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J A Hoffman

Publications and source records attributed to J A Hoffman.

12 recordsLinked to original sources
PubMed1992

The v-rel oncogene: insights into the mechanism of transcriptional activation, repression, and transformation.

The v-rel oncogene product from the avian reticuloendotheliosis virus strain T corresponds to a member of the Rel-related family of enhancer-binding proteins that includes both the mammalian 50- and 65-kDa subunits of the NF-kappa B transcription factor complex. However, in contrast to NF-kappa B, v-Rel has been shown to function as a dominant-negative repressor of kappa B-dependent transcription in many mature cell types. We now demonstrate that a highly conserved motif within the Rel homology domain of v-Rel containing a consensus protein kinase A phosphorylation site is required for DNA binding, transcriptional repression, and cellular transformation mediated by this oncoprotein. However, replacement of the serine phosphate acceptor within the protein kinase A site with an alanine did not alter any of these functions of v-Rel, suggesting that phosphorylation at this site is not central to the regulation of this oncogene product. Rather, the inactive mutations appear to identify a functional domain within v-Rel required for these various biological activities. It is notable that these same mutations do not impair the ability of v-Rel to heterodimerize with the 50-kDa subunit of NF-kappa B, suggesting that v-Rel-mediated transcriptional repression likely involves direct nuclear blockade of the kappa B enhancer rather than indirect alterations in the composition of preformed cytoplasmic NF-kappa B complexes. Paradoxically, when introduced into undifferentiated F9 cells, v-Rel functions as a kappa B-specific transcriptional activator rather than as a dominant-negative repressor. These stimulatory effects of v-Rel require both the conserved protein kinase A phosphorylation site and additional unique C-terminal sequences not needed for v-Rel-mediated repression in mature cells. Retinoic acid-induced differentiation of these F9 cells restores the repressor function of v-Rel. These opposing biological actions of v-Rel occurring in cells at distinct stages of differentiation may have important implications for the mechanism of v-Rel-mediated transformation occurring in avian splenocytes.

Amino Acid Sequence↗
PubMed1991

A tyrosine kinase physically associates with the beta-subunit of the human IL-2 receptor.

Cell surface expression of the high affinity IL-2R regulates, in part, the proliferative response occurring in Ag- or mitogen-activated T cells. The functional high affinity IL-2R is composed of at least two distinct ligand-binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). The IL-2R beta polypeptide appears to be essential for growth signal transduction, whereas the IL-2R alpha protein participates in the regulation of receptor affinity. We have prepared and characterized two mAb, DU-1 and DU-2, that specifically react with IL-2R beta. In vitro kinase assays performed with DU-2 immunoprecipitates, but not anti-IL-2R alpha or control antibody immunoprecipitates, have revealed co-precipitation of a tyrosine kinase enzymatic activity that mediates phosphorylation of IL-2R beta. Because both IL-2R alpha and IL-2R beta lack tyrosine kinase enzymatic domains, these findings strongly suggest that noncovalent association of a tyrosine kinase with the high affinity IL-2R complex. Deletion mutants of the intracellular region of IL-2R beta, lacking either a previously described "critical domain" between amino acids 267 and 322 or the carboxyl-terminal 198 residues (IL-2R beta 88), lacked the ability to co-precipitate this tyrosine kinase activity, as measured by phosphorylation of IL-2R beta in vitro. Both of these mutants also failed to transduce growth-promoting signals in response to IL-2 in vivo. Analysis of the IL-2R beta 88 mutant receptor suggested that a second protein kinase mediating phosphorylation on serine and threonine residues physically interacts with the carboxyl terminus of IL-2R beta. This kinase may be necessary but, alone, appears to be insufficient to support a full IL-2-induced proliferative response. These studies highlight the physical association of protein kinases with the cytoplasmic domain of IL-2R beta and their likely role in IL-2-induced growth signaling mediated through the multimeric high affinity IL-2R complex.

Animals↗
PubMed1989

Activation of the interleukin-2 receptor alpha gene: regulatory role for DNA-protein interactions flanking the kappa B enhancer.

The human interleukin-2 receptor alpha (IL2R alpha) gene is transcriptionally activated by both phorbol esters and the HTLV-I trans-activator (Tax) protein through a mechanism that involves the interaction of inducible DNA binding proteins with a kappa B-like enhancer element (-267 to -256). Using mutated IL2R alpha promoter constructs in transient transfection and DNA binding assays, we now demonstrate that sequences located immediately upstream and downstream of the kappa B enhancer also contribute to the regulation of IL2R alpha gene expression. One upstream sequence termed UE-1 is preferentially required for phorbol ester relative to Tax-induced activation and specifically interacts with a constitutively expressed 56-kD cellular factor. In contrast, two overlapping downstream elements between nucleotides -252 and -239 appear to be required for both phorbol ester and Tax-induced activation. One of these elements, an Sp1-like sequence, binds a constitutively expressed 100-kD T-cell protein consistent in size with Sp1 isolated from HeLa cells. The second element, located between the kappa B and Sp1 sites, resembles the decanucleotide core of the serum response element (SRE) from the c-fos gene and interacts with a constitutively expressed factor. Together, these findings implicate a functional role for multiple constitutively expressed DNA binding proteins, in addition to the inducible kappa B-specific factors, in the overall regulation of IL2R alpha gene activation.

Base Sequence↗
PubMed1987

Functional changes during acute rehabilitation in patients with stroke.

The purpose of this study was to analyze functional change levels and determine Spearman rank order correlation coefficients about information gleaned from physical therapy discharge notes for a group of 212 patients with stroke who received physical therapy during an acute rehabilitation stay. Functional changes were determined in the categories of wheelchair skills, transfer ability, bed (mat) mobility, and ambulation. Comparisons also were made between a subgroup of the most severely involved patients and a subgroup of the least involved patients. The correlations between these functional changes and days of physical therapy were determined. Four conclusions were deduced: 1) All patients improved functionally after a stroke, 2) the improvement was related to the amount of time spent in physical therapy, 3) the more severely involved patients exhibited a greater relationship between functional gains and days spent in physical therapy than the least involved patients, and 4) the least involved patients exhibited the most gains in function. The implications of these findings were discussed.

Activities of Daily Living↗
PubMed1984

LSD flashbacks.

Explore the source record for details and available documents.

Adolescent↗
PubMed1984

Emergency psychiatry training: the new old problem.

Unevenness in emergency psychiatry training is still an issue as borne out by a recent literature review. An emergency setting in a general hospital is described with its attendant problem areas for psychiatric residents' function and learning. An adaptable curriculum is reported that takes into account limits of time, finances, and faculty.

Crisis Intervention↗
PubMed1983

Crystallization of bovine pancreatic polypeptide.

Bovine pancreatic polypeptide, a 36-residue polypeptide hormone, was successfully crystallized for the first time. During purification by extensive dialysis against distilled water a surprisingly insoluble form of the peptide was obtained which led to its crystallization as orthorhombic needles up to 2 mm in length.

Amino Acid Sequence↗
PubMed1982

Glycoprotein inhibitors and iodophilic polysaccharide storage in group A Streptococcus pyogenes.

Inhibitors of glycoprotein synthesis in eucaryotic cells also inhibited iodophilic polysaccharide (IPS) storage in group A streptococcus pyogenes. Addition of bacitracin or amphomycin, known inhibitors of polyisoprenol phosphate metabolism or lipid-linked oligosaccharide synthesis, indicated that a key intermediate must be synthesized before IPS storage could be detected. Based on inhibitor action and energy requirements the intermediate was most likely an undecaprenol pyrophosphoryl maltosaccharide. Biosynthesis of the maltosaccharide had an ATP requirement as shown by arsenate action but IPS synthesis via amylomaltase was energy independent if the lipid-linked saccharides were preformed. Maltosaccharide acceptor site blockade with 2-deoxy-d-glucose immediately inhibited IPS storage, which demonstrated the need of acceptor glucose residues for transglycosylation activity of amylomaltase. Tunicamycin failed to inhibit IPS synthesis although it was added in lethal concentrations.

Anti-Bacterial Agents↗
PubMed1981

Enhancement of viral RNA-induced interferon production of L cells treated with insulin and amphotericin B methyl ester.

A study was initiated to develop a more efficient method of producing high-titered L cell interferon. The induction of interferon by viral infectious RNA could be augmented by pretreating the cell cultures with insulin and infecting in the presence of Amphotericin B methyl ester (AmBME). L cells were treated for 24 hr with different concentrations of insulin and then challenged with MM virus RNA suspended in a balanced salt solution with and without AmBME. The fluids were collected 48 hr after infection and assayed for interferon activity. Interferon production was markedly increased in insulin-treated cultures and that the increase was dose-dependent.

Amphotericin B↗