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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 379 records · Page 21Linked to original sources
PubMed1977

Photochemical conversion of sugar dimethylthiocarbamates into deoxy sugars.

Protected sugar derivatives having one free hydroxyl group may be deoxygenated at the alcoholic position by ultraviolet irradiation of the corresponding dimethylthiocarbamic esters; a concomitant process leads also to the original alcohol. Thus, on photolysis, the 6-dimethylthiocarbamate (1) of 1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose (3) gives 6-deoxy-1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose (2) together with 3. Likewise, the 4-dimethylthiocarbamate (6) of 1,6-anhydro-2,3-O-isopropylidene-beta-D-mannopyranose (8) gives a mixture of the 4-deoxy derivative 7 and the alcohol 8. 3-Deoxy-1,2:5,6-di-O-isopropylidene-alpha-D-ribo-hexofuranose (10) was obtained by irradiation of 3-O-(dimethylthiocarbamoyl)-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (9), and was accompanied by 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (11). The 3-deoxy-3-iodo analog (14) of 11 underwent conversion into 10 by photolysis, and the deoxy sugar 10 was also prepared from 3,3'-dithiobis(1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose) (12) by the action of Raney nickel. Photolysis of the 2-dimethylthiocarbamate (16) of methyl 3,4-O-isopropylidene-beta-L-arabinopyranoside (18 gave the 2-deoxy derivative (17), together with the parent alcohol 18, and the same pair of products was obtained by the action of tributylstannane on the 2-(methylthio)thiocarbonyl derivative (19) of 18, although the dimethylthiocarbamate 16 was unreactive toward tributylstannane.

Arabinose↗
PubMed1977

Menkes' Kinky hair syndrome: studies of copper metabolism and long term copper therapy.

A patient with Menkes' kinky hair syndrome was treated with oral CuSO4. Plasma copper, ceruloplasmin, red cell copper, and 24-hr urine copper excretion remained essentially unchanged. Intravenous copper infusion resulted in a rise of serum ceruloplasmin. During administration of a test meal of 64Cu(NO3)2, the patient was given alternately a volume of 0.9% NaCl or an equal volume of plasma intravenously. Radioactivity found in the blood was unchanged after each infusion period. During 427 days of subcutaneous copper, plasma p-phenylenediamine oxidase activity and plasma copper rose toward normal. Subsequent balance studies showed that the patient was in negative copper balance because of large losses in feces. Scanning electron microscopy demonstrated persistent pili torti.

Brain Diseases, Metabolic↗
PubMed1977

Effect of human monocytes and macrophages on Trypanosoma cruzi.

Studies were undertaken to determine whether Trypanosoma cruzi can invade and multiply within human monocytes and macrophages cultured in vitro and, if so, whether macrophages can be activated to inhibit the multiplication. A reticulotropic strain of T. cruzi was capable of infecting human monocytes and monocyte-derived macrophages. Intracellular multiplication was observed in both cell types when they were examined microscopically. An increase in the number of trypanosomes occurred in the supernatants as well, providing additional evidence of intracellular multiplication and cell disruption by the parasite. Activation of monocyte-derived macrophages was accomplished by incubating the monolayers in the presence of lymphocytes and streptokinase-streptodornase. These activated macrophages inhibited intracellular multiplication of T. cruzi and the number of T. cruzi in the supernatants of these monolayers was markedly decreased as well.

Adult↗
PubMed1976

Portal hypertension in vinyl-chloride production workers.

Portal hypertension was seen in seven patients who had been involved in the production of vinyl-chloride monomer for 4-15 years. Four presented with bleeding oesophageal varices. In liver biopsy specimens non-cirrhotic portal fibrosis was inconspicuous and was seen more clearly on wedge rather than needle biopsy specimens. The intrahepatic venous pattern was hardly distrubed. Three patients have done well following shunt surgery. In one patient an angiosarcoma developed, but fibrosis was a more common lesion and was probably not pre-malignant.

Adult↗
PubMed1976

Alterations in peripheral blood leucocyte distribution in response to local inflammatory stimuli in the rat.

Changes in peripheral blood leucocyte distribution were monitored following subcutaneous injections of turpentine and subcutaneous and intrapleural injections of dextran. The responses in all three groups were similar; marked increases in total counts occurred at 6 hr, due largely to significant increases in neutrophil counts. Increases in lymphocyte counts also occurred and were more marked in the dextran-treated animals. By 12 hr, total counts fell, due to drops in both neutrophil and lymphocyte counts. In both dextran groups, neutrophil counts rose again between 24 and 72 hr, but in the turpentine group the fall persisted until 96 hr before counts reached a second peak at 14 days. In all groups lymphocytes showed an increase again at 18-72 hr. The rise in neutrophil counts observed 6 hr after the injection of turpentine was shown to be due principally to premature release of neutrophils from the bone marrow maturation compartment. Depletion of this compartment resulted in a drop in numbers of circulating neutrophils between 6 and 12 hr, in spite of the continued release of progressively less mature cells. The recovery in neutrophil counts between 72 and 96 hr was thought to be the expression of an increase in the rate of stem cell division. The continued rise to a second peak at 7 days probably resulted from increased marrow cellularity. It is suggested that the fluctuations in peripheral blood leucocyte counts may influence the initial colonisation of the local inflammatory lesion. The increase in neutrophil counts at 6 hr corresponds with the time of maximum neutrophil emigration reported by other workers and the fall in counts at 12 hr corresponds with the time of decreased neutrophil emigration.

Adult↗
PubMed1976

Role of activated macrophages in resistance of mice to infection with Trypanosoma cruzi.

The role of the activated macrophage in resistance of mice to infection with Trypanosoma cruzi was investigated with use of mice that had not been infected with T. cruzi but whose macrophages were activated by Toxoplasma gondii or Besnoitia jellisoni. Mice with activated macrophages were significantly more resistant to intra-peritoneal challenge with the Tulahuen strain of T. cruzi than were controls. The role of serum factors in resistance to T. cruzi was excluded by the demonstration of no difference between survival of T. cruzi in serum from mice with activated macrophages and in that from controls. As the only modality of resistance to T. cruzi in this in vivo model appeared to be the activated macrophage, this cell was investigated in vitro. Activated macrophages were shown to be able to inhibit completely multiplication of T. cruzi, whereas significant multiplication of the parasite occurred in control macrophages. Both in vivo and in vitro data suggest that the activated macrophage may play a major role in resistance to infection with T. cruzi.

Animals↗
PubMed1976

Strain-dependent differences in murine susceptibility to toxoplasma.

Susceptibility of seven inbred and outbred strains of mice to infection with trophozoites of Toxoplasma gondii at two different doses was determined. Stroking strain differences in susceptibility and changes of susceptibility with dosage change were seen. The data are consistent with the hypothesis that this may be due to genetic factors.

Animals↗
PubMed1976

Monitoring liver disorders in vinyl chloride monomer workers using greyscale ultrasonography.

Recognition that vinyl chloride could be hepatotoxic led to a survey of workers to determine whether changes had been induced by past exposure, and to evaluate standard liver function tests as monitors of early liver abnormalities. Standard liver function tests were found to be unsuitable for the detection of such abnormalities in the population at risk. Of 487 workers examined, 102 (20-9%) had abnormalities on initial testing but only two were finally shown to have portal hypertension; in both cases, thrombocytopaenia provided the first diagnostic evidence since liver function tests were normal. Furthermore, 40 (35-7%) of 112 control subjects had initial test abnormalities. A sample of 19 workers with various exposures to vinyl chloride monomer were examined blind by greyscale ultrasonography. Five with minimal or no exposure were confirmed as normal but 12 of the remainder had abnormalities. These consisted of an enlarged portal vein (seven instances), splenomegaly (eight), and changes in hepatic texture (seven). Five of these 12 cases had previously been considered normal. It was concluded that greyscale ultrasonography had many advantages over standard methods for screening workers exposed to hepatotoxic chemicals, and should be the subject of a large scale evaluation.

Adult↗
PubMed1976

The influence of prostaglandin F-2alpha on pregnenolone metabolism by the autotransplanted ovary of the ewe.

Eight ewes each with an autotransplanted ovary received infusions of tritium-labelled pregnenolone (41 muCi/hr) for 8 hr into the artery supplying the ovary, together with prostaglandin (PG) F-2alpha (30 mug/hr) for 3 hr beginning 2 hr after the start of the pregnenolone infusion. All animals exhibited oestrus 2-3 days after the start of the experiment. During the PGF-2alpha infusion blood flow through the ovaries was increased by 13%, but subsequently returned to pre-infusion levels. Secretion rates of endogenous progesterone and 20alpha-hydroxypregn-4-en-3-one dropped rapidly 5 hr after the PGF-2alpha infusion had started from values of 250 mug/hr and 25 mug/hr to values below 60 mug/hr and 8 mug/hr, respectively. At this time the conversion of radioactive pregnenolone to progesterone was reduced by 50% of its initial value, but the secretion of endogenous pregnenolone and the formation of radioactive metabolites other than progesterone were not diminished. In 4 control animals, which received pregnenolone only, no changes in ovarian blood flow, steroid secretion rates, or in the conversion of labelled pregnenolone were observed. These results suggest a possible involvement of PGF-2alpha in the regulation of progesterone biosynthesis by an action on the 3beta-hydroxysteroid oxidoreductase-delta5(-4) isomerase enzyme system.

Animals↗
PubMed1976

Premature chromosome condensation in human leukemia.

Premature chromosome condensation (PCC) has previously been observed in tissue culture and is believed to arise from asynchronous mitotic activity in multinucleated cells in which the affected nucleus is in interphase and at least one nucleus is in metaphase. Such cells have been noted following fusion induced by virus infection, spontaneously, and after treatment with cytochalasin B. The phenomenon has also been observed in malignant pleural effusions, but has not previously been described as a feature of hematologic disease. In this study, we report the observations of PCC in seven patients. Six of these patients had either acute myeloblastic leukemia or acute myelomonoblastic leukemia in association with the features of erythroleukemia, i.e., leukoerythroblastic reaction in the blood, and erythroid multinuclearity, "megaloblastoid" changes, and PAS-positive staining of erythroid precursor cells in the bone marrow. In all patients, erythroid multinuclearity has been noted. However, not all patients with erythroleukemia exhibit PCC. In this series, three additional patients have had similar bone marrow morphologic changes without PCC. The finding of PCC in erythroleukemia may have important implications as to etiology of this disorder.

Aged↗
PubMed1976

Role of copper in mitochondrial iron metabolism.

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.

Animals↗
PubMed1975

Grey-scale ultrasonography for monitoring industrial exposure to hepatotoxic agents.

Industrial exposure to several potentially hepatotoxic agents, such as vinyl-chloride monomer may occur, and there is a need for non-vasive, diagnostic techniques to detect and monitor progressive pathological processes in liver or spleen. Grey-scale ultrasonography permits display of detailed anatomy and pathology in the liver, portal veins, and spleen. The combination of fine resolution, non-invasiveness, absence of ionising radiation hazard, and portable equipment makes the technique ideal for screening populations at risk.

Chemical Industry↗