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Biomedical subjects

S Kai

Publications and source records attributed to S Kai.

At least 91 records · Page 5Linked to original sources

[Bone marrow transplantation for MDS].

Five patients with myelodysplastic syndrome (RA: 4 cases, RAEB in T: 1 case) were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Median age was 20-y-o (11-31-y-o). All patients were prepared with cyclophosphamide and total body irradiation. Engraftment was documented in all patients. One patients (case 4, 31-y-o female) died of brain hemorrhage due to the thrombocytopenia refractory to platelet transfusion because of anti-platelet antibody in 34 days after BMT. A patient with RAEB in T was also died of respiratory failure from interstitial pneumonia on Day 173. One patient (case 1, 22-y-o, female) progressively became granulocytopenic and thrombocytopenic status after BMT. She suffered from life-threatening infection and then received a second bone marrow cell infusion from the same donor without any preparative conditioning. These results suggest that BMT could be the treatment of choice for MDS, especially for the patients with RA who have poor prognostic factors including life-threatening cytopenia and or cytogenetical abnormalities.

Adolescent↗

[Administration of haptoglobin in ABO incompatible bone marrow transplantation].

Haptoglobin was administered i.v. in 2 cases of ABO incompatible bone marrow transplantation for the prevention of hemoglobinuria due to acute hemolysis. The first case was a 25-year-old woman with severe aplastic anemia. The transplantation was both major and minor mismatch, where the donor was type A and the recipient was type B. The second case was a 31-year-old man with chronic phase of chronic myelogenous leukemia. The transplantation was major mismatch, where the donor was type B and the recipient was type O. After the administrations of haptoglobin 8,000 units we transfused bone marrow infusates from which incompatible erythrocytes were removed. Though prominent hemoglobinemia was observed in both cases, the serum haptoglobin values were not saturated and hemoglobinuria was not detectable. Haptoglobin appears to be useful for the prevention of acute renal failure associated with acute hemolysis in ABO incompatible bone marrow transplantation. Intravenous haptoglobin supplement therapy makes transplantation safer and may contribute to improve the recovery rate of total nucleated bone marrow cells after the erythrocyte depletion without worrying much about their contamination.

ABO Blood-Group System↗

A physiological marker for assessing anxiety level in humans: frontal midline theta activity.

The distinct theta rhythm in the frontal midline area during performance of mental tasks has been designated as Fm theta. Sixteen male university students who failed to show any appearance of Fm theta in 3 consecutive days were given diazepam 5 mg, amobarbital 80 mg, methylphenidate 15 mg and placebo, in a double-blind, crossover design. Scores were made on the state anxiety scale of STAI; EEGs were recorded before and during performance of an arithmetic addition. The test was repeated twice: before and one hr after drug administration. Fm theta appeared following the drug administration even in those who had never shown the appearance of Fm theta, and the appearance time of Fm theta increased in the following order: diazepam greater than amobarbital greater than placebo greater than methylphenidate. The scores of STAI decreased in the same order. The speed of performed tasks was increased by methylphenidate and placebo, but decreased by amobarbital and diazepam. These results suggest that relief from anxiety might be reflected in the appearance of Fm theta and that Fm theta might be a useful tool to measure the anxiety level in humans.

Adult↗

Teratogenic effects of carboplatin, an oncostatic drug, administered during the early organogenetic period in rats.

In the preceding study, no teratological effects against rat fetuses were observed when carboplatin, an oncostatic platinum coordination complex, was dosed to their dams from days 7 to 17 of gestation at a dose level of 4 mg/kg/day. However, there are a few reports which show the teratogenic action of carboplatin injected from days 6 to 15 of pregnancy at a dose level of 6 mg/kg/day. In the present study, carboplatin was administered intravenously to pregnant female Crj: CD (Sprague-Dawley) rats from days 6 to 9 or 7 to 10 of gestation at a dose level of 6 mg/kg/day in order to know the teratogenicity of this drug. Carboplatin were highly embryolethal in dams when dosed from days 6 to 9 of gestation, but not in animals when injected from days 7 to 10 of pregnancy. Carboplatin also produced external, internal and skeletal anomalies in fetuses such as gastroschisis, dilatation of cerebral ventricles, cleft sternum, fused ribs, malformed thoracic vertebra when administered from days 6 to 9 of gestation, but not in conceptuses when dosed from days 7 to 10 of pregnancy. However, the delayed ossification which was ascribed to the fetal growth retardation was observed in rats treated with this drug during both administration periods. These results suggest that carboplatin is embryotoxic, inducing intrauterine death and congenital malformations in rats, when injected during the early stages of gestation including day 6 of pregnancy.

Abnormalities, Drug-Induced↗

[Assay of erythropoietin in plasma by enzyme-linked immunosorbent assay].

Using an enzyme linked immunosolvent assay kit supplied by Toyobo Co., erythropoietin (EPO) concentration in plasma was measured. Normal 100 samples showed a logarithmic distribution in EPO concentrations and normal range was between 5.4-32.5 mU/ml (mean +/- 2 SD). Coefficient variations (C.V.) of 3 samples continuously assayed were 3.8%, 6.5%, and 9.1% and C.V. of 3 samples assayed day by day were 3.6%, 7.2%, and 11.5%. Dilution test revealed that 3 samples diluted to 75%, 50%, and 25% were on each line which go through zero point. After the addition of 5.0, 15.0, and 35.0 mU/ml of EPO to the 3 samples, assay of EPO revealed 95.5 +/- 6.3% (mean +/- SD) of recovery. Assay of EPO in plasma from 19 patients with aplastic anemia revealed that all samples were higher than normal range and that 4 samples from the patients with severe aplastic anemia (less than 8.0 g/dl of hemoglobin) showed higher than 3,000 mU/ml. Furthermore, 67% (14/21) of samples from patients with leukemia showed higher than normal range in EPO concentration. EPO concentration in plasma from 17 patients with chronic renal failure were within normal range although the patients showed anemia.

Adult↗

Bone marrow transplantation for patients with severe aplastic anemia and myelodysplastic syndrome.

A survey of the results of marrow transplantation for severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) in Japan is reported. Of the 152 patients with SAA, 109 were alive between 2 and 132 months following transplantation and the probability of survival at 5 years was 70% (for the patients with grafts from HLA-matched siblings) and 100% (for the patients with grafts from monozygous twins). Survival rate at 3 years for the patients with grafts from family members other than HLA-matched siblings was 46%. The chance of survival was influenced by conditioning regimen and recipient's age. Recipients with sustained engraftment had a significantly higher survival rate than those with graft failure (83% vs 11%, p less than 0.001). Since 1985, the results of transplantation from HLA-matched siblings have improved and the 3-year survival is more than 90% for patients under 20 years old. For MDS, the actuarial survival at 3 years was 42%. The chance of survival was not influenced by the FAB classification, patient's age, patient's sex, interval from diagnosis to transplant, karyotype anomaly or graft versus host disease.

Adolescent↗

[Reproduction studies of carboplatin (I)--Intravenous administration to rats prior to and in the early stages of pregnancy].

Carboplatin, an oncostatic drug, was administered intravenously to male Crj: CD (Sprague-Dawley) rats for 63 days and to female rats of the same strain for 14 days prior to mating at dose levels of 1, 2 and 4 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: 1. Carboplatin 2 mg/kg and higher suppressed body weight gains accompanied by the decreases in food and water consumption in male rats. Further, body weight gains were suppressed in female rats followed by the decreases in food consumption at the same dose levels. 2. Though there were no differences between dosed animals and controls regarding the organ weights, the incidence of necrosis of the tails around the injection site was increased in male rats at 4 mg/kg. 3. Carboplatin failed to affect the reproductive ability of both sexes. 4. As for fetuses, the mortality was elevated at 2 mg/kg and higher and the number of live fetuses reduced at 4 mg/kg, but the influences on prenatal development were not apparently observed for live fetuses even at the highest dose level. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against parent rats of both sexes and their offspring.

Animals↗

[Reproduction studies of carboplatin (II)--Intravenous administration to rats during the period of fetal organogenesis].

Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows: 1. Carboplatin 4 mg/kg suppressed the maternal body weight gains from day 13 through 20 of gestation. 2. Uterine weights were reduced in F0 dams at term at carboplatin 4 mg/kg. 3. Carboplatin 4 mg/kg brought the inhibition of fetal growth accompanied by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidences of unossified 5th and 6th sternum , as well as retarded ossification of sacrococcygeal vertebrae were also noted in this dose level. 4. The birth rate was reduced in neonates (F1) at carboplatin 4 mg/kg. 5. Body weight gains in male F1 rats were suppressed at carboplatin 4 mg/kg from 4 to 8 weeks of age. 6. Carboplatin 4 mg/kg decreased the brain weights on an absolute basis in female F1 rats, but failed to affect their postnatal differentiations, early behavioral developments, learning ability, motor activity or emotional development. 7. Reproductive ability in F1 rats of both sexes were not affected by carboplatin. 8. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the organogenetic period. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Animals↗

[Reproduction studies of carboplatin(III)--Intravenous administration to rats during the perinatal and lactation periods].

Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 21 of postpartum at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows: 1. Maternal body weight gains were suppressed during the former part of the lactation period at carboplatin 2 mg/kg and higher. 2. Thymic weights were decreased and lung weights were increased in dams (F0) at carboplatin 2 mg/kg and higher. Further, ovarian weights were reduced in dams (F0) at carboplatin 4 mg/kg. 3. Carboplatin failed to affect the parturition of F0 dams. 4. Carboplatin did not affect the viability of newborns (F1), and postnatal differentiations, early behavioral developments, learning ability, motor activity or emotional development in F1 animals. 5. Carboplatin 4 mg/kg brought a suppression of pituitary weights after mating in F1 male rats and decreases of adrenal and genital organ weights at weaning in F1 female rats, but failed to affect their reproductive ability. 6. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the perinatal and lactation periods. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against dams and 2 mg/kg/day against their offspring.

Adrenal Glands↗

[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↗

[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↗

[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↗