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Biomedical subjects

S Gross

Publications and source records attributed to S Gross.

At least 55 records · Page 3Linked to original sources
PubMed2000

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

BACKGROUND/AIMS: Human milk fortification has been advocated to enhance premature infants' growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. METHODS: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. RESULTS: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 +/- 2.1 vs. 144.4 +/- 2.5 ml/kg/day, mean +/- SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 +/- 1.3 and 20.4 +/- 1.2 g/day, p < 0.05; head circumference 1.0 +/- 0.1 and 0.8 +/- 0.1 cm/week; length 0.9 +/- 0.1 and 0.8 +/- 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. CONCLUSIONS: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Body Height↗
PubMed2000

Peripheral blood tumor cell load reflects the clinical activity of the disease in patients with carcinoma of the breast.

Peripheral blood was examined for the presence of tumor cells at multiple time points over a one-year period in 45 patients with a history of surgical resection of breast carcinoma. The number of circulating epithelial cells in 8 of 8 patients with clinically active disease concurred or preceded changes in the disease activity. In 12 of 37 patients with no evidence of disease epithelial cells were found at least at one time point at a frequency larger than the control group. One patient had a recurrence of the breast cancer 4 weeks after circulating epithelial cells were detected in the blood.

Antineoplastic Agents↗
PubMed1999

Inactivation of protein-tyrosine phosphatases as mechanism of UV-induced signal transduction.

UV irradiation of cells causes ligand-independent activation of receptor tyrosine kinases. On the basis of dephosphorylation kinetics, UV-induced inactivation of receptor-directed tyrosine phosphatases (PTP) has been proposed as the mechanism of receptor activation (Knebel, A., Rahmsdorf, H. J., Ullrich, A., and Herrlich, P. (1996) EMBO J. 15, 5314-5325). Here we show that four defined protein-tyrosine phosphatases (PTPs), SHP-1, RPTPalpha, RPTPsigma, and DEP-1, are partially inactivated upon UV irradiation of PTP-overexpressing cells. The dephosphorylation of coexpressed platelet-derived growth factor beta (PDGFbeta) receptor by RPTPalpha is inhibited upon UV irradiation. UV converts RPTPalpha into a substrate-trapping enzyme which can coprecipitate PDGFbeta receptor, similarly to the PTP mutant at the active-center cysteine: C433S. In agreement with the proposed mechanism that inactivation of PTPs accounts for receptor tyrosine kinase activation, no evidence for a UV-induced receptor cross-linking could be obtained in PDGFbeta receptor-enriched membrane micelle preparations and in PDGFbeta receptor overexpressing 293 cells. The intrinsic activity of PDGFbeta receptor kinase was required for the UV-induced enhancement of receptor phosphorylation, but was not changed upon UV irradiation. The data support a mechanism of UV-induced signal transduction involving inactivation of PTPs through an unknown reactive intermediate that oxidizes the conserved cysteine in the active sites of PTPs.

Animals↗
PubMed1999

The transmembrane protein tyrosine phosphatase RPTPsigma modulates signaling of the epidermal growth factor receptor in A431 cells.

Attenuation of epidermal growth factor receptor signaling by the ganglioside G(M3) has previously been found to involve activation of an unknown protein-tyrosine phosphatase (PTP). In transient expression experiments we tested different PTPs for activation towards EGF receptor by G(M3). The transmembrane PTP RPTPsigma but not RPTPalpha or the SH2-domain PTP SHP-1 exhibited elevated activity towards EGF receptor in G(M3)-treated cells. The possible relevance of RPTPsigma for regulation of EGF receptor signaling activity was further explored in stable A431 cells lines inducibly expressing RPTPsigma or RPTPsigma antisense RNA. RPTPsigma expression clearly reduced EGF receptor phosphorylation. Also, soft agar colony formation of respective cell lines was reduced upon RPTPsigma expression whereas RPTPsigma antisense RNA expression augmented both, EGF receptor phosphorylation and soft agar colony formation. In addition, RPTPsigma antisense RNA expression rendered A431 cells resistant to inhibition of EGF receptor phosphorylation by G(M3). We propose that RPTPsigma participates in EGF receptor dephosphorylation in A431 cells, becomes activated by G(M3) via an unknown mechanism and is thereby capable to mediate attenuation of EGF receptor phosphorylation by G(M3).

Animals↗
PubMed1999

[Pediatric research in an office-setting network--a new dimension in pediatric research in Israel].

Pediatric care in the community is gradually replacing traditional care in hospitals. Despite that, research activity in the community setting is minimal due to objective difficulties. These are mainly constraints of time, office work and lack of research-supporting logistics. In the past decade, throughout the world, primary physicians interested in research have grouped together and formed research networks. The aim of such networks is to support and promote research in the community. An Israel Pediatric Research in Office-Setting network (IPROS) was established 2 years ago by the Israel Ambulatory Pediatric Association (IAPA). Today, there are over 140 pediatricians listed in IPROS, representing the heterogeneous composition of pediatricians in Israel. The network's policy is defined by a joint steering committee. The committee is composed of IAPA representatives, senior network members and Schneider Hospital senior investigators. The research subjects are diverse, and represent common practical issues. Effective intra-net communication is vital to the existence of the network, and is accomplished by 3 modalities: 1) semiannual updates by mail, 2) e-mail, using an electronic mailing list to facilitate connection between members, 3) semi-annual meetings. Research budgets are derived from public sources like the Ministry of Health and IAPA, and private sources such as pharmaceutical companies. The administration of the network is supported by Schneider Children's Medical Center, and financed by IAPA.

Ambulatory Care↗
PubMed1999

An essential role for NF-kappaB in human CD34(+) bone marrow cell survival.

The transcription factor, NF-kappaB, is important for T-cell activation, B-cell maturation, and human immunodeficiency virus transcription and plays a role in alternatively mediating and protecting against apoptosis in a variety of cell types. However, a role for NF-kappaB in human CD34(+) bone marrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappaB that can be activated by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines, eg, tumor necrosis factor alpha, interleukin-3, and granulocyte-macrophage colony-stimulating factor. In addition, we demonstrate that NF-kappaB may be required for human CD34(+) bone marrow cell clonogenic function and survival. These results offer insight into a new role for NF-kappaB in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappaB activation as an adjunct to cancer chemotherapy should be approached with caution.

Adult↗
PubMed1999

The EIF3S3 gene encoding the p40 subunit of the translation initiation factor eIF3 has eight exons and maps to the Langer-Giedion syndrome chromosome region on 8q24, but is not the TRPS1 gene.

We have mapped the gene encoding the p40 subunit of the eukaryotic translation initiation factor eIF3 (EIF3S3) close to the distal border of the minimal critical region for tricho-rhino-phalangeal syndrome type I (TRPS I) on human chromosome 8q24. Because this location makes EIF3S3 a candidate for the TRPS1 gene, we have determined the genomic structure of the EIF3S3 gene and searched for gene deletions and mutations in patients with TRPS I. The gene has eight exons and is transcribed from telomere to centromere. No deletion could be detected in 32 unrelated patients with an apparently normal karyotype. Sequence analysis of all exons in 15 unrelated patients did not reveal any point mutation either. Our data exclude EIF3S3 as the TRPS1 gene.

Blotting, Northern↗
PubMed1999

A 28-kb deletion spanning D15S63 (PW71) in five families: a rare neutral variant?

Methylation analysis with probe PW71 (D15S63) is an established procedure to test patients suspected of having Prader-Willi syndrome or Angelman syndrome. Using this test, we have identified a 28-kb deletion spanning D15S63 in five independent families. Sequence analysis revealed identical breakpoints in all the families. The haplotype data are compatible with a common ancestral origin of the deletion in at least two families. The deletion was not found in 1, 000 unrelated controls. Although the deletion maps within the imprinting-center region, neither maternal nor paternal inheritance of the deletion appears to affect imprinting in proximal 15q. We conclude that the deletion is a rare neutral variant that can lead to false-positive results in the PW71-methylation test.

Adolescent↗
PubMed1999

The effect of intravenously administered magnesium on platelet function in patients after cardiac surgery.

UNLABELLED: After cardiac surgery, magnesium is often administered for prophylaxis and treatment of cardiac arrhythmias. Magnesium, however, inhibits platelet function in vitro and in healthy volunteers. We performed a randomized, blinded, and placebo-controlled study to investigate the effect of magnesium on platelet function in patients after cardiac surgery. We studied patients who underwent uneventful coronary revascularization with cardiopulmonary bypass on the first postoperative day. Before and after an infusion of either 5.4 mmol magnesium (n = 19) or saline (n = 20), platelet function was investigated by means of in vitro bleeding time, platelet aggregation, and flow-cytometric assays. In addition, to investigate platelet function in vitro, 1, 5, and 10 mM magnesium were added to platelet-rich plasma before and 24 h after surgery in 30 patients. Compared with the control group, magnesium prolonged the in vitro bleeding time (22%) and inhibited ADP- and collagen-induced platelet aggregation (13% and 17%), platelet P-selectin expression (18%), and the binding of fibrinogen to the platelet glycoprotein IIb/IIIa receptor (10%). Magnesium also led to significant dose-dependent inhibition of platelet aggregation (19%), P-selectin expression (14%), and fibrinogen binding (11%) before and after surgery in vitro. Although the antithrombotic effect of magnesium may be beneficial in patients after coronary revascularization, large-dose magnesium therapy should be carefully considered in patients with impaired platelet function and co-existing bleeding disorders. IMPLICATIONS: In a randomized, blinded, placebo-controlled study of patients 24 h after coronary artery bypass grafting, IV administered magnesium inhibited platelet function in vitro and in vivo.

Adenosine Diphosphate↗
PubMed1999

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.

BACKGROUND: The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS: In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS: Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS: The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Aging↗
PubMed1999

Bradykinin B(2) receptor-mediated mitogen-activated protein kinase activation in COS-7 cells requires dual signaling via both protein kinase C pathway and epidermal growth factor receptor transactivation.

The signaling routes linking G-protein-coupled receptors to mitogen-activated protein kinase (MAPK) may involve tyrosine kinases, phosphoinositide 3-kinase gamma (PI3Kgamma), and protein kinase C (PKC). To characterize the mitogenic pathway of bradykinin (BK), COS-7 cells were transiently cotransfected with the human bradykinin B(2) receptor and hemagglutinin-tagged MAPK. We demonstrate that BK-induced activation of MAPK is mediated via the alpha subunits of a G(q/11) protein. Both activation of Raf-1 and activation of MAPK in response to BK were blocked by inhibitors of PKC as well as of the epidermal growth factor (EGF) receptor. Furthermore, in PKC-depleted COS-7 cells, the effect of BK on MAPK was clearly reduced. Inhibition of PI3-Kgamma or Src kinase failed to diminish MAPK activation by BK. BK-induced translocation and overexpression of PKC isoforms as well as coexpression of inactive or constitutively active mutants of different PKC isozymes provided evidence for a role of the diacylglycerol-sensitive PKCs alpha and epsilon in BK signaling toward MAPK. In addition to PKC activation, BK also induced tyrosine phosphorylation of EGF receptor (transactivation) in COS-7 cells. Inhibition of PKC did not alter BK-induced transactivation, and blockade of EGF receptor did not affect BK-stimulated phosphatidylinositol turnover or BK-induced PKC translocation, suggesting that PKC acts neither upstream nor downstream of the EGF receptor. Comparison of the kinetics of PKC activation and EGF receptor transactivation in response to BK also suggests simultaneous rather than consecutive signaling. We conclude that in COS-7 cells, BK activates MAPK via a permanent dual signaling pathway involving the independent activation of the PKC isoforms alpha and epsilon and transactivation of the EGF receptor. The two branches of this pathway may converge at the level of the Ras-Raf complex.

Androstadienes↗
PubMed1999

Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1.

Using a cytochemical approach, we examined the role of tissue transglutaminase (tTgase, Type II) in the incorporation of latent TGF-beta binding protein-1 (LTBP-1) in the extracellular matrix of Swiss 3T3 fibroblasts in which tTgase expression can be modulated through a tetracycline-controlled promoter. Increased tTgase expression led to an increased rate of LTBP-1 deposition in the matrix, which was accompanied by an increased pool of deoxycholate-insoluble fibronectin. Matrix deposition of LTBP-1 could also be reduced by the competitive amine substrate putrescine. Immunolocalization at the fluorescence and electron microscopic level showed that extracellular tTgase is located at the basal and apical surfaces of cells and at cell-cell contacts, and that LTBP-1 is co-distributed with cell surface tTgase, suggesting an early contribution of tTgase to the binding of LTBP-1 to matrix proteins. LTPB-1 was also found to co-localize with both intracellular and extracellular fibronectin, and increased immunoreactivity for LTBP-1 and fibronectin was found in large molecular weight polymers in the deoxycholate-insoluble matrix of fibroblasts overexpressing tTgase. We conclude that regulation of tTgase expression is important for controlling matrix storage of latent TGF-beta1 complexes and that fibronectin may be one extracellular component to which LTBP-1 is crosslinked when LTBP-1 and tTgase interact at the cell surface. (J Histochem Cytochem 47:1417-1432, 1999)

3T3 Cells↗
PubMed1998

Regulated expression of tissue transglutaminase in Swiss 3T3 fibroblasts: effects on the processing of fibronectin, cell attachment, and cell death.

Tissue transglutaminase (tTgase) catalyzes the posttranslational modification of proteins by forming Ca2(+)-dependent intermolecular epsilon (gamma-glutamyl) lysine crosslinks; however, its physiological function is unclear despite increasing evidence for its involvement in the extracellular environment. To define where the enzyme is active and characterizes targets of crosslinking we have modulated tTgase expression in stably transformed Swiss 3T3 cell lines, generated by transfecting tTgase cDNA under the control of a tetracycline-regulated inducible promoter. Induced expression of tTgase enabled the detection of two pools of transglutaminase antigen, one intracellular and the other extracellular, which has a cellular distribution comparable to fibronectin. Incubation of cells with the fluorescent tTgase substrate fluorescein cadaverine indicated incorporation only in the extracellular matrix of healthy cells even though the amine was freely permeable to cells. Incorporation paralleled the deposition of fibronectin during fibril assembly when monitored by immunofluorescence. Fibronectin polymerization was confirmed by Western blotting. Cell surface-related tTgase was further demonstrated by preincubation of cells with tTgase antibody which led to inhibition of activity and cell attachment. Activation of the intracellular tTgase by increasing cytosolic Ca2+ using ionomycin resulted in cell death accompanied by extensive crosslinking in the cytoplasm, nucleus, and cell substratum contacts of induced cells. These dead cells were not typical of those undergoing apoptosis or necrosis since they remained adherent, preserved their microtubule network, and showed little DNA fragmentation. Modulation of expression of tTgase has indicated a possible physiological function for the enzyme in cell attachment, the crosslinking of fibronectin during fibril assembly, and the maintenance of cellular integrity in a novel form of cell death.

3T3 Cells↗
PubMed1998

Localization of GTP cyclohydrolase in monoaminergic but not nitric oxide-producing cells.

The first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis is GTP cyclohydrolase (GTPCH). BH4 serves as the essential cofactor for aromatic L-amino acid hydroxylases, such as tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), as well as for nitric oxide synthase (NOS). We hypothesized that to provide access to the cofactor, a close association exists between BH4-synthesizing and BH4-dependent enzymes, and we determined the relationship among GTPCH, neuronal NOS (nNOS), and TH in rat brain and adrenal gland using immunohistochemistry and in situ hybridization. Analyses of adjacent sections revealed specific localization of GTPCH in TH-containing cells of the substantia nigra, ventral tegmental area, hypothalamus, locus ceruleus, and adrenal medulla, and also in TPH-containing cells of the dorsal raphe nucleus and pineal gland. Thus, BH4 can be synthesized in all monoaminergic cells and is readily available for the enzymes requiring it. In contrast, analysis of adjacent sections showed that nNOS was not colocalized with GTPCH. Scattered nNOS-positive cells were found in the cortex, striatum, cerebellum, and olfactory bulb, all areas that receive monoaminergic innervation. The absence of GTPCH in nNOS cells suggests that nitric oxide-producing cells may either obtain biopterin from monoamine-containing processes which terminate in close proximity, or take up biopterin released into the blood. Double labelling of the same section for TH and nNOS revealed the TH nerve terminals connecting with the nNOS-positive cell bodies, suggesting the possibility that the BH4-containing nerve terminals may directly donate this cofactor to the nNOS-containing cells.

Adrenal Glands↗
PubMed1998

Structural analysis of inhibitor binding to human carbonic anhydrase II.

X-ray crystal structures of carbonic anhydrase II (CAII) complexed with sulfonamide inhibitors illuminate the structural determinants of high affinity binding in the nanomolar regime. The primary binding interaction is the coordination of a primary sulfonamide group to the active site zinc ion. Secondary interactions fine-tune tight binding in regions of the active site cavity >5 A away from zinc, and this work highlights three such features: (1) advantageous conformational restraints of a bicyclic thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached to a secondary sulfonamide group targeted to interact with hydrophobic patches defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact with His64, the catalytic proton shuttle. Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma.

Binding Sites↗
PubMed1998

[Feasibility of following up transfused patients].

The aim of this study was to assess the natural history of patients after transfusion and the acceptability of a standardized biological follow-up. In 1995, during 1 month, in 13 French hospitals, a follow-up at 3 and 6 months after blood transfusion was proposed to all blood recipients who had not received any blood transfusion within the past 6 months (eligible patients): screening for red cell antibodies, alanine aminotransferase (ALT) activity and specific viral markers of hepatitis B (hepatitis B surface antigen and antibody to hepatitis virus core antigen), of hepatitis C (antibodies) and of Human Immunodeficiency Virus (antibodies). At the beginning of the study, 296 patients were followed for 6 months. A complete follow-up was available at 3 months for 183 patients (62%), at 6 months for 168 (57%) and after 6 months, 198 patients (67%) have been once followed. Of eligible patients, 76% were alive at six months. After transfusion, the incidence of red cell alloantibodies and elevated ALT concentration were respectively 4% and 17%. At 6 months, one patient had Hepatitis B surface antigen; the responsibility of blood transfusion was excluded. Within the first 24 hours, 68 patients (23%) required another blood transfusion and 42% of units were transfused to patients with malignant disease. Our study quantifies in real conditions the difficulty of a biological follow-up in a transfused population, mostly composed of patients that could not be followed in the hospital where they were transfused.

Adult↗
PubMed1998

Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC). Here we describe the molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion. Heteroduplex and partial sequence analysis did not reveal any point mutations of the known IC elements, either. Interestingly, all of these patients represent sporadic cases, and some share the paternal (PWS) or the maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS patients informative for the grandparental origin of the incorrectly imprinted chromosome region and four cases described elsewhere, the maternally imprinted paternal chromosome region was inherited from the paternal grandmother. This suggests that the grandmaternal imprint was not erased in the father's germ line. In seven informative AS patients reported here and in three previously reported patients, the paternally imprinted maternal chromosome region was inherited from either the maternal grandfather or the maternal grandmother. The latter finding is not compatible with an imprint-switch failure, but it suggests that a paternal imprint developed either in the maternal germ line or postzygotically. We conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzygotic error, (2) that these cases have a low recurrence risk, and (3) that the paternal imprint may be the default imprint.

Angelman Syndrome↗