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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 55 records · Page 3Linked to original sources

[Medical education in clinical anesthesia].

We use an angiofiberscope (AFS), an echocardiography (ECG) and a transesophageal echocardiography (TEE) as useful and productive tools for medical education perioperatively. We employed these monitors in the training of 5th-year medical students on general anesthesia in the operating room. A special intratracheal tube with small lumen (3 mm in diameter) for AFS (2.2 mm in diameter), was used for monitoring airway. Medical students are interested in and concentrate their attention on the monitor screen which has a continuous image from AFS. ECG was used routinely to evaluate preoperative cardiac function, while TEE was used during operation. These monitors play very useful role in medical education for students.

Anesthesiology

[Successful combination therapy of cyclosporine and steroids in two cases with interstitial pneumonitis associated with polymyositis].

Cyclosporine is an immunosuppressive agent which is well-established in the transplantation of organs including kidney, liver and bone marrow. It acts by inhibiting the production of interleukin 2, thereby blocking both the development of cytotoxic lymphocytes, and the proliferation of helper T cells. T cell-mediated muscle damage is thought to be important in the pathogenesis of polymyositis. And activated cytotoxic T cells are thought to play an important role of polymyositis/dermatomyositis with active pneumonitis. It is thereby likely that cyclosporine would be effective in the management of polymyositis with interstitial pneumonitis. We have used cyclosporine in two cases of corticosteroids resistant polymyositis associated with pneumonitis. The first case was admitted because of the relapse of polymyositis. She was partially responded by the high dose of steroid, but showed decreased %DLCO and increased AaDO2 during the therapy. And oral cyclosporine was given with steroid. Within two weeks, serum creatinine kinase level was reduced to normal range, and the improvement of pneumonitis was observed. The second case was admitted because of the flare of pneumonitis. She was treated with high dose of steroid with insufficient response. And cyclosporine was prescribed. Within two weeks of treatment, her symptom was relieved, and blood gas analysis showed an improvement of pulmonary function. And steroid could be tapered. In both cases, the initial dose of cyclosporine was 200 mg/day, and the optimal trough level was thought to be ranged 100 to 150 ng/ml. In the second case, renal dysfunction was observed but it was recovered by the reduction of the dose of cyclosporine. No other side effect was appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporins

Alterations in bile ducts and peribiliary microcirculation in rats after common bile duct ligation.

The chronological changes in ductular epithelium and peribiliary capillary plexuses (PBPs) after bile duct ligation are not well understood. Therefore, we examined alterations in both intrahepatic bile ductules and peribiliary microcirculation in rats after ligation of the common bile duct using immunohistochemistry, transmission electron microscopes (TEM), and scanning electron microscopes (SEM). Ductular proliferations appeared first in the peripheral areas of the portal spaces and then gradually advanced along with increasing jaundice. Distorted configuration of the hepatic parenchyma with interconnecting stroma rich in irregular ductules developed 4 weeks after the ligation. Numerous biliary cell types and cells of types intermediate between hepatocytes and biliary cells together with poorly fenestrated capillary-type vessels appeared in the periportal parenchyma, in association with an increased number of canalicular-ductular junctions on TEM. These biliary cells were often found within the lobules and apart from the stroma. SEM examination of hepatic microvascular casts using methacrylated resin showed formation of irregular portal and periportal capillary networks, partly derived from coarsened sinusoids. Direct connections between the newly formed capillary networks and the pre-existing PBPs or sinusoids were numerous, although there were few direct connections between the capillary networks and the hepatic arterial branches. Thus, these proliferated ductules and newly formed complicated capillary networks might play an important role in the effective transport of biliary materials between hepatocytes and native bile ducts or proliferated ductules through the altered microcirculation after bile duct ligation.

Animals

[Endocrine effects of nicardipine on intraoperative hypertension under droperidol-fentanyl-ketamine (DFK) anesthesia].

Effects of nicardipine on endocrine functions were evaluated in 10 surgical patients who received surgeries under total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK). Plasma levels of norepinephrine (NE), epinephrine (E), plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (hANP) were measured following nicardipine injection during 30 minutes of intraoperative hypertension. When the systemic blood pressure exceeded 160 mmHg systolic and 95 mmHg diastolic for five minutes, 0.5 mg approximately 10 mg of nicardipine was administered for 30 minutes to maintain the systolic blood pressure below 160 mmHg. Following the injection of nicardipine a significant reduction by 20% in the mean systolic and diastolic pressure was observed. Mean heart rate increased by 5%, but the increase was not significant. Plasma NE increased significantly 1.7 time from the control level at 15 minute following the injection. Plasma levels of E, PRA, aldosterone and hANP showed no significant changes.

Adult

Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1).

A cDNA encoding a novel member of the cytochrome P-450 superfamily, Cyp3a-13, has been isolated from mouse liver cDNA library by hybridization screening. The Cyp3a-13 encoded 503 amino acid residues and shared 71% amino acid identity with Cyp3a-11. When Cyp3a-13 cDNA was expressed in CR119 cells which had been established as a cell line stably expressing NADPH-cytochrome P-450 reductase cDNA of guinea pigs, aflatoxin B1-dependent cytotoxicity was observed. This cytotoxicity was enhanced by alpha-naphthoflavone (7,8-benzoflavone), which is known to augment the CYP3A enzymatic activity. The results indicate that CYP3A in mice, which are relatively insensitive to aflatoxin B1, can activate aflatoxin B1 to a genotoxic product.

Aflatoxin B1

A novel form of mouse cytochrome P450 3A (Cyp3a-16). Its cDNA cloning and expression in fetal liver.

A complementary DNA clone coding for a novel form of cytochrome P450, Cyp3a-16, in mouse fetal livers was isolated and completely sequenced. This clone encoded a polypeptide of 504 deduced amino acids and showed 87.3% and 66.6% amino acid identities with mouse Cyp3a-11 and Cyp3a-13, respectively. Cyp3a-16 transcript was detectable before birth and remarkably diminished five weeks after birth in mice. We conclude that Cyp3a-16 is a fetal- and puberty-specific cytochrome P450 in mice.

Amino Acid Sequence

Transglucosylation with 6'-chloro-6'-deoxysucrose and immobilized isomaltulose-producing microorganisms using 2,2-dimethyl-1,3-dioxolane-4-methanol and its related compounds as acceptors. Steric and chemical requirement of the glucosyl acceptor.

Enantioselective and diastereoselective alpha-D-glucosylation of 2,3-O-isopropylidene-erythritol was observed in transglucosylation with a synthetic donor using three kinds of immobilized isomaltulose-producing microorganisms. Several related compounds, including an 2,3-O-isopropylidenated aldotetrose dimethyl dithioacetal and an aldotetronic acid ester were also glucosylated in moderate or good yield, depending on the microorganism utilized. Steric as well as functional group factors are discussed in relation to the substrate specificity of the glucosyl acceptor.

Carbohydrate Conformation

Cultured rat astrocytes possess Na(+)-Ca2+ exchanger.

Na(+)-Ca2+ exchange activity in its reverse mode was demonstrated in cultured rat astrocytes. Combination of ouabain (1 mM) and monensin (20 microM) caused a marked increase in 45Ca2+ uptake in astrocytes. 45Ca2+ uptake was also stimulated by lowering the external Na+ concentration. Ouabain plus monensin-stimulated 45Ca2+ uptake was blocked by 3,4-dichlorobenzamil (IC50, 16 microM), an inhibitor of Na(+)-Ca2+ exchanger, but not by nifedipine (0.1 microM). The stimulated-45Ca2+ uptake was observed even in K(+)-free medium, and external K+ at 5-10 mM caused a 2.2-fold increase in the uptake. Microspectrofluorimetry using the Ca(2+)-sensitive dye fura-2 showed that ouabain plus monensin increased intracellular Ca2+ concentration in single astrocytes. The Ca2+ signal was dependent on external Ca2+ (EC50, 1.4 mM), and blocked by 20 microM 3,4-dichlorobenzamil, but not by Ca2+ channel blockers (Cd2+, 20 microM; Ni2+, 100 microM). Antiserum of cardiac Na(+)-Ca2+ exchanger recognized 160 and 120-135 kDa proteins on SDS-polyacrylamide gel electrophoresis of astrocyte homogenate. Northern blot analysis revealed the presence of mRNA for the exchanger protein in astrocytes. These findings indicate that Na(+)-Ca2+ exchanger which is modulated by K+ is present in cultured rat astrocytes.

Amiloride

Unique T cell differentiation markers: gangliosides with cholera toxin receptor activity on murine fetal thymocytes.

Cholera toxin B subunit receptors (CTBR; gangliosides GM1a and GM1b-GalNAc-Gal) and GM1b-type gangliosides were examined during T cell development in BALB/c mice by FACS or TLC immunostaining. Sixty-two percent of CD4-8- early fetal thymocytes express CTBR [58% low affinity (GM1a+), 4% high affinity (GM1a2+)] at 13 days gestation (Day 13); GM1a2+ was expressed preferentially on Thy-1+ fetal thymocytes after Day 13. GM1a2+ Thy-1+ cells increased from 4% on Day 13 to 95% on Day 17. Surface GM1a2+ decreased beginning on Day 15 while GM1b-GalNAc-Gal (and CD4 and CD8) increased. GM1b-type+ cells increased from 8% on Day 13 to 51% on Day 17 and then decreased to 16% at 4 weeks; few asialo GM1+ cells (< 5%) are seen during gestation. Thus, synthesis of GM1a- and GM1b-type series was active until Days 15 and 17, respectively, and then was suppressed; GM1b-GalNAc-Gal was synthesized from GM1b following Gestational Day 15. GM1a- and GM1b-type identify immature T cells in mice, while GM1b-GalNAc-Gal identifies mature T cells.

Animals

Tunicamycin inhibits prostaglandin F2 alpha receptor-mediated phosphoinositide hydrolysis in cultured rat astrocytes.

Effect of tunicamycin, an inhibitor of N-linked glycosylation, on prostaglandin (PG) F2 alpha-stimulated phosphoinositide (PI) hydrolysis was examined in cultured rat astrocytes. Pretreatment of cultured astrocytes with tunicamycin (25-250 ng/ml) inhibited subsequent PGF2 alpha (1 microM)-stimulated PI-hydrolysis in concentration- and time-dependent manners. The inhibition completely recovered after removal of tunicamycin and re-incubation for 12 h. Tunicamycin pretreatment (100 ng/ml for 12 h) significantly blocked [35S]methionine incorporation into cultured astrocytes, but cell viability was not affected under the condition. Inhibitors of processing of N-linked sugar chains such as bromoconduritol, 1-deoxymannojirimycin, and swainsonine had no effect on PI response to PGF2 alpha. These observations suggest that PGF2 alpha receptor is N-linked glycosylated.

Animals

Klinefelter's syndrome and rheumatoid arthritis. Report of a case and review of the literature.

Our case report describes a patient with Klinefelter's syndrome (KFS) associated with rheumatoid arthritis (RA). He had active RA in 1985 but his arthritis almost subsided in 1993 without intensive treatments for RA as well as KFS. Recently, the lower levels of testosterone in male RA patients, especially at the active phase has been reported. However, it is still questionable whether hypogonadism is a predisposing factor or just a consequence of disease. Since our case had a mild clinical course, and since the incidence of RA associated with KFS is very rare in comparison with other rheumatic diseases, may suggest that the low levels of testosterone are not a predisposing factor to the activity of RA.

Adult

Effects of alcohol on lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin:cholesterol acyltransferase in high-density lipoprotein cholesterol elevation.

The mechanism whereby alcohol increases high-density lipoprotein cholesterol (HDL-C) levels is unclear. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) act on lipoprotein metabolism. The purpose of the present study is to determine which one or what combination of these factors is responsible for the rise in HDL-C levels following alcohol ingestion. After 3 weeks of abstinence, 12 men consumed 0.5 g/kg bw of alcohol per day for 4 weeks; 13 abstaining men served as controls. Mean plasma total cholesterol (TC) levels were unchanged in either group throughout the study. Among the alcohol consumers, plasma triglycerides (TG), HDL-C, apolipoprotein (apo) A-I and A-II levels increased significantly after 3 weeks of alcohol loading but were unchanged in the control group. High-density lipoprotein3 cholesterol (HDL3-C) levels increased significantly in the alcohol consumers after 4 weeks of alcohol loading whereas high-density lipoprotein2 cholesterol (HDL2-C) levels were unaffected. In the controls, neither HDL2-C nor HDL3-C changed significantly. Post-heparin plasma (PHP) LPL activity and mass increased significantly (P < 0.01) after the alcohol ingestion (controls remained unchanged) without changing LPL specific activity. HL, CETP and LCAT activities were unaffected in both groups. We conclude that of the factors considered, LPL contributed the most to the alcohol-induced rise in HDL-C.

Adult

Analysis of function of a human antigen-presenting cell by xenogeneic interaction with mouse T cells.

A human B cell line, ARH, was transfected with a murine major histocompatibility complex class II gene (I-A(k)). One of the transfectants, ARH5.5, which strongly expresses I-A(k) molecules was found to be capable of presenting soluble antigens to I-A(k)-restricted, antigen-specific murine helper T cell (Th) clones. When ARH5.5 was treated with either chloroquine or paraformaldehyde prior to the antigen pulse, it failed to present a protein antigen, ovalbumin, but retained the ability to present a peptide, indicating that the presentation was dependent on processing. The xenogeneic interaction of co-stimulatory molecules on the human antigen presenting cell (APC) and the murine Th cell was assessed by using antibodies against adhesion molecules. We found that the xenogeneic interaction of LFA-1/ICAM-1 acted as a strong co-stimulator of the antigen presentation by ARH5.5, while that of CD2/LFA-3 had only little stimulatory effect. These results suggest that the interaction between some of the adhesion molecules on APC and Th can cross the species barrier. The experimental system presented here is simple and useful for analyzing human APC function, separately from T cell function, especially when the dysfunction of APC associated with viral infection with human tropism is considered.

Amino Acid Sequence

Benign glandular peripheral nerve sheath tumor. A case report.

The glandular peripheral nerve sheath tumor is a rare variant of nerve sheath neoplasms in which the focally occurring glands are lined by cells showing divergent differentiation. The vast majority of the reported nerve sheath tumors harboring these glands have been malignant. We herein present a case of benign glandular peripheral nerve sheath tumor in a 43-year-old woman who had no evidence of von Recklinghausen's disease. Histologically, the tumor is composed of spindle cell component and collections of glandular component. The glandular component occupied the central two-thirds of the lesion and was lined by a single layer of nonciliated cuboidal or columnar cells. No mitotic figures were recognized in the spindle cell area. This spindle cell area had neurofibroma-like features rather than schwannoma. Many of the spindle cells had positive reaction products for S-100 protein. The glandular lining epithelium were positive for cytokeratins (CAM 5.2, AE1/AE3, PKK1) and EMA. Some epithelial cells were immunoreactive for CEA, chromogranin, somatostatin and Leu-7. These immunohistochemical findings support the neuroendocrine differentiation of the epithelial element from the schwannian component.

Adult

Effects of MS-551, a new class III antiarrhythmic drug, on programmed stimulation-induced ventricular arrhythmias, electrophysiology, and hemodynamics in a canine myocardial infarction model.

We examined the effects of MS-551 (1,3-dimethyl-6-[(2-[N-(2-hydroxyethyl)-3-(4- nitrophenyl)propylamino]ethylamino] 2,4(1H,3H)-pyrimidinedione hydrochloride), a new class III antiarrhythmic drug, on programmed electrical stimulation (PES)-induced ventricular arrhythmias, the effective refractory period (ERP), intraventricular conduction, and hemodynamics in a canine myocardial infarction (MI) model. MS-551 was administered intravenously (i.v.) in two consecutive doses; the first dose (low dose) was 0.5 mg/kg/min after a bolus injection of 0.3 mg/kg, and a second dose (high dose) was 0.1 mg/kg/min after a bolus injection of 0.3 mg/kg. PES induced ventricular tachycardia (VT) or ventricular fibrillation (VF) in 10 of 12 animals. MS-551 abolished or lessened the ventricular arrhythmias in 7 of 10 animals at both doses. ERP was significantly prolonged by MS-551 in both the normal and infarcted zones in a dose-dependent fashion. Ventricular conduction of a premature excitation induced by a premature stimulation with various coupling intervals was decreased only at a coupling interval approximating that of ERP. MS-551 at either low or high dose did not significantly change the heart rate (HR), mean blood pressure (MBP), cardiac output (CO), or maximum rate of increase in left ventricular pressure (LVP) significantly. MS-551 produced a suppression of the PES-induced ventricular arrhythmias through prolongation of ERP without having any significant effect on hemodynamics in a canine MI model.

Animals

An immunohistochemical study of sebaceous carcinoma with anti-keratin monoclonal antibodies: comparison with other skin cancers.

Formalin-fixed and paraffin-embedded tissue specimens of six cases of extraocular sebaceous carcinoma were studied immunohistochemically with eight anti-keratin monoclonal antibodies, 34 beta B4, 35 beta H11, Ks13.1, Ks19.1, PKK1, LP34, KL1 and AE1. The staining patterns of sebaceous carcinoma were compared with those of normal sebaceous glands and other skin cancers which should be distinguished from sebaceous carcinoma histopathologically. The other skin cancers compared were eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous cell carcinoma. Most cases of sebaceous carcinoma were stained with 35 beta H11, Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with 35 beta H11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was distinguishable from extramammary Paget's disease with underlying adenocarcinoma, squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but was not clearly distinguishable from malignant clear cell hidradenoma. These findings demonstrate that sebaceous carcinoma shows positive reactions with antibodies to simple epithelial keratin, probably as a result of neoplastic transformation, and that immunohistochemical examination using anti-keratin monoclonal antibodies is useful in distinguishing sebaceous carcinoma from several other skin cancers.

Acrospiroma