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.     

The modified outside-in suture: vertical repair of the anterior horn of the meniscus after decompression of a large meniscal cyst

This article describes a modified suture technique designed for the vertical repair of the anterior horn of the meniscus after arthroscopic decompression of a large meniscal cyst. This procedure comprises of three steps: first, the meniscus was pierced vertically using a suture hook and a No. 0 PDS suture. Second, both ends of the No. 0 PDS on the femoral and tibial surfaces of the meniscus were pulled to the outside of the joint capsule using a spinal needle preloaded with suture material. Finally, a skin incision was made adjacent to the suture materials, and both ends were tied. We recommend this technique not only for the vertical repair of the anterior horn of the meniscus after decompression of large meniscal cyst, but also to repair a longitudinal tear of the meniscus.     

Preservation of Bile Ductules Mitigates Bile Duct Loss

The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection. The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining. Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.     

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.     

Unlike hypoxia, hypoglycemia does not preferentially destroy GABAergic neurons in developing rat neocortex explants in culture

We tested whether hypoglycemia, like hypoxia, would preferentially destroy GABAergic nerve cells in the neocortex. To this end, rat neocortex explants dissected from 6-day-old rat pups and cultured up to a developmental stage approximately comparable to that of the newborn human neocortex, were exposed to hypoglycemia for different periods. Quantitative light microscopic and immunocytochemical evaluation of the cultures demonstrated that hypoglycemia does not preferentially destroy GABAergic but rather non-GABAergic neurons, a finding quite opposite to what was found after hypoxia. Recent biochemical data from other laboratories which seem to support this difference in neuronal vulnerability are discussed. It is concluded that perinatal hypoglycemia may not form such a serious threat with respect to the genesis of epilepsy as does hypoxia.