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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 235 records · Page 13Linked to original sources

[Paradoxical expansion of intracranial tuberculomas during chemotherapy].

A 45-year-old female patient was admitted to a hospital because of tuberculous meningitis in July, 1986. She was treated with chemotherapy (oral isoniazid, rifampicin, ethambutol and an intramuscular injection of streptomycin). Her consciousness was worsened at first, but later she improved aside from some disabilities (incontinence, gait disturbance, disorientation and dementia). She was transferred to National Higashisaitama Hospital in November, 1986. Since then we have continued the chemotherapy, and she has improved gradually. Initially her cranial computerized tomography (CT) revealed no intracranial tuberculoma and showed mild enhancement of basal cistern. About 4 months later, her CT showed many tuberculomas with ringed or nodular enhancement. About 13 months later almost all tuberculomas disappeared. But a few were found with homogeneous enhancement and were enlarged in spite of adequate chemotherapy. These tuberculomas were enlarged while the chemotherapy was continued, but later they were reduced in size. About 3 and a half years later, these tuberculomas disappeared without any calcifications. The above facts may suggest that intracranial tuberculoma could appear and be enlarged on cranial CT in spite of adequate chemotherapy during a course of tuberculous meningitis. They also suggest that continuation of adequate chemotherapy might improve tuberculomas.

Antitubercular Agents↗

[The appearance of "central core of respiratory muscle" in patients with respiratory failure].

We report the histological and histochemical features of core fibers present in respiratory muscles obtained from autopsy since 1980. Fifty autopsy cases of adults without neuromuscular disease were examined. "Central core" structure was present in 38 cases and absent in 12 cases. The duration of D.O.E. was greater than 1 month in 81.8% of core positive cases. In core negative cases, the duration of D.O.E. was less than 3 months. "Central core" structure were present in 80.0% of chronic respiratory failure cases and 41.7% of non-chronic cases. It is suggested that central core in respiratory muscles develops less than 3 months after the onset of D.O.E.

Adult↗

Alpha-adrenoceptor-mediated inotropism and beta-adrenoceptor-mediated inotropism in isolated rabbit ventricles: a comparison in mechanical effects and energetic efficiency.

We assessed alpha-adrenoceptor-mediated inotropism in comparison with beta-adrenoceptor-mediated inotropism in whole left ventricle. We used an isolated perfused isovolumic rabbit heart preparation, which enables one to assess contractility and time course of contraction as well as energetic efficiency. Left ventricular pressure (LVP) and volume were measured with an intraventricular fluid-filled balloon. Myocardial oxygen consumption was assessed from the oxygen tension of coronary effluent. Both isoproterenol (n = 7) and phenylephrine (n = 7) increased LV developed pressure (LVDP). Isoproterenol shortened the time to peak pressure (Tmax) from 171 +/- 6 to 142 +/- 7 ms (p less than 0.01) and the time constant of LV pressure decay (TBF) from 44.8 +/- 2.7 to 32.8 +/- 1.9 ms (p less than 0.01). In contrast, phenylephrine slightly but significantly prolonged Tmax from 178 +/- 4 to 184 +/- 4 (p less than 0.05) and did not alter TBF. Both isoproterenol and phenylephrine increased O2 consumption, whereas only phenylephrine increased the force-time integral from 14.0 +/- 1.5 to 17.2 +/- 2.1 g.s (p less than 0.01). These results confirmed in the whole heart preparation that alpha- and beta-adrenoceptor-mediated inotropisms had qualitatively different effects on the time course of contraction and energetic efficiency.

Animals↗

Reversal of established nephropathy in New Zealand B/W F1 mice by 15-deoxyspergualin.

The therapeutic effect of 15-deoxyspergualin (DSP) in old New Zealand Black/White F1 mice (B/W mice) with clinical nephropathy was studied and compared with cyclophosphamide (CY). The mice were treated with 0.05 ml phosphate-buffered saline, subcutaneously, four times/week, with DSP, 6 mg/kg body weight, s.c., four times/week, or with CY, 15 mg/kg, i.p., once a week, starting at the 28th week of age. They were serially semiquantitated for proteinuria, and serum IgG anti-dsDNA antibody was measured by ELISA. Spleen cell surface markers such as L3T4, Lyt2 and IgG were flow-cytometrically analyzed, and interleukin-2 (IL-2) activity in vitro was measured using CTLL cells. Kidney specimens were studied with light and immunofluorescence microscopy. The mice treated with either CY or DSP survived significantly longer than the control mice. L3T4+ cells in the DSP-treated mice at 40 weeks of age were significantly less than those in the 28-week-old control mice (p less than 0.05). In contrast, IL-2 generation in the three groups of mice showed no significant variations at 32-40 weeks of age. Serum anti-DNA antibody levels in both of the CY and DSP groups remained low and comparable with that in the 28-week-old mice, and the incidence of significant proteinuria decreased. Likewise, glomerular histology in the treated groups was improved compared with the 28-week-old control mice, and the deposition of IgG and C3 in the treated groups remained unchanged or further decreased. Accordingly, the renal (immuno)histological findings in the DSP group were quite comparable with or even better than those in the CY-treated mice. DSP may have suppressed the abnormal antibody production by modulating the T cell function(s), which is in contrast to the direct action against B cells due to CY.

Animals↗

Myocardial contractility and contraction duration are unrelated in the left ventricle with moderate pressure-overload hypertrophy.

Both myocardial contractility and contraction duration were assessed load-independently in isolated hypertrophic and control rat hearts. Hemodynamic parameters for isolated isovolumically contracting hearts were compared for 7 Wistar rats with DOCA-salt induced hypertrophy (LVH) and 7 controls. Loads were altered by changing the volume of an intraventricular balloon. Myocardial contractility was assessed in terms of the shortening-afterload (Sm-sigma aft), and the ejection fraction-afterload (EF-sigma aft) relations at common preloads, based upon the systolic myocardial stiffness concept. Indices of contraction duration (time to maximum stiffness, pressure time integral divided by peak pressure and the time required for left ventricular (LV) peak pressure to be reduced by a half) were prolonged in LVH. Multiple regression analyses indicated that the degree of hypertrophy was an independent determinant of the contraction duration. The Sm-sigma aft and EF-sigma aft relations at common preloads demonstrated normal contractility in the LVH group. The time constant of the fall in LV pressure and the diastolic myocardial stiffness remained normal in the LVH group. Thus, we introduced the new approach to load-independently assess both the myocardial contractility and the contraction duration in a whole ventricle. A prolonged contraction duration in the presence of normal myocardial contractility was observed in a ventricle with moderate pressure-overload hypertrophy.

Animals↗

Leuhistin, a new inhibitor of aminopeptidase M, produced by Bacillus laterosporus BMI156-14F1. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Leuhistin has been isolated from the culture broth of Bacillus laterosporus BMI156-14F1 as part of a program designed to find microorganism-produced inhibitors of aminopeptidase M (AP-M). It was purified by use of column chromatography on Sepabeads SP206, Amberlite IRC-50, MCI gel CHP-20P and Sephadex G-10 and then isolated as colorless needles. Leuhistin inhibits AP-M strongly and it also inhibits AP-A and AP-B weakly. It is competitive with the substrate, and the inhibition constant (Ki) was 2.3 x 10(-7) M.

Amino Acids↗

Poststatin, a new inhibitor of prolyl endopeptidase, produced by Streptomyces viridochromogenes MH534-30F3. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Poststatin, a new inhibitor of prolyl endopeptidase (PEP) was discovered in the fermentation broth of Streptomyces viridochromogenes MH534-30F3. It was purified by Diaion HP-20, Sephadex LH-20 and YMC-gel (ODS-A) column chromatography and then isolated as a colorless powder. Poststatin has the molecular formula C26H47N5O7. The IC50 value of poststatin against the PEP of partially purified porcine kidney was 0.03 microgram/ml. It has low acute toxicity. No deaths occured after iv injection of 250 mg/kg of this agent to mice.

Amino Acid Sequence↗

Poststatin, a new inhibitor of prolyl endopeptidase, produced by Streptomyces viridochromogenes MH534-30F3. II. Structure determination and inhibitory activities.

Poststatin, a new inhibitor of prolyl endopeptidase, has been isolated from the culture broth of Streptomyces viridochromogenes MH534-30F3. The structure of poststatin was defined as L-valyl-L-valyl-3-amino-2-oxovaleryl-D-leucyl-L-valine by analysis of spectral properties and chemical studies of poststatin and its derivatives. The alpha-keto group of postine in poststatin plays the most important role on the inhibitory mechanism.

Amino Acid Sequence↗

Preparation of alkyl-substituted pyrrolidone derivatives and their evaluation as transdermal penetration enhancers.

The preparation of novel transdermal penetration enhancers derived from 2-pyrrolidone were carried out, and the enhancing activities of drug permeation through the skin were evaluated by means of in vitro experiment. All the enhancers contain a short alkyl group, such as methyl, ethyl, propyl or butyl group, at 1-position and a dodecyl group at 3-position of 2-pyrrolidone ring. The enhancing activities were considerably influenced by the length of the short alkyl group at 1-position. 1-Propyl and 1-butyl-3-dodecyl-2-pyrrolidone showed the effective enhancement of penetration of indomethacin through the skin in 60 wt% ethanolic aqueous solution. Moreover, the similar enhancing activities of these compounds were also observed even in ethanolic vehicle.

Administration, Cutaneous↗

Preparations of phosphonate, phosphoramidate and phosphate derivatives and their evaluation as transdermal penetration enhancers.

Phosphonate, phosphoramidate and phosphate derivatives containing long alkyl groups were prepared, and their activities enhancing drug penetration through the skin were evaluated by means of in vitro experiments. The effect of chemical structure of these compounds on enhancing activity was investigated. Among the phosphonate and phosphoramidate derivatives, compounds having a hexadecyl group showed the most effective enhancement of transdermal penetration of indomethacin. For the phosphate derivatives, the enhancing activities were almost equal in the compounds containing dodecyl, tetradecyl and hexadecyl group. All the compounds having an octyl group were not effective in penetration enhancement. Diethyl hexadecylphosphonate and diethyl hexadecylphosphoramidate brought about the highest enhancing activities among these compounds, and the permeability coefficient of indomethacin was about 10-fold as much as that without enhancer. The relationship between the enhancing activities and the lipophilicities of these compounds was discussed.

Administration, Cutaneous↗

Folliculosebaceous cystic hamartoma. A distinctive malformation of the skin.

Five examples of a distinctive sebaceous malformation, designated "folliculosebaceous cystic hamartoma," form the basis of this study. Criteria are proposed for specific diagnosis of this hamartoma and for differentiation of it from sebaceous gland hyperplasia, steatocystoma, dermoid cyst of skin, and sebaceous trichofolliculoma.

Adult↗

Gangliosides administration causes sugar moiety-specific enzymatic changes in brain.

Exogenous gangliosides are known to affect the metabolism when administered to the body. To study the mechanism of this effect three types of gangliosides were administered intraperitoneally to mice and the changes in the enzyme activity of the cerebral tissues studied. The effect of GM2 from bovine brain was characterized by a decrease in the activity of various aminopeptidases, while GD3 from cow's milk caused an increase in the activity of sugar-related enzymes such as sialidase, glucosidase, and fucosidase. GM3 from horse erythrocytes showed intermediate effects between GM2 and GD3. Multivariate analysis showed that the effects of the three gangliosides are clearly separable statistically. These results which demonstrate the sugar moiety-specificity of gangliosides are discussed in relation to the A and B pathways of ganglioside synthesis.

Amino Acid Sequence↗

A case of adult T cell leukemia complicated by proliferative synovitis.

A 60-year-old woman was admitted to our hospital with symmetrical arthritis of the knees. During the 2 years preceding admission, she had experienced recurrent arthritis. A histological examination of her synovial tissue showed prominent villous proliferation of the synovial cells, prominent vascularity throughout and an inflammatory infiltrate composed of abnormal mononuclear cells. Three months later, she developed fever, skin eruptions, lymphadenopathy and hepatosplenomegaly. She also had hypercalcemia and there was abnormal lymphocytosis in her blood smears. She was diagnosed as having adult T cell leukemia. Parenteral chemotherapy treatment with adriamycin and cyclophosphamide gave remission of all the manifestations of disease, including arthritis. Her leukemia recurred, however, and she died 6 months after the diagnosis was made.

Antineoplastic Combined Chemotherapy Protocols↗

Mannostatin A, a new glycoprotein-processing inhibitor.

Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal alpha-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward alpha- and beta-glucosidase and galactosidase as well as beta-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal alpha-mannosidases, with estimated IC50's of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC50 of about 10-15 nM with p-nitrophenyl alpha-D-mannopyranoside as substrate, and about 90 nM with [3H]mannose-labeled GlcNAc-Man5GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate that the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity.

Animals↗

Preload dependence of fiber shortening rate in conscious dogs with left ventricular hypertrophy.

Employing the new concept of systolic myocardial stiffness, this study addresses the questions of linearity of the end-systolic stress-strain relations in left ventricular hypertrophy and the preload dependence of fiber shortening rate. Pressure overload hypertrophy was induced in six puppies by banding the ascending aorta. Ultrasonic crystals were implanted for measurement of short axis and wall thickness in the six dogs with hypertrophy and in five control dogs. A pressure catheter was inserted through the apex for left ventricular pressure measurement. Load was altered by graded infusions of phenylephrine in the setting of beta-adrenergic blockade. Linearity of the end-systolic stress-strain relations was observed in all cases, and preload-corrected shortening rate-afterload relations were derived from these stress-strain relations. Without preload correction, mid wall and endocardial shortening rate were depressed (p less than 0.05 and p less than 0.005, respectively) in the hypertrophy group. However, with preload correction at 35 g/cm2, there was no significant difference in shortening rate between the control and hypertrophy groups at afterloads of 150, 200 and 250 g/cm2. Endocardial shortening rate at a preload of 25 versus 35 g/cm2 demonstrated a preload dependence in both the control (p less than 0.04) and the hypertrophy group (p less than 0.01). Mid wall shortening rate displayed a preload dependence only in the hypertrophy group (p less than 0.05). It is concluded that end-systolic stress-strain relations are linear in control conditions and in hypertrophy, fiber shortening rate is preload-dependent and, thus, shortening rate-afterload relations currently used to assess myocardial contractility need to be modified to account for these preload effects.

Animals↗