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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 199 records · Page 11Linked to original sources
PubMed1998

Circumvention of multidrug resistance by a quinoline derivative, MS-209, in multidrug-resistant human small-cell lung cancer cells and its synergistic interaction with cyclosporin A or verapamil.

PURPOSE AND METHODS: To develop a clinically useful approach to circumvent P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MDR human small-cell lung cancer (SCLC), we examined the ability of a novel quinoline compound, MS-209, to reverse MDR by inhibition of P-gp function in combination with other MDR-reversing drugs using a cytotoxicity assay. RESULTS: We established MDR human SCLC cells by culture in medium with gradually increasing concentrations of adriamycin (ADM). Compared with the parental human SCLC cells, SBC-3, the MDR variant SBC-3 cells obtained (SBC-3/ADM) were highly resistant to various chemotherapeutic agents due to P-gp expression. MS-209 reversed the resistance to ADM and vincristine (VCR) of SBC-3/ADM and H69/VP cells in a dose-dependent manner. Moreover, MS-209 in combination with cyclosporin A (CsA) or verapamil (VER) synergistically enhanced the antitumor effects of ADM and VCR on SBC-3/ADM cells. MS-209 restored ADM incorporation and this effect was enhanced by CsA and VER, suggesting that these synergistic effects were due to competitive inhibition of P-gp function. CONCLUSION: MS-209 in combination with CsA or VER might increase the efficacy of these chemotherapeutic agents against MDR human SCLC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

News & notes. Efficient library construction with a TA vector and its application to cloning of the phytoene synthase gene from the cyanobacterium Spirulina platensis.

An efficient and simple method for constructing a genomic DNA library is presented by use of a TA cloning vector. It is based on sonicative cleavage of genomic DNA and modification of the fragment ends with Taq DNA polymerase, followed by ligation with a TA vector. This method was successfully applied to cloning of the phytoene synthase gene crtB from Spirulina platensis. The method is useful when the genomic DNA is not well digested with restriction enzymes owing to methylation or other reasons.

Alkyl and Aryl Transferases↗
PubMed1998

Surrogate thrombopoietin.

The extracellular domain of human c-Mpl, the receptor for thrombopoietin (TPO), was expressed as a chimeric protein with the interleukin-2 receptor alpha chain on the surface of murine B cell-line B300-19. BALB/c mice were immunized with cells expressing the chimeric protein. The IgG purified from the resulting immune serum immunoprecipitated human c-Mpl. The immune IgG supported proliferation of both stable transfectant Ba/F3 cells expressing whole c-Mpl molecules (c-Mpl-Ba/F3 No. 9) and UT7/TPO cells bearing naturally occurring c-Mpl, whereas it did not support the growth of the untransfected parental Ba/F3 cells. Cell growth was induced using 3 to 100 microg/ml of immune IgG in a dose-dependent manner, but this induction was decreased at doses higher than 100 microg/ml. Non-immune IgG did not affect cell growth of c-Mpl-Ba/F3 No. 9 cells. Although the Fab fragment of immune IgG also immunoprecipitated c-Mpl, it did not support cell growth at concentrations as high as 180 microg/ml, implying that the bivalent binding of receptors by antibodies is essential for cell proliferation. These results suggest that antibodies against human c-Mpl stimulate the proliferation and differentiation of megakaryocytes by their bivalent binding to receptors like TPO.

Animals↗
PubMed1998

Precise distribution of neuronal nitric oxide synthase mRNA in the rat brain revealed by non-radioisotopic in situ hybridization.

Regional distribution of neurons expressing neuronal nitric oxide synthase mRNA in the rat brain was examined by non-radioisotopic in situ hybridization, using digoxigenin-labeled complementary RNA probes. Clustering of intensely positive neurons was observed in discrete areas including the main and accessory olfactory bulbs, the islands of Calleja, the amygdala, the paraventricular nucleus of the thalamus, several hypothalamic nuclei, the lateral geniculate nucleus, the magnocellular nucleus of the posterior commissure, the superior and inferior colliculi, the laterodorsal and pedunculopontine tegmental nuclei, the nucleus of the trapezoid body, the nucleus of the solitary tract and the cerebellum. Strongly-stained isolated neurons were scattered mainly in the cerebral cortex, the basal ganglia and the brain stem, especially the medulla reticular formation. In the hippocampus, an almost uniform distribution of moderately stained neurons was observed in the granular cell layer of the dentate gyrus and in the pyramidal cell layer of the Ammon's horn, while more intensely stained isolated neurons were scattered over the entire hippocampal region. These observations can serve as a good basis for studies on function and gene regulation of neuronal nitric oxide synthase.

Animals↗
PubMed1998

Tubulointerstitial mast cell infiltration in glomerulonephritis.

Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis. Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3 cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA) nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r=0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury.

Adolescent↗
PubMed1998

Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation.

Although Ca2+-stimulated cAMP response element binding protein- (CREB-) dependent transcription has been implicated in growth, differentiation, and neuroplasticity, mechanisms for Ca2+-activated transcription have not been defined. Here, we report that extracellular signal-related protein kinase (ERK) signaling is obligatory for Ca2+-stimulated transcription in PC12 cells and hippocampal neurons. The sequential activation of ERK and Rsk2 by Ca2+ leads to the phosphorylation and transactivation of CREB. Interestingly, the Ca2+-induced nuclear translocation of ERK and Rsk2 to the nucleus requires protein kinase A (PKA) activation. This may explain why PKA activity is required for Ca2+-stimulated CREB-dependent transcription. Furthermore, the full expression of the late phase of long-term potentiation (L-LTP) and L-LTP-associated CRE-mediated transcription requires ERK activation, suggesting that the activation of CREB by ERK plays a critical role in the formation of long lasting neuronal plasticity.

Animals↗
PubMed1998

Synthesis and evaluation of nitro 5-deazaflavin-pyrrolecarboxamide(s) hybrid molecules as novel DNA targeted bioreductive antitumor agents.

A series of 6-nitro-5-deazaflavins bearing at N(3) or N(10) position the pyrrolecarboxamide(s) group as DNA minor groove binder has been synthesized. These hybrid molecules show similar redox properties to those of 6-nitro-5-deazaflavins with no pyrrolecarboxamide(s) group, suggesting that they generate stable one- and two-electron reduction product(s). Electrolytic reductions of the hybrid molecules were carried out at a controlled potential under anaerobic conditions in the presence of plasmid pBR322 DNA. Significant conversions of the supercoiled circular pBR322 DNA (form I) to the open circular DNA (form II) have been found by treatment with the reductively activated 6-nitro-5-deazaflavin derivatives. Their DNA damaging effects have been found to be enhanced as the number of pyrrolecarboxamide group as the DNA binder increases. Antitumor activities of the hybrid molecules towards KB and L1210 cells were evaluated in vitro. It has been found that the antitumor effects of the compounds on KB cells slightly change and those on L1210 cells decrease as the number of the pyrrolecarboxamide group increases. These results reveal that the combination of 6-nitro-5-deazaflavin molecule with the pyrrolecarboxamide(s) group increase the DNA binding properties of the compounds, giving rise to promoted DNA damaging effects, and also suggest that the combination would affect the capacity of the compounds to act as the substrate for intracellular reductases and/or the cellular uptake of the compounds.

Animals↗
PubMed1998

[Shigella dysenteriae strains possessing a new serovar (204/96) isolated from imported diarrheal cases in Japan].

Five Shigella strains isolated from stool cultures of imported diarrheal cases in Japan, did not react to any antisera of the established Shigella serovars. These strains had the typical biochemical characteristics of Shigella dysenteriae, and were biochemically identical. All strains were positive in the Sereny test and other tests for invasivness; these indicate that they can cause shigellosis in humans. The results of antigenic analysis revealed that they did not belong to any of the recognized or provisional serovars, and were serologically indistinguishable. They had the same drug-resistance pattern (CP.TC.SM.ABPC.ST) and plasmid-profile. Strain 96-204 is designated as the test strain for this new serovar.

Anti-Bacterial Agents↗
PubMed1998

Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.

PURPOSE: To evaluate the relationship of total-dose of daunorubicin (DNR) to the induction therapy and treatment outcome, we have administered individualized doses of DNR during induction treatment to patients with acute myelogenous leukemia (AML). PATIENTS AND METHODS: Ninety-two previously untreated adult patients with AML who entered our hospital were analyzed for the dose of DNR required to achieve complete remission (CR), the CR rate, disease-free survival (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2 daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara-C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS: Eighty-three of 92 patients with adult AML were assessable for this study. Sixty-three (76%) patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first course of induction therapy, and 11 patients required the second course of induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10-year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not influence the response to therapy and was not influenced by the initial WBC count or French-American-British (FAB) system classification. CONCLUSION: These results indicated that when the dose was linked to observed tumor response, the optimal dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7 days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.

Adolescent↗
PubMed1998

An autopsy case of cytokeratin 7-positive minute adenocarcinoma of the lung with systemic metastases.

We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin.

Biomarkers, Tumor↗
PubMed1998

Metabolism of transforming growth factor-beta in patients receiving hemodialysis especially those with renal osteodystrophy.

We evaluated the intraplatelet and plasma levels of transforming growth factor beta (TGF-beta) in patients with or without renal osteodystrophy (ROD) who were undergoing hemodialysis (HD). Intraplatelet and plasma levels of TGF-beta were examined before and after HD, and compared with those from healthy controls. Patients undergoing HD had significantly higher mean intraplatelet levels of TGF-beta before and after HD than did the healthy subjects (22.7 +/- 7.8 and 29.5 +/- 15.8 vs. 18.7 +/- 7.9 ng/10(5) platelets; p < .05). The mean intraplatelet and plasma levels of TGF-beta in patients after HD were significantly increased than those before HD and in healthy subjects (p < .05). Moreover, patients with ROD showed a significantly higher mean intraplatelet and plasma levels of TGF-beta than that without ROD (p < .05). To investigate the effects of TGF-beta on ROD in HD patients, we evaluated such parameters as parathyroid hormone (PTH) and alkaline phosphatase (ALP), which reflect the lesions of ROD. The mean intraplatelet level of TGF-beta was not correlated with either para-meter. Meanwhile, no correlation was observed between the intraplatelet level of TGF-beta and the hematocrit (Hct). Similarly, no correlation was observed between the intraplatelet levels of TGF-beta and the dose of erythropoietin (EPO) administered. These findings indicate that metabolism of TGF-beta occurs during HD and overproduction of TGF-beta may play an important role in the pathogenesis of ROD.

Blood Platelets↗
PubMed1998

Eye movement of perceivers during audiovisual speech perception.

Perceiver eye movements were recorded during audiovisual presentations of extended monologues. Monologues were presented at different image sizes and with different levels of acoustic masking noise. Two clear targets of gaze fixation were identified, the eyes and the mouth. Regardless of image size, perceivers of both Japanese and English gazed more at the mouth as masking noise levels increased. However, even at the highest noise levels and largest image sizes, subjects gazed at the mouth only about half the time. For the eye target, perceivers typically gazed at one eye more than the other, and the tendency became stronger at higher noise levels. English perceivers displayed more variety of gaze-sequence patterns (e.g., left eye to mouth to left eye to right eye) and persisted in using them at higher noise levels than did Japanese perceivers. No segment-level correlations were found between perceiver eye motions and phoneme identity of the stimuli.

Eye Movements↗
PubMed1998

[Clinical analysis of foreign patients with tuberculosis found in Chugoku-Shikoku area].

In this study, we investigated 45 foreign patients who had been diagnosed as having tuberculosis in Chugoku-Shikoku area during the past 12 years. Regarding regional characteristics, in Hiroshima prefecture an epidemic of tuberculosis was experienced among patients coming from South America, but antituberculous therapy was performed for 87% of the patients because of the high coverage of the health insurance scheme. But in Okayama prefecture, most of the patients were female and came from Asian countries, such as, the Philippines. Antituberculous therapy was not performed for nine patients because of no coverage of the health insurance scheme. In the other prefectures, only a few cases of tuberculosis were experienced, but in Yamaguchi prefecture two of three foreign patients were multidrug-resistant tuberculosis.

Adolescent↗
PubMed1998

[The diagnostic value of thoracoscopic examinations in tuberculous pleurisy].

We evaluated the diagnostic value of thoracoscopic examinations in eleven patients who had pleural effusion and were diagnosed as tuberculous pleurisy. The characteristic white or yellowish-white micronodules were observed by thoracoscopy in eight patients and all their biopsied tissue were compatible with tuberculosis. We had some cases which were not determined as tuberculous pleurisy from bacteriological examinations and were determined only from the thoracoscopic findings.

Adenosine Deaminase↗
PubMed1998

Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal osteodystrophy.

Pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy and 99mTc-hydroxymethylene diphosphonate (HMDP) bone scan were performed in one patient with renal osteodystrophy (ROD) before and after vitamin D3 pulse therapy. The bone scan showed diffusely increased tracer uptake in the whole skeleton, and no change of tracer distribution was noted before or after vitamin D3 pulse therapy. However, 99mTc(V)-DMSA scintigraphy revealed diffusely increased tracer uptake in the whole skeleton before therapy, and markedly decreased tracer uptake in the bones was seen at 5 mo after therapy. Increased uptake of 99mTc(V)-DMSA was observed at 7 mo after therapy, which reflected the laboratory findings. Technetium-99m-(V)-DMSA scintigraphy appeared to be more sensitive than the conventional 99mTc-HMDP bone scan in assessing the characteristics and therapeutic effect of bone disease in ROD.

Adult↗
PubMed1998

Enhancement of tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by combination with a humanized anti-glycoprotein IIb/IIIa monoclonal antibody, YM337, in a rhesus monkey model of coronary thrombosis.

We examined the effect of a humanized anti-glycoprotein IIb/IIIa monoclonal antibody, YM337, on thrombolysis with tissue-type plasminogen activator in a copper coil-induced coronary thrombosis model in rhesus monkeys. Fifty minutes after the formation of an occlusive thrombus, a test drug was administered by either i.v. bolus injection followed by continuous infusion (YM337, 0.25 mg/kg + 1.5 microg/kg/min) or i.v. bolus injection (aspirin, 17 mg/kg). Sixty minutes after induction of the occlusive thrombus, thrombolysis was initiated with tPA at a total dose of 0.5 mg/kg intravenously administered over 60 min, with 10% given as an initial bolus. The median time to reperfusion was significantly shortened by YM337 [saline, 60 min (n = 5); aspirin, 45 min (n = 5); YM337, 30 min (n = 5)]. The incidence of reocclusion was significantly decreased by YM337 (saline, 4/4; aspirin, 5/5; YM337, 1/5), and the median time to reocclusion was significantly prolonged by YM337 [saline, 30 min (n = 4); aspirin, 30 min (n = 5); YM337, 180 min (n = 5)]. YM337 significantly reduced the thrombus protein content at the end of experiment. ADP-induced platelet aggregation was completely inhibited by YM337. These results suggest that YM337 may be of clinical value as an adjunctive agent in thrombolytic therapy for patients with acute myocardial infarction.

Animals↗
PubMed1998

Levels of serum glycosaminoglycans in renal failure.

We measured the concentration of serum glycosaminoglycans (GAGs) in patients with glomerulonephritis, renal failure and on hemodialysis using the dye binding method. In glomerulonephritis, concentration of serum GAGs did not increase, and there was no correlation between serum and urinary GAGs. In patients with renal failure and hemodialysis, concentration of serum GAGs was significantly lower than in controls. Concentration of serum GAGs was correlated with concentration of serum albumin, which is an indicator of malnutrition in patients on hemodialysis. One month of hemodialysis did not affect the concentration of serum GAGs in patients with renal failure, but six months of hemodialysis increased the concentration of serum GAGs. These results suggest that matrix production is suppressed in renal failure with malnutrition.

Adult↗