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Biomedical subjects

S Miyagi

Publications and source records attributed to S Miyagi.

At least 19 recordsLinked to original sources

Alanine aminotransferase elevation not associated with fatty liver is frequently seen in obese Japanese women.

OBJECTIVE: To determine the prevalence of fatty liver and alanine aminotransferase (ALT) elevation in obese Japanese women and to clarify the factors contributing to fatty change and ALT elevation in the cohort. DESIGN: Cross-sectional and population-based study. SUBJECTS: From 4366 women who received their annual health check-up, 4211 women were selected for analysis. All 4211 women were negative for hepatitis virus markers. MEASUREMENTS: Peripheral blood cell counts, liver biochemical tests, fasting glucose, cholesterol and triglyceride levels, uric acids, glycosylate hemoglobin A1c, and ultrasound examination. RESULTS: Ultrasonographic evidence of fatty liver and ALT elevation was seen in 391 (9.3%) and 238 (5.7%), respectively, of the 4211 women. Frequencies of both fatty liver and ALT elevation increased with increase in the degree of obesity. The frequency of ALT elevation was higher in women with fatty liver than in women without fatty liver among the nonobese or mildly obese group. However, the frequency of ALT elevation was not significantly different between women with fatty liver and women without fatty liver among the severely obese group. Multivariate analysis showed that obesity, hemoglobin (> or = 14 g/dl), triglyceride (> or = 150 mg/dl), diabetes mellitus, and fatty liver were significant predictors of ALT elevation. However, only two variables, hemoglobin (> or = 14 g/dl) and presence of diabetes, were significant in the severely obese group. CONCLUSIONS: ALT elevation not associated with fatty liver was frequently seen in obese women, suggesting that obesity is directly associated with the elevated ALT level in Japanese obese women. In addition, hemoglobin (> or = 14 g/dl) was a strong predictor of ALT elevation in the severely obese group.

Adult↗

Replication of the rat aldolase B locus differs between aldolase B-expressing and non-expressing cells.

We previously reported a rat chromosomal origin of DNA replication (oriA1) that encompassed the aldolase B (AldB) gene promoter. Here, we examined utilization of oriA1 in AldB-expressing and non-expressing cells. The results suggested the occurrence of mutually exclusive regulation between DNA replication and transcription. Nascent strand abundance as assayed by competitive polymerase chain reaction using bromodeoxyuridine-labeled nascent DNA indicated that oriA1 is not utilized in AldB-expressing cells, while it is fired in non-expressing cells. In the latter non-expressing cells, the replication fork seemed to slow at 20-22 kb downstream of oriA1.

Animals↗

Structural analyses of the UTF1 gene encoding a transcriptional coactivator expressed in pluripotent embryonic stem cells.

The UTF1 is a transcriptional coactivator expressed mainly in pluripotent embryonic stem cells. Here, we have isolated a genomic DNA fragment carrying the UTF1 gene and found that the gene contains two exons interrupted by a short intron. The gene possesses four GC boxes, but no TATA box in the 5'-flanking region. This is reminiscent of a housekeeping gene type promoter and the functional relevance of these motifs is confirmed by the transient transfection analyses. As to the gene product, our analyses have led to the identification of two different species. One of them corresponds to the full-length protein, while the other is produced by utilizing the second methionine codon for the translation initiation. The oligo-capping analyses reveal multiple transcription start sites. Interestingly, some of them are localized downstream of the first methionine codon, indicating that such transcripts produce a protein starting from the second methionine codon. Chromosomal mapping analyses locate the gene at 7F5, the syntenic region of the human chromosome (10q26) where the human UTF1 gene is located.

Amino Acid Sequence↗

Uncoupling protein 3 and peroxisome proliferator-activated receptor gamma2 contribute to obesity and diabetes in palauans.

We examined the genetic contribution of single nucleotide polymorphisms (SNPs) of the energy metabolism-related genes, including beta 3 adrenergic receptor (beta3AR), apolipoprotein E (apo-E), promoter of uncoupling protein 3 (UCP3-p), peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) and leptin receptor (LEPR) to metabolic disorders, in 118 inhabitants of Palau. The data were statistically analyzed and ethnically compared to correlate SNPs and their metabolic parameters. UCP3-p (P < 0.01) and PPARgamma2 (p = 0.05) correlated with plasma HbA1c, and UCP3-p correlated with fasting blood glucose (P < 0.01) in males, but not in females. UCP3-p correlated with body fat (%) (P < 0.01) in females, but not in males. Plasma leptin levels and apo-E were correlated in both groups. The frequency of SNPs for PPARgamma2, LEPR, and UCP3-p are significantly different between Palauans and Caucasians.

Adipose Tissue↗

A novel growth-related nuclear protein binds and inhibits rat aldolase B gene promoter.

The promoter of the rat aldolase B (AldB) gene that confers liver-specific transcription has an additional role. It functions in vivo as an origin region of DNA replication in the cells in which the gene is repressed (Zhao, Y., Tsutsumi, R., Yamaki, M., Nagatsuka, N., Ejiri, S., Tsutsumi, K., 1994. Initiation zone of DNA replication at the rat aldolase B locus encompasses transcription promoter region. Nucleic Acids Res. 22, 5385-5390). This promoter/origin region has multiple protein-binding sites and, thus, binding of a particular set of protein factors in AldB-expressing or non-expressing cells seems to correlate with functional switch of this promoter/origin region. In the present study, we characterized two closely related proteins, termed AlF-C1 and AlF-C2, which are assumed to be involved in repression of the AldB gene. These two proteins share an identical amino acid sequence except for a 47-residue-insertion in AlF-C1, and are members of a gene family including heterogeneous nuclear ribonucleoprotein (hnRNP) and CCAAT-binding factor subunit A (CBF-A) genes. Bacterially expressed AlF-C1 can bind sequence-specifically to the AldB gene promoter, whereas AlF-C2 can only weakly. Transfection experiments using mammalian expression vectors showed that AlF-C1 down-regulates the AldB gene promoter in rat hepatoma cells, while AlF-C2 had no or little effect. Expressions of mRNAs encoding these two proteins are enriched in fetal livers and in regenerating livers. These results implied that AlF-C1 and/or C2 is involved in growth-regulated repression of the AldB gene.

Amino Acid Sequence↗

An overlapping set of DNA elements in the rat aldolase B gene origin/promoter regulates transcription and autonomous replication.

Promoter of the rat aldolase B (AldB) gene is centered on an origin of chromosomal DNA replication in vivo, and it directs autonomous replication upon transfection into cultured cells. Previous studies showed that the 200 bp promoter fragment is necessarily required for the autonomous replication. Here, we identified three cis-elements required for replication within the 200 bp promoter, using autonomously replicating plasmids carrying various mutations and deletions. One is an element that is previously defined as a regulatory element for liver-specific transcription (site C). Other two, purine-rich (site PPu) and A (T)-rich (site A/T) sequences, were those often found in eukaryotic origin regions. Sites C and PPu were found to bind specific nuclear factors in transfected cells, and the results of competitive binding assay implied direct or indirect interaction between sites C and PPu.

Animals↗

[Chemotherapy of Hansen's disease in Japan--present status].

In order to know leprosy chemotherapy status in Japan, three recently conducted Government-supported nation-wide survey, namely chemotherapy research group survey (Takizawa, 1994, 71 cases) follow up result of Takizawa's study (Miyagi, 1997, 59 cases) and leprosy patient registry (Goto, 1996, 130 cases) were compared and analyzed. For most fresh and relapse cases, multi-drug therapy were applied, among them rifampicin/dapsone or rifampicin/dapsone/clofazimine combinations were selected in about half of new cases and about 1/3 of relapse cases. In many cases dose and intervals were based on WHO protocol, however smaller dosage was used in some cases. Quinolone (ofloxacin) was used in 40% of cases during the therapy. Reversal reaction was observed in 7/71 cases and erythema nodosum leprosum was observed in 6/71 cases. In order to prevent chemotherapy-induced deformities, we propose a modified protocol for new cases accompanied by reactional status, which starts with clofazimine monotherapy and followed by WHO/MB.

Anti-Infective Agents↗

Sequence requirement for replication initiation at the rat aldolase B locus implicated in its functional correlation with transcriptional regulation.

Transcription promoter of the aldolase B gene was previously shown to be centered on an initiation region of DNA replication in rat hepatoma cells in vivo. Here, we defined an essential region required for replication in a plasmid form upon transfection. Deletion analyses around the origin region revealed that the proximal 200 bp promoter was necessary, but not sufficient for replication as flanking sequence restored replication activity. Therefore, the 200 bp region seemed to cooperate with the flanking sequence to play an important role in replication. Electrophoretic mobility shift assays using nuclear extracts from synchronously growing hepatoma cells showed that some protein factors bound to this region in a cell cycle-regulated manner. Since transcription of the aldolase B gene is repressed in the hepatoma cells, the cell cycle-regulated protein-binding is considered to be involved in regulation of replication initiation.

Animals↗

Effects of dietary phosphatidylcholine on memory in memory deficient mice with low brain acetylcholine concentration.

Data concerning the effect of phosphatidylcholine (PCh) administration on the improvement of memory in senile dementia of Alzheimer type are inconsistent, probably due to the different conditions under which studies were conducted. Animal studies provide a good model, but data on this is limited. We studied the effect of PCh on memory in memory deficient mice (Dull mice) with low brain acetylcholine (ACh) concentration and normal mice. Mice were fed 24% casein diet (control) or this diet supplemented with 2 or 8% egg yolk PCh from gestation (Experiment 1) and after weaning (Experiment 2). Memory acquisition and retention were studied by step-down type passive avoidance performance at 8 and 10 weeks old, respectively. Control group of Dull mice had poorer memories than that of the normal mice in Experiments 1 and 2. On the 2% PCh diet, Dull mice improved memory acquisition and retention in Experiment 1 and retention in Experiment 2. On the 8% PCh diet in Dull mice there was improvement of memory and retention in Experiment 1, but no effect was observed in Experiment 2 (P > 0.05). In the normal mice, the 2% PCh diet did not affect memory acquisition and retention, however on the 8% PCh diet, there was no or adverse effect. These results suggest that dietary supplementation of egg yolk PCh improves memory of Dull mice, particularly when given from gestation and that the 2% PCh diet elicits better response than the 8% PCh diet.

Acetylcholine↗

Simple detection of the 5S ribosomal RNA of Pneumocystis carinii using in situ hybridisation.

AIMS: To investigate the effectiveness of digoxigenin incorporated double stranded DNA probes produced by the polymerase chain reaction (PCR), for the detection of Pneumocystis carinii, using in situ hybridisation (ISH). METHODS: Formalin fixed, paraffin wax embedded sections of 26 human lung samples from 11 patients with P carinii pneumonia (PCP), and 15 with various types of fungal and viral pneumonia, were obtained during necropsy or transbronchial lung biopsy. Three additional PCP induced rat lung samples were also tested. PCR probes were prepared using the digoxigenin labelling mixture, and they were amplified from the DNA of a PCP induced rat lung after administration of dexamethasone, on the basis that 5S ribosomal RNA sequences are identical in human and rat P carinii. ISH was performed using this probe, and visualised using the digoxigenin nucleic acid detection kit. An immunohistochemical study using anti-human Pneumocystis monoclonal antibody was also carried out in parallel. RESULTS: ISH positively stained eight (of eight) lung necropsy specimens from patients with PCP, three (of three) transbronchial lung biopsy specimens from patients with PCP, and none of the three PCP induced rat lung specimens. In contrast, none of the specimens from patients with pneumonia caused by Aspergillus sp (n = 5), Candida sp (n = 4), Cryptococcus sp (n = 2), mucormycosis (n = 2), or cytomegalovirus (n = 2) were positive on ISH or immunohistochemistry. CONCLUSIONS: Using a digoxigenin labelled PCR probe for the entire 5S rRNA sequence in conjunction with conventional staining, ISH is highly reactive and specific for the diagnosis of PCP.

Animals↗

[Clinical evaluation on causes of death in patients with active pulmonary tuberculosis].

Seventy one patients with active pulmonary tuberculosis who died during the past 5 years (1989 to 1993) were evaluated on their causes of death. Twenty two patients (31%) died directly of tuberculosis, and among them, 18 patients (81%) of 22 patients who died of tuberculosis) had very advanced tuberculosis. The majority of them (64%) were old age over 70 years and were bedridden due mostly to cerebrovascular injuries. The serum level of albumin was low in all 17 patients in whom it was measured. Establishment of diagnosis of tuberculosis was delayed over one month after the onset of symptoms in 59% of patients who died of severe disease. Sixty one percent (11/18) of patients died within the first month after the initiation of chemotherapy and about 90% (16/18) died within 3 months. Two patients died from massive hemoptysis and other patients died of either respiratory failure or tuberculosis meningitis. From these observations it was found that very advanced tuberculosis was the major cause of death in patients who died of tuberculosis and that the advanced disease was chiefly caused by the delay on the establishment of diagnosis, and it was most important to detect tuberculosis as early as possible, with regular check up of chest X-ray and frequent examination for AFB (acid-fast bacilli) for tuberculosis suspected patients. On the other hand, the majority of patients (49/71) died of complicating medical problem unrelated to tuberculosis. Seventeen patients died from malignancy (seven lung cancer, four lymphoma, two laryngeal cancer, etc). Ten deaths were the result of bacterial superinfection. Other patients died from respiratory failure due to COPD, arteiosclerotic heart disease, or cerebrovascular injuries, etc. Two patients of old age died of hepatic failure possibly caused by adverse reaction of TB chemotherapy. It was found that diseases unrelated to tuberculosis were the cause of death in approximately 70% of patients with active tuberculosis, and it should be emphasized to detect early and to treat these diseases, in particular malignancy. And it is also imperative that the chemotherapy for TB must be instituted very carefully with frequent monitoring of liver function in patients with old age.

Adult↗

[A comparison of asthma deaths and near-fatal asthma attacks].

This study compares the characteristics of fatal asthma patients and those of near-fatal asthma patients who had experienced severe life threatening attacks. Data from 67 fatal asthma patients and 80 near-fatal asthma patients were analyzed. The mean age of fatal asthma cases were older than near-fatal asthma cases, 51.9 yrs and 44.3 yrs, respectively. Similarities of the two cases were seen in sex, type of asthma and severity of asthma. The experiences of previous life-threatening asthma did not differ in both groups (43.3% of fatal vs 40.0% of near-fatal). From the viewpoint of type of development of severe exacerbation, rapid exacerbation was more frequent in fatal cases than near-fatal cases, but acute exacerbation after unstable asthma was more in near-fatal asthma. Seventy-six percent of all asthma deaths occurred at home or on the way to the emergency department. The rate of delay of receiving medical care was significantly higher in fatal cases (72%) than near-fatal cases (26%). There was no significant difference in the frequency of medical management before fatal or near-fatal episode such as oxygen therapy, mechanical ventilation. Use of ambulance, visiting emergency department, previous hospitalization between the two groups. The profile of fatal cases was almost same to that of near-fatal cases except delay of receiving medical care. In conclusion, the analysis of near-fatal cases was very important to make clear the causes of asthma death.

Adult↗

Acute pneumonitis presumed to be silicone embolism.

A 39-year-old housewife who underwent intramammary injections of a proprietary silicone fluid mixture showed clinical and novel transbronchial lung biopsy (TBLB) findings. She presented with complaints of progressive dyspnea, dry cough, and pleuritic chest pain 2 days after the last silicone injections. The chest X-ray and CT scan showed diffuse interstitial infiltrates. TBLB demonstrated translucent, presumably silicone globules embolized within the pulmonary capillaries. The documentation of intramammary injections, the clinical and radiographic features of acute pneumonitis, and the histopathologic evidence by TBLB, may support the causal relationship between illicit injections and the silicone embolism. We discuss the pathogenesis and urge that this potentially toxic source of pulmonary embolism be removed.

Acute Disease↗