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Biomedical subjects

S I Roth

Publications and source records attributed to S I Roth.

At least 73 records · Page 4Linked to original sources

Spontaneous diabetes mellitus in the New Zealand white rabbit: preliminary morphologic characterization.

Electron microscopic studies on a closed colony of rabbits with an 18.5 per cent incidence of spontaneous onset insulin-dependent diabetes mellitus revealed that the beta-cells of the islets of Langerhans of the diabetic animals were hypergranulated. This finding contrasts with most other animal models of spontaneous diabetes mellitus which show degranulation of the beta-cells. There was no evidence of hyperplasia, insulitis, amyloid, or fibrosis of the islets by either light or electron microscopy. Correlation of our morphologic findings with physiologic data suggests a defect in insulin secretion. Rabbits with normal glucose metabolism showed a normal degree of granulation of their beta-cells. The alpha and delta cells were within normal limits in all animals. No other abnormalities associated with diabetes in humans or other animals were noted except for minimal fusion of the glomerular epithelial foot processes and mineralization of the proximal tubules and Bowman's capsules.

Animals↗

The parathyroid glands in multiple endocrine neoplasia type 2b.

The histologic features of 21 parathyroid glands obtained from 16 Mayo Clinic patients aged 2 to 52 years who had multiple endocrine neoplasia type 2b (MEN 2b) were evaluated. The findings were correlated with the patients' ages and with the serum concentrations of calcium (15 patients), phosphorus (14 patients), and immunoreactive parathyroid hormone (iPTH) (11 patients), and with the response of serum iPTH to calcium infusion (6 patients). We also studied the histologic features of 13 parathyroid glands obtained from 8 patients not seen at the Mayo Clinic with MEN 2b. The microscopic appearance of the glands was normal in patients under the age of 17; with increased age, the glands did not exhibit normal involution, and an appearance consistent with mild chief-cell hyperplasia was evident. This abnormality was not associated with clinical or laboratory manifestations of hyperparathyroidism. We presently believe that parathyroidectomy for the disorder is not justified.

Adolescent↗

Analysis of parathyroid hormone and its fragments in rat tissues: chemical identification and microscopical localization.

After intravenous injection of [(125)I]-iodo-parathyroid hormone in the rat, uptake of the hormone was greatest in the liver and kidneys. Uptake was rapid, reaching a maximal concentration by 4 and 8 min, respectively. Extracts, prepared from both these organs at intervals soon after the injection of intact hormone, showed three main radioactive peaks when samples were subjected to gel filtration under protein-denaturing conditions. The first peak coeluted with intact hormone. The second eluted at a position corresponding to the carboxy-terminal fragments previously described in plasma, and the last eluted at the salt volume of the column. Microsequence analysis of the radioiodinated fragments, a method that has proved valuable for chemically defining the circulating fragments resulting from metabolism of injected hormone, showed that extracts of liver and kidney, prepared at 4 and 8 min after injection of the intact hormone, contained different fragments. The radioiodinated fragments in liver extracts were identical to those previously reported in the plasma of rats and dogs, fragments resulting principally from proteolysis between positions 33 and 34, and 36 and 37 of the intact hormone. Although the same fragments were also present in the kidneys, they constituted less than 15% of the amount present in the liver. More than 50% of the labeled renal fragments consisted of a peptide whose amino-terminal amino acid was position 39 of the intact hormone, a fragment not present in plasma. The rate of appearance of radioiodinated fragments that were chemically identical to those in plasma was more rapid in the liver than in plasma. Correlation of these chemical analyses with studies of the localization of (125)I by autoradiography showed that at the times when the intact hormone and the carboxy-terminal fragments comprised nearly all of the (125)I-labeled moieties in the tissues, the proximal convoluted tubules of the kidney and sinusoidal lining cells of the liver, which probably are Kupffer cells, contained the highest concentration of (125)I. Preferential localization of immunoreactive parathyroid hormone to these tissue sites also was shown by immunoperoxidase staining in studies with unlabeled hormone. Our results suggest that, unless multiple renal mechanisms are present for release of hormonal fragments, one of which releases the circulating fragments preferentially, the liver, rather than the kidney, is principally responsible for generating the carboxy-terminal fragments in plasma after injection of intact hormone, and the Kupffer cells may contain the enzymes that hydrolyze parathyroid hormone.

Animals↗

Immunocytochemical localization of parathyroid hormone in bovine parathyroid glands and human parathyroid adenomas.

Light and electron microscopic localization of parathyroid hormone (PTH) in human and bovine parathyroid tissue has been achieved using an indirect peroxidase labeled antibody method. Granular deposition of the reaction product was found throughout the chief cell cytoplasm. There was no nuclear staining. At the ultrastructural level, parathyroid hormone localized by this method appeared to be largely confined to the secretory granules in the cytoplasm of cells. Mitochondria and nuclei were free of reaction product. Aggregated sacs of granular endoplasmic reticulum were minimally reactive, and Golgi apparatuses did not show reaction product.

Adenoma↗

Location of brown recluse venom attachment sites on human erythrocytes by the firritin-labeled antibody technique.

Brown recluse spider (loxosceles reclusa) venom has been demonstrated by a ferritin-labeled antibody technique to attach to human erythrocyte cell membranes. The number of individual attachment sites per cell is proportional to the concentration of the venom used to sensitize the erythrocytes. Structural changes in the red cell membrane are associated with the venom attachment. These sites may be related to the red cell hemolysis which sometimes occurs in the human as a result of the spider bite.

Animals↗

Epidermal regeneration and percutaneous water loss following cellophane stripping of reptile epidermis.

The histological and physiological effects of the removal of superficial corneous epidermal materials have been studied in several squamate species and a caiman. The gross and microscopic anatomy of the squamate integument has characteristics which make cellophane stripping inherently variable, but in general, when corneous materials were removed, they are replaced over a period of one to two weeks, by a tissue with the histological characteristics of the normal alpha-layer. This tissue may be produced by stimulated germinal activity and/or metaplasia of the other presumptive cell populations. In caiman, the thickness of the corneous tissues of the outer scale surface is reduced by stripping and the tissue is restored to normal in approximately two weeks by stimulated germinal proliferation. Measurements of cutaneous water loss (CWL) before, immediately after, and during two weeks post-trauma revealed the following. There is a sudden rise in CWL immediately after stripping, and values decline over the next two weeks as the corneous tissues are replaced. The results are interpreted as indicating that, as in mammals, the impermeability of the epidermis depends on the thickness of the corneous materials. In squamates it appears that the physiological barrier is the alpha-layer of the epidermal generation, and while the beta-layer cannot be excluded as playing some role in reducing the permeability of the integument, its role appears to be primarily mechanical.

Animals↗

The rapid identification of "normal" parathyroid glands by the presence of intracellular fat.

Staining of frozen sections of small parathyroid biopsies from patients with primary hyperparathyroidism with Sudan II or IV revealed the almost uniform presence of numerous prominent intracellular sudanophilic bodies in the chief cells of suppressed "normal" parathyroid glands. These sudanophilic bodies were generally absent from the abnormal chief cells of parathyroid adenomas and chief cell hyperplasias. This difference in intracellular lipid provides a rapid, reliable, and easy method for distinguishing at the time of parathyroid exploration between an adenoma which is always accompanied by "normal" parathyroid glands and a chief cell hyperplasia in which all of the glands are abnormal.

Adenoma↗

Mitotic activity in non-neoplastic melanocytes in vivo as determined by histochemical, autoradiographic, and electron microscope studies.

Mitotic figures were demonstrated in the differentiated melanocytes of normal epidermal and nonepidermal tissues without the presence of external stimuli. These dividine melanocytes were present in human and mouse skin, mouse hair, chick feathers, and embryonic chick retinal pigment epithelium. In normal adult human epidermis, dividing melanocytes, though rare, were found in the nonstimulated areas. L-3,4-dihydroxyphenylalanine reaction on the melanocytes during mitosis demonstrated activity of the melanin-forming enzyme, tyrosinase, and ultrastructural studies demonstrated the characteristic melanosomes in variour stages of maturation. Other ultrastructural characteristics of the melanocytes during mitosis, except for the Golgi apparatus, which was smaller and less complex, were similar to those seen in well-differentiated nondividing melanocytes. Autoradiographic studies of thymidine incorporation into mouse skin indicated that 0.7% of epidermal melanocytes, when slightly stimulated, are in the S phase. Thus, in vivo differentiation of non-neoplastic melanocytes (to produce pyrosinase and melanosomes) does not preclude their replication by mitotic division.

Animals↗

Effect of calcium and magnesium on deoxyribonucleic acid synthesis in rat parathyroid glands in vitro.

DNA synthesis in rat parathyroid glands in organ culture is significantly affected by the calcium concentration of the medium. 3-H-thymidine incorporation over a 46-hour period was more than 100 per cent greater at 1.3 mM calcium than at 3.0 mM calcium. Thymidine incorporation was greatest at 0.9 to 1.3 mM, and fell off sharply between 1.3 and 1.8 mM calcium. Variation of magnesium concentration between 0.3 and 1.5 mM had no appreciable effect on DNA synthesis at either 1.3 or 1.8 mM calcium. No effect on DNA synthesis in rat liver explants or mouse L cells was observed over these ranges of calcium concentration, but in cultured rat kidney fragments, an opposite effect of calcium was observed, i.e., DNA synthesis was more active at 3.0 mM calcium than at 1.3 mM calcium. Time course experiments showed that a significant difference between DNA synthesis rates in high and low calcium media was observable in parathyroid glands during the first 3 hours in culture, and persisted for at least 108 hours. The calcium effect on DNA synthesis was not mediated by any direct effect on the rate of thymidine uptake by the tissue. These results suggest that a small drop in ambient calcium concentration in vivo could significantly increase the rate of DNA synthesis in the parathyroid glands, and thus provide experimental support for the concept that parathyroid hyperplasia in chronic renal insufficiency is caused by lowered serum calcium levels.

Animals↗

An ultrastructural study of acid phosphatase activity in normal, adenomatous and hyperplastic (chief cell type) human parathyroid glands.

Acid-phosphatase-rich granules, separate from the parathyroid-hormone-containing secretory granules, have been demonstrated in the normal, adenomatous and primary hyperplastic human parathyroid glands. These granules are thought to represent lysosomes which are derived from the Golgi region. In the normal glands these granules are postulated to be associated with involution of the cell organelles during the normal secretory cycle. In the adenomatous and hyperplastic glands evidence is presented that these lysosomes are associated with the destruction of secretary granules and parthyroid hormone.

Acid Phosphatase↗

Effect of calcium on embryonic rat thyroid C cells in vitro.

The alterations in the ultrastructure of rat embryonic thyroid C cells in vitro produced by variation in the ambient calcium of the medium were studied. The thyroid C cells from 19-day-old rat fetuses were cultured for 48 hours in calcium concentrations of 2, 4, 6, 8 and 10 mg%. The C cells show a cyclic change in the ultrastructure. The resting cells have a sparse, dispersed granular endoplasmic reticulum, small Golgi apparatus and numerous secretory granules. The granules are emptied into the extracellular space followed by aggregation of the granular endoplasmic reticulum, enlargement of the Golgi apparatus, and reaccumulation of secretory products in granules. Varying the calcium concentration failed to change the proportion of cells in the various stages of the secretory cycle, though the mean number of secretory granules per unit area of cytoplasm fell proportionally with increasing ambient calcium concentration (y = -0.1675x +3.93). This decrease is largely due to a reduction in the number of cells with higher densities of secretory granules and corresponds to the direct increase in calcitonin content of the medium. This could indicate that secretion is directly stimulated in cells rich in secretory granules by a high calcium concentration. In contrast, these ultrastructural studies also indicate that, unlike the situation in the parathyroid chief cell, alteration of the ambient calcium concentration has little effect on the rate of synthesis of thyrocalcitonin by thyroid C cells.

Animals↗