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E Cesarman

Publications and source records attributed to E Cesarman.

At least 73 records · Page 4Linked to original sources
PubMed1994

Post-thymic T cell lymphomas frequently overexpress p53 protein but infrequently exhibit p53 gene mutations.

We recently demonstrated that only one of 36 T-cell neoplasms contained p53 gene mutations. Although p53 gene mutations are known to result in overexpression of the p53 gene product, we also recently discovered that p53 protein overexpression does not correlate with p53 gene mutations, but does correlate with proliferation (r = 0.92), in anaplastic large cell lymphoma. In view of these findings, we investigated 34 non-human T-cell lymphotropic virus type I (HTLV-I) related postthymic T-cell lymphomas immunohistochemically for p53 protein, using monoclonal antibody 1801, and for proliferation, using monoclonal antibody Ki-67, and quantitated the results with the CAS-200 computerized image analysis system. We evaluated the presence of mutations in conserved exons 5 to 9 of the p53 gene using single-strand conformation polymorphism analysis and DNA sequencing. p53 mutations were detected in three of 34 cases, including two that contained deletions. p53 protein overexpression was detected in 17 of 34 cases, including the three mutated cases, with reactivities ranging from 10% to 48%. However, many cases in which a structural alteration could not be detected demonstrated levels of p53 protein expression comparable to those cases that were mutated. Correlation of p53 protein expression and proliferation, as assessed by Ki-67 expression, in this group of lymphomas was poor (r = 0.34). Whether alternative mechanisms of p53 protein inactivation are causing phenotypic overexpression of the p53 protein in these malignant lymphomas is unknown, although preliminary studies do not support a major role for such mechanisms. Therefore, the etiology and the significance of p53 protein overexpression in the cases that lack a demonstrable mutation is unclear. Nevertheless, as in anaplastic large cell lymphoma, overexpression of the p53 gene product is not a reliable predictor of the presence of mutations in conserved portions of the p53 gene in non-HTLV-I associated post-thymic T-cell lymphoma.

Antibodies, Monoclonal↗
PubMed1993

CD30 (Ki-1) positive anaplastic large cell lymphomas in individuals infected with the human immunodeficiency virus.

BACKGROUND: CD30 (Ki-1) positive anaplastic large cell lymphoma (ALCL) has been only rarely described in HIV-positive patients. METHODS: The clinicopathologic features of eight ALCLs occurring in four AIDS and four HIV-positive patients were investigated. The phenotype of each neoplasm was determined by immunohistochemical methods. In three cases fresh tissue was available for molecular analysis. RESULTS: The ALCLs are a clinically heterogeneous group of T (4), B (1) and indeterminate (3) cell malignant lymphomas which presented in the skin (4), liver (1), lung (1), nasal cavity (1; also with bone marrow involvement) and peritoneal fluid (1). While most of the patients had aggressive disease, dying in a median of three months, two patients had either localized or regressing skin lesions. Molecular studies showed that two ALCLs, one of B cell and one of indeterminate cell lineage, contained clonal Epstein-Barr virus sequences. None of the ALCLs examined contained evidence of HTLV-1 or HIV integration nor did they exhibit c-myc or bcl-2 proto-oncogene rearrangements. No mutations or deletions of the p53 tumor suppressor gene were identified in the three cases studied. CONCLUSIONS: HIV-related ALCL represents a clinically heterogeneous group of T cell, B cell and null cell malignant lymphomas, distinct from the previously described categories of AIDS-associated NHL, that may expand the spectrum of lymphoid neoplasms associated with HIV-infection. Identification and investigation of other cases of HIV-associated ALCL is important to determine the nature of the relationship between HIV infection and the development of ALCL.

Adult↗
PubMed1993

High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma.

Strong immunohistochemical reactivity for p53 tumor suppressor gene product has been reported in a variety of different human malignancies including CD30- (Ki-1) positive anaplastic large cell lymphoma (ALCL). Although high levels of p53 protein have been interpreted as abnormal, rapidly proliferating benign and neoplastic lymphoid cells may have increased p53 expression in the absence of structural alterations. On the other hand, mutations in the p53 gene can lead to a lack of p53 protein production. Structural alterations of the p53 gene have not been documented in cases of ALCL and the mechanism for an abnormal pattern of p53 expression in these lymphomas has not been elucidated. Therefore, to determine whether an altered pattern of p53 expression correlates with mutations in the p53 locus in ALCL, we analyzed the expression of p53 protein immunohistochemically, compared it with the proliferation index using monoclonal antibody Ki-67, and assessed the presence of mutations in exons 5 though 9 of the p53 gene using a single-strand conformation polymorphism assay in a panel of 17 ALCLs. Furthermore, we studied the presence of allelic deletions of chromosome 17p by restriction fragment length polymorphism analysis. We found significant levels of p53 protein expression in 12 of the 15 cases studied, but identified mutations in only one of 17 cases. An allelic deletion in chromosome 17p was identified only in the one case containing a mutated p53 gene. Whereas the case containing structural alterations in the p53 gene did have strong p53 immunoreactivity, 11 cases that lacked p53 mutations in the regions examined also had significant levels of p53. Thus, our studies indicate that strong immunohistochemical reactivity for p53 is not a reliable indicator of the presence of structural alterations of p53 gene exons 5 through 9 in ALCL.

Adolescent↗
PubMed1993

Detection of immunoglobulin gene rearrangement of B cell non-Hodgkin's lymphomas and leukemias in fresh, unfixed and formalin-fixed, paraffin-embedded tissue by polymerase chain reaction.

BACKGROUND: The majority of B cell nonHodgkin's lymphomas (NHLs) are composed of a genotypically identical cell population characterized by a unique immunoglobulin (Ig) VDJ gene rearrangement which is customarily documented by Southern blot hybridization analysis of fresh tissue. Sometimes, however, this approach cannot be used because of an insufficient quantity of tissue or the unavailability of fresh tissue. Therefore, alternative strategies should be designed in order to overcome these limitations. EXPERIMENTAL DESIGN: One possible alternative is the identification of Ig VDJ products of normal and neoplastic B cells by polymerase chain reaction (PCR) using mixed oligonucleotide primers recognizing the framework III region or Ig variable heavy chain leader sequences and universal Ig heavy chain joining region (JH) oligonucleotide primers. To determine whether the respective DNA samples are suitable for PCR amplification, control and unrelated genes should also be investigated (exon 5 of the p53 gene). In this study, genomic DNA was extracted from a well characterized panel of 139 human B cell lymphoid leukemias and NHLs derived from fresh (84) and/or paraffin-embedded (55) tissue, 19 normal peripheral lymphoid tissues, 9 Epstein-Barr virus infected lymphoblastoid cell lines and, as negative controls, 11 T cell LLs. Clonal Ig gene rearrangement products were assessed for the presence of a distinct PCR fragment after framework III-JH PCR amplification and electrophoretic separation and by DNA sequencing of the cloned PCR-Ig fragments. RESULTS: Eighty-eight of the 139 (63%) B-NHLs consisting of 53/84 (63%) fresh, unfixed and 35/55 (64%) formalin-fixed, paraffin-embedded samples, exhibited distinct PCR bands. Using this approach we were able to identify a single clonal B cell population mixed with 1,000 nonB cells or 5 polyclonal B cells. There was no difference in the detection of monoclonality among different B-NHL categories. PCR fragments were not identified in any of 27 normal lymphoid tissues or 11 T-lymphoid leukemias. To detect a larger number of Ig gene rearrangement products, genomic DNA of 12 B-NHL/lymphoblastoid cell lines were investigated using VH-specific leader and JH oligonucleotides by PCR. A single PCR product was obtained in 9 of 12 (75%) cases and their clonality was documented by DNA sequencing of the cloned PCR fragments. The clonality of 11 of the 12 (92%) cases could be demonstrated using both PCR approaches. CONCLUSIONS: Our results suggest that the monoclonality of human neoplastic B cells can be efficiently evaluated by PCR equally well from fresh, unfixed and formalin-fixed, paraffin-embedded tissues. This technique should prove to be a powerful tool in clinical diagnosis and research as well as in the retrospective analysis of archival pathologic specimens.

Base Sequence↗
PubMed1992

Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations.

The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing adult T-cell leukemia/lymphoma (ATLL). However, the long latency period between infection and development of ATLL, as well as the small fraction of the infected population that actually develops this disease, suggest that additional factors are involved in its pathogenesis. Therefore, we performed a molecular analysis of 10 cases of ATLL presenting in a nonendemic area that were shown to have HTLV-I sequences by polymerase chain reaction as well as clonal T-cell receptor beta gene rearrangements. We analyzed these cases for alterations in some of the oncogenes and tumor suppressor genes frequently involved in hematopoietic neoplasia. Specifically, we used a single-strand conformation polymorphism assay to determine the presence of mutations in the p53 tumor suppressor gene, as well as the K-RAS, N-RAS, H-RAS, and c-myc oncogenes. In addition, we studied the c-myc gene for rearrangements by Southern blotting and assessed expression of the retinoblastoma (Rb) and p53 genes by immunostaining. Analysis of the c-myc gene and the RAS family of oncogenes did not show any alterations. Also, the Rb gene was expressed in all cases analyzed. However, we found mutations of the p53 gene in 3 of the 10 cases and these results were confirmed by sequence analysis. In two of these cases, we showed by restriction fragment length polymorphism analysis of chromosome 17p sequences that the p53 mutations were accompanied by a loss of heterozygocity. Also, these mutations correlated with an altered pattern of p53 expression. Thus, mutations in the p53 locus may be a cofactor for the development of ATLL in some cases, whereas the c-myc, Rb, and RAS genes do not appear to be involved in these neoplasms.

Alleles↗
PubMed1987

Mutations in the first exon are associated with altered transcription of c-myc in Burkitt lymphoma.

The c-myc proto-oncogene is involved in chromosomal translocations that are specifically and consistently found in Burkitt lymphoma. Although these translocations are thought to lead to a deregulation of c-myc expression, the structural and functional basis of this phenomenon has not been identified. Mutations in a specific region spanning approximately 70 base pairs and located at the 3' border of the first exon of translocated c-myc alleles were consistently detected in Burkitt lymphoma cells carrying classic (8:14) as well as variant (8:22 and 2:8) translocations. These structural alterations were accompanied by an altered pattern of c-myc transcription, namely, the removal of a block to transcriptional elongation that has been mapped to the same region. Thus, specific c-myc mutations leading to the alleviation of this block to transcriptional elongation may represent a general mechanism causing c-myc activation in Burkitt lymphoma.

Burkitt Lymphoma↗
PubMed1980

Entropy and the contractile state.

Entropy production must accompany the utilization of free energy in any cellular process and is a measure of the degree of randomness or molecular disorder within a system. A highly entropized system approaches equilibrium, is incapable of performing work, and never unrandomizes spontaneously. Therefore, chemical reactions are reversible only if the entropy of the system can be reduced through the expenditure of free energy and at the expense of an increase in the entropy of the surroundings. This concept is discussed in terms of energy production and utilization by myocardial cells under normal and diseased states.

Animals↗
PubMed1979

Cardiac arrhythmias associated with subarachnoid hemorrhage: prospective study.

This is a prospective study of cardiac arrhythmias in patients with acute subarachnoid hemorrhage (SAH) secondary to ruptured aneurysm. Twenty per cent of the patients had serious, life-threatening arrhythmias. However, 100% of the patients had some kind of cardiac arrhythmia. The arrhythmias occurred during the first 48 hours after SAH. Such arrhythmias occur in patients without overt, pre-existing heart disease, hypoxemia, or electrolyte imbalance. A prolonged Q-T interval is frequently observed in patients with SAH who develop serious ventricular arrhythmias. (Neurosurgery, 5: 675--680, 1979).

Acute Disease↗
PubMed1978

[Thermodynamics and electrophysiology of the nervous system].

This study expresses a theory designed to associate the fundamental thermodynamic concepts to the electrophysiology of the nervous system. An analogy is drawn between the thermodynamic and electrical events of the myocardial cell during its mechanical phases with those thermodynamic and electrical events of the nerve cell during conduction. Although the myocardial and nerve cells are designed to perform different functions, their processes of membrane potential activation and corresponding directions of thermodynamic and entropy changes are basically the same. A thermodynamic view of nerve cell "active" potential corresponds to a passive downhill process during which the entropy of the system (nerve cell) increases. In contrast, the so called "resting" membrane potential corresponds to an active uphill process. Thus, there is a paradox because the nerve cell is thermodynamically passive during the "active" membrane potential, whereas it is thermodynamically active during the "resting" membrane potential. It is suggested that inhibition in the nervous system may be considered a thermodinamically active process. If the negentropic process fails, the result is the malfunctioning or the final destruction of the system.

Energy Metabolism↗