Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

CYP2E1 and ALDH2 Genotypes and Alcohol Dependence in Japanese

The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C₁/C₂) and ALDH2 ( ALDH2*1/ALDH2*2 ), and the susceptibility to alcoholism. There was no significant difference in C₂ gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C₂ genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, the ALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (CJ were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C₂ allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207-211,1993).     

The prognostic significance of nuclear DNA content in non-small-cell lung carcinoma

The nuclear DNA content of paraffin-embedded specimens of primary non-small-cell lung carcinomas was analysed using flow cytometry in 210 patients (80 squamous cell carcinomas, 99 adenocarcinomas, 19 large cell carcinomas and 15 others). The relationship between nuclear DNA content and prognostic factors was studied using multivariate analysis with Cox's proportional hazard model. 1) The frequency of DNA aneuploidy was 77.3% among 210 patients, and it significantly (p less than 0.05) increased with advanced stage and the presence of lymph node metastasis. 2) The patients with DNA aneuploid tumors had a significantly (p less than 0.001) less favorable prognosis than those with DNA diploid tumors among 179 patients with non-small-cell lung carcinomas. Similar results were demonstrated in 79 patients with stage I carcinomas and in 85 patients who underwent absolute curative resection. 3) Multivariate analysis using Cox's proportional hazard model showed that DNA ploidy was an independent prognostic factor for survival. Especially in the patients with absolute curative resection, DNA ploidy was the most important prognostic factor. In conclusion, flow cytometric nuclear DNA content analysis provided useful biological information, and DNA ploidy was an important and major independent prognostic factor in non-small-cell lung carcinoma.     

Absent chondrodysplasia punctata in a male with an Xp terminal deletion involving the putative region for CDPX1 locus

This is a follow-up report on a male patient with a 46, Y, r(X) karyotype. Although he had no clinico-radiological features of X-linked recessive chondrodysplasia punctata (CDPX1), molecular studies revealed an Xp terminal deletion involving the putative region for the CDPX1 locus (PABX-DXS31). We suspect that the absence of CDPX1 may be attributable to the nature of the disease and the extreme short stature of the patient (mean – 5.6 S.D.). © 1993 Wiley-Liss, Inc.     

Characterization of retinol-binding protein in familial hypo-retinol-binding proteinemia

We reported previously familial hypo-retinol-binding proteinemia in a child who developed keratomalacia during measles infection. In the present study, we characterized serum retinol-binding proteins (RBPs) in the affected family members and compared these RBPs with those in the unaffected family members. Immunoblotting following SDS-polyacrylamide gel electrophoresis and isoelectric focusing demonstrated no differences in molecular weight and isoelectric point between the RBPs from the affected and unaffected family members, as far as RBPs were detected by antibody against standard RBP. Gel filtration revealed that all the RBPs in the serum of the affected family members made a complex with prealbumin.     

Ontogeny of behavioral sensitization to cocaine

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56–60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21–25 or 28–32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.     

Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation

Abstract:  We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.     

HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals.

BACKGROUND: The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. METHODS: In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. RESULTS: Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%). CONCLUSIONS: The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation.