Search PubMed⌕ Search

Biomedical subjects

H Nagata

Publications and source records attributed to H Nagata.

At least 253 records · Page 14Linked to original sources
PubMed1990

Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse.

A new water-soluble derivative of camptothecin, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), did not exhibit potent antitumor activity in vitro against experimental tumor cells. The 50% effective doses of CPT-11 against KB and L1210 cells were 1100 and 5500 ng/ml, respectively. These values were markedly higher than those of camptothecin (CPT, 0.98 and 3.7 ng/ml) or 7-ethyl-10-hydroxycamptothecin (SN-38, 0.37 and 3.6 ng/ml). CPT-11 was found to be converted into SN-38 in mouse serum. In vitro incubation of CPT-11 in mouse serum or tissue homogenate enhanced the growth-inhibitory activity much more than that expected from the concentration of CPT-11. This enhancement of the activity coincided with that expected from the SN-38 concentration in incubated serum or homogenate, though the contribution of CPT-11 could not be refuted. SN-38 is considered to play a major role in the antitumor activity when CPT-11 is incubated in serum or homogenate. The plasma CPT-11 concentration decreased biexponentially after i.v. administration of CPT-11 into mice with a biological half-life of 0.8 to 1.1 h. The area under the plasma CPT-11 concentration-time curve showed dose dependency. The SN-38 concentration decreased for the first 30 min after administration and was then maintained for a few hours at about 0.1 microgram/ml after i.v. administration of 20 and 40 mg/kg of CPT-11 followed by the log-linear terminal phase with a half-life of about 2 h which was independent of the dose. It is suggested that the maintenance of plasma SN-38 concentration might be necessary for it to exhibit antitumor activity in vivo.

Animals↗
PubMed1990

[Combination chemotherapy with methotrexate, vincristine, cis-platinum, cyclophosphamide, adriamycin, and bleomycin: MVP-CAB for disseminated urological cancer].

Twenty-eight evaluable patients with disseminated measurable malignancies of the genitourinary organs except testicular cancer were treated with MVP-CAB, between May 1985 and June 1988. Chemotherapy was given at 3 to 4 week intervals, as follows. On day 1, methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg/body were administered. On day 2, cis-platinum 50 mg/m2, on day 1 to 3, prednisolone 20 mg/body were also administered. The administration of bleomycin and adriamycin were limited to 90 mg/body and 400 mg/m2. The median age was 59 years. The median follow-up duration was 11 months. The primary lesions were urothelial tract cancer (19 patients), malignant lymphoma (1 patient), renal cell adenocarcinoma, penile cancer, prostatic adenocarcinoma, and leiomyosarcoma (2 patients each). CR was observed in 2 patients, and PR in 11 patients with urothelial tract cancer. The overall response rate was 68% (13/19). The response rates in primary and metastatic lesions were 56% (5/9) in primary, 73% (8/11) in lymph node, 71% (5/7) in lung, 67% (2/3) in liver, and 20% (1/5) in bone. The median duration of survival in the responders was 13.5 months, and in the non-responders was 5 months. The 1 year survival rate by Kaplan-Meier method was 70% in responders. On the other hand, the longest survival time in non-responders was 9 months. Marked improvement of survival time was noted in the responders. PR was observed in 1 patient with malignant lymphoma, prostatic adenocarcinoma, and leiomyosarcoma in each. The main toxic effect of MVP-CAB was bone marrow suppression. Leucopenia (WBC less than 4,000/mm3) was noted in 24 patients (86%), and 16 patients (57%) had a WBC count nadir below 2,000/mm3. Thrombocytopenia (plt less than 10 x 10(4)/mm3) was noted in 10 patients (36%). However, there were no deaths due to the bone marrow suppression.

Adult↗
PubMed1990

Serum CA-125 and 17 beta-estradiol in patients with external endometriosis on danazol.

Serum concentration of CA-125 and 17 beta-estradiol (E2) were measured by radioimmunoassay in 40 patients with stage III or IV endometriosis to evaluate their usefulness in assessing the outcome of disease. Patients were categorized into good responders and poor responders depending on the result of the second-look laparoscopy 8 weeks after danazol therapy. CA-125 decreased significantly in all subjects after initiation of treatment. However, after 12 weeks of treatment a significant increase (p less than 0.05) in serum CA-125 was noted in the poor-response subjects as compared to the good-response subjects. In addition, 8 weeks after treatment CA-125 levels in the poor-response group were significantly higher (p less than 0.001) than in the good-response group. On the other hand, in the good-response group, E2 levels decreased for 8 weeks during danazol therapy to return to almost basal levels after 12 weeks, while in the poor-response group E2 levels did not change as compared to pretreatment levels. We conclude that the determination of CA-125 and E2 may be helpful in assessing the response of patients with advanced endometriosis on danazol treatment.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Inhibitory effect of human plasma and saliva on co-aggregation between Bacteroides gingivalis and Streptococcus mitis.

The effect of human plasma and saliva on co-aggregation between Bacteroides gingivalis and Streptococcus mitis was studied by means of a turbidimetric assay. The co-aggregation activity was obtained from the maximum slope of the absorbance vs. time curve. Its dependence on pH, temperature, and ionic strength was examined, and the number of Bacteroides cells in relation to the number of Streptococcus cells resulting in optimal co-aggregation was established. Co-aggregation inhibition experiments showed that the co-aggregation activity was inhibited by l-arginine and l-lysine, although the activity was unaffected by the sugars tested. Human plasma and saliva were able to inhibit the co-aggregation in a dose-dependent reaction. Plasma exhibited the most potent inhibitory activity in these fluids. Fibrinogen was the most potent inhibitor of the plasma-derived proteins tested. These data suggest the possibility that the oral fluids may modulate the attachment of B. gingivalis to Gram-positive bacteria in periodontal pockets.

Adult↗
PubMed1990

[A study on immunoglobulin A in human milk. Relationship between the amount of IgA and perinatal factors including food intake].

The concentrations of IgA in human milk on the 5th or 6th day after delivery were measured in 117 women who delivered maturely, and the amount of IgA per 24 hours was calculated by multiplying the IgA concentration by the total milk volume of the same day. The relationship between the amount of IgA and perinatal factors, including food intake during the latter half of the pregnancy, were investigated. Subjects were divided into three groups (little, moderate, much) by the amount of IgA per 24 hrs and quantification theory II statistical analysis was applied to discriminate among the three groups using 13 factors concerning the perinatal period and food intake as explanatory variables. 1. The ratio of correct classification into the three groups was relatively high, suggesting that there is a relation between the amount of IgA in milk and perinatal and food intake factors. 2. Among the perinatal factors, the age, the gestation period and the number of experienced deliveries were effective for the amount of IgA. The obtained results showed that women 20-29 years old who had the first delivery after 38-40 weeks of gestation were liable to have the greatest amount of IgA in milk. 3. The amount of IgA of the women who ate less in the latter period of pregnancy compared with pre-pregnancy, or had a "less frequent intake of protein" was liable to be the greatest, and that of women with a "large volume" or "frequent protein intake" was liable to be greater than that of those with "the same volume" or "moderately frequent protein intake." The amount of IgA of the women with a "frequent intake of salted dried fish" was the greatest. The fact that the amounts of IgA of the women who "ate less" or had a "less frequent intake of protein" were liable to be the greatest was considered to show that toxemia or the tendency to near abortion or preterm delivery greatly affected the amount of IgA.

Adult↗
PubMed1990

[Abnormalities of axonal transport as pathogenesis of axonal degeneration in peripheral neuropathy].

Axonal transport is a universal property of nerve cells. Role of axonal transport abnormalities in the pathogenesis of peripheral neuropathies was discussed. Applications of isotope-labeling technique to the study of axonal transport in experimental neuropathy have provided insights into the pathogenesis of axonal degeneration. As a model of dying-back neuropathy, axonal transport has been studied in sciatic motor neurons of rats with neuropathy induced by p-bromophenylacetylurea (BPAU) using this technique. The velocity of rapid anterograde transport was unaffected in this neuropathy and amount of retrograde axonal transport was reduced. The lag time between precursor injection and the onset of transport was shorter in BPAU-treated rats than controls. Whereas, in experimental ethylene oxide (EO) neuropathy rats, rapid transport velocity was markedly reduced in spite of very mild results of morphometric study. Those rapid axonal transport abnormalities may explain some aspects of the pathogenesis of peripheral neuropathies. In BPAU neuropathy model, disturbance of assembly of membrane-limited vesicles in Golgi processing may play a role in turnaround defect which causes dying-back neuropathy. EO neuropathy model suggests the possibility of oxygen utilization disturbance may causes energy dependent rapid transport velocity. Moreover, environments surrounding axon are also important for function of axonal transport. Present information leads to the conclusion that abnormalities in the supply and deposition of transported materials occur in early course of peripheral neuropathy and may contribute to development of the neuropathy.

Animals↗
PubMed1990

[Relationships between the amount of total protein in human milk, the volume of produced milk and perinatal factors].

The concentrations of total protein in human milk on the 5th or 6th day after full-term delivery were measured on 184 women, and the amount of protein per 24 hours was calculated by multiplying protein concentration by 24-hour milk production for the same day. Relationships between the amount of protein, milk volumes and perinatal factors were investigated. 1. The mean values (and standard deviations) for total protein concentration and amount per 24 hours, and milk volumes were 1.89 (0.37) g/dl, 6.60 (2.71) g/24h, 353 (144) ml/24h respectively. A significant negative correlation was found between the concentration of protein and milk volumes. The amount of protein per 24 hours showed a considerably high positive correlation with milk volumes rather than with total protein concentration. 2. Among perinatal factors, the age of the mother and whether the delivery was abnormal affected significantly both the amount of protein and milk volumes. The amount of protein and milk volumes of women 30-39 years old, who delivered abnormally were both significantly reduced. The amount of protein for women who had hemoglobin concentrations less than 11.5 g/dl in the latter period of pregnancy was significantly high. However, significant difference disappeared when those women who had both abnormal delivery and birth weight of their baby was more than [mean + 1SD] were excluded.

Adult↗
PubMed1990

Sites of lymph follicle formation in the draining popliteal lymph nodes of mice locally injected with antigenic and mitogenic substances.

Our previous studies showed that some antigenic and mitogenic substances, when locally injected into mice, efficiently produced new lymph follicles outside pre-existing follicles in draining lymph nodes, whereas others had virtually no effect. In the present experiments, young adult male mice were injected with several antigens and mitogens in the rear footpad, and the number and development sites of newly produced lymph follicles in the draining popliteal nodes were studied using serial sections of the nodes obtained between 5 and 21 days after injection. In the unstimulated state, each popliteal node contained a limited number of lymph follicles which mostly lay in a portion of the peripheral cortex overlaying the deep cortex (this portion is referred to as the PCOU), whereas a portion of the peripheral cortex extending beyond the deep cortex (referred to as the PCBU) was underdeveloped with only occasional follicles. Mice treated with soluble PHA or fluid tetanus toxoid developed germinal centers in association with existing follicles but failed to produce new follicles. The PCBU of the draining nodes remained underdeveloped, and the number and distribution pattern of lymph follicles within a draining node were comparable to those in the control node. Animals treated with LPS (50 micrograms), Con A, alum-precipitated PHA or alum-precipitated tetanus toxoid produced significantly large numbers of new follicles outside pre-existing follicles in the draining nodes, the new follicles produced in the PCBU being generally more numerous than those in the PCOU. In these draining nodes, the peripheral cortex, comprising a number of follicles, was found to overlie the deep cortex and extend beyond the deep cortex towards the hilar region. In animals given a less effective stimulant, such as ferritin or a smaller dose of LPS (10 micrograms), the draining nodes produced a relatively small number of new follicles, most of which were formed in the PCBU. The present results indicate that in the mouse popliteal node, the PCBU is morphologically underdeveloped under normal conditions, but develops lymph follicles in response to exogenous stimuli more readily than the PCOU, and that substances efficient in inducing follicle formation can be regarded as capable of stimulating the development of the peripheral cortex.

Animals↗
PubMed1990

[Relation between localization of gastric mucosal lesions and microvascular disturbance].

Acute gastric mucosal lesions in the rats were produced by intermittent electrical stimuli to a main trunk of the left gastric artery (LGA), right gastroepiploic artery (RGEA) or a posterior branch of the left gastric artery (PLGA). The image processing analysis was applied to determine the relation between distribution of the lesions and perfusion area of the supplying artery to which electrical stimuli were given. Electrical stimuli of 50 Hz, 5 msec, 100 microA was supplied to the artery for 30 sc three times with 10 sec interval. A series of these stimuli was repeated three times. The mucosal blood flow measured with the laser doppler method in each perfusion area was reduced to less than 35% of the control value during the electrical stimuli for 30 sec. After the repeated electrical stimuli to LGA, 85.8 and 95.4% of the mucosal lesions were found in the mean and maximum perfusion area of LGA, respectively. Electrical stimuli to PLGA caused 84.5% and 95.3 of the lesions in the mean and maximum area of PLGA, respectively. Stimuli to RGEA caused 53.4% and 74.1% of the lesions in the mean and maximum perfusion area of RGEA. In the antrum, electrical stimuli to LGA, PLGA or RGEA produced 0%, 5.4% or 5.0% of the mucosal lesions. It is concluded that the corpus mucosal lesions induced by regional ischemia are distributed in the ischemic area.

Animals↗
PubMed1990

[A case of primary pulmonary hypertension with high venous thromboxane B2 concentration].

A 30-year-old male was admitted because of dyspnea, which had started three years before the admission. Chest roentgenogram showed prominence of the proximal pulmonary arteries and diminished vascularity of the peripheral pulmonary arteries. Electrocardiogram showed right axis deviation and right ventricular hypertrophy. Right heart catheterization revealed a markedly elevated pulmonary arterial pressure and pulmonary vascular resistance with normal capillary wedge pressure. Oximetry showed no evidence of intracardiac shunt. Perfusion lung scan revealed nonsegmental, patchy defects in both lungs. Pulmonary arteriography showed no evidence of pulmonary thromboembolism. From the above findings, primary pulmonary hypertension was diagnosed. Nifedipine, ISDN, prazosin, and captopril were administered to evaluate the short term-effect of he vasodilators. Nifedipine was found to be the most effective. The venous thromboxane B2 level was high. After oxygen therapy, venous thromboxane B2 level fell within the normal range following improvement of arterial oxygenation and decrease in venous FDP level. Hemodynamic changes induced by ice-water hand immersion showed marked increase in the mean pulmonary arterial pressure and total pulmonary arterial resistance. These results suggested that chemical mediators such as thromboxane, and pulmonary arterial vasospasm were involved in the pathogenesis.

Adult↗
PubMed1990

[Analysis of adhesive proteins on the surface membrane of platelet in malignant neoplasm].

Flow cytometry was used to detect fibrinogen (platelet associated fibrinogen: PAFbg) and fibronectin (PAFn) on the surface membrane of platelets in leukemia (9 cases), lung cancer (15 cases) and hepatoma (8 cases) patients (by one color analysis method), and simultaneously to investigate the binding of monoclonal anti-glycoprotein (GP) IIb/IIIa and anti-GP Ib antibodies (by two color analysis). All patient groups showed higher Fbg values than the normal control group, but no differences were found between patient groups. The values of Fbg and Fn showed a correlation, but the pattern of binding did not show a regular tendency in any patient group. There also was no significant correlation between Fbg values and the positive percentage of monoclonal anti-GPIIb/IIIa and anti-GPIb antibodies, and the binding of Fbg did not inhibit that of monoclonal antibody. The results suggest the following. 1. There are no differences in platelet activation in leukemia, lung cancer and hepatoma patients, and the degree of platelet activation is decided by the degree and the kind of stimulation. 2. The increase of both PAFbg and PAFn prove to the existence of activated platelet.

Blood Platelets↗
PubMed1990

[Chronic ITP with a remarkable response to vitamin C administration after splenectomy].

This report deals with a case of 23-year-old woman with chronic idiopathic thrombocytopenic purpura (ITP) showing a favorable response to vitamin C (VC) administration. She was treated with glucocorticoids and immunosuppressants, whereas inadequately controlled with its tolerable dosage. Next, she underwent splenectomy. However, there were only transient effects on platelet counts, so the therapy with ascorbate was carried out according to the report by Brox et al. The platelet counts increased to 20 x 10(4)/microliters after 4 months. Side effects of VC therapy did not occur.

Adult↗