Biomedical subjects

H Nakamine

Publications and source records attributed to H Nakamine.

At least 37 records · Page 2Linked to original sources

PubMed1995

[Abnormality of CD4 molecule--OKT4 epitope deficiency].

The individuals with OKT4 epitope deficiency are identified as incomplete (heterozygote carriers) and complete (homozygotes) by the difference in the number of OKT4 epitopes on the surface of lymphocytes. The incidence of homozygotes in the Japanese population was found to be 0.47% by examination of 1,478 random samples, and on the basis of this value, the incidence of heterozygotes was estimated to be 12.8% by the Hardy-Weinberg's formula. This deficiency was transmitted as an autosomal codominant trait. DNA from the lymphocytes with complete OKT4 epitope deficiency from the members of three families was sequenced, and a single nucleotide base substitution (CGG-->TGG) was found. This mutation was confirmed to be responsible for OKT4 epitope deficiency by using the mouse L cells transfected with mutant CD4 cDNA. The mutation results in arginine being replaced by tryptophan. Analysis showed different hydrophobicity at positions 239 and 240 from the control, probably giving rise to a conformational change in CD4 accounting for lack of reactivity with the OKT4 monoclonal antibody. The lymphocytes with OKT4 epitope deficiency did not show any abnormality in their susceptibility to HIV infection, the internalization of CD4 molecules by TPA-treatment, the capability of producing IL-2 in vitro, and the expression of IL-2 receptors (alpha/beta-chain) by PHA-stimulation.

CD4 Antigens↗

PubMed1994

Spontaneous complete regression of high grade non-Hodgkin's lymphoma. Morphologic, immunohistochemical, and gene amplification analyses.

BACKGROUND: Spontaneous regression of non-Hodgkin's lymphoma, occasionally reported in low grade groups, is a rare phenomenon in high grade groups. Clonal proliferation has not been confirmed in the majority of reported cases. In this woman, age 58 years, who had been diagnosed as having high grade immunoblastic lymphoma after excision of a single cervical lymph node, the remaining bilateral cervical, inguinal, and axillary adenopathy regressed completely without any cytotoxic treatments 22 days after biopsy. At the time of this writing, the patient has been free of disease for 24 months. METHODS: Clonality of the lymphoproliferation in the case was examined by immunohistochemistry and polymerase chain reaction (PCR) amplification using paraffin embedded biopsy material. Possible implications of Epstein-Barr virus in the pathogenesis of this process was examined also by PCR amplification and in situ hybridization. RESULTS: The proliferating lymphoid cells showed restricted expression of immunoglobulin (Ig) light chain and amplification of clonally rearranged V-D-J regions of Ig heavy chain gene. Epstein-Barr virus did not appear to be involved in the process. CONCLUSION: The present study shows that spontaneous complete regression of clonal lymphoproliferation that is morphologically a high grade lymphoma can occur.

Biopsy↗

PubMed1994

Immunohistochemical evaluation of bone morphogenetic protein (BMP) in mixed tumor of skin.

Immunohistochemical reaction of bone morphogenetic protein (BMP) was assessed in 19 cases of skin mixed tumor and 5 cases of skin appendage tumors by using monoclonal antibody raised against BMP. All cases of skin mixed tumor showed positive staining for BMP in modified myoepithelial cells located at the periphery of tubulo-ductal or solid structures, and in plasmacytoid or tumor cells in hyalinous structures. Chondroidally changed cells also showed a strong BMP immunoreactivity. Tumors originating from sweat glands were devoid of BMP immunoreactivity. It is concluded that BMP is synthesized and produced in modified or transformed myoepithelial cells in skin mixed tumor and participates in the process of chondroid changes in the tumor.

Adenoma, Pleomorphic↗

PubMed1994

[A prospective view for the new classifications of malignant lymphomas].

Malignant lymphomas, which are now apparently the neoplasms of the immune system, are not a single disease, but represent a group of entities. Because the cells of their normal counterparts undergo differentiation in a complex manner, the corresponding neoplasms are considerably heterogeneous in terms of clinicopathologic features and biologic behavior. Indeed, there are quite a few problems to be solved in the currently used classifications of malignant lymphomas. Their complexity and heterogeneity make it almost impossible, at present, to establish any single classification system which is both clinically useful and scientifically accurate. We, therefore, propose to establish separate clinical and scientific classifications. Our prospective view for the new scientific classification of malignant lymphomas is presented.

Hodgkin Disease↗

PubMed1994

[Detection of HTLV-1 provirus DNA in T-cell neoplasms].

Using polymerase chain reaction (PCR) amplification and Southern hybridization, gag, pol, env and pX region genes of HTLV-1 provirus were detected in T-cell malignancy such as adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides in leukemic phase (MF) and, CD8-leukemia. The gag, pol, and/or env regions, were not amplified in some cases of ATLL, which was considered to be induced by mutation, but not deletion. However, the pX-1 and pX-2 regions could be amplified in all cases examined. As it is suggested that the pX gene plays an important role in leukemogenesis, the mutation may not occur in this region gene. Interestingly, the pX-2 was amplified in the cases with MF and CD8-leukemia as well. The amplified products were hybridized to the HTLV-1 pX sequence, even though the products contained DNA fragments with a size larger than expected as well as those of an expected size. These results indicated the possibility that the virus having sequence identical with HTLV-1 pX is integrated in the tumor cells of MF and CD8 leukemia.

Base Sequence↗

PubMed1993

Autosomal codominant inheritance and Japanese incidence of deficiency of OKT4 epitope with lack of reactivity resulting from conformational change.

A large Japanese family in which some members were homozygous or heterozygous for OKT4 epitope deficiency was studied. Homozygotes, heterozygotes, and normal individuals were identified by differences in the number of OKT4 epitopes on the surfaces of lymphocytes. This deficiency was transmitted as an autosomal codominant trait. The internalization of CD4 molecules and the production of IL-2 by lymphocytes of these subjects were examined. The OKT4 epitope was not needed for internalization of CD4 molecules, and IL-2 was produced in the same amounts by these different kinds of subjects. DNA from four clones lacking OKT4 established from four individuals of this family was sequenced. As reported elsewhere for different subjects, a single nucleotide substitution (CGG-->TGG) was found in all four cell lines. The mutation results in arginine being replaced by tryptophan. Analysis showed different hydrophobicity at positions 239 and 240 from the control, probably giving rise to a conformational change in CD4 accounting for lack of reactivity with the OKT4 monoclonal antibody. The incidence of homozygotes in the Japanese population was found to be 0.47% by examination of 1478 random samples, and on the basis of this value, the incidence of heterozygotes was estimated to be 12.8%.

Amino Acid Sequence↗

PubMed1993

Prognostic significance of clinical and pathologic features in diffuse large B-cell lymphoma.

BACKGROUND AND METHODS: The diffuse large cell non-Hodgkin lymphomas are a heterogeneous group of neoplasms that are potentially curable. To identify important predictors of clinical outcome, the authors evaluated the clinical and pathologic features of 114 patients with newly diagnosed diffuse large B-cell lymphoma who were uniformly staged and treated with curative intent. The authors were particularly interested in determining whether any pathologic features added to the ability of the clinical features to predict patient survival. RESULTS: Several clinical and pathologic features were found to be associated with survival by univariate analysis. However, multivariate analysis disclosed that only the stage of disease and the symptom status were significantly associated with survival. Low stage and lack of B symptoms were favorable indicators of overall survival and failure-free survival. CONCLUSIONS: The authors suggest that the evaluation of pathologic features in diffuse large B-cell lymphoma has little prognostic utility and recommend that the pathology evaluation be limited to features that are useful for diagnostic purposes.

Aged↗

PubMed1993

Oncogene rearrangement in non-Hodgkin's lymphoma with a 14q+ chromosome of unknown origin.

Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkin's lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.

Adolescent↗

PubMed1993

Characterization of clonality of Epstein-Barr virus-induced human B lymphoproliferative disease in mice with severe combined immunodeficiency.

To improve the diagnostic accuracy and understanding of the pathogenesis of lymphoproliferative diseases (LPDs) occurring in immunosuppressed transplant recipients (post-transplantation LPD), clonality of Epstein-Barr virus-induced human LPDs in mice with severe combined immunodeficiency was examined by analyzing: 1) human immunoglobulin genes and their products, 2) the clonality of Epstein-Barr virus DNA, and 3) genetic alteration of c-myc or bcl-2 genes. A spectrum of clonality was found in the LPDs comparable with that reported for post-transplantation LPDs, although rearrangements of c-myc or bcl-2 genes were not detected. It is confirmed that this system is useful in terms of clonality for understanding the early phases in the pathogenesis of post-transplantation LPD or LPD in immune deficient patients.

Animals↗

PubMed1993

Regulation by cytokines of eosinophilopoiesis and immunoglobulin E production in mice.

Certain clinical disorders are associated with eosinophilia and hyperimmunoglobulinaemia of the immunoglobulin (Ig) E class, but others give rise to eosinophilia without hyperimmunoglobulinaemia. To investigate why there are two such patterns, we immunized BALB/c mice with ovalbumin plus tetanus toxid with aluminium hydroxide gel (alum) as adjuvant, which caused eosinophilopoiesis and hyperimmunoglobulinaemia, and also immunized mice with the same antigens and complete Freund's adjuvant (CFA), which caused only eosinophilopoiesis. The difference in the adjuvant brought about the two different patterns. Monoclonal antibodies to four cytokines were used to find that eosinophilopoiesis was mediated by interleukin-5 (IL-5), whichever the adjuvant, and that IgE production in mice treated with alum was regulated by both IL-4 and IL-5. The lack of increase in IgE production was not due to suppression by interferon-gamma (IFN-gamma) or by CD8+ T cells. By the polymerase chain reaction, both IL-4 and IL-5 mRNA were detected in cells from mice given alum, but only IL-5 mRNA was found in cells from mice given CFA. Thus, alum used as the adjuvant resulted in both eosinophilopoiesis and IgE production, but CFA resulted in eosinophilopoiesis alone. The dissociation between eosinophilopoiesis and IgE production shown in the mice given CFA could be due to the dissociation between the expression of mRNA of the cytokines IL-4 and IL-5 in vivo.

Adjuvants, Immunologic↗

PubMed1992

Immunophenotypic and genotypic characterization of lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) is a chronic dermatosis that histologically resembles malignant lymphoma. Thus far, only a few cases of LyP have been characterized in detail with regard to immunophenotype, genotype, and karyotype. OBJECTIVE: Our purpose was to study seven patients with LyP and compare the results to those reported in the literature. METHODS: Skin biopsy specimens were analyzed by frozen section immunohistochemical and molecular biologic techniques. Cytogenetic analysis was also performed in three cases. RESULTS: The atypical lymphoid cells consisted of activated helper T cells; four of the seven patients had lesions with a detectable clonal T-cell population. A peripheral T-cell lymphoma developed in one patient before the emergence of a genotypically different LyP T-cell clone. Cytogenetic studies were abnormal in one case of LyP and normal in another, whereas the karyotype of the lymphoma was abnormal. CONCLUSION: LyP is a preneoplastic proliferation of activated helper T cells, which is often clonal and may regress and expand with the development of new LyP clones or lymphoma.

Adolescent↗

PubMed1992

Richter's syndrome with different immunoglobulin light chain types. Molecular and cytogenetic features indicate a common clonal origin.

To investigate the issue of clonality in Richter's syndrome, phenotypic, molecular genetic, and cytogenetic studies were performed on tumor tissue from a patient with concurrent chronic lymphocytic leukemia and diffuse large cell lymphoma in a single lymph node specimen. The tumor was biphenotypic for immunoglobulin (Ig) expression with surface Ig lambda-positive chronic lymphocytic leukemia and surface and cytoplasmic Ig kappa-positive diffuse large cell lymphoma. DNA samples prepared from areas of the lymph node rich in chronic lymphocytic leukemia cells and diffuse large cell lymphoma cells were examined in parallel. Identical Ig heavy chain gene rearrangements were detected in the BamHI and EcoRI digests of the two samples, but the patterns of rearrangement were different in the HindIII and PstI digests. Because it is very unlikely that multiple rearranged Ig heavy chain gene fragments of identical size would be found in more than one enzyme digest from two independently derived B-cell clones, it is probable that the two processes originated from a single clone. Modifications after rearrangement probably accounted for the differing band sizes seen in the HindIII and PstI digests. These conclusions are supported by cytogenetic analysis, which revealed two clones with a common primary abnormality (trisomy 12), one of which also exhibited secondary abnormalities. Therefore, Richter's syndrome may represent a composite tumor of common clonal origin, even when differences in light chain expression are identified.

Aged↗

PubMed1992

The whale (Odontoceti) spleen: a type of primitive mammalian spleen.

Three spleens from two Odontoceti species were studied histo-anatomically. These spleens consisted of lymphatic nodules, the red pulp (broad sense), and the trabeculo-capsular system composed of the elasto-fibroleiomyocytic tissue. The periarterial lymphatic sheath (PALS) was unclear. Two layers, the intermediate zone and perivenous layer, were distinguishable in the red pulp (broad sense). The perivenous layer was narrow in width and consisted of venules and the intervascular reticular tissue rich in myeloid cells. The collecting and drainage veins were enclosed in this layer. The perivenous layer corresponds to the red pulp (narrow sense) of the common mammalian spleen and may be under involution in a process that probably relates to the remodelling of the intrasplenic vein. The pattern of the arteriovenous communication seemed to be closed, and no ellipsoids were noted around arterial terminals. The Odontoceti spleen has two venous drainage routes (hilar and capsular systems), suggesting a primitive state of evolution, and may be an additional example of the primitive mammalian spleen.

Animals↗

PubMed1992

Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.

In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model.

Animals↗

PubMed1991

SCID mouse model of Epstein-Barr virus-induced lymphomagenesis of immunodeficient humans.

Immunodeficient humans are at very high risk of developing Epstein-Barr virus (EBV)-induced lymphomagenesis. Severe combined immunodeficient mice (SCID) have been shown to develop lymphoproliferative disease (LPD) following transfer of peripheral blood leukocytes (PBL) with latent EBV. To study mechanisms of lymphomagenesis, we compared results of engraftment of PBL from normal donors and immunodeficient donors with X-linked lymphoproliferative disease (XLP). Graft-versus-host disease (GVHD) developed in 6 of 10 SCID mice 4 to 8 weeks following transfer of PBL from normal donors. In contrast, none of 9 mice engrafted with PBL from XLP patients with T-cell defects showed GVHD. LPD developed in mice regardless of the immune competence of the donors. The expression of EBV-encoded proteins, results of immunophenotyping, and karyotyping of the LPD lesions revealed lethal oligoclonal LPD owing to transfer of latent EBV in B cells in mice engrafted with PBL from seropositive donors. Polyclonal LDP developed in mice engrafted with PBL from seronegative patients which were infected with B95-8 virus 6 weeks after transfer of the cells. This model is useful for investigating mechanisms of EBV-induced LDP in immunodeficient patients.

Animals↗

PubMed1991

Atypical large plasma cells in lymph node granulomas in cat-scratch disease.

A histological variant of plasma cells found in the granulomas of cat-scratch disease (CSD) lymphadenitis is reported. Though the lesion shows the typical features of suppurative granulomatous lymphadenitis, many atypical giant cells which have abundant basophilic cytoplasm and bizarre nuclei with occasional multinucleated forms are noted among epithelioid histiocytes. The diagnosis of CSD lymphadenitis was confirmed by comparing clinical; histopathological, and histochemical (Warthin-Starry silver impregnation stain) studies on lymph node sections from five cases with features typical of the disease. Histochemical (methyl green-pyronine stain) and immunohistochemical examination provided several lines of evidence indicating that the atypical giant cells in our case were plasmacytic and confirmed that its proliferation was reactive, not neoplastic. Multinucleated giant cells were also occasionally present in the other five cases, but they had histological and immunohistochemical features of Langhans' type giant cells. We stress the importance of distinguishing such atypical large plasma cells from neoplastic cells.

Adolescent↗

PubMed1991

Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations.

Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma. A dendritic staining pattern within germinal centers was present in 25 of 26 routinely processed lymph nodes with reactive follicular hyperplasia. In contrast, dendritic staining with anti-NGFR was present within neoplastic follicles in only three of 28 follicular lymphomas. Staining of benign, residual germinal centers with anti-NGFR was present in mantle zone lymphoma and Hodgkin's disease. These findings suggest a possible role for the NGFR in the maturation and/or activation of normal DRCs. The loss of NGFR expression in most follicular lymphomas indicates that DRCs are altered as part of the neoplastic process. The possibility that DRCs may play a role in the pathogenesis of follicular lymphoma is suggested.

Dendritic Cells↗

PubMed1991

Immunoblastic lymphoma with abundant clear cytoplasm. A comparative study of B- and T-cell types.

The morphologic, phenotypic, molecular genetic, and clinical features of 34 cases of clear-cell immunoblastic lymphoma (IBLC) are described. Sixteen cases were of B-cell type (IBLC-B) and 18 cases were of T-cell type (IBLC-T). There were no significant differences in the morphologic characteristics of the neoplastic cells in the two types, although IBLC-B was less likely to be polymorphic than IBLC-T. Interfollicular proliferation, a higher mitotic rate, infiltration by eosinophils, and an increase in capillary-sized blood vessels were also features of IBLC-T, whereas necrosis and fibrosis were more extensive in IBLC-B. Patients with IBLC-B were predominantly female, whereas those with IBLC-T were predominantly male. The mean age was 62 years for those with IBLC-B and 46 years for those with IBLC-T. Patients with IBLC-B usually had lower-stage disease, but there was no significant difference in survival rate between those with IBLC-B and those with IBLC-T. Although most cases of IBLC have been considered to be of peripheral T-cell origin, the authors conclude that IBLC-B is more common than previously considered and that clear-cell morphologic characteristics are not a reliable indicator of T-cell type.

Cytoplasm↗