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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 631 records · Page 35Linked to original sources

Introduction of new genetic markers on human chromosomes.

The purpose of this study was to use DNA transfection and microcell chromosome transfer techniques to engineer a human chromosome containing multiple biochemical markers for which selectable growth conditions exist. The starting chromosome was a t(X;3)(3pter----3p12::Xq26----Xpter) chromosome from a reciprocal translocation in the normal human fibroblast cell line GM0439. This chromosome was transferred to a HPRT (hypoxanthine phosphoribosyltransferase)-deficient mouse A9 cell line by microcell fusion and selected under growth conditions (HAT medium) for the HPRT gene on the human t(X;3) chromosome. A resultant HAT-resistant cell line (A9(GM0439)-1) contained a single human t(X;3) chromosome. In order to introduce a second selectable genetic marker to the t(X;3) chromosome, A9(GM0439)-1 cells were transfected with pcDneo plasmid DNA. Colonies resistant to both G418 and HAT medium (G418r/HATr) were selected. To obtain A9 cells that contained a t(X;3) chromosome with an integrated neo gene, the microcell transfer step was repeated and doubly resistant cells were selected. G418r/HATr colonies arose at a frequently of 0.09 to 0.23 x 10(-6) per recipient cell. Of seven primary microcell hybrid clones, four yielded G418r/HATr clones at a detectable frequency (0.09 to 3.4 x 10(-6)) after a second round of microcell transfer. Doubly resistant cells were not observed after microcell chromosome transfers from three clones, presumably because the markers were on different chromosomes. The secondary G418r/HATr microcell hybrids contained at least one copy of the human t(X;3) chromosome and in situ hybridization with one of these clones confirmed the presence of a neo-tagged t(X;3) human chromosome. These results demonstrate that microcell chromosome transfer can be used to select chromosomes containing multiple markers.

Cell Line↗

Syncytium formation of human and non-human cells by recombinant vaccinia viruses carrying the HIV env gene and human CD4 gene.

We examined the ability of the various human and non-human cell lines to form syncytia upon coinfection with recombinant vaccinia viruses each carrying the HIV env and the human CD4 gene. We found that three human cell lines and one of three monkey cell lines exhibited syncytium formation, but that one human cell line, two monkey cell lines and all the rabbit and mouse cell lines examined did not. This indicated that factors other than HIV env and CD4 were participating in syncytium formation and that distribution of these factors was restricted by species and by the cell type in a species.

Animals↗

Different mechanisms involved in the positive inotropic effects of benzimidazole derivative UD-CG 115 BS (pimobendan) and its demethylated metabolite UD-CG 212 Cl in canine ventricular myocardium.

UD-CG 115 BS produced a positive inotropic effect in a concentration-dependent manner (EC50 = 9.2 x 10(-5) M, efficacy = 0.65) in isolated canine ventricular muscle. UD-CG 212 Cl also elicited a positive inotropic effect (EC50 = 1.9 x 10(-7) M, efficacy = 0.23); its potency was higher, but its efficacy was much less than that of UD-CG 115 BS. Although the effect of UD-CG 115 BS was not altered by a beta-adrenoceptor antagonist, bupranolol (3 x 10(-7) M), the response to UD-CG 212 Cl in high concentrations became transient in the presence of bupranolol: After reaching a peak, the force decreased gradually to the control level at greater than or equal to 10(-4) M. Both UD-CG 115 BS and UD-CG 212 Cl elevated the cyclic AMP level, but to a much smaller extent than other newly developed cardiotonic agents such as amrinone, milrinone, enoximone, and piroximone. Carbachol (3 x 10(-6) M) abolished the accumulation of cyclic AMP produced by these agents while it suppressed the maximum contractile response to UD-CG 115 BS by only 30%. The positive inotropic effect of UD-CG 212 Cl was converted to a negative effect by carbachol. Both UD-CG 115 BS and UD-CG 212 Cl produced a leftward shift in the concentration-response curve for the positive inotropic effect of isoproterenol. These results suggest that an elevation of cyclic AMP levels owing to cyclic AMP phosphodiesterase inhibition may be predominantly responsible for the positive inotropic effect of UD-CG 212 Cl but that a cyclic AMP-independent mechanism may contribute significantly to the positive inotropic effect of UD-CG 115 BS. UD-CG 212 Cl (greater than 3 x 10(-6) M) elicits a negative inotropic effect that is unmasked by beta-adrenoceptor blockade.

Animals↗

Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against Helicobacter pylori.

The activities of various types of antiulcer agents against Helicobacter pylori (formerly called Campylobacter pylori) strains were determined by an agar dilution method. Among the compounds tested, two benzimidazole proton pump inhibitors, lansoprazole (AG-1749) and omeprazole, were found to have significant activities against this organism. The activity of lansoprazole was comparable to that of bismuth citrate, with MICs ranging from 3.13 to 12.5 micrograms/ml, and fourfold more potent than that of omeprazole. A major metabolite and two acid-converted rearrangement products of lansoprazole also exhibited good activities comparable or superior to that of the parent compound. Exposure to lansoprazole of H. pylori growing in a liquid medium led to an extensive loss of viability without a reduction in culture turbidity and produced an aberrant bacterial morphology characterized by the irregular constriction of cells and the collapse of cell surface structures. The antibacterial activity of lansoprazole and its related compounds was selective against H. pylori; common aerobic and anaerobic bacteria and Campylobacter jejuni were not inhibited by 100 micrograms/ml.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Distribution of the HindIII restriction fragment length polymorphism among patients with systemic lupus erythematosus with different concentrations of CR1.

Sixty six patients with systemic lupus erythematosus (SLE) were genotyped using a HindIII restriction fragment length polymorphism identified by CR1.1 cDNA, then were followed up for an average of 50 months to evaluate the stability of their CR1 activities. The gene frequencies for the two alleles which correlate with the numeric expression of CR1 on the erythrocytes were not significantly different between 66 patients with SLE and 52 normal controls. A discrepancy between homozygosity for a high allele and a negative CR1 activity was found in many patients. These patients, however, had significantly lower concentrations of serum complement than did patients with a positive CR1, and some were in an active state of the disease. Furthermore, there were several patients in whom the CR1 activities changed from negative to positive together with an increase in serum complement. Our results suggest that the decreased expression of CR1 on erythrocytes in patients with SLE is not inherited, rather it is a consequence of the disease processes.

Blotting, Southern↗

Clinical significance of serum levels of a carbohydrate antigen, sialyl SSEA-1, in patients with fibrosing lung disease.

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

Adrenal Cortex Hormones↗

[Development of a liquid chromatography/multiple electrochemical detector (LCMC) and its application in neuroscience].

A liquid chromatographic system with multiple electrochemical detectors (LCMC) was newly developed for quantitating 20 to 30 neurochemicals simultaneously within 20 to 25 min from one sample derived from biological specimens. The device can be used for estimating neurofunctional changes in the central nervous system under the influence of CNS drugs, behavioral changes of experimental animals and psychic effects in clinical stages, etc. The system consists of four parallel liquid chromatographs with multiple electrochemical detectors. The first three systems determine catecholamines, indoleamines and related compounds. The fourth system is for measuring acetylcholine and choline with an internal standard. A new type of electrochemical detector was developed that consists of 4 electrodes set at a different potentials: each of the eluting components was identified by the variation of 4 current peaks on each electrode. Twenty-eight standard compounds, including four internal standards, could be clearly separated; and the detection limits of these compounds were at least 0.1 to 0.4 pmol per injection. In this report, the usefulness and applicability of this system were confirmed by measuring neurochemicals in the striatum of rats sacrificed either by decapitation or microwave irradiation and in the human ventricular cerebrospinal fluid of patients with Parkinson's disease and essential tremor.

Animals↗

Differences in the antisecretory actions of the proton pump inhibitor AG-1749 (lansoprazole) and the histamine H2-receptor antagonist famotidine in rats and dogs.

Antisecretory effects of a substituted benzimidazole, (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazole (AG-1749) were compared with those of a histamine H2-receptor antagonist, famotidine. AG-1749 inhibited acid formation regardless of the stimulant in isolated canine parietal cells, while famotidine inhibited the histamine-stimulated acid formation selectively. In pylorus-ligated rats, AG-1749 suppressed basal acid secretion, histamine-, bethanechol-, pentagastrin-, 2-deoxy-D-glucose- and stress (restraint and water-immersion)-induced acid secretion; ID50 values were 1.0-6.0 mg/kg. On the other hand, famotidine only partially inhibited the acid secretion induced by 2-deoxy-D-glucose or stress, although it suppressed the acid secretion stimulated by other secretagogues several times more potently than AG-1749. The antisecretory effect of AG-1749 lasted longer than that of famotidine, especially in the case of bethanechol-stimulated acid secretion. In Heidenhain pouch dogs, both AG-1749 and famotidine potently inhibited histamine-, bethanechol-, pentagastrin- and peptone meal-stimulated acid secretion, but the inhibitory effect of famotidine was short-lived in the case of bethanechol- and pentagastrin-stimulated acid secretion. These results suggest that AG-1749 persistently inhibits acid secretion induced by both peripheral and central stimuli and suggest that the antisecretory effect of famotidine depends on the nature of the stimuli.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of a proton pump inhibitor, AG-1749 (lansoprazole), on reflux esophagitis and experimental ulcers in rats.

The effects of (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy-2- pyridyl]methyl]sulfinyl]-1H-benzimidazole (lansoprazole, AG-1749) and famotidine on various experimental ulcers in rats were compared. AG-1749 inhibited reflux esophagitis; gastric lesions induced by water-immersion stress, aspirin or ethanol; and duodenal ulcers induced by cysteamine or mepirizole in a dose-dependent manner: the ID50 values were 0.7, 2.4, 0.7, 8.5, 1.1 and 0.3 mg/kg, p.o. or i.d., respectively. Famotidine inhibited reflux esophagitis with an ID50 value of 12.9 mg/kg, but did not cause 50% inhibition of ethanol-induced gastric lesions even at 100 mg/kg, although it showed almost the same or a little stronger potency on other experimental ulcers: ID50 values were 0.3-1.4 mg/kg. Significant aggravation of ethanol- or water-immersion stress-induced lesions was observed in rats given famotidine at 30 mg/kg twice daily for 4 days, but not in rats given AG-1749 at 10 mg/kg twice daily. Administration of AG-1749 for 14 consecutive days markedly accelerated the healing of acetic acid-induced gastric and duodenal ulcers, and the healing effect was significant at 10 and 30 mg/kg/day, p.o. Famotidine also accelerated the healing of ulcers, but its potency was less than that of AG-1749. The results of this study indicate that although AG-1749 is slightly less potent than famotidine in inhibiting acutely induced gastroduodenal lesions, this agent is superior to famotidine in promoting the healing of ulcers and in inhibiting reflux esophagitis and ethanol-induced gastric lesions.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Nilvadipine, a new calcium channel blocker, reduces ischemic brain injury in rats.

The effects of nilvadipine, a dihydropyridine type calcium channel blocker, on cerebral infarction induced by focal brain ischemia was studied in rats. The area of infarction was measured 24 hr after occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats using triphenyltetrazolium chloride. Nilvadipine, given immediately after MCA occlusion, reduced the area of infarction significantly at doses of 0.32 mg/kg (i.p.) and 3.2, 10 and 32 mg/kg (p.o.). Nicardipine suppressed the area of infarction at a dose of 32 mg/kg (p.o.). The results suggest that nilvadipine is effective against ischemic brain injury.

Animals↗

Population study of ambulatory blood pressure in a rural community in northern Japan.

A cross sectional survey was performed on ambulatory blood pressure (ABP) in a rural community in northern Japan. ABP was measured in 468 participants (148 men and 320 women, or 27.3% of the less than or equal to 20 year-old population in the study region) with a Colin ABPM 630, an ABP monitoring system. ABP was determined every 30 min for 24 hr. All-day average of 24 hr ambulatory systolic, (SBP) and diastolic BP (DBP) in these subjects were 121.5 +/- 11.8 and 71.7 +/- 8.0 mmHg (mean +/- S.D.), respectively. Ambulatory SBP and DBP levels increased gradually with an increase in age in both sexes. The age dependent increase in SBP was, however, extremely small in men compared with that in the casual SBP of the ordinary Japanese reported. The minimal age-dependent increase in ambulatory SBP in men reflects a high ambulatory SBP in those below 50 years-old as well as a minimal increase in ambulatory SBP in those over 50. Ambulatory SBPs in women were lower than those in men until they reach the age of 50 years. Ambulatory SBP levels in men and women were similar after their 60's. Ambulatory DBP tended to fall or remain at the same level after 60 years-old. Thus, a greater pulse pressure was observed in elderly subjects. Casual SBP and DBP in the ordinary Japanese were significantly higher than the daytime average ambulatory SBP and DBP in all age groups of both sexes in the population except those in their 20's. The results suggests that ABP has different clinical characteristics and may have a different clinical significance from casual BP.

Adult↗

Metallothionein concentrations and organ retention of mercury in the liver and kidney of the neonatal guinea pig after exposure to mercury vapor.

Neonatal guinea pigs were exposed to mercury vapor on the day of birth, and the following mercury distribution and concentrations of metallothioneins (MTs) in the liver and kidney were observed. In the liver, two hours after exposure, an appreciable amount of mercury accumulated and a substantial portion of this was associated with MTs. During postnatal development, the mercury concentration increased, whereas the hepatic concentration of MTs decreased. The mercury in the soluble fraction of the liver shifted from the region of MTs to the high-molecular-weight region and, finally, the mercury peak in the MT region was not detected. The kidney mercury concentration was high even 2 hr after the exposure and on days 3 and 7 postpartum. The peak concentration was observed on day 3 postpartum. The mean renal concentration of MTs in the mercury-exposed neonates was significantly higher than that of the control at all times observed. The changes in both the mercury level and the concentration of MTs were strongly correlated. Furthermore, most mercury in the soluble fraction was associated with MTs on day 7. These findings indicated enhanced synthesis of MTs in the kidney, but not in the liver, after mercury vapor exposure in the neonatal period, with corresponding elevated copper and zinc concentrations in the kidney.

Administration, Inhalation↗

Fiberoptic ductoscopy of the breast: a new diagnostic procedure for nipple discharge.

A fiberoptic ductoscopy system was successfully developed by means of which we were able to observe the duct cavity of the breast. Two kinds of silicafiberscopes with outer diameters 0.80 and 0.45 mm were used in the present study. Fiberoptic ductoscopy was applied to 52 ducts in 46 patients with nipple discharge for whom no tumor was palpable; the intraductal appearance could be observed in 47 ducts from 41 patients (90.3%). Fourteen ducts from 13 patients were operated upon and were histologically diagnosed as carcinoma (four cases), intraductal papilloma (nine ducts from eight patients) and mastitis (one case). The internal surface of a normal duct was lustrous and smooth. Cancer growing on the surface of a duct wall appeared white and was slightly elevated, forming a bridging structure. The intraductal papillomas formed intraductal solid nodules, being yellow in most cases and red at the site of hemorrhage. Fiberoptic ductoscopy can be used to recognize the growth of minute intraductal lesions in cases of nipple discharge. Clinical endoscopic diagnosis for minute intraductal lesions will make an important contribution to the early detection of cancer and the evaluation of nipple involvement in intraductal carcinoma.

Breast Neoplasms↗

The effects of beta-blockers and diazepam on heart rate of conscious conditioned rats.

1. Fischer male rats were trained to avoid shock in a shuttle box. After this procedure, a small ECG transmitter was incorporated under the skin of thorax. 2. In saline group, when in the shuttle box heart rate significantly increased, and decreased while exposed to the buzzer. 3. When beta-blocker (carteolol, pindolol, propranolol) was injected, heart rate did not increase after the rat was put in the shuttle box, but decreased after exposed to the buzzer. Change in heart rate was not shown when diazepam was injected. 4. These results indicated that diazepam is more effective than beta-blocker in terms of instability of heart rate in conditioned rats.

Adrenergic beta-Antagonists↗

[A clinical evaluation of the inorganic mercurialism--its pathogenic relation to amyotrophic lateral sclerosis].

The pathogenic relation of chronic mercurialism and amyotrophic lateral sclerosis (ALS) was evaluated clinically on 83 ex-mercury workers who were poisoned or exposed to mercury vapor about 18 years ago at one of the biggest mercury mines in Hokkaido, as well as on the causes of 65 expired workers in the cohort. The 83 ex-mercury workers were subdivided into two groups according to severity of mercury poisoning: 31 ex-workers who had been hospitalized for treatment of mercury poisoning and the remaining 52 ex-workers severely exposed to mercury vapor but not hospitalized. Neurologic examinations and measurements of mercury contents in the blood, urine, and hair samples in the 83 cases, failed to disclose any pathogenicity of mercury to ALS. Among these 148 including the 65 deceased cases, no ALS cases were found. Further clinical and epidemiological studies should be required on mercury poisoning as one of the risk factors in the development of ALS, especially in relation to selenium.

Aged↗

[A combined operation of coronary revascularization, abdominal aortic aneurysmectomy and femoro-popliteal bypass].

A 71-year-old male with abdominal aortic aneurysm, coronary artery disease and obstructive peripheral arteriosclerosis successfully underwent a combined operation of coronary artery bypass grafting (CABG), replacement of abdominal aortic aneurysm and femoro-popliteal bypass. In this combined operation, the right gastroepiploic artery (GEA) is suitable as a bypass graft, because a laparotomy is required for abdominal aortic aneurysmectomy. And the usage of arterial grafts such as GEA and the left internal thoracic artery (LITA) is reasonable in terms of avoiding hazardous proximal anastomosis and reducing the operating time.

Aged↗

Identification of high-affinity anti-IL-1 alpha autoantibodies in normal human serum as an interfering substance in a sensitive enzyme-linked immunosorbent assay for IL-1 alpha.

A highly reproducible, sensitive, and specific sandwich enzyme-linked immunosorbent assay (ELISA) for recombinant human IL-1 alpha (rhIL-1 alpha) has been developed. Results from this ELISA have demonstrated that the concentration of rhIL-1 alpha added to normal human serum (NHS) decreased by 16.3% after 3 h and 24.9% after 6 h at room temperature. Molecular exclusion column chromatography with Sephacryl S-300 HR revealed that 125I-labeled IL-1 alpha added to normal human serum rapidly formed higher molecular weight complexes without indication of proteolytic degradation. The observed reduction in immunoreactivity was correlated with this protein complex formation and accounted for the apparent instability of rhIL-1 alpha in NHS. Immunoblot analysis indicated that the molecular weight of the binding protein was 150-160K, and the IL-1 alpha binding activity was removed and recovered from NHS by Protein-G affinity chromatography; indicating that the binding protein was IL-1 alpha-specific IgG. The binding of 125I-labeled IL-1 alpha to the serum binding proteins could be inhibited by unlabeled IL-1 alpha (IC50 = 7.4 x 10(-11) M) but not by unlabeled IL-1 beta. Kinetic analysis with 125I-labeled IL-1 alpha revealed that the average binding affinity of these IL-1 alpha-specific IgGs was 4.7 x 10(10) M-1. These results suggest that these autoantibodies may interfere with the detection of IL-1 alpha in human serum by various assay systems and also could be a regulator of circulating IL-1 alpha.

Autoantibodies↗