Vascular endothelial growth factor (VEGF or vascular permeability factor), a direct-acting, endothelial cell-specific mitogen, has been suggested to be involved in development and maintenance of vasculatures in tumor neovascularization and in normal tissues. To investigate possible roles of VEGF in ischemic hearts, we studied induction of VEGF mRNA by ischemia and hypoxia using coronary artery-ligated hearts in vivo and perfused hearts and cultured myocardial cells in vitro. VEGF mRNA was potently induced by ischemia in the heart in vivo. In perfused hearts, maximum expression was rapidly induced (within 30 min) by transient reversible ischemia (5-10 min of ischemia) and lasted at least 3 h. Induction was also caused by hypoxia, which was confirmed in perfused hearts and cultured myocardial cells. These results suggest that induction of VEGF mRNA is upregulated by oxygen deprivation in the heart and that not only infarction but also chronic ischemia in the clinical setting could induce VEGF as a potent angiogenesis factor to stimulate coronary collateral formation.

Autoimmune lymphoproliferative syndrome (ALPS) is classically defined as a disease with defective FAS-mediated apoptosis (type I-III). Germline NRAS mutation was recently identified in type IV ALPS. We report 2 cases with ALPS-like disease with somatic KRAS mutation. Both cases were characterized by prominent autoimmune cytopenia and lymphoadenopathy/splenomegaly. These patients did not satisfy the diagnostic criteria for ALPS or juvenile myelomonocytic leukemia and are probably defined as a new disease entity of RAS-associated ALPS-like disease (RALD).

Background : Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after sildenafil citrate treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving sildenafil citrate for their erectile dysfunction (ED) and to assess the female partners' sexual function. Methods : Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. Results : Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with sildenafil citrate treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number ( P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. Conclusions : The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with sildenafil citrate treatment is poor despite an improvement of erectile function.

ABSTRACT:We report definitive diagnosis and effective chenodeoxycholic acid (CDCA) treatment of two Japanese children with 3␤-hydroxy-⌬ 5 -C 27 -steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum ␥-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3␤-hydroxy-⌬ 5 bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified four novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in one allele. Excessive 3␤-hydroxy-⌬ 5 -bile acids such as 3␤,7␣-dihydroxy-and 3␤,7␣,12␣-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3␤-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids were still detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with CDCA treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3␤-hydroxy-⌬ 5 -C 27 -steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of CDCA treatment at this critical time, before the late cholestatic stage. (Pediatr Res 68: 258-263, 2010) D eficiency of 3␤-hydroxy-⌬ 5 -C 27 -steroid dehydrogenase/ isomerase (3␤-HSD) was first described by Clayton et al. in 1987 (1). This inborn error of bile acid synthesis is very rare and shows autosomal recessive inheritance. The main findings in 3␤-HSD deficiency are low or normal concentrations of total bile acid and normal activity of ␥-glutamyltransferase (GGT) in serum, as well as absence of pruritus despite conjugated hyperbilirubinemia, elevated alanine aminotransferase (ALT), and fatty stools. In the synthesis of bile acids from cholesterol, 3␤-HSD catalyzes the second of a series of reactions leading to excretion of 3␤,7␣-dihydroxy-5-cholenoic acid (⌬ 5 -3␤,7␣-diol) and 3␤,7␣,12␣-trihydroxy-5-cholenoic acid (⌬ 5 -3␤,7␣,12␣-triol) in the urine. In the first reported patient, complete absence of 3␤-HSD activity was found by Buchmann et al. in 1990 (2) based on the study of cultured fibroblasts. In 2000, Schwarz et al. (3) reported that the same patient had a homozygous mutation representing a 2-bp deletion in exon 6 of the 3␤-HSD gene (HSD3B7) on chromosome 16p11.2-12. The human HSD3B7 gene contains six coding exons and encodes 369 amino acids; so far, 13 distinct mutations causing 3␤-HSD deficiency have been reported (4,5).Here, we report genetic analyses of two Japanese patients with 3␤-HSD deficiency: one previously reported patient (6,7) was diagnosed with 3␤-HSD deficiency by bile acid analysis and the ot...

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