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Biomedical subjects

H Masutani

Publications and source records attributed to H Masutani.

At least 73 records · Page 4Linked to original sources
PubMed1992

ADF (adult T cell leukemia-derived factor)/human thioredoxin and viral infection: possible new therapeutic approach.

ADF (adult T-cell leukemia-derived factor), originally defined as an inducer of interleukin 2 receptor/alpha (IL-2R/alpha), is a homologue of thioredoxin. ADF is constitutively produced by human lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV). ADF augments the proliferation of HTLV-I and EBV transformed cells as an autocrine growth factor. These data are indicative of the possible involvement of ADF in virus-related transformation of cells and their autocrine growth. On the other hand, thioredoxin contains a redox active disulfide and has a reducing activity in the presence of thioredoxin reductase and NADPH. To clarify the role of ADF/thioredoxin system in the viral transformation, we tested the effect of 13-cis-retinoic acid (RA), which is a competitive inhibitor of thioredoxin reductase, on the growth of ADF high producing cells. The expression of IL-2R/alpha on HTLV-I (+) cells was suppressed by RA. RA dose-dependently reduced the cell number and viability of ADF high producing lymphoid cells. Moreover, it had a suppressive effect on the proliferation of ADF high producing cells. It is suggested that RA has an inhibitory effect on the activation and the growth of cells producing ADF and that inhibition of the ADF/thioredoxin system may be a new therapeutic approach for retrovirus-related disorders.

Amino Acid Sequence↗
PubMed1992

Expression of adult T-cell leukaemia-derived factor, a human thioredoxin homologue, in the human ovary throughout the menstrual cycle.

An immunohistochemical study of the expression of adult T-cell leukaemia-derived factor (ADF), a human thioredoxin homologue, was performed in the normal human ovary throughout the menstrual cycle. Primordial follicles were negative for ADF. Both granulosa cells and theca interna cells at the stages of preantral and antral follicles contained ADF. The staining intensity of these cells was very strong in the preovulatory dominant follicle. After ovulation, both granulo-lutein and theca-lutein cells were positive for ADF. During pregnancy, the theca-lutein cells revealed very intense ADF staining. The theca interna cells of the atretic follicles showed ADF staining, while the granulosa cells of such follicles did not. These results suggest that ADF localizes in the ovarian steroidogenic cells which have the binding sites of either luteinizing hormone or follicle-stimulating hormone, and that ADF expression is closely associated with the activity of the ovarian steroidogenic cells.

Adult↗
PubMed1992

Lymphocyte transformation and thiol compounds; the role of ADF/thioredoxin as an endogenous reducing agent.

ADF (adult T-cell leukemia-derived factor), an inducer of IL-2R with growth promoting activity, is a homologue of thioredoxin which is involved in many thiol-dependent reducing reactions. ADF is constitutively produced and released by human lymphoid cell lines transformed by lymphocyte-tropic viruses, such as human T-lymphotropic virus type I (HTLV-I) and Epstein-Barr virus (EBV). We found that the viability and growth of these ADF high-producer cell lines (ATL-2, HUT102, MT-2, 3B6 and RPM18866) were highly dependent on L-cystine in the culture. In contrast to the relative cystine independency of ADF low-producer cells (Jurkat, Jijoye, U937 and K562), the growth of ADF high-producer cells was almost completely suppressed in L-cystine-free condition. Their viability and growth in L-cystine-free medium were markedly improved by 5 x 10(-5) M L-cysteine, 5 x 10(-5) M 2-ME or 10(-3) M GSH and partially by 10(-3) M DTT. The results demonstrate the requirement of reducing condition involving thiol compounds for the optimal growth of the virally transformed lymphoid cells. Furthermore, recombinant ADF (rADF) and suboptimal dose of 2-ME additively enhanced the growth of ATL-2 cells in L-cystine-free medium, implying the possible involvement of endogenous reducing agents such as ADF/thioredoxin homologue in the process of lymphocyte transformation/activation.

Cell Line↗
PubMed1992

Stria vascularis in Ménière's disease: a quantitative histopathological study.

To investigate the role of pathology of the stria vascularis in Ménière's disease, the vascularity and the cross-sectional area of the stria vascularis in a midmodiolar section of the cochlea were examined by histological observation and a computer-aided planimetric, respectively, in eight temporal bones from individuals with Ménière's disease and eight age-matched normal temporal bones. The number of vessels in the stria vascularis was significantly smaller in most of the cochlear turns in ears with Ménière's disease than in control ears, and the cross-sectional area of the stria vascularis in the same sections was significantly smaller in all the cochlear turns in ears with Ménière's disease than in controls. Furthermore, vascularity correlated significantly with the cross-sectional area of the stria vascularis in all the temporal bones examined. From these results it appears that poor vascularity of the stria vascularis is closely related to strial atrophy, and that these pathological findings might be important factors in the pathophysiology of Ménière's disease.

Adult↗
PubMed1992

Temporal bone histopathological findings in campomelic dysplasia.

Both temporal bones of a newborn (35 gestational weeks old) with campomelic syndrome were studied histopathologically. This is to our knowledge the second temporal bone report (third case) of this syndrome. The findings included: abnormal cartilagenous and osseous tissues and abnormality in the globuli interossei in the otic capsule; deformities of the vestibule and semicircular canals, probably due to compression by the abnormal cartilaginous tissue; hypoplastic cochlea and semicircular canals; aberrant course of the facial nerve; wide dehiscence of the facial canal in the tympanic portion; slight hypoplasia of the malleus and anomalies in the incus and stapes; and large epitympanic space. These findings closely resembled those of the first report, and suggest that: 1) campomelic dysplasia is a definite disease entity with consistent pathogenesis, and 2) similar otologic manifestations may be expected in the majority of patients with this syndrome.

Abnormalities, Multiple↗
PubMed1992

Dysregulation of adult T-cell leukemia-derived factor (ADF)/thioredoxin in HIV infection: loss of ADF high-producer cells in lymphoid tissues of AIDS patients.

Adult T-cell leukemia (ATL)-derived factor (ADF) is a multifunctional protein homologous to thioredoxin (TRX) with co-cytokine and thiol-dependent reducing activities. ADF/thioredoxin production is enhanced in T cells transformed by HTLV-I. We have examined the effect of HIV-1 infection on ADF/TRX expression using specific antibody against ADF/TRX. Lymph nodes from 5 AIDS and 1 AIDS-related complex (ARC) patients were examined. As a control, 8 HIV noninfected lymph nodes, including 3 cases with hyperplasia, were also examined. Immunohistopathological studies using normal HIV noninfected lymph nodes showed that ADF/TRX high-producer (ADFh) cells were macrophages and cells with dendritic morphology in the paracortical area. Abundant ADFh cells were observed in HIV noninfected hyperplastic lymph nodes. The number of ADFh cells was low in hyperplastic lymph nodes from an ARC patient. All of the lymph nodes of 5 AIDS cases were atrophic and the number of ADFh cells were extremely low. To verify these histochemical studies, we examined the effect of in vitro HIV infection on ADF/TRX expression in HTLV-I (+) T-cell lines. Western blot analysis showed that a reduction of ADF/TRX in HIV-1-infected SKT-1B and MT-2 cells, and the reduction inversely correlated with p24 antigen level. On the basis of the above in vivo and in vitro findings, we imply that the levels of ADF/TRX were down-regulated by HIV-1 infection and that the down-regulation may play a role for pathophysiology of HIV-infected individuals.

AIDS-Related Complex↗
PubMed1992

Immunohistochemical distribution of adult T-cell leukemia-derived factor/thioredoxin in epithelial components of normal and pathologic human skin conditions.

Tissues from normal human skin and various skin diseases were studied with the immunoperoxidase technique using an antibody to adult T-cell leukemia-derived factor (ADF), a homologue of human thioredoxin. Normal human skin showed positive immunostaining for ADF/thioredoxin in the outer root sheath of hair follicle, sebaceous glands, and secreting components of apocrine and eccrine sweat units, but not in the unexposed interfollicular epidermis and other parts of both hair follicles and the sweat units. Immunoreactivity of benign skin tumors gave similar distribution to their normal counterparts; trichilemmal cyst, nevus sebaceus, senile sebaceous hyperplasia, and mixed cell tumor were positive for immunostaining, whereas epidermal cyst and pilomatricoma were not. No immunoreactivity was detected in malignant skin tumors such as basal cell carcinoma and poorly differentiated squamous cell carcinoma. Solar keratosis, well-differentiated squamous cell carcinoma, some of metastatic lesions of squamous cell carcinoma, and extramammary Paget's disease reacted with the antibody. These immunoreactivities reflected numerous functions of thioredoxin in higher organisms. Our findings suggest that the expression of ADF/thioredoxin in both normal and abnormal human skin is related to epithelial cell differentiation.

Adult↗
PubMed1992

Myelodysplastic syndrome (MDS)-associated inhibitory activity on haematopoietic progenitor cells: contribution of monocyte-derived lipid containing macrophages (MDLM).

We studied myelodysplastic syndrome-associated inhibitory activity (MDS-IA), which inhibited colony formation in vitro of normal granulocyte-macrophage progenitors (CFU-GM). When adherent marrow cells were incubated with fetal calf serum for 21-24 d, monocyte-derived lipid containing huge macrophages (MDLM) developed. MDLM from MDS marrow (MDS-MDLMs) and their conditioned medium (MDLM-CM) consistently suppressed the growth of normal CFU-GM colony formation. MDS-IA was active on CFU-GM during the S-phase and relatively resistant to heating. Monoclonal antibody against H subunit (acidic) ferritin and polyclonal antibody against placental ferritin neutralized the inhibitory activity of MDS-MDLMs. In addition, cell lysates of MDS-MDLMs reacted to both monoclonal anti-H subunit ferritin and polyclonal anti-placental ferritin in Western blotting analysis, indicating that the inhibitory activity was predominantly acidic isoferritin. On the other hand, MDLMs obtained from normal bone marrow had a CFU-GM enhancing activity. These results suggest that MDS-MDLMs may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors, notably H subunit isoferritin.

Adolescent↗
PubMed1992

Dark cell pathology in Menière's disease.

The dark cells in the cristae of the semicircular canals were studied histopathologically in 9 temporal bones from individuals with Menière's disease (MD group), 7 temporal bones with endolymphatic hydrops from individuals without a history of Menière's disease (non-MD hydrops group), and 10 normal temporal bones (control group). The density of the dark cells was significantly lower in specimens in the MD group versus the non-MD hydrops group (Wilcoxon's ranking test, t = 90.5, p less than 0.01) and control group (Wilcoxon's ranking test, t = 50.0, p less than 0.01), and many of the dark cells were found to be abnormal in the specimens from the MD group. The difference in dark cell density between the non-MD hydrops group and control group, however, was not significant (Wilcoxon's ranking test, t = 75.0), and few cells in these groups were abnormal. It is speculated that the differences in density and the abnormalities in dark cell morphology might be either factors in the etiology of endolymphatic hydrops or results of Menière's disease. Other, unknown, factors must be postulated to produce endolymphatic hydrops in ears with hydrops but without MD.

Adult↗
PubMed1992

Microvasculature of normal and hydropic labyrinth.

The microvasculature of the inner ear in guinea pigs and humans was observed with a scanning electron microscope using corrosion casting method. Alterations in the inner ear vasculature which occurred in association with experimental endolymphatic hydrops were also investigated. The results thus obtained are summarized as follows: 1. In the cochlea and vestibule, the arteries, coiled arterioles, and the veins are endowed with their respective characteristic morphologic features and play a role in the regulatory mechanisms of circulation. 2. The point in humans which is most different from guinea pigs was that coiled arterioles in the cochlea and the coil-like traveling of the anterior vestibular artery is not outstanding. 3. Arteriovenous anastomoses were demonstrated to exist in lateral wall of cochlea and utricular macula, a finding suggesting the existence of a regulatory mechanism for local blood flow. 4. Endolymphatic hydrops was noted to be preferentially associated with vascular abnormalities in the lateral wall of the cochlear duct and in the saccular macula, among other vestibular structures.

Animals↗
PubMed1992

[Prevention of postoperative recurrence of hepatocellular carcinoma by adjuvant locoregional chemotherapy].

Postoperative adjuvant locoregional chemotherapy was performed on patients who underwent hepatic resection for hepatocellular carcinoma with permeation of tumor into portal vein and/or into hepatic vein and/or intrahepatic metastasis to prevent recurrence. Twenty patients received intra-hepato-arterial infusion of chemotherapeutic drugs or Lipiodol, or transcatheter arterial embolization as adjuvant therapy, and 25 patients did not receive the therapy. There was no significant difference in the recurrence rate between the two groups, and disease-free-survival would not be improved significantly by adjuvant therapy. But the disease-free-survival was improved in patients who underwent relative noncurative hepatectomies. Median duration from the hepatic resection to the recurrence was prolonged by adjuvant therapy, but no significant difference was noted between the two groups. Serious hepatic injury was a side effect of adjuvant therapy in one patient. Therefore great care was necessary when performing the therapy. Further study on choice of the drugs and methods was considered necessary to obtain more effective therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Adult T-cell leukaemia-derived factor/thioredoxin expression on the HTLV-I transformed T-cell lines: heterogeneous expression in ALT-2 cells.

Adult T-cell leukaemia (ATL)-derived factor (ADF), originally described as an inducer of interleukin-2 receptor-alpha (IL-2R alpha/Tac), has homology with the co-enzyme thioredoxin which is involved in many dithiol-dependent reducing processes. Using antibody against the C-terminal synthetic polypeptide of ADF and RNA probe of ADF, we examined the expression of ADF in various cell lines by immunofluorescence, immunohistochemical staining, Western blotting and in situ hybridization. ADF was intensely expressed on HTLV-I+ T-cell lines as compared with HTLV-I- T-cell lines. While the Epstein-Barr virus (EBV)+ B-lymphoblastoid cell lines were intensely positive for ADF, Burkitt-derived B cell line Jijoye with defective EBV was negative for ADF. Electron microscopic and photomicroscopic analysis of HTLV-I+ ATL-2 cells showed that ADF was localized on both the cell membrane and cytosol. In ATL-2 cells, a marked heterogeneity of ADF expression was observed. In in situ hybridization, heterogeneity of ADF messenger RNA (mRNA) expression was also demonstrated, indicating that ADF expression was regulated in the transcriptional level.

Blotting, Western↗
PubMed1991

Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells.

Adult T cell leukemia-derived factor (ADF) is a human homologue of thioredoxin with many biologic functions including IL-2R induction, growth promotion, thiol-dependent reducing activity, and radical scavenging activity. The regulatory effect of ADF on the cytotoxic activity of TNF was examined by using a human histiocytic lymphoma cell line, U937. When U937 cells were preincubated with recombinant ADF (rADF) (0.1-100 micrograms/ml) at 37 degrees C for 30 min, TNF-dependent cytotoxicity on U937 cells was markedly inhibited. This inhibitory effect was as high as 95% in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (rADF 100 micrograms/ml) and 85% in the 51Cr-releasing assay (rADF 10 micrograms/ml). After pretreatment of U937 cells with IFN-gamma to augment the sensitivity to TNF, an inhibitory effect of rADF was also found. When U937 cells were washed after preincubation with rADF, resistance to TNF-dependent cytotoxicity was still observed, indicating that rADF inhibited the sensitivity of U937 to TNF-dependent cytotoxicity rather than modifying TNF molecules. Scatchard analysis of TNF receptors on U937 cells using 125I-TNF showed that rADF modulated neither the density nor the affinity of the cell membrane significantly. rADF also reduced the cytotoxicity induced by anti-Fas IgM mAb which shows cytotoxicity quite similar to TNF. rADF (10 micrograms/ml) reduced 90% of the cytotoxicity by anti-Fas IgM mAb, without a detectable change either in Fas Ag expression (MFI 58.1 vs 53.3) or in the degradation of anti-Fas IgM mAb as determined by flow cytometric analysis. These findings indicated that the rADF-induced resistance to the cytotoxic effect of TNF and anti-Fas mAb was not related to the modulation of the TNF receptor or Fas Ag.

Antigens, Surface↗