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Shigeo Nakamura

Publications and source records attributed to Shigeo Nakamura.

At least 37 records · Page 2Linked to original sources
PubMed2006

Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma.

Aggressive adult T-cell leukemia/lymphoma (ATLL) such as acute and lymphoma types are fatal diseases with poor prognosis. Although these 2 subtypes feature different clinicopathologic characteristics, no detailed comparative analyses of genomic/genetic alterations have been reported. We performed array-based comparative genomic hybridization for 17 acute and 49 lymphoma cases as well as real-time quantitative polymerase chain reaction (PCR) to identify the target genes of recurrently amplified regions. Comparison of the genome profiles of acute and lymphoma types revealed that the lymphoma type had significantly more frequent gains at 1q, 2p, 4q, 7p, and 7q, and losses of 10p, 13q, 16q, and 18p, whereas the acute type showed a gain of 3/3p. Of the recurrent high-level amplifications found at 1p36, 6p25, 7p22, 7q, and 14q32 in the lymphoma type, we were able to demonstrate that CARMA1 is a possible target gene of the 7p22 amplification for the lymphoma type but not for the acute type. Furthermore, we found BCL11B overexpression in the acute type regardless of the 14q32 gain/amplification, but no or low expression of the gene in the lymphoma type. These results suggest that acute and lymphoma types are genomically distinct subtypes, and thus may develop tumors via distinct genetic pathways.

Adult↗
PubMed2006

A past history of gastric ulcers and Helicobacter pylori infection increase the risk of gastric malignant lymphoma.

Helicobacter pylori (H. pylori) is a causative agent for peptic ulcers as well as some types of gastric lymphoma; however, the relationship between a peptic ulcer history in combination with H. pylori infection and the risk of gastric lymphoma has not been fully evaluated. To examine this point, we conducted a case-control study with 645 patients histologically diagnosed as having malignant lymphomas and 3225 non-cancer controls. Plasma H. pylori IgG status was assessed for subgroups for which blood samples were available (116 cases and 114 controls). An association with a history of gastric, but not duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41, 95% confidence interval (CI): 3.12-9.39]. In the examination according to histological subtype, the OR was high for both gastric mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI: 2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95% CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of total gastric lymphoma was associated with H. pylori infection (OR = 5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and DLBCL (8 out of 9: 88.9%). Further, in subgroup analysis of subjects with H. pylori infection, gastric ulcer history, but not duodenal ulcer history was associated with the risk of gastric lymphoma (OR = 4.15, 95% CI: 1.02-16.89). In conclusion, we found a positive association with a past history of gastric ulcer and H. pylori infection for gastric lymphoma, while duodenal ulcer history was no association. These results suggested the risk of gastric lymphoma increased by interaction between H. pylori infection and gastric ulcer history. Further studies are warranted.

Adolescent↗
PubMed2006

Changes in androgen-producing cell size and circulating 11-ketotestosterone level during female-male sex change of honeycomb grouper Epinephelus merra.

11-ketotestosterone (11-KT), a potent male-specific androgen in fish, has important roles on spermatogenesis, male behavior, and nuptial coloration. The site of 11-KT synthesis and its role on male germ cell development during protogynous sex change is not clearly understood. We examined the dynamics of steroidogenic enzymes immunolocalization, viz cholesterol side-chain cleavage (P450scc), biomarker of steroids and cytochrome P45011beta-hydroxylase (P45011beta), downstream to 11-KT production, throughout the process of sex change in honeycomb grouper (Epinephelus merra). In female, P450scc immunoreactivity (-ir) was observed in the theca layer and tunica near blood vessels (BV). During the onset of sex change, P450scc reactive cells were observed in the remaining follicle layer of degenerated oocyte of the ovo-testis in early transitional (ET) and late transitional (LT). In male, P450scc-ir was localized in the interstitial Legdig cells of testis. P45011beta reactive cells were observed in the tunica near BV in female but not in theca layer. In ET and LT phases gonads, P45011beta localized in remaining follicle layer of degenerated oocyte and tunica near BV. On the other hand, in male, both interstices and tunica near BV showed strong signals against P45011beta. Moreover, in vivo and in vitro levels of 11-KT related with the changes in the nuclei diameter of P45011beta-positive cells in both tunica near BV and remaining follicle layer of degenerated oocyte to interstices during the progress of sex change. The present results suggest that 11-KT produced in the tunica near BV may provide the stimulus for female to degenerate oocytes and initiate sex change. However, 11-KT produced both in tunica near BV and remaining follicle layer of degenerated oocyte possibly plays critical role during testicular differentiation as well as gonadal restructuring at mid to late phases (ET to LT) of sex change in honeycomb grouper.

Androgens↗
PubMed2006

Immunoglobulin VH genes in thymic MALT lymphoma are biased toward a restricted repertoire and are frequently unmutated.

Thymic MALT lymphoma shows certain distinctive features among MALT lymphomas, such as expression of IgA isotype, consistent lack of API2-MALT1 gene fusion, and very strong association with autoimmune disease, especially Sjogren's syndrome. To help clarify the nature of the clonal lymphoid infiltrates, we analysed the usage and somatic hypermutation of the Ig heavy chain variable region (V(H)) genes in nine different cases. The V(H) rearrangement was potentially functional in all cases and was restricted to the V(H)3 family. V(H) usage was biased toward V(H)3-30 (five cases) and V(H)3-23 (three cases) segments, which have both been frequently expressed by autoimmune B cells. Somatic hypermutation was absent in five cases. Fewer than the expected replacement mutations were found in the framework regions in two cases, indicating a negative antigen selection pressure. Ongoing mutation was absent in all cases. D segment usage was varied, whereas J(H) segment usage was restricted to J(H)4. The observed patterns of V(H) usage and mutations suggested that specific antigens may play a pathologically relevant role in the genesis or progression of thymic MALT lymphoma.

Aged↗
PubMed2006

AH amyloidosis associated with lymphoplasmacytic lymphoma secreting a monoclonal gamma heavy chain carrying an unusual truncated D segment.

To date, the presence of amyloidosis associated with immunoglobulin heavy chain (AH amyloidosis) was reported in only 7 cases. Although AH amyloidosis is caused mainly by plasma cell dyscrasia, as in AL amyloidosis, we report a 61-year-old patient who presented with nephrotic syndrome caused by AH amyloidosis associated with lymphoplasmacytic lymphoma. Biochemical and molecular analyses of the deposited amyloid fibrils and heavy-chain genes of lymphocytes showed that proliferative lymphoma cells produced a gamma heavy chain, not a mu heavy chain, which carried an unusual truncated diversity (D) segment of the variable region. Our results indicate that production of the abnormal heavy chain caused by the partially deleted D segment gene is responsible for gamma heavy-chain-related amyloid fibril formation in this patient.

Amyloidosis↗
PubMed2006

Cytogenetic and clinicopathological characterization by fluorescence in situ hybridization on paraffin-embedded tissue sections of twenty-six cases with malignant lymphoma of small intestine.

OBJECTIVE: In small intestinal malignant lymphoma (SIML), the correlation between specific chromosomal abnormalities and clinicopathological features remains unclear. The aim of this study was to determine the frequency of chromosomal translocations involving the BCL1, BCL2, c-MYC, BCL6 and MALT1 genes by using fluorescence in situ hybridization directly on paraffin-embedded tissue sections (tissue-FISH). MATERIAL AND METHODS: Twenty-six cases diagnosed as having SIML between 1996 and 2003 were the subjects of the clinicopathological investigation conducted in this study. Tissue-FISH was performed with specific probes on paraffin-embedded tissue sections as described previously. RESULTS: The primary site was frequently located at the duodenum (9 cases, 35%). In accordance with the World Health Organization classification, 14 (53%) cases were diagnosed as having diffuse large B-cell lymphoma (DLBCL) and 6 (23%) as marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Macroscopically, DLBCL and MALT lymphoma displayed various macroscopic features. Cytogenetically, IGH-BCL2 translocation was detected in 3 (21%) out of 14 DLBCL cases, but in none of the MALT lymphomas. BCL6 translocation was detected in 5 (35%) of 14 DLBCL cases and in 1 (17%) of 6 MALT lymphoma cases (17%). API2-MALT1 translocation was detected in 1 (7%) of 14 DLBCL cases and in 1 (17%) of 6 MALT lymphoma cases. CONCLUSIONS: The duodenum was preferentially involved in SIML. DLBCL and MALT lymphoma showed various macroscopic features. Tissue-FISH analysis disclosed that DLBCL is cytogenetically heterogeneous. Furthermore, our study validated tissue-FISH as an additional promising diagnostic tool for detecting specific chromosomal translocations in NHL.

Adolescent↗
PubMed2006

Epstein-Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B-cell lymphoma.

Primary gastric diffuse large B-cell lymphomas are generally well controlled by non-surgical treatment with combination chemotherapy followed by radiotherapy. We have previously reported that over 90% of patients achieved complete response (CR) with this therapeutic strategy: three cycles of cyclophosphamide, adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy). Although the CR rate was very high, some patients still showed resistance to this combination therapy. In order to clarify the factors related to therapy resistance, we examined the relationship between Epstein-Barr virus (EBV), which was examined using an in situ hybridization technique, and the patients' clinical courses. Out of the 50 patients, four were EBV positive; over half of lymphoma cells were positive for EBV by in situ hybridization. Of the three EBV-positive patients, two showed progressive disease and one achieved partial response (PR). Two of the patients died of disease progression. The other patient achieved CR, but the lymphoma recurred with distant metastasis in the cerebellum 3 months after remission. In the present study, eight patients did not achieve CR or they relapsed, four patients showed progressive disease, one patient achieved PR, and three patients achieved CR with recurrence. Therefore, half of these unfavorable patients were EBV positive. This finding strongly indicated that EBV-associated gastric diffuse large B-cell lymphomas frequently show resistance to standard chemoradiotherapy, although some other adverse factors remain unclear.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Characterization of target genes at the 2p15-16 amplicon in diffuse large B-cell lymphoma.

Amplification of 2p has been observed as a recurrent alteration in diffuse large B-cell lymphoma (DLBCL). Whereas two candidate oncogenes, REL and BCL11A, have been investigated as targets for 2p amplification, the question remains as to whether the true target gene in the amplicon is REL, BCL11A or both. We previously identified frequent genomic gains of chromosomal 2p in 25 out of 99 DLBCL cases by means of genome-wide array comparative genomic hybridization (CGH). All of these 25 cases included recurrent copy number gain at 2p15-16. In the study presented here, cases were analyzed in greater detail by means of contig bacterial artificial chromosome (BAC) array CGH for the 4.5-Mb region at 2p15-16, which contained 33 BAC clones. We confined the minimal common region to 500-kb in length, where only the candidate oncogene REL, and not BCL11A, is located. Real-time quantitative PCR was carried out to investigate the correlation between genomic gain and expression. It showed a significant correlation for both genes, indicating that these two genes are common targets for the 2p15-16 amplicon. However, given the fact that REL is more frequently amplified than BCL11A, the REL gene may play a more important role than BCL11A in the pathogenesis of DLBCL.

Chromosomes, Artificial, Bacterial↗
PubMed2006

Follicular lymphoma frequently originates in the salivary gland.

The aim of the present study was to examine the clinicopathological presentations of follicular lymphomas (FL) of the salivary glands, as compared to mucosa-associated lymphoid tissue (MALT) lymphomas. A total of 27 primary salivary gland lymphomas were examined: 6 FL (five, grade 1; one, grade 2); 19 MALT lymphomas; and two diffuse large B-cell lymphomas. The FL patients ranged in age from 24 to 73 years, with a mean of 49 years, which was younger than that of MALT patients (mean: 64 years; P < 0.05). Four of the six FL arose from the submandibular gland, which was the origin of only five out of a total of 19 MALT lymphomas. One FL patient was in clinical stage (CS) IE, two in CS IIE, and two in CS III and IV. As regards the MALT lymphoma patients, 13 (68%) were in CS IE and five (26%) in CS IIE. None of the FL patients had clinical diagnosis of autoimmune disease but eight MALT lymphoma patients had autoimmune disease. The present study found a relatively high incidence of FL in the salivary glands. The observed differences in age of onset, background of autoimmune disease, and lesion site suggests that the pathogenesis of FL may differ from that of MALT lymphoma.

Adult↗
PubMed2006

Histological variety of floral variant of follicular lymphoma.

To further clarify the histopathological findings of the floral variant of follicular lymphoma (FVFL), we studied 13 Japanese cases. Two histological subtypes of neoplastic follicles of FVFL have been described: (i) A macrogerminal center pattern where the mantle zone lymphocytes were invaginated into the neoplastic germinal center, often reminiscent of a floral design. (ii) A microgerminal center pattern where the massive invasion of mantle zone lymphocytes resulted in almost complete breakage of the neoplastic follicles. In the former pattern, the neoplastic germinal center usually contained large clusters of tumor cells, whereas in the latter, small clusters of up to 20 tumor cells or isolated tumor cells were observed in the neoplastic germinal centers. Moreover, occasional tumor cells showed a lymphocytic and/or histiocytic Reed-Sternberg cell (L&H cells)-like morphology. Both types of neoplastic follicles were observed to a varying degree in most cases. The macrogerminal center pattern was predominant in nine cases (70%), whilst the microgerminal center pattern was predominant in only four cases (30%). Three lesions (23%) had a marginal zone component. Immunohistochemistry showed that atypical follicular center cells, including L&H cells, were CD3-, CD5-, CD10+, CD20+, CD43-, bcl-2+, cyclinD1-. The overall histological findings of the macrogerminal center are similar to those of florid progressive transformation of germinal center (PTGC), whilst the microgerminal center pattern is similar to that of nodular lymphocyte-predominant Hodgkin lymphoma. Initially, the differential diagnosis between FVFL and florid PTGC was emphasized. However, the present study indicates that nodal marginal zone B-cell lymphoma possessing floral follicles and nodular lymphocyte-predominant Hodgkin lymphoma should be added to the differential diagnosis of FVFL. The germinal center B-cell nature of FVFL is most clearly recognizable by immunohistochemistry, though histological appearance alone may cause some diagnostic problems.

Adult↗
PubMed2006

Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases.

We conducted clinicopathologic and immunohistochemical analyses of the prevalence of Epstein-Barr virus (EBV) among 24 patients with malignant lymphoma complicating systemic rheumatic diseases. (SRD) These 24 patients included 17 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 2 with systemic sclerosis (SS), and 2 with dermatomyositis (DM). There were 2 men and 22 women ranging in age from 30 to 86 years (mean: 64 years). The interval between the onset of rheumatic disease and that of malignant lymphomas ranged from 3 months to 35 years (mean: 142 months). The use of immunosuppressive drugs before the onset of malignant lymphoma was recorded in 15 patients. Among them, 5 patients received methotrexate (MTX) therapy. Malignant lymphomas were found at extranodal sites in 9 patients, and the disease was in the advanced stage in 17 patients. Histologic and immunohistochemical studies demonstrated that 18 cases (75%) were B-cell lymphoma (RA=12, SLE=2, SS=2, DM=2), 3 (12.5%) were peripheral T-cell lymphoma (RA=3), and 3 (12.5%) were classical Hodgkin lymphoma (RA=2, SLE=1). As in previous reports, there was an increased frequency of diffuse large B-cell lymphoma (50%) in the present series. Moreover, a majority of the diffuse large B-cell lymphomas exhibited activated B-cell phenotype. EBV-encoded small RNAs (Epstein-Barr early region [EBER]-) and/or LMP-1+tumor cells were identified in only 3 cases of classical Hodgkin lymphomas. Our findings suggested EBV-associated lymphoma comprised only a small fraction of all non-Hodgkin's lymphomas in the general SRD patient population.

Adult↗
PubMed2006

Intestinal diffuse large B-cell lymphoma associated with celiac disease: a Japanese case.

Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well known to be associated with celiac disease (CD), an enteropathic disorder with a propensity for certain racial and genetic backgrounds. CD is typically characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies in the sera, and microscopical findings of the intestinal mucosa, which resolve with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD and the associated NHL have been supposed to be quite rare, and studies concerning the frequency of CD or its relationship with NHL are scarce. We describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma associated with CD. Following multi-combined chemotherapy, the patient's lymphoma has been in a state of complete response, and his GI symptoms have improved with a GFD. This case suggests that the possibility of CD and its association with intestinal NHL should be kept in mind, even in Asian populations.

Aged↗
PubMed2006

Senile Epstein-Barr virus-associated B-cell lymphoproliferative disorders: a mini review.

Epstein-Barr virus (EBV) is associated with a number of malignant lymphomas, including Burkitt lymphomas, Hodgkin lymphomas (HLS), immunodeficiency-associated lymphoproliferative disorders (LPDs), and subset of diffuse large B-cell lymphomas. We have recently identified a series of elderly patients afflicted with EBV-associated (EBV-positive) B-cell LPDs in the absence of predisposing immunodeficiencies ; we have named these neoplasms "senile" EBV+ B-cell LPDs. The large series of patients with this disease (n=76) provided additional evidence that this neoplasia, with a median age of onset of 71 years, has the highest incidence in elderly patients aged >50 years, suggesting that this disease may be related to the immunological deterioration that occurs during the aging process. These lesions were pathologically characterized by varying numbers of Hodgkin and Reed-Sternberg (HRS)-like giant cells, often posing a diagnostic problem differentiating this condition from HL. Recent studies, however, have indicated that HL and non-Hodgkin lymphoma (NHL) may be more closely related than previously implied, promoting the general consensus that HRS cells are derived from B cells in most HL cases. The relationship between EBV+ HL and EBV+ B-cell LPDs remains to be clarified. This review provides a unique opportunity to highlight the gray areas between EBV+ HL and EBV+ B-cell LPDs. Further investigations are necessary to clarify the interrelationship, including their overlapping morphological and biological features.

Aged↗
PubMed2006

Molecular diagnosis of malignant lymphoma: mantle cell lymphoma, anaplastic large cell lymphoma, and marginal zone B-cell lymphoma of malt.

Malignant lymphoma is a heterogeneous category embracing three major types of lymphoid neoplasms: B cell neoplasms, T and NK cell neoplasms, and Hodgkin lymphoma. Within each type, distinct disease entities are defined based on a combination of morphology, immunophenotype, genetic features and clinical syndromes, the emphasis on which represents a new paradigm in the lymphoma classification of the World Health Organization (WHO). These lymphoma entities often have distinctive cytogenetic abnormalities, usually involving translocations that place a potential cellular oncogene under the influence of the immunoglobulin in some low-grade B-cell lymphomas. Both pathologists and oncologists are now concerned with better understanding each disease entity and its spectrum of morphology, genetic events, and clinical behaviors. Over the last decade, significant progress has been made in the molecular characterizations of mantle cell lymphoma, anaplastic large cell lymphoma, and marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which have not only provided insights into the pathogenesis of lymphomas, but also valuable data that could lead to therapies based on their clinical behavior.

Anaplastic Lymphoma Kinase↗
PubMed2005

Effect of zotepine on dopamine, serotonin and noradrenaline release in rat prefrontal cortex.

The present study examined the effect of zotepine, an atypical antipsychotic, on the in vivo release of monoamines in the prefrontal cortex of rats using microdialysis. Local perfusion of zotepine at 10 microM increased extracellular levels of serotonin (5-HT), as well as dopamine and noradrenaline, in the prefrontal cortex. However, systemic administration of zotepine did not affect 5-HT release, although it increased the dopamine and noradrenaline release. These results suggest that the prefrontal 5-HT system does not contribute to the antidepressant effect of zotepine. The difference in the effect of zotepine between local and systemic treatment is discussed.

Animals↗
PubMed2005

Plasmacytoid monocytes in cat scratch disease with special reference to the histological diversity of suppurative lesions.

It has been suggested that plasmacytoid monocytes (PMOs) play an essential role in T-cell-dependent immune response. Indeed, numerous PMOs are found in close topographical association with epithelioid cell granulomas in hypersensitivity-type granulomas, such as tuberculosis and sarcoidosis. The key pathologic process in cat scratch disease (CSD) usually involves a B-cell-associated granulomatous reaction. Histologically, CSD appears to exhibit a histopathologic diversity, including suppurative lesions without epithelioid cell granulomas (early lesion), in which the microabscesses were surrounded by monocytoid B-cells (MBCs), suppurative granulomas containing MBCs (intermediate lesion), and suppurative granulomas without MBCs (late lesion). However, the presence or absence of PMO in CSD has not been studied previously. We examined 14 cases of CSD. In early lesions, numerous clusters of PMO were detected in the MBCs. In intermediate lesions, both MBCs and PMOs were found to be decreased in number, while late lesions contained no or only a few MBCs and PMOs. Overall, these findings suggest that PMOs may play a role in MBC-associated granulomatous response and in hypersensitivity granulomatous response. Moreover, the association with MBCs and PMOs indicates a functional relationship of MBCs with PMOs in the formation of suppurative lesions in CSD.

Abscess↗
PubMed2005

Phase II study of oral fludarabine phosphate in relapsed indolent B-Cell non-Hodgkin's lymphoma.

PURPOSE: Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. PATIENTS AND METHODS: Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). RESULTS: Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. CONCLUSION: Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

Administration, Oral↗