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J Oyama

Publications and source records attributed to J Oyama.

At least 19 recordsLinked to original sources

Effects of paternal lymphocyte immunization on peripheral Th1/Th2 balance and TCR V beta and V gamma repertoire usage of patients with recurrent spontaneous abortions.

PROBLEM: The mechanism of immunotherapy for patients with recurrent spontaneous abortions is not well understood. In order to investigate the suppressor mechanism of paternal lymphocyte immunization, we examined peripheral blood lymphocyte subpopulations and the repertoire of T-cell receptor (TCR) gene segments. METHOD OF STUDY: Twelve patients with recurrent miscarriage were treated with immunization with paternal lymphocyte vaccinations three times during 12-14 weeks. Before and 2 weeks after the final inoculation, lymphocyte subsets and intra-cellular interferon (IFN)-gamma and/or interleukin (IL)-4 production were examined by flow cytometry. TCR V beta and V gamma repertoires were examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found no significant difference in CD4/CD8 ratios, prevalence of CD56+CD3+ or CD57+CD3+ cells (possible extrathymic T cells), gamma(delta)T cells, and CD5+ CD19+ (B-1) cells. However, by in vitro activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, peripheral CD4 cells demonstrated a significant decrease of IFN-gamma-producing T helper 1 (Th1) cells and an increase of IL-4-producing T helper 2 (Th2) cells after immunotherapy. Seven of nine patients who exhibited remarkable decreases in Th1/Th2 ratios became pregnant within 6 months after three courses of immunotherapy, and four women delivered healthy babies, while none of the three patients who exhibited an increased or unchanged Th1/Th2 ratio had full-term pregnancies (chi2 < 0.0001). Further, changes in usage of TCR V beta and V gamma gene segments were observed after immunotherapy in six patients examined. CONCLUSION: Our findings suggest a shift of Th1-dominant to Th2-dominant status by vaccination might play important roles in maintaining successful pregnancies. Induction of some T cells that utilize different TCR repertoires possibly suppresses maternal rejection reactions.

Abortion, Habitual↗

Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo.

OBJECTIVE: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. METHODS: Studies were performed in mongrel dogs, in which microspheres (MS, 15 microns in diameter) with and without interleukin-1 beta (IL-1 beta) were injected into the left main coronary artery (control and IL-1 beta group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. RESULTS: Immediately after the intracoronary injection of MS (10(6)/kg), LVEF equally decreased to approximately 30% in both the control and IL-1 beta group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1 beta group until day 7 (p < 0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg i.v.) and 1 and 2 days after IL-1 beta MS application (1 mg/kg i.v.) prevented the IL-1 beta-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1 beta group than in the control group at day 2 (p < 0.01), and OPC-6535 significantly suppressed the IL-1 beta-induced superoxide production (p < 0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1 beta but not in that with control MS. OPC-6535 abolished the IL-1 beta-induced formation of myocardial nitrotyrosine. CONCLUSION: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.

Analysis of Variance↗

Inhibition of adhesion molecules markedly ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo.

Adhesion molecules are key molecules for inflammatory cardiovascular diseases and are known to be up-regulated by inflammatory cytokines. However, the role of adhesion molecules in the cytokine-induced myocardial dysfunction in vivo remains unclear. This role was examined in our novel canine model, in which chronic treatment of the heart with IL-1 beta-bound microspheres (MS), but not control MS, causes sustained myocardial dysfunction in vivo. The expression of P-selectin (mRNA and immunoreactivity) was more prominent in the IL-1 beta group than in the control group (treated with control MS alone) after MS injection. The extent of neutrophil infiltration and myocardial myeloperoxidase (MPO) activity were significantly increased in the IL-1 beta group (P < 0.01). Pre-treatment with SLeX-OS (a novel oligosaccharide analog of sialyl LewisX) or PB1.3 (a monoclonal antibody to P-selectin) prevented the myocardial dysfunction and significantly suppressed the neutrophil infiltration and the increase in myocardial MPO activity induced by IL-1 beta (P < 0.01 each). These results indicate that adhesion molecules play an important role in the pathogenesis of the cytokine-induced sustained myocardial dysfunction in dogs in vivo.

Animals↗

Role of nitric oxide towards vasodilator effects of substance P and ATP in human forearm vessels.

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-L-arginine (4 or 8 mumol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of L-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-L-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of L-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Acetylcholine↗

L-arginine increases exercise-induced vasodilation of the forearm in patients with heart failure.

To determine whether L-arginine, a precursor of nitric oxide, can improve exercise-induced vasodilation of the forearm in patients with heart failure, we measured forearm blood flow in 9 patients with heart failure and in 7 age-matched control subjects before and after intra-arterial infusion of L-arginine. Resting forearm blood flow was significantly lower in patients with heart failure than in control subjects (2.34 +/- 0.85 (SD) vs 4.76 +/- 0.77 ml/min per 100 ml, p < 0.001). Endothelium-dependent vasodilation induced by acetylcholine was attenuated in patients with heart failure (p < 0.05). Exercise-induced vasodilation after handgrip exercise was significantly lower in patients with heart failure (p < 0.05). Intra-arterial infusion of L-arginine did not change basal forearm blood flow but significantly augmented acetylcholine-induced vasodilation in both patients with heart failure and control subjects (p < 0.05). Although L-arginine did not affect maximum forearm blood flow after handgrip exercise in control subjects (before, 26.2 +/- 13.5; after, 25.7 +/- 14.3; p = NS), it was increased in patients with heart failure (from 15.2 +/- 4.9 to 24.7 +/- 14.6, p < 0.01). The finding that L-arginine increased both acetylcholine- and exercise-induced vasodilation in patients with heart failure suggests that endothelial dysfunction might play an important role in impaired exercise-induced vasodilation in patients with heart failure.

Aged↗

[The prediction of the need for postoperative mechanical ventilation in patients with myasthenia gravis undergoing transsternal thymectomy].

During a sixteen-year period, 51 patients with myasthenia gravis underwent trans-sternal thymectomy including extended resection of the adipose tissue around thymus. Using the criteria of risk factors described by Leventhal and Kimura, a predictive score was assessed for our 51 patients. Leventhal's scoring system achieved an accuracy of 54.3%, a sensitivity of 20.0% and a specificity of 63.9%. And, Kimura's scoring system achieved an accuracy of 75.0%, a sensitivity of 81.8% and a specificity of 73.0%. From this study it was concluded that Kimura's scoring system is statistically more adaptive for Japanese than Leventhal's scoring system, and the Leventhal's accuracy may have increased by adding "bulbar symptoms" and "preoperative crisis" as other risk factors and by decreasing "points" for "duration of myasthenia" and "pyridoxamine dosage", and the "Kimura's " accuracy may have increased by decreasing "7 points" for preoperative crisis. Consequently, patients who received postoperative ventilation were compared with the group who did not, with respect to the 19 factors. Evidence is that Osserman's type, bulbar symptoms, preoperative crisis and preoperative % VC were influenced to require the postoperative ventilation, but sex, age, thymic histology, duration of myasthenia and pyridoxamine dosage were not any influenced to require the postoperative ventilation.

Adult↗

Isolation of Staphylococcus hyicus subsp. hyicus from pigs affected with exudative epidermitis and experimental infection of piglets with isolates.

Five strains of Staphylococcus hyicus subsp. hyicus were isolated: three strains (P-1, P-2 and P-3) from the crust on the body surface of 6-month-old pigs on a farm in Aomori prefecture, and two (P-5 and P-6) from both the crust on the body surface and the joint of a 1-month-old piglet with exudative epidermitis (EE) on another farm. The characterization of the isolates and the experimental infection of the piglets with strain P-1 were carried out. Subcutaneous inoculation with the bacterial suspension (10(10) CFU) produced EE to all nine piglets. Eight of them had exudation and exfoliation within 24 hr of infection. Histopathologically, disappearance of stratum corneum and necrosis with vacuolar degeneration of prickle cells were remarkable in the epidermis. Infiltration of neutrophils and lymphocytes were observed in the dermis. The results clearly indicate that S. hyicus is responsible for incrustation of the body surface of weanling pigs and exudative epidermitis in young piglets.

Animals↗

Thermoregulation in hypergravity-acclimated rats.

To determine the effect of hypergravity acclimation on thermoregulation, core temperature (Tc), tail temperature (Tt), and O2 consumption (VO2) were measured in control rats (raised at 1 G) and in rats acclimated to 2.1 G. When the animals were exposed to a low ambient temperature of 9 degrees C, concurrently with a hypergravic field of 2.1 G, Tc of rats raised at 1 G fell markedly by approximately 6 degrees C (to 30.8 +/- 0.6 degrees C) while that of the rats raised at 2.1 G remained relatively constant (falling only approximately 1 degree C to 36.4 +/- 0.3 degrees C). Thus prior acclimation to a 2.1-G field enabled rats to maintain Tc when cold exposed in a 2.1-G field. To maintain Tc, thermogenic mechanisms were successfully activated in the 2.1-G-acclimated rats as shown by measurements of VO2. In contrast, VO2 measurements showed that rats reared at 1 G and then cold exposed at 2.1 G did not activate thermogenic mechanisms sufficiently to prevent a fall in Tc. In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their Tc when exposed to a 5.8-G field or when exposed to prolonged cold exposure at 1 G. Results are interpreted as showing that when placed in a 2.1-G field, rats acclimated to 2.1 G can more closely maintain their Tc near 37 degrees C when cold exposed than can rats acclimated to 1 G. However, this enhanced regulatory ability of 2.1-G-acclimated rats over 1.0-G-acclimated rats is restricted to 2.1-G fields and is not observed in 1.0- and 5.8-G fields.

Adaptation, Physiological↗

Cardiac muscle ultrastructure and cyclic AMP reactions to altered gravity conditions.

Morphological and biochemical analyses of heart muscle of rats subjected to microgravity on Spacelab 3 (SL-3) flight and rats born and reared under increased gravity (1.7 G) conditions were compared with 1-G controls. Electronmicroscopic studies showed an increase in the number of lipid droplets and in areas of glycogen storage. Distribution changes of microtubules and cytoskeletal elements from both SL-3 and 1.7-G groups were observed. The high Km cyclic AMP phosphodiesterase activity was lower (P less than 0.05) in SL-3 heart muscle, and low Km activity was lower in 1.7-G males but was unaltered in females. Cyclic AMP-dependent protein kinase (cA-PK) activity was decreased in subcellular fractions of heart muscle of SL-3 animals. Recompartmentalization of cA-PK activity occurred in particulate tissue fraction of 1.7-G animals (70.3% of total for 1.7 G vs. 35.9% for controls). Phosphorylation of endogenous low-mobility proteins increased in SL-3 heart-soluble fractions. Photoaffinity labeling (18 h, 4 degrees C) decreased in type II cA-PK regulatory (R) subunits in both SL-3 and in 1.7-G male heart tissue particulate fractions. The 1.7-G female heart R subunit distribution did not differ from controls. These findings indicate that in heart muscle altered gravity conditions influenced physiological reactions similar to catecholamine-induced receptor-mediated hormonal responses.

Adenylyl Cyclases↗

Intrauterine fetal response to hypergravity by reduction of plasma prolactin levels in the rat.

Rats were conceived after adaptation to 3.14 g. Maternal and fetal plasma prolactin levels were reduced on day 22 of gestation in the rats exposed to hypergravity. The fact that fetuses in utero respond in the same way as their mothers indicates that they too are sensitive to hypergravity and that the bouyant condition of the fetus does not interfere with such external stimulus.

Animals↗

Increased gluconeogenesis in rats exposed to hyper-G stress.

The role of gluconeogenesis on the increase in plasma glucose and liver glycogen of rats exposed to hyper-G (radial acceleration) stress was determined. Overnight-fasted, male Sprague-Dawley rats (250-300 g) were injected i.p. with uniformly labeled 1 4C lactate, alanine, or glycerol (5 microCi/rat) and immediately exposed to 3.1G for 0.25, 0.50, and 1.0 hr. 1 4C incorporation of the labeled substrates into plasma glucose and liver glycogen was measured and compared to uncentrifuged control rats injected in a similar manner. Significant increases in 1 4C incorporation of all three labeled substrates into plasma glucose were observed in centrifuged rats at all exposure periods; 1 4C incorporation into liver glycogen was significantly increased only at 0.50 and 1.0 hr. The i.p. administration (5 mg/100-g body wt) of 5-methoxyindole-2-carboxylic acid, a potent gluconeogenesis inhibitor, prior to centrifugation blocked the increase in plasma glucose and liver glycogen during the first hour of centrifugation. The increase in plasma glucose and liver glycogen was also abolished in adreno-demedullated rats exposed to centrifugation for 1.0 hr. Propranolol, a beta-adrenergic blocker, suppressed the increase in plasma glucose of rats exposed to centrifugation for 0.25 hr. From the results of this study, it is concluded that the initial, rapid rise in plasma glucose as well as the increase in liver glycogen of rats exposed to hyper-G stress can be attributed to an increased rate of gluconeogenesis, and that epinephrine plays a dominant role during the early stages of exposure to centrifugation.

Adrenal Medulla↗

Hyper-G stress-induced hyperglycemia in rats mediated by glucoregulatory hormones.

Fasted male Sprague-Dawley rats, weighing 250-300 g, were exposed to 3.1 G for 0.25-24 h. During the first 24 h, there was a significant and sustained increase in plasma glucose, insulin, and glucagon. Plasma catecholamines showed significant increases only at 0.25 and 0.50 h, returning to control levels between 1.0-24 h; blood lactate paralleled the catecholamines' response. Plasma free glycerol showed a significant and sustained decrease during the first 24 h. Liver glycogen was significantly increased at 0.50 h, with progressively larger amounts accumulated as the exposure time was extended to 24 h. Diaphragm muscle glycogen was significantly decreased at 1.0 h, but showed a significant increase at 24 h. The isolated diaphragm muscle tissues from these rats were also studied in vitro to determine insulin effect on glucose uptake. Muscle tissues obtained from noncentrifuged controls and incubated with insulin (0.3 mU X ml-1) in the medium showed significant increases in glucose uptake; in contrast, muscle tissues from centrifuged rats showed no insulin effect on glucose uptake. It is concluded that the initial, rapid rise in blood glucose of rats exposed to hyper-G stress is mediated by increases in circulating catecholamines and glucagon, both potent stimulators of hepatic gluconeogenesis; and that the sustained hyperglycemia may be due in part to the inhibition of the insulin-stimulated uptake by muscle tissues.

Aerospace Medicine↗

Hypergravity induced prolactin surge in female rats.

Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study we found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats to HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

Animals↗

Effects of deceleration on the humoral antibody response in rats.

The purpose of this experiment was to determine the effects of hyper-gravity (hyper-G) followed by a return to normal gravity (deceleration) on the immune system of rats. Hyper-G was simulated by chronic centrifugation. Eighteen 35-d-old male rats were divided into three groups of six rats each. Two groups were exposed to 2.1 G and 3.1 G, respectively, for 28 d. The third group served as 1.0 G controls. Rats were removed from the centrifuge on day 29. All rats were immunized with sheep red blood cells (SRBC) on days 29, 42, and 57; rats were bled on days 36, 47, and 62. Hematocrits and anti-SRBC titers were determined each day the rats were bled. White blood cell (WBC) counts were determined on day 47. On day 63, all rats were sacrificed and organ:body mass ratios obtained for a number of organs. Centrifuged rats ate and gained significantly less. The organ:body mass ratios for the adrenal glands, kidneys, lungs, heart, and thymus were unaffected by deceleration. Although marginally significant (p less than 0.05) decreased organ:body mass ratios were found for the liver and spleen in the 3.1 G group, this effect may not be real, due to the small number of rats used. No significant differences were found in hematocrits, WBC counts, or anti-SRBC titers. These experiments indicate that deceleration does not adversely affect these particular aspects of the immune system. However, they do not preclude the possibility that other aspects of the immune system, such as interferon or complement, may be affected.

Acceleration↗

The unresponsiveness of the immune system of the rat to hypergravity.

The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

Adaptation, Physiological↗

Hypergravity effects on litter size, nursing activity, prolactin, TSH, T3, and T4 in the rat.

Hypergravity (HG) adapted rats were tested for mating ability, gestational time, fetal and newborn mortality, and nursing performances. Plasma and pituitary PRL and TSH and plasma T3 T4 were determined during 48 h peripartum. No difference was noticed in mating ability and gestation time. The number of fetuses was reduced in the HG rats (1 G- 12.9 +/- 0.5, 2.16 G-10.5 +/- 0.4, 3.14 G-9.4 +/- 0.5). None of the 3.14 G rats nursed their young, all of which were cannibalized. Of the 2.16 G rats, 50% nursed their pups, of which only half survived to weaning. The initial pituitary PRL of HG rats was lower than 1 G, but it increased postpartum, while the plasma PRL, which was very low, continued to decrease. Only postpartum was there a difference in plasma PRL between rats that previously nursed and those which did not nurse at 2.16 G. HG rats had lower T3 levels, indicating a hypermetabolic state during the peripartum, which worsened their normal relative hypothyroid state of pregnancy. Our conclusions are that exposure of pregnant rats to HG above 3 G has a lethal effect on the fetuses and newborns. Maternal PRL and T3 changes are possible reasons for this.

Adaptation, Physiological↗