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Biomedical subjects

L P Pertschuk

Publications and source records attributed to L P Pertschuk.

At least 37 records · Page 2Linked to original sources

Heterogeneity of steroid binding sites in prostatic carcinoma: morphological demonstration and clinical implications.

Prostatic neoplasms were studied for estrogen binding using four methods. Two employed fluorescent estrogen histochemical ligands, one was a new immunocytochemical technique using specific monoclonal antibodies to human estrophilin, and the last procedure was conventional biochemical dextran-coated charcoal assay. Results indicated that the fluorescent ligands recognized closely associated but separate estrogen-binding sites (putative type II sites) which in turn differed from the binding site measured biochemically. Studies with the monoclonal antibodies were nearly always negative, suggesting that prostatic estrogen receptor might vary antigenically from that present in breast and endometrium. Histochemical and biochemical androgen-binding studies were also compared and showed a close association. In the prediction of hormonal response in advanced prostate cancer both showed high sensitivity and low specificity. The addition of estrogen-binding data did not improve the predictive value of the androgen-binding histochemical assay. However, combining results of the biochemical and histochemical androgen-binding assays resulted in significant improvement of the specificity without loss of sensitivity, suggesting that there is a degree of positive interaction between the binding sites assayed by the two methods.

Androgens↗

Heterogeneity of estrogen binding sites in breast cancer: morphologic demonstration and relationship to endocrine response.

Breast cancer specimens from 184 patients were analyzed for estrogen binding by two different histochemical techniques using conjugates of estradiol, bovine serum albumin, and fluorescein. In one conjugate estradiol was bound at position 6, in the other at position 17. Results were in agreement in 64% (p less than .001), but obvious differences in ligand distribution were noted. Results were also correlated with estrogen receptor (ER) analysis by dextran-coated charcoal assay (DCC) and were in accord in 65% and 67% of specimens respectively (p less than .001). In 114 cases, the tissue samples were also studied with the estrogen receptor immunocytochemical assay (ERICA) of Greene and his colleagues, which employs monoclonal antibodies to ER protein. Results were in accord with DCC in 86% (p less than .001). The pattern of staining with ERICA differed from that of either histochemical method. In 43 cases assay results were correlated with clinical endocrine response. Overall, the best statistical prognostic parameters were obtained with ERICA. Analysis of combined assay results revealed that patients with assays positive by all techniques were the most likely to respond to hormonal treatment (p less than .001), whereas if one or more assays were negative the chances for a good response were significantly less favorable. These data suggest that DCC and ERICA are both a measure of the same estrogen binding site (type I) while the histochemical methods apparently identify two other separate and distinct sites (putative type II sites). A degree of positive interaction may exist between these multiple estrogen binding sites.

Binding Sites↗

Androgen binding in prostatic carcinoma by histochemistry: update 1985.

Fluorescent androgen ligands were employed to study putative androgen-binding (AB) sites in a number of men with prostatic adenocarcinoma. Results were compared with biochemical androgen receptor determinations in over 150 patients with agreement in 86% (p less than 0.001). AB by histochemistry correlated significantly with the outcome of hormonal manipulation (p less than 0.001) but not with response to radiation therapy (p = 0.55) or to 125I implantation (p = 0.54). There was a degree of positive interaction between histochemically and biochemically determined AB sites which produced a significant improvement in assay specificity (p less than 0.05). These findings indicate that the best method for prediction of hormone response in prostate cancer is provided by a combination of assay techniques.

Adenocarcinoma↗

Histochemical androgen binding assay in prostatic cancer.

A group of 60 patients with clinical stage C or D prostatic carcinoma was evaluated for androgen binding using a histochemical assay. Of the patients positive for binding 82 per cent either responded to hormonal therapy or remained stable, while 100 per cent of those negative for binding had progression. Of 6 men whose cancer was considered borderline positive 2 manifested a partial clinical response, while 4 had progression.

Androgens↗

Correlation of histochemical and biochemical analyses of androgen binding in prostatic cancer: relation to therapeutic response.

A histochemical technique for the detection of androgen binding in prostatic cancer was performed on specimens from 108 patients and compared with a biochemical method in a double blind study of 77. Statistical analyses showed a significant agreement between the two assay systems for the qualitative and quantitative presence or absence of specific androgen binding, as well as for the subcellular localization of binding in nucleus and/or cytoplasm. Although the number of cases studied was too small for statistical analysis, there appeared to be good correlation between histochemical androgen binding results and clinical response, or lack of response to hormonal manipulation in 20 patients with State C and Stage D carcinoma. No correlation was evident between androgen binding and tumor grade or clinicopathologic stage of disease of either histochemistry or biochemistry.

Adenocarcinoma↗

The histochemical localization of steroid binding sites in the pituitary gland of a teleost (the platyfish).

Specific binding sites for estrogen, testosterone, and progesterone have been demonstrated in the pituitary gland of mature male and female platyfish (Xiphophorus maculatus). With a histochemical procedure, fluorescent-steroid-hormone conjugates were localized in the cytoplasm and nucleus of the gonadotrops of the caudal pars distalis (CPD) and in cells of the pars intermedia (PI) previously demonstrated to contain immunoreactive gonadotropin. The specificity of the response was confirmed by means of competitive binding analyses and by using fluoresceinated BSA not linked to steroids. The physiological significance of steroid binding in the PI, as well as in the CPD, is discussed in the light of other recent studies on the pituitary gland of the platyfish.

Animals↗

Disseminated toxoplasmosis. Case report and review of the literature.

A 40-year-old man had disseminated toxoplasmosis preceded by miliary tuberculosis and associated with skin anergy. In previously reported cases of disseminated toxoplasmosis, the three organs most commonly involved were brain, heart, and lungs. The histopathologic picture of toxoplasmal lymphadenopathy was not present in our case or in previously reported cases. Therefore, we believe that the diagnosis of disseminated toxoplasmosis should not be rejected simply because of the likely absence of toxoplasmal lymphadenopathy in biopsy material. The thymus in our case was morphologically abnormal and showed features suggestive of an autoimmune process.

Adult↗

Immunohistologic and histochemical methods for detection of steroid binding in breast cancer: a reappraisal.

A review of the current literature on immunohistologic and histochemical methods for the detection of steroid hormone binding sites in breast cancer, reveals that many, but not all of the criteria for establishing hormone-receptor binding interactions have been met. These include tissue specificity, binding between labeled ligands and soluble receptor in vitro, correlations between histochemical and biochemical assays, as well as between histologic procedures and tumor hormone responsiveness. However, histochemical binding phenomena do not appear to follow classical receptor dogma in regard to the concentration of ligand required, or specificity of binding as determined by competitive binding assays. It is concluded that these histologic techniques may be detecting classical receptor that may be reacting differently than would be expected from biochemical analyses, Types II and III binding sites, and/or organelle and membrane-bound receptors. Certainly no current method should presently be promoted as a laboratory method for the detection of classical receptor. New immunocytologic procedures employing specific, antireceptor sera currently under development, may obviate many of the criticisms leveled against earlier methods.

Binding Sites↗

Immunohistologic diagnosis of sarcoidosis. Detection of angiotensin-converting enzyme in sarcoid granulomas.

Angiotensin-converting enzyme (ACE) was detected by indirect immunofluorescence examination. ACE was present in the cytoplasm of epithelioid cells in granulomas from 38 of 39 patients who had clinical sarcoidosis but not in any of 37 nonsarcoid granulomas, normal lymph nodes, or splenic controls. Intensity of staining with ACE antiserum was inversely proportional to the degree of fibrosis and was significantly less intense in fibrotic granulomas. The detection of ACE appears to be a distinct aid in establishing a definitive tissue diagnosis of sarcoidosis.

Clinical Enzyme Tests↗

Pulmonary hemorrhage in systemic lupus erythematosus.

Massive pulmonary hemorrhage confirmed by pathologic examination occurred in three of 12 patients with systemic lupus erythematosus (SLE) complicated by lung disease. Two patients died. Hemorrhage was clinically unrecognized in two cases. The third patient survived after an open lung biopsy and an increase in prednisone therapy. In the absence of hemoptysis, awareness of the possibility of pulmonary hemorrhage in patients with SLE and a high index of suspicion are necessary for early recognition of this uncommon but potentially fatal complication.

Adolescent↗

Histochemical assay of estrogen and progesterone receptors in breast cancer: correlation with biochemical assays and patients' response to endocrine therapies.

Estrogen (ER) and progesterone (PgR) receptors were assayed by histochemistry in primary, recurrent, and metastatic breast cancer. Ligand-conjugates composed of 17 beta-estradiol and 11 alpha-hydroxyprogesterone covalently linked to bovine serum albumin and labelled with fluorescein isothiocyanate were employed. Results were compared with those of conventional biochemical receptor assays and correlated for ER in 92% of 314 tumors and for PgR in 86% of 86 specimens. ER and PgR determinations by both assay systems were correlated with clinical response to various endocrine therapies in 40 women with Stage IV disease. The histochemical assay enabled successful prediction of response in 80% of cases including eight which could not be fully analyzed biochemically.

Adrenalectomy↗

Immunofluorescent detection of angiotensin-converting enzyme (ACE) in Gaucher cells.

The cellular localization of the elevated angiotensin-converting enzyme (ACE) in the spleen of a patient with Gaucher's disease was examined by immunofluorescence using an antibody prepared against highly purified human lung enzyme. Intense ACE-specific cytoplasmic fluorescence was observed in Gaucher cells, but not in various controls, indicating the localization of large quantities of enzyme in these cells. These results and the demonstrated capability of mononuclear phagocytes for marked induction of this enzyme suggest the possibility that induction of active synthesis of ACE in Gaucher cells may be responsible for the elevated enzyme levels in the serum and spleen of patients with Gaucher's disease.

Fluorescent Antibody Technique↗