PubMed Health⌕ Search

Biomedical subjects

E Goldsmith

Publications and source records attributed to E Goldsmith.

At least 19 recordsLinked to original sources
PubMed1999

Principles underlying a model policy on relationships between staff and service recipients in a mental health system.

OBJECTIVE: The authors participated in a work group to produce a model policy addressing the boundaries of relationships between staff and recipients of service in a public mental health system that provides and regulates services in a variety of treatment settings. METHODS: The chief medical officer of the New York State Office of Mental Health assembled a work group of administrators, clinicians, state officials, and a representative of service recipients. The group reviewed the professional literature and existing ethics guidelines and policies addressing relationships between staff members and service recipients and made recommendations for a new policy. RESULTS AND CONCLUSIONS: The work group formulated five guiding principles: prevention of the exploitation of recipients of services by staff; the right of recipients to be treated as competent autonomous human beings; recognition that certain developmental stages, treatment settings, and pre-existing relationships increase a service recipient's vulnerability to exploitation and call for more stringent regulation of staff actions; acceptance of a spectrum of permissible relationships for staff and recipients outside of the relationship dictated by the staff member's job description; and recognition of the difference between a relationship focused on treatment or service provision and other professional relationships between providers and current or former recipients. The principles were used to develop a model policy on relationships between staff and recipients that addresses both the organizational complexity and the recipient-centered rehabilitation model of a large state-operated mental health system.

Community Mental Health Centers↗
PubMed1998

A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation.

BACKGROUND: Mitogen-activated protein (MAP) kinases are ubiquitous components of many signal transduction pathways. Constitutively active variants have been isolated for every component of the extracellular-signal-regulated kinase 1 (ERK1) and ERK2 MAP kinase pathway except for the ERK itself. RESULTS: To create an activated ERK2 variant, we fused ERK2 to the low activity form of its upstream regulator, the MAP kinase kinase MEK1. The ERK2 in this fusion protein was active in the absence of extracellular signals. Expression of the fusion protein in mammalian cells did not activate endogenous ERK1 or ERK2. It was sufficient, however, to induce activation of the transcription factors Elk-1 and AP-1, neurite extension in PC12 cells in the absence of nerve growth factor, and foci of morphologically and growth-transformed NIH3T3 cells, if the fusion protein was localized to the nucleus. A cytoplasmic fusion protein was without effect. CONCLUSIONS: Activation of ERK2 is sufficient to cause several transcriptional and phenotypic responses in mammalian cells. Nuclear localization of activated ERK2 is required to induce these events.

3T3 Cells↗
PubMed1998

Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation.

The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon activation it translocates to the nucleus of the stimulated cell, where it phosphorylates nuclear targets. We find that nuclear accumulation of microinjected ERK2 depends on its phosphorylation state rather than on its activity or on upstream components of its signaling pathway. Phosphorylated ERK2 forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the nucleus, suggesting that dimerization is essential for its normal ligand-dependent relocalization. The crystal structure of phosphorylated ERK2 reveals the basis for dimerization. Other MAP kinase family members also form dimers. The generality of this behavior suggests that dimerization is part of the mechanism of action of the MAP kinase family.

Animals↗
PubMed1996

Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity.

To examine the specificity of MEKs for MAP kinase family members, we determined the abilities of several MEK isoforms to phosphorylate mutants of the MAP kinase ERK2 and the related kinase ERK3 which are modified in the phosphorylation loop. The ERK2 mutants included mutations of the two phosphorylation sites, mutations of the acidic residue between these two sites, and mutations that shorten the length of this loop. All mutants were tested for phosphorylation by six mammalian MEKs and compared with several wild type MAP kinases. MEK1 and MEK2 phosphorylate a majority of the ERK2 mutants. MEK2 but not MEK1 will phosphorylate ERK3. Alteration of the residue between the two phosphorylation sites neither dramatically affected the activity of MEK1 and MEK2 toward ERK2 nor conferred recognition by other MEKs. Likewise, reduction of the length of the phosphorylation loop only partially reduces recognition by MEK1 and MEK2 but does not promote recognition by other MEKs. Thus other yet to be identified factors must contribute to the specificity of MEK recognition of MAP kinases.

Amino Acid Sequence↗
PubMed1996

Characterization of a protein kinase that phosphorylates serine 189 of the mitogen-activated protein kinase homolog ERK3.

A novel protein kinase activity present in nuclear and cytosolic extracts has been identified and partially purified as a consequence of its tight binding to and phosphorylation of the extracellular signal-regulated protein kinase (ERK) 3. This novel protein kinase is inactivated by treatment with phosphoprotein phosphatase 2A. The ERK3 protein kinase was immunologically distinct from mitogen-activated protein (MAP) kinase/ERK kinases (MEK) 1 and 2 which phosphorylate the ERK3-related MAP kinases ERK1 and ERK2. This ERK3 kinase phosphorylated a single site on ERK3, Ser189, comparable to Thr183, one of the two activating phosphorylation sites of ERK2. To test the specificity of the ERK3 kinase, mutants of ERK3 and ERK2 were made in which the phosphorylated residues were exchanged. The double mutant S189T,G191Y ERK3, in which the phosphorylated residues from ERK2 replaced the comparable residues in ERK3, was phosphorylated by the ERK3 kinase but only on threonine. The ERK3 kinase did not phosphorylate ERK2 or ERK2 mutants. These findings indicate that although the ERK3 kinase is highly specific for ERK3, it does not recognize tyrosine, a feature that distinguishes it from MEKs that phosphorylate other ERK/MAP kinase family members.

Amino Acid Sequence↗
PubMed1989

Autophosphorylation activates the soluble cytoplasmic domain of the insulin receptor in an intermolecular reaction.

The cytoplasmic protein-tyrosine kinase domain of the insulin receptor (residues 959-1355) has been expressed as a soluble protein in Sf9 insect cells via a Baculovirus expression vector (Ellis, L., Levitan, A., Cobb, M.H., and Ramos, P. (1988) J. Virol. 62, 1634-1639). The purified protein is a monomer as judged by its behavior in sucrose gradients and on gel filtration in the presence or absence of protamine. The initial rate of autophosphorylation using 3 mM MgCl2 is increased 20-30-fold by protamine. A maximum of 4-5 mol of phosphate are incorporated per mol of enzyme. The activity of the enzyme as a function of phosphorylation state was studied for three substrates: a synthetic dodecapeptide derived from the sequence of the major autophosphorylation site in the insulin receptor, poly(Glu, Tyr), 4:1, and histone 2B. Autophosphorylation of the protein to a stoichiometry of 4-5 mol of phosphate/mol increases its enzymatic activity as much as 200-fold; a 30-fold increase in activity occurs upon addition of 1 mol of phosphate/mol. The activities of unphosphorylated enzyme with the three substrates are 3.4, 2.3, and 0.44 nmol/min/mg, respectively. The activities of the autophosphorylated enzyme with the three substrates are 175, 274, and 45 nmol/min/mg, respectively. Exposure of the autophosphorylated enzyme to ADP results in a loss of phosphate from the enzyme which is associated with a decrease in enzymatic activity. Autophosphorylation of the kinase in the presence or absence of protamine displays a marked dependence on enzyme concentration. Furthermore, the rate of autophosphorylation decreases as the viscosity of the solution increases. Taken together, these data suggest that phosphorylation occurs via an intermolecular reaction.

Adenosine Diphosphate↗
PubMed1987

Structure of the nucleotide activation switch in glycogen phosphorylase a.

Adenosine monophosphate is required for the activation of glycogen phosphorylase b and for release of the inhibition of phosphorylase a by glucose. Two molecules of adenosine monophosphate (AMP) bind to symmetry related sites at the subunit interface of the phosphorylase dimer. Adenosine triphosphate (ATP) binds to the same site, but does not promote catalytic activity. The structure of glucose-inhibited phosphorylase a bound to AMP and also of the complex formed with glucose and ATP is described. Crystallographic refinement of these complexes reveals that structural changes are associated with AMP but not ATP binding. The origin of these effects can be traced to different effector binding modes exhibited by AMP and ATP, respectively. The conformational changes associated with AMP binding traverse multiple paths in the enzyme and link the effector and catalytic sites.

Adenosine Monophosphate↗
PubMed1984

Crystallization of the gene 45 protein from the DNA replication fork of bacteriophage T4.

The gene 45 protein from bacteriophage T4 has been purified and is crystallized. This protein is part of the T4 DNA replication complex. The crystallized protein is active in complementation assays. X-ray diffraction analysis is in progress; data are measured for the native and several heavy atom derivatives. The crystals diffract to about 3.5-A resolution.

Crystallization↗
PubMed1981

Carcinoma arising in pilonidal sinuses.

Pilonidal carcinoma is an infrequent complication of pilonidal disease. The surgeon's suspicion should be raised in cases of longstanding pilonidal inflammation. The disease occurs most frequently in men. The lesion is often a well-differentiated squamous carcinoma. Wide excisions at the initial procedure following a brief period of local wound care, is the optimum treatment and increases the chances for a five-year survival. Definitive closure of the defect is delayed and accomplished by rotational flaps or skin grafts. It palpable nodes are present in the inguinal region they should be biopsied even though this does not necessarily connote metastasis. When inguinal node metastasis is present, this is associated with a poor prognosis. The incidence of occult node metastasis is not known because no prophylactic groin dissections were performed. Staged groin dissections were not associated with any long-term survivals. The series was too small to determine its palliative potential. Radiation therapy may palliate local bone or soft tissue recurrences. Re-excisions of local soft tissue recurrences can provide, in some instances, long disease-free intervals. Both topical and systemic chemotherapy were administered in more recent cases with poor results, but this series is not large enough to form conclusions for this modality of treatment.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Intelligence is universal in life.

Behaviorists assume that living things memorize random atoms of information (engrams), "reinforced" by success, just as in the neo-Darwinian mutation-selection process. On the contrary we have to recognize the existence of organized and systematic responses in the learning process (Krechevsky). The animals seek desperately to "understand the meaning" of the world around them, by widening its context. Intelligence is not an exclusive prerogative of human mind. The minds of insects operate in the same way as that of man. Even a cell has a sort of intelligence (Cuenot). Consciousness is a state of awareness associated with enhanced mental activity. It occurs also in other "higher" animals (Thorpe). However human themselves are non conscious of their basic underlying motivations. Unconscious or ineffable knowledge plays a great role in shaping our world-view and in determining our influence on the Gaian hierarchy.

Animals↗