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H Takashima

Publications and source records attributed to H Takashima.

At least 127 records · Page 7Linked to original sources
PubMed1994

[Collagen diseases complicated with myelodysplastic syndrome (MDS)--report of three cases].

We presented three cases of collagen diseases complicated with myelodysplastic syndrome (MDS). To our knowledge, MDS following collagen disease is very rare, and only seven cases have been reported previously. First case (a 40-years old woman) had suffered from rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome for 16 years. Second case (a 65-years old woman) had suffered from rheumatoid arthritis for 15-years. Third case (a 63-years old woman) had suffered from progressive systemic sclerosis for 16 years. These patients developed MDS. After onset of MDS, cytopenia progressed rapidly within half a year. In the types of MDS, case 1 and case 2 had refractory anemia and case 3 had refractory anemia with excess of blasts and a preleukemic state. Case 2 had a clonal abnormality of haemopoietic stem cells. It is unlikely that MDS in our cases are caused by mutant agents or irradiation. These results suggest MDS may be contributed to long-term immunodysfunction found in these collagen diseases.

Adult↗
PubMed1993

Kainic acid lesions increase reafferentation of the striatum by substantia nigra grafts.

Effects of kainic acid lesions of the striatum on reafferentation of the striatum produced by intraventricular substantia nigra (SN) grafts were investigated. Rats with unilateral 6-hydroxydopamine lesions of the SN received intrastriatal kainic acid lesions or sham lesions, and then received fetal (E16) SN or sciatic nerve grafts in the lateral ventricle. The depth of reafferentation of the striatum by catecholaminergic neurites from SN grafts was significantly increased in rats with kainic acid-induced striatal lesions, as compared to the sham-lesioned controls. No reafferentation was seen in the control animals with sciatic nerve grafts. These data suggest that striatal injury promotes the growth of dopaminergic neurites from SN grafts.

Afferent Pathways↗
PubMed1993

[Experimental studies on Nicaraven as radioprotector--free radical scavenging effect and the inhibition of the cellular injury].

In the present study, firstly the antioxidant effect of Nicaraven was observed by examining the direct free radical scavenging effect with ESR. Dose dependent effects were shown in scavenging both of superoxide and hydroxyl radicals. In the study to check whether Nicaraven inhibits hydroxyl radical formation or degrades the spin adduct of DMPO with hydroxyl radical, the effect of Nicaraven was suggested that it inhibited hydroxyl radical formation itself. Secondly, it was recognized fluorophotometrically that the inhibiting effect of the agent on the superoxide and hydroxyl radicals promoted damage to benzoate, deoxyribose and some amino acids. The inhibiting effect was nearly the same as that of mannitol. Furthermore, the inhibition of the cellular injury induced by ferrous sulphate was investigated in NIH3T3 cells. The addition of Nicaraven to the cells after 6 hours of reaction with FeSO4, the inhibition of the cellular injury was significant (p < or = 0.01). The effect of Nicaraven was recognized as a radioprotector in vitro. The agent suggested to be able to produce recovery from the damage induced by irradiation at the cellular level.

3T3 Cells↗
PubMed1993

Effect of human serum on the in vitro anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives as related to their lipophilicity and serum protein binding.

Several derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of various concentrations (10-50%) of human serum (HS). Although all HEPT derivatives proved to be highly potent inhibitors of HIV-1 in the presence of 10% fetal bovine serum, some of them were less inhibitory to HIV-1 replication in the presence of HS. The HEPT derivatives were found to be highly bound to HS proteins. Both the anti-HIV-1 activity and HS protein binding of the compounds appeared to be related to their lipophilicity.

Acetylcysteine↗
PubMed1993

Mixed haplotype A beta Z/A alpha d class II molecule in (NZB x NZW)F1 mice detected by T cell clones.

We have tried to demonstrate the existence of a mixed haplotype MHC class II molecule in (NZB x NZW)F1 (B/WF1) mice. When a large panel of keyhole limpet hemocyanin-specific T cell clones derived from B/WF1 mice was analyzed, several clones were shown to be restricted by a F1-specific A beta Z/A alpha d class II molecule. Autoreactive A beta Z/A alpha d-specific T cell clones were also obtained. The ability of the association and expression of A beta Z with A alpha d was confirmed by hybridoma and transfection experiments. Hybridoma cell lines created by fusion of NZW (H-2z) spleen cells with M12.C3 (a A beta d- variant cell line derived from M12.4.1 (H-2d) B lymphoma) cells expressed A beta Z determinants. Transfection of A beta Z genomic DNA to M12.C3 cells resulted in the expression of A beta Z determinants. These hybridoma cell lines and transfectants were able to stimulate A beta Z/A alpha d-specific T cell clones, suggesting the expression of A beta Z/A alpha d molecules on the cell surface. However, attempts to demonstrate the existence of mixed haplotype MHC class II molecules in B/WF1 mice by two-dimensional (nonequilibrium pH gradient gel electrophoresis/SDS-PAGE) gel electrophoresis analysis with the use of anti-class II mAb failed to demonstrate the existence of mixed haplotype A beta Z/A alpha d or A beta d/A alpha z class II molecules in B/WF1 mice. Analysis of mixture of TA beta Z cell and B/WF1 spleen cell lysates immunoprecipitated by anti-A beta Z mAb suggested that the amount of haplotype mixed A beta Z/A alpha d molecules in B/WF1 spleen cells is less than 1/10 that of haplotype matched A beta/A alpha pairs. Our results suggest that, although undetectable by biochemical analysis, small amounts of mixed haplotype A beta Z/A alpha d molecules exist in B/WF1 spleen cells. Also, T cell clones which recognize them exists in B/WF1 mice. Because autoimmune symptoms of B/WF1 mice are shown to be related to heterozygosity at the H-2 region, autoreactive T cell clones which recognize the mixed haplotype A beta Z/A alpha d class II molecule might be involved for the induction of autoimmunity in B/WF1 mice.

Animals↗
PubMed1993

Immortalized GABAergic cell lines derived from rat striatum using a temperature-sensitive allele of the SV40 large T antigen.

Embryonic striatal cells were immortalized using the A58 temperature-sensitive allele of the SV40 large T antigen. Two cell lines, M213-2O and M26-1F, with gamma-aminobutyric acid (GABA)ergic properties were selected from 85 clones thus developed. M213-2O is a multipolar, polygonal cell line which expresses SV40 large T antigen and glutamate decarboxylase (GAD) at the permissive temperature (33 degrees C) and GAD and MAP-2 immunoreactivity at the nonpermissive temperature (39.3 degrees C). M26-1F has a fibroblast-like morphology and expresses SV40 large T antigen and GAD both at the permissive and nonpermissive temperatures and MAP-2 immunoreactivity at the nonpermissive temperature. Both lines contain GABA as measured by reversed-phase HPLC and M213-2O expresses nipecotic-sensitive [14C]GABA uptake.

Alleles↗
PubMed1993

Granulocyte-macrophage colony-stimulating factor and interleukin-1 increase in cerebrospinal fluid, but not in serum, of HTLV-I-associated myelopathy.

Based on our previous finding of elevated interferon-gamma levels in the cerebrospinal fluid (CSF), but not in serum, of HTLV-I-associated myelopathy (HAM), we assayed serum and CSF levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in 20 HAM. GM-CSF and IL-1 also increased only in the CSF in 75% and 35%, respectively, of 20 HAM. TNF-alpha was not detected in any of the sera and CSFs. Multiple cytokines may be produced in the central nervous system and play an important role in HAM.

Adult↗
PubMed1993

Transient scoliosis in a child with juvenile rheumatoid arthritis.

An 8 year old girl was admitted to hospital complaining of arthralgia in a few large joints. According to the clinical course and serological tests, a diagnosis of a polyarticular type of juvenile rheumatoid arthritis was made. About 6 weeks after the onset, scoliosis was observed. The curvature regressed spontaneously over the following 6 months. Generally, scoliosis associated with juvenile rheumatoid arthritis has been noted a few years after the onset. A transient scoliosis in the early phase of this disease is rare.

Arthritis, Juvenile↗
PubMed1993

Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings.

A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium.

Adolescent↗
PubMed1993

Effect of the leukotriene receptor antagonist ONO-1078 on extravascular lung water after coronary ligation in dogs.

To determine whether or not leukotrienes are associated with pulmonary edema after coronary ligation in dogs, we studied the effects of a specific leukotriene C4/D4 antagonist, ONO-1078, on extravascular lung water, as measured by the thermal-dye double indicator dilution method (Extravascular thermal volume, ETV). Six dogs served as a sham control (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in 6 dogs (group 2), and in 6 others the coronary artery was ligated after pretreatment with ONO-1078 (1 mu/kg/min) (group 3). ETV and pulmonary arterial pressure were measured at control and 45 min after coronary ligation. In group 1, no significant change was found in ETV. Although there was no significant increase in pulmonary arterial pressure after coronary ligation, ETV significantly increased in groups 2 and 3. ETV increased more in groups 2 and 3 than in group 1, but there was no significant difference between groups 2 and 3. Thus, ONO-1078 did not effectively prevent the accumulation of extravascular lung water after coronary ligation, indicating that leukotrienes are not important mediators of pulmonary edema after myocardial ischemia.

Animals↗
PubMed1993

Selective and synergistic inhibition of human immunodeficiency virus type 1 reverse transcriptase by a non-nucleoside inhibitor, MKC-442.

In the search for 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives, we have found 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil (MKC-442) to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The IC50 value of MKC-442 for HIV-1 RT was 8 nM. MKC-442 did not inhibit HIV-1 RNase H, other RTs, or DNA polymerase alpha. Because its inhibitory pattern showed noncompetitive inhibition with regard to nucleotide substrates, its mode of action was considered to be allosteric inhibition. From the results of combination studies, MKC-442 was found to produce synergistic inhibition of HIV-1 RT with 3'-azido-2',3'-dideoxythymidine (AZT) 5'-triphosphate (AZT.TP). The dose of AZT.TP required for 50% inhibition was reduced to one tenth of control in the presence of a half dose of MKC-442. Although other allosteric inhibitors (Nevirapine, L-696,229, and R82,913) had the same specificity for enzyme inhibition, they did not show synergism with AZT.TP in the combination index and synergy plot analyses. Synergistic inhibition of HIV-1 replication by MKC-442 and AZT has also been observed in HIV-1-infected MT-4 cells. These results suggest that MKC-442 is a unique inhibitor of HIV-1 RT, and combination therapy with MKC-442 and AZT could be advantageous in the treatment of acquired immune deficiency syndrome.

Antiviral Agents↗
PubMed1992

Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out based on alkylation of HEPT with primary alkyl halides. Preparation of the 1-[(alkyloxy)methyl]-6-(phenylthio)thymine (26-31) and 1-[(alkyloxy)methyl]-6-(arylthio)-2-thiouracil (32-45) derivatives was carried out on the basis of LDA lithiation of 1-[(alkyloxy)-methyl]thymine (9-14) and 1-[(alkyloxy)methyl]-2-thiouracil (15-25) followed by reaction with diaryl disulfides. The oxidative hydrolysis of the 2-thiouracil derivatives gave 1-[(alkyloxy)methyl]-6-(arylthio)uracil derivatives (46-57). 1-Alkyl-6-(phenylthio)thymine (59-61) derivatives were prepared on the basis of alkylation of 6-(phenylthio)thymine (58). Methylation of the hydroxyl group of HEPT did not affect the anti-HIV-1 activity of HEPT. Substitution of the 1-(2-hydroxyethoxy)methyl group by ethyl, butyl, methoxymethyl, (propyloxy)methyl, and (butyloxy)-methyl groups somewhat improved the original anti-HIV-1 activity of HEPT. Substitution with ethoxymethyl and (benzyloxy)methyl groups further potentiated the activity [EC50: 1-(ethoxy-methyl)-6-(phenylthio)thymine (27), 0.33 microM; 1-[(benzyloxy)methyl]-6-(phenylthio)thymine (31), 0.088 microM]. When the 5-methyl group of 27 and 31 was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity was improved remarkably [EC50: 5-ethyl-1-(ethoxymethyl)-6-(phenylthio)-uracil (46), 0.019 microM; 5-ethyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (52), 0.0059 microM; 5-isopropyl-1-(ethoxymethyl)-6-(phenylthio)uracil (55), 0.012 microM; 5-isopropyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (56), 0.0027 microM]. Introduction of two m-methyl groups into the phenylthio ring also potentiated the activity.

Antiviral Agents↗
PubMed1992

Structure-activity relationships of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine analogues: effect of substitutions at the C-6 phenyl ring and at the C-5 position on anti-HIV-1 activity.

The effect of substitution on the pyrimidine moiety of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiothymine (HEPT-S) on anti-HIV-1 activity was investigated by synthesizing a series of 5-methyl-6-(arylthio) and 5-substituted-6-(phenylthio) derivatives. Preparation of the 5-methyl-6-(arylthio) derivatives was carried out based on either LDA lithiation of 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]thymine (3) and 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-2-thiothymine (4) followed by reaction with diaryl disulfides or an addition-elimination reaction of 1-[[2-(tert-butyldimethylsiloxy)ethoxy]-methyl]-6- (phenylsulfinyl)thymine (31) with aromatic thiols. Preparation of the 5-substituted-6-(phenylthio) derivatives was carried out based on either C-5 lithiation of the 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-6-(phenylthio)uraci l (41) with LTMP or the LDA lithiation of 5-alkyl-1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-2-thiouraci l derivatives 45-47. Substitution at the meta position of the C-6-(phenylthio) ring by the methyl group improved the original anti-HIV-1 activity of HEPT, and introduction of two m-methyl groups to the phenylthio ring further potentiated the activity [EC50: 6-[(3,5-dimethylphenyl)thio]-1-[(2-hydroxyethoxy)methyl]thymine (28), 0.26 microM; 6-[(3,5-dimethylphenyl)thio]-1-[(2-hydroxyethoxy)methyl]-2-thiothymin e (30), 0.22 microM]. When the 5-methyl group was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity of HEPT was also improved remarkably [EC50: 5-ethyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (48), 0.11 microM; 5-isopropyl-1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)-2-thiouracil (50), 0.059 microM; 5-ethyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (54), 0.12 microM; 5-isopropyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (56), 0.063 microM]. 6-[(3,5-Dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]thymine derivatives 51 and 57 and 6-[(3,5-dimethylphenyl)thio]-5-isopropyl-1-[(2- hydroxyethoxy)methyl]thymine derivatives 52 and 58 inhibited the replication of HIV-1 in the nanomolar concentration range.

Antiviral Agents↗
PubMed1992

Effects of adrenal medulla grafts on plasma catecholamines and rotational behavior.

The mechanisms by which adrenal medulla grafts influence the function of host brains in animal models of Parkinson's disease are unclear. To explore this issue, fragments of adrenal medulla or sciatic nerve were transplanted into the lateral ventricle of bilaterally adrenalectomized (ADX) or sham-ADX rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Additional control group received sham-transplantation surgery. Behavioral effects of these procedures were tested following administration of apomorphine, amphetamine, or nicotine. Plasma catecholamines were measured before and after transplantation surgery. In both ADX and sham-ADX rats, adrenal medulla grafts produced greater decreases in apomorphine-induced rotational behavior than did sciatic nerve grafts or sham-transplanted groups. Decreases in rotation were smaller in ADX than in sham-ADX animals, regardless of graft treatment. Plasma catecholamines increased after transplantation surgery in each of the sham-ADX groups, regardless of graft type. Increases in plasma dopamine concentrations were associated with decreases in rotational behavior. Five months after transplantation, grafted chromaffin cells demonstrated catecholamine fluorescence, tyrosine hydroxylase (TH) and chromogranin A immunoreactivities, and expression of TH mRNA. It is concluded that adrenal medulla grafts produce decreases in apomorphine-induced rotation through a combination of two independent effects. One is a specific effect of adrenal medulla grafts. The second is a nonspecific effect that requires an intact adrenal gland and may be related to increases in plasma catecholamine concentrations.

Adrenal Medulla↗
PubMed1992

Development of HTLV-I-associated myelopathy after blood transfusion in a patient with aplastic anemia and a recipient of a renal transplant.

We report the development of rapid progressive HTLV-I-associated myelopathy (HAM) after blood transfusion in two immunosuppressed patients, one of whom had aplastic anemia and the other was the recipient of a renal transplant receiving immunosuppressive chemotherapy. Spastic paraparesis developed 11 or 16 months after transfusion and rapidly progressed to a wheelchair-bound state. The present 2 cases suggest that the coexistent immunosuppression may play an important role in the rapid development of HAM in transfusion-acquired cases.

Adult↗
PubMed1992

Kawasaki disease in a father and son.

The pathogenesis and etiology of Kawasaki disease are unknown, but some studies suggest increased genetic susceptibility. The case is presented of an infant with Kawasaki disease whose father suffered from the same illness 21 years previously. The A, B and C loci of the HLA antigens were examined.

Adult↗
PubMed1992

Systemic interferon-alpha in the treatment of HTLV-I-associated myelopathy.

Treatment with interferon-alpha (IFN-alpha) was undertaken in 16 patients with human T-lymphotropic virus type I-associated myelopathy (HAM). All patients had progressive spastic paraparesis before treatment. Twelve patients were enrolled in an open therapeutic trial with a dose of 3.0 x 10(6) IU/day of IFN-alpha and 4 in a randomized, double-blind, multidose (3.0 x 10(6), 1.0 x 10(6) or 0.3 x 10(6) IU/day) trial. IFN-alpha was injected intramuscularly for 28 days. Eight of 12 patients enrolled in an open trial and 2 patients receiving a dose of 3.0 x 10(6) IU/day of IFN-alpha in a randomized trial showed clinical improvements during and after the treatment. The results showed that, although not for all patients, systemic IFN-alpha with a dose of 3.0 x 10(6) IU/day is effective in the treatment of HAM.

Adult↗