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Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 271 records · Page 15Linked to original sources

Pore properties of the Golgi membrane from lactating-rat mammary gland. Effects of pH and temperature and reconstitution into phospholipid vesicles.

Golgi-membrane vesicle penetration was studied by osmotic lysis. Pronounced temperature dependence of mannitol and mannoheptitol penetration over 0-37 degrees C gave linear Arrhenius plots, with activation energies of 75 and 117 kJ/mol respectively. Glucose penetration was constant over pH 5-9, but was respectively faster and slower at higher and lower pH values. Solubilized, dialysed, heat-stable extracts of Golgi membrane were reconstituted into egg yolk phospholipid membranes with apparent recovery of specific permeability. Penetration is interpreted in terms of a pore, for which the Renkin equation predicts a radius of about 0.54 nm.

Animals↗

Conservative approach to the elderly patient with burns.

A retrospective analysis of 55 elderly patients (more than 60 years of age) was undertaken to compare results of conservative management to standard operative treatment. Thirty-one percent of the patients died early from their injury. Twenty-three patients were treated without operation, with emphasis on careful outpatient wound care and physical therapy. The remaining 15 patients required excision and grafting of burn wounds or amputation. Conservatively managed patients had fewer complications, a shorter hospital stay, and functional results equal to the operative group. These results suggest that many elderly burn patients can be managed without operation with good outcome and lessened morbidity.

Aged↗

Stereoselective metabolism and pharmacogenetic control of 5-phenyl-5-ethylhydantoin (nirvanol) in humans.

Aromatic hydroxylation of 5-phenyl-5-ethylhydantoin (PEH) has been investigated in humans. Single oral doses of S-PEH (247 mumol) were given to seven extensive and seven poor hydroxylators of mephenytoin. Urinary recovery of PEH and 5-(4-hydroxyphenyl)-5-ethylhydantoin (4-OH-PEH) indicated that all extensive metabolizer subjects excreted appreciable quantities of 4-OH-PEH, whereas all poor metabolizer subjects had only trace amounts of 4-OH-PEH in their urine. Four extensive metabolizer subjects received dual radiolabeled (S-[14C]PEH, R-[3H]PEH) pseudoracemic (494 mumol R-PEH, 494 mumol S-PEH) PEH and had serial urine and blood samples collected over 16 days. The urinary excretion rates of S-PEH and S-4-OH-PEH had half-lives of approximately 4.5 days whereas those of R-PEH and R-4-OH-PEH were approximately 10 days. The initial S/R ratio of 4-OH-PEH in urine was 14:1 whereas that of PEH was 1:1. Stereoselective hydroxylation in these four subjects was confirmed by the negligible recovery of 4-OH-PEH after oral administration of R-PEH (494 mumol). After racemic administration, the sum of S-and R-PEH plasma concentrations declined biexponentially with half-lives of the alpha- and beta-phases being consistent with the total plasma concentration reflecting the sum of the different rates of elimination of the two enantiomers. These results are consistent with the hypothesis that the same drug metabolizing enzymes are involved in the aromatic hydroxylation of S-mephenytoin and S-PEH.

Adolescent↗

Identification of a large multigene family encoding the major sperm protein of Caenorhabditis elegans.

DNA fragments corresponding to genes encoding the MSP of Caenorhabditis elegans sperm have been isolated by recombinant DNA techniques. Analyses of individual genomic clones suggest that there are multiple MSP genes that are dispersed in the genome. From restriction enzyme digests of genomic DNA fractionated and hybridized with an MSP complementary DNA probe, there appear to be more than 30 MSP genes in the genome. Despite the occurrence of this large dispersed multigene family, the MSP messenger RNA from both males and hermaphrodites is homogene in size. There are at least three different proteins of identical molecular weight but different isoelectric point that cross-react with anti-MSP antisera. Each protein is a primary translation product with no detectable post-translational modifications, suggesting that at least three of the MSP genes are expressed.

Animals↗

The initiation of spermiogenesis in the nematode Caenorhabditis elegans.

Spermiogenesis in nematodes involves the activation of sessile spherical spermatids to motile bipolar amoeboid spermatozoa. In Caenorhabditis elegans males spermiogenesis is normally induced by copulation. Spermatids transferred to hermaphrodites as well as some of those left behind in the male become spermatozoa a few minutes after mating. Spermiogenesis can also be induced in vitro by the ionophore monensin (G.A. Nelson and S. Ward, 1980, Cell 19, 457-464) and by weak bases such as triethanolamine. Both triethanolamine and monensin cause a rapid increase in intracellular pH from 7.1 to 7.5 or 8.0. This pH increase precedes the subsequent morphological events of spermiogenesis. Triethanolamine or monensin must be present throughout spermiogenesis for all cells to form pseudopods, but once pseudopods are formed the inducers are unnecessary for subsequent motility. The pH induced spermiogenesis is inhibited by drugs that block mitochondria or glycolysis. Protease treatment can also induce spermiogenesis without increasing intracellular pH, apparently bypassing the pH-dependent steps in activation and the requirement for glycolysis. These results show that the initiation of spermiogenesis in C. elegans, like some steps in egg activation and the initiation of sea urchin sperm motility, can be induced by an increase in intracellular pH, but this pH change can be bypassed by proteolysis.

Animals↗

Pharmacokinetics of atracurium in acute hepatic failure (with acute renal failure).

The pharmacokinetic profile of atracurium was examined in six patients with acute hepatic and renal failure and compared with that in six normal patients after an i.v. bolus (mean dose 0.7 mg kg-1). The plasma concentrations were measured by high pressure liquid chromatography and the data fitted to a two-compartment pharmacokinetic model. The results from the two groups were not significantly different, giving a mean plasma elimination half-life of 22 min in patients with severe hepatic and renal failure and a mean of 21 min in the normal group.

Acute Kidney Injury↗

Pharmacokinetics of atracurium besylate in healthy patients (after a single i.v. bolus dose).

The plasma decay of atracurium besylate was examined in two groups of six patients. Group I received atracurium 0.6 mg kg-1 and group II 0.3 mg kg-1 as a single bolus dose i.v. The plasma concentrations were measured by high performance liquid chromatography. An individual two-compartment pharmacokinetic model was used for interpretation. The results from the two groups were not significantly different, giving overall mean values of 2 min (+/- 0.2 SEM) for the distribution half-life (T1/2 alpha), 19.9 min (+/- 0.6) for the elimination half-life (T1/2 beta), 5.5 ml min-1 kg-1 (+/- 0.2) for total clearance (Cl) and 157 ml kg-1 (+/- 7) for total distribution volume (Varea).

Adult↗

Conditions for tracheal intubation using atracurium compared with pancuronium.

Intubating conditions were compared using atracurium 0.6 and 0.8 mg kg-1 and pancuronium 0.08 and 0.1 mg kg-1 in 96 patients. They were randomly allocated and studied at 30, 45, 60 or 75 s after injection of the drug. Smooth intubation was not possible before 60 s with either drug and in 11 patients intubation could not be achieved at the chosen time. Atracurium 0.6 mg kg-1 and pancuronium 0.08 mg kg-1 gave comparable results. Atracurium 0.8 mg kg-1 gave intubating conditions comparable to those obtained with pancuronium 0.1 mg kg-1 at 45 and 75 s and slightly better conditions at 30 and 60 s.

Adolescent↗

Biosynthesis of galactinol by lactose synthetase.

1. myo-Inositol was galactosylated by UDP-galactose in the presence of alpha-lactalbumin plus rat mammary Golgi membranes enriched in galactosyltransferase (EC 2.4.1.22). 2. The isolated product migrated on GLC as two peaks of material, apparently identical to galactinol (galactosylinositol) isolated from rat milk. 3. These findings make it likely that in vivo lactose synthetase is responsible for converting inositol into galactinol within the Golgi lumen. 4. This is consistent with the ability of inositol to penetrate the Golgi membrane in vitro, and renders less likely a previously proposed role of beta-galactosidase (EC 3.2.1.23) in mammary galactinol synthesis.

Animals↗

Membrane flow during nematode spermiogenesis.

Two distinct types of surface membrane rearrangement occur during the differentiation of Caenorhabditis elegans spermatids into amoeboid spermatozoa. The first, detected by the behavior of latex beads attached to the surface, is a nondirected, intermittent movement of discrete portions of the membrane. This movement starts when spermatids are stimulated to differentiate and stops when a pseudopod is formed. The second type of movement is a directed, continual flow of membrane components from the tip of the pseudopod to its base. Both membrane glycoproteins and fluorescent phospholipids inserted in the membrane flow backward at the same rate, approximately 4 micrometers/min, although their lateral diffusion coefficients in the membrane differ by at least a factor of 5. These observations suggest that pseudopodial membrane movement is due to bulk flow of membrane components away from the tip of the pseudopod.

Animals↗

Caenorhabditis elegans spermatozoan locomotion: amoeboid movement with almost no actin.

The pseudopods of Caenorhabditis elegans spermatozoa move actively causing some cells to translocate when the sperm are dissected into a low osmotic strength buffered salts solution. On time-lapse video tapes, pseudopodial projections can be seen moving at 20-45 micrometers/min from the tip to the base of the pseudopod. This movement occurs whether or not the cell is attached to a substrate. Translocation of the cell is dependent on the substrate. Some spermatozoa translocate on acid-washed glass, but a better substrate is prepared by drying an extract of Ascaris uteri (the normal site of nematode sperm motility) onto glass slides. On this substrate more than half the spermatozoa translocate at a velocity (21 micrometers/min) similar to that observed in vivo. Translocating cells attach to the substrate by their pseudopodial projections. They always move toward the pseudopod; changes in direction are caused by changes in pseudopod shape that determine points of detachment and reattachment of the cell to the substrate. Actin comprises less than 0.02% of the proteins in sperm, and myosin is undetectable. No microfilaments are found in the sperm. Immunohistochemistry shows that some actin is localized in patches in the pseudopod. The movement of spermatozoa is unaffected by cytochalasins, however, so there is no evidence that actin participates in locomotion. Fertilization-defective mutants in genes fer-2, fer-4, and fer-6 produce spermatozoa with defective pseudopodial projections, and these spermatozoa are largely immotile. Mutants in the spermatozoa do not translocate. Thus pseudopod movement is correlated with the presence of normal projections. Twelve mutants with defective muscles have spermatozoa with normal movement, so these genes do not specify products needed for both muscle and nonmuscle cell motility.

Actins↗