N-terminal pro-brain natriuretic peptide predicts hospitalization for ischemic stroke in Japanese hemodialysis patients

Clinical and Experimental Nephrology - The association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and stroke in Japanese hemodialysis (HD) outpatients is unclear. Therefore, in...     

Hard metal asthma: cross immunological and respiratory reactivity between cobalt and nickel?

Eight asthmatic patients with hard metal asthma due to cobalt underwent bronchial provocation challenge with nickel sulphate. Seven patients developed a fall in FEV1 of 20% or more after inhaling nickel sulphate, four showing an immediate response and three a late response. Eight control subjects, including six asthmatic patients, with no history of hard metal exposure, showed no bronchoconstriction in response to a provocation challenge with nickel sulphate. Specific antibodies to nickel conjugated human serum albumin were present in four of the eight patients with sensitivity to cobalt conjugated human serum albumin but were absent from the serum of 60 unexposed asthmatic patients and 25 exposed symptom free workers. These results suggest that nickel as well as cobalt sensitivity plays a part in hard metal asthma.     

Direct effect of cadmium on citrate uptake by isolated rat renal brush border membrane vesicles

High incidence of multiple kidney stone formation has been observed among workers exposed to cadmium (Cd). Citrate is known to be a protective factor against renal stone formation. To study the direct effect of cadmium on citrate uptake by the renal brush border membrane, we exposed isolated rat renal brush border membrane vesicles (BBMV) to cadmium and determined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. Preincubation of BBMV with 2 and 10 mM CdCl₂ for 1 min significantly inhibited citrate uptake compared with that of BBMV without Cd. Analysis of the time course of citrate uptake during 30-min preincubation of BBMV with 0.5 mM Cd also revealed significant reduction of the uptake compared with that of the control BBMV without preincubation. These findings indicate that preincubation of BBMV with cadmium results in time-dependent and concentration-dependent inhibition of citrate uptake.     

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.     

Immunomodulation in mineral dust-exposed lungs: stimulatory effect and interleukin-1 release by neutrophils from quartz-elicited alveolitis.

Quartz deposition in the rat lung causes an intense and persistent neutrophil alveolitis leading to parenchymal fibrosis. Bronchoalveolar leucocytes (BAL) from quartz-exposed rat lungs were studied for their effects on splenic lymphocyte proliferation; titanium dioxide (TiO2) was used as a control, non-fibrogenic dust. Seven days after the intratracheal instillation of 1 mg of quartz or TiO2 suspended in phosphate-buffered saline (PBS), BAL were recovered by lavage; the effect of PBS alone was also studied. TiO2-elicited BAL (macrophages greater than 98%) inhibited splenocytes responding to suboptimal phytohaemagglutinin (PHA) more than PBS-elicited BAL (macrophages greater than 98%); the effect was dependent on the BAL:splenic lymphocyte ratio. Quartz-elicited whole BAL (macrophages 49%, neutrophils 51%), and an alveolar macrophage-enriched population with purity of 87% separated from it, were less inhibitory to splenocyte mitogenesis than PBS-elicited BAL. A neutrophil-enriched population, with a purity of 80%, markedly enhanced splenocyte response to PHA. In addition, whole quartz BAL and the macrophage-enriched population obtained from it enhanced the mitogenesis of T cell-enriched lymphocytes at a much lower BAL:lymphocyte ratio. The neutrophil-enriched quartz BAL enhanced mitogenesis substantially more than the whole or macrophage-enriched population from quartz-exposed lung. Supernatants from normal macrophages, PBS BAL, TiO2 BAL, quartz BAL and both alveolar macrophage and neutrophil-enriched quartz populations were assessed for interleukin-1 (IL-1) activity. Quartz-BAL, quartz macrophages and quartz neutrophils all produced significantly higher IL-1 levels than PBS BAL; the supernatants from quartz neutrophils, however, showed the highest IL-1 activity. These findings suggest that quartz-elicited bronchoalveolar leukocytes, especially neutrophils, enhance lymphocyte proliferation and that increased IL-1 secretion by these cells is likely to be the effector molecule involved. These findings have important implications for immune response in mineral dust-stimulated lung and for inflammatory lung disease in general.     

Anterior urethral recurrence of superficial bladder cancer: its clinical significance

The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.     

Loss of tolerance to a maternal kidney transplant is selective for HLA class II: evidence from trans-vivo DTH and alloantibody analysis

We studied late graft rejection in a patient who had received a kidney transplant 9–10 years earlier from his mother and who had been off all immunosuppressive drugs for 7 years at the time of graft rejection onset. The mother differed for one HLA-A (A3) and one HLA-B (B62) antigen but had only a subtype mismatch at the HLA-DRβ1 locus (donor: DRβ1*1104; recipient: DRβ1*1102). A gradual rise in serum creatinine from 1.8 to 2.0 mg/dl at year 9 prompted a biopsy, which was negative for rejection (focal infiltrates but no tubulitis). Ten months later the patient’s creatinine had risen to > 3.4 mg/dl, and a second biopsy revealed extensive tubulitis, cellular rejection, and glomerular sclerosis. Sonicates of donor leukocytes triggered no delayed-type hypersensitivity (DTH) response above background (PBMC only) in the patient’s peripheral blood leukocytes obtained prior to year 9. A gradual recovery of antidonor DTH response between year 9 and 10 closely paralleled the change from tolerant to rejection status. Antidonor antibody was also undetectable in serum prior to year 9, but a donor-reactive antibody did develop at year 10.2 shortly after the peak of DTH response. The serum level of soluble donor HLA class I B62 antigen rose > 10-fold over prerejection level at the time of the biopsy-proven rejection, suggesting a possible trigger for both the cellular and humoral immune response. Nonetheless, we found no evidence for the de-velopment of humoral or cellular immunity to maternal HLA class I. Instead, DTH analysis of memory T cells of the patient obtained after rejection showed that a single maternal HLA DRβ1*1104 allopeptide, differing by two amino acids in sequence from the peptide of the recipient (DRβ1*1102), stimulated a strong memory DTH response. Similarly, we found an anti-HLA class II donor-specific antibody in serum that appeared to be crossreactive with DRβ1*1104 and DRβ1*1101 but not with the recipient DRβ1*1102 antigen. The data support the idea of a profound unresponsive state at both the cellular (DTH) and humoral level toward maternal HLA class I antigens that was not reversed even during late cellular rejection, despite the release of high levels of soluble HLA class I. Furthermore, the data suggest that DTH recovery was a close correlate of the onset of rejection and this “indirect” alloresponse, like the anti-donor alloantibody response that followed, was directed not to noninherited maternal HLA-A,B antigens but to the maternal HLA DRβ1*1104 subtype.     

Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients

Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities such as the appearance of autoantibodies and complications of autoimmune diseases. Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, has been considered to play a role in the pathogenesis of autoimmune diseases. It has been found that serum soluble Fas (sFas) levels are elevated in silicosis patients (SIL) and the sFas message is dominantly expressed in peripheral blood mononuclear cells (PBMC) derived from these individuals. In the present study, one tried to detect alternatively spliced variant messages including typical sFas message and found four that were highly and frequently expressed, and which possess a signal peptide domain, but not transmembrane and signal transducing domains, in PBMC derived from SIL. Functional mutations were not detected in Fas and FasL genes in silicosis PBMC. Still, alternative spliced variants of the Fas gene including typical sFas message appear to play an important role in the immunological dysregulation in SIL.     

Importance of luxury flow for critically ill patients receiving a left ventricular assist system

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m² had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m² or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.