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Biomedical subjects

J B Hammond

Publications and source records attributed to J B Hammond.

At least 19 recordsLinked to original sources
PubMed1998

Hepatic encephalopathy and role of antibenzodiazepines.

The majority of pharmacological agents are designed to accomplish a specific effect based on the established mechanisms of a disease. However, there are a few examples in which investigation of a pharmacological action has led to a previously unknown mechanism, i. e. the drug effect was observed initially before its mechanism became known. For example, the opiates had been in use for their analgesic effect for centuries before the question of endogenous substances that might explain the presence of opiate binding sites in the central nervous system (CNS) was raised, leading to the discovery of the opioids. A somewhat analogous development has occurred in another investigative arena, the observation that the administration of the benzodiazepine antagonist, flumazenil, has reversed the encephalopathy of hepatic failure. This has refocused research to discover whether one or more endogenous substances that bind to the benzodiazepine receptor in the CNS are responsible for the inhibition of CNS function of advanced liver failure. The investigative impetus was initiated by observations that patients with liver failure were highly vulnerable to benzodiazepines; therapeutic dosages precipitated coma or near-coma, and this effect was prolonged. The question was raised whether any given patient presenting with a coma-like state associated with advanced liver dysfunction might have received a benzodiazepine in the recent past, under circumstances overlooked or not recorded, that might be a contributing factor to the patient's condition. This led to testing the effects of the antagonist, with transitory success in arousing patients or improving their level of stupor. Further inquiry revealed that this improvement in mental function occurred in the absence of prior exposure to benzodiazepines. There followed a search for endogenous substances capable of binding to the benzodiazepine receptor, with CNS inhibitory effects. These investigations have resulted in the identification of several substances that may play a role in encephalopathy and can be displaced from the CNS receptor by properly designed antagonists-an ongoing investigative effort.

Flumazenil↗
PubMed1994

Phospholipid antibodies in alcoholic liver disease.

Alcoholic liver injury has been reported to be directed preferentially against the proteins of the cell membrane, sparing the phospholipids. However, antiphospholipid antibodies against certain cell membrane phospholipids are known to be associated with a variety of diseases. We undertook this investigation to determine whether antiphospholipid antibodies were present in the serum of patients with alcoholic liver disease. We investigated seventy long-term alcoholic patients (> 80 gm ethanol/day for > 1 yr) and 8 normal nonalcoholic controls by means of enzyme-linked immunosorbent assay to determine whether serum antibodies were generated against the following membrane phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin) and phosphatidic acid. Group 1 comprised alcoholic patients with normal liver function (n = 13), group 2 comprised alcoholic patients with abnormal liver function (n = 16), group 3 comprised patients with alcoholic hepatitis or cirrhosis (n = 41) and group 4 comprised nonalcoholic controls (n = 8). The antibody prevalence was 15% in group 1, 31% in group 2, 81% in group 3 and 0% in group 4. In group 3, 20 of 41 patients had antibodies against several cell membrane phospholipids (i.e., phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, cardiolipin and phosphatidylinositol). The antiphosphatidylethanolamine isotype was IgA or IgM in 25 of 41 of these patients. Both IgA (p < 0.01) and IgM (p < 0.008) antiphosphatidylethanolamine correlated significantly with disease severity. Antiphospholipid antibodies in alcoholic patients seem to reflect disease progression and correlate significantly with disease severity.

Adult↗
PubMed1989

Clinical zinc deficiency during adequate enteral nutrition.

Deficiency of zinc (Zn), resulting in characteristic skin changes resembling those seen in acrodermatitis enteropathica, has been reported in patients on total parenteral nutrition, but rarely in patients on long-term enteral feeding. Reported here is a patient who developed characteristic skin changes while he was receiving what was considered to be a balanced liquid enteral diet. The skin rash resolved with Zn supplementation.

Enteral Nutrition↗
PubMed1988

Molecular characterization of four forms of phosphofructokinase purified from potato tuber.

Four forms of phosphofructokinase (PFK) have been purified to apparent homogeneity from tubers of potato (Solanum tuberosum cv. Record). Each had a final specific activity of about 200 mumol.min-1.mg-1 protein. Similar forms of PFK were found in partially purified extracts from tubers and leaves of other potato cultivars and related wild species. The relative molecular masses of three forms of PFK were about 200,000 whereas that of the fourth PFK was greater than 800,000. The four forms of PFK contained different proportions of four polypeptides which had apparent relative molecular masses of 46,300, 49,500, 50,000, and 53,000. These polypeptides gave different patterns of peptide fragments after chemical and proteolytic cleavage. Western blots and immunoprecipitation studies using antibodies raised against the individual polypeptides showed that all four are associated with PFK. Thus, potato tubers contain four distinct forms of PFK that differ in their subunit composition.

Antibody Formation↗
PubMed1988

Molecular Comparison of Pyrophosphate- and ATP-Dependent Fructose 6-Phosphate 1-Phosphotransferases from Potato Tuber.

The aim of this work was to compare the molecular properties of pyrophosphate:fructose 6-phosphate 1-phosphotransferase (PFP) and ATP:fructose 6-phosphate 1-phosphotransferase (PFK). Both enzymes were purified to apparent homogeneity from potato tubers (Solanum tuberosum cv Record). Neither PFP nor PFK preparations contained detectable activity of the other enzyme. PFP was composed of two polypeptides of apparent molecular weight 58,000 and 55,700 whereas PFK contained four polypeptides of apparent molecular weight between 46,300 and 53,300. Chemical cleavage of individual PFP and PFK polypeptides gave a different set of fragments for each polypeptide. On Western blots antisera against PFP failed to cross-react with any of the four PFK polypeptides, and antibodies against PFK failed to bind to either of the PFP polypeptides. Antibodies that immunoprecipitate PFP activity had no effect on PFK activity. Conversely, antibodies against the four PFK polypeptides precipitated the activity of PFK, but not that of PFP. This work shows that potato tuber PFP and PFK are composed of distinct, unrelated polypeptides and indicate that interconversion between PFP and PFK is unlikely.

Journal Article↗
PubMed1988

Effect of nizatidine and cimetidine on betazole-stimulated gastric secretion of normal subjects: comparison of effects on acid, water, and pepsin.

The effect of nizatidine, a new histamine H2 receptor antagonist, on gastric secretory function of eight normal subjects stimulated with betazole, was compared with that of cimetidine. Single oral doses of 75 mg, 150 mg, and 300 mg nizatidine, 300 mg cimetidine, and a placebo were administered on separate occasions 1 h before betazole stimulation. Gastric secretions were recovered in 15-min fractions for the ensuing 2 h, and the pH, H+ concentration and output, volume, and pepsin concentration and output were determined. Doses of 150 mg and 300 mg nizatidine depressed the secretory response significantly more than did cimetidine. The antisecretory effects of 75 mg nizatidine was no different than that of 300 mg cimetidine. Nizatidine 300 mg inhibited pepsin output significantly more than volume. Although pepsin concentration was reduced more than volume, the difference was not significant. These observations, in contrast to results of previous studies, suggest a direct inhibition of pepsin secretion, although to a lesser extent than that of acid.

Adult↗
PubMed1988

Effects of low temperature on the respiratory metabolism of carbohydrates by plants.

The effects of lowering the temperature from 25 degrees C to 2-8 degrees C on carbohydrate metabolism by plant cells are considered. Particular emphasis is placed on the mechanism of cold-induced sweetening in tubers of potato (Solanum tuberosum). Temperatures between 0 and 10 degrees C were shown to cause a marked reduction in the rate of respiration of a wide range of plant tissues. At these temperatures the ability of suspension cultures of soybean (Glycine max), and callus cultures and tubers of potato to metabolize [14C]glucose was appreciably diminished. The detailed distribution of 14C showed that lowering the temperature decreased the proportion of the metabolized [14C]glucose that entered the respiratory pathways and increased the proportion converted to sucrose. Pulse and chase experiments, in which [14C]glucose was supplied to potato tubers at 2 and 25 degrees C, showed that lowering the temperature led to accumulation of label in hexose 6-phosphates, which were subsequently converted to sucrose. The patterns of 14CO2 production from specifically labelled [14C]glucose supplied to soybean suspension cultures and disks of potato tuber suggested that lowering the temperature reduced the activity of glycolysis more than that of the oxidative pentose phosphate pathway. It is argued that the above experiments demonstrate that lowering the temperature not only reduces the rate of carbohydrate metabolism but also alters the relative activities of the different pathways involved. A disproportionate reduction in glycolysis at the lower temperatures is suggested. Mature tubers of many varieties of potato accumulate sucrose and hexose when stored between 2 and 10 degrees C. Starch is the source of carbon for this synthesis of sugar. We could not detect cytosolic fructose-1,6-bisphosphatase in potato tubers and suggest that carbon for sugar synthesis in the cold leaves the amyloplast, not as triose phosphate, but probably as a six-carbon compound. Evidence is presented that phosphofructokinase (EC 2.7.1.11) plays a major role in regulating the entry of hexose 6-phosphates into glycolysis in potato tubers. Phosphofructokinase was purified from potato tubers and shown to consist of four forms. Three of these forms were shown to have higher Q10 values over the range 2-6 degrees C than over the range 12-16 degrees C and are regarded as being cold-labile. No such cold-lability was detected for the key enzymes involved in sucrose synthesis and the oxidative pentose phosphate pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1983

Leaf Starch Metabolism during the Growth of Pepper (Capsicum annuum) Plants.

Levels of starch and sugars, and the activities of amylase and starch phosphorylase were measured in expanding leaves harvested in early morning and early evening during the growth of pepper (Capsicum annuum L.; cv ;Bellboy') plants. The differences between starch levels 1 hour after dawn and 1 hour after dusk increased during the period of initial fruit expansion. This diurnal starch difference was strongly correlated with post-dusk amylase activities in leaves at both stages of expansion. There was also a strong correlation between levels of amylase in immature and those in mature leaves throughout the experiment. Phosphorylase activity showed no direct relationship to leaf starch levels, and there was no similarity between activities in immature and mature leaves. An increase in photosynthesis during plant development was observed which could account for the increased starch synthesis at initial fruit expansion.

Journal Article↗
PubMed1983

Spinach Leaf Intra and Extra Chloroplast Phosphorylase Activities during Growth.

The amino terminal sequence of the spinach (Spinacia oleracea L. cv Bloomsdale Long Standing) leaf cytoplasmic phosphorylase was determined and shown to have little similarity to the known sequence of the potato tuber phosphorylase. The antigenic reaction of spinach chloroplast phosphorylase and rabbit muscle phosphorylase a to antiserum prepared against spinach leaf cytoplasmic phosphorylase was tested. Neither phosphorylase gave a positive reaction when tested by immunodiffusion or neutralization of enzyme activity. The two spinach phosphorylases were assayed throughout the growth of the plant. Activity of cytoplasmic phosphorylase increased 4- to 8-fold at 30 to 35 days from sowing. Enzyme protein levels, as measured by antibody neutralization, increased by a similar amount. There was no corresponding increase in chloroplast phosphorylase activity. The chloroplast phosphorylase varied in parallel with the chloroplast enzyme ADPglucose pyrophosphorylase. Starch levels were high during the earlier stages of growth and then fell to a constant low level just before the increase in cytoplasmic phosphorylase. The results are discussed with respect to the relationship and functions of the two phosphorylases.

Journal Article↗
PubMed1983

ATP-Dependent Proteolytic Activity from Spinach Leaves.

Spinach (Spinacia oleracea CV Bloomsdale Long Standing) leaf cytoplasmic starch phosphorylase and rabbit muscle phosphorylase a were inactivated by incubation with partially purified leaf extract in the presence of ATP and Mg(2+). The inactivating factor(s) were heat stable and susceptible to protease attack. Phosphorylase inactivation was prevented by incubation in the presence of p-aminobenzamidine and phenylboronic acid, or prolonged treatment with phenylmethylsulfonyl fluoride or leupeptin for the ATP-stimulated inhibitory activity. Mg(2+) -dependent inactivation was prevented by incubation with leupeptin, phenylmethylsulfonyl fluoride, p-aminobenzamidine, or 5'-adenylate. ATP-mediated inactivation of phosphorylase was stimulated by Mg(2+) with a reduction in the apparent K(m) for ATP. Casein-degrading activities with the same properties of ATP and/or Mg(2+) stimulation, heat stability, and susceptibility to proteinase inhibitors were detected suggesting that phorphorylase inactivation was due to proteolysis. The activity was greatest at about the time of flowering and also appeared to depend on the light regime.

Journal Article↗
PubMed1979

Chemical and electron microscopic studies of factors associated with the release of penicillinase from Staphylococcus aureus.

The effect of various factors such as sodium chloride, sodium citrate, pH, linase by Staphylococcus aureus ATCC 14458 was investigated. Penicillinase was measured at selected time intervals from supernates of cultures grown in Antibiotic Medium 3 broth containing various concentrations of salts or buffers or from supernates of cultures treated with lysostaphin and subsequently disrupted by French press treatment. Incubation of cells with media containing either sodium chloride (5, 10, and 15%), sodium citrate (5 and 10%), or organic buffers (Tris-HCl, 2.5, 5.0, and 7.5%; BES, 10 and 20%) resulted in a significant stimulation of the release of penicillinase when compared to control cells. It was also observed that pH 7.0-7.5 was optimal for penicillinase activity and release. From studies of enzymatic and mechanical disruption of cells, it was observed that an increase in ionic strength of the suspending medium to certain optimal levels appeared to stimulate the conversion of penicillinase to an extracellular form. Electron microscopic studies revealed that a large number of mesosomal vesicles seemed to be present in cells incubated for 4 hours in media containing various concentrations of sodium chloride. It is proposed that either appearance of vesicles or convolution of cell membrane, which may be caused by further synthesis of new membrane, is involved in stimulation of the synthesis and release of membrane-bound penicillinase.

Alkanesulfonates↗
PubMed1977

Pancreatitis following the intraductal injection of partially purified enterokinase in dogs.

Experimental pancreatitis (PT) is induced by proximal and distal duodenal closure in the bile-duct-ligated dog, by causing duodeno-pancreatic reflux of lumenal secretions. It has been postulated that trypsin and enterokinase (EK) in the secretions activate trypsinogen within the pancreas, producing PT. There is supporting evidence for trypsin, but EK has not previously been investigated. To determine whether EK alone could cause PT, we injected saline suspensions of partially purified EK, and other test materials, into the duct of Wirsung of dogs and after 24 hr examined their pancreases and estimated the increment in serum amylase. Following 0.5% EK, both PT and hyperamylasemia (HA) ensued; HA without PT occured when EK was inactivated by heat, administered with trypsin inhibitor (TI), or administered in more dilute solution. Injection of TI or of hog gastric mucin likewise leads to HA but not to PT. It is concluded that the PT observed was due to EK activity, and that therefore EK could contribute to the production of PT observed was due to EK activity, and that therefore EK could contribute to the production of PT in the closed-duodenal-loop model. The HA observed in the absence of PT is unexplained but appears to be related to the colloidal properties of the materials injected.

Amylases↗
PubMed1976

Carbohydrate metabolism in Agaricus bisporus (Lange) Sing: changes in soluble carbohydrates during growth of mycelium and sporophore.

Changes in the ethanol-soluble carbohydrate content of Agaricus bisporus mycelium and sporophores grown on semi-defined media and commercial compost were studied. The accumulation of mannitol in the sporophore during its growth was not accompanied by an increase in mycelial mannitol. The other major soluble carbohydrate of the sporophore, trehalose, decreased throughout the growth of the sporophore; a parallel decrease was observed in the mycelium. The main accumulation of mannitol was in the pileus and stipe of the sporophore and was accompanied by a decrease in the soluble protein content of these tissues. Before fruiting, glucose and sucrose were present in the mycelial samples in similar quantities to mannitol, but their levels decreased during fruiting. Small quantities of glucose were present in the sporophore. The results are discussed in relation to the possible functions of the soluble carbohydrates.

Basidiomycota↗