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Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 163 records · Page 9Linked to original sources
PubMed1998

Immunohistochemical localisation of advanced glycation end products in pulmonary fibrosis.

AIM: To investigate the presence and distribution of advanced glycation end products (AGE) in pulmonary fibrosis. METHODS: Lung tissue samples obtained from seven necropsy cases with idiopathic pulmonary fibrosis and seven with normal pulmonary parenchyma were examined immunohistochemically with a monoclonal antibody specific for AGE: 6D12. We also tested three cases with diffuse alveolar damage. RESULTS: All the specimens from cases with pulmonary fibrosis and diffuse alveolar damage showed strong AGE expression on macrophages. Lung specimens from normal parenchyma showed positive AGE immunoreactivity on macrophages from only two of seven cases. CONCLUSIONS: These findings suggest that AGE modified proteins accumulate in alveolar macrophages in patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.

Aged↗
PubMed1998

Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats.

Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 microliters at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE, 2 micrograms/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.

Animals↗
PubMed1998

Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1.

Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1(+/+) wild-type mice. Airway responsiveness was assessed through the concentration of an agonist required to double lung resistance (EC200 RL). Unexpectedly, airway responsiveness to methacholine was markedly enhanced in ET-1(+/-) heterozygous mice as compared with ET-1(+/+) wild-type mice (EC200 RL: 1.8 +/- 0.1 versus 21.6 +/- 5.6 mg/ml, p < 0.002). Pretreatment with the nitric oxide (NO) synthase inhibitor Ng-monomethyl-L-arginine (L-NMMA) significantly enhanced methacholine responsiveness in ET-1(+/+) wild-type mice, but not in ET-1(+/-) heterozygous mice. Meanwhile, there was no difference between ET-1(+/-) heterozygous mice and the wild-type mice in airway responsiveness to 5-hydroxytryptamine (5-HT). In sensitized mice, no significant differences in responsiveness to antigen were observed between the two groups. These findings suggest that the gene encoding ET-1 may be potentially involved in the etiology of airway hyperreactivity, and that the decrease in ET-1 concentration is associated with AHR to methacholine. In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology.

Airway Resistance↗
PubMed1998

Investigation of effects of anesthesia and age on aspiration in mice through LacZ gene transfer by recombinant E1-deleted adenovirus vectors.

To examine the role of disturbed upper airway reflexes in aspiration, we administered 20 microliters of the adenovirus (Ad) vector Ad-CMV-LacZ or 20 microliters of phosphate buffered saline (PBS) intranasally to C57 black mice. We investigated expression of the LacZ gene by this Ad vector in the nostrils of each mouse, with or without anesthesia. Under anesthesia, LacZ gene expression was detected in the lungs of every mouse given the Ad vector. However, no LacZ gene expression was found in the trachea or lungs of mice given the Ad vector without anesthesia. In mice given PBS or wild-type adenovirus transnasally during anesthesia, there was no LacZ gene expression in the nostrils, trachea, or lungs, suggesting that with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining, blue-stained cells indicated transferred LacZ gene expression. These results suggested that aspiration of intranasal solution into lower airways was caused by disturbed upper airway reflexes during anesthesia. This process can be analyzed by the distribution of LacZ gene expression in airways. We next examined the effect of age on anesthesia-induced aspiration. Twenty-six-mo-old mice exhibited more LacZ gene expression in their lungs than did 6-mo-old mice at a concentration of 0.5 to 4.0% halothane in 100% oxygen. This suggests that light anesthesia may depress upper airway reflexes and cause aspiration in older animals. This novel model of aspiration, generated with the Ad-CMV-LacZ vector, may be useful for elucidating the mechanism of development of aspiration pneumonia in relation to age-related impairment of upper airway reflexes.

Adenoviridae↗
PubMed1998

Altered glucose metabolism in the hippocampal head in memory impairment.

OBJECTIVE: To evaluate the relevance of hypometabolism in the hippocampal head to the pathophysiology of memory impairment. BACKGROUND: Neurofunctional imaging studies with an image reslicing technique provided by using software suggest that dysfunction of the amygdalohippocampal system causes memory impairment. However, metabolic and morphologic profiles of the whole hippocampal formation have not been evaluated in detail. METHODS: By tilting the gantry of a high-resolution PET scanner in a plane parallel to the hippocampal longitudinal axis determined beforehand by MRI, we performed quantitative measurement of glucose metabolism in the subdivisions of the hippocampal formation (head, body, tail) in 10 patients of normal intelligence with pure amnesia, in eight patients with AD, and in eight normal subjects. RESULTS: Although the volumes of the amygdala and hippocampal formation in pure amnesics were not different significantly from those of normal subjects, glucose metabolism in the head of the hippocampus was significantly lower in pure amnesics. In patients with AD, marked hypometabolism was found extending to the amygdala, the hippocampal head, and the parietotemporal cortex, along with amygdalohippocampal atrophy. CONCLUSION: Hippocampal head dysfunction plays an important role in memory impairment in amnesic patients. Further metabolic impairment over the amygdalohippocampal system and the surrounding association cortex reflects the pathophysiology of AD.

Adult↗
PubMed1998

Effect of ambroxol on oxygen radical production and generation by bronchoalveolar lavage cells in young and aged guinea pigs.

We examined the effect of ambroxol and age on oxygen radical production and generation with stimulation of phorbol-myristate acetate (PMA) by bronchoalveolar lavage (BAL) cells. Lung free cells including pulmonary alveolar macrophages were harvested from young (4-month-old) and aged (28-month-old) male guinea pigs using BAL. The oxygen radicals produced by BAL cells with or without stimulation of PMA were measured by the lucigenin-dependent chemiluminescence method using a photon counter. Oxygen radical production and generation by BAL cells were not different between young and aged guinea pigs. However, the oxygen radical generation after stimulation with PMA was greater than the oxygen radical spontaneous production both in young and aged animals. Ambroxol solution given into culture media containing BAL cells inhibited oxygen radical production and generation by BAL cells harvested from both young and aged guinea pigs in a concentration-dependent manner. Approximately 16-20 microM of ambroxol inhibited 50% of the production of oxygen radicals in vitro by BAL cells in young and aged guinea pigs, whereas a slightly greater amount of ambroxol was necessary to inhibit 50% of the PMA-induced oxygen radical generation in vitro by BAL cells in guinea pigs. These results indicate that ambroxol inhibits oxygen radicals produced by BAL cells from young and aged guinea pigs, and they suggest that ambroxol may be a possible therapeutic modality for ameliorating oxidant associated pulmonary disorders in young and aged patients.

Aging↗
PubMed1998

Inhibitory effect of ambroxol on superoxide anion production and generation by murine lung alveolar macrophages.

We examined the effect of ambroxol on superoxide anion production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells including lung alveolar macrophages were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The superoxide anion produced by lung alveolar macrophages with or without stimulation of PMA was measured by lucigenin-dependent chemiluminescence method using a photon counter. Ambroxol inhibited the superoxide anion production and generation by lung alveolar macrophages harvested from both F344 rats and guinea pigs in a dose-dependent fashion. Approximately 16 mumol/L of ambroxol inhibited 50% of superoxide production of lung alveolar macrophages in rats and guinea pigs, whereas a slightly greater dose of ambroxol, i.e., 18-26 mumol/L, was necessary to inhibit 50% of PMA-enhanced superoxide generation by lung alveolar macrophages. These results suggest that ambroxol acts as an antioxidant in murine lungs and may be a potential therapeutic option for reactive oxygen species-associated lung disorders including bronchial asthma.

Acridines↗
PubMed1998

[Influence of kyphosis on the age-related decline in pulmonary function].

To examine the influence of kyphosis on pulmonary function in the elderly, 300 consecutive healthy subjects (aged 20-94 years old) were evaluated using pulmonary function tests (TLC, VC, FEV1, RV) and static maximal pressures (PImax and PEmax). Kyphosis of the thoracic bones was measured at Cobb's angle. VC, FEV1. PImax and PEmax showed a significant age-dependent decline. Cobb's angle had a positive relationship with age and was negatively correlated with TLC, VC, FEV1 and PImax. Further, RV/TLC strongly correlated with Cobb's angle and PImax. Stepwise regression analysis revealed that the kyphotic angle was an independent determinant for PImax and RV/TLC. These results indicate that kyphosis significantly affects lung volume and maximal inspiratory pressure in the elderly and those affected should have careful assessment of their pulmonary function and respiratory pressures.

Adult↗
PubMed1998

[An animal model of aspiration and aspiration pneumonia using lacZ gene expression in lungs by adenoviral vectors].

To examine the relationship between disturbed upper airway reflexes and aspiration pneumonia, we administered a total volume of 20 microliters of Ad-CMV-lacZ (Ad vector) or 20 microliters of phosphate buffer solution (PBS) intranasal to C57 black mice. In nostrils, the lacZ gene expression was investigated in each mouse with or without anesthesia. Under anesthesia, the lacZ gene expression was detected by Xgal staining in the lungs of every mouse given the Ad vector. However, no gene expression was measured in the lungs of those given the Ad vector without anesthesia. In mice treated with PBS, there was no lacZ gene expression in the nostrils, trachea, or lungs, irrespective of anesthesia. These results suggest that unconsciousness or disturbed upper airway reflexes caused by anesthesia caused aspiration, resulting in an intranasal bolus that can reached the lower airways. This process can be analyzed in mice tracted with adenovirus vectors carrying the E. coli LacZ gene. Mice given Ad-CMV-lacZ transnasally can be used to study aspiration pneumonia in relation to unconsciousness.

Adenoviridae↗
PubMed1998

[Renal tubular acidosis type II secondary to gamma-light chain excretion in an elderly patient with multiple myeloma].

A 73-year-old woman was admitted to the geriatric ward of the University of Tokyo Hospital with anemia, osteepeina, and renal dysfunction. Although symptoms typical of multiple myeloma such as punched-out lesions and hyperproteinemia were not found, protein electrophoresis revealed that lambda type Bence-Jones protein was excreted in urine. Multiple myeloma was diagnosed. Furthermore, renal dysfunction was accompanied renal tubular acidosis type II (proximal type). Renal dysfunction in patient with multiple myeloma in usually caused by so-called myeloma casts in the distal tubules, but renal tubular acidosis type II is rarely observed. It is possible that injury of the proximal renal tubular eithelium by Bence-Jones protein resulted in renal tubular acidosis type II in this patient.

Acidosis, Renal Tubular↗
PubMed1998

Activin/follistatin and atherosclerosis--a review.

Activin-A, a member of the TGF-beta superfamily, has a variety of important biological functions. Concerning Møs, we demonstrated that MSR which has a key role in disposing of modified LDL is downregulated by activin-A. This leads to a decrease in binding, cell association, and degradation of Ac-LDL, resulting in the inhibition of foam cell formation. Follistatin, presumably by blocking the effect of intrinsic activin-A, upregulates MSR expression, thereby promoting Ac-LDL disposal and foam cell formation. Because both activin-A and MSR are induced during Mø differentiation, these results suggest that MSR expression is suppressed by simultaneous production of activin-A in an autocrine manner. In addition to Møs, activin-A and follistatin exert influences on SMCs and ECs. Examination of in vivo expression of activin-A and follistatin revealed that they are present in various atherosclerotic lesions, including human coronary arteries, suggesting that they are locally produced. Activin-A and follistatin are produced by Møs, SMCs, and ECs in vitro. Thus, the activin-A/follistatin system plays an important role in the development of atherosclerosis.

Activins↗
PubMed1998

Medical diagnostic system using Fuzzy Coloured Petri Nets under uncertainty.

We propose a medical diagnostic system using Fuzzy Coloured Petri Nets (FCPN) in this paper. For complex real-world knowledge Fuzzy Petri Net (FPN) models have been proposed to perform fuzzy reasoning automatically. However, in the Petri Net we have to represent all kinds of processes by separate subnets even though the process has the same behavior of other one. Real-world knowledge often contains many parts which are similar, but not identical. This means that the total PTN becomes very large. The kind of problems may be annoying for a small system, and it may be catastrophic for the description of large-scale system. To avoid this kind of problems we propose a learning and reasoning method using FCPNs under uncertainty. On the other hand to correct the rules of knowledge-based system hand-built classifier and empirical learning method both based on domain theory have been proposed as machine learning methods, where there is a significant gap between the knowledge-intensive approach in the former and the virtually knowledge-free approach in the later. To resolve such problems simultaneously we propose a hybrid learning method which is built on the top of knowledge-based FCPN and Genetic Algorithms (GA). To verify the validity and the effectiveness of the proposed system, we have successfully applied it to the diagnosis of intervertebral diseases.

Algorithms↗
PubMed1998

Changes in cerebral blood flow and postsynaptic muscarinic cholinergic activity in rats with bilateral carotid artery ligation.

UNLABELLED: Changes in both regional cerebral blood flow (rCBF) and postsynaptic muscarinic cholinergic activity in the rat brain were investigated after ligation of the common carotid arteries (CCAs) bilaterally with (15)O-labeled water (H2(15)O) and [11C]N-methyl-4-piperidylbenzilate, a potent muscarinic receptor antagonist. METHODS: PET was performed in the same Wistar rat, 7 days and 1 mo after the CCA ligation. Regional cerebral blood flow and the transfer coefficient k3, the rate of binding of 11C-NMPB, were measured, based on the autoradiographic method and the graphical plotting analysis, respectively. RESULTS: The levels of rCBF in the frontal cortex of the ligated group were significantly lower than those in the cerebellum and those in sham group, after 7 days and 1 mo postoperation. Although the level of k3 in the frontal cortex 7 days after operation was not altered, it decreased significantly after 1 mo in the ligated group. Neither cortical infarct nor cortical neuronal loss was observed histologically. CONCLUSION: Common carotid artery ligation in Wistar rats caused a prolonged cerebral hypoperfusion without degeneration of the cortical neurons and a later decline of postsynaptic cholinergic receptor activity. These findings suggest that the decline in the postsynaptic cholinergic activity that is associated with the prolonged reduction in the cerebral blood supply may reflect pathophysiology that is equivalent to the deterioration of cognitive function in patients with chronic cerebrovascular insufficiency.

Animals↗
PubMed1998

[Determinant factors of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD)].

The effects of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD) have not been fully elucidated. We examined the relationships between pulmonary function, static respiratory pressure, and dyspneic sensation during exercise in 48 patients with COPD. Dyspneic sensation during exercise was quantitated by a Borg scale slope (BSS, BS/VO2) and the threshold load of dyspnea (TLD). BSS was negatively correlated with VC, FEV1, V 25, RV/TLC (%). DLCO and PImax, whereas TLD was positively correlated with VC, FEV1, V 25, FRC and RV/TLC. Linear regression analysis revealed that FEV 1 and FRC were independent predictors for TLD, and that RV/TLC (%) was an independent predictor for BSS. These results suggest that an increase of air trapping as indicated by RV/TLC may be a major factor contributing to both decreased TLD and increased BSS, resulting in an increased sensation of dyspnea during exercise in patients with COPD.

Dyspnea↗
PubMed1998

Attachment of the sphenomandibular ligament to bone during intrauterine embryo development for the control of mandibular movement.

The present study examined the relationship between jaw movement and the site of attachment of the sphenomandibular ligament, which is involved in the control of lateral jaw movement. Major fibers of this ligament are attached to the sphenoid spine and the mandibular lingula. During early stages of embryonic development, however, this ligament is not attached to the sphenoid spine. No consensus has yet been reached concerning the time at which this ligament becomes attached to this spine. The present study was performed to resolve this question and to analyze the relationship of this event of jaw movement. Attachment of the sphenomandibular ligament to the sphenoid spine was observed in fetuses at a gestational age of about 8 months (32 weeks). This may be because fetuses undergo functional changes (initiation of jaw movement such as mastication and swallowing) at this gestational age. This finding suggests that the attachment of the sphenomandibular ligament to the sphenoid spine may be related to fetal jaw movements.

Embryonic and Fetal Development↗
PubMed1998

[Effects of thyroid hormone replacement therapy on nocturnal apnea in elderly patients with hypothyroidism].

Because the incidence of sleep apnea is known to increase in both hypothyroidism and with age, elderly hypothyroid patients may experience more sleep apnea than younger hypothyroidism patients. However, the features of nocturnal disturbed breathing in elderly hypothyroid patients have not been fully elucidated. Concise polysomnographic studies including respiratory movement and oxyhemoglobin saturation (SaO2) were done on 18 elderly subjects with hypothyroidism (73.6 +/- 5.9 years old) before and after thyroid hormone replacement therapy. Fourteen of the patients exhibited a significant incidence of nocturnal apnea. Lower incidence of nocturnal apnea and higher nocturnal nadir SaO2 were observed in the patients 3 to 6 months after thyroxine therapy. Although the levels of thyroid hormones returned to normal in the patients, 9 patients had more than 5 bouts of nocturnal apnea per hour after the hormone replacement therapy. Further, no relationship was found between the level of thyroid hormones and the frequency of nocturnal apnea. These results suggest that levels of thyroid hormones are not indicators of the potential severity of nocturnal apnea in elderly hypothyroid patients, and that sleep studies may be necessary to assess the efficacy of thyroid hormone replacement therapy in the treatment of nocturnal apnea.

Aged↗