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Biomedical subjects

A Takaki

Publications and source records attributed to A Takaki.

53 records · Page 3Linked to original sources
PubMed1983

Cleavage and inactivation of Factor IX by granulocyte elastase.

Radioiodinated Factor IX was cleaved by a crude sonicate from leukocytes. In the absence of calcium, fragments of less than 15,000 mol wt were seen from reduced samples on gel electrophoresis. After digestion in 2 mM calcium, however, electrophoresis of reduced samples showed, in addition to low molecular weight fragments, protein bands corresponding in size to heavy and light chains of Factor XIa-activated Factor IX. The cleaving activity in leukocyte sonicates was inhibited by soybean trypsin inhibitor, but only to a small extent by aprotinin. Granulocyte elastase was isolated from purified polymorphonuclear leukocyte granules by affinity chromatography on soybean trypsin inhibitor-agarose and further chromatography on carboxymethyl cellulose. The purified fraction contained two isozymes on acidic gels which cleaved both an ester sensitive to elastase and radiolabeled Factor IX. These two activities were inhibited by elastase-specific chloromethyl ketone. The isolated protease fraction rapidly inactivated apparent Factor IX activity in a coagulant assay system. The degree of inactivation correlated with the amount of intact, radiolabeled Factor IX cleaved. As with the crude sonicate, generation of the larger heavy and light chain-sized fragments was dependent upon calcium. To assess directly the effect of elastase on Factor IX, an immunospecific, active site-directed assay was developed. In this assay, the sample was incubated with solid-phase antibody to Factor IX and the amount of activated product was detected as that which had complexed with radioiodinated antithrombin III. In this system, exposure of Factor IX to Factor XIa showed progressive increase in the ability to bind antithrombin III, whereas after elastase, Factor XIa was unable to generate antithrombin III binding. The elastase-degraded Factor IX did not inhibit activation of additional Factor IX in clotting assays. When Factor IXa was incubated with elastase, binding of antithrombin III was decreased, corresponding to appearance of low molecular weight fragments on parallel samples that were reduced and electrophoresed. These data are consistent with elastase inactivating Factor IX by cleaving bonds near, but distinct from, bonds cleaved by Factor XIa.

Amino Acid Chloromethyl Ketones↗
PubMed1983

[A clinical study on surgical patients with disseminated intravascular coagulation: with special reference to the occurrence of major organ failures].

Among 113 consecutive patients with disseminated intravascular coagulation (DIC), twenty cases who developed this condition under surgical intervention are the subject of this study. At the onset of DIC, fourteen cases were suffered from severe infection. Coagulation study in these patients revealed decreased platelet counts and prolonged prothrombin time. There was marked increase in fibrinogen degradation products and positive ethanol gelation test was frequently observed. These findings were analogous to those found in the more chronic presentations of DIC in the patients with neoplastic diseases, however, plasma concentration of fibrinogen was normal. Antithrombin III level was extremely low in the patients with surgical DIC. The patients with DIC in surgery took acute or subacute courses with very high incidence of major organ failure. The patients with dysfunction of more than three organs were seen in eight of 20 cases. The lungs, kidneys, liver and gastrointestinal tracts were involved in the descending order of frequency. Fourteen patients died and six of these were autopsied. All had multiple fibrin thrombi in more than two organs. The numbers and sites of microthrombi in the major organs were well matched with the clinical manifestations. These results suggested that DIC might be one of the precipitating factors of multiple organ failure.

Acidosis↗
PubMed1977

Occurrence of disseminated intravascular coagulation (DIC) in obstructive jaundice and its relation to biliary tract infection.

Coagulation studies were done on 78 consecutive cases of obstructive jaundice with or without biliary tract infection. Among 26 cases with biliary tract infection 20 cases showed no bleeding tendency but remarkable hypercoagulability with decreased fibrinolytic activity. Other six cases developed diffuse bleeding tendency in addition to the signs of hypotension and multiorgan dysfunction such as oliguria, respiratory distress and mental confusion. Most showed marked coagulation defects characterized by thrombocytopenia, decreased fibrinogen, antithrombin III and plasminogen levels and narrowing of maximal amplitude in thrombelastogram as well as the increase of fibrin degradation products and positive soluble fibrin monomer complexes. All except one died and three cases were autopsied. In two cases postmortem examination revealed multiple fibrin thrombi in lungs and other organs. A cause of the development of bleeding tendency in obstructive jaundice presently observed may likely to be due to the occurrence of disseminated intravascular coagulation (DIC), i.e. hypercoagulability caused by the biliary tract infection is responsible.

Adult↗
PubMedDate not supplied

Adenylate cyclase activation promotes the recruitment of coronary vasodilator reserve and improves subendocardial contractility during coronary hypoperfusion.

This study was designed to examine the effects of an adenylate cyclase activator, NKH477, on epicardial and endocardial contraction and coronary blood flow (CoF) in the presence or absence of ischemia and to compare it to those of adenosine. We measured coronary pressures (CoP), coronary blood flow, epicardial and endocardial wall thickening (i.e., %EPWT and %ENWT, respectively, by sonomicrometry) in 18 anesthetized dogs. The left circumflex coronary artery was perfused with arterial blood using a pressure controlled servo pump. Propranolol (0.5 mg/kg) and atropine (0.25 mg) were used to minimize the neurogenic effects. CoP decreased from 100 mm Hg to 40 mm Hg with and without drugs. At CoP of 100 mm Hg, intracoronary infusion of NKH477 (10(-8) M/kg/min) produced a two-fold increase in CoF, but there were no changes in either the %EPWT or the %ENWT. During coronary hypofusion at coronary pressures equal to 40 mm Hg, NKH477 increased CoF from 16 +/- 2 to 28 +/- 4 mL/min (p < 0.05) and improved %ENWT significantly from 6 +/- 7 to 23 +/- 7% (p < 0.05). However %EPWT was not improved by NKH477. On the other hand, the intracoronary infusion of adenosine (10 micrograms/kg/min) increased CoF from 16 +/- 5 to 21 +/- 6 mL/min (p < 0.05) at CoP of 40 mm Hg. However, this dose of adenosine failed to improve %ENWT (16 +/- 10% vs. 14 +/- 10%, n.s.). Thus, the improvement of subendocardial function by NKH477 might be related to the improvement of subendocardial perfusion which could be induced by the potentiation of endogenously released adenosine as well as the direct vasodilator effect. This contrasts with the effects of exogenously administered adenosine, which failed to improve subendocardial contractility.

Adenosine↗
PubMedDate not supplied

Functional heterogeneity of the monkey lateral hypothalamus in the control of feeding.

Regional differences in the effects of electrical (ES) and chemical stimulation on execution of a bar-press feeding task, and in neuronal activity related to feeding, glucose sensitivity, and odor responsiveness were examined in the lateral hypothalamic area (LHA) of monkeys. In satiated animals, ES of the far lateral and ventral LHA induced bar-press feeding. In hungry animals, ES of the dorsal LHA suppressed the feeding task only during the stimulation period, but prolonged feeding suppression that occurred after ES of the ventromedial LHA. Microinjection of Na-glutamate into LHA sites where ES was effective in suppressing feeding had no effect, but it was effective in the medial hypothalamus. Glucose-sensitive (GS) neurons decreased in activity during bar pressing and/or during the ingestion period. Glucose-insensitive (GIS) neurons showed a cue-related excitation more often than GS neurons. Odor-responding GS and GIS cells were localized in ventromedial and lateral LHA sites, respectively. The present study suggests the regional heterogeneity of the LHA in feeding regulation, depending on both hunger and satiety states.

Animals↗
PubMedDate not supplied

The role of disseminated intravascular coagulation in shock induced by transfusion of human blood in dogs.

Hemolytic blood transfusion reactions were produced in 20 dogs. Animals transfused with human blood twice in a two-week interval demonstrated a significant increase in anti-human red blood cell agglutination titer at the time of the second transfusion. Eighteen dogs that survived from the first transfusion reaction were divided into two groups with or without heparin treatment. The hemolytic transfusion reaction in the sensitized animals was characterized by shock and multiple coagulation abnormalities. Heparin failed to prevent shock, hemoglobinemia and thrombocytopenia, and decreased the mortality rate in heparinized animals. Pathologic examination revealed that the thrombi in the splanchnic organs were less common in the heparinized dogs.

Agglutination Tests↗
PubMedDate not supplied

Immobilization stress may increase plasma interleukin-6 via central and peripheral catecholamines.

It has recently been reported that both physical and psychological stress elevate plasma interleukin (IL)-6 levels independently of endotoxemia, tissue damage, or inflammation. However, the mechanism of plasma IL-6 elevation in these models is poorly understood. In the present study, plasma IL-6 levels were measured using the IL-6-dependent murine hybridoma subclone B9 cell line, which is commonly used by other investigators. We first demonstrated that an immobilization (IM) stress, a typical physicopsychological stress, increased plasma IL-6 levels. Then the contribution of the hypothalamic-pituitary-adrenal (HPA) axis and the central and peripheral catecholaminergic systems in IM-induced plasma IL-6 elevation were examined because these mechanisms play important roles in host defense against stress. Blood samples were collected through an indwelling jugular venous catheter before, during, and after IM; the number of samples taken serially from each animal was 12-13. Blood cells were resuspended in a saline solution and injected into the animals through the same catheter after each blood collection in order to prevent loss of blood volume. After initiation of restraint, plasma IL-6 levels significantly increased at 60 min and peaked at 90 min in the animals immobilized for either 30 or 120 min. The peak levels of IM-induced plasma IL-6 in the animals immobilized for 120 min (1,905 +/- 414 U/ml) were significantly higher than those in the animals subjected to 30 min IM (837 +/- 95 U/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMedDate not supplied

Neuroimmunological effects of exposure to methylmercury forms in the Sprague-Dawley rats. Activation of the hypothalamic-pituitary-adrenal axis and lymphocyte responsiveness.

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 micrograms per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte prolife ration after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of (MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.

Administration, Oral↗