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Biomedical subjects

M Ohashi

Publications and source records attributed to M Ohashi.

At least 433 records · Page 24Linked to original sources
PubMed1984

[Effects of KC-404 on bronchial anaphylactic reactions].

The effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a] pyridine (KC-404), a new anti-allergic agent with a unique mode of action, on bronchial anaphylactic reactions were investigated in guinea pigs and rats. The inhibitory effects of orally administered KC-404 on systemic anaphylactic reaction caused by intravenous antigen and on anaphylactic bronchoconstriction caused by inhaled antigen in guinea pigs actively sensitized with egg albumin were observed at doses of 100 mg/kg and 10 mg/kg, respectively. When these animals were pretreated with diphenhydramine and atropine before antigen challenge, the inhibitory effects of KC-404 were markedly enhanced; doses as low as 0.25 to 0.5 mg/kg p.o. were effective in this situation. In guinea pigs similarly sensitized as above, KC-404 injected i.v. after the maximum development of antigen-induced constriction of airways resulted in a rapid dilatation. KC-404 was about 100 times as potent as aminophylline in this respect. KC-404 inhibited passive anaphylactic bronchoconstriction in rats mediated by an IgE antibody at an oral dose of 2.5 mg/kg. The inhibitory effect of KC-404 (10 mg/kg) persisted for at least 6 hr. These results indicate that KC-404 is orally effective in inhibiting anaphylactic bronchoconstrictions mediated by IgE as well as IgG antibodies. Furthermore, KC-404 is suggested to be able to control the SRS-A-induced component of bronchospasm.

Administration, Oral↗
PubMed1983

Regulation of human fetal testicular secretion of testosterone: low-density lipoprotein-cholesterol and cholesterol synthesized de novo as steroid precursor.

The results of the present investigation support the conclusion that low-density lipoprotein (LDL)-cholesterol facilitates androgen synthesis in human chorionic gonadotropin (hCG)-treated human fetal testicular tissue in vitro. Moreover, the number of LDL receptors and the rate of de novo synthesis of cholesterol are high during the period of active fetal testicular steroidogenesis and fall with advancing gestational age, suggestive of regulation by hCG.

Androstenedione↗
PubMed1983

In-beam electron ionization mass spectra of penicillins.

The characteristics of in-beam electron ionization mass spectra of 6-aminopenicillanic acid and several penicillins, which yield no detectable molecular ion peaks using a conventional direct-insertion probe, have been established. The spectra of all compounds studied, with the exception of amoxicillin, exhibited molecular ion or (M+1) peaks with spectral features similar to the reported methyl ester or amide derivatives of the compounds. The fragmentation of penicillin G on electron impact under in-beam conditions can be described on the basis of data from mass analyzed ion kinetic energy spectrometry. A desorption technique utilizing polyethylene glycol 4000 was used as a means of obtaining satisfactory spectra of ampicillin and amoxicillin.

Ampicillin↗
PubMed1983

Aphidicolin inhibits cell growth by accumulation of G2 cells.

In order to clarify in vivo target(s) of aphidicolin, the cell cycle phase at which normal human diploid cells were accumulated with this drug was examined by flow cytofluorometry. More than 80% of the cells moved through S phase and were accumulated at G2 phase at the drug dose under which growth of the cells was completely inhibited but there was no apparent cell death. On the other hand, at the higher dose, cell detachment occurred through the first entry of the cells to early S phase. Apparently, in vivo effects of aphidicolin are much more complicated than simple inhibition of DNA synthesis.

Aphidicolin↗
PubMed1983

Mode of protection of mice against herpes simplex virus type 2 infection by Propionibacterium.

We compared various strains of Propionibacterium with regard to protection of young adult mice against lethal infection with herpes simplex virus type 2 (HSV-2). Propionibacterium acnes, P. granulosum, and P. avidum were protective, while P. acidi-propionici and P. lymphophilum were ineffective. The protective effect proved to be in the cell wall fraction. Attempts were made to elucidate possible mechanisms of the protection using both effective and ineffective strains. The results strongly suggest that induction of interferon rather than activation of macrophages and natural killer cells by Propionibacterium pretreatment plays a crucial role, directly or indirectly, in protection against infection by herpes simplex virus. Propionibacterium only moderately protected newborn mice against HSV-2 infection.

Adjuvants, Immunologic↗
PubMed1983

Biosynthesis of cholesterol side-chain cleavage cytochrome P-450 in human fetal adrenal cells in culture.

An immunoglobulin G fraction from antiserum raised against cholesterol side-chain cleavage cytochrome P-450 (cytochrome P-450sec) purified from bovine adrenocortical mitochondria cross-reacted with human fetal adrenal cytochrome P-450sec in an Ouchterlony double diffusion system. This property of the immunoglobulin G fraction was used for the immunoisolation of cytochrome P-450sec of human fetal adrenal cells in culture. The molecular weight of the immunoisolate from [35S] methionine-labeled human fetal adrenal cells was similar to that of purified bovine adrenocortical cytochrome P-450sec (49,000). However the molecular weight of cytochrome P-450sec immuno-isolated from an in vitro translation system programmed by human fetal adrenal RNA was approximately 54,000, about 5,000 larger than that of the immunoisolate from radiolabeled cells. The rate of synthesis of cytochrome P-450sec by human fetal adrenal cells in culture, when incubated with ACTH (10(-6) M) for 36 h, was 2.5-fold greater than that by fetal adrenal cells incubated in the absence of ACTH. This result suggests that, as in the case of bovine adrenal cells, cytochrome P-450sec of human fetal adrenal tissue is synthesized as a larger molecular weight precursor which presumably undergoes processing to the mature form during translocation into the mitochondria. This synthesis is stimulated by ACTH, which is the putative trophic factor regulating human fetal adrenal steroidogenesis.

Adrenal Glands↗
PubMed1983

Pharmacological characterization of ionophore X537A-induced contractile responses in isolated rabbit taenia coli and aorta.

Pharmacological action of ionophore X537A was studied in taenia coli and aortic strips isolated from rabbit. These isolated smooth muscle preparations contracted by X537A (10(-5)-10(-4) M). A removal of Ca ions from the buffer solution considerably reduced the contraction of taenia coli but not that of aorta. D 600 (methoxyverapamil, 10(-6) M) was without any effect in the contraction of both tissues by X537A (10(-4) M). However, papaverine (10(-4) M) and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride, 10(-4) M) inhibited X537A (10(-4) M)-induced contraction markedly in taenia coli but slightly in aorta. Inhibitory effects of these drugs were reversed in taenia coli by increasing Ca ion concentration in buffer solution but not in aorta. X537A (10(-4) M)-induced contraction of aorta was not affected by a pretreatment of rabbit with reserpine and preincubation of the isolated preparations with guanethidine (10(-6) M) or prazosin (10(-7) M). These results suggest that ionophore X537A might produce the contraction through an increase of Ca influx in isolated rabbit taenia coli which are little or not affected by D 600, whereas the contraction of rabbit aorta induced by X537A is mainly due to facilitation of release of Ca sequestered intracellularly.

Animals↗
PubMed1983

The actions of sodium nitroprusside and diltiazem on calcium-, potassium- and histamine-induced contractile responses in isolated rabbit basilar artery, aorta, taenia coli and tracheal smooth muscle.

The effects of sodium nitroprusside (NaNP) and diltiazem on CaCl2-,KCl- and histamine-induced contractile responses were studied in isolated rabbit basilar artery, aorta, taenia coli and trachea. NaNP reduced CaCl2-induced maximal contractions in basilar artery and aorta, but little affected those in taenia coli and trachea. NaNP reduced histamine-induced maximal contraction markedly in aorta but slightly in basilar artery and taenia coli. The reduction in aorta was reversed by increasing CaCl2 contraction in bathing medium. NaNP inhibited histamine-induced contractions of basilar artery, aorta and taenia coli in Ca-free medium. Diltiazem reduced CaCl2-induced maximal contractions in basilar artery and aorta, whilst it caused a parallel shift of concentration-response curves for CaCl2 to the right in taenia coli and trachea. diltiazem reduced histamine-induced maximal contractions in basilar artery and taenia coli. These reductions were reversed by increasing CaCl2 concentration in bathing medium. Diltiazem strongly inhibited histamine-induced contraction of taenia coli in Ca-free medium. The effects of NaNP and diltiazem on KCl-induced contractions both in normal (Ca; 2.5 mM) and in high Ca (Ca; 12.5 mM) media were also studied. From the results obtained in this study, the actions of NaNP and diltiazem were considered to vary with the type of smooth muscle or the condition eliciting contraction. Their possible mechanisms were discussed in this paper.

Animals↗
PubMed1983

The actions of D 600, aspaminol and papaverine on calcium-, potassium- and histamine-induced contractions of isolated rabbit basilar artery, aorta, taenia coli and tracheal smooth muscle.

The effects of D 600, Aspaminol (1,1-diphenyl-3-piperidinobutanol hydrochloride) and papaverine on CaCl2-, KCl- and histamine-induced contractile responses of isolated rabbit basilar artery, aorta, taenia coli and tracheal smooth muscle were compared with each other. D 600 reduced CaCl2-induced maximal responses in basilar artery and aorta, and parallelly shifted the concentration-response curves for CaCl2 to the right in taenia coli and trachea. D 600 also reduced histamine-induced maximal contractions in basilar artery and taenia coli. These reductions were not reversed by increasing CaCl2 concentration in bathing fluids. High concentration of D 600 parallelly shifted the concentration-response curve for histamine to the right in aorta. Like D 600, Aspaminol, a nonspecific smooth muscle relaxant, parallelly shifted the concentration-response curve for histamine in aorta. Papaverine parallelly shifted the concentration-response curve for CaCl2 in taenia coli and reduced the maximal responses in other tissues. Papaverine also reduced histamine-induced maximal responses in basilar artery, aorta and taenia coli. Influences of these smooth muscle relaxants on histamine-induced contraction in Ca-free buffer solution and on KCl-induced contraction in normal and high Ca (Ca: 12.5 mM) buffer solution were also studied. From the results obtained in this study, the effects of smooth muscle relaxants are considered to vary with the type of smooth muscle or the condition eliciting contraction, and the possible mechanisms of the contractions were discussed.

Animals↗
PubMed1983

KC-404: a potential anti-allergic agent with antagonistic action against slow reacting substance of anaphylaxis.

The mode of action of a novel compound, 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (KC-404), as a potential anti-allergic agent has been investigated. KC-404 was shown to have a direct bronchodilator activity in guinea pig trachea in vitro and in anesthetized guinea pig in vivo. In addition, KC-404 had a fairly selective antagonistic action against slow reacting substance of anaphylaxis (SRS-A) on guinea pig ileum in vitro. In anesthetized guinea pigs, ED50 values for intravenously and intraduodenally injected KC-404 to inhibit SRS-A-induced bronchoconstriction were 0.0014 and 0.0065 mg/kg, respectively. Much higher doses were required to inhibit bronchospasms produced by histamine or particularly by acetylcholine. Orally administered KC-404, 0.001 to 0.1 mg/kg, also showed a selective inhibitory effect on increased vascular permeability by intradermal SRS-A in guinea pigs and rats. KC-404 inhibited the immunological release of mediators, notably SRS-A from sensitized guinea pig chopped lung in vitro at 10(-8) to 10(-4) g/ml. In vivo, the release of SRS-A, but not of histamine, mediated by a nonreaginic antibody in the peritoneal cavity of sensitized rats was inhibited by KC-404 at oral doses above 3 mg/kg. In a similar anaphylactic reaction but mediated by a reaginic antibody, KC-404 also inhibited SRS-A release at intraperitoneal doses of 2.5 to 10 mg/kg. The inhibitory activity on histamine release was less than half of that on SRS-A release. These results indicate that KC-404 is an orally active compound with a unique mode of action to inhibit preferentially both the effects and immunological release of SRS-A.

Animals↗
PubMed1983

Peripheral vascular disease in Japanese diabetics: screening by the Doppler ultrasonic technique.

The prevalence of peripheral vascular disease (PVD) was determined in 296 Japanese diabetics (mean age 55.2 years, range 19 to 79 years), using a Doppler ultrasonic technique. PVD was diagnosed in 11.5% of the diabetic patients (7.6% females, 14.6% males). In 88% of all patients with PVD, asymptomatic impaired circulation was diagnosed. There was a clear increase of PVD with age. It was found that the increase of PVD was gradual in patients under the age of 70, from 4.3% in the younger group to 10% in patients in their 7th decade, while the frequency of PVD rose sharply to 25% in patients in their 8th decade and over. The occurrence of PVD was significantly correlated with hypertension, hypertriglyceridemia and past obesity, but not with glycemic control, serum cholesterol levels or smoking habits. Also, PVD was closely associated with persistent proteinuria, retinopathy at a rather advanced stage and calcification of leg arteries. These findings suggest that the frequency of PVD in Japanese diabetics is lower by one third and progression of PVD is more gradual than that found in similar studies in Western countries. Another distinctive feature of PVD in Japanese diabetics was the markedly high percentage of asymptomatic cases.

Adult↗
PubMed1983

Studies of the human chorionic gonadotrophin-like substance of human pituitary glands and its significance.

Radioimmunoassays utilizing antisera specific for the carboxyl-terminal portion of human chorionic gonadotrophin (hCG) beta-subunit were used to measure the concentration in human pituitary extracts of an immunoactive hCG factor (hCG') which was different from human LH (hLH). The content of hCG' from different human pituitary pools collected between 1966 and 1979 was relatively constant at 0.5-1.1 microgram per gland. The hCG' concentrations observed in acetone-dried powder of individual human pituitary glands (0.4-26 ng/mg) were close to those reported for full-term placental powder. After separation and partial purification of human pituitary glycoprotein hormones, pituitary hCG' was found mainly in the crude human FSH (hFSH) fraction. It was separated from hFSH by diethylaminoethyl-cellulose chromatography at pH 7 and by gel filtration on Sephadex G-100. On gel filtration its molecular size was larger than that of hLH or hFSH and it was strongly bound to Concanavalin A-Sepharose. The most active preparations of pituitary hCG' obtained by these procedures were approximately 5 per cent as potent by specific radioimmunoassay as hCG purified from pregnancy urine. Although the hCG' content in individual pituitary glands was more variable than the hLH content, on average pituitary hCG' was estimated to be around 25- to 50-fold less than the content of hLH, hFSH or human TSH in the human pituitary gland.

Chorionic Gonadotropin↗
PubMed1983

A survived case of diabetes with nonclostridial gas gangrene.

A 56-year old diabetic patient of over 20 years duration was admitted with gangrene of right foot. About a month prior to admission he injured the fourth toe of the right leg when he cut the toe nail. Two weeks later necrotic ulcer was present on it with cellulitis and 2nd, 3rd and 5th toes were also affected. Then his entire right leg was swollen and he developed fever. In spite of the treatment with antibiotics and insulin, gangrenous lesions progressed and subcutaneous emphysema was palpable beneath the inflamed area. On the 9th hospital day amputation was carried out below the knee. He had a good recovery 6 weeks after the amputation. Aerobic and anerobic cultures from the foot yielded bacteroides and pseudomonas aeruginosa. Clostridia were not isolated. A review was also carried out on ten diabetic cases of nonclostridial gas gangrene in the lower limb in Japan.

Amputation, Surgical↗