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Biomedical subjects

M Muraki

Publications and source records attributed to M Muraki.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of TYB-2285 on early and late bronchial responses and airway hyperreactivity in actively sensitized guinea pigs.

1. The effect of a new antiasthmatic drug, TYB-2285 [3,5-bis (acetoxyacetylamino)-4-chlorobenzonitrile], on dual bronchoconstriction and airway hyperreactivity in actively sensitized guinea pigs was investigated. 2. Immediate and late bronchial responses were induced at 1-10 min and 4-7 hr after antigen inhalation, respectively. Guinea pigs were pretreated with TYB-2285 (300 mg kg(-1) PO, as a single dose or consecutively for 7 days). 3. The immediate bronchial response was inhibited only by a multiple administration of TYB-2285. Late bronchial response was inhibited by both administration methods. 4. The numbers of eosinophils, neutrophils and macrophages, but not lymphocytes, in the bronchoalveolar lavage fluid were increased at 4 hr after antigen inhalation. TYB-2285, given singly and consecutively, decreased the numbers of total cells, eosinophils, neutrophils and macrophages. 5. Sensitized guinea pigs showed significant airway hyperreactivity to inhaled histamine. This airway hyperresponsiveness was reversed by a single administration of TYB-2285. 6. Luminol-dependent chemiluminescence of airway-infiltrated cells was slightly inhibited by TYB-2285 (20 microg ml(-1)). 7. The present study shows that TYB-2285 inhibits late asthmatic response and airway hyperresponsiveness, presumably by inhibiting the accumulation and activation of eosinophils and other inflammatory cells.

Animals↗
PubMed1998

Role of GABA receptors in the bronchial response: studies in sensitized guinea-pigs.

BACKGROUND: Gamma-aminobutyric acid (GABA), an important inhibitory neurotransmitter in the mammalian central nervous system, is also found in peripheral tissues, including the lung. GABA has recently been shown to modulate the contraction of airway smooth muscle. OBJECTIVE: We studied the effect of GABA on the contractile properties of tracheal smooth muscle by measuring the tension of the trachea isolated from non-sensitized and ovalbumin (OA)-sensitized guinea-pigs under isometric conditions. METHODS: Guinea-pigs were sensitized by intraperitoneal doses of OA to prepare a bronchial asthma model. Tracheal spiral rings were prepared from the OA-sensitized as well as normal, non-sensitized guinea-pigs. Using the tracheal preparations, the effects of GABA and GABAa and GABAb receptor agonists (muscimol and baclofen) and antagonists (bicuculline and saclofen) on the basal tone of the trachea and on tracheal contraction induced by electrical field stimulation (EFS) were determined. The effect of GABA on tracheal contraction induced by exogenous acetylcholine was also studied. RESULTS: GABA and GABA agonists and antagonists had no effect on the basal tone of normal guinea-pig tracheae. Both GABAa and GABAb receptor agonists, as well as GABA, suppressed EFS-induced contraction of normal guinea-pig tracheae in a reversible, dose-dependent manner. Moreover, this suppression was reserved to the control level by either GABAa and GABAb receptor antagonists. In tracheal spiral ring prepared from OA-sensitized guinea-pigs, GABA and baclofen caused a smaller reversible inhibition of EFS-induced contraction than in normal tracheal spiral ring, while muscimol inhibited EFS-induced tracheal contraction to a similar extent to that observed in normal tracheae. GABA had no effect on the tracheal contractile response to acetylcholine. CONCLUSION: The results suggest that there may be a biological mechanism mediated by prejunctional GABAb receptors which attenuates cholinergic contraction of airway smooth muscle and that dysfunction of the receptors may underlie the airway obstruction in asthmatics.

Acetylcholine↗
PubMed1998

Postcontrast magnetic resonance imaging to predict progression of traumatic epidural and subdural hematomas in the acute stage.

OBJECTIVE: We investigated the possibility of predicting the progression of traumatic epidural hematomas (EDHs) and subdural hematomas (SDHs), in the acute stage, by using postcontrast magnetic resonance imaging (MRI) with gadolinium-diethylenetriaminepentaacetic acid. METHODS: From January 1990 through December 1996, 41 patients with 43 hematomas (21 EDHs and 22 SDHs) underwent postcontrast MRI within 24 hours after injury. T1-weighted MRI was performed by using the spin echo method, after the administration of 0.1 mmol/kg gadolinium-diethylenetriaminepentaacetic acid, immediately after computed tomographic scanning. RESULTS: All of the enhanced hematomas were enlarged, whereas nonenhanced hematomas, except for two SDHs with bleeding tendencies, remained unchanged or decreased in volume. The prediction rates for enlargement with this method were 100% (21 of 21) for EDHs and 91.0% (20 of 22) for SDHs. The sensitivity of this test in predicting enlargement was 100% (15 of 15) for EDHs and 81.8% (9 of 11) for SDHs. The specificity was 100% for both types of hematomas. The enlargement rates for diffusely enhanced hematomas were statistically greater than those for nonenhanced hematomas. All of the patients with diffusely enhanced hematomas, which were found during surgery to exhibit active bleeding points, experienced consciousness deterioration. CONCLUSION: We conclude that diffuse enhancement indicates extravasation from broken vessels that continue to bleed and that diffusely enhancing hematomas will be rapidly enlarged. We think that postcontrast MRI can be very useful for predicting the progression of acute EDHs and SDHs.

Acute Disease↗
PubMed1998

Theophylline suppresses the release of interleukin-4 by peripheral blood mononuclear cells.

To elucidate the mechanism of the anti-inflammatory effect of theophylline, peripheral blood mononuclear cells (PBMCs) collected from patients with bronchial asthma who had a RAST score for Dermatophagoides farinae (Df) > = 3 were stimulated with Df antigen, and the interleukin-4 (IL-4) production by the stimulated PBMCs was determined in the presence and absence of theophylline. The stimulated IL-4 production in the PBMCs was significantly suppressed by simultaneous treatment with theophylline (8 microg/ml). Furthermore, the intracellular 3',5'-adenosine monophosphate (cAMP) level following stimulation with Df was significantly higher in PBMCs simultaneously treated with theophylline (8 microg/ml) than in nontreated controls. These results suggest that theophylline suppresses the IL-4 production in inflammatory cells by increasing the intracellular cAMP level; this effect may thus provide an additional basis for the benefit of theophylline in antiasthmatic therapy.

Adult↗
PubMed1998

Plasma concentrations of brain natriuretic peptide in patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hyponatremia after subarachnoid hemorrhage (SAH) is commonly associated with diuresis and natriuresis, but the causes are still controversial. We investigated whether brain natriuretic peptide (BNP) was related to such hyponatremia. METHODS: Plasma BNP concentrations were measured by immunoradiometric assay in 18 patients at 0 to 2 days (period 1), 7 to 9 days (period 2), and > 14 days (period 3) after SAH. Plasma concentrations of antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and noradrenaline were also measured during period 2. RESULTS: The 11 patients with hyponatremia (serum sodium concentration of < 135 mEq/L) had much higher plasma BNP concentrations during each period than did healthy controls (P < 0.05), whereas the 7 patients with normonatremia did not show statistically higher values. In the patients with hyponatremia, the plasma BNP concentration during period 2 was statistically higher than that during periods 1 and 3 (P < 0.05). The plasma noradrenaline concentration during period 2 was higher in patients with hyponatremia than in those with normonatremia (P < 0.05), whereas the plasma concentrations of ADH and ANP during period 2 were not statistically different between the hyponatremic and normonatremic patients. CONCLUSIONS: We conclude that BNP may be related to hyponatremia associated with natriuresis following SAH. The increase of noradrenaline may promote the secretion of BNP.

Acute Disease↗
PubMed1997

X-ray structure of turkey-egg lysozyme complex with tri-N-acetylchitotriose. Lack of binding ability at subsite A.

The turkey-egg lysozyme (TEL) complex with tri-N-acetylchitotriose [(GlcNac)3] was co-crystallized from 1.5% TEL and 2 mM (GlcNac)3 at pH 4.2. The crystal structure was determined by molecular replacement and refined to an R value of 0.182 using 10-1.77 A data. The (GlcNac)3 molecule occupies the subsites A, B and C. At the subsites B and C, the sugar residues are bound in a similar manner to that found in the hen-egg lysozyme (HEL) complex. In contrast, the GlcNac residue at the subsite A is exposed to bulk solvent and has no contact with the protein molecule because the active residue Asp101 in HEL is replaced by Gly in TEL. A sulfate ion is bound in the vicinity of subsite B and forms hydrogen bonds with the sugar residue and the guanidino group of Arg61, assisting the binding of the sugar residue to subsite B. The active-site cleft of TEL is narrower than that of native TEL, thus attaining the best fit of the (GlcNac)3 molecule. The lack of binding ability of subsite A is discussed in relation to the catalytic properties of TEL. The result suggests that the cleavage pattern of oligosaccharide substrates in the catalytic reaction is regulated by the protein-sugar interaction at subsite A.

Journal Article↗
PubMed1997

Importance of van der Waals contact between Glu 35 and Trp 109 to the catalytic action of human lysozyme.

The importance of van der Waals contact between Glu 35 and Trp 109 to the active-site structure and the catalytic properties of human lysozyme (HL) has been investigated by site-directed mutagenesis. The X-ray analysis of mutant HLs revealed that both the replacement of Glu 35 by Asp or Ala, and the replacement of Trp 109 by Phe or Ala resulted in a significant but localized change in the active-site cleft geometry. A prominent movement of the backbone structure was detected in the region of residues 110 to 120 and in the region of residues 100 to 115 for the mutations concerning Glu 35 and Trp 109, respectively. Accompanied by the displacement of the main-chain atoms with a maximal deviation of C alpha atom position ranging from 0.7 A to 1.0 A, the mutant HLs showed a remarkable change in the catalytic properties against Micrococcus luteus cell substrate as compared with native HL. Although the replacement of Glu 35 by Ala completely abolished the lytic activity, HL-Asp 35 mutant retained a weak but a certain lytic activity, showing the possible involvement of the side-chain carboxylate group of Asp 35 in the catalytic action. The kinetic consequence derived from the replacement of Trp 109 by Phe or Ala together with the result of the structural change suggested that the structural detail of the cleft lobe composed of the residues 100 to 115 centered at Ala 108 was responsible for the turnover in the reaction of HL against the bacterial cell wall substrate. The results revealed that the van der Waals contact between Glu 35 and Trp 109 was an essential determinant in the catalytic action of HL.

Catalysis↗
PubMed1997

Brain metastasis in malignant pleural mesothelioma.

A 55-year-old male who had a remote history of occupational asbestos exposure consulted us because of chest pain. Chest X-ray revealed diffuse pleural thickening and pleural effusion on the right. A diagnosis of malignant mesothelioma, biphasic type was made by needle pleural biopsy. Fourteen months later, the patient died of brain metastasis. At autopsy, malignant mesothelioma of the pleura with metastasis to the brain and bilateral adrenal glands was observed. Brain metastases proven by autopsy are rare in cases of malignant mesothelioma. The ferruginous body count in the lung tissue was 16 per gram of wet weight.

Adrenal Gland Neoplasms↗
PubMed1996

Origin of carbohydrate recognition specificity of human lysozyme revealed by affinity labeling.

In order to reveal the origin of carbohydrate recognition specificity of human lysozyme by clarifying the difference in the binding mode of ligands in the active site, the inactivation of human lysozyme by 2',3'-epoxypropyl beta-glycoside derivatives of the disaccharides, N,N'-diacetylchitobiose [GlcNAc-beta-(1-->4)-GlcNAc] and N-acetyllactosamine [Gal-beta-(1-->4)-GlcNAc], was investigated and the three-dimensional structures of the affinity-labeled enzymes were determined by X-ray crystallography at 1.7 A resolution. Under the conditions comprising 2.0 x 10(-3) M labeling reagent and 1.0 x 10(-5) M human lysozyme at pH 5.4, 37 degrees C, the reaction time required to reduce the lytic activity against Micrococcus luteus cells to 50% of its initial activity was lengthened by 3.7 times through the substitution of the nonreducing end sugar residue, GlcNAc to Gal. The refined structure of human lysozyme labeled by 2',3'-epoxypropyl beta-glycoside derivatives of N,N'-diacetylchitobiose (HL/NAG-NAG-EPO complex) indicated that the interaction mode of the N,N'-diacetylchitobiose moiety in substites B and C in this study was essentially the same as in the case of the complex of human lysozyme with the free ligand. On the other hand, the hydrogen-bonding pattern and the stacking interaction at subsite B were remarkably different between the HL/NAG-NAG-EPO complex and human lysozyme labeled by the 2',3'-epoxypropyl beta-glycoside of N-acetyllactosamine (HL/GAL-NAG-EPO complex). The reduced number of possible hydrogen bonds as well as the less favorable stacking between the side chain of Tyr63 in human lysozyme and the galactose residue in the HL/GAL-NAG-EPO complex reasonably explained the less efficient ability of the 2',3'-epoxypropyl beta-glycoside of N-acetyllactosamine as compared to that of N,N'-diacetylchitobiose as an affinity labeling reagent toward human lysozyme.

Affinity Labels↗
PubMed1996

Assessment of serum CYFRA 21-1 in lung cancer.

BACKGROUND: Cytokeratins are the intermediate filaments of the cytoskeletal protein located in normal epithelia, tumor, and cultured cells. Recently, a fragment of cytokeratin subunit 19, referred to as CYFRA 21-1, detected in the serum of patients with nonsmall cell lung cancer, has been reported as a new tumor marker. This article reports the results of a study of serum fragment CYFRA 21-1, measured by immunoradiometric assay, as a marker of lung cancer. METHODS: One hundred fourteen patients with primary lung cancer, 6 patients with malignant solid tumor, 116 patients with a variety of benign diseases, and 29 normal individuals were entered into the study. Serum CYFRA 21-1 levels were obtained by means of immunoradiometric assay using the CYFRA 21-1 EIA (enzyme immunoassay) kit. In addition, we studied other tumor markers, including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE), as a means of lung cancer diagnosis. RESULTS: The diagnostic accuracy and sensitivity of serum CYFRA 21-1 for the detection of lung cancer were highest among the four markers. The serum CYFRA 21-1 levels were most highly elevated in lung carcinoma patients (in particular UICC Stage IV patients) across different histologic types and attained 85.1% sensitivity when using a threshold of 3.5 ng/mL. The diagnostic sensitivity for detecting lung carcinoma was substantially enhanced by means of combined assays of CYFRA 21-1 with CEA overall for lung cancer, with SCC for squamous cell carcinoma, and with CEA for adenocarcinoma. CONCLUSIONS: These findings suggest that serum assays of CYFRA 21-1 are clinically useful for the diagnosis of lung carcinoma.

Adolescent↗
PubMed1996

Revascularization in nontraumatic osteonecrosis of the femoral head.

To study the revascularization pattern of nontraumatic osteonecrosis, superselective angiography of the femoral medical circumflex artery was done twice on 13 hips for which no treatment had been given. Angiographic evaluation of the hips with early-stage osteonecrosis not visible on radiographs showed the absence of superior retinacular arteries from the stump in all hips. Penetration of small vessels was seen on 6 hips. Bony scintigraphy of 13 hips and magnetic resonance imaging of 9 hips were taken at about the same time. Bony scintigraphy and magnetic resonance imaging results were positive in 11 of 13 hips and in all 9 hips, respectively. The patients were observed until evidence of necrosis appeared on radiographs. When this sign became evident, a second angiography was conducted, which indicated the penetration of erratically formed vessels with increase in size in 12 hips. It was assumed that the blood supply from the superior retinacular arteries was interfered with in large areas of the femoral head and that revascularization started with the formation of small vessels, followed by further penetration of large vessels.

Adolescent↗
PubMed1996

Glioblastoma multiforme in the left frontal lobe subsequent to malignant lymphoma in the right orbit.

A 62-year-old male presented with glioblastoma multiforme in the left frontal lobe manifesting as motor aphasia, subsequent to a malignant lymphoma in the right orbit. He underwent subtotal removal of the right orbital mass presenting as right exophthalmos which was shown by histological examination to be non-Hodgkin's lymphoma. He received 30 Gy Lineac irradiation to the right orbit. His post-operative course was satisfactory. Magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) 7 months later demonstrated a small spotty enhanced lesion in the left frontal lobe. He developed motor aphasia 1 year after irradiation. MR imaging disclosed an enhanced mass in the left frontal lobe, which was totally removed. Histological examination revealed glioblastoma multiforme. Patients with malignant lymphoma may develop a subsequent second malignant tumor. MR imaging with Gd-DTPA is quite useful for early detection of a second brain tumor.

Brain Neoplasms↗
PubMed1995

Site-directed mutagenesis and sugar-binding properties of the wheat germ agglutinin mutants Tyr73Phe and Phe116Tyr.

Wheat germ agglutinin is a dimeric lectin composed of two identical subunits. Each subunit consists of four homologous hevein-like domains of 42 or 43 amino acids each. Amino acid residues at the same position in each domain involved in sugar binding are thought to play a similar role in sugar binding. In order to clarify the role of the amino acid residue at domain position 30 of wheat germ agglutinin isolectin 2 (WGA2) in sugar binding, two WGA2 variants each containing a mutation, either Tyr73-->Phe (domain B) or Phe116-->Tyr (domain C), were produced. The binding activity for (GlcNAc)3 and the three-dimensional structure of these mutants were characterized by comparing with the properties of wild-type WGA2. Equilibrium dialysis experiments using (GlcNAc)3 indicated that the mutation Tyr73-->Phe reduced the overall sugar-binding activity at both pH 5.9 and pH 4.7. In addition, positive cooperativity toward (GlcNAc)3 binding was observed at pH 4.7. In contrast, the mutation of Phe116-->Tyr increased the overall sugar-binding activity at pH 5.9, but reduced this activity at pH 4.7 without changing the number of sugar-binding sites. Positive cooperativity was not observed at pH 5.9 or pH 4.7. X-ray crystallographic analysis of mutant WGA2 revealed that the mutation of Tyr73-->Phe caused a side chain movement of the Glu115 residue of the opposite subunit that formed a hydrogen bond with Tyr73 in wild-type WGA2. No changes were observed in the backbone structure and the disposition of the benzene ring of Phe73. The mutation Phe116-->Tyr caused the formation of a new hydrogen bond between Tyr116 and Glu72 of the opposite subunit. The changes in the sugar-binding properties in WGA2 mutants are discussed in relation to the structural change at the binding site.

Base Sequence↗
PubMed1995

X-ray structure of turkey egg lysozyme complex with di-N-acetyl-chitobiose. Recognition and binding of alpha-anomeric form.

The crystalline complex of turkey-egg lysozyme (TEL) with di-N-acetylchitobiose (NAG2) was prepared by a soaking method and the structure was determined by X-ray analysis at 1.55 A resolution. The structure was refined to an R value of 0.175 by simulated annealing and energy minimization. The alpha-anomer of NAG2 is located at subsite D with the orientation perpendicular to the direction of the active-site cleft. The anomeric residue is deeply inserted into the cleft and the O1-H hydroxyl group is hydrogen bonded to the carboxyl group of Glu35 which is a catalytic residue. The other sugar residue protrudes outside the cleft and is in van der Waals contact with the beta-sheet region comprising of residues 43-53. The binding of NAG2 makes the active-site cleft 0.3-0.5 A narrower and suppresses the thermal motion of two lobes constructing the cleft. The NAG2 molecule is bound in a manner not assumed in the catalytic action of the enzyme and the geometry of binding indicates that the alpha-anomer blocks the active center and acts only as an inhibitor.

Journal Article↗
PubMed1994

Alteration of the substrate specificity of human lysozyme by site-specific intermolecular cross-linking.

Human lysozyme dimers were prepared by the intermolecular cross-linking of the monomer that contained the mutation of either Arg41 to Cys or Ala73 to Cys with a divalent maleimide compound. Among the three kinds of possible dimers only R41C-R41C dimer, in which the two catalytic clefts can come close to each other due to the proximity of the conjugation site to the active sites, turned out to be 2.3 times more specific to a polymer substrate, ethylene glycol chitin, as compared to an oligomer substrate, PNP-(GlcNAc)5. The result indicates that it is possible to alter the substrate specificity of an enzyme by artificially controlling the orientation of the active sites.

Alanine↗
PubMed1994

The effect of TYB-2285 on dual phase bronchoconstriction and airway hypersensitivity in guinea-pigs actively sensitized with ovalbumin.

The effect of a new anti-asthmatic drug, TYB-2285 (3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile), was investigated in ovalbumin-sensitized guinea-pigs. When guinea-pigs were pretreated with TYB-2285 (300 mg kg-1, p.o., single dose or consecutively for 7 days), the immediate asthmatic response was inhibited as demonstrated by diminished cyanosis, but not the bronchoconstriction. TYB-2285, given singly or consecutively, inhibited the appearance of late asthmatic response and the infiltration of inflammatory cells, such as eosinophils, into the airway. Additionally, airway hyper-responsiveness was also reversed by the single administration of TYB-2285. Luminol-dependent chemiluminescence of airway-infiltrated cells stimulated with A23187 was inhibited by TYB-2285 in a dose-dependent manner. The present study suggests that TYB-2285 inhibits late asthmatic response and airway hyperresponsiveness by inhibiting the accumulation of eosinophils and other inflammatory cells into the airway, and also by inhibiting the production of oxygen radicals from airway-infiltrated cells.

Animals↗