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Biomedical subjects

S Irino

Publications and source records attributed to S Irino.

At least 73 records · Page 4Linked to original sources
PubMed1991

Genomic rearrangement of the c-myc proto-oncogene in non-AIDS-related lymphoma in Japan.

Southern blot analysis was employed to analyze the structural alterations of the c-myc oncogene in genomic DNA derived from tumor specimens of 35 adults with pathologically classified and immunophenotyped non-AIDS-related, non-Hodgkin's lymphoma in Japan. In this study, seven cases (20%), including one peripheral T-cell lymphoma and six B-cell lymphomas of various histological types, were demonstrated to have additional c-myc fragments. An interesting feature is that c-myc rearrangements were found in three out of eight primary gastrointestinal lymphomas. Analyses with several restriction enzymes revealed that the breakpoints in these cases were clustered in a region spanning the first exon, first intron and nearby 5'-flanking sequences of the c-myc gene, suggesting that the alteration of this region may represent an important molecular event in activating the oncogenic potential of the c-myc gene.

Adult↗
PubMed1990

Induction of differentiation of HL-60 cells by protein kinase C inhibitor, K252a.

To clarify the role of protein kinase C and protein kinase A in cell proliferation and differentiation, the effects of K252a and its derivatives (K252b, KT5720), which have different inhibitory activity to these protein kinases, on the proliferation and differentiation of HL-60 cells were investigated. The proliferation and DNA synthesis of the HL-60 cells were inhibited by K252a in a dose dependent manner. However, K252b and KT5720 which are more specific inhibitors of protein kinase C or protein kinase A, respectively, had no observable effect on cell proliferation. K252a (40nM) enhanced the differentiation of HL-60 cells induced by 1,25(OH)2D3, retinoic acid and DMSO. K252b and KT5720 did not affect 1,25(OH)2D3-induced differentiation. K252a significantly inhibited the differentiation induced by PMA. These results demonstrate that K252a but not its derivatives can function as an antitumor drug and enhancer of the differentiation induced by various inducers.

Carbazoles↗
PubMed1990

Production of shorter mRNA for protein phosphatase 2A beta by alternative poly(A) addition.

Two types of cDNA clones of protein phosphatase 2A beta, PP-2A beta L and PP-2A beta S, were isolated from a rat testis cDNA library. PP-2A beta L was 1.8 kb in length and corresponded to the 2.0 kb mRNA that is the major species expressed in somatic tissues. PP-2A beta S was 1.3 kb in length and corresponded to the 1.4 kb mRNA that is the major species expressed in germ cells of the testis. Nucleotide sequencing of these two clones revealed that their open reading frames were identical. The only difference between these two cDNAs was at the 3' non-coding region due to alternative poly(A) addition: the 1.8 kb cDNA had a consensus poly(A) addition signal, AATAAA, but the 1.3 kb cDNA had an unusual poly(A) addition signal, probably with the sequence AATATA. These data suggest that in germ cells there may be some mechanism that utilizes the specific poly(A) addition signal.

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

Synergistic action of tiazofurin and retinoic acid on differentiation and colony formation of HL-60 leukemia cells.

Tiazofurin and retinoic acid synergistically induced differentiation and inhibited colony formation in HL-60 human promyelocytic leukemia cells in cell culture. The synergism was the result of different mechanisms of action, since the effect of tiazofurin, unlike that of retinoic acid, was prevented by addition of guanosine. Since it has been shown that tiazofurin down-regulated the expression of c-Ki-ras oncogene, and retinoic acid that of the myc oncogene, the joint impact of these drugs is of clinical interest particularly in end-stage leukemia where the therapeutic usefulness of tiazofurin has recently been demonstrated.

Antineoplastic Agents↗
PubMed1990

p75c-myb expression in leukemia-lymphoma cells correlated with proliferation and differentiation.

Monoclonal antibodies (McAbs) against a part of v-myb gene product were prepared for the detection of human c-myb gene product (p75c-myb). Western blotting analyses with these McAbs were performed on human leukemia-lymphoma cells. All T-cell lines were positive in p75c-myb expression. B-cell lines were variable, myeloid and erythroid cells were positive although the amount of expressed p75c-myb was less than the T-cell lines. Cells isolated from patients were positive in expression except for cells from acute myeloblastic leukemia with maturation (AML M2), acute hypergranular promyelocytic leukemia (AML M3) and erythroleukemia (AML M6) developed from myelodysplastic syndromes. Differences in p75c-myb expression seemed to depend upon the differentiation stage and distinctive lineage from which each cell line had been established. The p75c-myb expression in HL60 (acute promyelocytic leukemia cell line) showed remarkably high at logarithmic growth. When examined with HL60, p75c-myb expression significantly decreased during the differentiation induced by 12-O-tetradecanoylphorbol-13-acetate or retinoic acid. These results suggest that p75c-myb expression plays a crucial role in hematopoietic cell proliferation and differentiation and that multiple mechanisms including aberrant expression of p75c-myb is involved in leukemogenesis.

Antibodies, Monoclonal↗
PubMed1990

Effects of the antisense v-myb' expression on K562 human leukemia cell proliferation and differentiation.

Recombinant plasmids containing v-myb' (803 bp fragment of the 3' end of v-myb) were constructed to induce sense or antisense v-myb' RNA expression with dexamethasone in human cells. These plasmids were used as a tool for the investigation of the role of c-myb gene in human leukemia cell proliferation and differentiation. They were transfected by electroporation into the K562 human leukemia cell line derived from a patient with chronic myelogenous leukemia in blastic crisis. After induction of transcription by dexamethasone, the plasmid with antisense v-myb' repressed the expression of p75c-myb from the endogenous c-myb gene of K562 cells. It also reduced the proliferation rate of K562 cells to 50% of the control level, and induced these K562 cells to express the myelomonocytic differentiation cell surface marker CD13 and increased NBT reducing activity. The plasmid with sense v-myb' did not have an effect on p75c-myb expression, the proliferation of K562 cells or the expression of myelomonocytic differentiation phenotypes. These observations suggest that antisense v-myb' RNA represses p75c-myb expression and that a decrease of p75c-myb suppresses K562 cell proliferation and induces its differentiation towards the myelomonocytic lineage.

Antigens, Differentiation, Myelomonocytic↗
PubMed1990

Identification of members of the protein phosphatase 1 gene family in the rat and enhanced expression of protein phosphatase 1 alpha gene in rat hepatocellular carcinomas.

We isolated four kings of cDNA clones of isotypes of catalytic subunits of protein phosphatase 1 (PP-1) from rat liver and testis cDNA libraries. For the cloning, cDNA fragments of dis2ml and dis2m2, which encode mouse PP-1 catalytic subunit, were used as probes. Two of the four isotypes were thought to be derived from the same gene and produced by alternative splicing. Based on the comparative study of their nucleotide and deduced amino acid sequences with those reported, these cDNA clones were named rat PP-1 alpha, PP-1 gamma 1, PP-1 gamma 2 and PP-1 delta. The deduced amino acid sequences of these four cDNA clones showed about 90% identity. Their amino-terminal regions were highly conserved, and their differences were mainly in the carboxy-terminal regions. Furthermore, several amino acids located in the middle regions of the peptides were conserved in all the isotypes of the catalytic subunits of PP-1, PP-2A, PP-2B and PP-2C. These conserved regions are suggested to be the functional domains of the catalytic subunits of protein phosphatases. Rat hepatocellular carcinomas induced by a food mutagen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline showed increased expression of PP-1 alpha, but no increased expression of PP-1 gamma 1, PP-1 gamma 2 or PP-1 delta. Involvement of PP-1 alpha in hepatocarcinogenesis or in hepatic cell proliferation was suspected.

Amino Acid Sequence↗
PubMed1990

Evaluation of elastase and antielastase balance in patients with chronic bronchitis and pulmonary emphysema.

On the basis of the "protease-antiprotease imbalance" theory for the pathogenesis of pulmonary emphysema, we hypothesized that measurement of elastase burden and antielastase capacity in the alveolar space might correlate with emphysema. To evaluate this, the severity of emphysema, the elastase burden, and the elastase inhibitory capacity were estimated in 28 patients with chronic bronchitis and variable degrees of emphysema, none of whom had congenital deficiency of alpha-1-protease inhibitor, and all of whom underwent bronchoalveolar lavage. Emphysema was assessed by both computed tomography and diffusing capacity. To examine "elastase burden," elastase:alpha-1-protease inhibitor complex and free elastase activity in alveolar lavage fluids were measured. To evaluate "antielastase" capacity, elastase inhibiting capacity in alveolar lavage fluid was measured. Elastase burden correlated directly and antielastase capacity correlated inversely with emphysema. These data provide direct support for the "protease-antiprotease imbalance" theory of emphysema in a group of smokers without congenital deficiency of alpha-1-protease inhibitor.

Adult↗
PubMed1990

[An elderly case of small cell lung cancer showing complete response by oral administration of etoposide].

An 87-year-old female was admitted with left chest pain and dyspnea in January 1989. The chest X-ray film revealed complete atelectasis of the left lung. Bronchoscopic observation revealed a tumor which was bleeding easily at left main bronchus. Cytological findings of the bronchial aspirates showed small cell lung cancer. Because she was old and had some complications, she was difficult to treat by standard combination chemotherapy. Only etoposide at 150 mg/day was administered orally for 3 days (first course). After the first course the whole lung atelectasis improved; and after the second course (etoposide at 150 mg/day for 4 days) the tumor of the left main bronchus disappeared under endoscopic examination. Malignant cells were not detected in the bronchial aspirates and biopsy specimens. No severe side effect except for alopecia and mild gastrointestinal symptoms such as nausea and vomiting was noted. Myelosuppression was not evident. This case suggested that etoposide administered orally is useful in the treatment of small cell lung cancer especially in elderly patients with complications.

Administration, Oral↗
PubMed1990

[A co-operative study on prophylactic effect of oral administration of high-dose amphotericin B syrup for systemic fungal infection in patients with hematological neoplasms. Chugoku-Shikoku Study Group of Mycosis with Hematologic Disease].

The prophylactic effect of the oral administration of high-dose amphotericin B syrup for the systemic fungal infection was studied in 36 patients with hematological neoplasms. Twenty nine patients received 2,400 mg/day of Amphotericin B syrup for during the remission induction therapy. One patient received 1,200 mg/day, 3 received 800 mg/day and 3 received 400 mg/day of Amphotericin B syrup. The prophylactic effect was recognized in 24 of 36 patients, 66.7%. As adverse effects gastrointestinal symptoms such as nausea and vomiting, hypochloremia and hypopotassemia associated with hypochloremia was observed in one patient, respectively, however, they were all controllable. The blood levels of Amphotericin B in patients received 2,400 mg/day was 0.092 +/- 0.055 micrograms/ml (n = 40) on 7th day and 0.110 +/- 0.046 micrograms/ml (n = 21) on 28th day, respectively. The administration of high-dose of Amphotericin B syrup is expected not only for the prophylaxis but also for the treatment of the systemic fungal infection.

Administration, Oral↗
PubMed1990

[Ileocolic intussusception in a recurrent non-Hodgkin's lymphoma; report of a case].

The adult intussusception is rare. Here, we describe a case of an adult patient with ileocolic intussusception secondary to a recurrent lymphoma of the terminal ileum. The patient was a 42-year-old female, who had a history of the subtotal gastrectomy because of the primary gastric lymphoma. Eight months after the operation, she had a relapse in the abdomen and received the combination chemotherapy. She acquired the complete remission, but six months after the completion of the chemotherapy, she suffered from the right lower abdominal pain and diarrhea. Physical examination revealed a soft mass with tenderness in the right iliac fossa. Barium studies and abdominal computed tomography showed an ileocolic intussusception. At laparotomy, a 4.5 cm polypoid tumor was found in the terminal ileum and it passed through the ileocaecal valve to form an intussusception. Histologic examination disclosed the follicular lymphoma of medium-sized cell type. So far as we are aware, this is the first report of an adult patient with intussusception secondary to a lymphoma in Japan.

Adult↗
PubMed1989

Reversal of enzymic phenotype of thymidine metabolism in induced differentiation of U-937 cells.

Exposure of U-937 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in specific alterations in thymidine metabolism. Within 24 h after treatment with 1.62 x 10(-9) M TPA, the reciprocal alteration in the activities of opposing enzymes of thymidine metabolism observed during normal cell culture growth was reversed. In TPA-treated cells, the activities of anabolic enzymes thymidine kinase (EC 2.7.1.75)and thymidylate synthase (EC 2.1.1.45) declined with time linearly to 20 and 16% of those of untreated cells by 72 h. Incorporation of [3H]thymidine and [3H]deoxyuridine into acid-insoluble fractions also decreased in parallel with the decline in enzyme activities. In contrast, the activities of catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrothymine dehydrogenase (EC 1.3.1.2) increased. The rise in thymidine phosphorylase activity peaked at 48 h with 406% elevation over the control. The activity of dihydrothymine dehydrogenase was not altered for the first 24 h, but it increased up to 338% by 96 h. Immunotitration of dihydrothymine dehydrogenase with monoclonal antibody against this enzyme showed that the rise in activity in the differentiated cells was due to the increase in the amount of enzyme protein. No significant difference was observed in the Km values for the substrate of each enzyme between untreated and TPA-treated cells. These metabolic alterations during induced differentiation were in line with the changes in cell morphology and accompanied by an accumulation of the cells in G1 at the expense of S phase. These observations indicate that induced differentiation of U-937 cells results in a reversal of the enzymic phenotype of thymidine metabolism and suggest that emergence of thymidine metabolic imbalance may serve as an early marker of differentiation of these cells.

Cell Cycle↗