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Biomedical subjects

D Grant

Publications and source records attributed to D Grant.

At least 271 records · Page 15Linked to original sources
PubMed1988

Computed tomography of the brain, chest, and abdomen in the preoperative assessment of non-small cell lung cancer.

The benefit to be gained from carrying out computed tomography of brain and abdomen in addition to the chest has been evaluated retrospectively in 114 consecutive patients with non-small cell lung cancer who, on the basis of history, clinical examination, chest radiography, and bronchoscopy had been considered potentially operable. Computed tomography of the chest showed potentially inoperable tumour in 37 patients, of whom 25 had tumour confined to the chest. Three patients were shown to have malignant disease within the mediastinum and abdomen; five within the mediastinum and brain; and four within the mediastinum, abdomen, and brain. Computed tomography of the abdomen disclosed deposits in nine patients, but in only two were the abnormalities restricted to the abdomen. Computed tomography of the brain showed metastases in 10 patients, of whom only one had metastatic disease confined to the brain. Thus three patients had isolated deposits in the abdomen and brain. In 12 patients the identification of metastases in the abdomen and brain removed the need for mediastinoscopy. Preoperative computed tomography of the abdomen and brain detected occult metastases in 15 patients (13%) in this study. In three patients the extrathoracic abnormality proved the only contraindication to surgery, but in the other 12 it provided valuable corroborative evidence of incurability and facilitated the assessment of the mediastinal abnormality.

Abdominal Neoplasms↗
PubMed1987

Receptor-mediated endocytosis of enterokinase by rat liver. Preliminary characterisation of low-density endosomes.

The endocytosis of enterokinase by rat hepatocytes has been studied both in a perfused liver system and in the intact, anaesthetised animal. 10 min after administration of the enzyme, only 70% of the activity was cleared by the perfused liver, whereas clearance was total in the intact animal. In both cases, about 85% of the internalised enzyme co-purified with the smooth microsomes and virtually all (more than 90%) of the catalytic activity was latent and could only be detected in the presence of detergent. After 10 min, 22.5% of the activity remained with the sinusoidal plasma membrane in the case of the perfused liver, while for the intact animal this figure was only 10%, confirming the more efficient clearance of enterokinase in the intact animal. Further subcellular fractionation showed that in the anaesthetised animal 8% of the internalised enzyme was associated with a low-density Golgi-like endosomal compartment (prepared from the mitochondrial pellet), whereas the corresponding value for the perfused liver was only 2.5%. Enterokinase specific activity was also up to 50-times greater in the low-density endosomes prepared from the intact animal. A second low-density Golgi-like compartment (purified from the smooth microsomes) also contained latent enterokinase, which together with the endosomes derived from the mitochondria accounted for 20% of the total enterokinase internalised by the liver 10 min after its administration to the intact animal. The passage of enterokinase through these two low-density compartments was shown not to be synchronous with its passage through the peripheral (sinusoidal membrane) and internal endosomes (smooth microsomes). There were qualitative differences in marker enzymes and polypeptide composition between the mitochondria and microsome-derived low-density endosomes. The sub-fractionation of low-density fractions on shallow sucrose gradients revealed a complex enzyme and polypeptide heterogeneity both between and within fractions. There was an apparent density-dependent separation of enterokinase from galactosyltransferase and the asialoglycoprotein receptor which was coincident with marked changes in the polypeptide composition of the endosomal membranes, particularly in the 30-45 kDa range.

Animals↗
PubMed1987

Infrared spectroscopy of heparin-cation complexes.

Hydrated and partially hydrated films and aqueous solutions of heparin, heparans and N-desulphated preparations of these polymers were studied by near- and fundamental-region-i.r. spectroscopy in the presence of a range of countercations. The results suggest that ion binding is not explicable solely in terms of simple electrostatic theory, and that specific cation effects, and the hydration pattern of the polymer-cation complex need to be taken into account.

Cations↗
PubMed1987

Chronic toxicity/carcinogenicity study of carmine of cochineal in the rat.

Carmine was fed continuously to groups of 54 males and 54 females at dietary levels providing 50, 150 or 500 mg/kg body weight/day for up to 109 wk. As a control, groups of 90 males and 90 females were fed the basal diet for the same period. The rats were derived from parents fed the same dietary levels for 60 days before mating and throughout pregnancy and were thus potentially exposed in utero. There were no adverse effects upon survival, growth or intakes of food and water. No changes associated with treatment were found during the periodic measurement of haematology or renal function, or in the serum chemistry or organ weights at the end of the study. Tumour incidence was not affected, and variations in the distribution of the non-tumour pathology were not considered to be due to treatment. It was concluded that carmine administered to rats in utero and for up to 109 wk is not carcinogenic and that the no-untoward-effect level is 500 mg carmine/kg body weight/day.

Animals↗
PubMed1987

Three-generation reproduction study on carmine of cochineal in the rat.

Carmine was fed continuously to male and female rats over three generations at dietary concentrations that provided intakes of 50, 150 or 500 mg carmine/kg body weight/day. In adult animals of all generations there were no effects of treatment on body-weight gain, food and water intakes or fertility. At autopsy the weights and the gross and microscopic appearance of the organs were normal. In the teratological investigations, examination of the foetal skeletons of the F3 generation revealed a slightly more advanced stage of ossification in all treated groups compared to those of the control. Survival, growth and development of offspring were similar in each group apart from a slight delay in the time of tooth eruption in the 150- and 500-mg/kg groups of the first and second generations. This was not seen in the final generation. It is concluded that carmine had no untoward effects on the growth and fertility of adult rats, or on the ante- and postnatal development of their offspring when given continuously at doses of up to 500 mg/kg body weight/day in the diet throughout all phases of mating, gestation, lactation, weaning and adult life over three successive generations.

Abnormalities, Drug-Induced↗
PubMed1987

Teratogenicity and embryotoxicity study of carmine of cochineal in the rat.

Groups of 30 mated female rats were given daily doses of 0, 200, 500 or 1000 mg carmine/kg body weight by oral intubation throughout pregnancy. A group of 17 similar animals was given a solution of chlorides to provide an intake of sodium, potassium and ammonium equal to that resulting from the highest dose level of carmine. There were no effects of carmine treatment on body weights, pregnancy rates, pre-implantation losses, the average numbers of live young, litter weights or foetal weights. The group given the highest dose of carmine and the cation control had increased numbers of implantations and post-implantation losses. The latter was considered to be due to an inability to maintain the increased numbers of implantations rather than to an embryotoxic effect. The foetuses showed no malformations and those from the carmine-treated rats tended to have a slightly more advanced degree of ossification of certain skeletal elements than foetuses of the control animals. On the basis of the results obtained it is considered that there were no untoward effects on embryo development in rats given oral doses of up to 1000 mg carmine/kg body weight/day throughout pregnancy.

Abnormalities, Drug-Induced↗
PubMed1987

Long-term toxicity study of amaranth in rats using animals exposed in utero.

Groups of 90 (control) and 54 (treated) rats of each sex were given amaranth in their diet to provide daily intakes of 0 (control), 50, 250 or 1250 mg/kg for 111 wk (male) and 112 wk (female) after weaning. The rats had also been exposed to the same dose levels in utero, and their parents were exposed for 60 days before mating. The colouring had no adverse effects on fertility, haematological parameters, serum chemistry or incidence of tumours. All treated animals showed contamination of the fur and red colouring of the faeces and at the high dose only the faecal pellets were poorly formed. Rats in the high-dose group produced more pups, and the average pup weight was lower than that of the controls. Rats of the F1 generation given the highest dose level were slightly lighter than the controls despite a small increase in food and water intake. Both sexes given the highest dose level and males given 250 mg/kg/day had increased caecal weight. High-dose females excreted more protein in the urine after 18 months and on histopathological examination females in all treated groups showed an increased incidence of renal calcification and pelvic epithelial hyperplasia with degenerative changes. It is concluded that amaranth fed to rats at dose levels of up to 1250 mg/kg/day in the diet did not have any carcinogenic effect. However, because of the effect on the kidneys of the females it was not possible to establish a no-untoward-effect level in this study.

Amaranth Dye↗
PubMed1987

Three-generation toxicity study of rats ingesting Brown HT in the diet.

Brown HT was fed to rats of both sexes over three generations at dietary concentrations designed to provide daily intakes of 0, 50, 250 and 500 mg Brown HT/kg body weight/day. During the study a number of females died or failed to nurse their litters. This was so severe following the first mating of F1 adults that the animals were remated to provide the next generation. None of these effects were related to treatment. Body weight and food and water intakes were not adversely affected by treatment. No effects of treatment were seen on reproductive performance or foetal and pup development, apart from slight evidence of a treatment-related retarded ossification of the third sternebrae. Organ weights at autopsy showed two changes, one of which was increased kidney weights which, although not present in every generation, seemed to be related to treatment. The other, increased caecum weights, occurred in adult high-dose females of early generations, but not in males or later generations of the study. Apart from brown coloration of tissues, macroscopic and microscopic examination revealed no treatment-related changes. It was concluded that the no-untoward-effect level in the present study was 250 mg Brown HT/kg/day.

Abnormalities, Drug-Induced↗
PubMed1987

Teratogenicity and embryotoxicity study of Brown HT in the rat.

In a preliminary study, groups of ten female rats received daily doses of either water or solutions of Brown HT providing 250, 500 or 1000 mg Brown HT/kg body weight for 19 consecutive days. While there was no indication of overt toxicity, treated animals at all doses had brown discoloration of lymph nodes, caecum and colon. In the subsequent main study, groups of 30 female rats were given daily oral doses of 0 (water vehicle), 250, 500 or 1000 mg Brown HT/kg from day 0 to day 19 of pregnancy. There were no adverse effects on the numbers of implantations, pre- and post-implantation losses, litter weights, foetal numbers, foetal weights or sex ratio. No abnormalities related to treatment were found in either the skeleton or soft parts of the offspring. It is concluded that doses of up to 1000 mg Brown HT/kg/day given throughout pregnancy failed to exert detectable embryotoxicity or teratogenicity in rats.

Abnormalities, Drug-Induced↗
PubMed1987

Orthotopic liver transplantation in children.

Ten children, aged 3 to 16 years, were part of a group of 61 patients who received liver transplants at University Hospital in London, Canada between November 1982 and April 1986. All of the children received cyclosporine in combination with other agents for immunosuppression. Two children died of rejection, one child died from a lymphoma, and one child died from a hypoxic brain injury sustained during a respiratory arrest. Six children are currently alive from 4 months to 2 1/2 years following transplantation. All of the survivors have returned to a normal life style. With current surgical techniques and modern immunosuppression, hepatic transplantation has become the treatment of choice for patients with endstage irreversible liver disease. The extreme shortage of donor organs is now the major factor limiting the application of liver transplantation in children.

Adolescent↗
PubMed1987

A comparison of cyclosporine A and Nva2-cyclosporine (cyclosporine G) in a rat renal allograft model.

We compared CsG and CsA in the DA-to-Lewis rat renal allograft model. At equivalent oral doses, plasma radioimmunoassay (RIA) CsG levels were higher than CsA (P less than 0.02). Neither drug prevented rejection at doses of 5 mg/kg/day. CsG-treated rats had a higher rejection rate at doses of 7.5 mg/kg/day (P less than 0.05). Both drugs were equally effective in preventing rejection at doses of 10 mg/kg/day. Neither drug was nephrotoxic at the doses used in this study. CsG is a potent immunosuppressant, and thus a potential clinical successor to CsA. Since CsG and CsA provide equivalent immunosuppression at therapeutic doses, CsG's clinical significance will ultimately depend on its nephrotoxicity in man.

Animals↗