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Biomedical subjects

M Koike

Publications and source records attributed to M Koike.

At least 235 records · Page 13Linked to original sources
PubMed1994

Microsatellite instability in the progression of gastric carcinoma.

Seventy-six gastric carcinomas were analyzed with regard to whether or how microsatellite instability was associated with the development of the carcinoma. Microsatellite instability occurred as a late genetic alteration, with an incidence significantly higher in the advanced stage (17 of 51) than in the early stage (3 of 25; P < 0.05). Chromosomal losses on 5q and 17p, detected by polymerase chain reaction-restriction fragment length polymorphism, more frequently accompanied microsatellite instability (9 of 15 and 8 of 11, respectively), compared with carcinomas which lacked instability (5 of 28 and 9 of 30, respectively; P < 0.01 and P < 0.05, respectively). Epstein-Barr virus was observed in only 8 of 76 carcinomas, none of which was associated with microsatellite instability. No significant correlation was found between instability and the familial tendency to develop gastric carcinomas. Our results suggest that microsatellite instability might play a role in the progression of gastric carcinomas but not in Epstein-Barr virus-associated gastric carcinomas.

Adult↗
PubMed1994

Growth inhibition of SV40-transformed human keratinocytes by TGF-beta s is not linked to dephosphorylation of the Rb gene product.

We found that transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2 inhibited the growth of normal human keratinocytes and their SV40-transformed counterpart in a dose dependent manner. Both normal and SV-40 transformed keratinocytes accumulated in G1 when treated with TGF-beta s. The hyperphosphorylated form of Rb gene product (RB) was reduced by TGF-beta s in normal keratinocytes. In contrast, phosphorylation of RB was not essentially affected in SV-40 transformed cells. This uncoupling of growth kinetics and phosphorylation states of RB in SV-40 transformed keratinocytes suggests that RB is not the primary target of action for TGF-beta s and that additional factors or pathways may be involved in mechanisms of the growth inhibition.

Blotting, Western↗
PubMed1994

Chimeric anti-ganglioside GM2 antibody with antitumor activity.

Ganglioside GM2, which is one of the major gangliosides expressed on the cell surface of human tumors of neuroectodermal origin, has been focused on as a target molecule for passive immunotherapy. GM2 is thought to be one of the T-cell-independent antigens and to elicit only IgM antibody responses in rodents and humans. We have previously established two murine anti-GM2 monoclonal antibodies with high specificity and strong binding activity, KM696 and KM697, both of which are of the IgM class. Variable heavy and light chain complementary DNAs of these two murine monoclonal antibodies were cloned and used in the construction of mouse/human IgG1 chimeric antibodies, KM966 and KM967, respectively, in this study. One of the chimeric antibodies, KM966, retained strong and specific reactivity with GM2 and showed the similarity of the binding activity with tumor cell lines to that of the original murine monoclonal antibody. Indirect immunofluorescence staining of tumor cell lines with the chimeric KM966 revealed that the antigen was expressed in substantial amounts on pulmonary tumor cells and leukemia cells as well as neuroectodermal origin tumor cells. When human serum and human peripheral blood mononuclear cells were used as effectors in complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity, respectively, chimeric KM966 was fully effective in killing GM2-expressing tumor cells. In addition, i.v. injection of chimeric KM966 markedly suppressed the establishment of human tumor xenografts in nude mice. Taken together, chimeric KM966 is the first antibody of the human IgG class to ganglioside GM2 and has strong antitumor activity both in vitro and in vivo. It is likely that chimeric KM966 will be a useful agent for passive immunotherapy of human cancer.

Amino Acid Sequence↗
PubMed1994

Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential.

BACKGROUND: The molecular genetic changes associated with colorectal carcinoma are among the best understood of any common human cancer. The genetic changes during the late stages of colorectal carcinomas may be useful in clinical management for determining the metastatic potential of the carcinoma. METHODS: Tumor tissues were evaluated by restriction fragment length polymorphism (RFLP) analysis of chromosomes 5q, 17p, 18q, and 22q (n = 98), by reverse transcription-polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of the DCC gene (deleted in colorectal carcinoma) (n = 27) and by immunohistochemical analysis of p53 protein expression (n = 44). RESULTS: Loss of heterozygosity (LOH) on chromosomes 17p, 18q, and 22q, but not on 5q, was much more frequently detected in advanced carcinomas than in intramucosal carcinomas (P < 0.01). 17p LOH was significantly correlated with vascular invasion (P < 0.001), whereas 18q LOH was correlated with lymphatic invasion and hepatic metastasis (P < 0.01), and 22q LOH was correlated with lymph node metastasis (P < 0.05). LOH on 5q did not show a significant correlation with any factors of tumor invasion or metastasis. DCC expression was not observed in any of five hepatic metastasis or in five of seven advanced carcinomas that were accompanied by hepatic metastasis (10 of 12). However, a similar lack of expression was observed in only 5 of 15 carcinomas without hepatic metastasis (P < 0.05). p53 Expression was found to vary in both primary and metastatic carcinomas by immunohistochemistry. CONCLUSIONS: The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22q and RT-PCR analysis of DCC expression into messenger RNA) can be used to determine the metastatic potential of colorectal carcinomas.

Adult↗
PubMed1994

Immunoglobulin class switch of anti-ganglioside monoclonal antibody from IgM to IgG.

Ganglioside GM2, which is one of the major gangliosides expressed on cell surface of neuroectodermal-origin human tumors, has been focused on as a target molecule for passive immunotherapy. One of the problems in this area was that monoclonal antibodies (mAbs) raised against GM2 were of IgM class even if donors of B cells were varied in mouse, rat or human. We stimulated two kinds of mice hybridomas having membrane-bound anti-GM2 IgM on their surface with GM2 incorporated in synthetic liposomes in the presence of the mouse thymocytes to accelerate the class switch of immunoglobulins (Igs). After the stimulation, protein A-reactive clones were sorted out using a cell sorter. We finally isolated two class switch variants generating mouse IgG3, designated KM796 and KM750, from original hybridomas producing mouse IgM anti-GM2 mAbs, KM696 and KM697, respectively after over 20-time repetitions of the sorting. ELISA with 11 common gangliosides revealed that one of the variant, KM750, retained the same binding specificity to N-acetyl GM2 as that of the parental IgM, KM697. By ELISA using panel of anti-idiotype (Id) mAbs to anti-GM2 mAbs, KM750 was shown to retain the parental KM697 Id. Another variant KM796 almost lost its activity in purification process in acidic condition and changes in Id were suggested. In immunofluorescence assay, KM750 was confirmed to bind to GM2-expressing tumor cell lines. The class switch hybridoma has been stably cultured with the production of the IgG3-class mAb for more than 22 months.

Animals↗
PubMed1994

Pyothorax-associated pleural lymphoma. A case evolving from T-cell-rich lymphoid infiltration to overt B-cell lymphoma in association with Epstein-Barr virus.

BACKGROUND: Pyothorax-associated pleural lymphomas (PAPL) occur in patients with long-standing pyothorax. Epstein-Barr virus (EBV) plays an important role in its development. METHODS: An atypical case of PAPL is reported and its clinical features are compared with those of five cases of ordinary PAPL. RESULTS: The histology of the lymphoma changed from prominent T-cell infiltration to an overt B-cell lymphoma of diffuse, large cell-type. DNA studies of the lymphoma at the first presentation demonstrated dual rearrangement in the T-cell receptor beta (TCR beta) and immunoglobulin heavy chain J region (IgJH) genes. EBV genome analysis demonstrated monoclonal expansion of EBV-infected cells. EBV gene products were present only in large lymphocytes with B-cell phenotype. The same rearranged band of the IgJH gene, but not clonal rearrangement of the TCR beta gene, was observed in the overt B-cell lymphoma at the relapse. The same EBV-infected clone was observed throughout the course of the disease. The tumor was localized at the pyothorax wall, and cell-mediated immunity, reflected by a positive tuberculin reaction, was preserved only in the current case. CONCLUSIONS: T-cell-rich lymphoid infiltration in the current case is a variant of EBV-associated PAPL, which is infiltrated by reactive T-cells with clonal accentuation. This is the first documented case of EBV-associated PAPL evolving from T-cell-rich lymphoid infiltration.

Aged↗
PubMed1994

Abnormality of the alpha-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer's disease.

To test whether previously demonstrated reductions in the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC) in Alzheimer's disease (AD) brain also occur in morphologically normal AD tissues, we examined KGDHC in cultured skin fibroblasts from patients with familial AD (FAD). KGDHC activity was reduced by 44% in the FAD cells (p < 0.002) from the 4 families studied, including a within-kindred comparison of affected and escapee subjects in the chromosome 14q24.3-linked Nova Scotia kindred. The activities of several other glutamate- and glutamine-metabolizing enzymes were normal in the FAD cells, as was the activity of another mitochondrial multienzyme dehydrogenase complex, that for pyruvate. Mixing experiments indicated that the abnormality of KGDHC activity in FAD fibroblasts was not due to an inhibitor or to excess protease activity. KGDHC is a complex of three proteins. Immunoblots for the E2k component under conditions of optimal protease inhibition revealed the expected 46-kd species in both AD and non-AD fibroblasts, but the patient cells also regularly contained an additional 29-kd species that was absent or present in minimal amounts in the controls. Immunoblotting demonstrated no abnormalities in the E1k and E3 components. Other studies indicate that the human gene for E2k residues on chromosome 14q24.3, in a region associated with FAD in a number of families including the KGDHC-deficient Nova Scotia kindred. The persistence of abnormalities in KGDHC and particularly in its E2k component in FAD fibroblasts indicates that abnormalities of this autosomally coded nuclear component are an intrinsic part of the AD process, and the possible role of this abnormality in the pathogenesis of AD is discussed.

Alzheimer Disease↗
PubMed1994

Down-regulation of membrane immunoglobulin-associated proteins, MB-1, B29 and Lyn, in AIDS-lymphomas and related conditions.

B-lymphocytes infected with Epstein-Barr virus (EBV) can proliferate in immunocompromised hosts to form lymphomas (MLs). Similar MLs are produced in mice with severe combined immune deficiency (SCID) by transfusion of human lymphocytes infected with EBV (SCID-EBV-positive BML). Mb-1 and B29 are recently found transmembrane proteins associated with membrane immunoglobulins (mIg) on the surface of B cells. Lyn is a src family gene product expressed in B cells submembranously, in association with mIg, possibly through Mb-1/B29 heterodimer. These mIg-associated proteins (Mb-1, B29 and Lyn) are known to mediate antigenic stimulation through mIgs. We noted recently that Lyn is decreased selectively in around a half of SCID-EBV-positive BMLs. We extended this line of investigation to other mIg-associated proteins. Five acquired immunodeficiency syndrome (AIDS)-MLs and ten SCID-EBV-positive BMLs were first analysed by immunohistochemistry for the expression of Mb-1, B29 and Lyn. It was found that in AIDS-MLs, all the mIg-associated proteins were heavily down-regulated. In SCID-EBV-positive BMLs, Mb-1 was down regulated in six of ten, B29 in nine of ten and Lyn in six of ten, whereas no down-regulation was noted in eight EBV-free B MLs that were also maintained in SCID mice. An additional flow-cytometric study of two SCID-EBV-positive and two EBV-negative BMLs showed similar down-regulation in the former cases exclusively. Whereas mIg was also decreased in three of five SCID-EBV positive BMLs, it did not necessarily match the decrease of mIg-associated proteins, which contrasts with the recent finding that mIgs coexist with Mb-1 or B29. Some EBV-encoded proteins may activate host molecules located downwardly; this, in turn, may lead to the suppression of these upwardly-located mIg-associated proteins.

Adult↗
PubMed1994

Laterality of mental imagery generation and operation: tests with brain-damaged patients and normal adults.

The relationships between hemispheric function and components of the imagery process were examined in patients with unilateral right and left brain damage and in intact adult subjects. In the image generation condition, subjects were required to mentally generate Katakana letters corresponding to Hiragana letters displayed on a CRT. The results for the intact adults suggested a left hemisphere superiority, but the unilaterally brain-damaged subjects showed no hemispheric difference in this task. In the imagery operation task (transformation or lateral translation), subjects were asked to find a genuine Kanji among distractors (pseudo-Kanji) that were constructed from two Kanji radicals (themselves real Kanji) that were either displayed in reverse order or shifted apart. The results for both intact adults and patients with unilateral brain damage suggest the superiority of the right hemisphere.

Adult↗
PubMed1994

Immunodeficiency and IL-6 production by peripheral blood monocytes in multicentric Castleman's disease.

To study the pathogenesis of multicentric Castleman's disease (MCD), IL-6 producing cells and immune function were investigated in four MCD patients. The expression of IL-6 mRNA in one MCD lymph node was analysed by in situ hybridization. IL-6 mRNA expressing cells were scattered in the interfollicular areas and did not resemble plasma cells. Spontaneous IL-6 production was detected in the culture supernatants of peripheral blood mononuclear cells (PBMNC) from four patients. The IL-6 producing cells among the PBMNC were found to be monocytes by both in situ hybridization and immunohistochemistry. We evaluated immune function in four MCD patients. These studies show: (1) a negative PPD skin test in 3/4 patients, (2) decreased IL-2 production in 3/4 patients, (3) decreased T cell colony formation in 3/4 patients, (4) decreased NK activity and NK cell number in 2/4 patients, (5) increased soluble IL-2 receptor in 4/4 patients, and (6) decreased CD4/CD8 ratio in 3/4 patients. These results show that MCD resembles, in several ways, acquired immunodeficiency syndrome (AIDS).

Aged↗
PubMed1994

IL-5 and its receptor: which role do they play in the immune response?

IL-5 is a homodimeric glycoprotein that promotes proliferation and differentiation of activated B cells, and controls the production and functions of some other hematopoietic cells, such as Ly-1(CD5)+ B cells, eosinophils and basophils. In humans, IL-5 acts as a differentiation and growth factor for eosinophils, and is the major cytokine involved in the production of eosinophilia. IL-5 acts on its target cells through the specific receptor that is composed of two polypeptide chains, a and b. The alpha-chain is unique to IL-5, while the beta-chain is common to IL-5 receptor, IL-3 receptor and granulocyte-macrophage colony stimulating factor (GM-CSF) receptor.

Amino Acid Sequence↗
PubMed1994

CD5 expression in thymic carcinoma.

To determine the differences between the cellular characteristics of thymic carcinoma and thymoma, immunohistochemical analysis with lymphocyte markers (CD1a, 3, 4, 5, 8, 10, 20, 21, 25, 30, 57, and 72) was performed on 23 thymic epithelial tumors other than lymphocytic thymoma: overt thymic carcinoma (OC, n = 7), atypical thymoma (n = 5), and typical thymoma (epithelial or mixed thymoma, n = 11). Among the surface antigens examined, CD5, a type of receptor molecule that signals cell growth in T cells, was expressed in neoplastic epithelial cells of the thymus, in OC (seven of seven) and atypical thymoma (two of five), but not in typical thymoma. Double labeling immunofluorescence demonstrated expression of CD5 in cytokeratin-positive cells. The CD5 molecule extracted from an OC tumor showed the same molecular size as that in the spleen, but CD72, a ligand of CD5 on the surface of B cells, was not found in the epithelial cells of OC or atypical thymoma. Expression of CD5 was not observed in carcinomas of other organs, such as lung (n = 15), breast (n = 4), esophagus (n = 6), stomach (n = 6), colon (n = 9), and uterine cervix (n = 3). CD5 is closely related to morphological changes in thymic epithelial tumors and may play a role in the evolution of OC through receptor-ligand interaction.

Antigens, CD↗
PubMed1994

Epstein-Barr virus-associated gastric carcinoma and Epstein-Barr virus infection of the stomach.

BACKGROUND: Epstein-Barr virus (EBV) has been found to be associated with a type of gastric carcinoma (EBVaGC). However, many questions remain unanswered, such as epidemiology, and pathologic features of EBVaGC and the significance of EBV in the genesis of EBVaGC. EXPERIMENTAL DESIGN: Gastric carcinoma and non-neoplastic mucosa were evaluated to reveal the following issues: the incidence of EBVaGC in Japanese population, pathologic features and EBV genotype, clonality, and gene-expression in EBVaGC, localization of EBV in non-neoplastic stomach, and serum titer of anti-EBV antibodies in EBVaGC-carrying patients. RESULTS: Using PCR and EBER1 in situ hybridization, EBVaGC (definitely amplifiable EBV-DNA and positive EBER1-signal in the nuclei of carcinoma cells) was found in 8 of 72 gastric carcinomas (11%). The dominant genotype of EBV was type A (7/8), with type C (6/8), and F (8/8) restriction enzyme polymorphism, which are the predominant type of EBV found in throat washing of the general population in Japan. EBVaGC was found in the cardia (4/8) or body (4/8) of the stomach, and consisted of 7 advanced and 1 intramucosal carcinoma. By Southern blot analysis of EBVaGC hybridized with right- and left-side probe adjacent to the terminal repeats, EBV was present in a monoclonal episomal form in all of the EBVaGC. EBVaGC lacked expression of EBNA2 (0/8) and LMP1 (0/8) by immunocytochemistry. In non-neoplastic mucosa, EBER1 signal was identified in the infiltrating lymphocytes and shedding epithelial cells predominantly in fundic gland mucosa of patients with EBVaGC (8/8). Patients with EBVaGC showed high titers of anti-VCA IgG (8/8), anti-VCA IgA (2/8) and anti-EA IgG (7/8) antibodies just before surgery. CONCLUSIONS: EBV may infect the surface epithelium of the stomach through the reactivated EBV-carrying lymphocytes. EBV may be a factor initiating EBVaGC. Anti-EBV antibodies or EBER1 in situ hybridization may help to identify patients at high risk for EBVaGC.

Antibodies, Viral↗
PubMed1993

Allelic loss at chromosome band 8p21.3-p22 is associated with progression of hepatocellular carcinoma.

Human hepatocellular carcinomas (HCC) frequently show loss of heterozygosity at loci on the short arm of chromosome 8. To define a region on 8p commonly deleted in HCC, we used 20 restriction fragment length polymorphism markers to carry out detailed deletion mapping in 142 HCC. Of the 124 informative cases, 56 (45%) showed allelic losses in tumors. While more than half of them had lost alleles at every locus on the short arm, others lost them partially or interstitially. Common deletion of an 8-cM region flanked by cMSR-32 and cC18-245, at 8p21.3-p22, suggested the presence of a tumor suppressor gene(s) in this interval. Correlation between allelic losses on 8p and clinicopathological parameters were examined in the 51 cases for which detailed clinical data were available; allelic losses on 8p were observed in none of five tumors at stage T1 (0%), nine of 20 tumors at stage T2 (45%), and 17 of 26 tumors at stage T3/T4 (65%). A higher frequency of allelic losses on 8p was observed in poorly differentiated tumors (10/14, 71%) than in well differentiated tumors (3/13, 23%). The association of allelic losses on 8p with advanced clinical stage and poor differentiation implies that loss or inactivation of a tumor suppressor gene(s) on 8p may play a role in the progression of HCC.

Carcinoma, Hepatocellular↗