Rare site for an intramuscular lipoma.
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Child↗
Biomedical subjects
K Shiraki
Publications and source records attributed to K Shiraki.
In vitro and in vivo activities of anti-influenza virus compound T-705.
T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC(50)s) of 0.013 to 0.48 microg/ml, while it showed no cytotoxicity at concentrations up to 1,000 microg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC(50)s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 x 10(2) PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.
Amides↗
Ultrasound biomicroscopic study of ciliary body changes in the post-treatment phase of Vogt-Koyanagi-Harada disease.
AIMS: To investigate the usefulness of ultrasound biomicroscopy for evaluating changes in the ciliary body in patients with Vogt-Koyanagi-Harada disease. METHODS: Ultrasound biomicroscopy was used to evaluate 14 eyes of seven patients diagnosed with Vogt-Koyanagi-Harada disease. Cross sectional images of the ciliary body and thickness of the pars plana 3.0 mm posterior to the scleral spur were examined. Predicted thickness of the pars plana was obtained by multiple linear regression analysis of thickness in the acute phase and in the remission phase. RESULTS: In the active phase, the cross sectional images showed a shallow anterior chamber in eight of the 14 eyes, ciliochoroidal detachment in five eyes, and a thickened ciliary body in all 14 eyes. Internal reflectivity of the ciliary stroma was low, with ciliary processes being unclear in 13 eyes. One month after steroid treatment, slit lamp examination findings were normal in 14 eyes. 10 eyes of five patients were examined by ultrasound biomicroscopy at this stage. Ciliochoroidal detachment was no longer seen in any eye. Internal reflection of the ciliary stroma became relatively homogeneous, and the ciliary processes were seen, though not clearly. However, the pars plana remained thickened. The actual thickness was greater at 1 month after steroid treatment than the predicted thickness for the remission phase. In the remission phase, the internal reflection was homogeneous and the ciliary processes were delineated clearly in all 14 eyes. CONCLUSION: Objective, quantitative evaluation of the ciliary body is possible with ultrasound biomicroscopy during the course of Vogt-Koyanagi-Harada disease. Ultrasound biomicroscopy is useful in determining disease activity in the anterior segment and in monitoring the clinical course, and it may improve evaluation of the efficacy of treatment.
Adult↗
Polymorphism of CCR5 affecting HIV disease progression in the Japanese population.
Among several factors associated with HIV-1 disease progression, genetic polymorphism of CCR2, CCR5, and CXCR4 in HIV-1 infection has been found. Single-nucleotide polymorphisms (SNPs) in the CCR2, CCR5, and CXCR4 genes as well as a 32-base pair deletion in the open reading frame of the CCR5 gene are associated with HIV disease progression among Caucasians and African-Americans in North America and Europe. However, in populations other than Caucasians and African-Americans, SNPs have not been fully examined. In our study SNPs in CCR2 coding and CCR5 regulatory regions have been examined in 98 Japanese HIV-positive individuals. The alleles of CCR5 regulatory regions at -2135T and -2086G are associated with late onset of AIDS (p < 0.05; odds ratio for the early onset of AIDS, 0.502 and 0.404, respectively). In contrast to this, the allele of CCR5 at -2086A is associated with the early onset of AIDS (p < 0.05; odds ratio for the early onset of AIDS, 2.133). A haplotype including two alleles at -2135G and -2086G is associated with the late onset of AIDS (p < 0.05; odds ratio for the early onset of AIDS, 0.372). Thus we found that a CCR5 SNP and haplotype polymorphism affect HIV disease progression even in the Japanese population. This indicates that the CCR5 genetic polymorphism affecting disease progression should be studied in a wider range of population.
Alleles↗
Long-term persistence of cellular immunity to Oka vaccine virus induced by pernasal co-administration with Escherichia coli enterotoxin in mice.
A mutant of Escherichia coli enterotoxin induced cellular immunity to a live varicella vaccine (the Oka strain) as a mucosal adjuvant in mice. The persistence of this cellular immunity was investigated. A commercially available live Oka vaccine virus and toxin were administered once simultaneously via the nasal route, in mice. Ten or 12 months later, a delayed-type hypersensitivity to the vaccine virus was detected by footpad test, but an antibody neutralizing the varicella-zoster virus was not. When spleen cells from mice immunized with the vaccine and toxin were re-stimulated by live vaccine in vitro, their thymidine uptake and IL-2 production were higher than those from mice immunized with the vaccine alone, but lower than those of spleen cells prepared from mice 2 months after nasal administration. Production of IL-4 in these cells, however, was not induced by re-stimulation in vitro. These results suggest that although humoral immunity for Oka vaccine virus is only weakly induced by one co-administration of the vaccine and toxin, cellular immunity is induced and maintained over 1 year, though it declines with age. The nasal administration of the vaccine and toxin might be effective for maintaining cellular immunity to the varicella-zoster virus long term.
Administration, Intranasal↗
Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene.
We have cloned and sequenced a 5 kb genomic fragment in the 5'-flanking region of the human myosin phosphatase target subunit 1. The transcription initiation site (+1) was 268 bp upstream from the translation start site. In this promoter there are no canonical TATA or CAAT box elements but there is a high GC-rich sequence. Basal promoter activity was due to the GC-rich region that contained one Sp1 transcription factor binding site, thus demonstrating that the MYPT1 gene is a housekeeping gene. Luciferase reporter assays showed the presence of two regions for positive elements and one for a negative element.
Base Sequence↗
Construction of Oka varicella vaccine expressing human immunodeficiency virus env antigen.
Oka varicella vaccine has been used to confer active immunity to varicella-zoster virus (VZV) in healthy and immunocompromised hosts. Based on its attenuated nature, Oka varicella vaccine expressing human immunodeficiency virus (HIV) env antigen was constructed by inserting the HIVenv gene into the viral genome and its immunogenicity was assessed in guinea pigs. The HIVenv gene encoding 296-463 amino acids was inserted between the sequences of the hepatitis B surface antigen and the thymidine kinase gene of the cloned plasmid and the recombinant virus was isolated by cotransfection of the chimeric plasmid with viral DNA. Insertion of the HIVenv gene into the viral genome was confirmed by PCR and sequencing of the viral genome of the recombinant virus. The recombinant virus expressed 30k HIVenv fusion protein in its infected cells. In guinea pigs, immunization with the recombinant virus induced an antibody response to both the HIV antigen and the V3 peptide of gp120 as well as VZV gE:gI. Cell-mediated immunity to the HIV antigen and gE:gI was assessed by the cutaneous reaction representing delayed type hypersensitivity. Immunized guinea pigs responded well to both the HIV antigen and gE:gI. Thus the recombinant Oka varicella vaccine expressing the HIVenv antigen induced both a humoral and cell-mediated immunity to the HIV antigen similar to VZV as Oka varicella vaccine induces humoral and cell-mediated immunity to VZV in the vaccinees. This recombinant Oka varicella vaccine expressing the HIVenv antigen may be evaluated for its immunogenicity as one of the AIDS vaccine candidates.
AIDS Vaccines↗
In vivo antiviral activity of Stephania cepharantha against herpes simplex virus type-1.
The antiviral activity of a MeOH extract of Stephania cepharantha (root tubers), its CHCl3-soluble fraction (alkaloid fraction) and the major alkaloid FK-3000 (1) were investigated in BALB/c mice cutaneously infected with HSV-1 strain 7401H. At doses of 125 and 250 mg/kg body weight, p.o., the MeOH extract significantly delayed skin lesion on score 2 (vesicles in the local region), limited the development of further lesions on score 6 (mild zosteriform lesion) and prolonged the mean survival time of HSV-1 infected mice. After p.o. administration of the CHCl3-soluble fraction at doses of 25 and 50 mg/kg or FK-3000 (1) at 10 and 25 mg/kg, similar results were obtained. Although the alkaloid improved the survival of infected mice, it had a narrow therapeutic index.
Alkaloids↗
Immunization of the elderly to boost immunity against varicella-zoster virus (VZV) as assessed by VZV skin test reaction.
The utility of the VZV skin test in detecting individual susceptibility to varicella and zoster was determined. Its specificity particularly with regard to herpes simplex was also established. The VZV skin test was negative or weakly positive during the early stage of herpes zoster, and strongly positive during recovery from that disease. A small-scale clinical trial to immunize elderly individuals has been performed for the purpose of preventing herpes zoster, and, perhaps, severe post-herpetic neuralgia as well. Sixty individuals > or = 50 years old were screened for VZV antibodies by IAHA test and were given a VZV skin test for cell-mediated immunity. All were seropositive, but eight were skin-test negative. Thirty-seven individuals including the eight with negative skin tests were immunized with one dose of varicella vaccine (3.0 x 10(4) PFU/dose). After 5-7 weeks, the skin test reaction showed increased positivity, with a change in score from (-) to (+, ++) in 7/8 subjects, from (+) to (++, +++) in 3/5 subjects, and from (++) to (+++) in 6/10 subjects. Enhancement of the VZV antibody titer (defined as twofold or greater) was observed in all 15 vaccine recipients with a prevaccination titer of < or = 1:16, and in 19 of 24 subjects with a prevaccination titer of > or = 1:32. These results indicate that giving live varicella vaccine with a high viral titer can induce a good boost immunity particularly cell-mediated immunity to VZV in the elderly.
Aged↗
Primary localized amyloidosis of the small intestine presenting as an intestinal pseudo-obstruction: report of a case.
A 47-year-old man with primary amyloidosis confined to the small intestine is reported. Thickening of the folds and multiple polypoid protrusions were found in the duodenum by upper gastrointestinal endoscopy. Because the patient presented with a persistent intestinal pseudo-obstruction, partial jejunectomy was performed. Histological examination of the resected tissue revealed massive deposits of amyloid throughout the jejunal wall. Neither a predisposing condition nor any other sites of deposition were found, and primary amyloidosis of the small intestine was diagnosed. This rare form of amyloid deposition should be recognized so that an early diagnosis can be made.
Amyloidosis↗
Thinning and small holes at an impending tear of a retinal pigment epithelial detachment.
BACKGROUND: A tear of a retinal pigment epithelial detachment (PED) suddenly exposes a large area of bare Bruch's membrane. We report here the case of a patient whom we observed during the gradual, spontaneous development of a PED tear. METHOD: A 5.25-year case study of a 67-year-old woman with bilateral serous PEDs. RESULTS: Retinal pigment epithelial (RPE) thinning or small holes were seen along the PED margin in both eyes. Fluorescein angiograms showed intense hyperfluorescence without leakage, and indocyanine green angiography showed choroidal vessels through regions of RPE thinning or small holes. Optical coherence tomographs showed an interruption of a hyperreflective band corresponding to retinal pigment epithelium. A typical tear of the PED ensued later. CONCLUSION: Multiple, small regions of RPE thinning or holes along the margin of PED can be a sign of an impending PED tear.
Aged↗
Hepatocyte growth factor promotes epithelial morphogenesis and occludin linkage to the cytoskeleton in cultured retinal pigment epithelial cells.
BACKGROUND: Although hepatocyte growth factor (HGF) is also known as scatter factor, it induces epithelial morphogenesis in cultured bovine retinal pigment epithelial (RPE) cells. To elucidate the mechanism of epithelial morphogenesis, we investigated the influence of HGF on occludin, a major component of tight junctions. METHODS: RPE cells were plated on collagen type 1-coated chamber slides or dishes, 20 ng/ml HGF was added and the cells were incubated for 1 week. Cells were harvested at several time-points, and occludin expression was examined by immunohistochemistry. Detergent extraction protocols to identify the intensity of occludin linkage to the cytoskeleton were also used. Occludin expression was determined semiquantitatively by Western blotting. RESULTS: Fluorescence microscopy revealed that HGF treatment increased the levels of insoluble occludin at the cell borders after detergent extraction. These level of insoluble occludin and the associated epithelial morphology were maintained for more than 3 weeks after withdrawal of HGF, whereas cells not treated with HGF had a fibroblastic appearance. Western blotting also showed that insoluble occludin was more abundant in HGF-treated cells. Furthermore, immunoreactive bands of insoluble occludin were somewhat larger than those of soluble occludin, suggesting that insoluble occludin may be modified in comparison to soluble occludin. CONCLUSION: Our results suggest that HGF promotes linkage of occludin to the cytoskeleton. HGF may become a therapeutic candidate in physiological recovery of RPE cells and in preparation of RPE monolayers for transplantation.
Animals↗
Water drinking causes a biphasic change in blood composition in humans.
To investigate precisely the fluid shifts associated with water drinking in humans, we measured continuously blood density and plasma electrolyte concentrations using the mechanical oscillator technique and ion-selective electrodes, respectively, in healthy young volunteers before (10 min) and after (48 min) water drinking for a period of 2 min. Beat-by-beat blood pressure was also monitored throughout the experiment. Drinking 1 l tap water caused a transient increase in blood density immediately after the drinking episode (from 1051.1+/-0.5 g/l before drinking to 1051.8+/-0.5 g/l 4 min after the start of drinking, P<0.05), followed by a gradual reduction (1050.1+/-0.5 g/l at 31 min). This drinking-induced change paralleled those of haematocrit, plasma density and plasma volume. Plasma [Na+] and [Cl-] and osmolality decreased after drinking without transient increases and reached minima at about 30 min. A transient increase in mean arterial blood pressure was observed prior to the increase in blood density. These findings suggest that water drinking causes a biphasic change in plasma volume: initial haemoconcentration, probably due to sympathetic acceleration, followed by haemodilution due to the post-absorptive effect, and further suggest that the fluid shift associated with the initial haemoconcentration is isosmotic.
Adult↗
Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C?
PURPOSE: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention. METHODS: The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy. RESULTS: Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036). CONCLUSIONS: Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.
Adult↗
Increased plasma nitrate and nitrite concentrations in patients with hepatitis C virus infection.
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Hepatitis C↗
Images in hepatology. Acute schistosoma mansoni infection in the liver.
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Acute Disease↗
Hepatitis B genotypes in patients with acute hepatitis B virus infection.
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Acute Disease↗
p21WAF1/CTP1 expression and hepatitis virus type.
Since p21WAF1/CIP1 (p21) is a universal inhibitor of cyclin-dependent kinases and is regulated transcriptionally by p53, which is activated by DNA stress, its expression reflects DNA stress in chronic hepatitis. Recently an association with both hepatitis B and C virus and the expression of p53 or p21 was reported. We analyzed p21 expression in 18 cases of HBV-associated chronic liver diseases and 32 cases of HCV-associated chronic liver diseases by immunohistochemical analysis, and investigated the possible association between hepatocyte p21 expression and hepatic inflammation, fibrosis, and especially hepatitis virus type. The p21-positive hepatocytes were more numerous in areas of intense inflammation and spotty necrosis and areas close to fibrosis, and they increased according to the degrees of grading and staging. The p21 labeling index (LI) in patients with liver cirrhosis was significantly higher than that in patients with chronic hepatitis of both hepatitis viral types (5.84 +/- 0.61 vs 12.0 +/- 0.83, P < 0.0001 in hepatitis B, 10.28 +/- 0.80 vs 15.6 +/- 1.09, P = 0.0004 in hepatitis C), Furthermore, the p21 LI was significantly higher in HCV-associated liver disease than in HBV-associated liver disease in every group (4.02 +/- 0.48 vs 7.74 +/- 0.96, P = 0.021 in low grade group, 7.35 +/- 0.46 vs 12.8 +/- 0.57, P < 0.0001 in high grade, 12.0 +/- 0.83 vs 15.6 +/- 1.09, P = 0.034 in liver cirrhosis). In, conclusion, p21 expression was up-regulated by the stress of inflammation and fibrosis and might be influenced by viral proteins in human chronic liver disease.
Adult↗