Biomedical subjects

T Takano

Publications and source records attributed to T Takano.

At least 235 records · Page 13Linked to original sources

PubMed1997

Effect of serum cholesterol levels on meta-chlorophenylpiperazine-evoked neuroendocrine responses in healthy subjects.

This study was undertaken to test the hypothesis that serum cholesterol levels might be associated with serotonergic receptor function. The participants were 10 healthy male subjects. After an overnight fast, the subjects received meta-chlorophenylpiperazine (m-CPP) or identical placebo capsules orally in a randomized, double-blind, cross-over design. Blood was obtained for measurement of prolactin, cortisol, adrenocorticotropic hormone (ACTH), and cholesterol. There were some significantly positive correlations between serum cholesterol levels and hormonal responses to m-CPP administration. These results suggest that serum cholesterol levels may be positively associated with serotonergic receptor function.

Adrenocorticotropic Hormone↗

PubMed1997

Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor.

Lipoxins (LX) are bioactive eicosanoids that activate human monocytes and inhibit neutrophils. LXA4 is rapidly converted by monocytes to inactive products, and to resist metabolism, synthetic analogs of LXA4 were designed. Here, we examined the bioactivity of several LXA4 analogs in monocytes and found, for chemotaxis, 15(R/S)-methyl-LXA4 and 15-epi-LXA4 were equal in activity, and 16-phenoxy-LXA4 was more potent than native LXA4. Both 15(R/S)-methyl-LXA4 and 16-phenoxy-LXA4 were approximately 1 log molar more potent than LXA4 in stimulating THP-1 cell adherence (EC50 approximately 1 x 10(-10) M). Dimethylamide derivatives of the LXA4 analogs also possessed agonist rather than antagonist properties for monocytes. Neither LXA4 nor 16-phenoxy-LXA4 affected monocyte-mediated cytotoxicity. We cloned an LXA4 receptor from THP-1 cells identical to that found in PMN. Evidence of receptor-mediated function of LXA4 and the stable analogs in monocytes included desensitization of intracellular calcium mobilization to a second challenge by equimolar concentrations of these analogs, but not to LTB4. Increases in [Ca2+]i by LXA4 and the analogs were specifically inhibited by an antipeptide antibody to the LXA4 receptor; and both LXA4- and analog-induced adherence and increments in Ca2+ were sensitive to pertussis toxin. Together, these results indicate that the LXA4 stable analogs are potent monocyte chemoattractants and are more potent than native LXA4 in stimulating THP-1 cell adherence, at subnanomolar concentrations. Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4.

Amino Acid Sequence↗

PubMed1997

Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III.

We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,del(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient.

Abnormalities, Multiple↗

PubMed1997

Assignment of Alzheimer's presenilin-2 (PS-2) gene to 1q42.1 by fluorescence in situ hybridization.

Presenilin-2 (PS-2) was suggested to be localized on 1q31-42 based on linkage analysis and cDNA cloning. The final identification of PS-2 as the causal gene for early-onset familial Alzheimer's disease in Voga-German pedigrees was concluded based on the point mutation found in the candidate cDNA isolated from this familial AD. We present evidence of its physical genome mapping of PS-2 on chromosome 1q42.1 by fluorescence in situ hybridization method.

Alzheimer Disease↗

PubMed1997

Age-dependent susceptibility in mumps-associated hydrocephalus: neuropathologic features and brain barriers.

Central nervous system susceptibility to viral infection is often age dependent for unclear reasons. In this study, we examined the age-dependent susceptibility of the brain in mumps virus-induced hydrocephalus in hamsters, and evaluated the relationship between neuropathologic features and brain barriers using glial fibrillary acidic protein and zonula occludentes 1 (ZO-1) immunohistochemistry. In a group intracerebrally inoculated with mumps virus at 2 days of age, pathologic findings such as periventricular edema, ependymal cell loss, and ventricular dilation were more prominent and the distribution of mumps virus antigen was wider than in a group inoculated at 30 days of age. ZO-1-immunoreactive tight junctions in the hydrocephalic brains of the 2-day group were severely damaged in the choroid plexus and ependyma, and in white matter capillaries as early as 3 days after inoculation. These changes were not apparent in the hydrocephalic brains of the 30-day group. Prominent cortical dissemination of virus in the 2-day group was related to underdeveloped perivascular glial foot processes in brain parenchyma. Periventricular edema in the 2-day group was linked to ependymal and blood-brain barrier tight-junction permeability. Our results suggest that tight junctions in the early postnatal period are more immature and fragile than in the adult. We concluded that brain susceptibility in mumps virus-induced hydrocephalus is intimately related to the maturity of brain barriers.

Aging↗

PubMed1997

Increased intracellular Ca2+ is not coinherited with an inferred major gene locus for hypertension (ht) in the spontaneously hypertensive rat.

Hypertension is characterized by a complex mode of inheritance, consisting of the accumulation and interaction of major and minor genes. The existence of a single major gene locus (ht) has been demonstrated in the backcross analysis of spontaneously hypertensive rats (SHR) and normotensive Donryu rats. Intracellular Ca2+ concentration ([Ca2+]i) determines the tonus of vascular smooth muscle. It has been hypothesized that abnormal Ca2+ transport is an inheritable trait with profound influence on the development of hypertension. Backcross analysis between SHR and Donryu rats was performed to demonstrate ht and to dissect polygenic hypertensive traits through ht and abnormal intracellular Ca2+ metabolism. Among the parental strains, systolic blood pressure and thrombin-stimulated [Ca2+]i in platelets were significantly greater in SHR than in Donryu and F1 rats. The backcrossed rats were distributed into two clusters on a scattergram of blood pressure versus [Ca2+]i, demonstrating the existence of ht. The blood pressure level was correlated with thrombin-stimulated [Ca2+]i in each cluster. Increased [Ca2+]i in platelets was not coinherited with ht and was considered to be a minor inheritable hypertensive trait discriminated from ht. Therefore, [Ca2+]i in platelets is an inadequate marker for searching ht.

Animals↗

PubMed1997

Image-diagnosis: visualization of community health levels and the impacts of determinants thereof.

The objective of this study is to develop a tool that visualizes health-level of communities and the determinants thereof. We developed Image-Diagnosis, which consists of mapping and star-plotting procedures. This paper presents this method by applying the statistics in Tokyo. The mapping shows the spatial variance of health-level and health-determining factors; star-plotting depicts health-level, as the circle, and health-determining factors, as the arms, in a star-shaped diagram. The animation of star-plots presents variations in health levels resulting from the specified changes in health-determining factors according to the models. Potential contribution to the decision making in urban health policy was discussed.

Health Planning↗

PubMed1997

Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization.

Members of the nuclear factor of activated T cells (NFAT) are involved in the induction of a number of cytokine genes. We report here cDNA cloning and chromosomal localization of a murine homologue of human NFATx, designated as mNFATx1, and its splicing variants mNFATx2 and m delta NFATx. Northern blot analysis showed mNFATx1 to be predominantly expressed in the thymus. mNFATx1, but not m delta NFATx, produced in COS-7 cells, bound to all NFAT-binding sites of the interleukin (IL)-2 and IL-4 promoters tested. Immunofluorescence assay showed that both mNFATx1 and m delta NFATx introduced into COS-7 cells localized predominantly to the cytoplasm, but did translocate to the nucleus, either by cotransfection with an active form of calcineurin or wild-type calcineurin followed by stimulation with calcium ionophore. Translocation of mNFATx1 correlated well with activation of the murine IL-2 promoter; mNFATx1 translocated under conditions described above, in combination with phorbol 12-myristate 13-acetate, activated the transiently transfected murine IL-2 promoter. Thus, nuclear-translocated mNFATx1 is involved in activation of the IL-2 promoter. These results provide the first evidence for the requirement of calcineurin in the control of mNFATx imported from the cytoplasm to the nucleus and implies that mNFATx may possibly be a substrate of calcineurin in vivo.

Amino Acid Sequence↗

PubMed1997

Dissociation of Oct-1 from the nuclear peripheral structure induces the cellular aging-associated collagenase gene expression.

The cellular aging-associated transcriptional repressor that we previously named as Orpheus was identical to Oct-1, a member of the POU domain family. Oct-1 represses the collagenase gene, one of the cellular aging-associated genes, by interacting with an AT-rich cis-element in the upstream of the gene in preimmortalized cells at earlier population-doubling levels and in immortalized cells. In these stages of cells, considerable fractions of the Oct-1 protein were prominently localized in the nuclear periphery and colocalized with lamin B. During the cellular aging process, however, this subspecies of Oct-1 disappeared from the nuclear periphery. The cells lacking the nuclear peripheral Oct-1 protein exhibited strong collagenase expression and carried typical senescent morphologies. Concomitantly, the binding activity and the amount of nuclear Oct-1 protein were reduced in the aging process and resumed after immortalization. However, the whole cellular amounts of Oct-1 protein were not significantly changed during either process. Thus, the cellular aging-associated genes including the collagenase gene seemed to be derepressed by the dissociation of Oct-1 protein from the nuclear peripheral structure. Oct-1 may form a transcriptional repressive apparatus by anchoring nuclear matrix attachment regions onto the nuclear lamina in the nuclear periphery.

Base Sequence↗

PubMed1997

The effect of nasal continuous positive airway pressure on plasma endothelin-1 concentrations in patients with severe cardiogenic pulmonary edema.

We investigated the effects of nasal continuous positive airway pressure (CPAP) on plasma endothelin-1 (ET-1) concentrations in patients with cardiogenic pulmonary edema. Thirty patients were randomly assigned to two groups: 15 patients who received oxygen plus nasal CPAP (CPAP group), and 15 patients who received only oxygen by face mask (oxygen group). The heart rate and the mean pulmonary artery pressure decreased significantly in the CPAP group. The PaO2/ fraction of inspired oxygen (FIO2) ratio increased in the CPAP group (163 +/- 70 to 332 +/- 104, P < 0.01) after 6 h and was significantly higher than that in the oxygen group. Arterial plasma ET-1 concentrations decreased from 6.2 +/- 2.0 pg/mL to 4.8 +/- 1.7 pg/mL (P < 0.05) after 6 h and to 3.3 +/- 0.7 pg/mL (P < 0.01) after 24 h in the CPAP group. Arterial plasma ET-1 concentrations in the CPAP group compared with the oxygen group were significantly lower at 24 h. There was a correlation between the arterial plasma ET-1 concentrations and mean pulmonary artery pressure (r = 0.62, P < 0.001), and PaO2/FIO2 (r = -0.46, P < 0.01). Nasal CPAP led to an early decrease in plasma ET-1 concentrations, and improvement in oxygenation and hemodynamics.

Aged↗

PubMed1997

Amrinone improves lung compliance in patients receiving mechanical ventilation for cardiogenic pulmonary edema.

BACKGROUND: Decrease in lung compliance is one of the major causes of respiratory failure. We investigated whether amrinone could improve lung compliance. METHODS: We selected 20 consecutive patients with respiratory failure due to severe cardiogenic pulmonary edema to receive mechanical ventilation. Patients were administered a bolus injection (1 mg.kg-1) over 10 min followed by continuous intravenous infusion (10 micrograms.kg-1.min-1) of amrinone. Lung compliance, blood gas values, hemodynamic parameters, and sample plasma amrinone levels were assessed over a 120-min period after the onset of the continuous infusion of amrinone. RESULTS: Ten min following amrinone infusion, dynamic compliance (Cdyn) and static compliance (Cst) increased from 30 +/- 11 to 36 +/- 12 ml/cm H2O and from 37 +/- 12 to 42 +/- 13 ml/cm H2O, respectively (P < 0.01). Plasma amrinone levels reached a therapeutic level as vasodilator and positive inotropic effects at 10 min after amrinone infusion. The significant change in mean pulmonary artery pressure and pulmonary artery wedge pressure occurred later than the change in compliance of respiratory system. However, there were significant correlations between the mean pulmonary artery pressure and Cdyn (r = 0.36, P < 0.01) and Cst (r = 0.44, P < 0.01), as well as between plasma amrinone levels and Cdyn (r = 0.30, P < 0.05) and Cst (r = 0.41, P < 0.01). CONCLUSIONS: Amrinone-induced improvement in lung compliance was considered mainly to be due to an increase in the number of functioning lung units by improvement of the hemodynamics and a direct positive effect of amrinone on respiratory muscle contraction.

Aged↗

PubMed1997

The combination of external high-frequency oscillation and pressure support ventilation in acute respiratory failure.

BACKGROUND: Effective gas exchange can be maintained in animals by using external high-frequency oscillation (EHFO). The present study evaluates the effect of relatively long-term duration EHFO combined with pressure support ventilation (PSV) in patients with acute respiratory failure. METHODS: Twelve patients were ventilated with EHFO combined with PSV for 8 h at 60 oscillations.min-1, with a cuirass pressure of 36 cm H2O: -26 to +10 cm H2O (27 mm Hg: -19.5 to +7.5 mm Hg) and an inspiratory-to-expiratory ratio of 1:1. Blood gas values and hemodynamic parameters were measured. RESULTS: Significant increases were noted in cardiac index (3.0 +/- 0.7 to 3.2 +/- 0.7 1.min-1.m-2, P < 0.05) and stroke volume index (32 +/- 14 to 35 +/- 13 ml.m-2, P < 0.05) without changes in pulmonary artery wedge pressure at 1 h after EHFO. PaO2 (kPa)/FiO2 and PaCO2 improved from 21.9 +/- 7.5 to 26.8 +/- 8.0 (P < 0.05) at 2 h and from 6.9 +/- 1.7 to 6.1 +/- 0.9 (P < 0.01) at 30 min after EHFO, respectively. Breath sounds could be heard well throughout the lung fields after institution of EHFO. The mucous rales also decreased. CONCLUSIONS: As a method of ventilation for patients with acute respiratory failure, EHFO combined with PSV may have potential advantages over conventional mechanical ventilation when drainage of secretions if facilitated. Beneficial effects of EHFO may appear after several hours.

Aged↗

PubMed1997

Study of regional cerebral oxygen saturation during percutaneous cardiopulmonary support.

The purpose of this study was to evaluate the change of regional cerebral oxygen saturation (rSO2) during percutaneous cardiopulmonary support (PCPS) in patients with cardiogenic shock. Fifteen patients with cardiogenic shock were evaluated during PCPS by continuous monitoring of rSO2, systemic venous oxygen saturation (Svo2), and hemodynamics. The brain damage of these patients was also evaluated during and after PCPS. There were 10 males and 5 females. Their ages ranged from 57 to 79 years old (average: 60.0 +/- 14). Two patients were unconscious before PCPS, and 11 received intraaortic balloon pumping (IABP) before PCPS. The change of rSO2 was significantly correlated with the change of Svo2. The average of rSO2 was 64 +/- 3% at the stable hemodynamic condition. The rSO2 with pulsatile PCPS was higher than that with nonpulsatile PCPS. There was no correlation between brain damage and rSO2. The patients with low rSO2 (< 50%) that resulted in poor LV function could not be weaned from PCPS. In conclusion, the continuous monitoring of rSO2 during PCPS could be a useful tool.

Aged↗

PubMed1997

Induction of senescence-like phenotypes by forced expression of hic-5, which encodes a novel LIM motif protein, in immortalized human fibroblasts.

The hic-5 gene encodes a novel protein with Zn finger-like (LIM) motifs, the expression of which increases during cellular senescence. The ectopic expression of hic-5 in nontumorigenic immortalized human fibroblasts, whose expression levels of hic-5 were significantly reduced in comparison with those of mortal cells, decreased colony-forming efficiency. Stable clones expressing high levels of hic-5 mRNA showed higher levels of mRNAs for several extracellular matrix-related proteins, along with the alteration of an alternative splicing as seen in senescent cells and decreased c-fos inducibility. Furthermore, these clones acquired a senescence-like phenotype, such as growth retardation; senescence-like morphology; and increased expression of Cip1/WAF1/sdi1 after 20 to 40 population doublings. On the other hand, antisense RNA expression of hic-5 in human normal diploid fibroblasts delayed the senescence process. HIC-5 was localized in nuclei and had affinity for DNA. Based on these observations, we speculated that HIC-5 affected the expression of senescence-related genes through interacting with DNA and thereby induced the senescence-like phenotypes. To our knowledge, hic-5 is the first single gene that could induce senescence-like phenotypes in a certain type of immortalized human cell and mediate the normal process of senescence.

Alternative Splicing↗

PubMed1997

Developmental change of the nestin-immunoreactive midline raphe glial structure in human brainstem and spinal cord.

To elucidate the development of the midline raphe glial structure (MRGS) in human brainstem and spinal cord, immunohistochemistry was carried out in 10 developmentally normal brains (age range, 11 weeks postconception to 6 months) using antibodies to nestin and glial fibrillary acidic protein (GFAP). Nestin expression was most extensive in the youngest fetus (11 weeks postconceptional age, PCA), which showed strong immunoreactivity in radial glial fibers in the midline raphe and paramedian areas of brainstem and spinal cord. Nestin-immunoreactive radial glial fibers in the midline raphe gradually decreased in length and intensity, losing contact with the pial surface 20-24 weeks PCA. Radial glial cells in midbrain transformed into subependymal cells at 30 weeks PCA. Some fragments of radial fibers in brainstem and spinal cord could still be detected up to 30 weeks PCA. Weak GFAP immunoreactivity in the midline raphe was found in radial fibers in the dorsal midline of the midbrain and cervical spinal cord at 30 and 38 weeks PCA. This change of nestin positivity was thought to be due to the process remodeling the MRGS, not to the intracellular distribution and any identifiable clinical factors in the stillbirths. This irregularity in the appearance of the MRGS supports its proposed role as a guide for cell migration, a potential source of new astrocytes, and a barrier to aberrant decussation of growing axons.

Brain Stem↗

PubMed1997

ATP-dependent lysis of isolated lysosomes by basic substances and acidic ionophores.

We established an in vitro cell-free system with which to evaluate the effects of basic substances and acidic ionophores on the internal pH and integrity of FITC-dextran (FD)-loaded lysosomes isolated from the rat liver. In this system, basic substances and acidic ionophores not only increased the internal pH dose-dependently, but also disrupted the lysosomes in the presence of Mg-ATP, which was detected as the release of FD from lysosomes. All of the vacuoligenic bases and acidic ionophores, but none of the non-vacuoligenic bases or neutral ionophores disrupted the lysosomes, suggesting that this phenomenon is an vitro manifestation of vacuole formation induced in vivo by basic substances and acidic ionophores. Lysosome disruption required a functional proton pump as well as permeant anions. It was inhibited by inhibitors of the lysosomal proton pump, including bafilomycin A1, N-ethylmaleimide (NEM), and N, N'-dicyclohexylcarbodiimide (DCCD), or when permeant anions were replaced with impermeant anions. It was also suppressed by increasing the osmotic pressure of the surrounding medium, suggesting that it was caused by osmotic swelling of lysosomes induced by protonated bases or cations characteristic of particular ionophores that accumulated within lysosomes driven by the proton pump. Furthermore, this lysosomal disruption was inhibited by cytosolic factors. This phenomenon will provide an in vitro system for studies on osmoregulation and the intracellular dynamics of the lysosomal system, including membrane fusion.

Adenosine Triphosphate↗

PubMed1997

External high-frequency oscillation for hypercapnia after upper abdominal surgery.

The purpose of this study was to evaluate the efficacy of external high-frequency oscillation (EHFO) in patients with hypercapnia following upper abdominal surgery. Seven patients were ventilated with EHFO for 2 hr at 60 oscillations/min, with cuirass pressures of 36 cm H2O (-26 to +10), and an inspiratory to expiratory ratio of 1:1. Blood gases and cardiac functional parameters were examined during the 2 hr on EHFO. Pulmonary functional parameters were analyzed prior to the institution and after the termination of EHFO. PaCO2 significantly decreased from 61 +/- 8 mmHg to 48 +/- 7 mmHg after 10 min on EHFO (p < 0.01). PaO2 significantly increased from 74 +/- 10 mmHg 95 +/- 26 mmHg after 1 hr on EHFO (p < 0.01). The heart rate decreased significantly from 108 +/- 27 beats/min to 101 +/- 24 beats/min after 30 min on EHFO (p < 0.05). The FEV1 and FVC significantly increased from 1.09 +/- 0.54 L to 1.50 +/- 0.46 L (p < 0.01) and from 1.90 +/- 0.74 L to 2.18 +/- 0.60 L (p < 0.05), respectively. The other parameters of lung function also significantly improved after the termination of EHFO. The significant changes in all of the pulmonary functional parameters continued for 1 hr after the termination of EHFO. EHFO is an effective method of gas exchange which is associated with earlier return to preoperative lung function.

Aged↗

PubMed1997

Detection of thyroid-stimulating antibody using frozen stocks of Chinese hamster ovary cells transfected with cloned human thyrotropin receptor.

To measure thyroid-stimulating antibody (TSAb) in sera from patients with Graves' disease, we developed a new assay system with using frozen stocks of CHO-K1 cells. CHO-K1 cells transfected with cloned thyrotropin (TSH) receptor on a 96 well plate were frozen in Cell Banker and stored at -70 degrees C. Three days before the assay, they were thawed in the culture medium and allowed to grow in a monolayer until use. The medium was replaced with medium containing IgGs from the patients, then after 2 h, it was collected and concentrations of adenosine 3'-5'-cyclicmonophosphate (cAMP) were measured. This method is sensitive enough to detect TSAb and it is simpler and easier than the methods which use FRTL-5 cells.

Animals↗