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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 127 records · Page 7Linked to original sources

The use of renal cortical slices from the Fischer 344 rat as an in vitro model to evaluate nephrotoxicity.

The toxicity of several classical acute nephrotoxicants was evaluated in an in vitro system using renal cortical slices prepared from adult male Fischer 344 rats. Gentamicin, cephaloridine, 4-ipomeanol, potassium dichromate (K2Cr2O7), mercuric chloride (HgCl2), carbon tetrachloride (CCl4), and hexachlorobutadiene (HCBD) were preincubated with slices for 2 hr at 37 degrees C at concentrations ranging from 1 x 10(-6) to 1 x 10(-1) M. Following preincubation, slices were removed, rinsed in medium lacking the nephrotoxicant, and subsequently incubated for 90 min at 25 degrees C for physiological assessment of proximal tubular functions. Using a single preparation, slices were monitored for organic ion accumulation, gluconeogenesis, lipid peroxidation, and total glutathione (reduced and oxidized) concentrations. In addition, preincubation and incubation media were assessed for the presence of renal enzymes originating from brush border, cytosol, and lysosomes. The relative degree of toxicity in this model was consistent with nephrotoxic potency in vivo where HgCl2, K2Cr2O7 greater than HCBD greater than CCl4, cephaloridine greater than gentamicin greater than 4-ipomeanol. Effects on organic ion accumulation, gluconeogenesis, and glutathione concentrations occurred simultaneously for each toxicant. Toxicants produced different effects on enzyme release and malondialdehyde formation. These results suggest that toxicity produced in vitro is representative of in vivo nephrotoxicity and support the further use of this model to evaluate mechanisms of nephrotoxicity.

Acetylglucosaminidase↗

Plasma levels of beta-endorphin in white-tailed deer: seasonal variation and the effect of thyroxine, GnRH, dexamethasone and ACTH administration.

1. A distinct seasonal cycle of beta-endorphin (beta-E) was detected in plasma of four intact, male white-tailed deer. Peak levels (around 11 pg/ml) were observed in August and minimal concentrations (around 5 pg/ml) were detected in January and February. 2. The seasonal variation (which corresponds to intensity of antler growth) was more pronounced in the two mature bucks, as compared to the immature ones. 3. Intramuscular administration of synthetic thyroxine (in doses of 500, 750 and 1000 micrograms/deer) and GnRH (100 micrograms/deer) had generally no significant effect on the beta-E levels. 4. I.v. administration of dexamethasone (5 mg/deer) as well as i.m. injection ACTH (20 Int. Units/deer) significantly reduced beta-E levels.

Adrenocorticotropic Hormone↗

Antenatal fetal heart rate variation in relation to the respiratory and metabolic status of the compromised human fetus.

Three groups of women were delivered by caesarean section before labour: for an abnormal fetal heart rate (FHR) trace (21 cases, group 1), or for maternal deterioration in severe pre-eclampsia without gross fetal heart rate abnormalities (20 cases, group 2), or to avoid mechanical difficulties in labour at term (30 cases, group 3). The mean gestational ages of the first two groups were 32 weeks with a high proportion of infants small-for-gestational-age. In group 1, FHR variation (mean range of pulse intervals) was less than half (20.6 SE 1.2 ms) of the normal value at the same age (44.4 SE 1.5 ms). This was associated with hypoxaemia (mean umbilical artery PO2 of 6 mmHg at delivery), with evidence of compensation shown by an elevated amniotic fluid erythropoietin. The fetuses were hypoglycaemic and had greater umbilical artery blood alanine concentrations, but no large changes in adenine nucleotide or endorphin plasma concentrations. Although there was a minor degree of respiratory acidaemia at birth, there was not significant metabolic acidaemia. The results demonstrate that the reduced variation of 'suboptimal' and 'decelerative' fetal heart rate records is associated with fetal hypoxaemia and evidence of nutritional deprivation, but not with asphyxia.

Cesarean Section↗

Experimental infection of the nine-banded armadillo (Dasypus novemcinctus) with Schistosoma mansoni (Kenyan strain).

Eleven wild-caught nine-banded armadillos were infected with cercariae of the Kenyan strain of Schistosoma mansoni for 1-25 weeks. Distribution of eggs along and within the gut and liver was similar to that seen in human schistosomiasis. However, egg excretion was poor, eggs were small, rate of infection was low, and the prepatent period was long. From these data it is concluded that Dasypus novemcinctus is an inefficient reservoir host of S. mansoni.

Animals↗

The ultrastructure of the Schistosoma mansoni egg.

Helminth eggs have resisted analysis by electron microscopy because fixatives, dehydrating agents, and embedding media penetrate these eggs poorly. Slam-freezing at liquid nitrogen temperature followed by freeze-substitution and Spurr's medium embedment provides preservation of the internal structure of the Schistosoma mansoni egg shell, developing miracidium, and perimiracidial structures. The egg shell consists of the three previously described layers (outer microspinous, middle intermediately dense, and inner dense layers) with cribriform pores. A newly described layer (Reynolds' layer) develops subjacent the egg shell and is comprised of densely-packed branching filaments. A single layer of squamous cells (von Lichtenberg's envelope) closely adheres to Reynolds' layer. Between von Lichtenberg's envelope and the embryo is a space (Lehman's lacuna); this space is initially filled with electron-lucent fluid, but subsequently masses of granulofloccular material (Cheever bodies) develop; Cheever bodies are partially membrane bound. Epidermal plates differentiate from superficial cells of the embryonal cell mass, while epidermal ridges differentiate from cells just below the surface of the embryonal cell mass. The cytoplasmic layer (von Lichtenberg's envelope) interposed between the host extracellular fluid and the developing miracidia effect a barrier against a simple passive diffusion; this infers that complex macromolecules, such as schistosomal egg antigen, undergo active, and perhaps selective, transport in or out of the egg.

Animals↗

Evidence that post-transcriptional changes in the expression of mitogen regulated protein accompany immortalization of mouse cells.

Primary mouse embryo fibroblasts passed in culture go through a period of declining growth rate and then after a period of minimal proliferation begin to grow again, generating, under appropriate conditions, an immortal 3T3 line. The 3T3 cells, but not the primary mouse embryo fibroblasts, are able to synthesize and to secrete mitogen regulated protein (MRP, also known as proliferin). We report here that the level at which the change in gene expression occurs during this spontaneous immortalization process is post-transcriptional, reflecting a change in either RNA processing or transcript stability. To our knowledge, this is the first report of an alteration at the post-transcriptional level of gene expression that accompanies immortalization.

Animals↗

Rising detection rate of symptomatic Dukes' A colorectal cancers.

All 197 patients admitted to the Bristol Royal Infirmary during the 16 year period 1970-1985, and diagnosed as having Dukes' A colorectal cancers, were studied. The numbers diagnosed per year by 1985 were 20, compared with 9.4 per year for the period 1970-1979. This represented an increase in the percentage of Dukes' A cancers of all the colorectal cancers diagnosed from 8.3 to 15 per cent. The increase was largely due to better quality double contrast barium enemas and increased use of flexible sigmoidoscopy and colonoscopy. The operative mortality dropped from 17 to 3 per cent in the last 6 year period. The recurrence rate was 9.6 per cent of which 1 per cent were locally resected and crude 5 year survival was 90.4 per cent up to 1981.

Adolescent↗

Molecular cloning of a tumor promoter-inducible mRNA found in JB6 mouse epidermal cells: induction is stable at high, but not at low, cell densities.

From the mouse JB6 epidermal cell line C122 we have isolated a cDNA clone representing a 1.6-kilobase mRNA, called 2ar, that exhibits a biphasic induction in response to 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The first phase of induction in subconfluent cells is transient, peaking at 6 h after the addition of TPA and returning to noninduced levels by 24 h. When the cells reach plateau density, in the continued presence of TPA, this mRNA is reinduced and remains so upon continued exposure to the tumor promoter. Serum and certain growth factors also induce 2ar mRNA in serum-deprived quiescent fibroblasts. In vitro nuclear "run-on" transcription experiments indicate that the induction of 2ar mRNA is controlled at the transcriptional level.

Animals↗

Elevated plasma enteroglucagon alone fails to alter distal colonic carcinogenesis in rats.

The effect of physiologic increases of plasma enteroglucagon, induced by massive bypass or resection of small bowel, on large bowel cell turnover and carcinogenesis was studied in rats in which the distal colon was isolated as a mucous fistula. After injections of azoxymethane, either 85% end-to-side jejunoileal bypass, 85% jejunoileal resection, or sham bypass was performed. Controls underwent colonic transection and resuture, azoxymethane treatment, and then sham bypass. Thirty weeks later the plasma enteroglucagon level had almost trebled after jejunoileal bypass (p less than 0.001) and almost doubled after jejunoileal resection (p less than 0.002) when compared with sham bypass; sham values did not differ from controls. The median number of tumors per rat in the distal (defunctioned) colon fell from 2 to 0 (p less than 0.05). Segmental weight fell by 45% (p less than 0.001) and crypt cell production rate by 75% (p less than 0.001). Neither tumor yield nor adaptation was affected by jejunoileal bypass or jejunoileal resection. Plasma enteroglucagon has no effect on colonic cell turnover or carcinogenesis in the absence of luminal content.

Animals↗

Posttraumatic ulnar translation of the carpus.

Ulnar translation of the carpus is a rare posttraumatic carpal instability pattern, in which the entire carpus is displaced ulnarward on the radioulnar surface. No previous formal reports of this problem have been located although it has been described in general discussions of wrist instability. Seven men and one woman were diagnosed with this condition although the diagnosis was delayed from 2 to 23 months, an average of 7.3 months. Three patients were treated surgically before diagnosis; the other five patients were treated conservatively before diagnosis. At the time of definitive diagnosis the radiographs showed an ulnar translation of the carpus, which was quantified on the radiographs in all eight patients by the method of Chamay. Four patients had an attempt to repair the radiolunate and radiocapitate ligaments. One patient had a ligamentous augmentation of the radiocapitate ligament complex. Two patients had ligamentous repairs of a scapholunate dissociation; one of these had simultaneous radiocarpal ligamentous augmentation. The eighth patient had a radiolunate arthrodesis. Follow-up averaged 32 months. Three patients had formal wrist arthrodeses at 10, 13, and 26 months after initial ligamentous repair, which were considered treatment failures. In the remaining five patients, four had partial recurrent ulnar shift, which was seen radiographically. Of these, three patients rated the result as good, with near normal strength and returned to full activities while two obtained fair results, with minimal pain but decreased range of motion and decreased strength. One patient has shown progressive degenerative radiocarpal changes and may become a candidate for a limited or formal wrist arthrodesis.

Adult↗

Cooling prevents ischaemic testicular damage after spermatic cord clamping in rats.

A controlled trial was conducted on four groups of seven rats to evaluate any beneficial effect of cooling to 15 degrees C on testicular ischaemia induced by clamping of the spermatic cord for 2, 4, 6 or 8 h. At operation the microscopic appearance of the testes on unclamping was a poor guide to ultimate viability, whereas by the third day macroscopic and microscopic appearances concurred. When killed on the third day, testicular histology demonstrated that increasing periods of clamping led to gross ischaemia and infarction when testes were maintained at 37 degrees C, and this was reduced greatly by testicular cooling. For each period of clamping, maintenance of spermatogenesis, expressed in terms of Johnsen's histological scores, was significant (P less than 0.01), being 2 (37 degrees C) vs 5.3 (15 degrees C) for 8-h clamping. It is proposed that testicular cooling should be used during autotransplantation of testes in humans.

Animals↗

Low human fetal heart rate variation in normal pregnancy.

The fetal heart rates of 340 normal singleton pregnancies at 30-33 weeks gestation were screened using a microprocessor system on-line. Eleven fetuses (3.2%) with a heart rate variation less than the 5th centile were identified, of whom 10 were studied longitudinally. At 30-33 weeks the mean minute range of pulse intervals (a measure of fetal heart rate variation) was 31.4 (SE 1.5) ms compared with 51.0 (SE 3.4) ms in a randomly selected control group. The study group continued to have significantly lower fetal heart rate variation than controls on each of three subsequent occasions until delivery. There were no significant differences between the two groups in fetal outcome, which was good. This demonstrates that a small proportion of normal fetuses have consistently low heart rate variation, and helps to define the lower limit of the normal distribution of fetal heart rate variation. After delivery, there were no significant differences between heart rate or its variation between the two groups. We conclude that the lower prenatal heart rate variation in the study group was a consequence of the uterine environment.

Female↗

Ileal carcinoma and tuberculous ileitis.

A 76 year old woman presented with abdominal pain and weight loss. At laparotomy she was found to have an adenocarcinoma of the ileum arising in a segment of tuberculous ileitis. The possible significance of this association is discussed.

Adenocarcinoma↗

The development of a system for transillumination computed tomography.

A transillumination computed tomography system has been developed for studies of the breast, testes, neonatal skull and peripheral limbs. Initial experiments on test objects have emphasised the problems of scattering and geometrical dependence of lesion detection that are likely to be encountered in conventional diaphanography, but have demonstrated the feasibility of computed tomography as a means of improving the sensitivity of the transillumination technique. The problems of transillumination computed tomography have been addressed and further areas of research identified.

Humans↗

Relationships between dietary protein, dietary energy, rearing environment, and nutrient utilization by broiler breeder pullets.

The relationship between dietary energy and protein and their interaction with method of restriction and environment were studied. In Experiment 1, two isocaloric diets (2750 kcal/kg) formulated to contain either 13.5% or 15.5% protein were fed to broiler breeder pullets from hatching through 21 weeks of age. There were no significant differences in body weight due to dietary protein but chicks fed the 13.5% protein ration did require a significantly greater quantity of feed to produce an equivalent body weight. Sexual maturity, peak egg production, and egg size were not affected by the level of dietary protein but total egg production was significantly decreased in pullets fed the 13.5% protein diet. In Experiment 2, 2970 kcal/kg ration containing 15.5% protein was fed to pullets that were reared under two different lighting environments, natural daylength or 24 hr light for the first 7 days and 8 hr light per day thereafter. Pullets housed in the controlled environment and reared on an every-other-day restriction program had significantly improved feed utilization compared with similarly restricted birds kept under natural light. Environmental effects on feed utilization were not as great in the every day restriction treatment. Chicks exposed to natural daylight and fed 15.5% protein diets had similar caloric efficiencies (kcal/g) at 15 weeks of age in both experiments despite dietary density differences of 220 kcal/kg. This supports a hypothesis that above some minimal level of protein intake, caloric intake has the greatest control over body weight gain in restricted pullets, particularly where every-other-day feeding is used during part of the growing period.

Animal Feed↗

Pathogenesis of Sarcocystis falcatula in the budgerigar. I. Early pulmonary schizogony.

Sarcocystis falcatula is a protozoan parasite which obligatorily alternates its definitive host, the opossum (Didelphis virginiana), and a uniquely wide range of avian intermediate hosts. The disease produced by this coccidian parasite in intermediate hosts was studied in the budgerigar bird (Melopsittacus undulatus). The ultrastructure of pulmonary sporozoites, meronts and merozoites of this Sarcocystis species is described. Early schizogony occurs progressively in pulmonary capillary and in venular and venous endothelial cells.

Animals↗