Phorbol ester, not growth hormone releasing factor, consistently stimulates growth hormone release from somatotroph adenomas in culture

In order to study the mechanism of GH secretion from somatotroph adenoma cells, we have compared the effect of 12–O-tetradecanoyl phorboi-13-acetate (TPA) with that of growth hormone releasing factor (GRF) on GH secretion from human somatotroph adenoma cells cultured in monolayer. Pituitary adenoma cells were obtained from 13 patients with acromegaly undergoing surgery. On the 7th day of culture, the cells were exposed for 2 h to secretagogues. All 13 adenoma cell cultures (100%) responded to TPA (1·6–16·0 nmol/I) with a two- to six-fold increase in GH release (240·37% Increase of control: mean±SE). The response was detectable within 10 min, and was maximal at 2 h. Phosphollpase C (7·7 mmol/I) also stimulated a two-to ten-fold Increase In GH release in all four adenomas examined (100%). GH release was stimulated by GRF (2·0 nmol/I) in eight out of 12 adenoma cells (67%), but the magnitude of the responses to GRF (60·18% Increase of control: mean ± SE) were much smaller than that of TPA. Five out of 13 adenomas secreted detectable amount of PRL Into the medium and these five adenomas (100%) responded to TPA (16·0 nmol/I) with a two- to six-fold Increase. These observations indicate that the activation of protein kinase C is the consistent stimulator in GH and PRL secretion In human somatotroph adenoma cells. However, It is not determined whether the protein kinase C     

Adenocarcinoma of the proximal small intestine. A marker for familial and multicentric cancer?

BACKGROUND. Adenocarcinoma of the small intestine is uncommon. The Hawaii Tumor Registry (HTR) has identified 49 of these tumors since 1960, and the Japan-Hawaii Cancer Study (JHCS) has identified only four of these tumors among a cohort of 8006 Hawaiian-Japanese men followed up for a period of 22 years. Each of the four men reported by the JHCS had multicentric gastrointestinal cancers. METHODS. Newly diagnosed cancers are recorded separately by the HTR and JHCS, and linkage is maintained between the two files. Family histories are available from the JHCS, and these are supplemented by a state population file maintained by the Department of Genetics, University of Hawaii. RESULTS. Five men, all Japanese, were found to have carcinoma of the proximal small intestine. Each had multicentric carcinomas of the gastrointestinal tract. Carcinoma of the stomach and colon was found in the primary relatives of each of four men whose families lived in Hawaii. CONCLUSIONS. The familial clustering of uncommon neoplasms (small bowel carcinoma and multicentric large bowel carcinoma), and the concurrence of gastric and colonic carcinoma suggests that these subjects have a genetic trait that increases susceptibility to a broad range of carcinogens.     

Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.     

Longitudinal decline in pulmonary function in atopic cough and cough variant asthma

OBJECTIVE: Cough variant asthma and atopic cough are different clinical manifestations of eosinophilic airway inflammation presenting with isolated chronic non-productive cough. The aim of this study was to examine the longitudinal change in pulmonary function in cough variant asthma and atopic cough. METHODS: Longitudinal change in FEV1 was prospectively examined in 20 patients with cough variant asthma, 14 patients with atopic cough and 271 asymptomatic healthy subjects. All were lifetime non-smokers. Of the 20 cough variant asthma patients, 13 were taking long-term inhaled corticosteroid therapy (ICS) (beclomethasone dipropionate 615 +/- 58 micro g/day) and the other seven were not. Spirometry was taken at first visit, after cough was almost completely relieved on therapy, and at least once every year for 5 or more years afterwards. RESULTS: The slope of longitudinal change in FEV1 was not significantly different among cough variant asthma patients (- 0.029 +/- 0.007/year), atopic cough patients (- 0.021 +/- 0.022/year) and asymptomatic subjects (- 0.028 +/- 0.002 L/year). In patients with cough variant asthma, the slope in patients not taking inhaled corticosteroids (ICS) was 0.032 +/- 0.007 L/year, which was not significantly different from that in patients taking ICS (- 0.027 +/- 0.010 L/year). CONCLUSION: Pulmonary function decline is not greater in cough variant asthma than atopic cough and the normal population, and long-term ICS has no effect on the decline in cough variant asthma.     

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through, an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrorcyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern. blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.     

Prospective study of serum cholesterol and site-specific cancers.

From 1965 to 1968, 7716 Japanese-American men were examined and tested for serum cholesterol. After 22 years, 1380 incident cancer cases were identified. Of the site-specific cancers, only colon cancer cases had a significantly lower mean serum cholesterol value than that of noncases (213.0 mg/dl vs 219.0 mg/dl). When the study subjects were separated into either a low, middle or high group, based on their serum cholesterol values, there was a significant inverse trend for cases of oral/pharyngeal/esophageal cancer combined. The association was present for cases diagnosed within 10 years of examination (p = 0.012), but not for cases diagnosed after 10 years. This suggests that the inverse association is due to the metabolic effects of undiagnosed oral/pharyngeal/esophageal cancer upon serum cholesterol levels. These results are discussed in relation to other studies on serum cholesterol.     

Anterior interosseous nerve palsy after reduction and percutaneous pinning of open fractures of the radius and ulna.

We report a case of an anterior interosseous nerve palsy after closed reduction and percutaneous pinning of open fractures of the radius and ulna in an adult. Operative findings showed that the anterior interosseous nerve was trapped between the distal and proximal part of the fractured radius. Treatment by neurorrhaphy gave a satisfactory result.     

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.     

Localization and developmental expression of a novel protein kinase C delta gene.

The expression and localization of a novel protein kinase C delta (nPKC delta) mRNA were investigated using Northern blotting and in situ hybridization in the developmental process of mouse brain. In adult mice, nPKC delta was abundantly expressed in the thalamus, moderately in the pons and the cerebellum, but faintly in the cerebral cortex and the spinal cord. By in situ hybridization, the signals were observed specifically at the sensory and motor relay nuclei of the thalamus, the dorsal cochlear nuclei of the pons, and the molecular layer of the cerebellum. When developmental changes in the expression of nPKC delta gene were analyzed by in situ hybridization, it was not detectable in embryonic and neonatal brains, very weakly expressed in the thalamus in the first week, and highly expressed at two weeks of age. These results suggest that the gene expression of nPKC delta is strictly controlled by both the cell type and the developmental process.