken up in a compartment sensitive to mitochondrial inhibitors, which is not present in neutrophils depleted of nucleus and granules or cytoplasts. Upon stimulation PMN loaded with CTC exhibit a rapid, biphasic decrease in fluorescence that is dose dependent. The second phase of the response is not seen in neutrophil cytoplasts. These results suggest that internal stores of CTC are responsive upon stimulation and could account for the later decrease in CTC fluorescence, whereas the early phase of CTC changes represents the plasma membrane response.
Conditioned taste aversion and conditioned drinking: two independent and opposing effects of 5-hydroxytryptophan?
Four experiments were carried out to examine the effects of 5-HTP in a conditioned taste aversion (CTA) paradigm. Using two-choice tests to measure the CTA, administration of 5-HTP following consumption of a novel flavour caused aversions to saline and saccharin solutions. In single-choice tests 5-HTP reduced consumption of saccharin, sugar cubes and beef-flavoured stock cubes, but only reduced saline consumption if animals had been pretreated with the 5-HTP decarboxylase inhibitor benserazide or the 5-HT receptor antagonist xylamidine, both of which act peripherally. Benserazide did not attenuate the CTA in any experiment. The results are interpreted in terms of two competing behavioural effects of 5-HTP: a centrally-mediated CTA and a peripherally-mediated conditioned drinking response.
Hemodynamic observations in severe preeclampsia complicated by pulmonary edema.
Ten patients with severe preeclampsia complicated by pulmonary edema were studied with invasive hemodynamic monitoring. Eight of 10 patients developed pulmonary edema during the postpartum period. Five patients had alterations in the colloid osmotic pressure--pulmonary artery wedge pressure gradient related to elevations in the pulmonary artery wedge pressure and a reduction in the colloid osmotic pressure. Three patients had hemodynamic findings consistent with pulmonary capillary leak. Two patients had evidence of left ventricular failure. In three of the patients, the central venous pressure was significantly lower than the simultaneously determined pulmonary artery wedge pressure during the acute phase of the pulmonary edema.
The distribution of blood group substance H and CEA in colorectal carcinoma.
The distributional patterns of blood group substance H and carcinoembryonic antigen (CEA) in 20 colorectal carcinomas from 17 patients, were investigated. Prognosis in these cases was more obviously related to histologic classification and pathologic stage than to BGS and CEA distributional patterns or preoperative plasma CEA levels. The distribution of H and CEA was similar to that found by other investigators for A and B blood group substances with the exception that areas of identical localization could be shown in at least some areas of each tumor studied that was positive for both antigens. The relationship of CEA and BGS is as yet unknown, but it seems probable that they can occur simultaneously in the same tissue.
Neurological outcome correlated with spinal evoked potentials in a spinal cord ischemia model.
Occlusion of the abdominal aorta of the rabbit by inflating the balloon of a Swan-Ganz catheter positioned in the aorta is a simple and reliable method of producing spinal cord ischemia. The electrophysiological, neurological, and neuropathological correlates of ischemia with progressively longer durations and of ischemia after drug interventions were studied with the goal of developing an easily monitored, reproducible model for central nervous system ischemia. The percentage of animals developing paraplegia after varying periods of ischemia was zero after 15 minutes, 30% after 17 minutes, 33% after 20 minutes, 38% after 25 minutes, and 100% after 60 minutes of ischemia. After 25 minutes of ischemia the percentage of animals developing paraplegia was 87% when they were awake and not ventilated during ischemia and reperfusion, but dropped to 38% in animals that were paralyzed, sedated with ketamine, and ventilated, and when the metabolic acidosis that follows aortic occlusion was corrected during reperfusion. Pretreatment with thiopental, hypothermia, naloxone, methylprednisolone, and verapamil changed the percentage of animals developing paraplegia after 25 minutes of ischemia to 0%, 0%, 25%, 40%, and 100%, respectively. The component waves of the spinal somatosensory evoked potential (SSEP) disappeared sequentially during ischemia in the following order: P2, N4, N3, N2, and N1. After reperfusion, the SSEP components returned in reverse order of their disappearance. In the untreated animals, absence of the N3 wave for more than 10 minutes during ischemia was always followed by a neurological deficit. Pretreatment with thiopental or hypothermia permitted longer periods of electrophysiological silence without permanent neurological deficit. The ratio of the amplitude of N3 to N1 (N3/N1) was at least 70% of the control level, and N4 and P2 amplitudes were at least 30% of the control level at 120 minutes after reperfusion in all animals that had a normal outcome. Return of the N3/N1 amplitude to at least 90% of the control level or return of N3/N1 to 70% to 89% of control and P2 to at least 60% of control at 120 minutes after reperfusion reliably correlated with a normal 48-hour motor examination in animals with and without drug interventions.
Rostral spread of epidural morphine.
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