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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 487 records · Page 27Linked to original sources
PubMed1989

[Preclinical and clinical evaluation of toxicity and antitumor activity of cisplatin analogues].

Since the introduction of Cisplatin (CDDP) into clinical practice in 1972, CDDP has assumed an important role in the treatment of various tumors. But its renal toxicity has been proved to be a dose limiting factor. Thus the total number of courses which may be given is limited. For this reason, efforts have been made to develop CDDP analogues with reduced toxicities, especially renal toxicity, and more enhanced antitumor activity, and they are now reaching the clinical testing phase. Among them Carboplatin (CBDCA), 254-S, DWA 2114R and NK 121 have been well studied. These analogues were noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical analysis. As for cytotoxicity, their inhibitory effects on tumor growth in murine experimental system were similar or more to that of CDDP. Due to these data clinical trials have been carried out. Phase I studies have shown that these analogues are relatively free of renal toxicity as evaluated in preclinical studies and that their dose limiting factor is myelosuppression. Estimation of cross resistance to CDDP and antitumor spectrum have been studied at phase II trials which are ongoing. Interim reports have not shown that enhanced tumor activity or enlarged antitumor spectrum are expected.

Animals↗
PubMed1989

[Randomized multicenter trial of sequential methotrexate and 5-fluorouracil versus 5-fluorouracil alone in advanced gastric cancer].

In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.

Adult↗
PubMed1989

[Effects of ulinastatin on operative stress in major surgery].

Effects of ulinastatin on operative stress in upper abdominal surgery were investigated. The operation caused damages to the body functions such as enhancement of protein catabolism, hepatic dysfunction and pancreatic dysfunction, followed by elevation of GOT, GPT, LDH and serum amylase. The operative stress also decreased the total lymphocyte and T cell counts in the peripheral blood, and attenuated the lymphocyte transformation induced by phytohaemagglutinin (PHA) and concanavalin A (Con A). Ulinastatin 7500 u.kg-1 failed to decrease the elevation of plasma enzyme levels and the depression of immune function. But ulinastatin had no immunosuppressive effect like glucocorticoid and attenuated the decrease in plasma levels of protein and albumin. The results suggest that ulinastatin has an effect in modulating the enhancement of protein catabolism by operative stress.

Adult↗
PubMed1989

[The inhibitory effect of elastase on calcium increase in brain and spinal cord of rabbits with atherosclerosis induced by cholesterol-rich diet].

The aim of present experiment was to investigate the decalcified effects of exogenous elastase in liver, kidney and central nervous system (CNS) of rabbits with atherosclerosis experimentally induced by the modified procedure of Kritchevsky et al. Twenty five male rabbits, weighing approximately 2 kg, were divided into 6 groups. Animals were fed for 3 months with standard diet (group A), standard diet containing 1.5% cholesterol (group B) and 1.5% cholesterol-rich diet plus intraperitoneal (ip) daily administration of elastase 450 EL. U/kg (group C). Another groups were kept for 6 months with standard diet (group D), standard diet containing 0.67% cholesterol (group E) and 0.67% cholesterol-rich diet plus same dose of elastase (group F). The rabbits treated with cholesterol-rich diet were confirmed to be induced atherosclerosis biochemically as well as histologically. All groups were maintained under these conditions for experimental periods and allowed tap water. After 3 and 6 months, blood collected by cardiocentesis using ether anesthesia and then sacrificed to remove CNS and internal organs. Blood had stood for 1 hour at room temperature. Serum was separated by centrifugation at 3,000 rpm for 10 min to determine total cholesterol, triglyceride, phospholipids, HDL-cholesterol, and so on. Calcium contents in the cerebral frontal lobe, cerebellum, pons, spinal cord, liver and kidney were measured by neutron activation analysis method. In this experiment the amelioration of atherosclerosis by ip administration of elastase was ascertained. In rabbits given cholesterol-rich diet, calcium content in CNS tissues was higher than that of another tissues and paralleled to a rise of serum cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Antigenic phenotype and biological characteristics of two distinct sublines derived from a small cell lung carcinoma cell line.

Two sublines, SCLC-MOA1 (MOA1) and SCLC-MOA2 (MOA2), were established from the SCLC-MO cell line, which was originally derived from an oat cell type of small cell lung carcinoma (SCLC). SCLC-MO showed typical culture morphology of SCLC, growing as tightly packed floating aggregates, while both MOA1 and MOA2 grew as a monolayer. MOA2 showed markedly shorter culture doubling time and higher colony forming efficiency than SCLC-MO and MOA1. When transplanted into nude mice, both SCLC-MO and MOA1 showed intermediate cell type histology, while MOA2 showed a picture of large cell carcinoma as non-SCLC. As for biomarkers, SCLC-MO showed a transitional state between the classic and the variant types, while MOA1 was the variant type. In contrast, MOA2 lost the biomarker characteristic of SCLC, showing rather non-SCLC type. SCLC-MO expressed NE-150 neuroendocrine antigen, but lacked PE-35 panepithelial antigen which is generally present on SCLC. It lacked also OE-130 epithelial antigen which is generally absent from SCLC. Thus, the phenotype was NE-150+/PE-35-/OE-130-, which was different from the major phenotype of SCLC, NE-150+/PE-35+/OE-130-. MOA1 was weakly positive for PE-35, showing NE-150+/PE-35 +/- /OE-130-, while MOA2 was positive for OE-130, but lost NE-150, i.e., NE-150-/PE-35+/OE-130+, showing a non-SCLC phenotype. Thus, a good concordance was observed between the antigenic phenotype and the biological characteristics of these SCLC lines. The results altogether suggested that a part of large cell carcinoma in the tumor of the patient may be derived from SCLC. Karyotype analysis showed that there were several marker chromosomes including deletion of chromosome 3p shared by these three cell lines, supporting the belief that MOA1 and MOA2 originated from SCLC-MO. Southern blot analysis showed the amplification of the L-myc related gene, probably rearranged L-myc, in the primary SCLC tumor as well as in SCLC-MO and MOA1. Northern blot analysis showed the 2.2-kilobase transcripts hybridized with a L-myc probe were observed in SCLC-MO and MOA1, but not in MOA2. In contrast, the c-myc transcript was detected only in MOA2. The activity of the myc gene family may contribute to certain biological characteristics of SCLC.

Animals↗
PubMed1988

Effect of recombinant human erythropoietin on the anemia of chronic renal failure.

Phase I and Phase II studies of recombinant human erythropoietin (rhEpo) were conducted in normal volunteers and in anemic patients with chronic renal failure on maintenance hemodialysis. Three hundred U/person of rhEpo was administered intravenously to healthy normal volunteers in the Phase I study, resulting in no subjective or objective changes. In the Phase II study, 66 patients with chronic renal failure on maintenance hemodialysis with less than 20% hematocrit values were treated with rhEpo in doses of 50 U/kg to 200 U/kg two or three times a week. Hematocrit values increased significantly during the 12 weeks, and the patients' conditions improved. Patients previously requiring blood transfusions became transfusion-independent during our study. There were no obvious side effects, thus indicating the safety and efficacy of rhEpo in the anemia of chronic renal failure.

Adult↗
PubMed1988

Antitumor effects of human lymphoblastoid interferon on advanced renal cell carcinoma.

Human lymphoblastoid interferon alpha was administered intramuscularly at a dose of 3 times 10(6) units per day to 25 patients with advanced renal cell carcinoma. Six patients (24.0 per cent) showed objective responses, including 2 with complete regression of tumors. Nine patients (37.5 per cent) showed disease stabilization, while the disease progressed in 9 others (37.5 per cent). All tumor responses (2 complete, 4 partial and 2 mixed responses) were seen in lung, skin and liver metastases in patients whose primary tumors had been removed. Mean time to response was 87 +/- 74 days (range 28 to 240 days) and mean duration of response was 6.5 +/- 6.4 months (range 1 to greater than 20 months). Human lymphoblastoid interferon alpha was a potential active antitumor agent in patients with advanced renal cell carcinoma.

Adult↗
PubMed1988

Therapeutic effects of oral sorbent in undialyzed uremia.

The present study was carried out to clarify whether an oral sorbent, AST-120 (Kureha Chemical Ind Co, Tokyo), may postpone the initiation of dialysis therapy. The subjects were randomly divided into two groups, control and AST. The AST group consisted of 27 undialyzed uremic patients. Serum creatine concentrations (SCr) were 4.3 to 8.1 mg/dL (5.8 +/- 1.1 mg/dL, mean +/- SD). The control group consisted of 24 uremic patients who were not given AST-120 during the conservative therapy period before the initiation of hemodialysis. AST-120 (3.2 to 7.2 g/d) was administered to the patients in the AST group for 2.4 to 30.1 months (13.2 +/- 7.4) before the initiation of hemodialysis. The slopes of reciprocal creatinine v time in the control group were -1,251 +/- 856 x 10(-5) dL/mg/month during the 6 to 12 months before the initiation of dialysis therapy, and in the AST group, they were -1,004 +/- 1,012 x 10(-5) dL/mg/month before administration, and -347 +/- 509 x 10(-5) dL/mg/month after administration of AST-120 (P less than 0.01). All 24 patients in the control group and 21 of 27 in the AST group were introduced to hemodialysis. SCr and serum urea nitrogen (SUN) at the initiation of hemodialysis did not differ between the control and AST group: 10.8 +/- 2.6 and 11.0 +/- 2.2 mg/dL and 92.7 +/- 22.2 and 94.1 +/- 21.6 mg/dL, respectively. The times to the 50% undialyzed level were 5.0 months in the control group, and 14.3 months in the AST group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1988

Stimulation of CAM Photosynthesis in Kalanchoë blossfeldiana by Transferring to Nitrogen-Deficient Conditions.

Kalanchoë blossfeldiana Poelln. cv Hikan plants were grown hydroponically with nutrient solution containing 5 millimolar NO(3) (-) (or NH(4) (+)) for 1 to 2 months and then transferred to nutrient solution containing no nitrogen. CO(2) uptake at night, nocturnal increase in titratable acidity, and activity of phosphoenolpyruvate carboxylase increased after the transfer. Thus, transfer to nitrogen-deficient conditions stimulates Crassulacean acid metabolism (CAM photosynthesis) in K. blossfeldiana. The importance of the plant nitrogen status (nitrogen-withdrawal status) for induction and stimulation of CAM photosynthesis is discussed.

Journal Article↗
PubMed1988

Effect of vasopressin on atrial natriuretic peptide release and renal function in dogs.

To assess the effect of arginine vasopressin (AVP) and 1-deamino-8-D-AVP (DDAVP) on atrial natriuretic peptide (ANP) release, renal water and electrolyte excretion, and cardiovascular function, AVP and DDAVP were administered at a dose of 10 ng.kg-1.min-1 iv for 30 min into anesthetized dogs receiving saline infusion at a rate of 1 ml.kg-1.min-1 (n = 12). In the control study, saline was infused alone (n = 6). AVP potentiated the plasma ANP response to an increase in plasma volume produced by saline infusion, increased mean arterial blood pressure (MAP), and exaggerated the natriuresis and kaliuresis. DDAVP did not potentiate the increase in plasma ANP but enhanced the natriuresis without any rise in MAP. Saline alone increased plasma ANP as well as sodium and potassium excretion with no changes in MAP. Inulin and p-aminohippuric acid clearances did not change during these studies. The results suggest that in hydrated dogs, AVP may increase ANP release and arterial blood pressure via the vasopressor activity of AVP and potentiate the natriuresis and kaliuresis, but the increased ANP may play little role in the natriuresis.

Animals↗
PubMed1988

Effects of hemorrhage on vasopressin and Met-Enk releases in blood and cerebrospinal fluid in dogs.

To assess whether hemorrhagic shock causes simultaneous release of methionine enkephalin-like substance (MELS) and arginine vasopressin (AVP) both in cerebrospinal fluid (CSF) and circulating blood, continuous bleeding at a rate of 1 ml.kg-1.min-1 was undertaken for 40 min in anesthetized dogs (n = 6) and mean arterial pressure and heart rate were measured. In a time control study (n = 6), hemorrhage was omitted. Plasma AVP and MELS concentrations did not differ from CSF AVP and MELS in the control period in either the hemorrhage or the control groups. In the hemorrhage group, plasma AVP increased at 20 min and thereafter during the hemorrhagic shock, and plasma MELS increased at 30 and 40 min. No changes in AVP and MELS in the CSF occurred during hemorrhage, except a rise in AVP at 40 min. In the control group, AVP and MELS in the plasma and CSF did not change during the study, except for a rise in CSF AVP at 40 min. MELS was found in three forms: its large-molecular-weight form, methionine enkephalin, and metabolite; but the large-molecular-weight form was only observed in the CSF. These results showed that hemorrhage increases circulating MELS and AVP, but not MELS and AVP in the CSF, except for a slight rise in AVP during severe hypotension.

Animals↗
PubMed1988

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗