Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Effects of rabeprazole or famotidine during cardiac surgery on perioperative gastric and esophageal pH readings

Objectives: Upper gastrointestinal bleeding, particularly from a stress-induced duodenal ulcer, is an extremely important perioperative complication in cardiovascular surgery. Methods: In the present study, 33 patients undergoing elective open heart surgery between July 2000 and February 2001 were allocated to either a famotidine (FAM) or rabeprazole (RPZ) group to examine the perioperative gastric and esophageal pH readings, in conjunction with an investigation into the effect of infection with Helicobacter pylori (HP). Results: Postoperative upper gastrointestinal bleeding did not occur in either group, and the intraoperative and postoperative mean gastric pH readings, as well as the holding time pH> 6, suggested sufficient acid suppression by either drug. Gastric acid secretion was less strongly suppressed in HP-negative patients in the FAM group, but was unaffected by HP infection status in the RPZ group. Conclusion: The FAM group and RPZ group revealed a sufficient effect of gastric acid suppression. It was indicated that FAM had an insufficient effect of gastric acid suppression for HP-negative patients.     

Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas

The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA Immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, Including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-β, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved In the growth of certain non-neuronal carcinomas.     

Gangliosides of human melanoma: altered expression in vivo and in vitro

The ganglioside composition of human melanoma was analyzed in five sets of tumor specimens obtained directly from surgery, from the autologous tissue culture cell lines, and from the autologous cell lines grown in athymic nude mice. Total gangliosides of these 15 melanoma specimens were isolated and purified, and the amount of each component ganglioside was analyzed by thin-layer chromatography and a thin-layer chromatography scanner. The ganglioside composition of the five surgical melanoma specimens clearly exhibited different patterns from each other. Moreover, none of the autologous cultured melanomas possessed the same ganglioside composition as their original biopsied tumors. However, when these melanoma cell lines were transplanted into nude mice, the ganglioside composition was converted back to the same ganglioside pattern as in the original surgical specimens. The results support the view that changes in the ganglioside composition of melanoma during in vitro growth are caused by the culture environment rather than by selection of melanoma cells with a particular genotype. Reestablishment of the original ganglioside patterns after passage in nude mice provides clear evidence that in vivo expression of gangliosides is a conserved and stable function specified by the human melanoma cells.     

Prenatal diagnosis of Werdnig Hoffmann disease in China

Objective To establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA.
Methods Genetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.
Results The pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.
Conclusion This approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.