Biomedical subjects

Shigeo Nakamura

Publications and source records attributed to Shigeo Nakamura.

160 records · Page 9Linked to original sources

PubMed2002

Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin-6 as independent predictors of prognosis in aggressive non-Hodgkin's lymphoma.

Therapeutic approaches for non-Hodgkin's lymphoma (NHL) are currently based on the International Prognostic Index (IPI). Research on biological prognostic factors has been actively pursued in recent years, with serum vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) being identified as prognostic factors for NHL. Here, we determined that serum VEGF and IL-6 levels are independent prognostic factors for aggressive lymphoma. Compared with normal controls, serum VEGF and IL-6 levels were significantly higher in patients with aggressive lymphoma or adult T-cell leukemia/lymphoma. Furthermore, overall and disease-free survival rates for patients with high levels of VEGF or IL-6 were significantly poorer than for patients with low levels. In addition, the prognosis for patients with high levels of both serum VEGF and IL-6 was significantly poorer than that for patients with high levels of either VEGF or IL-6 or with low levels of both VEGF and IL-6. Multivariate analyses of a variety of prognostic factors, including the five IPI factors, revealed that serum VEGF and IL-6 were both independent prognostic factors for overall survival of aggressive lymphoma. Therefore, a combination of VEGF and IL-6 represents a useful prognostic factor for aggressive lymphoma.

Adolescent↗

PubMed2002

SPARC stimulates the synthesis of OPG/OCIF, MMP-2 and DNA in human periodontal ligament cells.

BACKGROUND: Osteonectin/secreted protein, acidic and rich in cysteine (SPARC) is expressed in periodontal ligaments. Therefore, a better understanding of the action of SPARC on periodontal ligament cells could help to elucidate remodelling and repair mechanisms in periodontal tissue. In the present study, we examined the effects of human platelet-derived SPARC (hp-SPARC) on the expressions of SPARC and osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF), alkaline phosphatase (ALPase) activity, matrix metalloproteinase-2 (MMP-2) production and DNA synthesis in cultures of human periodontal ligament (HPL) cells. METHODS: HPL cells at the sixth passage were exposed to hp-SPARC. The expression of OPG/OCIF and SPARC mRNAs was examined by Northern blot analysis. The protein levels for OPG/OCIF and MMP-2 were determined by Western blot analysis. ALPase activity was measured by the method of Bessey et al. DNA synthesis was estimated by incorporation of [3H] thymidine. RESULTS: Hp-SPARC enhanced OPG/OCIF synthesis at the protein and mRNA levels. Hp-SPARC also enhanced DNA and MMP-2 synthesis dose-dependently, but had little effect on ALPase activity and SPARC mRNA expression. CONCLUSION: SPARC may play a role in remodelling and repair of periodontal tissue by promoting proliferation and MMP-2 production. It may also regulate osteoclast formation through OPG/OCIF in periodontal ligament cells.

Alkaline Phosphatase↗

PubMed2002

Expression of cutaneous lymphocyte antigen is associated with a poor outcome of nasal-type natural killer-cell lymphoma.

Nasal and nasal-type natural killer (NK) lymphoma is a distinct clinicopathological entity mostly associated with Epstein-Barr virus. Cases that have widespread lesions are resistant to ordinary anti-cancer therapy and take a highly aggressive course. To date, there are no available data on the relationships between the localization, clinical outcome and expression of adhesion molecules in such cases. We examined the expression of cutaneous lymphocyte antigen (CLA) in 52 cases of NK-cell lymphoma. CLA was highly expressed in cutaneous cases. Also, the CLA+ group (n=29) had a much worse prognosis than the CLA- group (n=23), regardless of the primary site or clinical staging. Univariate analysis identified some significant prognostic factors, and multivariate analysis of these factors showed that the expression of CLA was an independent prognostic indicator. In conclusion, the present findings established that CLA is an independent and important prognostic factor in patients with NK-cell lymphomas.

Adolescent↗

PubMed2002

Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report.

We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sjögren's syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT.

Aged↗

PubMed2002

Cellular composition of subacute thyroiditis. an immunohistochemical study of six cases.

To clarify the cellular composition of subacute thyroiditis, histologic and immunohistochemical studies were performed. Histologically, the lesion presented a patchy distribution of non-caseous granulomas comprising colloid, small lymphocytes, neutrophils, macrophages with or without epithelioid features, and multinucleated giant cells of foreign body type. In addition, numerous plasmacytoid monocytes were closely associated with the granulomas. The giant cells were CD68+, thyroglobulin- and cytokeratin-. Usually, small lymphocytes in the granulomas are CD3+, CD8+, CD45RO+ cytotoxic T-cells. In the non-granulomatous lesion, the follicles were often infiltrated by CD8+ T-lymphocytes, plasmacytoid monocytes and histiocytes, resulting in disrupted basement membrane and rupture of the follicles. Lymphoid follicles with or without active germinal centers were not observed. Moreover, no residual follicular dendritic cell networks were detected by CD23 and CAN.42 immunostains. In the interfollicular area, scattered plasma cells were observed among infiltrating cells. Neither human herpes virus 8 nor EBER-positive cells were detected in the six patients. The findings of our study suggest that cellular immune response may play an important role in the pathogenesis of subacute thyroiditis.

Aged↗

PubMed2002

VH gene analysis in sporadic Burkitt's lymphoma: somatic mutation and intraclonal diversity with special reference to the tumor cells involving germinal center.

We analyzed the immunoglobulin heavy chain variable region (V(H)) gene in seven cases of sporadic Burkitt's lymphoma (sBL) to elucidate their cell of origin. In particular, we focused on the V(H) gene status of tumor cells involving adjacent germinal center (GC) by microdissecting histological sections. Among the seven V(H) genes V(H)1 family was found in two, V(H)3 in four, and V(H)4 in one. All rearranged V(H) genes demonstrated somatic mutations at percentages ranging from 1.4 to 7.5% (mean, 4.2%), which is a similar level to that seen in IgM-only B cells. Three out of four V(H) genes with more than 2% sequence difference from their corresponding germline counterpart showed evidence of antigen selection in their framework region 3. Three cases demonstrated signs of intraclonal diversity with a mutational frequency of 0.47-0.98%, which was 13.5-28.8 times as great as the Taq infidelity in our experimental conditions. However the level of somatic mutation and the effect of antigen selection on V(H) gene were diverse in these three cases, and the relationship between V(H) gene somatic mutation status and intraclonal diversity was unclear in sBL. In the analysis of microdissected tissues, all 20 tumor clones in the adjacent GCs showed additional replacement mutations in complementarity determining region 3, suggesting a role of antigen in tumor progression. This finding resembles the phenomenon that memory B-cells reenter into GC to undergo further affinity maturation. In contrast, 7/11 V(H) gene sequences irrelevant to GC were identical to those of the major tumor clone. Thus our findings suggested that sBL is derived from memory B-cells rather than GC B-cells, and that antigen stimulation is involved in the clonal expansion of a proportion of sBL.

Amino Acid Sequence↗

PubMed2002

Release from post-transcriptional gene silencing by cell proliferation in transgenic tobacco plants: possible mechanism for noninheritance of the silencing.

Transgenic tobacco plants that overproduce luciferase (Luc) frequently exhibit post-transcriptional gene silencing (PTGS) of luc. The silencing was observed over five generations and found not to be inherited but acquired by the next generation at a certain frequency. Luc imaging analysis of silenced plants revealed Luc activity only in proliferating tissues such as shoot meristem and developing flower. The luc gene expression has been recovered from silencing before development of germ cells, excluding a possible recovery from the PTGS at meiosis. A systemic silencing signal transferred from older tissue likely induces gene silencing of younger tissues in which cell proliferation has been completed. Only seeds maintained Luc activity, probably because of isolation from the silencing signal by a possible partition from the parent placenta. Calli newly induced from the leaf pieces of silenced plants recovered from the silencing and exhibited strong Luc activity similar to nonsilenced leaves, further indicating that the silencing cannot be maintained in proliferating cells. Thus release from PTGS in proliferating cells is a possible mechanism for noninheritance of silencing.

Cell Division↗

PubMed2002

Centroblastic and centroblastic/centrocytic lymphoma associated with a prominent epithelioid granulomatous response: a clinicopathologic study of 50 cases.

A minority of centroblastic and centroblastic/centrocytic cell lymphomas are accompanied by a prominent epithelioid cell response and were suggested to be a distinct variant of B-cell lymphoma of germinal center cell origin. To confirm the clinicopathologic significance of these mainly large B-cell lymphomas with an epithelioid cell response (LBCL-ER), we reviewed 50 patients with LBCL-ER and compared the results with those of 167 other diffuse large B-cell lymphomas (DLBCL) and 94 follicular lymphomas (FL) without epithelioid response. The patients with LBCL-ER showed a higher age distribution (median 71, P =.03), a female predominance (M:F = 18:32, P =.001) and less frequent involvement of extranodal sites >1 (P =.004) compared with those with DLBCL, and presented with a bulky mass of the affected lymph nodes in 54% of cases. They were also older (P =.0006) and more associated with the aggressive clinical factors such as serum LDH level and International Prognostic Index score than those with FL. Histologically, nine cases (18%) partially showed a follicular growth pattern, and the others (82%) were occupied by a diffuse growth pattern. The epithelioid cells were accumulated in large demarcated masses, partially imparting a lymphoepithelioid (Lennert) lymphoma-like appearance to some portions of the lesions in every case. Immunohistochemically, LBCR-ER was positive for CD20 in every case, CD10 in 43% of the cases, and BCL-2 in 56%. None of the tumor cells in the 40 cases tested expressed CD5 antigen. Immunostaining also often highlighted the remnants of the follicular dendritic cell network. The BCL-2 gene rearrangement was detected in only 19% of the cases examined. The survival curve of the cases of LBCL-ER was almost identical with that of DLBCL and was significantly inferior to that of FL. The centroblastic and centroblastic/centrocytic lymphoma with an epithelioid cell response may be regarded as the morphologic variant of DLBCL preferentially arising in the aged population and reflecting the disease progression of FL.

Adult↗

PubMed2002

The distinction between Burkitt lymphoma and diffuse large B-Cell lymphoma with c-myc rearrangement.

To compare immunophenotypic and molecular features between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with c-myc rearrangements (c-mycR DLBCL), we analyzed 18 cases of B-cell non-Hodgkin's lymphoma with c-mycR that were confirmed by chromosomal and/or Southern blotting analyses. The cases were histologically classified into 10 BLs and five DLBCLs. The remaining three cases could not be classified because of suboptimal quality of the surgical materials. BLs were from five adults and five children, whereas all DLBCLs were from adults. BLs were positive for CD20 (10/10 cases examined), CD10 (9/10), Bcl-2 (1/9), and Bcl-6 (10/10), whereas they were negative for CD3 (0/10) and EBV (0/8), by Epstein-Barr virus (EBV) EBER-1 RNA in situ hybridization. c-MycR DLBCLs were positive for CD20 (5/5), CD10 (2/5), Bcl-2 (3/4), and Bcl-6 (4/4), whereas none of them were positive for CD3 and EBV. A mean of MIB-1 index (MIB-1+ cells/neoplastic cells, %) of BLs (98.1%) was higher than that of c-mycR DLBCLs (66.3%; P <.0001). Somatic mutation of immunoglobulin heavy-chain gene variable region (VH gene) in BLs (four cases) ranged from 0.7 to 4.9% with an average value of 2.3%, whereas those in DLBCLs (three cases) from 8.2 to 32.0% with an average value of 17.0%. It is, therefore, concluded that a growth fraction of nearly 100%, as well as a monotonous proliferation of medium-sized cells and c-myc(R), should be of value in the diagnosis of BL, which is probably different from c-myc(R) DLBCL. In addition, CD10+, Bcl-2-, and low frequency of mutation of the VH gene could be helpful for the histologic distinction of BL from (c-mycR) DLBCL.

Adult↗

PubMed2002

Clinicopathologic comparison between the API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type.

Little is known about the clinicopathological differences between API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type. The aim of this study was to clarify those differences in gastric MALT lymphoma. Twenty-three patients with gastric MALT lymphoma were enrolled in a unicenter study. Helicobacter pylori (H. pylori) infection status and clinical stages were investigated. Antibacterial treatment was performed for every patient. Responsiveness of MALT lymphoma to this treatment was assessed by means of regular follow-up endoscopy combined with biopsy. All cases were examined for API2-MALT1 chimeric transcript by means of RT-PCR and sequencing analyses. H. pylori infection status was assessed as positive in 20 patients and negative in three. With regard to responsiveness to antibacterial treatment, complete remission was observed in two patients, partial remission in 12 and no change in nine. API2-MALT1 chimeric transcript was detected in seven patients, all of whom showed no change in response to antibacterial treatment. API2-MALT1 positivity was found to be significantly correlated with responsiveness to antibacterial treatment (P = 0.0001), absence of H. pylori infection (P = 0.0198), and gross cobblestone mucosa observed endoscopically (P = 0.0198). For the other factors (age, sex, dominant site of lesion, high-grade component, infiltrated layer of gastric wall, nodal involvement or clinical stages), there were no differences between API2-MALT1 chimeric transcript-positive and -negative cases. Gastric API2-MALT1 chimeric transcript-positive MALT lymphoma generally features unresponsiveness to antibacterial treatment, and is thought to be unrelated to H. pylori infection in its pathogenesis. Our findings indicate the presence of different clinical subtypes in gastric MALT lymphomas.

Adult↗

PubMed2002

MUM1/IRF4 expression is an unfavorable prognostic factor in B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

B-Cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL / SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV(H)), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = 0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV(H) status were independent unfavorable prognostic factors in patients with B-CLL / SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL / SLL. The biological role and mechanism of action of MUM1 in B-CLL / SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.

ADP-ribosyl Cyclase↗

PubMed2002

Lymph node lesion in adult-onset Still's disease resembling peripheral T-cell lymphoma: a report of three cases.

Adult-onset Still's disease (AOSD) is known to be a cause of fever of unknown origin. We describe the clinicopathologic, immunohistologic, and genotypic features of 3 patients with lymph node lesions from AOSD, which posed a serious diagnostic difficulty from peripheral T-cell lymphomas. The patients were 22-, 26-, and 63-year-old Japanese women. At the onset of disease, all patients had multicentric lymphadenopathy in association with clinical and laboratory findings suggestive of a malignant lymphoma. None of the patients developed malignant lymphomas during the follow-up period. Histologically, the lesions were characterized by paracortical hyperplasia with prominent vascular proliferation. In the paracortical area, there was a mixed infiltrate including small-to-medium-sized lymphocytes, variable numbers of eosinophils, plasma cells, and B immunoblasts. Polymerase chain reaction analysis demonstrated that neither clonal rearrangement of the T-cell receptor gamma-chain gene nor immunoglobulin heavy-chain rearrangement was detected in any patient. Although AOSD appears to be a rare systemic inflammatory disorder, the lymph node lesion should be added to the differential consideration of benign lymph node lesions simulating node-based peripheral T-cell lymphoma.

Adult↗

PubMed2002

Lymph node infarction associated with infectious mononucleosis: report of a case resembling lymph node infarction associated with malignant lymphoma.

A completely infarcted lymph node should alert the pathologist to the high possibility of malignant lymphoma. The lymph node lesion of infectious mononucleosis (IM) shows marked histologic diversity and occasionally may be confused with malignant lymphoma. We report a rare case of IM showing extensive lymph node infarction whose lymph node lesion was similar to lymph node infarction associated with malignant lymphoma. This case describes a 32-year-old Japanese man who had signs and symptoms consistent with IM, which he was later proven serologically to have, but whose cervical lymph node showed extensive lymph node infarction with a thin area of granulation tissue beneath the capsule. The infarcted tissue contained numerous eosinophilic ghosts of large lymphoid cells. The thin granulation tissue was composed of numerous small lymphocytes, plasma cells, and histiocytes, in addition to large lymphoid cells including immunoblasts and granulocytes. CD20, CD3, and CD45RO immunostains revealed the mixed B- and T-cell nature of the ghosts of large lymphoid cells in the infarcted tissue as well as viable large cells in the granulation tissue. The patient was free from disease after 50 months' follow-up.

Adult↗

PubMed2002

[Clinicopathologic features of intravascular large B-cell lymphoma in Japan: review of the special reference to the Asian variant].

The Asian variant of intravascular large B-cell lymphoma (IVL) is characterized by hemophagocytic syndrome, i.e. the clinical features include pancytopenia, hepatosplenomegaly, and rarely mass formation. It usually lacks any neurological abnormality or skin lesions, which are typical features of classical IVL. Sixty-seven cases of IVL reported in Japan since 1990 were classified into two groups, and their clinicopathologic features were compared. Forty-five cases of IVL that met the clinical and laboratory criteria for the Asian variant were classified into Group A (average: 66 yr; male: 62%), and 22 cases that did not meet the criteria were classified into Group C (average: 65 yr; male: 73%). Hemophagocytosis was described only in Group A. The positivity rates for bone marrow invasion, fever, hyperbilirubinemia and elevated levels of LDH and CRP were significantly (p = 0.0037, p < 0.0001, p = 0.0428, p = 0.0108 and p = 0.0008, respectively) higher in Group A than in Group C. On the other hand, the positivity rates for neurological abnormality and skin lesions were significantly (p < 0.0001 and p = 0.0011, respectively) higher in Group C than in Group A. Our reassessment of the reported cases of IVL in Japan identified two major categories of IVL: the classical form and the Asian variant.

Aged↗

PubMed2000

Clinical relevance of telomerase activity in primary gastric lymphoma.

BACKGROUND: To distinguish between low-grade lymphoma and reactive lymphoid infiltrate can be demanding for pathologists. Demonstration of B-cell monoclonality by polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain is useful as referential data. Telomerase activity, which is frequently detected in malignant tumors while being undetectable in normal tissues, may also have a supportive role in the diagnostic procedure, but has not been investigated in specimens of primary gastric lymphoma. METHODS: Telomerase activity was qualitatively and quantitatively evaluated, using fluorescence-based telomeric amplification assay protocol (TRAP) analysis, in 16 malignant lymphoma and related specimens, including 7 specimens of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, among which specimens before and after Helicobacter pylori eradication were evaluated from five patients. RESULTS: Telomerase activity was detected more frequently (6 of 7 specimens) at higher levels in high-grade lymphoma compared with low-grade MALT lymphoma. It was detected in 3 of 7 specimens of low-grade MALT lymphoma, but was undetectable either at the stage of Helicobacter pylori-induced gastritis or after H. pylori eradication therapy. CONCLUSION: Telomerase activity evaluated by fluorescence-based TRAP analysis was detectable late in the process of evolution of MALT lymphoma and was undetectable early in the process of regression. It was frequently and overtly elevated in high-grade lymphoma. Telomerase activity may have a role in confirming the histologic diagnosis of primary gastric lymphoma.

Journal Article↗

PubMedDate not supplied

Beneficial actions of hyaluronan (HA) on arthritic joints: effects of molecular weight of HA on elasticity of cartilage matrix.

Hyaluronan (HA) has viscoelastic, anti-inflammatory and protective actions in joint tissues, and is being widely used for treatment of OA and RA patients. However, the mechanisms underlying the pharmacological action of HA on OA and RA have not been fully understood. In this article, we review the molecular weight-dependent, anti-inflammatory actions of HA preparations - produced in Japan - in joint tissues, and show that the molecular weight of HA, but not its concentration, is crucial for maintenance of cartilage elasticity.

Animals↗