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Biomedical subjects

K Murase

Publications and source records attributed to K Murase.

At least 19 recordsLinked to original sources

Human fibroblast cells synthesize and secrete nerve growth factor in culture.

Using our enzyme immunoassay system developed for recombinant hNGF, we examined the synthesis and secretion of human NGF (hNGF) by human fibroblast (WS-1) cells. The amount of the factor secreted by WS-1 cells increased linearly and a significant amount of NGF was detected in the conditioned medium of WS-1 cultures. WS-1 NGF showed properties identical to those of recombinant human NGF in immunoreactivity and molecular weight. An increase in cell density or the withdrawal of serum from the culture medium caused a drastic decrease in the rate of NGF secretion. These results suggest that WS-1 cells are able to synthesize and secrete hNGF in culture and that the synthesis/secretion is regulated in a growth phase-dependent manner.

Cell Division

Developmental changes in nerve growth factor level in rat serum.

In serum, nerve growth factor (NGF) forms a complex with alpha 2-macroglobulin (alpha 2M), which formation inhibits the immunoreactivity between NGF and its antibodies. For measuring the serum level of NGF, it is thus necessary to liberate NGF from the NGF-alpha 2M complex and prevent reformation of such complex. The pretreatment of rat serum with 1 M guanidine hydrochloride for a few hours and operation of the enzyme immunoassay (EIA) in the presence of guanidine hydrochloride provided a reliable means for determination of the NGF level in serum. By this procedure we followed the serum NGF level in rats developmentally. It increased from prenatal day 2 to postnatal day 5 and decreased slightly at postnatal week 3, thereafter remaining constant throughout adulthood. In pregnant rats, the NGF level in serum increased threefold to fivefold before birth and then decreased rapidly. These data suggest that serum NGF level may reflect the demand for this molecule during establishment of the peripheral nervous system.

Aging

Effects of nefiracetam, DM-9384 on amnesia and decrease in choline acetyltransferase activity induced by cycloheximide.

The effects of nefiracetam, [N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide, DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre-training administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. It protected against CXM-induced inhibition of choline acetyltransferase activity in the cerebral cortex. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with AChergic neuronal system and enhancing protein synthesis in the brain.

Amnesia

Induction of tolerance to ischemia: alterations in second-messenger systems in the gerbil hippocampus.

Preconditioning the brain with sublethal ischemia protects against neuronal damage following subsequent ischemic insult. Using [3H]inositol 1,4,5-triphosphate (IP3), [3H]phorbol 12,13-dibutyrate (PDBu), [3H]cyclic adenosine monophosphate (cAMP) and [3H]rolipram, we performed quantitative autoradiography to determine postischemic alterations in second-messenger systems in the gerbil hippocampus following preconditioning the brain with sublethal ischemia. At 7 days of reperfusion, no alterations were observed in brains subjected to 2 min of forebrain ischemia which produced no neuronal damage. However, 3-min ischemia caused a 75% reduction in [3H]IP3 binding (p < 0.01 vs. control) and 15-25% reductions in [3H]forskolin (p < 0.01 vs. control), [3H]cAMP (p < 0.05 vs. control), and [3H]rolipram (p < 0.01 vs. control) binding in the CA1 subfield coincident with histopathological CA1 pyramidal cell destruction, but no significant alterations in [3H]PDBu binding. Preconditioning the brain with 2 min of ischemia followed by 4 days of reperfusion prevented both histopathological cell death and the reductions in binding following subsequent 3 min of ischemia. Interestingly, [3H]IP3 and [3H]rolipram binding in CA1 showed a transient reduction, by 30% and 20% (both p < 0.01 vs. control), respectively, in the early reperfusion period. This downregulation of the IP3 system may play a role in the protection against cell death.

Animals

[A case of acute right ventricular infarction and life-saving right ventricular assistance following emergency coronary revascularization and resection of a left ventricular aneurysm--discussion of indication and proper assist flow volume].

Right ventricular assistance (RVA) using centrifugal pump in combination with IABP was used to treat a patient who was difficult to wean from a cardiopulmonary bypass following emergency coronary revascularization and resection of a ventricular aneurysm performed to treat acute right ventricular infarction due to a PTCA complication. After 131 hours of RVA at 3.2 to 4.8 l/min, it was possible to remove the pump. No heparin was administered during this time, changing the pump head twice, was used for 64 and 50 hour period, no thrombi were detected either time. After being weaned from RVA, the patient developed severe respiratory dysfunction, but on the 10th postoperative day (POD) IABP was weaned, and on the 13th POD the artificial respirator was withdrawn. The results of the postoperative cardiac catheterization were favorable, the patient was discharged on the 57th POD, and has returned to society at the present time. The indications for RVA include a central venous pressure > 20 mmHg and a cardiac index < 1.8 l/min/m2, and tissue perfusion pressure and general preoperative condition should severe as guides. The higher the assisted flow volume the more efficacious in relieving ventricular load, but, since there is a limit to how much the left ventricle and lungs can withstand, it should not exceed levels which ensure the maintainance of cardiac output and tissue perfusion pressure.

Angioplasty, Balloon, Coronary

[Experience of intravascular ultrasound imaging on a stenosed saphenous vein graft].

A 73-year-old man underwent coronary-artery bypass grafting surgery on #4 PD and #7 with saphenous vein graft. Coronary arteriography and graft visualization performed on the 28th postoperative day revealed 75% concentric stenosis in the middle of the #4 PD graft. Before and after PTCA to the graft, examination by intravascular ultrasound imaging was performed and revealed that the stenosis was caused by fibrotic atheroma or thrombus. Intravascular ultrasound imaging appears to be useful in the field of cardiac surgery. It can be used in the follow-up of bypass grafts and also the detection of the entry site in dissecting aortic aneurysms. A brief review of the literature is given.

Aged

[A case of carcinosarcoma of the lung].

A 78-year-old man was admitted to our hospital with cough and left anterior chest pain. Chest X-ray examination on admission revealed a tumor shadow in the left upper lobe. Malignant tumor cells were observed on histopathological examination of a specimen obtained by bronchoscopic biopsy. Radiotherapy was performed but was not effective, and the patient died of respiratory failure 4 months after admission. Autopsy revealed a 15 cm diameter tumor with marked local invasion tendency without distant metastasis. Microscopically, the tumor consisted partly of squamous cell carcinomas, and partly of fibrosarcomas, composed of spindle cells and osteo-chondrosarcoma. The tumor was therefore diagnosed as carcinosarcoma. Immunohistochemical examination showed positive keratin and EMA staining only in the squamous cell carcinoma component of the tumor.

Aged

Kinetic behavior of technetium-99m-HMPAO in the human brain and quantification of cerebral blood flow using dynamic SPECT.

The kinetic behavior of 99mTc-hexamethylpropyleneamine oxime (HMPAO) in the human brain was investigated in 11 patients with various brain diseases (176 regions), using dynamic SPECT and a four-compartment model with five parameters (K1: rate constant for the transport of HMPAO from blood to brain, K2: backdiffusion from brain to blood, K3: conversion to a hydrophilic form in the brain, K5: conversion to a nondiffusible form in the blood, and fa: fraction of radioactivity attributable to the vascular compartment). Although K1 correlated well with cerebral blood flow (CBF) measured by the 133Xe inhalation method (Xe-CBF) (r = 0.888), its value was underestimated by 28.9% +/- 11.9%, indicating a low extraction fraction (E) for HMPAO. From E = K1/CBF, a regression equation of E = 0.857 - 0.00335. Xe-CBF was obtained. Significant correlations were observed for K2 versus Xe-CBF (r = 0.679), for K3 versus Xe-CBF (r = 0.483), for K3/(K2 + K3) versus Xe-CBF (r = -0.487), for K3/K2 versus Xe-CBF (r = -0.501), and for K2 + K3 versus Xe-CBF (r = 0.655), but not for K1/K2 versus Xe-CBF (r = 0.005). Thus, this model was useful for elucidating the kinetic behavior of HMPAO in the human brain, and correction for E appears to be indispensable for accurate CBF quantification using HMPAO.

Adult

[MR imaging of adrenal masses smaller than 5 cm. Characterization with T2 relaxation time at 1.5 T].

The T2 relaxation times of 28 adrenal masses smaller than 5 cm obtained using a 1.5 Tesla MR imaging system were analysed to evaluate the ability of this parameter to characterize the tissue masses. The adrenal masses included 13 nonhyperfunctioning adenomas, five hyperfunctioning adenomas, five metastatic tumors, two pheochromocytomas, one nodular hyperplasia, one ganglioneuroma, and one cyst. The mean T2 value of nonhyperfunctioning adenomas was almost the same as that of hyperfunctioning adenomas. A significant difference was found in T2 (p less than 0.01) between nonhyperfunctioning adenoma (50 msec +/- 7 msec; mean +/- S.D.) and metastatic tumor (63 msec +/- 11 msec), whereas there was no significant difference in mass size between them. The two pheochromocytomas and the ganglioneuroma, which were derived from adrenal medulla, had relatively long T2 of over 70 msec. The T2 values of nodular hyperplasia and adrenal cyst were 58 msec and 123 msec, respectively. Although the T2 values of metastatic tumors tended to be longer than those of nonhyperfunctioning adenomas, differentiation between them with a T2 of 60 msec was not necessarily possible, especially in smaller masses. The T2 values of two metastatic tumors of less than 2 cm indicated 50 msec levels. There seemed to be a correlation between mass size and T2 in metastatic tumors. In adenomas, however, no significant correlation was demonstrated. We conclude that the characterization of small adrenal masses by T2 at 1.5 Tesla is unsatisfactory in differentiating metastatic tumors from nonhyperfunctioning adenomas.

Adrenal Gland Diseases

Involvement of serotonergic neuronal systems in the anti-amnesic action of naftidrofuryl oxalate.

The effects of naftidrofuryl oxalate on cycloheximide- and 5-hydroxytryptophan (5-HTP)-induced amnesia were investigated using a passive avoidance task in mice. Naftidrofuryl oxalate significantly improved the cycloheximide-induced amnesia. This effect of naftidrofuryl oxalate was antagonized by 5-HTP, a serotonin (5-HT) precursor, and by p-chloroamphetamine (PCA), a 5-HT releaser. Single administration of 5-HTP in combination with pargyline, a monoamine oxidase inhibitor, induced amnesia (5-HTP-induced amnesia). This amnesia was attenuated by ritanserin, a 5-HT2-selective antagonist, but not by pindolol, a 5-HT1-selective antagonist. Naftidrofuryl oxalate also attenuated the 5-HTP-induced amnesia. A binding study revealed that naftidrofuryl oxalate inhibited the binding of [3H]ketanserin to 5-HT2 receptors in mouse brain synaptic membrane in a dose-dependent fashion (IC50 = 1.42 x 10(-7) M), but did not inhibit that of [3H]serotonin to 5-HT1 receptors. These results suggest that naftidrofuryl oxalate may attenuate cycloheximide- and 5-HTP-induced amnesia by blocking 5-HT2 receptor subtypes.

Amnesia

Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis.

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.

Animals

[Detection of common bile duct stones by hepatobiliary scintigraphy].

Hepatobiliary scintigraphy and direct X-ray cholangiography were compared in 29 patients with common bile duct (CBD) stones confirmed at surgery. The scintigraphic findings included no visualization of the biliary system (NV), pooling of bile in the biliary system (PB), prolonged transit time over 60 min (PTT), filling defect in the CBD image (FD), and reflux of bile toward the intrahepatic ducts after gallbladder stimulation (RB). The positive rates of NV, PB, PTT, FD, and RB in patients with CBD stones were 7%, 31%, 17%, 48%, and 14%, respectively. One or more of these five findings was found in 83%. Although the NV was a useful finding suggesting complete obstruction of the CBD, it shared little in the diagnosis of CBD stone. The positive rate of the PB was relatively high and it would be a useful finding as an indication of the presence of passage disturbance of the CBD. The PB was usually accompanied by the FD. The PTT had some usefulness in the detection of incomplete obstruction of the CBD in patients with a visualized gallbladder. In patients with no visualization of the gallbladder, however, the transit time tended to be shorter than that of gallbladder visualized patients. Therefore, the judgment of PTT in patients with no visualized gallbladder needed another criteria. The FD was the most frequent among the five findings and the sites of FD correlated well with CBD stones on direct X-ray cholangiography. The FD would be a reliable finding indicating CBD stone or CBD stenosis. Although the RB was a finding limited in patients with a visualized gallbladder, it seemed to be a helpful findings for the detection of CBD stone in patients with a mildly dilated CBD.

Adult

Pharmacological properties of YM461, a new orally active platelet-activating factor antagonist.

The antagonistic effect of YM461 [1-(3-phenylpropyl)-4-[2- (3-pyridyl)thiazolidin-4-ylcarbonyl]piperazine fumarate] against platelet-activating factor (PAF) was examined in several in vitro and in vivo systems. We found that YM461 inhibited [3H]PAF binding to rabbit platelet membranes with a pKi value of 8.90. YM461 inhibited PAF induced rabbit and human platelet aggregation with pA2 values of 7.52 and 7.29, respectively; the slopes of the Schild plots were 1.07 and 1.01, respectively. However, YM461 at 10(-4)M did not affect rabbit and human platelet aggregation induced by ADP, collagen, arachidonic acid or epinephrine. YM461 inhibited PAF induced death in mice with an ED50 (50% effective dose) value of 0.35 mg/kg p.o. YM461 at doses above 0.3 mg/kg i.v. inhibited PAF induced hypotension in rats. YM461 showed a dose-dependent inhibition of PAF induced hemoconcentration in rats with ED50 values of 0.15 and 0.21 mg/kg p.o., respectively, at 0.5 and 1 hr after oral administration. The anti-PAF effect of YM461 persisted more than 6 hr after 3 mg/kg p.o. in rats. YM461 inhibited the bronchoconstriction induced by PAF with an ED50 value of 1.2 mg/kg p.o. in anesthetized guinea pigs. Furthermore, the compound at doses above 3 mg/kg p.o. significantly inhibited antigen-induced anaphylactic asthma in conscious guinea pigs pretreated with mepyramine and propranolol. These results indicate that YM461 is a selective, potent and orally active PAF antagonist.

Administration, Oral

ECG-gated thallium-201 myocardial SPECT in patients with old myocardial infarction compared with ECG-gated blood pool SPECT.

We evaluated one of the merits of ECG-gated thallium-201 single photon emission computed tomography (g-T1 SPECT), i.e., the ability to appreciate left ventricular (LV) wall motion. LV wall motion assessed by g-T1 SPECT and by ECG-gated Blood Pool SPECT (g-BP SPECT) was classified into three grades and compared segment by segment. T1-201 uptake by g-T1 SPECT was also classified into three grades and compared with those of wall motion in g-BP SPECT. Fifty patients with prior myocardial infarction were injected intravenously at rest with 111 to 185 M Bq (3 to 5 mCi) of Tl-201. The left ventricular regions were divided into anterior, septal, inferior and lateral segments (50 patients X 4 segments = 200 segments in total). The grades of wall motion and Tl-201 uptake detected by g-Tl SPECT correlated well with those of wall motion in g-BP SPECT (94.5% and 85%, respectively). With g-Tl SPECT it was possible to evaluate left ventricular wall motion, providing clear perfusion images.

Adult

Intravascular malignant lymphomatosis: a case of T-cell lymphoma probably associated with human T-cell lymphotropic virus.

Intravascular malignant lymphomatosis (IML) is an unusual condition characterized by proliferation of lymphoma cells exclusively within the blood vessels. Most of the cases reported are of B-cell origin. We report a rare case of T-cell IML probably associated with human T-lymphotropic virus (HTLV-1) infection. The present case suggests that T-cell lymphoma and HTLV-1-associated lymphoma occasionally represent a form of intravascular proliferation.

Aged

Glutamate receptor agonist-induced inward currents in spinal dorsal horn neurons dissociated from the adult rats.

Inward currents to glutamate receptor agonists, quisqualate (QA), kainate (KA) and N-methyl-D-aspartate (NMDA) were examined in spinal dorsal horn neurons by whole-cell voltage-clamp techniques after acute dissociation. Neurons were dissociated from the superficial dorsal horn (laminae I/II) of the adult rat (8-16 weeks old) spinal cords by enzymatic and mechanical treatment. The KA-induced current was sustained during KA application, while the QA- and NMDA-induced currents were attenuated. The NMDA response was augmented dose-dependently by addition of glycine (10(-7)-5 X 10(-6) M) and became obscure in the absence of glycine. The NMDA current was depressed by D-2-amino-5-phosphonovaleric acid (APV). Analyses of dose-response curves of these inward currents indicate that both the QA and KA currents were competitively blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), while the NMDA current was blocked non-competitively.

2-Amino-5-phosphonovalerate

Early and delayed I-123 IMP SPECT in epileptic patients with partial seizures and normal CT.

Forty-six epileptic patients with partial seizures and normal CT underwent 48 examinations of early and delayed SPECT using I-123 IMP in the interictal phase. One of them underwent a follow-up SPECT in a more stable state compared to the first SPECT. Another patient, with informed consent, underwent a follow-up SPECT in combination with pharmacologic activation with bemegride. Early SPECT was performed 30 minutes after an IMP injection and delayed SPECT 4 to 4 1/2 hours later. Temporal changes in uptake pattern were visually classified into six types and compared with known patterns of SPECT uptake in relation to ischemic, hyperemic, and other changes. These were also correlated with the amount of epileptic activity seen on the EEG.

Adolescent

[Effects of YM-13650 on type I to type IV allergic reactions and immune responses in animals].

The effects of YM-13650 on experimental animal models of cell-mediated immune responses (type IV), antibody formation and type I to type III allergic reactions were investigated. YM-13650 in the dose range of 6.3 to 100 mg/kg, p.o., inhibited the picrylchloride-induced delayed type hypersensitivity (Pc-DTH) in mice when administered during the induction and the effector phases. The compound also inhibited the Pc-DTH enhanced by the pretreatment with cyclophosphamide, and even bilateral adrenalectomy failed to reduce the inhibitory effect of the compound on Pc-DTH in mice. YM-13650 in doses of 25 and 50 mg/kg, p.o., prolonged the survival time of allogenic skin grafts in mice. However, no significant effect was observed on hapten-specific IgE and HA antibody production and PFC formation in mice in doses up to 300 mg/kg, p.o. YM-13650 inhibited the passive Arthus reaction in guinea pigs and the reversed passive Arthus reaction in rats (type III). On the other hand, YM-13650 did not show any inhibitory effect on passive cutaneous anaphylaxis in rats (type I), Forssman shock in guinea pigs (type II) and carrageenin-induced paw edema in rats. These results indicate that YM-13650 suppresses not only cell-mediated immune responses but also type III allergic reactions without any influence on type I and type II allergic reactions as well as an acute inflammatory reaction.

Animals