Regulation of inner ear fluid in the guinea pig cochlea after the application of saturated NaCl solution to the round window membrane

The regulation of K⁺ and Na⁺ in the inner ear fluid of the guinea pig was studied after the application of saturated NaCl solution to the round window membrane. K⁺ and Na⁺ activities in the scala tympani increased rapidly and then decreased. K⁺ activity in the scala media increased immediately, but Na⁺ activity continued to increase during the period of observation. K⁺ activity in the scala vestibuli continued to increase in the observation period. Na⁺ activity in the scala vestibuli increased and then decreased. The endocochlear potential decreased immediately to approximately 20% of its initial level. Total activities of K⁺ and Na⁺ increased immediately and then decreased in both the scala tympani and scala media. The total activity of K⁺ and Na⁺ increased slowly and showed no regulatory decrease in the scala vestibuli. Thus, changing patterns in the total activity of K⁺ and Na⁺ were similar for the scala tympani and scala media, but not for the scala media and the scala vestibuli. Different patterns of K⁺ and Na⁺ activities among the three scalae indicate that their mechanisms for regulating inner ear fluid differ.     

Biochemical and genetic characterization of serologically untypable Streptococcus mutans strains isolated from patients with bacteremia

Four out of 522 streptococcal isolates from the peripheral blood of patients with bacteremia exhibited typical properties of Streptococcus mutans in terms of sucrose-dependent adhesion, expression of glucosyltransferases, fermentation profiles of sugars, the presence of surface protein antigen, and DNA-DNA hybridization. Two strains were determined as serotype f and e by immunodiffusion, whereas the other two isolates did not react with the specific antiserum to S. mutans serotype c. e. or f of the eight different serotypes of mutans streptococci. The latter two untypable isolates, however, expressed a new antigenic determinant that was different from serotype c/e/f specificity as revealed by immunodiffusion. Analysis of the cell wall polysaccharides revealed very low contents of glucose in the untypable isolates. Furthermore, Southern blot analysis demonstrated that the untypable strains lacked at least one gene corresponding to a glucose-adding enzyme. These results indicate that the serologically untypable nature is due to the loss of glucosidic residue from the serotype-specific polysaccharide antigens of S. mutans.     

Massive congenital intracranial teratoma diagnosed in utero

The authors describe a case of congenital intracranial teratoma. The patient was diagnosed to be hydrocephalic at 29 weeks' gestation, and to have a huge intraventricular mass lesion at 34 weeks' gestation. Subsequently, the patient underwent subtotal resection of the mass, resulting in a significant decrease in the remarkably elevated alpha-fetoprotein in serum and cerebrospinal fluid. Histological analysis revealed a malignant teratoma, also with alpha-fetoprotein-positive elements in the immunohistochemical study.     

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.

We have previously demonstrated that in mice, the decrease in serum thyroxine (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although the PCB-induced decrease in rats is generally thought to occur through induction of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the relationship between the decrease in serum T(4) level and the increase in UGT1A activity by PCB in rats, we examined the relationship using Wistar rats and Gunn rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total T(4) level was markedly decreased not only in the Wistar rats but also in the Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or 2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no significant difference in magnitude of the decrease between the two rat strains. At the same time, the level and activity of T(4)-UDP-GT were significantly increased by treatment with either KC500 or PentaCB in Wistar rats but not in Gunn rats. In addition, no significant change in the level of serum total triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment was observed in either Wistar or Gunn rats. Furthermore, significant decrease in the activity of hepatic type-I deiodinase, which mediates the deiodization of T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono- and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum protein (transthyretin), were detected. In conclusion, the present results suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The findings further suggest that the PCB-mediated decrease in serum T(4) level might occur, at least in part, through formation of the hydroxylated PCB metabolites. Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level might occur not only through the increase in hepatic T(4)-UDP-GT but also via formation of hydroxylated PCB metabolites.     

Neutralizing activity of bovine colostral antibody against verotoxin derived from enterohemorrhagic Escherichia coli O157:H7 in mice

The neutralization efficacy of bovine colostral antibody against verotoxin (VT) 1 and 2 was investigated. Cows were immunized with VT1 or VT2 fourteen times at 7-day intervals. A colostral antibody exhibiting high titers was obtained from immunized cows. Survival rates were evaluated in mice administered VT1 or VT2, and those infected with Escherichia coli (E. coli) O157:H7 producing VT1 or VT2. Survival rates after VT1 administration were 100% in the single-administration group, 90% in the repeat-administration group, and 78.6% in the control group. Survival rates after VT2 were 75.0% in the single-administration group, and 100% in the repeat-administration group. All mice in the control group died. Colostral antibody and fosfomycin (FOM) in the colostral antibody group and FOM and skim milk in the control group were administered three times per day for 5 days to mice infected with E. coli O157:H7 producing VT1 or VT2. Survival rates after inoculation with E. coli O157:H7 producing VT1 were 80.0% in the colostral antibody group, and 63.6% in the control group. Survival rates after inoculation with E. coli O157:H7 producing VT2 were 83.3% in the colostral antibody group, and 20.0% in the control group. The survival rate in mice without treatment following inoculation with E. coli O157:H7 producing VT2 was 88.2%.The survival rates in mice infected with E. coli O157:H7 strains producing VT1 or VT2 improved after administration of this colostral antibody, which exhibited neutralization efficacy against VT.     

Glomerular lesions associated with the Crow-Fukase syndrome

Summary Three cases of the Crow-Fukase syndrome without radiographic changes of multiple myeloma are reported, with special reference to the glomerular changes seen. Proteinuria was detected in one case, although decreased renal function was observed in all (GFR: 41.0, 62.0, 74.1 ml/min respectively) at the time of renal biopsy. Glomerular changes were similar in all three cases. The main characteristic changes were mesangial proliferation and thickening of the glomerular capillary walls. Pictures by light microscopy were therefore similar to that of MPGN. On electron microscopy, the thickened capillary walls showed circumferential mesangial interposition and the subendothelial zone was electron-lucent and contained small dense granules or flocculent deposits. By immunofluorescent microscopy, no immunoglobulins, complement components or light chain were detected in the glomeruli except in one case.     

BENEFICIAL EFFECT OF ORAL MESALAZINE POWDER ADMINISTRATION ON GASTRIC INVOLVEMENT OF BEHÇET's DISEASE

Behçet's disease (BD) is a multisystem immune‐mediated inflammatory disorder that involves the gastrointestinal tract. Although intestinal BD chiefly affects the ileocecum and colon, it may involve the entire alimentary tract. Upper gastrointestinal involvements of BD are not common, and its treatment has been rarely reported. Mesalazine is known to be an effective anti‐inflammatory agent for treatment of distal intestinal lesions of inflammatory bowel disease by its delayed drug release system. Here we show a case of chronic active, steroid‐dependent BD involving the upper gastrointestinal tract who was treated with ground mesalazine powder. Endoscopy performed 8 weeks after the treatment showed marked improvement of the gastric ulcers. This is the first report of intestinal BD treated with oral administration of mesalazine powder, and our results suggest that it may be a beneficial and effective new therapy for the upper gastrointestinal lesion of BD.     

Detection and genotyping of <Emphasis Type="Italic">Cryptosporidium</Emphasis> from brown rats (<Emphasis Type="Italic">Rattus norvegicus</Emphasis>) captured in an urban area of Japan

We investigated the prevalence and genotypes of Cryptosporidium parasite in 50 brown rats (Rattus norvegicus) inhabiting an urban area of Japan. Fecal samples collected from the animals were examined by an immuno-fluorescence assay (IFA). Genomic DNA was extracted directly from fecal sample of each animal and nested PCR was performed to amplify part of the 18S ribosomal RNA (18SrRNA) of the Cryptosporidium species. The detection rate was 8% by IFA and 38% by nested PCR. The sequence and phylogenetic analyses of 13 PCR products showed that the Cryptosporidium from brown rats were clustered into four distinct genotypes. Interestingly, one of the four genotypes was significantly distinct from the C. parvum and C. hominis genotypes. Our results suggest the existence of a new genotype of Cryptosporidium in brown rats.     

Ifi202, an IFN-inducible candidate gene for lupus susceptibility in NZB/W F1 mice, is a positive regulator for NF-kappaB activation in dendritic cells

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. The [New Zealand black (NZB) x New Zealand white (NZW)]F1 (BWF1) mouse has been recognized as an important animal model of human SLE. The T(h)1-prone phenotype of BWF1 mice has been shown to contribute to the development of the lupus. However, the molecular basis for T(h)1 skewing in BWF1 mice has not been clarified. We noticed that IL-6, IL-12 and other proinflammatory cytokines as well as IkappaB-zeta induction were higher in mature bone marrow-derived dendritic cells (BMDCs) from NZB and BWF1 mice than those from NZW mice. The expression of an IFN-inducible gene Ifi202, a candidate gene for lupus, was almost undetectable in NZW BMDCs. Thus, we hypothesized that Ifi202 is involved in elevated IL-12 production from BWF1 BMDCs. Overexpression of Ifi202 enhanced the LPS-induced IkappaB-zeta, IL-12p40 and NF-kappaB promoter activities, while anti-sense (AS) RNA against Ifi202 strongly suppressed them in a monocytic cell line, RAW 264.7. Furthermore, overexpression of Ifi202 enhanced LPS-induced IL-12p40 and IkappaB-zeta mRNA induction while Ifi202 AS RNA suppressed these in RAW 264.7 cells. In addition, forced expression of Ifi202 enhanced IL-12p40 mRNA induction in NZW BMDCs. Thus, Ifi202 is an important NF-kappaB activator in DCs and involved in IL-12 production, which may account for a T(h)1-prone phenotype of BWF1 mice.     

Pathological role of Toll-like receptor signaling in cerebral malaria

Toll-like receptors (TLRs) recognize malaria parasites or their metabolites; however, their physiological roles in malaria infection in vivo are not fully understood. Here, we show that myeloid differentiation primary response gene 88 (MyD88)-dependent TLR signaling mediates brain pathogenesis of severe malaria infection, namely cerebral malaria (CM). A significant number of MyD88-, but not TIR domain containing adaptor-inducing IFN-beta (TRIF)-deficient or wild-type (WT) mice survived CM caused by Plasmodium berghei ANKA (PbA) infection. Although systemic parasitemia was comparable, sequestration of parasite and hemozoin load in the brain blood vessels was significantly lower in MyD88-deficient mice compared with those in TRIF-deficient or WT mice. Moreover, brain-specific pathological changes were associated with MyD88-dependent infiltration of CD8+, CCR5+ T cells and CD11c+ dendritic cells, including CD11c+, NK1.1+ and B220+ cells, and up-regulation of genes such as Granzyme B, Lipocalin 2, Ccl3 and Ccr5. Further studies using mice lacking various TLRs suggest that TLR2 and TLR9, but not TLR4, 5 and 7, were involved in CM. These results strongly suggest that TLR2- and/or TLR9-mediated, MyD88-dependent brain pathogenesis may play a critical role in CM, the lethal complication during PbA infection.