Biomedical subjects

O Takahashi

Publications and source records attributed to O Takahashi.

At least 19 recordsLinked to original sources

PubMed1992

Late death after arterial switch operation for transposition of the great arteries.

Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.

Abnormalities, Multiple↗

PubMed1992

Reproductive and neurobehavioural effects in three-generation toxicity study of piperonyl butoxide administered to mice.

Piperonyl butoxide (PB) was administered continuously to mice from 5 weeks of age in the F0 generation to weaning of the F2 generation. PB was administered in the diet at levels of 0 (control), 0.1, 0.2, 0.4 and 0.8%. Selected reproductive, developmental and behavioural parameters were measured. Litter size and litter weight were reduced in higher-dosed groups, and the body weight of the pups in the lactation period was reduced in dosed pups in each generation. The survival index at postnatal day 21 of the group receiving 0.8% PB was reduced in each generation. The developmental and behavioural parameters in the lactation period were little different from those of the controls, apart from olfactory orientation in the F1 generation. However, in the F2 generation mice, surface righting, cliff avoidance and olfactory orientation were adversely affected in treatment groups. The results suggest that PB had adverse effects on reproductive, developmental and behavioural parameters of mice, with increasing effects in subsequent generations of offspring.

Administration, Oral↗

PubMed1992

Haemorrhages due to defective blood coagulation do not occur in mice and guinea-pigs fed butylated hydroxytoluene, but nephrotoxicity is found in mice.

Groups of ten male Slc:ddY mice were fed a purified diet containing butylated hydroxytoluene (BHT) at levels of 0, 1.35, 1.75, 2.28, 2.96, 3.85 or 5.00%. They were kept in cages with soft-wood chips as bedding for 30 days. Groups of five Slc:ddY male mice were kept in cages with stainless-steel wire-mesh bottoms (without wood-chip bedding) and fed BHT at 0, 0.5, 1.0 or 2.0% in the diet for 21 days. Male Crj:Hartley guinea-pigs were given a purified ration containing BHT at levels of 0, 0.125 or 0.25% (five animals per group) for 14 days, or at 0, 0.5, 1.0 or 2.0% for 17 days (six animals per group). When BHT was given to mice housed in the mesh-bottomed cages there were one, one and two deaths during the experiment in the 0.5, 1.0 and 2.0% dose groups, respectively. Lung haemorrhages were observed in these dead mice, but in all other mice and guinea-pigs no haemorrhages were found. Indices of prothrombin time and kaolin-activated partial thromboplastin time were significantly decreased by up to 30 and 40%, respectively, in the mice kept on wood-chip bedding, and by up to 40 and 60% in the mice kept in cages with wire bottoms. In guinea-pigs, the prothrombin index was significantly reduced only in the 1.0% BHT group. We conclude that the BHT-induced lung haemorrhages in mice are not caused by a severe reduction in the coagulation process, as they are in rats, and that BHT does not cause bleeding like that observed in rats. However, dose-related toxic nephrosis was found in mice given 1.35-5.0% BHT in the diet. The nephrotoxic ED50(1 month) was 2.3 g/kg body weight/day. The results suggest that an extremely large dose of BHT can cause renal toxicity in mice.

Animals↗

PubMed1992

Sub-acute toxicity of piperonyl butoxide in F344 rats.

Piperonyl butoxide, alpha-[2-(2-Butoxyethoxy)ethoxy]-4,5-methylenedioxy- 2-propyltoluene, is a pesticide synergist. F344 rats of both sex were maintained on diets containing 0, 0.6, 1.2 or 2.4% of piperonyl butoxide for 13 weeks. At the end of experimental period, they were necropsied. Selected organs were weighted and serum was analyzed by clinical chemistry. In male and female rats of the 2.4%-group, body weight gains were depressed, macroscopically, hepatomegaly was marked and liver weights were significantly higher than those of the control group. In male and female rats of all treated groups, relative kidney weights were significantly increased in a dose-dependent manner. Rats of the 2.4%-group had increased levels of albumin, cholesterol, urea nitrogen and gamma-glutamyl transpeptidase. Examination of livers of the male 2.4%-group by light microscopy showed enlarged hepatocytes with glassy cytoplasm and fatty deposition. On occasion, there was coagulative necrosis of a few hepatocytes in the periportal area and oval cell proliferation. The kidney of treated rats showed atrophy of epithelium in the proximal convoluted tubules. These results indicated that toxicity of piperonyl butoxide in rats was directed primarily to the liver and kidney.

Animals↗

PubMed1992

Effect of l-menthol on the permeation of indomethacin, mannitol and cortisone through excised hairless mouse skin.

The effect of l-menthol on the skin permeability of mannitol, cortisone or indomethacin was examined by an in vitro penetration technique with hairless mouse skin. The donor solution was prepared with phosphate buffered saline, ethanol:buffered saline (20:80, v/v) or ethanol:buffered saline (20:80, v/v) containing 1% (w/v) l-menthol. Although ethanol showed little enhancing effect, l-menthol in an aqueous ethanol vehicle at pH 7.4 increased the permeability coefficients of mannitol and indomethacin by about 100 times that of the control (an aqueous vehicle) and increased that of cortisone by about 10 times. l-Menthol, however, scarcely enhanced the penetration of indomethacin at pH 3.0, the majority of the species being in unionized form. These results suggested that the menthol-ethanol-aqueous system enhanced skin permeability through a direct effect on the polar and/or lipid pathways, while the thermodynamic activity of the penetrant molecule in the delivery vehicle might also influence the effectiveness of the penetration enhancer.

Administration, Cutaneous↗

PubMed1992

[The effect of sodium-4-[2-(2,3-dimethyl-4-[1-(4- isobutylphenyl)ethoxy]benzolamino)phenoxy] butyrate (ONO-3805) and antiandrogenic agents on the rat accessory sex organs].

The effects of sodium-4-[2-(2,3-dimethyl-4-[1-(4-isobutylphenyl) ethoxy]benzolamino)phenoxy]butyrate (ONO-3805), newly developed as a non-steroidal 5 alpha-reductase inhibitor, on rat accessory sex organs was compared with chlormadinone acetate (CMA) and non-steroidal antiandrogen, flutamide (FLU). ONO-3805 demonstrated excellent antiandrogenic activity which was similar to that of CMA in reducing the accessory sex organ weight. Moreover this agent did not show any significant effects on the serum testosterone level, but CMA and FLU changed it significantly. We previously reported the androgenic activity of antiandrogen (CMA, FLU, AA560, cyproterone acetate, medroxy progesterone, estrogen), but ONO-3805 is free of androgenic activity.

5-alpha Reductase Inhibitors↗

PubMed1992

[Total repair for truncus arteriosus].

Total repair for truncus arteriosus using an external conduit was performed in 12 patients from 1978 through 1989. Six cases were infants (mean age: 3.4 months) and 6 were children (mean age; 1 years 9 months). Two cases had Collet-Edwards type II truncus and the other 10 cases had type I truncus. One of the infants was associated with an interruption of the aorta and another had a severe regurgitation of the truncal valve (TrV). For external conduits, we used a non-valved conduit in one infant, a composite valved conduit of Dacron containing a heterograft valve in 4 children and a valved pericardial roll made of an autologous or porcine pericardium in 5 infants and 2 children. One infant with a severe regurgitation of the TrV needed valve replacement along with enlargement of the annulus of the TrV. One infant who had replacement of the TrV died early postoperatively. Another infant died 10 months after total repair due to an infection of an external conduit. Cardiac catheterization was performed in all 10 survivors. The mean value for the systolic pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.09 preoperatively to 0.36 +/- 0.09 postoperatively. Replacement of an external conduit was performed due to a conduit stenosis in 2 children and 1 infant, 10 years and 2 months, 7 years and 9 months, and 1 year and 8 months after the total repair, respectively. In one of these 2 children, replacement of the aortic valve was performed due to a severe aortic regurgitation. We conclude that our results of total repair for truncus arteriosus were satisfactory. However, it remains to be solved how to manage an infant with truncus arteriosus associated with a severe regurgitation of the TrV.

Bioprosthesis↗

PubMed1992

[Cardiac performance in total anomalous pulmonary venous connection].

Cardiac performance in 54 patients with total anomalous pulmonary venous connection was investigated by cardiac catheterization before and after surgery. 51 patients underwent intracardiac repair, and 17 of them died during or immediately after operation. According to the preoperative study, the left ventricular ejection fraction (LVEF) of surviving patients was significantly higher than that of patients who died, and the pulmonary arterial mean pressure of surviving patients was significantly lower than that of patients who died. However, there was no significant difference between the left ventricular end-diastolic volume (LVEDV), right ventricular ejection fraction (RVEF), and right ventricular end-diastolic volume (RVEDV) in surviving patients and those who died. Post-operative catheterization studies showed significant increases of LVEF and LVEDV compared to pre-operative figures. RVEF and RVEDV and pulmonary arterial mean pressure decreased significantly after surgery. It was concluded that preoperative cardiac performance of surviving patients was better than that of those who died, and post-operative cardiac performance of surviving patients was basically normal.

Blood Pressure↗

PubMed1991

[The effects of anti-androgen TZP4238 (17 alpha-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione) and its related compounds on the in vitro formation of androgen-receptor complex].

It was reported that a new steroidal anti-androgen, TZP4238 (17 alpha-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione), was 10 times stronger than chlormadinone acetate (CMA) as the in vivo anti-androgenic potential. To confirm this result, the effect of TZP4238 and CMA on ventral prostates of intact rats, or castrated ones treated by testosterone, was investigated. Our experiments demonstrated that TZP4238 was 3-5 times stronger than CMA. The effects of this compound on the androgen-receptor complex formation in the human and rat prostates were investigated and compared to the other anti-androgen and related compounds. An aliquot of cytosol or KCl extract from rat or human prostate was incubated with [3H]R1881 in the presence of various tested compounds. By means of dextran coated charcoal assay and sucrose density gradient centrifugation analysis, TZP4238 and TZP4239 showed a stronger inhibitory effect than other compounds except dihydrotestosterone. Judging from all these results, it was estimated that TZP4238 was 2-3 times stronger than CMA. The Scatchard plot analysis revealed that the inhibitory effect of TZP4238 was a competitive type. Between CMA and TZP4238, the difference of in vivo anti-androgenic potential was not identical with that of the inhibitory effect on the androgen-receptor complex formation.

Androgen Antagonists↗

PubMed1991

Retinofugal projections in the house musk shrew, Suncus murinus.

Retinofugal projections in the house musk shrew (Suncus murinus) were studied with the WGA-HRP method. After WGA-HRP injection into the vitreous cavity of one eye, terminal labeling was seen in the suprachiasmatic nucleus, dorsal and ventral lateral geniculate nuclei, pretectum and superficial layer of the superior colliculus. The terminal labeling in the suprachiasmatic nucleus was more marked on the side ipsilateral to the injection than on the contralateral side, whereas that in other regions was seen mainly on the contralateral side. A retino-intergeniculate leaflet projection was observed. No unequivocal terminal labeling was found in the lateroposterior thalamic nucleus.

Animals↗

PubMed1991

Distribution of axons showing calcitonin gene-related peptide- and/or substance P-like immunoreactivity in the sensory trigeminal nuclei of the cat.

Distribution of axons with calcitonin gene-related peptide (CGRP)-like and/or substance P (SP)-like immunoreactivity (LI) within the sensory trigeminal nuclei was examined in the cat before and after trigeminal rhizotomy. Axons with CGRP-LI or SP-LI were seen throughout the principal sensory trigeminal nucleus (Vp) and spinal trigeminal nuclei, including the medullary dorsal horn (MDH). They were densely distributed particularly in the dorsolateral part of the dorsal subnucleus of the Vp, ventromedial marginal zone of the ventral subnucleus of the Vp, dorsomedial and ventromedial parts of the oral spinal trigeminal nucleus, ventromedial and lateral marginal zones of the interpolar spinal trigeminal nucleus, and lamina I, outer part of lamina II and lamina V of the MDH. Most of the CGRP-LI axons exhibited SP-LI, while many SP-LI axons did not show CGRP-LI. After trigeminal rhizotomy, almost all CGRP-LI axons disappeared from the ipsilateral sensory trigeminal nuclei, while a considerable number of SP-LI axons remained intact throughout the nuclei; these SP-LI axons did not show CGRP-LI. The results indicate that CGRP-LI axons within the sensory trigeminal nuclei exhibit SP-LI and are of peripheral origin, and that SP-LI axons without CGRP-LI are of central origin.

Animals↗

PubMed1991

Some properties of rat platelet aggregation and effects of butylated hydroxytoluene, warfarin and aspirin.

The platelet aggregation characteristics of male Sprague-Dawley (Jcl:SD) rats were investigated. Epinephrine, ristocetin, serotonin and platelet-activating factor were ineffective in rat platelets. Heparinized platelet-rich plasma (PRP) was more sensitive than citrated PRP to three aggregating agents, ADP, collagen and arachidonic acid. Butylated hydroxytoluene (BHT) and BHT quinone methide (2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone) inhibited ADP- and collagen-induced aggregation at concentrations over 10(-3) M in vitro. The ADP-, collagen- and arachidonic acid (0.5-2.0 mM)-induced aggregations of PRP obtained from rats given 1.20% BHT in the diet for 7 days were normal, while arachidonic acid (3.9 mM)-induced aggregation of PRP from BHT-fed rats was significantly lower than control. PRP from rats given aspirin and warfarin also aggregated normally with ADP or collagen addition. These results suggest that heparinized PRP may be preferable in platelet aggregation analyses in rats and reaffirmed that effects on platelet aggregation may not play a key role in BHT-induced bleeding. Platelet aggregation capacity also does not necessarily reduce in haemorrhages induced by aspirin or warfarin.

Adenosine Diphosphate↗

PubMed1991

Rational design and synthesis of a novel class of active site-targeted HIV protease inhibitors containing a hydroxymethylcarbonyl isostere. Use of phenylnorstatine or allophenylnorstatine as a transition-state mimic.

A novel class of HIV-1 protease inhibitors containing a hydroxymethylcarbonyl (HMC) isostere were designed from the substrate transition state and synthesized. Phenylnorstatine [Pns; (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] and the 2S diastereomer, (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid, named allophenylnorstatine (Apns) were effective transition-state mimics, and incorporation of Pns-Pro or Apns-Pro at the P1-P1' site gave potent and specific HIV-1 protease inhibitors. In the inhibitory assays, the chemically synthesized [Ala67,95] HIV-1 protease was used.

Amino Acid Sequence↗

PubMed1991

[Voiding disturbance in elderly males examined by prostate mass screening. Gunma Urological Oncology Study Group].

Information about voiding disturbance was obtained from 34,140 elderly males in Gunma Aged Club Association (Q group) through a questionnaire and from 8,129 males by prostate mass screening for prostate disease (MS group) as to: (1) the characteristics of the subjects examined by the mass screening, (2) the relationship between the voiding disturbance and aging and (3) the frequency of voiding disturbance in the normal elderly males. In MS group, the percentage of young subjects, especially less than 60 years old, who complained voiding disturbance was higher than the expected percentage on the assumption that it increases with aging. The percentage of voiding disturbance in these young subjects was also higher than that of males in the same decade in Q group. In their past and present history, the percentage of benign prostatic hypertrophy (BPH) in these young subjects was higher than the expected percentage on the assumption that the incidence of BPH increases with aging. Judging from these results, it was estimated that they were not satisfied with the medical care by which they were treated or were being treated, and they received this mass screening to obtain consultation for their complains. Loss of the force was related with the prostate size estimated by digital rectal examination but not with aging. However, nocturia was well related with aging but not with the prostate size. Hesitancy, strain and dribbling were not apparently related with either the prostate size or aging. It was demonstrated that frequency of nocturia was 0 to 1 in less than 60 years old normal males, 0 to 2 in 60 to 79 years old ones and 0 to 3 in over 80 years old ones. The other symptoms studied in each decade were also analyzed and discussed.

Aged↗

PubMed1991

[Clinical analysis of male urethritis].

We reviewed 497 patients with male urethritis diagnosed between January, 1986 and March, 1989 at the Asama General Hospital. The incidence of gonococcal urethritis (GU) was 47.7%, and that of non-gonococcal urethritis (NGU) 52.3%. There was no difference in the age distribution between GU and NGU. Prostitutes were the most common source of the infection in both GU and NGU. Incubation periods were longer in NGU than in GU, statistically. Urethral discharge was the most common symptom. Purulent urethral discharge was seen more commonly than serous urethral discharge in GU. On the contrary, serous urethral discharge was more common in NGU. Penicillin-resistant gonococcus comprised 29.4% and mixed infection of the C. trachomatis existed 25.6% in GU. C. trachomatis was detected in 71.8% in NGU. In GU, new quinolones and penicillins were administered frequently. The effective rates 1 week after the administration were 80.6% and 83.3%, respectively. In NGU, new quinolones and minocycline were administered frequently. The effective rates were 70.4% and 85.3%, respectively. Ofloxacin (OFLX) showed the highest effective rate to NGU among the four new quinolones. The relapse rate for the two-week administration group was lower than that for the one-week-administration group, but the difference was not statistically significant.

Adolescent↗

PubMed1991

[The effects of antiprostatic agents on the accessory sex organs of rats treated with adrenal androgens].

It is well known that some adrenal androgens are converted into testosterone and dihydrotestosterone which are more powerful androgens than the adrenal androgens. However, most of the experiments to investigate the antiprostatic agents have been done on rats which secrete only a marginal amount of adrenal androgen. A study was performed to investigate the effects of antiprostatic agents on the action of the adrenals in rats. Non-sterodidal antiandrogens flutamide and 1-chloro-2-hydroxy-2-methyl-N-(3,4,5-trichlorophenyl)propanamide (AA560), steroidal anti-androgens, chlormadinone acetate (CMA) and 17 alpha-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione (TZP-4238) and 5 alpha-reductase inhibitor, sodium (-)-4[2-[2,3-dimethyl-4-[1-(4-isobutylphenyl)ethoxy]benzolamino ] phenoxy]butyrate (ONO-3805) and N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-l-ene-17 beta-carboxamide (MK-906) were tested in rats treated with dehydroepiandrosterone sulfate (DHEA-S) and androstenendione (A). In the noncastrated rats not treated with DHEA-S and A, all of these agents decreased the accessory organ weights in a dose dependent manner. In the rats treated with LHRH agonist and DHEA-S and A, all agents (3.3 mg/day) showed similar effects in intact rats. However nonsteroidal antiandrogens and TZP-4238 were stronger than the others. It was not clear whether this effect was mediated through the suppression of adrenal androgen action or the inhibition of physiological increase in testosterone caused by an LHRH agonist. The effects of Flu, ONO-3805, CMA and TZP-4238 on the accessory sex organs were investigated in castrated rats receiving DHEA-S and A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1991

[Cardiac performance before and after Jatene procedure for transposition of the great arteries: with specific reference to post-operative supravalvular pulmonary stenosis].

The cardiac performance was evaluated in patients who had received arterial switch operation (AS-op) for transposition of the great arteries (TGA) in their infancy with special attention to postoperative supravalvular pulmonary stenosis (SVPS). AS-op was performed in 36 infants; 13 with simple TGA and 23 with TGA accompanied with ventricular septal defect. Nine patients had undergone pulmonary arterial banding with systemico-pulmonary shunt. The mean age at surgery was 7 months. Postoperative catheterization was performed on average of 15 months after surgery. The end-diastolic volume (EDV) and ejection fraction (EF) of the left and right ventricles (LV, RV) were calculated from biplane cineangiograms. LVEDV and RVEDV were normalized and expressed as % of normals. SVPS was defined as peak systolic pressure gradient of 50 mmHg or higher between the RV and the pulmonary artery (PA). The mean LVEDV, RVEDV, LVEF and RVEF values were all within the normal range. Inverse correlation was observed between the peak systolic RV-PA pressure gradient and RVEF (n = 29, r = -0.84, p less than 0.001). SVPS after AS-op was observed in 8 patients (22%). Stenosis was observed at the site of anastomosis of the artery. In these cases, the diameter of the PA at the stenotic site decreased to 52% of the preoperative values. Branch stenosis of the PA was observed in 3 patients who had undergone surgery during the neonatal period. Generally, the results after AS-op were satisfactory in terms of cardiac performance. Postoperative SVPS was observed in 8 patients (22%) with decreased RVEF. Careful observations of the growth of PA after AS-op are mandatory.

Cardiac Surgical Procedures↗

PubMed1990

[A study of the androgenic activity of anti-androgen].

To investigate the androgenic activity of steroidal and nonsteroidal anti-androgens, the effect of several compounds on some parameters as an androgenic activity was measured in the ventral prostate (VP) and seminal vesicle gland (SV) of castrated male rats. Ornithine decarboxylase (ODC) activity, arginase activity, androgen receptor (AR) in cytosol and nucleus, histological examination and weight of accessory sex organs were used as parameters for androgenic activity. The ventral prostate weight was increased by the administration of not only steroidal anti-androgen, medroxyprogesterone (MPA), chlormadinone acetate (CMA) and cyproterone acetate (CPA), but also estradiol-17 beta(E2) and nonsteroidal anti-androgen, AA 560. However flutamide (Flu) failed to increase VP weight. In SV, the tendency to increase weight by the administration of these compounds was also observed. However, it was not obvious as in VP. It was proven by the measurement of the parameters that all tested compounds except Flu had an androgenic activity. It seems that the androgenic activity was caused by a different mechanism because the parameter response to the administrated compounds was not identical.

Androgen Antagonists↗