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Biomedical subjects

H Matsuda

Publications and source records attributed to H Matsuda.

At least 1,117 records · Page 62Linked to original sources

Murine granulocyte-macrophage and mast cell colony formation promoted by nerve growth factor.

The nerve growth factor (NGF) is widely distributed in the target tissues of sympathetic neurons. Hemopoietic organs such as the bone marrow (BM) and spleens are known to be innervated by noradrenergic sympathetic neurons. Some of their constitutive cells express NGF receptors (lymphocytes and stroma cells) and its biologic effects have been extensively studied in the immune system and inflammatory responses. However, the effects of NGF on hemopoiesis have been little examined. Recently, we demonstrated that NGF promoted mast cell colony formation from murine BM cells (BMC) or BMC-derived cultured mast cells and induced the phenotypic changes in standard hemopoietic assays. Besides, we demonstrated NGF-enhanced murine neutrophil survival and functional properties. In this study, in order to investigate NGF activities on neutrophil differentiation, we examined granulocyte-macrophage (GM) colony formation from murine BMC or spleen cells (SC) in the methylcellulose culture. We also assessed mast cell colony formation. GM colonies were counted on day 5 and mast cell colonies were counted on day 20 in culture. Although NGF alone (50 ng/ml) neither supported GM nor mast cell colony formation, addition of various doses of NGF to the suboptimal dose of pokeweed mitogen-stimulated SC-conditioned medium (2.5%) or interleukin 3 (50 U/ml), well-known colony-stimulating factors, increased the number of GM and mast cell colonies from both BMC and SC in a dose-dependent manner. These colony formation-enhancing effects of NGF were inhibited by the addition of neutralizing sheep anti-NGF antibodies. The results suggest that NGF may act to develop granulopoiesis including neutrophil and mast cell differentiation in cooperation with hemopoietic factor(s) during inflammatory processes.

Animals↗

Hypoperfusion and vasoreactivity in the thalamus and cerebellum after stroke.

BACKGROUND AND PURPOSE: Cerebellar hypoperfusion in the contralateral hemisphere after stroke is well studied and termed crossed cerebellar diaschisis. However, studies of hypoperfusion in the ipsilateral thalamus have been few. The purpose of this study was to investigate the prevalence of hypoperfusion and vasoreactivity to acetazolamide in the thalamus and cerebellum after stroke. METHODS: We studied cerebral blood perfusion in the thalamus and cerebellum of 14 patients with unilateral cerebral infarction using [123I]isopropyliodoamphetamine single-photon emission computed tomography (123I-IMP SPECT). We also administered acetazolamide-stressed 123I-IMP SPECT to determine vasodilator capacity in these two areas. Regions of interest were drawn over the bilateral thalami and bilateral cerebellar cortices, and asymmetry indexes were obtained. RESULTS: We found ipsilateral thalamic hypoperfusion in 12 (85.7%) and contralateral cerebellar hypoperfusion in 11 (78.6%) of 14 patients. Hypoperfusion was improved (p < 0.01 by the Wilcoxon signed rank test) in 11 (91.7%) of the 12 patients with ipsilateral thalamic hypoperfusion and in seven (63.6%) of the 11 patients with contralateral cerebellar hypoperfusion. CONCLUSIONS: Hypoperfusion in the ipsilateral thalamus and contralateral cerebellum is common, and vasoreactivity to acetazolamide is preserved in both the thalamus and the cerebellum with hypoperfusion.

Acetazolamide↗

Expression of intercellular adhesion molecule-1 in murine hearts with acute myocarditis caused by coxsackievirus B3.

A cell-mediated autoimmune mechanism has been strongly implicated in the pathogenesis of viral myocarditis. Using a murine model of myocarditis caused by coxsackievirus B3 (CVB3), we previously reported that the heart is infiltrated first by natural killer cells, which express a cytolytic factor, perforin, and then by activated T cells. This action may play an important role in the pathogenesis of the observed myocardial cell damage. Cell-cell contact and adhesion is required in immune responses, and intercellular adhesion molecule-1 (ICAM-1), which is a ligand for lymphocyte function-associated antigen-1 (LFA-1), plays an important role in this process. To investigate the essential role of the ICAM-1/LFA-1 pathway in the cell-mediated cytotoxicity involved in viral myocarditis, we examined by immunofluorescence the expression of ICAM-1 in murine hearts with acute myocarditis caused by CVB3. We also evaluated the induction of ICAM-1 in cultured cardiac myocytes treated with cytokines by immunofluorescence and Northern blot hybridization. Furthermore, we analyzed the effects of in vivo administration of anti-ICAM-1 mAbs on the inflammation associated with acute viral myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of ICAM-1 in myocardial cells. The expression of ICAM-1 in myocardial cells could be induced in vitro by IFN-gamma and TNF-alpha, which were shown to be synthesized by the infiltrating cells. In vivo treatment with F(ab')2 fragments of an anti-ICAM-1 mAb significantly reduced the myocardial inflammation induced by CVB3. These data strongly suggest that the expression of ICAM-1 in myocardial cells plays a critical role in the cell-mediated cytotoxicity involved in acute viral myocarditis.

Acute Disease↗

Experimental manufacture of a catheter for the measurement of blood flow rate.

The authors manufactured an experimental catheter to obtain blood flow rate, measuring not only the flow velocity but also the vessel diameter. This catheter consists of 3F Doppler and 7F external sheath catheters, and four thin wires 3 cm in length are attached to the catheters at both tips at a 90 degrees pitch. After the insertion of the catheter into the vessel, vessel diameter is calculated from the maximal width of the wires, which are expanded to a spindle shape inside the vessel; the maximal width is corrected with calibration metal markers also attached at the proximal site of the external sheath catheter. The flow velocity of the blood is calculated with the FFT (Fast Fourier Transform) analyzer. In experimental circuits as well as in the canine aorta, wires were adequately expanded, and the catheter was placed at the center of the tube or the aorta. The blood flow rate, which was calculated as a product of flow velocity and vessel diameter, was well correlated to that from the electromagnetic flowmeter, not only in the experimental circuits, but also in the canine aorta.

Animals↗

Inclusion complexation of p-hydroxybenzoic acid esters with 2-hydroxypropyl-beta-cyclodextrins. On changes in solubility and antimicrobial activity.

To obtain a transparent and effective solution of p-hydroxybenzoic acid esters (parabens), the use of 2-hydroxypropyl-beta-cyclodextrins (2-HP-beta-CyDs) as solubilizers with different degrees of substitution (D.S.) was surveyed. 2-HP-beta-CyDs significantly increased the aqueous solubility of four kinds of parabens (methyl < ethyl < propyl < butyl esters), where the solubilizing ability decreased with an increase in the D.S. of the 2-hydroxypropyl group in beta-CyD. The antimicrobial activity of the parabens tended to decrease by complexation with 2-HP-beta-CyDs. However, the activity could be maintained by lengthening the alkyl chain of the parabens. 1H- and 13C-nuclear magnetic resonance and circular dichroism spectroscopic studies suggest that the hydrophobic alkyl moiety of butyl paraben is preferably included in the cavity, and the phenol group extrudes from the cavity. The present results suggest that a suitable combination of 2-HP-beta-CyDs and hydrophobic, longer alkyl parabens is useful for the preservation of liquid formulations.

2-Hydroxypropyl-beta-cyclodextrin↗

Synthesis and pharmacological properties of N-[4-[4-(1H-indol-3-yl) piperidinoalkyl]-2-thiazolyl]alkanesulfonamides as novel antiallergic agents.

A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanesulfonamides (8--21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100 mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10 mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfon amide (8, FK613) for further development as a novel antiallergic agent. Clinical evaluation of FK613 is now in progress.

Anaphylaxis↗

Absolute stereostructures of trifoliones A, B, C, and D, new biologically active diterpenes from the tuber of Sagittaria trifolia L.

Four new biologically active diterpenes, trifoliones A, B, C, and D, were isolated from the tuber of Sagittaria trifolia L. together with three new glycosides, sagittariosides a and b and arabinothalictoside. Their stereostructures were determined on the basis of chemical and physicochemical evidence which included the application of a modified Mosher's method and an exciton chirality method. Trifoliones A, B, C, and D exhibited inhibitory effects on the histamine release from rat mast cells induced by compound 48/80 or calcium ionophore A-23187.

Animals↗

Elatosides A and B, potent inhibitors of ethanol absorption in rats from the bark of Aralia elata Seem: the structure-activity relationships of oleanolic acid oligoglycosides.

By monitoring the inhibitory effect on ethanol absorption in rats, new active saponins named elatosides A and B were isolated from the bark of Aralia elata Seem. together with elatosides C and D. The structures of elatosides A, B, C, and D were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of several oleanolic acid oligoglycosides on ethanol absorption have been examined and some structure-activity relationships have been found.

Absorption↗

[Effect of leaves of Ginkgo biloba on hair regrowth in C3H strain mice].

Effects of 70% ethanolic extract from leaves of Ginkgo biloba (GBE) on the hair regrowth in normal and high butter diet-pretreated C3H strain mice which posterior hair we shaved were investigated. GBE showed a promoting effect on the hair regrowth. GBE had the inhibitory effects on blood platelet aggregation, thrombin activity and fibrinolysis. GBE inhibited the increase of serum the triglyceride level in high cholesterol diet-treated rats. These results suggested that GBE promotes the hair regrowth and could be used as a hair tonic.

Administration, Cutaneous↗

Postoperative improvement in blood lactate threshold during exercise in a patient with pulmonary arteriovenous fistula.

A 13-year-old female patient with a pulmonary arteriovenous fistula (PAVF) of 24 percent shunt fraction (SF) underwent resection of segments 8 and 9 of the left lower lobe. Three months after the operation, the shunt became insignificant and PaO2 was normalized. In terms of the maximum work rate, maximum VO2 and the VO2-blood lactate relationship, this patient showed a remarkable postoperative improvement in the exercise capacity.

Adolescent↗

Ion channels in the luminal membrane of endothelial cells of the bull-frog heart.

Ion channels in the luminal membrane of intact endothelial cells of the bull-frog atrium were examined with single channel recordings. A class of outwardly rectifying channels and at least two types of ohmic channels were recorded without any stimulation by vasoactive substances. The slope conductances of the outwardly rectifying channel measured at potentials positive to and negative to the reversal potential were 36.4 +/- 8.8 and 7.5 +/- 2.2 pS, respectively (n = 35). This channel was a cation channel with poor selectivity between K+ and Na+ (PNa/PK = 1.04 +/- 0.08, n = 3). The open probability and mean open time increased as the membrane was depolarized. The two ohmic channels had single channel conductances of 175.3 +/- 17.7 (n = 21) and 9.5 +/- 1.8 pS (n = 11), respectively. The 175pS channel also failed to discriminate between K+ and Na+. Its open probability was voltage-independent. Internal Ca2+ affected none of the channels examined. The luminal membrane may have a population of ion channels different from the abluminal membrane. These characteristics were different from those so far described in the cultured endothelial cells from mammalian blood vessels.

Animals↗

[Anticholinergic therapy of urinary incontinence and urinary frequency associated with the elderly--with special reference to dementia].

Pharmacotherapy with anticholinergic agents was studied in a total of 80 patients aged 65 years or older with chief complaints of urinary frequency (4 patients) and/or ugency incontinence (76 patients). The subjects were 45 men and 35 women at the age ranging between 65 and 92 (mean 73.7). The patients received anticholinergic agents (terodiline hydrochloride 24 mg/day, oxybutynin hydrochloride 6 mg/day, propantheline bromide 60 mg/day separately or in combination) for more than two weeks. Subjective symptoms and objective findings were assessed before and after the administration. In addition, according to the result of Hasegawa's dementia rating scale the patients were divided into dementia group and non-dementia group for further evaluation of the study drugs. As a result, cystometrogram revealed significant increase of maximum bladder capacity in either dementia group or non-dementia group. There was no significant difference in rate of objective improvement between both groups. On the other hand, rate of subjective improvement was significantly higher in non-dementia group (40%) than in dementia group (15%). As mentioned above, improvement of cystometrogram findings was not associated with improvement of subjective symptoms in the demented patients. This suggests that the major cause of incontinence in demented patients is not the bladder dysfunction but the specific conditions of demented patients such as agnosia and apraxia.

Aged↗

A review of the present emergency medical care system in Japan.

EMT's in the United States initiate emergency treatment including patient resuscitation at accident locations. Such treatment has only recently become available in Japan. In 1992, Emergency Life Support Technicians (ELT's) became available in Japan. ELT's can now implement emergency treatment similar in scope to that of EMT's in the United States. We expect the rate of lifesaving resuscitation and subsequent rehabilitation will improve dramatically. The triage decision making process is designed to aid in choosing appropriate health care facilities. The highest available level of medical expertise should be brought into the triage decision making process. Throughout Japan, improvements in the emergency medical care system are being made in an ongoing process. The Tokyo Fire Department in particular has made great progress in updating and improving its system. It continues to investigate possible innovations which could lead to further improvements.

Data Collection↗

Effects of twenty-three drugs on the metabolism of FK506 by human liver microsomes.

We investigated the effects of 23 drugs on the metabolism of FK506 by human liver microsomes. Acyclovir, amphotericin B, cefixime, cefotaxime, ciprofloxacin, cyclosporin A, diltiazem, enoxacin, erythromycin, ethinyl estradiol, fluconazole, fosfomycin, kanamycin, lincomycin, loxoprofen, minocyclin, nifedipine, nilvadipine, norethindrone, ofloxacin, phenobarbital, prednisolone, or rifampicin was added to the reaction media at equimolar or at ten times an excess molar ratio of the substrate concentration; their effects on FK506 metabolism were examined. Drugs known to be the substrate of cytochrome P-450 3A inhibited the metabolism of FK506, and among the drugs tested, the inhibition by cyclosporin A and nifedipine was the strongest.

Anti-Infective Agents↗