Biomedical subjects
Publications and source records attributed to J F Williams.
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An investigation of the mechanism and quantitative contribution of the pentose phosphate pathway in the glucose metabolism of Morris Hepatoma 5123C is reported. Morris Hepatoma 5123C has an active non-oxidative segment of pentose pathway as judged by its ability to convert ribose 5-P to hexose 6-P in a standard assay. Based on compliance with qualitative and quantitative criteria, the cells exhibit the L-type pentose pathway reaction sequence rather than the F-type pathway. This compliance included the formation of intermediates characteristic of the L-type pathway, namely arabinose 5-P, octulose mono- and bisphosphates and sedoheptulose 1,7-bisphosphate, during the dissimilation of ribose 5-P to hexose 6-P. The intermediary role of arabinose 5-P was suggested by the incorporation of its carbon into various intermediates and products of the pentose pathway. Intermediary roles for ido octulose mono- and bisphosphates were supported by their participation in the reaction catalyzed by the phosphotransferase enzyme of the L-type pentose pathway. Presence of L-type PP reactions was further affirmed by 14C-prediction labelling experiments using [5-14C]- and [2-14C]glucose as specifically labelled substrates. Using two methods of measurement, the F-type pentose cycle made a negligibly small contribution to glucose metabolism, while the measured value of the L-type pentose pathway accounted for 30% (approx.) of the total glucose metabolism of these cells, a value consistent with the high activity of the enzymes of the L-type pentose pathway in Morris Hepatoma 5123C cells and the very high activity of the non-oxidative segment of the pathway in vitro. The findings validate the proposal that the L-type pentose pathway reactions constitute the non-oxidative segment of the pathway in Morris Hepatoma 5123C cells. Reasons involving pyruvate recycling reactions show why there is low incorporation of 14C-isotope in C-1 of glucose 6-P, when [4,5,6-14C]glucose and [6-14C]glucose are L-type PP test substrates in intact cells.
The phenomenon of "pyruvate recycling" is demonstrated in perfused rat liver, rabbit liver in situ and in Morris Hepatoma 5123TC cells and quantitatively measured using [2-14C]pyruvate and the method of Friedmann et al. (1971). Various metabolites, viz. lactate, DHAP, glucose, glucose 6-P and fructose 6-P were isolated and degraded following the metabolism of [2-14C]pyruvate and [2-14C]glycerol in order to assess the 14C-distributions imparted by "pyruvate recycling" reactions. The labelling of DHAP, lactate, glucose and glucose 6-P showed 14C randomizations consistent with the operation and the quantitative extent of "pyruvate recycling". These findings support the proposal that the actions of "pyruvate recycling" may account for the failure to find significant levels of 14C isotope at C-1 of glucose 6-P following the metabolism of [4,5,6-14C]- or [6-14C]glucose by L-type pentose pathway metabolism in aerobic intact tissues. "Pyruvate recycling" diminishes the measured value of the L-type pentose cycle in intact tissues and qualifies one of the mechanistic predictions of the L-type pentose pathway which was unravelled by tracing its reactions with labelled ribose 5-P and liver enzymes (Horecker et al., 1954; Williams et al., 1978a,b) in vitro. The demonstration of an association of L-type pentose pathway reactions with "pyruvate recycling" by way of the common reactions of their triose-P intermediates qualifies the superficial acceptance of the predictions of the L-type pathway in vitro for the distribution of isotopic labels by aerobic tissues in vivo.
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Adult males and females of Onchocerca gutturosa were implanted into the peritoneal cavity of mice, and their survival was determined at intervals thereafter by post-mortem examination. Ten of 17 animals receiving males dissected free of bovine host tissues contained live parasites at necropsy up to 4 months later. Female worms digested free from connective tissue by collagenase did not survive well, even though they appeared motile and intact before implantation; only 2 were alive 10 days later in 2 of 16 recipients. When males and females still contained within connective tissue capsules were implanted they survived for up to 2 months, and microfilariae were detected transiently in the skin of 2 recipient mice. The results suggest the feasibility of maintaining adult O. gutturosa in rodents by this means, provided exposure of worms to enzymes used to free them from host tissue is avoided.
Onchocerca volvulus infection of the residents of two villages in the Upper Atbara River region of Sudan (63.4% prevalence) was found to be medically and socially significant with a remarkable degree of pruritus and dermal pathology present. The severest skin changes, which were often confined to certain areas of the body, were most common in the teenage group (13-19 years). Quantitation of the clinical changes showed that the most severe alterations were present in patients with the lower levels of microfilariae in the skin (0.1-6 mf mg-1) rather than in those with higher levels. Nodules containing adult O. volvulus were found in many individuals, and often in clusters in older patients. Major losses of vision due to O. volvulus were not found, although microfilariae were frequently seen in the cornea and anterior chamber. The commonest corneal change was punctate keratitis, and this was most frequently seen in the teenage group. Trachomatous changes of eyelids and corneas were also seen. The prevalence values of O. volvulus infection in the two villages were significantly increased when, in addition to microfilarial presence in skin biopsies, onchocercal signs such as punctate keratitis, nodule presence and microfilariae in the anterior chamber were taken into consideration. This illustrates the need to consider factors other than skin snip parasitology in obtaining a diagnosis. This study also emphasizes the degree of severity that onchodermatitis can reach and that low levels of dermal microfilariae can be accompanied by very extensive skin changes without any loss of vision. The necessity of considering the severity of skin changes when defining tolerable levels of onchocerciasis in a community is discussed.
Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non-specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested. The levels of non-specific immune complexes (NS-IC) in these sera were measured by a solid phase radio-immunoassay and those of O. volvulus-specific immune complexes (OV-IC) by an assay measuring antibody-excess complexes using C1q-coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either the active destruction of microfilariae (acute changes), or the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method. A negative association between microfilarial load and immune complex level was found, with the higher levels of OV-IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV-IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the presence of ocular lesions. OV-IC levels varied considerably within each age group and from age to age. A weak positive association was detected between microfilarial load and parasite-specific IgG antibody concentration in the sera. On average younger individuals (less than 25 years) had the higher antibody levels with a gradual reduction in mean concentrations with age. The significance of these serological findings in terms of the pathogenesis of onchocerciasis is discussed.
Vascular endothelial cells regulate arterial diameter in vivo and in vitro. Stimulation of endothelial cell muscarinic receptors by acetylcholine results in the production and release of a nonprostaglandin metabolite of arachidonic acid that causes vascular smooth muscle relaxation. We examined femoral artery endothelium-dependent vasodilator responses in normal dogs and dogs with heartworm (Dirofilaria immitis) infection. Endothelium-dependent vascular reactivity was attenuated in dogs with D. immitis infection studied in the spring but not in the fall. The dilator response was inversely related to the number of female worms but not related to the presence of circulating microfilariae. Indomethacin markedly depressed responses to acetylcholine in dogs with D. immitis but did not alter acetylcholine-induced dilation in normal dogs. These data suggest that D. immitis releases substances that alter distal arterial endothelial cell arachidonic acid metabolism. The seasonal pattern may reflect the onset of maximal reproductive activity in the spring and its decline as the vector season ends in the fall.
Parasitological and clinical observations were made on residents of Pongo Nuer, a village in the province of Bahr El Ghazal, southwestern Sudan. Of 202 skin biopsies, 189 (94%) were positive for microfilariae of Onchocerca volvulus. Nodules were most common around the pelvic girdle and rare on the limbs or head. Microfilarial intensities, ranging up to 1,094 mf/mg of skin, were highest at the iliac crest and shoulder; they increased rapidly in childhood but then appeared to reach a plateau maintained through adult life. Nodule presence and number, especially at multiple sites, was significantly related to skin microfilarial intensity. Dermal manifestations of O. volvulus infection were widespread and severe, ranging from acute maculopapular eruptions to chronic, diffuse, and degenerative changes, even in young adults. However, high skin microfilarial intensities were found in asymptomatic individuals; conversely, lowest intensities were in those with severest maculopapular lesions, suggesting that host response was a major determinant of disease outcome. Microfilariae were detected in the cornea or anterior chamber of the eyes of one third of those examined in all age groups, but lesions of the posterior segment, including optic neuritis, chorioretinitis, and pigmentary abnormalities, were considered responsible for visual deficits in the population sample. Some pathologic changes in the anterior segment attributable to microfilariae were more common in the young than in adults but there was no preponderance of sclerosing keratitis in adults, contrary to expectations in hyperexposed individuals in a Sudan savannah zone. The best correlate of the presence of microfilariae in the eye was the intensity of infection in shoulder skin snips. Little value could be derived from data on outer canthus samples, either in terms of severity of ocular infection or disease. Microfilaremia was common (76%) but in only one case was attributed to O. volvulus; the remainder were due to Mansonella perstans.
The activity of ornithine-oxo-acid aminotransferase (OAT) in the liver and kidneys of rats was notably decreased as a consequence of tumor bearing. The decrease in the activity of OAT was closely related to a concomitant decrease in the rate of synthesis of the enzyme in both host tissues, while the rate of enzyme degradation remained unchanged. These results are concluded to be consistent with the proposal that host tissues of tumor-bearing animals may become "dedifferentiated," and in this example the mechanism of the expression of the dedifferentiation involved the significant decrease in specific enzyme production.
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There was a consensus between the Panel and the participants in the audience as follows: All animal use should be reviewed by an Animal Care Committee. The policies and procedures of that Committee must, in the letter and in the spirit of federal guidelines, be developed by each institution, or group of institutions, mindful of its own operational practices and should apply to all research using animals, irrespective of the source of funds. The ACC will be accountable to the public at large for the conduct of animal research. To obtain the support of the community, the ACC must have the active support of the institution, both administratively and financially, and its own academic community who must be involved in ACC activities and, where possible, in the development of its policies and procedures. Education is essential. The Committee must understand its obligations and duties especially as they relate to confidentiality and internal freedom of discussion (this applies particularly to lay members). The faculty, staff, and students must understand the protective role of the Committee for both the community and animal subjects. The institutional community must be prepared to accept the responsibilities of animal use and so accept the need for education and updating in appropriate techniques and experimental design. Individual institutions and organizations, such as the Scientists Center for Animal Welfare, can and will provide information and guidance to those seeking assistance.
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Bulimia is a serious and prevalent eating disorder in the adolescent population. The pediatrician is often in a position to make the initial diagnosis of bulimia but must suspect the disorder in light of subtle physical evidence. Denial and embarrassment reduce the likelihood of self-report of symptoms. Hand lesions resulting from self-induced emesis have a distinctive configuration and appearance. Noting these characteristic lesions during a physical examination should alert a physician to the diagnosis of bulimia or to an exacerbation of symptoms in a patient whose condition was previously diagnosed.
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The prevalence, intensity and clinical manifestations of onchocerciasis were investigated in three village communities along the Bahr El Arab and its tributaries in Southern Darfur, Western Sudan. Onchocerca volvulus has not been reported from this region before. Over 300 people were examined and the selection of patients was aimed at obtaining a cross-sectional view of the disease at all ages and in both sexes. Prevalence rates were high (67.5%, 28.6% and 32% in Titribi, Radom and Kafia Kingi, respectively). The intensity of infection in young adults was generally about 30 mf/mg, but ranged up to 100 mf/mg. Infections were detected in subjects as young as two years old; about one quarter of those sampled in Titribi had nodules, mostly in the pelvic region. Clinical signs of acute and chronic dermal changes were especially marked in Titribi. This village was located closest to the breeding sites, which appear in the rainy season only. More than a third of those samples had severe pruritus and showed many self-inflicted excoriations. Both anterior and posterior eye segment changes were detected in each community, and cases of onchocercal blindness were attributed to sclerosing keratitis and to optic and chorioretinal atrophy. One case typical of intensely localized disease was seen, where the affliction was unilateral and severe with oedema and pigment changes, but very few microfilariae present. Onchocerciasis appears to be well established in this region and has apparently caused abandonment of some settlements in recent years.(ABSTRACT TRUNCATED AT 250 WORDS)
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