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Biomedical subjects

M Koide

Publications and source records attributed to M Koide.

At least 163 records · Page 9Linked to original sources

Covalent labeling of the cocaine-sensitive catecholamine transporter.

Xylamine is an alkylating agent that is a substrate for and specific irreversible inhibitor of the cocaine-sensitive catecholamine transporter that functions in catecholamine reuptake into neurons and PC12 cells. [3H]xylamine prominently labels nine PC12 proteins; the relative xylamine-alkylation of a Mr 54,000 protein was decreased by cocaine and increased in the case of a PC12 variant, B9, which is deficient in catecholamine transport. [3H]xylamine labels no such protein in another transport variant, MPT1. We propose that this Mr 54,000 protein 1) is a component of the catecholamine transporter, 2) is present in B9 cells but in a conformation that reduces transporter activity and makes alkylation by xylamine more likely, and 3) is absent in MPT1 cells. Nerve growth factor treatment restores transporter activity in B9 cells but not in other transporter-deficient variants.

Alkylation↗

Fasting prevents acute pancreatitis induced by cerulein in rats.

We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.

Acute Disease↗

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats.

We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.

Acute Disease↗

Mechanism of abnormal postexercise systolic blood pressure response and its diagnostic value in patients with coronary artery disease.

To define the factors that affect an abnormal postexercise systolic blood pressure (SBP) response and to verify the diagnostic value of that response in patients with coronary artery disease (CAD), we studied 33 normal subjects, eight patients with hypertension who had no CAD, and 42 patients with documented CAD who underwent supine leg exercise testing. SBP recovery ratios were derived by dividing the values obtained 1 and 3 minutes after exercise by the peak value. The upper normal limit of the SBP ratio was defined by two standard deviations from the mean for 33 normal subjects. The specificity of this criterion for identifying patients with CAD was 97% and the sensitivity was 60%. None of the eight patients with hypertension showed an abnormal postexercise SBP response. At peak exercise the pulmonary artery wedge pressure was significantly greater in the patients with CAD having an abnormal response. In multiple regression analysis the exercise pulmonary artery wedge pressure, the exercise SBP, and the systemic vascular resistance after exercise were determining factors for an abnormal SBP response. Three-vessel disease was more common in patients with an abnormal response. Results of this study indicate that an abnormal postexercise SBP response appears to be determined by (1) the extent of exercise-induced impairment of left ventricular function and (2) peripheral vascular tone during recovery. This study also suggests that this criterion can increase the specificity of supine exercise testing in patients with CAD including those with hypertension and might provide a marker for the severity of impaired left ventricular function by exercise in CAD.

Adult↗

Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris.

We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise.

Adult↗

Effects of L-364,718 on pancreatic exocrine and endocrine secretion in the rat.

We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors. Similarly, binding of N-methylscopolamine to pancreatic acini was not inhibited by L-364,718. In the isolated perfused pancreata, L-364,718 inhibited CCK-8-stimulated pancreatic exocrine secretion and insulin release. The inhibitory effects of L-364,718 were more potent for insulin release than for exocrine secretion and persisted even after the removal of L-364,718 infusion. These results clearly demonstrate that L-364,718 is a specific, potent, and prolonged antagonist of CCK's stimulatory actions on pancreatic acinar and B cells.

Amylases↗

Proglumide analogues CR 1409 and CR 1392 inhibit cholecystokinin-stimulated insulin release more potently than exocrine secretion from the isolated perfused rat pancreas.

The effects of proglumide-related cholecystokinin (CCK) receptor antagonists CR 1409 and CR 1392 on CCK-octapeptide (CCK-8)-stimulated immunoreactive insulin (IRI) release and exocrine secretion were examined simultaneously in the isolated perfused rat pancreas. The CR 1409, at concentrations of 10-100 nM, significantly inhibited CCK-8 (100 pM) stimulation on IRI release but failed to inhibit the stimulatory effect of CCK-8 on both pancreatic juice flow and protein secretion. Increasing concentrations of CR 1409 inhibited both CCK-8-stimulated IRI release and exocrine secretion. Half-maximal inhibition was observed with approximately 2 nM for IRI release and 1 microM for protein secretion. When a higher dose (1 nM) of CCK-8 was used, the inhibitory effect of 10 nM CR 1409 on CCK-8-stimulated IRI release was abolished, whereas 10 microM CR 1409 retained significant inhibitory effect. Furthermore, 1 microM carbachol-induced IRI release was not altered by the addition of 10 microM CR 1409. The CR 1392 also had an inhibitory effect on both CCK-8-stimulated IRI release and exocrine secretion. The concentration of CR 1392 that caused half-maximal inhibition of CCK-8-stimulated IRI release was 300 times lower than that of exocrine secretion. In addition, 1 microM carbachol-stimulated IRI release was not altered by 100 microM CR 1392. Thus, the inhibitory effects of CR 1409 and CR 1392 on IRI release were mediated through the interaction at the CCK receptor and were more potent than those on juice and protein secretion. This study suggests, therefore, that CCK receptors on B cells might be different from those on acinar cells in terms of their relative affinities for antagonists.

Animals↗

Immunohistochemical study of peptide-containing nerves in the gastrointestinal tract of the Japanese field vole, Microtus montebelli.

The distribution and relative frequency of nerves containing immunoreactivity for substance P (SP), vasoactive intestinal polypeptide (VIP), gastrin-releasing polypeptide (GRP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and menthionine-enkephalin (MENK) were studied by immunohistochemistry in the gastrointestinal tract of the herbivorous Japanese field vole, Microtus montebelli.

Animals↗

Regulatory effect of cholecystokinin on subsequent insulin binding to pancreatic acini.

We investigated the regulatory effect of cholecystokinin (CCK) on subsequent insulin binding to pancreatic acinar cells. Rat isolated acini were preincubated with various concentrations of CCK octapeptide (CCK-8) at 37 degrees C. Acini were then washed, resuspended in the binding buffer, and incubated with 8.3 pM 125I-labeled insulin for 60 min at 37 degrees C. Pretreatment with CCK-8 caused inhibition of subsequent 125I-insulin binding that was time and concentration dependent. Significant inhibition was observed with 3 pM CCK-8. Computer analysis of the competition-inhibition study with a nonlinear least-squares curve-fitting program revealed that CCK-8 pretreatment of acini reduced the receptor affinity of the high-affinity binding site. This inhibitory action of CCK-8 was not due to the alteration in degradation or internalization of the tracer. When acini were pretreated with 100 pM CCK-8 for 120 min at 4 degrees C, a reduction in the receptor affinity of the high-affinity binding site was also observed. In pancreatic membrane prepared from acini preincubated with 100 pM CCK-8 for 120 min at 37 degrees C, displacement of 125I-insulin (83 pM) by unlabeled insulin (24 degrees C, 1 h) revealed that CCK-8 inhibited 125I-insulin binding by altering the receptor affinity of the high-affinity binding site. In acinar preparations the inhibitory effect of CCK-8 on 125I-insulin binding was abolished when acini were preincubated with CCK-8 and CCK receptor antagonist L 374718 at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hemodynamic mechanisms of antianginal action of calcium channel blocker nisoldipine in dynamic exercise-induced angina.

To investigate the mechanism of antianginal action of the calcium channel blocker nisoldipine and to determine the reproducibility of the clinical and hemodynamic events induced by supine leg exercise, 30 patients with stable effort angina pectoris were studied. They were divided into two groups; one group of 19 patients received a single 10-mg dose of nisoldipine orally, and the other group of 11 patients received a single dose of placebo orally. Chest pain was induced in all of 30 patients during the control exercise test. After nisoldipine administration, chest pain was not induced in 13 of 19 patients and was of lessened severity in five patients with the same work load as those performing control exercise. ST segment at peak exercise showed less severe depression after nisoldipine. Systemic vascular resistance was reduced by 38% (p less than 0.001) at rest and 22% (p less than 0.001) at peak exercise, and coronary vascular resistance was reduced by 31% (p less than 0.01) at rest and 18% (p less than 0.01) at peak exercise. Pulmonary artery wedge pressure fell from 6 +/- 1 to 3 +/- 1 mm Hg (p less than 0.001) at rest and from 28 +/- 3 to 11 +/- 2 mm Hg (p less than 0.001) at peak exercise. Coronary sinus flow at rest and myocardial oxygen uptake both at rest and during exercise was not modified by nisoldipine. However, coronary sinus flow at peak exercise increased significantly from 219 +/- 24 to 249 +/- 31 ml/min (p less than 0.01) after nisoldipine, and myocardial oxygen uptake was not significantly changed despite decreased coronary vascular resistance. The clinical and hemodynamic events induced by the exercise during invasive studies (except pulmonary artery wedge pressure at rest) were reproducible after placebo administration. Our data demonstrate that increased coronary blood flow could be the major mechanism of the antianginal action of nisoldipine in supine leg exercise-induced angina.

Adult↗

Severe hypersensitivity to mosquito bites associated with natural killer cell lymphocytosis.

A 2-year-old girl showed exaggerated skin reactions to mosquito bites and associated general symptoms, including a high temperature, lymphadenopathy, and hepatosplenomegaly. Peripheral blood lymphocytes contained a high percentage of CD2+, CD3-, CD4-, CD8-, CD11b+, CD16+, CD38+, CD56+, CD57-, and HLA-DR+ large granular lymphocytes that exhibited a marked natural killer cell activity. Immunohistochemically, biopsy specimens taken from the lesional skin demonstrated an infiltrate of the cells bearing the natural killer cell phenotype, indicating a role of these cells in the development of the abnormal skin reactions to mosquito bites and other systemic manifestations. Our case suggests that natural killer cell lymphocytosis may show severe hypersensitivity to mosquito bites as the most outstanding manifestation.

Animals↗

[Second serogroup of Legionella pneumophila isolated from a patient with fulminant pneumonia].

A 67-year-old female was admitted to our hospital, because of high fever and dry cough. She had undergone semiradical hysterectomy and radiation therapy for carcinoma of the uterine cervix one year previously. Her chest roentgenograms on admission showed lobar consolidation of the left upper lobe. Antibiotics were administered but her general condition and pulmonary consolidation did not improve. As Legionellosis was highly suspected, we performed bronchoscopic examinations. Bronchial mucosa was almost normal with no secretion, and Legionella was isolated from the specimen obtained bronchoscopically. Six days later, L. pneumophila serogroup 2 was isolated and identified from an intratracheal aspiration, and serological diagnosis was made by indirect immunofluorescence antibody. We could also detect the bacteria in the BALF by immunofluorescence microscopy and in the tissue of the TBLB specimen with the ABC method.

Aged↗

Loxiglumide. A new proglumide analog with potent cholecystokinin antagonistic activity in the rat pancreas.

D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylami no)-5- oxopentanoic acid (CR 1505; loxiglumide) is a newly developed analog of proglumide. We examined the inhibitory effects of loxiglumide on pancreatic exocrine function in the isolated pancreatic acini and the isolated perfused pancreata of rats. Loxiglumide inhibited cholecystokinin octapeptide (CCK-8)-stimulated amylase release and, similarly, binding of [125I]CCK-8 to isolated rat pancreatic acini. Loxiglumide was about 3000 times more potent than the reference substance proglumide, but was about 1000 times less potent than L-364,718, another new CCK antagonist having benzodiazepine ring, in inhibiting CCK-8-stimulated amylase release. The inhibitory effect of loxiglumide displayed competitive kinetics and was specific for CCK in that the effects of other receptor secretagogues or agents bypassing receptors were not altered. The inhibitory effect of loxiglumide was fully reversible in isolated acini. However, the pancreata perfused with 10 microM loxiglumide for 20 min did not respond to CCK-8 for more than 20 min even after the removal of loxiglumide infusion. In contrast, an immediate increase in pancreatic exocrine secretion was observed after proglumide removal. Loxiglumide appeared to be bound to the receptors on acinar cells in a slowly dissociating state. These results indicate that loxiglumide acts as a potent, competitive, and specific CCK antagonist on the exocrine pancreas and, because of its prolonged inhibitory action, may be useful as a therapeutic agent in pancreatic disease.

Amylases↗

The important role of left ventricular relaxation and left atrial pressure in the left ventricular filling velocity profile.

To evaluate the determinants of left ventricular filling, left ventricular filling velocity was measured by pulsed Doppler flowmetry during catheterization of the right and left sides of the heart in 37 patients with cardiac disease before and during leg elevation. During leg elevation, despite no significant change in the time constant of isovolumic relaxation (T), the peak rapid filling velocity (PVRF) increased in association with an increase in pulmonary wedge pressure (PWP), but the peak atrial filling velocity was unchanged. The PVRF correlated with the pulmonary wedge V wave - left ventricular minimum pressure difference (r = 0.68) and in multivariate regression with both T and mean PWP (R = 0.73). These results indicate that left ventricular filling is determined by both left ventricular relaxation and left atrial pressure and that an increase in left atrial pressure changes the left ventricular filling velocity profile in a manner that mimics the pattern with normal diastolic function.

Adult↗

Primary intrasellar microgerminoma detected by magnetic resonance imaging: case report.

A case of primary intrasellar germinoma in a 24-year-old woman is presented. Her initial symptoms were diabetes insipidus and headaches. The neurological examination found no abnormalities, but the endocrinological examination disclosed a deficiency in growth hormone secretion. Her skull x-ray revealed a normal sella turcica, and a computed tomographic scan revealed no abnormal mass in the pituitary fossa, but a slightly enlarged stalk. Magnetic resonance imaging revealed a small tumor in the posterior lobe. Transsphenoidal exploration revealed a germinoma in the posterior pituitary lobe. Six cases of primary intrasellar germinoma, including our case, were reviewed. Our case is considered to be the smallest intrasellar germinoma yet reported.

Adult↗

[A strain of Pseudomonas vesicularis isolated from shower hose which supports the multiplication of Legionella].

In Japan, a fatal case due to Legionella micdadei was first recognized in our laboratory in 1986. On the epidemiological study just after the case, no Legionella was detected from the environmental samples of the patient's residence, such as shower water, tank water and so on. In the course of prospective investigations, no Legionella was isolated, but many organisms were grown on BCYE alpha and MWY agar plates. In the retrospective study, one of these organisms was found to support satellite growth of Legionella on BCYEagar without L-cysteine. This was the isolate from the shower hose and identified as Pseudomonas vesicularis with the biochemical and DNA-DNA hybridization test. And P. vesicularis type strain ATCC11426 also supported satellite growth of Legionella. Especially in the water supply system, the existence of P. vesicularis seemed to be effective on the growth of Legionella. It must be taken into consideration that efforts made to isolate the nutrient produced organisms as well as Legionella are needed.

Legionella↗

Adrenergic regulation of calcium-deficient hypertension in chick embryos.

Chick embryos rendered calcium deficient by long-term culture outside the eggshell develop hypertension and tachycardia (R. Tuan and H. Q. Nguyen, J. Exp. Med. 165: 1418-1423, 1987). To characterize the hypertension of cultured shell-less (SL) chick embryo, we have compared their cardiovascular response to adrenergic drugs with normal (NL) embryos at day 14 of incubation. Blood pressure and pulse rate were measured before and after administration of norepinephrine (NE), phentolamine (PA), isoproterenol (IP), and propranolol (PP). Base-line blood pressures (systolic and diastolic) were uniformly higher in SL than NL embryos. In both embryos, blood pressure was elevated by NE and PP but lowered by IP and PA; pulse rates were decreased by PP and PA and increased by NE and IP. Pharmacological sensitivity to NE and PA, based on their effective dosages and magnitude of response in blood pressure and pulse rate, was higher in SL embryos. On the other hand, the embryos did not differ significantly in their sensitivity to IP and PP. The plasma concentration of catecholamines was considerably higher in SL embryos. Although serum calcium was lower in SL embryos, myocardial calcium content was not significantly different. Thus the cardiovascular function of SL embryos is likely to be under more sensitive and potentiated alpha-adrenergic regulation, perhaps a result of different calcium handling by several tissues (e.g., myocardium). These properties of the SL chick embryo indicate that it is a novel and useful experimental system to study the relationship between calcium homeostasis and development of hypertension.

Animals↗

Effects of a new proglumide analogue CR 1392 on pancreatic exocrine secretion in the rat.

The effects of proglumide analogue. CR 1392, on pancreatic exocrine secretion were studied in the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, CR 1392 caused a parallel rightward shift of the dose-response curve for amylase secretion stimulated by cholecystokinin octapeptide (CCK-8). CR 1392 inhibited maximally stimulated amylase release by CCK-8 (100 pM) in a concentration-dependent manner, with a half maximal inhibition (ID50) at 8.0 +/- 0.6 microM. CR 1409, another proglumide analogue, also caused a concentration-dependent inhibition (ID50: 3.2 +/- 0.4 microM). Although CR 1409 was about 2.5-fold more potent than CR 1392 in inhibiting the stimulated amylase release, 1 mM CR 1409 caused 107.4 +/- 0.9% increase in amylase release, suggesting acinar cell damage. CR 1392 (1 mM) also caused 19.9 +/- 2.3% increase in amylase release, but was less toxic than CR 1409. The antagonism produced by CR 1392 was selective for CCK and had no effect on amylase release stimulated by other receptor secretagogues or by agents bypassing receptors. CR 1392 added 20 min after the CCK-8 stimulation rapidly abolished pancreatic exocrine secretion in both isolated acini and isolated perfused pancreas. Although the inhibitory effect of CR 1392 was fully reversible in the isolated acini, the pancreata perfused with 100 microM CR 1392 for 20 min did not respond to the subsequent stimulation with CCK-8 for more than 20 min. These results indicate that CR 1392 is a potent, competitive, specific and long acting antagonist of CCK in rat pancreas.

Amylases↗