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M Kondoh

Publications and source records attributed to M Kondoh.

At least 73 records · Page 4Linked to original sources
PubMed1993

Ro 09-1470 is a selective inhibitor of P-450 lanosterol C-14 demethylase of fungi.

Ro 09-1470 is a new antifungal agent that belongs to a series of compounds characterized by a tetrahydropyran skeleton with glycine and alkenyl side chains and that inhibits P-450 lanosterol C-14 demethylase (P-450(14DM)) of fungi (Y. Aoki, T. Yamazaki, M. Kondoh, Y. Sudoh, N. Nakayama, Y. Sekine, H. Shimada, and M. Arisawa, J. Antibiot. 45:160-170, 1992; S. Matsukuma, T. Ohtsuka, H. Kotaki, H. Sawairi, T. Sano, K. Watanabe, N. Nakayama, Y. Itezono, M. Fujiu, N. Shimma, K. Yokose, and T. Okuda, J. Antibiot. 45:151-159, 1992). We have studied the compound's mode of interaction with fungal P-450(14DM) and its selectivity for the fungal versus mammalian P-450 enzymes. Ro 09-1470 bound to the Saccharomyces cerevisiae P-450(14DM) by coordinating to the heme with one-to-one stoichiometry. Unlike the azole compounds, it interacted with both ferric and ferrous heme. It was active also against the P-450(14DM) of Candida albicans. Ro 09-1470 preferentially inhibited the yeast P-450(14DM), showing a 50% inhibitory concentration (IC50) of 0.47 to approximately 1.1 microM, which is much lower than the IC50s for rat hepatic P-450s catalyzing cholesterol biosynthesis (IC50 = 341 microM), p-nitroanisol O-demethylation (> 1,000 microM), aniline hydroxylation (> 1,000 microM), and aminopyrine N-demethylation (920 microM). The degree of selectivity for yeast P-450 was higher than that of ketoconazole.

Animals↗
PubMed1993

Decreased expression of human melanoma-associated antigen ME491 along the progression of melanoma pre-canceroses to invasive and metastatic melanomas.

ME491 expression was examined by immunohistochemistry in the different stages of various types of human malignant melanomas. In addition, the primary and metastatic lesions in five patients were studied to compare the ME491 antigen expression between these lesions in a single patient. A large proportion of cells from melanoma pre-canceroses showed strong ME491 expression, whereas the proportion of negatively stained tumour cells increased in the melanomas invading the dermis and in metastatic melanomas. In addition, a comparison of five sets of primary tumour and its metastatic lesion revealed decreased expression of this antigen in metastases. These results show that the reduction or loss of ME491 antigen expression is associated with increased invasiveness and metastatic ability of human malignant melanoma, suggesting that ME491 may act as an anti-metastatic gene.

Adult↗
PubMed1993

[Prevalence of hepatitis C virus and human immunodeficiency virus infection among Japanese female prostitutes].

To investigate the incidence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection in Japanese sexual workers, 191 out of 194 female prostitutes working in a certain district of the Tokyo metropolitan area were tested for anti-HCV, anti-hepatitis B virus (HBV), anti-HIV and anti-Treponema pallidum (TP). They were also interviewed with regard to their past history of blood transfusion, vaccination against HBV, liver diseases and repeated skin piercing treatments such as tattooing, acupuncture and intravenous drug use. Sera from 300 female blood donors (aged 20 s-40 s), of the same district, collected during the same year, were assessed for comparison. Incidence of seropositives for anti-HCV and anti-TP were found to be significantly high in the prostitute group (11.0% and 16.2%, respectively) compared to the control (0% for both). Anti-HBV seropositives were 14.1% in the prostitute group and 12.7% in the control group without significant difference and none of our subjects were found to be anti-HIV positive. Among HCV infected only 5 experienced repeated skin-piercing treatment and none underwent blood transfusion. From these results it is concluded that HCV has a potential for being transmitted by heterosexual contact, although the exact risk for infection needs to be determined by further investigation.

Adult↗
PubMed1992

Malignant hyperthermia caused by intravenous lidocaine for ventricular arrhythmia.

We encountered a case of malignant hyperthermia caused by intravenous lidocaine which had been administered as treatment for a ventricular arrhythmia. The patient, a 72-year-old male, was admitted with chronic renal failure and aortic valvular stenosis. His chronic renal failure progressed, and congestive heart failure developed, and ventricular arrhythmias occurred frequently. For the treatment of these arrhythmias, lidocaine was injected and continuous infusion was started. Despite initial improvement in symptoms and laboratory data following hemofiltration, refractory ventricular tachycardia occurred. The patient was treated with large doses of lidocaine. His body temperature rose to a maximum of 41.7 degrees C, and generalized muscular twitching was observed before he lost consciousness. Serum and urinary myoglobin levels became elevated. This abnormally high fever was relieved only by dantrolene sodium. After we made a diagnosis of malignant hyperthermia and stopped the lidocaine infusion, the high fever resolved quickly. It is important to note that malignant hyperthermia can be caused by lidocaine and amide-linked local anesthetics.

Aged↗
PubMed1992

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. II. Mode of action.

From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi.

Candida albicans↗
PubMed1992

[Rat brain concentrations of monoamines and their metabolites after chronic administration of diazepam and tandospirone].

Tandospirone has been reported as a serotonergic antianxiety drug with a different pharmacological mechanism from benzodiazepines. In the present study, the brain concentrations of monoamines and their metabolites were measured, comparing control rats and two groups of rats which were given tandospirone (10 mg/kg, ip) and diazepam (5 mg/kg, ip) each for 14 days. After sacrifice, brains of all animals were cut and divided into three portions, i.e. the cortex (COR), cerebellum (CER) and subcortical structures and brain stem (SS & BS). The concentrations of COR and SS & BS were measured using a Neurochemicalanalyzer (NCA, ESA, Inc., USA) with a reverse-phase column (Neurocolumn, Niko Bioscience Inc.). In the COR, 3-O-MDOPA (3-O-methyldopa) increased in the tandospirone group. In the SS & BS, 3-O-MDOPA increased in the diazepam and tandospirone groups. 5HIAA (5-hydroxyindoleacetic acid), DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid) decreased in the tandospirone group.

Animals↗
PubMed1992

[On trigger experience of a group of anxiety neurotics--its psychopathology and therapeutic utilization].

There is a group of anxiety neurotics, characterized by trigger experience (specific experience that triggers the anxiety attack at the initial phase of the illness). These are the patients, whose chief clinical manifestation is anxiety attack and anticipatory anxiety, with the additional feature of the recognizable trigger experience. Because of this additional feature, psychotherapeutic approach is often made in these cases. In this article, we present 7 such cases, in which we attempted psychotherapeutic approach with the special emphasis on the reconstruction of their trigger experience. Then we discuss the characteristics of the trigger experience and the therapeutic utilization of its reconstruction. The basic structure of their trigger experience is as follows. 'The experience of being taken by surprise, and shaken off something, which they believed to be, or tried to believe to be, firm and secure to them'. This 'something' is mainly concerned with their self-image. The self-image of 'the person who is healthy and has nothing to do with death, disease and madness' is common to all cases. But they also get different features, and can be divided into 3 subtypes, according to the difference in their self-images. 1. Compulsive-phobic type (case 1, 2, 3); 'the harmless person without impulsiveness and aggression'. 2. Hysterical type (case 4, 5, 6); 'the good mother, doing their best for their children, suppressing their own desire'. 3. Narcissistic type (case 7); 'the manly, energetic and ambitious person'. Symbolically speaking, in the contrast of 'ordinariness and extraordinariness', 'something familiar and something unfamiliar and uncanny', they exclude 'extraordinariness, something unfamiliar and uncanny', and rely only on 'ordinariness, something familiar'. They are clinging to the world of 'ordinariness', and thrown into confusion and anxiety when they catch a glimpse of the world of 'extraordinariness', which they have tried desperately to exclude from their life until then. Therapeutic efficacy of the reconstruction of the trigger experience is summarized in 3 factors as follows. 1. Explanation of their pathogenesis. It is a grave shock to them that the anxiety attack has occurred 'out of the blue' and 'with no reason'. In addition to the general explanation of the pathogenesis of anxiety neurosis, it is a relief to them that the explanation for each individual is possible. 2. Reinforcement of the transference cure ('faith care'). By putting into words what they did not make explicit until then, their belief in the therapist is intensified, and the function of the therapist of endowing them with the basis of security is reinforced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Crystallization and preliminary X-ray study of a double-shelled spherical virus, rice dwarf virus.

Rice dwarf virus (RDV) is a double-shelled spherical plant virus consisting of 46,000 Mr capsid and 114,000 Mr core proteins and minor structural proteins, and containing 12 genome segments of double-stranded RNA. The virus has been crystallized in the cubic space group I23 with a = 789 A. There are two particles per unit cell, each positioned on a point of 23 symmetry. Packing considerations showed that the diameter of the virus particle is 693 A. The crystals diffract to at least 6.5 A resolution.

Capsid↗
PubMed1991

Characterization of endothelin receptor subtypes.

Scatchard-plot analysis of [125I]ET-1 and [125I]ET-3 binding to rat lung membranes exhibited almost the same Kd values whereas the concentration of the binding sites of ET-1 is approximately four times higher than that of ET-3. This result suggests the presence of at least two distinct subtypes of ET receptors: an ET-1-specific type and an ET-3-specific or ET-1 and ET-3 nonselective type. On the other hand, in rat brain membranes, a curvilinear Scatchard plot was obtained for [125I]ET-3 in contrast to a linear plot for [125I]ET-1. This finding also demonstrates the existence of the two different receptor subtypes having the same affinity for ET-1, but one of which has a high affinity and the other has a low affinity for ET-3. Moreover, these data indicate that an ET receptor subtype exists in rat brain different from the subtype in rat lung. To obtain the bases for a further detailed characterization of the receptor, we have purified the rat lung ET receptor to homogeneity by ET-1-affinity chromatography. The purified receptor exhibits a molecular mass of 45 kDa, in good agreement with that estimated from the affinity labeling.

Animals↗
PubMed1990

Isolation of anti-endothelin receptor monoclonal antibodies for use in receptor characterization.

Monoclonal antibodies reactive with endothelin (ET) receptors have been prepared by immunization of mice with rat lung membranes. Of four clones isolated, three clones preferentially recognized 32,000-dalton ET receptor and the other has a higher affinity for the 45,000-dalton receptor. The binding of 125I-ET-1 to detergent-solubilized ET receptors which were adsorbed to the antibodies was displaced by increasing concentrations of unlabeled ET isopeptides. These results demonstrate that the four clones specific for the receptor have the potential to be a useful tool in the characterization of ET receptors.

Animals↗
PubMed1990

Affinity labelling of endothelin receptor and characterization of solubilized endothelin-endothelin-receptor complex.

Chick cardiac membranes were affinity labelled by cross-linking to membrane-bound 125I-endothelin-1 with disuccinimidyl tartarate. SDS/PAGE and autoradiographic analysis of the 125I-endothelin-1-labelled material in the presence or absence of 2-mercaptoethanol revealed one major labelled band, corresponding to a molecular mass of 53 kDa, whose appearance was dose-dependently inhibited by the addition of unlabelled endothelin-1 (1-100 nM). Subtracting the molecular mass of 125I-endothelin-1 and disuccinimidyl tartarate, the binding protein appeared to have a molecular mass of 50 kDa. To investigate further the molecular properties of endothelin receptor, the 125I-endothelin-1-endothelin-receptor complex was solubilized from chick cardiac membranes using the detergent digitonin. Sucrose gradient sedimentation of the solubilized complex indicated a sedimentation coefficient of 13 S, whereas the complex of (+)-[3H]PN200-110, a dihydropyridine derivative, and dihydropyridine-sensitive Ca2+ channels sedimented at 22 S. A monoclonal antibody raised against dihydropyridine-sensitive Ca2+ channels from the chick brain did not immunoprecipitate the 125I-endothelin-1-endothelin-receptor complex. These data suggest that endothelin receptor is clearly distinct from dihydropyridine-sensitive Ca2+ channels and endothelin has its own specific 50-kDa receptor.

Affinity Labels↗
PubMed1989

Two different forms of endothelin receptors in rat lung.

We provided evidence for the presence of two distinct types of rat endothelin (ET) receptors having different molecular masses by affinity labelling of rat lung membranes with 125I-ET-1, ET-2 and ET-3 and SDS-PAGE followed by autoradiography. One type, which is 44 kDa has a higher affinity for ET-1 and -2 than ET-3, whereas the other type, which is 32 kDa, preferably interacts with ET-3 rather than ET-1 and -2.

Affinity Labels↗
PubMed1989

Two distinct types of endothelin receptors are present on chick cardiac membranes.

Competitive displacement experiments of 125I-endothelin (ET)-1, -2, or -3 binding to chick cardiac membranes were performed with unlabeled ET-1, -2, -3, and sarafotoxin S6b (STX) as competitors. 125I-ET-1 and -2 binding was competitively inhibited by increasing concentrations of these unlabeled peptides in the same order; i.e. ET-2 greater than or equal to ET-1 greater than ET-3 greater than STX. In contrast, the order of potency in displacing 125I-ET-3 binding was ET-3 greater than ET-2 greater than or equal to ET-1 greater than STX. Affinity labeling of the membranes by cross-linking with 125I-ET-1 and -2 via disuccinimidyl tartarate yielded one major specific band with an apparent Mr = 53,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. On the other hand, affinity labeling with 125I-ET-3 showed that two major and one minor bands of Mr = 34,000, 46,000, and 53,000, respectively, were specifically labeled. These results indicate the presence of two distinct types of ET receptors, one of which has higher affinity for ET-1 and -2 than ET-3 and the other is conversely ET-3-preferring.

Animals↗
PubMed1989

[Clinical study of combination chemotherapy with mitomycin C, vindesine and cisplatin (MVP therapy) in advanced non-small cell lung cancer].

Thirty-seven patients with inoperable non-small cell lung cancer were treated with the combination chemotherapy (MVP therapy) with mitomycin C (8 mg/m2), vindesine (3 mg/m2 X 2) and cisplatin (60 mg/m2). The partial responders were 13 cases (35%), and the median survival time was 271 days. In this study the cisplatin dose was less than in any other report of "MVP" therapy. But both the response rate and the median survival time did not differ from those reported elsewhere. The side effects (bone marrow suppression, renal toxicity, etc.) were mild, and did not prevent the continuance of this therapy. Thus, we could repeat more than 6 courses of "MVP" therapy for 8 patients. Nowadays, it is difficult to obtain complete responders with any chemotherapy for inoperable non-small cell lung cancer. To prolong lives of patients and maintain good quality of life, we recommend chemotherapy with low toxicity in often-repeatable courses.

Adult↗
PubMed1989

Effect of chlorpromazine on transmigration of mitochondrial aspartate aminotransferase in rat liver.

Cholestatic liver injury was experimentally induced in rats by administration of chlorpromazine (CPZ). The peak activity of mitochondrial aspartate aminotransferase (AST) released in serum was found to precede the peak of total AST activity. The liver mitochondria obtained from rats treated with CPZ was fractionated into two subfractions: one containing the intermembrane space, and the other containing the matrix and the membranes. As a results, the relative activity of AST in the intermembrane space was significantly increased at 12 h after CPZ administration. This result suggests that mitochondrial AST, which is dominantly located in the mitochondrial matrix, transmigrated to the intermembrane space via the inner membrane under the effect of CPZ administration.

Animals↗
PubMed1988

Microassay for GM1 ganglioside beta-galactosidase activity using high-performance liquid chromatography.

A simple and sensitive assay for GM1 ganglioside (GM1) beta-galactosidase activity was devised by direct measurement of released D-galactose using high-performance liquid chromatography (HPLC). GM1 beta-galactosidase activity in crude samples such as brain homogenates could be measured by this method. After incubation of brain homogenate for 1 h with GM1 at 37 degrees C and pH 4.4 in the presence of sodium taurodeoxycholate, the reaction was terminated by heating at 100 degrees C for 2 min and the supernatant from the centrifuged sample was analysed directly by HPLC. D-Galactose isolated by HPLC was converted into a fluorescent compound by a post-column reaction with arginine at 150 degrees C and the fluorescence intensity at 430 nm was measured with excitation at 320 nm. By this method 10 pmol of D-galactose could be measured and the fluorescence intensity was linear up to 1 mmol of D-galactose. Using this method, the optimal conditions for the activity of this enzyme were re-examined. As an application, the enzyme activity in the brain of a patient with GM1 gangliosidosis was examined. This method can be applied to any natural substrates, glycolipids or glycoproteins, the terminal galactose of which is hydrolysed by this enzyme.

Brain↗