Search PubMed⌕ Search

Biomedical subjects

Makoto Uchiyama

Publications and source records attributed to Makoto Uchiyama.

At least 19 recordsLinked to original sources
PubMed2004

Fc receptor-mediated accumulation of macrophages in crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody administration in WKY rats.

Anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats is characterized by glomerular accumulation of CD8(+) T cells and monocytes/macrophages, followed by crescent formation. The mechanism of leukocyte accumulation after antibody binding to GBM is still unclear. To unveil an involvement of Fcgamma receptors (FcgammaR) in leukocytes recruitment we examined the expression of FcgammaR in glomeruli and the effects of the administration of F(ab')(2) fragment of anti-GBM antibody or FcgammaR blocking on the initiation and progression of this model. A gradual increase of FcgammaR mRNA expression in glomeruli during the time course of disease suggested their significance in the development of glomerulonephritis. Glomerular lesions and proteinuria were induced only in rats injected with intact IgG of anti-GBM antibody, but not with the F(ab')(2) fragment. In vivo blocking of FcgammaR by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of FcgammaR (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry FcgammaR2-expressing cells in glomeruli were identified as macrophages, but not CD8(+) T cells. The expression of FcgammaR1 and 3 was significantly decreased, and that of FcgammaR2 became undetectable in CD8(+) T cell-depleted rats. Thus, CD8(+) T cells may stimulate FcgammaR expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc-FcgammaR interaction in glomerular recruitment of macrophages and following induction of anti-GBM glomerulonephritis in WKY rats.

Animals↗
PubMed2004

Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), whereas the closely related virus HTLV-2 has not been associated with such malignant conditions. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) much more efficiently than does HTLV-2 Tax2. By using a differential display analysis, we isolated MAGI-3 as a Tax1-inducible gene in Rat-1 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed that Tax1 induced MAGI-3 in Rat-1 cells. MAGI-3 has multiple PDZ domains and interacted with Tax1 but not Tax2 in 293T cells. The interaction of Tax1 with MAGI-3 was dependent on a PDZ domain-binding motif, which is missing in Tax2. The interaction of Tax1 with MAGI-3 altered their respective subcellular localization, and moreover, the interaction correlated well with the high transforming activities of Tax1 in Rat-1 cells relative to Tax2. MAGI-3 mRNA and the allied MAGI-1, but not MAGI-2, were expressed in HTLV-1-infected T-cell lines. Our results suggest that the interaction of Tax1 and MAGI-3 alters their respective biological activities, which may play a role in transformation by Tax1 as well as in the pathogenesis of HTLV-1-associated diseases.

Amino Acid Motifs↗
PubMed2004

Effect of oral camostat mesilate on hematuria and/or proteinuria in children.

The effects of camostat mesilate (CM), a derivative of gabexate mesilate developed for oral use, on primary glomerulonephritis (GN) and chance hematuria and/or proteinuria were evaluated. Fourteen patients (6 males, 8 females) with a mean age of 11 years and 3 months (range 4-16 years) were enrolled. Histological and clinical diagnoses of the 14 patients were as follows: IgA nephropathy 3, non-IgA GN 2, and asymptomatic significant microscopic hematuria [more than 100 red blood cells per high-power field (x400)] with or without proteinuria 9. They were consecutively treated with oral CM (100 mg twice a day) when they were confirmed to have continuous significant microscopic hematuria and/or proteinuria after a few months of observational follow-up. Urinary findings were normalized in 10 of the 14 patients (85.7%) between 1 month 1 week and 10 months (mean 4 months) after administration of CM. Hematuria cleared in 11 of 13 patients, and proteinuria disappeared in 4 of 5 patients. The mean duration of CM administration was 21.7 +/- 9.1 months (range 4-37 months). At present, 3-12 years after discontinuation of CM therapy, their urinary findings remain normal at 9 years 10 months to 26 years 6 months of age. In conclusion, there appears to be an association between the oral use of CM and reduction in significant microscopic hematuria and/or proteinuria. Oral CM therapy could represent a practical primary care approach to chance hematuria and/or proteinuria in children.

Administration, Oral↗
PubMed2004

Double leukemias simultaneously showing lymphoblastic leukemia of the bone marrow and monocytic leukemia of the central nervous system.

A rare case of different leukemias simultaneously occurring in the bone marrow (BM) and the central nervous system (CNS) was encountered. A 4-year-old girl was diagnosed with acute lymphoblastic leukemia and achieved a complete remission with chemotherapy. Two years after diagnosis, she was found to have acute monocytic leukemia at first relapse in the BM. One month after the second course of induction therapy, lymphoblastic leukemia in the BM and monocytic leukemia in the CNS were found simultaneously. Chromosomal analysis of leukemia cells in the BM and CNS showed distinct results. The mechanism of double leukemias occurring was obscure, although a lineage switch, therapy-related, or de novo leukemia could be considered as possibilities. Double leukemias should be kept in mind when leukemias relapse in several sites.

Biomarkers, Tumor↗
PubMed2004

Obese Japanese children have low bone mineral density after puberty.

The purpose of this study was to determine the relationship between BMD and childhood obesity. We examined 1070 obese children (722 boys and 348 girls) aged 7 to 15 years. Their mean relative weight, as a percentage of the standard weight for age, height, and sex, was 152.9 +/- 14%. BMD was assessed, by a digital image processing method, in the second metacarpal bone of the left hand. We compared our results with those of healthy nonobese Japanese children based on both chronological and bone age. Mean BMD values for bone age in the obese children were significantly higher than those in control groups in boys aged 11 years and under and girls 9 years and under. On the other hand, in boys over 12 years old, BMD values for bone age were lower than those in the control groups. In girls over 11 years old, BMD values tended to be lower than those in the control groups. In conclusion, we studied the BMD of obese children from the point of view of advanced bone age. Our results showed that BMD was higher than in prepubertal obese children, but a low BMD value was found after puberty, due to poor gain of BMD during puberty. It is important to prevent obesity in childhood in order to prevent the low BMD after puberty.

Adolescent↗
PubMed2004

Time estimation during nocturnal sleep in human subjects.

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.

Adolescent↗
PubMed2004

A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders.

Recent studies have shown that functional variations in clock genes, which generate circadian rhythms through interactive positive/negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIepsilon), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIepsilon induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIepsilon gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIepsilon. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIepsilon with the S408N variation was approximately 1.8-fold more active than wild-type CKIepsilon. These results indicate that the N408 allele in CKIepsilon plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

Adult↗
PubMed2004

Self-help groups reduce mortality risk: a 5-year follow-up study of alcoholics in the Tokyo metropolitan area.

The present study aimed to determine whether alcoholics who attend self-help groups experience fewer deaths than those who do not. Subjects were patients from the Alcoholism Treatment Program (ATP) of Matsuzawa hospital. A cohort of alcoholic patients recruited into a prospective study was followed from April 1994 to March 1999. A total of 469 alcoholic patients met the International Classification of Diseases (10th edition) criteria for alcohol dependency. Of these, 94 patients refused to participate in the study, leaving a total of 375 participants. After discharge from the ATP and a complete explanation of the present study, subjects decided whether to attend a self-help group (SHG) or not. The SHG comprised 208 subjects, and the non-self-help group (NSHG) comprised 167 subjects. Outcomes were evaluated with regard to death during follow-up for a mean of 2.4 years. Death was ascertained through the records of the Setagaya Department of Health and Welfare center, Matsuzawa hospital and other hospitals, and through personal contact with informants, relatives, and significant others of subjects. Deaths were confirmed for 47 NSHG subjects and only five SHG subjects. NSHG displayed a significantly decreased cumulative survival compared with SHG (P < 0.0001). Cox proportion hazard analysis was used to examine variables that may help to predict mortality among alcoholics. Alcoholics who attended self-help groups differed from those who did not, with regard to mortality experience. Attending a self-help group represented the most important predictor of prognosis for alcoholics.

Adult↗
PubMed2004

The role of lymphocytes in the experimental progressive glomerulonephritis.

BACKGROUND: Glomerular accumulation of leukocytes, including lymphocytes, is a common feature in most types of glomerulonephritis. However, the role of lymphocytes in progressive glomerulonephritis has not been elucidated. We examined the role of lymphocytes in the development of progressive mesangial proliferative glomerulonephritis induced by two injections of monoclonal antibody 1-22-3 in rats. METHODS: To elucidate the role of lymphocytes, circulating lymphocytes were depleted using specific monoclonal antibodies to rat lymphocytes prior to the induction of progressive glomerulonephritis. The effects of lymphocyte depletion on proteinuria and glomerular alterations were assessed 7 and 56 days after the induction of progressive glomerulonephritis. RESULTS: Significant glomerular accumulation of CD4+ T cells, CD8+ T cells, and ED3+-activated macrophage were observed after the induction of glomerulonephritis. Depletion studies showed that continuous treatment with anti-CD5, anti-CD4, or anti-CD8 treatment reduced proteinuria and ameliorated the glomerular lesions on day 56. Depletion of CD4+ T cells also reduced glomerular accumulation of CD8+ T cells and ED3+-activated macrophages, and reduced glomerular expression of mRNA for interferon-gamma (INF-gamma) (63.0% in anti-CD5 and 62.3% reduction in anti-CD4). Transit lymphocyte depletion limited in early stage of progressive glomerulonephritis demonstrated that CD4+ T-cell depletion, but not anti-CD8 treatment prevented glomerular injuries 56 days after the induction of progressive glomerulonephritis. CONCLUSION: CD4+ T cells played a central role in the development of progressive glomerulonephritis, controlling recruitment and activation of CD8+ cytotoxic cells and/or macrophages.

Animals↗
PubMed2004

Deactivation by benzodiazepine of the basal forebrain and amygdala in normal humans during sleep: a placebo-controlled [15O]H2O PET study.

OBJECTIVE: The authors' goal was to identify differences in regional brain activity between physiological and benzodiazepine-induced sleep to clarify the brain structures involved in the drug's hypnotic effect. METHOD: Using positron emission tomography, they compared regional cerebral blood flow during non-REM sleep in nine volunteers treated with placebo or triazolam, a short-acting benzodiazepine, in a double-blind, crossover design. RESULTS: Blood flow in the basal forebrain and amygdaloid complexes was lower during non-REM sleep when subjects were given triazolam than when they were given placebo. CONCLUSIONS: The hypnotic effect of the benzodiazepines may be mediated mainly by deactivation of the forebrain control system for wakefulness and also by the anxiolytic effect induced by deactivation of the emotional center.

Adult↗
PubMed2004

[Serial MEG change in a boy with Landau-Kleffner syndrome].

We report a 7-year-old boy with Landau-Kleffner syndrome (LKS), with emphasis on the effect of therapy and serial MEG. The equivalent current dipoles (ECDs) of spike discharges accumulated in the bilateral Heschl gyri, predominantly on the right. Although spike discharges on the scalp EEGs disappeared by treatment with clonazepam and sodium valproate, the auditory agnosia did not improve. Therapeutic trials with conventional antiepileptic drugs were unsuccessful. A high-dose corticosteroid was effective, with disappearance of ECDs, appearance of auditory evoked fields (AEF) in the bilateral Heschl gyri on MEG, and improvement of behavioral problems and amelioration of acquired aphasia. The clinical course of this patient suggests that MEG findings are useful not only in making precise diagnosis of LKS but also in assessing and predicting the effects of treatment.

Anticonvulsants↗
PubMed2003

Circadian rhythms in humans' delta sleep electroencephalogram.

Eight healthy young male volunteers entered a 20-40 min ultrashort sleep-wake schedule for 78 h in the time-isolation facility. Rectal temperature was continuously recorded. Sleep electroencephalograms (EEGs) obtained during 20 min nap trials were stored in the computer and later analyzed by fast Fourier transform. A two-way repeated-measures ANOVA (with day and time-of-day as the repeated measures) revealed significant circadian rhythms in the powers of sigma and delta sleep EEGs, and in rectal temperature. These results obtained under conditions in which behavioral confounding factors of retiring and rising were experimentally minimized suggest that the circadian pacemaker contributes to determining the hours of day when one can sleep deeply.

Adult↗
PubMed2003

Glomerular vasculopathy after unrelated cord blood transplantation.

A 1-year-old boy with hemophagocytic lymphohistiocytosis exhibited proteinuria 1 month after unrelated cord blood cell transplantation, which persisted without hematuria. Laboratory study showed an increase of factor VIII-related antigen and total plasminogen activator inhibitor, suggesting endothelial injury. Histological examination of autopsy materials showed increased mesangial matrices and double-contoured basement membranes, and ultrastructurally, swelling of the endothelial cells and widening of the subendothelial space with mesangial interposition. Thrombosis was not observed at any of the sites. This case may be vasculopathy distinct from thrombotic microangiopathy (TMA) or a variant form of TMA following blood stem cell transplantation (BSCT). This vasculopathy should be considered in the differential diagnosis of proteinuria in the early stages after BSCT.

Basement Membrane↗
PubMed2003

Circadian fluctuation of time perception in healthy human subjects.

Previous studies suggested that various psychophysiological factors have influences on human time perception. In particular, working memory loads, time of day, body temperature, and mood were known as important modifiers of time perception. The purpose of this study is to elucidate factors affecting the short-term time perception under controlled condition. Fourteen healthy young male adults participated in this study. Time perception sessions (TPS) were conducted 4 times at 0900, 1300, 1700 and 2100 h. The TPS consisted of five 10-s time production trials under five different conditions (control trial, those with reward, and 3 different dual-load working memory tasks). Subjective status was assessed using visual analogue scales (VAS). To verify a participant's vigilance state, an alpha attenuation coefficient (AAC) was calculated. Two-way repeated measures ANOVA for produced time revealed a significant main effect of session, but no effect of task or interaction. Although produced time was not correlated with AACs or VAS scores, there was a significant negative correlation between produced time and core body temperature. These results suggest that human short-term time perception may be more influenced by circadian rhythm than working memory load or psychophysiological status.

Adult↗
PubMed2003

Characterization of assembly of recombinant type IV collagen alpha3, alpha4, and alpha5 chains in transfected cell strains.

BACKGROUND: Alport syndrome is caused by mutations in type IV collagen alpha3, alpha4, and alpha5 genes. Immunohistochemical analyses of kidney sections from normal individuals and Alport syndrome patients have suggested that the alpha3(IV), alpha4(IV), and alpha5(IV) chains form a heterotrimer in the glomerular basement membrane (GBM) and that a defect in any one of the chains disrupts the assembly of the three chains, resulting in Alport syndrome. METHODS: We established stable transformants of HEK293 cells that expressed mouse alpha3(IV) and/or alpha4(IV) and/or alpha5(IV) chains. Using cell extracts and culture media of these cells, experiments were performed to determine whether or not the alpha3(IV) and alpha4(IV) chains were coimmunoprecipitated with the alpha5(IV) chain. Moreover, we examined complex formation of mutant alpha5(IV) chain containing either a deletion or substitution mutation with the alpha3(IV) and alpha4(IV) chains. RESULTS: The established cell strains were named according to their transfected alpha(IV) chains. The alpha3(IV) and alpha4(IV) chains were coimmunoprecipitated with the alpha5(IV) chain in alpha345 cells but not in alpha35 and alpha45 cells. These chains were not coimmunoprecipitated with the alpha5(IV) chain, which lacked either a collagenous domain or NC1 domain. The ability of the alpha5(IV) chain with either a G1182R or C1573R substitution, corresponding to previously reported mutations in Alport syndrome patients, to form a complex with alpha3(IV) and alpha4(IV) chains was diminished. CONCLUSION: The findings indicate that alpha3(IV), alpha4(IV), and alpha5(IV) chains form a complex, which is a heterotrimer, and that a defect in complex formation might be one of the molecular mechanisms underlying the pathogenesis of Alport syndrome.

Amino Acid Substitution↗