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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 667 records · Page 37Linked to original sources

[Reproductive and developmental toxicity studies of buspirone hydrochloride (I)--Oral administration to rats during the period of fetal organogenesis].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at the same dose level. 2. Liver weights were increased in F0 dams at term at buspirone 12 mg/kg and higher. Besides, brain, pituitary, adrenal and ovarian weights were increased in F0 dams at term at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the inhibition of fetal growth followed by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidence of skeletal abnormalities such as nodular and wavy ribs and unossified 5th and 6th sternum , as well as retarded ossification of cervical vertebrae, forelimbs and hindlimbs were also noted in this dose level. Also, the retarded ossification was observed at 12 mg/kg. 4. Buspirone failed to affect the parturition of F0 dams. 5. Buspirone did not function the viability of newborns (F1), and postnatal differentiations, learning ability, motility, motor activity or emotional development in F1 animals. 6. Body weight gains were depressed in female F1 rats from 4 to 9 weeks of age and food consumption was decreased in male F1 rats from 6 to 8 weeks of age at buspirone 75 mg/kg. 7. Buspirone 75 mg/kg produced suppressions of brain weights at 10 weeks of age in male and female F1 rats and lung weights at weaning in male F1 rats. Spleen weights were increased in female F1 rats at 10 weeks of age at the same dose level. However, buspirone failed to affect their reproductive ability. 8. F2 neonates derived from F1 rats whose dams had ever received buspirone during the period of fetal organogenesis showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗

[Reproductive and developmental toxicity studies of buspirone hydrochloride (II)--Oral administration to rats during perinatal and lactation periods].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F0 dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F0 dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F1 neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F1) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F1), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F1 rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F1 rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F1 rats, but failed to affect their reproductive ability. 7. F2 neonates derived from F1 rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗

Lipoma in the cerebellopontine angle--case report.

The authors report a case of a cerebellopontine (CP) angle lipoma with a very unusual histological appearance. The 38-year-old male patient suffered vertigo, left tinnitus, and left hearing disturbance. Computed tomography and magnetic resonance imaging showed a nonenhanced low-density area and a high-intensity region in the left CP angle, respectively. The tumor, which was only partially removed because of its tight adhesion to the VIIIth nerve and brainstem, consisted of mature lipocytes and contained a piece of cartilage, which is highly unusual.

Adult↗

[Evaluation of renal function in children with primary VUR up to two years old].

The function of 99 refluxing kidneys of 61 children up to two years old at the time of diagnosis was evaluated by 99mTc-DMSA renoscintigraphy, urinary beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG) and N-acetyl-beta-D-glucosamidase (NAG). High grade reflex (grade IV, V) was found in 45% of the cases. 76%, 51% and 92% of the cases showed abnormally high value of urinary beta 2-MG, alpha 1-MG and NAG, respectively. These results indicate that they have already had tubular dysfunction at the time of diagnosis. DMSA renoscintigraphy of 82 refluxing kidneys of 49 children was performed. Of these, 48% had renal scar and 28% had serious renal dysfunction [DMSA uptake rate less than 18%]. 10-20% of low grade VUR had less than 18% DMSA uptake rate. Two patterns were noticed in the group in which urinary beta 2-MG ranged 0.33-1.0. One was characterized by good bilateral renal function with slight tubular damage and the other serious renal dysfunction with fixed tubular damage. No remarkable recovery of the renal function was noticed after antireflux operation in the second pattern cases. In many cases, in which urinary beta 2-MG was more than 1.0, improvement of DMSA uptake rate was noticed after antireflux operation.

Child, Preschool↗

[Study on the localization of human papillomavirus DNA in the vulvar disease by means of in situ hybridization].

We investigated human papillomavirus (HPV) DNA of vulvar diseases obtained from 18 cases of condyloma acuminatum, 3 cases of hyperplastic dystrophy without atypia, 4 cases of lichen sclerosus, 4 cases of Bowenoid papulosis, one case of Bowen disease and 8 cases of squamous cell cancer by in situ hybridization with biotinylated HPV 6, 11, 16 and 18 DNA probes. The results of in situ hybridization analysis showed that HPV 6/11 was positive in 94.4% (17/18) of condyloma acuminatum. In 17 cases of HPV 6/11 positive condyloma acuminatum, 3 cases were positive for HPV 16 and one for HPV 18, respectively. HPV 16 was positive in 75.0% (3/4) of Bowenoid papulosis and one case of Bowen disease was positive for HPV 18. In two cases of Bowenoid papulosis which were positive for HPV 16, cervical carcinoma in situ containing HPV 16 DNA sequences was also found during the follow up period. In 8 cases of squamous cell cancer, 2 cases were positive for HPV 18, one for HPV 16 and one for HPV 6/11. All cases of hyperplastic dystrophy without atypia and lichen sclerosus were negative for HPV DNA. Our results suggested HPV is closely associated with vulvar neoplasia.

Adolescent↗

[Single dose oral toxicity study of BMY-28100 in juvenile rats and dogs].

In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose-related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats].

In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[Immunological properties of BMY-28100 and cefepime].

Immunogenicity, eliciting antigenicity and cross-reactivity of new cephem antibiotics, BMY-28100 and cefepime, were studied by means of passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and active systemic anaphylaxis in guinea pigs, and of PCA in mice and the results were compared with those obtained with reference antibiotics. In addition, the direct Coombs' reaction of the human blood was examined in vitro for the test antibiotics as compared with reference antibiotics. The results obtained are summarized as follows: 1. Immunogenicity Immunogenicity of unconjugated antibiotics was examined using the corresponding conjugates with bovine gamma-globulin (BGG) as eliciting antigen. When used as emulsions with Freund's complete adjuvant, cephalothin (CET) and benzylpenicillin (PCG) produced IgG1 and IgM antibodies in guinea pigs. However, cefepime as well as cephalexin (CEX) did not produce these antibodies, and BMY-28100 showed slightly active sensitization only for anaphylactic shock. In BALB/c and C3H/He mice, BMY-28100 and cefepime failed to produce antibodies under the experimental condition while IgE antibody formation to CET was observed. 2. Eliciting antigenicity Unconjugated CET and PCG provoked anaphylactic signs in guinea pigs sensitized with their conjugates with rabbit serum albumin (RSA). Cefepime, however, provoked no anaphylactic shock and BMY-28100 as well as CEX showed slight signs. In the other systems examined, no reactions were observed when elicited with BMY-28100, cefepime or the reference antibiotics. 3. Immunological cross-reactivity BMY-28100 did not cross-react with the reference antibiotics. While the antiserum to the RSA conjugate of CET provoked weak cross-reaction on PHA with the BGG conjugate of cefepime, the antiserum to the RSA conjugate of cefepime failed to react with the BGG conjugate of CET. Other cross-reactivities of cefepime were not observed against the reference antibiotics. 4. In vitro direct Coombs' reaction BMY-28100 did not induce the Coombs' reaction of the human blood in vitro at the testable concentration of 10 mg/ml. Cefepime or cefazolin (CEZ) caused no reaction even at a high concentration of 80 mg/ml, while CET and PCG caused a positive reaction at 10-40 mg/ml and 60 mg/ml, respectively. As shown above, immunogenicity and eliciting antigenicity of BMY-28100 and cefepime were somewhat weaker than CET and PCG but similar to CEX, and cross-reactivities of the test antibiotics with these reference antibiotics were not observed in general. The ability of BMY-28100 to give a positive reaction in the Coombs' test was weaker than that of CET, and that of cefepime was weaker than CET and PCG and equivalent to CEZ.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Analysis of patients with resected small-size (less than or equal to 2 cm in diameter) peripheral type lung cancer lesions].

From 1953 to 1985, a total of 1289 patients with primary carcinoma of the lung underwent surgical treatment. Of these 116 (8.9%) had small-sized (less than or equal to 2 cm in diameter) peripheral type lung cancer lesions. This study had three purposes: 1) to analyse how small-sized lung cancer lesions were detected; 2) to evaluate the reliability of diagnosis of small-sized cancer lesions; and 3) to evaluate pre- and post-prognostic factors of such patients compared with patients with peripheral type lung cancer lesions 2.1-3 cm in diameter. Of the 115 patients with small-sized lung cancer lesions were detected in the course of mass surveys. Cytopathological diagnosis in 75% of the patients resulted from transbronchial brushing cytology. The 5-year survival rate of patients who underwent resection of small-sized peripheral type lung cancer lesions was 70% (2.1-3 cm; 52%). Various factors such as histologic type, nodal involvement, pleural involvement, pathological stage, and success of the operation were shown to significantly affect survival. A comparison of two groups, i.e., those with lesions smaller than 2 cm in diameter and those with lesions 2.1-3 cm in diameter, showed the rate of lymph node metastasis to be significantly different. Of the patients with peripheral lung cancer lesions smaller than 2 cm who underwent surgery, 21% had peribronchial, hilar, or mediastinal lymph node metastasis. On the other hand, lymph node metastasis was seen in 43% of cases with peripheral lung cancer lesions 2.1-3 cm in diameter who underwent surgery.

Humans↗

[Three cases of left atrial myxoma].

Three cases of left atrial myxoma are presented. All of them were diagnosed by echocardiography, computed tomography and cardiovascular angiography. At operation, origin of the tumors were found to arise from the vicinity of the fossa ovalis in two cases and the lower atrial septum in the other. Three different operative maneuvers were used in these three cases. In the first case, the left atrium was incised and the tumor was removed submucosally. In the second case, the left and right atrium were incised and the tumor was removed with atrial septum. In the third case, only the right atrium was incised and the tumor was removed with atrial septum. In comparison of these three different maneuvers, we conclude that the second case was most appreciable, because the operator could see whole sight of the left atrial cavity and whole contour of the tumor and remove the tumor completely without destruction. All these patients have done well for periods of follow-up ranging from 10 to 37 months.

Female↗

[Rapid measurement of human parathyroid hormone-(1-84) by immunoradiometric assay for use in intraoperative determination of hyperfunctioning parathyroid glands].

Rapid measurement of serum intact parathyroid hormone concentration was achieved by modification of an immunoradiometric assay for the hormone. Incubation of serum samples for 15 min at 37 degrees C under shaking gave optimal results in terms of assay variance and reproducibility: intra-assay CVs were less than 10% over the hormone concentrations of 11-1,600 pg/ml; intra- and inter-assay CVs for two control sera at different hormone levels were less than 12%. The minimal detectable hormone concentration was found at 27.8 pg/ml. The serum hormone levels of 43 subjects (31 health subjects, 9 patients with primary hyperparathyroidism, and 3 patients with secondary hyperparathyroidism) determined by either rapid or regular assay well correlated with each other (r2 = 0.979, p less than 0.001). In two patients with parathyroid adenoma serum intact PTH levels fell rapidly to 12.1% of the preoperative values 20 min after ligation of the vascular pedicle to the hyperfunctioning glands. We conclude that the modified assay protocol allows rapid, accurate, and simple estimation of intact PTH concentrations, and can be used as an intraoperative measure to aid both diagnosis and surgical cure of hyperparathyroidism.

Chi-Square Distribution↗

[A case of type C Niemann-Pick disease].

We diagnosed a 3-year-old boy as type C Niemann-Pick disease by studies on cultured fibroblasts; sphingomyelinase activity was almost normal, but esterification of exogenously administered cholesterol was deficient. Also sparse cultures of his fibroblasts developed a relatively intense fluorescence with filipin that was not observed either in normal or type B Niemann-Pick fibroblasts. We tried to treat him with dimethylsulfoxide (DMSO), 100 mg-120 mg/day for a year, but it had clinically insufficient effect on our case.

Child, Preschool↗

[A case of ventricular septal defect with tricuspid regurgitation complicating infective endocarditis].

A unique case of 52-year-old woman with a ventricular septal defect associated with tricuspid regurgitation complicating infective endocarditis was reported. Under cardiopulmonary bypass, the VSD was closed directly and tricuspid valve was replaced with a Carpentier-Edwards valve. Intraoperative examination showed that the VSD was perimembranous type (5 mm in diameter), all three leaflets were destroyed and one chordae of anterior leaflet was ruptured. Her postoperative course was uneventful and she has been well.

Cardiopulmonary Bypass↗

Amino acid sequence of the dimeric hemoglobin (Hb I) from the deep-sea cold-seep clam Calyptogena soyoae and the phylogenetic relationship with other molluscan globins.

The deep-sea cold-seep clam Calyptogena soyoae has two homodimeric hemoglobins (Hbs I and II) in erythrocytes. The complete amino acid sequence of Hb I has been determined. It is composed of 144 amino acid residues, has a high content of hydrophobic residues, and a calculated molecular weight of 16,350 including a heme group. The sequence of Calyptogena Hb I showed high homology (42% identity) with that of Calyptogena Hb II (Suzuki, T., Takagi T. and Ohta, S. (1989) Biochem. J. 260, 177-182), although it has a long insertion of seven residues in the C-terminal region compared with Hb II. On the other hand, it showed low homology (12-20% identity) with other molluscan globins. As well as Hb II, Calyptogena Hb I lacked the N-terminal extension of 7-9 residues characteristic of molluscan intracellular hemoglobins, and the distal (E7) histidine was replaced by glutamine. A phylogenetic tree was constructed from 13 molluscan globins belonging to the five families Aplysiidae, Galeodidae, Potamididae, Arcidae and Vesicomyidae. The globin sequences of Calyptogena (Vesicomyidae) were found to be rather distant from other globin sequences, suggesting that they might conserve a primitive form of molluscan globins.

Amino Acid Sequence↗

Multiple deletions in mitochondrial DNA at direct repeats of non-D-loop regions in cases of familial mitochondrial myopathy.

Muscle mitochondrial DNAs from two brothers with mitochondrial myopathy associated with peripheral neuropathy had multiple deletions, most of which started in non-D-loop regions, unlike in an autosomal dominant mitochondrial myopathy (Zeviani, M. et al., Nature 339, 309 (1989)). The non-D-loop regions with deletions were amplified by the polymerase chain reaction and the resulting fragments were subcloned and then sequenced. At least 12 deletions of different lengths in different sites were found. However, all the deletions were flanked by short direct repeats (4-12 base pairs).

Base Sequence↗

Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease.

Immunoblotting studies on mitochondria prepared from the striata of patients who died of Parkinson's disease were performed using specific antisera against Complexes I, III and IV. In 4 out of 5 patients with Parkinson's disease, the 30-, 25- and 24-kDa subunits of Complex I were moderately to markedly decreased. No clear difference was noted in immunoblotting studies on subunits of Complexes III and IV between the control and Parkinson's disease. Deficiencies in Complex I subunits seem to be one of the most important clues to elucidate pathogenesis of Parkinson's disease.

Corpus Striatum↗

Alpha 3 beta 3 complex of thermophilic ATP synthase. Catalysis without the gamma-subunit.

A complex of the alpha- and beta-subunits of thermophilic ATP synthase showed about 25% of the ATPase activity of the alpha beta gamma complex. The alpha 3 beta 3 hexamer structure was analyzed by sedimentation (11.2 S) and gel filtration (310 kDa). Dilution of the alpha beta complex caused dissociation of the complex and rapid loss of ATPase activity which was restored by addition of the gamma-subunit. A previous method using urea for isolating the subunits resulted in an alpha beta complex with lower activity than that prepared by over-expression of the genes. The alpha beta-ATP complex was formed from the alpha beta complex, ADP and Pi in the presence of dimethyl sulfoxide.

Bacteria↗