Major histocompatibility complex class II antigens on renal cell cancer--immunohistochemical study and effect on their expression by interferon

Products of major histocompatibility complex (MHC) play important roles in immune reaction. Class II MHC antigens serve as restriction elements for cells presenting antigens to CD4-positive helper T cells and also as histocompatibility antigens responsible for graft rejection. Furthermore, it was reported that expression of class II antigens on tumor cells increases immunogenicity in the murine system. In an attempt to investigate the relationship between renal cell cancer (RCC) and host's immune responses, we examined the expression of class II MHC antigens on RCC tissues of 30 cases and tumor cell lines. Immunohistochemical study showed that class II antigens were detected on 29 out of 30 RCC tissues to various degrees with an order of positivity DR greater than DP greater than DQ but not normal renal tubular cells. Significant correlation was found between the expression of DQ or DP and the degree of lymphocyte infiltration. Three lines of RCC were examined by flowcytometric analysis, and were found to lack class II antigens. In KRC/Y and ACHN, however, HLA-DR-positive cells and in KRC/Y a smaller number of HLA-DP-positive cells were found when these cells were treated with interferon-gamma but not interferon-alpha. The result suggests that the expression of class II antigens on RCC might be modified by interferon-gamma which is produced by tumor infiltrating lymphocytes or administrated for cancer treatment. Their expression is considered to affect host's immune response to RCC.     

Pharmacokinetics of amikacin in children and neonates

To evaluate pharmacokinetics of amikacin (AMK), one of the aminoglycoside antibiotics, children with ages from 2 days to 11 years were treated with various doses by various administration routes, and both plasma and urinary levels of AMK were determined. The following is a summary of the results obtained: 1. Of 6 children, three were treated with 2.0 mg/kg of AMK by a 30-minute intravenous drip infusion, and the other 3 with 4.0 mg/kg by a 60-minute. Peaks of average plasma levels were observed at the ends of the infusions in both cases, and their levels were 9.23 and 13.67 micrograms/ml, respectively, showing a dose-dependency. Both half-lives and areas under plasma concentration-time curves (AUCs) were similar to those of adults. However, the volume of distribution (Vd) showed a lower value than that of adults. Peaks of average urine levels were 149.3 micrograms/ml with 2.0 mg/kg in 0-2 hours after the start of the infusion and 223.3 micrograms/ml with 4.0 mg/kg in 2-4 hours. Average urinary recovery rates within 6 hours after the start of the infusion were 95.4% with 2.0 mg/kg and 85.7% with 4.0 mg/kg. These recoveries were equal to or higher than that of adults. 2. When 3.0, 4.0 and 6.0 mg/kg of AMK were administered to 3 groups of mature or premature babies by intramuscular injection, average peak levels of AMK in plasma were 6.26, 8.61 and 12.60 micrograms/ml, respectively, at 30 minutes after the injection, showing dose-dependency. In these groups, the younger the day age after birth was, the longer the half-life became. The AUCs were larger as the half-life became longer. The Vd was larger than that in the intravenous drip infusion group, but, any particular was not observed. Average peak levels of AMK in urine were 78.83 micrograms/ml at 4-6 hours with a dose level of 3.0 mg/kg, 99.17 micrograms/ml at 2-4 hours with 4.0 mg/kg and 139.20 micrograms/ml at 0-2 hours with 6.0 mg/kg. Average urinary recovery rates within 6 hours were 36.57% with 3.0 mg/kg, 34.67% with 4.0 mg/kg and 43.77% with 6.0 mg/kg. These recovery rates were markedly lower than those observed in adults and children. One of the causes of this low recovery is that mature and premature babies have immature renal functions. 3. When 3.0 mg/kg of AMK was administered to three premature babies by a 30-minute intravenous drip infusion, the average peak plasma levels was 7.61 micrograms/ml at the end of the drip infusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Elective cesarean as a risk factor for transfusion after delivery of twins

We examined deliveries of twins to identify factors most strongly associated with an increased risk of transfusion. We reviewed the obstetric records of 511 twin deliveries at the Japanese Red Cross Katsushika Maternity Hospital from 2003 through 2007. After 18 (3.5%) of these deliveries, transfusions were required. Transfusion was significantly more likely after elective cesarean delivery at a gestational aged of 37 weeks or more (odds ratio, 4.85; 95% confidence interval, 1.87-12.61). Emergency cesarean delivery (at > or =37 weeks' gestation) was not associated with an increased risk of transfusion. The delivery mode of twins should be carefully considered because of the increased risk of transfusion after elective cesarean delivery at a gestational age of 37 weeks or more.     

A Gln/Arg polymorphism at codon 349 of the hBUBR1 gene

We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene, encoding a protein kinase required for spindle assembly checkpoint function. The observed heterozygosity was estimated to be 45% in the Japanese population. This polymorphism may be helpful for genetic studies of many cancer types in which chromosomal instability is observed. Received: October 19, 1998 / Accepted: October 24, 1998     

Mutations in the gene encoding KIAA1199 protein,an inner-ear protein expressed in Deiters’ cells and the fibrocytes,as the cause of nonsyndromic hearing loss

We report three possibly disease-causing point mutations in one of the inner-ear-specific genes, KIAA1199. We identified an R187C mutation in one family, an R187H mutation in two unrelated families, and an H783Y mutation in one sporadic case of nonsyndromic hearing loss. In situ hybridization indicated that the murine homolog of KIAA1199 mRNA is expressed specifically in Deiters cells in the organ of Corti at postnatal day zero (Pn) P0 before the onset of hearing, but expression in those cells disappears by day P7. The signal of KIAA1199 was also observed in fibrocytes of the spiral ligament and the spiral limbus through to P21, when the murine cochlea matures. Thus, the gene product may be involved in uptake of potassium ions or trophic factors with a particular role in auditory development. Although the R187C and R187H mutations did not appear to affect subcellular localization of the gene product in vitro, the H783Y mutation did present an unusual cytoplasmic distribution pattern that could underlie the molecular mechanism of hearing impairment. Our data bring attention to a novel candidate for hearing loss and indicate that screening of mutations in inner-ear-specific genes is likely to be an efficient approach to finding genetic elements responsible for deafness.Nucleotide sequence data reported herein are available in the DDBJ/EMBL/GenBank databases; for details, see the electronic eatabase section of this article.     

Mucoepidermoid carcinoma of the subglottis. An ultrastructural study

A well-differentiated mucoepidermoid carcinoma of the subglottis of a 77-year-old man was studied by light and electron microscopy. The tumor consisted of mucous cells, epidermoid cells, and intermediate cells of both differentiation. Mucous cells formed glands and cystic spaces filled with mucin. Abundant tonofibrils in aggregates were observed in tumor cell cytoplasms when they were differentiated into epidermoid cells. Epidermoid cells varied in differentiation.