Galanin immunoreactivity in neuroendocrine tumors.

We investigated immunoreactivity for galanin, a 29-amino acid peptide, in formalin-fixed, paraffin-embedded sections of 123 neuroendocrine tumors. Galanin-immunoreactive cells were found in one of 12 hypothalamic gangliocytomas, nine of 18 adrenal pheochromocytomas, nine of 14 pituitary corticotroph adenomas, and one of two thymic endocrine tumors. In pheochromocytomas, galanin-immunoreactive cells were seen either singly or in clusters. In corticotroph adenomas, many tumor cells were positive for galanin, indicating colocalization of corticotropin and galanin in the same tumor cells. No galanin-immunoreactive cells were noted in four extra-adrenal paragangliomas; 10 medullary carcinomas of the thyroid; 35 endocrine tumors arising in the lung, pancreas, and gastrointestinal tract; and 28 pituitary adenomas composed of cells other than corticotrophs. In nontumorous counterparts of these neuroendocrine tumors, galanin immunoreactivity was observed in nerve cells of the hypothalamus, nerve fibers of the duodenum, and adenohypophyseal cells corresponding to corticotrophs. These findings indicate that galanin expression in neuroendocrine tumors is uncommon and restricted to some tumor types.     

Fine structural features of secretion in adenomas of human pituitary gland

Ultrastructural investigation of 274 human pituitary adenomas and 39 nontumorous adenohypophyses revealed two distinct types of secretion. Exocytosis was characteristic of prolactin cell adenomas, mixed growth hormone-prolactin cell adenomas, acidophil stem cell adenomas, and nontumorous prolactin cells. The second type, termed "transmembrane effusion," was noted in corticotroph, thyrotroph, gonadotroph, undifferentiated cell adenomas, and oncocytomas, as well as nontumorous corticotrophs, thyrotrophs, and gonadotrophs. It differed from that of prolactin cells and resembled diacrine secretion of gastrointestinal gastrin cells and membrane release in the neurohypophysis. In adenomatous and nontumorous growth hormone cells, neither exocytosis nor transmembrane effusion were apparent, hence a third type of release is suggested. Electron microscopic study of release mechanisms is helpful in the differential diagnosis of pituitary adenomas, since discharge of secretory products is not identical in the various tumor types.     

Further evidence of inactivity of hypothalamo-pituitary-thyroid axis in snell dwarf mice

The effects of hemithyroidectomy (hemiTX) and complete thyroidectomy (TX) on the cellular composition and the mitotic activity of the anterior pituitary gland were examined in genetically thyrotropin (TSH)-deficient female Snell dwarf mice (dw/dw) and in phenotypically normal female mice (?/+) from the same strain. In normal (nondwarf) mice, both hemiTX and TX reduced the percentage of acidophilic (orange G-positive) cells and increased the percentage of thyrotropic (aldehyde fuchsin [AF]-positive) cells, whereas the percentage of gonadotrophs (PAS-positive cells) and chromophobes (unstained cells) was not affected. Both interventions increased the mean mitotic activity rate (MMAR) of the anterior pituitary lobe. This effect was related to the enhancement of the MMAR of acidophilic cells and, particularly, thyrotropic cells. The MMAR of thyrotrophs in thyroidectomized normal mice was significantly higher than that in sham-TX controls or in hemithyroidectomized animals. In Snell dwarf mice, neither hemiTX nor TX affected the percentage of the various cell categories (PAS-positive, unstained, and extremely rare AF-positive cells) in the anterior pituitary lobe. Furthermore, neither hemiTX nor TX substantially influenced the MMAR of the gland. No mitotic figures were found in the AF-positive cells. Since the AF-positive cells in the anterior pituitary of dwarf mice completely failed to respond to hemiTX or TX, we believe they are not true thyrotropic cells. Using electron microscopy, we confirmed a lack of somatotrophs, mammotrophs, and normal thyrotrophs in the anterior pituitary of Snell dwarf mice. The results provide morphological evidence of inactivity of the hypothalamo-pituitary-thyroid axis in Snell dwarf mice.     

The pars tuberalis of the human pituitary

Summary Forty autopsy pituitaries were studied to elucidate the histology, immunocytology and ultrastructure of pars tuberalis in subjects with normal and abnormal endocrine homeostasis. Pars tuberalis consisted mainly of gonadotrophs interspersed with few corticotrophs and thyrotrophs, histologically resembling those of pars distalis. Somatotrophs and lactotrophs were not identified. There were no histologic differences attributable to age or sex. In cases of glucocorticoid excess, pars tuberalis corticotrophs showed Crooke's hyalinization. Following castration or hypophysectomy, pars tuberalis gonadotrophs exhibited more intense immunostaining for FSH¹ and LH than did normals. Ultrastructural analysis revealed gonadotrophs and corticotrophs showing no evidence of active secretion; immunoelectron microscopy demonstrated FSH, LH and ACTH in secretory granules. By light microscopy, squamous nests, often identified in pars tuberalis, were positive for immunoreactive keratin; cells at their periphery contained FSH, LH or ACTH, indicating derivation of nests by squamous metaplasia from gonadotrophs and corticotrophs. By electron microscopy, clusters of epithelial cells containing desmosomes and tonofilaments were surrounded by granulated gonadotrophs.Human pars tuberalis cells represent mainly a subpopulation of gonadotrophs possessing all organelles required for synthesis and storage of hormones but showing ultrastructural features of functional inactivity; the reasons for this inactivity and for the formation of squamous nests remain unexplained.     

Urgent colonoscopy for the diagnosis and treatment of severe diverticular hemorrhage

BACKGROUND: Although endoscopy is often used to diagnose and treat acute upper gastrointestinal bleeding, its role in the management of diverticulosis and lower gastrointestinal bleeding is uncertain. METHODS: We studied the role of urgent colonoscopy in the diagnosis and treatment of 121 patients with severe hematochezia and diverticulosis. All patients were hospitalized, received blood transfusions as needed, and received a purge to rid the colon of clots, stool, and blood. Colonoscopy was performed within 6 to 12 hours after hospitalization or the diagnosis of hematochezia. Among the first 73 patients, those with continued diverticular bleeding underwent hemicolectomy. For the subsequent 48 patients, those requiring treatment received therapy, such as epinephrine injections or bipolar coagulation, through the colonoscope. RESULTS: Of the first 73 patients, 17 (23 percent) had definite signs of diverticular hemorrhage (active bleeding in 6, nonbleeding visible vessels in 4, and adherent clots in 7). Nine of the 17 had additional bleeding after colonoscopy, and 6 of these required hemicolectomy. Of the subsequent 48 patients, 10 (21 percent) had definite signs of diverticular hemorrhage (active bleeding in 5, nonbleeding visible vessels in 2, and adherent clots in 3). An additional 14 patients in this group (29 percent) were presumed to have diverticular bleeding because although they had no stigmata of diverticular hemorrhage, no other source of bleeding was identified. The other 24 patients (50 percent) had other identified sources of bleeding. All 10 patients with definite diverticular hemorrhage were treated endoscopically; none had recurrent bleeding or required surgery. CONCLUSIONS: Among patients with severe hematochezia and diverticulosis, at least one fifth have definite diverticular hemorrhage. Colonoscopic treatment of such patients with epinephrine injections, bipolar coagulation, or both may prevent recurrent bleeding and decrease the need for surgery.     

Angiogenesis in Endocrine Neoplasms

Angiogenesis promotes the growth of tumors, because it both facilitates oxygenation and nutrient flow, and removes metabolic waste. During the past two decades, as the importance of tumor vascularity became recognized, angiogenesis and the relationship between blood vessels and tumor progression received increasing attention. It was found that isolated tumor tissues failed to expand beyond few millimeters unless vascularized, whereupon vascularization they exhibited a rapid growth. Extensive research focusing on the relationship between tumor proliferation and the formation of new vessels has initially been undertaken to assess the role of angiogenesis in the progression of breast carcinomas. Significant results emerged from these investigations, and similar studies were extended to other tumor types, such as melanomas, cervical and pulmonary carcinomas, and so on. It is of note that angiogenesis as it relates to endocrine tumors has so far been limited to pituitary neoplasms, thyroid carcinomas, and pheochromocytomas. The purpose of the article is to provide a brief review of angiogenesis and to summarize available data regarding its role in the growth off endocrine neoplasms.     

Advanced age negatively influences mesenteric lymph node T cell responses after burn injury

While the pathophysiology of burn injury is well established in young adults, the factors that contribute to pathogenesis and increased death in elderly burn patients are not defined. The purpose of this study is to determine the effects of burn injury on mesenteric lymph node (MLN) T cell responses in young and aged mice. MLN is a cluster of lymph nodes that drains various parts of the intestine and is known to play role in clearance bacteria originating from the intestinal lumen. Results presented here suggest a significant suppression in Con A-induced MLN cell proliferation and IL-2 production in uninjured aged mice compared with uninjured young mice. Following 24 h after injury, although, a significant decrease in lymph node cell proliferation and IL-2 production was observed in both young and aged mice compared with their respective sham-injured animals, the suppression was more in aged mice. In addition we found a reduction in IFN-gamma, a Th-1 cytokine by MLN T cells from aged burned mice relative to young burn (P<0.05) or sham-injured mice (P<0.01). The Th-2 cytokine IL-4, on the other hand, was significantly increased in both young and aged burn-injured mice MLN T cells compared with their respective sham-injured mice. These results show that burn injury causes a greater suppression in MLN T cells ability to proliferate and a more pronounced shift to Th-2 phenotype in aged mice as compared with young mice. Such decreases in T cell functions may impair MLN's ability to clear the bacterial pathogens originating from intestine and thereby contribute to increased pathogenesis in injured host.     

Identifying BAC clones for diagnosis of conventional renal cell carcinoma by FISH

AIMS: The new classification of renal cell tumours relies on tumour-specific genetic alterations, which can be detected by different techniques. For diagnosis of conventional renal cell carcinoma by FISH we have isolated BAC clones from the chromosomal regions of interest. METHODS AND RESULTS: A BAC library was screened by microsatellites mapped to the smallest overlapping regions of loss of heterozygosity (LOH) at chromosomes 3p, 5q, 6q, 8p, 9p and 14q. Positive BACs were tested by carrying out FISH in normal cells for signal/noise ratio. Subsequently, 11 conventional and two papillary renal cell carcinomas were analysed by the new diagnostic BAC set and the results were compared with those obtained by microsatellite allelotyping. The diagnostic value of FISH was comparable to that of microsatellite analysis in nearly all tumours except those with extreme chromosomal polyploidization. CONCLUSIONS: We conclude that both FISH and microsatellite analyses are helpful to strengthen the diagnosis of conventional renal cell carcinoma. However, both techniques may have some disadvantage in a special setting.     

Longitudinal variability of human immunodeficiency virus type 1 RNA viral load measurements by nucleic acid sequence-based amplification and NucliSens assays in a large multicenter study

Human immunodeficiency virus type 1 (HIV-1) RNA measurements were evaluated within an externally controlled multilaboratory program. Three external standards (1.5 x 10(3) to 1.5 x 10(6) copies/ml) were included in 814 assay runs by four laboratories. Results indicate that HIV-1 RNA levels can be measured with a precision equal to that of the pre-highly active antiretroviral therapy era (standard deviations, +/-0.16 to 0.25 log10 units).