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.     

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.     

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.     

Effective segmental chemoembolization of advanced hepatocellular carcinoma with tumor thrombus in the portal vein

Purpose: Evaluate therapeutic results of transcatheter segmental hepatic artery chemo-oily-embolization (segmental TAE) against advanced hepatocellular carcinomas (HCC) accompanied by portal tumor thrombus (PTT). Methods: Segmental TAE was performed in nine patients with hepatic cirrhosis and advanced HCCs accompanied by PTT. Four subsegmental portal branches were obstructed by PTT in three patients, and two were obstructed in the remaining six patients. TAE was performed into the targeted segmental hepatic artery followed by embolization with gelatin sponge particles. Results: In one patient undergoing subsequent resection, a marked anticancer effect on the PTT was demonstrated histologically. In the eight other patients who did not undergo subsequent resection, the cumulative survival rates were 67% at 6 months, 44% at 1 year, and 22% at 2 years. No serious complications were noted. Conclusions: This therapeutic approach is thought to be a useful treatment for HCC with PTT, because it reinforces anticancer effects and can be performed more safely than conventional transcatheter arterial embolization.     

Experience with 1904 laparoscopic cholecystectomies at a private hospital

The purpose of this paper is to describe our recent experience in performing laparoscopic cholecystectomies of which we performed 1904, from January 1991 to May 1997, at our private hospital, mainly to treat cholecystolithiasis. The patients included 1563 with gallbladder stones (82.0%), 82 with cholecystocholedocholithiasis (4.3%), 104 with adenomyomatosis (5.5%), 132 with polyps (6.9%), and 23 with gallbladder cancer (1.3%). A difficult pericholecystic dissection led to conversion to open surgery in 61 patients. The average operation time was 63 min. Bile duct injury or cystic artery bleeding occurred in 3 patients with acute cholecystitis, and small intestine injury occurred in 1 patient, while bile leakage or a right subphrenic abscess occurred in 6 patients postoperatively. Although this series included 69 patients with previous upper abdominal surgery, 14 with liver cirrhosis, 267 with a nonvisualized gallbladder, and 148 with acute cholecystitis, the overall conversion rate was only 3.2% and morbidity only 0.5%. Although almost all patients with cholelithiasis are now considered potential candidates for a laparoscopic cholecystectomy, difficulties during cholecystectomy have been encountered in patients with acute cholecystitis. Surgeons should thus be fully prepared to convert to open surgery whenever difficulties are encountered, in order to avoid complication.