Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 397 records · Page 22Linked to original sources

PubMed1994

Role of endogenous adenosine in hypoxic ventilatory response in humans: a study with dipyridamole.

To examine the role of endogenous adenosine in hypoxic ventilatory response, we measured, in nine normal young adults, ventilatory responses to isocapnic progressive hypoxia and subsequent sustained hypoxia [arterial O2 saturation (SaO2); 80%, 20 min] with and without pretreatment with dipyridamole in a double-blind crossover fashion. Dipyridamole, an adenosine uptake blocker, was expected to enhance the effect of endogenous adenosine. Pretreatment with dipyridamole (0.5 mg/kg) significantly augmented the slope of the ventilatory response to isocapnic progressive hypoxia from 0.35 +/- 0.13 (SE) to 0.70 +/- 0.25 l.min-1.%fall of SaO2(-1) (P < 0.01), although there were no significant changes in resting ventilation. On the other hand, minute ventilation, when expressed as a percentage of peak ventilation, declined to 68.4 +/- 4.3% with dipyridamole at the 9-11th min of sustained hypoxia, which was significantly lower than the 90.2 +/- 8.3% with a placebo (P < 0.05), and finally reached 56.1 +/- 7.2% with dipyridamole and 78.7 +/- 9.2% with the placebo (P < 0.1) at the 18-20th min of sustained hypoxia. In an attempt to more specifically examine the role of adenosine, aminophylline (5 mg/kg), an adenosine receptor antagonist, was injected before pretreatment with dipyridamole in four subjects. Aminophylline infusion abolished or at least attenuated the effect of dipyridamole in all four subjects. These data suggest that endogenous adenosine has a modulatory role in hypoxic ventilatory response in adult humans.

Adenosine↗

PubMed1994

Effect of aminophylline on plasma [K+] and hypoxic ventilatory response during mild exercise in men.

To examine the role of endogenous adenosine on the hypoxic ventilatory response (HVR) enhanced during exercise, we measured HVR at rest and during mild exercise (12.5 W) in nine healthy men in a supine position after pretreatment with aminophylline (5 mg/kg), an adenosine receptor blocker, or dipyridamole (0.6 mg/kg), an adenosine uptake blocker, by using a 3-day double-blind placebo-controlled design. Although HVR was enhanced during exercise on all occasions, HVR with aminophylline [0.42 +/- 0.07 (SE) l.min-1.%fall-1 of arterial O2 saturation] was significantly lower than that with placebo (0.64 +/- 0.13 l.min-1.%fall-1) or dipyridamole (0.64 +/- 0.08 l.min-1.%fall-1) during exercise (P < 0.05 for both) at similar end-tidal PCO2 on the 3 days but not at rest. We then examined the changes in plasma K+ concentration ([K+]) and catecholamines, the other possible endogenous potentiators of the carotid body activity. The exercise- and hypoxia-induced increases in plasma [K+] were significantly lower with aminophylline (0.23 +/- 0.09 meq/l) than with the placebo (0.51 +/- 0.10 meq/l) or dypyridamole (0.58 +/- 0.13 meq/l) (P < 0.05 for both). We therefore conclude that aminophylline attenuates the enhancement of HVR during mild exercise and that this might be due to its attenuating effect on exercise- and hypoxia-associated increases in plasma [K+] rather than due to its antagonizing effect on endogenous adenosine.

Adolescent↗

PubMed1994

Genetic association between agouti locus and adrenal X zone morphology in SM/J mice.

We provide evidence for a genetic link between the adrenocortical X zone and the agouti (a) locus on chromosome 2 in the segregating inbred mouse strain SM/J. This strain has been established and maintained while keeping heterozygosity (Aw/a) at the a locus and is, therefore, of advantage in assessing the effects of these alleles upon physiological phenomena. In Aw/a (white-bellied agouti) or a/a (black) virgins, X zones were composed exclusively of nonvacuolated cells, while they contained vacuolated cells only in Aw/Aw. This suggested that the a locus might control the X zone morphology on the SM/J genetic background and that the a (nonagouti) allele is dominant in vacuolation of cells in this zone. The a locus might have a novel function in the control of the adrenocortical X zone cell turnover in addition to the well-known function controlling the coat color.

Adrenal Cortex↗

PubMed1994

A case of 11q-syndrome associated with abnormalities of the retinal vessels.

A case of 11q- syndrome associated with abnormalities of the retinal vessels similar to those of familial exudative vitreoretinopathy was followed from 6 months to 3 years of age. The patient was a female infant born at 39 weeks of gestation and weighing 2,360 g without oxygen therapy. A chromosomal analysis showed a 46,XX,del(11)(q23.3). An ocular examination revealed exotropia and a positive kappa angle of the left eye with psychomotor retardation. An abnormal pattern of the retinal vessels and an avascular retina was observed in the periphery of both eyes. Therefore we concluded that the abnormalities of the retinal vessels may be related to the deletion of the long arm of chromosome 11.

Chromosome Aberrations↗

PubMed1994

Current smoking of elderly men reduces antioxidants in alveolar macrophages.

Alveolar macrophages were prepared from 15 healthy elderly male current smokers 60.9 +/- 9.9 yr of age (mean +/- SD). Alveolar macrophages from 11 elderly male nonsmokers 66.7 +/- 8.1 yr of age served as controls. Production of oxygen radical species was higher in alveolar macrophages from current smokers than in those from nonsmokers in the presence and absence of phorbol myristate acetate (29.8 +/- 15.5 versus 13.7 +/- 8.2 mumol/10(6) cells and 3.8 +/- 1.6 versus 2.2 +/- 1.2 mumol/10(6) cells, respectively, p < 0.01). Decreases in antioxidant activity were observed in cells from smokers versus those from nonsmokers for Cu, Zn-superoxide dismutase (114 +/- 41 versus 210 +/- 73 units/mg protein, respectively, p < 0.01), glutathione S-transferase (0.217 +/- 0.091 versus 0.368 +/- 0.017 units/mg protein, p < 0.01), and glutathione peroxidase (0.736 +/- 0.779 versus 1.590 +/- 0.879 units/mg protein, p < 0.05). Immunologic estimation showed a decrease in the levels of Cu, Zn-superoxide dismutase in cells from smokers (104.3 +/- 46.4 versus 184.1 +/- 64.4 ng enzyme/mg protein, respectively, p < 0.01). Northern blot analysis of Cu, Zn-superoxide dismutase mRNA showed no apparent difference between the two groups, suggesting not the inactivation of this enzyme but a reduction of the translational step or increased proteolysis. The oxidant and antioxidant imbalance observed in elderly male current smokers may be a factor in the pathogenesis of respiratory tissue injury caused by smoking.

Aged↗

PubMed1994

A case of pulmonary AV fistula. Possible involvement of adenosine in hyperventilation.

A 21-yr-old man with multiple pulmonary AV fistulae presented with moderate hypoxemia with chronic hyperventilation, which continued even after sufficient oxygenation by 100% O2 inhalation. The infusion of aminophylline, an adenosine receptor blocker, not only increased PaCO2 from 35 to 39 mm Hg but also depressed the magnitude of hypoxic ventilatory response (HVR). After a surgical removal of the major fistulae, PaCO2 increased to 42 mm Hg. At this time, aminophylline increased the resting ventilation and slightly augmented the HVR value, which was opposite to the findings of preoperation. Dipyridamole, which potentiates endogenous adenosine by inhibiting its cellular uptake, increased the magnitude of HVR both before and after the operation. We propose that the hyperventilation observed in this case can at least in part be attributed to the ventilatory stimulation by endogenous adenosine, which presumably passed through the fistulae without being metabolized in the pulmonary circulation.

Adenosine↗

PubMed1994

Failure to transfer multiple sclerosis into severe combined immunodeficiency mice by mononuclear cells from CSF of patients.

To confirm the reported transfer of multiple sclerosis (MS) by CSF cells, we injected CSF cells from six MS patients in the exacerbation stage into the cisterna magna of 18 severe combined immunodeficiency mice. No clinical neurologic abnormalities or light- or electron-microscopic pathologic changes were present in any transferred mice, and the reported results could not be reproduced.

Adult↗

PubMed1994

Local disposition of a new xanthine oxidase/xanthine dehydrogenase inhibitor, BOF-4272, in rat liver.

The local hepatic disposition of BOF-4272, a newly developed xanthine oxidase (XO)/xanthine dehydrogenase (XDH) inhibitor, was evaluated in the rat perfusion system following pulse input of the drug into the portal vein. The elution time profiles from the liver into the hepatic vein were analyzed by dispersion models. The disposition of BOF-4272 through the rat liver was represented by a two-compartment dispersion model based on the Akaike's Information Criterion (AIC). The area under the concentration time curve (aucH) of BOF-4272 was proportional to the dosing amount, and the mean transit time was constant from 62.5 up to 500 micrograms/liver, which demonstrates that the local hepatic disposition of BOF-4272 is linear in this dosing range. The local disposition parameters were precisely estimated at the dosing amount of 250 micrograms/liver using several rats. These parameters in the dispersion model were correlated to the local moment characteristics. The hepatic recovery ratio (FH) was 22.8 +/- 3.2% and the mean transit time (tH) was 0.112 +/- 0.008 min, which show that the influx of BOF-4272 into the liver is efficiently large.

Animals↗

PubMed1994

Respiratory load compensation during hypercapnic ventilatory response in pulmonary emphysema.

The purpose of this study is to examine the relationship between mechanical factors and the load compensation during hypercapnia in emphysema. In 36 clinically stable patients, we conducted pulmonary function tests and hypercapnic ventilatory response (HCVR) tests with and without inspiratory flow-resistive loading (IRL) (17 cm H2O/L/s). The mean value of HCVR significantly decreased with IRL, while that of the mouth occlusion pressure (P0.1) response increased. Regardless of IRL, the HCVR values were correlated with FEV1/FVC and airway resistance. The load compensation, evaluated by the ratio of the HCVR value and the P0.1 response before and after IRL, was inversely correlated with percent FRC (r = -0.38, r = -0.39; both p < 0.05). Breathing pattern analysis at the end-tidal pressure of carbon dioxide of 55 mm Hg elicited the decrease of (tidal volume/inspiratory time (VT/TI) and the increase of TI and TI/TTOT. Although the absolute changes of VT and f were inconsistent among subjects, each relative ratio before and after IRL was correlated again with percent FRC (r = -0.46, r = 0.44: both p < 0.01). Therefore, the position of the inspiratory muscles at the onset of inspiration may influence the load compensation during hypercapnia in emphysema.

Aged↗

PubMed1994

[Thermal insulation of clothing for seated and standing postures].

The purpose of this study is to examine the effects of body posture on thermal insulation of clothing. Clothing ensembles including skirts were mainly investigated. A new thermal manikin was developed for this study. This manikin was able to change her body posture without increasing or decreasing her surface area. By changing posture from standing to seated, the total thermal insulation of clothing (It) was decreased by around 1.4%. The surface thermal resistance at nude (Ia) was increased by 8%. As a result, the basic thermal insulation of clothing (Icl) was decreased by 14%. The main reason for the decrease of basic thermal insulation (Icl) when the posture of thermal manikin changes from standing to seated was the increase of Ia at nude. The total thermal insulation of clothing for each body posture (Iti), when standing and seated, were compared. The parts affected by the changed posture were abdomen, hip and thighs, and especially under the skirt of 61cm length, the knees were most affected.

Adult↗

PubMed1994

A simple method for screening assessment of skin and eye irritation.

A stepwise, simple screening test for skin and eye irritations, suitable for industrial chemicals or pesticides which are not required to be examined for their exact potential irritancy levels, was developed. The efficacy of the test was evaluated using 15 chemicals including typical irritants (acetic acid, ammonia, chloroacetic acid, dioxane, ethanolamine, formaldehyde, formic acid, hydrogen peroxide, phenol, phosphoric acid, propionic acid, sodium hydroxide, sodium hypochlorite, sulfuric acid, and trichloroacetic acid). Chemicals were chosen so as to represent irritants which act by different mechanisms (i.e., strongly acidic, alkaline, reactive to protein, oxidizing etc.). The method consisted of physicochemical tests and animal tests using rats, mice or guinea pigs, namely, a skin irritation test, an intradermal reaction test and an eye irritation test in a sequential manner such that further tests are not required if a positive result is obtained in earlier steps. Results obtained between two laboratories using this method were very similar. Comparison of our results with the data obtained by the conventional method using rabbits showed fairly good coincidence. The method was shown to be useful in assessing skin and eye irritation of chemicals and causes minimal suffering to animals.

Animals↗

PubMed1994

A congenital variant of thrombotic thrombocytopenic purpura in two siblings.

We describe two siblings affected by chronic relapsing thrombotic thrombocytopenic purpura from infancy. The elder brother, a 12-year-old boy had 50 such episodes characterized by acute onset of fever, headache, drowsiness, vomiting, dark urine, thrombocytopenia and anemia. The younger sister, a 6-year-old girl, had 8 episodes with the same clinical manifestations. Petechiae and ecchymoses on the extremities were present throughout their lives. Furthermore, anemia with evidence of red blood cell fragmentation and thrombocytopenia were present chronically. Periodical transfusion of frozen fresh plasma prevented recurrent episodes. These cases suggest that there is a congenital variant of thrombotic thrombocytopenic purpura.

Child↗

PubMed1994

Scanning electron microscopy of the organelles of rat incisor odontoblasts--in particular the tubulo-vesicular elements.

The fine structure of rat odontoblasts (OBs) showing the developmental sequence of cellular maturation along the long axis of the incisor was studied. The cytomorphological changes and relationships of the intracellular components, particularly the membranous component, were investigated mainly by scanning electron microscopy (SEM) using the AODO (A: aldehyde prefixation; O: osmium tetroxide postfixation; D: dimethyl sulfoxide (DMSO) freeze-fracture; O: osmium tetroxide maceration) method and transmission electron microscopy (TEM) using the conventional methods. The following results were obtained: 1) The elongated young OBs were highly polarized and characterized by well-developed concentric cisternal granular (rough) endoplasmic reticulum (rER) layers and Golgi complex. SEM showed the rER was continuous to the agranular (smooth) ER (sER). 2) Transformation of the concentric rER to a tubular network was closely related to the maturation and secretory activity of the OBs. 3) Many branched and elongated tubular mitochondria were observed in the supranuclear region of young OBs. On the other hand, many round-to-ovoid mitochondria were observed particularly in the distal clear area of old OBs. 4) SEM also revealed tubulo-vesicular elements, which are believed to be structures relating to secretory and absorptive functions, composed of secretory granules and small tubules, having connections with the cell membrane in both young and old OBs. Furthermore, the small tubules were continuous with the larger sER tubules in the distal clear area and cell process of the OBs. 5) Using TEM, long lysosomes, various cytosomes and multivesicular bodies (MVBs) were usually observed in the peripheral region and in the distal cytoplasm and major processes of the OBs. The present SEM and TEM studies indicated the MVBs were closely associated with sER tubules of the tubulo-vesicular elements. 6) Both TEM and SEM showed cytosegresomes containing laminated ER and other organelles particularly in the distal clear area of old OBs. 7) SEM also showed some thin lateral branchings of the OBs running along the fine matricial fibrils, as well as matrix-vesicle-like structures deeply invaginated at the basal portion of the cell processes and distributed in the predentine. The present morphological study demonstrated a three-dimensional configuration of the structures relating to secretory and absorptive functions of young and old OBs.

Animals↗

PubMed1994

FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity.

A novel antitumor bicyclic depsipeptide, FR901228, was isolated from a broth culture of Chromobacterium violaceum No. 968 as colorless prisms and the molecular formula was determined as C24H36N4O6S2. This antibiotic reverted the transformed morphology of a Ha-ras transformant to normal, and exhibited prominent antitumor activities against murine and human tumor cell lines both in vitro and in vivo.

3T3 Cells↗

PubMed1994

[Usefulness of twenty-four-hour home monitoring of oxygen saturation in patients with chronic obstructive pulmonary disease].

The clinical usefulness of 24 hr home monitoring of oxygen saturation (SaO2) with pulse oximeter was studied in 48 outpatients with COPD. In addition, doppler echocardiography for measurement of acceleration time (AcT), which inversely correlates with mean pulmonary arterial pressure, a 6-minute walk test, and an exercise study on a bicycle ergometer were performed in 26, 17, and 14 patients, respectively. Nadir SaO2 and the total time during which SaO2 was below 90% were calculated to estimate diurnal and nocturnal oxygen desaturation (diurnal nadir SaO2, diurnal TSaO2 < 90%, nocturnal nadir SaO2, and nocturnal TSaO2 < 90%). Relations between the indices of desaturation measured during home monitoring and dyspnea grade (Fletcher-Hugh-Jones), awake PaO2, AcT, Hb, Ht, and oxygen desaturation during the exercise tests were also studied. Diurnal nadir SaO2 was lowest and diurnal TSaO2 < 90% was longest in the group with dyspnea grade IV. In the other groups, various degrees of oxygen desaturation were observed, even within groups. Diurnal nadir SaO2 and nocturnal nadir SaO2 correlated with awake PaO2, but not with diurnal TSoO2 < 90%. Diurnal nadir SaO2 was similar to nadir SaO2 during the exercise tests. AcT, hemoglobin, and hematocrit correlated with diurnal oxygen desaturation but not with nocturnal oxygen desaturation. From the above findings, we conclude that pulmonary hypertension may be associated with diurnal oxygen desaturation, and that home monitoring of SaO2 is useful for the detection of oxygen desaturation not predicted from dyspnea grade and PaO2 while awake.

Aged↗

PubMed1994

[Nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome].

A successful nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome is reported. A 36-year-old woman developed a DeBakey type-I aortic dissection in October 1987. We replaced the ascending aorta and resuspended the aortic valve urgently, when she had not been diagnosed with Marfan's syndrome. In August 1989, we replaced the distal portion of the descending aorta and the infra-renal abdominal aorta because of dilatation in the diameter of these regions. In September 1990, she had sudden severe chest pain. Computed tomography and Doppler ultrasonography revealed that a new aortic dissection developed in the aortic arch and the descending aorta (three-channeled dissection) and that the new false lumen compressed the true and the old false lumens obstructing the blood flow to the abdominal aorta. She was immediately placed an axilo-femoral bypass, and in January 1991 she underwent the arch and descending aorta replacement using permanent bypass to the supra-aortic branches and partial extracorporeal circulation (first reported by Larmi et al). Postoperative course was satisfactory, and she has been well at 3 years after the operation. Because progressive dilatation of an untreated dissecting aorta is common in patients with Marfan's syndrome, aggressive replacement of the diseased aorta is indicated in these patients.

Adult↗

PubMed1994

Protection against natural killer cells by interferon-gamma treatment of K562 cells cannot be explained by augmented major histocompatibility complex class I expression.

Prior study has revealed that the expression of certain major histocompatibility complex (MHC) class I molecules on the membranes of normal or transformed cells can prevent natural killer (NK)-cell-mediated killing. This has been explained by either (1) the target interference model, or (2) the effector inhibition model. In both cases, MHC class I molecules are concerned but the precise mechanisms are still unclear. The erythroleukaemia K562 cell is known as a NK-sensitive target. This sensitivity has been explained mostly as being due to lack of MHC class I antigens on the K562 membrane. However, several recent studies have indicated that the expression of MHC class I antigens on the cell does not solely explain the protection against NK cells. To elucidate the mechanism of NK-cell-mediated killing, we investigated the killing profiles of the K562 cells by NK cells. Previous studies indicated that the NK-sensitive K562 cells can express some MHC class I antigens on their surface, and become protective against NK-cell killing after treatment with human interferon-gamma (hIFN-gamma). In the present study, we show that this resistance is not rendered by MHC class I expression, because addition of anti-MHC class I monoclonal antibodies (mAb) in the killing assay of hIFN-gamma-treated K562 cells, which express MHC class I antigens as the target, did not restore the sensitivity to NK cells. Moreover, we show that spontaneously occurring K562 clones which could not express MHC class I antigens even after hIFN-gamma treatment, could be protected after treatment with the cytokine. Taken together, these results strongly suggest that the susceptibility of K562 cells to NK cell killing is due to some elements distinct from those related to MHC class I antigens.

Antibodies, Monoclonal↗

PubMed1994

Anti-Ro/SS-A antibody-positive interstitial pneumonitis in a non-lupus patient.

We describe a 42-year-old anti-Ro/SS-A antibody positive non-lupus patient who developed interstitial pneumonitis in combination with several common clinical features with previously reported lupus pneumonitis patients whose anti-Ro/SS-A antibodies were positive, while whose antinuclear antibodies were negative. We consider that these patients may belong to a same new clinical entity. A variety of characteristic manifestations related to anti-Ro/SS-A antibodies has been reported in patients with systemic lupus erythematosus (SLE) and other connective tissue diseases [1] [2], and an association between these antibodies with pulmonary parenchymal involvement has been reported by Hedgpeth and Boulware in patients with SLE [3] [4]. We report here a 42-year-old non-lupus male patient with pulmonary fibrosis who presented with anti-Ro/SS-A antibodies.

Adult↗