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Biomedical subjects

J F Williams

Publications and source records attributed to J F Williams.

At least 109 records · Page 6Linked to original sources
PubMed1990

Depression of endothelium-dependent relaxation by filarial parasite products.

Endothelium-dependent relaxation is depressed in the femoral artery of dogs with heartworm, Dirofilaria immitis, infection. Moreover, in infected dogs, the mechanism of relaxation is different. Because D. immitis is located primarily in the pulmonary circulation, these findings suggested that D. immitis releases biologically active mediators that alter distal endothelium-dependent relaxation. We tested this hypothesis in vitro. Rings of rat aorta were exposed to D. immitis (alone, in 1,000 mol wt or 100 mol wt cutoff dialysis tubing, and bioassay with conditioned medium). D. immitis alone depressed relaxation to acetylcholine, carbachol, and A23187. Nitroglycerin relaxation was not affected. Depression of acetylcholine relaxation was seen with D. immitis alone, in 1,000 mol wt dialysis tubing, and bioassay with conditioned medium. However, acetylcholine relaxation with D. immitis in 100 mol wt dialysis tubing was not different from control. It appears that D. immitis releases a small, stable, biologically active factor that alters endothelium-dependent relaxation. Its exact nature is unknown. The study of endothelial cell behavior in filariasis and modulation of endothelial cell function by filarial factors may provide important clues in understanding the pathogenesis of parasitic diseases.

Acetylcholine↗
PubMed1990

Defective insulin receptor function in down-regulated HepG2 cells.

Insulin receptors on the surface of down-regulated HepG2 cells were studied, and multiple defects of receptor function were demonstrated. Insulin treatment led to a 58% decrease in cell surface receptor number, and the remaining receptors exhibited a 50% decrease in insulin internalization and degradation on a per receptor basis. Down-regulated cells internalized 36% of receptors photolabeled with 125I-NAPA-insulin vs. 56% of labeled receptors in control cells, indicating a 40% decrease in ligand-mediated receptor internalization. Total cellular receptors purified from down-regulated cells by wheat germ affinity chromatography demonstrated a 20% decrease in maximal autophosphorylation. Assessment of autophosphorylation of cell surface receptors in intact cells by restimulation of cells with insulin at 12 C (a temperature nonpermissive for receptor recycling), followed by immunoblotting with antiphosphotyrosine antibodies revealed a decrease of approximately 70% in insulin-stimulated autophosphorylation compared with controls. This method also revealed a comparable decrease in insulin-stimulable tyrosine phosphorylation of pp185, a putative endogenous substrate. When receptors were stimulated to undergo autophosphorylation with 125I-NAPA-insulin in intact cells and then solubilized, only 11% of 125I-NAPA-insulin receptor complexes from down-regulated cells were immunoprecipitated with antiphosphotyrosine antibodies compared with 35% of labeled control receptors. These results indicate that treatment with high concentrations of insulin results in the accumulation on the cell surface of a population of receptors that display multiple functional abnormalities. This probably results from preferential internalization and degradation of kinase-competent insulin receptors causing an accumulation of kinase-incompetent receptors on the cell surface. These receptors may in part be responsible for the postbinding defects in insulin action observed in down-regulated cells.

Affinity Labels↗
PubMed1990

Effect of postoperative radiation on the incorporation of tibial bone grafts in the rabbit.

A dose of 48 Gy of X-irradiation given over two to five weeks after grafting caused no significant delay in the rate of healing and only a small and statistically non-significant decrease in the torsional strength of the graft-bone junction of either vascularised or non-vascularised bone grafts of the tibiae of rabbits. Healing was faster and the union between the graft and adjacent bone developed torsional strength significantly more rapidly with vascularised than with non-vascularised grafts. These findings suggest that postoperative radiotherapy is unlikely to have a significantly deleterious effect on the healing of bone grafts used to repair defects produced by excision of malignant bone tumours.

Animals↗
PubMed1990

Cysticerci of Taenia mustelae in the fox squirrel.

The liver of a fox squirrel (Sciurus niger rufiventer) contained many clear, spherical cysts approximately 1 mm in diameter throughout the parenchyma. On dissection, most of these exhibited a dense, white area with four muscular suckers at a single point on the bladder. Based on the size of the organisms, the characteristically tiny hooks on the scolex and the location of the cysts in this host, the parasites were identified as cysticerci of Taenia mustelae. This is the first report in this host. The parasites were surrounded by an intense inflammatory response consisting primarily of lymphocytes mixed with some eosinophils, and early deposition of fibrous connective tissue.

Animals↗
PubMed1990

Pentose phosphate pathway in rat colonic epithelium.

The colonic cells of the large intestine are one of the most proliferative tissues of the animal body. The pentose pathway has an essential role in cell division and growth being the only pathway forming ribose 5-P necessary for all nucleotide and nucleic acid sunthesis. The pentose pathway may also provide reducing potential as NADPH for biosynthesis and C-3- C-8 glycolyl compounds. The maximum catalytic capacities of the reactions of the non-oxidative pentose pathway for the conversion of ribose 5-P to hexose and triose phosphates by the proximal and distal colon under feeding and starvation regimes are among the highest in the animal body. The qualitative presence of the oxidative pentose pathway was assessed by measurement of the C-1/C-6 ratio value of 1.67-1.82. Enzymes of the F-type and L-type pentose pathways are present in colonocytes and their maximum catalytic activities in colonocyte cytosol are reported. The contribution of the F-type pentose cycle to the total glucose metabolism of colonocytes, measured by the specific yield method, is negligibly low (approximately 1.5%). Colonic epithelial cells use glucose at a high rate (7.1 +/- 0.33 mumol min-1g-1 dry wt) and 79% of the glucose is converted to lactate. Arabinose 5-P has an intermediary role in the formation of keto pentose, sedoheptulose and hexose phosphates from ribose 5-P by colonocyte cytosol. The intermediary and reaction products of [1-13C] ribose 5-P dissimilation by colonocytes is investigated by 13C NMR spectroscopy. The 13C positional isotope distributions show labelling of C-1 and C-3 of hexose 6-phosphates consistent with either the theoretical predictions of the F-type pentose pathway or of the activities of exchange reactions catalysed by transketolase and/or transaldolase. Measurements of exchange reactions showed that the C-1/C-3 labelling of these compounds is mostly, if not wholly, attributable to exchange catalysis by these group transferring enzymes. The results suggest that the F-type PC has little role in the glucose metabolism of colonocytes and pentose phosphate formation may thus occur by a contribution (approx 20% of the total glucose metabolism) by the alternate L-type pathway.

Animals↗
PubMed1990

Tentative identification of the toxohormones of cancer cachexia: roles of vasopressin, prostaglandin E2 and cachectin-TNF.

A proposed role for the hypothesized toxohormone/s (Vasopressin, Prostaglandin E2 and TNF-Cachectin) in the development and maintenance of cancer cachexia was investigated in rats bearing the Walker 256 carcinosarcoma. Elevated levels of arginine vasopressin and prostaglandin E2 in the plasma and urine were associated with reduced hepatic ketogenesis, fatty acid oxidation and increased fatty acid esterification. The oxidation of branched chain amino acids by the muscle tissue of tumour bearing rats was increased and attributed to the enhanced activity of muscle branched chain keto-acid dehydrogenase. Concerted actions by the triology of factors (AVP, PGE2, Cachectin-TNF) are proposed to instigate a sequence of reactivities that lead to the clinical symptoms of muscle and adipose tissue wasting, together with the negative nitrogen balance characteristic of the cachectic state.

Amino Acids, Branched-Chain↗
PubMed1990

Pediatric heart transplantation.

Since the introduction of cyclosporine in the early 1980s, there has been a surge of activity in the field of pediatric heart transplantation. Careful patient selection has resulted in operative and short-term patient survival comparable to that achieved in adult transplant programs. The results of neonatal heart transplantation have been exciting and encouraging; neonates may require less immunosuppressive therapy than older infants and children. Transplantation clearly offers the chance of survival and significant rehabilitation to children with end-stage heart disease. Long-term management issues include the effects of chronic immunosuppressive therapy on growth and development and renal function, and the time-related risk of rejection, infectious complications, neoplasms, and graft atherosclerosis.

Child↗
PubMed1989

Effects of intermediary metabolites and electron transport inhibitors on action of chloroquine on Brugia pahangi and Onchocerca volvulus.

We examined the possibility that chloroquine is interfering with aerobic energy-generating processes in the adult filarial parasites, Brugia pahangi and Onchocerca volvulus. Using motility of these parasites as an assay of drug effect, we found that micromolar concentrations of chloroquine caused significant paralysis, but only in alkaline medium (pH 8.4). The addition of 12 mM glutamine or 10 mM albizziin to the medium completely antagonized drug-induced paralysis. In addition, in B. pahangi, all of the tricarboxylic acid cycle intermediates (10 mM) except citrate and pyruvate antagonized the effect of chloroquine on motility; in O. volvulus, oxaloacetate as well as glutamine inhibited the effect of the drug. The effect of chloroquine on both parasites was enhanced when it was used in combination with 10 microM acivicin, a glutamine antimetabolite. Here motility of B. pahangi was reduced significantly within 24-48 hr at acidic (6.8) neutral (7.4) and alkaline (8.4) pH. This effect was partially reversible by glutamine (12 mM). Motility of O. volvulus was reduced to near zero within 4 hr with this drug combination. Antimycin A and rotenone, both electron transport inhibitors, also synergized with chloroquine at any pH to produce paralysis in B. pahangi. The effects of the rotenone and chloroquine combination were reversed in the presence of 10 mM succinate. However, glutamine (12 mM) was unable to antagonize the effects of chloroquine plus antimycin A on the motility of B. pahangi. These findings suggest that chloroquine may be inhibiting aerobic energy metabolism in the filariae, possibly at the level of electron transport. Furthermore, since chloroquine is well-tolerated but only weakly filaricidal in vivo, the data indicate that use of this drug in combination with other inhibitors of aerobic energy metabolism may be a chemotherapeutically useful approach to the treatment of filariases.

Amino Acids, Diamino↗
PubMed1989

Carbon dioxide embolism treated with hyperbaric oxygen.

We report a case of suspected carbon dioxide embolism occurring during laparoscopy. Among the sequelae was neurological dysfunction felt to be secondary to paradoxical embolization. The patient was treated with hyperbaric oxygen therapy. Hyperbaric oxygen should be considered when confronted with a clinically important gas embolism.

Adult↗
PubMed1989

pH-dependent uptake and macrofilaricidal effects of chloroquine on adult filarial parasites in vitro.

Uptake and macrofilaricidal effects of chloroquine (CQ) and other aminoquinolines were found to be highly pH dependent in Brugia pahangi, Acanthocheilonema viteae, Onchocerca volvulus, and Dirofilaria immitis. Using [3H]CQ, it was found that all of the parasites took up more drug under alkaline conditions (RPMI 1640 at pH 8.4) than in neutral (pH 7.4) or acidic (pH 6.8) media. Differences were seen in the amount of drug taken up among the filariae studied. B. pahangi and A. viteae took up 7 times more chloroquine per milligram of tissue than did O. volvulus, and 30 times more than D. immitis during a 60-min incubation period at pH 8.4. Sensitivity to the aminoquinolines also increased with increasing media pH, and was measured using parasite motility as an indicator of drug efficacy. Potency of chloroquine against B. pahangi increased 100-fold at pH 8.4 compared to pH 7.4. A. viteae and O. volvulus showed similar sensitivity to chloroquine compared to B. pahangi; D. immitis was less sensitive. While uptake of chloroquine was linear from pH 6.8 to 8.4, B. pahangi was unaffected by 32 microM of the drug below pH 7.6; at any pH above this, motility of this parasite was completely inhibited. Calculations of the internal pH of this parasite indicated that it shifted upwards significantly with changes in media pH. It was concluded that these shifts in internal pH may render parasites more sensitive to the effects of chloroquine.

Animals↗
PubMed1989

Dirofilaria immitis: alteration of endothelium-dependent relaxation in the in vivo canine femoral artery.

Pathogenic mechanisms in filarial diseases are complex and poorly understood. While examining endothelium-dependent vasodilatory responses in the in vivo canine femoral artery, we noticed that dogs with Dirofilaria immitis infection had altered vascular responsiveness. The results reported here extend our original observations on vascular reactivity in dogs with D. immitis infection (L. Kaiser, J. F. Williams, E. A. Meade, and H. V. Sparks, 1987, American Journal of Physiology 253, H1325-H1329). In noninfected dogs, acetylcholine binds to the luminal endothelial cell muscarinic receptor. This results in release of a nonprostaglandin endothelium-derived relaxing factor. The relaxing factor causes an increase in vascular smooth muscle guanylate cyclase and relaxation. However, in dogs with D. immitis infection the mechanism of relaxation to acetylcholine is different. At least two endothelium derived relaxing factors are involved: the major factor is a prostaglandin; the second factor works through vascular smooth muscle cGMP. These data suggest that adult D. immitis release pharmacologically active factors that can alter distal endothelial cell function. The notion that filarial products may alter the physiological function of endothelial cells should be considered in the pursuit of improved understanding of pathogenic mechanisms of filariasis.

Acetylcholine↗
PubMed1989

Formation of ketone bodies by resting lymphocytes.

1. Both beta-hydroxy-beta-methylglutaryl-coenzyme A synthase and lyase activities are present in rat mesenteric lymphocytes: all of the synthase and almost all (80%) of the lyase were present in the mitochondrial compartment of the cell. 2. A high rate of acetoacetate formation was observed in mesenteric lymphocytes incubated in vitro for 60 min in the absence of added substrate; addition of pyruvate or glutamine increased the "endogenous" rate of acetoacetate formation by about 30%. 3. The rates of ketone body formation are similar to maximal rates observed for rat liver. 4. It is suggested that the high rate of endogenous acetoacetate production occurs from long chain fatty acids: this suggestion is consistent with the reported high "endogenous" rate of O2 consumption by lymphocytes. 5. Of the pyruvate metabolized via pyruvate dehydrogenase in lymphocytes, ca 50-70% could be accounted for as acetoacetate, acetate, 3-hydroxybutyrate and citrate: the fate of the remainder is not known. 6. There was a high rate of endogenous acetoacetate formation by isolated mitochondria from these cells. 7. The rate was doubled by addition of pyruvate or butyrate; it was trebled by addition of propionate, ADP or carbonyl cyanide trichloro-methoxyphenylhydrazone; but it was decreased by addition of antimycin A or glutamine. 8. It is suggested that the high rates of acetoacetate formation in these cells acts as a dynamic "buffer" system for the acetyl coenzyme A (CoA) concentration: that is, acetyl CoA is always available for fatty acid synthesis, cholesterologenesis, chain extension of fatty acids or acetylation of proteins (e.g. for covalent control of their activity) which will be demanded at different stages of the cell cycle. 9. This is another example of branch-point sensitivity in control in cells with the potential for rapid cell division.

Acetoacetates↗
PubMed1989

The impaired tolerance of the recently infarcted rat heart to cardioplegic arrest: the protective effect of orotic acid.

After myocardial infarction, a reduced mass of non-infarcted myocardium remains to maintain cardiac output. This acutely stressed, non-infarcted myocardium exhibits many metabolic disturbances, and undergoes a process of acute hypertrophy. These stress-induced disturbances may reduce the tolerance of the heart to the global ischaemia of cardioplegic arrest and may explain the increased mortality and morbidity associated with cardiac surgery in patients with recent myocardial infarction. We postulated that orotic acid, a pyrimidine precursor which augments the rate of protein synthesis during hypertrophy, might improve the response of the recently infarcted heart to cardioplegic arrest. Myocardial infarction was induced in rats by coronary ligation, and after 2 days or 3 days the hearts were excised and perfused on the working heart apparatus. After measurement of work capacity, the hearts underwent 1 hour of hypothermic cardioplegic arrest. Post-arrest function was then measured and expressed as a percentage of the pre-arrest value. A group of sham-operated, non-infarcted hearts served as controls. There were two distinct findings: (1) when subjected to hypothermic cardioplegic arrest 2 days after myocardial infarction, hearts recovered only 49% of pre-arrest function, compared with 80% recovery in non-infarcted controls (P less than 0.001). Three days after infarction, recovery had improved to 68% (P less than 0.01 vs. 2 days, P less than 0.05 vs. non-infarcted). (2) Treatment with oral orotic acid following infarction augmented recovery from cardioplegic arrest to 83%, 2 days after infarction (P less than 0.001 vs. untreated) and to 87%, 3 days after infarction (P less than 0.01 vs. untreated).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of post placement on endodontically treated teeth.

The effect of endodontic therapy, post-hole preparation, and post placement on tooth models of maxillary central incisors was investigated. Two-dimensional photoelastic analysis of birefringent models, under load in a polariscope, indicated the relative stress magnitudes and concentrations at the cervical and apical regions. Within the limits of the method, the results suggest that enlargement of the canal increases cervical stresses and that post placement will decrease stresses in this region. Nevertheless, conservative enlargement of the root canal may render post placement unnecessary for largely intact teeth. Post length appeared more important than post diameter in determining relative stresses at the cervical region. However, short wide posts led to elevated stress concentrations in this region. Post placement beyond two thirds of the root depth did not further decrease cervical stresses but usually increased stresses in the apical region.

Crowns↗
PubMed1989

Effect of endotoxin to differentially affect cytochrome P-450 monooxygenase activities of untreated rats and animals induced with phenobarbital or 3-methylcholanthrene.

The effect of endotoxin in decreasing the cytochrome P-450-dependent metabolism of aniline, aminopyrine and ethoxycoumarin was examined in untreated rats, and in rats pretreated with either phenobarbital or 3-methylcholanthrene. Ethoxycoumarin metabolism was determined at two substrate concentrations (5 microM and 500 microM) to determine the effect of endotoxin on the high and low affinity enzyme activities. In untreated animals, endotoxin depressed both aniline and ethoxycoumarin metabolism by the high and low affinity enzymes by approximately 70%, but aminopyrine was decreased by only 47%. In phenobarbital pretreated rats, endotoxin decreased enzyme activities less than in untreated animals. Aniline metabolism and low affinity ethoxycoumarin metabolism were decreased by only 24%, and aminopyrine metabolism was decreased by 35%. The high affinity ethoxycoumarin metabolism was least affected, being decreased by only 12%. In 3-methycholanthrene pretreated rats, aniline and ethoxycoumarin (500 microM) metabolism were decreased by approximately 45%, but aminopyrine metabolism was only decreased by 20%. In these animals, endotoxin did not significantly affect the activity of ethoxycoumarin metabolism assayed with the low substrate concentration. Endotoxin decreased total cytochrome P-450 level of untreated rats by 32%, of phenobarbital pretreated rats by 39%, and in 3-methylcholanthrene pretreated animals the decrease was only 21%. Heme oxygenase activity of untreated animals was induced most by endotoxin administration and least in phenobarbital treated rats. The data suggest that endotoxin may differentially affect the various isozymes of cytochrome P-450 associated with the metabolism of aniline, aminopyrine and ethoxycoumarin. The results also suggest that the isozymes associated with these activities in untreated, phenobarbital or 3-methylcholanthrene pretreated rats may differ in their sensitivity to the effect of endotoxin.

Animals↗
PubMed1989

The regulation of fatty acid and branched-chain amino acid oxidation in cancer cachectic rats: a proposed role for a cytokine, eicosanoid, and hormone trilogy.

Some postulates of a hypothesis concerned with the deregulation of muscle turnover by the hypoketonemia of cachectic tumor-bearing rats were examined. Plasma concentrations of ketone bodies (D-(3)-hydroxybutyrate + acetoacetate) in rats bearing the Walker 256 carcinosarcoma were reduced by 45% (P less than 0.001) whereas the concentrations of triglyceride and free fatty acids were elevated by 223% (P less than 0.001) and 335% (P less than 0.001), respectively. Parallel with the changes in plasma, the livers of tumor-bearing animals showed decreased concentrations of KB by 35% (P less than 0.05) and increased concentrations of TG and FFA by 49% (NS) and 15% (NS), respectively. In comparison with values for the control liver (fed ad libitum), the perfused liver of animals bearing the Walker 256 tumor formed 42% (P less than 0.05) and 75% (P less than 0.05) less ketone bodies and CO2, respectively, from oleate, while TG formation was enhanced by 33% (P less than 0.001). There was two- to threefold (P less than 0.001) enhancement of [1-14C]leucine oxidation in vivo by the tumor-bearing animals. The activities of branched-chain amino acid aminotransferase and branched-chain keto acid dehydrogenase were elevated by 70% (P less than 0.001) and 560% (P less than 0.001) respectively in the gastrocnemius muscle of the tumor-bearing animals. The results of the investigation supported a second proposal of the hypothesis, namely, that cancer-induced cachexia resulted in the notable elevation in the concentration of arginine vasopressin that was accompanied by parallel increases in the plasma, urine, and muscle concentrations of prostaglandin E2. The proposals of the original hypothesis have been augmented to include roles for PGE2 and the cytokine cachectin/tumor necrosis factor which may engineer all of the events depicted in the original hypothesis.

Amino Acids, Branched-Chain↗
PubMed1989

Comparative study of the use of prefabricated bone tendon grafts and conventional tendon grafts in flexor tendon reconstruction.

In tendon grafting the weakest area is the junction between the grafted tendon and bone. In dogs a strong union between tendon and bone can be produced by threading the flexor carpi radialis tendon through a hole drilled in the radius. In experimental repair of canine flexor tendons, 3 weeks after operation the strength of the union between a composite bone-tendon graft prepared in this way is double that of the bone-tendon junction of a conventional graft. Use of prefabricated bone-tendon grafts should permit earlier postoperative movement and limit formation of adhesions between a tendon graft and its bed.

Animals↗