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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 739 records · Page 41Linked to original sources
PubMed1994

Pinacidil attenuates positive inotropic but not chronotropic responses to norepinephrine in isolated dog atrial and ventricular preparations.

We investigated whether pinacidil, a K+ATP channel opener like acetylcholine and adenosine, attenuated the positive chronotropic and inotropic responses to norepinephrine in isolated, blood-perfused dog atrial and ventricular preparations. Pinacidil (0.01-0.3 mumol) decreased atrial and ventricular contractile force to a much greater extent than sinus rate in a dose-related manner. Pinacidil dose-dependently attenuated increases in atrial and ventricular forces induced by norepinephrine but not increases in sinus rate. Pinacidil similarly attenuated the positive atrial and ventricular inotropic responses to Bay k 8644 and CaCl2. The pinacidil doses producing a fifty percent decrease (ED50) of the atrial and ventricular contractile force were not significantly different from the respective pinacidil doses producing a fifty percent inhibition (ID50) of the positive inotropic responses to norepinephrine, Bay k 8644 and CaCl2. Ouabain (5 and 15 nmol) did not affect the decreases in atrial and ventricular contractile force in response to pinacidil. These results suggest that the K+ATP-channel activator pinacidil, unlike acetylcholine or adenosine, functionally attenuates increases in ventricular and atrial contractile force in the responses to norepinephrine and other cardiotonics due to shortening of the action potential duration induced by K+ATP-channel activation in the dog heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Test performances of three diagnostic procedures in evaluating thyroid nodules: physical examination, ultrasonography and fine needle aspiration cytology.

A retrospective study was performed to determine the reliability of physical examination (PE), ultrasonography (US) and fine-needle aspiration cytology (FNA) in the evaluation of thyroid nodules. Preoperative diagnoses of 252 euthyroid patients comprised 126 with benign lesions, 114 with papillary carcinoma and 12 with follicular carcinoma made by PE, US and FNA were reviewed. The specificity of PE, US and FNA for malignancy was 98%, 90% and 98%, respectively. The sensitivity of PE, US and FNA for malignancy was 63%, 78% and 80%. The sensitivity for papillary carcinoma of the three procedures was 68%, 83%, 88%, whereas that for follicular carcinoma was 25%, 25%, 8%, respectively. When all the test results were negative, the likelihood ratio favoring papillary carcinoma was 0.008 whereas that favoring follicular carcinoma was 0.6. The histological category of carcinoma should be considered when evaluating diagnostic procedures for thyroid nodules. No negative test result is conclusive for ruling out the possibility of follicular carcinoma.

Biopsy, Needle↗
PubMed1994

A rapid colorimetric assay for carcinoembryonic antigen (CEA)-mediated cell adhesion and analysis of CEA domains involved in the adhesion.

A colorimetric microadhesion assay that allows the quantitative determination of carcinoembryonic antigen (CEA)-mediated homophilic cell adhesion to CEA immobilized on 96-well polyvinyl chloride plates is described. Chinese hamster ovary (CHO) cells transfected with a full-length CEA cDNA were used as indicator cells. After dislodging nonadherent cells, specifically bound cells were quantified by a colorimetric analysis based on the ability of live cells to reduce the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to a blue formazan product. The domains of CEA responsible for the homophilic cell adhesion were analyzed by inhibition assays using anti-CEA monoclonal antibodies whose reactive domains were already known. The involvement of domain N and possibly subdomain A3 of CEA in the homophilic cell adhesion has been suggested.

Animals↗
PubMed1994

Follow-up laparoscopy in patients with ovarian cancer.

Between 1982 and 1990, two hundred and fourteen consecutive laparoscopies were performed on 75 patients with epithelial ovarian cancer when the disease appeared to be clinically in complete remission according to simultaneous CT scan or ultrasonography. Evaluation were based on macroscopic findings through the laparoscope, by cytologic examination of ascitic and peritoneal washings and by intraperitoneal biopsy. The results were positive in 34 laparoscopies for 19 patients, suspicious in 15 laparoscopies for 13 patients and negative in 164 laparoscopies. the intraperitoneal recurrence rate after negative second-look laparoscopy was 14.0% as a whole, and 4.5% in cases with more than two consecutive negative evaluations. Serum CA-125 levels exhibited and elevation in 28 of 34 positive laparoscopies before treatment and remained within the normal range in 22 (78.6%) of the 28 cases after treatment despite positive follow-up laparoscopies. The repeated laparoscopies offer the advantage of lowering the false negative rate. This will enable early detection of intraperitoneal recurrence, better prognoses and reduction of unnecessary laparotomies.

Female↗
PubMed1994

Effect of gastric mucosal blood flow on the pathogenesis of ammonia in Helicobacter pylori-induced gastric mucosal injury.

PURPOSE: We investigated the effects of the gastric mucosal blood flow on the pathophysiology of ammonia-induced gastric mucosal damage. DESIGN: The study was designed to show whether the damaging effect of ammonia, a product of Helicobacter pylori urease, on the gastric mucosa is increased by the decrease in gastric mucosal blood flow in rats subjected to ischemia. RESULTS: Although ammonium chloride at concentrations of 15-60 mmol/l produced no significant macroscopical lesion in normotensive rats, it caused severe macroscopic hemorrhagic gastric lesions in the stomachs of rats subjected to ischemia. Exposure of the stomach to the combination of ischemia and ammonium chloride (60-600 mmol/l, pH adjusted to 7-9 with sodium hydroxide) produced macroscopic hemorrhagic lesions. However, exposure of the mucosa to the combination of ischemia and sodium hydroxide (60-600 mmol/l, pH was reduced to 7-9 with hydrochloric acid) produced no significant lesions. CONCLUSIONS: These results indicate that the mucosal lesions observed in patients infected with H. pylori are not caused by the alkalinity of H. pylori-produced ammonia and suggest that concomitant infection with H. pylori in the ischemic stomach may lead to the development of ulceration in these patients.

Ammonium Hydroxide↗
PubMed1994

Angiotensin II type 1 receptor messenger RNA levels in human blood cells of patients with primary and secondary hypertension: reference to renin profile.

OBJECTIVES: The relationship between plasma renin activity, plasma angiotensin II (Ang II) or aldosterone levels and peripheral blood cells (mononuclear leucocytes and platelets) Ang II type 1 (AT1) receptor messenger RNA (mRNA) levels were examined in both primary and secondary hypertensive patients. DESIGN AND METHODS: The subjects were 30 patients with primary hypertension, five with primary aldosteronism, five with renovascular hypertension and five normotensive controls with renal cell carcinoma. Blood was collected from each patient for estimation of plasma renin activity and plasma Ang II and aldosterone concentrations, and for isolation of mononuclear leucocytes and platelets, which were then used to measure AT1 receptor mRNA with reverse-transcription polymerase chain reaction. RESULTS: Platelet AT1 receptor mRNA levels were inversely correlated with plasma Ang II levels, and mononuclear leucocyte receptor mRNA levels were positively correlated with plasma Ang II levels in patients with primary hypertension. In contrast, in secondary hypertension both platelets and mononuclear leucocytes AT1 receptor mRNA, which were elevated, were reduced after removal of the adrenal tumour or correction of stenosis of the renal artery. CONCLUSIONS: Platelet AT1 receptors, which were used to reflect physiologically important sites such as vascular smooth muscle, were shown to be regulated in a different manner from mononuclear leucocyte receptors. In patients with primary aldosteronism and renovascular hypertension the plasma aldosterone level was shown to be an important factor upregulating AT1 receptor mRNA.

Adrenal Glands↗
PubMed1994

[The effect of intraperitoneal and intra-aortic chemotherapy for unresectable gastric cancer].

Regional chemotherapy was given 16 unresectable gastric cancer patients. Two types of the chemotherapy, intraperitoneal (IP) and intraaortic (IA) administration, were carried out. The control group was comprised of 17 patients. The response of the chemotherapy for primary tumor was 36.4% in the IP group and 20% in the IA one. Among these patients, 2 of 11 in IP and 1 of 5 in IA were able to resect the primary tumor. The 50% survival time of IP, IA and control was 347, 227 and 78 days, respectively. One-year survival rates of IP, IA and control were 68%, 29% and 0%, respectively. IP showed a significantly longer survival rate than controls (p < 0.001). All but one patient was able to stay at home. Intraperitoneal chemotherapy showed both local and systemic effects in unresectable gastric cancer.

Aged↗
PubMed1994

Inhibition of prophenoloxidase-activating enzyme from Bombyx mori by endogenous chymotrypsin inhibitors.

Inhibitory activities for the activation of prophenoloxidase with its activating enzyme were detected in the gel-filtration fractions of hemolymph from Bombyx mori. The fractions with the highest activity contained chymotrypsin inhibitors; CI-13a, 13b, and 13c. They inhibited the activation of prophenoloxidase. The activating enzyme affected a synthetic substrate for trypsin, Boc-Gln-Ala-Arg-MCA: Km = 0.62 mM. CI-13c partially suppressed the peptidase activity.

Amino Acid Sequence↗
PubMed1994

Enhanced permeability of tetragastrin across the rat intestinal membrane and its reduced degradation by acylation with various fatty acids.

Three types of chemically modified tetragastrin (TG) with fatty acids such as acetyl-TG, caproyl-TG and lauroyl-TG were synthesized and their in vitro intestinal permeability characteristics were estimated by a modified Ussing chamber system using the isolated intestinal membrane of rats. The penetration of TG across the large intestine was increased by conjugation with acetic acid and caproic acid but not lauric acid. Lauroyl-TG, a highly lipophilic derivative, exhibited low permeability across the intestinal membrane. A "bell-shaped" profile was observed between the apparent permeability coefficients and lipophilicity of the acyl-TG derivatives. The stability of acyl-TG derivatives was examined in homogenates of the jejunum, proximal and distal large intestine, liver and plasma. The half-lives for the proteolysis of the TGs were significantly prolonged by chemical modification with fatty acids in each homogenate. Thus, the chemical modification of TG with some fatty acids not only increases the lipophilicity of TG but also reduces its degradation, which resulted in increased intestinal absorption. The extent of the conjugates' hepatic first-pass metabolism was evaluated by gastric acid secretion activities after i.v. and intraportal administration. The amount of gastric acid secretion after intraportal administration of TG was significantly reduced in comparison with that after i.v. administration. On the other hand, conjugation with caproic acid slightly suppressed TG's hepatic first-pass metabolism, which suggests that chemically modified TGs with fatty acids would be more stable than the native TG in the systemic circulation after intestinal absorption.

Acylation↗
PubMed1994

Vertebral bone-marrow changes in degenerative lumbar disc disease. An MRI study of 74 patients with low back pain.

We carried out MRI studies of 74 patients with end-plate and vertebral bone-marrow changes associated with degenerative lumbar disc disease. Abnormalities were classified into type A, with decreased signal intensities, and type B, with increased signal intensities on T1-weighted spin-echo images. Twenty-seven (73%) of the 37 patients with type-A changes had low back pain, in contrast to only four (11%) of the 37 patients with type-B changes. Lateral flexion-extension radiographs showed hypermobility in 26 patients (70%) with type-A changes, and in only six (16%) with type-B changes. Type-A changes correlated with segmental hypermobility and low back pain, while type-B changes were more common in patients with stable degenerative disc disease.

Adolescent↗
PubMed1994

[Effect of neuroleptanaesthesia on endocrine-metabolic response during upper abdominal surgery].

The effects of neuroleptanaesthesia on endocrine-metabolic changes during elective gastrectomy was investigated, comparing with those of epidural anaesthesia. Nine patients were given neuroleptanaesthesia and fifteen patients given thoracic epidural analgesia combined with general anaesthesia. We evaluated the levels of stress hormones, insulin and blood glucose. Epidural anaesthesia suppressed the increase of catecholamine, but neuroleptanaesthesia did not inhibit the elevation of the catecholamines. In neuroleptanaesthesia group, glucagon and growth hormone increased during surgery, and the levels of these hormones were significantly higher than those of epidural analgesia group. Blood glucose increased during operation in both groups. In epidural anaesthesia, the levels of insulin and insulin/glucose ratio were kept higher than those of neuroleptanaesthesia group, but this was not statistically significant. Lactate/pyruvate ratio and free fatty acid did not show any significant change during the study in both groups. These results suggest that neuroleptanaesthesia is not a suitable method for upper abdominal surgery.

Adult↗
PubMed1994

[Comparison of immunogenic regions in TSH receptor for Graves' IgG and Hashimoto's IgG].

Immunogenic regions in human TSH receptor responsible for autoimmune thyroid disease have been studied using synthetic TSH receptor-related peptides. Eight different peptides corresponding to segments of the extracellular domain of TSH receptor were synthesized. Immunoglobulin G (IgG) of patients with Graves' disease significantly bound to peptide #1 (32-56) compared with IgG of control subjects, and IgG of three of eight patients with Graves' disease showed increased binding to peptide #5 (309-337). In contrast, IgG of patients with Hashimoto's thyroiditis significantly bound to peptide #8 (333-359). The binding rates of Hashimoto's IgG to peptide #8 positively correlated with both MCHA and TGHA titers. These results suggest that heterogeneity of binding sites in TSH receptor for autoimmune thyroid disease may be responsible for pathophysiology of hyperthyroidism and hypothyroidism.

Binding Sites, Antibody↗
PubMed1994

Cerebral uptake of 99mTc-bicisate in patients with cerebrovascular disease in comparison with CBF and CMRO2 measured by positron emission tomography.

The regional brain uptake of 99mTc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethyl ester (99mTc-bicisate) measured by single photon emission computed tomography (SPECT) was compared with the regional CBF and CMRO2 measured by positron emission tomography in patients with cerebrovascular disease. Nine patients with the diagnosis of cerebral ischemic disorders (n = 7) or cerebral hemorrhage (n = 2) were studied. 99mTc-Bicisate brain uptake correlated with CBF and CMRO2. However, 99mTc-bicisate uptake did not reflect CBF in the single lesion showing luxury perfusion, which seemed to resemble a CMRO2 image. Though quantitative analysis showed the nonlinear correspondence of 99mTc-bicisate brain uptake with CBF and CMRO2, this correspondence could be corrected into a more linear relationship using a correction factor. 99mTc-Bicisate washout from the brain had no correlation to CBF and CMRO2. This diffuse decreasing washout rate was approximately 15% during the first hour after injection. By using the lipophilic fraction of arterial blood and a linearized correction of 99mTc-bicisate SPECT images, the feasibility of obtaining a factor-related CBF and CMRO2 was suggested from our data. These results suggested that 99mTc-bicisate had good characteristics for routine clinical use with SPECT to display the brain function in patients with neurological disorders.

Aged↗
PubMed1993

Participation in cellular prostaglandin synthesis of type-II phospholipase A2 secreted and anchored on cell-surface heparan sulfate proteoglycan.

Rat-liver-derived BRL-3A cells, which express both type-II phospholipase A2 (PLA2) and cytosolic PLA2 (cPLA2), generated prostaglandin E2 (PGE2) in the presence of fetal calf serum. When the cells were treated with tumor necrosis factor (TNF), PGE2 generation was greatly stimulated. The production of PGE2 observed in both cases was suppressed by a type-II PLA2-specific inhibitor, thielocin A1. Appreciable amounts of type-II PLA2 were released into the medium from the TNF-stimulated cells when heparin was added extracellularly. The release of type-II PLA2 from TNF-stimulated cells was also found in the presence of heparan sulfate or dextran sulfate, whereas other glycosaminoglycans showed no effects under the same conditions. These findings suggest that type-II PLA2 expressed in BRL-3A cells mostly associates with the cell surface by binding to cellular heparan sulfate proteoglycan. Removal of cell-surface-associated type-II PLA2, by either extracellular addition of heparin or by prior treatment of the BRL-3A cells with heparitinases, resulted in marked reduction of PGE2 synthesis in the cells. Exposure of BRL-3A cells to thrombin also induced the apparent secretion of type-II PLA2, and thrombin-stimulated PGE2 generation was suppressed by heparin effectively. Type-II PLA2 secreted and attached to heparan sulfate on the cell surface may therefore play an essential role in PGE2 synthesis by BRL-3A cells.

Animals↗
PubMed1993

Goniodomin A induces modulation of actomyosin ATPase activity mediated through conformational change of actin.

Goniodomin A, one of the polyether macrolides, isolated from the dinoflagellate Goniodoma pseudogoniaulax stimulated skeletal actomyosin ATPase activity 2-3 times, with a peak at 3 x 10(-8) to 3 x 10(-7) M. The effect of goniodomin A was dependent on the concentration of actin, but not of myosin. The actomyosin ATPase activity was increased by pretreatment of actin (but not of myosin) with goniodomin A. Goniodomin A induced a sustained and concentration-dependent increase in the fluorescence intensity (excitation wavelength, 277 nm; emission wavelength, 329 nm) of actin. The maximum response was obtained with concentrations of goniodomin A in the 10(-5) to 10(-4) M range in the presence of 5 microM F-actin. However, the ATPase activity and fluorescence intensity of myosin were not changed by goniodomin A at concentrations from 10(-8) to 10(-5) M. Interestingly, goniodomin A induced a remarkable but transient increase in the fluorescence intensity of actomyosin in a concentration-dependent manner, with a peak at 3 x 10(-7) M. This profile was quite similar to that found in the stimulation of the actomyosin ATPase activity induced by goniodomin A. To investigate further the effect of goniodomin A, actin was labeled with N-(1-pyrenyl)iodoacetamide. Goniodomin A at 10(-6) M had no effect on the fluorescence intensity of pyrenyl-actin (excitation wavelength, 365 nm; emission wavelength, 407 nm), but increasing concentrations of goniodomin A to 3 x 10(-6) M remarkably decreased its intensity. This effect was potentiated by heavy meromyosin. Actin molecules treated with goniodomin A were completely sedimented by mild centrifugation (for 15 min at 12,000 x g). Electron microscopic observations suggest that actin filaments associate with each other to form a gel in the presence of 3 x 10(-6) M goniodomin A. The conformational change of actin molecules, resulting from stoichiometric binding of goniodomin A to actin monomers in filaments, may modify the interaction between actin and myosin.

Actins↗
PubMed1993

Triggering of degranulation in mast cells by exogenous type II phospholipase A2.

We have previously shown the possibility that endogenous type II phospholipase A2 (PLA2) might participate in degranulation in mast cells (MC) (Murakami, M., et al. 1992. Eur. J. Biochem. 209:257). Now we have examined whether or not exogenously added type II PLA2 triggers MC degranulation. When rat peritoneal connective tissue MC (CTMC) were exposed to purified rat type II PLA2 at concentrations of more than 10 micrograms/ml, significant release of histamine was observed, whereas PGD2 was not generated under the same conditions. Mouse peritoneal CTMC as well as bone marrow-derived immature MC also responded to PLA2. Preincubation of CTMC with tyrosine kinase inhibitors, genistein, and herbimycin A, but not with pertussis toxin, resulted in abolition of the sensitivity to PLA2. The ability of type II PLA2 to induce histamine release was inhibited by an antibody or chemicals, both of which blocked the catalytic activity of type II PLA2. Heparin or an antibody recognizing the heparin-binding domain of type II PLA2 also suppressed the MC-degranulating activity, probably due to inhibition of binding of PLA2 to the cells. The interaction between heparan sulfate on cell surface and the heparin-binding domain of type II PLA2 may be important for the induction of exocytosis. The catalytic domain of the enzyme is also crucially important for the degranulation induction. Furthermore, we found that nerve growth factor, one of the potent regulators of MC function, significantly potentiated type II PLA2-induced histamine release from rat CTMC. These results suggest the possible role of extracellular type II PLA2 in activation of CTMC primed with nerve growth factor at inflamed sites.

Animals↗