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Biomedical subjects

N Uike

Publications and source records attributed to N Uike.

At least 55 records · Page 3Linked to original sources

Angiocentric immunoproliferative lesions of the lymph node.

Clinicopathologic features in 14 cases of lymph node-involved angiocentric immunoproliferative lesions (AILs) are reported. They were selected from 900 cases of lymphoproliferative disorders registered at the Department of Pathology, Fukuoka University. Four cases showed a histologic feature of AIL grade II (AIL-II) and 10 had angiocentric lymphoma (AIL-III). Immunohistologically, transformed B cells were mixed with a large number of small T cells in AIL-II. In AIL-III, there were five cases with B-cell lymphoma, and three had peripheral T-cell lymphoma with no expression of natural-killer (NK)-associated antigens. In the remaining two cases, lymphoma cells expressed both T-cell- and NK-associated antigens. These findings indicate that lymph node-involved AILs are rarely occurring (1.6%) and phenotypically different from sinonasal and cutaneous AILs. Furthermore, NK-associated antigen-positive AILs were found to rarely involve the lymph node. For Epstein-Barr virus (EBV) infection, seven cases of AILs showed many atypical lymphocytes that were positive for EBV-encoded RNA (EBER-1) by using the in situ hybridization analysis. Among them, six cases had latent membrane protein (LMP) positive and EBV nuclear antigen 2 (EBNA-2) negative atypical lymphocytes. The pattern of latent EBV infection was similar to that of Hodgkin's disease, but differed from those of sinonasal T-cell lymphoma and other subtypes of non-Hodgkin's lymphoma. Clinically, 12 patients, including all 4 AIL-II, died within 22 months of the onset of the disease, despite intensive therapy, suggesting that lymph node-involved AILs have a poor prognosis.

Adult↗

AILD-like dysplasia transformed in AILD-type T cell lymphoma in an HTLV-1 carrier: usefulness of interferon-alpha.

A 61-year-old Japanese woman who was an HTLV-1 carrier had angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like dysplasia that transformed into AILD-type lymphoma after 3 years. Complete remission was achieved with interferon-alpha (IFN-alpha) treatment following a previous combination of anticancer drugs. IFN-alpha was also effective for maintenance therapy after this complete, albeit transient, remission. From clinical and pathological studies on AILD patients, it appears that AILD may in some cases be the consequence of an immune dysfunction caused by HTLV-1 infection and that AILD-type lymphoma is a malignant disorder of peripheral T cell clones different from those T cells incorporating the HTLV-1 virus.

Antineoplastic Combined Chemotherapy Protocols↗

[Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and combinations of IPM/CS and other drugs for treating bacterial infections in patients with hematopoietic disorders].

One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained. 1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were not significant differences between the two groups with respect to the background. 2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant. 3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment. The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

Adolescent↗

Loss of the cyclin-dependent kinase 4-inhibitor (p16; MTS1) gene is frequent in and highly specific to lymphoid tumors in primary human hematopoietic malignancies.

The cyclin-dependent kinase 4-inhibitor (CDK41; p16; or MTS1) gene has been proposed as a candidate for a tumor-suppressor gene located in chromosome 9p21, a frequently deleted region in a wide spectrum of human cancers, including leukemias. Recent studies disclosed that it was frequently deleted or mutated in a variety of primary human cancers, including acute lymphoblastic leukemia. The purpose of this study is to figure out the precise manners and frequencies of p16 gene inactivation in diverse hematopoietic tumor types and thus to clarify its significance in development of human hematopoietic malignancies. A total of 410 tumor specimens from patients with primary hematopoietic malignancies were examined for deletions of the p16 gene as well as the neighboring p15 gene and the nearby interferon alpha gene by Southern blot analysis. Tumor-specific mutations or small deletions of the p16 gene were also studied in 74 patients using single-strand conformation polymorphism analysis and direct sequencing. Loss of the p16 gene was most frequently observed among the three genes examined and was found in 59 of the 410 patients: 2 of 134 with acute myelocytic leukemia, 41 of 105 with acute lymphocytic leukemia, 2 of 15 with chronic lymphocytic leukemia, 5 of 14 with adult T-cell leukemia, 4 of 33 with non-Hodgkin's lymphoma, 3 of 8 with mixed-lineage leukemia, and 2 of 61 with chronic myelocytic leukemia. In 16 of the 59 patients, the p16 deletions occurred due to rearrangements within the small region between the p15 exon 2 and the p16 exon 2. Tumor-specific mutations or small deletions of the p16 gene were not detected in the 74 patients examined, including 12 of 14 patients with hemizygous deletions of the gene. Loss of the p16 gene is frequent in and highly specific to lymphoid malignancies (54 of 183 [30%] in lymphoid tumor v2 of 219 [1%] in myeloid tumors; P < .0001). The deletion analyses strongly suggest that the p16 gene is a tumor-suppressor gene located in chromosome 9p21 that is involved in development of human lymphoid tumors. Gene deletions but not minute mutations should be the predominant mechanism of p16 gene inactivation in these types of tumors.

Adolescent↗

CD30-positive anaplastic large cell lymphoma in a human T-cell lymphotropic virus-I endemic area.

Clinicopathological and cytogenetic studies were performed on specimens from 43 patients with CD30-positive anaplastic large cell lymphoma (ALCL). All patients were born and lived in a human T-cell lymphotropic virus (HTLV)-I endemic area. Twenty-one patients (48.8%) had serum anti-HTLV-I antibody suggesting the presence of adult T-cell leukemia/lymphoma (ATL). Seventeen of them showed a clonal integration of complete HTLV-I proviral DNA by the Southern blot hybridization method in materials obtained by biopsy. Their ages ranged from 37 to 81 years (median, 67.0), and they frequently presented with lymphadenopathy (82.4%) and extranodal tumors with (76.5%) as well as with rare leukemic changes (5.9%). Immunohistologically the lymphoma cells in 15 ATL patients showed a T-cell phenotype. In only one patient (5.9%) was there an expression of epithelial membrane antigen (EMA) in most of the lymphoma cells. Cytogenetically aberration of chromosome band 5q35 was not found in seven patients with HTLV-I proviral DNA. The overall median length of survival was 11.9 months for the patients with HTLV-I proviral DNA, indicating a worse prognosis compared with that of the age-matched patients with negative anti-HTLV-I antibody (P < .01). The specimens of the patients with HTLV-I proviral DNA had unique clinicopathological and cytogenetic features. These findings suggested that T-cell ALCL with HTLV-I proviral DNA should be considered to represent the lymphoma type of ATL.

Adult↗

Angiocentric immunoproliferative lesions of the skin show lobular panniculitis and are mainly disorders of large granular lymphocytes.

Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin were studied. Histologically, three patients were grouped into AIL grade II (AIL-II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients' specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in nine patients possessed electron-dense membrane bound granules in electron microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7, and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta receptor in four, a pore-forming protein in four, and CD30 in three patients. The remaining two AIL-III patients had B-cell lymphoma. By the Southern blot analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta-gene or a deletion of its germline. The preceding results in nine of 11 patients suggest that abnormal or neoplastic large granular lymphocytes with the characteristics of T and NK cells have an important role in producing the angiocentric/angiodestructive features and lobular panniculitis. Clinically, all three patients with AIL-II and four with AIL-III showed liver dysfunction, cytopenia, and abnormal coagulopathy during the clinical course. Five patients with AIL-III died within 8 months. The histological grading of AIL, patients' age, and limited clinical stage of the disease seem to correlate with response to the treatment and prognosis.

Adolescent↗

CD30 (Ki-1) expression in adult T-cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics.

Twenty-one patients with CD30 (Ki-1) positive lymphoma were studied from a group of 91 patients with adult T-cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium-sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM-1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T-cell leukaemia/ lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T-cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T-cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM-1) expression by the lymphoma cells.

Adult↗

Genetic changes in atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia in the same patients.

The transition between atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia (AILD) was studied in serial lymph node biopsy specimens from five patients using DNA analysis with Southern blot analysis, polymerase chain reaction, chromosomal analysis, and immunophenotyping. The chromosomal analysis showed additional abnormalities as the disease progressed to those present initially, and immunological staining showed a corresponding increase in the numbers of CD4- and Ki67-positive cells. In the first biopsy from each patient a diagnosis of atypical hyperplasia with AILD was made and lymphoma excluding by the finding of only a few atypical lymphoid cells and the preservation of follicles with germinal centres. DNA analysis of lymph nodes at this stage showed either germ lines or oligoclonal rearrangements of the T-cell receptor (TCR) and immunoglobulin heavy chain genes. In the final biopsy, when a diagnosis of lymphoma with AILD was made, either a monoclonal rearrangement of the TCR was observed or one of the rearranged bands had increased in density. These results suggest selective proliferation of a clone of abnormal cells may account for the progression of atypical hyperplasia to lymphoma with AILD.

Base Sequence↗

Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults.

We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.

Adolescent↗

Heterogeneity of Epstein-Barr virus infection in angioimmunoblastic lymphadenopathy type T-cell lymphoma.

To investigate the relationship of Epstein-Barr virus (EBV) and angioimmunoblastic lymphadenopathy with dysproteinemia, we performed DNA analysis using the polymerase chain reaction (PCR), Southern blot, in situ hybridization, and immunohistochemical analysis of lymph nodes in five patients who were followed up and biopsied more than once. In the course of the disease, nodal architecture diminished, cellular atypia worsened, and clear cells increased in number. In the DNA analysis of the receptor genes, the clonal population increased in number. EBV nucleic acid sequences were found by either PCR or in situ hybridization in all examined nodes. The number of EBV-positive cells varied widely among the cases and throughout the course of the disease in the same patients. The analysis of EBV terminal repeats or lymphocyte-determined membrane antigen genes showed polyclonal populations of EB-infected cells. EBV-positive cells possessed intermediate- to large-sized nuclei, and the cells with large nuclei, especially, expressed latent membrane protein of EBV. These large cells varied among the cases. Double-labelling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed B-cell antigen (CD20). The presence of EBV seems to be associated with the selective defects of the immune system, rather than with the direct pathogenesis of angioimmunoblastic lymphadenopathy.

Base Sequence↗

Gene expression of erythropoietin in hepatocellular carcinoma.

A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. Histological and immunocytochemical examination showed that the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO. The erythrocytosis improved and the high serum EPO level decreased after resection of the tumor. This is the first demonstration of EPO mRNA expression in hepatocellular carcinoma tissue by RT-PCR.

Aged↗

[A comparative study of imipenem/cilastatin sodium BID vs QID in the treatment of infections associated with hematopoietic disorders].

Using the envelope method, we allocated 125 patients with infections accompanied by hematopoietic disorders into two groups treated with imipenem/cilastatin sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were 54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0% (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID, efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No significant difference in response rates were observed between the two groups. 3. Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21 strains, in group QID. The eradication rates after treatment with IPM/CS was 100% in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients in group BID and 3 in group QID. Laboratory examination revealed abnormal values in 9 patients in group BID and 6 in group QID. However, all of the side effects disappeared after the suspension or discontinuation of IPM/CS. The efficacies of IPM/CS therapy for severe infections in patients with hematopoietic disease were similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.

Adult↗

[Bone marrow transplantation for a patient with ALL from her 75-year-old mother using cryopreserved bone marrow cells].

We report a 42-year-old woman with acute lymphoblastic leukemia who received allogeneic bone marrow transplantation (BMT) in the first remission from her 75-year-old, HLA-identical, MLC-non-reactive mother. Considering the difficulty to obtain a sufficient number of bone marrow cells from such an old donor, we harvested the cells (2.31 x 10(8)/kg) on day -37 and cryopreserved them until use. BMT was performed on June 3rd, 1993 after conditioning regimen with total body irradiation, high-dose AraC and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxisis was attempted by cyclosporin A and short-term methtrexate. Her hematopoietic recovery was favorable with no signs and symptoms of GVHD as far as day 218.

Adult↗

Establishment of a human myeloma cell line with growth-promoting activity for bone marrow-derived fibroblastoid colony-forming cells.

A human myeloma cell line, PCM6, was newly established from peripheral blood of a patient with advanced IgG myeloma by addition of recombinant interleukin-6 (IL-6) in culture. PCM6 cells had a morphology typical of mature plasma cells. Cytogenetic and surface marker studies confirmed that PCM6 cells were identical to fresh myeloma cells. Coculture of PCM6 cells with normal bone marrow mononuclear cells resulted in increased colony size of bone marrow-derived fibroblastoid colony-forming cells (CFU-F). Conditioned medium of PCM6 (PCM6-CM) cells increased the CFU-F colony size in a dose-dependent manner. The activity was labile to trypsin treatment but was heat stable (60 degrees C, 30 minutes). Molecular weight of the activity was approximately 165 kd by Sephacryl S-300 gel filtration. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), and IL-1 beta were not detectable in the conditioned medium. These findings suggest that in some myeloma cases, bone marrow stroma may be affected by CFU-F growth-promoting activity.

Antigens, Surface↗

Parvovirus B19-associated haemophagocytosis in Evans syndrome: aplastic crisis accompanied by severe thrombocytopenia.

A 36-year-old man who had been treated for Evans syndrome (ES) developed an aplastic crisis caused by acute human parvovirus B19 (HPV) infection. Profound thrombocytopenia (8.0 x 10(9)/l) followed with a sudden increase in platelet-associated IgG (PAIgG) (1376.9 ng/10(7) plts). Bone marrow examination revealed a considerable number of haemophagocytic histiocytes without any disturbance of megakaryopoiesis. To our knowledge this is the first case of aplastic crisis with virus-associated haemophagocytosis in a patient with ES, which provides an interesting insight into the mechanisms for thrombocytopenia in HPV infection.

Adult↗

[Report of two cases presenting with myelodysplastic syndrome during treatment of recurrent breast cancer].

Two women with recurrent breast cancer presenting with myelodysplastic syndrome (refractory anemia) during chemotherapy were reported. At diagnosis of myelodysplastic syndrome, white blood cell count, hemoglobin and platelet count were 3,300/mm3, 4600/mm3, 5.5 g/dl, 6.3 g/dl, 1.1 x 10(4)/mm3 and 6.8 x 10(4)/mm3, respectively, in case 1 and 2. Bone marrow taps showed hypercellular marrows with dysplastic changes of erythrocytes, granulocytes and megakaryocytes in both cases. Before the occurrence of the myelodysplastic syndrome, both patients received various cytotoxic agents (mitomycin C: 77 mg, 108 mg; cyclophosphamide: 34,400 mg, 40,000 mg; doxorubicin: 340 mg, 460 mg; methotrexate: 410 mg, 700 mg; and vincristine: 9.5 mg, 14 mg, in case 1 and 2, respectively). One patient died 2 months after the onset of the myelodysplastic syndrome, and the other died 3 months after due to progression of metastatic breast cancer. Risk-benefits analysis of chemotherapy, especially adjuvant chemotherapy, should be performed in cases of breast cancer.

Adult↗