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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 37 records · Page 2Linked to original sources

Assessment of endothelium-derived relaxing factor from human coronary arteries using the anti-platelet aggregatory effect.

Responses of human and canine washed platelets to thrombin in the presence and absence of human and canine coronary arteries were examined to establish a simple indirect measurement system for endothelium-derived relaxing factor (EDRF). Isolated rings of coronary arteries were obtained from either adult dogs or recipient hearts of cardiac transplant patients. The addition of small segments of canine and human coronary arteries with intact endothelia inhibited thrombin-induced platelet aggregation, but those with disrupted endothelia did not. Pretreatment of human and canine coronary arteries with the cyclo-oxygenase inhibitor indomethacin markedly attenuated the observed effect. The anti-platelet aggregatory effect of indomethacin-pretreated coronary artery was enhanced by acetylcholine or histamine, stimulators of EDRF production, or superoxide dismutase, which prolongs the half-life of EDRF, and inhibited by the EDRF inhibitor hemoglobin. These results suggest that endothelial cells of the human coronary artery, like the canine coronary artery, can produce EDRF which inhibits platelet aggregation, and that this simple experimental model is useful to examine the effect of environmental chemicals on EDRF in the human coronary artery.

Animals

Injury to cultured human vascular endothelial cells by copper (CuSO4).

The effect of copper sulfate (CuSO4) on cultured human vascular endothelial (HVE) cells and cultured human fibroblasts (HAIN-55) was investigated. HVE cells were collected from umbilical veins by enzymatic digestion with collagenase. The viability, subsequent growth and DNA synthesis of both cell types were inhibited concentration-dependently by the addition of copper. The cytotoxic effect of copper on the morphology of these cells was also concentration-dependent. However, the cytotoxic effect of copper on the viability, subsequent growth and DNA synthesis was greater in HVE cells than in HAIN-55 cells. These results suggest that HVE cells are more susceptible to concentration-dependent copper cytotoxicity than HAIN-55 cells are, and that copper could induce vascular endothelial injury, which may be involved in the pathogenesis of cardiovascular disease.

Cardiovascular Diseases

Prostaglandin F2 alpha- and phorbol 12-myristate-13-acetate-stimulated progesterone production by cultured human luteal cells in the mid-luteal phase: prostaglandin F2 alpha increases cytosolic Ca2+ and inositol phosphates.

While prostaglandin F2 alpha (PGF2 alpha) has been thought to be a natural luteolysin in non-primates, a luteolytic effect in the human corpus luteum is less evident. We therefore investigated the action of PGF2 alpha on monolayer cultures of human luteal cells obtained from mid-luteal phase corpora lutea. PGF2 alpha increased basal and human chorionic gonadotrophin (hCG)-stimulated progesterone production by human cultured luteal cells. A potent tumour-promoting phorbol ester, phorbol 12-myristate-13-acetate (PMA), also stimulated progesterone production by cultured human luteal cells. Although human luteal cells were incubated for 24 h with PMA, hCG was still able to stimulate the production of progesterone by PMA-pretreated cells. However, PMA pretreatment blocked the ability of PGF2 alpha to stimulate progesterone production. It is possible that the luteotrophic effect of PGF2 alpha may be mediated, in part, by the activation of protein kinase C. Addition of PGF2 alpha to suspensions of human luteal cells preincubated with myo-[2-3H]inositol promoted an increase in labelled inositol phosphates. PGF2 alpha also rapidly increased intracellular free Ca2+ in human luteal cells loaded with the fluorescent Ca2+ probe, fura-2. We conclude that PGF2 alpha and PMA stimulate progesterone production and that PGF2 alpha increases the intracellular free calcium and inositol phosphates of human cultured luteal cells in the mid-luteal phase.

Calcium

Renal artery aneurysm: the significance of abdominal bruit and use of color Doppler.

A case of renal artery aneurysm is presented. The patient had no hypertension and no signs of arteriosclerosis obliterans or aortitis syndrome, except for abdominal bruit. A saccular aneurysm, 1 cm in diameter, was demonstrated by two-dimensional and color Doppler ultrasound and documented by angiography. The aneurysm was embolized by a steel coil. The abdominal bruit, though uncommon, is a very important bed-side sign of renal artery aneurysm, if the patient exhibits no arteriosclerosis obliterans or aortitis syndrome. Ultrasound Doppler is very useful in screening for aneurysm.

Aneurysm

Hemodynamic changes due to afterload reduction as a predictor of exercise capacity in patients with dilated cardiomyopathy.

Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r = 0.64), heart rate (r = -0.58) and plasma norepinephrine concentration at rest (r = 0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r = -0.84, r = 0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters.

Adult

Repeated intracerebral hemorrhage associated with impaired platelet aggregation--report of two cases.

The authors report two cases of hypertensive intracerebral hemorrhage (ICH) repeated at the same site within 1 or 2 days causing death in a 53-year-old male and a 48-year-old female. In both cases, platelet aggregation was significantly impaired. Acquired platelet dysfunction may be important in the expansion of hemorrhage in patients with repeated hypertensive ICH. In such cases administration of normal platelets may be required to prevent devastating hemorrhage.

Blood Platelet Disorders

WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. no. 89009. II. Biological characterization and pharmacological characterization of WS009 A and B.

WS009 A and B, produced by Streptomyces sp. No. 89009, were found to be competitive and specific antagonists against endothelin (ET)-1 receptors in in vitro studies and also active in in vivo studies. Furthermore, WS009 A and B were specific antagonists for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues.

Animals

WS9326A, a novel tachykinin antagonist isolated from Streptomyces violaceusniger no. 9326. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

Data from several studies suggest that tachykinins may play an important role in the pathophysiology of airway diseases, especially asthma. Our aim is to discover tachykinin antagonists which exhibit therapeutically useful anti-asthmatic activity. In our search for activities inhibiting the binding of [3H]substance P to guinea-pig lung membrane preparations, we have found that the fermentation product, WS9326A, isolated from Streptomyces violaceusniger, is a potent tachykinin receptor antagonist.

Animals

WS9326A, a novel tachykinin antagonist isolated from Streptomyces violaceusniger no. 9326. II. Biological and pharmacological properties of WS9326A and tetrahydro-WS9326A (FK224)

WS9326A binds competitively to [3H]substance P (NK-1 receptor) binding sites on guinea-pig lung membranes (IC50 = 3.6 x 10(-6) M), and acts as a tachykinin antagonist in various functional assays. WS9326A inhibited tracheal constrictions produced by exogenously added substance P and neurokinin A, with IC50 values of 9.7 x 10(-6) M and 3.5 x 10(-6) M, respectively. WS9326A inhibited neurokinin A-induced bronchoconstriction in a dose dependent manner when administered to guinea-pigs intravenously together with neurokinin A, and was also effective in preventing capsaicin-induced bronchoconstriction, which is known to be caused by release of endogenous tachykinins (substance P and neurokinin A). FK224 (tetrahydro-WS9326A; catalytic hydrogenation of WS9326A gave FK224) was more potent than WS9326A in the [3H]substance P receptor binding assay using guinea-pig lung membrane (IC50 = 1.0 x 10(-7) M).

Animals

WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS-7338 A, B, C and D, novel endothelin receptor antagonists, have been isolated from fermentation broth of Streptomyces sp. No. 7338. These antagonists were purified from the culture mycelium by extraction with acetone, followed by carbon column chromatography and HPLC. Among them, WS-7338 B showed good activity in an endothelin receptor binding assay with an IC50 of 2.7 x 10(-7) M.

Amino Acid Sequence

WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. II. Biological characterization and pharmacological characterization of WS-7338 B.

WS-7338, produced by Streptomyces sp. No. 7338, was found to be a competitive and specific antagonist against ET-1 receptors in in vitro studies and WS-7338 B is also active in vivo. Furthermore, WS-7338 B was a specific antagonist for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues.

Animals

Measurement of serum IgE antibodies against Japanese cedar pollen (Cryptomeria japonica) in Japanese monkeys (Macaca fuscata) with pollinosis.

IgE antibodies against allergens of Japanese cedar (Cryptomeria japonica, CJ) pollen in the serum of seven Japanese monkeys (Macaca fuscata) with pollinosis were measured by fluorometric indirect enzyme-linked immunosorbent assay (ELISA). All of the monkeys were found to have specific IgE to the crude pollen antigen. The specific IgE levels were well correlated with those determined by the Pharmacia CAP system. IgE antibodies were then assayed with two kinds of purified allergens (Cry j I and Cry j II) by the ELISA. We found that five monkeys had specific IgE to both allergens, although the other two had IgE only to Cry j I or Cry j II; there is different immune responsiveness to the two major allergens in the monkeys.

Allergens

[Repeated arterial infusion chemotherapy for inoperable hepatocellular carcinoma using implantable drug delivery system].

We performed a clinical evaluation of repeated arterial infusion chemotherapy using an implantable drug delivery system for 41 patients with inoperable hepatocellular carcinoma (HCC). About half of our patients could not undergo transcatheter arterial embolization (TAE) because of extreme tumor extension and/or accompanying advanced cirrhosis. In most patients we implanted a 5 Fr. catheter non-surgically and connected it to an implanted injection port through a subcutaneous tunnel. The treatment schedule was weekly or biweekly intrahepatic one-shot administration of mitomycin C, adriamycin, 5-fluorouracil and epirubicin. The response rate (CR + PR) was 24.4%. The median survival period was 401.1 days. The 6 month, 1-year and 2-year survival rates were 73%, 48% and 24%, respectively. There were no severe side effects nor complications. The implantable drug delivery system will contribute not only to improved therapeutic efficacy for inoperable HCC but also improve the quality of life for patients.

Adult

Object losses and resolutions of women in middle adulthood.

Women in middle adulthood frequently experience loss of objects during this life stage, and thus their psychiatric disorders are often related to object losses. This paper presents three cases of women in middle adulthood whose onset of illness was precipitated by object loss and discusses the psychodynamics, nature of their object loss and mourning process. All three cases presented symptoms of depressive anxiety, paranoid reaction and hypochondriacal anxiety, however, the onset of their illness was related to losses of objects. In addition, it was found that they had not resolved grief towards other losses in the past which preceded the object loss that precipitated the illness. Furthermore, the patients found new objects after completing their mourning process. However, these were not new objects, but rather a rediscovery of objects which they had lost in the past. Such findings are thought to be useful, not only in the treatment of women in middle adulthood, but also in elucidating psychiatric disorders which are precipitated by loss of objects.

Aging

Resolution of developmental tasks pertaining to prolongation of adolescence.

The establishment of ego identity is a developmental task of primary importance in adolescence. Adolescence is considered to be a period of psychosocial moratorium for the establishment of ego identity and incorporation into adult society. Some youths are known to consciously or unconsciously extend this period of psychosocial moratorium in order to escape incorporation, prolonging the resolution of developmental tasks associated with adolescence. This paper discusses the psychodynamics of the prolongation of adolescence through presentation of the therapeutic consultation of a male patient in his early 30's prolonging establishment of ego identity, or in particular, that of work identity. Analysis in this case revealed that the prolongation of adolescent mentality was deeply related to the wound of narcissism peculiar to adolescence. Additional comments are given on the therapeutic mechanism of therapeutic consultation.

Adolescent