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Biomedical subjects

D Roberts

Publications and source records attributed to D Roberts.

At least 379 records · Page 21Linked to original sources

Studies on the growth of Vibrio cholerae biotype eltor and biotype classical in foods.

The growth of Vibrio cholerae biotype eltor and biotype classical was studied in a range of cooked foods, shellfish and raw vegetables, incubated at 22 degrees, 30 degrees and 37 degrees C. Both biotypes grew in all cooked foods but growth was not demonstrated on raw shellfish. The organism multiplied on some vegetables to levels of the order of 10(6)/g. The classical biotypes of V. cholerae showed a longer lag period than the eltor biotype in some foods particularly when incubated at 22 degrees C. The eltor biotypes reached a higher level in the stationary phase than the classical biotypes.

Asia↗

Factors contributing to outbreaks of food poisoning in England and Wales 1970-1979.

Epidemiological data accompanying reports of more than 1000 outbreaks of food poisoning have been studied to determine the factors which most frequently contributed to the outbreaks. Preparation of food in advance of needs combined with improper storage and inadequate cooking, cooling and reheating were the most common factors. Infected food handlers did not play a significant role except in instances of S. aureus food poisoning.

Disease Outbreaks↗

Cytotoxicity of 5-fluoro-5'-O-nitro-2'-deoxyuridine, a new fluorinated pyrimidine derivative, in L1210 cultures.

5-Fluoro-5'-O-nitro-2'-deoxyuridine (FdUMN), a neutral isostere of 5-fluoro-2'-deoxyuridine 5'-monophosphate, inhibited the growth of L1210 cultures. The inhibition of L1210 cultures by FdUMN was prevented by thymidine, but not by 2'-deoxyuridine. Like 5-fluoro-2'-deoxyuridine (FdUrd), FdUMN inhibited the incorporation of 2'-deoxyuridine into DNA, but the onset of this inhibition was not immediate, as was seen with FdUrd. FdUMN did not inhibit the activity of purified thymidylate synthetase from Lactobacillus casei and was a poor inhibitor of thymidylate synthetase activity in homogenates of L1210 ascites cells. However, after incubation with homogenates of these cells and subsequent addition of ATP, FdUMN inhibited this enzyme effectively. These results indicate that intracellular activation of FdUMN is required for its inhibition of thymidylate synthetase.

Animals↗

Carcinoma in situ of the vulva. The search for viral particles.

Biopsy specimens taken from eight women with squamous-cell carcinoma in situ of the vulva were studied with transmission electron microscopy for the presence of viral particles. In one of the specimens a 150-nm-diameter viruslike particle was found. The exact nature of this particle was not clear, but it could have represented an immature herpesvirus particle. In seven specimens no evidence of viral particles was detected. These findings provide further evidence that the positivity of vulvar carcinoma in situ for herpesvirus antigen is not due to the presence of whole virus particles.

Adult↗

Symptom relief and the placebo effect in the trial of an anti-peptic drug.

In order to determine some of the factors involved in the response of duodenal ulcers to placebo treatment, the following factors were studied prospectively during a double-blind, placebo-controlled trial: demographic data; duration of illness and effect of treatment; expectation of success or failure of the new drug; presence of psychiatric problems; and suggestibility. Healing (measured by endoscopy) occurred in 37 patients, 17 of whom were receiving placebo; relief of symptoms occurred in 35 patients, 16 of whom were receiving placebo. There was no significant difference between drug and placebo. Healing was significantly associated with relief of symptoms but with no other variable. Relief of symptoms was more common in male patients and in those from higher social classes, as well as in patients who expected a complete cure and those without evidence of psychiatric problems. the natural history of the disease may be different in these patients. Unexpectedly, suggestibility was not associated with healing or relief of symptoms in the patients receiving placebo.

Adult↗

Effect of methotrexate and 1-beta-D-arabinofuranosylcytosine on pools of deoxyribonucleoside triphosphates in L1210 ascites cells.

Pools of deoxyribonucleoside triphosphates in L1210 cells were assayed for drug-induced changes that might indicate the metabolic basis for retention of 1-beta-D-arabinofuranosylcytosine triphosphate by these cells after treatment with methotrexate (MTX) and 1-beta-D-arabinofuranosylcytosine (ara-C). Within 20 min after treatment with MTX, the pool of deoxythymidine triphosphate (dTTP) had decreased by about 50% and during the next 8 hr decreased slowly to 30% of its initial level. When MTX-induced decreases in the cellular contents of deoxycytidine triphosphate (dCTP), deoxyadenosine triphosphate (dATP), and deoxyguanosine triphosphate (dGTP) were normalized to percentages of the initial levels, they coincided with the second slower phase of decrease in dTTP. During the study, levels of both dTTP and dCTP remained constant in cells from mice treated with 0.9% NaCl solution, whereas levels of both dATP and dGTP decreased. MTX caused a significantly more rapid decrease in the level of dATP than did 0.9% NaCl solution but not in the level of dGTP. Over a 9-hr period, after injection of ara-C, levels of both dTTP and dCTP doubled while levels of both dATP and dGTP remained unchanged. When ara-C and MTX were administered together, levels of dTTP, dATP, and dGTP did not change significantly, and the increase in dCTP was only 25% of the increase after treatment with ara-C alone. Thus, the most striking change in deoxyribonucleoside triphosphate pools after combined administration of MTX and ara-C was an increase in dCTP concentration that reached about one-fourth the concentration achieved with ara-C alone. We suggest that MTX, by attenuating the ara-C-induced increase in dCTP, caused a change in the allosteric regulation of either deoxycytidine kinase or deoxycytidylate deaminase (or both), thereby potentiating the activity of ara-C.

Animals↗

The kinetics of effector binding to phosphofructokinase. The binding of Mg2+-1,N6-ethenoadenosine triphosphate to the catalytic site.

1. The binding of the fluorescent ATP analogue, Mg2+-1,N6-etheno-ATP, to the catalytic site of rabbit skeletal muscle phosphofructokinase has been studied by stopped-flow fluorimetry [Roberts & Kellet (1979) Biochem. J. 183, 349--360]. 2. Binding of Mg2+-1,N6-etheno-ATP to the catalytic site is consistent with a two-step mechanism of the type: (formula: see text); in which the diffusion-controlled binding of ligand, L, is accompanied by prior interconversion of enzyme from one form, E, to another, E. 3. The allosteric activators, phosphate and cyclic AMP, which promote an R-type conformation, appear to stabilize slightly different conformations, R and R' respectively. 4. The binding of Mg2+-1,N6-etheno-ATP to the catalytic site is strongly affected by its binding to the inhibitory site. The rate constant for the displacement of Mg2+-1,N6-ethenol-ATP from the catalytic site, k32, is 470 +/- 35 s-1 for the R' conformation, whereas it is 6.0 +/- 0.09 s-1 for the T conformation induced by binding of Mg2+-1,N6-ethenol-ATP to the inhibitory site.

Adenosine Triphosphate↗

The kinetics of effector binding to phosphofructokinase. The influence of effectors on the allosteric conformational transition.

1. The extent of the allosteric transition from the R into the T conformation of rabbit skeletal muscle phosphofructokinase induced by Mg2+-1,N6-etheno-ATP was determined by stopped-flow fluorimetry from the amplitude of the slow phase of the Mg2+-1,N6-etheno-ATP fluorescence enhancement [Roberts & Kellet (1979) Biochem. J. 183, 349--360]. 2. The amplitude of the slow phase was decreased by low concentrations of the activators cyclic AMP and fructose 1,6-bisphosphate, but increased in a complex manner by the inhibitor citrate. 3. Mg2+-1,N6-etheno-ATP and Mg2+-ATP are unable to induce the T conformation to a detectable extent in the presence of saturating cyclic AMP, but can do so readily in the presence of saturating fructose 1,6-bisphosphate. 4. The conformational transitions induced in enzyme alone by different ligands were observed by changes in intrinsic protein fluorescence. In general, an R-type conformation has diminished protein fluorescence compared with a T-type conformation. 5. Mg2+-ATP exerts a complex effect on protein fluorescence; both the enhancement at low concentrations and the quenching at high concentrations of Mg2+-ATP result from the binding of Mg2+-ATP to the inhibitory site and the ensuing allosteric transition. Enhancement reflects the extent of the allosteric transition and involves both tyrosine and tryptophan, probably in the region of the active site; quenching reflects occupation of the inhibitory site and involves tyrosine at the inhibitory site. 6. The mechanism of the allosteric transition from the R into the T conformation induced by Mg2+-1,N6-etheno-ATP at low concentrations occurs predominantly by a 'prior-isomerization' pathway; at higher concentrations a limited contribution from a 'substrate-guided' pathway occurs. 7. The allosteric behaviour of phosphofructokinase with respect to Mg2+-ATP and Mg2+-1,N6-ethenol-ATP binding may be accounted for in terms of the simple, concerted model.

Adenosine Triphosphate↗

Effect of VM-26 on the haematological responses of mice to L1210 leukaemia.

The haematological responses of BDF1 mice were monitored after i.v. or i.p. inoculation of L1210 leukaemic cells. Although a marked decrease in haematocrit was observed in mice given L1210 by either route, the anaemia was most pronounced after the i.p. route. The leucocyte count was more markedly increased after i.v. inoculation than after i.p. inoculation. The number of platelets decreased following either route, but was more depressed by i.v. inoculation. When mice were treated with VM-26 on Day 4 and i.p. inoculation of 10(6) L1210 cells, the haematological responses were altered. VM-26 prevented the accumulation of haemorrhagic ascites fluid and the precipitous decline in haemotacrit. However, the number of leucocytes increased dramatically, most significantly during the 48 h before death. VM-26 caused a temporary restoration of platelet count to near baseline levels. By the time of death, however, a second decrease in platelets had occurred. The results suggest that the haematological response of mice to L1210 leukaemic cells varies according to the route of inoculation, and that these tumour-induced haematological responses of the host can be modified by treatment with VM-26.

Animals↗

The determination of regional and age variations in the rate of desquamation: a comparison of four techniques.

The measurement of the rate of desquamation is an important parameter for epidermal cell kinetic considerations. In order to obtain such information, we have compared 2 existing techniques with a new one and with a modification of a little-used technique for determining the rate of cell loss from the stratum corneum. We have also studied regional and age variations in desquamation in normal skin. The results of the studies performed show there was a strong positive correlation between the "chamber" technique (which measures passive desquamation) and the "scrub" technique (measuring forced desquamation). There was similar strong negative correlation for the scrub technique and the dansyl chloride fluorescence method which measures stratum corneum renewal.

Abdomen↗