PubMed Health⌕ Search

Biomedical subjects

C R Savage

Publications and source records attributed to C R Savage.

At least 55 records · Page 3Linked to original sources
PubMed1995

Predictors of cognitive change in older persons: MacArthur studies of successful aging.

This study used a linear structural relations modeling technique (LISREL) to examine longitudinal data for 1,192 persons from a community-based population. The goal was to test the ability of an a priori model to predict cognitive change over a 2.0- to 2.5-year period in older adults aged 70-79 at the initial evaluation. The model included 22 demographic, physical, and psychosocial variables as predictors of cognitive function and cognitive change. The study used an exploratory-confirmatory design, enabling cross-validation of the model developed in the exploratory set in the confirmatory sample. Structural equation modeling analyses identified 4 endogenous model variable (education, strenuous activity, peak pulmonary expiratory flow rate, and self-efficacy) as direct predictors of cognitive change over the study period.

Aged↗
PubMed1995

The Massachusetts General Hospital (MGH) Hairpulling Scale: 1. development and factor analyses.

We developed the MGH Hairpulling Scale to provide a brief, self-report instrument for assessing repetitive hairpulling. Seven individual items, rated for severity from 0 to 4, assess urges to pull, actual pulling, perceived control, and associated distress. We administered the scale to 119 consecutive patients with chronic hairpulling. Statistical analyses indicate that the seven items form a homogenous scale for the measurement of severity in this disorder.

Adult↗
PubMed1995

Phenomenology of intentional repetitive behaviors in obsessive-compulsive disorder and Tourette's disorder.

BACKGROUND: Recent evidence suggests that obsessive-compulsive disorder (OCD) and Tourette's disorder are related and have overlapping clinical features. The purpose of this study was to test the following hypotheses regarding intentional repetitive behaviors in these two disorders: (1) In OCD without comorbid Tourette's, they are preceded by cognitive phenomena and autonomic anxiety, but not sensory phenomena, and (2) in Tourette's without comorbid OCD, they are preceded by sensory phenomena, but not cognitive phenomena nor autonomic anxiety. METHOD: Fifteen adult OCD outpatients without tics and 17 adult Tourette's outpatients without OCD were evaluated with a structured interview. Questions assessed cognitive, sensory, and affective experiences related to intentional repetitive behaviors. RESULTS: Five of 17 Tourette's subjects were excluded because they had only unintentional or occasionally intentional tics. All OCD patients reported some cognitions preceding their intentional repetitive behaviors, whereas only 2 of 12 Tourette's patients reported cognitions. In comparison, all Tourette's patients reported sensory phenomena preceding repetitive behaviors, and none of the OCD patients reported such sensations. In addition, 13 OCD patients reported at least mild autonomic anxiety associated with their repetitive behaviors, whereas no Tourette's patients reported such symptoms. CONCLUSION: Intentional repetitive behaviors in OCD differ from those in Tourette's and are associated with cognitive and autonomic phenomena. Sensory phenomena preceded intentional repetitive behaviors in Tourette's but not in OCD patients. The dimensions examined in this study (cognition, sensory phenomena, and autonomic anxiety) may represent valid clinical factors for characterization of repetitive behaviors in OCD and Tourette's.

Adult↗
PubMed1994

Low-level sensory processing in obsessive-compulsive disorder: an evoked potential study.

This study used visual and auditory evoked potentials (VEP and AEP) to study low-level sensory processing in a group of 15 unmedicated subjects with obsessive-compulsive disorder (OCD) and 30 age-matched, gender-matched, and handedness-matched normal controls. EPs were recorded to flash (VEP) and binaural click (AEP) stimulation. OCD subjects were found to have significantly shorter latencies on N1 and P2 of the AEP, and no differences were found in the VEP. Results indicate abnormal information processing states in OCD during low-level auditory processing, but not during low-level visual processing. Neural generators of the VEP and AEP are briefly reviewed and results are discussed in relation to current neurobiological models of OCD.

Acoustic Stimulation↗
PubMed1994

Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography.

BACKGROUND: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD). METHODS: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state. RESULTS: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood flow during the OCD symptomatic state vs the resting state in right caudate nucleus (P < .006), left anterior cingulate cortex (P < .045), and bilateral orbitofrontal cortex (P < .008); increases in the left thalamus approached but did not reach statistical significance (P = .07). CONCLUSIONS: These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cingulate cortex in the pathophysiology of OCD and in mediating OCD symptoms.

Adult↗
PubMed1993

Epidermal growth factor receptors lose ligand binding ability as WI-38 cells progress from short-term to long-term quiescence.

WI-38 cells, density arrested for short periods of time, can be stimulated to re-enter the cell cycle by epidermal growth factor (EGF) alone. However, cells density arrested for longer periods have a prolonged prereplicative phase when serum stimulated and cannot be stimulated by EGF alone. Radio-ligand binding studies performed on WI-38 cells showed that actively growing cells bind [125I]EG at relatively low levels that increase to a maximum as the cells become contact inhibited. As the cells enter a state of deeper quiescence, EGF binding falls to one-third to one-fifth the short-term growth arrested levels, remaining constant thereafter. The EGF-receptor complexes internalize more slowly in long-term growth arrested cells, and the rate of ligand association to the receptor is lower than short-term growth arrested cells. The amount of EGF receptor protein in lysates of equal numbers of both short- and long-term quiescent cells remains the same. These results suggest that the failure of long-term growth arrested cells to respond to EGF is not due to dramatic changes in the amount of receptor protein during prolonged quiescence but more likely to an alteration in the ability of these receptors to bind ligand and/or activate the EGF signal transduction pathway.

Cell Cycle↗
PubMed1993

Computer-based neuropsychological screening for AIDS dementia complex.

OBJECTIVE: To test the efficacy of reaction time (RT) measures as a screening test for AIDS dementia complex (ADC). DESIGN AND METHODS: Forty-two patients with mild-to-moderate ADC and 33 healthy HIV-1-seronegative control subjects took a computer-administered battery of four RT measures: simple RT, choice RT, and two types of sequential RT (1 and 2). RESULTS: The performance of the ADC group was significantly worse than that of the control group on all four RT measures, but not all tasks were equally sensitive. The two tests of sequential RT were found to be the best discriminators, and receiver operating characteristic curves analyses indicated that the optimal cut-off z score was 1.0 for both tests. CONCLUSIONS: These preliminary results suggest that computer-based RT, using these two measures of sequential RT, may provide a sensitive method of detecting HIV-1-associated cognitive deficits.

AIDS Dementia Complex↗
PubMed1993

Molecular surface tailoring of biomaterials via pulsed RF plasma discharges.

A pulsed RF plasma glow discharge is employed to demonstrate molecular level controllability of surface film deposits. Molecular composition of plasma deposited films is shown to vary in a significant manner with the RF duty cycle. Three fluorocarbon monomers are used to illustrate the process. All three exhibit a trend towards increased surface CF2 content with decreasing pulsed RF duty cycle, including exclusion of oxygen. Significant variations in carbon-fluorine surface functionalities are obtained over a controllable range of film thickness. Film growth rate measurements reveal the occurrence of surface reactions during significant portions of the off portion of the duty cycle. Albumin adsorption on fluorocarbon-treated PET films is unchanged from PET controls for a 100-fold range of bulk concentrations and 60-fold range of adsorption times. However, increased retention of albumin is observed following incubation with protein-denaturing sodium dodecyl sulfate solution, the retention decreasing with increasing bulk concentration of albumin. The increased retention of albumin suggests the treated surfaces may have promise as biocompatible materials.

Adsorption↗
PubMed1989

Epidermal growth factor receptor binding is not a simple one-step process.

The binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture were measured at 4 degrees C. Initial binding rates as a function of hormone concentration allowed estimation of simple two-state on-off rate constants of 1.2 x 10(6) M-1 s-1 and 4.9 x 10(-3) s-1, respectively. These two-state parameters gave inadequate computer fits to long term kinetic and equilibrium-binding data, suggesting that an additional process(es) was occurring. Nonlinear equilibrium Scatchard plots and transient "pseudo-Scatchard" plots taken at pre-equilibrium times support the idea that at least one other process is occurring during receptor binding. 125I-EGF-receptor dissociation kinetic plots were biphasic, yielding rate constants of 1.5 x 10(-2) s-1 and 5.6 x 10(-5) s-1 with the ratio of the two components changing with the time of initial incubation with 125I-EGF. Application of a ternary complex model which assumed complexation of the bound receptor with a cell surface interaction molecule gave satisfactory fits to all data.

Animals↗
PubMed1989

Epidermal growth factor immunoreactive material in the rat brain. Localization and identification of multiple species.

Brains of adult male rats were dissected into five distinct regions: brainstem, cerebellum, hippocampus, diencephalon, and telencephalon. Epidermal growth factor-like immunoreactivity was isolated and characterized by radioimmunoassay and nondenaturing polyacrylamide gel electrophoresis. Radioimmunoassay indicated levels of standard rat epidermal growth factor equivalents ranging from 0.99 to 0.33 ng/g wet weight of brain tissue. Competition curves were not parallel to those generated with standard rat epidermal growth factor, indicating a lack of structural identity between the immunoreactive material in the brain and standard rat epidermal growth factor. Extracts of submandibular gland and blood did, however, produce parallel competition curves. Electrophoresis indicated the presence of multiple bands of immunoreactive material in each of the regions of the brain. The major bands of activity migrated to positions distinct from that of standard rat epidermal growth factor. This is the first demonstration of multiple forms of epidermal growth factor-like immunoreactive material in the central nervous system.

Animals↗
PubMed1989

Intralesional cyclosporin in psoriasis: effects on T lymphocyte and dendritic cell subpopulations.

On each of 10 patients with untreated plaque psoriasis, two symmetrical plaques were injected with cyclosporin A or placebo on six occasions over 12 days, in a double-blind manner. Biopsies taken from these lesions at 14 days were examined for differences in cellular composition using a double-labelling immunofluorescent technique. The cyclosporin-injected plaques cleared significantly better than those injected with placebo (P less than 0.001). In the epidermis of the cyclosporin-injected plaques, total and HLA-DR+ CD4+ and CD8+ T cell numbers were significantly decreased compared to corresponding plaques treated with placebo (total CD4+, total CD8+, DR+ CD4+, P less than 0.01; DR+ CD8+, P less than 0.02). Similarly, T lymphocyte numbers in the dermis were decreased in the cyclosporin compared to placebo-treated plaques; the reduction in total CD4+ and DR+ CD8+ T cell numbers was statistically significant (P less than 0.05). Although total numbers of epidermal dendritic cells were not significantly altered, the DR+CD1- dendritic cell subpopulation was markedly decreased (P less than 0.01) and DR-CD1+ dendritic cells increased (P less than 0.05) in the plaques injected with cyclosporin compared to corresponding placebo-treated plaques. These findings show that cyclosporin injected in situ is effective in clearing psoriasis and probably exerts this beneficial effect by its action on T lymphocytes. A suitable topical preparation that allows penetration of the drug should prove helpful in the treatment of psoriasis.

Adult↗
PubMed1987

Proteolytic processing of epidermal growth factor within endosomes.

Following binding to its plasma membrane receptor, epidermal growth factor is transferred into three biochemically distinct endosomal compartments in a temporal fashion prior to delivery to the lysosomes. During this migration, the ligand undergoes sequential proteolytic processing resulting in the removal of six amino acid residues from the carboxy terminus. Individual events in the processing occur in different endosomal compartments. Incubations conducted in the presence of methylamine result in the retention of the ligand in an early endosomal compartment and processing is limited to the removal of the carboxy terminal arginine residue. This identification of specific processed forms of radiolabeled epidermal growth factor within distinct endosomal compartments demonstrates the compartmentalization of the presumed proteases which may serve as biochemical markers for these endosomal populations.

Cell Compartmentation↗
PubMed1986

Structural characterization and exposure of aromatic residues in epidermal growth factor from the rat.

Aromatic amino acid residues in epidermal growth factor (EGF) isolated from the rat have been investigated by proton n.m.r. and nuclear Overhauser methods at 500 MHz and by photochemically induced dynamic nuclear polarization (photo-c.i.d.n.p.) experiments at 360 MHz. Rat EGF contains six aromatic residues, i.e. one histidine and five tyrosine residues. pH titration data allow identification of the histidine imidazole ring protons, whereas two-dimensional n.m.r. correlated spectroscopy establishes connectivities between tyrosine ring (2,6) and (3,5) proton resonances. Photo-c.i.d.n.p. data give evidence for solvent exposure of the one histidine and the five tyrosine residues in rat EGF. Nuclear Overhauser experiments and pH titration data suggest proximity relationships among four of the tyrosine residues and the histidine residue. These data indicate the presence of a clustered, aromatic, structural domain on the protein surface and may provide a clue to the understanding of the functional structure of EGF.

Animals↗
PubMed1986

Isolation of rat epidermal growth factor (r-EGF): chemical, biological and immunological comparisons with mouse and human EGF.

Rat epidermal growth factor, (r-EGF), was isolated from adult male rat submandibular glands, with final yields of 4-6 mg r-EGF from 20 to 25 g wet weight of tissue. Amino acid analysis of r-EGF indicated a high degree of homology with murine EGF (m-EGF) and human EGF, (h-EGF). However, r-EGF contains 49 amino acid residues, versus 53 for human and murine EGFs, and lacks two characteristic tryptophan residues present in the other two species. The lack of tryptophan residues did not affect cellular binding or mitogenic activity or r-EGF. Polyclonal antisera to each of the three separate species demonstrated crossreactivity with the other species of EGF. A sensitive radioimmunoassay was developed for r-EGF which can detect 25 pg of hormone.

Amino Acids↗
PubMed1986

Intracellular modification of 125I-labeled epidermal growth factor by normal human foreskin fibroblasts.

Intracellular processing of 125I-labeled epidermal growth factor (EGF) in normal human foreskin fibroblasts was examined after incubation with saturating concentrations of [125I]EGF. This report describes the column chromatographic separation of multiple processed forms of EGF generated by human foreskin fibroblasts and their structural characterization. More than 95% of the cell-bound [125I]EGF was converted into multiple forms, which were separated into four distinct peaks of radioactivity using columns of Bio-Gel P-150 equilibrated with 0.2% sodium dodecyl sulfate. These were designated peaks 1-4. Cellular generation of these four peaks was dependent on culture conditions. Differences in absolute and relative amounts of peaks 1-4 were observed as a function of time of incubation at 37 C. In addition, chromatographic profiles of cell-associated 125I varied in relation to cell density. The radioactivity in peak 1 comigrated with 125I-labeled native EGF on nondenaturing polyacrylamide gels (pH 9.5), whereas peaks 2 and 3 exhibited more rapid electrophoretic mobilities. Electrophoretic mobilities of the radioactivity in peaks 2 and 3 were indistinguishable from those of chemically prepared derivatives of [125I]EGF which were lacking either one or six amino acid residues from the carboxyterminus, respectively. The EGF receptor bound the radioactive material in peak 2 with an affinity equal to or greater than that of EGF; however, the radioactivity in peak 3 was bound to a much lesser extent. The radiolabel in both peaks 2 and 3 was greater than 95% precipitable by antiserum to native EGF. The labeled material in peak 4 was composed of [125I]monoiodotyrosine, 125I-, and an unidentified peptide. None of the radiolabeled compounds in peak 4 interacted with the EGF receptor or with antiserum to native EGF.

Animals↗
PubMed1986

Effects of anti-insulin receptor antibodies (AIRA) on downregulation and turnover of insulin receptors on cultured hepatocytes.

We have studied the effects of two polyclonal anti-insulin receptor antibodies (AIRA) on insulin receptor downregulation and turnover in rat hepatocytes in primary culture. Downregulation was determined by measurement of insulin binding after acid washing of cells to remove AIRA. Insulin receptor turnover was estimated by measurement of insulin binding after inhibition of synthesis of functional receptors with tunicamycin (0.5 micrograms/ml). Exposure of hepatocytes to AIRA (both sera were of comparable effectiveness) resulted in progressive, time- and dose-dependent losses of insulin binding (maximal loss was about 55% after 24 h of incubation with AIRA diluted 1:25). Cycloheximide (100 microM) prevented AIRA-mediated downregulation. The t1/2 of disappearance of cell surface insulin binding capacity determined with tunicamycin was 8.0 h. Addition of insulin (1000 ng/ml) or AIRA to tunicamycin reduced the t1/2 to 2.6 h (insulin), 2.2 h (patient B10), and 2.0 h (patient 1). These data suggest that AIRA downregulated insulin receptors on cultured hepatocytes by accelerating their rate of disappearance, inhibition of protein synthesis prevented AIRA-mediated downregulation, and downregulation by AIRA of insulin binding may be partially responsible for the desensitization of target cells to some of the insulin-like actions of these autoantibodies.

Animals↗