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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 73 records · Page 4Linked to original sources
PubMed1999

Maturational disturbance of chondrocytes in Cbfa1-deficient mice.

Cbfa1, a transcription factor that belongs to the runt-domain gene family, plays an essential role in osteogenesis. Cbfa1-deficient mice completely lacked both intramembranous and endochondral ossification, owing to the maturational arrest of osteoblasts, indicating that Cbfa1 has a fundamental role in osteoblast differentiation. However, Cbfa1 was also expressed in chondrocytes, and its expression was increased according to the maturation of chondrocytes. Terminal hypertrophic chondrocytes expressed Cbfa1 extensively. The significant expression of Cbfa1 in hypertrophic chondrocytes was first detected at embryonic day 13.5 (E13.5), and its expression in hypertrophic chondrocytes was most prominent at E14.5-16.5. In Cbfa1-deficient mice, whose entire skeleton was composed of cartilage, the chondrocyte differentiation was disturbed. Calcification of cartilage occurred in the restricted parts of skeletons, including tibia, fibula, radius, and ulna. Type X collagen, BMP6, and Indian hedgehog were expressed in their hypertrophic chondrocytes. However, osteopontin, bone sialoprotein, and collagenase 3 were not expressed at all, indicating that they are directly regulated by Cbfa1 in the terminal hypertrophic chondrocytes. Chondrocyte differentiation was severely disturbed in the rest of the skeleton. The expression of PTH/PTHrP receptor, Indian hedgehog, type X collagen, and BMP6 was not detected in humerus and femur, indicating that chondrocyte differentiation was blocked before prehypertrophic chondrocytes. These findings demonstrate that Cbfa1 is an important factor for chondrocyte differentiation.

Animals↗
PubMed1999

Transradial coronary intervention in Japanese patients.

The objectives of this study was to test the feasibility and safety of transradial coronary intervention (TRI) in Japanese patients. We compared the results of TRI in 1,791 lesions (1,360 patients) between November 1995 and December 1997 with those of transfemoral coronary intervention (TFI) in 966 lesions (793 patients) between April and October 1995. We also examined the radial artery pulse in 294 patients 1-2 weeks after TRI by palpation and Doppler examination. Arterial puncture, coronary artery cannulation, lesion, and patient success rates were similar in both groups. No significant difference was noted in the major complication rate. Local complications were significantly lower in the TRI group (0.3% vs. 3.3%, P < 0.001). Doppler studies of the radial artery were performed in 294 patients chosen at random. In the first 234 patients, the sheath was pulled out 3 hr after the procedure, and in the last 60 patients, immediately after the procedure; radial artery occlusion rates were 5% and 0%, respectively. In conclusion, TRI seems safe and feasible in Japanese patients.

Aged↗
PubMed1999

Capsular block syndrome with external blockage of the capsular opening by a ciliary sulcus fixated posterior chamber lens.

PURPOSE: To report capsular block syndrome with external blockage of the capsular opening by a posterior chamber lens fixated in the ciliary sulcus. METHOD: Case report. RESULTS: In an 89-year-old man who had undergone cataract surgery, a posterior chamber lens was accidentally fixated in the ciliary sulcus after continuous curvilinear capsulohhexis and phacoemulsification/aspiration. The next day, capsular block syndrome was noted along the posterior chamber lens optic, which was blocking the capsular opening from the outside. CONCLUSION: In all previously reported eyes with capsular block syndrome, the posterior chamber lens had been placed inside the lens capsule to block the continuous curvilinear capsulorhexis opening from the inside.

Aged↗
PubMed1999

Relationships between apolipoprotein(a) phenotype and increase of lipoprotein(a) by troglitazone.

Troglitazone is a new oral hypoglycemic agent that reduces insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). However, this agent increases serum lipoprotein(a) [Lp(a)], which is known as an atherogenic lipoprotein. The relationships between the response of Lp(a) to troglitazone and the apolipoprotein(a) [apo(a)] phenotype were investigated in this study. Nineteen NIDDM patients were treated with troglitazone for 4 weeks. Lp(a) increased significantly from 20.1+/-16.5 mg/dL to 44.1+/-31.9 mg/dL (P<.001) in all study patients. Lp(a) increased from 25.7+/-34.2 mg/dL to 50.1+/-38.7 mg/dL (P = .03) in patients with smaller apo(a) phenotypes (S1S4 to S2S4). Lp(a) also increased from 17.5+/-12.0 mg/dL to 41.3+/-29.6 mg/dL (P<.01) in patients with larger apo(a) phenotypes (S3 to S4). Therefore, the increase of Lp(a) by troglitazone may be independent of the apo(a) phenotype.

Adult↗
PubMed1999

Purification of the antigenic components of pigeon dropping extract, the responsible agent for cellular immunity in pigeon breeder's disease.

BACKGROUND: Pigeon breeder's disease (PBD) is a lung disease caused by inhalation of antigens derived from pigeons. OBJECTIVE: This study was undertaken to characterize the responsible component of pigeon dropping extract (PDE) for PBD. METHODS: First, crude PDE was applied to SDS-PAGE followed by immunoblotting by using antibodies in bronchoalveolar lavage (BAL) fluid. Second, 9 bands of PDE were separated by SDS-PAGE and used for antigen-induced PBMCs. Finally, amino-terminal sequencing was conducted on an isolated 21-kd protein by 2-dimensional electrophoresis. RESULTS: Immunoblots with BAL fluid from patients with PBD identified 9 bands. Similar patterns were observed by using BAL fluid from 10 control patients (9 with summer-type hypersensitivity pneumonitis or idiopathic pulmonary fibrosis and 1 asymptomatic breeder), except for the 21-kd protein, which was detected in 10 patients with PBD and 1 asymptomatic breeder. The stimulation indices of PBMCs determined by using proteins electroeluted from the 9 bands were higher in patients with PBD than in the 10 control patients. The 21-kd protein was separated into 5 spots by 2-dimensional electrophoresis; these spots were all reactive with BAL fluid from patients with PBD as determined by immunoblotting. The sequence of the 21-kd protein had 57% identity to a Saccharomyces cerevisiae chromosome X reading frame. A synthetic peptide, derived from the amino acid sequence of the N-terminal of the native protein, induced significant proliferation of PBMCs obtained from 5 patients with PBD, but not with PBMCs obtained from control patients. CONCLUSION: The 21-kd protein is the only protein that identified individuals exposed to pigeons by immunoblotting. Only PBMCs from patients with PBD showed significant proliferation to the 21-kd protein and to the synthetic peptide on the basis of the N-terminal sequence of the native peptide. The 21-kd protein will be an important antigen for studies on the epidemiology, diagnosis, and pathogenesis of PBD.

Animals↗
PubMed1999

Blood-retinal barrier and autofluorescence of the posterior polar retina in long-standing pseudophakia.

PURPOSE: To study the physiological state of the retina in long-standing pseudophakic eyes using blood-retinal barrier (BRB) disruption and autofluorescence as parameters. SETTING: Miyake Eye Hospital, Nagoya, Japan. METHOD: This retrospective, case-controlled study sought to determine whether ultraviolet (UV)-light-filtering and blue-light-filtering intraocular lenses (IOLs) had different outcomes in severity of BRB disruption and autofluorescence of the posterior polar retina than clear (untreated) IOLs. RESULTS: Mean sodium fluorescein transmittance in eyes with untreated IOLs was 3.7 ng/mL +/- 2.2 (SD) 3 years after surgery (n = 40) and 3.5 +/- 1.8 ng/mL 8 years after surgery (n = 18). In eyes with a UV-filtering IOL, the values were 2.4 +/- 1.5 ng/mL (n = 39) and 2.6 +/- 2.0 ng/mL (n = 14), respectively. Eyes with a UV-filtering IOL had significantly lower transmittance (P < .01-< .05). Mean transmittance 5 years after surgery was 4.2 +/- 1.9 ng/mL in eyes with an untreated IOL (n = 31), 3.2 +/- 2.1 ng/mL in eyes with a UV-filtering IOL (n = 30), 2.8 +/- 1.9 ng/mL in eyes with a Menicon blue-light-filtering IOL (n = 20), and 2.6 +/- 1.8 ng/mL in eyes with a Hoya blue-light-filtering IOL (n = 21). The eyes with a UV-filtering and the blue-light-filtering IOLs had significantly lower transmittance than those with an untreated IOL (P < .01-< .05); the eyes with a Hoya IOL had a statistically lower mean than those with the UV-filtering IOL (P < .05). Mean autofluorescence was 44.9 +/- 6.8 (n = 14), 49.5 +/- 6.1 (n = 6), 53.0 +/- 11.9 (n = 15), and 64.5 +/- 13.2 (n = 7) at 1, 4, 9, and 14 years after surgery, respectively; there was a significant difference between 1 and 9 years and between 1 and 14 years (P < .05). CONCLUSION: Eyes with a UV-filtering or blue-light-filtering IOL had a lower incidence of BRB disruption than eyes with an untreated IOL. Autofluorescence increased with age, even in eyes with UV-filtering IOLs.

Aged↗
PubMed1999

Argatroban increases nitric oxide levels in patients with peripheral arterial obstructive disease: placebo-controlled study.

Intravenous argatroban infusion therapy is widely used for the restoration of peripheral microcirculation in patients with peripheral arterial obstructive disease (PAOD). We investigated the effect of argatroban infusion therapy on plasma levels of nitric oxide (NO) and nitrosylhemoglobin (HbNO) in patients with PAOD compared with a placebo-treated PAOD group. The chemiluminescence method was used to determine plasma NO and HbNO. Argatroban was administered as a continuous intravenous infusion for 60 minutes and repeated daily over a period of 2 weeks in 10 patients with PAOD. Treatment significantly improved the clinical signs and symptoms. Serial thermograms showed a 1-2 degrees C rise in the temperature of the affected legs in all patients immediately after intravenous argatroban infusion therapy. Enhancement of the peripheral circulation was maintained after the end of argatroban infusion for up to 90 minutes despite elimination of argatroban from the circulation. Furthermore, there was a progressive and significant increase in the mean concentration of plasma NO in PAOD patients after commencement of argatroban infusion (baseline, 58.0 +/- 13. 7;90 minutes after infusion, 65.7 +/- 13.4 microM; P < 0.01). HbNO significantly increased from a baseline value of 1063 +/- 126 to 1460 +/- 250 nM at 30 minutes after infusion (P < 0.01). However, the level of HbNo decreased thereafter, although it remained significantly elevated, even at 90 minutes after the end of argatroban infusion. Our results suggest that argatroban may lead to increased HbNO and plasma NO, and this may contribute to the improved microcirculation in PAOD patients.

Aged↗
PubMed1999

Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis.

Tissue factor (TF) is an initiator of the extrinsic cascade of blood coagulation. Although recent studies have revealed a relationship between metastatic properties and TF expression in some neoplastic cells, the significance of TF in lung cancer, especially in non-small-cell lung cancer (NSCLC), is still unclear. In this study, TF was detected in NSCLC cell lines by functional study, Western blot analysis and immunocytochemical staining. TF levels in eight NSCLC cell lines were also quantitated by enzyme-linked immunosorbent assay (ELISA), and TF expression was evaluated in 55 specimens of surgically resected NSCLCs. NSCLC cell lines derived from metastatic lesions produced high levels of TF (48.3+/-23.5 ng 10(-6) cells, mean +/- s.e.m.), whereas those derived from primary lesions produced low levels of TF (0.2+/-0.1 ng 10(-6) cells). Immunohistochemical studies disclosed significantly stronger staining for TF in cells from NSCLC patients with metastasis than in those without metastasis. Among the 28 patients with metastasis, ten were strongly positive, 16 were moderately positive and two were negative for TF. In contrast, among the 27 patients without metastasis, only two were strongly positive, 18 were moderately positive and seven were negative for TF. Therefore, malignant cells from patients with lung cancer produce various levels of TF, and TF may play an important role in the metastatic process.

Biomarkers, Tumor↗
PubMed1999

A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1.

BACKGROUND: It is now becoming clear that the circadian rhythm of behaviours and hormones arises from a rhythm at the level of gene expression, and that mammals and Drosophila essentially use homologous genes as molecular gears in the control of circadian oscillation. In Drosophila, the period and timeless genes form a functional unit of the clock and its autoregulatory feedback loop for circadian rhythm. However, in mammals, the counterpart of timeless has not been found. RESULTS: We have isolated a mammalian homologue of timeless, mTim, from the mouse brain. mTim is highly expressed, with a weak or absent rhythm in the suprachiasmatic nucleus, the mammalian circadian centre. In the retina, mTim mRNA was found to be expressed with a circadian rhythm, and a particularly robust cycle was observed in the presence of light/dark cycles. We demonstrated that mTIM physically associates with mPER1 in vitro and in the nuclei of cultured COS7 cells. CONCLUSIONS: We have reported the isolation of the mouse timeless cDNA, the expression of the mTim mRNA and an interaction of mTIM with mPER1. These results indicate that the autoregulatory feedback mechanism of circadian oscillation of the period gene may also be conserved in mammals.

Amino Acid Sequence↗
PubMed1999

Does the production of nitric oxide contribute to the early improvement after a single low-density lipoprotein apheresis in patients with peripheral arterial obstructive disease?

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose (DSC) column is commonly performed for extracorporeal removal of LDL in hypercholesterolemic patients with peripheral arterial obstructive disease. We investigated whether the use of heparin or nafamostat mesilate as anticoagulants in a single LDL apheresis produced different clinical effects, or brought about the production of bradykinin and endogenous nitric oxide (NO) in these patients. LDL apheresis was performed in ten patients with peripheral arterial obstructive disease. We measured plasma levels of bradykinin, NO and nitrosylhemoglobin as well as skin temperature. Plasma levels of bradykinin increased 12-fold during LDL apheresis with heparin, but did not increase during LDL apheresis with nafamostat mesilate. LDL adsorption resulted in an immediate rise in skin temperatures (1-2 degrees C) of the lower ischemic legs irrespective of the type of anticoagulant used, and this persisted after the end of LDL apheresis for up to 60 min. There was a progressive and significant increase in plasma NO after the commencement of single LDL apheresis in both groups (heparin group: 64.0 +/- 17.3 micromol/l at baseline, 73.3 +/- 15.2 micromol/l 60 min after apheresis, P<0.005; nafamostat mesilate group: 65.0 +/- 18.8 micromol/l at baseline, 75.5 +/- 17.5 micromol/l 60 min after apheresis, P<0.001). On the other hand, levels of nitrosylhemoglobin increased significantly after 1000 ml of plasma treatment but the level decreased thereafter, although it was significantly higher than baseline 60 min after LDL apheresis. Our results suggest that a single LDL apheresis enhanced peripheral microcirculation, probably as a result of increased production of NO, irrespective of changes in bradykinin release.

Aged↗
PubMed1999

Mediastinal fibromatosis presenting with superior vena cava syndrome.

We encountered a fatal case of mediastinal fibromatosis in a 67-year-old female in whom there was aggressive infiltration into the large vessels, nerves and pericardium. She presented with the superior vena cava syndrome, Horner's syndrome, paralysis of bilateral vocal cords and diaphragm and heart failure. Mediastinoscopical examination revealed an extremely firm tumor adhering to the sternum, trachea and brachiocephalic artery. She died of severe heart failure due to the disturbed dilatation of the heart and ventilatory insufficiency. Although mediastinal fibromatosis is very uncommon and sometimes difficult to diagnose at an early stage, physicians should be aware of this disease for the differential diagnosis of mediastinal tumors.

Aged↗
PubMed1999

Sequential changes in bronchoalveolar lavage cells and cytokines in a patient progressing from acute to chronic bird Fancier's lung disease.

A 65-year-old pigeon breeder who presented with acute hypersensitivity pneumonitis refused to give up contact with pigeons and her lung disease, which had initially improved in hospital in response to removal from pigeons, progressed to chronic interstitial fibrosis. Bronchoalveolar lavage lymphocytes fell from 50.0% of total cells in December 1986 to 27.1% in February 1990. The ratio of CD4+/CD8+ lymphocytes shifted from 0.43 to 1.47. Furthermore, IL-6 and TNF-alpha were elevated initially and were much higher at the second time point. These data pointed to the importance of CD4+ lymphocytes, IL-6 and TNF-alpha in the development of pulmonary fibrosis.

Acute Disease↗
PubMed1999

Insulin resistance and classic risk factors in type 2 diabetic patients with different subtypes of ischemic stroke.

OBJECTIVE: In addition to classic risk factors (e.g., hypertension), insulin resistance is an important risk factor for the development of atherosclerosis. To investigate the risk factors for ischemic stroke in type 2 diabetes, we measured insulin sensitivity and several risk factors in 94 Japanese type 2 diabetic patients with different types of stroke. RESEARCH DESIGN AND METHODS: Stroke was classified by magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography into the following subtypes: 1) patients with normal MRI and MR angiography (NOR; n = 30), 2) patients with lacunar infarction (LAC; n = 28), 3) patients with atherothrombotic infarction (ATI; n = 22), and 4) patients with large-artery atherosclerosis (LAA; n = 14). Insulin sensitivity was assessed by the K index of the insulin tolerance test (KITT). RESULTS: Patients with LAC, ATI, and LAA were significantly older and were more likely to be hypertensive than patients with NOR. Significantly higher insulin resistance was observed in patients with LAC, ATI, and LAA than in patients with NOR (KITT 2.21 +/- 0.17, 2.10 +/- 0.17, 2.19 +/- 0.25, and 3.25 +/- 0.21% per min, respectively, P < 0.001). Adjustment for age, sex, BMI, and duration of diabetes did not influence this result. Multiple logistical regression analysis showed that insulin resistance was an independent risk factor for all subtypes of ischemic stroke in type 2 diabetic patients. The same analysis showed that a high pulse pressure was a risk factor for LAC, postprandial C-peptide (hyperinsulinemia) was a risk factor for ATI, and longstanding hyperglycemia was a risk factor for LAA.

Age Factors↗
PubMed1999

Differences in heart rate variability between young and elderly normal men during graded head up tilt.

An autoregressive spectral analysis of heart rate variability (HRV) was used to analyze the differences in autonomic functions during graded head up tilt (HUT) between young and elderly men. After recording at the 0 degree position, the table was rotated to an upright position. The incline of the table was increased progressively to 15 degrees, 30 degrees and 60 degrees. The data obtained from seven young subjects (mean age of 20.0 years) and nine elderly subjects (mean age of 63.3 years) were analyzed. The high frequency components expressed by normalized units (HFnu) were used as the parasympathetic indicators, and HFnu decreased with tilt angle in both age groups. These results suggested that parasympathetic withdrawal have an important role in adaptation to an upright posture in both age groups. However, mean HF amplitude at the 0 degree position in elderly men was not significantly different from that of young men at 60 degrees tilt. A significant interaction effect (age group x tilt angle) was found for mean HF amplitude. The increase of the low frequency components expressed by normalized units (LFnu) and the LF-to-HF ratio in elderly subjects from 0 degree to 15 degrees seemed to be larger than that in young subjects. Sympathetic activities may be sensitive to lower levels of orthostatic stress in the elderly, and the elderly workers are easily affected by a change in workload. Therefore, keeping the workload lower and constant may be recommended to avoid excessive sympathetic activation among the elderly.

Adolescent↗
PubMed1999

[Multiple cavities in myocardium of left ventricle after irradiation therapy for breast cancer: a case report].

A 68-year-old woman was admitted to our hospital with congestive heart failure. She had been diagnosed with hypertrophic cardiomyopathy 12 years ago in another hospital. She had received irradiation therapy for left breast cancer 33 years ago after resection of her left breast. Echocardiography revealed left ventricular hypertrophy and wall motion hypokinesis, and multiple cavities in the myocardium of the left ventricle, interventricular septum, and anterior wall. Some cavities were observed to connect to the left ventricular cavity and Doppler echocardiography showed slow velocity flows in them different from that of the coronary artery. The pathologic diagnosis was severe sclerosis of the left coronary artery, especially the left descending artery and its branch, which was the area with irradiation. Histopathology revealed sclerotic changes of the coronary artery causing acute and chronic myocardial infarction, and incomplete regeneration and hypertrophy of cardiac cells. There was no sign of hypertrophic cardiomyopathy. Myocardial degeneration and deciduation were present next to the cavities connected to left ventricle-like fistulas.

Aged↗
PubMed1999

Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons.

Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.

Adenoviridae↗
PubMed1998

Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323.

The proto-oncogene product Cbl has emerged as a potential negative regulator of the Syk tyrosine kinase; however, the nature of physical interactions between Cbl and Syk that are critical for this negative regulation remains unclear. Here we show that the phosphotyrosine-binding (PTB) domain within the N-terminal transforming region of Cbl (Cbl-N) binds to phosphorylated Tyr323 in the linker region between the Src homology 2 and kinase domains of Syk, confirming recent results by another laboratory using the yeast two-hybrid approach (Deckert, M., Elly, C., Altman, A., and Liu, Y. C. (1998) J. Biol. Chem. 273, 8867-8874). A PTB domain-inactivating point mutation (G306E), corresponding to a loss-of-function mutation in the Caenorhabditis elegans Cbl homologue SLI-1, severely compromised Cbl-N/Syk binding in vitro and Cbl/Syk association in transfected COS-7 cells. Using heterologous expression in COS-7 cells, we investigated the role of Cbl PTB domain binding to Syk Tyr323 in the negative regulation of Syk. Co-expression of Cbl with Syk in COS-7 cells led to a dose-dependent decrease in the autophosphorylated pool of Syk and in phosphorylation of an in vivo substrate, CD8-zeta. Unexpectedly, these effects were largely due to the loss of Syk protein. Both the decrease in Syk and CD8-zeta phosphorylation and reduction in Syk protein levels were blocked by either G306E mutation in Cbl or by Y323F mutation in Syk. These results demonstrate a critical role for the Cbl PTB domain in the recruitment of Cbl to Syk and in Cbl-mediated negative regulation of Syk.

Binding Sites↗