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Biomedical subjects

A Murayama

Publications and source records attributed to A Murayama.

At least 37 records · Page 2Linked to original sources
PubMed1998

The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3.

25-Hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase) catalyzes hydroxylation, mainly in the kidney, of 25-hydroxyvitamin D3 [25(OH)D3] into 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonal form of vitamin D, acting as a key enzyme of vitamin D biosynthesis. Reflecting its biological significance, this enzymatic activity is differentially regulated by several factors involving calcium homeostasis, though the molecular mechanism is poorly understood. In our recent study (K. Takeyama, et al., 1997), we cloned the cDNA of mouse 1 alpha-hydroxylase, and this led us to investigate the regulation of gene expression and the function of the promoter of this gene. Here we report the isolation of the 5' flanking region of the human 1 alpha-hydroxylase gene and the identification of the human 1 alpha-hydroxylase promoter by a primer extension assay. We found that in the identified promoter, a positively regulatory region to parathyroid hormone (PTH) and calcitonin and a negatively regulatory region to 1 alpha,25(OH)2D3 are located around -4 and -0.5 kb, respectively. Thus, we provide direct evidence that the positive and negative regulation of 1 alpha-hydroxylase gene expression by hormones takes place at transcriptional levels through two distinct promoter regions.

Animals↗
PubMed1998

Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets.

BACKGROUND: Pseudovitamin D-deficiency rickets is characterized by the early onset of rickets with hypocalcemia and is thought to be caused by a deficit in renal 25-hydroxyvitamin D3 1alpha-hydroxylase, the key enzyme for the synthesis of 1alpha,25-dihydroxyvitamin D3. METHODS: We cloned human 25-hydroxyvitamin D3 1alpha-hydroxylase complementary DNA (cDNA) using a mouse 1alpha-hydroxylase cDNA fragment as a probe. Its genomic structure was determined, and its chromosomal location was mapped by fluorescence in situ hybridization. We then identified mutations in the 1alpha-hydroxylase gene in four unrelated patients with pseudovitamin D-deficiency rickets by DNA-sequence analysis. Both the normal and the mutant 1alpha-hydroxylase proteins were expressed in COS-1 cells and were assayed for 1alpha-hydroxylase activity. RESULTS: The gene for 25-hydroxyvitamin D3 1alpha-hydroxylase was mapped to chromosome 12q13.3, which had previously been reported to be the locus for pseudovitamin D-deficiency rickets by linkage analysis. Four different homozygous missense mutations were detected in this gene in the four patients with pseudovitamin D-deficiency rickets. The unaffected parents and one sibling tested were heterozygous for the mutations. Functional analysis of the mutant 1alpha-hydroxylase protein revealed that all four mutations abolished 1alpha-hydroxylase activity. CONCLUSIONS: Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene are a cause of pseudovitamin D-deficiency rickets.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1998

Mucosal bile duct carcinoma with superficial spread.

We describe a case of mucosal bile duct carcinoma with superficial spread in a 69-year-old man with gallstone pancreatitis. The patient was seen at the hospital because of abdominal pain, fever, and jaundice. Endoscopic retrograde cholangiography (ERC) demonstrated a protruding lesion in the lower third of the common bile duct (CBD) showing wall irregularity suggestive of malignancy. Percutaneous transhepatic cholangioscopy (PTCS) disclosed a papillary tumor with granular mucosa extending continuously to the middle third of the CBD. Cholangioscopic biopsy specimens taken from both the papillary tumor and surrounding granular mucosa revealed papillary adenocarcinoma. After this assessment of extent of cancer by PTCS, we performed pancreatoduodenectomy with extrahepatic bile duct resection and regional lymph node dissection. Pathology examination revealed papillary adenocarcinoma limited to the mucosal layer. The resected margin of the bile duct was free of tumor. We also reviewed 25 cases of early mucosal bile duct carcinoma described in detail in the Japanese literature, and we discuss the diagnostic advantages of PTCS.

Adenocarcinoma, Papillary↗
PubMed1998

The importance of 25-hydroxyvitamin D3 1 alpha-hydroxylase gene in vitamin D-dependent rickets.

Vitamin D plays a role in a wide variety of biological events such as calcium homeostasis, bone formation and cellular differentiation. An active form of vitamin D acting as a ligand specific vitamin D receptor (VDR), 1 alpha,25(OH)2D3, is biosynthesized from cholesterol, and during this biosynthesis a renal 25-hydroxylation at the final stage by 25-hydroxyvitamin D3 1 alpha-hydroxylase is critical. Recent studies isolated the cDNA encoding 1 alpha-hydroxylase from several species, and revealed that this enzyme belongs to a member of the cytochrome p450 enzyme superfamily, with highest homologies to the p450 hydroxylases for vitamin D derivatives. One of three kinds of hereditary rickets (vitamin D-dependent rickets type I) displays an autosomal recessive trait and clinical features consistent with a defect of 1 alpha-hydroxylase activity, and the genetic analysis of the type I patients identified missense mutations of the 1 alpha(OH)ase gene that results in a loss of this enzymatic activity.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1998

Molecular flexibility of retinoic acid under white fluorescent light.

Among the series of metabolic analogs of the eccentric cleavage pathway of beta-carotene with different side chain lengths, retinoic acid was shown to have exceedingly higher molecular flexibility to undergo photoisomerization into the geometrical isomers under white fluorescent light. When irradiated with white fluorescent lamps (1,200 lx), the velocity of photoisomerization of all-trans-retinoic acid (8.4 x 10(-7) mol/L.min) was exceedingly higher than those of the other analogs: ionylideneacetic acid (4 x 10(-8) mol/L.min), ionylidenecrotonic acid (3.0 x 10(-7) mol/L.min), all-trans-beta-apo-14'-carotenoic acid (1.7 x 10(-7) mol/L.min), all-trans-beta-apo-12'-carotenoic acid (1.3 x 10(-7) mol/L.min), and all-trans-beta-apo-8'-carotenoic acid (0.1 x 10(-7) mol/L.min). beta-Carotene did not undergo photoisomerization under the experimental conditions. The molecular flexibility of retinoic acid is assumed to be an important basis of the mechanism of action of retinoic acid.

Chromatography, High Pressure Liquid↗
PubMed1997

Photoisomerization of retinoic acids in ethanol under room light: a warning for cell biological study of geometrical isomers of retinoids.

Photoisomerization of all-trans-retinoic acid and the geometrical isomers [9-cis-retinoic acid, 11-cis-retinoic acid, 13-cis-retinoic acid and 9,13-di-cis-retinoic acid] in ethanol and their biological effects on F9 teratocarcinoma cells were analyzed. The rates of photoisomerization of the retinoic acids illuminated by fluorescent lamps (1,200 lx) increased in inverse proportion to their concentrations. When the ethanolic solution of all-trans-retinoic acid (10(-5) M) was kept under illuminated condition, the equilibrium mixture of the geometrical isomers of retinoic acid [all-trans-retinoic acid 25%, 9-cis-retinoic acid 10%, 11-cis-retinoic acid 10%, 13-cis-retinoic acid 30%, 9,13-di-cis-retinoic acid 5% and unidentified compound 20%] formed at around 30 min. The apparent velocity of the photoisomerization was approximately 8 x 10(-7) mol/L.min. Equilibrium mixtures with similar compositions were obtained by the photoisomerization of other geometrical isomers. The geometrical isomers produced by the photoisomerization possessed significantly different biological effects in the induction of differentiation of F9 cells into parietal endoderm-like cells: activities of 9-cis-retinoic acid (ED50, 8 x 10(-7) M), 11-cis-retinoic acid (ED50, 8 x 10(-7) M), and 13-cis-retinoic acid (ED50, 8 x 10(-7) M) were approximately 1/10 of all-trans-retinoic acid (ED50, 8 x 10(-8) M), and activity of 9,13-di-cis-retinoic acid (ED50, 1 x 10(-5) M) was 1/100 of the level of all-trans-retinoic acid. Further, the retinoic acids acted with each other additively on F9 cells.

Animals↗
PubMed1996

The Drosophila tamou gene, a component of the activating pathway of extramacrochaetae expression, encodes a protein homologous to mammalian cell-cell junction-associated protein ZO-1.

In Drosophila sensory organ development, the balance of activities between proneural genes and repressor genes defines a proneural cluster as a population of competent cells for neural development. In this study, we report the isolation and analysis of the tamou (tam) gene that encodes a cell-cell junction-associated protein, which is homologous to mammalian ZO-1, a member of the membrane-associated guanylate kinase homolog family. The tam mutation reduces the transcription of a repressor gene, extramacrochaetae, and causes enlargement of a proneural cluster where supernumerary precursor cells emerge, resulting in extra mechanosensory organs in the fly. These results suggest that the membrane-associated Tam protein is involved in the signaling pathway that activates emc expression.

Amino Acid Sequence↗
PubMed1996

mRNA differential display reveals Krox-20 as a neural plasticity-regulated gene in the rat hippocampus.

The prolonged maintenance of hippocampal long-term potentiation depends on de novo protein and RNA synthesis, indicating an involvement of altered gene expression in long-lasting plastic changes in synaptic efficacy. We have used an mRNA differential display technique to identify a set of genes that are induced by neural activity in the rat hippocampus. Sixteen independent cDNAs were isolated whose mRNA level was markedly modulated by convulsive seizure. One of these encodes Krox-20, a zinc finger DNA binding protein. High frequency tetanic stimulation of perforant pathway, which elicited a persistent long-term potentiation (>10 h), rapidly induced expression of krox-20 mRNA in the hippocampus of urethane-anesthetized rat. The increase in krox-20 mRNA was transient and NMDA receptor-dependent. These results suggest a role for krox-20 in the maintenance of long-term potentiation.

Amino Acid Sequence↗
PubMed1996

Myocardial ischemia due to vascular systemic amyloidosis: a quantitative analysis of autopsy findings on stenosis of the intramural coronary arteries.

A case is reported of a 65 year old man who suffered myocardial ischemia resulting from extensive stenosis of the intramural coronary arteries secondary to systemic vascular involvement by primary amyloidosis. In the myocardium, there were multiple fibrotic foci scattered mainly in the subendocardial region of the ventricle. Intramural coronary arteries were stenotic or occlusive due to amyloid-induced luminal narrowing, but there was no significant stenosis of the epicardial coronary arteries. Quantitative analysis of amyloid deposits in the intramural coronary arteries demonstrated that occlusive arteries were predominant in the surrounding area of myocardial fibrosis, and the extent of coronary stenosis by amyloid deposition was significantly more severe than in hearts of the five control patients who had coronary amyloidosis without myocardial fibrosis. These results indicate that myocardial fibrosis originates from coronary ischemia due to vascular amyloid deposition. This is the first time that the relationship between myocardial lesions and coronary amyloid deposition has been elucidated using histopathologic quantitative analysis.

Aged↗
PubMed1995

Biological activity of (all-E)-beta-apo-12'-carotenoic acid and the geometrical isomers on human acute promyelocytic leukemia cell line HL-60.

(all-E)-beta-Apo- 12'-carotenoic acid and a series of the geometrical isomers were synthesized and their biological activities to inhibit growth and to induce differentiation of human acute promyelocytic leukemia cell line HL-60 were analyzed. It was found that (all-E)-beta-apo- 12'-carotenoic acid (I, Fig. 1) and (15' -Z)-apo- 12'-carotenoic acid (II, Fig. 1) showed strong activity both in inhibition of growth and the induction of differentiation. The biological activity of (13'-Z)-beta-apo- 12'-carotenoic acid (III, Fig. 1) was modest, while that of (13', 15'-di-Z)-beta-apo- 12'-carotenoic acid (IV, Fig. 1) was negligible. (all-E)-beta-Apo- 12'-carotenoic acid and the geometrical isomers acted additively with (all-E)-retinoic acid, and synergetically with (9-Z)-retinoic acid. In accord with our previous report, biological activities of (all-E)-beta-apo- 14'-carotenoic acid (V, Fig. 1) and of (15-Z)-beta-apo- 14'-carotenoic acid (VI, Fig. 1) were very weak. It was indicated that (all-E)-beta-apo- 12'-carotenoic acid, an intermediate metabolite of excentric cleavage pathway of beta-carotene, per se may exert the biological function.

Carotenoids↗
PubMed1993

Rapid growth of left ventricular thrombus leading to fatal heart failure in six hours.

A left ventricular (LV) thrombus grew rapidly over chronic endocarditis 2 months after anterior myocardial infarction. Echocardiograms demonstrated a rapidly growing LV thrombus an eventual obstruction. Despite anticoagulant/thrombolytic therapy, the patient died of acute LV failure. Histopathologically, a fresh thrombus overlay thickened endocardium with massive T lymphocyte infiltration over healed infarction.

Chronic Disease↗
PubMed1993

New retinoids inhibiting the growth of human acute promyelocytic leukemia cell line HL-60 without inducing differentiation.

A series of acid homologs with longer side chain length was synthesized and their biological activities to inhibit growth and to induce differentiation of human acute promyelocytic leukemia cell line HL-60 were analyzed. It was found that ethyl alpha-retinylidene propionate (E) shows interesting activity. This compound inhibited growth of HL-60 cells with almost the same potency of retinoic acid. However, unlike retinoic acid, the potency of this compound to induce differentiation of HL-60 cells into neutrophiles was almost negligible. Ethyl alpha-retinylidene propionate (E) is an unprecedented retinoid which inhibits growth of HL-60 cells without inducing cell differentiation. The Z isomer [ethyl alpha-retinylidene propionate (Z)] also showed similar unique effects on HL-60 cells. Interestingly, both of the E and Z isomers of alpha-retinylidene propionic acid showed only very weak activities to inhibit growth and to induce differentiation of HL-60 cells. It was suggested that ethyl alpha-retinylidene propionate acts on HL-60 cells in the intact form without suffering hydrolysis, and also that the ester group plays important role for the unique activity. Biological activities of retinylidene acetic acid (E and Z) which lacks methyl group at alpha-position of alpha-retinylidene propionic acid, on HL-60 cells were weaker than those of the isomers of alpha-retinylidene propionic acid. Esterification of the isomers of retinylidene acetic acid resulted in further decrease of biological activities. Biological activities of ethyl retinoate on HL-60 cells were also very weak. It was indicated that methyl group present at alpha-position of ethyl alpha-retinylidene propionate plays an important role for the unique biological activity. It was further indicated that the effect of esterification of carboxyl group of retinoids on the biological activity is not constant, but varies depending on the structure. Pretreatment of HL-60 cells with ethyl alpha-retinylidene propionate (E) apparently did not influence the process of induction of differentiation of HL-60 cells into neutrophiles by retinoic acid. It was further shown that ethyl alpha-retinylidene propionate (E) prolongs the time necessary for induction of differentiation of HL-60 cells by retinoic acid, but does not influence the level of final rate of differentiation.

Cell Differentiation↗
PubMed1991

Molecular cloning, sequencing and expression in Escherichia coli of the odontoglossum ringspot virus coat protein gene.

The sequence of the 3'-terminal 1865 nucleotides of the genome of the tobamovirus odontoglossum ringspot virus (ORSV) was determined. This sequence contained two open reading frames (ORFs), 912 and 477 nucleotides long. The 912 nucleotide ORF has been identified as the cell-to-cell transport protein gene. The 477 nucleotide ORF was expressed in Escherichia coli, and the product was detected by antibodies specific for the coat protein of ORSV. The amino acid sequence of protein encoded by this ORF shares 84% similarity with the tobacco mosaic virus (TMV) (vulgare) coat protein. The 3'-terminal untranslated region of ORSV comprises 414 nucleotides, 210 nucleotides more than that of TMV (vulgare) RNA.

Amino Acid Sequence↗
PubMed1991

Identification of the coat protein gene of bean golden mosaic geminivirus.

An open-reading frame designated 1R1, on DNA component 1 of bean golden mosaic geminivirus (BGMV), has been identified as the coat protein gene. A DraI restriction fragment of BGMV DNA1 that includes 1R1 was inserted into the SmaI pKK223-3 expression vector. The 32 kD protein expressed in Escherichia coli cells reacted with antibodies to the BGMV capsid polypeptide and behaved identically to purified capsid protein in western blots.

Animals↗
PubMed1989

A rapid cross-sectioning and freeze-clamping device for the beating canine heart.

A new sampling method of cross-sectioning the canine heart in situ was developed. A mechanical device, driven by spring power, enabled cross-sectioning of a short-axis plane of the beating canine heart (4 mm thick) with high speed rotating blades, at a pre-determined phase of the cardiac cycle, and instantaneous freeze-clamping (2.4 mm thick) with pre-cooled aluminum blocks, all within 120 ms. By this method, the anatomical structures of the sample were well preserved. Transmural metabolism and flow distribution were instantaneously fixed and high resolution of the two-dimensional redox state was obtained by application of NADH fluorescence photography. Micro-samplings from the desired portion of the cross-sectional slice were possible at -190 degrees C. NADH fluorescence of the samples did not increase from the surface to 1.2 mm in depth, confirming that there was no ischemic artifact. With the present technique, a heart sample in which transmural metabolism, and the redox state, are fixed and visualized is attainable, thus providing a new tool for the study of myocardial ischemia.

Adenine Nucleotides↗