A dose of 2.5 g of gamma-hydroxybutyric acid (GHB) was administered intravenously to 6 healthy male volunteers. A significant increase in plasma GH was observed at 30, 45, 60 and 90 min after injection. The plasma prolactin level increased significantly at 45 and 60 min after GHB injection. These responses were not found after the saline vehicle injection in the same subjects. It is conceivable that GHB could modify the release of serotonin from the nerve terminals and then stimulate the release of GH and prolactin.

Gastric cancer with the invasive micropapillary carcinoma (IMPC) pattern has been reported to be a variant with poor prognosis and rapid progression. To the best of our knowledge, only 4 cases of gastric cancer from Japan and 11 cases from Korea have been reported to contain the IMPC pattern. In the present study, 4 cases of gastric cancer containing the IMPC pattern from 2 Japanese men and 2 Japanese women are reported. The cancer tissues, including a recurrent lesion in 1 case and lymph node metastases in 2 other cases, were examined immunohistochemically to identify suitable markers for demonstrating the peculiar "inside out" pattern of IMPC and for analyzing HER2 expression. A characteristic IMPC pattern occupied more than 10% of each cancer tissue in these 4 cases. Lymphatic invasions were very often detected; in fact, lymph node metastases were detected in 3 out of 4 cases. The unique "inside out" pattern in IMPC was clearly revealed in all cases by staining with antibodies to both epithelial membrane antigen (EMA) and KL-6, but not with an antibody to CD10. HER2 was positive in 3 of 4 cases with the IMPC pattern, including cases with a recurrent lesion or lymph node metastases. Fluorescence in situ hybridization (FISH) analyses disclosed positive results in case 1, and case 3 including lymph node metastatic foci. Highest FISH titer was 6.8 in case 1, revealing marked amplification of HER-2 gene. Four cases of gastric cancer with the IMPC pattern were reported. EMA and KL-6, but not CD10, were particularly useful markers for visualizing the characteristic "inside out" pattern of the IMPC pattern in stomach cancers, similar to the markers for breast and urinary bladder cancers.

Three isoforms of carbonic anhydrase-related protein (CA-RP) are evolutionally well conserved among the CA gene family but lack classical CA activity. Although the biological function of CA-RPs is unknown, overexpression of CA-RP VIII has been reported in certain tumor types. Based on the finding that CA-RPs are commonly expressed in the neuronal cells, we investigated expression of all three CA-RPs in gastrointestinal stromal tumor (GIST). In contrast to no detectable signal of any of the three CA-RPs in intestinal cells of Cajal, immunohistochemical analysis showed distinct cytoplasmic expressions of CA-RPs VIII and XI in 13 (59%) and 20 (91%) of 22 GIST tissue specimens, respectively. The positive signals for both CA-RPs VIII and XI were more intense in the periphery than in the central part of GISTs, whereas no significant signal for CA-RP X expression was observed in any of the GISTs. These expression patterns of CA-RPs were consistently observed by reverse transcription-polymerase chain reaction-Southern blot and immunocytochemistry in the cultured GIST cell line GIST-T1. Ectopic expression of CA-RP XI in GIST-T1 cells induced cell proliferation and invasion in vitro. These findings indicate that CA-RP XI plays a role in the development of GIST.

The effects of various neurogenic peptides and neurotransmitter substances on the release of ACTH induced by hypothalamic corticotropin releasing factor (HY-CRF) were investigated using monolayer cultured anterior pituitary cells. Test substances were given in combination with 0.05-0.1 hypothalamic extract (HE)/ml, because HE evoked a significant ACTH release and a linear dose response relationship was demonstrated sequentially between 0.0165 HE/ml and 0.5 HE/ml. Relative high doses of lysine-vasopressin showed a slight additive effect on the release of ACTH induced by 0.1 HE/ml. Leu-enkephalin, dopamine, prostaglandin E1 and E2 slightly reduced the release of ACTH induced by HY-CRF, but the inhibitory effect of these substances were not dose-related. Other tested substances including luteinizing hormone releasing hormone, thyrotropin releasing hormone, somatostatin, melanocyte stimulating hormone release inhibiting factor, beta-endorphin, neurotensin, substance P, vasoactive intestinal polypeptide, angiotensin II, norepinephrine, serotonin, acetylcholine, histamine and gamma-amino butyric acid showed neither agonistic nor antagonistic effect on the release of ACTH induced by HY-CRF. These results indicate that the release of ACTH is controlled specifically by HY-CRF and corticosterone, and modified slightly by some other substances such as vasopressin and prostaglandins, and that the effect of most other neurogenic peptides and neurotransmitter substances is negligible or non-physiological at the pituitary level.

No abstract