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Biomedical subjects

R A Feldman

Publications and source records attributed to R A Feldman.

At least 19 recordsLinked to original sources
PubMed1995

Identification of a new adapter protein that may link the common beta subunit of the receptor for granulocyte/macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 to phosphatidylinositol 3-kinase.

Binding of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) to its receptor induces the rapid activation of phosphatidylinositol-3 kinase (PI 3-kinase). As hGM-CSF receptor (hGMR) does not contain a consensus sequence for binding of PI 3-kinase, hGMR must use a distinct mechanism for its association with and activation of PI 3-kinase. Here, we describe the identification of a tyrosine-phosphorylated protein of 76-85 kDa (p80) that associates with the common beta subunit of hGMR and with the SH2 domains of the p85 subunit of PI 3-kinase in hGM-CSF-stimulated cells. Src/Yes and Lyn were tightly associated with the p80.PI 3-kinase complex, suggesting that p80 and other phosphotyrosyl proteins present in the complex were phosphorylated by Src family kinases. Tyrosine phosphorylation of p80 was only detected in hGM-CSF or human interleukin-3-stimulated cells, suggesting that activation of p80 might be specific for signaling via the common beta subunit. We postulate that p80 functions as an adapter protein that may participate in linking the hGM-CSF receptor to the PI 3-kinase signaling pathway.

Binding Sites↗
PubMed1995

Multi-laboratory comparison of eight commercially available Helicobacter pylori serology kits. Helicobacter pylori Serology Study Group.

The performance of eight commercially available EIA kits in detecting antibody to Helicobacter pylori was evaluated by a panel of 17 laboratories using serum from 59 patients selected from endoscopy clinics in Belgium, Ireland, Italy, the Netherlands and Switzerland. Each laboratory received a randomly numbered set of sera and was ignorant of the culture results of the patients. The performance of the kits was assessed in terms of diagnostic accuracy compared to culture (measured by sensitivity and specificity), the inter-laboratory variability in diagnostic accuracy and the number of laboratories that experienced problems in using the kits. Grey zone results, which are routinely used to highlight the uncertain interpretation of results that lie near the cut-off point between positive and negative diagnoses, were accounted for in the analysis. Laboratories experienced practical problems in using some kits, whilst other kits were found to have high inter-laboratory variation or low diagnostic accuracy. There was no single kit that performed better on every criterion than the others. The Orion kit was a good all-round performer, whilst the Roche kit was excellent at detecting positive results, although it had a slightly raised false-positive rate.

Evaluation Studies as Topic↗
PubMed1994

Interaction of the c-fes proto-oncogene product with the interleukin-4 receptor.

Interleukin-4 (IL-4) regulates proliferation and differentiation of a variety of hematopoietic cell lineages through binding to the IL-4 receptor (IL-4R). Recently, we have demonstrated that IL-4 induces tyrosine phosphorylation of several proteins including the IL-4R and also induces association of phosphatidylinositol-3 kinase with the IL-4R. Since IL-4 induces tyrosine phosphorylation, we speculated that some tyrosine kinase may associate with the IL-4R. In this study, we demonstrate that IL-4 induces tyrosine phosphorylation of a protein closely related to, or identical to the c-fes protooncogene-encoded protein tyrosine kinase (FES). Furthermore, tyrosine phosphorylated FES or the closely related protein is found associated with the IL-4R. We also demonstrate that FES associates with the IL-4R in COS7 cells transfected with cDNA expression plasmids encoding these two proteins and in transfected COS7 cells IL-4 augments association of FES with the IL-4R and tyrosine phosphorylation of both FES and the IL-4R. Through a deletion analysis of the IL-4R we have identified a putative FES-binding site in the cytoplasmic domain of the IL-4R.

Animals↗
PubMed1992

Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site.

Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.

Adenosine Triphosphate↗
PubMed1992

Diagnosis and treatment of Ogilvie's syndrome after lumbar spinal surgery. Report of three cases.

Three patients who developed Ogilvie's syndrome following lumbar spinal surgery are described. Ogilvie's syndrome, also known as pseudo-obstruction of the colon, is characterized by massive cecal distention without mechanical obstruction. If this condition is not recognized and not promptly treated, it may be complicated by cecal perforation, a life-threatening hazard. The etiology, diagnosis, management, and potential relationship between lumbar spinal surgery and Ogilvie's syndrome are discussed.

Adult↗
PubMed1990

Isolation and DNA sequence of a gene encoding alpha-trichosanthin, a type I ribosome-inactivating protein.

alpha-Trichosanthin (alpha-TCS) is a ribosome-inactivating protein that has recently been shown to inhibit the replication of human immunodeficiency virus. We have isolated a gene encoding alpha-TCS and have determined its DNA sequence. The data indicate that alpha-TCS is synthesized as a preproprotein consisting of 289 amino acids, the first 23 residues of which comprise a putative secretory signal peptide. The last 19 residues comprise a carboxyl extension that has not been reported to be associated with the mature protein and that may be processed in the endoplasmic reticulum or Golgi apparatus of cells producing alpha-TCS. The mature protein consists of 247 amino acids. The sequence predicted by translation of the DNA sequence agrees with and confirms the primary sequence determined recently on the protein. The molecular clone for alpha-TCS will facilitate directed mutational analyses that may provide information on how this peptide, and other ribosome-inactivating proteins, function. These studies may also lead to the development of therapeutic agents with altered activities and/or improved properties for in vivo use.

Amino Acid Sequence↗
PubMed1990

Selective potentiation of c-fps/fes transforming activity by a phosphatase inhibitor.

Human c-fps/fes when expressed at sufficiently high levels in NIH 3T3 cells can induce cellular transformation. To probe the mechanism of action of the c-fps/fes product NCP92, we have examined the biological and biochemical consequences of stabilizing phosphotyrosine in cells that overexpress NCP92. In this study we report that when cells expressing c-fps/fes are incubated with low concentrations of sodium vanadate, a tyrosine phosphatase inhibitor, the transforming activity of c-fps/fes can be potentiated by nearly two orders of magnitude. This effect was associated with a threefold increase in the level of phosphotyrosine in NCP92 and its major cellular substrates. Unlike c-src, NCP92 had a single tyrosine phosphorylation site, and vanadate treatment induced its phosphorylation in vivo. This was found to have a positive effect on NCP92 kinase specific activity, but at the low concentrations of vanadate that were used, this effect was very small. The results are consistent with the hypothesis that potentiation was a consequence of the stabilization of phosphotyrosine in critical targets of transformation of NCP92, rather than from a direct effect of vanadate on NCP92 kinase. The potentiating effect of vanadate was relatively specific for c-fps/fes; this reagent did not affect the high transforming activity of gag-v-fps/fes, nor did it enhance the less active c-ras, c-src, or EGF receptor genes, although the latter two genes encode tyrosine kinases. The specificity of the biological response of c-fps/fes to the stabilization of phosphotyrosine suggests that this molecule has a distinct mode of regulation and mechanism of action.

Animals↗
PubMed1989

The automatic internal cardioverter defibrillator (AICD): description and guidelines for interaction during cardiac arrest.

The development and increasing use of the automatic implantable cardioverter defibrillator (AICD) represents a major therapeutic advance for management of recurrent ventricular tachycardia and ventricular fibrillation. However, the AICD sensing functions that determine appropriate energy discharge may complicate resuscitation from cardiac arrest. This care report illustrates a properly functioning AICD interfering with the resuscitation of a 67-year-old man. In the presence of persistent ventricular tachycardia and ventricular fibrillation or successful conversion to a supraventricular tachycardia with pulses that exceed the rate cutoff, it may be helpful to inactivate the AICD with a magnet to prevent unneeded discharges during resuscitation and stabilization.

Aged↗
PubMed1989

A highly efficient retroviral vector allows detection of the transforming activity of the human c-fps/fes proto-oncogene.

We have constructed an efficient new retroviral vector containing strong promoting elements derived from the Friend murine leukemia virus (F-MuLV) long terminal repeat (LTR) and have used the vector to demonstrate that overexpression of human c-fps/fes can transform established mouse cells. When a c-fps/fes cDNA was cloned into the vector, this viral DNA and the recovered virus induced very high levels of the c-fps/fes product NCP92 and tumorigenic transformation of NIH 3T3 cells. Compared with an isogenic vector under control of a Moloney MuLV-derived LTR, the vector driven by the F-MuLV LTR induced 3- to 10-times-higher levels of expression of c-fps/fes, a higher level of phosphotyrosine in cellular proteins, and a virus whose transforming activity was 2 orders of magnitude greater. We conclude (i) that normal c-fps/fes can induce morphologic transformation and that its transforming activity is a function of the level of expression of NCP92 and (ii) that the vector based on the F-MuLV LTR is more efficient than the vector driven by a Moloney MuLV LTR in inducing high levels of expression and measurable biological activity.

Animals↗
PubMed1986

Occurrence and distribution of serotypes of the Arizona subgroup of Salmonella strains in the United States from 1967 to 1976.

The Salmonella Arizona subgroup contains gram-negative enteric bacteria that are closely related to other salmonellae biochemically, serologically, and genetically. Although the Arizona subgroup may be isolated from a wide variety of nonhuman and human sources, the arizonae are uncommonly recognized as human pathogens, and surprisingly little is known about their epidemiology. From 1967 through 1976, the Centers for Disease Control received 858 Arizona subgroup cultures from human and nonhuman sources representing 143 different serotypes in 33 somatic groups; several serotypes had not been previously reported. The 374 cultures from humans represent 71 different serotypes; extraintestinal isolates were present in 31 (44%) serotypes. Compared with data from a previous 20 years of surveillance, the proportion of Arizona subgroup strains isolated from stools, blood, and other sites was remarkably stable, but several serotypes showed marked changes in their frequency of isolation. In total, the ratio of extraintestinal to intestinal isolates was 0.37, but marked serotype-specific variation was noted, suggesting differences in virulence associated with serotype.

Amphibians↗
PubMed1986

Antipeptide antiserum identifies a widely distributed cellular tyrosine kinase related to but distinct from the c-fps/fes-encoded protein.

We raised antibodies directed against a synthetic peptide representing an amino acid sequence of the conserved kinase domain of the transforming protein of Fujinami sarcoma virus (FSV) (P140). The antiserum obtained specifically recognized FSV-P140 and its cellular homolog and in addition, it recognized a new cellular protein of 94,000 daltons (NCP94) in avian and mammalian cells. NCP94 was found to be associated with a cyclic nucleotide-independent protein kinase activity that was specific for tyrosine residues. Although NCP94 and FSV-P140 share antigenic determinants, NCP94 is not a cellular homolog of FSV-P140: NCP94 and the previously identified c-fps/fes product were different in their tryptic fingerprints and in their tissue specificities. Thus, the function of NCP94 in normal cells is probably different than that of the c-fps/fes product. NCP94 was expressed in every tissue and cell line that was examined. In chickens, NCP94 levels were highest during embryonic development and NCP94 expression was high in gizzard, brain, and spleen throughout embryonic and adult life. The universal expression of NCP94 suggests that this protein may be involved in an essential function of normal cells. NCP94 may be a new cellular tyrosine kinase of the src gene family.

Amino Acid Sequence↗
PubMed1985

Specific expression of the human cellular fps/fes-encoded protein NCP92 in normal and leukemic myeloid cells.

We have found that both an antibody directed against a synthetic peptide representing an amino acid sequence of the conserved kinase domain of transforming protein P140 of Fujinami sarcoma virus and a regressing tumor antiserum recognized the products of the c-fps/fes genes of both avian and mammalian cells. The anti-peptide antibody also recognized a 94-kilodalton protein that was related to but distinct from the c-fps/fes product in structure and in tissue distribution. A 92-kilodalton protein, NCP92, was found to be the mammalian counterpart of the previously identified avian c-fps/fes protein NCP98 by its structural similarity to NCP98, its associated tyrosine kinase activity, and its similar tissue distribution. The highest levels of NCP92 were found in tissue macrophages and in bone marrow. In bone marrow NCP92 expression was restricted to cells of the monocyte/macrophage and granulocyte lineages. That the expression of NCP92 is limited to these cell types was confirmed by the analysis of murine and human hematopoietic tumors representing different cell lineages: NCP92 was positive in leukemic cells of granulocytic and monocytic origin but not in B-lymphocytic, T-lymphocytic, or erythroid tumor cells. The expression of NCP92 seems to be related to the capacity of myeloid cells to differentiate and to respond to certain colony-stimulating factors.

Animals↗
PubMed1985

Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years.

Forty-eight patients underwent electrical stimulation of the brain for treatment of chronic pain between 1978 and 1983. Average pain duration prior to treatment was 4.5 years. Before selection for this procedure patients underwent pain treatment in a multidisciplinary pain center, intensive psychological and psychiatric evaluation, and assessment of pain responsiveness to intravenous administration of placebo, morphine, and naloxone. A total of 71 electrodes were placed in the 48 patients at a variety of stimulating targets, including the periaqueductal gray matter, periventricular gray matter, thalamus, and internal capsule. Seventy-two percent of patients experienced complete or partial pain relief. In addition, 59% of patients were able to discontinue narcotic usage. Twenty-five percent of patients returned to normal physical activities and another 33% showed marked improvement in functional capacity. Follow-up periods ranged from 2 to 60 months; with a mean follow-up period of 20 months. A variety of relatively minor complications occurred, but no mortality or permanent sequelae were experienced. No patient's pain was made worse as a result of electrical stimulation. Electrical stimulation of the brain offers a safe and relatively effective method for the treatment of chronic pain in appropriately selected patients, who are unresponsive to other forms of therapy.

Adult↗
PubMed1984

Unpasteurized milk. The hazards of a health fetish.

Meaningful differences in nutritional value between pasteurized and unpasteurized milk have not been demonstrated, and other purported benefits of raw milk consumption have not been substantiated. Conversely, the role of unpasteurized dairy products in the transmission of infectious diseases has been established repeatedly. To effectively counsel patients attracted by the health claims made for raw milk, practicing physicians must understand both the rationale used by proponents of raw milk and the magnitude of the risk involved in drinking raw milk.

Animals↗
PubMed1984

Importance of host factors in human salmonellosis caused by multiresistant strains of Salmonella.

Antimicrobial resistance patterns of Salmonella isolates from persons in randomly selected urban and rural counties in the United States were examined along with clinical and epidemiological characteristics of the host. Multiresistant strains, isolated from 66 (12.2%) of 542 persons evaluated, were associated with five of 20 variables in univariate analyses: serotype heidelberg, host of Hispanic origin, host exposure to penicillins within four weeks before stool culture, age greater than or equal to 60 years, and regular antacid use. By multiple linear regression, the first three variables were each significantly associated with infections due to multiresistant Salmonella. One or more of the last three variables, thought to be host factors that may promote disease, were present for persons yielding 38% of multiresistant strains but only 12% of sensitive strains (P less than .001). The relatively large proportion of multiresistant Salmonella among isolates from persons with these risk factors suggests that to cause disease, resistant organisms are more dependent than are sensitive organisms on host characteristics.

Adolescent↗