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Biomedical subjects

T Hirai

Publications and source records attributed to T Hirai.

At least 73 records · Page 4Linked to original sources
PubMed2001

Transactivation of core binding factor alpha1 as a basic mechanism to trigger parathyroid hormone-induced osteogenesis.

During 28-day culture of bone marrow- and calvaria-derived osteoblasts, the constant presence of parathyroid hormone (PTH)(1-34) retarded differentiation and nodule formation (NF) in a dose-dependent fashion (C-phase). In contrast, addition of PTH(1-34) in late stage cultures (from day 10 to 21) accelerated NF (A-phase). The stable production of such an A-phase allowed us to study the mechanism of bone anabolic action of PTH(1-34). Subcellular localization studies of core binding factor alpha1 (Cbfa1) and reporter assays provided the results indicating that in the A-phase, PTH(1-34) triggers its bone anabolic action via enhancement of Cbfa1 transactivation. RT-PCR and Northern blot analyses revealed that alkaline phosphatase, osteocalcin and bone sialoprotein expression decreased in the C-phase and increased in the A-phase; however, expression of other bone proteins (Cbfa1, PTH/PTH-related peptide-receptor, osteopontin, collagen I alpha1, collagen I alpha2, vitamin K-dependent gamma-glutamyl carboxylase) did not change in a phase transition-related manner. Ovariectomized osteopenic mice, treated with PTH(1-34) (4 and 40 microg/kg, s.c., every other day, 4 or 6 weeks), recovered lost bone, displayed elevated nuclear localization of Cbfal in tibiae without alteration of its cytosolic level and exhibited upregulation of expressions of the same set of proteins (alkaline phosphatase, osteocalcin and bone sialoprotein) in femora. These results obtained by a concerted study in vitro and in vivo suggest that PTH triggers its osteogenic action via promotion of the transactivation of Cbfa1.

Alkaline Phosphatase↗
PubMed2001

A novel rhamnose-binding lectin family from eggs of steelhead trout (Oncorhynchus mykiss) with different structures and tissue distribution.

An L-rhamnose-binding isolectin named STL3 (subunit Mr, 21.5 k) was isolated from eggs of the steelhead trout (Oncorhynchus mykiss) in addition to STL1 (subunit Mr, 31.4 k) and STL2 (subunit Mr, 21.3 k) that had been already isolated. STLs were composed of noncovalently linked subunits. The primary structures of STL1 and STL3 were analyzed by the combined use of protein sequencing and cDNA sequencing. A cDNA encoding STL2, of which the protein sequence had been previously studied, was also analyzed. The STL1 subunit (289 amino acid residues) had different structural properties compared to those of the STL2 subunit (195 amino acid residues) and the STL3 subunit (195 amino acid residues); e.g., the number of repeated domain (three for STL1, and two for STL2 and STL3), although all of them were composed of tandemly repeated homologous domains (40 to 53% identities). The lectin levels in various tissues and during the embryonic development showed that STL1 had different distribution and expression profiles from those of STL2 and STL3. Although STL1 could be detected in several tissues and serum of both male and female steelhead trout, STL2 and STL3 were only abundant in the ovary. STL2 and STL3 levels dramatically decreased just after hatching, however, the STL1 level increased temporarily. These results indicate that the multiple lectins from eggs of the steelhead trout form a novel rhamnose-binding lectin family with different structures and tissue distribution to share distinct functions in eggs.

Amino Acid Sequence↗
PubMed2001

Milk basic protein promotes bone formation and suppresses bone resorption in healthy adult men.

Milk contains several components effective for bone health. In the previous in vitro and in vivo studies, we have shown that milk whey protein, especially its basic protein fraction (milk basic protein [MBP]), promoted bone formation and suppressed bone resorption. This present study examines the effect of MBP on the biochemical markers of bone metabolism in healthy adult men. Experimental beverages containing MBP (300 mg of MBP a day) were given to 30 normal healthy adult men for 16 days. The serum osteocalcin concentration had increased significantly after 16 days of ingesting the experimental beverage containing MBP. Urinary cross-linked N-teleopeptides of type-I collagen (NTx) excretion had decreased significantly after 16 days of ingesting MBP. The urinary NTx excretion was related to the serum osteocalcin concentration after 16 days of ingestion. These results suggest that MBP promoted bone formation and suppressed bone resorption, while maintaining the balance of bone remodeling.

Adult↗
PubMed2001

A transesophageal echocardiographic study on risk factors for stroke in elderly patients with atrial fibrillation: a comparison with younger patients.

STUDY OBJECTIVES: Atrial fibrillation (AF) becomes an increasingly important cause of stroke as patients get older. The aim of the study was to determine whether risk factors of cerebral embolism among elderly patients with AF differed from those of younger patients by using transesophageal echocardiography (TEE). DESIGN AND SETTING: Cross-sectional study at a university hospital. METHODS: Cardiovascular lesions with the potential for thromboembolism in patients with AF were investigated using TEE. Left atrial spontaneous echocardiographic contrast (SEC), peak flow velocity in the left atrial appendage (LAA-flow), and aortic atherosclerosis of the thoracic aorta were assessed in 67 elderly (> or = 70 years old) and 135 younger (< 70 years old) patients. All patients underwent either brain CT (n = 54) or MRI (n = 148) to assess presence of cerebral infarction. RESULTS: Cerebral infarction due to embolism was noted in 113 patients with AF. There was a higher prevalence of cerebral embolism in elderly patients when compared with younger patients (78% vs 45%; p < 0.001). Cerebral embolism found in younger patients was associated with high grade of SEC and lower LAA-flow (p < 0.05). In addition to these TEE findings, aortic atherosclerosis was more severe in elderly patients with cerebral embolism than in those without cerebral embolism (p < 0.0001). By multivariate logistic analysis, LAA-flow was an independent predictor of cortical infarction in younger patients, but not in elderly patients, whereas aortic atherosclerosis was a useful marker in predicting embolic risk in elderly patients. CONCLUSIONS: TEE findings indicative of left atrial blood stasis were useful to identify the embolic risk of younger patients with AF, while atherosclerosis of the thoracic aorta appears to be an important marker for cerebral embolism in elderly patients.

Age Factors↗
PubMed2001

Properties of internal speed control and psychophysiological response during continuous forearm rotation movement.

This study investigated the properties of speed control and psychophysiological response when subjects changed movement speed internally. The task consisted of a continuous forearm rotational movement, which 14 women performed under 3 conditions, namely, (1) Preferred: the subject performed the task at a freely selected speed, (2) Slow: the subject changed the speed in two steps from preferred to a slower pace (slow, then very slow), (3) Fast: the subject changed the speed in two steps from preferred to a faster pace (fast, then very fast). Rotation speed and the coefficient of variation were measured to evaluate within-subject variability. Under the Preferred condition, there were no significant differences in rotation speed or coefficient of variation during the trials. However, under Slow and Fast conditions, the standard variation scores and coefficient of variation indicated different tendencies. Under the Fast condition, although the standard variation increased with the faster speed, the coefficient of variation decreased. On the other hand, the coefficient of variation increased under the Slow condition. Preferred speed had a significant positive relationship to the slow, very slow, fast, and very fast speeds. Heart rate (R-R interval) and EEG spectral intensity measurements showed no significant changes among the three conditions: however, respiration frequency significantly increased during Fast as compared to Preferred and Slow conditions. These results suggest that a preferred speed for continuous movement exists and that it is closely related to internal speed control as a psychological criterion. Furthermore, different movement speeds may reflect different psychophysiological responses.

Adult↗
PubMed2001

Myocardial lipid metabolism in compensated and advanced stages of heart failure: evaluation by canine pacing model with BMIPP.

UNLABELLED: The normal myocardium uses primarily fatty acid as its energy source, but, as heart failure develops, the myocardial fatty acid metabolism is limited. In this study, impairment of the lipid metabolism in heart failure was serially evaluated with 123I-(rho-iodophenyl)3-(R,S)-methylpentadecanoic acid (BMIPP), a radioiodinated fatty acid analog. METHODS: Rapid ventricular pacing was introduced in 10 beagle dogs. Dogs were subjected to hemodynamic assessment and measurement of catecholamine before and after pacing. After 1 wk (group A; n = 4) and 4 wk (group B; n = 6) of pacing, BMIPP was injected directly into the left anterior descending artery; its extraction, retention, and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using high-performance liquid chromatography. These factors were compared with those of healthy control animals (group C; n = 6). RESULTS: The left ventricular ejection fraction and cardiac output decreased significantly in groups A and B after pacing. The pulmonary capillary wedge pressure did not change in group A but increased significantly in group B. Plasma norepinephrine increased progressively as heart failure developed but did not reach statistical significance. The washout rate in the early phase increased, significantly in groups A and B compared with that of group C. Extraction and retention of BMIPP did not change in group A. In group B, extraction tended to decrease and retention decreased significantly compared with that of group C. The levels of full metabolite formed by complete oxidation of BMIPP decreased, and backdiffusion of BMIPP increased significantly in groups A and B compared with that of group C. Myocardial blood flow did not change among the three groups. CONCLUSION: Our study indicates that myocardial fatty acid oxidation begins to be inhibited and that washout of BMIPP increases in the compensated stage of left ventricular dysfunction but that myocardial extraction and retention of fatty acid are definitely impaired in the advanced stage of heart failure. Therefore, as assessed by BMIPP, the myocardial lipid metabolism is related to the pathophysiology of the development and worsening of heart failure.

Animals↗
PubMed2001

[Treatment of lymph node metastasis from the viewpoint of surgical oncology].

We have investigated methods to predict lymph node metastasis in early gastric cancer. First, the efficacy of fluorescence in situ hybridization (FISH) using the dual-color method was evaluated as a potential marker of lymph node metastasis in 20 early gastric cancers. A significant increase in the fraction of cells with a decrease in p53 was observed in early gastric cancer compared with normal tissues. More importantly, a significant increase in the fraction of cells with p53 deletion was observed in patients with lymph node metastasis. The predictive accuracy was 45%. Second, the relationship between the degree of expression of biological markers and lymph node metastasis was examined. High expression of p27 and cyclin E had a strong correlation with lymph node metastasis. Moreover, all patients with combined high expression of p27, cyclin E, and matrix metalloproteinase-9 had lymph node metastasis. However, these represented only 21% of cases with lymph node metastasis. Difficulty in the clinical use of these biological markers to detect lymph node metastasis depends on the feedback mechanism of cell cycle regulators or heterogeneity of the lesion. These problems should be resolved in the near feature.

Cell Cycle Proteins↗
PubMed2001

[Undescended testicular tumor found by torsion of the testis: a case report].

A 37-year-old man was admitted with a painful mass in his left inguinal region. He had an undescended testis on the left side. Six months earlier, he had noted that his left inguinal testis was larger, and he had suddenly developed pain in the left inguinal region. The levels of AFP, hCG beta and LDH were normal. We diagnosed a left undescended testicular tumor and torsion of the left testis. Left inguinal high orchiectomy showed a torsion of the left testis and histopathological examination of the specimen revealed seminoma.

Adult↗
PubMed2001

[Renal metastasis originating from pulmonary carcinoma: a case report].

A 61-year-old woman, who had undergone total right pneumonectomy 22 months before due to lung cancer (adenosquamous cell carcinoma) was admitted for macroscopic hematuria. Abdominal CT showed two renal tumors in the right kidney. Right radical nephrectomy was performed, because no imaging study showed any other metastasis. Pathological examination revealed adenosquamous cell carcinoma, which was the same pathology as the lung cancer had been. She died of the left lung metastasis 24 months after right radical nephrectomy. Her prognosis was thought to have been prolonged by the operation of right radical nephrectomy.

Carcinoma, Adenosquamous↗
PubMed2001

[A new therapeutic approach to advanced and recurrent gastric cancer by TS-1].

In the present study, we demonstrate the treatment results of TS-1 on 22 gastric carcinoma patients (15 far advanced and 7 recurrent patients) from June 1999 to December 2000. TS-1 was administered at 75 mg/m2/day, twice daily per body for 28 days followed by a 14-day interval (1 cycle). Successful treatment was obtained in from 1 to 11 cycles, and we obtained 9 (47.4%) partial responses (PR), 7 stable disease (NC) and progressive disease (PD) among 19 evaluable patients. PR was obtained in 7 (58.3%) out of 12 primary lesions of the stomach. We also obtained 1 CR of liver metastasis and 4 PR of 9 distant lymph node metastases (44.4%). Moreover, malignant ascites disappeared in 4 (57.1%) out of 7 cases and PR was obtained in 3 (50%) out of 6 measurable cases of peritoneal disease. In addition, two patients had hydronephrosis which improved after 1 cycle of TS-1 treatment. The adverse effects observed were grade 3 bone marrow suppression in three cases, severe diarrhea in one case, one case of liver dysfunction and a few cases of nausea and vomiting. These results indicate that the oral tegafur compound, TS-1, is a new therapeutic tools for advanced and recurrent gastric carcinomas, especially peritoneal disease.

Administration, Oral↗
PubMed2001

[Prostatic carcinoma presenting as neck lymph node metastases: report of two cases].

We report two cases of prostatic carcinoma presenting as neck lymph node metastases. Case 1: A 56-year-old man was admitted to our hospital with the chief complaint of left lower abdominal pain. A lymph node was palpable on the left side of the neck swollen. Rectal examinations revealed prostatic stony-hard mass. Computed tomography showed a swollen neck and paraaortic lymph nodes on the left side. PSA level was 380 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma, and neck lymph node biopsy also revealed metastatic adenocarcinoma. We diagnosed him with prostatic carcinoma stage D2 (LYM). He underwent hormonal therapy (TAB) but died 13 months later. Case 2: A 66-year-old man was admitted to our hospital with the chief complaint of a large palpable mass on the left side of the neck. Resection of this mass revealed metastatic adenocarcinoma. Rectal examination revealed no malignant lesions, but the PSA level was high, 1,700 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma. Computed tomography revealed paraaortic and pelvic lymph node metastases and bone scintigram revealed abnormal uptake, bone metastases. We diagnosed him with prostatic carcinoma stage D2 (LYM OSS). We performed bilateral testectomy followed by hormonal therapy (TAB). The lymph node metastases disappeared after 4 months of therapy.

Adenocarcinoma↗
PubMed2000

Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1.

Human histone deacetylases I (HDAC1) and II (HDAC2) are homologous proteins (84% identity) that catalyze release of acetyl groups from modified N-terminal lysines of core histones. Histone deacetylation is correlated with both transient and persistent states of transcriptional inactivity (i.e. silencing) in many eukaryotes. In this study, we analyzed complexes containing HDAC1 and HDAC2 to identify the proteins most stably associated with these deacetylases. Complex cI (9.5 S) contained transcriptional corepressor CoREST/kiaa0071 and a protein homologous to FAD-dependent oxidoreductases, kiaa0601. Complex cII (15 S) contained >/=15 proteins, including CHD3/4 (Mi-2), Mta-L1, RbAp48/46, and MBD3, characteristic of vertebrate nucleosome-remodeling complexes. Under native conditions, cI and cII may contain HDAC1, HDAC2 or both; these can be dissociated to cI and cII core complexes containing only HDAC1 or HDAC2. The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex. A model is proposed in which HDAC1 core complexes can be targeted to methylated DNA via MBD2 with recruitment of HDAC2 occurring through formation of HDAC1/2 cII dimers. We note that the cI component CoREST/kiaa0071 and the cII component Mta-L1 share a region of homology that includes a SANT domain; this domain may play a role in complex assembly.

Amino Acid Sequence↗
PubMed2000

The three-dimensional map of microsomal glutathione transferase 1 at 6 A resolution.

Microsomal glutathione transferase 1 (MGST1) is representative of a superfamily of membrane proteins where different members display distinct or overlapping physiological functions, including detoxication of reactive electrophiles (glutathione transferase), reduction of lipid hydroperoxides (glutathione peroxidase), and production of leukotrienes and prostaglandin E. It follows that members of this superfamily constitute important drug targets regarding asthma, inflammation and the febrile response. Here we propose that this superfamily consists of a new class of membrane proteins built on a common left-handed four-helix bundle motif within the membrane, as determined by electron crystallography of MGST1 at 6 A resolution. Based on the 3D map and biochemical data we discuss a model for the membrane topology. The 3D structure differs significantly from that of soluble glutathione transferases, which display overlapping substrate specificity with MGST1.

Amino Acid Motifs↗
PubMed2000

Structural determinants of water permeation through aquaporin-1.

Human red cell AQP1 is the first functionally defined member of the aquaporin family of membrane water channels. Here we describe an atomic model of AQP1 at 3.8A resolution from electron crystallographic data. Multiple highly conserved amino-acid residues stabilize the novel fold of AQP1. The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constriction of the pore diameter to about 3 A over a span of one residue. The atomic model provides a possible molecular explanation to a longstanding puzzle in physiology-how membranes can be freely permeable to water but impermeable to protons.

Amino Acid Sequence↗
PubMed2000

Cloning, functional characterization, and expression of thyrotropin receptors in the thyroid of amago salmon (Oncorhynchus rhodurus).

Two thyrotropin receptor cDNAs (sTSH-Ra and sTSH-Rb) were cloned from thyroid tissue of the amago salmon, Oncorhynchus rhodurus. sTSH-Ra and sTSH-Rb showed the highest degrees of sequence homology to mammalian TSH receptors. Functional characterization in COS-7 cells transiently transfected with sTSH-Ra or sTSH-Rb showed the largest increase in cAMP when exposed to bovine TSH. RT-PCR analysis demonstrated that sTSH-Ra and sTSH-Rb were expressed in the basibranchial region, but not in the ovary, testis, liver, kidney or brain. In situ hybridization revealed that sTSH-Ra and sTSH-Rb were exclusively expressed in thyroid follicular epithelial cells of amago salmon undergoing smoltification. These results indicated that the cloned cDNAs encode functional TSH receptor proteins. This is the first report of isolation of TSH receptor molecules from nonmammalian vertebrates.

Amino Acid Sequence↗
PubMed2000

Exercise-induced negative U waves in precordial leads as a marker of viable myocardium in patients with recent anterior myocardial infarction.

Patients with recent anterior myocardial infarction and a significant stenosis in the left anterior descending coronary artery were divided into two groups according to the presence (Group A, n=24) or absence (Group B, n=77) of negative U waves in the precordial leads during exercise stress test to compare the coronary arteriographic findings. Both total occlusion of the left anterior descending coronary artery (79% vs. 31%, P<0.01)) and good (index=2, 3) collateral circulation to the territory of this artery (92% vs. 36%, P<0.01) were observed more often in group A than in group B. In order to determine whether detection of exercise-induced negative U waves in precordial leads can predict the presence of viable myocardium, the 56 patients (20 of group A and 36 of group B) with total or subtotal occlusion of the left anterior descending coronary artery were studied further. The coronary arteriographic and exercise 201Tl scintigraphic findings were compared between the groups. Good collateral circulation to the territory of this artery was observed significantly (P<0.05) more often in group A (100%) than in group B (61%). Patients with multivessel disease were significantly (P<0.05) more prevalent in group A (70%) than in group B (33%). The incidence of a significant partial redistribution in the anteroseptal area in the 20Tl images 4 h after exercise was significantly (P<0.01) higher in group A (85%) than in group B (39%). In 29 patients with anterior Q-wave myocardial infarction and exercise-induced ST elevation in precordial leads, a significant 201Tl redistribution in the anteroseptal area was observed in 8 (80%) of 10 patients of group A in contrast to only 4 (21%, P<0.05) of 19 in group B. In the diagnosis of the viability associated with 201Tl redistribution in the anteroseptal area by the finding of exercise-induced negative U waves, the sensitivity was 67% and the specificity was 88% in these patients. We conclude that exercise-induced negative U waves in precordial leads are a convenient and specific marker for the presence of viable myocardium in patients with recent anterior myocardial infarction.

Collateral Circulation↗
PubMed2000

Exercise-induced U-wave alterations as a marker of well-developed and well-functioning collateral vessels in patients with effort angina.

OBJECTIVES: We sought to determine whether exercise-induced U-wave alterations are observed in association with well-developed and well-functioning collateral vessels. BACKGROUND: Although exercise-induced electrocardiographic (ECG) U-wave alterations including negative and prominent U waves have been established as a marker of significant or critical narrowing of a major coronary artery, the relation between this finding and the degree of collateral development has not yet been determined. METHODS: Patients with stable effort angina were divided into two groups according to the presence (group A, n = 46) or absence (group B, n = 79) of exercise-induced either negative or prominent U waves in the precordial leads; the clinical profiles, coronary angiographic findings and also ischemic status during 60 s of coronary balloon occlusion were compared between the two groups. RESULTS: The incidence of severe angina (CCS [Canadian Cardiovascular Society] class III or IV) was higher (p < 0.05) in group A (52%) than in group B (32%) patients. Good collateral vessels (Rentrop grade 2 or 3) into the perfusion territory of the culprit vessel were observed more frequently (p < 0.05) in group A (70%) than in group B (43%) patients. Coronary balloon angioplasty was carried out in 23 patients of group A and 40 patients of group B. Both ischemic ST changes (52% vs. 85%) and angina (57% vs. 80%) during balloon inflation were less (p < 0.05) frequently observed in group A than in group B. The incidence of no apparent myocardial ischemia with ST deviation or angina during the balloon inflation was higher (p < 0.05) in group A (39%) than in group B (10%) patients. In the prediction of the absence of myocardial ischemia during balloon inflation by the presence of exercise-induced U-wave alterations, the sensitivity was 69% (9/13) and the specificity was 72% (36/50) in the study patients. CONCLUSIONS: Exercise-induced U-wave alterations are a marker for well-developed collateral circulation in patients with stable but severe effort angina. This finding is also highly predictive of the absence of myocardial ischemia during transient coronary balloon occlusion and possibly of low-risk for development of acute myocardial infarction or hemodynamic instability upon abrupt closure of the culprit coronary artery.

Angina Pectoris↗