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Biomedical subjects

J Halper

Publications and source records attributed to J Halper.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1984

Primary arteriopathy in Takayasu's disease.

Three patients with classic Takayasu's arteritis affecting the aorta and its major branches were found to have a unique small pulmonary arteriopathy characterized by deficiency of the outer media, with capillary ingrowth both here and in the thickened fibrosed intima. In one patient there was also evidence of a mononuclear cellular arteritis of the affected arteries and widespread focal angiomatoid like lesions. Another patient had similar, but less well-defined dilatation lesions. This patient's major coronary arteries showed an active arteritis with ingrowth of reparative granulation tissue capillaries into both media and intima, yielding an appearance not dissimilar to that seen in the small pulmonary arteries. The outer pulmonary artery medial defects observed in our patients bear some similarity to experimental acute immune-complex arteritis and may thus provide tenuous evidence for an autoimmune basis for Takayasu's disease.

Adult↗
PubMed1983

Transforming growth factors in solid human malignant neoplasms.

Surgically removed solid human benign and malignant neoplasms and nonneoplastic tissues were examined for the presence of transforming growth factors (TGFs). TGFs are polypeptide growth factor-like substances which cause the appearance of a reversible neoplastic phenotype in nontransformed, anchorage-dependent cells in culture, including the induction of the ability to grow while suspended in semisolid medium. Acid-ethanol extracts from adenocarcinomas of the breast, colon, kidney, and ovary; fibrosarcoma and leiomyosarcoma; Hodgkin's lymphoma; fibroadenoma of the breast; uterine leiomyoma; and nonneoplastic kidney and lung were found to cause growth in soft agar of both nontransformed mouse AKR-2B and rat NRK cells. This colony-stimulating activity, where tested, was heat and acid stable but was destroyed by trypsin and dithiothreitol treatment, indicating that the activity is due to a polypeptide with disulfide bonds. Extracts from several of the tumors provided sufficient material for purification by molecular sieve chromatography. Peaks of colony-stimulating activity from a Bio-Gel P-60 column eluted with 1 M acetic acid were detected in the M, 3,000 to 25,000 range with the apparent molecular weight varying depending on the type of tumor being studied and the indicator cells used. The data suggest that at least three TGFs are present in human tumors. Evidence is presented differentiating these TGFs into TGFa, which has selective activity for stimulating AKR-2B cells, and TGFn, which has selective activity for stimulating NRK cells. The NGFn activity was further subdivided into a TGFns fraction and TGFnl fraction, denoting small (less than 6,000) and large (12,000 to 20,00) apparent molecular weights, respectively. The TGFa and TGFnl activities were present in malignant and nonneoplastic (kidney and lung) tissue, whereas the TGFns activity predominated in benign neoplasms. These TGFs exhibited no competition with epidermal growth factor for binding to the epidermal growth factor receptor, and the TGFnl activity was potentiated by epidermal growth factor.

Animals↗
PubMed1983

Epithelial tissue-derived growth factor-like polypeptides.

SW-13 cells, derived from a human adenocarcinoma of the adrenal cortex, formed only a few small colonies when suspended in soft agar at low cell densities. The number and size of colonies increased dramatically following stimulation with serum-free medium conditioned by SW-13 cells, indicating the possibility of autostimulation in these malignant cells. Evidence is presented suggesting that SW-13 cells form progressively growing soft agar colonies upon stimulation by epithelial tissue-derived growth factor-like polypeptides. Both acid-ethanol extracts and conditioned media from three human carcinoma cell lines (A431, D562, and A549) caused similar increases in colony number and size of SW-13 cells. Extracts from 26 of 32 freshly excised human carcinomas and five freshly excised nonneoplastic human kidneys and one human lung stimulated soft agar growth of SW-13 cells as well. None of the nine extracts from nonepithelial human solid malignant tumors stimulated SW-13 cells. However, a benign nonepithelial tumor (uterine leiomyoma) caused a low level of soft agar growth of SW-13 cells. Cell extract from A204 human sarcoma cells and both conditioned medium and acid-ethanol cell extract from A375 human melanoma cells lacked SW-13 activity, whereas medium conditioned by A204 cells stimulated soft agar growth of SW-13 cells. Chemical and physical treatment data indicated that the epithelial tissue-derived growth factor-like substances are acid- and heat-stable polypeptides with disulfide bonds. The major peak of this activity had an apparent molecular weight of 20,000 to 22,000 and was clearly separable from transforming growth factors reported previously which stimulate colony formation by nontransformed mouse AKR-2B and rat NRK cells. The major peaks of SW-13, NRK, and AKR-2B activity could be separated by high-performance liquid chromatography. This SW-13 activity induced irreversible anchorage-independent growth of SW-13 cells and an increase in DNA synthesis as measured by [3H]thymidine incorporation.

Adenocarcinoma↗
PubMed1983

Invasive disease caused by Trichosporon beigelii.

An immunocompromised patient had cellulitis that was unresponsive to conventional antimicrobial therapy. Skin biopsy specimens and fungal blood cultures revealed the offending organism as Trichosporon beigelii. Recognition of this opportunistic pathogen in immunocompromised patients is important.

Humans↗
PubMed1982

Spontaneous in vitro differentiation of antigen-specific lymphocytes from a patient with immunoglobulin M gammopathy.

Recently we have identified two monoclonal immunoglobulin M (IgM) proteins that bind Klebsiella polysaccharides. The lymphocytes of one of these patients (M.A.Y.) were available for study. A substantial proportion of the B lymphocytes isolated from this patient's peripheral blood also bound Klebsiella polysaccharides with a pattern of specificity identical to that of the monoclonal IgM, and reacted with an anti-idiotypic antiserum directed against this IgM. Stripping the surface immunoglobulin from these lymphocytes eliminated this reactivity. Although no plasma cells were detected in the freshly isolated peripheral blood lymphocytes of this patient, plasma cells binding Klebsiella polysaccharide appeared after 7 d of in vitro culture. This occurred regardless of whether the cultures were supplemented with autologous plasma, normal human plasma, or fetal calf serum. Pokeweed mitogen neither stimulated nor inhibited the in vitro differentiation of the monoclonal B lymphocytes into plasma cells. This differentiation was, however, abrogated by F(ab')2 fragments of anti-human IgM and by anti-idiotypic antibodies, as well as by the Klebsiella polysaccharide with which the monoclonal IgM reacted.

Aged↗
PubMed1981

Naturopaths and childhood immunizations: heterodoxy among the unorthodox.

Many families at a community clinic in Seattle reported that they were choosing not to immunize their children at the advice of practitioners of naturopathy. To learn more about this alternate form of health care, a review of the available literature on naturopathy was undertaken and interviews were conducted with individual naturopaths in the state of Washington. Naturopaths vary widely in their training, practices, and philosophy of healing. Many are opposed to routine immunization because they view immunization programs as unnatural, unnecessary, and elitist. Other practitioners, however, did not actively discourage parents from immunizing their children. Pediatricians must be aware of the growing popularity of naturopathic medicine in their care of families, and in their role as advocates for children.

Attitude to Health↗
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↗