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.     

MR imaging of renal cell carcinoma: associations among signal intensity, tumor enhancement, and pathologic findings

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation.     

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.     

Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease.     

Production and release of infectious hepatitis C virus from human liver cell cultures in the three-dimensional radial-flow bioreactor

Lack of efficient culture systems for hepatitis C virus (HCV) has been a major obstacle in HCV research. Human liver cells grown in a three-dimensional radial-flow bioreactor were successfully infected following inoculation with plasma from an HCV carrier. Subsequent detection of increased HCV RNA suggested viral replication. Furthermore, transfection of HCV RNA transcribed from full-length cDNA also resulted in the production and release of HCV virions into supernatant. Infectivity was shown by successful secondary passage to a new culture. Introduction of mutations in RNA helicase and polymerase regions of HCV cDNA abolished virus replication, indicating that reverse genetics of this system is possible. The ability to replicate and detect the extracellular release of HCV might provide clues with regard to the persistent nature of HCV infection. It will also accelerate research into the pathogenicity of HCV, as well as the development of prophylactic agents and new therapy.     

The expression of vascular endothelial growth factor-A and -C, and receptors 1 and 3: correlation with lymph node metastasis and prognosis in tongue squamous cell carcinoma

We determined whether the expression of VEGF-A and -C and their receptors, Flt-1 and Flt-4, are associated with primary tumor size, regional lymph node metastasis, distant metastasis and prognosis in patients with tongue carcinoma. The expression of VEGF-A and -C, and their receptors, Flt-1 and Flt-4, in biopsy specimens taken from 73 patients with tongue carcinoma were examined by immunohistochemical staining. VEGF-A expression was associated with distant failure and VEGF-C expression correlated with locoregional recurrence and distant failure. Furthermore, VEGF-C expression was associated with lymph node recurrence in N0 cases. Multivariate analysis revealed that VEGF-C expression was an exclusively independent factor influencing lymph node metastasis. In terms of the overall 5-year survival rate, there was no significance correlation between the overall 5-year survival rate and expression of VEGF-A, Flt-1 and Flt-4 expression, whereas there was a significant difference between VEGF-C-positive and VEGF-C-negative cases (VEGF-C-positive, 51.7% vs VEGF-C-negative, 94.2%). Furthermore, there was a significant difference between positive and negative expression for both VEGF-A and VEGF-C. Multivariate analysis revealed that lymph node metastasis and VEGF-C expression were exclusive, independent factors influencing the overall survival rate. VEGF-C expression may be a predictive factor of regional lymph node recurrence and prognosis in patients with tongue carcinoma.