The significance of HLA-DRB1 matching in clinical renal transplantation.

We analyzed the genotype for HLA-DRB1 alleles by digestion of polymerase chain reaction-amplified genes with the restriction endonucleases (PCR-RFLP) method to investigate the influence of HLA-DR antigen "splits" at the DRB1 gene level on the incidence of acute graft rejection in the renal transplant. For all patients, the incidence of acute rejection was proportional to the number of the serological HLA mismatch (0% in patients with two-haplotype match; 18% with HLA-A, -B, and -DR zero mismatch; 33% with HLA-DR zero mismatch; and 48% with HLA-DR one mismatch). For the patients with serological HLA-DR zero mismatch, the incidence of acute rejection in patients with HLA-DRB1 one mismatch (10/13: 77%) was significantly higher than that in those with zero mismatch (2/27: 7%). It was concluded that genotyping for HLA-DRB1 alleles would be beneficial in predicting acute rejection in patients with serological HLA-DR zero mismatch, although no difference was noted in the graft survivals.     

Oxygen uptake and carbon dioxide elimination during epinephrine-induced arrhythmias in humans

Key words  cardiac arrhythmias - oxygen uptake - carbon dioxide elimination     

Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.     

A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation

The authors report a patient carrying a missense mutation in exon 10 of tau that causes a substitution at codon 301 (P301S). Although the patient shares the rapidly progressive frontotemporal dementia of the other reported pedigrees with P301S, the clinical phenotype is unique in that parkinsonism was a major symptom in the early stage and because behavioral symptoms with dementia became prominent 2 years after the onset of the disease. This study substantiates the notion that tau mutations at codon 301 can show various phenotypes.     

Recurrence of rapidly progressive glomerulonephritis probably associated with two different kinds of drugs

We describe a rare case that developed a rapidly progressive glomerulonephritis twice in a 69-year-old man during a course of treatment, first with allopurinol and then with piperacillin. The cessation of each treatment was followed by spontaneous recovery in renal function. A renal biopsy showed crescentic glomerulonephritis with mild tubulointerstitial change and a skin biopsy showed leukocytoclastic vasculitis. This is, to our knowledge, a very rare case of crescentic glomerulonephritis, probably associated with vasculitis during a course of treatment with two different kinds of drugs.     

Effects of transforming growth factor beta-1 and all-trans-retinoic acid on androgen-induced development of neonatal mouse bulbourethral glands in vitro

Effects of transforming growth factor beta-1 (TGF-beta1) and all-trans-retinoic acid (All-trans-RA) on development of bulbourethral glands (BUGs) of neonatal mice were investigated in vitro. BUGs from 0-day-old male mice were cultured for 6 days in serum-free, chemically defined medium containing transferrin and bovine serum albumin, supplemented with 5alpha-dihydrotestosterone (DHT; 10-8 M) and insulin (10 microg/mL) alone or in combination. Prior to culture, BUGs from 0-day-old mice consisted of a simple epithelial rudiment encapsulated by mesenchyme. Epithelial growth and ductal branching occurred in BUGs cultured in medium containing DHT and insulin or DHT alone, but epithelial branching did not occur in BUGs cultured in the presence of insulin alone. Addition of TGF-beta1 at concentrations of > 5 ng/mL (0.2 x 10-9 M) to medium containing both insulin and DHT, inhibited the expected increase in overall size of BUGs, epithelial area and ductal branching in a dose-dependent manner. TGF-beta1 also decreased [3H]-thymidine labelling indices of both epithelium and mesenchyme. TGF-beta1 at 10 ng/mL elicited these inhibitory effects on BUGs cultured in medium containing DHT alone. Addition of All-trans-RA (10-8 to 10-6 M) to the medium containing DHT plus insulin, or DHT alone did not exert significant effects on either overall size of BUGs or epithelial growth and ductal branching. All-trans-RA at 10-6 M decreased the [3H]-thymidine labelling index of mesenchyme of BUGs cultured in medium with DHT plus insulin or DHT alone, but did not decrease the [3H]-thymidine labelling index of epithelium. The present results indicate that TGF-beta1 inhibits androgen-induced epithelial and mesenchymal growth as well as epithelial morphogenesis of BUGs from neonatal mice. Such an inhibitory effect of TGF-beta1 is not mimicked by All-trans-RA at physiological concentrations.