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Biomedical subjects

J F Williams

Publications and source records attributed to J F Williams.

At least 163 records · Page 9Linked to original sources
PubMed1986

The metabolic significance of pentose cycle measurements in perfused liver.

The controversial dissension concerning the nature of the pentose cycle in liver is investigated. The metabolism of [2-14C]Glc and [1-14C]Rib in chronically perfused normal and regenerating rabbit liver and acutely perfused rat liver are used to test the mechanistic predictions and contribution of the F-type pentose cycle. 14C was traced in Glc, Glc 6-P, Fru 6-P, glycogen and Rib 5-P. None of the data complied with the critical theoretical limits set for the C-1/C-3 ratio (the identity badge of the F-type pentose cycle or pathway) for all values of F-type PC from 0-100%. Thus apparent F-type PC measurements using the Katz & Wood method gave a wide scatter of calculated values. The 14C distributions in Rib 5-P do not conform with the predictions of the F-type PC but are in agreement with the many previous results of similar experiments reported by Hiatt and co-workers. In perfused rat liver the C-1/C-3 constants in Glc 6-P and glycogen also failed to conform with F-PC theory following the metabolism of [2-14C]Glc. The metabolism of [5-14C]Glc and distribution of 14C in Glc 6-P and glycogen showed that L-type PC was 18%, in close agreement with a previous published value of 22% for rat hepatocytes. Metabolism of [6-14C]Glc and [4-14C]Glc (as [4,5,6-14C]Glc) showed that Pyruvate Recycling was active in perfused rat liver. None of the data from these comprehensive investigations can confirm the results of the recent study reported by the Landau laboratory on the pentose pathway metabolism of Glc and Rib in perfused rat liver.

Animals↗
PubMed1985

Angiostrongylosis in a greyhound.

Angiostrongylus vasorum infection was diagnosed at necropsy of a Greyhound imported from Ireland. Granulomatous masses and pulmonary arterial thrombosis were associated with adult and larval stages of metastrongyle nematodes. Hemorrhages, widespread in subcutaneous tissue and muscle masses and at serosal surfaces, were suggestive of the onset of the bleeding disorder that has been seen in angiostrongylosis in Europe. The mollusks that can serve as intermediate hosts are known to be common in the United States, and therefore establishment of this parasite from imported racing or breeding stock is possible.

Angiostrongylus↗
PubMed1985

Peritoneal cestodiasis in a dog.

An unusual case of progressive abdominal distention due to massive infection with proliferating cestode larvae is reported in an imported Italian Greyhound. Cystic parasites, first detected incidentally at ovariohysterectomy, eventually infiltrated most abdominal organs and entered the pericardium. Morphologic, histologic, and electromicroscopic observations did not permit definitive identification of the parasites; however, they were not typical of the larval forms of species of either Taenia or Mesocestoides, which have been associated with this rare condition in the United States.

Animals↗
PubMed1985

Identification and measurement of D-glycero D-ido octulose 1,8-bisphosphate: D-altro-heptulose 7-phosphotransferase enzyme in tissues with L-type pentose phosphate pathway activity.

The enzyme D-glycero D-ido octulose 1,8-bisphosphate:D-altro-heptulose 7-phosphotransferase (abbreviated to phosphotransferase, PT) catalyses the transfer of the phosphate ester group at C-1 between altro-heptulose (sedoheptulose) and octulose phosphate intermediates of the L-type pentose pathway. Using synthetically prepared and 14C-labelled octulose mono- and bisphosphates, two methods are described for the measurement of the catalytic capacity of the PT reaction operating in both the "forward" and "reverse" modes of L-type pentose pathway operation. PT activity was found in normal, regenerating and foetal rat liver, rat heart, rat epididymal fat pad, rat kidney, brain and skeletal muscle, extracts of C. fusca, pea leaf and a variety of tumour tissues. The highest activity of the enzyme was found in the neoplasms. The Michaelian kinetic constants, temperature and pH optima for the reaction of the enzyme from rat liver together with an assortment of its substrate specificities have been determined. Vanadate anion was found to inhibit the enzyme and the pattern of inhibition suggests that the PT may act by a sequential mechanism. Neither arabinose 5-phosphate nor inorganic phosphate showed any effect on the catalytic activity of the PT enzyme in liver.

Animals↗
PubMed1985

Onchocerciasis in Sudan: the Abu Hamed focus.

The current status of onchocerciasis in Abu Hamed, Northern Province, Sudan, was studied. Of 208 persons attending out-patient clinics in villages in this region, 71 were microfilariae-positive on skin snips or had palpable nodules. Microfilariae and worms in nodules were identified as Onchocerca volvulus. No microfilariae were seen in peripheral blood. Most nodules and microfilariae were found in the pelvic region, but the intensity of infection was uniformly low (av. less than 3 mf/mg). Despite this, signs of onchocercal dermatitis were common and severe, especially over the buttocks. Papular eruptions and scarring often appeared to lead to black-grey hyperpigmentation, but no cases were seen of the unilateral, hyper-reactive 'sowda' described in Arabs in Yemen. No microfilariae were detected in the eyes of any of the patients who had positive outer canthus snips. Serum retinol concentrations were normal but mildly elevated concentrations of serum IgG, IgM and IgA were detected in many patients. Immunoglobulin E values in a sample of 20 microfilariae-positive patients were markedly higher than normal, with most in the 4,000 to 15,000 U/ml range. Eosinophil levels in differential counts of peripheral blood from the 208 villagers were markedly elevated. In skin snip surveys of over 400 villagers and school pupils, sample prevalence rates of 2 to 17.5% were recorded. Simulium biting was seasonal (November to May) and peaked in March. Over-all, the results indicate that O. volvulus infection persists in the Abu Hamed region as a serious cause of skin disease in the absence of other complicating filariases.

Adolescent↗
PubMed1985

Induction of tolerance in mice and rats to the effect of endotoxin to decrease the hepatic microsomal mixed-function oxidase system. Evidence for a possible macrophage-derived factor in the endotoxin effect.

Daily administration of low, non-lethal doses of bacterial endotoxin to mice and rats has been shown to induce tolerance to the effect of an acute challenge dose of endotoxin to decrease the hepatic microsomal drug metabolizing activity, the level of cytochrome P-450, and to increase heme oxygenase activity. The serum collected at various times after injection of endotoxin into control animals when injected into untreated animals markedly depressed aniline hydroxylase activity, ethylmorphine N-demethylase activity, and the level of cytochrome P-450. Tolerant animals were not affected by the post-endotoxin serum injection, suggesting the decreased activity caused by the serum in untreated animals was probably due to endotoxin contained in the serum. Injection of tolerant mice and rats with supernatant medium obtained from cultures of peritoneal macrophages incubated with 100 micrograms/ml of endotoxin caused a loss of hepatic microsomal drug-metabolizing activity, and a decrease in the level of cytochrome P-450. These results suggest that peritoneal macrophages release a factor in response to endotoxin that mediates the decreased hepatic mixed-function oxidase activity.

Animals↗
PubMed1985

14C labelling of octulose bisphosphates by L-type pentose pathway reactions in liver in situ and in vitro.

The complete reaction sequence of the pentose pathway in vitro was studied by incubating [1-14C] ribose 5-phosphate with rat liver enzyme preparation and assessed by both the rate and extent of formation of the glucose 6-P product. The reactions formed, as intermediates, the 1,8-bisphosphates of D-glycero D-ido octulose (D-g D-i Oct) and D-glycero D-altro octulose, both heavily labelled at C-4 with 14C isotope during the 12h incubation. The formation of the octulose phosphates and the specificity of their isotopic labelling confirms an important prediction of, and contribution by reactions of the L-type pentose phosphate pathway (L-PP) in liver in vitro. Infusion in situ of [6-14C] glucose into the liver of the anaesthetized rabbit resulted in the formation of high specific activity [8-14C] D-g D-i Oct 1,8-P2. The specificity of labelling indicates that the octulose intermediate is formed according to the options of the L-PP mechanism of glucose metabolism in intact liver.

Animals↗
PubMed1985

The significance of sedoheptulose 1,7-bisphosphate in the metabolism and regulation of the pentose pathway in liver.

Rat liver cytosolic enzyme preparation catalyses the formation of sedoheptulose 1,7-P2 (60% of total heptulose-P formed) from hexose 6-P and triose 3-P (reverse mode of pentose pathway operation). Smaller amounts of sedoheptulose 1,7-P2 are also formed from ribose 5-P during the non-oxidative synthesis of hexose 6-P (forward pentose pathway operation). The apparent absence of erythrose 4-P in biological systems may be explained by its contribution to carbons 4,5,6 and 7 of sedoheptulose 1,7-P2 as well as its pronounced ability to exist in dimeric form. Apart from the aldolase catalyzed formation of sedoheptulose 1,7-P2, 6-phosphofructokinase also catalyses its formation from sedoheptulose 7-P and fructose 1,6-bisphosphatase catalyses its dephosphorylation. These three enzymes may contribute to the regulation of carbon flux through the near equilibrium reactions of the non-oxidative pentose phosphate pathway in vivo. The phosphotransferase enzyme of the L-type pentose pathway is also able to catalyse the interconversion of sedoheptulose mono and bisphosphates via D-glycero D-ido octulose-P.

Animals↗
PubMed1984

Glucose and glutamine metabolism in rat thymocytes.

The metabolism of glucose and glutamine in freshly prepared resting and concanavalin A-stimulated rat thymocytes was studied. Concanavalin A addition enhanced uptake of both glucose and glutamine and led to an increase in oxidative degradation of both substrates to CO2. With variously labelled [14C]glucose, it was shown that the pathways of glucose dissimilation were equally stimulated by the mitogen. A disproportionately large percentage of the extra glucose taken up was converted into lactate, but concanavalin A also caused an increase in the oxidation of pyruvate as judged by the enhanced release of 14CO2 from [2-14C]-, [3,4-14C]- and [6-14C]-glucose. Addition of glutamine did not affect glucose metabolism. The major end products of glutamine metabolism by resting and mitogen-stimulated rat thymocytes were glutamate, aspartate, CO2 and NH3. Virtually no lactate was formed from glutamine. Concanavalin A enhanced the formation of all end products except glutamate, indicating that more glutamine was metabolized beyond the stage of glutamate in the mitogen-activated cells. Addition of glucose caused a significant decrease in the rates of glutamine utilization and conversion into aspartate and CO2 in the absence and in the presence of concanavalin A. In the presence of glucose, almost all nitrogen of the metabolized glutamine was accounted for as NH3 released via the glutaminase and/or glutamate dehydrogenase reactions. In the absence of glucose, part (18%) of the glutamine nitrogen was metabolized by the resting and to a larger extent (38%) by the mitogen-stimulated thymocytes via a transaminase or amidotransferase reaction.

Animals↗
PubMed1984

A 13C-n.m.r. study of intermediates in the L-type pentose phosphate cycle.

The structures in aqueous solution of all major contributing forms of D-altro-heptulose 1,7-diphosphate, and D-glycero-D-altro and D-glycero-D-ido-octulose 1,8-diphosphates have been established by 13C-n.m.r. spectroscopy. Assignments to individual carbon atoms were made with the aid of isotopically enriched analogues and by comparison with related sugars.

Heptoses↗
PubMed1984

Effect of procainamide on myocardial contractile function and digoxin inotropy.

The effect of procainamide and digoxin, singly and together, on peak active force and rate of force development of isolated right ventricular papillary muscles from adult cats was examined. Procainamide (1.5 X 10(-5) M) increased force and rate of force development in each muscle with further increments in performance up to 2.4 X 10(-4) M in most muscles. The maximal increases in force (+/- SEM) averaged 75 +/- 13% above control values. Essentially no response to procainamide was observed when basal levels of contractile state were increased by increasing stimulus frequency or calcium concentrations of the bathing solution. Propranolol (10(-6) M) markedly reduced and verapamil (10(-7) M) abolished the inotropic effect of procainamide. Exposing muscles to procainamide (1.5 or 3 X 10(-5) M) before or after the administration of digoxin (2 or 4 X 10(-7) M) did not alter the inotropic action of either drug. Thus, procainamide in concentrations that are in the therapeutic range in human patients has potent positive inotropic effects that may be masked at high levels of contractile state. This action of procainamide appears to be due to an effect on calcium channels, which in part may be due to beta-adrenergic receptor stimulation. These concentrations of procainamide do not alter the inotropic response to digoxin.

Animals↗
PubMed1984

Glucose 6-phosphate formation by L-type pentose phosphate pathway reactions of rat liver in vitro: further evidence.

An investigation of the mechanism in vitro of the non-oxidative segment of the pentose phosphate pathway using [5-14C]ribose 5-phosphate as a prediction labelling substrate with rat liver enzyme preparation is reported. Glucose 6-phosphate formed during the initial 0.5 h of reaction was heavily labelled in C-1 and thus is consistent with the prediction of the liver (L)-type pentose phosphate pathway (theoretically C-1/C-6 = 0.5). The reaction sequences of the fat (F-) type pentose phosphate pathway exclusively confine 14C to C-6 of glucose 6-phosphate. The presence of L-type reactions was further affirmed by the formation of D-arabinose 5-phosphate and D-glycero-D-ido-octulose phosphate which were identified and measured during the initial 2 h of incubation using gas liquid chromatography. After 3 h the concentration of 14C in C-1 of glucose 6-phosphate gradually declined and by 17 h of incubation the ratio of 14C in C-1/C-6 was 0.1. Possible reasons for the late changes in 14C-isotope distributions towards a pattern consistent with a contribution of F-type pentose phosphate pathway are given.

Animals↗
PubMed1984

A monoclonal antibody to a human breast tumor protein released in response to estrogen.

A panel of monoclonal antibodies was produced against cell surface antigens of the MCF-7 human breast cancer cell line. The monoclonal antibodies were selected by their ability to bind to live, intact MCF-7 cells in solid-phase radioimmunoassay, and to bind to human breast cancer cells in paraffin sections. One monoclonal antibody, designated UCD /AB 6.11, identified two cellular antigens and one extracellular antigen from MCF-7, and bound to 18 of 20 breast cancers in paraffin sections. The two cellular antigens were associated with Mr 54,000 and Mr 56,000 proteins, which could be identified in Western blots, and were localized to the cell surface by immune precipitation of lactoperoxidase-iodinated plasma membrane proteins. The extracellular antigen, a Mr 52,000 protein, was slightly more acidic and was only found in the media from estrogen-stimulated cells. Estrogen did not appear to have an effect on the production of the cell-associated antigens, Mr 54,000 and 56,000 proteins. We postulate that the cellular antigens are precursors to the secreted Mr 52,000 protein.

Animals↗
PubMed1984

Lectin binding to cystic stages of Taenia taeniaeformis.

Studies of membrane glycoconjugates of Taenia taeniaeformis were initiated by assays of the lectin binding characteristics of 35-day-old cysticerci. Parasites fixed in glutaraldehyde were incubated with one of the following FITC-labelled lectins: Concanavalin A (Con A), Lens culinaris agglutinin (LCA), Ricinus communis agglutinin (RCA), peanut agglutinin (PNA), fucose binding protein (FBP) and wheat germ agglutinin (WGA) and either their specific or a nonspecific sugar. Ultraviolet microscopy revealed that only Con A and LCA bound in large amounts to the surface of cysticerci. This binding was partly inhibited by the specific sugar, but the nonspecific sugar had little effect. The lectin not removed by either of the sugars may have been bound nonspecifically to the charged glycocalyx. Lectins were primarily bound on the anterior third of the parasite around the scolex invagination. Kinetic studies of lectin interactions were carried out with LCA and RCA by spectrophotofluorometric analysis of the amount bound specifically or nonspecifically over a range of lectin concentrations. Lens culinaris lectin binding was found to be specific and involve 2 receptors which showed large differences in their affinity for lectin and prevalence on the surface. Ricinus communis lectin did not bind specifically but nonspecific interactions were observed. Adherence of small numbers of host cells was shown to have no measurable effect on the lectin binding characteristics. The results suggest that the major surface carbohydrates exposed are D-mannose and/or D-glucose residues with the other sugar groups poorly represented. This relatively homogeneous surface may have implications for the antigenicity of the parasite in its host.

Animals↗
PubMed1984

Lipid and protein composition of the surface tegument from larvae of Taenia taeniaeformis.

A tegumental fraction from fully developed larvae of Taenia taeniaeformis was recovered by low speed centrifugation following incubation of the parasites in a 0.1% solution of digitonin. Scanning electron microscopy of the parasite carcass revealed no surface microtrichs, and transmission electron microscopy indicated that the subtegumental layer was undamaged. The tegumental fraction, judging from the distribution of 3H-Concanavalin A, was enriched for surface components, exhibited low succinic dehydrogenase activity, and an electron microscopic examination of the pellet showed a slightly expanded but intact distal tegumental layer. The fraction, which made up 3.0% of the dry weight of the parasite, consisted of 52% protein and 32% lipid. Thirty-three proteins, ranging in Mr from 9,000 to 276,000 daltons, were detected after sodium dodecyl sulfate solubilization and polyacrylamide gel electrophoresis. Seven of these proteins were glycoproteins. Cholesterol, phosphatidylethanolamine, phosphatidylserine, and glycosphingolipids were the major lipids.

Animals↗