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M D Reis

Publications and source records attributed to M D Reis.

36 records · Page 2Linked to original sources
PubMed1994

Alterations of the p53 tumor suppressor gene in diffuse large cell lymphomas with translocations of the c-MYC and BCL-2 proto-oncogenes.

Diffuse large cell lymphomas are aggressive tumors of B-cell origin. In some cases they arise from low-grade follicular lymphomas carrying the t(14;18) translocation, an event that leads to the overexpression of the BCL-2 gene product. More frequently, however, they lack the t(14;18) translocation. Rearrangements of the c-MYC proto-oncogene and mutations of the p53 tumor suppressor gene have also been documented in these lymphomas. This study examines the extent to which alterations in the BCL-2, c-MYC, and p53 genes co-exist within individual lymphomas. Eight diffuse large cell lymphoma cell lines and 11 diffuse large cell lymphoma tumors were assessed for genetic alterations in these three genes. Our results indicate that there is a heterogeneity in the oncogene/suppressor gene profile among diffuse large cell lymphomas. Two cell lines and one tumor carried alterations in all three genes, one cell line carried alterations of c-MYC and p53, and one primary tumor and one cell line carried p53 mutations and the t(14;18). Single alterations of BCL-2 and p53 were also observed. Another cell line had no alterations in any of these genes. The heterogeneity indicates that varied mechanisms may be involved in the generation of diffuse large cell lymphomas.

Base Sequence↗
PubMed1993

Positive antiglobulin test in association with sulindac: involvement of the Rh factor.

We investigated the development of a positive direct antiglobulin test associated with the use of the nonsteroid anti-inflammatory drug sulindac. The drug was shown to be the cause of the positive direct antiglobulin test using red cells treated in vitro with solutions of native sulindac and its two major metabolites. Serum from the patient contained sulindac-dependent red cell antibodies which could not be demonstrated when red cells having the Rh phenotype D-- were employed in the test procedure. An eluate prepared from the patients' red cells reacted against untreated red cells having common Rh phenotypes, but not against target red cells with the Rh phenotypes D-- or Rh null. The eluate showed stronger reactivity against the cells having common Rh phenotypes when they were treated with solutions of a metabolite of sulindac, but failed to react against treated red cells having the Rh phenotype D-- or Rh null. The results of our investigations point to an interaction between sulindac and/or its metabolites and Rh structures on the red cell membrane as the initial step in the production of drug dependent and autoantibodies leading to the positive direct antiglobulin test.

Coombs Test↗
PubMed1993

Detection of occult lymphoma in the peripheral blood and bone marrow of patients with untreated early-stage and advanced-stage follicular lymphoma.

PURPOSE: The object of this study was to compare the relative sensitivities of morphologic, immunophenotypic, gene rearrangement, cytogenetic, and polymerase chain reaction (PCR) analyses in the detection of lymphoma cells in the bone marrow and peripheral blood of patients with follicular lymphoma. PATIENTS AND METHODS: Bone marrow and peripheral-blood samples from 28 newly diagnosed patients with follicular lymphoma referred from several different medical centers were assessed. Routine morphologic assessment was performed initially and the remainder of the sample was aliquoted for DNA extraction to be used for gene rearrangement and PCR analyses and for immunophenotypic and cytogenetic analyses where a sufficient amount of sample remained. RESULTS: Morphologic assessment of the bone marrow was positive for lymphoma cells in 11 of 28 patients. PCR amplification of t(14;18) breakpoint DNA detected lymphoma cells in 17 of 24 patients assessed. Morphologic assessment detected lymphoma cells in three bone marrow samples that were negative by PCR. PCR analysis was the only method able to detect circulating lymphoma cells in peripheral blood at diagnosis and was positive in 15 of 24 samples. The other methods of assessment did not show lymphoma in any samples in which lymphoma was not detected by morphologic or PCR analysis. Lymphoma cells were found in the bone marrow and/or peripheral blood as frequently in early-stage patients as in advanced-stage patients. CONCLUSION: PCR amplification of t(14;18) breakpoint DNA together with morphologic assessment had the highest yield of detecting lymphoma cells in the bone marrow and/or peripheral blood of our population of newly diagnosed patients with follicular lymphoma. The clinical significance and prognostic importance of lymphoma cells detected by PCR in the bone marrow and/or peripheral blood of newly diagnosed follicular lymphoma patients awaits long-term follow-up data of these and additional patients.

Base Sequence↗
PubMed1993

Sensitive and reproducible detection of occult disease in patients with follicular lymphoma by PCR amplification of t(14;18) both pre- and post-treatment.

The t(14;18) chromosomal translocation occurs in most follicular non-Hodgkin's lymphomas and places the Bcl-2 gene on chromosome 18q21 into the immunoglobulin JH region on chromosome 14q32. This translocation can be exploited to detect clonal malignant cells bearing this genetic alteration. A polymerase chain reaction (PCR) assay amplifying over the major breakpoint region (mbr) and minor cluster region (mcr) was developed and optimized. In this report, the sensitivity and reproducibility of this semiquantitative assay, performed on a relatively large number of clinical samples is shown. A titration curve of DNA made from a t(14;18)- cell line admixed with increasing ratios of a t(14;18)+ cell line was used to demonstrate that one t(14;18)+ cell in 100,000 t(14;18)- cells could reproducibly be detected. Occult lymphoma cells, not detected by standard morphologic analysis, were demonstrated in almost two-thirds of the bone marrow and peripheral blood specimens obtained from untreated patients with follicular lymphoma. Of 11 bone marrow samples assessed, seven were positive for occult disease by PCR amplification over the mbr and one was positive over the mcr. Of these six positive marrow samples, only three had been reported positive by standard morphologic criteria. In addition, seven of nine peripheral blood samples assessed were positive over the mbr and one additional sample was positive over the mcr. None of these were morphologically positive. Seven of the above patients would have been upstaged if these results were utilized for staging, including two of three patients with stage I or stage II disease. PCR-detectable occult disease persisted in four of four patients assessed both pre- and post-treatment, even after aggressive multi-drug combination chemotherapy in two of these patients. The clinical significance of detecting this occult disease must await the study of larger numbers of patients and the clinical outcomes of patients with occult disease and patients without occult disease.

Base Sequence↗
PubMed1992

Deletion of the long arm of chromosome 5 in essential thrombocythemia.

A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q-, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q- syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q- was the only clonal abnormality seen at diagnosis.

Biopsy↗
PubMed1992

A lineage-specific t(1;14)(q21;q32) as an early event in development of B-cell clonal expansion.

We report a patient in whom a cell line of 47,XY,+X,t(1;14)(q21;q32) constitution was found in a lymph node excised from the neck. Histologic examination and immunophenotyping both in situ and by flow cytometry failed to confirm a diagnosis of B-cell lymphoma, but Southern analysis indicated the presence of B-cell clonal expansion. These observations support the concept that primary chromosomal abnormalities occur in clonal expansions in the very earliest stages of tumorigenesis.

B-Lymphocytes↗
PubMed1991

"Jumping" translocations involving band 3q13.3 in a case of acute monocytic leukemia.

We report a case of acute monocytic leukemia (FAB-5a) with a very aggressive clinical course and multiple chromosomal abnormalities. There were several sublines, each with trisomy 8 and a translocation involving 3q13.3 as a common breakpoint region. This region is an uncommon site of chromosomal breakage in malignancies and has not hitherto been reported as a breakpoint site in "jumping" translocations.

Aged↗
PubMed1990

Oncogene involvement in myelodysplasia and acute myeloid leukemia.

The clonal malignancies of acute myeloid leukemia and the myelodysplastic syndromes are associated with numerous chromosomal and oncogenic abnormalities. Activation of oncogenes has been demonstrated, although there is little evidence that this alone causes malignant transformation of diploid cells as a consequence. Patterns of abnormalities can be seen as the patient progresses from myelodysplastic syndrome to acute myeloid leukemia, but no unique or invariant findings have been described. Chromosomal changes, with the exception of some translocations, are neither disease nor lineage specific. At this time the data provide good support for the multistep view of carcinogenesis, and there is indirect or circumstantial evidence for the presence of tumor suppressor genes on 5q and 7q. The continued study of these clonal hematological disorders will provide considerable insight into mechanisms of tumorigenesis and possibly may lead to new modes of therapy, for example, through altering the microenvironment, interfering with deranged signal transmission, or introducing antioncogenes.

Acute Disease↗
PubMed1990

T cell receptor and immunoglobulin genes in hematologic malignancies.

In this review, we discuss the structure, organization and activation of the immunoglobulin (Ig) and T cell receptor (TCR) genes and the use of DNA probes derived from these genes as tools to determine clonality and cell lineage in hemopoietic malignancies. We also examined briefly the participation of immunoglobulin and TCR genes in chromosomal aberrations present in many lymphoproliferative disorders, often involving protooncogenes and potentially of tumorigenic consequences.

Animals↗
PubMed1989

Transfusion of ABO-incompatible platelets causing severe haemolytic reaction.

Not infrequently clinical demand dictates that patients receive transfusions of ABO-incompatible platelets when there is a short supply of group-specific platelets. This carries a risk of causing a haemolytic reaction, as illustrated in the clinical case we report. In discussing this potential complication, we suggest a strategy for avoiding it.

ABO Blood-Group System↗
PubMed1988

Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice: forbidden clones revisited.

MRL-lpr/lpr mice spontaneously develop a lethal form of systemic lupus erythematosus associated with massive lymphadenopathy, polyclonal B-cell activity, autoantibody production and antibody-dependent tissue injury. The sequence of events leading to B-cell proliferation and pathogenic autoantibody production are not clearly defined--abnormalities of both B and T cells have been observed. Isolation of individual T-cell clones would facilitate analysis of the cellular events involving both B and T cells that lead to autoantibody production. For this purpose, an autoreactive T-cell line (ARTC-1) was derived from the splenocytes of an unimmunized MRL-lpr/lpr mouse and maintained in culture by stimulation with syngeneic antigen presenting cells, without exogenous antigens. By T-cell receptor analysis it was demonstrated that ARTC-1 cells developed as a clone even through no attempt was made to clone them in vitro: Southern blot analysis of ARTC-1 revealed a single rearrangement of the TcR beta chain locus with the other TcR beta chain gene remaining in the germline configuration. Northern blot analysis confirmed these findings and demonstrated that ARTC-1 utilized C beta 1 J beta 1.3 exclusively. ARTC-1 had atypical MHC requirements for activation: antigen-presenting cells bearing both I-Ak and I-Ek major histocompatibility complex class II antigens were required for maximal proliferation of the ARTC-l clone. Activated ARTC-l secreted soluble factors that induced B-cell proliferation, immunoglobulin secretion, and anti-DNA antibody production. Unregulated cells of the AR-TC1 type could, therefore, lead to polyclonal B-cell activation and autoantibody production in vivo in the absence of exogenous antigenic stimulation.

Animals↗
PubMed1987

Monoclonality in human T-cell disorders.

The genes coding for the T-cell antigen receptor have recently been cloned. They have proven to be invaluable tools for the study of the molecular mechanisms governing T-cell recognition of foreign antigens associated with histocompatibility antigens. In addition, they have also provided sensitive means of detecting clonal cell populations and determining cell lineage. In this review we describe the general organisation of these genes, the results of their utilization in the analysis of hematological pathologies, and discuss the possible implications of the involvement of these genes in translocations observed in certain T-cell malignancies.

Humans↗
PubMedDate not supplied

Athymic mice express a high level of functional gamma-chain but greatly reduced levels of alpha- and beta-chain T-cell receptor messages.

T lymphocytes differentiate and mature in the thymus. It is here that thymocytes with reactivities to self antigens are eliminated and those with specificities to 'altered' self-major histocompatibility complex (MHC) gene products are positively selected. The selections are presumably carried out on the basis of their T-cell antigen receptors (TcR). The genes of the alpha- and beta-chain T-cell antigen receptors have been cloned. A third T-cell specific gene capable of undergoing somatic rearrangement has also been identified; the role of this third gene is not known. An order of expression of gamma, beta, then alpha is found during T-cell ontogeny. But although alpha- and beta-chain messages are often functional, gamma transcripts are rarely functional in thymocytes or mature T cells. To define the sequential order of expression of these genes further and to continue the search for a possible role for the TcR gamma gene products, we investigated the expression of 'functional' alpha-, beta- and gamma-chain transcripts in young athymic mice. These mice express an undetectable amount (less than one in 8 X 10(5) spleen messages) of 'full-length' alpha- and beta-chain T-cell receptor transcripts, but an increased level of expression of 'full-length' gamma chain messages. Nucleotide sequence analysis of four gamma complementary DNAs show that all four gamma transcripts sequenced are functional. These findings suggest that gamma gene products may be important in a prethymic or extrathymic pathway and may represent a second type of T-cell recognition, possibly in a lineage in which alpha and beta genes are not used.

Aging↗
PubMedDate not supplied

Verrucous cyst.

A verrucous cyst is an unusual, histopathologically distinctive, epidermoid cyst characterised by verrucous changes in its wall. We report two cases of verrucous cysts in different patients, one on the back and the other on the cheek. Clinically, the lesions were thought to represent an epidermoid cyst and a basal cell carcinoma, respectively. Histologically, we found in both cases an intradermal epidermoid cyst lined by a stratified squamous epithelium with focal cytopathogenic viral changes, consisting of papillomatosis, ortho- and parakeratosis, and hypergranulosis. One case also showed, within the squamous areas of the hyperplastic epithelium, occasional squamous eddies. These histopathological features support the diagnosis of verrucous cyst, which may represent a manifestation of human papillomavirus infection. This virus may induce cyst formation or just infect a pre-existing one.

Adult↗