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Biomedical subjects

S Goldsmith

Publications and source records attributed to S Goldsmith.

At least 19 recordsLinked to original sources
PubMed1999

The mosaic of brain glial hyperactivity during normal ageing and its attenuation by food restriction.

Food restriction of adult rodents increases lifespan, with commensurate attenuation of age-related pathological lesions in many organs, as well as attenuation of normal ageing changes that are distinct from gross lesions. Previous work showed that chronic food restriction attenuated age-associated astrocyte and microglial hyperactivity in the hippocampal hilus, as measured by expression of glial fibrillary acidic protein and major histocompatibility complex II antigen (OX6). Here, we examined other markers of astrocyte and microglial activation in gray and white matter regions of ad libitum-fed (Brown Norway x Fischer 344) F1 male rats aged three and 24 months and chronic food-restricted rats aged 24 months. In situ hybridization and immunohistochemical techniques evaluated glial expression of glial fibrillary acidic protein, apolipoprotein E, apolipoprotein J (clusterin), heme oxygenase-1, complement 3 receptor (OX42), OX6 and transforming growth factor-beta1. All markers were elevated in the corpus callosum during ageing and were attenuated by food restriction, but other regions showed marked dissociation of the extent and direction of changes. Astrocytic activation, as measured with glial fibrillary acidic protein expression (coding and intron-containing RNA, immunoreactivity), increased with age in the corpus callosum, basal ganglia and hippocampus. Generally, food restriction attenuated the age-related increase in glial fibrillary acidic protein messenger RNA and immunoreactivity. Food restriction also reduced the age-related increase in apolipoprotein J and E messenger RNA and heme oxygenase-1 immunoreactivity in the basal ganglia and corpus callosum. However, astrocytes in the hilus of the hippocampus showed an age-related decrease in apolipoprotein J and E messenger RNA, which was further intensified by food restriction. The age-associated microglial activation measured by OX6 and OX42 immunoreactivity was reduced by food restriction in most subregions. The localized subsets of glial age changes and effects of food restriction comprise a mosaic of ageing consistent with the regional heterogeneity of ageing changes reported by others. In particular, age has a differential effect on astrocytic and microglial hyperactivity in gray versus white matter areas. The evident mosaic of glial ageing and responses to food restriction suggests that multiple mechanisms are at work during ageing.

Aging↗
PubMed1999

Typical household vacuum cleaners: the collection efficiency and emissions characteristics for fine particles.

The issue of fine particle (PM2.5) exposures and their potential health effects is a focus of scientific research because of the recently promulgated National Ambient Air Quality Standard for PM2.5. Before final implementation, the health and exposure basis for the standard will be reviewed by the U.S. Environmental Protection Agency within the next five years. As part of this process, it is necessary to understand total particle exposure issues and to determine the relative importance of the origin of PM2.5 exposure in various micro-environments. The results presented in this study examine emissions of fine particles from a previously uncharacterized indoor source: the residential vacuum cleaner. Eleven standard vacuum cleaners were tested for the emission rate of fine particles by their individual motors and for their efficiency in collecting laboratory-generated fine particles. An aerosol generator was used to introduce fine potassium chloride (KCl) particles into the vacuum cleaner inlet for the collection efficiency tests. Measurements of the motor emissions, which include carbon, and the KCl aerosol were made using a continuous HIAC/Royco 5130 A light-scattering particle detector. All tests were conducted in a metal chamber specifically designed to completely contain the vacuum cleaner and operate it in a stationary position. For the tested vacuum cleaners, fine particle motor emissions ranged from 9.6 x 10(4) to 3.34 x 10(8) particles/min, which were estimated to be 0.028 to 176 micrograms/min for mass emissions, respectively. The vast majority of particles released were in the range of 0.3-0.5 micron in diameter. The lowest particle emission rate was obtained for a vacuum cleaner that had a high efficiency (HEPA) filter placed after the vacuum cleaner bag and the motor within a sealed exhaust system. This vacuum cleaner removed the KCl particles that escaped the vacuum cleaner bag and the particles emitted by the motor. Results obtained for the KCl collection efficiency tests show > 99% of the fine particles were captured by the two vacuum cleaners that used a HEPA filter. A series of tests conducted on two vacuum cleaners found that the motors also emitted ultra-fine particles above 0.01 micron in diameter at rates of greater than 10(8) ultra-fine particles/CF of air. The model that had the best collection efficiency for fine particles also reduced the ultra-fine particle emissions by a factor of 1 x 10(3).

Air Pollution, Indoor↗
PubMed1998

A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome.

OBJECTIVE: To provide a preliminary assessment of the efficacy and safety of fludrocortisone acetate treatment of chronic fatigue syndrome. DESIGN: A placebo-controlled, double-blind, random-allocation crossover trial of 6 weeks of fludrocortisone. SETTING: An outpatient clinical trials unit. PATIENTS: Twenty-five participants with chronic fatigue syndrome (mean age, 40 years; 19 [76%] women; mean duration of illness, 7.0 years) were recruited from a research and clinic registry. Five patients withdrew from the trial. INTERVENTIONS: All participants were scheduled to receive fludrocortisone acetate (0.1-0.2 mg) or a placebo for 6 weeks in each treatment. MAIN OUTCOME MEASURES: Self-administered questionnaires were completed at the beginning and end of each treatment arm that asked patients to rate the severity of their symptoms on a visual analogue scale. The Medical Outcomes Study 36-Item Short-Form Health Survey, a reaction time test, and a treadmill exercise test were used to assess functional status. Blood pressure, heart rate, and plasma norepinephrine levels were obtained at baseline. Blood pressure and heart rate were recorded at the end of the exercise test and monitored at all subsequent visits. RESULTS: At baseline, the study participants reported symptom severity greater than 5 for most symptoms, and all had evidence of marked functional impairments. No improvement was observed in the severity of any symptom or in any test of function for the 20 participants who completed both arms of the trial. Blood pressure and heart rate readings were unaffected by treatment, and plasma norepinephrine levels did not differ from those of a healthy control group. The incidence of adverse experiences was similar in the fludrocortisone and placebo arms of the trial. CONCLUSION: Low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome.

Adult↗
PubMed1998

An atomic model of fimbrin binding to F-actin and its implications for filament crosslinking and regulation.

Using a new procedure that combines electron-density correlation with biochemical information, we have fitted the crystal structure of the N-terminal actin-binding domain of human T-fimbrin to helical reconstructions of fimbrin-decorated actin filaments. The map locates the N-terminal calcium-binding domain and identifies actin-binding site residues on the two calponin-homology domains of fimbrin. Based on this map, we propose a model of a fimbrin crosslink in an actin bundle and its regulation by calcium.

Actins↗
PubMed1998

Efficacy of Nicardipine for Long-Term Therapy of Chronic Stable Angina.

BACKGROUND: Although angina is a chronic disease, most clinical trials evaluating antianginal therapy are of a few weeks or months in duration. METHODS AND RESULTS: To evaluate the effects of nicardipine, a second-generation dihydro-pyridine calcium channel blocker, as long-term therapy, patients with chronic stable angina were treated for 1 year with open-label nicardipine. Anginal symptoms were controlled with 20 mg tid in 24%, 30 mg tid in 34%, and 40 mg tid in 42%. Of 72 patients completing the 1-year trial, only 14 (19%) had required the addition of long-acting nitrates for control of symptoms. The remaining 57 patients, who had anginal symptoms controlled with nicardipine alone, were continued into the 3-week, double-blind period and were randomized to continue their usual dose of nicardipine or placebo. Throughout the 1-year, open-label treatment period, the number of anginal episodes and exercise parameters of angina were significantly reduced with nicardipine. CONCLUSIONS: During the double-blind period, the patients who continued on nicardipine had significantly greater exercise time and time to onset of angina than patients who were randomized to placebo. The exercise parameters in the patients randomized to placebo were improved over baseline after 1 year of therapy; however, the improvement with nicardipine was significantly greater.

Journal Article↗
PubMed1997

Beta 4 integrin transfection of UM-UC-2 (human bladder carcinoma) cells: stable expression of a spontaneous cytoplasmic truncation mutant with rapid loss of clones expressing intact beta 4.

The alpha 6 beta 4 integrin is a component of the hemidesmosome, the anchoring structure in the basal membrane of epithelial cells. alpha 6 beta 4 expression is frequently altered in neoplastic cells. It is sometimes lost and sometimes overexpressed, which suggests that disruption of normal function is involved in neoplastic transformation. To examine the effect of this integrin on the growth and behavior of malignant cells that have lost beta 4, we transfected a full-length beta 4 cDNA into the UM-UC-2 cell line that expresses alpha 6 but not beta 4. Although large numbers of clones were obtained when a control vector was used in the transfection, only 12 clones could be isolated that expressed beta 4. Of these, only two beta 4-positive clones, clones 8 and 11, persisted long enough for further study. Clone 8 cells initially expressed beta 4, but within 2 weeks, all positive cells were lost from the culture. Clone 11 persisted in culture and retained strong surface expression of alpha 6 beta 4. Biochemical analysis and Western blotting revealed that this clone contained a truncated form of beta 4 that had lost the distal cytoplasmic domain. We conclude that expression of wild-type beta 4 in UM-UC-2 inhibits cell growth, presumably by an integrin-mediated signaling pathway. Clone 11 escaped from normal signaling because the cytoplasmic domain, a region essential for basal polar localization, was lost. The alpha 6 beta 4 integrin appears to have tumor suppressor activity in epithelial tumors.

Antigens, CD↗
PubMed1995

An interdisciplinary mental health consultation team in a nursing home.

The Mental Health Consultation Team (MHCT) at the Portland Veterans Affairs Medical Center nursing home is an interdisciplinary group of mental health professionals and primary care providers established to triage mental health consultations, improve communication between consultants and primary care providers, help staff translate consultants' recommendations into patient care, and furnish education in the management of mental health problems. The MHCT has decreased the demands for formal psychiatry and psychology consultations while increasing mental health services through innovative use of existing staff.

Activities of Daily Living↗
PubMed1993

Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease.

Receptor autoradiography was used to quantify the number of dopamine D2 receptors labeled with [125I]epidepride in the medial temporal lobe of seven cases of Alzheimer's disease in comparison to eight cases of neurologically intact controls. The Alzheimer's disease cases showed the greatest losses of D2 receptors in the basolateral nucleus of the amygdala and molecular layer of the dentate gyrus and the smallest differences from controls in the perirhinal region and subiculum. The loss of D2 receptors in the hippocampus and amygdala of cases with Alzheimer's disease in concert with alterations in dopaminergic innervation could contribute to the clinical symptoms of this disorder.

Alzheimer Disease↗
PubMed1990

Equivalence of five forms of the Selective Reminding Test in young and elderly subjects.

This study evaluated the equivalence of five forms of the Selective Reminding Test, a widely used measure of verbal learning, 45 normal young and 45 normal elderly subjects were randomly administered three of the five test forms on three separate sessions. The five forms generally correlated well with one another and were of comparable difficulty, suggesting adequate test equivalence. Four of the five forms were particularly well matched.

Adolescent↗
PubMed1989

Personality disorders: issues in assessment.

The multiaxial system adopted in DSM-III (American Psychiatric Association 1980) has fostered much research in the area of the assessment of personality disorders. This paper will address issues and controversies that have an impact on the assessment of personality. Topics to be discussed in this paper include (1) a review of and comparison between categorical and dimensional approaches to personality classification; (2) discussion of differing viewpoints regarding the most appropriate way to conceptualize Axis II diagnoses, with emphasis on their relationship with Axis I and II conditions; and (4) a review of between Axis I and II conditions; and (4) a review of different assessment instruments.

Humans↗