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Biomedical subjects

E May

Publications and source records attributed to E May.

At least 19 recordsLinked to original sources
PubMed1995

Mutations clustered in exon 5 of the p53 gene in primary nasopharyngeal carcinomas from southeastern Asia.

Mutations in the p53 tumor suppressor gene play an important role in the development of many common human malignancies. In nasopharyngeal carcinomas (NPC), p53 gene mutations were not detected in primary tumors, with one exception for a primary tumor displaying a p53 mutation at codon 280, whereas p53 mutations were identified in some metastatic and nude mouse-passaged NPC specimens. In the present report, 41 NPC primary tumors of the undifferentiated carcinoma nasopharyngeal type (UCNT; 21 from Hong Kong and 20 from Guangxi, southeastern China) were studied. Four point mutations that result in amino acid substitutions were identified by PCR amplification of exons 2-9 and direct DNA sequencing, combined with PCR-single-strand conformation polymorphism analysis. The 4 mutations detected were clustered within the DNA stretch from codon 175 to 177. Our data, taken together with those of others, suggest that mutation in p53 may occur in NPC at various points during tumorigenesis. Alternative mechanisms of p53 inactivation in NPC are also possible.

Animals↗
PubMed1995

p53 protein accumulation in European hepatocellular carcinoma is not always dependent on p53 gene mutation.

BACKGROUND/AIMS: Immunohistochemical reactivity for p53 protein is common in various human malignancies and often related to p53 gene mutation. However, in some tumor types, accumulation of wild-type p53 has been shown. Previously, we analyzed 96 European hepatocellular carcinomas using immunohistochemistry and found that 31% of these tumors overexpressed p53 in the cell nucleus. The aim of the present study was to establish whether p53 positivity correlates with the presence of structural p53 gene abnormalities in European hepatocellular carcinoma. METHODS: DNA from 20 tumors, 10 with strong immunostaining and 10 with undetectable staining for p53, was extracted from frozen sections, and the entire coding portion of the p53 gene was sequenced. RESULTS: Five of the 10 tumors containing high levels of p53 protein showed missense point mutations. The remaining 5 tumors with high p53 levels showed the wild-type coding sequence. One of the 10 tumors containing undetectable levels of p53 protein had a 1-base pair deletion in the splice acceptor site of intron 4. CONCLUSIONS: The results strongly suggest that, in European hepatocellular carcinomas, stabilization of the p53 protein depends on factors other than p53 gene mutation, such as binding to other molecules of cellular or viral origin.

Adult↗
PubMed1995

Regression of transplant coronary artery disease during chronic HELP therapy: a case study.

This report concerns a heart transplant patient with hypercholesterolemia who showed rapid development of a severe transplant coronary artery disease. The patient received 10 mg pravastatine per day. Quantitative coronary angiography analyses of 4 serial angiograms clearly demonstrated that in the first 2.5 years following surgery, there was a rapid simultaneous progression in both the transplant coronary disease, involving the entire coronary system, and the development of segmental stenotic lesions. During one year of weekly heparin-mediated extracorporeal LDL-cholesterol precipitation (HELP) therapy in addition to diet and pravastatine therapy, the serum low density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and fibrinogen levels could be reduced from 185 +/- 45 mg/dl, 138 mg/dl and 248 mg/dl, respectively, to interval values of 136 +/- 17 mg/dl, 48 +/- 15 mg/dl, and 185 +/- 44 mg/dl, respectively [interval value = (the concentration after HELP + the concentration before the next HELP treatment):2]. This therapy halted further progression of coronary diameter throughout the whole coronary system and brought about marked regression of segmental obstructive lesions.

Arteriosclerosis↗
PubMed1995

Human estrogen receptor messenger RNA variants in both normal and tumor breast tissues.

By using the PCR-SSCP technique we characterized various ER-specific RNA species present in a series of primary breast cancers, as well as in cell lines established from breast carcinomas and in mammary gland tissues from healthy specimens. A series of six truncated messenger RNAs generated by alternative splicing was characterized. These RNAs correspond to specific deletions of one (exons 2-7, except exon 6) or two (exons 3 + 4) exons. All these RNA variants are observed in each one of the analyzed RNAs, regardless of origin. In addition, the relative amount of these different variants in ER + tumors is comparable to that measured in ER - tumors and healthy mammary gland tissues. This data suggests that tumor progression is not related to the emergence of any of the ER mRNA variants.

Alternative Splicing↗
PubMed1995

Nonisotopic competitive RT-PCR assay to measure MDR1 gene expression.

We report an original application of competitive reverse transcription-polymerase chain reaction (RT-PCR) for the quantification of MDR1 mRNA in clinical specimens by simultaneous reverse transcription and PCR amplification of cellular RNA with decreasing amounts of an internal standard. The competitor RNA shares the same MDR1 primer sequences as the cellular mRNA, but yields a different-sized PCR product. This allows resolution of the amplified cDNA fragments after agarose gel electrophoresis and ethidium bromide staining. The concentration of MDR1 mRNA is derived from the ratio between the intensities of the bands corresponding to the amplified products. We have used this assay to measure MDR1 expression in breast carcinomas and assessed the precision, sensitivity, and accuracy of the method. Competitive RT-PCR is a simple, highly specific, nonradioactive procedure for the quantification of MDR1 mRNA and is particularly suitable for use in the clinical laboratory.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

[P53 and cancers].

The p53 gene, located on chromosome 17p 13.1 and coding for a nuclear 393 amino-acids phosphoprotein acts to constrain or antagonize cell growth, and as such, is a tumor suppressor gene. In fact, inactivation of p53 tumor suppressor gene is a common event in the development of all or most types of human cancers. About half of cell cancer cases analysed thus far involve missense mutation of one p53 allele combined with the deletion of the second allele, and many of the remaining cases involve a functional inactivation of p53 protein through non mutational mechanisms. The importance of p53 as an inherited cancer susceptibility gene has been demonstrated in Li-Fraumeni syndrome. In some circumstances, it has been shown that in response to DNA damage, the p53 level in the cell increases considerably and induces a cell growth arrest late in G1 phase. This cycle arrest allows the altered DNA to be repaired before entry of the cell into S phase. This function of p53 helps to insure the genomic stability of the cell. Mutations in p53 eliminate this response and result in enhanced frequency of genomic rearrangements. In other circumstances wild type p53 may act by triggering cell death by apoptosis. The p53 protein exerts its physiological functions through various biochemical activities. These include its ability to be a site-specific transcriptional transactivator as well as a repressor of transcription. The oncoproteins derived from several oncogenic DNA viruses including SV40 large T antigen, the adenovirus E1B protein, and papillomavirus E6 protein, as well as specific cellular gene products e.g. mdm2 form complexes with the p53 protein, causing its inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Genes, Tumor Suppressor↗
PubMed1994

Estrogen receptors (ER) in human breast cancer. The significance of a new prognostic factor based on both ER protein and ER mRNA contents.

BACKGROUND: The response to endocrine therapy is not entirely predictable from the estrogen receptor (ER) and progesterone receptor (PgR) status of primary breast tumors. The authors previously proposed a new prognostic factor, ER.R, which was based on both ER protein and mRNA levels. A previous analysis of 88 primary breast carcinomas showed that ER.R permits the identification of a subset of ER-positive women with a higher risk of early relapse. The purpose of the present study was to confirm the prognostic significance of ER.R. METHODS: Estrogen receptor protein levels were determined for 171 patients with primary breast cancer either by radio-ligand binding assay (ER-LBA) or enzyme immunoassay (ER-EIA). Estrogen receptor, pS2, and c-erbB-2 mRNA were measured by Northern blot analysis. RESULTS: ER.R factor is determined by calculating the ratio of the values (ER protein in fentomoles per milligram of total proteins) to (ER mRNA in picograms per 4 micrograms of total RNA). A cutoff value of 1.5 (protein levels measured by ER-LBA) or 3 (protein levels measured by ER-EIA) discriminate the two ER.R1 (lower ratio) and ER.R2 (higher ratio) subgroups, which present a significantly lower and higher risk of early relapse, respectively. No association was found between ER.R status and either PgR status or c-erbB-2 and pS2 expression. According to a Cox multivariate analysis for disease free survival, the two stronger factors in predicting a poor prognosis were c-erbB-2 overexpression and ER.R2. In the present analysis, ER.R2 was a stronger predictor of recurrence than was ER negativity. CONCLUSIONS: In accordance with the authors' first published data, the analysis of a larger population with a longer follow-up showed that ER.R2 keeps its significance to predict a poorer outcome for a patient, regardless of which assay was used to quantify ER.

Breast Neoplasms↗
PubMed1994

Concomitant p53 gene mutation and increased radiosensitivity in rat lung embryo epithelial cells during neoplastic development.

A rat lung cell population had been treated with benzo(a)pyrene, and a set of different epithelial cell lines was derived from it. These cell lines carried either a wild-type or mutant p53 gene and represented grading states of neoplastic development. We demonstrate here that the cells lacking both wild-type p53 alleles display a significant decrease in survival after gamma-irradiation with doses of 2 to 12 Gy, compared with their counterparts carrying wild-type p53 alleles. This is the first reported model in which cells bearing a mutation of the p53 gene display enhanced sensitivity to ionizing radiation.

Animals↗
PubMed1994

[Comparative biometric studies of school children from Kenya and Braunschweig].

Constitution and growth biology of 6 to 7 years old children from a European city ("Braunschweiger Längsschnitt") and a country with rather original habits (extreme rural area of Kenya, "Abaluya"--administrative name of Bantuid tribes from W-Kenya--out of the region of Idakho and Tiriki, elevated in spring 1990) were comparatively studied. To achieve comparability in physique and body height, the elevated data were "allometrically standardized". The statistical parameters and the results of correlation statistics were shown by comparing the two groups of children. This paper is thought to be the first attempt of a more extensive study in which further more comparative data from other age groups of children and different ecological factors as climate or nutrition should be involved in the analysis. At least the knowledge of standardized data is a cogent assumption to judge about constitution, typology and health of populations.

Anthropometry↗
PubMed1992

Simian virus 40 T antigen activates the late promoter by modulating the activity of negative regulatory elements.

Late promoter activity measured before viral DNA replication results from a complex involvement of negative and positive cis-acting elements located both in the enhancer and in the 21-bp repeats. GC motifs located within the 21-bp repeats act in cooperation with sequences overlapping the early TATA box to down-regulate the late promoter activity. Analysis of insertion mutants indicates that the late promoter might be negatively regulated at least partially by the early promoter machinery. The GTI motif located within the enhancer as well as the GC motifs lose the ability to down-regulate the late promoter in the presence of T antigen. Results obtained with tsA58 protein indicate that two different domains of T antigen are involved in the negative autoregulation of the early promoter activity and in the release of the down-regulation of the late promoter by the GC motifs.

Animals↗
PubMed1992

p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas.

The nuclear phosphoprotein p53 is an important regulator of cell proliferation in normal cells. Interestingly, the gene encoding p53 has usually undergone mutations in a wide range of tumor types. Recent studies of the p53 gene in Burkitt's lymphomas have demonstrated that mutations are extremely common, and in fact it is rare that both alleles of the p53 gene in these tumors are not inactivated by mutation or deletion. We present here genetic data regarding the status of the p53 gene in the Burkitt lymphoma cell line, Raji. As is typical for this type of tumor, both alleles have undergone point mutations. Further, statistical analysis of available data from a large number of Burkitt's lymphomas indicates an apparent tumor-specific distribution of p53 mutations. The possibility that specific mutations of the p53 gene may be important for different tumor types is discussed.

Alleles↗
PubMed1992

[The interpretation of morphometric data of 10- to 13-year-old school children from the survey year 1978 of the Braunschweig Longitudinal Study].

The paper represents a cross-sectional study from a sample of 1800 out of 3000 school-children from the Braunschweiger Längsschnitt. In this methodical approach we first eliminate approximately the influence of age and stature on the raw data from all body measurements with regression equations. The transformed data were attached to three "types" named 'below normal', 'normal', and 'above normal', in course of which 'normal' means all cases in the range of the standard deviation, whereas the two other "types" are corresponding to the adjacent ranges of values. Subsequently each transformation on the mean of age and stature a discriminant analysis has been performed grouping the cases by the "types" of the width of pelvis, resp. shoulders. There were found great influences of the stature on the chosen measures of width in our investigated class of age. They could be made clear alone by using allometrical methods. Only before correction of the body height the given grouping is supported by other variables, at which different sets of variables dominate the discriminant functions for boys and girls. Out of this new aspects and considerations result for the understanding of the physique and the physique typologies, which would be significant in our opinion for acceleration phenomenon as well as for the comparative examinations on populations.

Age Factors↗
PubMed1991

Immunological evidence for the association between simian virus 40 115-kDa super T antigen and hsp70 proteins in rat, monkey, and human cells.

Immunological evidence was provided that in subclone 7 cell line, which is derived from SV40 transformed cells, 115-kDa super T antigen, a transformation-competent, elongated form of large T antigen was physically complexed with hsp70 proteins. This conclusion was first based on the coimmunoprecipitation from unstressed or heat shocked subclone 7 cells of both super T antigen and hsp70 proteins. This was observed with any one of a set of anti-T monoclonal antibodies reacting to determinants located either in the C-terminal region or in the N terminal region. Reciprocally coimmunoprecipitation of both hsp70 and super T was also observed in the anti-hsp70 peptide serum-immunoprecipitate. The formation of complexes between hsp70 proteins and super T antigen in subclone 7 cells was also confirmed by Western blot experiments. Moreover, when expressed in cell lines originating from human (Hela cells) or monkey (CV1P cells) species following transfection with the relevant plasmid, super T antigen again displayed the ability to associate with hsp70 proteins. Considering that super T antigen was obtained in laboratory experiments as a stable evolutionary variant of SV40 large T antigen, it is suggested that the marked ability of super T antigen to associate with heat shock protein could be selectively advantageous under certain conditions.

Animals↗
PubMed1991

Characterization of SV40 enhancer motifs involved in positive and negative regulation of the constitutive late promoter activity; effect of T-antigen.

By analyzing the late promoter activity of a series of nonreplicative recombinants mutated within the different enhancer motifs of SV40 we identified both positive and negative regulatory elements. In the absence of T-antigen, the motifs Sph and/or octamer, and to a lesser extent the motifs GTI and P, account for the constitutive expression of the late promoter. The motif GTII overlaps elements that negatively regulate the expression of the late promoter. These results indicate that the late promoter is down-regulated not only at the level of the GC motifs but also at the enhancer level. Moreover, we showed that T-antigen interacts with both positive and negative regulatory elements.

Antigens, Viral, Tumor↗