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Biomedical subjects

H Nagata

Publications and source records attributed to H Nagata.

At least 19 recordsLinked to original sources
PubMed1992

Inhibitory effect of noradrenaline on acute liver injury induced by carbon tetrachloride in the rat.

The effect of exogenous noradrenaline (NA) on acute liver injury was investigated in rats receiving a single dose of carbon tetrachloride (CCl4). Animals were divided into the following groups: (I) no treatment, used for plasma catecholamine assay; (II) received CCl4 only; (III) treated with CCl4 plus noradrenaline (NA). Plasma levels of catecholamine (CA) were elevated in both groups II and III, particularly in NA: average value at 33 h after the exposure of CCl4 increased to 290-fold of the control in group II and to 513-fold in group III. Subsequently, the levels of NA decreased with time, and were comparatively well-preserved in the rats of group III. Hepatic changes observed in the animals of group II were as follows: destruction with reduced number in rough endoplasmic reticulum; destruction and disappearance of cristae in mitochondria, and numerous fat droplets (shown by electron microscopy); histologically observed marked centrilobular necrosis with steatosis followed by progression with time; and microangiographically demonstrated deranged intrahepatic microvasculature. By contrast, these changes were successfully prevented by NA treatment (group III). Furthermore, histologically observed centrilobular change was restored with time. It was concluded that, in a deranged state, NA takes a form quite dissimilar to ordinary state: Na exerts for hapatoprotective and is highly involved in liver injury.

Animals↗
PubMed1992

Effects of injected antibody against the platelet glycoprotein IIb/IIIa complex on monkey platelet fibrinogen.

Four monkeys were injected for a 10-day period with the Fab fragment of a murine monoclonal antibody (NNKY 1-32) which inhibits the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa complex. Platelet fibrinogen levels were assessed quantitatively by electroimmunoassay and qualitatively by immunoelectron microscopy. The platelet fibrinogen level fell to 9.0 +/- 2.8% of the control level after antibody administration. Immunoelectron microscopy showed that the injected antibody was localized on the inner surface of the platelet alpha-granule membrane. Our findings suggest that the GP IIb/IIIa complex can be internalized by alpha-granules and that it may mediate the endocytosis of plasma fibrinogen by platelets.

Animals↗
PubMed1992

Effects of ticlopidine on monoclonal anti-CD9 antibody-induced platelet aggregation and microparticle generation.

We analyzed the effects of ticlopidine on platelet aggregation and on microparticle (MP) formation when platelets were exposed to a monoclonal anti-CD9 antibody (NNKY1-19) in vitro. Even when NNKY1-19-induced platelet aggregation was completely inhibited by preincubation with anti-GPIIb/IIIa antibody or Arg-Gly-Asp-Ser, or by using washed platelets from a Glanzmann's thrombasthenia patient, the formation of MP was still observed. Prostaglandin E1 and protein kinase C antagonists (H-7 and staurosporine) inhibited both NNKY1-19-induced aggregation and MP formation. Ticlopidine or aspirin plus apyrase scarcely affected NNKY1-19-induced platelet aggregation, except to prolong the lag time. However, ticlopidine significantly inhibited MP formation (p less than 0.01). These results suggest that ticlopidine inhibits NNKY1-19-induced MP formation by a different mechanism to that of the other antagonists, and that this mechanism is unrelated to the inhibition of platelet aggregation.

Adenosine Triphosphate↗
PubMed1992

Differences between platelet and microparticle glycoprotein IIb/IIIa.

Glycoprotein (GP) IIb and IIIa are major constituents of the platelet membrane which are involved in forming the fibrinogen receptor on activated platelets. We used flow cytometry to study the effects of ethylene-diamine tetraacetic acid (EDTA) on the membrane GPIIb/IIIa complexes of platelets and microparticles, and to study the effects of cations on dissociated GP complexes. Microparticles were detected by both the volume signal and by fluorescence using an FITC-conjugated anti-GPIb antibody (NNKY5-5). When platelets were stimulated with ADP, calcium ionophore A23187, or thrombin, fibrinogen binding to the platelet surface increased markedly. However, fibrinogen binding to microparticles showed little increase in response to such agonists. Microparticle GPIIb/IIIa complexes were dissociated by incubation with EDTA at 37 degrees C but did not reassociate after treatment with divalent cations (Ca2+, Mg2+, and Mn2+) in contrast to platelet GPIIb/IIIa complexes. These results suggest that some interaction of GPIIb/IIIa and linked structures like the platelet cytoskeleton may be involved in the reassociation of dissociated GPIIb and GPIIIa, perhaps explaining the failure of reassociation of microparticle GPIIb/IIIa (i.e., the fibrinogen binding to microparticles).

Adenosine Diphosphate↗
PubMed1992

Rapid axonal transport velocity is reduced in experimental ethylene oxide neuropathy.

Chronic exposure of rats to ethylene oxide (EO) causes distal axonal neuropathy of lumbosacral primary sensory neurons. To study the pathogenesis of this neuropathy, we measured rapid axonal transport in peripheral nerves. Rats were exposed for 6 h to 500 ppm EO in a chamber three times a wk for 15 wk. Rapid axonal transport and quantitative histological alterations of peripheral nerves were studied. After [35S]methionine injection into the dorsal root ganglion, the velocity of rapid anterograde axonal transport of radioisotope-labeled protein was measured. The velocity in the rats exposed to EO was 33% less than that in control rats exposed to filtered room air. However, histological differences were slight. Morphometric studies showed that in EO-exposed rats, only the distal portions of the sural nerve had significantly greater incidental degeneration of myelinated fibers than did controls. There were significantly fewer large myelinated fibers only in the distals peroneal nerve. Therefore, a decrease in the velocity of anterograde axonal transport, related to these slight histological abnormalities of the peripheral nerve, may play a causative role in the development of the distal axonal neuropathy owing to chronic EO exposure.

Animals↗
PubMed1992

CA-125 in menstrual discharge in patients with chronic pelvic pain.

CA-125 levels in menstrual discharge were determined in 55 patients with chronic pelvic pain to evaluate whether this test would be useful in differentiating between pelvic pain due to endometriosis and other causes. Of the 28 women with endometriosis, 25 (89%) had CA-125 concentration greater than or equal to 72,000 units/ml. The frequencies of elevated levels in Stage I, Stage II and Stages III/IV were 85.7, 85.7 and 92.8%, respectively. When used for the detection of endometriosis, the test had a sensitivity of 89.3% and a specificity of 96.3%. These results suggest that CA-125 in menstrual discharge may be helpful in the evaluation of women with chronic pelvic pain.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Role of platelet activating factor on the fibrinolytic activation in the pathogenesis of gastric mucosal damage induced by endothelin-1.

We have examined the hypothesis that the release of tissue type plasminogen activator may play a prominent role in endothelin induced gastric mucosal injury. We determined tissue type plasminogen activator activity in the regional blood sample and the concentration of platelet activating factor in the gastric mucosa after the administration of endothelin-1 in a range of 50-500 pmol/kg into the left gastric artery of male Wistar rats. Endothelin-1 increased the tissue type plasminogen activator release and platelet activating factor formation, and induced subsequent gastric mucosal haemorrhagic change in a dose dependent manner. In addition CV-6209, a selective platelet activating factor blocker, attenuated the activation of regional tissue type plasminogen activator and the development of mucosal damage induced by endothelin-1. The results of this study showed that tissue type plasminogen activator activation may play an important role in the pathogenesis of endothelin induced mucosal injury of rat stomach, and suggest that the platelet activating factor may be involved in the process of regional fibrinolytic activation induced by endothelin-1.

Animals↗
PubMed1992

Intestinal microcirculatory changes during fat absorption and the effect of cholecystokinin inhibitor.

The major objective of this study was to estimate how microvascular changes occur in the intestinal segment in relation to fat absorption and also to assess the role played by cholecystokinin (CCK) in fat-induced intestinal hyperemia. A 12-cm loop of rat middle small intestine was exposed to a 120-min infusion of oleic acid micelle solution containing [14C]oleic acid. Time-course changes of vascular diameter and red blood cell (RBC) velocity of submucosal arterioles, venules, and periglandular and muscular capillaries were determined simultaneously in their different order of branching by using intravital microscopy equipped with a high-speed video camera system. Lymphatic transport of oleic acid was also monitored by collecting lymph from intestinal lymphatics. The instillation of micelle produced significant dilatation of submucosal arterioles and venules and significant increase in RBC velocity in submucosal microvessels and periglandular capillaries at 15 to 30 min after the fat instillation. This corresponds well to the appearance of [14C]oleic acid in intestinal lymph. This microvascular dilatation and RBC velocity increase continued throughout the exposure to fat and started to attenuate 30 min after restoration to saline infusion. There was also heterogeneity in microvascular responses among different orders of branches to fat administration, and RBC velocity increase was not observed in muscular capillaries. Local intra-arterial infusion of CCK inhibitor, loxiglumide (CR 1505, 10 mg.kg-1.h-1), significantly attenuated both fat-induced microvascular dilatation and RBC velocity increase but not the fat absorptive function. Our results indicate that CCK plays a significant role in intestinal hyperemia induced by fat absorption. However, CCK-mediated intestinal microvascular change was not a prerequisite for fat absorption.

Animals↗
PubMed1992

Lymph follicles and germinal centers in popliteal lymph nodes and other lymphoid tissues of germ-free and conventional rats.

A study was conducted to evaluate the influence of natural exogenous antigen stimulation on the development of lymph follicles in the peripheral lymphoid organs of the rat. The number of lymph follicles and germinal centers per popliteal node as well as the morphological features of popliteal nodes, mesenteric nodes and Peyer's patches were compared between 8-week-old male Sprague-Dawley rats reared in germ-free, specific pathogen-free (SPF) and conventional environments. In mesenteric nodes and Peyer's patches from conventional and SPF rats, almost every follicle contained a germinal center. In the mesenteric nodes from germ-free rats, only 9 of 195 lymph follicles examined contained a germinal center, but interestingly, in Peyer's patches all the lymph follicles examined showed a fairly well developed germinal center. The popliteal nodes from germ-free rats had no germinal centers and each node contained about 80 lymph follicles. In six conventional rats and two of five SPF rats used, the number of lymph follicles per popliteal node usually ranged from 100 to 130, and some lymph follicles contained a germinal center. However, in the other three SPF rats the popliteal node on both sides showed no germinal center, and each contained almost the same number of lymph follicles as the popliteal nodes of other SPF and conventional rats. The present results are consistent with the view that even in the absence of exogenous antigen stimulation, a regional lymph node of the germ-free rat develops a substantial number of primary lymph follicles by way of a non-immunological cellular activity, and that natural exogenous antigens may influence the development of lymph follicles by stimulating the cellular activity rather than evoking the humoral immune responses.

Animals↗
PubMed1992

How blood viscosity influences changes in circulation during pregnancy?

The changes of whole blood viscosity and plasma viscosity were studied in 15 normal non-pregnant women, and 120 normal pregnant women ranging from 8 to 39 weeks of gestation. The values of whole blood viscosity during normal pregnancy were significantly lower from 20 to 31 weeks of gestation than those in the other periods of gestation, and there was a positive correlation between whole blood viscosity and hematocrit. Plasma viscosity, however, did not change significantly during pregnancy. There was no correlation between whole blood viscosity and plasma viscosity, and there was also no correlation between plasma viscosity and plasma fibrinogen concentration. These findings suggest that decreases in whole blood viscosity, resulting from the change of packed-cell volume, may strongly contribute hemorheologically to the decrease in peripheral resistance during the second trimester.

Blood Circulation↗
PubMed1992

[Investigation of the incidence of aberration in various indication for prenatal cytogenetic analysis].

In order to evaluate the role of prenatal cytogenetic analysis for the management of pregnant women, we studied the incidence of chromosomal aberration in 1,258 cases. In 502 cases with advanced maternal age (at least 35 years older), 12 (2.4%) cases of chromosome aberration were detected. The incidence of chromosomal aberration in the cases with women who had a previous child with chromosome aberration, women who had given birth to a congenital malformation child, and women who had ultrasonographic abnormalities were 3.0% (8/271), 0% (0/103) and 11.7% (36/307), respectively. Of cases with advanced maternal age, the incidence of chromosome aberration is 0% (0/21) at age 35, 0% (0/22) at age 36, 19% (1/52) at age 37, 2.2% (2/92) at age 38, 10% (1/102) at age 39, 1.3% (1/75) at age 40, 5.3% (3/56) at age 41, 6.9% (3/43) at age 42, 4.4% (1/23) at age 43 and 6.7% (1/15) at age 44. These results indicate that the incidence of chromosome aberration increases with maternal age. On the basis of these data, we recommend medical practice to offer prenatal diagnosis to all women who will be 37 or older. In the cases of fetal anomaly, they were diagnosed by ultrasonographic examination, the high incidence of chromosome aberration was detected in comparison with another group. Therefore, the prenatal cytogenetical analysis may also be performed in these cases.

Adult↗
PubMed1992

[Effects of food intake, dietary habits and life style on health status as determined by clinical blood tests of adult men].

A survey of the frequency of various kinds of foods, dietary habits, life style, and health status was performed on 2,049 men aged from 40 to 59 living in an urban area who were participants in a "human dock" medical checkup. The relationships between these factors and health status were studied in order to identify a particular life style associated with good health status. The instrument utilized in this survey was a special form of a structured questionnaire. The results are summarized below. 1. The frequency of various kinds of foods were correlated with the kind of breakfast eaten, dietary habits, physical exercise habits, daily physical activity, smoking, and occupation. The strongest correlation to frequency of various kinds of foods was found to be with the kind of breakfast eaten and dietary habits. 2. Dietary habits were also correlated to various aspects of life style: smoking, drinking, the frequency of various kinds of foods, kind of breakfast eaten, daily physical activity, sleeping hours, habits related to physical exercise, and the frequency of meals eaten away from home. Dietary habits correlated most closely with the frequency of various kinds of foods and daily physical activity. The frequency of various kinds of food and dietary habits were found to correlate with various aspects of life style, and those subjects with good overall life styles were also found to have desirable dietary life styles. The correlation of desirable dietary habits, food intake and a suitable life style with good health status was confirmed by the results of clinical blood tests used as an index of health status.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Chemical Analysis↗
PubMed1991

Microparticle generation during in vitro platelet activation by anti-CD9 murine monoclonal antibodies.

We used flow cytometry and two anti-CD9 murine monoclonal antibodies (NNKY1-19, MALL13) to investigate the glycoprotein composition and the potential functions of microparticles (MP) released by platelets exposed to these antibodies in vitro. NNKY1-19 produced aggregation with characteristics similar to those noted in previous reports. The action of MALL13 on platelets in platelet-rich plasma (PRP), however, differs from that of other anti-CD9 antibodies. The normal fluctuation in the MALL13-induced change in optical density disappeared when complement was present. MALL13-induced effect for platelet in PRP was not inhibited by preincubation with monoclonal anti-GPIIb/IIIa antibody, but was inhibited in washed platelets (WP). Furthermore, following MALL13 stimulation in PRP platelets, the amount of buffer LDH markedly increased and electron microscopy findings showed vacuoles appearing inside the platelets. These results suggest that MALL13 has at least two effects on platelets that differ for PRP platelets and WP. The number of MP released was increased by the addition of anti-CD9 antibodies. MP surfaces were found to be rich in CD9 protein. MALL13 stimulation lead to a significant increase in the binding of C1q and C3 to platelets and caused the production of MP to occur more rapidly than it did the exposure of fibrinogen binding sites in the presence of complement. The analysis of the relationship of MP to anti-CD9 monoclonal antibody may be useful in the investigation of the relationship between platelet function and coagulation regulation.

Antibodies, Monoclonal↗
PubMed1991

Involvement of superoxide anion and platelet-activating factor in increased tissue-type plasminogen activator during rat gastric microvascular damages.

The role of tissue-type plasminogen activator (t-PA) was investigated in the gastric ulcer formation induced by microvascular derangement. The rat stomach was exposed and repeated electrical stimuli (irritation) were applied on the small arterial wall close to the lesser curvature to induce mucosal ischemia followed by hyperemia. The t-PA activity in the regional blood of the stomach was significantly elevated as early as 5 min after the irritation. Immunohistochemical study using anti-t-PA monoclonal antibody revealed that t-PA was detectable in the endothelial cells of capillaries and collecting venules, suggesting the involvement of endothelium-mediated fibrinolytic activity in the irritation-induced ulcer formation. Pretreatment of SOD or allopurinol significantly attenuated the irritation-induced t-PA activation, suggesting that the t-PA activity was modulated by xanthine oxidase-associated superoxide anions. CV-6209, a selective antagonist of platelet-activating factor (PAF), also prevented the activation of t-PA as well as ulcer formation, providing a concept that PAF may be associated with the local fibrinolytic activation which may cause hemorrhagic changes in the gastric mucosal microvasculature. The present study supports the hypothesis that increased t-PA activity may reflect the microvascular endothelial damages caused by vasomotor derangement and suggests that oxygen-derived free radicals may participate in the regulation of endothelium-derived fibrinolytic activities in the mucosal microvasculature.

Animals↗
PubMed1991

Antiplatelet autoantibody-related microparticles in patients with idiopathic (autoimmune) thrombocytopenic purpura.

We used flow cytometry to detect antiplatelet antibody-related microparticles (MP) in 56 patients with idiopathic thrombocytopenic purpura (ITP). We measured MP in platelets following various types of stimulation in two experimental systems. In one system washed platelets were incubated with normal serum which included the complement system, and in the other, washed platelets were incubated with Tyrode's buffer. There were no differences between the two measurement systems in the degree of increase in MP using various agonists. An increase in MP using ITP plasma was found in 12 out of 56 patients. In particular, four patients showed a significant increase in MP in washed platelets (WP) plus serum. Furthermore, the increase in platelet-associated IgM (PAIgM) was significant in these patients. There was also a definite positive correlation between PAIgM and the percentage of MP of WP plus serum. On the other hand, no specificity for MP formation with anti-GPIIb/IIIa or anti-GPIb autoantibodies was observed. IgM antibody-related MP appear to exist in some patients with ITP.

Adolescent↗
PubMed1991

Involvement of platelet-activating factor in endothelin-induced vascular smooth muscle cell contraction.

This study was designed to elucidate the participation of platelet-activating factor (PAF) in endothelin-induced vascular constriction in vivo and in vitro. The microvascular hemodynamic changes in rat mesentery induced by the superfusion of endothelin-1 (ET-1) were visualized through an intravital microscopic system. It was revealed in vivo that ET-1 in a range of 100 fM-10 pM caused a sustained arteriolar constriction in a dose-dependent manner. Pretreatment with CV-6209, a selective PAF antagonist, significantly attenuated the constrictive change in arterioles. Changes of intracellular Ca2+ mobilization after treatment with ET-1 were investigated in vitro using a cell line (A-10 cell) derived from rat arterial smooth muscle cells. ET-1 caused a prompt rise in the fura-2-associated fluorescence intensity in the individual A-10 cell and it fell to a lower plateau level that was still higher than the baseline value. CV-6209-pretreated cells did not show the rapid-phase mobilization of Ca2+, but showed the slow late phase of Ca2+ activation. The present study demonstrates that PAF may be involved in endothelin-induced microvascular constriction by mediating the mobilization of Ca2+ in vascular smooth muscle cells.

Animals↗
PubMed1991

Synergistic action in platelet activation induced by an antiplatelet autoantibody in ITP.

We detected an autoantibody which activated normal platelets in a patient with immune thrombocytopenic purpura and investigated the mechanism by which this autoantibody mediated platelet activation. The patient's IgG induced platelet aggregation and ATP secretion in normal platelet-rich plasma (PRP). IgG-induced aggregation was inhibited by aspirin (ASA), apyrase, a protein kinase C (PKC) inhibitor and two anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibodies. The increase of aequorin-detected intraplatelet Ca2+ induced by the patient's IgG was extremely slight. Phosphorylation of a 40 kDa protein was induced by the patient's IgG without any obvious phosphorylation of a 20 kDa protein, and was inhibited by a PKC inhibitor but not by ASA. With ASA-treated normal PRP, the patient's IgG failed to induce aggregation itself, but enhanced ADP- or STA2-induced aggregation. Western blotting and immunoprecipitation experiments showed that the patient's IgG reacted to a protein of 36 kDa. These results suggest that the platelet activation induced by this autoantibody depended on both the selective activation of PKC and the slight Ca2+ mobilization induced by thromboxane A2 synthesis, while the aggregation depended on secretion induced by the synergistic action of the above two mechanisms and was mediated through GP IIb/IIIa.

Adenosine Triphosphate↗