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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 253 records · Page 14Linked to original sources
PubMed2000

[Minimally invasive direct coronary artery bypass grafting using subxiphoid approach].

We report twelve cases of minimally invasive coronary artery bypass grafting via small laparotomy using right gastroepiploic artery (RGEA) to the right coronary artery. Seven patients were operated on without partial sternotomy (N group), and lower partial sternotomy with Octopus 2 stabilization system was used in five of the cases (P group). Postoperative Doppler echographic imaging or angiographic study showed all RGEA grafts were functioning well in P group. However, graft occlusion was observed in two of the cases in N group. Inferior partial sternotomy combined with Octopus 2 stabilization system produce a clear surgical view, which avoids of both full-sternotomy and cardiopulmonary bypass. This method might be useful especially for reoperation.

Aged↗
PubMed2000

[Role of small dense low-density lipoprotein in coronary artery disease patients with normal plasma cholesterol levels].

OBJECTIVES: The relationship between plasma low-density lipoprotein (LDL) cholesterol and the risk of coronary artery disease (CAD) is known, but the other characteristics of LDL, particularly particle size and density, are unclear. The relationship between small dense LDL phenotype and non-diabetic, normocholesterolemic CAD was investigated in 70 patients with angiographically documented CAD, and 38 age-matched control subjects. METHODS: Peak LDL particle diameter was determined by using 2-16% polyacrylamide gradient gel electrophoresis. Small dense LDL phenotype was defined as particle diameter equal to or less than 255 A. RESULTS: LDL particle diameters in patients with CAD were significantly smaller than those in controls (252.4 +/- 6.9 vs 259.3 +/- 8.8 A, mean +/- SD, p < 0.0001). Prevalence of small dense LDL was markedly higher in patients with CAD (72%) than in subjects without CAD (24%). CAD patients had significantly lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels (39.3 +/- 8.8 vs 49.8 +/- 12.0, 108.1 +/- 20.6 vs 122.9 +/- 20.1 mg/dl), and higher lipoprotein (a) and apolipoprotein B levels (28.8 +/- 30.4 vs 16.8 +/- 18.8, 96.5 +/- 21.8 vs 80.2 +/- 14.9 mg/dl) than non-CAD subjects, whereas total cholesterol, LDL-cholesterol, triglyceride, remnant-like particle cholesterol and insulin levels were not increased in CAD patients compared with non-CAD subjects. Stepwise regression analysis revealed that LDL particle size was the most powerful independent determinant of CAD (F value = 20.04, p < 0.0001). Logistic regression analysis revealed that small dense LDL phenotype [relative risk (RR) of 7.0, 95% confidence interval (95% CI) 2.4-20.1], low HDL-cholesterol (RR of 5.6, 95% CI 2.1-15.2), and increased apolipoprotein B (RR of 5.8, 95% CI 1.8-18.5) were independently associated with incidence of CAD. CONCLUSIONS: High prevalence of small dense LDL is a leading cause of CAD with even normal cholesterol levels.

Aged↗
PubMed2000

Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant human erythropoietin in hemodialysis patients.

AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is usually achieved as a target level during recombinant human erythropoietin (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a product of cerebral blood flow and arterial oxygen content (CaO2). The regional cerebral blood flow (rCBF) in each region of interest was measured by positron emission tomography and CaO2 was calculated from hemoglobin concentration, arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2 (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to 11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y = 55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By using these correlations, the hemispheric oxygen delivery was expressed as a function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION: The present study indicated that Ht of about 35% is required for a better oxygen delivery to the brain metabolism during anemia correction with rHuEPO.

Anemia↗
PubMed2000

[CADASIL: clinical analysis of CADASIL and CADASIL-like disorders in Japan].

To clarify the characteristics of CADASIL in Japan, we performed clinical and genetic investigations for six patients from 5 Japanese families diagnosed as CADASIL. We identified that the onset of focal neurologic deficits ranged from 38 to 63 years old (mean 49 +/- 9.4 yrs) and the occurrence rates of main neurologic symptoms and signs were 1/6 for migraine, 3/6 for recurrent stroke episodes, 6/6 for dementia, and 4/6 for pseudobulbar palsy. The marked narrowing of retinal arteries were observed in 3/6. The notch 3 mutations were all found in exon 4. Although other several families shared similar phenotype of CADASIL, there were no deposition of granular osmiophilic materials within the basal lamina of smooth muscle cells in the arterioles of biopsied muscle and no mutations in the cording regions of notch 3 gene. We investigated prospectively the incidence of CADASIL and CADASIL-like disease in Kumamoto district from 1999 to 2000. One thousand and thirty four patients with stroke were hospitalized in 6 hospitals which have stroke care unit. Among them, 7 patients fulfilled the criteria that were less than 60 years old, lacunar strokes and/or TIA, presence of a family history, and no risk factors such as hypertension, diabetes mellitus, and hyperlipidemia. One of seven patients was diagnosed as CADASIL by DNA analysis. It was suspected the incidences of CADASIL and CADASIL-like disease were not so rare in Japan.

Cerebral Infarction↗
PubMed1999

Contribution of mGluR1 to the basal activity of a mouse cerebellar Purkinje neuron.

The physiological role of mGluR1-induced inward current in a Purkinje neuron was studied in a cerebellar slice preparation. In a voltage-clamp condition, application of a mGluR1 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induced both the transient and sustained phases of inward currents, which were blocked by simultaneous application of a mGluR1 antagonist 7-(hydroxyimino)cyclopropa(b)chromen-1a-carboxylate ethyl ester (CPCCOEt). Application of CPCCOEt alone reduced the holding inward current, suggesting that a subset of mGluRls is activated in a resting condition. In a current-clamp condition, DHPG increased the frequency of action potentials, whereas CPCCOEt decreased it. These results suggest that the basal mGluR1 activity contributes to the action potential firing by maintaining the sustained inward current in a Purkinje neuron.

Action Potentials↗
PubMed1999

No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage.

We studied six patients after intracerebral hemorrhage (ICH) and eight controls using positron emission tomography (PET) with to determine whether a zone of tissue hypoxia, possibly representing "penumbral" tissue, exists surrounding an intracerebral hemorrhage. None of the stroke patients, studied 24 to 43 hours after symptom onset, nor any of the controls exhibited areas of tissue hypoxia on 18F-fluoromisonidazole PET images. These findings may have implications for the treatment of intracerebral hemorrhage with neuroprotective strategies.

Aged↗
PubMed1999

Effect of anion binding on iodopsin studied by low-temperature fourier transform infrared spectroscopy.

The effect of anion binding on iodopsin, the chicken red-sensitive cone visual pigment, was studied by measurements of the Fourier transform infrared spectra of chloride- and nitrate-bound forms of iodopsin at 77 K. In addition to the blue shift of the absorption maximum upon substituting nitrate for chloride, the C=C stretching vibrations of iodopsin and its photoproducts were upshifted 5-6 cm(-)(1). The C=NH and C=ND stretching vibrations were the same in wavenumber between the chloride- and nitrate-bound forms, indicating that the binding of either chloride or nitrate has no effect on the interaction between the protonated Schiff base and the counterion. The vibrational bands of iodopsin in the fingerprint and the hydrogen out-of-plane wagging regions were insensitive to anion substitution, suggesting that local chromophore interactions with the anions are not crucial for the absorption spectral shift. In contrast, bathoiodopsin in the chloride-bound form exhibited an intense C(14)H wagging mode, whose intensity was considerably weakened upon substitution of nitrate for chloride. These results suggest that binding of chloride changes the environment near the C(14) position of the chromophore, which could be one of the factors in the thermal reverse reaction of bathoiodopsin to iodopsin in the chloride-bound form.

Anions↗
PubMed1999

Entire course and distinct phases of day-lasting depression of miniature EPSC amplitudes in cultured Purkinje neurons.

The cerebellar long-term depression (LTD) is the long-lasting reduction of transmission efficacy at the granule neuron-Purkinje neuron (G-P) synapses and is a candidate mechanism for the motor learning. Despite extensive studies on its induction and expression mechanisms, it has not been known how long the LTD lasts. The LTD is accompanied by the decrease in the postsynaptic responsiveness to glutamate, the transmitter at G-P synapses. Therefore, during the LTD, the amplitude of miniature EPSCs (mEPSCs) at G-P synapses should decrease. We studied the depression of mEPSC amplitudes (DME) as a possible contributing factor for the LTD and found that the conditioning treatment of cultured cerebellar neurons with 50 mM K(+) and 100 microM glutamate, an analogous condition used to induce the LTD, induced the long-lasting DME. The mEPSC amplitudes recovered to the original level 48 hr after the 5 min conditioning treatment. Changing the duration of the conditioning revealed that the DME consisted of two distinct phases: the early phase lasting for a few hours and the late phase for >1 d. The latter was distinguished from the former by its requirement of prolonged conditioning treatment and syntheses of mRNA and protein for the induction. There were critical periods for mRNA and protein syntheses. The critical period for protein synthesis was much longer than that for mRNA synthesis. These results demonstrate that the DME lasts for 1-2 d and that it consists of two phases, whose induction and maintenance mechanisms are distinct.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Engagement of Gab1 and Gab2 in erythropoietin signaling.

Several signaling cascades are activated during engagement of the erythropoietin receptor to mediate the biological effects of erythropoietin. The members of the insulin receptor substrate (IRS) family of proteins play a central role in signaling for various growth factor receptors and cytokines by acting as docking proteins for the SH2 domains of signaling elements, linking cytokine receptors to diverse downstream pathways. In the present study we provide evidence that the recently cloned IRS-related proteins, Gab1 and Gab2, of the Gab family of proteins, are rapidly phosphorylated on tyrosine during erythropoietin treatment of erythropoietin-responsive cells and provide docking sites for the engagement of the SHP2 phosphatase and the p85 subunit of the phosphatidylinositol 3'-kinase. Furthermore, our data show that Gab1 is the primary IRS-related protein activated by erythropoietin in primary erythroid progenitor cells. In studies to identify the erythropoietin receptor domains required for activation of Gab proteins, we found that tyrosines 425 and 367 in the cytoplasmic domain of the erythropoietin receptor are required for the phosphorylation of Gab2. Taken together, our data demonstrate that Gab proteins are engaged in erythropoietin signaling to mediate downstream activation of the SHP2 and phosphatidylinositol 3'-kinase pathways and possibly participate in the generation of the erythropoietin-induced mitogenic responses.

Adaptor Proteins, Signal Transducing↗
PubMed1999

A novel oncostatin M-inducible gene OIG37 forms a gene family with MyD118 and GADD45 and negatively regulates cell growth.

Oncostatin M (OSM) is a member of the IL-6 family cytokines that use gp130 as a common signal transducer and exhibits both growth stimulatory as well as growth inhibitory activity depending on the cells. To analyze the mechanism of OSM function, we isolated immediate early responsive genes upon OSM stimulation. Here we describe the novel OSM-inducible gene OIG37 that is related to MyD118 and GADD45. The MyD118 gene has been described as an immediate early gene induced by IL-6 in M1 monocytic cells, and GADD45 was identified as a gene induced by UV or gamma-ray irradiation. Both are considered to function in growth arrest and/or DNA repair. Although the expression of OIG37, MyD118, and GADD45 was rather ubiquitous, it was differentially regulated. As the gp130 mutant defective for activating the STAT3 pathway showed the reduced induction of OIG37 by cytokine stimulation and expression of dominant negative STAT3 inhibited the induction of OIG37 by OSM, STAT3 is involved in OIG37 induction by IL-6 family cytokines. To examine the function of OIG37, we expressed it in NIH3T3 and IL-3-dependent BaF3 cells and found that OIG37 suppressed cell growth without any evidence of apoptosis. Whereas both MyD118 and OIG37 suppressed cell growth in both cell lines, suppression by OIG37 was more efficient than by MyD118. Immunoprecipitation experiments indicated that OIG37 associates with p21, a cyclin-dependent kinase inhibitor, and proliferating cell nuclear antigen.

Amino Acid Sequence↗
PubMed1999

13S condensin actively reconfigures DNA by introducing global positive writhe: implications for chromosome condensation.

Xenopus 13S condensin converts interphase chromatin into mitotic-like chromosomes, and, in the presence of ATP and a type I topoisomerase, introduces (+) supercoils into DNA. The specific production of (+) trefoil knots in the presence of condensin and a type II topoisomerase shows that condensin reconfigures DNA by introducing an ordered, global, (+) writhe. Knotting required ATP hydrolysis and cell cycle-specific phosphorylation of condensin. Condensin bound preferentially to (+) supercoiled DNA in the presence of ATP but not in its absence. Our results suggest a mechanism for the compaction of chromatin by condensin during mitosis.

Adenosine Triphosphatases↗
PubMed1999

Molecular basis underlying functional pleiotropy of cytokines and growth factors.

Cytokines and growth factors play pivotal roles in cell growth, differentiation, and cell survival. Ligand binding to the receptors induces dimerization or oligomerization of the receptors, resulting in the activation of a variety of signal transduction pathways. The interplay among these multiple signals is critically involved in the biological activities of cytokines and growth factors. In this minireview, I discuss two models. One is the "receptor conversion model": The complex of cytokine and its soluble form of receptor acts like a cytokine with novel target specificity. The other is the "orchestrating model": Cytokines can simultaneously generate contradictory signals in the same target cells and the balance of each contradictory signal may determine the final output of cytokine signals to express unified biological activity. These mechanisms are part of the molecular basis underlying functional pleiotropy of cytokines and growth factors.

Cytokines↗
PubMed1999

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1.

Interleukin-6 (IL-6)-type cytokines lead to growth arrest of human A375 melanoma cells. The present study demonstrates that this effect depends on the activation of STAT transcription factors. We observed a correlation between the extent of growth inhibition exerted by IL-6, IL-6 plus soluble IL-6 receptor or oncostatin M (OSM) and the intensities of STAT3 and STAT1 signals. A truncated chimeric receptor retaining only the membrane-proximal region of gp130, the common signal transducer of IL-6-type cytokines, did neither activate STATs nor mediate growth arrest of stable transfectants. These functions were restored by the addition of short STAT recruitment modules comprising critical tyrosine residues from gp130 (Y767, Y814). A receptor carrying tyrosine module Y759 of gp130 effectively mediated activation of the phosphatase SHP-2 but did not alter cell growth. Overexpression of dominant negative forms of STAT3 but not STAT1 abrogated the inhibitory effect of OSM and IL-6 in A375 cells. In addition, we have identified the cyclin-dependent kinase inhibitor p27/Kipl as a novel target to be regulated by IL-6-type cytokines. Stimulation-dependent upregulation of p27 mRNA occurred STAT3-dependently. Also p27 protein accumulated which coincided with the disappearance of hyperphosphorylated retinoblastoma protein in three human melanoma cell lines sensitive to IL-6-type cytokines.

Antigens, CD↗
PubMed1999

Developmentally regulated expression of a nonmuscle myosin heavy chain IIB inserted isoform in rat brain.

The alternatively spliced isoform of the nonmuscle myosin II heavy chain B (MHC-B) with an insert of 21 amino acids at the 50- to 20-kDa junction of the globular region of myosin has been demonstrated to be expressed specifically in the central nervous system (CNS) in chicken. To explore the role of this B2 inserted isoform (MHC-B(B2)), immunoblot and immunoprecipitation analyses were performed using specific antibodies and extracts from rat tissues. MHC-B(B2) is present throughout the CNS, but is less abundant in the cerebrum and not expressed in the olfactory lobe at all. In the developing rat brain, MHC-B(B2) is expressed from postnatal day 10 (P10) in the cerebellum and increases markedly from P14. The appearance of MHC-B(B2) in the cerebrum (P28) is later than in the cerebellum. Additionally, we show that myosin IIB(B2) is homodimeric in its heavy chain subunit composition. These results suggest that myosin IIB(B2) might participate in cell motility in the neuronal cells of the mature CNS.

Alternative Splicing↗
PubMed1999

Endovascular stent-graft placement for the treatment of acute aortic dissection.

BACKGROUND: The standard treatment for acute aortic dissection is either surgical or medical therapy, depending on the morphologic features of the lesion and any associated complications. Irrespective of the form of treatment, the associated mortality and morbidity are considerable. METHODS: We studied the placement of endovascular stent-grafts across the primary entry tear for the management of acute aortic dissection originating in the descending thoracic aorta. We evaluated the feasibility, safety, and effectiveness of transluminal stent-graft placement over the entry tear in 4 patients with acute type A aortic dissections (which involve the ascending aorta) and 15 patients with acute type B aortic dissections (which are confined to the descending aorta). Dissections involved aortic branches in 14 of the 19 patients (74 percent), and symptomatic compromise of multiple branch vessels was observed in 7 patients (37 percent). The stent-grafts were made of self-expanding stainless-steel covered with woven polyester or polytetrafluoroethylene material. RESULTS: Placement of endovascular stent-grafts across the primary entry tears was technically successful in all 19 patients. Complete thrombosis of the thoracic aortic false lumen was achieved in 15 patients (79 percent), and partial thrombosis was achieved in 4 (21 percent). Revascularization of ischemic branch vessels, with subsequent relief of corresponding symptoms, occurred in 76 percent of the obstructed branches. Three of the 19 patients died within 30 days, for an early mortality rate of 16 percent (95 percent confidence interval, 0 to 32 percent). There were no deaths and no instances of aneurysm or aortic rupture during the subsequent average follow-up period of 13 months. CONCLUSIONS: These initial results suggest that stent-graft coverage of the primary entry tear may be a promising new treatment for selected patients with acute aortic dissection. This technique requires further evaluation, however, to assess its therapeutic potential fully.

Acute Disease↗
PubMed1999

Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells.

HM1.24 antigen has been identified as a surface molecule preferentially expressed on terminally differentiated B cells, and its overexpression is observed in multiple myeloma cells. The HM1.24 antigen is, therefore, expected as a most potent target molecule for antibody-based immunotherapy for multiple myeloma. Here, we have identified the cDNA for human HM1.24 antigen and also analyzed its gene structure including the promoter region. The HM1.24 antigen is a type II membrane glycoprotein, which has been reported as a bone marrow stromal cell surface antigen BST2, and may exist as a homodimer on myeloma cell surface. Although a reason for the overexpression in myeloma cells is not understood, very interestingly, the promoter region of the HM1.24 gene has a tandem repeat of three cis elements for a transcription factor, STAT3, which mediates interleukin-6 (IL-6) response gene expression. Since IL-6 is a differentiation factor for B cells, and known as a paracrine/autocrine growth factor for multiple myeloma cells, the expression of HM1.24 antigen may be regulated by the activation of STAT3. Importantly, a humanized anti-HM1.24 antibody effectively lysed the CHO transformants which expressed HM1.24 antigen as high as human multiple myeloma cells, but not the cells with lower antigen expression. This evaluation shows that ADCC heavily depends on the expression level of target antigens and, therefore, the immunotherapy targeting the HM1.24 antigen should have a promising potential in clinical use.

Amino Acid Sequence↗