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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 55 records · Page 3Linked to original sources

Aberrant expression of a fetal glycoprotein 68 in hepatocellular carcinoma: a comparative study on the expression of alpha-fetoprotein and carcinoembryonic antigen.

A rat IgG2a monoclonal antibody against a stage-specific fetal glycoprotein with a molecular mass of 68 kDa (FGP68) was produced and applied to paraffin sections. This monoclonal antibody was used to compare the expression of FGP68 with that of both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in 75 hepatocellular carcinomas (HCCs). Seventy-five primary HCCs from patients aged 36 to 77 years were examined. Formalin-fixed, paraffin-embedded tissue sections were used for immunohistochemical analyses. Histologically, 6 cases of HCC were classified as type I according to the Edmondson and Steiner criteria, 57 cases as type II, and 12 cases as type III. The cancer tissues showed positive reactions with the antibody against FGP68. Approximately one-third of the HCCs (26/75) contained tumor cells that expressed FGP68 -(21/57 for Edmondson and Steiner type II; 4/12 for type III; and 1/6 for type I) - and positive immunoreactivity was observed in the cytoplasm of the cancer cells. Twenty-five of the 75 HCCs had tumor cells that expressed AFP and there was a significant correlation between FGP68 expression and AFP expression. Twenty-three of the 75 HCCs had tumor cells that expressed CEA and there was no significant correlation between FGP68 expression and CEA expression. No positive reactions for FGP68, AFP and CEA were observed in samples of non-neoplastic liver tissues. Based on the possibility that stage-specific FGP68 plays an important role in liver embryogenesis, FGP68-expressing tumor cells might ontogenetically revert to more primitive cells.

Adult↗

[Cardiac liposarcoma at the right ventricular outflow tract (RVOT) following lipomatous hypertrophy of the interatrial septum (LHIS); report of a case].

A 23-year-old man, presenting with a 10-year history of a cardiac lipoma (lipomatous hypertrophy of the interatrial septum: LHIS), complained of anterior chest discomfort. Echocardiography and magnetic resonance imaging revealed remarkable hypertrophy of the interatrial septum (IAS) and posterior wall of the right atrium (RA), massive pericardial adipose tissue, and mild aortic valve insufficiency caused by compression of the tumor on the right ventricular outflow tract (RVOT). We performed surgical resection of the tumor stemming from the RVOT following removal of a large amount of the pericardial fat tissue (1,794 g), and then undertook biopsies of the IAS and the posterior wall of the RA. Pathological examination showed the right ventricular (RV) tumor to be liposarcoma and confirmed the benign nature of the biopsy tissues. We herein report a rare case of cardiac liposarcoma following LHIS in a young patient.

Adipose Tissue↗

Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats.

The role of nitric oxide (NO) in the etiology of ulcerative colitis is controversial with reports of the improvement and aggravation of colonic lesions by inducible NO synthase (iNOS) inhibitors. In the present study, we compared the effect of the selective iNOS inhibitor aminoguanidine and the nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on a dextran sulfate sodium (DSS)-induced model of colitis in rats. Experimental colitis was induced by a 3% DSS-solution added to drinking water for 7 days. Aminoguanidine (5 approximately 20 mg/kg) and L-NAME (10 mg/kg) were administered p.o. twice daily for the first 3 days, the last 3 days or all 6 days of DSS treatment. Body weight and severity of colitis (diarrhea, bloody feces) were observed over a period of 7 days. DSS treatment resulted in severe colonic lesions, accompanied by diarrhea, bloody feces, decrease of body weight and colon shortening. All of the parameters investigated improved significantly with aminoguanidine treatment at 20 mg/kg for 6 days or the last 3 days of DSS-treatment, but L-NAME did not significantly affect the colitis during these periods. When L-NAME or aminoguanidine was given in the first 3 days of DSS treatment, the colonic lesions were slightly aggravated by L-NAME but not affected by aminoguanidine. The expression of iNOS mRNA was observed from the 3(rd) day of DSS treatment. These results suggested that endogenous NO exerts a biphasic influence on DSS-induced colitis, depending on the NOS isoenzyme; a beneficial effect of NO derived from constitutive NOS and a detrimental effect of NO produced by iNOS in the development of colitis.

Animals↗

The quantity and diversity of infectious viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages.

To detect the major sites of viral replication in immunodeficiency virus-infected individuals, we quantified proviral DNA and infectious viruses using quantitative PCR and a plaque assay, respectively, in various tissues of SHIV(KU-2)-infected monkeys in the early and AIDS stages of infection. Compared the quantity of infectious virus among PBMC and the lymphoid tissues, the mesenteric lymph node had the largest number of infectious viruses at the AIDS stage more than at the early stage of infection. These results suggested that the gastrointestinal tract was a major site of viral replication. In the brain, proviral DNA was detected at the early and AIDS stage of infection, but infectious viruses were detected at only the AIDS stage. Moreover, we analyzed the nucleotide sequences of the env V3 region in infectious virus clones isolated from each plaque. The viruses in the lymphoid tissues of the monkey that developed AIDS diverged from the inoculated virus and had the same three amino acid substitutions. However, the viruses in the brain were almost identical to the inoculated virus, suggesting that the virus entered the brain early after infection and persisted without replication and genetic diversion until the AIDS stage.

Amino Acid Sequence↗

Comparison of PCR-amplified JC virus control region sequences from multiple brain regions in PML.

The authors report a 14-year-old boy with Wiskott-Aldrich syndrome complicated by progressive multifocal leukoencephalopathy after allogeneic bone marrow transplantation. Several therapeutic approaches were attempted, but there was no response. The patient died 2 months after the onset of neurologic symptoms. We detected three distinct, rearranged regions of JC virus in the cerebellum, occipital lobe, and brainstem. These findings suggest that the brain lesions had three independent origins.

Adolescent↗

Neuropathological analysis in spinal muscular atrophy type II.

We performed a neuropathological analysis, including in situ nick end labeling (ISEL) and immunohistochemistry, of two cases of clinicogenetically confirmed infantile spinal muscular atrophy (SMA) type II. Both cases showed severe reduction of the motor neurons and gliosis in the spinal cord and brain stem, although the occurrences of central chromatolysis and ballooned neurons were not frequent. Clark's and lateral thalamic nuclei, which are usually altered in SMA type I, were spared, whereas Betz cells in the precentral gyrus and large myelinated fibers in the lateral funiculus were reduced in number. Regarding apoptosis, only the younger case demonstrated a few ISEL-positive nuclei in the dorsal horn, with reduced Bcl-x expression level in the Purkinje cells. Unlike SMA type I, the expression of neurofilaments was not disturbed and the reduction in synaptophysin expression level in the anterior horn was mild. An oxidative stress-related product was deposited in atrophic motor neurons in the spinal cord, and neurons with nuclei immunoreactive for 8-hydroxy-2'-deoxyguanosine were found in the lateral thalamus. In contrast, the expression of glial glutamate transporters was not altered. These data suggest that oxidative stress and, to a lesser extent, apoptotic cell death, but not disturbed neurofilament metabolism or excitotoxicity, may be involved in neurodegeneration in SMA type II.

Adult↗

Exogenous leptin inhibits the secretion of pancreatic juice via a duodenal CCK1-vagal-dependent mechanism in anaesthetized rats.

Leptin originally described as product of the ob gene has been shown to be expressed in various tissues including the gastrointestinal tract. In this study, we investigated the influence of leptin on the secretion of pancreatic juice in biliary-pancreatic duct cannulated anaesthetised rats and in dispersed rat pancreatic acini in vitro. Exogenous leptin was given in boluses intravenously with or without CCK-8 (12 pmol kg(-1) body weight) in the presence or absence pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. Administration of leptin (0.1, 1 and 10 microg kg(-1) body weight) did not affect the volume of bile and pancreatic juice while the protein and trypsin outputs were reduced in a dose-dependent manner. In the rats, leptin inhibited CCK-8 stimulated protein and trypsin outputs stronger than the basal pancreatic secretion. The inhibition by leptin was abolished by the pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. In contrast, leptin did not affect basal and CCK-8-stimulated amylase release from the dispersed rat pancreatic acini in vitro. In conclusion, the results of the present study suggest that leptin does not act directly on the rat pancreatic acinar cells but inhibits the secretion of pancreatic enzymes acting indirectly via a neurohormonal CCK-vagal-dependent mechanism.

Amylases↗

Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype.

OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. RESULTS: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. CONCLUSIONS: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.

Adult↗

Increased frequency of CD3/8/56-positive umbilical cord blood T lymphocytes after allo-priming in vitro.

Umbilical cord blood (UCB) or adult peripheral blood mononuclear cells (PBMC) were repeatedly stimulated by HLA-mismatched allogeneic Epstein-Barr virus (EBV)-transformed cell lines, and the bulk responders or single-cloned cells were immunophenotypically analyzed by flow cytometry. One month after the allo-stimulation, not in PBMC but in UCB, the proportion of CD3/8/56 triple positive T lymphocytes significantly increased. Furthermore, UCB clones exhibited those unique CD3/8/56 markers at an extremely higher frequency than PB clones. They showed as much strong killing activity against allo-stimulators as conventional PB CD56-negative, CD8 T-cell clones, whereas they did not kill the other target, Raji cells. UCB CD3/8/56 T cell clones produced a smaller amount of interferon-gamma compared with PB CD4 or PB CD8 T cell clones. We concluded that CD8 T cells coexpressed with CD56 marker expanded after allo-priming in vitro and would become one of the graft-versus-host (GVH) effectors after UCB transplantation.

CD3 Complex↗

Determination of the subthreshold state contribution in 13C(alpha,n)16O, the main neutron-source reaction for the s process.

The reaction rate of the stellar reaction 13C(alpha,n)16O, which is currently considered to be the main neutron source for the slow (s) process at low energies, has been rederived using the direct alpha-transfer reaction 13C(6Li,d)17O leading to the subthreshold state at 6.356 MeV in 17O. The contribution of the subthreshold state is found to be much smaller than the currently accepted predictions for the main neutron source of the s process, indicating less of a role of this reaction as the neutron source for the s-process scenario in low-mass stars at the asymptotic giant branch.

Journal Article↗

Endoplasmic reticulum chaperone-specific monoclonal antibodies for flow cytometry and immunohistochemical staining.

Endoplasmic reticulum (ER) chaperones of the antigen processing machinery play a crucial role in HLA class I antigen complex assembly and antigen presentation. The characterization of the expression of these chaperones in normal tissues and malignant lesions has been hampered by the lack or limited availability of ER chaperone-specific monoclonal antibodies (mAb) that are suitable for immunohistochemical staining. To overcome this limitation, we have generated human calnexin, ERp57, calreticulin and tapasin-specific mAb-secreting hybridomas from BALB/c mice immunized with peptides and recombinant proteins. The mAb TO-5, TO-2, TO-11 and TO-3 were shown to be specific for calnexin, ERp57, calreticulin and tapasin, respectively, as they react specifically with the corresponding immunizing peptides in ELISA and with the corresponding proteins when tested with human lymphoid cell lysates in Western blotting. Furthermore, the reactivity of the four mAb with the corresponding intracellular antigens yielded intracellular staining when the mAb were tested with formalin-fixed, microwave-treated and saponin-permeabilized cells in indirect immunofluorescence and with formalin-fixed, paraffin-embedded tissue sections in the immunoperoxidase reaction. These results suggest that the ER chaperone-specific mAb we have developed are useful probes for characterizing the expression of ER chaperones of the antigen processing machinery in normal and pathological cells. This information will contribute to defining the effects of abnormalities in their expression on HLA class I antigen expression and function and on the interactions of target cells with the host's immune system.

Animals↗

Modeling and CFD prediction for diffusion and adsorption within room with various adsorption isotherms.

This paper presents physical models that are used for analyzing numerically the transportation of volatile organic compounds (VOCs) from building materials in a room. The models are based on fundamental physicochemical principles of their diffusion and adsorption/desorption (hereafter simply sorption) both in building materials and in room air. The performance of the proposed physical models is examined numerically in a test room with a technique supported by computational fluid dynamics (CFD). Two building materials are used in this study. One is a VOC emitting material for which the emission rate is mainly controlled by the internal diffusion of the material. The other is an adsorptive material that has no VOC source. It affects the room air concentration of VOCs with its sorption process. The floor is covered with an emission material made of polypropylene styrene-butadiene rubber (SBR). An adsorbent material made of coal-based activated carbon is spread over the sidewalls. The results of numerical prediction show that the physical models and their numerical simulations explain well the mechanism of the transportation of VOCs in a room.

Adsorption↗

Analysis of visitation frequency through particle tracking method based on LES and model experiment.

As ventilation efficiency in a room is not always uniformly distributed, an index for measuring ventilation efficiency at a concerned point or in a concerned local domain is required. Local ventilation efficiency is often represented by the rate of the averaged concentration of the local domain to that of exhausted air from the room. From the age theory of air, it is well known that the averaged concentration in a room corresponds to the mean staying time of contaminant. Evaluating the domain-averaged concentration (Cdomain) means evaluating the average staying time of the contaminant in the domain. It can be only one part of the whole room and can be considered as an occupied zone. Visitation frequency (VF) and the average staying time of the contaminant for one visitation in the local domain (Tp) are introduced to analyze the average staying time of the contaminant in the local domain. The value of VF is strongly affected by the position of the local domain in the room; that is, the position of the local domain in the whole flow field of the room. Tp represents the property of the flow pattern in the local domain. As the indication of VF and Tp represent the mechanism for forming the domain-averaged concentration, they are deeply related to local purging flow rate, which represents the airflow rate for defining the domain-averaged concentration. As VF and Tp are related to the contaminant transportation property, it is effective to analyze them by particle tracking method. A CFD method of large eddy simulation (LES) was thereby carried out in this study. The prediction result by LES is also validated by a precise model experiment. In this paper, the detailed analysis of VF and Tp is carried out on the basis of the particle tracking method utilizing the LES result in order to clarify the mechanism of the domain-averaged concentration. The analyzed room has one supply inlet and one exhaust outlet. A clear re-circulating flow, generated by the forced ventilation, is observed in the room. The value of VF is examined with three types of local domains in the room model. In the room model, VF shows a value of 5.70 when the local domain occupies half of the room. It becomes smaller when the size of the local domain is reduced.

Air Movements↗

Lack of clinical utility of minimal residual disease detection in allogeneic stem cell recipients with childhood acute lymphoblastic leukemia: multi-institutional collaborative study in Japan.

The clinical utility of minimal residual disease (MRD) measurements following allogeneic stem cell transplantation (SCT) in childhood ALL is controversial. We therefore performed a multi-institutional study of MRD in bone marrow samples taken before SCT and at 1, 3, 6 and 12 months after SCT. Case-specific clonal rearrangements of IgH and TCR genes and expression levels of Wilms' tumor 1 (WT1) mRNA were determined by PCR or RT-PCR methods. In total, 95 cases met all criteria for analysis of informative IgH/TCR markers and quantitative WT1 mRNA expression levels. During the 2-year (median 414 days) study period, 20 patients relapsed. Although the proportion of patients with a positive IgH/TCR result before SCT was significantly reduced at 1 month after treatment (P<0.001), attesting the efficacy of SCT, serial measurements of IgH/TCR rearrangements did not correlate with leukemic relapse. Clonal switch was demonstrated in 11 of the 14 patients with bone marrow relapse, indicating that the poor predictive power of the MRD assay most likely reflected the loss of PCR targets. WT1 expression was not related to either MRD detection by IgH/TCR assays or to clinical leukemic relapse. The clinical value of serial MRD monitoring would be limited in ALL patients undergoing SCT.

Adolescent↗

Complete resolution of severe chronic active Epstein-Barr virus infection by cultured, activated donor T lymphocyte infusion after nonmyeloablative stem cells allografting.

A patient with chronic active Epstein-Barr virus (EBV) infection was treated by allogeneic SCT from an HLA-identical sibling donor, using a nonmyeloablative regimen. Even on day 70, mixed chimerism remained together with a quite high viral load. On days 76 and 90, donor lymphocytes were infused after short-term culture with OKT3 plus recombinant IL-2. At 8 days after the last dose, all hematopoietic cells were shown to be donor-type dominant; thereafter, the viral load started to decrease and finally disappeared. Anti-mHA-specific CTLs were generated in vitro, which were shown to be effective in eradicate viral-infected recipient T lymphocytes.

Adult↗

Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation.

To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early=29, late=48, both=4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (p=0.0079, odds ratio (OD)=5.109, 95% confidence interval (CI)=1.533-17.030), busulfan (BU) (p=0.0015, OD=3.336, 95% CI=1.584-7.027), BU+CY (p=0.0001, OD=4.369, 95% CI=2.055-9.292), antithymocyte globulin (p=0.0009, OD=3.368, 95% CI=1.642-6.911), nonradiation (p=0.0163, OD=2.564, 95% CI=0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (p=0.0001, OD=7.519, 95% CI=2.847-19.858), and bladder irrigation (p=0.0001, OD=4.950, 95% CI=2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P<0.001) than Mesna alone (p=0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (p=0.0105, OD=5.301, 95% CI=1.477-19.026) and bladder irrigation (p=0.0001, OD=9.469, 95% CI=3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i). high-dose BU as well as CY is a cause of HC, (ii). protective bladder irrigation has an opposite effect, and (iii). Mesna possibly has a toxic effect on bladder mucosa.

Adolescent↗

Childhood Helicobacter pylori infection in a murine model: maternal transmission and eradication by systemic immunization using bacterial antigen-aluminium hydroxide.

In humans, transmission of Helicobacter pylori is thought to occur largely during childhood. Infected mothers are generally considered to be the main source of the pathogen. However, little is known about when and how often maternal transmission of H. pylori occurs during childhood. In the present study, we examined these issues in an experimental murine model. Pregnant C57BL/6 mice, infected experimentally with H. pylori, delivered and nursed their litters. The stomachs of the infants were isolated and assessed for transmission of H. pylori. We also investigated the effect of systemic immunization using H. pylori antigen-aluminium hydroxide (AlOH) with regard to providing anti-H. pylori immunity and eradicating the maternally transmitted bacteria in infants. Polymerase chain reaction (PCR) was used to examine the presence of transmitted bacteria and their eradication. Maternal transmission of H. pylori varied widely during the nursing period, but almost all litters showed bacterial transmission at 2 weeks postpartum. Systemic immunization with bacterial antigen-AlOH eradicated the bacteria in most litters; this immunization induced a local decrease of Th2 cytokines and a local increase of Th1 cytokines in the gastric tissue, as determined by ELISA. Our results indicate that our H. pylori vaccine provides not only protection, but also eradication of the already transmitted H. pylori.

Aluminum Hydroxide↗