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Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 253 records · Page 14Linked to original sources
PubMed1986

Cationic activation of galactosyltransferase from rat mammary Golgi membranes by polyamines and by basic peptides and proteins.

Galactosyltransferase (EC 2.4.1.22) requires bivalent metal ions for its activity. However, preparations of this enzyme solubilized from Golgi membranes of lactating rat mammary gland were shown to be activated not only by Mn2+, Ca2+ and Mg2+, but also by spermine, spermidine, lysyl-lysine, ethylenediamine and other diaminoalkanes, and by a range of basic proteins and peptides, including clupeine, histone, polylysine, ribonuclease, pancreatic trypsin inhibitor, cytochrome c, melittin, avidin and myelin basic protein. Both N-acetyl-lactosamine synthetase and lactose synthetase activities were enhanced. A basic protein fraction was isolated from bovine milk and shown to activate galactosyltransferase at low concentrations. The polyanions ATP, casein, chondroitin sulphate and heparin reversed the activation of galactosyltransferase by several of the above substances. Galactosyltransferase, assayed as a lactose synthetase, showed a 10-fold greater affinity for glucose when Mn2+ ions were replaced by clupeine or by ribonuclease as cationic activator. Evidence was obtained for the presence of an endogenous cationic activator in solubilized Golgi membrane preparations which evoked a similar low apparent Km,glucose. The findings are discussed in the light of cationic activations of glycosyltransferases generally, of the porous nature of the Golgi membrane, and of the unlikelihood of bivalent metal ions being the physiological activators of galactosyltransferase. It is suggested that the natural cationic activator of lactose synthetase may be a secretory protein acting in a manner analogous to the enzyme's activation by alpha-lactalbumin. A scheme is proposed for the two-stage synthesis of lactose and phosphorylation of casein within the cell, to accommodate the apparent incompatibility of these two processes.

Animals↗
PubMed1986

Neither a germ line-specific nor several somatically expressed genes are lost or rearranged during embryonic chromatin diminution in the nematode Ascaris lumbricoides var. suum.

Ascaris lumbricoides var. suum is a parasitic nematode of pigs. Its embryos undergo chromatin diminution between the third and fifth cleavages, resulting in the loss of about 30% of the DNA from all somatic precursor cells while the germ line DNA stays intact. Most of the eliminated DNA has been shown to be satellite sequences. Theodor Boveri [(1910) In "Festschrift fur R. Hertwig, III," Vol. 3, pp. 131-214, Fischer] proposed that functions essential only to the germ line might be lost from the soma. We have examined this proposal by cloning a gene encoding the major sperm protein (MSP) using a cloned MSP gene from Caenorhabditis elegans as a probe. The MSP appears to be expressed only in the testis of Ascaris, as it is in Caenorhabditis. Actin and alpha tubulin were also cloned to serve as somatically expressed gene controls. By probing Southern blots of somatic and germ line DNA with these cloned genes, it was found that none of them was lost or rearranged during chromatin diminution. Thus at least one germ line-specific gene is neither lost nor rearranged during chromatin diminution. We also found that the two nematode species differ widely in their numbers of both MSP and actin genes. Caenorhabditis has greater than 30 MSP genes, but Ascaris has no more than three; whereas Ascaris has many more actin genes than Caenorhabditis.

Actins↗
PubMed1986

Monoclonal antibodies that recognize a polypeptide antigenic determinant shared by multiple Caenorhabditis elegans sperm-specific proteins.

Four monoclonal antibodies that are directed against antigens present in sperm and absent from other worm tissues were characterized. Antibody TR20 is directed against the major sperm proteins, a family of small, abundant, cytoplasmic proteins that have been previously described (Klass, M. R., and D. Hirsh, 1981, Dev. Biol., 84:299-312; Burke, D. J., and S. Ward, 1983, J. Mol. Biol., 171:1-29). Three other antibodies, SP56, SP150, and TR11, are all directed against the same set of minor sperm polypeptides that range in size from 29 to 215 kD. More than eight different sperm polypeptides are antigenic by both immunotransfer and immunoprecipitation assays. The three antibodies are different immunoglobulin subclasses, yet they compete with each other for antigen binding so they are directed against the same antigenic determinant on the multiple sperm proteins. This antigenic determinant is sensitive to any of six different proteases, is insensitive to periodate oxidation or N-glycanase digestion, and is detectable on a polypeptide synthesized in vitro. Therefore, the antigenic determinant resides in the polypeptide chain. However, peptide fragments of the proteins are not antigenic, thus the determinant is likely to be dependent on polypeptide conformation. The antigenic determinant shared by these proteins could represent a common structural feature of importance to the localization or cellular specificity of these proteins.

Animals↗
PubMed1986

Membrane and cytoplasmic proteins are transported in the same organelle complex during nematode spermatogenesis.

During the development of pseudopodial spermatozoa of the nematode, Caenorhabditis elegans, protein synthesis stops before differentiation is completed. Colloidal gold conjugates of monoclonal antibody SP56, which binds to the surface of spermatozoa, and TR20, which recognizes the major sperm cytoplasmic protein (MSP), were used to label thin sections of testes embedded in Lowicryl K4M in order to follow polypeptides from their synthesis early in spermatogenesis to their segregation to specific compartments of the mature cell. Both antigens are synthesized in primary spermatocytes and are assembled into a unique double organelle, the fibrous body-membranous organelle (FB-MO) complex. However, the antigens are localized in different regions of this FB-MO complex. As described in detail, the assembly of proteins into the FB-MO complex allows both membrane and cytoplasmic components to be concentrated in the spermatids after meiosis. Then, the stepwise disassembly of this transient structure ensures delivery of each component to its final destination in the mature spermatozoan: MSP filaments in the fibrous body depolymerize, releasing MSP into the cytoplasm and the membranous organelles fuse with the plasma membrane, delivering SP56 antigen to the surface.

Animals↗
PubMed1986

Pharmacokinetics of atracurium and its metabolites.

The pharmacokinetic profile of atracurium was studied in normal patients and in patients with renal failure, renal-hepatic failure, or hepatic disease. Its short elimination half-life was not significantly altered by renal failure, but in patients with severe liver disease elimination of its metabolites was prolonged, necessitating care during long-term i.v. infusions in patients with hepatic dysfunction.

Atracurium↗
PubMed1986

Reversible agranulocytosis due to meprobamate.

A 52 year old man admitted to hospital in a toxic state, was found to have agranulocytosis, which recovered when an analgesic containing meprobamate was stopped. The patient was known to have had similar symptoms 9 months previously when the drug was first used, thereby demonstrating an idiosyncratic reaction to meprobamate.

Agranulocytosis↗
PubMed1986

Comparison of two methods of islet preparation and transplantation in dogs.

Seventy-nine mongrel dogs underwent total pancreatectomy. Fifteen dogs served as apancreatic controls and died 7.0 +/- 4.2 days later (mean +/- SD). The pancreases of 44 dogs (group 1) were intraductally distended by manual injection of Hanks' balanced salt solution (HBSS). Thereafter each organ was mechanically disrupted and subjected to collagenase digestion as described by Mirkovitch et al. The pancreases of 20 dogs (group 2) were intraductally distended and subsequently perfused with collagenase by a roller pump. The organs were then mechanically disrupted and filtered through screens as described by Horaguchi et al. The resulting tissue suspensions were injected into the spleens of the dogs as autotransplants in both groups, by direct punction of the splenic capsule in group 1 and by retrograde infusion via a splenic vein tributary in group 2. The functional outcome was better in group 2 than in group 1, as assessed by the number of animals that became normoglycemic after transplantation [15/20 (75%) vs. 13/44 (30%); P = .0025]. The degree of islet purification, as measured by an increase in the tissue insulin/amylase ratio, was higher in group 2, and in both groups it was higher in normoglycemic than in hyperglycemic animals. The percent engraftment [i.e., amount of insulin recovered from spleen as percent of tissue transplanted (mean, 15.4% in group 1 and 14.5% in group 2) or as percent of original pancreas (mean, 4.9% in group 1 and 4.4% in group 2)] was low in both groups but again was higher in normoglycemic than in hyperglycemic animals within each group. In conclusion, both the degree of engraftment and purification and the route of implantation influenced the functional outcome after dispersed pancreatic islet autotransplantation to the spleen of totally pancreatectomized dogs, with purified tissue injected retrogradely functioning better than unpurified tissue injected directly.

Amylases↗
PubMed1985

Role of fructose 2,6-bisphosphate in mammary gland of fed, starved and re-fed lactating rats.

The fructose 2,6-bisphosphate (Fru-2,6-P2) content and intracellular concentration of lactating mammary gland was measured in fed, starved and re-fed rats. There was little or no change on starvation, and about 1.5-fold rise on re-feeding, contrasting with estimated glycolytic changes of about 10-fold. The 6-phosphofructokinase (PFK-1) activity of mammary extracts was highly sensitive to added Fru-2,6-P2 under all conditions examined, and appeared to approach saturation at physiological concentrations of this effector. The activity of mammary PFK-1 measured under optimal and 'physiological' conditions suggested that this enzyme operates in vivo at about 24% of maximal rate, and is likely to be an important rate-limiting factor in mammary glycolysis.

Animals↗
PubMed1985

Treatment of endometriosis with danazol: report of a 6-year prospective study.

Presented are the results of a 6-year prospective study designed to evaluate the effectiveness of danazol for the treatment of endometriosis. Ninety-six patients completed 6 months of therapy at a dosage of 800 mg daily, and 107 patients completed therapy with 400 mg daily. No difference was reported in the incidence of side effects, regardless of dosage. Gross resolution of disease (as determined by second-look laparotomy or laparoscopy) was evaluated in 110 patients and found to be similar, regardless of dosage. Ovarian endometriosis greater than 1 cm was observed to respond significantly less well to danazol than peritoneal or ovarian disease less than 1 cm. Pregnancy rates for 157 patients with no other discernible causes of infertility were slightly higher for the 800-mg danazol regimen than for the 400-mg regimen. In patients with mild disease, the use of danazol alone resulted in pregnancy rates lower than those achieved with conservative surgery alone. Its use preoperatively for all stages of disease resulted in slightly higher pregnancy rates than when conservative surgery alone was employed. Danazol was less effective when used postoperatively. No differences were observed between three classification schemes in their ability to predict subsequent prognosis for conception.

Adult↗
PubMed1985

10-Ketonaltrexone and 10-ketooxymorphone.

Ethylketocyclazocine (1) has greater kappa/mu selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from naltrexone 3-methyl ether and oxycodone, respectively. Bioassays in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum and in the mouse vas deferens, in addition to brain binding assays, demonstrated that 10 and 11 were far less potent than naltrexone (2) and oxymorphone (3) at mu sites and also had little affinity for kappa and delta sites. It is concluded that introduction of the 10-keto group in naltrexone and oxymorphone diminished opioid effects at all binding sites.

Animals↗
PubMed1985

Neuromuscular blockade in dystrophia myotonica with atracurium besylate.

The anaesthetic management of a young woman with dystrophia myotonica is described. The use of atracurium and monitoring of neuromuscular block allowed suxamethonium and neostigmine to be avoided, and thereby to reduce the risk of myotonic contractions. No adverse sequelae were observed.

Adult↗
PubMed1985

Sudden death due to isolated adrenal tuberculosis.

A 65 year old man admitted to hospital for investigation of pleural thickening was found to have carcinoma of the prostate with metastases. Before investigations were completed the patient collapsed unexpectedly with hypotension. A post mortem examination revealed tuberculosis of both adrenal glands without evidence of tuberculosis in any other organ.

Adrenal Gland Diseases↗
PubMed1984

Lactose and fatty acid synthesis in lactating-rat mammary gland. Effects of starvation, re-feeding, and administration of insulin, adrenaline, streptozotocin and 2-bromo-alpha-ergocryptine.

Lactose synthesis and fatty acid synthesis in intact lactating-rat mammary gland were measured simultaneously by incorporation of [U-14C]glucose and of both [U-14C]glucose and 3H2O respectively. Both processes were almost abolished by overnight starvation. Self-re-feeding caused recovery of lipogenesis to 100% of normal by 2 h and to 170% by 5 h. Lactose synthesis recovered to 80% of normal by 5 h. Food intubated to starved rats caused partial recovery in 3 h, standard diet favouring lactose synthesis and sugars favouring lipogenesis. Casein and starch were ineffective. Olive oil intubated to fed rats suppressed lipogenesis greatly and lactose synthesis slightly. Paraffin oil or water partly mimicked these effects. Adrenaline (subcutaneous) decreased lipogenesis from glucose, whereas insulin (subcutaneous) caused hypoglycaemia associated with loss of lactose synthesis but unchanged fatty acid synthesis. Streptozotocin and 2-bromo-alpha-ergocryptine (CB-154) impaired lipogenesis but not lactose synthesis. The results are interpreted in terms of competition for intracellular glucose by biosynthetic pathways for lactose and fat, and the possible implications for variations in milk composition are discussed.

Animals↗