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M Seto

Publications and source records attributed to M Seto.

At least 181 records · Page 10Linked to original sources

Immunohistochemical analysis of cyclin D1 protein in hematopoietic neoplasms with special reference to mantle cell lymphoma.

Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non-neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin-fixed paraffin-embedded sections, using the microwave oven heating method. Positive neoplastic cells were found in 60 (74%) of 81 cases of non-Hodgkin's lymphoma. The positivity pattern was nuclear in 17 (85%) of 20 cases of mantle cell lymphoma in which cytoplasmic staining was also seen. This pattern of cyclin D1 positivity was in contrast to the negative staining of normal reactive mantle zones. In the other cases, positivity appeared to lie within the cell cytoplasm without nuclear staining, and most of the nodal follicular and diffuse B-cell lymphomas variously expressed PRAD1/cyclin D1. In contrast, the reaction was absent in a significant number of T-cell and extranodal B-cell lymphomas. Immunolocalization of PRAD1/cyclin D1 expression appears to be a useful diagnostic adjunct to discriminate mantle cell lymphoma from other non-Hodgkin's lymphomas.

Antigens, CD↗

Monoclonal antibody against PRAD1/cyclin D1 stains nuclei of tumor cells with translocation or amplification at BCL-1 locus.

Mouse monoclonal antibodies were produced against the bacterial product encoded by human PRAD1/cyclin D1 gene, which is known to be involved in tumors with translocation or amplification at BCL-1 locus of 11q13. The immunizing antigens used were GST-PRAD1 and T7 gene 10-PRAD1 fusion products. Four antibodies were reactive with both PRAD1 fusion products and cell lysates of B-cell tumor cell lines with t(11;14)(q13;q32) and a breast cancer cell line with 11q13 amplification, on immunoblotting. An immunofluorescence study showed that only one of them stained nuclei of cells with 11q13 abnormalities. Since this antibody proved applicable for conventional paraffin-embedded tissue sections, immunohistologic staining of various lymphoma tissues was performed. Eight of 11 mantle cell lymphomas showed intermediate to strong positivity and 6 of the positive cases demonstrated characteristic staining patterns that were either predominantly nuclear or both nuclear and cytoplasmic. The nuclear staining pattern was not observed with other types of lymphoma and thus may correlate with PRAD1 mRNA overexpression.

Antibodies, Monoclonal↗

[Thirty seven cases of respiratory syncytial virus infection hospitalised and 7 severe cases with apneic attacks].

We studied 37 cases of respiratory syncytial virus infection hospitalized during the period January 1, 1989 and March 31, 1993. 37 patients were 0-4 years old on admission. Fever, positive CRP and elevation of BSG were frequent in patients aged 8 months-4 years old. Patient more than 8 months of age didn't need supplementation of oxygen. Of the 37 patients, we had one case who had hyponatremia and six cases who were admitted with severe apneic attacks required incubation. Of the six cases, one patient had delayed neurological deterioration after anoxia due to apneic attacks. He, followed up for 4 years, have serious residual deficits including spastic quadriplegia, delayed development and epilepsy. Variety of factors, including premature birth, young postnatal age and milk feeding appeared to be significant risk factors for sever infections of RSV. In RSV infection, apneic attacks can cause near-miss SIDS. So, we stress the importance of careful and rapid diagnosis for all infants less than 8 months of age.

Apnea↗

Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide?

A patient with secondary acute myelomonocytic leukemia after treatment with chronic oral etoposide (VP-16) for lung cancer is reported. The leukemic cells showed a t(9;11)(p22;q23) translocation. Southern blot analysis revealed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a chimeric mRNA between the MLL gene at 11q23 and LTG9 (MLLT3/AF-9) gene at 9p22. The patient was successfully treated with a VP-16 based regimen. This case is instructive in the understanding of the leukemogenesis of VP-16-related leukemias.

Administration, Oral↗

[Secondary leukemia after etoposide treatment involved MLL gene rearrangement].

The 11q23 chromosomal abnormality is frequently observed in infantile leukemia and secondary leukemia, and the translocation associated gene in infantile leukemia is called mixed-lineage leukemia (MLL) gene. A 50-year-old man was admitted because of left axillary lymphadenopathy and IBL like T cell lymphoma was diagnosed by lymph node biopsy. The patient responded to the LSG-9 protocol with complete remission. After 10 months he was readmitted because of fever and was diagnosed acute myeloblastic leukemia by bone marrow aspiration. Chromosome analysis revealed 11q23 abnormality, suggesting that the leukemia was induced by etoposide treatment. Southern blot analysis demonstrated DNA rearrangement in the MLL gene at 11q23. It was suggested that the breakpoint region of the MLL gene in secondary leukemia is the same as that of infantile leukemia.

Chromosomes, Human, Pair 11↗

Local application of calcium antagonists inhibits intimal hyperplasia after arterial injury.

The local effect of the calcium channel antagonist diltiazem and the protein kinase inhibitor 1-5-(isoquinoline sulfonyl)-5-homopiperazine HCL (HA1077) on neointimal formation after arterial injury were investigated by the use of a perivascular drug-delivery system. Bilateral carotid artery balloon injury was produced in 130 rats. In six groups of 10 rats each, diltiazem or HA1077 at three doses (low, 0.2 mg; medium, 1 mg; high, 5 mg) was mixed with the drug-delivery polymer poly(vinyl) alcohol and applied to the adventitial surface of the injured right carotid artery enclosed by a Silastic cuff; 10 control animals received polyvinyl alcohol only in the silastic cuff. In all animals, the contralateral injured artery without the cuff served as a control. At 10 and 20 days after the injury, the intimal cross-sectional area was determined from light microscopic sections for the injured segment of both carotid arteries. In six additional groups of 10 rats each, treated as above, levels of diltiazem and HA1077 in plasma were measured at periods from 1 hour to 5 days after perivascular application. At 10 days after endothelial injury, animals receiving high-dose diltiazem or HA 1077 (5 mg) demonstrated significant reductions in neointimal area compared with polyvinyl alcohol controls for both treated and contralateral untreated vessels. At 20 days after injury, neointimal hyperplasia was inhibited only on the treated side in both high-dose groups. Perivascular diltiazem and HA1077 at lower doses (1 or 0.2 mg) did not affect neointimal area at 10 or 20 days in either treated or untreated arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Nuclear proteins binding to a novel target sequence within the recombination hotspot regions of Bcl-2 and the immunoglobulin DH gene family.

The chromosomal breakpoints of follicular lymphomas carrying the t(14;18)(q32;q21) are known to be clustered within a 150-bp region in the major breakpoint region (mbr) of the Bcl-2 oncogene. We have demonstrated that nuclear proteins specifically bind to a novel target sequence within this 150-bp region and a region of Dxp genes, members of the immunoglobulin (Ig) diversity (DH) gene family. One protein, designated BCLF-1, appears to be specifically expressed in lymphoid lineage cells. Two other proteins, BCLF-2 and -3, bind only to the complementary single strand of the target sequence. The manner in which these proteins interact with the target sequence is similar to the interaction of the ReHF-1 and -2 proteins to the signal-like sequence at the chromosomal breakpoint junctions in patients with the t(8;14)(q24;q11) and t(1;14)(p32;q11) translocations. It was further suggested that the BCLF-1 is quite similar to or identical to the ReHF-1. It is therefore hypothesized that these conserved target sequences found in recombination hotspot regions may define novel sequence motifs recognized by two classes of DNA binding proteins. One class of DNA binding proteins is specifically expressed in lymphoid cells while the other class binds to the complementary single strand DNA. These binding activities may play a crucial role in chromosomal translocation in lymphoid neoplasms.

Base Sequence↗

Rearrangement of bcl-2 genes in malignant lymphomas in Chinese patients.

BACKGROUND: Only a small percentage of Asian patients with non-Hodgkin lymphoma may have follicular type disease. According to molecular analysis done recently, the incidence of rearrangement of bcl-2 gene in patients with follicular lymphoma was lower in Japan than in the United States, suggesting possible geographic or racial differences between Asian and Western populations. The current study was undertaken to obtain data from Taiwan to compare with data from Japan, Hong Kong, and Western countries. METHODS: Using probes of genomic 5' bcl-2, major breakpoint region (mbr) and minor breakpoint cluster region (mcr) for the breakpoint cluster region of the bcl-2 gene, genomic DNA samples from 55 patients with B-cell lymphoma (17 with follicular type and 38 with diffuse type) were analyzed by Southern blot analysis. RESULTS: Eleven patients had bcl-2 gene rearrangement, including 9 of 17 (52.9%) patients with follicular lymphoma and 2 of 38 (5.3%) patients with diffuse B-cell lymphoma. Nine patients had the breakpoint located within the mbr, one at both the mbr and the 5' bcl-2 regions, and the other had bcl-2 translocation with involvement of the mcr. DNA fragment of bcl-2 was found to comigrate with JH genes in all patients with follicular lymphoma and diffuse lymphoma who had bcl-2 rearrangement at mbr. The remaining patient who had bcl-2 translocation at mcr had no comigration with JH, Jk, or C lambda genes. CONCLUSIONS: Despite the low incidence of follicular lymphoma in Chinese patients, the incidence of bcl-2 gene involvement was higher in patients from Taiwan than in those from Japan and Hong Kong, but similar to the incidence of those from Western countries.

Adolescent↗

Long-range mapping of the 11q23 region involved in chromosome aberrations in human tumors by pulsed-field gel electrophoresis with a yeast artificial chromosome.

We have previously demonstrated that the RCK gene involved in t(11;14)(q23;q32) and the more centromeric MLL/ALL1 gene involved in t(4;11)(q21;q23) and t(11;19)(q23;p13) are localized on different adjacent NotI fragments by using pulsed-field gel electrophoresis (PFGE) analysis with the yeast artificial chromosome (YAC) clone yB22B2. The PFGE analysis using the YACs of YTY17 containing the prophobilinogen deaminase (PBGD), CBL2 and THY1 genes and yB22B2 allowed the following ordering of genes and breakpoints from CD3 to THY1 on 11q23: cent-CD3-ALL/MLL1-RCK-PBGD-CBL2-THY1, and the establishment of a long-range restriction map covering these genes. In addition, we showed that the FLI1 region involved in the t(11;22)(q24;q12) in Ewing's sarcoma was more telomeric region that the THY1 gene by analyzing somatic cell hybrids carrying the 11q- and/or 14q+ chromosome of the t(11;14)(q23;q32) translocation, and by PFGE analysis of the YAC clone YTY17.

Acute Disease↗

Intimal hyperplasia enhances myosin phosphorylation in rabbit carotid artery.

We examined physiological events in the hyperplastic artery, using a method based on the mechanical responsiveness and myosin light-chain phosphorylation in response to various stimulants. Six weeks after endothelial denudation by ballooning of the right carotid artery, strips of this artery with moderate intimal hyperplasia (intimal area was 30-50% of medial area in 20 of 28 rabbits) were used for experiments. Strips from the left carotid served as the normal control. When the hyperplastic artery was stimulated with 30 microM PGF2 alpha, the maximal tension (232.4 +/- 49.1 mg/mg dry wt, mean +/- SD) was significantly higher (P < 0.05) than that of the control (129.5 +/- 16.4 mg/mg). The maximal extent of myosin light-chain monophosphorylation (45.4 +/- 8.9%) and diphosphorylation (10.9 +/- 5.2%) in the hyperplastic artery was significantly higher (P < 0.05) than that in the control artery (33.0 +/- 4.8 and 4.0 +/- 4.8%, respectively). The monophosphorylation of the myosin light chain in the hyperplastic artery was sustained for up to 20 min, while that in the control artery decreased to the basal level within 20 min. Similar observations were obtained by stimulation with 60 mM K+ or 30 microM norepinephrine. Dose-response curves of the development of tension in the hyperplastic artery to various agonists (K+, PGF2 alpha, norepinephrine) shifted upward the curves for the control artery. These results suggest that qualitative changes in the characteristics of smooth muscle cells may occur in the intimal hyperplastic portion, including a hyperreactive contraction associated with enhanced and sustained phosphorylation of the myosin light chain.

Animals↗

Isolation of a novel cDNA clone showing marked similarity to ME491/CD63 superfamily.

A novel cDNA clone, A15, was isolated by the differential screening of a cDNA library of an immature T cell line, HPB-ALL using radioactive cDNA probes from the mRNA of either HPB-ALL or peripheral blood lymphocytes. It hybridized to a single mRNA species of about 2.0 kilobases which is expressed in HPB-ALL cell line, but not in the PBL or a promyelocytic leukemia cell line, HL-60. The A15 gene codes for a protein of 244 amino acids which contains four potential transmembrane domains and four possible N-linked glycosylation sites. A computer-aided comparison showed a marked similarity to several other membrane proteins: CD9, CD37, CD53, TAPA-1, Sm23, CO-029, and ME491/CD63.

Amino Acid Sequence↗

Isolation and characterization of mouse CD7 cDNA.

The human CD7 antigen is a glycoprotein, M(r) 40,000, expressed on the surface of peripheral blood T-lymphocytes and thymocytes, and is the earliest surface antigen to appear on T-cell lineage cells. In this study, putative mouse CD7 cDNA was identified based on its similarities with human CD7. Five independent clones originating from the same mRNA species were isolated (designated as mCD7) by screening a mouse thymocyte cDNA library with human CD7 cDNA, J61, under moderate stringency. The longest insert of a 995 base pair had an open reading frame of 210 amino acids. Northern blot analysis using the mouse CD7 cDNA probe demonstrated a single 1.2 kilobase mRNA in the thymus, spleen, bone marrow, and small intestine. The protein deduced from mCD7 cDNA consisted of the leader, extracellular, transmembrane, and cytoplasmic domains of 24, 126, 21, and 39 amino acids, respectively, based on the hydrophobicity plot and the structure of human CD7. The extracellular domain contained three potential N-glycosilation sites, while the cytoplasmic domain contained one potential protein kinase C phosphorylation site. The amino acid sequence had 45.5% similarity with human CD7, while the similarities for the individual domains ranged from 49.2% to 63.2%. The six highly conserved regions, which may possibly be involved with still unknown CD7-mediated functions, were located in the extracellular and cytoplasmic domains.

Amino Acid Sequence↗

Novel interleukin-2 dependent T-cell line derived from adult T-cell leukemia not associated with human T-cell leukemia virus type I.

A novel interleukin-2 (IL-2)-dependent T-cell line, WHN2, was established from a patient with adult T-cell leukemia (ATL) not associated with human T-cell leukemia virus type I (HTLV-I). Neither the original leukemic cells nor the WHN2 cells showed proviral integration in their cellular DNAs by Southern blot analysis. The surface phenotype showed that both the original leukemic cells and the WHN2 cells had a common phenotype of ATL, i.e., positive for CD2, CD4, human leukocyte antigen DR (HLA-DR) and CD25, but negative for CD8, a characteristic of helper/inducer T-cells. Most of the chromosomal abnormalities of the original leukemic cells were maintained in the WHN2 cell line. Furthermore, Southern blot analysis of the T-cell receptor beta-chain gene rearrangement revealed that the original leukemic cells and WHN2 cell line had identical patterns, suggesting that the WHN2 cell line was truly derived from the original leukemic cells. Dose-dependent growth on IL-2 was demonstrated, and at the maximal stimulation, the number of cells doubled within three days. This IL-2-dependent growth was inhibited by the simultaneous existence of anti-IL-2 receptor alpha and beta chain antibodies. These results indicate that the character of the WHN2 cell line is similar to that of the cell lines derived from ATL associated with HTLV-I. Thus, the HTLV-I-negative ATL cell line, WHN2, should be useful in the comparative study of the pathogenesis of ATL associated with or without HTLV-I.

Aged↗

Molecular cloning of 19p13 breakpoint region in infantile leukemia with t(11;19)(q23;p13) translocation.

We studied the breakpoint regions involved in t(11;19)(q23;p13) translocation associated with infantile leukemias. Southern blot analysis with the partial cDNA clone for the MLL gene at 11q23 which we had isolated previously detected gene rearrangements in all three cell lines and three leukemia samples from the patients with t(11;19) translocation, indicating that these breakpoints were clustered within the 8.5 kb BamHI germline fragment detected by the probe. To study the breakpoint region, a genomic library of one of the cell lines, KOCL-33, was made. We have isolated the der(19) allele containing the breakpoint as well as the germline alleles at 19p13 and 11q23. Using the genomic probes on chromosome 19 near the breakpoint, Southern blot analysis was performed. The breakpoints at 19p13 of the two other cell lines and the three leukemia samples were not located within 36 kilobases of the KOCL-33 breakpoint, although pulsed-field gel electrophoresis showed that the breakpoints of all three cell lines were on the same NruI fragment of 230 kilobases. These results showed that the breakpoints at 19p13 were not clustered like those at 11q23 in t(11;19) translocation.

Base Sequence↗

Overexpression of PRAD1 in a mantle zone lymphoma patient with a t(11;22)(q13;q11) translocation.

The PRAD1 gene identified from the chromosome band 11q13 region was previously demonstrated to be overexpressed in cell lines with t(11;14)(q13;q32) translocation and was suggested to be a candidate BCL-1 gene. We report here one case of mantle zone lymphoma with a t(11;22)(q13;q11), a variant translocation at the BCL-1 locus, having the PRAD1 overexpression. By analogy with the c-myc gene in Burkitt's lymphoma and the BCL-2 gene in follicular lymphoma, this case supports strongly the idea that the PRAD1 is the candidate BCL-1 gene.

Aged↗

[An outbreak of Pseudomonas sepsis associated with nosocomial infection in a pediatric ward].

A five-year old girl, diagnosed with fever of unknown origin (FUO), was transferred to our hospital due to a deterioration in her general condition. Pseudomonas cepacia (P. cepacia) was detected in her blood culture and she soon recovered after imipenem cilastatin (IPM/CS) administration. When the former hospital was informed of the results of her blood cultures, we learned that five other cases of FUO had occurred there within the previous two weeks in noncompromised children. Except for one case, Pseudomonas species was detected in their blood cultures. P. cepacia was found in one case, Pseudomonas aeruginosa (P. aeruginosa) was detected in two other cases, and both P. cepacia and P. aeruginosa were demonstrated in the other patient. Although the origin of the bacteria is unknown, it may have spread to the children through a contaminated liquid reservoir or medical devices.

Bacteremia↗

Treatment of myasthenia gravis: a comparison of the natural course and current therapies.

Ninety-five patients with generalized myasthenia gravis were followed for 10 years to evaluate the long term effects of prednisolone, thymectomy, or both, and they were compared with a group only with anticholinesterase treatment. Only 15.0% of the patients with anticholinesterase alone had showed improvement 10 years after the onset, but more than 60% of those treated with prednisolone, thymectomy, or both showed improvement. Especially thymectomy induced complete remissions at 10 years after surgery in more than 20% of the patients. There was no difference between the histology of the thymi and clinical severity, or anti-acetylcholine receptor (AChR) antibody titer. In patients who showed improvement classified "good" of higher 10 years after thymectomy with or without prednisolone, anti-AChR antibody titers swiftly decreased to 37.8% of the value before surgery, and remained low thereafter. This result suggests that the marked decrease in anti-AChR antibody titers within 1 month after thymectomy is a favorable prognostic sign in myasthenia gravis patients who have undergone thymectomy.

Adolescent↗