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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 397 records · Page 22Linked to original sources
PubMed2000

Effects of NKH477 on endothelin-1-induced renal responses in anaesthetized dogs.

1. Intrarenal arterial infusion of a direct adenylate cyclase activator (NKH477; 300 ng/kg per min) increased renal blood flow, urine flow rate and urinary sodium excretion in anaesthetized dogs. 2. Intrarenal arterial infusion of endothelin (ET)-1 (2 ng/kg per min) reduced basal values of these parameters and glomerular filtration rate, which were recovered by the addition of NKH477 during ET-1 infusion. 3. These results demonstrate that NKH477 can counteract ET-1-induced antinatriuresis, mainly by restoring glomerular filtration.

Anesthesia↗
PubMed2000

Bilateral testicular tumors in androgen insensitivity syndrome.

We report on a case of complete androgen insensitivity syndrome with bilateral testicular tumors and a point mutation in the androgen receptor gene. A bilateral gonadecotmy was performed and both of the resected tumors were histologically diagnosed as pure seminoma. Direct sequencing of amplified exons E-G of the androgen receptor gene from the resected tumor identified a CGA to CAA substitution in exon E, resulting in arginine to glutamine replacement at codon 752. To our knowledge, this is the first reported case of androgen insensitivity syndrome with bilateral testicular tumors.

Androgen-Insensitivity Syndrome↗
PubMed2000

Comparison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle.

OBJECTIVE: To evaluate the effects of tolterodine, vamicamide and temiverine, novel antimuscarinic drugs developed for the treatment of frequency and urinary incontinence, on human detrusor smooth muscle. Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. Using an organ-bath technique, the effects of various drugs on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in the detrusor strips were investigated. RESULTS: Carbachol (0.001-10000 micromol/L) caused concentration-dependent contractions in human detrusor smooth muscles. Tolterodine (0.01-10 micromol/L), vamicamide (0.01-10 micromol/L), temiverine (0.01-1 micromol/L) and atropine (0.001-1 micromol/L) caused parallel shifts to the right of the concentration-response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA2 values was atropine = tolterodine > vamicamide > temiverine. Tolterodine, vamicamide and atropine did not inhibit the maximum contractile responses to carbachol, while temiverine (10 micromol/L) significantly inhibited the maximum contractions. Tolterodine (0.001-1 micromol/L) and vamicamide (0.01-10 micromol/L) did not inhibit the KCl- (80 mmol/L) and CaCl2-induced (5 mmol/L) contractions, while temiverine (0.01-10 micromol/L) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contractions in human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 1 micromol/L atropine, tolterodine and vamicamide did not inhibit the contractions induced by electrical field stimulation at all frequencies, while temiverine (10 micromol/L) significantly inhibited the contractions. CONCLUSION: Tolterodine and vamicamide inhibited contractions of human detrusor smooth muscles only through their antimuscarinic action, while temiverine had both antimuscarinic and calcium-antagonist actions. Furthermore, these novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.

Aged↗
PubMed2000

Histamine induces melanogenesis and morphologic changes by protein kinase A activation via H2 receptors in human normal melanocytes.

Hyperpigmentation frequently accompanies chronic or acute inflammation. A number of inflammatory mediators have been shown to stimulate melanin synthesis in human melanocytes. Although histamine is ubiquitous as an inflammatory factor, its involvement in pigmentation remains obscure. In this work, we examined the effects of histamine on cultured human melanocytes. Treatment of human melanocytes with 0.1-10 microM histamine evoked morphologic changes and increases in tyrosinase activity. The concomitant increases in melanin content of the histamine-treated melanocytes indicated an elevation of melanin synthesis by tyrosinase activation. These stimulatory effects of histamine were completely inhibited by an H2 antagonist, famotidine, whereas H1 and H3 antagonists had no inhibitory effect whatsoever. In addition, an H2 agonist, dimaprit, induced the same degree of melanogenesis as histamine at concentrations of 0.1-10 microM. We observed an increase in the intracellular cAMP contents of human melanocytes induced by histamine via the H2 receptors. We know that this cAMP accumulation and subsequent protein kinase A activation plays a critical role in histamine-induced melanogenesis, because a specific protein kinase A inhibitor, H-89, completely suppressed these stimulatory effects of histamine, and because dibutylic cAMP, a specific protein kinase A activator, stimulated human melanocytes as potently as histamine. Taken together, we show here that histamine induces melanogenesis of human cultured melanocytes by protein kinase A activation via H2 receptors.

Cell Division↗
PubMed2000

Long-term magnetic resonance imaging after temporomandibular joint discectomy without replacement.

PURPOSE: The intracapsular changes in patients who underwent discectomy without disc replacement were evaluated by magnetic resonance imaging (MRI) to determine the long-term outcome of this procedure. PATIENTS AND METHODS: Thirty-three patients observed for an average of 9 years 4 months (5 to 24 years) and 10 asymptomatic volunteers underwent MRI using T1- and T2-weighted images and 3-dimensional fast imaging with a steady precession sequence (FISP-3D) technique. The intracapsular changes, especially those in the joint space, were compared with the postoperative clinical findings. RESULTS: MRI examination of the temporomandibular joint in the 33 patients (35 joints) indicated the presence of tissue with an intermediate or high signal intensity in the joint space. This tissue covered the articular surface of the condyle and fossa. Thirty-two joints had no pain or only occasional, mild pain (3 joints). No patient had severe joint pain or a low signal intensity in the joint space on MRI examination. There was no correlation between joint noise and the presence of a tissue deformity in the joint space. MRI of 2 patients with limited mouth opening showed tissue with high signal intensity in the joint space as well as an exostosis on the eminence and hypertrophy of the condyle. CONCLUSION: Long-term success is possible with discectomy without replacement. This appears to be attributable to the formation of new tissue between the condyle and fossa that acts as a pseudodisc.

Adult↗
PubMed2000

Nitric oxide enhances PGI(2)production by human pulmonary artery smooth muscle cells.

To evaluate the effect of exogenous nitric oxide (NO) and endogenous NO on the production of prostacyclin (PGI(2)) by cultured human pulmonary artery smooth muscle cells (HPASMC) treated with lipopolysaccharide (LPS), interleukin-1(beta)(IL-1(beta)), tumor necrosis factor alpha (TNF(alpha)) or interferon gamma (IFN(gamma)), HPASMC were treated with LPS and cytokines together with or without sodium nitroprusside (SNP), NO donor, N(G)-monomethyl-L-arginine (L-NMMA), NO synthetase inhibitor, and methylene blue (MeB), an inhibitor of the soluble guanylate cyclase. After incubation for 24 h, the postculture media were collected for the assay of nitrite by chemiluminescence method and the assay of PGI(2)by radioimmunoassay. The incubation of HPASMC with various concentrations of LPS, IL-1(beta)or TNF(alpha)for 24 h caused a significant increase in nitrite release and PGI(2)production. However, IFN(gamma)slightly increased the release of nitrite and had little effect on PGI(2)production. Although the incubation of these cells for 24 h with SNP did not cause a significant increase in PGI(2)production, the incubation of HPASMC with SNP and 10 microg/ml LPS, or with SNP and 100 U/ml IL-1(beta)further increase PGI(2)production and this enhancement was closely related to the concentration of SNP. However, stimulatory effect of SNP on PGI(2)production was not found in TNF(alpha)- and IFN(gamma)- treated HPASMC. Addition of L-NMMA to a medium containing LPS or IL-1(beta)reduced nitrite release and attenuated the stimulatory effect of those agents on PGI(2)production. MeB significantly suppressed the production of PGI(2)by HPASMC treated with or without LPS or IL-1(beta). The addition of SNP partly reversed the inhibitory effect of MeB on PGI(2)production by HPASMC. These experimental results suggest that NO might stimulate PGI(2)production by HPASMC. Exogenous NO together with endogenous NO induced by LPS or cytokines from smooth muscle cells might synergetically enhance PGI(2)production by these cells, possibly in clinical disorders such as sepsis and acute respiratory distress syndrome.

Cells, Cultured↗
PubMed2000

Clinical impact of cyclosporine cellular pharmacodynamics in minimal change nephrotic syndrome.

BACKGROUND: Cellular pharmacodynamics of cyclosporine (INN, cyclosporin) is considered to be closely implicated in clinical efficacy of the drug in kidney transplantation and other immunologic disorders. We applied this strategy to patients with minimal change nephrotic syndrome to predict individual clinical efficacy of cyclosporine. METHODS: Drug sensitivity tests were carried out with peripheral blood mononuclear cells from 31 patients with minimal change nephrotic syndrome. The 50% lymphocyte-mitosis inhibition of cyclosporine on in vitro blastogenesis of peripheral blood mononuclear cells stimulated with concanavalin A were estimated, and interpatient variations of 50% lymphocyte-mitosis inhibition were evaluated. The relationship between cyclosporine-50% lymphocyte-mitosis inhibition and clinical outcomes indicated a decrease of urinary protein and the period required for complete remission under cyclosporine therapy was examined in 14 patients. We also evaluated the correlation between cyclosporine-50% lymphocyte-mitosis inhibition and interleukin-2 production and percentages of interleukin 2 receptor-positive peripheral blood mononuclear cells in vitro. RESULTS: Cyclosporine 50% lymphocyte-mitosis inhibition on peripheral blood mononuclear cell blastogenesis deviated largely between patients from 0.2 to 86.0 ng/mL. We found a statistically significant negative correlation between cyclosporine-50% lymphocyte-mitosis inhibition in vitro and decreasing rates of urinary protein at 1 week after onset of cyclosporine administration (r = -0.655, P < .02). When we arbitrarily divide the 14 patients who received cyclosporine therapy according to their median 50% lymphocyte-mitosis inhibition of cyclosporine into two groups, that is, a high-sensitivity group (50% lymphocyte-mitosis inhibition < 18.1 ng/mL, n = 6) and a low-sensitivity group (50% lymphocytemitosis inhibition > 18.1 ng/mL, n = 8), the period required for complete remission was significantly shorter in the high-sensitivity group (P < .03). The 50% lymphocyte-mitosis inhibition of cyclosporine on interleukin-2 production in culture medium was correlated with 50% lymphocyte-mitosis inhibition of the drug on peripheral blood mononuclear cell blastogenesis (r = 0.806, P < .02). Decreasing rates of interleukin-2R-positive cells by cyclosporine treatment in vitro were negatively correlated with peripheral blood mononuclear cells blastogenesis in the presence of the drug (r = -0.694, P < .02). CONCLUSIONS: Peripheral blood mononuclear cell response to cyclosporine in vitro is closely related to clinical efficacy of the drug in minimal change nephrotic syndrome. Peripheral blood mononuclear cell resistance to cyclosporine was correlated with ability of the cells to express interleukin 2 and interleukin 2R.

Adult↗
PubMed2000

CT scores of emphysema and oxygen desaturation during low-grade exercise in patients with emphysema.

PURPOSE: We evaluated the usefulness of CT for assessing oxygen desaturation during walking in patients with emphysema. MATERIAL AND METHODS: The study comprised 32 patients with emphysema (mean age 67+/-6 years). Serial CT images of 5 mm were obtained from the apex to the basal regions of the lung during deep inspiration. The severity of emphysema was scored by four physicians according to a visual method. A six-minute walking test and oxygen desaturation (pSO2) measurements were performed. RESULTS AND CONCLUSION: The mean CT score of the four observers was significantly correlated with the nadir pSO2 and deltapSO2, but did not correlate with the total distance walked. These results suggest that CT may be used for the assessment of oxygen desaturation during low-grade exercise in patients with emphysema.

Aged↗
PubMed2000

Increased chromatid-type chromosomal aberrations in mouse m5S cells exposed to power-line frequency magnetic fields.

PURPOSE: To investigate the induction of chromosomal aberrations in mouse m5S cells after exposure to power-line frequency magnetic fields (extremely low frequency magnetic fields; ELFMF) at high-flux densities. MATERIAL AND METHOD: m5S cells were either untreated or pretreated during the G1 phase with mitomycin C (MMC, 1 microM) for 1 h or 3 Gy X-rays, and then exposed to ELFMF at three different flux densities (5 and 50 mT at 60 Hz, 400 mT at 50 Hz) for 40 h. Unexposed control cells were incubated for the same period in a conventional CO2 incubator. Chromosomal aberrations were analysed in the first post-treatment metaphases. Cell kinetics were assessed by DNA flow cytometry and the mitotic index. RESULTS AND CONCLUSIONS: ELFMF enhanced the formation of spontaneous and MMC- or X-ray-induced chromosomal aberrations, in a flux-density-dependent manner. Statistically significant increases in the frequency of chromosomal aberrations were observed in cells exposed to 400 mT ELFMF with respect to unexposed controls. The aberrations induced by ELFMF were mostly chromatid-type, not chromosome-type. The cells exposed to 400 mT ELFMF exhibited a three-fold higher level of chromatid-type aberrations than did the unexposed cells. Flow cytometric and mitotic index analyses revealed that the S or G2 arrest following MMC or X-irradiation was more profound in ELFMF-exposed cells than in unexposed cells. Our results suggest that ELFMF can interfere with post-replication repair, resulting in increased levels of chromatid-type chromosomal aberrations induced spontaneously and by DNA damaging agents.

Animals↗
PubMed2000

Administration of human chorionic gonadotropin with a controlled-release function to immature rats for application in male infertility therapy.

Biodegradable poly(DL-lactic acid) (PLA) devices with controlled release of human chorionic gonadotropin (hCG) were fabricated in a 2-mm cylinder form by the meltpressing technique. The devices fabricated were inserted subcutaneously in the backs of immature rats. It was found that the serum level of testosterone (T) remained constant at approximately 0.7 ng/ml for an experimental period of 14 days, resulting in greater Leydig cell production of testosterone. This was also suggested from the results of immunohistochemical observation of the testis and weight changes of prostates, such as the ventral prostates and seminal vesicle.

Absorbable Implants↗
PubMed2000

Retroperitoneoscopic excision of a mesenteric cyst.

Mesenteric cysts are rare intra-abdominal lesions. We present a case of a mesenteric cyst that was discovered by abdominal computed tomography (CT) and excised by retroperitoneoscopic surgery. There have been 10 reports of excision of mesenteric cysts by laparoscopy in the literature, but retroperitoneoscopic resection of such cysts has not been reported. This case suggests that when a mesenteric cyst arises from the ascending or descending colon, the retroperitoneal approach has a lower risk of traumatizing the bowel than does the laparoscopic intra-abdominal approach, and it does not have to compress other intra-abdominal organs.

Adult↗
PubMed2000

PNAD-CSS: a workbench for constructing a protein name abbreviation dictionary.

MOTIVATION: Since their initial development, integration and construction of databases for molecular-level data have progressed. Though biological molecules are related to each other and form a complex system, the information is stored in the vast archives of the literature or in diverse databases. There is no unified naming convention for biological object, and biological terms may be ambiguous or polysemic. This makes the integration and interaction of databases difficult. In order to eliminate these problems, machine-readable natural language resources appear to be quite promising. We have developed a workbench for protein name abbreviation dictionary (PNAD) building. RESULTS: We have developed PNAD Construction Support System (PNAD-CSS), which offers various convenient facilities to decrease the construction costs of a protein name abbreviation dictionary of which entries are collected from abstracts in biomedical papers. The system allows the users to concentrate on higher level interpretation by removing some troublesome tasks, e.g. management of abstracts, extracting protein names and their abbreviations, and so on. To extract a pair of protein names and abbreviations, we have developed a hybrid system composed of the PROPER System and the PNAD System. The PNAD System can extract the pairs from parenthetical-paraphrases involved in protein names, the PROPER System identified these paris, with 98.95% precision, 95.56% recall and 97.58% complete precision. AVAILABILITY: PROPER System is freely available from http://www.hgc.inc.u-tokyo.ac.jp/service/tooldoc /KeX/intro.html. The other software are also available on request. Contact the authors. CONTACT: mikio@ims.u-tokyo.ac.jp

Databases, Factual↗
PubMed2000

Properties of quadruplex oligonucleotides with anti-HIV-1 activity.

A phosphorothioate oligonucleotide composed of deoxyguanosine and thymidine was identified as an inhibitor of HIV-1 infection at an early stage of the HIV-1 replication cycle in vitro. The phosphodiester and phosphorothioate chimeric oligonucleotides were found to be potent inhibitors of several steps of HIV-1 infection: the interaction with CD4 and the chemokine receptor, the reverse transcriptase activity, and the integrase activity. To elucidate the mechanism of the anti-HIV-1 function of these oligonucleotides in terms of their structure, we focussed on their G-serial sequences and investigated the characteristics of their solution structures. These oligonucleotides were proved to be able to adopt G-quadruplex structures by UV and CD measurements. We presume that the anti-HIV-1 activities of these oligonucleotides are consequently attributable to G-quadruplex formation.

Anti-HIV Agents↗
PubMed2000

Nitric oxide underlies the differentiation of PC12 cells induced by depolarization with high KCl.

Nitric oxide (NO) acts as a cytostatic agent to induce neuronal differentiation of PC12 cells after nerve growth factor (NGF) treatment. We newly subcloned PC12K cells that extended neurites after depolarization with high KCl. Here we present evidence that the neuronal differentiation of PC12K cells caused by depolarization with high KCl is mediated by endogenous NO. The outgrowth of neurites was significantly inhibited by 2 mM N-nitro-L-arginine methyl ester (L-NMAE), and 10 mM L-NAME was necessary for complete inhibition. The inhibition of NGF-dependent neurite outgrowth by L-NAME was abolished by depolarization of cells with KCl. The expression of neuronal- and endothelial-NO-synthase in PC12K cells was confirmed by immuno-cytochemical and immuno-blotting analyses with the respective monoclonal antibodies. However, the expression of inducible-NO synthase was not observed in PC12K cells cultured with high KCl under the depolarization conditions with 45 mM KCl. We observed the increase of NO in the differentiated PC12K cells using diaminofluorescein, a novel fluorescent indicator for NO.

Animals↗
PubMed2000

Nucleocytoplasmic shuttling of the aryl hydrocarbon receptor.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that acts in concert with the AhR nuclear translocator (ARNT), and alters gene expression in response to environmental contaminants such as 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We have previously shown that AhR contains both a nuclear localization signal (NLS), AhR(13-39), and a nuclear export signal (NES), AhR(55-75), in its NH(2)-terminal region. In this study, we obtained direct evidence for the nucleocytoplasmic shuttling of AhR and show the biological significance of the shuttling in terms of the transcriptional activation of its target gene, CYP1A1. When AhR(13-75) fused with glutathione S-transferase (GST)-green fluorescent protein (GFP) was microinjected into the nucleus of a polykaryotic of BHK21 cell, the GST-AhR(13-75)-GFP migrated from one nucleus to the other. This event, nucleocytoplasmic shuttling, was completely inhibited in the presence of leptomycin B (LMB). The interaction between chromosome region maintenance 1 (CRM1) and endogenous AhR was shown by immunoprecipitation with antibodies to AhR followed by immunoblot analysis with antibodies to CRM1. The inhibition of the nuclear export of AhR by LMB repressed the transcriptional activation of the CYP1A1 gene. The findings suggest that nuclear-cytoplasmic shuttling of AhR is essential for the inducible expression of the CYP1A1 protein.

Animals↗
PubMed2000

FtsH recognizes proteins with unfolded structure and hydrolyzes the carboxyl side of hydrophobic residues.

FtsH of Escherichia coli is an essential membrane-integrated ATP-dependent protease. We cloned a gene for an FtsH homolog (T. FtsH) from Thermus thermophilus HB8, expressed it in E. coli, and purified the expressed protein. ATPase activity of T.FtsH was activated by proteins with unfolded structure ( alpha-casein and pepsin), and T.FtsH digested these proteins in an ATP-, Zn(2+)-dependent manner. alpha-Lactalbumin was digested by T.FtsH when it was largely unfolded, but not in its native form. Analysis of the proteolytic products revealed that, in most cases, T.FtsH cleaved the C-terminal side of hydrophobic residues and produced a characteristic set of small peptides (<30 kDa) without releasing a large intermediate. Thus, T.FtsH recognizes the unfolded structure of the proteins and progressively digests them at the expense of ATP. A soluble domain of T.FtsH, which lacked the N-terminal two transmembrane helices, was also prepared but was found to retain neither ATPase nor protease activities. Thus, the membrane segment appeared to be indispensable for these activities of T.FtsH.

ATP-Dependent Proteases↗