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Biomedical subjects

Y Kusunoki

Publications and source records attributed to Y Kusunoki.

At least 145 records · Page 8Linked to original sources
PubMed1988

Immunological responses of aging Japanese A-bomb survivors.

Immune response parameters were studied on 1341 A-bomb survivors residing in Hiroshima, Japan. Mononuclear cells were isolated from venous blood and tested for interleukin-2 production; lymphocytes were purified and tested for natural killer (NK) cell activity and interferon (IFN) production; and serum was tested for IFN and circulating immune complex (CIC) levels. Statistical analyses were performed for each type of assay using a linear models procedure including sex, age at the time of the bomb, radiation exposure, all the interaction variables, and the categorical variable day-of-assay in the model. The findings showed that (1) none of the immunologic variables were significantly affected by radiation exposure; (2) NK activity and CIC levels were positively associated with age; and (3) NK activity was on average higher for males than females. The data exemplify the difficulty in reaching firm conclusions concerning associations with radiation exposure when the dependent variable exhibits a large degree of interindividual and day-of-assay variability.

Aging↗
PubMed1988

[Chemotherapy of small cell lung cancer].

The recent results of chemotherapy for SCLC were reviewed in this paper. The combination chemotherapy with some highly active drugs can be summarized as follows: response rate 74-94% in limited disease (LD) and 63-90% in extensive disease (ED), complete response 39-57% in LD and 20-48% in ED, median survival 10-21 months in LD and 7-12 months in ED. To overcome drug resistance in the treatment of SCLC, non-cross resistant alternating chemotherapy has been explored. In our institute, a randomized study of continuous vs alternating regimen for SCLC was carried out from August 1982 to March 1985. This resulted in the acknowledged superiority of the alternating regimen in CR rate and the overall response rate, but no differences in survival. A current study comparing the standard chemotherapy with cyclophosphamide, adriamycin and vincristine (CAV) to alternating CAV with etoposide (E) and cisplatin (P) has suggested an advantage for alternating chemotherapy, with a statistically superior response rate and survival. The high-dose (HD) chemotherapy for SCLC is also a new strategy to improve the current treatment results. We are now studying the efficacy of HD-E (1.0-1.5 g/m2) with or without P (80-120 mg/m2) for relapsed SCLC. The result suggested that HD-E and P is an effective treatment modality as a salvage therapy. The search for new active drugs is another important way to improve the treatment results. Since 1986, a phase II study of Carboplatin has been performed in Japan. The ongoing data suggest that Carboplatin is a highly active agent against SCLC. Finally, further research will be necessary to investigate novel modalities in order to achieve a breakthrough in the current status.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Restorative effect of muroctasin, MDP-Lys (L 18), on leukopenia caused by anticancer chemotherapy in lung cancer--comparative study by envelope method].

Muroctasin, a derivative of MDP, is known to augment the number of WBC via colony-stimulating factor. Muroctasin has been expected to be promising for application to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by chemotherapy combination, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on days 4, 7 and 15 after commencement of the study. WBCs in H and L groups showed greater recovery than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin-treated groups. A portion of immature neutrophil in bone marrow was also increased by muroctasin treatment. In the present study, the usefulness of muroctasin in leukopenia was indicated when administered at dosages of 200 micrograms for 6 days.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

[Studies on an appropriate intra thoracic administration of cisplatin and sodium thiosulfate in malignant pleural effusion].

Twenty-eight patients with malignant pleural effusion received instillation of cisplatin (CDDP) into the pleural cavity to examine the pharmacokinetics and side effects of CDDP Thirteen patients received high-dose CDDP (120 mg/m2-160 mg/m2) in combination with sodium thiosulfate (STS), while 15 others received CDDP alone (80 mg/m2). Total Pt and non-protein-bound Pt (free Pt) concentrations in the pleural effusion and plasma were determined by flameless atomic absorption spectrometry. In one patient, Pt concentrations of intact CDDP and STS-bound CDDP were determined using high performance liquid chromatography and flameless atomic absorption spectrometry. Instillation of CDDP at 160 mg/m2 into the pleural cavity was achieved by concurrent use of STS in the large dose (STS 20 g/m2 1 hr later, totalling 625-fold molar ratio to CDDP). When CDDP was combined with STS, there was alleviation in hematological, renal and auditory toxicity but not in nausea, vomiting or anorexia. When CDDP was instillated into the pleural cavity at 150 mg/m2 (in combination with STS equivalent to 200-fold molar ratio to CDDP), a high Pt concentration of intact CDDP could be maintained in the pleural effusion over a prolonged period of time, recording 8.80 micrograms/ml even as late as 12 hr after instillation. On the other hand nearly all of the free Pt concentration for the first 2 hr was considered to be due to intact CDDP. Once systemically administered, STS quickly moved into the pleural effusion, binding with CDDP in the pleural cavity and thus probably reducing its anti-tumor effect. STS did not greatly affect the plasma concentration of total Pt when it was administered at a 100-fold molar ratio to CDDP, yielding only p poor effect. Our findings suggest that malignant pleural effusion could be effectively treated by the instillation of CDDP 80 mg/m2 into the pleural cavity.

Aged↗
PubMed1987

Characterization of a mammalian mutant with a camptothecin-resistant DNA topoisomerase I.

DNA topoisomerase I was purified to near homogeneity from a clonal line of human lymphoblastic leukemia cells, RPMI 8402, that is resistant to camptothecin, a cytotoxic alkaloid from Camptotheca acuminata, and compared with that of the parent wild-type cells. As assayed by relaxation of the supercoiled plasmid DNA and by formation of enzyme-linked DNA breaks, the purified enzyme from the resistant cells was shown to be greater than 125-fold as resistant to camptothecin as the wild-type enzyme, comparable to a cellular resistance index of about 300. Therefore, the cellular resistance appears to be due to the resistance of the enzyme. The amount of the immunoreactive enzyme protein in whole extract appeared to be reduced to less than half that of the wild-type enzyme. These results establish that DNA topoisomerase I is the cellular target of camptothecin and that DNA topoisomerase I is essential for the survival of mammalian cells.

Camptothecin↗
PubMed1987

Delayed effects of low-dose radiation on cellular immunity in atomic bomb survivors residing in the United States.

Several parameters of cellular immune function were assessed among persons who survived the 1945 atomic bombs in Hiroshima and Nagasaki but who now reside in the United States. The subjects in this study were exposed to various low doses (T65D) of radiation at the time of the bomb. More than half received an estimated 0 Gy (S0 group). Of those exposed to more radiation (S+ group), nearly 90% received less than 0.50 Gy (50 rad). Lymphocytes were isolated from the peripheral blood of these individuals and were assessed for the following parameters of cellular immunity: mitogenic response to phytohemagglutinin, mitogenic response to allogeneic lymphocytes, natural cell-mediated cytotoxicity (NCMC), and interferon production. In every case, the response of the S+ group was greater than that of the S0 group, although only the difference for NCMC was statistically significant. Results of studies presently being performed on A-bomb survivors residing in Hiroshima do not confirm this difference. Therefore, it is difficult to say whether the increase in natural cytotoxicity observed among the American and not the Japanese A-bomb survivors exposed to very low doses of radiation is a hormetic effect which was modulated by post-radiation environmental conditions or a result of selective migration.

Cytotoxicity, Immunologic↗
PubMed1987

[Serial measurements of serum carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) during chemotherapy of patients with inoperable lung cancer].

Serial measurements of serum CEA levels were analyzed in 226 patients with inoperable lung cancer (115 small cell carcinomas, 64 adenocarcinomas, 37 squamous cell carcinomas and 10 large cell carcinomas) during chemotherapy. Of all patients, 29.1% had pretreatment CEA levels greater than or equal to 5 ng/ml. In all of the patients with complete response, and 15 (68.2%) of 22 patients with partial response whose pretreatment CEA levels were 5 ng/ml or higher, CEA levels fell to below 5 ng/ml. All of 17 patients who showed a decrease greater than 50% in serum CEA levels during chemotherapy showed a shrinkage of more than 50% in the tumor burden. Serial serum CEA level measurements were useful as an indicator of response to chemotherapy in advanced lung cancer. Serial serum NSE levels were measured in 36 patients with small cell lung cancer. Pretreatment NSE levels were elevated to more than 10 ng/ml in 83.1% of all patients. A transient rise in serum NSE levels occurred in 22 out of 33 patients measured on the third day during initial chemotherapy. Serum NSE levels greater than or equal to 10 ng/ml declined to within the normal range in all patients responding to the chemotherapy. The survival in patients whose NSE levels (greater than or equal to 10 ng/ml) fell to within the normal range for more than four weeks was longer than that in other patients. Serial measurements of serum NSE levels were thus useful for monitoring the response to chemotherapy in cases of small cell lung cancer.

Adenocarcinoma↗
PubMed1987

[Studies on the appropriate administration of cisplatin based on pharmacokinetics and toxicity].

Ninety-six patients with non-small cell lung cancer were treated with cisplatin (80-150 mg/m2). The pharmacokinetics of cisplatin were studied in 27 of these patients. Cisplatin was administered intravenously for 30-120 min. Plasma concentrations of total platinum and ultrafilterable (non-protein-bound) platinum were monitored by flameless atomic absorption spectrophotometry. Maximum total platinum levels in plasma were attained at the end of infusion, and thereafter decayed in a biphasic fashion, with an initial phase half-life (t1/2 alpha) of 10.2 to 14.6 min and a secondary phase half-life (t1/2 beta) of 41.7 to 81.3 h. The half-life was prolonged as the dosage was increased. Non-protein-bound platinum was rapidly cleared to below the measurable level within 4 hours at 80 mg/m2 and 120 mg/m2 of cisplatin, but declined in a biphasic manner, with t1/2 alpha of 31.2 min and t1/2 beta of 20.1 h at 150 mg/m2 of cisplatin. Toxicities were increased according to dosage, and decreased with a 50 mg/m2 X 3 days regime. Nephrotoxicity and ototoxicity were the dose-limiting factors in the single-dose escalation scheme used. In conclusion, the optimal dosage of cisplatin appeared to be 120 mg/m2 considering its toxicity.

Adult↗
PubMed1986

Alternating non-cross resistant chemotherapy for small cell lung cancer.

After stratification for the extent of disease, previously untreated patients with small cell lung cancer randomized to receive therapy with the four-drug combination of cyclophosphamide, oncovin, nimustine hydrochloride (ACNU), and procarbazine (CONP) every four weeks (continuous regimen) or to receive CONP alternating with the three-drug combination of etoposide (VP-16), adriamycin and cisplatin (VAD) at four-week intervals (alternating regimen). Sixty-nine patients were entered in the study. Of 34 evaluable patients receiving the continuous regimen, six (17.6%) achieved complete response (CR) and 16 (47.1%) achieved partial response (PR). Of 31 evaluable patients receiving the alternating regimen, 10 (32.3%) achieved CR, and 16 (51.6%) achieved PR. There was a tendency in favor of the alternating regimen in CR and over-all response rates (0.05 less than p less than 0.1). There were no significant differences between the regimens in response duration or survival. The projected median survival times were 9.2 months and 9.4 months for the continuous and alternating regimens, respectively. One patient receiving the continuous regimen and three receiving the alternating regimen have been living for more than two years. The major toxicity was myelosuppression in both regimens. One patient died of hemorrhage due to thrombocytopenia during induction with CONP, and one patient died of cisplatin-induced renal failure. We conclude that alternating non-cross resistant chemotherapy leads to improved CR and response rates, but does not improve survival.

Adult↗
PubMed1986

[Clinical evaluation of imipenem/cilastatin sodium in children].

Nine pediatric patients with moderate or severe bacterial infections (3 septicemia or bacteremia, 2 pyelitis, 2 tonsillitis, 1 pneumonia and 1 pyothorax) in hospital were treated with MK-0787/MK-0791. The drug was administered intravenously by 30 or 60 minutes drip infusion in 3 or 4 divided doses totalling 24 mg/24 mg-70.2 mg/70.2 mg per kg/day. Clinical effectiveness were excellent in 4 cases, good in 2 cases, poor in 2 cases and not evaluated in 1 case. The overall efficacy rate was 75%. A slight decrease of WBC was observed in 1 case. It was concluded that MK-0787/MK-0791 was a useful antibiotic for the treatment of infections in pediatric practices. Pharmacokinetics of intravenously administered MK-0787/MK-0791 was studied in 2 other cases. The MK-0787/MK-0791 was administered intravenously by 30 or 60 minutes drip infusion to 2 cases at a dose of 10 mg/10 mg/kg. The mean half-life (T1/2) of MK-0787 was 1.03 hours and MK-0791, 0.69 hour. The mean urinary recovery rate of MK-0787 within 6.5-7 hours after administration was 62.5% and MK-0791, 76.7%.

Adolescent↗
PubMed1986

[A randomized control study of the antiemetic efficacy of betamethasone versus methylprednisolone].

A randomized control study of the antiemetic activity of betamethasone (B) vs. methylprednisolone (MP) was carried out. Fifty-six patients receiving CDDP (60 mg/m2-80 mg/m2) were entered. B (8 mg/body on day 1, 4 mg/body on days 2 and 3) was administered intravenously in 18 patients, and MP (1,000 mg/body on day 1, 500 mg/body on days 2 and 3) was administered intravenously in 19 patients. Severe vomiting occurred in 5 of the 19 (26.3%) with MP, 10 of the 18 (55.6%) with B, and 11 of 19 (57.9%) controls. Severe nausea occurred in 3 of the 19 (15.8%) with MP, 6 of the 18 (33.3%) with B, and 5 of the 19 (26.3%) controls. Methylprednisolone was thus considered effective (P less than 0.05) for CDDP-induced emesis.

Betamethasone↗
PubMed1985

[Effectiveness of cefotaxime in pediatric infectious diseases].

Cefotaxime (CTX) was administered to 117 pediatric patients. Although 26 of these patients were excluded from the clinical evaluation of the study because other antimicrobial agents were given concomitantly with CTX or because no infectious diseases were proved, these cases were evaluated for adverse effects of the drug. The remaining 91 cases were evaluated for clinical effect; pneumonia in 56 cases, septicemia in 5, suspected septicemia in 5, meningitis (aseptic cases included) in 3, urinary tract infection in 5 and other diseases in 17. No pathogenic organisms were identified in any of the pneumonia cases, even either by bacterial culture or other laboratory test methods. Pathogens of septicemia were E. coli in 3 cases, K. pneumoniae in 1 and E. agglomerans in 1. Those of urinary tract infections were E. coli in 3 cases, a mixed infection of S. aureus and an unidentified species of Gram-negative rods in 1, and unknown in 1. Clinical effectiveness rates of CTX were 78.6% in pneumonia and 100% in septicemia, suspected septicemia and urinary tract infections. One patient with purulent meningitis caused by H. influenzae was also treated with CTX successfully. Adverse reactions and abnormal laboratory findings were observed in 12 cases (12/117 = 10.3%); rash in 2 cases, vomiting in 1, abdominal pain in 1, diarrhea in 5, granulocytopenia and thrombocytopenia in 1, eosinophilia in 3 and elevation of liver enzymes (GOT and LDH) in 1.

Bacterial Infections↗
PubMed1985

[Response and pharmacokinetics of cisplatin instilled into the pleural cavity].

The response and pharmacokinetics of cisplatin instilled into the pleural cavity were studied in 11 patients with malignant pleural effusion; 10 patients had primary lung cancer and one had breast cancer. All of them were adenocarcinoma histologically. In five of the 11 patients effusion disappeared and its cytology became negative for malignancy after four weeks. In the other six patients effusion was reduced and its cytology became negative for malignancy after four weeks. Toxicity was almost similar to that in systemic administration of cisplatin but a few patients had chest pain and fever possibly due to local irritation. The pharmacokinetics showed that a high concentration of cisplatin (free-form, 48.9 micrograms/ml) was maintained over a long period (free from (t 1/2) beta = 33.6 hours) in the pleural cavity. This was regarded as the reason for the high response to this therapy. The intrapleural instillation of cisplatin into the pleural cavity therefore seems to be an effective modality for malignant pleural effusion.

Aged↗