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Biomedical subjects

S Irino

Publications and source records attributed to S Irino.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of the combination of acivicin and cis-diamminedichloroplatinum(II) on thymidylate synthesis of A549 lung cancer cells.

Compared to either compound alone, the combination of acivicin and cis-diamminedichloroplatinum(II) markedly enhanced the inhibition of the activities of thymidylate synthase and thymidine kinase, the enzymes involved in the final steps of the de novo and salvage pathways in pyrimidine metabolism in A549 lung cancer cells. The enhancement of enzymic inhibition paralleled that of cell growth inhibition. These results indicate that the combination of these drugs can inhibit the capacities of the pyrimidine pathways, resulting in an efficient reduction of DNA synthesis.

Antimetabolites↗
PubMed1989

Behavior of activities of thymidine metabolizing enzymes in human leukemia-lymphoma cells.

The behavior of the activities of thymidine metabolizing enzymes, dihydrothymine dehydrogenase (EC 1.3.1.2) and thymidine phosphorylase (EC 2.4.2.4) for thymidine degradation, thymidine kinase (EC 2.7.1.75) and thymidylate synthase (EC 2.1.1.45) for DNA synthesis, was elucidated in cytosolic extracts from normal human lymphocytes and 13 human leukemia-lymphoma cell lines. In the normal human lymphocytes, the activities of dihydrothymine dehydrogenase, thymidine phosphorylase, thymidine kinase, and thymidylate synthase were 6.88, 796, 0.30, and 0.29 nmol/h/mg protein, respectively. In leukemia-lymphoma cell lines, the activities of synthetic enzymes, thymidine kinase, and thymidylate synthase, increased two- to 79-fold and 22- to 407-fold of the normal lymphocyte values. In contrast, the activities of the catabolic enzymes, dihydrothymine dehydrogenase and thymidine phosphorylase, decreased to 5-42% and 3-38% of the values of normal lymphocytes. As a result, the ratio of activities of thymidine kinase/dihydrothymine dehydrogenase was elevated by 7- to 1170-fold, respectively. Thus, reciprocal behavior in the activities of the opposing enzymes in thymidine metabolism was observed in human leukemia-lymphoma cells. Polyclonal and monoclonal antibodies against dihydrothymine dehydrogenase were prepared and studies on immunotitration of this enzyme with these antibodies showed that the enzyme protein amount in Jurkat leukemic cells was 36% of that of normal lymphocytes. This was in good agreement with the decrease in the activity of the enzyme to 32%, indicating that the decrease in activity in the leukemic cells was due to the decline in the amount of enzyme protein. The metabolic imbalances in thymidine utilization appear to be characteristic of human leukemia-lymphoma cells. These observations should confer selective advantages to the lymphoproliferating cells and mark out the catabolic, as well as the synthetic, enzymes as important targets in the design of chemotherapy.

Dihydrouracil Dehydrogenase (NAD+)↗
PubMed1989

Reversal of enzymic phenotype of thymidine metabolism in induced differentiation of HL-60 cells.

Exposure of HL-60 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in specific alterations in thymidine (TdR) metabolism. Within 12 h after treatment with 1.62 nM TPA, the reciprocal alteration in the activities of opposing pathways of TdR metabolism observed during normal culture cell growth was reversed. In TPA-treated cells, the activities of anabolic enzymes, TdR kinase (TK; EC 2.7.1.21) and thymidylate synthase (TS; EC 2.1.1.45), declined to 15% and 18% of those of untreated cells by 96 h. Incorporation of 3H-TdR and 3H-deoxyuridine also decreased in parallel with decline in enzyme activities. In contrast, the activities of catabolic enzymes, TdR phosphorylase (TP; EC 2.4.2.4) and dihydrothymine dehydrogenase (DHT DH; EC 1.3.1.2), increased to 399% and 318% by 96 h. Immunotitration of DHT DH with monoclonal antibody showed that the rise in activity in the differentiated cells was due to the increase in protein amount. Kinetic properties of the enzymes were not altered during differentiation. These metabolic alterations were accompanied by an accumulation of the cells in G1 at the expense of S-phase. Present data indicate that induced differentiation of HL-60 cells results in a reversal of enzymic phenotype of TdR metabolism due to a consequence of decreased proliferation and suggest that emergence of TdR metabolic imbalance may serve as early markers of differentiation of these cells.

Cell Cycle↗
PubMed1989

[Adriamycin, cisplatin, and etoposide combination chemotherapy for small cell lung cancer].

Twenty-three patients with small cell lung cancer (11 with limited disease and 12 with extensive disease) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated at 3- or 4-week intervals for 3 to 5 treatment cycles. Among 22 evaluable patients, 5 showed complete response and 17 had a partial response (response rate 100%). The median response duration of 12 extensive disease patients was 21 months. There were 5 survivors for more than 2 years. Toxicity included moderate to severe hematologic toxicity, alopecia, nausea and vomiting. This combination chemotherapy appears to be optimal for the treatment of small cell lung cancer.

Aged↗
PubMed1989

[Peripheral neuropathy caused by cisplatin in patients with lung cancer].

The correlation between peripheral neuropathy and cisplatin (CDDP) was elucidated in 27 patients with primary and metastatic lung cancer, who were treated with Adriamycin 30 mg/m2 day 1, CDDP 80 mg/m2 day 1, and VP-16 70 mg/m2 day 1-5 every 4 weeks. The incidence of peripheral neuropathy was 33% (9 of 27 patients) and it increased to 60% in the patients who received over 320 mg/m2 of CDDP, demonstrating a positive correlation between the incidence of this toxicity and the total dose of CDDP. However, no significant relation was observed between the grade of neuropathy and CDDP. The neuropathy was manifested in the sensory system of the distal extremities and was developed into proximal portions. The peripheral neuropathy with grade 3 was irreversible, resulting in the dose-limiting factor of this regimen.

Adult↗
PubMed1989

[A case of pulmonary tuberculosis in a long-term survivor with small cell carcinoma of the lung].

A 64-year-old woman complained of chest pain, back pain and dry cough. Chest X-ray film showed marked left hilar enlargement and left pleural effusion. Biopsy of the bronchial mucosa and demonstrated small cell carcinoma of the lung. Treatment with cisplatin, adriamycin and etoposide led to regression of symptoms and chest X-ray findings within 3 months. She received maintenance chemotherapies at the outpatient clinic for 2 years after the first therapy. Thirty-months after the first admission, chest X-ray film showed multiple small nodules in the left upper lobe. Chest tomography and high-resolution computed tomography showed acinar or lobular nodules disseminated in the left upper lobe. Mycobacterium tuberculosis was obtained from bronchoalveolar lavage fluid of the left upper lobe. Pulmonary tuberculosis in a long-term survivor of small cell carcinoma of the lung is very rare.

Carcinoma, Small Cell↗
PubMed1989

Small intestinal perforation in Wegener's granulomatosis.

Wegener's granulomatosis is a disease characterized by necrotizing vasculitis and granulomatous inflammation. Gastrointestinal (GI) involvement is uncommon in this disorder. Only a few cases of perforation of GI tract have been reported, but vasculitis has not been demonstrated to be a cause of perforation in these cases. We report a case of Wegener's granulomatosis in which a single perforation in the terminal ileum was disclosed on laparotomy and active necrotizing vasculitis was found in the submucosal layer of the resected specimen.

Adult↗
PubMed1989

The role of Ca2+ and protein kinase C in the differentiation of HL-60 cells induced by 1 alpha,25(OH)2D3 and diltiazem.

The roles of calcium (Ca2+) and protein kinase C in the differentiation of HL-60 cells induced by 1 alpha,25(OH)2D3 (D3) and/or a Ca2+ antagonist, diltiazem(D-cis, L-cis), were elucidated. D3 and diltiazem (100 microM) inhibited cell proliferation, and diltiazem enhanced the D3-induced differentiation. There was no difference in potency between the two isomers of diltiazem in the enhancing activity, in spite of their different pharmacological activity. The concentration of free Ca2+ in the HL-60 cells following D3 and/or diltiazem treatment significantly increased. A protein kinase C inhibitor, H-7, inhibited the phenotypic differentiation induced by D3. These results suggest that Ca2+ and protein kinase C play an important role in the differentiation of HL-60 cells induced by D3 and diltiazem.

Calcitriol↗
PubMed1989

[Evaluation of the elastase: alpha 1-antitrypsin balance in patients with bacterial pneumonia using bronchoalveolar lavage].

This study was designed to evaluate the elastase: alpha 1-antitrypsin balance in patients with bacterial pneumonia. To accomplish this, bronchoalveolar lavages were performed in patients with pneumonia and normal non-smokers. Cell differentiation counts and elastase/alpha 1-antitrypsin balances in alveolar lavage fluid were examined. To quantify antielastase capacity, total immunoreactive alpha 1-antitrypsins and active alpha 1-antitrypsins were measured in alveolar lavage fluids. To quantify elastase burden, elastase: alpha 1-antitrypsin complexes and enzymatic elastase activities in alveolar lavage fluids were measured. Significantly increased proportions of neutrophils were recovered from the alveolar lavage fluids of patients with pneumonia compared to normal non-smokers. In alveolar lavage fluids of patients with pneumonia, alpha 1-antitrypsin was inactivated and enzymatic elastase activities were demonstrated. It was concluded that elastase: alpha 1-antitrypsin imbalance do occur in alveolar lavage fluids of patients with pneumonia.

Adult↗
PubMed1989

[High-resolution computed tomography for diagnosing pulmonary complications in patients with lung cancer].

The diagnostic value of high-resolution computed tomography has been assessed in 10 lung cancer patients with pulmonary infiltrates. This method was used to evaluate the radiographic appearance of the new pulmonary disease. The expectorated sputum of each patient was examined for a bacteriologic and cytologic diagnosis. In some patients, the flexible bronchofiberscopy that was accompanied by bronchoalveolar lavage was performed so as to establish the etiologic diagnosis. In conclusion, high-resolution computed tomography was found to be useful in diagnosing pulmonary complications in lung cancer patients.

Adult↗
PubMed1988

Physiological role of growth hormone (GH)-releasing factor and somatostatin in the dynamics of GH secretion in adult male rat.

To investigate the physiological role of GRF and somatostatin (SRIF) in GH secretion in adult male rats, we prepared in vitro models using the perifusion system of cultured rat anterior pituitary cells exposed to various combinations of human GRF-(1-44)NH2 (hGRF) and SRIF. We studied the following three models on GRF secretion: 1) pulsatile GRF secreted at 1-h intervals, 2) pulsatile GRF secreted at 3-h intervals, and 3) GRF continuously secreted. When 5-min pulses of 20 nM GRF were delivered at 1-h intervals, the responses to GRF gradually declined. The addition of continuous 20 nM SRIF with short pauses prevented this attenuated response and produced high peaks of GH at 3-h intervals. When 5-min pulses of 20 nM GRF were delivered at 3-h intervals, three high peaks of GH were observed regardless of the addition of SRIF. Pretreatment with GRF pulses enhanced the peaks of GH during SRIF pauses. When 20 nM GRF was continuously delivered, a rapid attenuated response to GRF was observed. Although the addition of continuous 20 nM SRIF with short pauses produced three small peaks of GH, these results were caused by the post-SRIF rebound release. These observations suggest that preexposure to prolonged SRIF can prevent an attenuated response to repeated GRF pulses, and that pretreatment with GRF pulses enhances post-SRIF rebound release.

Animals↗
PubMed1988

Alteration of p60c-src expression in human leukemia-lymphoma cells correlated with induced differentiation.

Expression of cellular src-gene product (p60c-src) in human leukemia-lymphoma cell lines was analysed by flow cytometry using a monoclonal antibody (McAb), H2B4 which recognizes p60c-src protein in human cells. In several human leukemia-lymphoma cell lines (K562, Namalva, HL60, U937), p60c-src expression was higher than in peripheral mononuclear cells from healthy volunteers. Some non-lymphoid leukemia cells can be induced to differentiate into monocyte-macrophages by 12-O-tetradecanoyl phorbol-13-acetate (TPA). K562 cells were also induced to differentiate not only morphologically but also functionally into monocyte-macrophages by TPA. Flow cytometric analyses using the McAb H2B4 revealed that the amount of p60c-src expression in K562 cells markedly decreased during TPA induced differentiation. The activity of protein kinase associated with p60c-src in K562 cells was determined employing IgG of immunized rabbit serum specific for p60c-src. The immunized rabbit IgG heavy chain phosphorylation by protein kinase also decreased after the induced differentiation. We detected p60c-src protein in acute lymphoid leukemia cells as well as acute non-lymphoid leukemia cells freshly isolated from patients. The amount of p60c-src protein decreased in some acute non-lymphoid leukemia cases, but it increased in others after TPA induced differentiation. No correlation was observed between FAB classification of acute leukemias and the amount of endogenous p60c-src expression.

Cell Differentiation↗
PubMed1988

[Treatment of myelodysplastic syndrome and acute myelogenous leukemia with vitamin D3 [1 alpha(OH)D3]].

It is known that 1 alpha, 25(OH)2D3 is an inducer of nonlymphoid leukemic cell differentiation to monocyte-macrophage-like in vitro. The effects of oral administration of 4.5-15 micrograms/d 1 alpha (OH)D3, which is converted to 1 alpha, 25(OH)2D3 in vivo by liver cells, on leukemic cells were studied in two patients with AML and one with RAEB. In these three cases, 1 alpha (OH)D3 reduced the number of leukemic cells in the bone marrow and aggregated the dispersed chromatin of leukemic cells as heterochromatin. Furthermore, this drug induced atypical lymphocyte-like cells, which were considered to be differentiated from leukemic cells in case 1, and improvement of pancytopenia in case 3. While hypercalcemia developed during 1 alpha (OH)D3 therapy in case 1, it disappeared within three days after discontinuation. We also studied the in vitro effects of 1 alpha, 25 (OH)2D3 on leukemic cells freshly isolated from the bone marrow in these three cases. After incubation with 10(-8) M 1 alpha, 25(OH)2D3 at 37 degrees C for 72 h, the number of adherent cells on the bottom of Petri dishes had increased. These cells were quite similar to monocyte-macrophages. These leukemic cells, after differentiation induced by 1 alpha, 25(OH)2D3, reacted strongly with monoclonal antibodies My-4 and My-7. Both 100 microM D-cis and L-cis diltiazem (calcium channel blocker) enhanced the differentiation of HL-60 cells induced by 1 alpha, 25 (OH)2D3. There was no significant difference between D-cis and L-cis diltiazem with regard to this enhancing effect. The cytoplasmic free Ca2+ concentration in HL-60 cells induced by 1 alpha, 25(OH)2 D3 and/or diltiazem, was increased significantly as compared with that in HL-60 cells incubated without inducers.

Administration, Oral↗
PubMed1988

Molecular genetic and immunohistochemical analyses of a case of multicentric Castleman's disease.

Whether Castleman's disease is primarily hyperplastic or neoplastic in nature is a matter of controversy; however, the classical localized form has been thought clinically benign in itself, because it can be cured by local therapy. Recently, a multicentric form of the disease has been reported and has received attention because of its aggressive clinical course and high incidence of developing malignant lymphoma. Here, we describe a case of multicentric Castleman's disease which occurred in a 24-year-old Japanese man. To ascertain whether a monoclonal population was present or not, we performed a molecular genetic analysis of the genes encoding the T-cell receptor and the immunoglobulin, as well as a conventional immunohistochemical analysis. Using these sensitive methods, no monoclonal population could be found. The findings suggest that our case represents a reactive rather than a neoplastic disorder.

Adult↗
PubMed1988

[Therapeutic effect of ranimustine (MCNU) on essential thrombocythemia and polycythemia vera].

Seven patients with essential thrombocythemia and two patients with polycythemia vera were treated with ranimustine (MCNU). MCNU was given intravenously by drip infusion at a dose of 40-80 mg/m2 with intervals arranged in terns of the counts of both white blood cell and platelets. All cases with essential thrombocythemia obtained complete response, but the cases with polycythemia vera needed the combination of phlebotomy. The therapeutic effects were maintained for 2-5 months. No serious side effect was recognized except in two cases (22%) of mild nausea. Our study indicates that MCNU is useful for chemotherapy of chronic myeloproliferative disorders, especially, essential thrombocythemia.

Adult↗