Biomedical subjects

Y Ohe

Publications and source records attributed to Y Ohe.

At least 145 records · Page 8Linked to original sources

PubMed1991

The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor.

The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy. The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60%. In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses. It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%). The administration of antibiotics was required for about 7 days to patients with febrile episodes. Sepsis was experienced in five courses, in which the neutrophils were all zero. All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy.

Adult↗

PubMed1991

[The relation between myelotoxicity and performance status or aging in chemotherapy of non-small cell lung cancer].

One hundred eighty six patients of non-small cell lung cancer treated with cisplatin-based chemotherapy were analyzed. Significant incidence of anemia was observed in PS 2-3 patients as compared to PS 0-1 cases. Incidence of thrombocytopenia was significant in cases 70 or more years old as compared those less than 50 years old. No correlation was detected between myelotoxicity and aging.

Aged↗

PubMed1991

[Feasibility study of quality of life (QOL) instrument in patients with advanced lung cancer].

We have studied the feasibility of the QOL measurement for the group of patients with advanced lung cancer using the QOL questionnaires modified from FLIC (Functional Living Index Cancer). The 16-items instrument showed that the Cronbach's alpha of all categories were over 0.6. as the quality of reliability. Using the principal component method of multivariate analysis, four major factors were identified as a part of the construct validity. We concluded that the QOL of patients with advanced lung cancer under the clinical research setting can be evaluated using this questionnaires even in Japan which has different cultural background from the Western Countries.

Adult↗

PubMed1990

Effect of aspartame on N-methyl-D-aspartate-sensitive L-[3H]glutamate binding sites in rat brain synaptic membranes.

Aspartame (L-aspartyl-L-phenylalanine methyl ester), an artificial low-calorie sweetener, was shown to dose-dependently inhibit L-[3H]glutamate binding to its N-methyl-D-aspartate-specific receptors. L-Aspartic acid, a major endogenous metabolite of aspartame, inhibited the binding more stronger than aspartame, while the other metabolites, L-phenylalanine and methanol, had no effect at the same concentration. Aspartame caused a significant change in the affinities of L-[3H]glutamate binding without altering the Vmax values of the binding, suggesting the inhibition is competitive. These in vitro findings suggested that aspartame may act directly on the N-methyl-D-aspartate-sensitive glutamate recognition sites in the brain synaptic membranes.

Animals↗

PubMed1990

Decreased accumulation as a mechanism of resistance to cis-diamminedichloroplatinum(II) in human non-small cell lung cancer cell lines: relation to DNA damage and repair.

The mechanism of resistance to cis-diamminedichloroplatinum(II) (CDDP) is still controversial, although several kinds of processes have been proposed. For elucidation of the mechanism of CDDP resistance in CDDP-resistant human non-small cell lung cancer cells (PC-9/0.5, 7.1-fold resistant), we examined the formation of DNA interstrand cross-links (ICL), one kind of DNA damage induced by CDDP, its repair, and intracellular accumulation of CDDP. We measured the frequency of CDDP-induced ICL by means of the alkaline elution technique and the amount of intracellular platinum for intracellular accumulation of CDDP by means of atomic absorption spectrophotometry in PC-9 (parental cell) and PC-9/0.5 cells. Formation of ICL in PC-9 cells exposed to 5 micrograms of CDDP per ml for 6 h was 5.85 times that in PC-9/0.5 cells. On the other hand, the ability to repair CDDP-induced ICL was identical in both cell lines. Intracellular accumulation studies revealed that PC-9 retained 5.07 times as much platinum as that in PC-9/0.5 after 3-h exposure to CDDP. It was conjectured that the decrease in the intracellular accumulation of CDDP might be the main cause of CDDP resistance in PC-9 cells, since the decreased accumulation was paralleled by the decreased level of ICL.

Carcinoma, Non-Small-Cell Lung↗

PubMed1990

Human G-CSF produced by adherent cells in the presence of human recombinant GM-CSF.

Adherent cells (AdCs) in blood from normal volunteers produced granulocyte-macrophage (GM) colony-stimulating activity (CSA) in the presence of 10 ng/ml of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in vitro. GM-CSA produced by adherent cells in the presence of GM-CSF reached a plateau level on day 6. Colonies stimulated by adherent cell-conditioned medium (AdC-CM-GM-CSF), which had been harvested after 6 days of incubation of AdCs with rhGM-CSF, were granulocyte predominant. When phagocyte-depleted marrow mononuclear cells (PD-M-MNCs) were cultured with AdC-CM-GM-CSF and anti-rabbit serum against rhGM-CSF, 99% of the colonies on day 7 were exclusively composed of neutrophils. When 2 X 10(4) PD-M-MNCs were cultured in a medium containing AdC-CM-GM-CSF, AdC-CM-GM-CSF + anti-GM-CSF, AdC-CM-GM-CSF + anti-G-CSF, or AdC-CM-GM-CSF + both of the anti-bodies, the PD-M-MNCs formed (mean +/- SD) 100 +/- 2.0%, 64.3 +/- 2.5%, 38.6 +/- 0.4%, and 6.0 +/- 0.4% GM colonies, respectively. Furthermore, northern blot analysis revealed that AdCs incubated with 10 ng/ml of rhGM-CSF for 6 h expressed much more mRNA of G-CSF than those without the CSF. These data indicated that AdCs in blood produce G-CSF in the presence of GM-CSF.

Blotting, Northern↗

PubMed1990

Phase II study of (glycolate-O,O') diammineplatinum(II), a novel platinum complex, in the treatment of non-small-cell lung cancer.

A total of 68 patients with non-small-cell lung cancer who either had not previously been treated (38) or had undergone prior therapy (30) were treated in a phase II study of (glycolate-O,O') diammineplatinum(II) (NSC 375 101D; 254-S), a new platinum complex. The drug was given as a single intravenous infusion at a dose of 100 mg/m2 every 4 weeks. All 68 patients could be evaluated for response and 62, for toxicity. Objective responses were seen in 10 of 68 cases (14.7%; 95% confidence interval, 7.3%-25.4%), and the median duration of response was 15 weeks (range, 8-23 weeks). The response rates were similar for previously untreated and treated patients (13% and 17%, respectively), including three previously treated with cisplatin. Myelosuppression was the dose-limiting toxicity. Thrombocytopenia (less than 100,000 platelets/mm3) and leukocytopenia (less than 3,000 WBC/mm3) were observed in 22 (35%) and 18 (29%) patients, respectively. Mild to moderate nausea and vomiting occurred in 45 cases (73%). No significant renal or neurotoxicity was observed. We conclude that as a single agent, 254-S is well tolerated but appears to have marginal activity against non-small-cell lung cancer.

Adenocarcinoma↗

PubMed1990

Monoclonal antibody to pseudouridine used to develop a radioimmunoassay.

Pseudouridine, a component of tRNA, was modified to yield the derivatives: succinyl, palmitoyl pseudouridine, and protein conjugates. These derivatives were used in preparation of monoclonal antibodies specifically directed to pseudouridine. MAbs from three hybridomas (OAL 881, 812 and 814) were established and shown to be directed to pseudouridine, uridine and uracil. OAL 881 was equally reactive with the three substrates, OAL 812 showed the same reactivity for pseudouridine and uracil, while OAL 814 showed a reactivity mainly for pseudouridine. MAb OAL 814 was used in a radioimmunoassay (RIA) system unique for pseudouridine. A good dose-response curve was observed in the range between 31.3 and 2000 nmol/ml. Intra- and inter-assay CV values were below 4.1% and 7.4% respectively, and good results were obtained from recovery of added material and dilution tests. The ratio of pseudouridine/creatinin in urine was significantly higher in patients with cancer than in normal subjects.

Antibodies, Monoclonal↗

PubMed1990

Subcutaneous administration of recombinant human granulocyte colony-stimulating factor (KRN8601) in intensive chemotherapy for patients with advanced lung cancer.

The efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rh G-CSF, KRN8601) given subcutaneously was evaluated in patients with advanced lung cancer undergoing intensive chemotherapy. Twenty-nine and 30 patients with or without prior therapy were enrolled in this study. At dose levels of 50, 90 and 130 micrograms/m2 of rh G-CSF for 14 consecutive days after chemotherapy, the mean neutrophil nadir counts, the mean neutrophil nadir ratios and the duration of neutropenia (days of less than 1000/mm3) were significantly improved. No significant differences were seen in frequency and duration of febrile episodes (greater than 38 degrees C). When rh G-CSF is given subcutaneously, the dose required for an equal effect in alleviating neutropenia is 50% of that required when it is given intravenously. The monocyte counts in the peripheral blood were also significantly increased after chemotherapy cycles with rh G-CSF. The cumulative plasma concentration of rh G-CSF showed a decrement after 7-9 days despite maintenance of the same dose of rh G-CSF for the entire 14 days. In conclusion, 50-130 micrograms/m2 of sc rh G-CSF increased the neutrophil nadir count and shortened the duration of neutropenia in patients undergoing intensive chemotherapy for lung cancer without intolerable side effects.

Adult↗

PubMed1990

Prediction from creatinine clearance of thrombocytopenia and recommended dose in patients receiving (glycolato-O,O')-diammine platinum (II) (NSC 375101D).

Thrombocytopenia is the most serious dose-limiting toxicity of (glycolato-O,O')-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues. A total of 38 patients treated with 100 mg of 254-S per m2 in a clinical phase II study were retrospectively analyzed to determine the factors influencing thrombocytopenia. Performance status, sex, age and prior chemotherapy did not affect either the percent reduction of platelets or the nadir platelet count. However, creatinine clearance (Ccr.: ml/min) was found to be a predictive variable for thrombocytopenia. There was a significant relationship between nadir platelet count and Ccr. (R2 = 0.637) or relative dose [RD = (dose of 254-S: mg/m2)/Ccr.] (R2 = 0.707). From these observations, the following equations for predicting nadir platelet count associated with administration of 254-S were proposed. [Nadir platelet count] = -64,264.7 + 2,783.4 x [Ccr.] (A) log [Nadir platelet count] = -1.6743 log [RD] + 5.32 = -1.6743 log [Dose/Ccr.] + 5.32 (B) If we administer 100 mg of 254-S per m2 to a patient with Ccr. of less than 40.3 ml/min, thrombocytopenia of grade 3 or more according to the Eastern Cooperative Oncology Group (ECOG) criteria (less than 50,000/mm3) can be predicted from equation (A). In these patients, dose modification using equation (B) is recommended.

Adult↗

PubMed1990

Recognition of the polypeptide core of mucin by monoclonal antibody MUSE11 against an adenocarcinoma-associated antigen.

Monoclonal antibody (MAb) MUSE11 detects an adenocarcinoma-associated antigen and is useful for the serodiagnosis of pancreas cancer. We established a sandwich enzyme immunoassay using MAb MUSE11 and MAb DF3 against a breast cancer-associated mucin core protein as a catcher and a tracer, respectively. With this assay system, the binding of the tracer MAb DF3 to an antigen in the human kidney tissue lysate was clearly inhibited by MAb MUSE11. In addition, MAb MUSE11 showed a significant binding activity to the synthetic peptide corresponding to the tandem repeat of a human epithelial mucin core protein. These data suggest that MAb MUSE11 could detect the polypeptide core of a mucin, and may be of use for studying mucin as a gene product.

Adenocarcinoma↗

PubMed1990

c-Ha-ras down regulates the alpha-fetoprotein gene but not the albumin gene in human hepatoma cells.

We studied the effects of transfection of the normal c-Ha-ras gene, rasGly-12, and its oncogenic mutant, rasVal-12, on expression of the alpha-fetoprotein (AFP) and albumin genes in a human hepatoma cell line, HuH-7. The mutant and, to a lesser extent, the normal ras gene caused reduction of the AFP mRNA but not the albumin mRNA level in transfected HuH-7 cells. Cotransfection experiments with a rasVal-12 expression plasmid and a chloramphenicol acetyltransferase reporter gene fused to AFP regulatory sequences showed that rasVal-12 suppressed the activity of enhancer and promoter regions containing A + T-rich sequences (AT motif). In contrast, rasVal-12 did not affect the promoter activity of the albumin and human hepatitis B virus pre-S1 genes even though these promoters contain homologous A + T-rich elements. ras transfection appeared to induce phosphorylation of nuclear proteins that interact with the AFP AT motif, since gel mobility analysis revealed the formation of slow-moving complexes which was reversed by phosphatase treatment. However, similar changes in complex formation were observed with the albumin and hepatitis B surface antigen pre-S1 promoters. Therefore, this effect alone cannot explain the specific down regulation of the AFP promoter and enhancer activity. ras-mediated suppression of the AFP gene may reflect the process of developmental gene regulation in which AFP gene transcription is controlled by a G-protein-linked signal transduction cascade triggered by external growth stimuli.

Antibodies, Monoclonal↗

PubMed1990

Lack of correlation between interferon levels induced by polyribonucleotides and their antimetastatic effect.

The inhibitory effect of poly(A)poly(U) on the pulmonary metastasis of B16-F10 melanoma was examined in comparison with that of poly(I,C)-L,C and poly(I)poly(C). The correlation between interferon (IFN) level and antimetastatic effect was also investigated. Intraperitoneal injection of poly(A)poly(U) (50 mg/kg) into C57BL/6 mice 24 h before intravenous inoculation of B16-F10 melanoma (1 X 10(5] caused a significant decrease (p less than 0.01) in the number of pulmonary nodules 14 days after tumor challenge. But poly(I,C)-L,C (1 or 0.2 mg/kg) and poly(I)poly(C) (5 mg/kg or 1 mg/kg) did not. From the kinetic study of IFN levels induced by polyribonucleotides, poly(I,C)-L,C showed the most potent IFN-inducing activity, followed by poly(I)poly(C) and poly(A)poly(U), in this order. Plasma IFN reached a peak at 6 h and still continued to be detected at 24 h after intraperitoneal injection of the polyribonucleotides. Against B16-F10 melanoma, the cytotoxicity of spleen cells stimulated by poly(A)poly(U) (50 mg/kg) was significantly (p less than 0.05) higher than that of spleen cells stimulated by poly(I)poly(C) (5 mg/kg) both at 12 and 24 h after intraperitoneal injection of those agents. The above results that there is no correlation between the IFN levels induced by polyribonucleotides and their antimetastatic effect. More extensive study of poly(A)poly(U) might give more fruitful results, which will give valuable information for future clinical trials of this lowly toxic promising agent.

Animals↗

PubMed1990

[Study on visible-light curing soft resins consisting of fluoropolymers. 2. Effect of fluoroalkyl alpha-fluoroacrylate monomers].

New experimental visible-light cured soft resins were prepared by combining a vinylidene fluoride/hexafluoropropylene copolymer (2-6 F), or a vinylidene fluoride/tetrafluoroethylene/hexafluoropropylene copolymer (2-4-6 F) with 2,2,3,3-tetrafluoropropyl alpha-fluoroacrylate (4 FFA), 2,2,3,3,3-pentafluoropropyl alpha-fluoroacrylate (5 FFA), 2,2,3,3,4,4,5,5-octafluoropentyl alpha-fluoroacrylate (8 FFA), or 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptyl alpha-fluoracrylate (12 FFA). Some properties of the resins prepared were measured to determine whether they would be candidate materials for the soft denture liner. Water contact angles increased with the increase in the number of fluorine atoms contained in the monomers: 85-90 degrees in 4 FFA, 90-93 degrees in 8 FFA, and 92-93 degrees in 12 FFA. Softer resins were obtained with 2-4-6 F, especially by the combination with 8 FFA giving the softest resin with a hardness of 43-46 (JIS A). Water sorption after 10 weeks was considerably low: 0.4-2%: 0.4-0.9% in 4 FFA/2-6 F and about 2% in 8 FFA/2-4-6 F. Solubility was 0.2-0.4% in the resins with 4 FFA and 1.0-1.4% with 8 FFA or 12 FFA. Amount of residual monomer was low, and the maximum was 0.4% in the resin with 12 FFA. Thus hardness and water sorption of the resins prepared were superior to those of the commercial soft materials.

Denture Liners↗

PubMed1990

[Study on visible-light curing soft resins consisting of fluoropolymers. (3) Application of low molecular weight fluoropolymer].

New experimental visible-light cured soft resins were prepared by combining a low molecular weight vinylidene fluoride/hexafluoropropylene copolymer (2-6 FL), or vinylidene fluoride/tetrafluoroethylene/hexafluoropropylene copolymer (2-4-6 FL) with 2,2,3,3-tetrafluoropropyl alpha-fluoroacrylate (4 FFA), or 2,2,3,3,4,4,5,5-octafluoropentyl alpha-fluoroacrylate (8 FFA). Some properties of the resins prepared were measured to determine whether they would be candidate material for a soft denture liner. Water contact angle was 90-92 degrees with 4 FFA, and 90-94 degrees with 8 FFA. The resins combined with 2-4-6 FL were sufficiently soft: 42-46 (JIS A hardness) in 4 FFA, and 33-39 in 8 FFA. Generally the hardness decreased by 5-10 with the use of a low molecular weight of fluoropolymer. Water sorption after 10 weeks was 0.8-1.2% in 2-6 FL/4 FFA, 1.3-1.7% in 2-6 FL/8 FFA, about 1% in 2-4-6 FL/4 FFA, and about 2% in 2-4-6 FL and 8 FFA. Solubility was 0.4-0.5% in 2-6 FL/4 FFA, 0.3-0.4% in 2-4-6 FL/4 FFA, 1.5-1.9% in 2-6 FL/8 FFA, and 1.1-1.5% in 2-4-6 FL/8 FFA. Amount of residual monomer was very low, and the maximum was 0.1%. Tensile strength of the resins was reduced to 40-70% of that of the similar resins obtained in the previous study. Thus softer resins could be prepared by using lower molecular weight fluoropolymers.

Denture Liners↗

PubMed1990

[Study on visible-light curing soft resins consisting of fluoropolymers. 1. Effect of fluoroalkyl methacrylate monomers].

New experimental visible-light cured soft resins were prepared by combining 4 kinds of fluoroalkyl methacrylate monomers with a vinylidene fluoride/hexafluoropropylene copolymer, or a vinylidene fluoride/tettrafluroethylene/hexafluoropropylene copolymer. Some properties of the resins prepared were examined to determine their value as a soft denture liner material. Water contact angles were more than 90 degrees in all cases and increased with the increase in the number of fluorine atoms in the fluoroalkyl groups. Hardness (JIS A) was less than 50 for the softes resin. Water sorption after 10 weeks was 3-4.5 wt %. Solubility 0.1-0.3 wt% and amount of residual monomer 0.2 wt% were very low. The properties of these new experimental resins were comparable or superior to the commercial soft materials available.

Acrylic Resins↗

PubMed1990

Negative phase II study of 5-fluorouracil with high-dose leucovorin in non-small cell lung cancer.

Fourteen patients with inoperable or recurrent non-small cell lung cancer (NSCLC) were treated with 5-fluorouracil (5-FU) plus high-dose leucovorin (LV). The administration schedule was 2 h infusion of LV at a dose of 500 mg/m2 and 30 min infusion of 5-FU at a dose of 600 mg/m2 given 1 h after the start of the LV infusion. This regimen was followed weekly, six times. No objective (complete or partial) response was seen in any of the patients. Ten patients showed no change and there were four with progressive disease. One patient experienced grade 3 leukopenia after two courses of treatment. Another experienced grade 2 leukopenia. One patient experienced grade 2 vomiting and six, skin pigmentation. Other myelosuppressive effects and non-hematologic toxicities, including diarrhea and mucositis, were mild. It was concluded that the schedule of 5-FU with high-dose LV therapy employed could not be expected to produce a response rate greater than or equal to 20% against NSCLC. 5-FU plus high-dose LV therapy was, therefore, considered to be ineffective against NSCLC with the schedule of administration followed.

Adult↗

PubMed1990

[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↗