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J F Williams

Publications and source records attributed to J F Williams.

At least 73 records · Page 4Linked to original sources
PubMed1994

Radiologic evaluation of the liver and gastrointestinal tract in rats infected with Taenia taeniaeformis.

In rats infected with the cestode Taenia taeniaeformis, hepatomegaly results from development of parasitic cysts in the liver. Diffuse nodular mucosal hyperplasia in the glandular region (corpus and antrum) of the stomach, and gross thickening of the intestinal mucosa also result. Between postinfection days (PID) 21 and 84, radiologic observations were made after oral administration of a barium sulfate suspension in T taeniaeformis-infected rats and in age/sex-matched controls. There was radiographic evidence of hepatic enlargement at PID 21. Enlargement of the gastric folds was first observed along the greater curvature of the stomach at PID 35. Fimbriation of small intestinal mucosal surfaces resulted from thickening of the intestinal villi and was observed in the duodenum at PID 21. Intestinal motility was assessed, and contractions were counted, using image intensification fluoroscopy, then were recorded on videotape. There were no significant differences between control and infected rats for gastric emptying time, intestinal transit time, and number of intestinal contractions per minute. Barium contrast radiography clearly indicated large gastric folds, thickening of the small intestinal villi, and hepatic enlargement, and was useful for assessing gastrointestinal motility.

Animals↗
PubMed1993

Deletion of exon 21 of the insulin receptor eliminates tyrosine kinase activity but preserves mitogenic signaling.

To study the function of exon 21 of the insulin receptor, a mutant human insulin receptor lacking this domain was constructed. The mutant HIR delta E21 cDNA was transfected into Rat-1 fibroblasts and stable cell lines were selected. The HIR delta E21 receptors were expressed on the cell surface, and they bound insulin with the same affinity as did the wild-type-expressing cell line, hIRcB. The HIR delta E21 receptors did not display detectable autophosphorylation or kinase activity, and as expected, internalization was impaired and metabolic signaling properties were absent. Unexpectedly, insulin's ability to stimulate DNA synthesis in cells expressing HIR delta E21 receptors was far greater than that in the parental Rat-1 cells and equal to that measured in the hIRcB cell line. The enhanced mitogenic signaling properties of the HIR delta E21 receptors was confirmed by showing that treatment of HIR delta E21 cells with a human-specific insulin-mimetic anti-insulin receptor antibody also led to enhanced DNA synthesis. Thus, although no insulin receptor autophosphorylation or kinase activity was detectable in HIR delta E21 cells, these cells displayed enhanced insulin-induced mitogenic signaling. These results suggest that an alternative non-kinase-dependent stimulus-response pathway exists for the long-term biological effects of insulin.

Animals↗
PubMed1993

Differential effect of chronic nicotine administration on brain cytochrome P4501A1/2 and P4502E1.

The effects of chronic nicotine administration on the enzymatic activities and immunoreactivities of P4501A1/2 and P4502E1 were determined in microsomal fractions from brain regions and liver. Chronic nicotine increased 7-ethoxyresorufin O-deethylase activity and P4501A1/2 immunoreactivity in hippocampus and brain stem, decreased values in cerebral cortex, thalamus, and striatum, and did not affect parameters in other brain regions. In contrast, N-nitrosodimethylamine N-demethylase activity from nicotine-injected rats increased in all brain regions examined, and this increase was associated with increased P4502E1 immunoreactivity. Chronic nicotine did not alter either enzyme activities or immunoreactivities of these isoforms in hepatic microsomes.

Animals↗
PubMed1993

Exchange reactions catalyzed by group-transferring enzymes oppose the quantitation and the unravelling of the identify of the pentose pathway.

1. The distributions and rates of transfer of carbon isotopes from a selection of specifically labelled ketosugar-phosphate substrates by exchange reactions catalyzed by the pentose and photosynthetic carbon-reduction-pathway group-transferring enzymes transketolase, transaldolase and aldolase have been measured using 13C-NMR spectroscopy. 2. The rates of these exchange reactions were 5, 4 and 1.5 mumol min-1 mg-1 for transketolase exchange, transaldolase exchange and aldolase exchange, respectively. 3. A comparison of the exchange capacities contributed by the activities of these enzymes in three in vitro liver preparations with the maximum non-oxidative pentose pathway flux rates of the preparations shows that transketolase and aldolase exchanges exceeded flux by 9-19 times in liver cytosol and acetone powder enzyme preparations and by 5 times in hepatocytes. Transaldolase was less effective in the comparison of exchange versus flux rates: transaldolase exchange exceeded flux by 1.6 and 5 in catalysis by liver cytosol and acetone powder preparations, respectively, but was only 0.6 times the flux in hepatocytes. 4. Values of group enzyme exchange and pathway flux rates in the above three preparations are important because of the feature role of liver and of these particular preparations in the establishment, elucidation and measurement of a proposed reaction scheme for the fat-cell-type pentose pathway in biochemistry. 5. It is the claim of this paper that the excess of exchange rate activity (particularly transketolase exchange) over pathway flux will overturn attempts to unravel, using isotopically labelled sugar substrates, the identity, reaction sequence and quantitative contribution of the pentose pathway to glucose metabolism. 6. The transketolase exchange reactions relative to the pentose pathway flux rates in normal, regenerating and foetal liver, Morris hepatomas, mammary carcinoma, melanoma, colonic epithelium, spinach chloroplasts and epididymal fat tissue show that transketolase exchange may exceed flux in these tissues by factors ranging over 5-600 times. 7. The confusion of pentose pathway theory by the effects of transketolase exchange action is illustrated by the 13C-NMR spectrum of the hexose 6-phosphate products of ribose 5-phosphate dissimilation, formed after 30 min of liver enzyme action, and shows 13C-labelling in carbons 1 and 3 of glucose 6-phosphate with ratios which range over 2.1-6.4 rather than the mandatory value of 2 which is imposed by the theoretical mechanism of the pathway.

Animals↗
PubMed1993

The effect of orotic acid treatment on the energy and carbohydrate metabolism of the hypertrophying rat heart.

1. Adenine nucleotide concentrations in normal and one day hypertrophied hearts of untreated, orotic acid (OA), uridine, uracil, dihydroorotate and reserpine pretreated rats were measured. OA treatment increased the ADP concentration 5-fold in one day hypertrophied hearts. Neither uracil, uridine, dihydroorotate nor reserpine treatments changed ADP or total adenylate concentrations at one day of hypertrophy. 2. The adenine nucleotide ratio (ANR) at 0.263 x 10(3) M-1 and the energy charge (0.66) were at their lowest values in OA and in reserpine treated one day hypertrophying hearts. The temporal decline in the indices of energy metabolism corresponded with the OA induced maximum stimulation of contractility and maximum rates of protein, RNA and glycogen synthesis. 3. The phosphorylation state of the adenine nucleotides (PSAN) was both the most sensitive and the best predictive index of the cellular energy status in normal and hypertrophying hearts. The pronounced ability of OA treatment to energize myocyte cytoplasm was shown by the 9- and 6-fold greater values of PSAN over ANR in one and three day hypertrophied hearts. The enhanced PSAN may be the key factor in the mechanism of OA induced enhancement of contractile and synthetic functions of the heart in compensatory hypertrophy. 4. The development of myocardial hypertrophy in untreated rats resulted in a 36% reduction in the cytoplasmic NAD/NADH ratio. In rats treated with OA this redox couple of the hypertrophying heart was more oxidized and was increased by 30% to restore it to the value range of normal heart. 5. The regulatory status of the glycolytic pathway in untreated and OA treated hypertrophying hearts was assessed by comparisons of the mass action ratio (MAR) and equilibrium constants for each of the individual glycolytic reactions. There was an OA induced 2.7-fold increase in glycogen, UDP-glucose and total uridine nucleotides in hypertrophied hearts. The concentrations of seven out of ten glycolytic intermediates, including pyruvate and lactate were increased as a consequence of OA treated hypertrophy. Glycolytic flux was not stalled, rather the pathway was "more open" permitting greater throughput of intermediates with individually increased levels of selected metabolites. OA stimulated hypertrophy did not change the canonical control of glycolysis by the activities and individual MAR values of phosphofructokinase and pyruvic kinase. 6. Elevated levels of Glu 6-P, Fru 6-P and DHAP can force glycolytic intermediate entry into the non-oxidative reaction segment of the pentose pathway (PP), thereby elevating Rib 5-P concentration by reversal of the conventional flux direction of PP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1993

A clinical classification and grading system of the cutaneous changes in onchocerciasis.

Although onchocerciasis is one of the most important diseases of the skin and eye in the tropical world, to date there has been no formal consensus regarding the description and terminology of skin lesions. Furthermore, the contribution of cutaneous pathology to the morbidity and socio-economic effects of the disease has been largely neglected. We present a clinical classification and grading system for recording the cutaneous changes of onchocerciasis, and propose that this system be used as a standard method of description to convey clinical information between workers in all endemic areas to assist local and comparative research.

Acute Disease↗
PubMed1993

The chronic administration of nicotine induces cytochrome P450 in rat brain.

The objective of these studies was to determine whether chronic administration of nicotine altered the cytochrome P450 (P450) monooxygenase system in rat brain. Male Sprague-Dawley rats received injections of nicotine bitartrate (1.76 mg/kg, s.c., twice daily for 10 days), and total cytochrome P450 content, the activity of NADPH-cytochrome c reductase, and the activities and relative abundance of P4502B1 and P4502B2 (P4502B1/2) were determined in microsomal fractions from rat brain. The content of P450 increased significantly (p < 0.02) in all brain regions examined from nicotine-injected rats; the largest increase (208% of control) was in frontal cortex and the smallest increase (122% of control) in cerebellum. The activity of NADPH-cytochrome c reductase was unaltered by nicotine administration. Benzyloxyresorufin O-dealkylase (BROD) and pentoxyresorufin O-dealkylase (PROD) activities, mediated by P4502B1/2, increased significantly (p < 0.02) following nicotine administration; the largest increase (213-227% of control) was in frontal cortex. Western blots of microsomal proteins indicated that the increase in enzymatic activity was associated with an increase in content of P4502B1/2 immunoreactive proteins. In contrast to brain, total P450 content, activities of NADPH-cytochrome c reductase, BROD, and PROD, and levels of P4502B1/2 immunoreactive proteins in liver were unaffected by chronic nicotine administration. Results indicate that chronic nicotine administration regulates the expression of P4502B1/2 in brain and that at the dose schedule used this effect occurs without a demonstrable effect on the hepatic P450 monooxygenase system.

Animals↗
PubMed1993

Effects of glucocorticoids on lymphocyte metabolism.

The immunosuppressive effect of glucocorticoids has been widely reported; however, the mechanism of action of these hormones on the immune system has not been fully established. In the present study, the effect of glucocorticoids on glucose, glutamine, and pyruvate metabolism in lymph node lymphocytes was investigated. Addition of dexamethasone to the incubation medium did not alter glucose and glutamine metabolism but inhibited pyruvate utilization by 40%. This latter effect took 1 h to occur and remained for up to 6 h, even after removal of dexamethasone from the culture medium. Measurements of the activity of pyruvate dehydrogenase in lymphocytes and the rate of [1-14C]-pyruvate conversion into 14CO2 in incubated lymphocyte mitochondria demonstrated that glucocorticoids decrease pyruvate utilization by inhibiting the activity of this key regulatory enzyme. The effect of such an inhibition of pyruvate utilization on the function of cells of the immune system remains to be clarified.

Animals↗
PubMed1993

Deletion of the insulin receptor beta-subunit acidic domain results in enhanced metabolic signaling.

The contribution of the insulin receptor beta-subunit acidic domain, amino acids 1262-1291, to receptor function was analyzed. A mutant insulin receptor complementary DNA lacking this domain was created. Rat-1 fibroblasts were stably transfected with plasmids containing the mutant insulin receptor complementary DNA and clonal cell lines derived (hIR1262). Compared with cells overexpressing the wild type insulin receptor, metabolic signaling was enhanced in hIR1262 cells whereas the mitogenic response to insulin was unchanged. hIR1262 had normal kinase activity and insulin-stimulated receptor internalization in spite of substantially reduced autophosphorylation (70% decreased in vitro). Additionally, polylysine, a polycation postulated to interact with the insulin receptor beta-subunit acidic domain, increased autophosphorylation and facilitated insulin-induced phosphorylation of calmodulin in the wild type as well as the hIR1262 receptors. We conclude: 1) The acidic domain is not the site of interaction between the insulin receptor and polycations. 2) Removal of the acidic domain leads to enhanced metabolic signaling but 3) unchanged mitogenic activity. 4) The defect in autophosphorylation is not correlated with a defect in kinase activity. Thus, the observed changes in biological signaling indicate that specific pathways diverge at the level of the receptor itself and that neither kinase activity or biological activity necessarily correlates directly with diminished autophosphorylation when the tyrosine kinase domain remains intact.

Animals↗
PubMed1993

Effect of serum from dogs infected with Dirofilaria immitis on endothelium-dependent relaxation of rat aorta in vitro.

Endothelium-dependent relaxation of canine femoral artery in vivo is depressed in dogs infected with Dirofilaria immitis (heartworms). In vitro, endothelium-dependent relaxation of aorta from rat is depressed in the presence of adult heartworms or heartworm-conditioned media. The depression of relaxation is attributable, in part, to a low molecular weight, biologically active product that is released by the adult parasites. Because heartworms reside in the right heart and pulmonary arteries, biologically active factors produced by the parasites could circulate and alter endothelial cell function. The hypothesis that filarial factors in serum from heartworm-infected dogs depress endothelium-dependent relaxation was tested. Rings of thoracic aorta from rats were constricted by use of norepinephrine, and cumulative dose-response relationships to methacholine and nitroglycerin were evaluated in the presence of serum from heartworm-infected dogs or serum from noninfected (control) dogs. Nitroglycerin relaxation was not different; however, methacholine relaxation was significantly depressed in rings exposed to serum from heartworm-infected dogs when compared with that of controls. These results supported the hypothesis suggested that circulating filarial factors have the potential to influence the behavior of any endothelial cell surface.

Acetylcholine↗
PubMed1993

Anatomic features and radiographic observations of gastric emptying and small intestinal motility in the rat.

This study presents the first report of the identification of anatomic structures on survey radiographs of the abdomen of the rat, along with detailed barium contrast studies of the gastrointestinal tract in normal rats. The rats (49 to 112 days old) were chemically restrained with a combination of 0.71 mg ketamine hydrochloride/g of body weight and 0.5 mg of acetylpromazine maleate injected intramuscularly. Following sedation, a 36% (wt/vol) micropulverized barium sulfate suspension was administered via a stomach tube at a dose of 0.02 ml/g of body weight. The radiographic features of the gastrointestinal tract were enhanced after coating of the mucosal surfaces with the high-density barium suspension. Internal structures of the stomach and mucosal surfaces of the intestine were clearly identified. The barium contrast study was used to establish gastrointestinal transit times. The mean gastric emptying time was 11 +/- 4.27 (SEM) min and mean intestinal transit time was 5 +/- 0.75 (SEM) h. Image intensification fluoroscopy was used to observe patterns of small intestinal motility and to establish small intestinal contraction rates. Prominent cluster of circular contractions were primarily observed in the jejunum, and wave-type peristalsis was primarily observed in the duodenum. Isolated circular contractions and weak segmentation patterns were observed in the ileum. The mean contraction rate per minute was observed to be 14 +/- 2.12 (SEM) in the jejunum. We propose that under the conditions of the current study, radiographic investigation of gastrointestinal function in rats is a feasible and inexpensive procedure.

Animals↗
PubMed1993

Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells.

The human leukaemic cell line HL60 undergoes differentiation to granulocyte-like cells in response to dimethylsulphoxide (DMSO). The rates of glucose and glutamine utilization were studied in HL60 cells that were either undifferentiated or fully differentiated by 9 days exposure to DMSO. Differentiation did not alter the rate of utilization of exogenous glucose, approximately 75% of which was converted to lactate in each case. The activities of hexokinase, phosphofructokinase, pyruvate kinase and citrate synthase were similarly unaffected. In contrast, the activity of the oxidative segment of the pentose-phosphate pathway was enhanced by differentiation, and no glycogen synthase activity could be detected. These observations are consistent with the significantly lower content of glycogen, the increased activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and the increased oxidation of [1-14C] glucose relative to [6-14C] glucose in the differentiated cells. Glucose utilization was depressed by exogenous glutamine but, at the same time, glutamine utilization was enhanced by glucose in both cell types; these reciprocal effects were more pronounced in the undifferentiated HL60 cells. Glucose utilization may be depressed in the presence of glutamine as a result of the allosteric inhibition of a rate-limiting step of glycolysis (eg. phosphofructokinase). In spite of having glutaminase activity twice that of their differentiated counterparts, the uptake of glutamine by undifferentiated HL60 cells was low, especially when it was the sole substrate. The stimulation of glutaminolysis by glucose may be due to activation of mitochondrial glutamine transport. A large proportion of the glutamine utilized by both cells contributed to a net accumulation of glutamate, aspartate and alanine, whilst up to 35% was oxidized to CO2. In contrast, almost all of the glucose utilized was converted to lactate and very little was oxidized. The high rates of glycolysis and glutaminolysis observed before and after differentiation may not contribute primarily to energy production but may supply, in undifferentiated cells, substrates for biosynthetic processes that generate nucleic acid precursors or, in the case of differentiated cells which synthesize reactive oxygen intermediates, substrates that maintain NADP in a reduced state.

Cell Differentiation↗
PubMed1993

Longitudinal study of onchocerciasis in Bebeka-Ethiopia.

This paper describes the morbidity, intensity and prevalence of onchocerciasis in an endemic area of Ethiopia, using a cross-sectional study (n = 425) and a longitudinal cohort study (n = 98). During the study period (February-October 1987), the increase in intensity and in number of cases with dermal lesions was highly significant (p < 0.005) when compared with the increase in the microfilarial positivity rate (p < 0.1). Since the serial increase in dermatologic problems was not directly correlated with an increase in O. volvulus microfilarial prevalence or intensity, it is suggested that hyper-sensitivity responses to repeated Simulium bites might exacerbate onchocercal dermal lesions. The controversy concerning Simulium bites as a cause of lesions mimicking those due to O. volvulus parasites is discussed.

Adolescent↗
PubMed1993

Glutamine-supported motility of adult filarial parasites in vitro and the effect of glutamine antimetabolites.

The survival in culture of adult female Brugia pahangi, Acanthocheilonema viteae, and Onchocerca volvulus and adult male Onchocerca gibsoni was assessed by measuring parasite motility. Survival of all species was maximal in a nutritionally complex medium (RPMI-1640). All species survived for up to 48 hr in a simpler medium in which the only energy source was 10 mM glutamine; motility in this medium was dependent upon pH. For the species of Onchocerca, motility was maintained better in the presence of glutamine as the sole energy source than in glucose-only medium. Motility of B. pahangi incubated in 10 mM succinate was equivalent to that seen with 10 mM glutamine, but no other tricarboxylic acid intermediate supported this parasite in vitro. Antimycin A (1 microM) and potassium cyanide (KCN, 100 microM) paralyzed B. pahangi incubated in 10 mM glutamine, an effect antagonized by glucose. KCN at 10 or 100 microM was effective also against Onchocerca gutturosa in glutamine-only medium. Several glutamine antimetabolites reduced motility of B. pahangi by 72 hr. This inhibition was prevented by 2 mM glutamine. However, the inhibition of motility in the species of Onchocerca caused by these compounds was attenuated only partially by glutamine. These data demonstrate that, under certain conditions, filarial nematodes can utilize non-sugar substrates as energy sources. The differential sensitivity seen among these organisms to mitochondrial toxins and glutamine antimetabolites may be related to the extent to which they can use these alternative substrates to generate energy.

Animals↗
PubMed1993

Effects of various dietary fatty acids on enzyme activities of carbohydrate and glutamine metabolism and the metabolic response of lymphocytes and macrophages during Walker-256 ascites cell tumour growth in rats.

It was previously shown that polyunsaturated and saturated fatty acid rich diets affected metabolic and functional changes in macrophages and a variety of immune tissues (thymus, mesenteric lymph nodes and spleen). This study reports metabolic and functional changes in peritoneal macrophages and lymphocytes of Walker-256 ascites cell tumour-bearing rats which were fed (a) normal balanced diet (3% fat), (b) diet enriched (15% fat) with polyunsaturated fatty acids or (c) diet fortified (15% fat) with saturated fatty acids. Neither of the fatty acid enriched diets affected macrophage migration following tumour cell implantation and ascitic cell growth. However both of these fortified fatty acid regimes enhanced the production of H2O2 by macrophages and lymphocytes. The maximum catalytic capacities of hexokinase, glutaminase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were measured in resident and tumour activated macrophages and lymphocytes obtained from rats fed the three fatty acid dietary regimes during seven days of tumour ascites cell growth. Tumour growth caused an increase in the activities of all of the above enzymes in macrophages irrespective of the fatty acid composition of the diet and notably decreased, independent of dietary fatty acid composition, the activities of the enzymes in lymphocytes. Only glutaminase activity in the lymphocytes of tumour bearing animals fed an unsaturated fatty acid-rich diet was not reduced, but was increased by 78%. Moreover macrophages from control rats fed an enriched polyunsaturated fatty acid diet had increased hexokinase activity (21%), decreased glutaminase (48%) and citrate synthase (decreased 41%) relative to the activities of these enzymes in macrophages of animals maintained on a balanced fatty acid diet. The feeding of both fatty acid rich diets did not modify the pattern of lymphocyte responses during the growth of tumour cells in these animals. None of the fatty acid diets modified the growth rate nor the yield of tumour cells in the peritoneal cavity.

Animals↗
PubMed1993

Evaluation of expandable leadwires for pediatric cochlear implants.

The development of cochlear implants for use in very young children (1-2 years old) will require techniques designed to accommodate temporal bone growth. Previous anatomic studies have shown that the leadwire of a cochlear implant must be capable of expanding up to 20 mm between the round window and the implanted receiver-stimulator in response to skull growth. In the present study morphologic and biomechanical evaluation of five expandable leadwire designs was conducted following their implantation in young cats. Two helical shaped leadwire designs frequently exhibited extensive fibrous tissue adhesions and broke during long-term implantation. In contrast, thin, flexible Silastic envelopes were effective in minimizing tissue adhesions. Residual V- and Z-shaped leadwires, placed in these envelopes, showed little evidence of fibrous tissue adhesions following implantation periods of up to 2 years. Moreover, these leadwires readily expanded both during the growth of the animal and when biomechanical expansion studies performed at the completion of the implant period. These expandable leadwire designs appear to be appropriate candidates for use in pediatric cochlear implants.

Animals↗
PubMed1992

Pulmonary arteriovenous fistula: mechanical ventilation and hypoxemia.

Pulmonary arteriovenous malformation (PAVM) is an uncommon congenital anomaly. As PAVM is a direct communication between branches of the pulmonary artery and vein, major disturbances in gas exchange can result. We present a patient with an unsuspected PAVM who came to our institution for drainage of a brain abscess. Arterial blood gas analysis during and after surgery demonstrated a large alveolar-arterial gradient for oxygen in the absence of any obvious pulmonary pathology while the patient was receiving positive pressure ventilation (PPV). Oxygenation improved considerably upon resumption of spontaneous ventilation. A diagnosis of PAVM was made subsequently. We conclude that positive pressure ventilation can worsen right to left shunting in patients with PAVM.

Adult↗