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.     

Stochastic resonance with differential code in feedforward network with intra-layer random connections.

We examined stochastic resonance with a differential coding scheme using a multilayer feedforward neural network which is composed of intra-layer connections. We show that the network, with random synaptic connections in each layer, encodes an input signal into a spike coherence that represents temporal differences among the inputs. We also demonstrate that both internal and external noise enhance the detection of weak signals. Finally, we discuss how the feedforward network with intra-layer random connections is similar to a membrane in its sensitivity to and amplification of a change in stimulus and suggest that the intensity of internal noise may be tuned in a real brain.     

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.