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Biomedical subjects

A M Goldstein

Publications and source records attributed to A M Goldstein.

At least 127 records · Page 7Linked to original sources
PubMed1989

A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. II. Linkage analysis.

We conducted genetic linkage analyses of breast cancer in 20 pedigrees, each having at least one case of bilateral breast cancer diagnosed before 50 years of age. We tested for linkage using inheritance models from previous segregation analyses, incorporating differences in risk based on menopausal status into the analyses. We tested for heterogeneity by predividing the data set based on the interval between diagnoses of the proband's two primaries (less than 1 year (synchronous) versus at least 2 years (asynchronous], and on the histological types of breast cancer in the pedigrees. Very tight linkage could be excluded between breast cancer and ABO, GC, GPT, MNS, and PGM1 for some of the different linkage analyses. A maximum lod score of +1.01 (at theta = 0.001) between ACP1 and a breast cancer susceptibility locus was seen in the asynchronous all-cases subsample.

Breast Neoplasms↗
PubMed1988

A competitive enzyme-linked immunoassay (ELISA) for the measurement of soluble human interleukin-2 receptors (IL-2R, Tac protein).

A solid-phase, competition enzyme-linked immunosorbent assay (ELISA) was established for the quantitative measurement of soluble (human) interleukin-2 receptors (IL-2R). The ladder of reagents from the solid phase up consisted of: (1) recombinant DNA-derived, purified IL-2R, (2) sample-containing soluble IL-2R and fluorescein isothiocyanate (FITC)-conjugated monoclonal antibody, 7G7/B6, directed against the IL-2R, (3) alkaline phosphatase-conjugated rabbit anti-FITC, and (4) substrate. This ELISA was compared with a 'sandwich' ELISA for soluble IL-2R. The competitive ELISA was less sensitive than the 'sandwich' assay, being capable of measuring 5000 versus 31 U/ml, respectively. While both anti-Tac and 7G7/B6 in the IL-2R-containing sample inhibited the 'sandwich' assay, only 7G7/B6 inhibited the competition assay. Anti-mouse immunoglobulin enhanced the 'sandwich' assay and inhibited the competitive assay; both effects could be overcome by the addition of normal mouse immunoglobulin in the sample buffer. Studies of a patient's serum receiving anti-Tac as therapy for the adult T cell leukemia demonstrated that rises in the level of IL-2R occurring with anti-Tac therapy, as measured with the competition assay, were masked in the 'sandwich' assay. This competition ELISA will be useful for measuring soluble IL-2R levels in patients receiving anti-Tac as therapy for various immunologic disorders.

Antibodies, Monoclonal↗
PubMed1988

Possible heterogeneity in the segregation pattern of breast cancer in families with bilateral breast cancer.

We investigated the segregation pattern of breast cancer in families with bilateral breast cancer, classifying families with respect to menopausal status (premenopausal versus postmenopausal) and the interval between diagnosis of the two primary tumors in the probands. Probands were "synchronous" if both primaries were diagnosed within 1 year; "asynchronous" if the interval was at least 2 years. Results for four complex segregation analyses are here presented; the findings support heterogeneity in the transmission of breast cancer. In the asynchronous premenopausal-cases-only analysis, a dominant Mendelian gene can explain the breast cancer pattern. A recessive gene is sufficient to describe the breast cancer distribution in the synchronous premenopausal-cases-only analysis. The synchronous all-cases and the asynchronous all-cases analyses add postmenopausal cases of breast cancer to the premenopausal ones, considering any case to be affected. In the asynchronous all-cases analysis, neither the single-locus model nor the mixed model (that is, a major locus plus other factors, genetic and/or cultural) without generation differences in heritability can be rejected by the unrestricted mixed model with generation differences in heritability. For the synchronous all-cases analysis, a mixed model with generation differences in heritability is necessary to explain the breast cancer transmission. Potential sources of error and possible interpretations are discussed.

Breast Neoplasms↗
PubMed1987

A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. I. Segregation analysis.

A complex segregation analysis was conducted of breast cancer in 200 families with bilateral breast cancer. Results for two analyses are presented. The first analysis considered only premenopausal cases of breast cancer as affected. The results indicate that mendelian transmission of a single locus is not sufficient to explain the distribution of premenopausal breast cancer seen. A mixed model, i.e., a major locus plus other transmission (genetic and/or cultural), is necessary to explain the distribution. The second analysis added postmenopausal cases of breast cancer to the premenopausal ones, thus considering all breast cancer cases to be affected with the same disorder. The all-cases analysis is unable to reject a mixed model with no generation differences in heritability when tested against the general model, which allows for generation differences (i.e., the likelihoods for the two models were not significantly different). Approaches to studying etiologic heterogeneity in segregation analysis and results of other segregation analyses of breast cancer are presented.

Breast Neoplasms↗
PubMed1986

Cleft lip with or without cleft palate: reanalysis of a three-generation family study from England.

The study population consists of 424 three-generation families originally ascertained through nonsyndromic cleft lip with or without cleft palate (CL +/- P) surgical probands by Carter et al [J Med Genet 19:246-261, 1982] in London, England. Carter et al proposed that the multifactorial threshold model (MF/T) could explain the data. The goal of our study was to test that hypothesis, plus alternatives, rigorously. Two approaches were used: 1) Carter et al had proposed that these data were consistent with the predictions of the MF/T as presented by Carter [Br Med Bull 25:52-57, 1969]. However, we tested those predictions using standard chi 2 tests and found statistically significant departures from the predictions in these families. 2) Complex segregation analysis under the mixed model was performed. Again, the MF/T model could be rejected, as could a model of a major locus alone. The best-fitting model included both major locus and multifactorial components. When the data were analyzed in two parts based on the proband's phenotype (CL vs CL + P) there was some evidence of heterogeneity in that there was a significant proportion of sporadic cases in the families of CL probands but not in the families of CL + P probands. Our results provide no support for the MF/T model. The results from segregation analyses of CL +/- P in these families were most consistent with autosomal major gene inheritance plus multifactorial contributions.

Cleft Lip↗
PubMed1986

Serine protease inhibitors of North American leeches.

Serine protease inhibitors in extracts from three North American leeches, Nephelopsis obscura, Erpobdella punctata and Hemopis marmorata have been separated by anion exchange chromatography and the activity pattern against human granulocyte elastase and porcine chymotrypsin and trypsin determined. All three leech species contained a major peak with anti-trypsin activity, but Hemopis was unique in that the trypsin inhibitor was equally active against chymotrypsin. Nephelopsis was rich in anti-elastase activity of two types, one which was also active against chymotrypsin, and one which was a specific elastase inhibitor. Erpobdella contained inhibitors against elastase and chymotrypsin but with major activity against the latter.

Animals↗
PubMed1985

The fibrous skeleton of the corpora cavernosa and its probable function in the mechanism of erection.

The corpora cavernosa contain a fibrous skeleton composed of tunica albuginea with its fibrous columns, periarterial and perineural fibrous sheaths, and an intraparenchymal fibrous framework attached to all fibrous elements of the corpora cavernosa. This anatomical arrangement probably plays an important part in the firmness of the corpora cavernosa during erection. The fibrous framework, due to its numerous attachments to the deep surface of the tunica albuginea and its columns, when stretched during erection, prevents bending and deformation of the corpora cavernosa.

Adolescent↗
PubMed1984

Special microanatomical features surrounding the intracorpora cavernosa nerves and their probable function during erection.

The nerves of the corpora cavernosa have anatomical characteristics different from other nerves. The intracavernous nerves are located in fibrous tunnels into which numerous fibrous bundles establish attachments. These bundles are part of the fibrous meshwork included in the corpora cavernosa. We suspect that during erection, when the corpora fill with blood and high intracavernous pressure develops, the aforementioned meshwork of fibrous bundles attached to all fibrous elements of the corpora, including the tunica albuginea and the perineural fibrous tunnels, stretches and prevents compression of the intracavernous nerves.

Adolescent↗
PubMed1983

High pressure within corpus cavernosum in man during erection. Its probable mechanism.

Corpus cavernosum pressure in man during erection has not been measured previously with a noninvasive technique. Using such a technique it has been shown that during erection in young men intracavernosal pressure has peaks of at least ten times higher than the systemic systolic pressure. These findings indicate that during erection the intracavernosal circulation is contained, at least partially, within a closed system, separated from the general circulation. Also erection cannot be the result of circulatory function only.

Adult↗