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Biomedical subjects

Y Miyoshi

Publications and source records attributed to Y Miyoshi.

At least 145 records · Page 8Linked to original sources
PubMed1995

Functional properties of a mutant T3 receptor beta (R338W) identified in a subject with pituitary resistance to thyroid hormone.

Previously, we identified a point mutation of the T3 receptor (TR) beta gene (R338W) in a patient with pituitary resistance to thyroid hormone (PRTH). The mutation existed in one of two hot spot areas in TRbeta gene where clusters of mutations have been found in subjects with generalized resistance to thyroid hormone (GRTH). Interestingly, R338W induces the phenotypical features responsible for PRTH. In the present study, we examined the functional properties of R338W in comparison with those of a GRTH-mutant, K443E. The levels of thyroid hormones and inappropriately elevated TSH (SITSH) were similar between subjects with K443E and R338W. Transcriptional activities and dominant negatives potencies were measured by CAT assay in CV1 cells transfected with each mutant TRbeta1 or along with wild-type TR. When a reporter gene containing T3-responsive elements (TRE), TRE-pal2, DR4 or myosin heavy chain alpha subunit, was used, transcriptional activation induced by R338W was higher than that by K443E. At 50 nM T3, K443E decreased the transcriptional activity of wild-type TRbeta1 on TRE-pal2 by 31.5%, while R338W reduced by 13.6% (n = 15, P < 0.05). Co-expression of retinoid X receptor (RXR) alpha increased transcriptional activity of R338W and K443E, but not of wild-type TRbeta1. Dominant negative activity on TRE-TSHalpha subunit of R338W was milder than that of K443E. When T3-binding activities of mutant TRbeta1s expressed in the cells were assayed under the same cell conditions for CAT assay, both mutant TRbeta1 showed remarkably reduced activity with no difference between the two. Gel mobility shift assay using TRE-DR4 showed poor homodimer formation of R338W. Heterodimerization with RXRalpha was similar between R338W, K443E and wild-type TRbeta1. The result of the present study suggested that R338W had relatively mild transcriptional and dominant negative activities on several TREs including TRE-TSHalpha subunit. We also showed poor homodimerization of R338W, which might be related to its weak dominant negative potency.

Adult↗
PubMed1995

Neovascularization of rat fetal neocortical grafts transplanted into a previously prepared cavity in the cerebral cortex: a three-dimensional morphological study using the scanning electron microscope.

Neovascularization within syngeneic rat fetal neocortical grafts transplanted into a previously prepared cavity in the cerebral cortex was studied 1 to 3 months after transplantation, utilizing scanning electron microscopy of vascular corrosion casts. The grafts were easily identified and the outer surface of the grafts, especially at the host-graft interface, was surrounded by large regenerated vessels of leptomeninges and connective tissue (e.g. dura). Large vessels originating from the choroid plexus also coated the grafts in animals whose lateral ventricles had been opened at the time of cavitation. These large regenerated vessels were mainly observed on the surface of the grafts, and they ramified markedly to form capillary networks in the vicinity of the host-graft interface. Occasionally several relatively large regenerated vessels were noted to extend into the grafts, and to ramify and connect with graft capillary networks having the same features as that of the host brain. Moreover, direct vascular connections between host capillaries and those within the grafts were observed. In some animals, arteries and arterioles which fed the grafts were identified in the perimeter of the grafts with their characteristic morphology. The interior microvasculature structure of the grafts was largely composed of the capillary network of graft origin, and of several relatively large penetrating vessels originating from the regenerated leptomeningeal vessels or the vessels of the choroid plexus. The present study demonstrated that the blood supply to the solid grafts transplanted into the previously prepared cavities originated primarily from the regenerated host vessels. These host vessels perfused the intrinsic graft vessels via new anastomoses which formed predominantly at the host-graft interface.

Animals↗
PubMed1995

Three-dimensional morphological study of microvascular regeneration in cavity wall of the rat cerebral cortex using the scanning electron microscope: implications for delayed neural grafting into brain cavities.

The present study was carried out to quantify the subsequent vascular regeneration around a lesion cavity made in the rat cerebral cortex and to decide the origin of the regenerated microvessels. A quantitative study utilizing computerized image analysis after microvascular perfusion with India ink indicated approximately 25 and 160% increase of the vascular density adjacent to the cavity compared to the contralateral cortex at 4 and 21 days, respectively, after lesioning. The microvasculature around the cavity was also evaluated by scanning electron microscopy of vascular corrosion casts. Newly formed leptomeningeal vessels began to grow down toward the floor of the cavity 4 days after lesioning and nearly covered the walls of the cavity 21 days after lesioning. A neovascular network of leptomeninges and connective tissue (e.g., dura) was formed as a roof over the cavity. Numerous branches of these newly formed vessels and prominent anastomoses with the capillary network in the walls and floor of the cavity were observed. Newly formed vessels also originated from the choroid plexus in cases where the lateral ventricle had been opened at the time of lesioning. These results document the plasticity of the vascular system in the cerebral cortex after a mechanical injury. The regenerated vascular network may offer a suitable condition for survival of transplanted tissues.

Animals↗
PubMed1995

[Association of chronic neutrophilic leukemia and myeloma with fibrillar inclusions in granulocytes].

A 57 year-old-female was incidentally found to have leukocytosis in September 1988. Physical examination revealed anemia and marked hepatosplenomegaly. Her WBC count was 33,400/microliters with 95% mature neutrophils showing toxic granules. Her neutrophil alkaline phosphatase score was 482, and serum VB12 14,600 pg/ml. Serum immunoglobulin concentrations were 582 mg/dl for IgG, 3,628 mg/dl for IgA and 48 mg/dl for IgM. IgA was determined as monoclonal origin of lambda type. Bone marrow aspiration revealed a hypercellular marrow with active granulocytopoiesis and increased plasma cells. Cytogenetic study revealed normal karyotype. The bcr rearrangement was negative for bone marrow cells. An electronmicroscopy demonstrated fibrillar inclusions in granulocytes. We diagnosed this case as a chronic neutrophilic leukemia (CNL) associated with multiple myeloma. She was treated with a course of low dose busulfan without beneficial response. She was admitted for development of huge subcutaneous hematoma of left waist in October 1990. Laboratory findings were: Hb 7.0 g/dl, WBC 55, 300/microliters, Platelets 3.3 x 10(4)/microliters, and IgA 6,607 mg/dl. She required frequent transfusions. She died of pneumonia in July 1991. The peculiar fibrillar inclusions with CNL has not been reported so far. The origin and significance of such structure remains uncertain.

Female↗
PubMed1994

Effect of host age upon the degree of nigrostriatal dopaminergic system recovery following cografts of adrenal medulla and pretransected peripheral nerve.

Accumulation of nerve growth factor (NGF) has been reported to occur at the distal stump of pretransected peripheral nerve. We performed adrenal medullary grafts or cografts of adrenal medulla and distal stump of pretransected peripheral nerve into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated young or aging mice. We subsequently compared the survivability of chromaffin cells and the degree of host dopaminergic (DA) fiber recovery in relation to host age. In both young and aging hosts, adrenal medullary chromaffin cells cografted with pretransected peripheral nerve survived better than those in adrenal grafts alone. Host DA fiber recovery, however, showed less recovery and more restriction around the grafted site in aging compared with young hosts. We conclude that pretransected peripheral nerve can enhance the survivability of cografted chromaffin cells both in young and in aging hosts, but that DA fiber recovery is more limited in aging hosts compared to young hosts.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Central terminations of low-threshold mechanoreceptive afferents in the trigeminal nuclei interpolaris and caudalis of the cat.

Previous studies indicate that vibrissa, nonvibrissa, guard hair, hairy skin, and periodontal ligament afferents give rise to morphologically distinct terminal arbors in the trigeminal nuclei principalis (Vp) and oralis (Vo) in the cat. The present study describes the extent to which morphological and functional relationships exist in the nuclei interpolaris (Vi) and caudalis (Vc). Twenty-two fibers were physiologically characterized and stained by intra-axonal HRP injection techniques. The fast adapting (FA) vibrissa (VF) afferents gave rise to compact and circumscribed arbors in Vi and Vc. These tended to be larger in Vc than in Vi. The slowly adapting (SA) vibrissa (VS) afferents in Vi and Vc had more widespread and larger arbors than those of the VF afferents. The VS arbors in Vc tended to be larger and less circular than those in Vi. Guard hair (GH) afferents gave rise to circumscribed arbors in both nuclei, but those in Vc tended to have larger and more circular arbors than those in Vi. Down hair (DH) afferents gave rise to small, circumscribed arbors or a few distinct patches of boutons within a small area in Vi; arbors in Vc were less extensive and "stringy." Unlike other afferents, DH arbors were larger in Vi than in Vc, but smaller than those of GH afferents in either nuclei. The SA hairy skin (SS) afferents had arbors that were widespread with a few distinct patches of boutons; the arbors in Vc were larger than those in Vi. The arbors of SS afferents were smaller than those of VS and GH afferents in both nuclei. Like GH afferents, FA periodontal ligament (PF) afferents gave rise to large and circumscribed arbors in Vi, although the arbors in Vc were smaller and less dense. The present study demonstrated significant functional and morphological relationships for primary afferents in Vi and Vc, thus suggesting that sensory information from each of the distinct fiber or functional classes is processed in a characteristic manner in the individual nuclei.

Afferent Pathways↗
PubMed1994

Germ-line and somatic mutations of the APC gene in patients with Turcot syndrome and analysis of APC mutations in brain tumors.

The Turcot syndrome (TS) is a rare, probably autosomal recessive, disorder characterized by development of primary neuroepithelial tumors of the central nervous system (CNS) and numerous adenomatous colorectal polyps. To examine the possible involvement of mutations of the APC gene, which is responsible for familial adenomatous polyposis (FAP), in Turcot syndrome, we examined DNAs from TS patients for alterations in this gene by means of ribonuclease protection analysis. Germ-line APC mutations were detected in each of three unrelated cases of TS, and additional (somatic) mutations were observed in colonic adenomas that had developed in one of these patients. However, no somatic mutations in APC were found among 91 neuroepithelial tumors (medulloblastoma, glioblastoma, astrocytoma, and oligodendroglioma), whether sporadic or associated with TS. These results suggest that the APC gene is associated with pathogenesis of one feature of TS, but that at least one other gene is responsible for the genesis of neuroepithelial tumors in the CNS.

Adenomatous Polyposis Coli↗
PubMed1994

Efficacy of pretransection of peripheral nerve for promoting the survival of cografted chromaffin cells and recovery of host dopaminergic fibers in animal models of Parkinson's disease.

Nerve growth factor (NGF) concentration in the distal stump of the transected peripheral nerve has been shown to increase more than 20 times one day after transection. We performed adrenal medullary alone grafts or cografts of adrenal medulla and acutely transected or pretransected (24 h before) sciatic nerve into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and compared the survival of chromaffin cells and the recovery of the host-intrinsic dopaminergic fibers using tyrosine hydroxylase immunocytochemistry and high-performance liquid chromatography. We also performed peripheral nerve alone grafting (acutely transected or pretransected) for comparison. Adrenal medullary chromaffin cells cografted with pretransected sciatic nerve survived better than those in adrenal grafts alone or those cografted with acutely transected sciatic nerve. Host dopaminergic fiber recovery was also most prominent in mice cografted with pretransected peripheral nerve. Animals receiving grafts of peripheral nerve alone showed limited recovery of host dopaminergic fibers and the degree of recovery was lower than that of animals receiving cografts of adrenal medulla with pretransected peripheral nerve. We conclude that pretransected peripheral nerve enhanced the survival of cografted chromaffin cells and this increased survival led to promote the recovery of host-intrinsic dopaminergic fibers. This grafting procedure might be promising in application to patients with Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

3,5,3'-Triiodothyronine stimulates retinoic acid-induced differentiation in HL-60 cells.

The human acute promyelocytic leukemia (APL) cell line HL-60 differentiates to functionally mature granulocytes by incubation with all-trans-retinoic acid (RA). Since T3 and RA are important in cell differentiation and development, and since their receptors are highly homological, we investigated the T3 effects on RA-induced HL-60 cell differentiation. Although T3 alone did not induce cell differentiation, RA-mediated differentiation was significantly enhanced in the presence of 10(-7) M T3. This effect of T3 was considered to be mediated, at least in part, by increased intracellular cAMP, since the phosphodiesterase inhibitor enhanced, and the protein kinase A antagonist partially blocked, T3 potentiation. When HL-60 cells were pretreated with RA for 20 h, T3 alone stimulated the cell differentiation. The time-course study showed that incubation with RA for 12 h was necessary for HL-60 cells to be primed to respond to T3 for differentiation. The present finding that T3 potentiates RA-induced HL-60 cell differentiation may raise the possibility that T3 supplement increases clinical remission in APL patients who are treated with RA.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Alcohol intake and serum lipids in a Japanese population.

BACKGROUND: Previous epidemiological and clinical studies have shown that alcohol, which increases high density lipoprotein (HDL) cholesterol levels, has an anti-atherogenic effect. But data on the effects of alcohol on low density lipoprotein (LDL) cholesterol are scarce. In this paper a cross-sectional study on the associations of alcohol in graded doses with serum lipids in a Japanese population is presented. METHODS: The daily alcohol intake of 832 Japanese men aged 35-59 was determined and the subjects were divided into five categories according to their daily alcohol consumption. The associations of alcohol intake and the kind of alcoholic beverage with serum lipids were determined by multiple regression analyses taking into consideration the differences of other confounding factors, i.e. age, body mass index (BMI) and smoking. RESULTS: Serum triglycerides and HDL-cholesterol were higher (P < 0.001) with higher alcohol intake while LDL-cholesterol was lower (P < 0.01). In multiple regression analysis, after adjusting for age, BMI and number of cigarettes smoked per day, HDL-cholesterol and the ratio of HDL-cholesterol to LDL-cholesterol were found to have a significant positive relationship with daily alcohol consumption (P < 0.001) and LDL-cholesterol to have a significant negative relationship (P < 0.001). The kind of alcoholic beverage had no significant relationship with serum HDL-cholesterol and LDL-cholesterol; however, serum triglycerides were found to be significantly lower in those who drank beer (P < 0.05). CONCLUSIONS: Alcohol drinkers have a higher HDL-cholesterol level and lower LDL-cholesterol level than non-drinkers. This anti-atherogenic lipid profile in alcohol drinkers may be explained by the effect of alcohol on serum lipids independent of age, BMI and smoking.

Adult↗
PubMed1994

Effects of vesnarinone (OPC-8212) on Ca(2+)-activated K channels and cytosolic Ca2+ in cultured smooth muscle cells from porcine coronary artery.

Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation.

Amrinone↗
PubMed1994

IgA nephropathy associated with portal hypertension in liver cirrhosis due to non-alcoholic and non-A, non-B, non-C hepatitis.

A 69-year-old female was admitted to our hospital because of leg edema, proteinuria (2.1 g/day), and gross hematuria. She had non-alcoholic liver cirrhosis of unknown etiology. Esophageal varices also were found. Examination of the renal biopsy specimen revealed mesangial proliferative glomerulonephritis with IgA deposits. Propranolol was administered orally to reduce portal hypertension, resulting in a progressive decrease in urinary microalbumin excretion. This case suggests that portal hypertension is involved in the pathogenesis of IgA nephropathy in liver cirrhosis.

Aged↗
PubMed1994

[Relationship between occupational factors and medical indicators related to arteriosclerotic diseases].

The relationship between occupational factors and indicators related to arteriosclerotic diseases which include blood pressure, total cholesterol, triglyceride, HDL-cholesterol, body mass index, and HMS (Hitachi mental health scale) score. The study subjects were 7226 male electric company employees (40 to 59 years old). Records of annual health examinations were reviewed, and those of 3553 blue-color workers and 1860 white-color workers were used for analyses. The main results were as follows: Work style (overtime work and frequency of business trips) was strongly related to life style. Overtime work and walking time from home to the workplace did not relate to indicators of arteriosclerotic diseases. However, frequency of business trips, working posture and job category were related to most of the indicators. Smoking and frequency of drinking were strongly related to the indicators in both blue-color and white-color workers. In both blue-color and white-color workers, HMS score was not related to work style, but related strongly to psychological factors. In white-color workers, HMS were also related to life style. In addition, this study suggests that a cohort study about the progress of arteriosclerotic diseases in middle-aged workers is necessary, and that more accurate information on work style should be obtained for further investigation.

Adult↗
PubMed1994

[Megaloblastic anemia due to folate deficiency associated with hereditary spherocytosis].

A 19 years old male admitted to our hospital with fever, abdominal pain in May 1991. Physical examination revealed anemia, jaundice and marked splenomegaly. Severe pancytopenia with macrocytic hyperchronic anemia was noted along with elevated LDH and reduced serum folate. Blood smear showed nucleated RBCs, but only few microspherocytes. Bone marrow showed erythroid hyperplasia with remarkable megaloblastic changes. Megaloblasts were negative for PAS stain. Chromosome analysis revealed normal karyotype. Erythroleukemia was suspected initially, but his general condition as well as hematological data improved following 10 units of RBC transfusion. Following brief folic acid supplements, numerous microspherocytes became evident, typical osmotic fragility test revealed a pattern for hereditary spherocytosis. These observations led us to the diagnosis of hereditary spherocytosis complicated by megaloblastic anemia due to folate deficiency. As he developed folate deficiency again 10 months later, splenectomy were performed. The anemia improved after splenectomy.

Adult↗
PubMed1994

[Cytological features and prognosis of megakaryoblastic leukemia].

Nine patients with acute leukemia showing 10% or more positive blast cells with platelet peroxidase (PPO) or CD41b were diagnosed as megakaryoblastic leukemia. Three patients transformed from myelodysplastic syndromes or myeloproliferative disorders. The PPO positivity ranged from 7 to 55% (median 45%), and that for CD41b was 1.6 to 67.0% (median 16.4%). Because electron microscopic myeloperoxidase or glycophorin A were also positive in some patients, and also because CD41b positivity was often discordantly lower than PPO positivity, a possibility of mixed leukemia demonstrating myeloid or erythroid differentiation was suggested in 6 of these cases. As for the treatment results, all 3 pediatric cases who received combination chemotherapy achieved complete remission (CR). Among 6 adult cases CR was obtained in only one patient to whom low-dose cytosine arabinoside was administered. The remaining adult patients who received combination chemotherapy died relatively early.

Adult↗