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Biomedical subjects

A Nakai

Publications and source records attributed to A Nakai.

At least 91 records · Page 5Linked to original sources
PubMed1995

Quercetin suppresses heat shock response by down regulation of HSF1.

A bioflavonoid quercetin suppressed the stress response in heat-shocked cells and we have investigated the inhibitory mechanism in this report. After treatment of cells with nonlethal concentrations of quercetin, the binding of heat shock factor (HSF) to the heat shock element (HSE) was inhibited as detected by gel shift assay. We examined whether quercetin inhibits heat shock response by inhibiting HSF trimer-formation and found it was not the case. Instead, pretreatment of the cells with quercetin caused a decrease in the level of HSF1, especially of the constitutively phosphorylated form. This decrease was more prominent in heat-shocked cells than in control cells. These data suggest that (1) quercetin does not affect the trimer formation of HSF1, and (2) the decline of the HSF1-HSE complex might be linked to the decrease of HSF1 levels caused by quercetin.

Blotting, Western↗
PubMed1995

MRI findings of Zellweger syndrome.

A patient with Zellweger syndrome, who manifested marked dilatation of the lateral ventricles, observed at 34 weeks gestation by fetal ultrasonography, is reported. Postnatal magnetic resonance imaging revealed marked colpocephaly and hypogenesis of the posterior part of the corpus callosum. However, pachygyria was limited to the perisylvian regions. Biochemical diagnosis was based on increased serum very-long-chain fatty acids, 2-hydroxysebacic aciduria, and the detection of the ghosts of peroxisomal membrane in cultured fibroblasts. The patient was classified as belonging to group B of this syndrome by complementation study.

Female↗
PubMed1995

The DNA-binding properties of two heat shock factors, HSF1 and HSF3, are induced in the avian erythroblast cell line HD6.

Avian cells express three heat shock transcription factor (HSF) genes corresponding to a novel factor, HSF3, and homologs of mouse and human HSF1 and HSF2. Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both. HSF3 is constitutively expressed in the erythroblast cell line HD6, the lymphoblast cell line MSB, and embryo fibroblasts, and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock. Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer, whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer. Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1. As occurs for HSF1, heat shock leads to the translocation of HSF3 to the nucleus. HSF exhibits the properties of a transcriptional activator, as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4-HSF3 protein on a GAL4 reporter construct. These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock.

Animals↗
PubMed1995

Expression and phosphorylation of BiP/GRP78, a molecular chaperone in the endoplasmic reticulum, during the differentiation of a mouse myeloblastic cell line.

To determine the functional significance of endoplasmic reticulum chaperones in hematopoietic cells, we analyzed the expression and post-translational modification of BiP/GRP78 and GRP94 as well as the cytoplasmic chaperones HSP70 and HSC70 during the differentiation of a mouse myeloid leukemia cell line, M1. The amounts of BiP/GRP78 and GRP94 increased several-fold when M1 cells were induced to differentiate into macrophage-like cells by treatment with interleukin-6 (IL-6). Synthesis began to increase at 4 hr after IL-6 treatment. The phosphorylated form of BiP/GRP78 increased during the later stages of differentiation. These data suggested that the chaperone activity of BiP/GRP78 and GRP94 may be needed for differentiated macrophage-like cells or for the differentiation event itself, and that functionally different BiP/GRP78 accumulate during the differentiation of M1 cells.

Animals↗
PubMed1995

Dexamethasone-induced changes in glucose transporter 4 in rat heart muscle, skeletal muscle and adipocytes.

To clarify the effect of glucocorticoid on glucose transporters (GLUT) in adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle, skeletal muscle and adipocytes during long-term administration of dexamethasone and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and the low-density microsome fraction were measured by Western blotting using anti-GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of rat were unchanged by treatment of dexamethasone. In the adipocytes the level of GLUT4 in plasma membrane was changed, but it was decreased in the low-density microsome fraction. Although adipocytes are less involved in blood sugar regulation than skeletal muscle, this finding suggests that glucose metabolism in Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.

5'-Nucleotidase↗
PubMed1995

Effects of thyroid hormone on coenzyme Q and other free radical scavengers in rat heart muscle.

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state. Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured. A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2-. These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat.

Animals↗
PubMed1995

Changes in calmodulin concentration and cyclic 3',5'-nucleotide phosphodiesterase activity in skeletal muscle of hyper- and hypothyroid rats.

Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases remains unclear, but several findings suggest that the catecholamine-beta-receptor-cAMP system or other messenger systems are disturbed in these diseases. In this context, we evaluated changes in the cyclic 3',5'-nucleotide metabolic enzyme, cyclic 3',5'-nucleotide phosphodiesterase (PDE) and calmodulin concentrations in skeletal muscles of hyper- and hypothyroid rats. Activities of cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats, and calmodulin concentration was high in hyperthyroid and low in hypothyroid rats, as compared with normal rats. DE-52 column chromatographic analysis showed that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in hyperthyroid rats, but the activities in peaks I and II were unchanged. These findings indicate that cAMP and calmodulin may have some role in skeletal muscle function in the hyperthyroid state, and that cAMP and calmodulin-dependent metabolism may be suppressed in the hypothyroid state.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Diffuse leukodystrophy with a large-scale mitochondrial DNA deletion.

An 8-year-old girl with progressive ataxia and bulbar palsy showed diffuse white-matter lesions in the occipital to parietal lobes on magnetic resonance imaging. Since she had slightly elevated lactate in the cerebrospinal fluid, a muscle biopsy was done which revealed scattered ragged-red fibres and focal cytochrome c oxidase deficiency. Southern blot and polymerase-chain-reaction analyses revealed a large-scale mitochondrial DNA deletion, which was 6990 base-pairs in length with 6 base-pair (-TCATCG-) direct repeats at the junctions. Mitochondrial DNA mutation should be considered as one of the candidate causes for diffuse leukodystrophy in children.

Base Sequence↗
PubMed1994

cDNA sequences encoding human fructose 1,6-bisphosphatase from monocytes, liver and kidney: application of monocytes to molecular analysis of human fructose 1,6-bisphosphatase deficiency.

Fructose 1,6-bisphosphatase deficiency is an autosomal recessive inherited disorder of gluconeogenesis. We could isolate cDNAs encoding human fructose 1,6-bisphosphatase from normal monocytes, liver and kidney, but not from normal lymphocytes. The cDNAs contained an open reading frame coding for 338 amino acids, and their nucleotide sequences in monocytes and liver were identical. G644C645 nucleotides in this sequence were the same as those of cDNA from HL-60 cells, although our result differed from a previous report (M. El-Maghrabi et al. (1993) J. Biol. Chem. 268, 9466-9472) on an alteration to C644G645 nucleotides in human liver cDNA resulting in a change of Gly-214 to Ala-214 in the enzyme. The Gly-214 (GGC) residue was therefore conserved in the enzymes hitherto isolated from humans and other animals. Analysis of monocytes in seven patients with fructose 1,6-bisphosphatase deficiency showed a DNA fragment with apparent normal size in two sisters but no detectable DNA fragment in the other five patients. Monocytes were thus useful as an alternative source for mRNA from human liver for the molecular analysis of fructose 1,6-bisphosphatase deficiency.

Alanine↗
PubMed1994

Acylcarnitine profile in tissues and body fluids of biotin-deficient rats with and without L-carnitine supplementation.

Since biotin-deficient (BD) rats are a good animal model for human multiple carboxylase deficiency and have low plasma free carnitine levels, short-chain acylcarnitine profiles in biotin-deficient rats with L-carnitine supplementation (BDC rats) and BD rats were investigated by fast-atom bombardment and tandem mass spectrometry and gas chromatography/mass spectrometry. By the latter method, 3-hydroxyisovalerylcarnitine was identified in BD rats, and showed the greatest accumulation among short-chain acylcarnitines in tissues of BD rats, while the tissue levels of propionic acid were more markedly elevated than those of 3-hydroxyisovaleric acid. The tissue levels of 3-hydroxyisovaleryl-carnitine were significantly lower and those of propionyl-carnitine were somewhat higher in BDC rats than in BD rats, while the tissue levels of propionic acid and 3-hydroxyisovaleric acid in BDC rats were lower than those in BD rats. These changes were more apparent in kidney than in other tissues. The amounts of urinary excretion of acylcarnitines were markedly larger, and those of 3-hydroxyisovaleric acid were somewhat smaller in BDC rats than in BD rats, while those of propionic acid were very low in BD and BDC rats as compared with those of 3-hydroxyisovaleric acid. It seems that the relationship between the concentrations of 3-hydroxyisovalerylcarnitine and those of propionylcarnitine reflects the unique metabolism of the related metabolites in tissues, especially in kidney, which may be influenced by their urinary excretion and the availability of free carnitine. These data in biotin deficiency suggest that carnitine supplementation is possibly beneficial for patients with holocarboxylase synthetase deficiency who respond incompletely to biotin therapy.

Acetylcarnitine↗
PubMed1994

Cushing's syndrome with cortisol hypersecretion from one of bilateral adrenocortical adenomas: report of a case.

We report herein the case of a 40-year-old man with Cushing's syndrome, diagnosed by clinical manifestations and endocrinological studies, who was found to have bilateral adrenocortical adenomas, one of which hypersecreted cortisol. The Cushing's syndrome was therefore attributed to primary adrenocortical disease, and the right adrenal tumor was resected and histologically diagnosed as a so-called black adenoma. After resection of the right tumor, the left adrenal tumor showed no signs of cortisol hypersecretion for the 23 months of follow-up until the patient died of peritonitis subsequent to the rupture of a duodenal ulcer. The left adrenal tumor was examined at autopsy and found to be a cortical adenoma. These data imply that the adrenal adenomas developed primarily from the adrenal gland itself, and that one of the tumors was well differentiated and secreted excess hormones, while the other remained in cell proliferation without hypersecretion.

Adrenal Gland Neoplasms↗
PubMed1994

Uncooked cornstarch treatment for hepatic phosphorylase kinase deficiency.

UNLABELLED: A 5-year-old boy with short stature, hepatomegaly and motor weakness due to hepatic phosphorylase kinase deficiency is described. Laboratory data showed mild hypoglycaemia and metabolic acidosis, hepatic dysfunction, and a low insulin-like growth factor-I level. Mild hypoglycaemia, marked ketosis and insufficient growth hormone secretion were revealed at night. Serum total and free carnitine levels were low and the acyl/total carnitine ratio was high. Urinary acylcarnitine profile using fast atom bombardment and tandem mass spectrometry showed increased excretion of acetylcarnitine and dicarboxylylcarnitines. These endocrinological and metabolic abnormalities and clinical symptoms were improved with uncooked cornstarch treatment. CONCLUSION: Uncooked cornstarch treatment may be helpful in hepatic phosphorylase deficiency.

Child↗
PubMed1994

Tyrosine hydroxylase indicates cell differentiation of catecholamine biosynthesis in neuroendocrine tumors.

The intracellular localization of tyrosine hydroxylase (TH), which is the rate limiting enzyme in catecholamine (CA) biosynthesis, and its activity in various adrenal and other neuroendocrine tumors was studied. TH was strongly localized in adrenal medulla, pheochromocytoma, and paraganglioma, but was scatteredly expressed in neuroblastoma. TH was not detected in adrenocortical tumors, ganglioneuroma, and other neuroendocrine tumors. Neuron specific enolase (NSE) was found in all neuroendocrine tumors, but Grimelius staining showed only the secreting granules of the tumor cells. TH activity was significantly high in pheochromocytoma and paraganglioma as compared with that in normal adrenal gland, whereas TH activity was low in a neuroblastoma and was undetectable in other tumors. These findings indicate that TH correlates well with the biosynthetic function of CA in the tumor cell and, thus, both the immunostaining of TH and the measurement of its activity in adreno-medullary and related tumors may provide some information about the process of cell differentiation in these tumors.

Adrenal Gland Neoplasms↗
PubMed1994

A case of familial thyroxine binding globulin excess associated with growth hormone deficiency.

A 7 years 3 months old Japanese boy with familial thyroxine binding globulin (TBG) excess associated with growth hormone (GH) deficiency is reported. The patients height was 106.4 cm (-2.86 s.d.) and his bone age was 5 years and 3 months. He had no goiter and his developmental milestones were normal. The serum thyroid stimulating hormone (TSH) was 2.8 microU/mL, triiodothyronine (T3) 3.1 ng/mL, thyroxine (T4) 23.4 micrograms/dL and free T4 1.8 ng/dL. The serum TBG level was beyond 80.0 micrograms/mL, with normal TSH response to the thyrotropin-releasing hormone (TRH) test. Familial study revealed that his grandmother, mother, uncle, younger sister and younger brother had high TBG and T3 levels, thus an X-linked co-dominant transmission was suggested. The peak GH responses to insulin and clonidine hydrochloride were 5.8 and 8.2 ng/mL, respectively. The mean nocturnal GH concentration was 2.5 ng/mL. His growth velocity increased from 4.8 to 8.4 cm/year and his serum TBG levels decreased gradually after human growth hormone (hGH) treatment.

Body Height↗