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Biomedical subjects

S Mizuno

Publications and source records attributed to S Mizuno.

At least 163 records · Page 9Linked to original sources

Sequence variation in the small-subunit rRNA gene of Plasmodium malariae and prevalence of isolates with the variant sequence in Sichuan, China.

By two PCR-based diagnostic methods, Plasmodium malariae infections have been rediscovered at two foci in the Sichuan province of China, a region where no cases of P. malariae have been officially reported for the last 2 decades. In addition, a variant form of P. malariae which has a deletion of 19 bp and seven substitutions of base pairs in the target sequence of the small-subunit (SSU) rRNA gene was detected with high frequency. Alignment analysis of Plasmodium sp. SSU rRNA gene sequences revealed that the 5' region of the variant sequence is identical to that of P. vivax or P. knowlesi and its 3' region is identical to that of P. malariae. The same sequence variations were also found in P. malariae isolates collected along the Thai-Myanmar border, suggesting a wide distribution of this variant form from southern China to Southeast Asia.

Animals↗

In vitro secretion of cytokines by human bone marrow: effects of age and estrogen status.

It has been proposed that cytokines mediate the acceleration of bone loss following menopause. Because of the intimate relationship between bone marrow stromal cells and bone tissue, it is possible that marrow cells and their products contribute to the bone microenvironment and influence the regulation of bone cell differentiation and activity. We examined the production of cytokines by bone marrow stromal cells from a total of 37 women and 15 men undergoing total hip replacement for noninflammatory joint disease. Low-density mononuclear cells were isolated from bone marrow and were cultured in phenol red-free alpha MEM medium supplemented with 10% FBS and antibiotics. Constitutive secretion of interleukin-6 (IL-6) was positively correlated with age in a series of 8 women and 5 men measured by bioassay (r = 0.98; P < 0.01) and in a series of 18 women and 10 men measured by immunoassay (r = 0.56; P < 0.01). The pattern of cytokine production by bone marrow stromal cells was examined in detail in 23 postmenopausal women, aged 49-88 yr. Basal secretion of immunoreactive IL-6 and IL-11, but not granulocyte-macrophage colony-stimulating factor, increased with time in culture. Exogenous IL-1 beta stimulated secretion of IL-6 and IL-11 in a saturable, dose-dependent manner. Secretion of soluble IL-6 receptor was not correlated with secretion of IL-6, either constitutively or in the presence of IL-1 beta. In 4 of 14 samples, IL-1 beta also stimulated secretion of granulocyte-macrophage colony-stimulating factor. IL-1 beta was undetectable in 7 of 9 cultures during the 2-week culture period. IL-6 did not stimulate secretion of IL-1 beta in the 7 cultures tested. Cells were dependent upon serum for viability and growth and were not sustained by a serum substitute (1% insulin-transferrin-selenium-BSA). Cells grown in medium with 10% FBS and supplemented with 1% insulin-transferrin-selenium-BSA secreted 10-fold more IL-6 than cells grown in serum alone. Marrow from 7 women receiving estrogen replacement therapy showed lower constitutive secretion of IL-6 (75%; P < 0.006) and IL-11 (43%; P < 0.05) than marrow from age-matched controls and had blunted stimulation of IL-6 and IL-11 secretion by exogenous IL-1 beta. These data indicate distinct patterns of cytokine production by human marrow stromal cultures dependent upon age and estrogen status.

Adult↗

Effect of herbimycin A on tyrosine kinase receptors and platelet derived growth factor (PDGF)-induced signal transduction.

Herbimycin A is widely used as an inhibitor of Src family protein tyrosine kinases but is also reported to induce the downregulation of epidermal growth factor (EGF) receptor number in A431 cells without inhibiting its tyrosine kinase activity. To determine the specificity of the receptor downregulation, we examined its effect on a variety of cell lines which express different levels of EGF receptor and on other tyrosine kinase receptors. Long-term herbimycin A treatment decreased the amounts of all the tyrosine kinase receptors examined in a dose-dependent manner. It also reduced ligand-stimulated receptor autophosphorylation in accordance with the reduction in the receptor level. Herbimycin A inhibited platelet derived growth factor (PDGF)-induced tyrosine phosphorylation of cellular proteins and DNA synthesis in NIH3T3 cells but did not affect the serum-stimulated DNA synthesis. PDGF-induced tyrosine phosphorylation and activation of c-Src was inhibited but the protein level of c-Src was not reduced by herbimycin A. The reduced level of c-Src kinase activity correlated with the levels of both PDGF receptor and DNA synthesis. These results indicate that the herbimycin A treatment selectively downregulates receptor tyrosine kinases, independent of the number of receptors, and suggest that c-Src is to some degree involved in the selective inhibition of PDGF-induced mitogenesis by herbimycin A.

3T3 Cells↗

Development of emulsion type new vehicle for soft gelatin capsule. I. Selection of surfactants for development of new vehicle and its physicochemical properties.

Screening of surfactants was carried out to develop an oil in water (o/w) emulsion type new vehicle for a soft gelatin capsule (SGC), using polyethyleneglycol 400 (PEG 400) as hydrophilic phase and medium chain triglyceride (Miglyol 810), propyleneglycol dicaprylate (Sefsol 228) or soybean oil as hydrophobic phase (PEG 400: hydrophobic phase: surfactant = 87:10:3) and by means of simple homogenization. Polyoxyethylene (20) cetylether (BC-20TX), which can form homogeneous and viscous white gels using the above hydrophilic and hydrophobic phase combination, was selected as a model surfactant for developing the new vehicle. Using Miglyol 810 as hydrophobic phase, a model new vehicle formulation (PEG 400:water:Miglyol 810: BC-20TX = 77:10:10:3) was prepared, and its physicochemical properties were evaluated. The particle size distribution of the new vehicle, after diluting about 3000 times with water, ranged from about 0.5 to 50 microns. Furthermore, the new vehicle had thixotropic property at room temperature (about 25 degrees C) and temperature-dependent gel-sol transforming property with the transformation temperature of about 37 degrees C. These properties meet the requirement for encapsulation of the new vehicle in SGC and suggest that it can be expected to form the o/w emulsion state in the aqueous environment in the stomach. The rheological properties would also make it advantageous for use in other dosage forms such as suppository, cataplasm or liniment.

Capsules↗

The correlation between coronary stenosis index and flow-mediated dilation of the brachial artery.

We examined the relationship between flow-mediated dilation (FMD) of the brachial artery and the extent and severity of coronary artery disease (CAD). Using high-resolution ultrasonography, we measured FMD and nitroglycerin-induced brachial artery dilation. We studied 121 patients (77 men, 44 women; mean age 64+/-11 years, range 25-79 years) who underwent coronary arteriography. The extent and severity of CAD were assessed by the coronary stenosis index (CSI). The adjusted FMD correlated inversely with CSI (rs=-0.63, p<0.0001). Multivariate analysis demonstrated that the adjusted FMD was an independent predictor of CSI. The adjusted FMD was 10.2+/-4.8% in patients without CAD (n=32), 7.7+/-6.0% in patients with single-vessel disease (n=31), 5.2+/-5.5% in patients with double-vessel disease (n=29), and 2.0+/-3.9% in patients with triple-vessel disease (n=29). The adjusted FMD was significantly lower in the double- (p<0.01) and triple-vessel (p<0.0001) disease groups than in patients without CAD. The adjusted FMD was significantly lower in the triple-vessel disease group than in the single-vessel disease group (p<0.001). Based on our results, as coronary atherosclerosis becomes more severe, the adjusted brachial artery FMD becomes more severely impaired.

Adult↗

Effects of dermatan sulfate, a heparin cofactor II mediated thrombin inhibitor, on the endotoxin-induced disseminated intravascular coagulation model in the rat: comparison with low-molecular weight heparin, nafamostat mesilate and argathroban.

Effects of dermatan sulfate (DS) on the endotoxin-induced disseminated intravascular coagulation (DIC) rat model were compared with those of low-molecular weight heparin (LMWH), nafamostat mesilate (NM) and argathroban (AR). At doses of 5, 10 or 20 mg/kg/4 hr, DS significantly ameliorated the decrease of fibrinogen (Fbg), the increase of fibrin-fibrinogen degradation products (FDP) and except at the highest dose (20 mg/kg/4 hr), the prolongation of thrombin clotting time (TCT). It also decreased the glomerular fibrin deposits (%GFD) at doses of 10 or 20 mg/kg/4 hr. LMWH suppressed the decrease of Fbg and the increase of FDP at doses of 1.4 or 2.8 mg/kg/4 hr. Only the highest dose of LMWH suppressed the decrease of the platelet count (PL), the prolongation of prothrombin time, and improved the %GFD. AR suppressed the decrease of PL and improved the %GFD. At the dose required to improve the %GFD, DS (5, 10 mg/kg/4 hr) significantly suppressed the prolongation of TCT, which is related to the bleeding frequency, while LMWH and AR further increased the prolongation of the TCT. These results suggest that DS has potential as a therapeutic drug with a lower hemorrhagic risk as compared with LMWH and AR in the treatment of DIC.

Animals↗

Production of superoxide and nitric oxide by alveolar macrophages in the bleomycin-induced interstitial pneumonia mice model.

To elucidate the potential role of superoxide (O2-) and nitric oxide (NO) in the pathogenesis of interstitial pneumonia, the quantity of O2- and NO produced by the alveolar macrophages (AM) were determined in the bleomycin (BLM)-induced interstitial pneumonia mouse model. The production of O2- and NO increased on days 7, 14 and 21 after BLM injection. Strong expression of peroxynitrite (ONOO-) was seen in AM by using immunostaining for nitrotyrosine. The hydroxyproline contents increased on day 21 after BLM injection. O2- and NO are thought to play an important role in the pathology of fibrosis.

Animals↗

[Quinolinic acid depolarizes the spinal motoneurons of newborn rats by activating NMDA receptors].

Quinolinic acid (QA), a tryptophan metabolite, is known to be present in many regions of the mammalian central nervous system (CNS). However, its role is still unclear. In order to evaluate the physiological role of QA in CNS, the present study was undertaken to examine its action on the spinal motoneurons of newborn rats in vitro. It wa found that QA depolarized spinal motoneurons directly. Its potency was the same as that of glutamic acid at the same concentrations. The depolarization induced by QA was strongly inhibited by 2-amino-5-phosphonovalerate (AP5), an NMDA receptor antagonist. The effect of quinolinic acid was, on the other hand, not inhibited by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), a non-NMDA receptor antagonist, in the presence of glycerine. These results indicate that the NMDA receptor is responsible for the QA-induced-depolarization. The possible role of QA as a transmitter is discussed.

2-Amino-5-phosphonovalerate↗

Differential expression of genes for aromatase and estrogen receptor during the gonadal development in chicken embryos.

In birds, differentiation of embryonic gonads is not as strictly determined by the genetic sex as it is in mammals, and can be influenced by early manipulation with a sex steroid hormone. Thus administration of an aromatase inhibitor induces testis development in the genetic female, and administration of estrogen induces a left ovotestis in the genetic male embryo. Another feature of avian gonadogenesis is that only the left ovary develops in most species. Molecular mechanisms underlying these features at the level of gene expression have not been elucidated. In this paper, we present evidence that a gene for aromatase cytochrome P-450, an enzyme required for the last step in the synthesis of estradiol-17beta, is expressed in medullae of the left and right gonads of a female chicken embryo, but not in those of a male chicken embryo, and that an estrogen receptor gene is expressed only in epithelium (and cortex later, in the female) of the left, not the right, gonad of both sexes, but the expression in the male left gonad is temporary and restricted to an early stage of development. Differential expression of these two genes serves well to explain the above features of gonadal development in birds. Furthermore, in ovo administration of estradiol-17beta from the 5th to the 14th day of incubation does not cause expression of the estrogen receptor gene in the right gonad of chicken embryos of either sex, suggesting that the absence of expression of the estrogen receptor gene in the right gonad is not the result of down-regulation, but may be regarded as an important cause of the unilateral ovarian development.

Animals↗

Mortality risks of oesophageal cancer associated with hot tea, alcohol, tobacco and diet in Japan.

To clarify mortality risks of oesophageal cancer associated with hot tea, alcohol, tobacco and diet, further analyses on the data from a large prospective cohort study in Japan were conducted. The subjects for analysis were 220,272 men and women aged 40 to 69 at the baseline of 1965. There were 440 oesophageal cancer deaths during the period from January 1966 to December 1981. Person-years at risk were 3,065,182 in total. Rate ratio and 95% confidence interval adjusted for attained age, prefecture, occupation and sex were (RR (95% CI)): 1.6 (1.2-2.0) for hot tea (drinking green tea at high temperatures) in comparison with not-hot tea (drinking green tea at moderate temperatures); 2.4 (1.8-3.1) for daily (4 times/week or more) alcohol drinking in comparison with non-drinking; and 2.3 (1.7-3.1) for heavy smoking (15 cigarettes/day or more) in comparison with non-smoking. Dose-response relationships were found in alcohol drinking and smoking among men and women (p for trend; p < 0.001). The rate ratios were not significantly associated with the dietary factors except for green-yellow vegetables (1-3 times/month or less in comparison with daily; RR = 2.0, 95% CI: 1.2-3.1), where a no dose-response trend was observed (p = 0.45). In comparison based on the binary variables, the RR for the subjects with daily alcohol drinking and current smoking was 3.9 with 95% CI of 2.7 to 5.4, relative to those exposed to neither habit. The joint effect of alcohol drinking (A) and smoking (S) was more than additive (A*S > A + S: 3.9 > 1 + (1.0-1) + (1.6-1)). Further sub-analysis showed that the RR for the subjects with daily alcohol drinking, current smoking and hot tea was 5.7 with 95% CI of 3.7 to 8.9, when the reference was the subjects with not-daily alcohol drinking, non-smoking and not-hot tea. Similar results were obtained from further adjustment of green-yellow vegetables. It is concluded that mortality risks of oesophageal cancer in the present cohort were substantially associated with thermal effect of hot tea, alcohol drinking, smoking and lower consumption of green-yellow vegetables. This finding suggests that life-style modification for smoking and dietary habits is essential to reduce the risks of oesophageal cancer in Japan.

Adult↗

Preventive effect of ACE inhibitor on interstitial myofibroblast formation and matrix deposition in a nephrotic model.

The nephrotic mouse (ICGN strain) is a useful model for progressive nephrotic syndrome (NS). In the present study, we demonstrated the preventive effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, on the progression of renal dysfunction and tubulo-interstitial fibrosis in the NS mice. Administration of enalapril (5 mg/dL in drinking water) to the 4-week-old NS mice for a 4-week-period did not improve their nephrotic symptoms such as albuminuria and hypoalbuminemia, but significantly suppressed the increases in blood urea nitrogen and serum creatinine levels. Renal histopathology demonstrated that the administration of the ACE inhibitor significantly attenuated the progression of the tubular and interstitial lesions (tubular dilatation, luminal cast accumulation and interstitial expansion) rather than the glomerular sclerotic changes. The suppression of the increase in blood urea nitrogen level by enalapril depended on the attenuated tubular injury rather than on the unchanged glomerular matrix deposition. Immunohistochemical examination revealed that the administration of the ACE inhibitor suppressed the formation of myofibroblasts, identified by the alpha-smooth muscle actin-positive cells, in the interstitial spaces. Consequently, interstitial matrix deposition was significantly reduced in the NS mice treated with enalapril. From the results obtained with the spontaneous nephrotic model, we emphasize a possibility that ACE inhibitor may be effective for attenuating progression of renal dysfunction and fibrosis in human NS, even if the ACE inhibitor fails to improve nephrotic symptoms such as albuminuria and hypoalbuminemia.

Angiotensin-Converting Enzyme Inhibitors↗

The novel enzymatic 3''-N-acetylation of arbekacin by an aminoglycoside 3-N-acetyltransferase of Streptomyces origin and the resulting activity.

Kanamycin group antibiotics were subjected to enzymatic acetylation by a cell free extract containing an aminoglycoside 3-N-acetyltransferase, AAC(3)-X, derived from Streptomyces griseus SS-1198PR. Characterization of the incubated reaction mixtures by TLC and antibiotic assay revealed that a product retaining activity was specifically formed from arbekacin, an anti-MRSA semisynthetic aminoglycoside. The structural determination demonstrated that acetylation occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino group in dibekacin as in the case of kanamycin. These results should reflected the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in arbekacin and amikacin, but absent in dibekacin and kanamycin. The 3"-N-acetylation is the first finding in the enzymatic modifications of aminoglycoside antibiotics. 3"-N-Acetylarbekacin showed antibiotic activity as high as that of 2'-N-acetylarbekacin reported previously, whereas 3"-N-acetylamikacin showed no substantial activity. Thus, our results illuminated a novel aspect of arbekacin distinct from the other aminoglycosides.

Acetylation↗

Occult intestinal bleeding imaged by technetium-99m-HSA-D radionuclide angiography: a case report.

Radionuclide angiography (RNA) with 99mTc-diethylenetriamine pentaacetic acid human serum albumin (99mTc-HSA-D) is a sensitive screening method for diagnosing systemic perfusion abnormalities. Sometimes the results produce unexpected information. This information is helpful when considering the clinical perfusion pathophysiology. Recently, we were able to detect an intestinal bleeding lesion clearly for a patient by using RNA.

Aged↗

[C-MOS flat-panel sensor for real time X-ray imaging].

Flat-panel, self-scanning, solid state diagnostic x-ray imaging devices using complementary metal-oxide-semiconductor (C-MOS) arrays are under investigation. A unit device with a 5 cm by 5 cm sensor area was developed and tested. The device consists of a CsI scintillator and C-MOS detector arrays. The detector arrays are composed of a regular arrangement of pixels (256 x 256), each of which is made of a C-MOS photodiode sensor coupled to a C-MOS FET (field effect transistor). A common FET gate line is connected to all the FET gates along each column. A common date line is connected to all the FET drains of each row. The source contact of each FET is connected to that of its corresponding photodiode. A positive gate pulse applied to a gate turns on all FETs connected to the date lines. The readout continues column by column. Correlated double sampling circuits and an offset variance compensation circuit were installed to reduce noise. A sampling speed of 15 frames per second and spatial resolution of 2.5 line per mm were achieved. Noise level and maximum signal were 1.5 mV rms and 1.8 V, respectively. Image quality was considered acceptable for clinical use. It is also discussed how to fabricate a large area sensor with the unit device.

Humans↗

[Two cases of two-year-old girls with hypoxic ischemic encephalopathy induced by convulsive status].

We reported two cases of two-year-old girls with hypoxic ischemic encephalopathy. Their symptom was coma induced by seizures with respective factors. CT image on subacute stage showed the decreased density of the whole brain except for the primary sensorimotor cortex and the occipital lobe. MRI and CT images on chronic stage revealed generalized atrophy with no abnormal density areas. 99mTc-ECD SPECT on chronic stage showed low perfusion in the whole brain except for the primary sensorimotor cortex and the occipital lobe, in which areas brain tissue is considered to be injured easily in hypoxic ischemic encephalopathy. The paradoxical distribution of abnormal cerebral perfusion areas in our cases was reported in this paper.

Brain↗