Biomedical subjects

T Kadota

Publications and source records attributed to T Kadota.

At least 127 records · Page 7Linked to original sources

PubMed1986

[Toxicity studies of VP 16-213 (I)--Acute toxicity in mice, rats and rabbits].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was examined for its oral, subcutaneous or intravenous acute toxicity using Slc : ICR mice, Crj : CD (Sprague-Dawley) rats and JW-NIBS rabbits of both sexes. The summarized results obtained are as follows: A mode of manifestation of toxic effects was classified into immediate-type symptoms predominantly caused by the carrier and delayed-type symptoms predominantly caused by VP regardless of animal species and routes of administration, excluding the case of intravenous dosing to rabbits. Referring to the delayed-type toxic signs, depilation, diarrhea and suppression of body weight increase were observed for mice and rats regardless of administration routes, and diarrhea was noted in rabbits by oral route. Necropsy of three species of animals and histopathology on rabbits revealed thymic and splenic atrophy in mice and rats as well as thymic atrophy and inflammatory changes of intestine in rabbits dying by oral administration. The drug-related cause of death for mice and rats seemed to be due to the cytocidal action of VP as an oncostatic drug, but the cause of death for rabbits by oral administration was considered to be somewhat different from that for mice and rats. LD50 values (mg/kg) were as follows, showing oral toxicity in rabbits being rather potent as compared with that in mice or rats: (table; see text).

Administration, Oral↗

PubMed1986

[Toxicity studies of VP 16-213 (V)--Intravenous three-month toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 0.05, 0.15, 0.5 and 1.5 mg/kg/day for three months with the object of examining its toxicity and the reversibility of toxic effects. For the purpose of comparison, vincristine (abbr. to VCR) was administered in the same manner at a dose level of 0.02 mg/kg/day. The summarized results obtained are as follows: VP 1.5 mg/kg brought anemia as well as suppression of body weight increase and food intake, and 0.5 and 1.5 mg/kg increased water consumption. However, no drug-related deaths occurred. VP 0.5 and 1.5 mg/kg predominantly decreased red blood cell count and white blood cell count accompanied with lowered lymphocyte fraction which was agreeable to the findings on bone marrow. VP 1.5 mg/kg increased platelet count. VP 1.5 mg/kg lowered total serum protein content and elevated A/G ratio. VP 0.15 mg/kg and higher decreased testicular weight; 0.5 and 1.5 mg/kg brought thymic atrophy, suppression of spermatogenesis, tubular atrophy and hydropic change in testis. VP 1.5 mg/kg induced decrease of sperms in number and appearance of giant cells in epididymis. Above-described changes excluding the findings on testis and epididymis were shown to be generally reversible. Most of the findings for a reference drug, VCR, were qualitatively comparable to those for VP. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 0.05 mg/kg/day against male rats and 0.15 mg/kg/day against female rats.

Anemia↗

PubMed1986

[Toxicity studies of VP 16-213 (II)--Oral one-month subacute toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 3, 10, 30 and 100 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought soft stool. VP 100 mg/kg decreased body weight and feed intake, and induced diarrhea, depilation and so forth. Furthermore, half of the animals at this dose level died showing systemic debility and emaciation. VP 30 and 100 mg/kg predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 10 mg/kg and higher lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 10 mg/kg and higher caused thymic atrophy and a decrease in testicular weight; 30 and 100 mg/kg brought suppression of spermatogenesis; and 100 mg/kg predominantly induced appearance of giant cells in epididymis, hypoplasia of bone marrow, ileocecitis, and atrophy of prostate, seminal vesicle and splenic germinal centers. Above-described changes excluding exacerbation of the findings on testis and epididymis were shown to be generally reversible. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against rats of both sexes.

Administration, Oral↗

PubMed1986

[Reproduction studies of VP 16-213 (I)--Oral administration to rats prior to and in the early stages of pregnancy].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to male Crj : CD (Sprague-Dawley) rats for 64 days and to female rats of the same strain for 15 days prior to mating at dose levels of 1, 3 and 10 mg/kg/day. These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summarized results obtained are as follows: VP 10 mg/kg suppressed the body weight increase in females from day 8 of pre-mating through day 20 of gestation, but did not affect the body weight in males. VP 10 mg/kg decreased the organ weights of testes, epididymides and thymus in males and induced atrophy of these organs macroscopically, but did not affect their reproductive performances. As for fetuses, VP 10 mg/kg elevated the mortality and induced anophthalmia, microphthalmia and dilated lateral ventricles, as well as suppressed their growth and the ossification processes of sternums, sacral and coccygeal vertebrae, metacarpus, thoracic vertebrae and pubis. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against parent rats of both sexes and their offspring.

Administration, Oral↗

PubMed1986

[Reproduction studies of VP 16-213 (II)--Oral administration to rats during the period of fetal organogenesis].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 10 mg/kg suppressed the maternal body weight increase from day 12 through 20 of gestation. VP 10 mg/kg brought the inhibition of fetal growth accompanied by the lowered values in body weight and body length. Furthermore, the elevated incidences of skeletal anomalies and unossified 5th and 6th sternums, as well as retarded ossification of thoracic vertebrae were also noted in this dose level. VP 10 mg/kg induced anophthalmia, microphthalmia and dilated lateral ventricles in fetuses (F1), as well as unilateral anophthalmia in offspring (F1). VP 10 mg/kg increased the days required for opening of eyelids and descending of testes in offspring (F1), but failed to affect their learning ability, motility, motor activity or emotional development. VP 10 mg/kg suppressed the growth of genital organs in F1 rats of both sexes, but failed to affect their reproductive ability or gestation period. As for F2 newborns derived from F1 rats whose dams had ever received VP 10 mg/kg during the period of fetal organogenesis, the number of implantations and survivors as well as birth indexes lowered due to changes in these items restricted to a few litters. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.

Administration, Oral↗

PubMed1986

[Reproduction studies of VP 16-213 (III)--Oral administration to rabbits during the period of fetal organogenesis].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to pregnant JW-NIBS rabbits from day 6 through 18 of gestation at dose levels of 0.3, 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 3 and 10 mg/kg elevated the maternal mortality dose-responsively. VP 3 mg/kg and lower doses failed to affect the fetal growth and ossification processes, and did not induce drug-dependent external and visceral anomalies as well as skeletal variations and anomalies. Based on these results, the no-effect dose levels of VP under the present experimental condition were estimated to be 1 mg/kg/day against dams and 3 mg/kg/day against fetuses.

Administration, Oral↗

PubMed1986

[Reproduction studies of VP 16-213 (IV)--Oral administration to rats during the perinatal and lactation periods].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 10 mg/kg induced thymic atrophy in dams. VP failed to affect the parturition of dams. VP 10 mg/kg lowered the viability of newborns (F1) on postpartum day 3 and increased the days required for descending of testes, but failed to affect the growth of genital organs, learning ability, motility motor activity or emotional development. VP 10 mg/kg brought a transient suppression of body weight increase in pregnant F1 rats, but failed to affect their reproductive ability and parturition. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Long-term rearing F1 rats derived from VP-treated dams manifested no delayed toxicity including carcinogenicity. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.

Administration, Oral↗

PubMed1986

[Reproduction studies of VP 16-213 (V)--Intravenous administration to rats prior to and in the early stages of pregnancy].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to male Crj: CD (Sprague-Dawley) rats for 61 days and to female rats of the same strain for 14 days prior to mating at dose levels of 0.05, 0.2 and 0.8 mg/kg/day. These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summarized results obtained are as follows: Body weight increases were suppressed at the dose level of VP 0.8 mg/kg in males and females. VP 0.2 and 0.8 mg/kg decreased the thymic weight and 0.8 mg/kg decreased testicular and epididymal weight in males showing macroscopic atrophy of these organs, but these doses failed to affect the reproductive ability and so on in parent rats. As for fetuses, VP 0.8 mg/kg elevated the mortality, decreased the number of survivors and suppressed their growth. Furthermore, this dose raised the incidences of anophthalmia, microphthalmia, dilated lateral ventricles and unossified 5th and 6th sternums, as well as brought retarded ossification of sternums, cervical vertebrae, sacral and coccygeal vertebrae, metacarpus and thoracic vertebrae. Based on these results, the no-effect dose levels of VP under the present experimental condition were estimated to be 0.05 mg/kg/day against parent rats of both sexes and 0.2 mg/kg/day against their offspring.

Animals↗

PubMed1986

[Reproduction studies of VP 16-213 (VI)--Intravenous administration to rats during the perinatal and lactation periods].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 0.05, 0.2 and 0.8 mg/kg/day. The summarized results obtained are as follows: VP 0.2 and 0.8 mg/kg suppressed the body weight increase and brought thymic atrophy in dams. VP failed to affect the states of birth of newborns (F1). In F1 offspring, VP 0.8 mg/kg increased the days required for testicular descending and vaginal opening, and suppressed the body weight increase, but failed to affect the growth of genital organs, reproductive ability, learning ability, motility, motor activity or emotional development. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 0.05 mg/kg/day against dams and 0.2 mg/kg/day against their offspring.

Animals↗

PubMed1986

[Toxicity studies of VP 16-213 (III)--Oral six-month chronic toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 1, 3, 10 and 30 mg/kg/day for six months with the object of examining its chronic toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought transient diarrhea, anemia and depilation. Some animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 3 mg/kg and higher predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 30 mg/kg lowered total serum protein content and elevated A/G ratio in males, and lowered serum alkaline phosphatase activity in females. VP 10 and 30 mg/kg predominantly induced thymic atrophy, testicular atrophy with suppression of spermatogenesis and tubular atrophy, a decrease in epididymal weight, and splenic erythropoiesis. Above-described changes excluding the findings on testis and epididymis in VP 30 mg/kg group were shown to be generally reversible. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 1 mg/kg/day against rats of both sexes.

Administration, Oral↗

PubMed1986

[Toxicity studies of VP 16-213 (IV)--Intravenous one-month subacute toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 0.15, 0.50, 1.5 and 4.5 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. For the purpose of comparison, vincristine (abbr. to VCR) was administered in the same manner at dose levels of 0.04 and 0.08 mg/kg/day. The summarized results obtained are as follows: VP 0.50 mg/kg and higher suppressed body weight increase and food intake dose-responsively. VP 4.5 mg/kg brought depilation and anemia, and some of male animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 0.50 mg/kg and higher decreased white blood cell count accompanied with lowered lymphocyte fraction, and 1.5 and 4.5 mg/kg predominantly decreased red blood cell count. VP 1.5 and 4.5 mg/kg lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 0.50 mg/kg and higher predominantly decreased testicular weight, and 1.5 and 4.5 mg/kg predominantly brought thymic atrophy, hypoplasia of bone marrow and testicular atrophy with suppression of spermatogenesis and tubular atrophy. VP 4.5 mg/kg induced atrophy of germinal centers and hemosiderosis in spleen, and epididymal atrophy with decrease of sperms in number and appearance of giant cells. Above-described changes excluding the findings on testis and epididymis were generally reversible. Most of the findings for a reference drug, VCR, were similar to those for VP, and their severities brought by VP 1.5 and 4.5 mg/kg were comparable to those by VCR 0.04 and 0.08 mg/kg, respectively. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 0.15 mg/kg/day against rats of both sexes.

Anemia↗

PubMed1986

[Laparoscopic diagnosis and evaluation of danazol therapy of endometriosis in sterility].

In twenty two sterile women, endometriosis externa were diagnosed and classified laparoscopically. Classifying the severity of endometriosis by Beecham's and/or Sugimoto's classification, 17 cases were declared mild and only 5 cases severe (one was stage IV and the others were stage III by Beecham's classification, and 4 were grade III by Sugimoto's classification). All these patients were treated with Danazol (Bonzol) 400 mg/day or 300 mg/day for about 24 weeks. Four weeks after the termination of Danazol administration, the effects of Danazol therapy were examined according to the number of blueberry spots, adhesion severity and chocolate cyst size under re-laparoscopy, as well as dysmenorrhea and other complaints. The results were as follows: Dysmenorrhea was relieved in 60.0% of 15 cases, Blueberry spots were decreased or paled in 88.9% of 18 cases, Adhesion was weakened or partially separated spontaneously in 71.4% of 7 cases, Chocolate cyst size became smaller in 85.7% of 7 cases, The patient complained of mild side-effects, namely acne in 45.5% of cases, a weight gain of more than 2 kg in 54.5%, and hoarseness developed in one. The results of laboratory tests performed before and during the treatment remained slightly abnormal or within normal limits.

Adult↗

PubMed1986

[Diagnosis and treatment of colorectal cancer using monoclonal antibodies].

The clinical usefulness of monoclonal antibodies was discussed from the viewpoint of serodiagnosis, immunohistochemistry, radio immunodetection and therapy. Monoclonal antibodies against carcinoembryonic antigen (CEA) were shown to be more beneficial than polyclonal antibodies. Carbohydrate antigens such as CA 19-9 or CA 50 were also available as tumor markers of colorectal cancer to a certain extent.

Antibodies, Monoclonal↗

PubMed1985

[The effect of a synthetic progestin (R 2323) on gonadal and endometrial cells in vitro and in vivo].

Gestrinone (R 2323) is a synthetic progestogen, and noteworthy agent for endometriosis treatment. The effect of this reagent on cultured cells from porcine granulosa, human endometrial and endometrial carcinoma origin was investigated concerning their hormonal activities and cell proliferations. Also, the effect of gestrinone on the serum levels of gonadotropins and gonadal steroids in patients with XY gonadal dysgenesis (Swyer's syndrome) and uterine myoma was studied. The monolayer cell colony established from the endometrial tissue fragments was positively stained by PAS similar to the secretory phase endometrium by 10 ng/ml gestrinone in the culture media. Endometrial carcinoma cells from a 65-year-old patient were proliferated by gestrinone at the concentration of 50 ng/ml in the culture media. The effect of gestrinone on the secretions of progesterone and estradiol-17 beta with or without hCG/testosterone from the cultured porcine granulosa cells was also investigated. Progesterone secretions were stimulated at the 50 ng/ml concentration of gestrinone, especially in association with hCG. Nonetheless, at the concentration of 500 ng/ml, those were inhibited. The secretions of estradiol-17 beta were stimulated by this reagent both with and without testosterone in dose-dependent manners. The effect of 25 mg gestrinone administration for 3 days on the levels of LH, FSH, progesterone and estradiol-17 beta in a patient with XY gonadal dysgenesis was as follows. Both LH and FSH levels gradually decreased, whereas estradiol-17 beta level was increased. The same dosage of this reagent was administered to a patient with uterine myoma on her menstrual days 7, 8, and 9.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Bone disorders in spontaneously hypertensive rat.

The bones of adult (26 weeks old) spontaneously hypertensive rats (SHR) were examined chemically and histologically by comparing them with those of the corresponding normotensive Wistar-Kyoto (WKY) rats. The mean cortical thickness, the mean ash weight per unit bone volume, and the ash as percentage of dry weight of femur were significantly lower in SHR than in WKY. Besides, the percent cortical area measured on tibial cross-section was also reduced in SHR compared with WKY. These findings strongly suggest that the development of osteoporotic bone disorders exists in adult spontaneously hypertensive rats.

Animals↗

PubMed1985

Phosphorylation of a clathrin light chain of coated vesicles in the presence of histones.

Coated vesicles isolated from bovine brain contained a protein kinase(s) which phosphorylated phosvitin and an endogenous protein with a molecular weight (Mr) of 48,000. A clathrin light chain (Mr 33,000), a constituent of the coat structure of the coated vesicles, was also phosphorylated when histone was added to the incubation medium. The clathrin light chain was phosphorylated with GTP as well as ATP as the phosphoryl donor. The phosphorylation reaction was inhibited by heparin. An additional 1.35 mol of PO4/mol was incorporated into the clathrin light chain which had contained approximately 1.5 mol of PO4/mol when the coated vesicles were incubated with ATP, Mg2+, and histone. Phosphoamino acid determination revealed the presence of 32P-phosphorylated threonine and serine in phosvitin, threonine in the endogenous protein (Mr 48,000) and serine in the clathrin light chain (Mr 33,000).

Adenosine Triphosphate↗

PubMed1985

Properties of protein kinases in brain coated vesicles.

Coated vesicles prepared from bovine brain contained cyclic nucleotides- and Ca2+-calmodulin-independent protein kinases which in the presence of Mg2+ catalyzed the phosphorylation of an endogenous 48,000 Mr protein of coated vesicles (C-48), phosvitin and troponin T. Phosvitin was phosphorylated either in the presence of ATP or GTP. The phosphorylation of C-48, on the other hand, was specific for ATP. Heparin inhibited the phosphorylation of phosvitin but not that of C-48. Mn2+ inhibited the phosphorylation of phosvitin, while Mn2+ substituted for Mg2+ in the phosphorylation of C-48. When the coated vesicles were prepared in the presence of NaF, C-48 contained 2.5-2.8 mol of phosphate/mol. On incubation with Mg2+ and ATP, C-48 incorporated 1.2-1.6 mol of phosphate/mol. With C-48 as a substrate, the value of its apparent Km for ATP was 6 microM. With phosvitin as a substrate, the value of its apparent Km was 20 microM. The phosphorylated amino acid residues in the phosvitin were identified as serine and threonine. Phosphothreonine was detected in C-48. These results suggest that brain coated vesicles possess two different classes of protein kinase, a casein kinase II and C-48 kinase.

Adenosine Triphosphate↗

PubMed1985

Imino acid and related alicyclic amine levels in biological fluids.

Imino acid and related alicyclic amine concentrations in blood and urine of mammals including humans were concurrently determined by a selected ion monitoring technique. Nanomole levels of proline and pipecolic acid, and pyrrolidine and piperidine as well, were found in human urine. Proline levels but not pipecolic acid levels were higher in blood of humans than in urine. Pyrrolidine and piperidine levels in blood of humans were picomole levels and much lower than those in urine. Similar tendencies were also recognized when these 4 compounds were analyzed using animal blood and urine, although the levels were generally higher in animals than in humans. Significantly high concentrations of the imino acids and the amines were found also in animal semen.

Amines↗