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Biomedical subjects

T Hosoi

Publications and source records attributed to T Hosoi.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Renal tubular acidosis type II secondary to gamma-light chain excretion in an elderly patient with multiple myeloma].

A 73-year-old woman was admitted to the geriatric ward of the University of Tokyo Hospital with anemia, osteepeina, and renal dysfunction. Although symptoms typical of multiple myeloma such as punched-out lesions and hyperproteinemia were not found, protein electrophoresis revealed that lambda type Bence-Jones protein was excreted in urine. Multiple myeloma was diagnosed. Furthermore, renal dysfunction was accompanied renal tubular acidosis type II (proximal type). Renal dysfunction in patient with multiple myeloma in usually caused by so-called myeloma casts in the distal tubules, but renal tubular acidosis type II is rarely observed. It is possible that injury of the proximal renal tubular eithelium by Bence-Jones protein resulted in renal tubular acidosis type II in this patient.

Acidosis, Renal Tubular↗
PubMed1998

[Pathogenesis of osteoporosis and risk factors].

Osteoporosis is defined as a disease with low bone mineral density (BMD) and the increased probability for non-traumatic fractures in elderly. BMD in the elderly is theoretically determined by the BMD reached in younger era and the rate of bone loss in the later life. Both of peak bone mass and bone loss rate are known to be affected by environmental factors as well as genetic factors. In addition, both factors are assumed to interact each other. Prevention and treatment of osteoporosis would be fascilitated by understanding both of these factors.

Aged↗
PubMed1997

A novel RING finger protein, BFP, predominantly expressed in the brain.

RING finger is a variant zinc finger motif present in a new family of proteins including transcription regulators. A genomic DNA fragment containing RING finger motifs was identified by the polymerase chain reaction using degenerate primers. Using this fragment as a probe, we have isolated a novel cDNA from rat brain library. The predicted open reading frame contains a RING finger domain at its N-terminal portion. The corresponding transcript was detected predominantly in the brain and therefore was designated brain finger protein (bfp). An antibody raised against a recombinant bfp reveals the presence of the bfp in the brain. Interestingly, the bfp is induced during retinoic acid-mediated differentiation of P19 embryonal carcinoma cells into neural cells. These findings suggest the possible involvement of bfp in some aspects of neural cell regulation.

Amino Acid Sequence↗
PubMed1997

Phosphorylation states of microtubule-associated protein 2 (MAP2) determine the regulatory role of MAP2 in microtubule dynamics.

Phosphorylation-dependent regulation of microtubule-stabilizing activities of microtubule-associated protein 2 (MAP2) was examined using optical microscopy. MAP2, purified from mammalian brain, was phosphorylated by either cAMP-dependent protein kinase (PKA) or cyclin B-dependent cdc2 kinase. Using PKA, 15 mol of phosphoryl groups was incorporated per mole of MAP2, but about 70% of the phosphates was distributed to the projection region. Using cdc2 kinase, 7-10 mol of phosphoryl groups was incorporated per mole of MAP2, and more than 60% of the phosphates was distributed to the microtubule-binding region. Both types of phosphorylation similarly reduced binding activity of MAP2 onto microtubules. Direct observation of individual microtubules using dark-field microscopy showed that interconversion between the polymerization phase and the depolymerization phase was repeated in both unphosphorylated and PKA-phosphorylated MAP2. In cdc2 kinase-phosphorylated MAP2, however, the phase transition from depolymerization to polymerization occurred with difficulty, with the result being that the half-life of individual microtubules was as short as in the absence of MAP2. Examination of spontaneous polymerization of microtubules using dark-field microscopy showed that the microtubule-nucleating activity of MAP2 was reduced by PKA-dependent phosphorylation and was completely abolished by cdc2 kinase-dependent phosphorylation. These observations show that cdc2 kinase-dependent phosphorylation inhibits both the microtubule-stabilizing activity and the microtubule-nucleating activity of MAP2, while PKA-dependent phosphorylation affects only the microtubule-nucleating activity of MAP2.

Animals↗
PubMed1997

The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2.

Smith-Magenis syndrome (SMS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to 17p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS.

Abnormalities, Multiple↗
PubMed1997

Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and postmenopausal women.

In order to analyze the role of the estrogen receptor (ER) gene allelic polymorphisms on bone mineral density (BMD), 173 pre- and postmenopausal women were divided into four groups according to their menstrual status (group A: premenopausal women; group B: late premenopausal women; group C: postmenopausal women who had menopause for 5 years or less; and group D: postmenopausal women who had menopause for more than 5 years), and the relationship between ER gene polymorphism and lumbar spine BMD, the percent annual change in BMD and biochemical markers were studied. The restriction fragment length polymorphism (RFLPs) were represented as Xx (XbaI) and Pp (PvuII), with upper case and lower case letters signifying the absence or presence of restriction sites, respectively. In group A, the Xx genotype had significantly higher BMD (p < 0.01) than the xx genotype, but the difference was lost in groups B, C, and D. Because the percent annual change in BMD of group A was 0.052% and was not statistically different among genotypes, it is suggested that RFLP by Xba I is closely linked with peak bone mass that was attained during the subject's late thirties. In group B, serum N-region osteocalcin (N-OC) levels and the percent annual change in BMD showed a significantly larger increase than that of group A, indicating postmenopausal bone loss had commenced. Because the N-OC level of the Xx genotype was significantly higher than that of the xx genotype (p < 0.05), and the percent annual change in BMD of the Xx genotype showed a tendency to increase (p = 0.072), it is suggested that the high BMD of the Xx genotype is rapidly lost during menopausal transition. There were no significant relationships between RFLP and BMD in groups C and D, and between RFLP and BMD in groups C and D, and between RFLP by PvuII and BMD. The present study suggests that the Xx genotype is involved in accretion of BMD during young adulthood, but the effect was lost during menstrual transition.

Adult↗
PubMed1997

Case-control study of risk factors for hip fractures in the Japanese elderly by a Mediterranean Osteoporosis Study (MEDOS) questionnaire.

A case-control study of hip fracture among the Japanese elderly was carried out in order to assess the risk factors for fractures. On the data obtained from 249 cases and 498 controls matched with ethnicity, sex, age, and residential area, significant risk factors on the lifestyle by multivariate analyses included drinking more than three cups of coffee daily, living in rural areas in the past, sleep disturbance, stroke with hemiplegia, and sleeping in a (Western-type) bed. In contrast, in addition to possession of a large body mass index, moderate alcohol intake and eating fish appeared to be associated with a reduced risk of hip fracture. In conclusion, some traditional Japanese lifestyle characteristics may prevent hip fractures among the Japanese elderly.

Aged↗
PubMed1997

Acute myocardial infarction due to vasospasm in a 13-year-old-boy.

We describe an unusual case of acute myocardial infarction due to vasospasm in a 13-year-old boy. He was admitted to our hospital with severe congestive heart failure and shock. He had experienced a feeling of chest oppression with dyspnea while running, which grew worse. He then lost consciousness and was brought by ambulance to our intensive care unit. He had had similar but milder episodes of chest oppression months earlier. The family history revealed that his father had died suddenly from hypertrophic cardiomyopathy and that his grandmother also had hypertrophic cardiomyopathy. On admission, the patient was bathed in a cold sweat, his pulse was weak, and his blood pressure was too low to measure. Coarse crackling and wheezing were audible in both lung fields. Administration of catecholamine and intra-aortic balloon pumping failed to stabilize the hemodynamic variables, but percutaneous cardiopulmonary support proved to be lifesaving. Coronary arteriography performed during his convalescence showed on evidence of atherosclerosis. The acetylcholine provocation test ultimately revealed a diagnosis of acute myocardial infarction due to vasospasm.

Acetylcholine↗
PubMed1997

Association of bone mineral density with apolipoprotein E phenotype.

The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese women aged 47-82 years (64.0 +/- 1.0 years, mean +/- SE). The Apo E phenotype was analyzed by the isoelectric focusing method, followed by immunoblotting. The relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or estrogen receptor (ER) gene genotypes was also studied in the same population. The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these phenotypes into three categories: Apo E4-/- (E3/2 and E3/3, n = 217, Apo E4 +/- (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body height, and years since menopause were not significantly different among these three categories. The lumbar BMD values in these three groups were significantly different in the order of E4-/- (0.91 +/- 0.01 g/cm2), E4 +/- (0.85 +/- 0.02 g/cm2), and E4+/+ (0.83 +/- 0.06 g/cm2) (p = 0.031). The same trend was also observed for the Z score of the total BMD (p = 0.022). The serum level of intact osteocalcin in E4+/+ (15.2 +/- 5.7 ng/ml) was higher than in E4-/- (7.7 +/- 0.3 ng/ml) or E4 +/- (7.7 +/- 0.7 ng/ml) (p = 0.004 by analysis of variance). However, there were no other significant differences in the serum or urinary levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to be higher than in the other two groups (p = 0.05). There were no significant associations of the VDR and ER genotypes with the Apo E4 phenotype. A multivariate linear regression analysis revealed Apo E4 to be a significant, independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4 allele on the Z score of the lumbar BMD (-0.493 +/- 0.152) was not significantly different from that in the AAB of VDR (-0.616 +/- 0.225) or PPxx of ER (-0.785 +/- 0.314). In conclusion, the Apo E4 allele is associated with a low bone mass in postmenopausal Japanese.

Aged↗
PubMed1996

Chromosome mapping of human (ZNF179), mouse, and rat genes for brain finger protein (bfp), a member of the RING finger family.

The bfp, a member of the RING finger family, has been shown to be predominantly expressed in brain and up-regulated in neural differentiation of P19 embryonic carcinoma cells. Chromosome mapping of the bfp gene by fluorescence in situ hybridization reveals that human BFP (ZNF179) is located at 17p11.2, mouse Bfp at 11B1.3, and rat BFP at 10q22. These results provide additional evidence that the mouse 11B region displays conserved linkage homology with the 17p11.2 region of the human genome and the 10q22 region of the rate genome.

Amino Acid Sequence↗
PubMed1996

Identification of a novel isoform of estrogen receptor, a potential inhibitor of estrogen action, in vascular smooth muscle cells.

Clinical and experimental studies showed that estrogen has antiatherogenic effects. We previously demonstrated that the estrogen receptor (ER) mRNA and protein are expressed in vascular smooth muscle cells (VSMC) derived from rat aorta. Here, the expression of isoforms of the ER was examined in VSMC. Reverse transcriptase-polymerase chain reaction using specific primers for rat ER cDNA was performed from RNA of rat VSMC. This revealed the existence of ER cDNA that is shorter than the wild-type ER cDNA. Sequencing of the amplified products identified three isoforms of the ER and the wild-type ER. These ER mRNA isoforms lacked the region corresponding to exon 4, exon 4 and 5, and exon 3 and 4. Therefore, they were designated as ERdelta4 isoform, ERdelta4/5 isoform and ERdelta3/4 isoform, respectively. Chloramphenicol acetyltransferase assay was performed with these ER isoforms constructed into the expression vector and the reporter plasmid containing the estrogen responsive element. The assay showed that these ER isoforms lost estrogen-dependent transactivation activities and that ERdelta4/5 isoform has a inhibitory effect on normal estrogen action when it was cotransfected with the wild-type ER. These ER isoforms might be involved in the regulation of VSMC by estrogen.

Amino Acid Sequence↗
PubMed1996

Association of bone mineral density with polymorphism of the estrogen receptor gene.

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of the estrogen receptor (ER) gene and its relation to bone mineral density (BMD) were examined in 238 postmenopausal healthy women aged 45-91 years (66.3 +/- 0.6 years, mean +/- standard error of the mean [SEM]) in Japan. The RFLPs were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. In the PPxx genotype (n = 18), Z score values of BMD were significantly lower than those for other genotypes (n = 220) (lumbar spine, -0.746 vs. -0.065 [p = 0.022]; total body, -0.482 vs. 0.308 [p = 0.002]). We classified the subjects into three genotypes with allelic haplotype: homozygote of the Px haplotype was expressed as the 11 genotype, heterozygote of the Px haplotype as the 10 genotype, and the one lacking the Px haplotype as the 00 genotype. The PpXx genotype was not included in this analysis because the allelic haplotypes are uncertain. The Px haplotype was associated with a low BMD in postmenopausal women (Z score for the lumbar spine, -0.746 vs. -0.279 vs. 0.083, for the 11, 10, 00 genotypes, respectively [p = 0.029]; Z score for the total body, -0.482 vs. 0.164 vs. 0.427, respectively [p = 0.003]). We suggest that some variation of the ER gene linked to these RFLPs is associated with low BMD and that this at least partly explains the cause of postmenopausal osteoporosis in Japanese women.

Aged↗
PubMed1996

Immunolocalization of transforming growth factor-beta in the bone tissue.

Fetal mouse calvarias were cultured in a medium containing fetal calf serum, 1,25(OH)2D3 and parathyroid hormone in 5% CO2 incubator at 37 degrees C for 5 days. The calvarias were then fixed in a buffered paraformaldehyde solution and the periostea were removed. A polyclonal antibody against transforming growth factor-beta (TFG-beta) and a second antibody labeled with fluorescein isothiocyanate were used to detect TGF-beta. As a result, a specific staining was observed only in the shielding zone covered by osteoclasts in the bone resorption lacunae and in the extracellular matrix adjacent to the osteoclasts. These findings suggested the local delivery and possible activation of TGF-beta by osteoclasts in tissue.

Animals↗
PubMed1996

Immunohistochemical detection of activin A in osteoclasts.

Production of a member of transforming growth factor-beta (TGF-beta) superfamily, activin A, was examined in the bone tissue by using reverse transcriptase polymerase reaction. As a result, specific bands were detected showing the presence of activin A mRNA in the bone tissues. In order to localize the production site of activin A in the bone tissues, we tried to immunolocalize activin A in fetal mouse calvaria cultured in a medium containing fetal calf serum, 1 alpha-25(OH)2 vitamin D2 and parathyroid hormone. In these cultured calvaria, bone tissues including bone-resorbing osteoclasts in vitro were observed. Positive staining demonstrating the presence of activin A resided inside of the multinucleated cells in the bone resorbing lacunae, suggesting the production of activin A in osteoclasts. Activin A was also localized immunohistochemically in the osteoclast-like multinucleated cells developed in vitro. These results suggest that osteoclast produce activin in the bone tissues and that activin may play some roles by autocrine and/or paracrine manner in bone metabolisms.

Activins↗
PubMed1996

[Recent progress in treatment of osteoporosis].

Osteoporosis is a multifactorial disease. Understanding the genetic and environmental background of this disease is essential for prevention and treatment. We examined the relationship between polymorphisms of the estrogen receptor gene, bone mineral density, and markers of boe metabolism in postmenopausal women. Restriction fragment length polymorphisms of the estrogen receptor (ER) gene and its relation to bone mineral density were examined in 238 postmenopausal healthy women (66.7 +/- 0.9 yr, mean +/- standard error of the mean) in Japan. In those with the PPxx genotype, Z score values of bone mineral density were significantly lower than those for other genotypes (lumbar spine; p = 0.005, total body; p = 0.013). Dinucleotide repeat polymorphisms in the upstream region of ER gene were related to bone mineral density and to bone metabolic markers. These data suggest that some variation of the ER gene linked to these genetic markers is associated with the pathogenesis of postmenopausal osteoporosis. In addition, we focused on the role of vitamin K as a nutritional factor for bone metabolism. Japanese fermented beans, Natto, contain larage amounts of vitamin K2. We found a significant positive correlation between the level of vitain K2 in serum and the habit of eating Natto in postmenopausal women in the Toyo area. Natto may contribute to the prevention of osteoporosis.

Aged↗
PubMed1996

Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis.

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.

Activins↗
PubMed1995

Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis.

We investigated the association between dinucleotide (thymine-adenine) repeat polymorphism lying upstream of human estrogen receptor (ER) gene and bone mineral density (BMD) as well as biochemical markers for bone metabolism in 144 healthy postmenopausal Japanese women. The genotype was classified into 'A' through 'R' according to the number of the repeats, from 10 to 27. BMD was expressed in Z score (a deviation from the weight-adjusted average BMD of each age using the standard deviation as a unit). The people having genotype C (12 repeats of thymine-adenine) allele (n = 15) had significantly lower Z score of spine BMD (mean +/- SD; -1.11 +/- 1.3 vs. -0.06 +/- 1.2; p < 0.01) and of total body BMD (-0.58 +/- 1.0 vs. 0.31 +/- 0.9; p < 0.01) than those without this genotype (n = 129). They also had significantly higher levels of serum intact osteocalcin, urinary pyridinoline, and urinary deoxypyridinoline. These results suggest that genetic variation at the ER locus may be associated with some determinants for BMD and bone metabolism in postmenopausal women.

Aged↗