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Biomedical subjects

S Kawashima

Publications and source records attributed to S Kawashima.

At least 307 records · Page 17Linked to original sources

Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients.

The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P less than 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units x3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU-E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.

Adult↗

An endogenous inhibitor of calcium-activated neutral protease in UMX 7.1 hamster dystrophy.

An endogenous inhibitor for calcium-activated neutral protease (CANP) from skeletal and cardiac muscles of muscular dystrophic hamsters (UMX 7.1) was compared with that from normal control animals at 4 and 10 weeks of age by Western blotting using antibody raised against CANP inhibitor. Fragmented CANP inhibitor was found in dystrophic skeletal muscles in all cases at both ages, while only intact inhibitor was detected in the skeletal muscle of the normal hamsters. A total absence of intact inhibitor was shown in one 10-week-old dystrophic hamster. In contrast, there was little difference in CANP inhibitor from heart between dystrophic and control hamsters at 4 weeks. However, fragmentation similar to that in skeletal muscle was seen in the heart inhibitor in a few of the 10-week-old dystrophic hamsters.

Animals↗

Surgical treatment of abdominal aortic aneurysm in the high-risk patient.

In an attempt to define the preoperative risk factors that predictably influence mortality after aneurysmectomy, this study reviews the surgical management of abdominal aortic aneurysms in a series of 110 consecutive patients who underwent elective resection. The preoperative risks to be added to the present study included pulmonary insufficiency, renal dysfunction, advanced age of over 80 years, ischemic heart disease, and associated other diseases such as thoracic aneurysms, atherosclerosis of the limbs and malignant tumors. Forty-six patients had one of these risk factors (one-risk group), 17 had two (two-risk group), and 9 had three (three-risk group). The operative mortality rates were 4.2 per cent for the high-risk patients and 0 per cent for the patients at no risk. As the number of risk factors increased, aneurysm repair was associated with an increased operative mortality; being 2.2 per cent in the one-risk group, 5.9 per cent in the two-risk group and 11.1 per cent in the three-risk group. The common risk factor in patients who died after aneurysmectomy was pulmonary insufficiency which induced prolonged periods of assisted ventilation. Thus, the optimal management of high-risk patients, particularly those with pulmonary insufficiency, may reduce the mortality after aneurysmectomy.

Aged↗

Animal model of uterine adenomyosis: is prolactin a potent inducer of adenomyosis in mice?

Uterine adenomyosis is a benign lesion but a serious disease for women, because the symptoms are characterized by abnormal bleeding, pain, cramps, and sterility. Thus elucidation of the mechanisms involved in the development of the disease would contribute to improved management and treatment and prophylaxis of this lesion. A mouse model, in which ectopic pituitary isografting is associated with an increase in the plasma level of prolactin, is useful for a rapid and frequent induction of uterine adenomyosis and can be used to study the origin of this lesion.

Animals↗

Changes in arginine vasotocin content in the pituitary of the Medaka (Oryzias latipes) during osmotic stress.

Changes in the arginine vasotocin (AVT) neurons of the medaka, Oryzias latipes, during osmotic stress were studied by means of immunohistochemistry and radioimmunoassay. AVT neurons were identified by their immunoreactivity to anti-arginine vasopressin serum, which crossreacts with AVT. When freshwater (FW)-adapted fish were transferred to seawater (SW), the number of immunoreactive magnocellular neurons decreased, while the cell nuclear size increased. AVT content in the pituitary significantly decreased 2 hr or 1 day after transfer to SW, but returned to approximately the initial level 1 week after transfer. However, when SW-adapted fish were transferred to FW, the number of immunoreactive magnocellular neurons increased from 1 hr after readaptation to FW, but the cell nuclear size failed to show significant changes. AVT content in the pituitary significantly increased 1 or 2 hr after transfer. These results seem to indicate that AVT secretion in the medaka was temporarily accelerated by exposure to SW and inhibited immediately after transfer to FW.

Adaptation, Physiological↗

Development of uterine adenomyosis after treatment with dopamine antagonists in mice.

Development of uterine adenomyosis was studied in SHN mice treated with psychotherapeutic drugs, sulpiride and perphenazine, and gastroenteric drug, metoclopramide, which act as dopamine antagonists to increase prolactin release from the pituitary gland. Administration of these drugs twice daily for 40-70 or 40-90 days of age induced an elevation in serum level of prolactin. Furthermore, the treated mice showed a prolongation of metestrous plus diestrous phase and a high incidence of uterine adenomyosis compared with vehicle-treated control mice. These results indicate that hyperprolactinemia produced by continuous treatment with psychotherapeutic and gastroenteric drugs is responsible for the occurrence of irregular estrous cycles and the genesis of uterine adenomyosis in mice.

Animals↗

Effect of vitamin E on the accumulation of fluorescent material in cultured cerebral cortical cells of mice.

The effect of vitamin E on the accumulation of lipofuscin-containing fluorescent material in the mouse cerebral cortical cells in primary culture was studied. Fluorescent material was extracted in ethanol:diethylether (3:1) and autofluorescence intensity of the extracts was measured by a spectrofluorophotometer. Although vitamin E at the concentration of 0.005 IU/ml was not effective, 0.01 IU/ml vitamin E inhibited the accumulation of fluorescent material. Fluorescent material accumulation was reduced to 76.3-86.4% of the control level in 6-, 12-, or 18-day treatment of 0.01 IU/ml vitamin E. High doses of vitamin E (0.05 or 0.1 IU/ml) were toxic for cultured cells. Ethanol, the vehicle of vitamin E, at the final concentration of 0.005% was also effective on the reduction of fluorescent material accumulation (81.0% of the control level at 18 days). The inhibitory effects of vitamin E as well as ethanol on the accumulation of fluorescent material in cultured cells are explained by their nature as free radical scavengers.

Animals↗

Elevated plasma beta-endorphin levels in patients with congestive heart failure.

Recent experimental studies show that the opioid system is important to the pathophysiology of cardiovascular impairment in congestive heart failure. Plasma beta-endorphin levels were measured in 37 patients with congestive heart failure and compared with those of 21 age- and gender-matched normal subjects. The relation of plasma beta-endorphin levels and cardiac function at rest and exercise capacity was assessed in 17 of the patients with dilated cardiomyopathy. Exercise capacity was determined by symptom-limited maximal treadmill exercise with expired gas analysis. Plasma beta-endorphin levels were elevated and correlated with the patients' New York Heart Association functional cardiac status (control: 14.0 +/- 4.4 pg/ml; class II: 17.9 +/- 3.6 pg/ml; class III: 28.3 +/- 8.8 pg/ml; class IV: 46.7 +/- 14.6 pg/ml, mean +/- SD). No relation was found between plasma beta-endorphin levels and left ventricular systolic performance as assessed by M-mode and Doppler echocardiography. Plasma beta-endorphin levels were negatively correlated with cardiac output determined by Doppler echocardiography and positively correlated with systemic vascular resistance (r = -0.733, r = 0.747, respectively, both p less than 0.001), but not correlated with calf blood flow as measured by a plethysmography. A good correlation was found between plasma beta-endorphin levels at rest and exercise capacity. The correlations with peak oxygen consumption, anaerobic threshold, and peak rate-pressure product were r = -0.721, -0.672, and -0.674, respectively (p less than 0.01). The data show that plasma beta-endorphin levels are elevated in patients with congestive heart failure and reflect, to some degree, the severity of the disease.

Echocardiography↗

Coronary pressure-flow, pressure-function, and function-myocardial oxygen consumption relations in postischaemic myocardium.

STUDY OBJECTIVE: The aim was to study coronary pressure-flow, pressure-myocardial wall motion and myocardial wall motion-myocardial oxygen consumption relations in postischaemic myocardium with prolonged myocardial dysfunction (stunned myocardium) in comparison with normal myocardium. DESIGN: Regional myocardial wall thickening was measured with ultrasonic crystals, and postischaemic myocardial dysfunction was achieved by occlusion of a carotid-left anterior descending coronary artery bypass (15 min) and reperfusion (30 min). Coronary perfusion pressure was decreased in 10 mm Hg steps by constricting the bypass before and after producing postischaemic myocardial dysfunction. At each constriction step, coronary flow, regional wall thickening, and regional myocardial oxygen consumption in the area perfused by the left anterior descending artery were measured. EXPERIMENTAL MATERIAL: 12 anaesthetised open chest mongrel dogs, weighing 12-16 kg, were studied. MEASUREMENTS AND MAIN RESULTS: At the basal level, myocardial wall thickening of postischaemic myocardium was depressed compared to normal myocardium, at 18.5(SD 8.9)% v 1.3(7.1)%, p less than 0.01. With coronary stenosis, wall thickening gradually decreased at a coronary pressure below 60 mm Hg in normal myocardium, but remained unchanged until mean coronary pressure was reduced to 50 mm Hg in postischaemic myocardium. Myocardial wall thickening of postischaemic myocardium was always more depressed than normal myocardium. At any level of coronary pressure, coronary flow in postischaemic myocardium was not different from normal myocardium. There was no difference in regional myocardial oxygen consumption between normal and postischaemic myocardium at any level of coronary pressure. However, regional myocardial oxygen consumption in postischaemic myocardium was higher than in normal myocardium performing similar levels of myocardial wall thickening. CONCLUSION: The coronary pressure-function relation but not the pressure-flow relation changed in postischaemic myocardium after a 15 min coronary occlusion. Regional myocardial oxygen consumption was relatively increased in postischaemic myocardium.

Animals↗

[Myocardial protection with verapamil in open cardiac surgery--a clinical study for the optimal use].

To determine the optimal use of Verapamil as a myocardial protective agent during open heart surgery, patients were divided into 3 groups of 15 patients each of the same severity and operative difficulty. In group I, Verapamil was added to the blood cardioplegia in a concentration of 1 mg/L. In group II, 0.2 mg/kg of verapamil was added in the pump prime and in group III, in addition to the same amount of pump prime, an additional 0.1 mg/kg of Verapamil was added to the bypass circuit at 60 minutes after the start of bypass and continuous drip of 0.5 micrograms/kg/min for 24 hours after surgery. Only group III continued to maintain an effective concentration of verapamil, that was said in a range between 15 and 100 ng/ml in the serum during and after surgery. It is suggested from the present study that recommendable verapamil administration is as in group III with no severe arrhythmias, significantly less usage of catecholamines without mortality.

Cardiac Surgical Procedures↗

[Nonsurgical removal of the embolized catheter fragments from the heart and great vessels].

Embolized catheter fragments in the heart and great vessels were successfully removed in seven patients by nonsurgical techniques. All procedures for the retrieval were completed without complications or difficulty using instruments such as multipurpose grasping forceps, stone basket, loopsnare and myocardial biopsy catheters. Embolized catheter fragments should be removed promptly before fatal complications develop, and can be taken off safely and simply by nonsurgical technique.

Aged↗

Immunohistochemical distribution of calcium-activated neutral proteinases and endogenous CANP inhibitor in the rabbit hippocampus.

Intracellular accumulation of Ca2+ after brain ischemia is regarded as one of the principal causes of neuronal death, but details of the intracellular events occurring after Ca2+ accumulation have not yet been described. We propose that a calcium-activated neutral proteinase which can degrade neuronal cytoskeletal proteins might link Ca2+ accumulation and irreversible injury of the neuronal intracellular structure. First, therefore, we examined the distribution of calcium-activated neutral proteinase in normal brains. Immunohistochemical distribution of calcium-activated neutral proteinases (CANP) with high and low sensitivity to Ca2+ (muCANP and mCANP) and of endogenous CANP inhibitor was investigated in the dorsal hippocampus of the rabbit. muCANP-immunoreactivity was detected in almost all of the pyramidal cells and granule cells and in some other neurons. A full-length staining from perikarya to dendrites was shown in muCANP-positive neurons. mCANP-immunoreactivity was found mainly in four kinds of hippocampal interneurons: 1) basket cells in the stratum oriens of Ammon's horn, 2) pyramidal basket cells at the boundary of pyramidal cell layer and stratum oriens, 3) polymorphic cells in the hilar region of dentate gyrus, and 4) pyramidal or fusiform basket cells at the inner boundary of the granule cell layer and the hilar region. The distribution of these four kinds of neurons was similar to that of parvalbumin-containing GABAergic neurons. CANP inhibitor immunoreactivity was confined to pyramidal cells in the CA3-CA3c region and some hilar neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The structure-function relationship between peptide aldehyde derivatives on initiation of neurite outgrowth in PC12h cells.

We have previously shown that, among many protease inhibitors examined, only a leupeptin analogue, Ac-Leu-Leu-Nle-al (ALLNal), induces neurite outgrowth in PC12h cells. Since this neurite outgrowth is different from that induced by nerve growth factor (NGF) in terms of morphology and persistence, the existence of a specific protease which regulates neurite formation in PC12h cells was expected. A set of 10 ALLNal analogue peptide protease inhibitors was synthesized and examined for their potency in inducing neurite outgrowth in PC12h cells. Substitution of the N-terminal acetyl residue in ALLNal by benzyloxycarbonyl (Z) increased the activity by about 4 times. For Z-Leu-Leu-X-al, neurite outgrowth was induced in the following order: Leu greater than Phe greater than Nva greater than Val = Ile = Nle greater than Ala greater than Gly at the X residue. The potency of Z-Leu-Leu-Leu-al (ZLLLal) was 50-fold stronger than that of ALLNal. ZLLLal provides a strong tool for characterizing this new type of protease.

Adrenal Gland Neoplasms↗

Binding sites for calcium-activated neutral protease on erythrocyte membranes are not membrane phospholipids.

In order to explore the binding sites for calcium-activated neutral protease (CANP) with high calcium sensitivity (muCANP) on the inner surface of human erythrocyte membranes, we analyzed the binding of muCANP to two kinds of membranes modified by treatment with phospholipase C or Triton X-100. Binding analyses were performed using an immunoblot technique. The amount of muCANP bound to phospholipase C-treated inside-out vesicles was essentially the same as that bound to untreated inside-out vesicles. It was also observed that muCANP binds to Triton X-100-treated membranes, in which most of the integral proteins and glycerophospholipids are removed while the lining proteins remain intact. In both types of modified membrane, the bound muCANP was rapdily converted to an active form by autolysis at physiological free Ca2+ concentrations. These results indicate that the binding sites for muCANP on the inner surface of erythrocyte membranes consist of components other than membrane phospholipids. In addition, it is suggested that one of the binding sites for muCANP is some lining protein.

Animals↗

Effects of prolactin and bromocryptine on the regulation of testicular luteinizing hormone receptors in mice.

The binding of luteinizing hormone (LH) to testicular homogenates increased gradually in mice from 15 to 60 days of age, while the level at 90 days was almost the same as that at 60 days. The plasma concentration of prolactin (PRL) increased significantly from 15 to 40 days and thereafter remained constant. In order to ascertain the influence of PRL on testicular receptors for LH, bromocryptine was injected subcutaneously for 10 days into immature (20-day-old) and adult (90-day-old) mice. In 20-day-old mice, treatment with bromocryptine significantly reduced the plasma levels of PRL but had no significant effects on the binding of LH to receptors in 30-day-old mice. However, in 90-day-old mice, treatment with bromocryptine led to a significant reduction in numbers of receptors for LH 10 days later. There was no difference in dissociation constants (Kd) between groups of oil-injected (Kd = 6.5 x 10(-10) M) and bromocryptine-injected (Kd = 4.6 x 10(-10) M) mice. The reduction in binding of LH per testis of 100-day-old mice after treatment with bromocryptine was eliminated by the simultaneous administration of ovine (o) PRL. The plasma level of follicle-stimulating hormone (FSH) in 100-day-old mice, which tended to be decreased as a result of treatment with bromocryptine, was markedly increased by treatment with oPRL. There were no distinct changes in binding of FSH in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Subcellular distribution of acetylcholinesterase in Alzheimer's disease: abnormal localization and solubilization.

AChE activity was detected mainly in membrane-bound fractions in the frontal cortex of autopsied control or Alzheimer brain as well as rat cerebral cortex. However, the distribution of AChE among various membrane fractions was different between control and Alzheimer brains. The highest specific activity was detected in the fraction enriched with senile plaque, which was obtained from the Alzheimer brain by sonication, solubilization with detergent and centrifugation on a sucrose density gradient. The senile plaque enriched fraction was incubated with purified collagenase or protease and centrifuged at 100,000 g for 60 min. More than 50% of AChE activity was detected in the supernatant fraction. AChE in the supernatant solution showed a property of G4 isozyme. AChE might probably be anchored to the senile plaque through its collagen tail and be solubilized with collagenase or protease, producing a G4 isozyme.

Acetylcholinesterase↗