Biomedical subjects

C Egwuagu

Publications and source records attributed to C Egwuagu.

5 recordsLinked to original sources

PubMed1996

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals↗

PubMed1995

Malignant and nonmalignant brain tissues differ in their messenger RNA expression patterns for ERCC1 and ERCC2.

Perturbation of the DNA repair process appears to be responsible for the occurrence of a number of human diseases, which are usually associated with a propensity to develop internal malignancies and/or disorders of the central nervous system. We have been interested in the possibility that a subtle abnormality in DNA repair competency might be associated with the transformation of nonmalignant cells to the malignant state. To study this question, we assayed malignant and nonmalignant brain tissues from 19 individuals for mRNA expression levels of the human DNA repair genes ERCC1, ERCC2, and XPAC and for differential splicing of the ERCC1 transcript. We separately compared expression levels of these genes in the following situations: concordance of expression within malignant tissues; concordance of expression within nonmalignant tissues; concordance between malignant and nonmalignant tissues within individuals of the cohort; and concordance of gene expression between two nonmalignant tissue sites within a single individual. Linear regression analyses of mRNA values obtained suggested orderly concordance of these three DNA repair genes in nonmalignant tissues within the patient cohort and an excellent concordance of these genes between two separate biopsy sites from the same individual. In contrast, malignant tissues showed disruption of concordance between the full-length ERCC1 transcript and ERCC2, which have excision and helicase functions, respectively. Furthermore, within the same individuals, malignant tissues were discordant with nonmalignant tissues for ERCC1 and ERCC2, although concordance for XPAC was preserved. These data suggest that one molecular characteristic of human malignancy may be the disruption of the normal relationship between the excision and the helicase functions of the nucleotide excision repair pathway.

Brain↗

PubMed1993

Expression of excision repair genes in non-malignant bone marrow from cancer patients.

The patterns of expression of 3 human DNA-repair genes (ERCC1, ERCC2, ERCC6) were assessed in 52 bone-marrow specimens obtained from cancer patients prepared for autologous bone-marrow transplantation. Marrow was collected prior to the initiation of treatment in patients with sarcoma or testicular cancer; marrow was collected after initial cytoreductive therapy for patients with non-Hodgkin's lymphoma, Hodgkin's disease, and other tumors. Slot-blot analysis of marrow RNA showed a bimodal pattern of ERCC1, ERCC2 and ERCC6 gene expression with relative expression values ranging more than 200-fold. This pattern was seen in all patient groups and appeared to be independent of whether or not patients had received prior chemotherapy. In all patient groups, when expression was low for ERCC1, expression was also low for ERCC2 and ERCC6, suggesting that expression of these genes may be coordinated within an individual although they are located on two different chromosomes. Southern blot analyses of Pst I digests of DNA from 6 bone-marrow samples indicate no differences in ERCC1 gene copy number between high expressors and low expressors. There is absence of restriction fragment length polymorphism for ERCC1 suggesting that the different levels of expression in high and low expressors were not due to major deletions or rearrangements of the ERCC1 gene. We conclude that expression of these ERCC genes may vary widely between individuals, and that within an individual, their expression may be linked and coordinated by a common regulatory mechanism.

Bone Marrow↗

PubMed1992

ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients.

BACKGROUND: ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents. PURPOSE: Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance. METHODS: Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene. RESULTS: Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders. CONCLUSION: We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.

Blotting, Southern↗

PubMed1983

African trypanosomes contain calmodulin which is distinct from host calmodulin.

Studies were initiated to determine whether African trypanosomes utilize Ca2+ fluxes to coordinate complex morphological and biochemical life cycle changes. We have identified the ubiquitous intracellular Ca2+ receptor, calmodulin, in two developmental stages of Trypanosoma brucei rhodesiense. The transition from rapidly dividing, slender bloodstream trypomastigotes to slow growing procyclics in axenic culture was accompanied by changes in specific calmodulin content (3 micrograms/mg cell protein to 1 microgram/mg cell protein, respectively) and a shift in intracellular calmodulin distribution, Trypanosome calmodulin is physically and functionally distinct from that of host tissues, including bovine brain and rat erythrocytes. It is similar to but distinct from Tetrahymena calmodulin. Comparisons among these proteins isolated from the four sources were made using the following criteria: (1) mobility on sodium dodecyl sulfate discontinuous polyacrylamide gels; (2) Ca2+-induced conformational changes; (3) CNBr-cleavage fragments; (4) activation of bovine brain cyclic nucleotide phosphodiesterase in both a Ca2+-dependent and calmodulin-dependent manner; (5) activation of human erythrocyte (Ca2+ + Mg2+)-ATPase; and (6) inhibition of calmodulin activity by trifluoperazine and penfluridol. Trifluoperazine but not trifluoperazine sulfoxide was cytotoxic to trypanosomes in vitro. Half maximal effect occurred at 15 microM. We conclude that calmodulin is a functional component of Africal trypanosomes and suggest that it plays an important role in mediating the host-parasite relationship.

3',5'-Cyclic-AMP Phosphodiesterases↗