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Biomedical subjects

R Maekawa

Publications and source records attributed to R Maekawa.

13 recordsLinked to original sources
PubMed1992

Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II?

Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DR beta on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.

Aged↗
PubMed1992

A case of an undifferentiated small cell carcinoma of the esophagus with a primary abdominal mass.

This paper reports a case with an undifferentiated carcinoma of the esophagus which primarily developed symptoms due to metastatic lesions. The case was a 59-year-old woman with a primary manifestation of an abdominal mass and with subsequent dysphagia. A protruding lesion with ulceration was found at the lower third of the thoracic esophagus by endoscopic examination and was histologically proved to be an undifferentiated carcinoma by biopsy. The abdominal mass was initially thought to be due to metastasis to an abdominal lymph node based on the diagnosis image finding at admission, but it was consequently found by autopsy to be a metastatic tumor in the liver. Therefore, undifferentiated carcinoma of the esophagus should be take into account for differential diagnosis of an abdominal mass.

Abdominal Neoplasms↗
PubMed1991

Myeloid progenitor cell growth characteristics and effect of G-CSF in a patient with congenital cyclic neutropenia.

A 17-year-old male with congenital cyclic neutropenia was treated with recombinant human granulocyte colony stimulating factor (G-CSF) administered subcutaneously at 1 to 2 micrograms/kg per day. The peak and nadir counts of neutrophils and the peak counts of monocytes were significantly elevated, and the period of cycling decreased from 3 to 2 weeks. Bone marrow culture studies revealed the following abnormalities in granulocytic progenitor cells (CFU-G): a decrease in the concentrations of G-cluster forming cells, stimulated by a maximal dose of G-CSF, and a tendency of abnormally low responsive growth of the CFU-G to lower concentrations of G-CSF and GM-CSF. Our findings suggest that administration of G-CSF at relatively low doses overcomes or compensates for these abnormalities, though not completely, as fluctuation in the neutrophil counts persisted.

Bone Marrow↗
PubMed1990

Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus.

Cytotoxic T lymphocytes (CTL) play an important role in recovery from a number of viral infections. They are also implicated in virus-induced immunopathology as best demonstrated in lymphocytic choriomeningitis virus (LCMV) infection of adult immunocompetent mice. In the present study, the structure of the T-cell receptor (TCR) in LCMV-specific CTL in C57BL/6 (B6) mice was investigated. Spleen T cells obtained from LCMV-infected mice were cultured in vitro with virus-infected stimulator cells and then stained with anti-TCR V beta antibodies. A skewing of V beta usage was noticeable in T cells enriched for their reactivity to LCMV, suggesting that particular V segments are important for the recognition of LCMV T-cell epitopes in B6 mice. To gain more detailed information on the structure of the TCR specific for LCMV epitopes, we studied CTL clones. It has been shown that approximately 90% of LCMV-reactive CTL clones generated in H-2b mice are specific for a short peptide fragment of the LCMV glycoprotein, residues 278 to 286, recognized in the context of the class I major histocompatibility complex molecule, Db. Four CTL clones possessing the specificity were randomly selected from a collection of clones, and their TCR genes were isolated by cDNA cloning or by the anchored polymerase chain reaction. All four clones were found to use V alpha gene segments belonging to the V alpha 4 subfamily. By RNA blot analysis, two more clones with the same specificity were also shown to express the V alpha 4 mRNA. In contrast, three different V beta gene segments were used among the four clones examined. J beta 2.1 was used by three of the clones. Although amino acid sequences in the V(D)J junctional regions were dissimilar, aspartic acid was found in the V alpha J alpha and/or V beta D beta J beta junctions of all four of these clones, suggesting that this residue is involved in binding the LCMV fragment. Restricted usage of V alpha and possibly J beta segments in the CTL response to a major T-cell epitope of LCMV raises the possibility that immunopathology in LCMV infection can be treated with antibodies directed against such TCR segments. Thus, similar analysis of the TCR in other virus infections is warranted and may lead to therapeutic strategies for immunopathology due to virus infections.

Amino Acid Sequence↗
PubMed1989

Distinct antitumor mechanisms of recombinant interleukin-2 on recombinant interleukin-2-activated killer-sensitive and -resistant murine tumors.

The antitumor mechanism of recombinant human interleukin-2 (rIL-2) was studied using two murine tumor systems. Meth 8 tumor cells were easily lysed in vitro by rIL-2-activated killer (AK) cells, which mainly consisted of Thy1.2+, Lyt2.2+, L3T4- T cells, and asialo GM1+ natural killer (NK) cells; on the other hand, X5563 tumor cells were only slightly lysed in vitro by AK cells under the same conditions. One of these two tumors was inoculated i.d. into C3H/HeN mice and then rIL-2 (5 X 10(4) J.U./mouse/day) was repeatedly injected s.c. For AK-sensitive Meth 8-bearing mice, rIL-2 therapy starting 1 day after tumor inoculation was more effective for the growth than the therapy starting 7 days later and the therapeutic effect was abrogated by in vivo treatment with anti-asialo-GM1 serum. In contrast, for mice bearing AK-resistant X5563 tumor cells, delayed administration starting on day 7 or later was more beneficial than earlier administration on day 1 or 4. This treatment schedule resulted in complete tumor regression in a dose-dependent manner including significant inhibition of metastases in the spleen and/or lymph nodes. These therapeutic effects of rIL-2 on X5563 were not seen in T-depleted mice with anti-mouse thymocyte serum but were found in NK-depleted mice upon treatment with anti-asialo-GM1 serum. The results of these studies showed that the growth of AK-sensitive Meth 8 tumor was inhibited by AK cells, while the growth and metastases of AK-resistant X5563 tumor was inhibited by tumor-specific T cells, which were generated after tumor development and activated by rIL-2 therapy, rather than AK cells.

Animals↗
PubMed1988

Distinct antitumor mechanisms of recombinant murine interferon-gamma against two murine tumor models.

The antitumor activity of recombinant murine interferon-gamma (rMuIFN-gamma) against B16 melanoma and EL4 thymoma, which display different sensitivities in in vitro tests, was studied. In antiproliferation tests, B16 cells were highly sensitive to rMuIFN-gamma and growth was markedly inhibited at as low as 10 U/ml, whereas EL4 cells resisted treatment even at concentration as high as 10(4) U/ml. One of these two tumors was inoculated i.d. into C57BL/6 mice and then rMuIFN-gamma (10(4) units) was repeatedly injected s.c. starting 1 day after the tumor inoculation. For the B16-bearing mice, tumor growth was markedly suppressed and the mean survival period was prolonged, but cured mice were not observed. For mice bearing EL4 cells, the therapeutic effects were more pronounced and cured mice were observed. The EL4-cured mice showed in vivo protective immunity against EL4 tumors but not against P815 tumors, indicating tumor specificity. Histologically, a large number of lymphocytes had infiltrated the necrotic tumor mass. These results indicated that rMuIFN-gamma may have not only a direct effect but also an indirect effect in host-mediated murine response on the growth of murine tumor cells under in vivo conditions.

Animals↗
PubMed1988

Differential efficacies of recombinant murine interferon-gamma and recombinant human interleukin 2 against EL4-bearing mice.

The effects of treating tumor-bearing mice with recombinant murine interferon-gamma (rMuIFN-gamma) and recombinant human interleukin-2 (rIL2) were compared using EL4 thymoma with the same mouse model. Successive administration of rMuIFN-gamma (10(4) units) starting 1 day after tumor inoculation was highly effective, while rIL2 (5 x 10(4) Jurkat units) starting 7 days later produced potent suppression of tumor growth leading to complete cure in about 50% of the mice treated with either of two agents. These results showed that the effectiveness of these lymphokines differed depending on the time of their administration. Furthermore, the therapeutic effect of rIL2 against tumor-bearing mouse was poorer in T-cell-deficient nude mice than in B6 mice and NK-cell-deficient beige mice, whereas the effect of rMuIFN-gamma was poorer in beige mice than in B6 and nude mice. These results suggest that the role of NK cells in the tumor regression caused by the treatment of rMuIFN-gamma is much more important than that of other activated lymphocytes, and that the antitumor activity of rIL2 may be due to the generation of T-cell-related lymphocytes. Our results reveal that combination therapy with rMuIFN-gamma and rIL2 can induce a synergistic effect on EL4-bearing mice.

Animals↗
PubMed1986

Effect of recombinant interleukin 2 (R-IL2) on in vivo growth of murine myeloma X5563.

The present study deals with the effect of recombinant interleukin 2 (R-IL2) on in vivo growth of murine myeloma X5563. Administration of R-IL2 (5 X 10(4) J.U./mouse per day) s. c. starting 1 day after X5563 inoculation i.d. had a marginal effect on the growth of X5563, and all the mice repeatedly given R-IL2 from day 1 to day 17 died. However, daily administration of R-IL2 starting 7 days after the tumor inoculation was highly effective and significantly lengthened survival time compared with the control mice injected with vehicle alone. About 50% of the treated mice were completely cured, and survived for more than a month after the therapy ceased. In a representative experiment, where the growth of X5563 was slow because of the small number of inoculated tumor cells, all the mice (n = 6) given R-IL2 from day 11 to day 23 showed complete cure of the established X5563 solid tumor. These mice showed in vivo protective immunity and in vitro cytotoxic T cell responses to X5563 tumor antigens. Histologically, a large number of macrophages and lymphocytes had infiltrated the area around the necrotic X5563 tumor mass in the mice which had received R-IL2 therapy. These results suggest that repeated injections of R-IL2 at the local site after tumor development can augment antitumor immunological responses and subsequently induce tumor regression.

Animals↗
PubMed1986

Suppressive effect of ultraviolet-B-irradiation of epidermal cells on the induction of contact sensitivity.

Contact sensitivity to trinitrophenyl (TNP) hapten was induced by subcutaneous (s.c.) administration of TNP-modified syngeneic spleen cells or epidermal cells (EC) (TNP-EC). Intraperitoneal (i.p.) inoculation of TNP-EC resulted in a comparable response, whereas i.p. administration of TNP-spleen cells or TNP-modified-ultraviolet (UV)-preirradiated EC (TNP-UV-EC) failed to induce TNP-contact sensitivity responses. The present study investigates the effect of UV-irradiation on the potential of EC for inducing the contact sensitivity response. Exposure of BALB/c mouse EC in vitro to 1600 J/m2 of UV-B before they were modified with TNP had no discernible effect on the Ia-positivity and viability of EC. Coexistence of TNP-UV-EC had no inhibitory effect upon the contact sensitivity response induced by TNP-EC via the i.p. route. The absence of suppressor cell generation was substantiated by the adoptive transfer of spleen cells from mice administered TNP-UV-EC i.p. to normal syngeneic mice. The effect of interleukin 1 (IL-1) or epidermal cell-derived thymocyte-activating factor (ETAF) in restoring the ability of TNP-UV-EC to induce contact sensitivity was examined. IL-1 or ETAF administered along with TNP-spleen cells i.p. induced a potent contact sensitivity response, whereas the same preparations of IL-1 or ETAF were unable to restore the contact sensitivity induction by TNP-UV-EC. The results are discussed in the context of UV-induced cell surface changes of the Langerhans cell population.

Animals↗
PubMed1986

Expression of H-2 antigens and inducibility of antitumor immune responses in various tumor cell clones established from methylcholanthrene-induced fibrosarcomas.

A large number of fibrosarcoma cell lines was established in vitro from a tumor mass induced freshly by inoculating 3-methylcholanthrene (MCA) subcutaneously (sc) into C3H/HeN mice, and more than five clones were isolated from each cell line by the limiting dilution technique. The present study investigated a) qualitative and quantitative comparison of the immunogenicity [tumor-associated transplantation antigen (TATA) activity] of different tumor clones and b) the relationship between such immunogenicity and the expression of H-2 class I antigens. When TATA were compared between different clones from the same tumor, these TATA were revealed to be cross-reactive to each other. On the other hand, the comparison of TATA between clones from different tumors demonstrated the existence of individually unique TATA in these clones. In addition to qualitative heterogeneity of TATA from different tumors, the magnitude of immunogenicity was also heterogeneous in the individual clones established. Whether or not such quantitative heterogeneity of immunogenic strength was related to the expression of H-2 (class I) antigens was examined by flow microfluorometry studies using anti-H-2k antibodies. The results demonstrated that there was no correlation between TATA activity capable of inducing in vivo tumor resistance and the expression of H-2 antigens. This contrasted with parallelism between the expression of H-2 antigens and inducibility of cytotoxic T lymphocytes (CTL) or lysability of tumor cell clones by CTL. These results are discussed in the context of the cellular mechanism of tumor cell eradication in vivo and the regulation of cell surface H-2 expression in vitro and in vivo.

Animals↗
PubMed1979

[Superimpose of images by appending two simple video amplifier circuits to color television (author's transl)].

Images are very useful to obtain diagnostic informations in medical fields. Also by superimposing two or three images obtained from the same patient, various informations, for example a degree of overlapping and anatomical land mark, which can not be found in only one image, can be often found. In this paper characteristics of our trial color television system for the purpose of superimposing X-ray images and/or radionuclide images are described. This color television system, superimposing two images in each different color consists of two monochromatic vidicon cameras and 20 inches conventional color television in which only two simple video amplifier circuits are added. Signals from vidicon cameras are amplified about 40 dB and are directly applied to cathode terminals of color CRT in the television. This system is very simple and economical color displays, and enhance a degree of overlapping and displacement between images. As one of typical clinical applications, pancreas images were superimposed in color by this method. As a result, size and position of pancreas was enhanced. Also X-ray image and radionuclide image were superimposed to find exactly the position of tumors. Furthermore this system was very useful for color display of multinuclides scintigraphy.

Amplifiers, Electronic↗