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Biomedical subjects

M Tsuda

Publications and source records attributed to M Tsuda.

At least 19 recordsLinked to original sources
PubMed1996

Diazepam pretreatment suppresses morphine withdrawal signs in the mouse.

The effect of diazepam on the development of physical dependence on morphine and on the naloxone-precipitated increase in cortical NA turnover were investigated in mice. Co-administration of diazepam (1-4 mg/kg, i.p.) during chronic morphine treatment suppressed the expression of naloxone (3 mg/kg, s.c.)-precipitated withdrawal signs (jumping, exploratory rearing and weight loss). However, a single injection of diazepam (4 mg/kg, i.p.) in morphine-dependent mice did not affect the expression of naloxone-precipitated withdrawal signs. The 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) level and noradrenaline (NA) turnover (MHPG/NA) in the cerebral cortex were increased by naloxone (3 mg/kg) challenge. These increases in the cortical MHPG level and NA turnover were significantly prevented by co-administration of diazepam (4 mg/kg, i.p.) during chronic morphine treatment. These findings suggest that the co-administration of diazepam during chronic morphine treatment may prevent some neurochemical changes in the central noradrenergic system during chronic morphine treatment, and may suppress the development of physical dependence on morphine. Therefore, the inhibitory action of GABA via benzodiazepine binding sites may play an important role in the development of physical dependence on morphine.

Adrenergic alpha-Agonists↗
PubMed1995

Diagnostic usefulness of postexercise systolic blood pressure response for detection of coronary artery disease in patients with electrocardiographic left ventricular hypertrophy.

Patients with left ventricular (LV) hypertrophy often have a positive result on exercise testing despite a normal coronary arteriogram. This indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. We evaluated the usefulness of the postexercise systolic blood pressure (BP) response for detection of CAD in 51 patients with both electrocardiographic evidence of LV hypertrophy and positive ST depression on treadmill exercise testing. Coronary cineangiograms showed normal coronary arteries in 23 patients (45%) (group 1) and significant CAD in 28 patients (55%) (group 2). The systolic BP ratio (systolic BP at 3 minutes of recovery divided by systolic BP at peak exercise) was significantly higher in group 2 than in group 1 (1.01 +/- 0.19 vs 0.80 +/- 0.09; p < 0.001). Analysis of the relative cumulative frequency revealed that a systolic BP ratio of 0.86 was the cutoff point for distinguishing a patient with CAD from one with normal coronary arteries. The sensitivity, specificity, and accuracy of a systolic BP ratio > or = 0.86 for detection of CAD in patients with LV hypertrophy were 79%, 83%, and 82%, respectively. Our results suggest that the use of an abnormal BP ratio, in combination with ST depression, improves the accuracy of treadmill exercise testing for detecting CAD in patients with electrocardiographic evidence of LV hypertrophy.

Adult↗
PubMed1995

A positive regulatory gene, pvdS, for expression of pyoverdin biosynthetic genes in Pseudomonas aeruginosa PAO.

In response to iron limitation Pseudomonas aeruginosa PAO induces production of pyoverdin, a low-molecular-weight siderophore able to capture ferric ion with a very high affinity. The pvd genes involved in the pyoverdin biosynthesis are organized in a chromosomal region termed the pvd region, and expression of some pvd genes is regulated at the transcriptional level. Two sets of promoter regions for the pvd genes were defined that were transcriptionally derepressed under iron-limiting conditions. Analysis of transcription from such promoters in Escherichia coli led to isolation and identification of a positive regulatory gene, pvdS, for expression of the pvd genes, and pvdS was localized in the pvd region. A genomic pvdS mutant of PAO, constructed by allelic exchange mutagenesis, produced no pyoverdin and did not allow transcription from the pvd promoters. Nucleotide sequence analysis revealed that PvdS shows considerable similarity to FecI of E. coli, a positive regulator for transcription of the fec (ferric citrate transport system) operon. The promoter region of pvdS has the sequence that matches well the consensus binding site for the E. coli Fur protein, a global negative regulatory protein that represses the transcription of the iron-repressible genes. Consistent with the presence of such a consensus sequence, addition of iron repressed transcription of the pvdS gene in P. aeruginosa.

Amino Acid Sequence↗
PubMed1995

Blockade of morphine-induced place preference by diazepam in mice.

The effects of diazepam on morphine-induced place preference were examined in mice. Pretreatment with diazepam (2 mg/kg i.p.) 30 min prior to morphine injection significantly abolished the morphine (5 mg/kg s.c.)-induced place preference, and this effect of diazepam was antagonized by pretreatment with flumazenil. In addition, pretreatment with diazepam prevented the morphine (5 mg/kg s.c.)-induced increase in dopamine turnover in the limbic forebrain. These results suggest that pretreatment with diazepam may suppress the rewarding effects of morphine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Degradation of polyetherurethane by subcutaneous implantation into rats. II. Changes of contact angles, infrared spectra, and nuclear magnetic resonance spectra.

In vivo degradation of polyetherurethanes (PEUs) was studied using two kinds of PEUs, U-3 and U-8, coated on a base film of ethylene/vinyl alcohol copolymer (EVAL). U-3 is a nonsegmented PEU prepared from 4,4'-diisocyanatodiphenylmethane (MDI) and poly(tetramethylene oxide) (PTMO 1000). U-8 is a segmented PEU prepared from MDI, PTMO 1000, and 1,4-butanediol. Previous studies of PEUs were conducted using gel permeation chromatography and scanning electron microscopy. In this study, the explanted materials were examined with contact angle measurement, ATR-FTIR, and nuclear magnetic resonance (NMR) spectroscopies. All data obtained by these methodologies indicate that the PTMO/MDI oligomers diffused to the material surface in the early stage of implantation. Then, the low-molecular-weight fraction of the oligomers leached out from the surface to the exudate. Degradation became dominant after 2-4 weeks. In the case of PU-8, the PTMO fraction decreased approximately 35-40% from the surface at 24 weeks postimplantation. In the case of PU-3, the loss of coating material (U-3) on the base film (EVAL) was observed after 10 weeks. The PTMO fraction of the surface U-3 remained on EVAL at 6 weeks postimplantation, however, it was 64% of the initial material. The molecular weight of the U-3 remaining on EVAL also decreased. Degradation of U-3 occurred more rapidly than that of U-8. The data obtained with our materials were insufficient in determining evidence of oxidative degradation with IR or NMR spectra.

Animals↗
PubMed1995

GAP-43 mRNA suppression by the ribozyme in PC12 cells and inhibition of evoked dopamine release.

We constructed a ribozyme designed to cleave the GAP-43 mRNA and which contained a bacteriophage T7 transcription terminator at its 3' site to maintain stability. The ribozyme was overexpressed in PC12 cells by pEF-BOS, a powerful mammalian expression vector. Consequently, PC12 cells overexpressing the GAP-43 ribozyme revealed a drastic decrease in the levels of GAP-43 mRNA expression, and the evoked dopamine release was significantly suppressed in these cell lines. These results support the previous observations that GAP-43 is associated with Ca-dependent dopamine release in PC12 cells, and the ribozyme expression system used in the present study was demonstrated to be useful for suppression of the functions of specific mRNAs and exploration of specific gene products.

Animals↗
PubMed1995

Lipopolysaccharide-associated elevation of serum and urinary nitrite/nitrate levels and hematological changes in rats.

The objective of this study was to assess the relationship between lipopolysaccharide (LPS)-induced elevation of nitric oxide (NO) levels and hematological changes. Twenty-four h following i.p. treatment of LPS (1 mg/kg body wt.), nitrite/nitrate (NO2-/NO3-) levels in the serum and urine of rats were, respectively, increased to 11 and 50 times those of control. Time-dependent decrease of white blood cells (80% of control), lymphocytes (40% of control), and platelets (35% of control) was also observed, while a significant increase of neutrophils (330% of control) and monocytes (650% of control) occurred during the 24-h post-treatment period. These results suggest that LPS-induced increase of NO2-/NO3- levels and coincident hematological changes may compromise immune functions.

Animals↗
PubMed1995

Similarities and differences between the effects of ipriflavone and vitamin K on bone resorption and formation in vitro.

The effects of ipriflavone and vitamin K on bone metabolism were examined using a culture system. Vitamin K1 and vitamin K2 (10(-7)M-10(-5)M) inhibited both the activation of mature osteoclasts and the formation of new osteoclasts without affecting the growth of progenitor cells in cultures of mouse unfractionated bone cells. The inhibitory effects of vitamin K on bone resorption were similar to those of ipriflavone and were not affected by the vitamin K antagonist warfarin. When ipriflavone was added to the culture medium in combination with vitamin K2, an additive inhibitory effect on bone resorption was observed. An additive effect was also observed in organ cultures of mouse calvaria. On the other hand, ipriflavone, but neither vitamin K1 nor vitamin K2, stimulated cellular alkaline phosphatase (ALP) activity on rat bone marrow stromal cells under culture conditions in which cells subsequently form mineralized bone-like tissue. Vitamin K1 and vitamin K2 also did not modulate the stimulatory effect of ipriflavone on the ALP activity of the cells. These results suggest that the inhibitory effects of vitamin K on bone resorption are similar to those of ipriflavone through mechanisms that may be independent of the gamma-carboxylation system, while the effects of vitamin K on osteoblast phenotype expression are different from those of ipriflavone.

Acid Phosphatase↗
PubMed1995

Transient disappearance of complete right bundle branch block during exercise in a patient with old inferior wall myocardial infarction.

To date, there has been no report of temporary disappearance of right bundle branch block (RBBB) during exercise. A patient with old infero-posterior myocardial infarction is described in whom complete RBBB disappeared transiently during treadmill exercise testing. No chest pain or significant ST-T changes occurred during and after the exercise periods. Any of the following mechanisms could have been involved: (1) the patient's complete RBBB might have been bradycardia-dependent, (2) an exercise-induced increase of sympathetic tone might have produced a temporary improvement of the conduction disturbances, or (3) the exercise might have elicited conduction disturbances in the main left bundle branch, which could have concealed a conduction delay in the main trunk of the right bundle branch.

Bundle-Branch Block↗
PubMed1995

Involvement of protein kinase C in Ca(2+)-signaling pathways to activation of AP-1 DNA-binding activity evoked via NMDA- and voltage-gated Ca2+ channels.

Stimulation of cultured cerebellar granule cells with N-methyl-D-aspartate (NMDA) or kainic acid (KA) leads to activation of activator protein-1 (AP-1) DNA-binding activity, which can be monitored by an increase in 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive element (TRE)-binding activity, in concert with c-fos induction. For this increase in TRE-binding activity, Ca2+ influx across the plasma membrane is essential. Treatment of cells with an intracellular Ca2+ chelator, BAPTA-AM, abolished this increase. Close correspondence between the dose-response curves of 45Ca2+ uptake and TRE-binding activity by NMDA or KA suggested that Ca2+ influx not only triggered sequential activation of Ca(2+)-signaling processes leading to the increase in TRE-binding activity, but also controlled its increased level. Stimulation of non-NMDA receptors by KA mainly caused Ca2+ influx through voltage-gated Ca2+ channels, whereas stimulation of NMDA receptors caused Ca2+ influx through NMDA-gated ion channels. The protein kinase C (PKC) inhibitors staurosporine and calphostin C inhibited the increase in TRE-binding activity caused by NMDA and KA at the same concentration at which they inhibited that caused by TPA. Furthermore, down-regulation of PKC inhibited the increase in TRE-binding activity by NMDA and KA. Thus, a common pathway that includes PKC could, at least in part, be involved in the Ca(2+)-signaling pathways for the increase in TRE-binding activity coupled with the activation of NMDA- and non-NMDA receptors.

Animals↗
PubMed1995

Marked increase in urinary excretion of nitrate and N-nitrosothioproline in the osteogenic disordered syndrome rats, lacking ascorbic acid biosynthesis, by administration of lipopolysaccharide and thioproline.

Urinary excretions of nitrate and N-nitrosothiazolidine-4-carboxylic acid (N-nitrosothioproline; NTPRO) were determined in rats with osteogenic disordered syndrome (ODS, od/od), lacking L-ascorbic acid (ASC) biosynthesis, after i.p. administration of Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) followed by thiazolidine-4-carboxylic acid (thioproline, 20 mg/rat). L-Ascorbic acid-sufficient ODS rats showed the excretion of nitrate and NTPRO at the levels of 20.3 +/- 7.9 mumol/24h and 369 +/- 111 pmol/24 h respectively, whereas the levels of nitrate and NTPRO in ASC-deficient (scorbutic) rats increased to 54.7 +/- 5.6 mumol/24 h (P < 0.01) and 796 +/- 367 pmol/24 h (P < 0.05) respectively. Administration of L-arginine further increased urinary excretion of nitrate and NTPRO while D-arginine showed no effect. NG-Monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS), strongly inhibited endogenous formation of both nitrate and NTPRO. These results indicate that increased excretion of NTPRO in ODS rats stimulated by LPS involves induction of NOS leading to an increase in endogenous formation of reactive nitrogen oxides such as N2O3, a potent nitrosating agent at physiological pH conditions. Increased NOS activities in the plasma and various tissues of ODS rats were observed 5 h after treatment with LPS. The possibility of extragastric N-nitroso compound formation in inflammation sites is discussed.

Animals↗
PubMed1995

Inhibitory action of lansoprazole and its analogs against Helicobacter pylori: inhibition of growth is not related to inhibition of urease.

The proton pump inhibitors omeprazole and lansoprazole and its acid-activated derivative AG-2000, which are potent and specific inhibitors of urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), inhibited the growth of H. pylori. The growth was inhibited not only in urease-positive clinical isolates but also in their urease-negative derivatives which had no urease polypeptides. AG-1789, a derivative of lansoprazole with no inhibitory activity against H. pylori urease, also inhibited the growth of both strains even more strongly than the urease inhibitors lansoprazole and AG-2000. Furthermore, the antibacterial activity of omeprazole and lansoprazole was not affected by glutathione or dithiothreitol, which completely abolished the inhibitory activity of lansoprazole against H. pylori urease. These results indicated that the inhibitory action of these compounds against the growth of H. pylori was independent from the inhibitory action against urease.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Genetic and physical mapping of genes involved in pyoverdin production in Pseudomonas aeruginosa PAO.

Pseudomonas aeruginosa PAO was mutagenized with Tn1737KH, a type I transcription probe transposon containing a promoterless lacZ (beta-galactosidase) gene, and 24 insertion mutants that did not grow under iron-deficient conditions were isolated. None of the culture supernatants from any mutants contained pyoverdin, a low-molecular-weight siderophore able to sequester ferric iron at very high affinity, and the growth defects of the mutants were all phenotypically recovered by the addition of the culture supernatant from the wild-type strain. These phenotypes led to the inference that all the mutants had defects in the genes (pvd genes) for production of pyoverdin. In some pvd::Tn1737KH mutants, high levels of beta-galactosidase activities were observed, and such activities were drastically reduced by the addition of ferric ion in the culture media, indicating that the expression of at least some pvd genes is regulated at the transcriptional level. Molecular cloning and physical analysis of the chromosomal fragments with Tn1737KH insertions allowed us to allocate all the mutations within a 103-kb region, referred to as the pvd region, that was found to locate at 47 min on the genetic map of PAO. Further physical mapping and Southern analysis showed that there is a 10-kb overlap between the pvd region and the 125-kb catA region described by Zhang and Holloway (C. Zhang and B. W. Holloway, J. Gen. Microbiol. 138:1097-1107, 1992). We could hence illustrate the physical map of the P. aeruginosa chromosome with a size of 218 kb.

Amino Acid Sequence↗
PubMed1995

Sphingolipid bases. A revisitation of the O-methyl derivatives of sphingosine. Isolation and characterization of diacetate derivatives, with revised 13C nuclear magnetic resonance assignments for D-erythro-sphingosine.

As described by Carter et al. (J. Biol. Chem. 1951. 192: 197-207), O-methyl derivatives of sphingosine are formed upon acid hydrolysis of sphingolipids in the presence of methanol. In the present study, we have isolated four O-methyl ethers of C18-sphingosine by medium pressure liquid chromatography of their diacetate derivatives, i.e., (2S,3R,4E)-1-acetoxy-2-acetamido-3-methoxy-4-octadecene, its (2S,3S) epimer, (2R,3E,5R)-1-acetoxy-2-acetamido-5-methoxy-3-octadecene, and its (2R,5S) epimer. Structures were determined by physical, chromatographic, and spectral properties. The 5-O-methyl ethers, which were the predominant byproducts of sphingolipid hydrolysis, were easily distinguished from the 3-O-methyl ethers by chromatography, and all four isomers could be differentiated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. NMR analysis of the original N-acetate and diacetate samples of O-methylsphingosines I and II of Carter et al. demonstrated that they correspond to the 5-O-methyl ethers (2R,5R and 2R,5S, respectively), with purities of approximately 90-99%. Resolution enhancement of the 126-MHz 13C NMR spectra of the O-methyl ethers and D-erythro-C18-sphingosine (Ia) afforded distinct signals for nearly all carbon atoms. 13C NMR assignments of carbons 7-15 were made from their lanthanide-induced shifts, and revised assignments for olefinic carbons of Ia were established based upon 1H-13C shift correlation experiments.

Magnetic Resonance Spectroscopy↗
PubMed1995

[A clinical experience of DNA probe method for identifying Mycobacterium avium and Mycobacterium intracellulare].

In Japan the number of patient infected with M. avium complex (MAC) has been increasing in contrast to a decrease of pulmonary tuberculosis. DNA probe method enabled us be able to differentiate an isolated MAC into M. avium and M. intracellulare. From 1991 to 1992, we performed an investigation to apply this new technique of the DNA probe method on 52 patients of atypical mycobacteriosis diagnosed as infected with MAC by the ordinary method at the Higashi Nagoya National Hospital. The group consisted of 27 males and 25 females. M. avium infection was found in 39 patients (M. avium group) and M. intracellulare in 16 patients (M. intracellulare group). No significant gender difference was found between two groups. The M. avium group showed more complications in contrast to the M. intracellulare group. As complications in the M. avium group, pulmonary aspergillus infection, bacterial pneumonia and bronchiectasis were found in 4, 3 and 2 cases, respectively. The rate of drug resistance to antituberculosis drugs was high in the both groups. Chemotherapy with isoniazid (INH) rifampin (RFP) and streptomycin (SM) in five patients, that with INH, RFP and ethambutol (EB) in three were found to be effective after 4 months treatment. Three patients in M. avium group died of respiratory failure, aspergillus infection and renal failure. In contrast the prognosis of patients in the M. intracellulare group seemed to be better as there was no fatal case. We conclude that DNA probe method is useful to differentiate between M. avium and M. intracellulare, and enable us to select more appropriate selection of the chemotherapy and to assess of the prognosis.

Aged↗
PubMed1995

Evaluation of a new bismuth-free triple therapy in nude mice and humans.

OBJECTIVES: To evaluate the efficacy of a new triple therapy (amoxycillin, metronidazole, plaunotol) in eradicating Helicobacter pylori in a nude mouse model and in humans. MATERIALS AND METHODS: In an animal study we used 215 nude mice infected with H. pylori to assess the ability of single, dual and triple therapy to eradicate H. pylori from the mouse stomach. The number of H. pylori in the mouse stomach and extent of the gastritis was assessed from 1 to 4 weeks after treatment. In a human study, we enrolled 78 H. pylori-positive patients with recurrent peptic ulcer diseases, 29 of whom were given triple therapy (amoxycillin and metronidazole for 1 week and plaunotol for 4 weeks). Patients in the control group (n = 49) were given a histamine H2-receptor antagonist. All patients were assessed 5 and 11 months after completion of therapy. RESULTS: In the mouse model, both the number of H. pylori and the gastritis score were significantly lower in the triple therapy group than in any other treatment group assessed 1-4 weeks after completion of therapy. In the human study, the triple therapy eradicated H. pylori from the stomachs of 25 out of 29 patients (86%), compared to the control group in which none of the 49 patients were free of H. pylori in the stomach 11 months after completion of therapy. There were no reported side effects with this triple therapy. None of the H. pylori-eradicated patients showed a recurrence of peptic ulcer disease; three of the four patients whose H. pylori was not eradicated by triple therapy showed a peptic ulcer recurrence within the study period, whereas 16 out of 49 patients in the control group had a peptic ulcer recurrence. CONCLUSIONS: This new triple therapy was effective in the eradication H. pylori, had very few side effects and greatly reduced the rate of recurrent peptic ulcers.

Amoxicillin↗