Search PubMed⌕ Search

Biomedical subjects

J Rosen

Publications and source records attributed to J Rosen.

At least 91 records · Page 5Linked to original sources
PubMed1994

Rapid activation of the interferon-gamma signal transduction pathway by inhibitors of tyrosine phosphatases.

Induction of gene expression by interferon-gamma involves the activation of a latent cytoplasmic transcription factor, p91, by phosphorylation on a single tyrosyl residue. This phosphorylation triggers dimerization, nuclear translocation, and the binding of p91 to interferon-gamma response elements present in the promoters of induced genes. Phosphorylation of p91 requires the activation of two tyrosine kinases, JAK1 and JAK2, that themselves become phosphorylated on tyrosyl residues shortly after interferon-gamma binds to its receptor. The importance of tyrosine phosphorylation in this pathway prompted us to investigate the role of protein tyrosine phosphatases in the regulation of the pathway. We find that in the absence of interferon-gamma, treatment of cells with an inhibitor of tyrosine phosphatases causes a rapid and potent activation of the components of the interferon-gamma signal transduction pathway and induces an interferon-gamma-responsive gene. This suggests that tyrosine phosphatases act both to repress the interferon-gamma signal transduction pathway in the absence of interferon-gamma and to downregulate the pathway after interferon-gamma induction.

Base Sequence↗
PubMed1994

CT-1501R selectively inhibits induced inflammatory monokines in human whole blood ex vivo.

The effect of (R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (CT-1501R; the nonproprietary name for CT-1501R approved by the United States Name Council is lisofylline), an inhibitor of second messenger signaling through phosphatidic acid, on release of endogenous mediators important in the systemic inflammatory response syndrome (SIRS) was studied using the human whole blood ex vivo assay system. Human blood was stimulated with various endotoxin preparations, zymosan, or protein A, and the levels of secreted monokines were measured by enzyme-linked immunosorbent assay. CT-1501R inhibited tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6 release in a dose-dependent manner and was active with all stimuli tested including Salmonella and Escherichia coli-derived endotoxin, endotoxin from both rough and smooth E. coli strains, as well as zymosan and protein A. CT-1501R inhibited monokine release by approximately 50% at 200 microM and 30% at 50 microM and was independent of the relative potency of stimulus. CT-1501R also inhibited IL-1 alpha or IL-1 beta induction of either TNF-alpha or IL-1 beta and inhibited the synergistic effects of stimulation with both human IL-1 beta and murine TNF-alpha on release of human TNF-alpha. Inhibition of monokine release following stimulation with monokine(s) was, in general, greater than that achieved with lipopolysaccharide (LPS) stimulation. Northern blot analysis showed decreased mRNA accumulation of TNF-alpha and IL-1 beta in CT-1501R-treated samples following LPS stimulation suggesting that CT-1501R acts at least in part, at the pretranslational level. In contrast, CT-1501R does not inhibit LPS-stimulated IL-8 or IL-1 receptor antagonist (IL-1ra) release in human whole blood or IL-1 alpha-induced release of PGE2 in human foreskin fibroblast cells. These data suggest that CT-1501R may be of use for clinical intervention in SIRS.

3T3 Cells↗
PubMed1994

YY1 represses beta-casein gene expression by preventing the formation of a lactation-associated complex.

Site-specific mutagenesis of the highly conserved milk box (-140 to -110) region suggested that beta-casein expression is regulated by a hormone-mediated relief of repression (M. Schmitt-Ney, W. Doppler, R. K. Ball, and B. Groner, Mol. Cell. Biol. 11:3745-3755, 1991). However, when this sequence was placed upstream of a heterologous thymidine kinase promoter, it activated reporter gene expression. This apparent paradox was resolved when the trans-acting factor YY1, capable of acting as both a positive and negative regulator, was shown to interact with the milk box region, using bacterially expressed YY1 and specific oligonucleotide and antibody competition experiments. Second, it was demonstrated that extracts prepared from several cell types contained a protein(s) interacting with the mammary gland-specific factor (MGF) binding site, previously shown to be required for beta-casein promoter activity (Schmitt-Ney et al., Mol. Cell. Biol. 11:3745-3755, 1991). Sequence analysis of this site revealed similarity to the gamma interferon-activated sequence, suggesting that MGF may be related to the stat91 signaling protein. Finally, using an oligonucleotide encompassing both the YY1 and MGF sites, we detected a slow-mobility complex only in extracts from mammary glands at late pregnancy and lactation (lactation-associated complex [LAC]). Site-specific mutation of the YY1 binding site led to an enhancement in LAC DNA binding activity, while mutation of the MGF site decreased detectable LAC. These results support a model in which lactogenic stimuli lead to a decrease in YY1 binding, and subsequent increased formation of LAC at a nearby binding site, to stimulate beta-casein transcription.

Animals↗
PubMed1994

The Delirium Rating Scale in a psychogeriatric inpatient setting.

The Delirium Rating Scale (DRS) has been shown to be a valid instrument for identifying and grading the severity of delirium in patients admitted to a general hospital for medical or surgical treatment. However, its accuracy in identifying delirium among elderly patients admitted to a psychiatric hospital for evaluation and treatment of psychiatric illness has not been previously addressed. The DRS was administered to 791 elderly patients who were consecutively admitted to a psychogeriatric unit; 70 met DSM-III-R criteria for delirium. A DRS threshold score of > or = 10 correctly identified delirious patients with a sensitivity of 94% and a specificity of 82%. Both psychosis and cognitive impairment appeared to falsely elevate the DRS score in this population.

Aged↗
PubMed1994

Reliability of NINDS-AIREN clinical criteria for the diagnosis of vascular dementia.

We evaluated the reliability of clinical diagnoses using the recently standardized criteria for the diagnosis of vascular dementia (VaD) developed by the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN). Two neurologists and two psychiatrists independently reviewed clinical data abstracted from those of 42 demented subjects participating in a longitudinal study of dementia at the University of Pittsburgh. For each patient we abstracted the clinical data on a standardized form. Each physician diagnosed each case according to the NINDS-AIREN criteria, using both clinical information and MRIs. We calculated the interrater agreement for all two-way combinations of clinicians with kappa statistics, which ranged from 0.46 (moderate agreement) to 0.72 (substantial agreement). The moderate reliability observed in this study may be attributable to patient-, clinician-, or criteria-centered sources of variance.

Aged↗
PubMed1994

Canine choledochotomy closure with diode laser-activated fibrinogen solder.

BACKGROUND: An alternative to mechanical stapling or hand suturing is needed to permit laparoscopic common bile duct exploration. We evaluated the strength and healing characteristics of canine choledochotomies sealed with a fibrinogen solder and a diode laser. METHODS: After creation of a 0.5 cm longitudinal choledochotomy, the edges were coapted with forceps, and a fibrinogen solder mixed with indocyanine green dye was applied. The solder was sealed in place with an 810 nm diode laser (125 W/cm2). RESULTS: Immediate mean leakage pressure was 264 +/- 7 mm Hg compared with 83 +/- 66 mm Hg in suture controls. This increased to 364 +/- 115 mm Hg at 2 days and was more than 510 mm Hg at 7 days. On histologic examination rapid reabsorption of the solder with no signs of inflammation or stenosis was seen. No episodes of dehiscence or peritonitis occurred. CONCLUSIONS: Laser soldering provides a watertight choledochotomy closure with adequate immediate strength allowing a reliable, technically feasible common bile duct exploration via a laparoscopic approach.

Animals↗
PubMed1993

Peripheral nerve regeneration across 14-mm gaps: a comparison of autograft and entubulation repair methods in the rat.

A study was conducted to compare the regeneration across 1.4-cm peroneal nerve gaps in rats, repaired with sutured autografts or with artificial nerve grafts. The artificial models were composed of a biodegradable passive conduit made of glycolide trimethylene carbonate, filled with either phosphate-buffered saline or a collagen extracellular matrix. Functional recovery was evaluated by walking track analysis throughout the experiment. After 9 months, the nerves were analyzed by electrophysiology and by qualitative and quantitative histology. Walking track analysis demonstrated the three repair methods to provide statistically equivalent recovery, except at day 195 post-engraftment, when the collagen-filled conduit was superior to the saline-filled conduit. Electrophysiologically, the autograft was superior to the collagen-filled conduit, while the collagen- and saline-filled conduits were equivalent. Quantitative histology demonstrated that normal intact nerve had larger mean myelinated axonal diameters but an equal number of axons to the three repair methods, and that the repair methods were statistically equivalent. While the repair methods had similar histologic and functional outcomes, combined standardized scoring demonstrated that the autograft was superior to the statistically-equivalent entubulation repairs. A collagen gel may serve as an ideal matrix in which to suspend neurotrop(h)ic factors or cells.

Action Potentials↗
PubMed1993

Treatment of nortriptyline's side effects in elderly patients: a double-blind study of bethanechol.

A double-blind, placebo-controlled study of bethanechol was conducted in 26 elderly depressed patients being treated with nortriptyline. Patients receiving bethanechol had reduced subjective complaints of anticholinergic side effects and showed a trend toward improvement on an objective measure of salivary flow. The potential use of bethanechol in older patients to reduce morbidity and improve compliance with medication regimens is discussed.

Aged↗
PubMed1993

As-needed dosing of antipsychotic drugs: limitations and guidelines for use in the elderly agitated patient.

OBJECTIVE: To review the as-needed dosing of antipsychotic drugs. Because insufficient data are available to evaluate this therapy, alternative strategies in managing acute agitation in elderly patients are suggested. DATA SOURCES: A MEDLINE search of English-language articles published between 1966 and June 1992 was used to identify studies and reviews of antipsychotic drugs administered in single doses or intermittently. STUDY SELECTION: Because of the paucity of data, all studies obtained were reviewed. Those addressing the use of drug holidays (chronic dosing with days without drug) were excluded. DATA EXTRACTION: No data are available regarding the efficacy of as-needed dosing of antipsychotics in elderly agitated patients; thus, data obtained from treating acutely psychotic patients are described, and differences between this population and elderly agitated patients are discussed. DATA SYNTHESIS: Antipsychotics are used frequently to control agitated behavior in elderly patients, although double-blind studies have not consistently demonstrated the superiority of active drug over placebo. CONCLUSIONS: Rigorous placebo-controlled trials of the safety and efficacy of as-needed dosing of antipsychotics are needed. As-needed dosing of any drug to control behavior should be reserved only for infrequent, sustained agitation that cannot be linked to an eliciting event. Orders for such dosing must include definitive, detailed directions for nursing personnel specifying target behaviors, maximum daily dosages, and monitoring parameters for assessing efficacy and adverse effects.

Aged↗
PubMed1993

Effects of a history of heavy alcohol consumption on Alzheimer's disease.

Neuropsychological and psychiatric evaluations were made of 39 subjects with possible Alzheimer's disease and a history of excessive alcohol consumption (AD + ETOH), who had been abstinent or had drunk minimally for at least three months before evaluation, and 225 patients with probable Alzheimer's disease (PAD) of comparable age, years of education, and baseline global impairment. At baseline, there were no significant differences between the groups in terms of age of onset of dementia, neuropsychological test scores, or current behavioural or psychiatric symptoms. One year later, no differences in rates of decline between 20 abstinent AD + ETOH patients and 88 PAD subjects could be shown. Thus, past heavy alcohol consumption does not appear to modify the presentation of dementia of the Alzheimer's type, nor does it modify progression over a one-year interval.

Aged↗
PubMed1993

Anergy compromises screening for tuberculosis in high-risk populations.

Anergy may occur in groups at high risk for tuberculosis, compromising tuberculin skin testing. Within New York City's correctional system, anergy prevalence was 25% among opiate users referred to detoxification programs and 3% in the general population. Correlates of anergy were recent weight loss and needle sharing. The high prevalence of anergy among opiate users compromises the utility of tuberculosis screening and suggests the need for routine chest x-rays to detect pulmonary tuberculosis in some high-risk-populations.

Adult↗
PubMed1993

Nortriptyline in the hospitalized elderly: tolerance and side effect reduction.

This article describes two separate but related studies regarding the use of nortriptyline (NT) in the treatment of depressed elderly inpatients. The first study assesses medication tolerance to NT during the acute treatment of late-life depression. The second describes a placebo-controlled study of the effect of bethanechol in reducing antimuscarinic side effects of NT. Antidepressant pharmacotherapy was considered for 72 patients with late-life depression; 17 (24%) did not receive NT; 5 (7%) because of absolute or relative medical contraindications. Of the 55 patients who started on NT, 9 percent had side effects that necessitated medication discontinuation. A separate sample of 26 elderly depressed patients being treated with NT participated in a double-blind, placebo-controlled trial of bethanechol. Patients receiving bethanechol had reduced subjective complaints of anticholinergic side effects and showed improvement on an objective measure of salivary flow.

Aged↗