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Biomedical subjects

J Halper

Publications and source records attributed to J Halper.

At least 19 recordsLinked to original sources
PubMed1992

Neuroendocrine and behavioral responses to challenge with the indirect serotonin agonist dl-fenfluramine in adults with obsessive-compulsive disorder.

Neuroendocrine and behavioral responses to a single 60-mg oral dose of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated adults with obsessive-compulsive disorder (OCD) and neuroendocrine results contrasted with those in normal control subjects. Net fenfluramine-induced prolactin release did not differ significantly between OCD patients and normal controls. Prolactin responses in the OCD group were not significantly correlated with baseline Yale-Brown Obsessive Compulsive Scale scores for either obsessions or compulsions, but were positively correlated with the baseline Hamilton Depression Scale score and Hamilton Anxiety Scale score. No clear difference in the severity of patients' obsessions or compulsions was found following challenge with fenfluramine versus placebo. Although the present study does not demonstrate a serotonergic abnormality in OCD, this may be more a reflection of limitations of the test procedures than evidence that central nervous system (CNS) serotonergic function is normal in the disorder.

Adult↗
PubMed1992

Transforming growth factor e: amino acid analysis and partial amino acid sequence.

Our previous studies have demonstrated that transforming growth factor e (TGFe) acts as a mitogen for epithelial and fibroblastic cells in both monolayer and soft agar. We have also identified TGFe in both normal and neoplastic tissues of mostly epithelial origin, and in body fluids. In this study we report on the purification of TGFe to homogeneity from bovine kidney using a multistep purification protocol which utilizes high performance electrophoresis chromatography in the final step. Amino acid analysis of TGFe revealed high content of proline, aspartate and glutamate. Examination of partial amino acid sequence indicated no similarity to other, already characterized, growth factors.

Adrenal Cortex Neoplasms↗
PubMed1992

Presence of growth factors in human pituitary.

Recent reports indicate that fibroblast growth factors known to be present in the pituitary in high levels regulate the action of growth hormone and prolactin. New data also suggest a regulatory role in the pituitary for other growth factors, such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). Since in most systems cooperation of several growth factors is required for their optimal function, we sought to demonstrate the presence of certain growth factors in the pituitary. Acid ethanol extracts from approximately 50 autopsy-derived human pituitaries were subjected to molecular sieve chromatography and were tested for growth factors. Low molecular weight protein (10 micrograms) eluted from the molecular sieve column contained 10-20 ng material binding to the EGF/TGF-alpha receptor as determined by the EGF/TGF alpha radioreceptor binding assay which represents 11 ng EGF/TGF alpha per pituitary. By Western blotting we found EGF but could not document the presence of TGF-alpha in this material. Radioimmunoassay for insulin-like growth factor I detected 0.4-0.8 ng insulin-like growth factor-I/100 micrograms extract. TGF-beta eluted between 14,000 and 20,000 M(r) at levels of 3-4 ng/pituitary. Its ability to inhibit growth of CC164 mink lung cells was abolished by antibody to TGF-beta 1 but not by antibody raised against TGF-beta 2. The detection of platelet derived growth factor was equivocal and not fully reproducible. We have partially purified TGFe from the pituitary; it stimulated soft agar growth of carcinoma SW-13 cells, and it followed an elution pattern identical to bovine kidney TGFe on molecular sieve column and high pressure liquid and high performance electrophoretic chromatography. Our data show that in addition to fibroblast growth factors, the human pituitary contains other growth factors, such as EGF/TGF-alpha, TGF-beta, insulin-like growth factor I, and TGFe.

Autopsy↗
PubMed1990

Purification of transforming growth factor type e.

Transforming growth factor type e (TGFe) is a heat- and acid-stable polypeptide with an apparent molecular weight of 22,000, which stimulates the proliferation of certain epithelial and mesenchymal cells in monolayer and soft agar. TGFe has been purified to homogeneity. Initial acid-ethanol extraction of bovine kidney was followed by batch ion-exchange chromatography utilizing Bio Rex 70 resin. The activity eluted from the Bio Rex 70 resin was concentrated and diafiltered using an Amicon concentrator equipped with an S1Y10 spiral membrane, then was further purified by Bio-Gel P-60 molecular sieve chromatography. Active fractions from molecular sieve chromatography were pooled and purified by heparin-Sepharose affinity chromatography, followed by reverse-phase high-performance liquid chromatography using a microbore C-8 column. The final purification step involved electro-elution of TGFe separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Purity of TGFe was assessed to be greater than 90%.

Animals↗
PubMed1990

Specific binding of [3H]heparin to human carcinoma SW-13 and other mammalian cells.

This study reports on the specific binding of [3H]heparin to human adrenocortical carcinoma cell line SW-13. Heparin binding to SW-13 cells is specific, saturable, and time- and temperature-dependent with maximum binding occurring between 90 and 120 min at 22 degrees C. Scatchard analysis revealed two classes of binding sites. The apparent Kd for high-affinity receptors is 2.14 x 10(-8) M with 1.48 x 10(6) sites per cells. Six other tested mammalian cell lines also have specific binding sites for heparin.

Adrenal Cortex Neoplasms↗
PubMed1990

Mitogenic effects of transforming growth factor type e on epithelial and fibroblastic cells--comparison with other growth factors.

Transforming growth factor type-e (TGFe) is a novel TGF which was first described as a growth factor possibly involved in autocrine stimulation of anchorage-independent growth of carcinoma cells. Its later identification in normal tissues, plasma, and platelets suggested a role for TGFe in normal cell growth. This study shows that TGFe stimulates both anchorage-dependent and -independent growth of epithelial and fibroblastic cells of nonneoplastic origin. The mitogenic activity of TGFe in monolayer is slightly less than that of basic fibroblast growth factor, equipotent to that of epidermal growth factor, and greater than that of IGF-1. TGFe acts as a progression factor for both AKR-2B and Balb-3T3 cells. TGFe is also a potent mitogen for normal human epidermal keratinocytes and may therefore play a role in epidermal growth and regeneration.

Animals↗
PubMed1989

Modulation of growth of human carcinoma SW-13 cells by heparin and growth factors.

This study reports on the effects of heparin, basic and acidic fibroblast growth factors (bFGF and aFGF, respectively), and transforming growth factor type-e (TGFe) on the growth of a human adrenocortical carcinoma cell line, SW-13. Heparin has previously been shown to inhibit growth in several cell types, including smooth muscle cells, certain fibroblasts, and epithelial cells, and to modulate the effects of fibroblast growth factors. Whereas bFGF and aFGF bind tightly to heparin and elute from a heparin-Sepharose column with 2 M NaCl and 1.6 M NaCl, respectively, TGFe binds to heparin with lower affinity and can be eluted from heparin-Sepharose column with 0.5 M NaCl. TGFe is a polypeptide unrelated to FGF, is present in neoplastic and nonneoplastic tissues, and stimulates the growth of certain epithelial cells and fibroblasts in soft agar and monolayer. Since the growth of SW-13 cells is stimulated by TGFe and by bFGF, we hypothesized that heparin would inhibit the growth of SW-13 cells by binding to these growth factors and that the effects of heparin could be overcome with the addition of either growth factor. Our experiments confirmed that heparin inhibits the growth of SW-13 cells. A dose-dependent growth inhibition was observed in both monolayer and soft agar. The inhibition in monolayer was partially reversed upon heparin withdrawal. The effects of heparin in both monolayer and soft agar were at least partially overcome by TGFe and by basic or acidic FGF. Overall protein synthesis does not appear to be affected by heparin as measured by [35S]methionine uptake. In contrast, epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) were unable to overcome heparin-induced inhibition both in monolayer and in soft agar. Heparin also inhibited [3H]thymidine incorporation in AKR-2B and partially inhibited AKR-2B cell stimulation by TGFe; however, it further potentiated the already potent stimulation by bFGF. We propose that heparin, TGFe, bFGF, and aFGF modulate the growth of SW-13 cells and possibly of other epithelial cells in complex ways and that heparin-like substances present in the extracellular matrix play an important role in the control of epithelial growth.

Adrenal Cortex Neoplasms↗
PubMed1989

Estrogen and progesterone receptors in meningiomas: comparison of nuclear binding, dextran-coated charcoal, and immunoperoxidase staining assays.

We studied the status of estrogen (ER) and progesterone (PR) receptors in meningiomas removed from 52 patients, comparing dextran-coated charcoal (DCC), nuclear binding (NB), and immunoperoxidase (IP) assays. Each of the assays was performed independently by investigators well-experienced with these assays. The NB assay is a new assay that measures functional steroid receptors--that is, the activation of the receptor and its binding to the nucleus. The assay is very sensitive and requires a relatively small amount of tissue as compared with the DCC assay. In agreement with data from other studies. PR were detected in most meningiomas by all 3 methods: in 69% of the cases by NB, in 76% by DCC, and in 89% by IP. ER were detected in only a few cases: in 33% by NB, in 2% by DCC, and in none by the IP assay. The agreement for PR sites was 62% for all 3 assays; it was 66% between the NB and DCC assays, 67% between the NB and IP assays, and 86% between the DCC and IP assays. Of 26 cases that were positive by the DCC assay, 6 (23%) were negative by NB. The overall agreement for all three ER assays was 65%. The data suggest that the majority of meningiomas contain high-affinity receptors for progesterone, that estrogen receptors are present in only a few meningiomas, and that some of these estrogen and progesterone receptors appear to be functional.

Adolescent↗
PubMed1987

Purification and characterization of a novel transforming growth factor.

Previous studies have indicated that an autostimulatory transforming growth factor was required for the optimal growth of SW-13 adrenal carcinoma cells in soft agar. The production of SW-13 colony-stimulating activity by other human malignant cell lines of both epithelial and mesenchymal origin has been demonstrated. Evidence was presented indicating that the stimulating activity detected in crude acid-ethanol extracts was an acid- and heat-stable polypeptide requiring disulfide bonds for full activity. This activity was detected more frequently in tumors and human cancer cells in culture of epithelial origin than of mesenchymal origin and in a variety of nonneoplastic tissues. In the present study, this activity, termed epithelial transforming growth factor (TGFe) because of its ability to stimulate soft agar growth of certain epithelial cells, was partially purified from bovine kidney. Fourfold purification of the kidney acid-ethanol extract with 50% maximal growth-stimulatory activity of 10 micrograms was achieved using molecular sieve chromatography where TGFe eluted with an apparent molecular weight of 20,000-25,000. The next purification step, molecular sieve high performance liquid chromatography, yielded a 50% maximal growth-stimulatory activity of 50 ng and an 800-fold purification from the initial acid-ethanol extract. TGFe eluted in the Mr 11,000 range. Reversed phase high performance liquid chromatography with a C18 column was then used, yielding a single or double peak of SW-13 colony-stimulating activity at 30-35% acetonitrile. The degree of purification was 11,000-fold with a 50% maximal growth-stimulatory activity of 3.5 ng. Analysis of the peak on 12.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a major and sometimes single band with a molecular weight of 23,000-25,000. Extraction of protein from the polyacrylamide gel demonstrated that only the Mr 23,000-25,000 band stimulated soft agar growth of SW-13 cells. The biological activity of the partially purified TGFe was found to differ from other known growth factors with regard to its ability to stimulate soft agar growth of SW-13 cells with the exception of basic fibroblast growth factor (FGF). The acid lability of FGF, the different molecular weights of these two growth factors, the lack of stimulation of soft agar growth of A431 cells, and the lack of binding of TGFe to FGF receptors indicated that TGFe was not related to basic FGF. Partially purified TGFe was also found to stimulate soft agar growth of two squamous cell carcinoma lines, A431 and D562, and the mouse embryo-derived AKR-2B cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Gland Neoplasms↗
PubMed1986

Meningio-angiomatosis: a report of six cases with special reference to the occurrence of neurofibrillary tangles.

We report six cases of meningio-angiomatosis, a disorder of the cerebral cortex of probable malformative origin frequently associated with neurofibromatosis and either asymptomatic or associated with a seizure disorder. The patients, three males and three females, ranged from 10 to 70 years of age at diagnosis. The lesion was an incidental autopsy finding in two patients; four subjects had a seizure disorder which improved following surgical resection of the cortical lesion. In five instances the process was unifocal; one patient with neurofibromatosis had multifocal involvement. Grossly, the lesions were firm, sharply demarcated, transcortical plaques with leptomeningeal calcifications in five cases. The cortical plaques showed characteristic features of meningio-angiomatosis, i.e. a circumscribed, proliferating microvasculature with perivascular meningothelial cell proliferation and fibrosis. In five cases Alzheimer's neurofibrillary change in neurons was present both within the plaques and in the surrounding cortex. Neither senile plaques nor granulovacuolar degeneration were noted. Electron microscopy in one case demonstrated typical intraneuronal accumulations of neurofilaments with regular constrictions. Intracortical vessels lined by endothelial cells with tight junctions were surrounded by pericytes and meningothelial cells. The significance of neurofibrillary tangles described in a variety of disorders, and the factors stimulating their production in the present cases are unknown.

Adolescent↗
PubMed1978

Contrasting patterns of newer histocompatibility determinants in patients with rheumatoid arthritis and systemic lupus erythematosus.

The Ia alloantigens as measures of different alleles of loci in the major histocompatibility complex were determined in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). The Ia specificities of reagents used were defined by their pattern of reaction with lymphoblastoid lines derived from normal donors homozygous for HLA-D determinants. The reagent specificities included those associated with a single Dw type as well as those reacting with a single specificity shared by several Dw types. Patients with RA had a marked elevation in the frequency of alloantigens detected by reagent sera that recognize various determinants shared by cell lines from HLA-Dw4, Dw7, or Dw10 individuals (Ia 4-7-10). The frequency of mixed lymphocyte culture alleles Dw4 and Dw10 was found to be increased; however this elevation did not approach the higher frequency for the serologically determined antigens of the Ia 4-7-10 group. In contrast, patients with SLE had an increased frequency of reactions with the reagent alloantisera defined by reactions with either HLA-Dw2 or Dw3 positive cell lines. The data suggest that immunogenetic factors are relevant to both groups of patients, but that these are entirely distinct for each disease.

Arthritis, Rheumatoid↗
PubMed1978

Patterns of expression of human "Ia-like" antigens during the terminal stages of B cell development.

The "Ia-like" antigens characteristically present on the membrane of B lymphocytes were shown to be absent in most terminally differentiated Ig-producing plasma cells. This was most evident in analyses of myeloma plasma cells that uniformly lacked the Ia-antigens. Also, in B lymphoid cell lines, the lymphoblasts were uniformly Ia-positive but the plasma cells were negative. In contrast, however, the majority of plasma cells produced after pokeweed mitogen stimulation remained positive. Plasma cells in tonsil and in the tissue of peripheral blood of patients with Wladenström's macroglobulinemia were also sometimes Ia-positive although the majority were negative. Studies of membrane IgM and IgD indicated a similar loss in some instances. However, the SIg and Ia antigens were not invariably associated. These results lead to the conclusion that Ia-antigens are differentiation antigens for B cells and are usually lost by the end stage cells in this series.

B-Lymphocytes↗
PubMed1977

Expression of Ia-like antigen molecules on human granulocytes during early phases of differentiation.

Human B lymphocyte antigens analogous to the murine Ia determinants were found on myeloblasts and promyelocytes but not on more mature granulocytes. This was apparent by fluorescent staining with both human alloantisera and rabbit antisera to the isolated Ia-like proteins. The cells of patients with chronic myelocytic leukemia showed this difference especially clearly. Separation of the myeloblasts and promyelocytes by multistep density gradient fractionation produced a marked enrichment of the positive cells. The remaining cells from higher density fractions were more-mature neutrophils that were essentially negative. In acute myeloid leukemia, in which myeloid cells early in differentiation predominate, the vast majority of cells were strongly positive. Similar results were obtained with normal bone marrow cells. Here also, only the early forms of the myeloid series separated by gradient centrifugation had Ia antigens. Evidence was also obtained for the presence of Ia determinants on cells with the appearance of early erythroid precursors. Support for the presence of the Ia determinants on granulocyte-macrophage committed stem cells was provided by the inhibition of granulocyte colony formation in agar cultures following preincubation of normal bone marrow with antiserum and complement. Cross absorptions with purified preparations of immature cells provided evidence for the close similarity of the antigenic determinants on both myeloblasts and B cells. A 28,000-37,000-dalton bimolecular complex obtained from myeloblast membranes contained the Ia determinants and was similar to that obtained from peripheral blood B cell membranes.

B-Lymphocytes↗
PubMed1976

Studies with B-cell allo- and hetero-antisera: parallel reactivity and special properties.

The expression of B-cell antigens on various cell populations was studied through the use of human alloantisera and with heteroantisera raised to preparations of the alloantigen bearing molecules isolated from B-cell lines. The allo-and hetero-antisera competed with each other in blocking experiments and gave closely parallel results, reacting with normal and leukemic B lymphocytes, monocytes, E-rosette-negative acute lymphatic leukemias, all acute and certain chronic myelogenous leukemias, and a minor population of cells in fetal spleen and liver. These highly immunogenic surface components appeared to comprise the dominant B- cell specific plasma membrane determinants. Neither type of antiserum reacted with any but a minor population of normal or pokeweed-mitogen-transformed T cells, fetal thymic lymphocytes, E-rosette-positive acute lymphatic leukemias, or Sezary-cell leukemia. Through the use of these antisera evidence was obtained that Fc-receptor-bearing Ig-negative lymphocytes were divisible into two groups according to the presence or absence of the B-cell antigens. Both hetero- and allo-antisera blocked binding of immune complexes or antibody-coated ox erythrocytes to Fc receptors on B cells. F(ab')2 fragments of the heteroantibodies strongly inhibited antibody-dependent cell-mediated killing.

Animals↗