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Biomedical subjects

R Knight

Publications and source records attributed to R Knight.

At least 127 records · Page 7Linked to original sources

Cytogenetic effects of cyclamates.

PHA-stimulated human peripheral lymphocytes were used as a model system for assessing the in vitro effects of calcium cyclamate. Techniques of autoradiography, cytological staining, cell counting, liquid scintillation and karyotyping were used to study the cytogenetic damage and biochemical effects of calcium cyclamate when assayed in 24 hour intervals for 96 hours. The cells were exposed to 10(-2) and 10(-3) molar concentrations of calcium cyclamate in TC 199 medium with fetal calf serum and antibiotics. These studies were carried out in three (3) phases. Phase I was primarily orientation studies of the effects of cyclamates and included running preliminary test checks, the establishment of parameters of dosage, assessing growth patterns and selecting key chromosomal aberrations. Sixty four (64) of the metaphase spreads showed morphologically detectable changes and aberrations. It was also noted that the addition of cyclamate increased mitotic rate of lymphocyte cells in cultures. Phase III arranged research designs to determine more precise characterization of chromosomal observations and morphological effects. Among other findings it was noted that of 13 types of observations only ten were found in the experimental group. The introduction of cyclamates increased the stability of the leucocyte cultures. These studies reinforced the findings on the increase of mitotic rate. Phase III extended protocols to include autoradiography and scintillation counting. It was determined that calcium cyclamate impaired the synthesis of deoxribonunucleic acid (as depicted by decreased incorporation of tritiated thymidine), reduced grain counts in autoradiographs and increased chromosome aberrations in cyclamate treated PHA stimulated peripheral blood lymphocytes in vitro. Morphological changes and growth rates showed significant effects. These studies indicate that calcium cyclamate has variable significant effects on leucocytes growth and chromosome morphology.

Autoradiography↗

Diazepam/beta-adrenoceptor antagonist interactions.

The effects of diazepam on the pharmacokinetics and pharmacodynamics of two lipophilic beta-adrenoceptor antagonists (propranolol and metoprolol) and a hydrophilic beta-adrenoceptor antagonist (atenolol) were compared in 12 subjects. Administration of propranolol and metoprolol produced small increases in the AUC0-8h for diazepam compared with placebo (P less than 0.05 for metoprolol). Atenolol had no significant effect on the AUC0-8h for diazepam. The increase in the AUC0-8h was accompanied by increases in the plasma concentrations of N-desmethyldiazepam. Diazepam had no significant effect on the pharmacokinetics of either propranolol or atenolol. The pharmacokinetic interaction could be attributed to inhibition of diazepam metabolism by the lipophilic beta-adrenoceptor antagonists. The pharmacodynamic studies showed that when compared with placebo or atenolol there was a significant impairment of kinetic visual acuity (KVA) when diazepam was co-administered with metoprolol. Although there was a significant correlation (P less than 0.02) between plasma concentrations of diazepam and impairment of KVA, the pharmacodynamic interactions may not be due solely to the small pharmacokinetic interaction observed.

Adolescent↗

The effect of free and protected oils on the digestion of dietary carbohydrates between the mouth and duodenum of sheep.

Sheep fitted with rumen and re-entrant duodenal cannulas were given diets of approximately 200 g hay and 400 g concentrate mixture alone, or supplemented daily with 40 g linseed or coconut oils free or protected with formaldehyde-casein in a 5 x 5 Latin-square arrangement. Chromic oxide paper was given as a marker at feeding time and passage to the duodenum of neutral-detergent fibre (NDF) and different sugars were estimated from the values for constituent:marker at the duodenum. Contributions of microbial carbohydrates to these flows were estimated from amounts of RNA present. The carbohydrate composition of mixed rumen bacteria from sheep rumen digesta were similar regardless of diet. Of the sugars entering the duodenum all the rhamnose and ribose and 0.51, 0.24 and 0.35 of the mannose, galactose and starch-glucose respectively, were contributed by the microbes. Virtually all the arabinose, xylose and cellulose-glucose were contributed by the diet. For sheep receiving the basal ration, coefficients of digestibility between mouth and duodenum, corrected where necessary for microbial contribution, were 0.95, 0.66, 0.67, 0.62, 0.45 and 0.51 for starch-glucose, mannose, arabinose, galactose, xylose and cellulose-glucose respectively. Corresponding values when free-oil-supplemented diets were given were 0.95, 0.55, 0.38, 0.55, 0.01 and -0.02 respectively. Values for diets supplemented with linseed oil or coconut oil did not differ significantly. Addition of protected oils to the basal feed also resulted in depressed digestibilities of dietary structural sugars but to a far lesser extent than those observed with the free oils. Apparent digestibility of NDF was altered in the same direction as those of the main structural sugars, averaging 0.50, 0.17 and 0.29 in animals receiving the basal, free-oil-supplemented or protected-oil-supplemented diets respectively. The reasons for the difference between NDF and discrete carbohydrate analytical totals are discussed.

Animals↗

The influence of polycyclic hydrocarbons on the activity of NAD(P)H-dehydrogenating enzymes in rat thymus. A biochemical and histochemical study.

The action of benzo(a)pyrene, 3-methylcholanthrene and 7,12-dimethylbenzo(a)anthracene in the activity of the rat thymus D-T diaphorase (EC 1.6.99.2) and the NAD(P)H cytochrome C (EC 1.6.99.3) reductases of particulate fractions were studied in intact and adrenalectomized animals. These polycyclic hydrocarbons increased severalfold the activity of the D-T diaphorase in intact and adrenalectomized animals. The activities of the particulate enzymes were not affected by the carcinogens. Dicumarol suppresses the inducing effects of benzo(a)pyrene and adrenalectomy does not influence the inducing effects of benzo(a)pyrene and 3-methylcholanthrene. The histological distribution of the enzyme NAD(P)H-nitroblue tetrazolium reductase was studied and a marked increase in its activity in lymphocytes, macrophages and epithelial cells was found after the administration of the carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Recognition and regulation of progenitor marrow elements by NK cells in the mouse.

The cytotoxicity of radiolabelled YAC-1 target cells by natural killer (NK) cells from the spleens of immunocompetent CBA mice is inhibited by unlabelled YAC-1 competitor cells, but not by resting bone marrow from syngeneic or allogeneic adult mice. Rapidly proliferating haemopoietic cells recovered from the spleens of lethally irradiated, bone marrow-reconstituted CBA mice, however, compete strongly in the NK assay. The competitive ability of early regenerating marrow correlates with the presence of an increased percentage of morphologically immature cells of mixed lineages. Competition declines in reconstituted spleens recovered more than 10 days after engraftment, as the proportion of immature elements falls towards that of resting marrow. Although the numbers of unlabelled YAC-1 cells required to produce equivalent competition of unstimulated and interferon-activated NK killing are similar, 10 times fewer regenerating marrow competitors compete cytotoxicity by unstimulated NK effectors to the same degree as interferon activated cells. The numbers of granulocyte-macrophage colonies formed in soft agar by regenerating marrow is also influenced by prior incubation of the marrow cells with NK effector populations. Spleen cells from homozygous athymic mice produce the same effect as cells from their heterozygous littermates. These data suggest that NK cells recognize and regulate the differentiation of progenitor elements within the marrow.

Animals↗

Comparative efficacy of albendazole against Fasciola hepatica in sheep and calves: relationship to serum drug metabolite levels.

Calves were given albendazole (ABZ) daily in feed at levels of 0,3 or 5 mg kg-1 day-1. None of the ABZ treatment levels was significantly effective in reducing Fasciola hepatica burdens. A dose rate of 5 mg kd-1 day-1 did significantly reduce the fecal egg count. Measurements of serum drug levels from calves following a single dose of ABZ showed ABZ levels to be low, but sulfoxide and sulfone metabolites of ABZ were present in (significant) larger quantities. The total available sulfoxide present in calves, however, was much lower than in sheep receiving the same dose of ABZ. Measurements of serum metabolite levels from sheep and calves which were given daily low-level doses of ABZ also indicated that the serum sulfoxide levels of calves were much lower than those of sheep receiving the same ABZ dose. These results indicated that ABZ is not an effective prophylactic treatment for bovine fascioliasis and the differences in efficacy between sheep and cattle correlated with the differences in serum metabolite levels.

Albendazole↗

Aphasia in a prelingually deaf woman.

A left parietal infarct in a prelingually deaf person resulted in an aphasia for both American Sign Language (ASL) and written and finger-spelled English. Originally the patient had a nearly global aphasia affecting all language systems. By five to seven weeks post-onset her symptoms resembled those of hearing aphasics with posterior lesions: fluent but paraphasic signing, anomia, impaired comprehension and repetition, alexia, and agraphia with elements of neologistic jargon. In addition, there was a pronounced sequential movement copying disorder, reduced short-term verbal memory and acalculia. In general, the patient's sign errors showed a consistent disruption in the structure of ASL signs which parallels the speech errors of oral aphasic patients. We conclude that most aphasic symptoms are not modality-dependent, but rather reflect a disruption of linguistic processes common to all human languages. This case confirms the importance of the left hemisphere in the processing of sign language. Furthermore, the results indicate that the left supramarginal and angular gyri are necessary substrates for the comprehension of visual/gestural languages.

Aged↗

Mortality in relation to the functional capacities of people with disabilities living at home.

The mortality experienced by a group of 1534 impaired people identified by means of a census-type survey of all households in the City of Canterbury is related to the degree of difficulty in carrying out selected self-care activities as reported by the impaired people. Although not entirely consistent, the findings in relation to people in their own homes agree with previously reported findings among patients in long-stay hospitals and residents in institutions that increasing difficulties in self-care (and therefore of dependency) are associated with increased mortality rates. These findings suggest that there is no clear boundary between some services for disabled people and those for terminal care, and that many severely handicapped people at home require co-ordinated and flexible care from nurses, social workers, and doctors.

Activities of Daily Living↗

Immune deficiency in fetal alcohol syndrome.

In a review of 13 documented cases of fetal alcohol syndrome (FAS), an increased incidence of life-threatening bacterial infections as well as a propensity to minor infections was observed. Five of 13 patients had had at least one episode of pneumonia, two had meningitis, and one had sepsis. A comprehensive immunologic evaluation of FAS was completed, and results were compared to an age-matched control group of children with intrauterine growth retardation without FAS. Children with FAS were shown to have decreased E rosette-forming lymphocytes (35 +/- 5% versus 55 +/- 5% or 1328 +/- 274 versus 2333 +/- 112 per mm3), low EAC rosette-forming lymphocytes (15 +/- 2% versus 18 +/- 1% or 524 +/- 109 versus 740 +/- 75 per mm3), and diminished mitogen-induced stimulation responses to mitogens: 31616 +/- 5337 versus 58076 +/- 4455 cpm for phytohemagglutinin, 17582 +/- 5436 versus 35018 +/- 5346 for pokeweed mitogen, and 32460 +/- 7044 versus 54996 +/- 5531 for concanavalin A, P less than 0.05. Nine patients had dysgammaglobulinemia, FAS subjects also had a marked eosinophilia (624 +/- 154 versus 72 +/- 27 mm3). Other parameters of immune function including absolute lymphocyte and neutrophil counts, total hemolytic complement, delayed cutaneous hypersensitivity, and nitroblue tetrazolium dye reduction assays, were not different from control children. Impairment of immunity may explain an increased susceptibility to infection in FAS.

Antibody Formation↗