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Biomedical subjects

J Halper

Publications and source records attributed to J Halper.

At least 19 recordsLinked to original sources
PubMed2000

Cellular localization of gene expression for progranulin.

Granulins, also called epithelins, are 6-kD peptides with growth modulatory effects on a variety of cells. The granulin/epithelin precursor supports tumorigenesis in appropriate cell models and is the only growth factor able to overcome the cell cycle block that occurs in murine fibroblasts after deletion of a functional IGF-1 receptor. However, little is known of the role of granulin/epithelin gene products in vivo. To understand the physiological role of granulins it is essential to know the cell types and conditions in which it is expressed. We examined granulin/epithelin gene expression in adult rodents by in situ hybridization. The granulin/epithelin precursor is constitutively expressed in a number of epithelia, particularly in the skin, GI tract, and reproductive system. Other epithelia express the gene less strongly. Progranulin is expressed in immune cells in vivo and in specific neurons in the brain, including Purkinje cells, pyramidal cells of the hippocampus, and some cerebral cortical neurons. Little expression was detected in muscle cell, connective tissue, or endothelium. Cumulatively, these results define the basal gene expression of a new growth factor system and suggest that the progranulin/epithelin gene is multifunctional, with important constitutive roles in epithelial homeostasis, reproductive, immunological, and neuronal function.

Animals↗
PubMed1999

Expression of TGFalpha in meningiomas.

The objective of this study was to examine the expression of transforming growth factor alpha (TGFalpha), a mitogen for many cell types, and its receptor in basic subtypes of meningiomas as well as in meningiomas of varying grade. Formalin-fixed tissues from 26 meningiomas including 15 benign (5 meningothelial, 5 transitional, and 5 fibrous variants), 6 atypical, and 5 malignant examples were immunohistochemically examined for both TGFalpha protein and EGF/TGFalpha receptor protein. In addition, in situ hybridization (ISH) was used to detect TGFalpha mRNA expression. Immunostaining for TGFalpha was strongest in fibrous and atypical meningiomas, followed closely by transitional and malignant tumors. Only weak reactivity was observed in the meningothelial variant. In all but 4 tumors (2 fibrous, 2 atypical), ISH showed TGFalpha mRNA to be present, the signal being stronger in malignant than in conventional or atypical tumors. Lastly, immunostaining for EGF/TGFalpha receptor was positive in all tumors studied. Strong TGFalpha protein expression in meningiomas is commonly associated with fibrous morphology. Although the frequent detection of both TGFalpha protein and its mRNA, as well as of EGF/TGFalpha receptor within tumors of all type and grades, suggests that TGFalpha serves to promote tumor growth, its possible role in tumorigenesis or malignant progression is uncertain. In summary, demonstration of these substances is of no utility in the classification or grading of this common tumor because the differences in their expression among the various meningioma subtypes were not statistically significant.

Adult↗
PubMed1999

The presence of transforming growth factor e in bovine mammary gland.

Transforming growth factor e (TGFe) was demonstrated immunohistochemically in the bovine mammary gland, mainly in the glandular and ductal epithelium. In the teat, its expression was largely limited to the skin keratinocytes, ductal epithelium and ductal glands. It is suggested that this growth factor plays a role in lactation.

Animals↗
PubMed1999

Development of chicken antibodies to bovine interferon alpha.

We have developed chicken polyclonal antibody to bovine interferon alpha (IFNalpha). Five hundred microg of recombinant bovine IFNalpha suspended with complete Freund's adjuvant was used in the first immunization round. A suspension of the same amount of IFNalpha and incomplete Freund's adjuvant was used for all subsequent boosters. The antibody was purified from egg yolks using polyethylene glycol precipitation. The first reactive antibody appeared several weeks after the first immunization. The antibody is specific for IFNalpha in immunoblotting, it is also useful in ELISA and immunohistochemistry. This method provides a fast, cheap and efficient alternative to development of monoclonal antibodies to conserved mammalian antigens.

Animals↗
PubMed1997

Helplessness, self-efficacy, cognitive distortions, and depression in multiple sclerosis and spinal cord injury.

The aim of this study was to determine if learned helplessness, self-efficacy, and cognitive distortions would predict depression in a sample of 80 individuals with multiple sclerosis (MS) and 80 individuals with a spinal cord injury (SCI). As MS and SCI usually present with disparate disease courses and etiologies, a secondary objective was to determine if individuals with MS would exhibit greater levels of helplessness, cognitive distortions, and depression and lower levels of self-efficacy than those with SCI. Results indicated that helplessness and self-efficacy significantly predicted depression for both the MS and SCI groups after controlling for confounding variables. Cognitive distortions had no independent effect, indicating that cognitive distortions may have caused feelings of helplessness and low self-efficacy and, in this way, had indirect effects on depression. The MS group exhibited significantly greater levels of depression and helplessness and significantly lower levels of self-efficacy than the SCI group. It was hypothesized that it may have been the combination of an unpredictable course of disease activity and the possibility of being affected by MS in many different ways that produced greater feelings of depression, helplessness, and low self-efficacy in the MS group.

Adaptation, Psychological↗
PubMed1997

Expression of growth factors in chicken growth plate with special reference to tibial dyschondroplasia.

Immunoreactive growth factors were identified in chick embryonic cartilage and bone, and in the growth plate of normal tibiotarsi and tibiotarsi affected with tibial dyschondroplasia (TD). A specific pattern of temporal and spatial expression was observed for each growth factor. Transforming growth factor beta and alpha (TGF beta and TGF alpha) and epidermal growth factor (EGF) were briefly expressed in chondrocytes of early chick embryos. Immunolabelling for TGF beta then gradually shifted into cartilaginous matrix and was not observed in cytoplasm of hypertrophic chondrocytes until the late embryonic and post-hatch stages. The distribution and intensity of TGF beta labelling was the same in chondrocytes of the TD and normal growth plate. Insulin-like growth factor I (IGF-I) labelling persisted from the early embryonic stage to the end of the mid-stage and then disappeared from chondrocytes. IGF-I appeared again in chondrocytes 1-2 days before hatching. After hatching, the labelling intensified in prehypertrophic and hypertrophic chondrocytes. TD lesions displayed IGF-I in the distal region, mainly in chondrocytes around small blood vessels. EGF reappeared in proliferative and hypertrophic chondrocytes of the mid-embryonic stage. By day 18 after hatching, EGF was present mainly in prehypertrophic and hypertrophic chondrocytes. EGF was demonstrated only in distal proliferative and early prehypertrophic chondrocytes of the dyschondroplastic growth plate. TGF alpha was identified in hypertrophic chondrocytes adjacent to the periosteum and in the distal tip of the mid-embryonic growth plate. With progressing ossification, TGF alpha labeling intensified in the embryonic hypertrophic chondrocytes. In the TD growth plate at day 18 after hatching, TGF alpha expression was limited to 1-3 concentric layers of chondrocytes surrounding blood vessels.

Animals↗
PubMed1996

Postprandial Vomiting and Abdominal Pain.

A 14-year-old Asian female presented with complaints of abdominal pain that was intermittent, crampy, periumbilical, without radiation, and aggravated by eating. She had been vomiting "green-colored" material 4 days earlier, after meals, associated with abdominal pain. On hospital day 3, after no improvement was noted, an upper GI series demonstrated an obstruction at the third portion of the duodenum. She was evaluated for an eating disorder, but further history failed to elicit diagnostic criteria. She responded favorably to total parenteral nutrition and symptoms were relieved with changes in position. Her symptoms and diagnostic studies were consistent with the diagnosis of superior mesenteric artery (SMA) syndrome.

Journal Article↗
PubMed1995

Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.

OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response. RESULTS: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo. CONCLUSION: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.

Adolescent↗
PubMed1995

Identification of a membrane-associated receptor for transforming growth factor type E.

We have identified the receptor for epithelial type transforming growth factor (TGFe). TGFe, a member of the epithelin/granulin family of proteins, is present primarily in tissues of epithelial origin. It is a powerful mitogen for epithelial and fibroblastic cells. TGFe, iodinated using an immobilized glucose oxidase-lactoperoxidase method, was chemically crosslinked to receptors on membranes isolated from SW-13 adrenal carcinoma cells by the crosslinker disuccinimidyl suberate (DSS). The receptor appears to be a protein which migrates at an apparent molecular weight of approximately 170-175 kDa under reducing and nonreducing conditions in SDS-polyacrylamide gels.

Animals↗
PubMed1993

Purification of epithelial-type transforming growth factor by micro-preparative electrophoresis chromatography.

The purification and recovery of biologically active epithelial-type transforming growth factor (TGFe) is described. In the final phase of purification, micropreparative electrophoretic chromatography was employed using a Tris-glycine-sodium dodecyl sulfate buffer system in an automated instrument. Briefly, partially purified protein preparations were separated in 2.5 x 50 mm, 10% polyacrylamide gel in electrophoresis tubes installed in the apparatus, electrophoresed under constant current of 1.5 mA for 400 min and recovered by automated fractionation and collection of the eluant from the tube gel. Aliquots of the eluted fractions were assayed in a biological system using SW-13 cell growth stimulation as an indicator of the presence of biologically active TGFe. Using the above procedure, TGFe was purified to within 95% homogeneity as assessed by silver-stained sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Animals↗
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↗