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Biomedical subjects

M Miwa

Publications and source records attributed to M Miwa.

At least 199 records · Page 11Linked to original sources
PubMed1989

Occurrence of platelet-activating factor (PAF) in normal rat stomach and alteration of PAF level by water immersion stress.

We detected platelet-activating substance in gastrointestinal areas, which was confirmed to be platelet-activating factor (PAF) on the basis of the following findings: 1) it comigrated with authentic PAF on thin-layer chromatography; 2) it did not aggregate PAF-desensitized platelets; and 3) its activity was completely antagonized by the receptor antagonists CV3988 and L-652,731. The level of PAF was determined with a bioassay method based on the release of [3H]serotonin from washed rabbit platelets. In the normal rat stomach, the level of PAF was high in the antrum (940 +/- 200 nmol PAF/mol phosphorus of original phospholipids), especially in the antral mucosa (1801 +/- 426 nmol/mol phosphorus of original phospholipids). The stomach PAF level was significantly altered by water immersion stress. Stress for a period of 1 h was associated with a decrease in the antral PAF level to 39 +/- 7% of that of untreated controls. This low PAF level persisted during stress. On the other hand, in the corpus, stress for periods of 1 and 3 h was associated with decreases in the PAF content, and further stress (7 h) resulted in restoration of the PAF level to normal. Furthermore, 7 h of stress was associated with distinct hemorrhagic lesions, which were prevented by CV3988 infused i.v. before the stress. This is the first report of an association between a decrease of the endogenous PAF level in animal tissues and tissue damage.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1989

Multi-step carcinogenesis model for adult T-cell leukemia.

The age-specific occurrence of adult T-cell leukemia (ATL) was analyzed using 357 cases collected during nationwide surveys carried out between 1982 and 1985 in Japan. A simple Weibull distribution function fitted well as a model. The mode of ATL onset was log-linear in this model and the curves for males and females overlapped completely. The presence of age-dependent accumulation of leukemogenic events within human T-cell leukemia virus type 1-immortalized T cells was suggested prior to the development of ATL, and the approximate number of independent leukemogenic events in ATL is estimated to be five. This stochastic analysis supported a multi-step carcinogenesis as an appropriate model for ATL.

Adult↗
PubMed1989

Serum platelet-activating factor acetylhydrolase activity in rats with gastric ulcers induced by water-immersion stress.

Platelet-activating factor (PAF) acetylhydrolase is an enzyme which hydrolyzes PAF to yield inactive lysoPAF. This study focused on the influence of water-immersion stress on serum PAF acetylhydrolase activity. The enzyme activity was determined by measurement of [3H]acetate produced from 1-O-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of the radioactive substrate and albumin with trichloroacetic acid. The onset of water-immersion stress caused the development of gastric lesions associated with a significant increase in serum PAF acetylhydrolase activity. Serum PAF acetylhydrolase may leak into the blood from some tissues in rats with gastric injury induced by water-immersion stress and might control the action of PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1989

[Influence of theophylline and corticosteroid preparations on serum PAF acetylhydrolase activity in asthmatic children].

In our previous papers, we reported that serum PAF acetylhydrolase (PAF AH) activity in severely asthmatic children was lower than that in healthy or mildly asthmatic children, and that this enzymatic activity might be one of the factors that induce more severe respiratory symptoms in asthmatic children. In this study, we investigated the influence on PAF AH activity of theophylline and corticosteroid preparations, which are frequently used for the treatment of patients with bronchial asthma. Serum PAF AH activity and theophylline concentration were measured before and 3,4,6, 12 h after administration of a sustained-release theophylline preparation to 8 asthmatic children. Although the theophylline concentration was increased significantly at 3, 4 and 6 h after administration, PAF AH activity was unchanged, and there was no correlation between the two parameters. We then measured PAF AH activity in 6 asthmatic children before and 5 and 48 h after intravenous injection of 100 mg hydrocortisone succinate, and found no change in enzymatic activity. Furthermore, PAF AH activity in two severely asthmatic patients, who were being given low-dose corticosteroid on alternate days, was measured at regular intervals for 10 months in one case and 5 months in the other. The PAF AH activity showed no significant change in this period. These results show that PAF AH in asthmatic children is very stable, and is not affected by either theophylline or corticosteroid preparations.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1988

Induction of poly(ADP-ribose) polymerase gene expression in lectin-stimulated human T lymphocytes is dependent on protein synthesis.

The poly(ADP-ribose) polymerase mRNA level in quiescent T lymphocytes was low, but was significantly higher than that in B lymphocytes or monocytes. When T lymphocytes were stimulated with phytohemagglutinin, a prompt increase in the mRNA level was observed from 4 hours after stimulation. The level of poly(ADP-ribose) polymerase mRNA reached a maximum in the late G1 phase about 1-2 days after lectin stimulation, and then decreased gradually returning to the basal level 10 days after lectin stimulation. Cycloheximide abrogated increase in poly(ADP-ribose) polymerase gene expression suggesting that a newly synthesized protein(s) was involved in poly(ADP-ribose) polymerase gene induction in lectin-stimulated T lymphocytes.

B-Lymphocytes↗
PubMed1988

DNA blotting analysis of human retroviruses in cerebrospinal fluid of spastic paraparesis patients: the viruses are identical to human T-cell leukemia virus type-1 (HTLV-1).

The structure of the integrated provirus in cell lines established from the cerebrospinal fluid (CSF) of patients with human T-cell leukemia virus type-1 (HTLV-1)-associated myelopathy (HAM) was analyzed. The digestion patterns with 3 restriction endonucleases, Sac I, Eco RI and PstI, of the proviruses integrated in T-lymphoid cell lines derived from the CSF of 4 HAM patients were similar to those of HTLV-1 from adult T-cell leukemia (ATL) patients. Integrated proviruses in one of these cell lines derived from the CSF were further analyzed in detail with 2 more restriction enzymes, BamHI and Sma I. The results indicate that the retrovirus found in lymphocytes of the CSF from patients with HAM are very similar, if not identical, to HTLV-1 found in the leukemic lymphocytes of ATL patients.

Cell Line↗
PubMed1988

Location of platelet activating factor binding in rat liver.

Autoradiographs of tissue slices from livers perfused with 1 x 10(-9) M-1-O-[3H]octadecyl-2-acetyl-sn-glycero-3-phosphocholine ([ 3H]18:0-sn-3-AGEPC) indicate that binding of this agonist is localized in the portal venules in anterograde perfused livers, and in the central venules in retrograde perfused livers. The pattern of silver grains in anterograde perfused liver was not affected significantly by prior exposure to 100-fold excesses of unlabelled 16:0- or 18:0-sn-3-AGEPC, 16:0-sn-1-AGEPC, or a 1000-fold excess of U.66985. [3H]18:0-sn-3-lyso-GEPC produced the same pattern of binding as the acetylated analogue. Measurement of glucose release stimulated by 16:0-sn-3-AGEPC demonstrated that the retrograde perfused liver was nearly 1000-fold less sensitive to this compound than the anterograde perfused liver. Exposure of the livers to bovine serum albumin prior to 5 x 10(-11) M-[3H]18:0-sn-3-AGEPC resulted in inhibition of stimulated glucose release, and decreased both the amount of label retained in the livers and the amount of silver grains over the portal sinusoidal cells without affecting the amount of grains seen over all other regions of the liver. Glucose release from primary monolayer cultures of hepatocytes or suspensions of liver slices was not stimulated by 16:0-sn-3-AGEPC. The results suggest that specific binding of [3H]18:0-sn-3-AGEPC is restricted to the portal side of the liver microvasculature, the majority of binding is nonspecific, and the biological response to AGEPC requires an intact and perfused vasculature.

Animals↗
PubMed1988

Release of acetylhydrolase from platelets on aggregation with platelet-activating factor.

Acetylhydrolase, the enzyme which inactivates platelet-activating factor (PAF, 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine), was selectively released from bovine platelets by aggregation with physiological concentrations (0.1-10 nM) of PAF with no cell lysis. The release of the acetylhydrolase paralleled that of serotonin. The acetylhydrolase released was active over a broad pH range (pH 5.4-8.6) and was not affected by Ca2+ (1-4 mM) or EDTA (1-8 mM). The Km value of the enzyme was 4.6 microM. Net specific acetylhydrolase activity recovered in the 130,000 x g supernatant after stimulation with PAF could be determined in the presence of EDTA without the activity of Ca2+-dependent phospholipase A2 which was also released from the cells at the same concentration of PAF. The acetylhydrolase was inhibited competitively by specific PAF antagonists, rac-3-(N-n-octadecylcarbamoyloxy)-2-methyoxypropyl-2-thiazolioe thyl phosphate (CV-3988) and (2RS)-1-O-hexadecyl-2-O-ethyl-3-O-(7-thiazolinoheptyl)-glycerol methanesulfonate (ONO-6040). Their Ki values for the enzyme were 1.17 microM and 0.84 microM, respectively. The release of the enzyme could also be detected when the platelets were aggregated with ADP (2.3 microM) or thrombin (0.5 unit). These results suggest that the enzyme released from the aggregated platelets to the blood plasma may also have a physiological function cooperating with the plasma acetylhydrolase.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1988

Concurrent adult T-cell leukemia and acute myeloblastic leukemia.

A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.

Antibodies, Viral↗
PubMed1988

A soluble-factor(s) secreted by a human skin cancer cell line supports clonal growth of adult T-cell leukemia cells.

Leukemic cells from four out of eight patients with adult T-cell leukemia (ATL) were successfully grown by cocultivation with HSC-I cells, a human skin cancer cell line, in the presence of interleukin-2. Three of these four cultures of growing cells showed rearrangement of the T-cell receptor beta-chain gene like the original leukemic cells in vivo, and also showed conservation of the patterns of HTLV-I integration of the original leukemic cells in vivo. Cell-to-cell contact between HSC-I cells and leukemic cells was not necessary for growth of the leukemic cells. The results indicate that some soluble growth factor secreted by HSC-I cells and interleukin-2 are required for the in vitro growth of leukemic cells from some patients with adult T-cell leukemia.

Adult↗
PubMed1988

Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.

Platelet-activating factor (PAF) acetylhydrolase has been recognized as an enzyme that inactivates PAF. We developed a convenient and reproducible method for determining human serum PAF acetylhydrolase activity. The assay was based on measurement of [14C]acetate produced from 1-O-alkyl-2-[14C]-acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of radioactive substrate and albumin with TCA. The apparent Km value of PAF acetylhydrolase (near the physiological concentration of serum protein) was 1.5 X 10(-4) M PAF. 32 subjects with serum PAF acetylhydrolase deficiency were found among 816 healthy Japanese adults. The low PAF acetylhydrolase activity in the deficient serum might not be due to the presence of enzyme inhibitor. Both the sensitivity to PAF and the metabolism of PAF in platelets from PAF acetylhydrolase-deficient subjects were almost the same as those of normal subjects. Deficiency in serum PAF acetylhydrolase appeared to be transmitted by autosomal recessive heredity among five Japanese families. Among healthy adults, healthy children, and asthmatic children, who were grouped into five classes on the basis of respiratory symptoms (remission, wheezy, mild, moderate, and severe groups), the probability of PAF acetylhydrolase deficiency was significantly higher in groups with severe symptoms (moderate and severe) (P less than 0.01). These results suggest that deficiency of serum PAF acetylhydrolase might be one of the factors leading to severe respiratory symptoms in asthmatic children.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1988

Nucleotide sequence analysis of a provirus derived from HTLV-1-associated myelopathy (HAM).

Human T-cell leukemia virus type 1 (HTLV-1) is known to be associated with adult T-cell leukemia (ATL). Recently, HTLV-1-associated myelopathy (HAM) was described as a neurological disease with which an etiological association of HTLV-1 is suspected. A provirus genome was cloned from a lymphoid cell line derived from the cerebrospinal fluid of a patient with HAM, in order to examine in detail the etiological virus associated with HAM. The nucleotide sequence of the long terminal repeat (LTR), protease, env and pX regions of the provirus shows over 97% homology with that of HTLV-1 derived from ATL. These results suggest that this provirus, derived from a patient with HAM, belongs to the same species as HTLV-1 derived from patients with ATL.

Amino Acid Sequence↗
PubMed1988

[Antitumor activity and toxicity to the immune system and intestine, of the fluorinated pyrimidines FUra, 5'-DFUR, tegafur and UFT].

Antitumor activity and the toxicities of 5-fluorouracil (FUra) and its depot form derivatives with different mechanisms such as 5'-DFUR, tegafur and UFT, were compared in mice, and the therapeutic indices were measured. 5'-DFUR was less toxic to immune organs and the functions than those by other fluorinated pyrimidines. The therapeutic indices of 5'-DFUR obtained by using parameters of particular side effects, reduction of the number of GM-CFU in the bone marrow, shrinkage of the thymus, functional disorders in the immune systems, were several times higher than those of tegafur and UFT. On the other hand, there were no marked differences in the intestinal toxicities among the compounds. 5'-DFUR was only about two times less toxic on the intestinal tract than tegafur and UFT when the incidence-of diarrhea and damage to the duodenum were compared. These studies suggest that the difference in the mechanisms converting to FUra is a result of the toxicities causing different extent.

Animals↗
PubMed1988

[Comparative studies on the antitumor activity of the fluorinated pyrimidines 5'-DFUR, tegafur, UFT and FUra on various murine tumors].

Antitumor activities of fluorinated pyrimidines by oral administration were compared with various murine tumor models. 5'-Deoxy-5-fluorouridine (5'-DFUR) showed a better antitumor activity in terms of the growth inhibition and increase of the survival time than those of 5-fluorouracil(FUra), tegafur and UFT, particularly with respect to the chemotherapeutic indices. The activity of these fluorinated pyrimidines were further investigated in more detail with mice bearing colon 26 adenocarcinoma to suggest some means to optimize their treatment regimens in clinical trials. 5'-DFUR showed the activity irrespective of the size of tumor mass at the time of start of therapy. Additionally only 5'-DFUR was safely administered to the mice daily for long period up to more than 100 days, suppressing the tumor growth and increasing the survival to great extent.

Animals↗
PubMed1988

Clinicopathologic, immunophenotypic, and immunogenotypic analyses of immunoblastic lymphadenopathy-like T-cell lymphoma.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is a distinct peripheral T-cell lymphoma, which closely resembles angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and/or IBL, but is characterized by focal or sheet-like proliferation of immunoblasts and pale cells of T-cell nature. In this report, 36 patients with IBL-like T-cell lymphoma were analyzed. The disease is clinically characterized by generalized lymph node swelling, hepatosplenomegaly, fever, skin rash, polyclonal hypergammaglobulinemia, marked male predominance, predilection for the elderly, and poor prognosis. There was no association with human T-cell leukemia virus type I or human immunodeficiency virus. IBL-like T-cell lymphoma may be divided into two categories (CD4+ type and CD8+ type) by surface marker analysis. It can also be divided into three categories on the basis of the histologic findings of distribution of morphologically recognizable tumor cells: nine cases of "inconspicuous type," six cases of "patchy type," and 21 cases of "diffuse type." Two cases of "inconspicuous type" converted later to "diffuse type." DNA hybridization analyses in the ten recent cases revealed that three of four "inconspicuous types" and five of six "diffuse types" showed clonal rearrangement of T-cell receptor-beta chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T cells.

Adult↗
PubMed1987

Nucleotide sequence of a full-length cDNA for human fibroblast poly(ADP-ribose) polymerase.

The complete nucleotide sequence of human fibroblast poly(ADP-ribose) polymerase cDNA was determined. The cDNA contains an open reading frame for a 1014 amino acid polypeptide. In the DNA binding domain of poly(ADP-ribose) polymerase, there are predicted alpha-helix-turn-alpha-helix structures and two sequences each of about 100 amino acids that are similar to each other containing potential cysteine-zinc DNA binding structures. Within the 3' untranslated region, there is an AT-rich sequence containing ATTTA, a possible mRNA destabilizer.

Amino Acid Sequence↗
PubMed1987

Molecular cloning of cDNA for human poly(ADP-ribose) polymerase and expression of its gene during HL-60 cell differentiation.

Human placental poly(ADP-ribose) polymerase was purified and the NH2-terminal amino acid sequences of 16 KDa and 40 KDa chymotryptic peptides were determined. Screening of a lambda gt11 cDNA library of normal human placenta with a 51-mer oligodeoxyribonucleotide yielded one clone with a 1.8 Kb insert and two clones with 2.1 Kb inserts. The amino acid sequence deduced from the nucleotide sequence of the 1.8 Kb insert exactly matched the determined amino acid sequences. From a Northern blot analysis, a single 3.6 Kb mRNA was detected in HL-60 cells. Furthermore, the RNA expression of the poly(ADP-ribose) polymerase gene was shown to decrease during the granulocytic differentiation of HL-60 cells upon induction by retinoic acid.

Amino Acid Sequence↗