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Biomedical subjects

J G Sharp

Publications and source records attributed to J G Sharp.

At least 127 records · Page 7Linked to original sources

The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats.

The objective of these experiments was to determine the effects of neonatal thymectomy on the induction of experimental autoimmune orchitis in inbred rats of the Fischer 344 and Lewis strains. It was found that thymectomy alone in Lewis rats, and thymectomy followed by immunization with testicular extract in both Lewis and Fischer 344 rats, led to the development of autoimmune orchitis, as indicated by decreased testes weights, increased serum spermagglutinating antibody titers and histopathological changes in the testes. These data indicate that rats of the Lewis strain are genetically predisposed to the development of autoimmune orchitis, and thymectomy alone leads to active manifestations of the disease, which are further enhanced by subsequent immunization with testicular extract. In Fischer 344 rats, thymectomy followed by immunization leads to indications of early signs of experimental autoimmune orchitis. This is in contrast to experimentally induced autoimmune diseases in other model systems, where previous investigators have reported that thymectomy lessens or prevents induction of autoimmune disease. It is suggested that these differences may be related to the timing of thymectomy with regard to differences in the time of appearance of sperm antigens (at puberty) as compared to pre-natal and early neonatal appearances of other autoantigens.

Animals↗

Lymphocyte fluorescent profiles (LFP): a possible screening technique in neoplasia.

A technique involving fluorescent protein staining and microfluorometry has been developed for measuring the lymphocyte fluorescent profile (LFP) of peripheral blood lymphocytes. In contrast to normal humans who display a regular bell-shaped curve, the profile from patients with cancer is irregular, showing a bimodal distribution of fluorescence, with a significant population of cells fluorescing at a higher relative intensity. It is suggested that this elevation in protein concentration is due to an immune response to the presence of a neoplasm, and thus this technique may prove to be a useful indicator of malignancy.

Adult↗

Inverse relationship between splenomegaly and stem cell compartment size in mice treated with nitrogen mustard.

Following the administration of similar doses of nitrogen mustard (4 mg/kg) to different strains of mice, wide variations in the subsequent degree of splenomegaly were observed, implying strain differences in the role of the spleen in the compensatory erythropoietic response to haematopoietic stress. This investigation was undertaken to determine whether or not these differences were related to the size of the haematopoietic stem cell compartment size in the various strains of mice. Groups of 4 different strains of mice (Swiss Webster, A/J, C57BL/6J and CS1/ASH) were injected i.v. with nitrogen mustard (4 mg/kg body weight) and autopsied at regular intervals up to 20 d post-injection. At autopsy, the wet weight of the spleen was determined. Subsequently, groups of the same 4 strains of mice were exposed to single doses of wholebody gamma-irradiation in the range of 500-900 rads. 9 d after gamma-irradiation the mice were autopsied, their spleens removed, and the number of endogenous spleen colonies determined. The greatest degree of splenomegaly was observed in the C57BL/6J mice. The Swiss Webster mice showed no splenomegaly during the time period studied. There existed a linear inverse relationship between the maximum degree of splenomegaly observed and the dose of wholebody gamma-irradiation required to completely eliminate endogenous spleen colonies. This data is in accord with the hypothesis that there exists an inverse relationship between the extent of splenomegaly observed following haematopoietic stress and the haematopoietic stem cell compartment size.

Animals↗

Stereoscopic anatomy: evaluation of a new teaching system in human gross anatomy.

Traditionally, human gross anatomy teaching has revolved around anatomical dissection. Unfortunately, during the last decade a number of medical schools have experienced a decrease in the number of hours allotted to gross anatomy instruction compounded by a shortage of anatomical donors. This, in turn, has served to increase the difficulties of providing students with truly effective anatomical instruction. To help overcome this problem, a stereoscopic slide-based auto-instructional program has been developed as a substitute for dissection. Evaluation data suggest that this program, while having minor limitations in terms of anatomical orientation, does provide a viable alternative to dissection.

Anatomy↗

Compensation by the residual intestine after intestinal resection in the rat. I. Influence of amount of tissue removed.

Thirty days after resection of 10 to 80% of the midportion of the small intestine, excluding the duodenum, several cell kinetic parameters were investigated in the residual intestine. The degree of intestinal response increased in a stepwise fashion as the amount of tissue removed was increased. The response involved marked increases in: DNA synthesis per crypt expressed as disintegrations per minute of tritium (3H) reflecting (3H)thymidine incorporation, cells per crypt column, 3H-labelled cells per crypt column, cells per villus column, and thickness of all intestinal wall components. These changes occureed throughout the small intestine even at lesser resections. ""Crypt profiles'' reflected changes in cell counts, but when the labeling frequency of proliferative cells was expressed as a percentage of the total crypt height, there was no change. The total number of crypts in the duodenum remained unchanged and the total number of cyrpts in the residual jejunum plus ileum decreased proportionally to the amount of tissue removed. Intestinal compensation occurred by increasing the size of the structures present in the residual intestine, not by increasing the number of structural units.

Adaptation, Physiological↗

Compensation by the residual intestine after intestinal resection in the rat. II. Influence of postoperative time interval.

The sequence of events which comprise the early response of the residual intestine to 70% resection of the combined jejunum and ileum was investigated. Animals were killed at 2,4,6,8, and 12 postoperative days. Marked increases in DNA synthesis expressed as disintegraions per minute per crypt, cells per cyrypt column, labeled cells per crypt column, thickness of intestinal wall components, and cells per villus column were apparent as early as 2 to 4 postoperative days. By 12 days, the values had reached the 30-day postoperative levels found in earlier experiments, indicating that a new steady state had already been reached. Jejunal and ileal crypts responded nearly the same during the first 12 days with their sizes increasing to about 150% of control values. However, although jejunal villus cell counts increased to 125% of controls, the ileal villus cell counts increased to 180% of controls, indicating that the sizes of the two crypt and villus epithelial cell populations are independently controlled.

Adaptation, Physiological↗

The incidence, pathology and transplantation of hepatomas in CBA mice.

Two hundred and seventy-five male CBA/Birmingham mice including 84 mice over 80 wk of age were autopsied at intervals over the whole range of their natural life span of about 2 1/2 yr. Body weight increased progressively up to 30 wk of age when a plateau value of 30-40 g was attained. Subsequent to 80 wk a slight, progressive decrease was observed. The thymus showed a profound increase in size from about 5 mg at birth to approximately 60 mg by the 3rd wk. Thereafter, the weight of the thymus decreased, rapidly at first, to reach 20-30 mg by 15 wk of age. The thymus weight then decreased more slowly to around 10 mg by the 80th wk. The spleen weight reached a plateau value of 50-60 mg by 4 wk and this was maintained until the 80th wk. In mice older than 80 wk varying degrees of splenomegaly were observed. Histologically, the areas of white pulp in these spleens were very prominent, suggestive of an on-going immune response. It was possible to associate this splenomegaly with the appearance of gross and microscopic evidence of hepatomas. No hepatomas were observed prior to 80 wk, but between 80 and 120 wk the incidence increased progressively; and all the mice whose age at autopsy exceeded 120 wk had hepatomas. Histologically the hepatomas showed marked nuclear plemorphism with occasional mitotic figures. Thrombi, areas of avascular necrosis and collections of inflammatory cells were observed. The tumour metastasised to the lung in 12% of cases. The doubling time of the hepatoma in situ was estimated as 1-6 wk (range 1-3-1-8 wk). These hepatomas were transplantable and grew with a doubling of 2-25 wk in syngeneic adult recipients. To test if the more rapid progressive growth of the tumour in situ in old CBA mice might have resulted from a breakdown in "immunological surveillance" the same tumour was transplanted simultaneously to a group of young and old recipients. The tumour grew more slowly (doubling time, 2-5 wk) in the old recipients. This result would not appear to support the hypothesis of a prolonged breakdown of immunological surveillance as the cause of the progressive increase in the incidence and growth of these tumours in situ in old mice.

Age Factors↗

Training teachers in the anatomical sciences.

A number of medical schools have initiated workshops to improve faculty teaching skills. Little effort, however, has been directed toward the pedagogical training of graduate students who are destined to become future medical science teachers. To help solve this problem, the faculty of the Department of Anatomy in the University of Nebraska College of Medicine recently developed a prototype teacher training program for graduate students in anatomy. Through formal course work and practical classroom experience, students are developing the skills requisite for effective teaching of the anatomical sciences. Student and faculty response to the training program has been enthusiastic, and the objectives and structure of the program can be applied to the production of competent and skilled teachers in other areas of the basic and clinical sciences.

Anatomy↗

Effects of hypophysectomy on DNCB-induced contact sensitivity in rats.

Cell-mediated immunity in hypophysectomized (HYX) and non-hypophysectomized (NHYX) rats was assessed by measuring lymph node weight and lymph node cellular proliferation responses to cutaneous application of the skin sensitizer dinitrochlorobenzene (DNCB). Differences were found in the lymph node weight assay, with the responses of the HYX rats being significantly lower than the responses of the NHYX rats. There were, however, no significant differences as measured by the lymph node cellular proliferation assay. An explanation for these contradictory results was sought by examining dose-responsiveness to DNCB. It was found that, over a range of doses of DNCB, HYX rats showed a linear dose-response relationship in terms of both lymph node weight and lymph node cellular proliferation. No dose-responsiveness was observed in NHYX rats. Since HYX rats required a greater degree of antigenic stimulation to achieve a response level equivalent to that of NHYX rats, it may be concluded that HYX rats are immunodeficient at lower antigen levels.

Animals↗

Prolonged effects of nitrogen mustard on mouse haematopoietic and lymphoid tissues.

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 mug (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration during the second week post-injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age-matched controls from 20-30 d, 46-73 d, and 75-100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40-50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10-18 d post-injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.

Animals↗