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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 343 records · Page 19Linked to original sources
PubMed1993

Effect of GM-CSF on TNF-alpha and IL-1-beta production by alveolar macrophages and peripheral blood monocytes from patients with sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown origin characterized by activated T-lymphocytes and macrophages. Macrophage/monocyte-derived cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to be involved in the pathogenesis of sarcoidosis. Although the production of TNF-alpha and IL-1 by alveolar macrophages (AM) and peripheral monocytes (PM) in response to lipopolysaccharide (LPS) in sarcoidosis has been well demonstrated, the production of these cytokines in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) has not been delineated. The present studies were designed to examine the regulatory effect of GM-CSF on TNF-alpha and IL-1 beta production by AM and PM from patients with pulmonary sarcoidosis. Amounts of TNF-alpha and IL-1 beta in the culture supernatants of unstimulated AM from patients with sarcoidosis were significantly higher than those from normal subjects, whereas, there was no difference in the amounts of TNF-alpha and IL-1 beta in the culture supernatants of PM between patients with sarcoidosis and normal subjects. The amounts of TNF-alpha and IL-1 beta in the culture supernatants of GM-CSF or LPS-stimulated AM and PM were significantly higher than those of similarly stimulated AM and PM from normal subjects. This hyperresponsiveness of AM and PM to GM-CSF in patients with sarcoidosis might be relevant to the pathogenesis of sarcoidosis.

Adult↗
PubMed1993

Insulin-like growth factor I receptors in human cardiac myocytes and their relation to myocardial hypertrophy.

Specific binding sites for insulin-like growth factor I (IGF-I) and their expression during cardiac myocyte hypertrophy were studied by autoradiographic analysis of right ventricular biopsy specimens from patients with hypertrophic cardiomyopathy (9 cases), dilated cardiomyopathy (8 cases), and sick sinus syndrome (5 cases). Frozen specimens were cut into 5 microns-thick sections and thaw-mounted on albumin-coated slides. After incubation with [125I]IGF-I, with or without excess cold IGF-I, autoradiography was performed, and grains over myocytes were counted microscopically. Binding of [125I]IGF-I was inhibited in a dose-dependent manner by unlabeled IGF-I and competed for by IGF-I > IGF-II > insulin. The maximal grain density was higher in hypertrophic cardiomyopathy (186 +/- 47/1.8 x 10(-2) mm2) than in dilated cardiomyopathy (124 +/- 13/1.8 x 10(-2) mm2) or sick sinus syndrome (98 +/- 18/1.8 x 10(-2) mm2) (p < 0.01). There was a strong correlation between the maximal grain density and the diameter of right ventricular myocytes in hypertrophic cardiomyopathy (r = 0.83), but no similar correlation was observed in dilated cardiomyopathy or sick sinus syndrome. These data suggest that IGF-I receptors are present in adult human cardiac myocytes, and that IGF-I receptors are related to the development of myocyte hypertrophy in hypertrophic cardiomyopathy.

Adolescent↗
PubMed1993

Selective killing of murine leukemic cells by adenosine triphosphate (ATP): a study of the value of autologous bone marrow transplantation.

To assess the value of adenosine triphosphate (ATP) for ex vivo purging of leukemic cells in autologous bone marrow transplantation, its biological effects on the murine leukemic cell lines (WEHI3B and L1210) and normal murine bone marrow hemopoietic stem cells (CFU-C and CFU-S) were studied. After treatment with 4 mM of ATP for 6 h, the number of viable WEHI3B cells decreased to less than 0.1% of that of the control. Furthermore, 3H-thymidine incorporations were also completely inhibited in both WEHI3B cells and L1210 cells. These phenomena were related to the concentration and exposure period of ATP. Treatment of bone marrow mononuclear cells with ATP under the same condition reduced the number of CFU-C, day 9 CFU-S and day 12 CFU-S to only 58.5 +/- 8.7%, 92.6 +/- 8.2% and 83.5 +/- 28.5%, respectively, with no change in the number of marrow nucleated cells. Although the effect of ATP is not entirely specific to leukemic cells, these findings provide evidence that ATP is useful for purging residual tumor cells in autologous bone marrow transplantation.

Adenosine Triphosphate↗
PubMed1993

Genetics and obstructive sleep apnea syndrome: a study of human leukocyte antigen (HLA) typing.

To investigate the possible influence of genetics in subjects with obstructive sleep apnea syndrome (OSAS), HLA-A, B, C, and DR antigens were studied in 32 Japanese subjects with OSAS. The frequency of HLA-A2 antigen was markedly increased in the patients with OSAS compared with normal controls (81.3% vs 40.6%) and compared with the Japanese population (40.7%), Pc < 0.035 and Pc < 0.007, respectively. HLA-B39 was found more frequently in OSAS patients than in the Japanese population (Pc < 0.018), but not in the controls. No significant deviation was observed in the frequencies of HLA-C and DR antigens between the OSAS patients and the controls. We conclude that genetics is important in the development of OSAS.

Adult↗
PubMed1993

[The role of G-CSF in host defense mechanisms of the elderly].

It has been generally agreed that the elderly had a greater susceptibility, morbidity, and mortality in regard to a variety of bacterial infections. To clarify the host defence mechanism in the elderly, we studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil functions, the production of G-CSF by peripheral blood monocytes in response to lipopolysaccharide (LPS) and the serum levels of G-CSF in patients with bacterial pneumonia. There was no significant difference in the phagocytic activity of neutrophils between the elderly and control young adults. rhG-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both group. Killing activity of neutrophils assessed by the new nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment with rhG-CSF resulted in an increase of killing activity in the elderly, raising their response to a level compatible to that of young adults pretreated with rhG-CSF. The amount of G-CSF in the culture supernatants from LPS-stimulated peripheral blood monocytes of the elderly was significantly lower than that of young adults (p < 0.05). The serum levels of G-CSF in the acute phase of bacterial pneumonia in the elderly were significantly lower than those of young adults (p < 0.01). These results indicated that impaired monocyte function may contribute, at least in part, to susceptibility to bacterial infection in the elderly.

Adult↗
PubMed1993

[Cerebral and testicular myeloblastoma formation in relapsing acute myeloid leukemia (M1) with t(8;21)].

This paper reports a relapsed case of acute myeloid leukemia with intracranial, testicular and intestinal tumor formation. A-56-year-old male, diagnosed as M1 on September, 1988, entered complete remission on October 14, 1988, aided by JAL-SG and AML-85 regimen. Blast cells with Auer rods demonstrated 8;21 translocation lacking 11q with 30 of 30 analyzed bone marrow cells, and the following antigen pattern: CD5+, CD19+, CD33+, CD56+, HLA-DR+. After 4 courses of post remission therapy, the maintenance therapy was discontinued because of his liver dysfunction. He was discharged on May, 1989, and was seen as an out patient. He complained of left hemiplegia and was re-admitted on September 30, 1989. Though the bone marrow was in complete remission on September 4th, CT scan and MRI demonstrated intracranial tumor formation. Bone marrow relapse occurred on October 27th, eventually resulting in his death on November 18th. Autopsy showed intracranial, testicular and intestinal tumor formation and blast cell invasion into the liver, spleen and kidneys. We analyzed the characteristics of 14 cases with intracranial tumor formation previously reported. The focal neurological symptoms reflecting the intracranial tumor mass effect were considered to be important initial signs. CT scan was a useful tool for diagnosis. The average age of the 14 cases was 38, 9 and the male/female ratio was 9:5. Six of 9 cases, diagnosed by FAB classification, were M2 and one of the 6 cases in whom chromosomes of blast cells were examined had t(8;21). Though irradiation seemed effective for the reduction of tumor mass, the patients' prognosis was poor.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1993

[A "retinoic acid syndrome" observed in two cases of acute promyelocytic leukemia].

Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents. Her symptoms continued for 44 days and complete remission was achieved 53 days after commencing ATRA therapy. The second case was a previously untreated 46-year-old male. His case had been diagnosed as adult respiratory distress syndrome and he had been treated with prednisolone. His symptoms rapidly improved and complete remission was achieved 38 days after the ATRA therapy. This was the first report of patients in Japan considered to have developed "retinoic acid syndrome (RAS)". In our five APL cases treated with ATRA, the syndrome was not always accompanied by peripheral blood leukocytosis even though the two cases with RAS showed higher leukocyte counts than the other two cases without RAS and also had DIC. We should pay attention to the severe respiratory symptoms that develop in APL patients after ATRA treatment and immediate steroid therapy is required for such patients.

Adult↗
PubMed1993

[Improvement of biventricular heart failure in a case of obstructive sleep apnea syndrome by nasal CPAP therapy].

A 42-year-old male patient with obstructive sleep apnea syndrome (OSAS) suffering from biventricular heart failure is reported. He had been treated for OSAS with conventional therapy. However, he complained of severe dyspnea in association with extreme weight gain and general edema. Therefore, he was admitted to our department. He weighed 168 kg on admission, and marked edema was observed. Chest film revealed significant dilatation of the cardiac silhouette and pleural effusion. PaO2 was 37 mmHg and PaCO2 was 66 mmHg. Polysomnography showed an apnea index of 58.3 and severe oxygen desaturation during sleep. Right heart catheterization showed elevation of mean pulmonary artery pressure mPAP: 55 mmHg) and pulmonary capillary wedge pressure (Pcwp: 33 mmHg) suggesting biventricular heart failure. Digitalization and diuretic therapy were immediately initiated. In addition, nasal CPAP was applied to this patient during sleep, and sleep apnea and oxygen desaturation were almost completely reversed. Significant diuresis was observed, and blood gas data and sleep disturbance were improved. Fifty-nine days after admission, his weight had decreased to 96 kg, and mPAP and Pcwp decreased to 32 and 23 mmHg, respectively. This case demonstrates that nasal CPA is an effective tool for the treatment severe OSAS patients.

Adult↗
PubMed1993

Elevation of soluble IL-2 receptor and IL-4, and nonelevation of IFN-gamma in sera from patients with allergic asthma.

To determine whether the predominant in vivo activation of Th1 subset or Th2 subset in peripheral blood occurs in patients with allergic asthma, we measured serum levels of Th1 cell-derived interferon-gamma (IFN-gamma) and Th2 cell-derived interleukin-4 (IL-4). In addition, serum levels of soluble interleukin-2 receptor (sIL-2R) released from activated T cells were measured to determine a potential source of these cytokines. The elevation of serum IL-4 levels and nonelevation of serum IFN-gamma levels were observed in patients with allergic asthma compared with normal control subjects. A significant correlation between serum IL-4 levels and serum sIL-2R levels was observed in these patients. These results suggest that there is allergen-induced in vivo activation of Th2-like cells in peripheral blood of patients with allergic asthma.

Adult↗
PubMed1993

[Traffic accidents in obstructive sleep apnea patients and effect of nasal CPAP treatment].

We studied the traffic accident rates and daytime sleepiness in obstructive sleep apnea syndrome (OSAS) patient, and evaluated the effectiveness of long-term nasal CPAP treatment. Traffic accidents were observed in 42% of 14 male OSAS patients (46 +/- 7 years old) and near-miss accidents were also observed in 64% during the past three years. Stanford Sleepiness Scale showed 4.7 +/- 1.0, suggesting marked excessive daytime sleepiness (EDS). During NCPAP treatment for 11 +/- 9 months, no traffic and near-miss accidents were reported. After NCPAP treatment, SSS decreased to 2.0 +/- 0.8, and the score of Uchida-Kraeplin test for the evaluation of working ability increased significantly. These results suggest the improvement of EDS and working ability following NCPAP treatment. We conclude that OSAS patients have the tendency of daytime sleepiness and high traffic accidents rates, and NCPAP treatment is effective to improve such problems.

Accidents, Traffic↗
PubMed1993

[Effects of high doses of beclomethasone dipropionate in bronchial asthma].

To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.

Adult↗
PubMed1993

[Influence of airway temperature and humidity of hyperventilation induced bronchoconstriction in rabbits].

It has been suggested that humidity and temperature of inspired air is important in determining the severity of hyperventilation induced bronchoconstriction (HIB). To investigate whether water loss or heat loss from airway plays more important role to induce HIB, we compared the effect of temperature and humidity of inspired air on HIB, in sensitized and non-sensitized rabbits. Inspired air containing 5% CO2 was conditioned to dry or humidified and to temperature of 9 degrees C or 25 degrees C during isocapnic hyperventilation. In sensitized rabbits, marked bronchoconstriction was observed when inspired air dry regardless of temperature. We conclude that 1) HIB is produced in sensitized rabbits and 2) humidity rather than temperature of inspired air is more important to induce HIB.

Animals↗
PubMed1993

[Effect of surfactant on mouse alveolar macrophage cytotoxicity].

Surfactant has been shown to have several immunologic activities in addition to its property of lowering tension. To investigate the effect of surfactant on alveolar macrophage cytotoxicity against tumor cells, we compared the cytolytic activity, tumor necrosis factor (TNF) activity and L-arginine-dependent NO2- production of mouse alveolar macrophages in the presence of surfactant with those of alveolar macrophages alone. Furthermore, we measured the concentrations of inositol-1,4,5, triphosphate (IP3) and diacylglycerol (DG) both of which are second messengers of intracellular signals. Cytolysis, TNF activity and NO2- production were enhanced by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). This enhancement was further increased by addition of surfactant. The surfactant did not enhance the concentration of IP3, but enhanced that of DG in alveolar macrophages activated by LPS or IFN-gamma. These data suggest that surfactant upregulated the enhancement of alveolar macrophage cytotoxicity by LPS and IFN-gamma, and this effect was related to an increase in the concentration of DG in activated alveolar macrophages.

Animals↗
PubMed1993

[Enhanced generation of leukotriene B4 by neutrophils stimulated by calcium ionophore A23187 after adding prostaglandins].

To investigate the interaction of arachidonic acid metabolites, we examined the production of LTB4 in neutrophils after stimulation with PGE2, PGF2 alpha and TXB2. The subjects were 23 asthmatic patients (atopic: 11, non-atopic: 12), 7 non-asthmatic atopic patients and 5 healthy controls. The production of LTB4 in neutrophils induced by calcium ionophore A23187 significantly increased in the asthmatic and non-asthmatic atopic patients. Healthy controls showed no significant increase in production of LTB4. The optimal levels of TXB2, PGF2 alpha, and PGE2 for LTB4 production were 10 ng/ml, 10 ng/ml and 0.1 ng/ml, respectively. When no TXB2, PGF2 alpha and PGE2 were added, LTB4 production tended to be greater in the asthmatics and non-asthmatic atopic patients than in the controls. By the addition of 10 ng/ml of TXB2, 10 ng/ml of PGF2 alpha, or 0.1 ng/ml PGE2, production of LTB4 by calcium ionophore A23187 stimulation was significantly increased in the asthmatics, and there was no such trend in the non-asthmatic group. These results suggest that LTB4 production from neutrophils may be enhanced by TXB2, PGF2 alpha and PGE2.

Adult↗
PubMed1993

Purification from liver microsomes from untreated cynomolgus monkeys of cytochrome P450 closely related to human cytochrome P450 2B6.

A cytochrome P450 (P450) (referred to as P450CMLa) was purified and characterized from hepatic microsomes from untreated cynomolgus monkeys (Macaca irus). The final preparation was electrophoretically homogeneous and its estimated minimum molecular mass was 49.5 kDa. The amino-terminal amino acid sequence of the protein (first 34 residues) closely resembled that of the protein encoded by the 2B6 cDNA from humans (94%). This protein was cross-reactive with antibodies raised against P450 2B1 (P450 b), P450 2B11 (P450 PBD-2), and P450GP-1, which were purified from hepatic microsomes from phenobarbital-pretreated rats, beagle dogs, and guinea pigs, respectively. Also, the antibody raised against P450CMLa was able to cross-react with P450 2B1, P450 2B11, and P450GP-1. P450CMLa was capable of catalyzing benzphetamine N-demethylation and testosterone 16 beta-hydroxylation in a reconstituted system. Anti-P450CMLa antibody inhibited the activity of testosterone 16 beta-hydroxylase but not the activities of testosterone 2 beta- and 6 beta-hydroxylases in liver microsomes from cynomolgus monkeys. The content of P450CMLa, as estimated by immunoblot analysis, was 70 pmol/mg (about 5% of total P450). The protein immunoreactive with the anti-P450CMLa antibody was also present in liver microsomes from Japanese monkeys, baboons, common marmosets, and common squirrel monkeys. In liver microsomes from common squirrel monkeys, the content of protein immunoreactive with the anti-P450CMLa antibody and the activity of testosterone 16 beta-hydroxylase were effectively increased by pretreatment with phenobarbital. The antibody against P450CMLa strongly inhibited the activity of testosterone 16 beta-hydroxylase in liver microsomes not only from untreated cynomolgus monkeys but also from phenobarbital- and pregnenolone 16 alpha-carbonitrile-pretreated common squirrel monkeys. These results indicated that the P450CMLa purified here is very similar to the forms of P450 classified into the 2B subfamily, in its amino-terminal amino acid sequence, catalytic activities, and immunochemical properties.

Amino Acid Sequence↗