Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 19 recordsLinked to original sources

PubMed2003

Altered aquaporin 4 expression in muscles of Fukuyama-type congenital muscular dystrophy.

This study was undertaken to investigate the expression of aquaporin 4 (AQP4) in the muscle plasma membrane of children with Fukuyama-type congenital muscular dystrophy (FCMD) at protein and mRNA levels. The biopsied six muscles with FCMD, six histochemically normal muscles and eight disease control muscles were analyzed by means of immunoblots, immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). Immunoblots showed that the band of FCMD muscle extracts stained with anti-AQP4 antibody was faint in comparison with that of normal muscle extracts. The immunohistochemistry revealed that most of the FCMD myofibers showed negative immunostaining with anti-AQP4 antibody, although the partially positive immunostaining of sporadic FCMD myofibers was noted. The immunoreactivity was positive with anti-dystrophin and anti-beta-spectrin antibodies in almost all FCMD myofibers. The quantitative RT-PCR demonstrated that the AQP4 mRNA level of the FCMD muscles was markedly reduced. On the basis of these findings, we conclude that the expression of AQP4 in FCMD myofibers is reduced and the reduced content of AQP4 mRNA in FCMD muscles may be related to the decreased expression of AQP4 at the muscle plasma membrane of FCMD myofibers.

Aquaporin 4↗

PubMed2003

Paroxetine as a 5-HT neuroendocrine probe.

RATIONALE: Acute administration of 40 mg paroxetine (a selective serotonin reuptake inhibitor) reportedly increases plasma cortisol in human subjects. This suggests that paroxetine may be a useful tool to probe brain serotonin function. OBJECTIVE: To investigate a dose-response relationship for paroxetine administration, and to determine whether a lower dose of paroxetine is sufficient to increase plasma ACTH and cortisol. METHODS: Twenty subjects were tested on three occasions in a double-blind, cross-over design receiving: (a) placebo, (b) paroxetine 20 mg and (c) paroxetine 40 mg administered orally at 8.00 a.m. In addition, five of the 20 subjects received paroxetine 20 mg plus cyproheptadine (a 5-HT(2) receptor antagonist) 4 mg and four subjects were given paroxetine 40 mg plus cyproheptadine 4 mg in an open manner. Plasma ACTH and cortisol levels were measured prior to administration and every hour for 6 h thereafter. RESULTS: Paroxetine, particularly 20 mg rather than 40 mg, significantly increased plasma ACTH and cortisol. Paroxetine 40 mg but not 20 mg caused significantly more nausea than the placebo. Cyproheptadine attenuated ACTH and cortisol responses to 20 mg but not to 40 mg paroxetine. CONCLUSIONS: Low-dose (20 mg) paroxetine has greater potential utility than larger doses as a neuroendocrine challenge test. The endocrine responses to paroxetine are probably mediated at least partially by 5-HT(2A/2C) receptors.

Adrenocorticotropic Hormone↗

PubMed2003

63Cu nuclear relaxation in the quantum critical point system CeCu5.9Au0.1.

63Cu NQR measurements of the 63Cu T1 are reported for the quantum critical point system CeCu5.9Au0.1 over temperatures ranging from 0.1 up to 4.2 K. Below approximately 1 K the magnetization recovery exhibits a stable, nonexponential decay function which we believe signals the onset of 2D quantum critical fluctuations, as has been noted in the literature. We find T1(-1) is proportional to T0.75 for the region T < 1 K. The observed temperature dependence is in agreement with a phenomenological model of non-Fermi liquid behavior based on the uniform susceptibility but is inconsistent with calculations based on susceptibility peaks identified via neutron scattering experiments.

Journal Article↗

PubMed2003

Expression of nuclear factor of activated T cells mRNA in maternal peripheral blood cells.

PROBLEM: In T lymphocytes, nuclear factor of activated T cells (NF-AT) regulates the induction of cytokine genes upon antigenic stimulation. This study was designed to analyse the relationship between NF-AT and pregnancy. METHOD OF STUDY: With informed consent, peripheral blood cells (PBCs) were obtained from non-pregnant (n = 114), pregnant (n = 604), and puerperal women (n = 52). The expression of NF-AT2 and NF-AT3 mRNAs in PBCs was measured by a quantitative reverse transcriptase-polymerase chain reaction method. RESULTS: In the early pregnancy period, in successful pregnancy, both NF-AT2 and NF-AT3 mRNAs increased significantly, whereas in cases of spontaneous abortion they did not change significantly. After peaking, they decreased gradually and were re-elevated in the ninth and tenth gestational month. In the puerperal period, NF-AT3 mRNAs decreased, but NF-AT2 mRNA showed a comparatively high expression level. CONCLUSION: These findings suggested that in humans NF-AT signal transduction might be involved in alloantigenic recognition and tolerance and play important roles, especially in the early and late period of pregnancy.

Actins↗

PubMed2003

Overexpression of a DEAD box/RNA helicase protein, rck/p54, in human hepatocytes from patients with hepatitis C virus-related chronic hepatitis and its implication in hepatocellular carcinogenesis.

Hepatitis C virus (HCV) infection is the most common cause of chronic hepatitis, which frequently progresses to hepatocellular carcinoma. The pathogenesis of its persistent infection and tumour progression has not been fully characterized yet. The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8. The RCK protein, rck/p54, which is a 54-kDa cytoplasmic protein belonging to the DEAD box/RNA helicase family, is considered to facilitate the translation of mRNA(s) of genes for cell proliferation and malignant transformation not only in B-cell lymphomas having the t(11;14) translocation but also in other solid tumours. The aim of this work was to examine the involvement of rck/p54 in carcinogenesis of hepatocellular carcinoma from HCV-related chronic hepatitis. We examined the expression of rck/p54 in 29 cases of HCV-related chronic hepatitis and eight cases of hepatocellular carcinoma by immunohistochemistry and Western blot analysis. Twenty-six of 29 cases with HCV-related chronic hepatitis and all cases with hepatocellular carcinoma tested overexpressed rck/p54 protein. The expression of rck/p54 was lowered by treatment with IFN-alpha in two cases who showed the decrease in HCV RNA levels. These findings suggest that rck/p54 protein is possibly involved in the replication of HCV genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas.

Adult↗

PubMed2003

Increasing cell membrane potential and GABAergic activity inhibits malignant hepatocyte growth.

Increasing hepatocyte membrane potentials by augmenting GABAergic activity inhibits nonmalignant hepatocyte proliferative activity. The objectives of this study were to document 1) potential differences (PDs) of four malignant hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines, and 3) effects of restoring malignant hepatocyte PDs to levels approximating those of resting, nonmalignant hepatocytes. Hepatocyte PDs were documented in nonmalignant and malignant (Chang, HepG2, HuH-7, and PLC/PRF/5) hepatocytes with a fluorescent voltage-sensitive dye and GABAA receptor expression by RT-PCR and Western blot analyses. Compared with nonmalignant human hepatocytes, all four malignant cell lines were significantly depolarized (P < 0.0001, respectively). Only PLC/PRF/5 cells had detectable GABAA-beta3 receptor mRNA expression and all cell lines were negative for GABAA-beta3 receptor protein by Western blot analysis. Stable transfection of Chang cells with GABAA-beta3 receptor cDNA resulted in significant increases in PD and decreases in proliferative activity as manifest by decreased [3H]thymidine and bromodeoxyurieine incorporation rates, 4-[3-(4-lodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate activity, a lower mitotic index, prolongation of cell-doubling times, and attenuated growth patterns compared with cells transfected with vector alone. Colony formation in soft agar and the number of abnormal mitoses were also significantly decreased in GABAA-beta3 receptor transfected cells. The results of this study indicate 1) relative to healthy hepatocytes, malignant hepatocytes are significantly depolarized, 2) GABAA-beta3 receptor expression is absent in malignant hepatocyte cell lines, and 3) increasing the PD of malignant hepatocytes is associated with less proliferative activity and a loss of malignant features.

Carcinoma, Hepatocellular↗

PubMed2002

Single-bubble sonoluminescence from noble gas mixtures.

Light emission intensities from single-bubble sonoluminescence at room temperature, water dissolved with admixtures of pairs of noble gases, He-Ar and He-Xe, were measured as a function of mixing ratio to search for effects of species segregation occurring during the violent bubble collapse. The observed relative effect on the light emission intensity is surprisingly greater in He-Ar than in a He-Xe mixture.

Journal Article↗

PubMed2002

Hemophagocytic syndrome as the primary clinical symptom of Hodgkin's disease.

It is now well recognized that hemophagocytic syndrome (HPS) is occasionally associated with malignant lymphomas. However, its association with Hodgkin's disease has been only rarely reported. We present here a 72-year-old woman manifesting with HPS as the primary and solitary clinical symptom of Hodgkin's disease. She had been suffering from high-grade fever and anemia for more than a month. Based on the findings in bone marrow aspirates, she was diagnosed as having HPS. In spite of extensive surveys including various cultures, serological tests for collagen disease, abdominal and cardiac sonography, chest computed tomography (CT), and renal biopsy, the origin of the fever was not determined. She was treated with steroid pulse therapy and then referred. Radiological studies revealed only mild hepatosplenomegaly and small lymph node swellings around celiac and common hepatic arteries. Reevaluation of the bone marrow specimen revealed the infiltration of small numbers of CD30-, CD15-, and EBER-1-positive large-sized lymphocytes with bizarre nucleus. Under the diagnosis of Hodgkin's disease, she was treated with combination chemotherapy containing pirarubicin, cyclophosphamide, vincristine, and prednisolone. However, it was not effective and she died of rapidly progressive hepatic failure on the 5th day of the chemotherapy. Autopsy was performed, which showed proliferation of lymphoma cells in para-aortic lymph nodes. We believe that diagnostic survey to rule out the underlying lymphoma should be vigorously performed for patients with hemophagocytic syndrome of unknown origin.

Aged↗

PubMed2002

Low-density spin susceptibility and effective mass of mobile electrons in Si inversion layers.

We studied the Shubnikov-de Haas (SdH) oscillations in high-mobility Si-MOS samples over a wide range of carrier densities n approximately (1-50)x10(11) cm(-2), which includes the vicinity of the apparent metal-insulator transition in two dimensions (2D MIT). Using a novel technique of measuring the SdH oscillations in superimposed and independently controlled parallel and perpendicular magnetic fields, we determined the spin susceptibility chi(*), the effective mass m(*), and the g(*) factor for mobile electrons. These quantities increase gradually with decreasing density; near the 2D MIT, we observed enhancement of chi(*) by a factor of approximately 4.7.

Journal Article↗

PubMed2002

Fatal reactivation of hepatitis B virus following cytotoxic chemotherapy for acute myelogenous leukemia: fibrosing cholestatic hepatitis.

Hepatitis B virus (HBV) is a well known pathogen that sometimes causes fulminant hepatitis in patients undergoing cytotoxic chemotherapy. Fibrosing cholestatic hepatitis (FCH) is a recently recognized unique variant of viral hepatitis, which has been occasionally reported in HBV-infected recipients of liver, renal, or bone marrow transplantation. We present here a 48-yr-old male in whom HBV was reactivated during post-remission chemotherapy for acute myelogenous leukemia, which resulted in rapidly fatal outcome. He manifested with deterioration of liver function in association with enormous replication of HBV. Liver biopsy showed marked ballooning of hepatocytes, cholestasis, and periportal fibrosis with minimum infiltrates. Immunostaining revealed that hepatocytes were strongly positive for hepatitis B surface antigen. Under the diagnosis of FCH, he was treated with lamivudine and interferon beta, which was not effective. Autopsy showed severe atrophy of the liver and marked degeneration of hepatocytes. Hematologists should be aware that FCH is a fatal complication that can develop under post-chemotherapy immunosuppressed conditions. Although there is no convincing evidence, prophylactic administration of lamivudine seems to be a reasonable strategy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Indirect conductimetric assay of antibacterial activities.

The applicability of indirect conductimetric assays for evaluation of antibacterial activity was examined. The minimal inhibitory concentration (MIC) obtained by the indirect method was consistent with that by the direct conductimetric assay and the turbidity method. The indirect assay allows use of growth media, which cannot be used in the direct conductimetric assay, making it possible to evaluate the antibacterial activity of insoluble or slightly soluble materials with high turbidity, such as antibacterial ceramic powders.

Anti-Bacterial Agents↗

PubMed2002

A new liquid embolic material for liver tumors.

PURPOSE: To evaluate the feasibility of a new liquid embolic material, Onyx, for treating liver tumors. MATERIAL AND METHODS: Onyx is a mixture of 6% (w/v) ethylene-vinyl-alcohol copolymer dissolved in anhydrous dimethyl sulfoxide (DMSO) with 28% (w/v) tantalum powder. In addition to 6% Onyx, we also tried 4%, 2% and 1% solutions, prepared by adjusting the amount of DMSO. We used 15 white rabbits with liver tumors created by percutaneous injection of VX2 tumor cells. In 4 groups with 3 rabbits in each, the liver arteries were embolized with 6%, 4%, 2% and 1% Onyx, respectively, and in 3 rabbits DMSO alone was injected. The injections were performed just proximal to the bifurcation of the proper hepatic artery, followed by celiac arteriography. Post mortem, the livers were examined by soft-tissue radiography, and liver-tissue section microscopy. RESULTS: The maximum number of arterial branching points passed by embolic material in either the right or left hepatic arteries was 11, 15 and 16, for 6%, 4% and 2% Onyx, respectively, but was non-measurable for 1% Onyx. Minimum diameters of arteries reached by 6%, 4%, 2% and 1% Onyx in tumorous areas were 40 microm, 35 microm, 20 microm and 10 microm, respectively, and in non-tumorous areas 35 microm, 5 microm, 5 microm and 5 microm, respectively. CONCLUSION: This study suggests that Onyx may be feasible for treatment of hepatic tumors.

Animals↗

PubMed2002

Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver failure.

Fluroquinolone antibiotics have been reported to have antiviral properties against RNA viruses, including hepatitis C virus (HCV). In the present study, five patients with advanced liver disease secondary to chronic HCV received 500 mg daily of oral ciprofloxacin for 30 days. Serum HCV-RNA levels and liver enzyme abnormalities remained largely unchanged. Thus, the role of fluoroquinolones as antiviral agents for chronic HCV in patients with advanced liver disease appears to be limited.

Alanine Transaminase↗

PubMed2001

Kinetic analysis of the bactericidal action of heated scallop-shell powder.

Shell powder of scallop (Patinopecten yessoensis) was exposed to heat treatment at between 200 and 1000 degrees C, and the bactericidal action of the powder slurry was investigated. Shell powder heated at 700 degrees C or higher exhibited bactericidal action against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Bacillus subtilis (vegetative cells). The death of bacteria in the shell powder slurry followed first-order reaction kinetics, and the apparent death rate constant (k) was determined. An increase in exposure temperature enhanced the bactericidal action. The bactericidal action is due to calcium oxide that is converted from calcium carbonate, which is the main component of the shell powder, by heat treatment. The slurry temperature is found to significantly affect the bactericidal action of the shell powder. The slope of the Arrhenius plot of k for E. coli and S. aureus that were grown at 37 degrees C exhibited a discontinuous point at approximately 22 degrees C, at which the values of activation energy for the death of bacteria in the powder slurry changed. This temperature corresponds to that of the phase transition of cell membrane lipids. The bactericidal action of the shell powder is greater than that of a NaOH solution of identical pH. Although the pH of the shell powder slurry is high, the slurry was considered to possess other antibacterial mechanisms in addition to that of alkalinity.

Bacteria↗

PubMed2001

Association between three functional polymorphisms of dopamine D2 receptor gene and tardive dyskinesia in schizophrenia.

The dopamine D2 receptor (DRD2) gene is considered one of the candidate genes contributing to the development of tardive dyskinesia (TD). In the present study, we investigated the genetic association between three functional polymorphisms (Ser311Cys, -141C Ins/Del and TaqI A) in the DRD2 gene and TD (200 patients with schizophrenia: 44 with TD and 156 without TD). No significant difference in the allelic and genotypic distribution between patients with TD and those without TD was observed. However, we found a slightly significant association between the -141C Ins/Del polymorphism and the total Abnormal Involuntary Movement Scale (AIMS) score (P = 0.037). The significant association between the -141C Ins/Del polymorphism and the total AIMS score did not remain after the regression analysis was taken into account (P = 0.14). Our results suggest that that three functional polymorphisms in DRD2 may not play a major role in the occurrence of TD.

Alleles↗

PubMed2001

Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions.

Direct measurements revealed low oxygen tensions (0.5-4.5% oxygen) in murine lymphoid organs in vivo. To test whether adaptation to changes in oxygen tension may have an effect on lymphocyte functions, T cell differentiation and functions at varying oxygen tensions were studied. These studies show: 1) differentiated CTL deliver Fas ligand- and perforin-dependent lethal hit equally well at all redox conditions; 2) CTL development is delayed at 2.5% oxygen as compared with 20% oxygen. Remarkably, development of CTL at 2.5% oxygen is more sustained and the CTL much more lytic; and 3) hypoxic exposure and TCR-mediated activation are additive in enhancing levels of hypoxia response element-containing gene products in lymphocyte supernatants. In contrast, hypoxia inhibited the accumulation of nonhypoxia response element-containing gene products (e.g., IL-2 and IFN-gamma) in the same cultures. This suggests that T cell activation in hypoxic conditions in vivo may lead to different patterns of lymphokine secretion and accumulation of cytokines (e.g., vascular endothelial growth factor) affecting endothelial cells and vascular permeabilization. Thus, although higher numbers of cells survive and are activated during 20% oxygen incubation in vitro, the CTL which develop at 2.5% oxygen are more lytic with higher levels of activation markers. It is concluded that the ambient 20% oxygen tension (plus 2-ME) is remarkably well suited for immunologic specificity and cytotoxicity studies, but oxygen dependence should be taken into account during the design and interpretation of results of in vitro T cell development assays and gene expression studies in vivo.

Animals↗

PubMed2001

High sensitivity of mouse neuronal cells to tetanus toxin requires a GPI-anchored protein.

Tetanus neurotoxin (TeNT) produced by Clostridium tetani specifically cleaves VAMP/synaptobrevin (VAMP) in central neurons, thereby causing inhibition of neurotransmitter release and ensuing spastic paralysis. Although polysialogangliosides act as components of the neurotoxin binding sites on neurons, evidence has accumulated indicating that a protein moiety is implicated as a receptor of TeNT. We have observed that treatment of cultured mouse neuronal cells with the phosphatidylinositol-specific phospholipase C (PIPLC) inhibited TeNT-induced cleavage of VAMP. Also, we have shown that the blocking effects of TeNT on neuroexocytosis can be prevented by incubation of Purkinje cell preparation with PIPLC. In addition, treatment of cultured mouse neuronal cells with cholesterol sequestrating agents such as nystatin and filipin, which disrupt clustering of GPI-anchored proteins in lipid rafts, prevented intraneuronal VAMP cleavage by TeNT. Our results demonstrate that high sensitivity of neurons to TeNT requires rafts and one or more GPI-anchored protein(s) which act(s) as a pivotal receptor for the neurotoxin.

Animals↗

PubMed2001

Localization of sarcoglycan, neuronal nitric oxide synthase, beta-dystroglycan, and dystrophin molecules in normal skeletal myofiber: triple immunogold labeling electron microscopy.

In order to investigate the mode of existence of the sarcoglycan complex, neuronal nitric oxide synthase (nNOS), beta-dystroglycan, and dystrophin in the normal skeletal myofiber, we examined the ultrastructural localization and mutual spatial relationship of nNOS, beta-dystroglycan, dystrophin, and the individual components of the sarcoglycan complex by using triple immunogold labeling electron microscopy. Each molecule of alpha-, beta-, gamma- and delta-sarcoglycans is located intracellularly or extracellularly near the muscle plasma membrane mostly in accordance with the sarcoglycan antigenic sites against which the antibodies were generated. The association of different two and/or three sarcoglycan molecules out of alpha-, beta-, gamma- and delta-sarcoglycan molecules was frequently observed. Each molecule of nNOS, beta-dystroglycan, and dystrophin was ultrastructurally noted along the cell surface of normal skeletal myofibers. Moreover, the close relation of a sarcoglycan molecule with beta-dystroglycan and dystrophin, and the association of nNOS with dystrophin were also confirmed ultrastructurally. Thus, this study demonstrated that the constituting molecules of the sarcoglycan complex, nNOS, beta-dystroglycan, and dystrophin existed in the form of a cluster at the normal muscle plasma membrane. The association of nNOS with dystrophin and its associated glycoproteins may form a macromolecular signaling complex at the muscle plasma membrane.

Amino Acid Sequence↗