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Biomedical subjects

S Lehrer

Publications and source records attributed to S Lehrer.

At least 19 recordsLinked to original sources
PubMed1992

Past pregnancy is associated with axillary node involvement in women with breast cancer.

In 186 women with breast cancer, there was a progressive increase in the proportion of axillary nodal involvement as the number of pregnancies increased from zero to two or more (P = 0.026). Logistic regression analysis demonstrated that this effect was independent of the known relationship of age and tumor size to nodal involvement. Race and history of breast feeding had no influence on nodal involvement.

Axilla↗
PubMed1992

Diminished ratio of estrogen receptors to progesterone receptors in breast carcinomas of women who have had multiple miscarriages.

We examined the relationship of a history of miscarriage to the ratio of tumor estrogen receptors to progesterone receptors in 74 women with breast carcinoma evaluated between 1988 and 1990. Only women who had been pregnant and whose tumor contained both estrogen and progesterone receptors were included. Women with breast carcinoma and a history of two to four miscarriages had significantly lower ratios (less than 1) of tumor estrogen receptors to progesterone receptors than women with a history of zero or one miscarriage (greater than 1). This finding may be the result of a genetic anomaly in breast cancer patients that also affects the uterine environment during the reproductive years.

Abortion, Habitual↗
PubMed1991

Incidence of an estrogen receptor polymorphism in breast cancer patients.

We previously identified a polymorphism in the human estrogen receptor (ER) gene, within the coding region for the protein's amino terminal B-domain. In estrogen receptor-positive (ER+) breast tumors, the variant allele was preferentially associated with lower levels of ER, and was clinically correlated with frequent spontaneous abortions. DNA sequencing revealed a point mutation that changes codon 86 from Ala to Val and a silent mutation in codon 87. Because we initially detected the variant allele by analyzing RNA, only those tissues in which the ER gene is actively expressed were suitable for genotype analysis. We now describe an assay that uses genomic DNA as the substrate for determining the ER B genotype, DNA containing the polymorphic region of the ER gene is amplified by the polymerase chain reaction, then the amplified DNA is hybridized with radiolabeled oligonucleotide probes complementary to the wild type and variant ER alleles. This method allowed us to determine the ER B genotype of women with ER+ and ER- tumors, starting with minute amounts of DNA from frozen or paraffin embedded tissues. ER B genotyping was also performed on women without breast cancer using DNA extracted from blood cells. The combined results from analyses of RNA and DNA from 300 breast cancer patients showed that 12% were heterozygotes. In the ER+ group (n = 183), 11.5% carried the variant gene compared to 12.8% in the ER-negative group (n = 117) (chi 2 = 0.11; df = 1; p greater than 0.25).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1991

Adjuvant effects of dimethyl dioctadecyl ammonium bromide, complete Freund's adjuvant and aluminium hydroxide on neutralizing antibody, antibody-isotype and delayed-type hypersensitivity responses to Semliki Forest virus in mice.

Outbred mice were inoculated subcutaneously with inactivated Semliki Forest virus (SFV) in saline and combinations of the virus with complete Freund's adjuvant (CFA) aluminium hydroxide (Al) and dimethyl dioctadecyl ammonium bromide (DDA). The immune response was evaluated for delayed-type hypersensitivity, for total ELISA antibodies and antibody-isotypes and for neutralizing antibodies. DDA was the most efficient adjuvant in inducing DTH, CFA the second and Al induced a DTH response that was only slightly higher (statistically not significant) than that induced by the inactivated virus without adjuvants. All adjuvants enhanced the production of ELISA antibodies to similar levels. However, the levels of neutralizing antibodies induced were low in mice which were inoculated with the inactivated SFV alone or mixtures of the virus with Al. DDA induced high levels of neutralizing antibodies and CFA induced intermediate levels. The pattern of antibody-isotypes induced by DDA and CFA was different from the pattern induced by the inactivated virus or by the virus mixed with Al: DDA and CFA induced low amounts of IgG1 antibodies and relatively higher amounts of IgG2a and IgG2b antibodies while the inactivated virus and the mixture of the virus with Al induced higher proportions of IgG1 antibodies. In sera from convalescent mice the majority of antibody activity resided in the IgG2a and IgG2b immunoglobulin subclasses, while IgG1 antibodies were undetectable.

Adjuvants, Immunologic↗
PubMed1990

Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer.

To examine whether a variant human oestrogen receptor gene, which differs from the wild-type gene in the B region, was associated with spontaneous abortion, obstetric histories of breast cancer patients with this variant were compared with those of breast cancer patients with the wild-type gene. In women with the B-variant, 50% of pregnancies ended in spontaneous abortion, compared with 10% for women homozygous for the wild-type gene. B-variant women also had a higher proportion of spontaneous abortions and a higher number of spontaneous abortions per woman than did those with the wild-type gene.

Abortion, Habitual↗
PubMed1990

Serologically defined linear epitopes in the E2 envelope glycoprotein of Semliki Forest virus.

A set of 41 overlapping peptides, representing the complete sequence of SFV-E2 protein were synthesized and analyzed in the ELISA test against murine anti-SFV sera. No single peptide was recognized by all antisera. Eight peptides were found to be highly reactive with hyperimmune anti-SFV sera. Six out of the eight peptide sequences coincide with the most hydrophilic regions of SFV-E2. Out of these, four peptides (amino acid positions 16-35, 61-80, 166-185, 286-305) that contain the least number of alphavirus conserved residues were selected. This panel constitutes the minimal number of peptides necessary and sufficient for specific recognition of hyperimmune mouse anti-SFV sera.

Antigens, Viral↗
PubMed1989

Activity of pp60c-src protein kinase in human breast cancer.

Because there is elevation of pp60c-src activity in breast carcinoma tissue, we analyzed primary breast cancer tissue samples from 30 women to determine whether pp60c-src activity correlated with specific clinical parameters. We found that tumors with a progesterone receptor had higher pp60c-src activity than tumors without such a receptor. But there was no association of pp60c-src activity with the presence of an estrogen receptor or of nodes, or with menopausal status or age. The function of pp60c-src in normal cells and in breast cancer is unknown, as is the significance of our finding of an association of elevated pp60c-src activity and the presence of progesterone receptors.

Adult↗
PubMed1988

A variant estrogen receptor messenger ribonucleic acid is associated with reduced levels of estrogen binding in human mammary tumors.

An analysis of the human estrogen receptor (ER) mRNA was performed on 71 human breast tumors using an RNase protection assay. Complementary DNA clones to the human estrogen receptor (lambda R8 and lambda R3) were used to generate small antisense 32P-labeled RNA molecules that were hybridized to the tumor RNA. We determined the relative amounts of ER mRNA in each tumor by measuring the amount of RNases A and T1 resistant hybrids. Moreover, because RNase A has the ability to cleave single-base mismatches within RNA/RNA duplexes, we were able to use the assay to screen for possible mutations or deletions in the ER mRNA. A significant correlation was found between the ER mRNA levels and the estrogen binding concentrations determined by a dextran-coated charcoal assay (r = 0.68; P less than 0.0001; n = 58). We also identified a subpopulation of tumors in which a mismatch in the ER mRNA was detected. This message modification, in the B region of the message, significantly correlated with low levels of estrogen binding. This result suggests that the observed B variant might lead to the production of receptors with altered properties.

Breast Neoplasms↗