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Biomedical subjects

Y Taguchi

Publications and source records attributed to Y Taguchi.

At least 73 records · Page 4Linked to original sources
PubMed1998

Differences in bone resorption after menopause in Japanese women with normal or low bone mineral density: quantitation of urinary cross-linked N-telopeptides.

The objective of this study was to examine the value of NTx, a urinary cross-linked N-telopeptides of type I collagen, as a marker of bone resorption. We assessed changes in pre- and postmenopausal bone resorption by evaluating the correlation of NTx with L2-4 bone mineral density (BMD) in a total of 1100 Japanese women, aged 19-80 years [272 premenopausal (45.2 +/- 6.2 years) and 828 postmenopausal (59.5 +/- 6.2 years)]. Postmenopausal women were divided into three groups based on the range of BMD (normal, osteopenic, and osteoporotic). Within each group, subjects were further segregated according to years since menopause (YSM). NTx values were then evaluated for each group. Our results showed that BMD was significantly decreased (P < 0.05) and NTx was significantly increased (P < 0.01) after menopause in age-matched analysis. Consistent with a previous report, NTx was inversely correlated with BMD for the entire cohort of study subjects (r = -0.299), although NTx correlated better with premenopausal than postmenopausal BMD (r = -0.240 versus r = -0.086). This may have been due to the fact that elevated values of NTx were exhibited over the entire range of BMD present in the postmenopausal women, suggesting that NTx might respond faster to the estrogen withdrawal than BMD. In all postmenopausal women, regardless of the range of BMD, the increase in NTx reached a peak within 5 YSM. After 11 YSM, however, NTx remained elevated in the osteoporotic group but it decreased in the osteopenic group, and showed no significant change in the group of postmenopausal women with normal BMD. These findings suggest that bone resorption is dramatically increased within 5 years after menopause but remains increased only in osteoporotic women.

Absorptiometry, Photon↗
PubMed1998

A heterogeneity in serum osteocalcin N-terminal fragments in Paget's disease: a comparison with other biochemical indices in pre- and postmenopause.

An osteocalcin (OC) nitrogen (N)-terminal sandwich enzyme immunoassay that employs anit-N-20 (amino acids 1-20) polyclonal and monoclonal antibodies has been developed. This assay has demonstrated the existence of a heterogeneity in the OC N-terminal fragments observed in the serum of a patient with Paget's disease and a normal child. The elevation of the serum OC N-terminal value that occurs in Paget's disease was considered to be comparable to the serum alkaline phosphatase (ALP) elevations that also occur. The size of the peaks corresponding to N-terminal OC fragments in Paget's serum decreased 3 months after bisphosphonate treatment. Serum levels of OC N-terminals, and other biochemical indices, were determined for 67 premenopausal and 181 postmenopausal Japanese women. Serum OC N-terminal levels increased significantly (41.2%) in postmenopausal women compared with age-matched premenopausal women. These results strongly suggest that serum OC N-terminal levels reflect bone turnover rates when bone resorption is dominant.

Adolescent↗
PubMed1998

Endothelin-1 enhances pressor responses to norepinephrine: involvement of endothelin-B receptor.

We investigated the effects of endothelin-1 (ET-1) on pressor responses to norepinephrine (NE) in perfused rat mesenteric arteries. Perfusion of the arteries with a subpressor dose of ET-1 (3 x 10(-10) M) for 15 min markedly enhanced the pressor responses to NE (10(-6) and 3 x 10(-6) M), and this effect was significantly prevented by BQ788 (10(-6) M) but not by FR139317 (10(-6) M). In DOCA-salt hypertensive rats, exogenous ET-1 had little effect on pressor responses to NE. Pressor responses to NE (10(-6) M) were significantly increased in DOCA-salt rats compared with those in normotensive rats. This increased response to NE was reduced to the level of normotensive rats by BQ788. FR139317 was without effect on the increased responses. These results suggest that ET-1 enhances contractile responses to NE through ETB receptors. Moreover, this phenomenon is stimulated tonically by endogenous ET-1 in DOCA-salt hypertensive rats and may contribute to the maintenance of hypertension in these rats.

Adrenergic alpha-Agonists↗
PubMed1998

Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.

Alleles↗
PubMed1998

Serum soluble interleukin-6 receptor and biochemical markers of bone metabolism show significant variations during the menstrual cycle.

We examined sequential changes of bone-resorbing cytokines and bone metabolic markers and the effect of ovarian hormones on bone metabolism during the menstrual cycle in 10 healthy Japanese women, aged 22-43 yr, with normal ovarian function. Serum soluble interleukin-6 receptor (sIL-6R) showed a significant variation; a rise during the early and late follicular periods followed by a fall during the early luteal period (P = 0.0423, P = 0.0334) and an increase during the mid and late luteal periods. There were significant changes in the levels of markers of bone formation: a rise in serum bone-specific alkaline phosphatase (ALP) during the mid and late follicular (P = 0.0265) periods and a fall in serum carboxyl-terminal propeptide of type I procollagen (PICP) during the midluteal period (P = 0.0161). As for the levels of bone resorption markers, urinary type I collagen C-telopeptide breakdown products (CTx) and free deoxypyridinoline (D-Pyr) decreased significantly during the early and midfollicular periods, urinary free D-Pyr and serum pyridinoline cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) (P = 0.0440) increased significantly during the early luteal period, and urinary CTx, free D-Pyr, and serum ICTP decreased significantly during the late luteal period (P = 0.0170-0.0008). The serum PTH level was significantly higher during the follicular than the luteal period (P = 0.0132). Serum sIL-6R significantly correlated with urinary CTx (r = 0.190, P < 0.05) and serum ALP (r = 0.209, P < 0.05) and serum estradiol with intact osteocalcin (r = 0.309, P < 0.0005) and serum ALP (r = 0.181, P < 0.05). These observations strongly suggest that cyclic variations in the levels of bone formation and resorption markers and of a bone-resorbing cytokine may be modulated by cyclic changes in serum steroid hormones during the menstrual period. In addition, the specific days of biochemical events in the menstrual cycle are crucial for evaluating osteoclastic and osteoblastic activities in pre- and perimenopausal women or in women starting GnRH agonist therapy.

Adult↗
PubMed1998

Antihypertensive effect of sesamin. III. Protection against development and maintenance of hypertension in stroke-prone spontaneously hypertensive rats.

The antihypertensive effect of sesamin, a lignan from sesame oil, was examined using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking water. Each group was further divided into two groups: normal-diet group and sesamin-diet group. Systolic blood pressure of all animals was monitored once weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal damage were evaluated. In the salt-loaded group, sesamin feeding significantly suppressed the development of hypertension, and efficient suppression was maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old). The left ventricle plus septum weight-to-body weight ratio was slightly but significantly lowered by sesamin feeding. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, wall thickness and wall area of these vessels were significantly decreased by the sesamin feeding. Histological renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall were often observed in the normal-diet group, but this damage was efficiently reduced in the sesamin-fed animals. On the other hand, in the salt-unloaded group, only a slight and nonsignificant suppressive effect of sesamin on the development of hypertension was observed. Although the wall area of the aorta was significantly decreased by the sesamin feeding, other vascular parameters were not ameliorated. The incidence of histological renal damage tended to decrease in sesamin-fed animals, but these alterations were not statistically significant. Thus, sesamin feeding was much more effective as an antihypertensive regimen in salt-loaded SHRSP than in unloaded SHRSP, thereby suggesting that sesamin is more useful as a prophylactic treatment in the malignant status of hypertension and/or hypertension followed by water and salt retention.

Animals↗
PubMed1998

[A case of sellar T cell type malignant lymphoma].

A case of primary T cell type malignant lymphoma of the sellar region was reported. This 53-year-old male was admitted to our neurosurgical service because of slowly progressive occipitalgia and diplopia over the previous 5 months. On admission neurological examination revealed a slight limitation of the lateral movement of the left eye. Endocrinological examination showed no abnormalities. Despite a mild neurological deficit, a CT scan revealed an extensive bony destruction around the sellar region including the dorsum sellae, the bilateral petrous apices, and the upper two thirds of the clivus. Magnetic resonance imaging (MRI) disclosed that the tumor was slightly hypointense on T1-weighted image, isointense on T2-weighted image, and faintly and homogeneously enhanced after administration of Gd-DTPA. Since the tumor was enhanced faintly on MRI, it was diagnosed as an invasive pituitary adenoma, but it was thought that chordoma and germinoma should be considered. The patient underwent a transsphenoidal surgery. A firm, grayish and avascular tumor was partially removed. The histopathological examination using monoclonal surface marker of the specimen revealed the tumor was stained with UCHL-1 and CD3 antibodies directed against T cells, and diagnosed as T cell type malignant lymphoma of the sellar region (diffuse, large cell type; LSG). Postoperatively he received radiation therapy. His symptoms much improved and no regrowth of the residual tumor has been found in follow-up studies to the present. Primary malignant lymphomas very rarely occur in the skull base. As far as we are aware, this is the only second case of primary T-cell lymphoma in the sellar region reported so far in the medical literature. Although preoperative diagnosis is extremely difficult because of a paucity of data, malignant lymphomas should be kept in mind in the differential diagnosis of sellar tumors, especially if neuroimaging studies show an extensive bony destruction in the skull base.

Combined Modality Therapy↗
PubMed1998

[Eosinophil count in induced sputum samples as a marker of airway inflammation and adequacy of corticosteroid inhalation treatment in asthmatic patients].

We tried to use eosinophil counts in induced sputum samples as a marker of airway inflammation, and as a guide for reducing inhaled corticosteroids in patients with well-controlled persistent asthma. The eosinophil count in induced sputum smears was defined as follows: Eos%; eosinophil percentage of 200-400 leukocytes in properly cell-separated fields, TEC; total eosinophil counts in the 5 most eosinophil-dense high power view fields (x 400). First, the eosinophil count in induced sputum samples was compared between 29 asthmatic subjects treated with inhaled corticosteroid and 15 age- and sex-matched healthy controls. Second, inhaled corticosteroid was reduced by 50% in 20 patients with green-zone asthma (morning PEF > 80% of patient's best PEF). PEF measurements were followed prospectively for 12 weeks thereafter. Once PEF decreased below 70% of their best PEF, subjects were considered as treatment "failures". Both Eos% and TEC were significantly higher than in the controls, even in well-controlled (morning PEF > 80% of their best) asthmatic patients (p = 0.001, 0.03). The chance of treatment "failure" was significantly higher in those having more eosinophils (Eos% > 10%, TEC > 100) in their initial induced sputum sample (p = 0.03, 0.001). Airway inflammation still persists in many well-controlled chronic asthmatic patients, and induced sputum eosinophilia predicts an early decrease of PEF after reduction of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1998

[Secondary osteoporosis in gynecology].

Several diseases and medications are known to induce secondary osteoporosis. Among them, same situations are related to gynecological field. They include Turner's syndrome, anorexia nervosa, ovarian dysfunction, oophorectomy, GnRH agonist therapy, and osteoporosis associated with pregnancy. We briefly describe these secondary osteoporosis in this article as follows. Several studies have found osteoporosis to be a common complication of Turner's syndrome and hormone replacement therapy has been used as a possible management; in anorexic patient, low body weight, prolonged amenorrhea, early onset of anorexia nervosa, and hypercortisolism have been reported to be risks for bone demineralization; since oophorectomy which is a common intervention in gynecology leads osteoporosis, it is important to prevent osteoporosis caused by surgery as well as postmenopausal osteoporosis; GnRH agonist, which induces estrogen deficient state and affect bone mass, is commonly used as a management for endometriosis and leiomyoma of uterus; associated with pregnancy, post-pregnancy spinal osteoporosis and transient osteoporosis of the hip are clinically considered to be important and heparin therapy and magnesium sulfate therapy are commonly employed during pregnancy, affecting calcium homeostasis.

Anorexia Nervosa↗
PubMed1998

[Significance of serum surfactant protein-D (SP-D) level in patients with pulmonary tuberculosis].

Elevated levels of serum surfactant protein-D (SP-D) have been previously reported in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis. To determine whether the same change is seen in other pulmonary diseases, especially pulmonary tuberculosis (TB), we measured the serum SP-D levels in active pulmonary TB (smear and/or culture: positive), acute interstitial pneumonia (AIP), IPF, acute exacerbation of IPF, hypersensitivity pneumonitis (HP), pneumoconiosis, bronchiectasis, and bacterial pneumonia by an enzyme-linked immunosorbent assay using monoclonal antibodies to human lung SP-D, and compared them with those of healthy elderly subjects over 50 years of age. The SP-D level in the healthy elderly subjects was 57.6 +/- 38.4 ng/ml (mean +/- SD, n = 287). The levels in patients with active pulmonary TB (140.6 +/- 18.2 ng/ml, n = 49), AIP (1,021 ng/ml, n = 1), IPF (307.0 +/- 180.7 ng/ml, n = 42), acute exacerbation of IPF (817.7 +/- 283.6 ng/ml, n = 3), and HP (716.6 +/- 548.8 ng/ml, n = 4) were significantly higher than those in the healthy elderly controls (p < 0.05), whereas those of pneumoconiosis, bronchiectasis, and bacterial pneumonia, 121.9 +/- 92.8 ng/ml (n = 8), 93.9 +/- 72.9 ng/ml (n = 11), and 72.7 +/- 3.4 ng/ml (n = 4), respectively, showed no significant difference with the controls. In active pulmonary TB, the percentage of patients whose serum SP-D levels were over 134.6 ng/ml (mean + 2SD of healthy elderly controls) was 34.7%, and therefore we considered the serum SP-D level was not useful for the diagnosis of pulmonary TB. However, it was significantly higher in the patients with cavity formation than in those without (p < 0.05), and there was a significant positive correlation between the serum SP-D level and the number of tubercle bacilli in the sputum (r = 0.416, p = 0.00165), erythrocyte sedimentation rate at 1 hr (r = 0.489, p < 0.01), and CRP level (r = 0.383, p = 0.003). These findings suggest that the serum SP-D level is a useful indicator of the disease activity in pulmonary TB.

Aged↗
PubMed1997

Platelets enhance contractility in perfused rat mesenteric arteries: involvement of endothelin-1.

We investigated the effects of platelet supernatant on pressor responses to norepinephrine in isolated perfused rat mesenteric arteries. Perfusion of the arteries with platelet supernatant for 2 h markedly enhanced the pressor responses to norepinephrine (10(-6) and 3 x 10(-6) M). This enhancement was significantly inhibited by phosphoramidon (10(-4) M), an endothelin converting enzyme inhibitor. Both BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1-methoxycarbonyltryptophanyl-D-norleucine] (10(-6) M), an endothelin ET(B) receptor antagonist, and bosentan (Ro47-0203, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2-bipyri midin-4-yl]-benzenesulfonamide) (10(-5) M), a nonselective endothelin receptor antagonist, also prevented the potentiation of responses to norepinephrine evoked by platelet supernatant, but FR 139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-+ ++methylpentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) (10-6 M), an endothelin ET(A) receptor antagonist, had little effect. Suppressor doses of endothelin-1 (3 x 10(-10) M) or sarafotoxin S6c (S6c) (3 x 10(-10) M) potentiated significantly the norepinephrine-induced vasoconstriction, in the same preparation. Moreover, supernatant-induced enhancement of pressor responses to norepinephrine was markedly suppressed by TGF-beta1 neutralizing antibody. Transforming growth factor-beta1 (TGF-beta1) (40 pM) also significantly enhanced the pressor responses to norepinephrine (10(-6) M) and this enhancement was significantly inhibited by phosphoramidon. These results suggest that platelet-derived TGF-beta1 stimulates the vascular production of endothelin-1 and thereby enhances vasoconstrictor responses to norepinephrine. Platelet-induced enhancement of vasoconstrictor responses to norepinephrine seems to be mainly mediated by endothelin ET(B) receptor, in rat mesenteric arteries.

Animals↗
PubMed1997

Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow.

Both estrogen and androgen exert their antiosteoporotic effects, at least in part, by inhibiting IL-6 production, thereby suppressing osteoclastogenesis. Several observations, however, suggest that besides increased IL-6 production, sensitivity of the osteoclastogenic process to this cytokine is altered after ovariectomy. Based on this and evidence that the ligand-binding subunit of the IL-6 receptor (gp80) is a limiting factor for the actions of IL-6 on bone, we hypothesized that sex steroids regulate expression of the IL-6 receptor as well. We report that 17beta-estradiol or dihydrotestosterone in vitro decreased the abundance of the gp80 mRNA as well as the mRNA of the signal-transducing subunit of the IL-6 receptor (gp130) in cells of the bone marrow stromal/osteoblastic lineage, and also decreased gp130 protein levels. These effects did not require new protein synthesis. In contrast to sex steroids, parathyroid hormone stimulated gp130 expression; this effect was opposed by sex steroids. Consistent with these findings, ovariectomy in mice caused an increase in expression of gp80, gp130, and IL-6 mRNAs in ex vivo bone marrow cell cultures as determined by quantitative reverse transcription (RT)-PCR, and confirmed on an individual cell basis using in situ RT-PCR. The demonstration of increased expression of the IL-6 receptor after loss of sex steroids provides an explanation for why IL-6 is important for skeletal homeostasis in the sex steroid-deficient, but not replete, state.

Animals↗
PubMed1997

Amino acid substitutions in the first transmembrane domain (TM1) of P-glycoprotein that alter substrate specificity.

Recently, we showed that the amino acid at position 61 in TM1 of human P-glycoprotein is important in deciding the substrate specificity of this protein. In this work, we investigated whether the amino acids other than His61 in TM1 of P-glycoprotein are also essential in the function of this protein. Nine amino acids residues, from Ala57 to Leu65 in TM1, were independently substituted to Arg, and analyzed the drug resistance of cells stably expressing each of these mutant P-glycoproteins. The mutant P-glycoproteins Ile60 --> Arg, His61 --> Arg, Ala63 --> Arg, Gly64 --> Arg, and Leu65 --> Arg were normally processed and expressed in the plasma membrane. Substrate specificities of mutant P-glycoproteins Gly64 --> Arg and Leu65 --> Arg were quite different from that of the wild type, and similar to that of the His61 --> Arg mutant, while the Ile60 --> Arg and Ala63 --> Arg mutant P-glycoproteins showed similar substrate specificities to that of the wild-type P-glycoprotein, suggesting that not only the amino acid residue at position 61 but also those at position 64 and 65 are also important in deciding the substrate specificity of P-glycoprotein. These three amino acids His61, Gly64, and Leu65 would form a compact region on an alpha-helix arrangement of TM1. These results suggest that a region consisting of His61, Gly64, and Leu65 in TM1 would participate in the formation of the recognition site for substrates of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Alteration of substrate specificity by mutations at the His61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein.

In CFTR, a member of the ABC superfamily and a chloride channel, amino acid substitutions in its transmembrane domains 1 and 6 (TM1, TM6) have been reported to modulate the anion selectivity or ion conductance of the ion channel. In P-glycoprotein, no amino acid substitution in TM1, but some in TM6, have been reported to modify the substrate specificity of this protein. In this work, we demonstrated the involvement of His61, which is in the middle of the predicted TM1, in the function of P-glycoprotein. His61 was replaced by all other amino acid residues, and each of the mutant cDNAs was introduced into drug-sensitive human carcinoma cells, KB3-1. The drug-resistance profile of cells stably expressing each mutated P-glycoprotein was investigated by comparing their relative resistance to vinblastine, colchicine, VP16, and adriamycin. The resistance to vinblastine was increased by replacing His61 by amino acids with smaller side chains, while it was lowered by replacing by amino acids with bulkier side chains. The reverse effect was observed for resistance to colchicine and VP16. The resistance to adriamycin was increased by replacing by amino acids with bulkier side chains except Lys or Arg, which have a basic side chain. We also showed that the replacement of His61 by Phe and Lys greatly impaired the efflux of calcein AM, while the replacement had no effect on the efflux of rhodamine 123. These results suggest that an amino acid residue at position 61 in TM1 is important in deciding the substrate specificity of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Clonal selection of HIV type 1 variants associated with resistance to foscarnet in vitro: confirmation by molecular evolutionary analysis.

Foscarnet (trisodium phosphonoformate, PFA) is an effective inhibitor of retroviral reverse transcriptase (RT) and is known to block the replication of human immunodeficiency virus type 1 (HIV-1). In this article we analyzed the evolutionary process in generating HIV-1 strains related to drug resistance, using PFA as a selective pressure. PFA inhibited virus replication and protected the virus-induced cell killing, but it did not completely eliminate HIV-1 during the course of 7 weeks of treatment. The nucleotide sequence of the 859-bp DNA fragment spanning the core region of the HIV-1 pol gene was determined for 51 clones obtained from genomic DNA of the HIV-1-infected cells at different time points during PFA treatment. The nucleotide sequence analysis documented the presence of a minor HIV-1 variant prior to the PFA treatment. Molecular evolutionary techniques were utilized to analyze how the minor HIV-1 clones became predominant during this evolutionary process under the selective pressure of PFA. A phylogenetic tree analysis divided these 51 HIV-1 clones into 3 groups. One of the groups consisted of the clones associated with the resistance to PFA. The clones belonging to this group became predominant over time during the course of PFA treatment. Thus, the acquisition of PFA resistance by HIV-1 was considered to be due to clonal selection. Furthermore, among the various amino acid substitutions observed, the substitution of arginine at position 172 by lysine (Arg172Lys) clearly distinguished this group from the others. Since the consistent amino acid substitution observed here has not been identified in the HIV-1 strains resistant to other RT inhibitors, PFA in combination with other RT inhibitors is considered to be a feasible candidate for a convergent combined chemotherapy against HIV-1 in the treatment of patients with AIDS and related conditions.

Amino Acid Sequence↗