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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 811 records · Page 45Linked to original sources

Effects of energy restriction on mouse mammary tumor virus mRNA levels in mammary glands and uterus and on uterine endometrial hyperplasia and pituitary histology in C3H/SHN F1 mice.

We investigated the effects of energy restriction on the pituitary-ovarian axis and on a hormone responsive gene, the mouse mammary tumor virus (MMTV). Female C3H/SHN F1-hybrid mice, known to display a high incidence of mammary tumors, ate an energy-restricted diet (48 kcal/wk) or a control diet (95 kcal/wk) beginning at the time of weaning. By 67 wk of age, 12 of 32 mice in the control group, but none of the 33 mice in the energy-restricted group, had developed mammary tumors. Six tumor-free mice from each group were studied in detail at 67 wk of age. All six tumor-free control mice, but none of the six energy-restricted mice, showed uterine endometrial hyperplasia at autopsy. Mice subjected to energy restriction did not display an estrous cycle. The average levels of MMTV mRNA in mammary glands and uteri were strongly reduced by energy restriction. MMTV mRNA levels in mammary glands from control mice were two orders of magnitude lower than those in mammary tumors. Energy restriction lowered the percentage of pituitary mammatropes and suppressed proliferation of mammatropes with advancing age. Energy restriction thus appeared to inhibit endometrial hyperplasia and to decrease MMTV production at the mRNA level in the mammary glands and in the uterus. These effects may be a consequence of hormonal changes originating at the pituitary-ovarian axis.

Animals↗

Interstitial deletion of the short arm of chromosome 4 in a boy with mild psychomotor retardation and dysmorphism.

A 17-month-old boy is reported with 46,XY,del(4) (p15.2p15.32). He had mild psychomotor retardation and multiple minor anomalies, without growth retardation or microcephaly, which differs from the classical 4p--syndrome (Wolf-Hirschhorn syndrome). The activity of dihydropteridine reductase, a genetic marker for chromosome 4p15.3, was half that in a normal control.

Chromosome Deletion↗

Carnitine deficiency in inherited organic acid disorders and Reye syndrome.

A large quantity of propionylcarnitine in the urine of patients with propionic acidemia and methylmalonic aciduria was demonstrated. The amount excreted depended on the administered L-carnitine dose from 25 to 75 mg/kg/day. A high level of propionylcarnitine was also detected in the amniotic fluid of fetuses at risk of methylmalonic aciduria. Glutaric aciduria type 1 was characterized by excessive urinary excretion of glutarylcarnitine. In a neonate with glutaric aciduria type 2, several specific acylcarnitines were detected in the urine. These included isovaleryl-, acetyl-, isobutyryl-, and butyrylcarnitine as major carnitine esters and glutaryl-, and octanoylcarnitine as minor components. However, the pattern of acylcarnitines excreted changed from isovalerylcarnitine (via leucine) to isobutyrylcarnitine (via valine) during early life. In patients diagnosed as Reye syndrome, tissue carnitine deficiency was not always recognized and no decrease in the free/total carnitine ratio was found in the liver or muscle. The clinical and pathophysiological manifestations seen in these disorders are considered to relate to mitochondrial activity. Therefore, it is necessary to measure acylcarnitine fractions in the urine in order to obtain more precise information about mitochondrial function because carnitine and acylcarnitine compounds may express the metabolic state of mitochondria.

Amino Acid Metabolism, Inborn Errors↗

Structure and pulmonary toxicity relationship on O,O-dimethyl S-alkyl phosphorothioate esters.

The structure-pulmonary toxicity relationship was investigated using three different O,O,S-trimethylphosphorothioate (OOS-TMP) analogues, which is known to induce a typical mortality pattern (delayed death) and pulmonary injury; O,O-dimethyl S-ethyl (OOS-DMEP), O,O-dimethyl S-propyl (OOS-DMPP), and O,O-dimethyl S-butyl (OOS-DMBP) phosphorothioates. The mortality pattern in rats dosed with OOS-DMEP was similar to the "delayed death" pattern: the LD50s in rats for OOS-DMEP decreased dramatically from more than 200 mg/kg within 24 hr to 41.1 (males) or 13.8 (females) mg/kg 7 days after treatment while the LD50s in rats for OOS-DMPP and OOS-DMBP did not. Histopathological examinations revealed that OOS-DMEP induced pulmonary oedema and bleeding at a dose of 1/2 LD50 by 72 hr after dosing while the other two compounds did not. Thus, it was concluded that OOS-DMEP induces pulmonary injury, thereby eliciting the "delayed death" mortality pattern.

Animals↗

Identification and purification of arginine deiminase that originated from Mycoplasma arginini.

A lymphocyte blastogenesis inhibitory factor, (LBIF), was purified from the culture supernatant of human histiocytic lymphoma U937 by fast protein liquid chromatography. In this study, we demonstrated, first, that LBIF originated from a mycoplasma, Mycoplasma arginini, infecting U937 cells, and second, that LBIF bore the arginine deiminase activity. The implication of in vivo immunosuppression induced by arginine-utilizing mycoplasma species is discussed.

Animals↗

The SLP1 gene of Saccharomyces cerevisiae is essential for vacuolar morphogenesis and function.

The SLP1 gene, which is involved in the expression of vacuolar functions in the yeast Saccharomyces cerevisiae (K. Kitamoto, K. Yoshizawa, Y. Ohsumi, and Y. Anraku, J. Bacteriol. 170:2687-2691, 1988), has been cloned from a yeast genomic library by complementation of the slp1-1 mutation. The isolated plasmid has a 7.8-kilobase BamHI-BamHI fragment that is sufficient to complement several characteristic phenotypes of the slp1-1 mutation. The fragment was integrated at the chromosomal SLP1 locus, indicating that it contains an authentic SLP1 gene. By DNA sequencing of the SLP1 gene, an open reading frame of 2,073 base pairs coding for a polypeptide of 691 amino acid residues (Mr, 79,270) was found. Gene disruption of the chromosomal SLP1 did not cause a lethal event. Vacuolar proteins in the delta slp1 mutant are not processed to vacuolar forms but remain in Golgi-modified forms. Carboxypeptidase Y in the delta slp1 mutant is localized mainly to the outsides of the cells. delta slp1 mutant cells have no prominent vacuolar structures but contain numerous vesicles in the cytoplasm, as seen by electron microscopy. Genetic and molecular biological analyses revealed that SLP1 is identical to VPS33, which is required for vacuolar protein sorting as reported by Robinson et al. (J. S. Robinson, D. J. Klionsky, L. M. Banta, and S. D. Emr, Mol. Cell. Biol. 8:4936-4948, 1988). These results indicate that the SLP1 (VPS33) gene is involved in the sorting of vacuolar proteins from the Golgi apparatus and their targeting to the vacuole and that it is required for the morphogenesis of vacuoles and subsequent expression of vacuolar functions.

Amino Acid Sequence↗

Effect of blood filling in intramyocardial vessels on coronary arterial inflow.

The influence of the filling condition of the unstressed volume (UV) of intramyocardial vessels on the diastolic coronary arterial pressure-flow relationship was analyzed. UV is defined as the blood volume at zero transmural pressure. In seven anesthetized, paced dogs with induced heart block, coronary artery inflow was occluded so that blood in the UV was displaced into the coronary vein by myocardial contraction. After pacing was turned off, coronary perfusion pressure was increased stepwise to seven target pressures (20-90 mmHg). After reperfusion, left anterior descending coronary arterial (LAD) flow reached an initial quasi-steady level, but great cardiac venous (GCV) flow was absent (UV-unfilled phase). With reappearance of the GCV flow (UV-filled phase), LAD flow decreased to a final steady level. Pressure-flow relationships during both phases were linear (r = 0.97-0.99). The inverse of the slope of the pressure-flow relationship during the UV-filled phase, 0.69 +/- 0.08 mmHg.min.ml-1, was significantly higher than that during the UV-unfilled phase, 0.55 +/- 0.06 mmHg.min.ml-1 (P less than 0.01), although the zero-flow pressure intercepts were similar (18.9 +/- 1.8 mmHg for UV filled vs. 19.9 +/- 2.2 for UV unfilled). These results indicate that diastolic coronary arterial inflow is impeded by a blood volume within intramyocardial vessels that exceeds the UV.

Animals↗

Decrease in hepatic mitochondrial redox state by massive infusion of citrate-phosphate-dextrose solution in jaundiced rabbits.

To clarify the mechanism of metabolic derangement by massive blood transfusion to the damaged liver, the changes in the hepatic mitochondrial redox state, as reflected in arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), were studied in jaundiced rabbits by infusion of massive citrate-phosphate-dextrose (CPD) solution. The jaundiced rabbits received common bile duct ligation (BDL group), and the sham group had a simple exploration of the bile duct. CPD solution was infused for 3 h at a rate of 9 ml/kg/h in each group. As metabolic parameters, blood gas, pyruvate, lactate, citrate and ketone body ratio were analyzed in the arterial blood. During the course, arterial ketone body ratio decreased significantly (p less than 0.01) in the BDL group with severe metabolic acidosis, while it was maintained at high value in the sham group with metabolic alkalosis. Organic acids were more highly accumulated in the BDL group than in the sham group. These results suggested a hepatodepressant effect of massive blood transfusion, especially in the damaged liver.

Acidosis↗

[In vitro metabolism of an antiallergic agent, emedastine difumarate, in rats and guinea pigs].

In order to clarify the interspecies differences in the metabolism of emedastine difumarate (KG-2413), in vitro metabolism was studied with liver preparations of rats and guinea pigs. The activities of hydroxylase, N-oxidase and N-demethylase, of emedastine were evaluated with liver 9000 x g supernatant and microsomes. As the results, the orders of activities were as follows; 5-hydroxylase greater than or equal to N-oxidase greater than 6-hydroxylase greater than N-demethylase in rats, and N-oxidase much greater than N-demethylase greater than 6-hydroxylase greater than 5-hydroxylase in guinea pigs. Emedastine N-oxide, little excreted into the urine of rats, was largely formed in vitro, so it was assumed that N-oxide reduction was important in vivo. The reductase activity of emedastine N-oxide was evaluated, and compared with N-oxidase activity of emedastine. In rats, the reductase activity was nearly equal to the N-oxidase activity, and relatively high even under aerobic conditions. On the other hand, in guinea pigs, the reductase activity was lower than the N-oxidase activity. It was considered that relative activities of the N-oxidation of tertiary amine in a 1,4-diazepine ring of emedastine and the reduction of N-oxide once formed were one of the factors of interspecies differences of metabolism of emedastine in rats and guinea pigs.

Animals↗

[Contamination of urban air in a snowy district with 1-nitropyrene and particulate matter during the winter].

Nitroarenes, potent rodent carcinogens, have attracted much attention as environmental contaminants. Recently, simultaneous exposure to dust have been found to potentiate tumorigenicity of nitroarenes in rats (14). We hypothesized that inhabitants of northwestern Japan may be exposed to such substances in winter. First, we sought to develop a sensitive yet time saving method to determine nitroarene concentrations in airborne particulate matter. The method developed used a high-performance liquid chromatograph equipped with a fluorescence detector. By on-column catalytic reduction, using silica coated with platinum and rhodium, 1-nitropyrene (1-NP), 1,3-dinitropyrene, 1,6-dinitropyrene, and 1,8-dinitropyrene were effectively reduced to their amino derivatives which were easily detectable with the fluorescence detector. The lowest detectable limits found using the present method were on the order of picograms for individual compounds. Subsequently, we sought to determine the concentrations of nitroarenes using the new method on airborne particulate matter during the period from November to April. Samples were collected at sampling sites on road with high-volume air samplers for 24 hours or 72 hours in four different rural areas in Iwate Prefecture. At one location in the city of Morioka, samples were collected at the height of 25 m from the ground. Among the four nitropyrenes mentioned above, only 1-NP was detected in the samples. The concentrations of 1-NP and airborne particulates changed significantly in all examined areas in parallel with the rise and fall of the frequencies of studded tire use. The highest 1-NP and airborne particulate concentrations were 1.210 pg/m3 and 1,291 micrograms/m3, respectively, being recorded at the busiest road in Kitakami. In contrast, the lowest values were 38 to 66 pg/m3 for 1-NP and 54 to 94 micrograms/m3 for airborne particulates in Morioka, being recorded in November and April, respectively. The mutagenicities of extracts of airborne particulate matter showed similar trends. Thus, exposure situations with high concentrations of dust and 1-NP were confirmed to occur in Iwate. Finally, the risk posed by 1-NP in airborne particulate matter was estimated using the equation proposed by Cuddihy and McClellan (37) and was found to range from 3.12 x 10(-2) to 24.2 x 10(-2) lung cancer/year/10(6) people. Although the estimated risk due to 1-NP is relatively small, further surveillance is highly recommended in those areas since heavy dust exposure also occurs there.

Air Pollutants↗

Probable assignment of the dihydropteridine reductase gene to 4p15.31.

We report the dihydropteridine reductase (DHPR) activity in cases with interstitial deletion of the short arm of chromosome 4. Case 1 with the segment 4p15.32-4p16 deleted has normal DHPR activity. Case 2 with 4p15.2-4p15.32 deleted has reduced DHPR activity, less than 50% of normal.

Chromosome Banding↗

Glutaric aciduria type II: autopsy study of a case with electron-transferring flavoprotein dehydrogenase deficiency.

An autopsy study of glutaric aciduria type II in a 62-day-old Japanese boy is presented. The diagnosis was made by analysis of organic acids in the urine. Immunoblot analysis of liver homogenate confirmed the diagnosis, revealing absence of electron-transferring flavoprotein dehydrogenase. The major findings were fatty changes of variable degree in many organs and tissues, the most severe being found in cardiac myocytes, hepatocytes, renal tubular epithelium, and skeletal muscle fibers. Other pertinent findings included multicystic and dysplastic kidney, pulmonary alveolar proteinosis, and spongiosis and gliosis of the spinal cord. The thymus was markedly depleted, and lymphocytes in the lymph nodes were mainly B cells. Although some of these changes may have been secondary to the sepsis and immunosuppression complicating 2 months of intensive care, the abnormal organic acid metabolism with severe acidosis may have been a significant contributing factor.

Acidosis↗

Pemphigus vulgaris associated with pregnancy. A case report from Japan.

We present a case of pemphigus vulgaris which developed during pregnancy. The newborn infant was normal. Bullous lesions were successfully treated by pulse therapy with high-dose corticosteroids. This is, to our knowledge, the first report in English from Japan describing pemphigus vulgaris associated with pregnancy.

Adult↗

[Biological properties of two newly established cell lines (RMUG-S, RMUG-L) from a human ovarian mucinous cystadenocarcinoma].

Two morphological different cell lines (RMUG-S and RMUG-L) have been established from a human ovarian mucinous cystadenocarcinoma. CA-125 and CEA were demonstrated in the patient's serum. PAS, Alcian blue and mucicarmine positive substances were observed in the original tumor and two cultured cells. The modal chromosomal numbers of RMUG-S and RMUG-L were stable in the hypodiploid and hyper-triploid ranges, respectively. Radioimmunoassay and immunocytochemical staining revealed that RMUG-S and RMUG-L mainly produced CA-125 and CEA, respectively. In CBA nude mouse, RMUG-S and RMUG-L cells mainly produced poorly-differentiated adenocarcinoma, but in mucinous cystadenocarcinoma was detected in part of the RMUG-L tumor.

Animals↗

[The significance of cerebral white matter lesions in vascular dementia--from psychiatric aspects].

The significance of cerebral white matter lesions in vascular dementia was mentioned, based on the findings of 50 autopsied cases at Yokuhukai Geriatric Hospital. Neuropathology of vascular dementia is classified to 5 types, i.e. 1) lacunar type, 2) cortical type, 3) cortico-white matter type, 4) white matter type, and 5) Binswanger type. Our findings on 50 patients revealed no lacunar type, cortical type in 8 cases, cortico-white matter type in 19, white matter type in 9, and Binswanger type in 14. The fact that 42 patients out of 50 showed some lesions involving the cerebral white matter suggested the important role of the white matter lesions in the pathogenesis of dementia of vascular type. Our cases also indicated that Binswanger type be commonly observed, although dementia of this type has been thought to be very rare since Binswanger (1894) and Alzheimer (1902) had reported similar patients. The patients with cerebral white matter lesions develop more marked dementia, especially of frontal and parieto-occipital type, than ones with cortical lesions, but the characteristics of symptoms of white matter and Binswanger type remain to be fully clarified.

Aged↗