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N Uike

Publications and source records attributed to N Uike.

At least 37 records · Page 2Linked to original sources

["Hetero to homo" allogeneic bone marrow transplantation from a related donor with two HLA loci mismatch].

We describe a 46-year-old HLA-homozygous female patient with CML who received a bone marrow transplant from her son, who had two HLA (A, B) loci mismatch. After conditioning with total body irradiation plus cyclophosphamide, the patient received 4.8 x 10(8) bone marrow cells/kg. Cyclosporin and short-term methotrexate were used for GVHD prophylaxis. She successfully established rapid engraftment with no acute GVHD, and later developed chronic but mild GVHD. Family members with two HLA loci mismatch may be considered as candidate donors for "hetero to homo" bone marrow transplantation.

Bone Marrow Transplantation↗

[Adult acute lymphoblastic leukemia presenting a near haploid karyotype].

Thirty cases of childhood acute lymphoblastic leukemia (ALL) with a near haploid karyotype (< 30 chromosomes) have been reported so far. However, despite a few cases of severely hypodiploid (30-39 chromosomes) ALL, no near haploid cases have been reported in adult patients. Here, we describe a 64-year-old woman with ALL (L2, CD10+ 19+ 34+ HLA-DR+) presenting a near haploid karyotype of 27, X, +X, +6, +10, +21/54, idem x 2. She died of septic shock during complete remission 6.5 months after the diagnosis.

Female↗

A new multiple myeloma cell line, MEF-1, possesses cyclin D1 overexpression and the p53 mutation.

BACKGROUND: The t(11;14)(q13;q32) translocation with cyclin D1 overexpression commonly is found in multiple myeloma (MM) and in mantle cell lymphoma (MCL). Several reports have shown that p53 mutations in MCL lead to blastoid transformation and a worse prognosis; however, the role of p53 mutations in MM with t(11;14) is unclear. METHODS: In this study the authors describe a patient with MM with t(11;14) and a p53 mutation at presentation and characterized a cell line, MEF-1, established from this patient. Immunohistochemical analysis of p53 and cyclin D1 proteins was performed. The p53 gene was analyzed by polymerase chain reaction-single strand conformation polymorphism and direct sequencing. The expression of cyclin D1 mRNA was examined by Northern blot analysis. RESULTS: MEF-1 had t(11;14) with overexpression of cyclin D1 mRNA and produced immunoglobulin kappa-light chain. MEF-1 had a mutation in exon 7 (codon 255-257) of the p53 gene, which was noted in the patient's myeloma cells. CONCLUSIONS: p53 mutations may be important genetic events in disease progression of MM with t(11;14). The MEF-1 cell line may be a useful tool to study mechanisms of progression in MM based on abnormalities of the cyclin D1 gene.

Aged↗

Clonal identities and multiple isotype transcripts in hematological diseases revealed by a single-strand conformation polymorphism analysis of the immunoglobulin heavy chain messenger signals.

A single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified products of immunoglobulin (Ig) heavy chain rearrangements can be used to analyze B cell clonalities and clonal identities of B cells from different samples. However, the usefulness of the PCR-SSCP analysis is not fully assessed in B cell malignancies. For example, we did not know whether the PCR-SSCP method can be used to detect tumor-related clones in peripheral blood of patients with multiple myeloma and Waldenström's macroglobulinemia. In addition, because genomic DNA is used in the PCR-SSCP method, we could obtain no information about the isotype of the expanded B cell clone. In this study, we combined the reverse transcriptase (RT)-PCR of immunoglobulin heavy chain transcripts with an SSCP analysis and thus analyzed eight healthy individuals, five patients with B chronic lymphocytic leukemia, four patients with multiple myeloma and three patients with Waldenström's macroglobulinemia. Clonal B cell populations were detected as discrete bands in the RT-PCR-SSCP analysis that can be readily detected over the background of polyclonal rearrangements. Circulating tumor-related clones were detected in all but one peripheral blood sample from multiple myeloma and Waldenström's macroglobulinemia patients and B cell clones in peripheral blood and bone marrow from these patients showed a similar mobility on SSCP gel. Because the transcripts of different isotypes were separately analyzed, we could thus determine the isotype of B cell clones as well. When monoclonal Igs of different isotypes were detected in the individual samples, we analyzed the relationship of each monoclonal band by excising the band and then further analyzing it by a PCR-SSCP analysis. RT-PCR amplification in conjunction with the SSCP analysis is thus considered to be a useful method to detect and characterize the B cell clones in hematological diseases.

Aged↗

Cases of cutaneous and nasal CD56 (NCAM)-positive lymphoma in Japan have differences in immunohistology, genotype, and etiology.

CD56 (NCAM)-positive lymphoma frequently involves the skin and nasal area. This study shows it is likely that the clinicopathologic features of this lymphoma are distinctive to each of the primarily involved sites. Sixteen cutaneous and 11 nasal cases of CD56-positive lymphoma were examined. In 10 cutaneous cases, the lesions consisted of pleomorphic large-cell lymphoma that expressed CD3epsilon (CD3), CD2 (LFA2), CD4, CD122 (IL-2B receptor), TIA1, perforin, and granzyme B and displayed angiocentric/angiodestructive features. Lobular panniculitis was found in 8 of these cases, and 6 cases showed other organ involvement. The remaining 6 cutaneous cases consisted mostly of CD3epsilon- and CD4-positive, CD2-, CD122-, and TIA1-negative large blastic lymphoma, having less angiodestruction and panniculitis. Bone marrow invasion and leukemic changes were found in 4 of these cases during the clinical course. All 11 nasal cases showed pleomorphic small and medium-size lymphoma cells with angiodestructive features and were positive for CD3epsilon, CD2, CD122, TIA1, perforin, and granzyme B. CD4-positive lymphoma was found in 4 of these cases. Only 3 nasal cases showed other organ involvement. Genotypically, 2 of the 4 cases examined in the first cutaneous group, 3 of the 4 cases examined in the second cutaneous group, and only 1 of the 11 nasal cases showed rearrangement of the TcRCbeta gene by the Southern blot method. Only 2 cutaneous cases with panniculitis and all 11 nasal cases showed a positive nuclear signal for EBV-encoded RNA (EBERs) by in situ hybridization. Thus, two types of cutaneous CD56-positive lymphoma were found, each having a unique cell characteristic, genotype, and EBV infection pattern that differed from that of nasal-type lymphoma.

Adult↗

Gene expression of erythropoietin in renal cell carcinoma.

A 57-year-old man with renal cell carcinoma and erythrocytosis showed a high serum level of erythropoietin (EPO). High EPO signal was observed on Northern blot analysis and RT-PCR in the total RNA extracted from the renal tumor. Immunohistochemical staining also demonstrated tumor tissue with high immunostaining of EPO. Nucleotide sequences of EPO cDNA in the tumor were normal. To date, only one report has discussed the nucleotide sequences of a tumor's EPO gene; it showed mutant EPO cDNA in hepatocellular carcinoma tissue. This is the first demonstration of normal EPO cDNA in renal cell carcinoma.

Carcinoma, Renal Cell↗

[Detection of t(3 ; 21) (q26 ; q22) with AML1/EVI1 mRNA during progression of myelodysplastic syndrome to acute myeloid leukemia].

A 74-year-old woman had myelodysplastic syndrome (MDS) in 1986. In June 1994, she suffered exacerbation of pancytopenia with no chromosomal abnormalities, but AML1/EVI1 chimeric mRNA was detected by RT-PCR. Two months later, an increase in bone marrow blasts (5%) was noted, and chromosomal analysis detected t(3 ; 21) (q26 ; 22), del(7) (q22), del(11) (q23). In 1995, the marrow blasts increased to 30% and the patient died of disease progression. The AML1/EVI1 gene has been shown to cause blast crisis in chronic myelogenous leukemia. This case suggested that the AML1/EVI1 gene may be involved in the progression of MDS together with del(7) (q22) and del(11) (q23).

Acute Disease↗

Soluble Fas in the serum of patients with non-Hodgkin's lymphoma: higher concentrations in angioimmunoblastic T-cell lymphoma.

The soluble form of Fas (sFas) can block apoptosis induced by the Fas ligand in vitro. A recent report demonstrated that mice injected with sFas displayed autoimmune features. Therefore, an elevated serum concentration of sFas may be associated with lymphoproliferation and autoimmune diseases. We measured the serum concentrations of sFas in 77 patients with non-Hodgkin's lymphoma (NHL) [8 angioimmunoblastic T-cell lymphoma (AIL), 12 T-cell NHL, 53 B-cell NHL, and 4 natural killer-cell NHL]. Elevated concentrations of sFas were detected only in AIL, which is frequently accompanied by autoimmune diseases (P < 0.005 compared with age-matched controls). A possible association of sFas and autoimmune features in AIL is discussed.

Aged↗

Successful treatment of a patient with cardiac lymphoma who presented with a complete atrioventricular block.

A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma.

Aged↗

Establishment of a novel B cell clonality analysis using single-strand conformation polymorphism of immunoglobulin light chain messenger signals.

The remarkable diversity of the complementarity determining region (CDR) 3 of the immunoglobulin (Ig) heavy (H) chain gene rearrangements has been exploited to identify the clonal populations of B cells in B cell malignancies. However, when B cell malignancies of different categories were examined, the overall detection rate was found to be approximately 70%. The development of a simple clonality analysis using Ig light (L) chain CDR3 diversity has been hampered due to the sparseness of knowledge regarding the sequence of Vkappa and Vlambda gene segments and the restriction of L chain CDR3 length. Based on the recently reported Vkappa and Vlambda gene sequences, we designed Vkappa and Vlambda framework 3 consensus primers. We combined the reverse transcriptase polymerase chain reaction (RT-PCR) of IgL chain transcripts with a single-strand conformation polymorphism (SSCP) analysis and then analyzed samples from patients with B cell malignancies. Clonal B cell populations were detected as discrete bands, and identical clones showed a similar mobility in a RT-PCR SSCP analysis. This method was thus found to be a useful supplement to the previously described approach of VH gene amplification for detecting clonal B cell populations. By using SSCP, we were able to determine the clonal identities of B cell expansion in different samples.

Arthritis, Rheumatoid↗

Adult T-cell leukemia-lymphoma successfully treated with 2-chlorodeoxyadenosine.

Adult T-cell leukemia-lymphoma (ATL) is resistant to currently available chemotherapy and has a poor prognosis. We describe here a patient with ATL successfully treated with 2-chlorodeoxyadenosine (2-CdA). A 75-year-old Japanese male with an acute type of ATL, who had become resistant to the initial cytotoxic chemotherapy, was treated with 2-CdA administered by continuous drip infusion of 0.09 mg/kg/d for seven consecutive days in one month (one cycle). After three cycles of treatment, partial remission (PR) was achieved. Surprisingly, 249 days after the administration of 2-CdA, ATL cells completely disappeared from the peripheral blood. PR was maintained during 10 weeks until evidence of a new lymphadenopathy. No remarkable toxicity of 2-CdA occurred.

Aged↗

[Biclonal myeloma].

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Bence Jones Protein↗

Case-control study of leukemia and diagnostic radiation exposure.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

Adolescent↗

Immunoglobulin class switch from IgA1 to IgG2 and simultaneous association with Bence Jones proteinuria in the escape phase in a myeloma patient treated with interferon alpha.

Immunoglobulin (Ig) class switch from alpha1 to gamma2 associated with kappa-type Bence Jones proteinuria was evident in the escape phase of an IgA1 myeloma patient treated with interferon alpha (IFN alpha). The additional M-protein, IgG2-kappa, level rapidly increased and was associated with Bence Jones proteinuria, whereas monoclonal IgA1-kappa progressively declined. The N-terminal 21 amino acid sequences of the kappa-chains of monoclonal IgA1, IgG2 and the Bence Jones protein were the same. The N-terminal 15 amino acid sequence of the gamma2-chain was identical to that of the alpha1-chain. Based on these findings, the IgA1 myeloma cells underwent a class switch in CH gene expression from alpha1 to gamma2 with cell differentiation in vivo. The mechanism of the Ig class switching is discussed from three points of view: (1) Increase in immature and plasmablastic myeloma cells in the escape phase is susceptible to Ig class switching by the T-cell-derived cytokines. (2) We presumed that administered IFN alpha increased the amounts of secreted IFN gamma from the Th1 cells. (3) Due to a large quantity of IFN gamma, an inducer of Cgamma2 germline transcript, Ig class switching occurred stepwise from the alpha1 constant region gene to the next 3'CH gamma2 gene.

Aged↗

Phase I study of cladribine (2-chlorodeoxyadenosine) in lymphoid malignancies. Cladribine Study Group.

Cladribine (2-chlorodeoxyadenosine;) is a purine analogue with clinical activity against hairy cell leukemia, chronic lymphocytic leukemia and indolent lymphoma. To clarify the toxicity profiles of cladribine, we conducted a phase I and pharmacological study of cladribine with a schedule of seven-day continuous intravenous infusion every 28 days up to a maximum of three cycles. We enrolled 10 previously-treated patients with various lymphoid malignancies. No dose-limiting toxicity (grade 4 hematologic and/or grade 3 or more non-hematologic) was observed in the three patients who received 0.06 mg/kg/day (Level 1). Of the seven patients who received 0.09 mg/kg/day (Level 2), one patient developed grade 4 hypoxemia and grade 4 thrombocytopenia, and another developed grade 4 neutropenia. Of the seven patients treated at Level 2, one with cutaneous T-cell lymphoma attained complete remission, and one with mantle cell lymphoma, one with chronic lymphocytic leukemia and one with adult T-cell leukemia-lymphoma attained partial remission. A pharmacokinetic analysis of the seven patients without leukemic cells showed that their area under the concentration versus time curves of plasma cladribine increased dose-dependently from 2661.3 +/- 300.4 nM x h at Level 1 (n = 3) to 3411.3 +/- 341.0 nM x h at Level 2 (n = 4) (P = 0.034). We conclude that the recommended phase II dose of cladribine (0.09 mg/kg/day as a seven-day continuous i.v. infusion) in Caucasian patients can be safely administered to Japanese patients. The encouraging results prompted us to plan subsequent phase II studies of cladribine against adult T-cell leukemia-lymphoma, hairy cell leukemia and indolent lymphoma.

Aged↗

High occurrence of primary malignant neoplasms in patients with adult T-cell leukemia/lymphoma, their siblings, and their mothers.

BACKGROUND: Attempts were made to clarify the correlation between human T-cell leukemia/lymphoma virus (HTLV)-1 infection and malignant oncogenicity other than adult T-cell leukemia/lymphoma (ATL) in a case-control study. METHODS: The occurrence of primary malignant neoplasms (MN) in 110 ATL patients, their parents, and 430 siblings was compared with HTLV-1 seronegative non-Hodgkin's lymphoma (NHL) patients, their parents and 867 siblings. The chi-square test, odds ratio (OR), and 95% confidence intervals (CI) were used to determine the statistical significance of differences in the occurrence of the primary MN among ATL patients, HTLV-1 seronegative NHL patients, their siblings, and their parents. RESULTS: The occurrence of primary MN in the ATL patients was higher than the occurrence in HTLV-1 seronegative NHL patients (P = 0.0036; OR = 2.91; 95% CI: 1.42, 6.02). In siblings of the ATL patients, there was a higher occurrence of primary MN than in siblings of the HTLV-1 seronegative NHL patients (P < 0.0001; OR = 3.35; 95% CI: 2.01, 5.58). In mothers of the ATL patients, there was a higher occurrence of primary MN than in mothers of the HTLV-1 seronegative NHL patients (P = 0.0063; OR = 2.55; 95% CI: 1.30, 5.00), but not in fathers (P = 0.1602; OR = 1.68; 95% CI: 0.81, 3.47). CONCLUSIONS: There is an increased risk of primary MN in ATL patients, their siblings, and their mothers.

Aged↗

Inactivation of multiple tumor-suppressor genes involved in negative regulation of the cell cycle, MTS1/p16INK4A/CDKN2, MTS2/p15INK4B, p53, and Rb genes in primary lymphoid malignancies.

It is now evident that the cell cycle machinery has a variety of elements negatively regulating cell cycle progression. However, among these negative regulators in cell cycle control, only 4 have been shown to be consistently involved in the development of human cancers as tumor suppressors: Rb (Retinoblastoma susceptibility protein), p53, and two recently identified cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2. Because there are functional interrelations among these negative regulators in the cell cycle machinery, it is particularly interesting to investigate the multiplicity of inactivations of these tumor suppressors in human cancers, including leukemias/lymphomas. To address this point, we examined inactivations of these four genes in primary lymphoid malignancies by Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. We also analyzed Rb protein expression by Western blot analysis. The p16INK4A and p15INK4B genes were homozygously deleted in 45 and 42 of 230 lymphoid tumor specimens, respectively. Inactivations of the Rb and p53 genes were 27 of 91 and 9 of 173 specimens, respectively. Forty-one (45.1%) of 91 samples examined for inactivations of all four tumor suppressors had one or more abnormalities of these four tumor-suppressor genes, indicating that dysregulation of cell cycle control is important for tumor development. Statistical analysis of interrelations among impairments of these four genes indicated that inactivations of the individual tumor-suppressor genes might occur almost independently. In some patients, disruptions of multiple tumor-suppressor genes occurred; 4 cases with p16INK4A, p15INK4B, and Rb inactivations; 2 cases with p16INK4A, p15INK4B, and p53 inactivations; and 1 case with Rb and p53 inactivations. It is suggested that disruptions of multiple tumor suppressors in a tumor cell confer an additional growth advantage on the tumor.

Adolescent↗