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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 685 records · Page 38Linked to original sources

[Subtotal cor triatrium with left partial anomalous pulmonary venous connection--successful correction in an infant].

This report concerns a 10-month-old infant with subtotal cor triatrium associated with left sided partial anomalous pulmonary venous connection to the innominate vein. In the operation, we found that the fossa ovalis existed between the right atrium and the accessory atrial chamber. We performed a radical operation which consisted of a resection of the intra-left-atrial diaphragma and a anastomosis of the vertical vein to the left atrium. His postoperative course was uneventful, and the result was satisfactory. We have presented and reviewed our case, and then discussed the embryogenesis and the hemodynamics. To our knowledge, our case represents the first successful surgical repair of this combination of defects in Japan.

Brachiocephalic Veins↗

Ipsilateral corticocortical projections of fibers which course within Probst's longitudinal bundle seen in the brains of mice with congenital absence of the corpus callosum: a study with the horseradish peroxidase technique.

In the brains of mice with congenital absence of the corpus callosum, Probst's longitudinal bundle is always present in both cerebral hemispheres. In this research, the ipsilateral corticocortical projections by the fibers in this bundle were studied by iontophoretical injections of horseradish peroxidase into different loci in the neocortex of acallosal mouse brains. Our results show that the 'intrinsic' association fibers seen in normal mice are preserved unchanged in acallosal mice and that in these mice, a considerable portion of the fibers arising from a particular cortical region and coursing in Probst's bundle terminate ipsilaterally in the same area as do the 'intrinsic' association fibers from that region. Furthermore, careful comparison of the labeling patterns in acallosal and normal mice revealed that ipsilaterally labeled cells in acallosal mice are distributed as in similarly injected normal mice. This fact strongly suggests that in spite of the presence of ipsilateral corticocortical projections by the fibers in Probst's bundle, the overall pattern of intrahemispheric connections in the neocortex of acallosal mice is not different from that of normal mice. Thus, from the present findings it can be concluded that in congenitally acallosal mouse brains, the ipsilateral corticocortical projections of fibers which arise from a given cortical region and course within Probst's longitudinal bundle are formed only in areas that also have the 'intrinsic' association projections from that region.

Agenesis of Corpus Callosum↗

Suppression in the expression of a male-specific cytochrome P450, P450-male: difference in the effect of chemical inducers on P450-male mRNA and protein in rat livers.

Hypophysectomy of male adult rats caused a 70% decrease in the hepatic level of mRNA hybridized to two specific oligonucleotide probes for the sequence of coding and 3'-noncoding regions of P450(M-1) (H. Yoshioka et al., (1987) J. Biol. Chem. 262, 1706-1711), which corresponds to P450-male. Treatment of hypophysectomized male and female rats with subcutaneous injection of human growth hormone twice a day for 7 days increased the mRNA to a level similar to that of normal male rats. In contrast, the mRNA was decreased by treatment with continuous infusion. These results correlated well with those on the amounts of P450-male protein, indicating that growth hormone regulates the hepatic level of P450-male protein mainly by acting at the pretranslational step. Treatment of adult male rats with phenobarbital (PB), dexamethasone (Dex), or 3-methylcholanthrene (MC) decreased the content of P450-male protein by 68, 36, and 46%, respectively. The content of P450-male protein was also decreased to 65% in Dex-treated hypophysectomized male rats, but was not changed by treatment of hypophysectomized male rats with PB or MC, suggesting that PB and MC decrease P450-male protein through a pituitary growth hormone-mediated process. However, the level of mRNA hybridizable to the P450-male oligonucleotide probe was not decreased, but rather it increased in PB- or Dex-treated hypophysectomized male rats. A similar inconsistent change in protein and mRNA was also observed in PB-treated normal rats. These results indicate that PB and Dex have an additional effect of increasing the hepatic level of the specific mRNA of P450-male/(M-1) or a closely related form. Noncoordinate changes in the level of P450-male protein and mRNA also suggest that the hepatic level of P450-male protein is regulated by plural mechanisms: pretranslational and translational regulation in which pituitary growth hormone and/or other endocrine factors are involved.

Animals↗

Thyroid hormone suppression of hepatic levels of phenobarbital-inducible P-450b and P-450e and other neonatal P-450s in hypophysectomized rats.

Mechanism of developmental suppression of cytochrome P-450 (P-450) in rat livers was studied using Western blots. The contents of phenobarbital (PB)-inducible P-450b and P-450e, expressed constitutively in livers, were higher in neonate than in adult rats. The contents were also 10 approximately 50 fold higher in hypophysectomized than in intact adult male rats. Administration of L-triiodothyronine (T3, 50 micrograms/kg) or human growth hormone (4 U/kg) reversed almost completely the increased amounts of P-450b and P-450e. T3-induced suppression was also observed on two other neonatal P-450s (P-450 6 beta-1 and P-448-H), which are expressed in neonatal periods in livers. The postnatal developmental profiles of hepatic P-450b were correlated inversely with that of serum free T3 level in rats reported (Walker et al. (1980) Pediat. Res. 14, 249). These results suggest, in addition to pituitary growth hormone (Yamazoe et al. (1987) J. Biol. Chem. 262, 7423), the possible involvement of T3 on the suppressive regulation of PB-inducible and other neonatal P-450s.

Animals↗

Cytochrome P450 in livers of diabetic rats: regulation by growth hormone and insulin.

The effects of pituitary and pancreatic hormones on the change in hepatic cytochrome P450s were studied in alloxan- or streptozotocin-induced male rats. In two major sex-specific forms, P450-male and P450(6 beta-1), the former was decreased in chronic (5 week) diabetes to only less than one-third of controls and the latter was also reduced in early (1 week) diabetes. In contrast, a main phenobarbital-inducible form, P450b, was enhanced 25- to 30-fold in these diabetic rats. 3-Methylcholanthrene-inducible P448H was also elevated 3-fold in alloxan-induced diabetes. These changes in hepatic contents of P450-male, P450-6 beta-1, and P450b, which are under the regulation of pituitary growth hormone, associated well with the reported results of time-dependent changes in growth hormone levels in diabetes (G.S. Tannenbaum (1981) Endocrinology 108, 76-82), suggesting that the change in growth hormone level is a factor responsible for alterations in hepatic cytochrome P450s. Normalizing effects of insulin on these forms were also studied. Treatment of diabetic rats with insulin reversed the decreased amounts of both P450-male protein and mRNA. Insulin also normalized hepatic contents of P450b, P4506 beta-1, and P448H. However, the treatment of hypophysectomized rats with insulin had no effect, and treatment of diabetic rats with growth hormone or a suppressing agent of somatostatin, cysteamine, showed trivial effects on P450-male and P450b. These results suggest that insulin does not act directly as a substitute of growth hormone, but exerts its effect indirectly through the normalization of a growth hormone-mediated process(es) in diabetic rats.

Alloxan↗

A histopathological study on the prognosis of childhood IgA nephropathy and glomerular basement membrane lesions.

Seventy-three patients with IgA nephropathy (IgAGN), under the age of 15 years at the time of the discovery of the disease, were investigated with respect to glomerular basement membrane (GBM) lesions. Irregular attenuation or widening of GBM, especially on the epithelial side, was observed in 28 cases (38%). These two changes are referred to as lysis of GBM and were considered to be the primary and specific changes among the GBM lesions in IgAGN. GBM thickening with layering of lamina densa was found in 37 of 73 cases (51%), but this change has been observed in other types of glomerular diseases. GBM lesions similar to those seen in IgAGN were also observed in Henoch-Schönlein purpura nephritis (HSPN) and poststreptococcal acute glomerulonephritis (PSAGN). Lysis of GBM was observed only in IgAGN, HSPN and PSAGN. Subepithelial and intramembranous deposits appeared to have an important role in the development of these GBM lesions. The presence of GBM lesions was correlated with a high incidence of cellular crescents but not with other clinical or light microscopic findings. The presence of these GBM lesions in IgAGN does not have a significant effect on the prognosis, at least in childhood. The affected GBM seemed to recover without leaving any significant residual damage in most cases. In the long-term prognosis of the disease non-immunological factors, such as ageing or hypertension, seem to be important.

Adolescent↗

Restriction fragment length polymorphisms on the q24-q28 region of X chromosome among Japanese population.

Restriction fragment length polymorphisms were studied among the Japanese population using 12 polymorphic DNA probes on the q24-q28 region of X chromosome. The frequency distribution for probes p22-33, p482.6a, p43-15, 52A, pPM101, cX33.2 and cpx234, was the same as that for Caucasians, and that for probes 4D-8 and St14-1 (MspI) was slightly different (p less than 0.05). However, it was quite different (p less than 0.01) for probes p114.12, St14-1 (TaqI), 36B-2 and MN12. Probe p114.12 showed no HindIII polymorphism for the Japanese people. On the contrary, probe MN12, which has a low PIC value (0.15) for Caucasians, was found to be useful for Japanese (PIC value = 0.50). These results suggest that 7 DNA probes (p482.6a, p43-15, 52A, St14-1, p114.12 (BclI), 36B-2 and MN12) are useful (PIC greater than 0.42) for linkage analysis of X-linked disease in Japan.

Blotting, Southern↗

Restriction fragment length polymorphisms of X chromosome among Japanese population.

Restriction fragment length polymorphisms were studied among the Japanese using 13 polymorphic DNA probes on the X chromosome. For 6 probes (pPA4B, cpX203, p58-1, pHPGK-7e, cpX289 and 7b) the allelic frequencies were the same as those for Caucasians, but they were quite different (p less than 0.01) for 4 probes (dic56, pOTC (MspI), pTAK8B and pXG-16 (HindIII)). No polymorphisms were observed for 4 probes (pG95 alpha 1-7dIII/RI (n (chromosome number studied) = 54), pXG-16 (TaqI) (n = 50, p8 (n = 108), and pXG-17 (n = 76). These results suggest that not a small number of DNA probes currently available are useless for linkage analysis in Japan.

DNA Probes↗

Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus.

The metabolism of glutathione and activities of its related enzymes were studied in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM). A decrease in the levels of the reduced form of glutathione and an increase in the levels of glutathione disulfide were found in erythrocytes of diabetics. To elucidate these changes in the levels of glutathione, synthetic and degradative processes were studied. The activity of gamma-glutamylcysteine synthetase was significantly lower in diabetics than in normal controls. The activity of glutathione synthetase of each group was the same. The rate of outward transport of glutathione disulfide in diabetics decreased to approximately 70% of that of normal controls. The activity of glutathione reductase decreased in diabetics. These data suggest that the decrease in the levels of reduced form of glutathione in erythrocytes of diabetics is brought about by impaired glutathione synthesis and that the increase in the levels of glutathione disulfide is brought about by the decreased transport activity of glutathione disulfide through the erythrocyte membrane together with a decrease in the activity of glutathione reductase. These data also suggest that the impairment of glutathione metabolism weakens the defense mechanism against oxidative stress in erythrocytes of diabetics.

Adult↗

Low dose 1-hexylcarbamoyl-5-fluorouracil (HCFU) recommended for cirrhotic patients with hepatocellular carcinoma.

The metabolism of 1-hexylcarbamoyl-5-fluorouracil (HCFU), a drug prescribed for treating patients with hepatocellular carcinoma (HCC), was studied in relation to liver function, with the objective of clarifying the occurrence of any adverse side-effects on the central nervous system. Twenty-five HCC patients were administered 3.4 mg/kg HCFU once orally, after which the blood levels of HCFU and its derivatives (5-FU, CPEFU, CPRFU, HHCFU, OHCFU and F-beta-alanine) were serially measured using high performance liquid chromatography. The area under the concentration curve (AUC) of HCFU in the group of ICG R15 greater than or equal to 30% (group 2) was 5.35 +/- 1.73 h.micrograms/ml, a value which was significantly higher than the 2.60 +/- 1.19 h.micrograms/ml recorded for the group of ICG R15 less than 30% (group 1) (P less than 0.001). The AUC of HCFU had a significant positive correlation with the value of ICG R15 (P = 0.002) or the serum total bilirubin (P = 0.0005). The AUC of 5-FU showed no difference between the two groups. The AUC of CPRFU in group 2 was 0.16 +/- 0.25 h.micrograms/ml, a value significantly lower than the 0.48 +/- 0.39 h.micrograms/ml in group 1 (P = 0.023). There was no correlation between the AUC of other derivatives and the markers of liver function. These data suggest that, in patients with advanced cirrhosis, the accumulation of HCFU is related to the occurrence of side-effects from the administered drug, ingested over a long-term period. Therefore, when HCFU is given to cirrhotic patients with both HCC and 30% or more ICG R15, a careful monitoring for side-effects is required.

Antineoplastic Agents↗

Freeze-mount microautoradiographic study in the mouse hippocampus after intravenous injection of tritiated 2-deoxyglucose and glucose.

Differences in the uptake of tracers from radioactive 2-deoxyglucose ([1,2-3H] and [2,6-3H]), and glucose ([1-3H], [3-3H]) into hippocampal regions were investigated by freeze-mount microautoradiography after 45 min for 2-deoxyglucose, and after 15 and 45 min for glucose. Silver grains were assessed quantitatively by an image analyser. (1) The radioactivity (silver grains/mm2) in the stratum lacunosum-moleculare of Ammon's horn from 2-deoxyglucose autoradiograms was significantly higher than that in other hippocampal regions (P less than 0.01), while lowest in the hilus fascia dentata (P less than 0.01). (2) Autoradiograms of [1-3H]glucose and 15 min of [3-3H]glucose showed the radioactivity in the dentate molecular layer to be significantly higher than that in other regions, excepting the stratum lacunosummoleculare (P less than 0.05). (3) The 2-deoxyglucose and 45-min glucose autoradiograms showed intensely labeled perikarya of pyramidal cells in the CA3a sector. (4) Radioactivity in the dentate granular layer from the 45-min autoradiogram of [3-3H]glucose was significantly higher than that in the molecular layer (P less than 0.05). The results imply that the metabolic fate of glucose, i.e. whether it is mainly used for energy production or amino acid synthesis, depends on each structure of the hippocampus.

Animals↗

Golgi study on the homozygote (Ml/Ml) of macular mutant mouse.

The macular mutant mouse shows X-linked recessive inheritance and its hemizygote (Ml/y) is considered to be an appropriate model of Menkes kinky hair disease (MKHD). In this study the homozygote (Ml/Ml) was bred by coupling CuCl2-treated Ml/y with Ml/+ and was clinically and neuropathologically examined. The Ml/Ml had white fur color and curly whiskers from day 3, showed ataxia and tonic seizure on day 8 and gradually lost weight after day 10. It died with severe emaciation around day 15. These clinical features were improved by CuCl2 injection. Quantitative analysis showed that the dendritic arborization of the pyramidal cell in the treated Ml/Ml was delayed on days 14, 20, 30, 45 and 90 in comparison with that of the age-matched +/y. In the cerebellum of the Ml/Ml on day 14, some of the Purkinje cells showed abnormal changes such as somal sprouts, spine-like structures on the surface of the soma and stem dendrites, thick stem dendrites, multiple focal swellings of the stem and distal dendrites, reduction in the size of dendritic trees and axonal focal swellings. These changes were gradually improved in the Ml/Ml with CuCl2 treatment after day 20, with the exception of the multiple focal swellings of the stem and distal dendrites. The dendritic focal swelling gradually decreased after day 45. These clinical and neuropathological features of the Ml/Ml are almost same as those of the Ml/y. In our mutant mouse, when the treated Ml/Ml is coupled with the treated Ml/y all offspring from the Ml/Ml are genetically Ml/y or Ml/Ml. Our study indicates that these fetal mice may be useful for studying the pathological and biochemical condition of prenatal MKHD.

Animals↗

Phosphorylation of casein components by tyrosine-specific protein kinases.

The phosphorylation of different caseins by a number of tyrosine-specific kinases has been studied. The different kinases showed a range of specificities, suggesting differences in recognition mechanisms. The site of phosphorylation of alpha s2-casein by one phosphorylase has been identified, and compared with analogous sites in other proteins.

Caseins↗

Role of growth hormone in modulating the constitutive and phenobarbital-induced levels of two P-450(6)beta (testosterone 6 beta-hydroxylase) mRNAs in rat livers.

The role of growth hormone in the expression of two forms of hepatic cytochrome P-450(P-450), P-450(6)beta-1(6 beta-3), and P-450(6)beta-4, was investigated using RNA blots. The level of P-450(6)beta-1(6 beta-3) mRNA was twenty times higher than that of P-450(6) beta-4 mRNAs in untreated male rat livers. The levels of P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs were increased two fold and three fold, respectively, by hypophysectomy of adult male rats. By intermittent injection of human growth hormone (hGH) into hypophysectomized male rats, both mRNAs were decreased to the level of normal rats, and almost disappeared after continuous infusion of hGH. In female rats, these two mRNAs were not detected, but were increased remarkably by hypophysectomy. The increases in these mRNAs were almost abolished after continuous infusion of hGH in hypophysectomized female rats. The effect of hGH on PB-mediated induction of P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs was also examined. The PB-mediated increases in P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs were higher in hypophysectomized male rats (2.5-fold and 10.9-fold, respectively) than in normal male rats (1.5-fold and 5.2-fold, respectively). Thus, the levels of P-450(6)beta-1(6-beta-3) and P-450(6)beta-4 mRNAs were 4.1-fold and 7.3-fold, respectively, higher in PB-induced hypophysectomized rats than in normal male rats. Concerning the postnatal developmental profiles, P-450(6)beta-1(6 beta-3) mRNA was detectable at neonate and reached a maximal level at around 17 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Reversal of hypersplenism following orthotopic liver transplantation.

The purpose of this study was to clarify the effect of orthotopic liver transplantation on hypersplenism. In a 1-year period from July 1, 1986 to June 30, 1987, 196 adult patients underwent 233 orthotopic liver transplantations. Of the 58 patients with hypersplenism who were analyzed in this study, hypersplenism was more commonly associated with postnecrotic cirrhosis than other kinds of liver disease (55.3% (47/85) vs. 14.5% (11/76); p less than 0.001). Postoperative platelet counts were statistically higher than preoperative values (p less than 0.05). The latest platelet counts were more than 100,000/mm3 in 53 patients (91.4%). Of the eight patients whose preoperative and postoperative spleen volumes could be compared, all showed the reduction in the spleen size (p less than 0.02). We conclude that orthotopic liver transplantation, which is a radical surgical procedure for portal hypertension, reverses hypersplenism.

Adult↗

Very long-chain fatty acids in erythrocyte membrane phospholipids in adrenoleukodystrophy.

Mass fragmentography was used to analyze the very long-chain fatty acid (VLCFA) composition of erythrocyte membrane phospholipids. The VLCFA content decreased in the order sphingomyelin (SM), phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The tetracosanoic acid (C24:0) and hexacosanoic acid (C26:0) content of both SM and PC in patients with adrenoleukodystrophy (ALD) were significantly higher than those in controls. The VLCFA content of PE was too small, in comparison with those of SM, to be accurately determined.

Adrenoleukodystrophy↗