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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 307 records · Page 17Linked to original sources
PubMed1992

[A case of primary intracranial malignant melanoma showing leptomeningeal dissemination].

A 28-year-old woman was hospitalized in drowsy state with signs of increased intracranial pressure. CT scans revealed diffuse increased density with marked enhancement in the subarachnoid space, as well as ventricular dilatation. V-P shunt operation was performed to control intracranial pressure. Repeated cytological examinations of CSF couldn't determine the tumor origin. CT scan of thoracic spine showed a cystic tumor in its dorsal aspect. T2-weighted MRI revealed multiple spotty low intensity, specific to melanin granules, throughout the whole spine. Her thoracic spine was explored, and the intradural tumor was partially removed. Histopathological examination revealed the tumor cell which had dark nucleus with conspicuous nucleolus and cytoplasmic granules. These findings were compatible with malignant melanoma. Her general condition were deteriorated progressively and she died about 5 months after her admission. Postmortum examination showed diffuse leptomeningeal invasion of dark tumor throughout the entire central nervous system, and metastasis to peritoneum and omentum via V-P shunt system. Histopathological examination proved the tumor to be malignant melanoma. Electrone microscopic examination also revealed melanosome in the cytoplasm. Primary intracranial malignant melanoma is divided in two groups, nodular type and leptomeningeal type. In the latter type, early diagnosis is very difficult, just as in our case, because only a little tissue specimen can be obtained. In a case of leptomenigeal carcinomatosis, possibility of primary malignant melanoma, though rare, should always be kept in mind, and specific staining such as Fontana-Masson's staining should be tried.

Adult↗
PubMed1992

ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B-cells.

Although closure of the ATP-sensitive K+ (K+ ATP) channel produced by glucose metabolism in the B-cell has been considered mediating the major signal for glucose-induced insulin release, evidences indicating the existence of the K+ ATP channel-independent, insulinotropic action of glucose have recently been accumulated. Namely, glucose stimulates insulin release by the B-cell with a full inhibition of the K+ ATP channel closure by diazoxide, a K+ ATP channel opener, provided cytosolic calcium is elevated. Glucose clearly elicits insulin release even if the K+ ATP channel is maximally inhibited by high concentration of sulfonylurea. In this case, glucose-induced insulin release is associated with net increase, not decrease, of K+ outflow, indicating glucose is opening K+ channels. Thus, closure of the K+ ATP channel is highly unlikely to be the mechanism responsible for the insulinotropic action of glucose under these conditions. The K+ ATP channel-independent glucose action is dependent upon physiological glucose concentration (2-30 mM) and the degree of cytosolic calcium elevation. The K+ ATP channel-independent, glucose-induced insulin release shows gradually increasing monophasic pattern which temporally resembles the second phase response of glucose-induced insulin release. The role of glucose metabolism in the K+ ATP channel-independent glucose action remains to be established. Glucose action at the B-cell can now be subdivided into two classes: one is the K+ ATP channel-dependent and the other is the K+ ATP channel-independent. The two branches may be mutually interrelated to cause normal, biphasic insulin secretion.

Adenosine Triphosphate↗
PubMed1992

Partial liver transplantation from living related donors.

Living related liver transplantation was performed in five cases between June 1989 and July 1991 at Shinshu University Hospital. All of the donors were fathers of the patients and blood type was identical in each case. All of them were discharged from the hospital 2 weeks after hepatectomy without any complications. They started to work 2 months after surgery. Four recipients are surviving but one died. Three are enjoying daily life 17 months after LT in case 1, 5 months after LT in case 4, and 4 months after LT in case 5. Case 2 is still in the hospital 14 months after LT. Advantages of LRLT we noted were (1) cases can be performed totally electively and allow full preparation for the family and the transplant team, (2) primary graft nonfunction has not been observed to date, and (3) 38 patients received the chance of liver transplantation in their own country, which under current legislation would not otherwise have been possible. Disadvantages of LRLT were (1) partial hepatectomy was performed in healthy persons, and (2) retransplantation is difficult.

Biliary Atresia↗
PubMed1992

[Unexpected air embolism during an aneurysmal operation in supine position--a case report and a speculation about its pathogenesis].

The occurrence of air embolism in supine position operation is extremely rare. We reported a case of air embolism during the operation of a ruptured middle cerebral artery aneurysm in supine position. A 58-year-old woman was admitted to our hospital in semicomatous state. A CT scan revealed diffuse subarachnoid hemorrhage. Cerebral angiogram showed a middle cerebral artery aneurysm. Massive pinkish foamy sputum and butterfly shadow on chest x-ray strongly suggested an association of neurogenic pulmonary edema (NPE). Barbiturate therapy and controlled ventilation with positive end-expiratory pressure (5cmH2O) were started. Her airway pressure was about 35cmH2O. Decrease of pinkish foamy sputum and an improvement of chest x-ray findings on the next day encouraged us to perform a clipping operation. Just before a clip application, air bubbles were observed to pass through the middle cerebral artery under the microscope. Subsequently cardiac standstill was brought out. Fortunately, she was resuscitated, and a clip application was finished. A postoperative CT scan revealed an infarction in the middle cerebral artery area. A postoperative cerebral angiogram showed occlusion of a temporal branch of the right middle cerebral artery, P1 portion of the left posterior cerebral artery, and the right superior cerebellar artery. We speculated that high endotracheal pressure brought out pulmonary alveolar rupture, and in spite of supine position operation massive air, which flowed into systemic circulation from ruptured alveoli, caused cerebral infarction and cardiac arrest. We consider that unrecognized air embolism might be the one of the factors influencing the prognosis of severe subarachnoid hemorrhage, especially in the cases associated with neurogenic pulmonary edema.

Embolism, Air↗
PubMed1991

Effect of active vitamin D3 on the levels of NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein.

Effect of 1 alpha-OH-vitamin D3 (1 alpha-OH-D3) and 1,25-(OH)2-vitamin D3 (1,25-(OH)2-dihydroxycholecalciferol)(1,25-(OH)2-D3) on the levels of NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) was studied in rats and cultured dRLh cells. Deprivation of rats from vitamin D decreased the activity of cytosolic NADPH-dependent T3 binding in rat kidney and liver. The decrease was restored by administration of 1 alpha-OH-D3(0.2 micrograms/kg). The activity of cytosolic NADPH-dependent T3 binding was increased in the dRLh cells by addition of 1,25-(OH)2-D3 to the culture medium. The maximal binding capacity (MBC) was increased by 1,25-(OH)2-D3 without changes in the affinity constant. These results suggested that active vitamin D3 plays an important role in the regulation of cellular T3 translocation through increasing the binding capacity of NADPH-dependent cytosolic T3-binding protein.

Animals↗
PubMed1991

Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism.

BACKGROUND: Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS: The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS: The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.

Adolescent↗
PubMed1991

Purification of cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding protein(CTBP) which regulates nuclear T3 translocation.

The NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding protein(CTBP) was purified from rat kidney using Mono Q-Sepharose, Red sepharose and T3 affinity chromatography. CTBP which was partially purified by Red Sepharose column chromatography was adsorbed to T3 affinity column in the presence of 50 uM NADPH. The CTBP was eluted from the gel with the buffer which did not contain NADPH. One molecule of the purified CTBP(58 kDa) bound one molecule of T3 with 2.44 x 10(9) M-1 of affinity constant. The purified CTBP was activated not only by NADPH but also by NADP in the presence of dithiothreitol. The NADPH-activated form did not transfer T3 to nuclei, whereas NADP transformed the NADPH-activated CTBP to active form which was able to transfer T3 to nuclei. These results suggested that CTBP-dependent transport of T3 to nucleus is controlled by NADPH and NADP.

Animals↗
PubMed1991

The observation of endothelial cells in vein grafts by the en face silver staining method.

The introduction of en face silver staining to microsurgery has provided useful, detailed information about endothelial cells with regard to their size, shape, and number. With this staining method, endothelial cells of rat vein grafts have been morphologically investigated following division of the site of observation into three areas: the recipient artery, the proximal part of the vein graft, and the midportion of the vein graft. The results show that the arterial endothelial cells are small and spindle-shaped, whereas the cells in the proximal vein graft location are larger. Finally, large, rounded endothelial cells are seen in the midportion of the graft. These results are quantitated through a computerized graphic analysis system, which provides estimations of the cell size, Feret's diameters, and irregularities in the cell borders. The combination of en face silver staining and computerized graphic analysis has been especially useful for comparing minute changes that occur in recovering/regenerating endothelial cells.

Animals↗
PubMed1991

Cellular binding proteins of thyroid hormones.

Cellular binding proteins of thyroid hormones are present in the cell nucleus, cytosol, cell membrane, and mitochondria. While nuclear binding is proven to mediate hormone action, the exact roles of the other binding sites remain to be established. Nuclear receptor associates with DNA, core histone, and nuclear matrix and preferentially distributes in transcriptionally active chromatin due to interaction with H1 histone. Of particular importance is the binding of nuclear receptor to specific DNA sequences of target genes, termed thyroid-responsive elements. The binding is stabilized by non-receptor nuclear protein. Upon binding thyroid hormone, nuclear receptor is activated through alterations in the steric configuration, leading to changes in the rate of transcription of the target genes. Multiple nuclear receptor forms exist with likely distinct functional roles. Cytosolic thyroid hormone binding proteins are also heterogeneous. One form is under the control of cell metabolism (NADP and NADPH) and it may have a role in transport of the hormone to mitochondria and nucleus. Membrane-linked thyroid hormone binding proteins may have dual functional roles: one is to mediate hormone action and the other is to support active uptake of hormones by cells. Mitochondrial function may be regulated by thyroid hormone through mitochondrial binding sites in cooperation with nuclear receptor-mediated pathway. Further studies are required to elucidate the exact functional roles of non nuclear thyroid hormone binding proteins.

Animals↗
PubMed1991

Adolescent pregnancy and growth of progeny in rats.

The relationship between very young adolescent mothers and their progeny was studied in terms of fetal development and pup growth. The mothers used in this study had just attained puberty and were still growing; their body weight was about half that of normal full-grown adult females. Still, they were able to conceive and to maintain gestation but growth and skeletal development of their fetuses was significantly retarded. Adolescent dams took in more food during gestation, and about 60% of the intake was used to meet their own growth and development need rather than that of their progeny. During lactation, adolescent dams took in about the same amount of food as did the control, but the pups they were suckling gained significantly less weight than did pups suckled by the control. Retardation of growth and development during gestation, and the continued retardation during lactation, can best be explained by an overall nutritional competition between adolescent dams and their offspring.

Animals↗
PubMed1991

Mass screening in Japan increased the detection of infants with neuroblastoma without a decrease in cases in older children.

Analysis of data from the Kanto-Ko-Shin-Etsu Branch of the Japan Children's Cancer Registry revealed that mass screening for neuroblastoma increased the detection of cases in infants younger than 1 year from about 25% before screening to about 50%, and the percentage of neuroblastomas among all pediatric cancers almost doubled, from approximately 10% to 19.3%. However, when the cases found on screening were subtracted, the numbers after the onset of mass screening were similar to those before screening. It is likely that neuroblastoma mass screening has identified a unique type of tumor, which may not be recognized without mass screening, rather than that it has contributed to the earlier diagnosis of tumors in older children.

Age Factors↗
PubMed1991

Prader-Willi syndrome with del(15)(q11,q13) associated with hepatoblastoma.

A case of Prader-Willi syndrome who later developed hepatoblastoma is reported. Prader-Willi syndrome was suspected because of hypotonia, hypopigmentation, and undescended testes when he was a newborn infant. The diagnosis was confirmed by chromosome analysis, which showed 46XY del(15)(q11, q13). When he was 1 year 4 months old, a liver tumor and high serum AFP were found. At operation a large tumor arising from the caudate lobe was found and the tumor was totally resected. After completion of the hepatectomy, he developed circulatory collapse of unknown cause and died shortly after the operation. Histopathologic examination revealed that the tumor was composed of two components, well differentiated cells and poorly differentiated cells. The well differentiated part did not dominate the poorly differentiated part, so it was diagnosed as poorly differentiated hepatoblastoma. This is the first reported case of Prader-Willi syndrome with a pediatric malignant tumor.

Carcinoma, Hepatocellular↗
PubMed1991

Purification and characterization of thyroid hormone-responsive rat hepatic proteins.

Bernal et al. identified two proteins in rat hepatic nuclear extract, t- and n-proteins, that were enriched by thyroidectomy or T3 treatment, respectively. We purified these proteins, raised monospecific antibodies, and characterized them by Western blotting. Anti-n and anti-t-protein antibodies did not recognize t- and n-proteins, respectively. The n-protein was present in nuclear and cytosolic fractions, was present at low levels in the microsomal fraction, and was absent in the mitochondrial fraction of rat liver. The t-protein was more abundant in mitochondrial and microsomal fractions than in the nuclear fraction. The t-protein had the same molecular mass and shared immunological properties with peroxisomal enoyl-coenzyme-A (CoA) hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. The total cellular amount of n-protein increased 12 h after the administration of 1 microgram T3/100 g BW to thyroidectomized rats. Induction was obvious at 0.1 microgram T3/100 g BW after 24 h. Maximal induction was observed at 0.3 microgram T3/100 g BW. The n-protein was induced when thyroidectomized rat liver was perfused with 10(-7) M T3 for 6 h, excluding the possibility that the effect of T3 was mediated by an extrahepatic factor. The n-protein was detected in liver and brain, but not in kidney, heart, testis, or spleen. However, the amount of n-protein in brain was not thyroid hormone dependent. Hepatic n-protein does not correspond to any other T3-responsive protein in terms of its molecular mass and intracellular localization and may be a novel T3-responsive protein.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1991

A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein (CTBP; 5.1S) in rat liver: a comparison with 4.7S NADPH-dependent CTBP.

A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) was purified by sequential fractionation of rat liver cytosol on Q-Sepharose, phenyl-Sepharose, red-Sepharose, and polyacrylamide gel electrophoresis under nondenaturing conditions. The CTBP had a sedimentation coefficient of 5.1S, a Stokes' radius of 35 A, and a calculated mol wt of 76,000. The apparently homogenous protein consisted of a dimer of a polypeptide chain with a mol wt of 38,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NADPH increased both the affinity and maximal binding capacity for T3 in the 5.1S CTBP. The maximal activity to bind T3 was obtained by 3.0 x 10(-8) M NADPH. The calculated maximal affinity constant was 2.4 x 10(9) M-1, and the maximal binding capacity was 21,000 pmol T3/mg 5.1S CTBP. The order of affinity of iodothyronine analogs to the 5.1S CTBP was as follows: D-T3 greater than L-T3 greater than L-T4 greater than triiodothyroacetic acid. The optimal pH for T3 binding was 7.2-7.5. Ca2+, Mg2+, and Mn2+ (0.1-10 mM) did not influence T3 binding to CTBP. Zn2+ (1.0 mM), however, inhibited the binding. These results suggested that 5.1S NADPH-dependent CTBP, which is distinct from 4.7S CTBP that had been purified in our laboratory from rat kidney, is present in rat liver.

Animals↗
PubMed1991

Ontogenesis of the high affinity NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein in rat.

Studies were undertaken to define the concentration of the high affinity NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) in various tissues of adult rats and in those of developing rats. The maximal binding capacity (MBC) for T3 binding was calculated from the data obtained by Scatchard analysis of T3 binding to the charcoal-extracted cytosol in the presence of 50 microM NADPH. There were no significant differences in the affinity constant among various tissues, whereas the MBC was different among tissues in adult rats. When the levels of MBC were expressed by moles/DNA concentration, the order was as follows; kidney greater than heart greater than or equal to cerebrum greater than or equal to liver much greater than testis greater than cerebellum greater than spleen. The CTBP was not detected before birth in liver, heart, and spleen. The CTBP in these tissues emerged 5 days after the birth, and increased during 6 weeks after the birth. The CTBP in kidney was not detected before birth but was detected at the time of birth. The level of MBC in kidney increased during 3 weeks after the birth. In contrast, the CTBP was detected 5 days before birth, and the level of MBC increased at the time of birth both in cerebrum and cerebellum. The MBC in cerebrum gradually decreased after birth, but began to increase again 2 weeks after the birth. The level of MBC in cerebellum did not increase again. These results suggested that the target tissues of thyroid hormone are enriched with NADPH-dependent CTBP, and that the changes in the concentration of the CTBP are related to the growth of tissues. It was speculated that the CTBP has a specific function in cerebrum at the time of birth although the action of the CTBP is not certain.

Animals↗
PubMed1991

Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) regulation of insulin receptor function: phosphorylation of insulin receptor with A kinase decreases the insulin binding activity.

The effect of phosphorylation of insulin receptor with adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) on its insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro. A 95 KDa protein was phosphorylated by stimulation of insulin receptor kinase. This protein was also phosphorylated by A kinase. Analysis of phosphoamino acid showed that tyrosine residue(s) was phosphorylated by activation of insulin receptor kinase, whereas phosphoserine and phosphothreonine were dominantly generated by activation of A kinase. [125I] Iodoinsulin binding activity was decreased by prior phosphorylation of the receptor with A kinase. Scatchard analysis showed that the affinity for insulin was decreased by the phosphorylation with A kinase. Although the maximal activity of insulin receptor kinase was not affected by phosphorylation with A kinase, the insulin concentration which induced half maximal activity (ED50) of the receptor kinase was increased by the phosphorylation with A kinase. These results suggested that counter regulatory hormones whose actions are mediated by the generation of adenosine 3',5'-cyclic monophosphate regulate the insulin binding to the alpha subunit through phosphorylation of the beta subunit of insulin receptor.

Adenosine Triphosphate↗
PubMed1991

Evidence for the presence of protein kinases which stimulate phosphorylation of c-erb A protein in rat kidney nuclei.

Protein kinases were separated from rat kidney nuclear extract by hydroxylapatite column chromatography. Five (I-V) different protein kinases were isolated when histone was used as a substrate. Two (I and III) of them stimulated phosphorylation of c-erb A-beta protein (50 kDa) expressed in Escherichia coli. The c-erb A product has an activity of high affinity T3 binding. One (I) of the kinases was dependent on cyclic adenosine 3',5'-monophosphate (cyclic AMP). The other kinase (III) was not dependent on cyclic nucleotides. The latter kinase was eluted from hydroxylapatite column with 0.05 M PO4 at pH 7.4. The sedimentation coefficient(s) estimated by continuous sucrose density gradient centrifugation was approximately 6.0 Km values for ATP were estimated by double reciprocal analyses, which gave 110.0 microM in the protein kinase I (in the presence of 10(-6) M cyclic AMP) and 25 microM in the protein kinase III, respectively. The data showed that 1.0 mol phosphate was incorporated into 80 mol of c-erb A protein (50 kDa) either in the presence of protein kinase I (with 10(-6) M cyclic AMP) or in the presence of protein kinase III. These results suggested that there are protein kinases for c-erb A protein, whose functional properties are similar to those of nuclear T3 receptor, in rat kidney nuclei.

Adenosine Triphosphate↗