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Biomedical subjects

M Ohtaka

Publications and source records attributed to M Ohtaka.

At least 37 records · Page 2Linked to original sources

Glucose modulation of aldose reductase mRNA expression and its activity in cultured calf pulmonary artery endothelial cells.

We examined the effect of glucose on aldose reductase mRNA expression and its activity in calf pulmonary artery endothelial cells. After the cells were exposed to 18 mmol/l glucose, aldose reductase mRNA expression began to increase at 6 h, reached a maximum (about 2.4-fold increase) at 12 h, and thereafter gradually decreased. Aldose reductase activity was found to strongly correlate with aldose reductase mRNA expression after cells were exposed to 18 mmol/l glucose. In contrast, aldose reductase mRNA expression was significantly decreased following exposure to 55 mmol/l glucose. Aldose reductase activity was also decreased at 24 h after 55 mmol/l glucose. The increase in aldose reductase mRNA level caused by glucose was inhibited by 1 microgram/ml of actinomycin D. These phenomena appear to be glucose-specific since neither 3-O-methylglucose nor fructose affected the levels of aldose reductase mRNA. We clearly demonstrate that aldose reductase mRNA level and its activity are modulated by glucose in calf pulmonary artery endothelial cells. Our data suggest that activation of aldose reductase in endothelial cells may contribute to the development of diabetic macroangiopathy.

3-O-Methylglucose↗

Aldose reductase mRNA expression and its activity are induced by glucose in fetal rat aortic smooth muscle (A10) cells.

The induction of aldose reductase (AR) mRNA expression and its activity by glucose were investigated in fetal rat aortic smooth muscle (A10) cells. The increase in the expression of AR mRNA was observed at 6 h, and reached a maximum (2.3 fold) at 12 h after exposure to 80 mM glucose. On the other hand, increase in AR activity was observed at 12 h and reached a maximum (2 fold) at 48 h after exposure to 80 mM glucose. AR mRNA levels as well as its activity increased almost linearly in a concentration dependent manner up to 80 mM. Although not significant, there was a consistent increase in AR mRNA level and its activity at 23.75 mM glucose. There was a good correlation between AR mRNA level and AR activity. In the presence of 1 microgram/ml actinomycin D, the increase in the expression of AR mRNA level by glucose was almost completely abolished, suggesting its transcriptional regulation by glucose. Other osmolytes were also effective in inducing AR mRNA expression as well as its activity at 80 mOsm/kg. Therefore, the increase in AR mRNA level and its activity by glucose in A10 cells may be a response to the increase in osmolarity.

Aldehyde Reductase↗

The regulation of two distinct glucose transporter (GLUT1 and GLUT4) gene expressions in cultured rat thyroid cells by thyrotropin.

We investigated the glucose transporter mRNAs expressed in FRTL5, a rat thyroid cell line, and their regulation by TSH by means of the polymerase chain reaction. FRTL5 cells as well as rat thyroid tissue expressed three types of glucose transporter mRNAs: GLUT1 or erythrocyte/HepG2/brain isoform, GLUT2 or pancreatic beta-cell/liver isoform, and GLUT4 or muscle/fat isoform. GLUT1 mRNA predominated, GLUT4 mRNA was minor, and GLUT2 mRNA expression was faint. Incubation of FRTL5 cells with TSH induced a time- and concentration-dependent increase in GLUT1 mRNA levels, while GLUT4 mRNA levels were decreased. The response of GLUT1 mRNA to TSH was evident at 3 h, and the maximal response was achieved at 12 h. TSH at a dose of 1 mU/ml elicited an approximately 3-fold increase in GLUT1 mRNA levels. (Bu)2cAMP (1 mM), 8-bromo-cAMP (1 mM), and forskolin (50 microM) mimicked the effect of TSH on GLUT1 and GLUT4 mRNA levels. The increase in GLUT1 mRNA by TSH was correlated with the increase in GLUT1 protein and the increase in 2-deoxyglucose transport activity. These observations suggest that in thyroid cells, TSH stimulates glucose transport at least in part by enhancing GLUT1 gene expression, and that the effect of TSH on GLUT1 and GLUT4 mRNA levels is mediated by a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗

All-trans-retinoic acid induced enrichment of functionally normal neutrophils in vivo in a patient with acute promyelocytic leukemia.

A patient with resistant acute promyelocytic leukemia was treated with all-trans-retinoic acid (45 mg/m2 per day for 42 days) and obtained complete remission at day 14. Analysis of the neutrophils from the patient at day 7 demonstrated that they were indistinguishable from neutrophils from normal individuals as far as this is assessed by presently available functional tests. Furthermore, the degree of peroxidase positivity of neutrophils obtained from the patient was similar to control values. Thus, taken together with the hematologic features, all-trans-retinoic acid induces leukemic promyelocytes to become functionally normal neutrophils. This therapy is particularly suitable in obtaining complete remission in patients with acute promyelocytic leukemia with neutropenia with or without previous chemotherapy.

Female↗

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: a pilot study which raises important questions.

Acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosome (Ph+ ALL) were treated with a combination of antineoplastic drugs recommended for both myeloid and lymphoid leukemia (BHAC-DMPV: behenoylcytosine arabinoside, daunorubicin, 6-mercaptopurine, prednisolone, and vincristine). Ph+ ALL patients with chromosome breaks which occur within the major breakpoint cluster region (M-BCR rearranged Ph+ ALL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, four of seven patients with Ph+ ALL had M-BCR rearrangement, and all achieved complete remission with karyotypic normalization. Subsequent cytogenetic analysis during complete remission in two ALL patients with M-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained remission status. This cytogenetic-hematological discrepancy led us to consider that M-BCR rearranged Ph+ ALL might be a variant of chronic myelogenous leukemia, therefore, three Ph+ ALL patients with M-BCR rearrangement were treated with IFN-alpha after achieving complete remission. In contrast, only one of three patients with M-BCR non-rearranged Ph+ ALL obtained complete remission.

Adult↗

Cytogenetic findings in adult acute leukemia and myeloproliferative disorders with an involvement of megakaryocyte lineage.

Cytogenetic analyses were performed on 12 adult patients with abnormal megakaryoblastic proliferation which was detected by ultrastructural cytochemical study (platelet peroxidase) and platelet-megakaryocytes-specific monoclonal antibodies (TP-80, Plt1, AN51, and KOR-77). The patients consisted of two patients with myelodysplastic syndromes (MDS), three with acute megakaryoblastic leukemia (AMKL), six with megakaryoblastic transformation in Philadelphia-positive chronic myelogenous leukemia (CML-meg-BC), and one case of chronic myeloproliferative disorder (CMPD). Among them, an inversion of the long arm of chromosome 3 [inv(3)(q21q26)] was found in one AMKL patient with a normal platelet count. Chromosome change at band 3q26 was also found in one MDS patient without thrombocythemia. Furthermore, the long arm of chromosome 13, where rearrangements in myelofibrosis are clustered (13q12----q22) was seen in one MDS patient. Trisomoy of chromosome 19 was found in one AMKL patient and three CML-meg-BC patients. These findings indicate that cytogenetic abnormalities involving 3q26, 13q, and trisomy 19 are associated with hematologic neoplasia with megakaryocytic lineage in adult patients, although these abnormalities were not related to the survival of the patients. During the period of this study, two acute myelogenous leukemia patients (AML-M2 and AML-M5b) with chromosome rearrangements at band 3q21 and thrombocythemia were found, indicating that chromosome abnormality at band 3q21 is related to quantitative platelet dysfunction, whereas that at 3q26 is related to hematologic malignancies with a proliferation of megakaryocytic lineage.

Adolescent↗

Rhabdomyolysis associated with Crohn's disease.

Three cases of Crohn's disease (CD) which showed an elevation of creatine phosphokinase (CPK) during the course were reported. In two cases, elevations of serum myoglobin and aldolase were also observed which indicated rhabdomyolysis. Rhabdomyolysis occurred unrelated to the activity of CD and it was asymptomatic. It was unable to identify an apparent known cause for rhabdomyolysis. All three cases were under elemental diet (ED) but the causality of ED for rhabdomyolysis was uncertain. So far as we know, there is no report on rhabdomyolysis during ED treatment and there are only two reports in which rhabdomyolysis was documented in CD. The latter was rhabdomyolysis due to electrolyte depletion secondary to malabsorption in CD which was not encountered in our cases. Our department dealt only three cases of CD and all of them had an elevation of CPK which had been measured as one of routine blood chemistry in our hospital. These observations led to a following conclusion that subclinical rhabdomyolysis may be one of extra-intestinal complications of CD.

Adolescent↗

Dietary risk factors of stroke and hypertension in Japan -- Part 1: Methodological assessment of urinalysis for dietary salt and protein intakes.

In our attempt to design a method which would be more reliable than dietary survey interviews when estimating salt and protein intakes in a population survey, a urinalysis-related study was done on volunteers. Urinary sodium (Na), urea nitrogen (UN) and inorganic sulfate (SO4), all indices of dietary salt, protein and sulfoamino acids, respectively, were confirmed to reflect the nutritional condition. Interaction between salt and protein was not observed at least at the dietary levels used in the present study (for salt, 0.33 and 0.1 g/kg body weight/day; for protein, 1.6 and 0.7 g/kg body weight/day). Excretion of components was delayed several days or more after dietary ingestion, and nutritional estimation by urinalysis, therefore, may not be so much affected by daily variables in the diet intake. Further, partial urine samples proved to have a highly significant correlation with 24-hour (hr) urine, as for urinary Na, potassium (K), SO4, UN and their creatinine (Cr) ratios, thus indicating the availability of partial urine samples as substitutes for 24-hr urine specimens. Thus, urinalysis is a more readily facilitated, more scientific and more quantitative method for epidemiological nutritional surveys.

Adult↗

Dietary risk factors of stroke and hypertension in Japan -- Part 2: Validity of urinalysis for dietary salt and protein intakes under a field condition.

Utility of urinalysis as a method for estimating dietary salt and protein intakes was examined in volunteers from farming and fishing villages in Japan and the data was compared to findings in a survey on diets. We found that partial urine samples and even a fasting single spot urine in the a.m. could serve as valid substitutes for 24-hour (hr) urine collections. Further, significant correlations were obtained between levels of salt in the diet estimated by survey interviews and urinary sodium (Na) and between interview-estimated dietary total or animal protein and urinary inorganic sulfate (SO4). In comparative studies between farming and fishing villages, almost the same findings, higher salt in a farming village and higher animal protein in a fishing village, were obtained in the urinalysis and the survey on diets. These findings clearly indicate that urinalysis, as a method for estimating dietary salt and protein intake in population surveys, has distinct advantages.

Adult↗

Dietary risk factors of stroke and hypertension in Japan -- Part 3: Comparative study on risk factors between farming and fishing villages in japan.

General medical examinations were performed in two rural areas of Shimane Prefecture in Japan, one was a farming village and the other a fishing village where incidences of death due to stroke differed, higher in the former and lower in the latter. Comparisons were made on salt and protein intake by analyzing the fasting single spot urine collected in the morning and by blood tests. Urine samples were analyzed for sodium (Na), potassium (K), urea nitrogen (UN), inorganic sulfate (SO4) and creatinine (Cr) and blood samples for cholesterol (Chl), triglyceride (TG), hematocrit (Ht) and hemoglobin (Hb). Blood pressure, Na/Cr, Na/K and Ht were higher in the farming village and K/Cr, UN/Cr, SO4/Cr, SO4/UN, Chl and TG were higher in the fishing village. These findings indicate the higher salt intake and lower intake of K, animal protein and fat in the farming village. This typical dietary pattern of the Japanese may explain the higher incidence of hypertension and stroke in the farming village.

Adult↗

Vectorcardiographical and pathological approach to the relationship between cardiac hypertrophy and coronary arteriosclerosis in spontaneously hypertensive rats (SHR).

To study the pathophysiology and the pathogenesis of hypertensive cardiac diseases such as cardiac hypertrophy and ischemic heart diseases, and to determine the relationship between these cardiopathies, spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) were used as models. Vectorcardiography was applied to the rat according to orthogonal Takayasu lead system and "vectorcardiography for small animals" with a good reproducibility was established. Characteristic vectorcardiogram (VCG) was obtained from 5-month-old SHR, compared with normotensive Wistar-Kyoto rats (WK). Left superior (posterior) deviation of QRS vector usually with ST-T changes was recognized as LVH (Left Ventricular Hypertrophy) pattern of SHR and such corresponded to the pathological findings of the increased heart weight and the increased weight and thickness of the left ventricular wall, and also to the high blood pressure. Macroscopical morphological features of the heart were also studied. Chest roentgenography showed and increased cardiothoracic ratio (CTR) and the protrusion of the left ventricular portion in the posteroanterior cardiac silhouette of SHR. The horizontal view of the chest, cross-sectioned by the apparatus of whole body autoradiography, PMV-cryomicrotome 450 MP, indicated the left anterior orientation of the interventricular septum in rats, as is the case in humans, and the clockwise rotation of the left ventricular cavity in SHR, compared with WK. The coronary arterial wall thickening with narrowed lumen was noted even in the prehypertensive 1-month-old SHR. Such correlated well with the wall thickening of the left ventricle. From these vectorcardiographical and morphological studies on SHR and SHRSP, genetic hypertension was ascertained to be significant not only for cardiac hypertrophy but for the coronary arterial wall thickening, both of which may also enhance the myocardial lesions in SHR, particularly in SHRSP.

Animals↗

Stroke-prone SHR (SHRSP) as models for clinical and epidemiological studies on hypertension-related cardiac diseases in humans.

Spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) were vectorcardiographically and pathologically studied for myocardial lesions with left ventricular hypertrophy, and findings were compared with those in normotensive Wistar-Kyoto rats (WK). Characteristic vectorcardiogram (VCG) in adult SHR was left superior (posterior) deviation of major QRS portion usually with ST-T changes, which corresponded to the pathological findings such as increased weight of the heart and the left ventricle. In old SHRSP, VCG showed deformity and deviation of QRS loop with prolonged P and QRS durations, and ST-T changes which corresponded to the pathological findings of myocardial degeneration or fibrosis with aggravated left ventricular hypertrophy. Such myocardial lesions were vectorcardiographically followed up in the ageing process and compared with findings in cases of induced, acute myocardial infarction. Vascular or tissue lesions of the brain, the kidney and the heart were clarified to be organ specific and to be related. Vector- or electrocardiogram are parameters for predicting cerebral stroke and/or ischemic heart diseases in humans. Primary prevention and appropriate therapy should be concomitantly considered.

Aging↗

Preservation of normal gas exchange with hemodilution in patients with pulmonary hypertension.

The relationship between the plasma colloid osmotic pressure/pulmonary capillary wedge pressure difference (PCOP-PCWP) and the development of gas exchange abnormalities was examined prior to, during, and after cardiac operations in 13 patients with pulmonary hypertension owing to mitral and/or aortic valvular disease. Alveolar-arterial oxygen tension gradient [P(A-a)DO2] and pulmonary shunt fraction (Qs/Qt) were used as indices of gas exchange impairment owing to accumulated lung water. During the baseline period, PCOP-PCWP was -8.5 +/- 2.6 mm Hg; P(A-a)DO2, 352.5 +/- 30.1 mm Hg; and Qs/Qt, 17.0% +/- 1.5%. There were no significant correlations between PCOP-PCWP and P(A-a)DO2 or Qs/Qt at any time during the study. Thus PCOP-PCWP does not predict susceptibility to lung water accumulation reliably in patients with pulmonary hypertension, and other protective factors may contribute to unimpaired gas exchange, even in the setting of profound hemodilution and low PCOP.

Adult↗