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Biomedical subjects

S Lehrer

Publications and source records attributed to S Lehrer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Breast cancer and family history: a multivariate analysis of levels of tumor HER2 protein and family history of cancer in women who have breast cancer.

BACKGROUND: The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). METHODS: We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. RESULTS: HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56 +/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. CONCLUSIONS: The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.

Biomarkers, Tumor↗
PubMed1995

Breast cancer and family history: levels of lipid-associated sialic acid in plasma and absent family history of breast cancer in women who have breast tumors.

BACKGROUND: Breast cancer has a strong genetic component, and at least two breast cancer genes exist. But these genes probably play little role in most breast cancers. Other factors, such as environmental estrogens and diet, may cause the genetic changes involved in the genesis of sporadic breast cancer. A method of observing genetic changes indirectly might be to measure tumor markers known to be associated with breast cancer. METHODS: We measured, by biochemical extraction and partition, lipid-associated sialic acid in plasma (LASA-P), a circulating tumor marker, in a group of 239 women with benign or malignant breast tumors. RESULTS: The concentration of LASA-P was elevated in women with both benign and malignant tumors and no family history of breast cancer (p = 0.046, one-way ANOVA). Because LASA-P levels rise with age and number of pregnancies, we analyzed our data using multiple linear regression. Benign versus malignant character of the tumor, family history of breast cancer, number of pregnancies, and age were the independent variables. Family history of breast cancer had a significant effect on LASA-P levels (p = 0.0146) independent of the effects of age (p = 0.011), number of pregnancies (0.012), and whether the tumor was benign or malignant (p = 0.31). CONCLUSIONS: We hypothesize that elevated LASA-P in women with breast tumors and no family history of breast cancer is a result of the genetic changes occurring in nonfamilial breast cancer. These genetic changes, possibly related to environmental estrogens or other environmental factors, are distinct from the changes due to mutations of BRCA1 or other familial breast cancer genes. Moreover, the elevation of LASA-P suggests that the surface membranes of breast cancer may differ in composition. Further study may lead to exact characterization of the genetic and cell membrane changes associated with familial and nonfamilial breast tumors, and perhaps to better methods of breast cancer prevention and treatment.

Adolescent↗
PubMed1994

Gynecologic manifestations of Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome is a chronic, inflammatory autoimmune disease in which the salivary and lacrimal glands are progressively destroyed by lymphocytes and plasma cells. Because women are affected 10 times more often than men, we studied gynecologic manifestations of Sjögren's syndrome. STUDY DESIGN: One thousand questionnaires were sent to women with Sjögren's syndrome in New York, New Jersey, Connecticut, and Pennsylvania. Five hundred thirty-nine women responded. RESULTS: Women with Sjögren's syndrome reported significant vaginal dryness. There was no relationship of Sjögren's syndrome to either the incidence of infertility or miscarriage, although the 4% incidence of congenital anomalies in offspring was relatively high. Of the congenital anomalies, nine of 19 (47%) were cardiac. A long menstrual cycle (> 35 days) was associated with infertility and neuropathy. CONCLUSIONS: The vaginal dryness in women with Sjögren's syndrome is not surprising, because the nasal and esophageal mucosae are also dry in this disorder. The relationship of infertility to a long menstrual cycle may simply indicate the presence of ovulatory dysfunction or inadequate luteal phase unrelated to Sjögren's syndrome. The relationship of neuropathy to a long menstrual cycle may be related to repeated, prolonged estrogen or progesterone exposure during the long cycles or to involvement of hypothalamic-pituitary-ovarian function.

Female↗
PubMed1994

Association of an estrogen receptor variant with increased height in women.

There is an association between a B region allele (here called the B' allele) of the estrogen receptor (ER) and a history of spontaneous abortion in women with ER positive breast cancer, but no such association for women with ER negative tumors or women without breast cancer. In this study we compared the heights of women carrying the B and B' alleles. The B' allele was identified by polymerase chain reaction to amplify genomic DNA around the polymorphic region of the ER gene, followed by allele specific oligonucleotide hybridization. This analysis used DNA obtained from blood lymphocytes. Women carrying the B' allele were significantly taller than those carrying the wild type allele (B allele). Multiple linear regression also demonstrated that this association remained (p = 0.017), controlling for the effects of age and race. Since the B' ER allele results from a silent mutation, a second mutation, segregating with it, no doubt plays a role in producing the high incidence of spontaneous abortion we reported previously and the height difference we report here. This second mutation might lie within the estrogen receptor itself or within one of the genes nearby.

Adolescent↗
PubMed1993

Association between pregnancy-induced hypertension and asthma during pregnancy.

OBJECTIVE: Pregnancy-induced hypertension is an important cause of maternal mortality, intrauterine growth retardation, and perinatal mortality. We examined the relationship between pregnancy-induced hypertension and asthma. STUDY DESIGN: The study population consisted of 24,115 women without a history of chronic systemic hypertension who were delivered of live born and stillborn infants at Mount Sinai Medical Center between January 1987 and December 1991. Pregnancy-induced hypertension was defined as blood pressure of at least 140/90 mm Hg or an increase of > or = 30 mm Hg in systolic pressure or > or = 15 mm Hg in diastolic pressure. RESULTS: There was a significant association between pregnancy-induced hypertension and asthma during pregnancy (chi 2 = 17.86, p < 0.001). In addition, there was a significant upward trend in the incidence of asthma during pregnancy in women without, with moderate, and with severe pregnancy-induced hypertension (Mantel-Haenszel chi 2 = 11.8, p = 0.001). Logistic regression analysis demonstrated that the association between pregnancy-induced hypertension and asthma during pregnancy persisted after adjustment for the confounding factors of race or ethnicity, maternal age, parity, and prepregnancy weight (adjusted odds ratio 2.52, 95% confidence interval 1.47 to 4.35, p = 0.0008). An association between pregnancy-induced hypertension and a history of asthma was also found (chi 2 = 11.2, p = 0.001). However, after adjustment for potential confounders, this association failed to achieve statistical significance (adjusted odds ratio 1.2, 95% confidence interval 0.97 to 1.53, p = 0.083). CONCLUSION: Both pregnancy-induced hypertension and asthma might be caused by a third factor affecting smooth muscle reactivity.

Asthma↗
PubMed1993

Estrogen receptor variant and hypertension in women.

Eighty-eight women visiting a gynecologist were tested for an estrogen receptor B-variant allele. The women were ethnically and racially homogeneous to a large degree. They were from a suburb of Long Island, and most were white. The 12% incidence of hypertension in women with the estrogen receptor wild-type allele is comparable to the 13-32% incidence in the general population of women aged 55-64 years. However, the 48% incidence of hypertension in women with the estrogen receptor B-variant allele is considerably higher than in the general population of women in this age group. We conclude that the presence of the estrogen receptor B-variant allele might have increased the prevalence of hypertension in the women in this study.

Age Factors↗
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↗