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Biomedical subjects

Makoto Uchiyama

Publications and source records attributed to Makoto Uchiyama.

At least 19 recordsLinked to original sources

The Japanese Centenarian Study: autonomy was associated with health practices as well as physical status.

OBJECTIVES: To investigate the prevalence of centenarians who have preserved activities of daily living (ADLs) and good cognitive and psychosocial status in Japan. DESIGN: Census-based survey. SETTING: Cross-Sectional Investigation of Half of All Japanese Centenarians Study, 2000. PARTICIPANTS: A nationwide census-based study was conducted of all of the male centenarians and a random sample of half of all the female centenarians who were included in the National Census of Japan. After excluding those who had died and whose addresses could not be identified, 1,907 centenarians (53.0%) participated in the present visitation interview survey. MEASUREMENTS: ADLs, cognitive status, and psychosocial status. Centenarians who have preserved ADLs and good cognitive and psychosocial status were defined as autonomous centenarians. RESULTS: Of the study subjects, 10.4% were judged to be autonomous centenarians. Multiple logistic regression analyses revealed that autonomy in centenarians was associated with better visual acuity, getting regular exercise, spontaneous awakening regularly in the morning, preserved masticatory ability, having no history of drinking, having no history of severe falls after the age of 95, more frequent intake of protein, living at home, and being male. It was also demonstrated that autonomous centenarians were not associated with appetite, vegetable or seaweed intake, smoking habits, auditory capacity, body mass index, or present illness. CONCLUSION: These findings suggest that health practices play an important role in preserving ADLs and good cognitive and psychosocial status after reaching the age of 100 and should be useful for establishing an educational program for the ever-increasing "super elderly" population in Japan.

Activities of Daily Living↗

Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.

Adolescent↗

Increased mutations of CD72 transcript in B-lymphocytes from adolescent patients with systemic lupus erythematosus.

Recent studies have shown that B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE). Abnormal expression of molecules engaging in B-cell receptor (BCR) signaling and resultant hyperactivity of B cells has been reported in both mouse models of lupus and patients with SLE. CD72 on B cells is unique in that it regulates BCR signaling both positively and negatively. We analyzed the expression of CD72 protein and mRNA in peripheral blood B cells from adolescent patients with SLE. The expression level of CD72 on B cells of the patients was decreased compared with that on B cells of controls. Sequence analysis of CD72 mRNA showed significantly increased nucleotide mutations, including both nucleotide substitutions and deletions. Almost all (95.6%) of the CD72 transcripts from the patients had different nucleotide sequences from those of the wild type. About half (41.3%) of the mutations were point mutations located close to the sequence of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which negatively regulates BCR signaling. These results indicate that increased nucleotide mutation of CD72 mRNA accounts for the decreased expression level of CD72 in B cells, and it might be related to hyperactivity of B cells in patients with SLE.

Adolescent↗

Magnetoencephalography in patients with tuberous sclerosis and localization-related epilepsy.

PURPOSE: To clarify the usefulness of magnetoencephalography (MEG) for diagnosis of the spatial relations between spike foci and suspicious epileptogenic tubers on MRI in patients with tuberous sclerosis (TS) and to compare MEG spike foci with single-photon emission computed tomography (SPECT) findings. METHODS: We analyzed magnetic fields of epileptic spike discharges in 15 patients with TS and localization-related epilepsy (LRE) by using MEG (a whole-head 204-channel magnetometer system). We investigated the spatial relation between the equivalent current dipoles (ECDs) of interictal spike discharges and visible cortical tubers on MRI. We also compared results of MEG and MRI with SPECT findings. RESULTS: MEG detected a cluster of ECDs around one cortical tuber in six of 15 patients and clusters of ECDs around two cortical tubers in five patients. Interictal SPECT was disappointing in detection of epileptic foci in TS. However, MEG spike foci showed spatial consistency with ictal hyperperfusion areas in two patients. Three patients with single ECD clusters underwent surgical treatment: two have been seizure free, and one has obtained seizure reduction of >90%. CONCLUSIONS: ECDs were located around visible tuber nodules. MEG enabled precise localization of the epileptic foci and provided crucial information for surgical treatment in patients with TS and partial epilepsy. TS patients showing a single ECD cluster on MEG may be appropriate candidates for surgical treatment.

Adolescent↗

Brain developmental abnormalities in Prader-Willi syndrome detected by diffusion tensor imaging.

OBJECTIVE: The purpose of this work was to detect brain developmental abnormalities in Prader-Willi syndrome by using diffusion tensor imaging based on a high-field MRI system. METHODS: Eight patients with Prader-Willi syndrome and 8 age- and gender-matched normal control subjects were examined using a high-field (3.0 T) MRI system. Trace value and fractional anisotropy were assessed simultaneously in multiple representative brain regions: the deep gray matter (putamen, caudate head, and dorsomedial thalamus) and the white matter structures (frontal and parietal white matter, posterior limb of internal capsule, and corpus callosum). RESULTS: In Prader-Willi syndrome patients, trace value was found to be significantly higher in the left frontal white matter and the left dorsomedial thalamus, whereas fractional anisotropy was significantly reduced in the posterior limb of the internal capsule bilaterally, the right frontal white matter, and the splenium of the corpus callosum. The observed diffusivity characteristics indicate developmental abnormalities in these areas, which are highly consistent with the clinical features of Prader-Willi syndrome. CONCLUSIONS: The study provides the first objective evidence that Prader-Willi syndrome patients indeed have developmental abnormalities in specific areas of the brain, providing a new window toward understanding the pathophysiology of Prader-Willi syndrome.

Adolescent↗

The relationship between depression and sleep disturbances: a Japanese nationwide general population survey.

OBJECTIVE: Among the existing epidemiologic studies that have examined the relationship between depression and sleep disturbances, there are few nationwide studies that have been conducted on subjects representing the general population. The present study was therefore conducted to clarify the relationship between depression and sleep disturbances, in particular the relationship between depression and both sleep duration and subjective sleep sufficiency, using a large sample representative of the general population. METHOD: The survey was conducted in June 2000, using self-administered questionnaires, targeting a population that was selected randomly from among 300 communities throughout Japan. Among the respondents, data from 24,686 individuals aged 20 years or older were analyzed. The Center for Epidemiologic Studies Depression Scale was used to assess the presence of depression. Sleep status, including sleep duration, subjective sleep sufficiency, and the presence or absence of insomnia symptoms, was evaluated. RESULTS: Those whose sleep duration was less than 6 hours and those whose sleep duration was 8 hours or more tended to be more depressed than those whose sleep duration was between 6 and 8 hours. Thus, sleep duration exhibited a U-shaped association with symptoms of depression. As subjective sleep sufficiency decreased, symptoms of depression increased, indicating a linear inverse-proportional relationship. CONCLUSION: The fact that sleep duration and subjective sleep sufficiency exhibited different relationships with symptoms of depression indicates that these 2 sleep parameters each have their own significance with regard to depression. These findings may be useful in the medical management of mental diseases.

Adult↗

Effect of benzodiazepine hypnotic triazolam on relationship of blood pressure and Paco2 to cerebral blood flow during human non-rapid eye movement sleep.

We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (Paco2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (non-REM) sleep. Nine young normal volunteers were treated in a randomized, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow wave (stages 3 and 4) sleep, we measured mean arterial blood pressure (MAP), Paco2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, Paco2 increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain decreased more during stage 2 than slow wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During triazolam-induced stage 2 sleep, absolute CBF of the cerebral white matter correlated more strongly to both MAP and Paco2 than during placebo sleep and also correlated more strongly to both MAP and Paco2 than absolute CBF of the occipital cortex. In the frontal white matter, during triazolam-induced stage 2 sleep compared to wakefulness, absolute CBF was significantly better correlated to MAP, but not to Paco2. During triazolam-induced stage 2, the cerebral white matter may receive a modulated CBF regulation having the strengthened relationship of Paco2 to CBF and, more locally, the frontal white matter may depend precariously on CBF regulation.

Adult↗

The sialoadhesin (CD169) expressing a macrophage subset in human proliferative glomerulonephritis.

BACKGROUND: Sialoadhesin (Sn; CD169) is a lectin-like receptor whose expression is restricted to subsets of tissue and inflammatory macrophages. We have previously identified accumulation of Sn+ macrophages as an important marker of disease progression versus remission in rat mesangial proliferative nephritis. The current study examined the significance of Sn+ macrophages in human proliferative glomerulonephritis. METHODS: Frozen kidney sections from normal adult human kidney (n = 4) and pediatric nephropathy (n = 40) were stained for total macrophages (CD68+ cells), Sn+ macrophages, CD3+ T-cells and collagen type I by immunofluorescence. Leukocyte infiltration and the severity of glomerular lesions and interstitial damage were scored. A second protocol biopsy was performed in 27 cases and clinical and biopsy-based data obtained. RESULTS: Sn+ macrophages were absent from glomeruli in normal adult human kidney and in thin basement membrane disease (n = 4), but were detected in 4 of 9 cases of purpura nephritis; 7 of 17 IgA nephropathy; 5 of 5 membranoproliferative glomerulonephritis, and 5 of 5 lupus nephritis. Sn+ macrophages were localized in areas of focal glomerular and interstitial damage. Two-colour immunostaining confirmed that Sn+ cells are a subset of total CD68+ macrophages. The number of glomerular Sn+ macrophages correlated with the degree of proteinuria and glomerular lesions (r = 0.44, P = 0.0045 and r = 0.82, P<0.0001; respectively), while interstitial Sn+ macrophages correlated with the degree of proteinuria and interstitial damage (r = 0.59, P<0.0001 and r = 0.75, P<0.0001; respectively). Combined immunostaining revealed that interstitial Sn+ macrophages and CD3+ T-cells co-localized in areas of tubulointerstitial damage with increased type I collagen deposition. There was significant correlation between the number of interstitial Sn+ macrophages and CD3+ T-cells (r = 0.74, P<0.0001). Most patients responded to a 2 year period of glucocorticoid therapy with a reduction in proteinuria and glomerular lesions and this correlated with the reduction in the number of glomerular Sn+ macrophages. CONCLUSION: This study has identified Sn+ cells as a macrophage subset whose accumulation in the kidney correlates with proteinuria and histologic damage. These results, together with recent findings from animal studies, suggest that Sn+ macrophages may play an important role in progressive renal disease.

Adolescent↗

Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: a study of 57 consecutively diagnosed cases.

STUDY OBJECTIVES: The objective of this study was to clarify the clinical features of sighted patients with non-24-hour sleep-wake syndrome. DESIGN: Clinical analyses of consecutive patients suffering from non-24-hour sleep-wake syndrome. SETTING: The sleep disorders clinic at Kohnodai Hospital, National Center of Neurology and Psychiatry, Japan. PATIENTS: Fifty-seven patients who were diagnosed consecutively as having non-24-hour sleep-wake syndrome between 1991 and 2001 were included in the study. MEASUREMENTS AND RESULTS: The clinical features and sleep characteristics of the patients were analyzed. A semistructured psychiatric interview that included the criteria for Axis I or II disorders of Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised was conducted, and relationships between psychiatric problems and non-24-hour sleep-wake syndrome were analyzed. The patient cohort included 41 (72%) men and 16 (28%) women. The onset of non-24-hour sleep-wake syndrome had occurred during the teenage years in 63% of the cohort, and the mean ( +/-SD) period of the sleep-wake cycle was 24.9 +/- 0.4 hours (range 24.4-26.5 hours). The mean sleep length of the patients was 9.3 +/- 1.3 hours, and 44% of them had a sleep length of between 9 and 10 hours. Psychiatric disorders had preceded the onset of non-24-hour sleep-wake syndrome in 16 patients (28%); of the remaining 41 patients, 14 (34%) developed major depression after the onset of non-24-hour sleep-wake syndrome. CONCLUSIONS: These results represent the first detailed clinical review of a relatively large number of sighted patients with non-24-hour sleep-wake syndrome.

Adult↗

Impact of sociocultural factors on hospital length of stay in children with nephrotic syndrome in Japan.

Hospital length of stay (LOS) of Japanese inpatients is extraordinarily long, partly because of the nature of the health insurance system in Japan. We investigated factors that affect the LOS in Japan, taking pediatric nephrosis as an example. The characteristics of 78 hospitalized children with steroid-sensitive nephrotic syndrome were studied. The median LOS of the patients was 47 days. Most of the patients' mothers (92.3%) stayed in hospital during admission to care for their children. Using multivariate Cox's regression analysis with time-dependent covariates, non-working mother and smaller number of siblings were found to be factors significantly associated with prolonged LOS. These factors are presumed to allow the mothers to care for their hospitalized children for a long period. No medical or clinical factors played a significant role in the prolonged LOS. These results suggest that sociocultural factors have a greater influence on the LOS in Japan than do medical factors such as disease course, coexisting illness, complications, and treatment response.

Child↗

Circannual variation in the onset and relapse of steroid-sensitive nephrotic syndrome.

Idiopathic nephrotic syndrome is the most common form of nephrotic syndrome in children, but little is known about the etiology of the disease. To obtain new insights into the etiology of the disease, we studied circannual patterns of initial episodes and relapses of steroid-sensitive nephrotic syndrome (SSNS). From 1986 to 2003, there were 45 children with SSNS in our hospital, and they experienced 43 relapses during that period. Initial episodes of SSNS were found to show significant circannual variation with an autumn peak both by Roger's test and Freedman's test, and the circannual pattern was more obvious in patients with high serum IgE levels. Chronological evaluation by means of Fourier analysis showed a clear circannual pattern. In contrast, relapses of SSNS showed circannual variation with a spring peak, which was a result of a high frequency of relapses after upper respiratory infections in January. These results suggest that circannual variation in initial episodes of SSNS might be associated with allergic predisposition, whereas circannual variation in relapses might be associated with preceding upper respiratory infections.

Adolescent↗

Diurnal fluctuation of time perception under 30-h sustained wakefulness.

Previous studies have reported that time perception in humans fluctuates over a 24-h period. Behavioral changes seem to affect human time perception, so that the fluctuation in human time perception may be the result of such changes due to self-determined activities. Recently, we carried out a study in which a healthy human cohort was asked to perform simultaneously loaded cognitive tasks under controlled conditions, and found that time perception decreased linearly from morning to evening. In addition, the variations in time perception were not a consequence of behavioral changes. It remains to be elucidated whether diurnal variations in time perception are a consequence of circadian rhythm or of some homeostatic changes that are attributable to accumulated wake time. The effects of circadian rhythm on time perception were investigated in eight healthy young male volunteers by conducting 10-s time production tasks under 30-h constant-routine conditions. Core body temperature and serum melatonin and cortisol levels were measured during the course of the study. Produced time exhibited a diurnal variation and was strongly correlated with circadian variations in core body temperature and serum melatonin levels. These results suggest that human short-term time perception is under the influence of the circadian pacemaker.

Adult↗

Prevalence of human metapneumovirus and influenza virus infections among Japanese children during two successive winters.

BACKGROUND: Human metapneumoviruses (hMPVs) are recognized as a leading cause of respiratory infections in young infants in many countries. The objective of this study was to identify links between hMPV and influenza virus infections among children with influenza-like illness. METHOD: This study was conducted in 2 influenza seasons (2002-2003 and 2003-2004) at 2 pediatric outpatient clinics in Niigata city, Japan. Nasopharyngeal swabs or aspirates were collected from influenza-like illness patients, and hMPV and influenza were detected by reverse transcription-polymerase chain reaction (RT-PCR). A nucleotide sequence of 352 nucleotides segment of the F gene was performed. RESULTS: A total of 765 influenza viruses and 84 hMPV were identified from 1498 nasopharyngeal swabs or aspirates by virus isolation and RT-PCR, respectively. hMPV-positive rates in patients with influenza-like illness were 5.7 and 5.2% in the 2002-2003 and 2003-2004 seasons, respectively. Epidemic curves of influenza and hMPV patients showed similar patterns with peaks in February in 2 influenza seasons. hMPV infections occurred frequently in infants and school children. Approximately 46% of hMPV patients were coinfected with influenza A viruses, but those coinfected cases were not clinically distinct from the others. No coinfection with influenza B viruses was found. Phylogenetic analysis of the hMPV fusion gene sequences revealed that 2 distinct hMPV cocirculated and that completely identical strains in subgroup A were observed over 2 years. CONCLUSIONS: HMPV plays an important pathogenic role in patients with influenza-like illness in winter seasons, often in coinfections with influenza A viruses.

Child↗

Daytime sleepiness, sleep habits and occupational accidents among hospital nurses.

AIM: This paper reports a study to determine the prevalence of excessive daytime sleepiness and sleep habits among hospital nurses and to analyse associations between excessive daytime sleepiness and different types of medical error. BACKGROUND: It has been reported that sleep disorders, and the tiredness and sleepiness brought about by sleep disorders may be associated with occupational accidents. However, to our knowledge, there has so far been no report on associations between sleep disorders, excessive daytime sleepiness in particular, and occupational accidents among hospital nurses. METHODS: The study was a cross-sectional study targeting 4407 nurses working in eight large general hospitals in Japan. An anonymous self-administered questionnaire was used to investigate their sleep patterns and experience of occupational accidents. The data were collected in 2003. RESULTS: The prevalence of excessive daytime sleepiness among hospital nurses in the present study was 26.0%. A statistically significant relationship was observed between having or not having occupational accidents during the past 12 months and excessive daytime sleepiness. Multiple logistic regression analyses on factors leading to occupational accidents during the past 12 months showed statistically significant associations between (1) drug administration errors and (2) shift work and age, between (1) incorrect operation of medical equipment and (2) excessive daytime sleepiness and age, and between needlestick injuries and age. CONCLUSIONS: Excessive daytime sleepiness is an important occupational health issue in hospital nurses. It is possible that occupational policies and health promotion measures, such as a provision of sleep hygiene advice and social support at worksites, would be effective in preventing occupational accidents among hospital nurses.

Accidents, Occupational↗

Bone marrow cells contribute to regeneration of damaged glomerular endothelial cells.

BACKGROUND: There is accumulating evidence that adult bone marrow (BM) cells show unexpected plasticity, and can differentiate into a wide range of specialized cells. In the case of intrinsic renal glomerular cells, BM-derived cells have been reported to differentiate into both mesangial cells and podocytes. However, there is controversy on recruitment of glomerular endothelial cells, although endothelial cells in other tissues are known to be recruited from the BM. METHODS: Sprague-Dawley (SD) rats and SD rats made chimeric by transplantation of bone marrow cells from enhanced green fluorescent protein (EGFP) transgenic littermate rats, were injected with anti-Thy-1.1 antibody, followed by unilateral nephrectomy (1-kidney model). Chimeric rats used in 1-kidney model were sacrificed for histologic examination at weeks 2, 4, 8, and 11. We examined isolated glomeruli and frozen sections of kidneys from rats of each group at weeks 2 and 11 by confocal laser scan microsopy (CLSM), both immunohistologically and three dimensionally. RESULTS: In the 1-kidney group, using chimeric rats transplanted with EGFP(+) bone marrow cells, most rats died, presumably of uremia, after 8 to 11 weeks. A CLSM study using isolated glomeruli and frozen sections of kidneys revealed that bone marrow-derived PECAM-1(+), RECA-1(+) cells, and OX-7(+) cells contributed to the structural support for the glomerular capillaries during the chronic course. Global glomerular sclerotic lesions and diffuse tubular atrophic changes, with interstitial cell infiltration, were remarkable at weeks 8 and 11. CONCLUSION: Bone marrow-derived endothelial progenitor cells participated in glomerular endothelial cell turnover after severe damage. Treatment that could target bone marrow-derived endothelial progenitor cells and promote angiogenesis in regions of progressive glomerular lesions may be a promising therapeutic approach for preventing end-stage renal disease.

Animals↗

Usefulness of serum adiponectin level as a diagnostic marker of metabolic syndrome in obese Japanese children.

This study aimed 1) to investigate the relationship between serum adiponectin levels and metabolic disorders and 2) to clarify the usefulness of serum adiponectin level as a diagnostic marker of metabolic syndrome in obese Japanese children. One hundred obese boys aged 8 to 13 years were examined. Serum adiponectin levels were measured by radioimmunoassay using a commercial kit. Abdominal fat thickness (maximum preperitoneal fat thickness: P(max); minimum subcutaneous fat thickness: S(min)) was measured by ultrasonography. The relationships between adiponectin and clinical characteristics were analyzed by simple regression. The relationships between anthropometric measurements and metabolic disorders were analyzed among three groups divided according to adiponectin percentile. The prevalence of metabolic syndrome was also analyzed, with metabolic syndrome defined as the presence of three or more complications of obesity. The criteria for metabolic syndrome by adiponectin were subjected to a receiver operating characteristic (ROC) analysis. Body weight, waist circumference, P(max), alanine aminotransferase and fasting serum insulin were all inversely correlated with adiponectin. There were significant differences in the prevalence of severe obesity, the accumulation of visceral adipose tissue, hyperinsulinemia, high serum low density lipoprotein-cholesterol, the number of complications of obesity and the prevalence of metabolic syndrome among the three groups. The area under the ROC curve for adiponectin was 0.672 +/- 0.055 and the cut-off value was 6.65 microg/ml. Hypoadiponectinemia was associated with visceral fat accumulation and metabolic syndrome in obese Japanese boys. Evaluation of adiponectin might contribute to an early intervention for obese children with metabolic syndrome.

Adiponectin↗