Changes in the volume and histology of retractile testes in prepubertal boys

Testicular development was studied in prepubertal boys with retractile testes. Testicular volume, the diameter of the seminiferous tubules and the number of spermatogonia in the tubules were decreased in cases of unilateral retractile testis, when compared with values for the contralateral normally descended testis. On the other hand, in patients with a unilateral retractile testis and contralateral inguinal testis, there was no difference in the developmental parameters between the two testes. These results suggest that the retractile testis has developmental failures characteristic of a cryptorchid testis and therefore requires orchiopexy.     

The limitation of staged repair in the surgical management of congenital complex heart anomalies with aortic arch obstruction

OBJECTIVE: Severe aortic arch obstruction including an interrupted aortic arch in congenital complex heart anomalies remains a challenge in surgical management. METHODS: Treatment and outcomes in 75 consecutive patients who underwent an aortic arch repair as the first step of the staged repair protocol between 1975 and 2000 were reviewed. Their ages at repair ranged from 1 day to 8.5 months. RESULTS: Cross-sectional postoperative follow-up data were available in all the patients. The follow-up period ranged from 0 to 27.6 years (mean: 7.3 +/- 7.3 years). There were 20 postoperative hospital deaths (27%) and 7 late deaths. The Kaplan-Meier estimate of survival was 81.3% +/- 4.5% at 1 month, 68.0% +/- 5.4% at 1 year, 65.0% +/- 5.5% at 5 years, 63.1% +/- 5.7% at 10 years, 63.1% +/- 5.7% at 20 years. By Cox regression analysis, body weight of 2.5 kg or less is the only independent determinant of postoperative mortality (p = 0.04, multivariable odds ratio: 2.50, [95% confidence interval: 1.02-6.1]). The aortic arch morphology, the primary cardiac lesion, or date of operation did not reach a statistically significant level to show correlation with mortality. Reintervention to reconstruct the aortic arch was performed at 9 occasions in 8 of the 55 patients who survived the primary operation (14.5%). The Kaplan-Meier estimate of the reintervention-free rate was 91.3% +/- 4.2% at 5 years, 85.5% +/- 5.6% at 10 years, 75.6% +/- 8.2% at 20 years. Using multivariable Cox regression analysis, interrupted aortic arch (versus aortic coarctation) was the only independent predictor of a shorter time to reintervention (p = 0.001, multivariable odds ratio: 16.1, [95% confidence interval: 3.2-80.2]). CONCLUSIONS: The staged repair protocol was associated with significant limitations in patient survival and with the development of recurrent aortic arch obstruction. Thus, a primary repair protocol may serve as an alternate approach, especially in patients with low weight or with an interrupted aortic arch.     

Effects of Right Ventricular Failure on Renal Function During Pneumatic Left Ventricular Assist

Abstract: In an experimental dog model of acute biventricular failure, the effects of left ventricular (LV) assist on renal hemodynamics and function were evaluated. After the induction of severe cardiac failure by multiple ligation of the coronary arteries, LV assist with a 40 ml pneumatic pulsatile pump was initiated, and the aortic flow was maintained at control values. The right atrial pressure (RAP) rose to 21.3 mm Hg with the appearance of profound right ventricular (RV) failure. Renal arterial blood flow (RAF) decreased to about 60% of the control value after 2 h of LV assist. The urine volume decreased and renal function deteriorated progressively. RV assist decreased the RAP to 4.8 mm Hg, and the reduced RAF recovered. After 3 h of RV assist, the RAF returned to initial values and the urine volume increased, but renal function did not recover. Advanced biventricular failure with elevated RAP during LV assist reduced renal perfusion and impaired renal function and may be an indication for early RV assist     

Hepatic angiomyolipoma developing during the follow-up of ulcerative colitis: Report of a case and review of the literature

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5×7.5×7cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.     

Intrahepatic Delivery of Glutathione by Conjugation to Dextran

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of -glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.     

Genomic structure around joining segments and constant regions of swine T-cell receptor alpha/delta (TRA/TRD) locus

A complete genomic region of 131.2 kb including the swine T-cell receptor alpha/delta constant region (TRAC/TRDC) and joining segments (TRAJ/TRDJ) was sequenced. The structure of this region was strikingly conserved in comparison to that of human or mouse. All of the 61 TRAJ segments detected in the human genomic sequence were detected in the swine sequence and the sequence of the protein binding site of T early alpha, the sequence of the alpha enhancer element and the conserved sequence block between TRAJ3 and TRAJ4 are highly conserved. Insertion of the repetitive sequences that interspersed after the differentiation of the species in mammals such as short interspersed nucleotide elements is markedly suppressed in comparison to other genomic regions, while the composition of the mammalian-wide interspersed sequences is relatively conserved in human and swine. This observation indicates the existence of a highly selective pressure to conserve this genomic region around TRAJ throughout the evolution of mammals.     

Disease associations and altered immune function in CD45 138G variant carriers

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.     

Contribution of Asian mouse subspecies Mus musculus molossinus to genomic constitution of strain C57BL/6J, as defined by BAC-end sequence-SNP analysis

MSM/Ms is an inbred strain derived from the Japanese wild mouse, Mus musculus molossinus. It is believed that subspecies molossinus has contributed substantially to the genome constitution of common laboratory strains of mice, although the majority of their genome is derived from the west European M. m. domesticus. Information on the molossinus genome is thus essential not only for genetic studies involving molossinus but also for characterization of common laboratory strains. Here, we report the construction of an arrayed bacterial artificial chromosome (BAC) library from male MSM/Ms genomic DNA, covering approximately 1x genome equivalent. Both ends of 176,256 BAC clone inserts were sequenced, and 62,988 BAC-end sequence (BES) pairs were mapped onto the C57BL/6J genome (NCBI mouse Build 30), covering 2,228,164 kbp or 89% of the total genome. Taking advantage of the BES map data, we established a computer-based clone screening system. Comparison of the MSM/Ms and C57BL/6J sequences revealed 489,200 candidate single nucleotide polymorphisms (SNPs) in 51,137,941 bp sequenced. The overall nucleotide substitution rate was as high as 0.0096. The distribution of SNPs along the C57BL/6J genome was not uniform: The majority of the genome showed a high SNP rate, and only 5.2% of the genome showed an extremely low SNP rate (percentage identity = 0.9997); these sequences are likely derived from the molossinus genome.     

Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the human matrix Gla protein (MGP) locus

Matrix Gla protein (MGP) is an 84-residue, vitamin K-dependent protein expressed by chondrocytes and vascular smooth muscle cells, and is a potent regulator of calcium deposition in cartilage and arterial wall. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human MGP gene. This polymorphism will be useful in genetic studies of arteriosclerosis and osteoporosis. Received: November 5, 1997 / Accepted November 27, 1997