Pathology of the endocrine pancreas.

An immunocytochemical analysis of 94 pancreatic endocrine tumors revealed that 73 tumors were multicellular. Significant amounts of somatostatin and human pancreatic polypeptide were found by radioimmunoassay in extracts of 19 and 17 tumors resp., in addition to the hormone causing the clinical syndrome. Numerous tumors contained ductular structures. In the surrounding pancreatic parenchyma a proliferation of small ducts and budding-off from the ductular epithelium of endocrine cells was often observed. These features are hallmarks of nesidioblastosis of the endocrine pancreas which is a hyperplasia. In multiple endocrine neoplasia I hyperplasia of the endocrine pancreas is combined with larger nodules, currently labeled tumors. On the basis of these findings it is conceivable that pancreatic endocrine tumors are not primarily neoplastic and autonomous but that they are rather of hyperplastic origin.     

Plasma transferrin levels in abnormal endocrine states. II. The changes in various endocrine states

The clinical significance of the measurement of plasma transferrin (Tf) in patients with hypophysial disorders was reported in our previous paper. In the present study, we determined plasma Tf levels in 55 patients with various endocrine states and considered their clinical significance compared with plasma somatomedin-C (SM-C) levels. Plasma Tf levels decreased significantly in patients with anorexia nervosa (P less than 0.02), hyperthyroidism (P less than 0.05), primary hypothyroidism (P less than 0.05), and Cushing's syndrome (P less than 0.05), while they were elevated significantly in pregnancy (P less than 0.01) or females using estrogens (P less than 0.05). The former two declines were considered a reflection of the malnutritional state since a significant negative correlation was observed between plasma Tf levels and the percentile deficit from the ideal body weight in patients with anorexia nervosa (P less than 0.01), or between plasma Tf and elevated T3 levels which induce hypermetabolism in patients with hyperthyroidism (P less than 0.01). A significant correlation was observed between the SM-C and Tf levels in these subjects (including normal controls and patients with hypophysial disorders) as a whole (r = 0.79, P less than 0.001). These data indicate that plasma Tf is changeable according to the endocrine and nutritional conditions with good correlation to the SM-C, and it is suggested that Tf also operates as a growth factor in vivo.     

Facultative polyploidy in endocrine tissues.

Adrenal tissue from 44 autopsies and 30 biopsies of thyroid gland were analyzed by flow--and scanning-cytophotometry. Most nuclei were diploid and the 4C fraction ranged from 1.9 to 6.1% according to the technique, but with no significant difference between controls and adenomas, hyperplasias, adenomatous goiters, or two carcinomas of the thyroid gland. The only significant increase of 4C fraction was found in normal adrenals of patients above 50 years of age (P less than 0,025). Similarly constant was the proportion of 8C nuclei which ranged from 0.5 to 1.3 per thousand. However, in one of 23 adenomatous goiters a total polyploidization was was observed. Comparable results in the literature show that the thyroid gland like the epithelium of seminal vesicles can facultatively become polyploidized, in contrast to the obligatory polyploid orgnas namely the liver and heart. This is not related to malignancy.     

Some endocrine aspects of the thymus gland.

In studies of the mouse thymus, lymphocyte mitoses are seen to be most frequent in the thymus cortex. There is evidence from thymic grafts that a hypothetical factor, thymopoietin, may stimulate mitosis of thymic lymphocytes. It is a factor which is postulated to act in conjunction with the PAS-positive mesenchymal reticular cells and epithelial reticular cells of the cortex. The thymus medulla is necessary for the integrity of thymic grafts, and may also elaborate a secretion for maintaining the cellular functions of the gland. Thymectomy has been used as a gauge for judging normal thymic function and results, in the mouse, in lymphopenia, degeneration of spleen and lymph nodes, delayed rejection of skin allografts, reduced ability of spleen cells to mount the graft versus host reaction, and reduced primary immune response to certain antigens. Correction of these deficiencies offers a means of evaluating various thymic extracts and grafts. Lymphocytosis-stimulating hormone (LSH) is known to maintain the peripheral lymphoid organs and cause lymphocytosis in the thymectomized animal. Diffusion chamber studies of thymic grafts also show restored lymphoid tissue by a cell-free factor (CIF). These two factors may be the same and probably represent the basis of the highly purified lymphocyte-stimulating proteins, LSHr and LSHh, which restore the L/P ratio in thymectomized animals and may stimulate lymphopoiesis in spleen and lymph nodes. LSHr, unlike LSHh, increases the total lymphocyte count. LSHr has been found to increase the humoral antibody response in neonatal mice both by the PFC technique and by direct hemolysis of sheep erythrocytes. Homeostatic thymic hormone (HTH) is a thymic extract of small molecular weight and contains nucleic acid. In the thymectomized guinea pig it has been found to maintain normal levels of lymphocytes in the blood, spleen and lymph nodes, to restore antibody titers to typhoid H antigen and to restore the toxic allergic reaction. Thymic humoral factor (THF) is of smaller molecular weight (less than 1,000) and probably is not a protein. It also enhances lymphoid proliferation in neonatally thymectomized mice. There is evidence that THF participates in humoral antibody formation because it stimulates PFC formation from neonatally thymectomized mice after inoculation with sheep erythrocytes. Its effects on cell-mediated immunity are seen from findings that injection of THF restores the ability of thymectomized mice to reject skin allografts. THF enables spleen cells from thymectomized or neonatal animals to mount the graft versus host reaction, and causes maturation of bone marrow cells and spleen or lymph node cells so that they can participate in the graft versus host reaction. It has been reported to stimulate lymphocytes to kill isogeneic tumor cells in vitro. Thymosin is protein extracted from the thymus. It has been found to alleviate leukopenia slightly and provide some improvement in lymphoid histology in thymectomized mice...     

Biogenic amines in the guinea pig endocrine pancreas.

Pancreata of guinea-pigs were investigated for the presence and cellular distribution of biogenic amines. Out of the established endocrine cell types only insulin (B-) cells contained immunoreactivity for serotonin and noradrenaline. However, the B-cells' content of both amines was quite variable. Serotonin was also confined to enterochromaffin (EC-) cells. No immunoreactivity for dopamine or histamine was present in any islet cell. Treatment of guinea-pigs with Ro-4-4602 led to a marked decrease of serotonin and noradrenaline in pancreatic endocrine cells. The present findings suggest that serotonin and noradrenaline are involved in the function of the endocrine pancreas, particularly of islet B-cells.     

Multiple endocrine neoplasias in the era of translational medicine.

Medicine is an ever changing art, continuously adjusting to the shifting principles of philosophy and constant discoveries of science; it was beautifully said by Hippocrates: "... medicine does not do the same thing at this moment and the next..." Unabated dissemination of information is the only way that patients are assured that physicians will continue to practice medicine that reflects contemporary science. In the field of Multiple Endocrine Neoplasias (MENs), this is at least in part accomplished by biennially held International Workshops. The articles led by this editorial are the second and last installment of a collection of state-of-the-art presentations given in the course of the ninth such workshop that was held in Bethesda, MD, June 19-22, 2004. In addition to serving as an introduction to the articles that were written by some of the leaders in the field, the text of the editorial review that follows also supports the notion that MENs are poised to lead translational research in endocrinology: these disorders have benefited remarkably from the discoveries of the human genome project and are at a unique position to take advantage of new modalities in basic and clinical science.     

Lithium accumulation in some endocrine tissues.

Lithium levels were measured in several tissues of rats after oral lithium administration for various periods of time. The lithium levels in the brain approached those of the serum while there was a marked accumulation of lithium in the pituitary and thyroid glands. When lithium was stopped there was no noticeable lag in clearance for any of the tissues examined, with the pituitary maintaining a significant elevation of lithium over the serum levels. Animals receiving lithium had higher levels of adrenal corticosterone under quiescent conditions and higher levels of plasma corticosterone thirty minutes after a brief electric footshock.     

Metabolic feedback in mammalian endocrine systems.

Information processing through feedback loops is an integral part of most endocrine systems, and ranges from simple negative loops to complex combinations of negative and positive loops. Moreover, feedback may occur at local (paracrine) or long-distance sites, and with multiple time-domains. Traditionally, feedback is visualized as one hormone stimulating release of a second hormone, which then circulates in the blood to carry out various biological activities, one of which is to inhibit further secretion of the first hormone. This represents a fail-safe mechanism to protect the organism against the potentially damaging effects of uncontrolled secretion of many of the common hormones, some of which are highly catabolic or anabolic. However, it is becoming increasingly apparent that the products of catabolism and anabolism may themselves participate in the feedback process in either a feed-forward or feedback manner. For example, free fatty acids are liberated by the action of growth hormone, and in turn are potent inhibitors of growth hormone secretion (feedback). On the other hand, stress activates adrenal cortical and medullary secretion, which also promotes lipolysis, but in this case the liberated free fatty acids may actually stimulate the system further (feed-forward). Similarly, glucose has been shown to directly inhibit the activity of several different endocrine pathways, and must now be considered an integral part of the overall regulatory mechanism involved in fine-tuning secretion and possibly production of hormones. By constructing models of feedback of increasing complexity, it is possible to make predictions about previously unrecognized relationships between hormones and products of metabolism.     

Microscopic organization of epithelial endocrine cells of the gastrointestinal tract mucosa in lower vertebrates. I. Epithelial endocrine cells of the stomach of the common frog

The quantity, histotopography and submicroscopic organization of endocrine cells in various mucosal epithelium sections of frog were studied using light and electron microscopy. It is shown that the majority of endocrine cells per square millimetre is located in the proximal part of the stomach. Eight types of endocrine cells depending on the submicroscopic structure of secretory granules are defined.