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Biomedical subjects

J Shih

Publications and source records attributed to J Shih.

At least 19 recordsLinked to original sources
PubMed2005

Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms.

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for intractable epilepsy. However, the optimal range of device duty-cycles [on/(on + off times)] is poorly understood. The authors performed a multicenter, randomized trial of three unique modes of VNS, which varied primarily by duty-cycle. The results indicate that the three duty-cycles were equally effective. The data support the use of standard duty-cycles as initial therapy.

Cough↗
PubMed2003

A phase I trial of weekly paclitaxel, 13- cis-retinoic acid, and interferon alpha in patients with prostate cancer and other advanced malignancies.

PURPOSE: Based on prior studies demonstrating the effect of 13- cis-retinoic acid and interferon alpha (CRA/IFN) in decreasing the expression of the antiapoptotic protein bcl-2, our prior clinical study of CRA/IFN with paclitaxel (TAX) administered every 3 weeks, and data demonstrating increased activity of weekly TAX against prostate cancer, we designed a phase I study of weekly TAX in combination with CRA/IFN in patients with prostate cancer and other advanced malignancies. To develop a marker of drug effect, we assessed bcl-2 downregulation in patient peripheral blood mononuclear cells (PBMC). METHODS: Enrolled in the study were 14 patients with prostate cancer or other advanced malignancies, and 13 were treated with 1 mg/kg CRA on days 1 and 2, 6 MU/m(2) IFN subcutaneously on days 1 and 2, and TAX at increasing doses on day 2 each week for 6 weeks out of an 8-week cycle. The effect of CRA/IFN on bcl-2 expression was assessed in PBMCs by immunoblotting. RESULTS: The combination of CRA/IFN and TAX was well tolerated. Dose-limiting toxicities (DLT) in the first cycle of therapy included one patient with fever and neutropenia, and one patient with grade 4 hypertriglyceridemia. The recommended phase II dose of TAX in this combination was 80 mg/m(2). Of 13 patients assessable by tumor markers or scans, 5 had stable disease and 2 had a biochemical partial response including a patient with a decrease in PSA of >50% while on study. The assessment of patient PBMC bcl-2 was feasible in ten patients. CONCLUSIONS: This is the first study in which the safety and clinical activity of weekly TAX combined with CRA/IFN has been demonstrated. The assessment of PBMC bcl-2 is feasible in this weekly chemotherapy schedule

Aged↗
PubMed2001

Association and aggregation analysis using kin-cohort designs with applications to genotype and family history data from the Washington Ashkenazi Study.

When a rare inherited mutation in a disease gene, such as BRCA1, is found through extensive study of high-risk families, it is critical to estimate not only age-specific penetrance of the disease associated with the mutation, but also the residual effect of family history once the mutation is taken into account. The kin-cohort design, a cross-sectional survey of a suitable population that collects DNA and family history data, provides an efficient alternative to cohort or case-control designs for estimating age-specific penetrance in a population not selected because of high familial risk. In this report, we develop a method for analyzing kin-cohort data that simultaneously estimate the age-specific cumulative risk of the disease among the carriers and non-carriers of the mutations and the gene-adjusted residual familial aggregation or correlation of the disease. We employ a semiparametric modeling approach, where the marginal cumulative risks corresponding to the carriers and non-carriers are treated non-parametrically and the residual familial aggregation is described parametrically by a class of bivariate failure time models known as copula models. A simple and robust two-stage method is developed for estimation. We apply the method to data from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med 336:1401-1408] to study the residual effect of family history on the risk of breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline mutations. We find that positive history of a single first-degree relative significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6-2.6) but has little or no effect on the carriers.

BRCA2 Protein↗
PubMed2001

C-reactive protein and other markers of inflammation among patients undergoing HELP LDL apheresis.

Studies reveal important prognostic relationships between C-reactive protein (CRP) and atherosclerotic complications. A prospective trial of familial hypercholesterolemic patients treated with Heparin-induced Extra-corporeal Low-Density Lipoprotein Precipitation (HELP, B. Braun Melsungen) therapy was undertaken to evaluate the short- and long-term effects on CRP. Four patients received LDL apheresis therapy on an alternate week basis for 6 months. Pre- and post-treatment serum high sensitivity (hs) CRP levels (IMx(R), Abbott Laboratories), LDL-C, triglycerides, and fibrinogen were measured. Pre- and post-treatment mean serum levels of LDL-C were 281+/-76 and 98+/-34 mg/dl; triglycerides 191+/-64 and 123+/-50 mg/dl; fibrinogen 332+/-46 and 117+/-31 mg/dl, respectively. Before and after apheresis mean serum levels of hsCRP were 8.99+/-7.88 and 3.15+/-3.16 mg/ml, respectively, representing a 65% decrease. After 6 months of therapy, pre-treatment hsCRP showed an overall mean level decrease of 49%. Preliminary results indicate that LDL apheresis results in a rapid and long-term decrease of serum hsCRP levels.

Blood Component Removal↗
PubMed2001

A bivariate cure-mixture approach for modeling familial association in diseases.

For modeling correlation in familial diseases with variable ages at onset, we propose a bivariate model that incorporates two types of pairwise association, one between the lifetime risk or the overall susceptibility of two individuals and one between the ages at onset between two susceptible individuals. For estimation, we consider a two-stage estimation procedure similar to that of Shih (1998, Biometrics 54, 1115-1128). We evaluate the properties of the estimators through simulations and compare the performance with that from a bivariate survival model that allows correlation between ages at onset only. We apply the methodology to breast cancer using the kinship data from the Washington Ashkenazi Study. We also discuss potential applications of the proposed method in the area of cure modeling.

Age of Onset↗
PubMed2000

Comparative risk assessment: an international comparison of methodologies and results.

Comparative risk assessment (CRA) is a systematic procedure for evaluating the environmental problems affecting a geographic area. This paper looks beyond the U.S. border and examines the experience with CRAs conducted in various developing countries and economies in transition, including Bangkok, Thailand, Cairo, Egypt and Quito, Ecuador, as well as other locations in Eastern Europe, Asia and Central and South America. A recent pilot CRA conducted in Taiwan is also considered. Comparisons are made of both the methodologies and the results across the relatively diverse international literature. The most robust finding is that conventional air pollutants (e.g., particulate matter and lead) consistently rank as high health risks across all of the CRAs examined. Given the varied nature of the settings studied in the CRAs, including level of economic development, urban-rural differences, and climate, this finding is particularly significant. Problems involving drinking water are also ranked as a high or medium health risk in almost all the countries studied. This is consistent with the results of analyses conducted by the World Bank suggesting contamination, limited coverage and erratic service by water supply systems. Beyond the major air pollutants and drinking water, the CRA results diverge significantly across countries. A number of problems involving toxic chemicals, e. g., hazardous air pollutants, rank as high health risks in the US but do not appear as consistent areas of concerns in the other countries studied. This likely reflects the so-called "risk transition" - the shift from sanitation and infection disease problems to those involving industry, vehicles and toxic substances - that often occurs with economic development. It may also reflect the greater information about sources of toxic pollutants in the U.S. For other problems, there are important differences across the developing countries and economies in transition. For example, hazardous and (industrial) non-hazardous waste issues ranked as medium or low health risks in all the countries studied, except for Taiwan where unmanaged toxic waste sites were considered to pose high risks. While the generally low ranking is consistent with the notion that few people are directly exposed to hazardous and (industrial) non-hazardous waste, it is not entirely surprising that views might be different in Taiwan, where space is so limited and population density is so high. We suggest that the wide range of findings likely reflect genuine differences among the countries studied. However, we cannot entirely rule out the possibility that some of the observed similarities (and differences) arise from the (relatively) common methodologies employed.

Animals↗
PubMed2000

A comparison of the pectate lyase genes, pel-1 and pel-2, of Colletotrichum gloeosporioides f.sp. malvae and the relationship between their expression in culture and during necrotrophic infection.

Extracellular pectic lyase and polygalacturonase activities of Colletotrichum gloeosporioides f.sp. malvae were detected in broths containing mallow cell wall extract, pectin or glucose as the carbon source. The initial pH of the broth as well as the carbon source had major influences on pectinase enzyme activities. In the host, only pectic lyase activity was detected, which began at the end of the biotrophic phase and increased in the necrotrophic phase of infection. Two full-length pectate lyase cDNAs, pel-1 and pel-2, were cloned from the fungus. Both genes showed similar patterns of expression when the fungus was grown in mallow cell-wall extract and pectin medium, and the only major difference in expression in culture was that only pel-2 was expressed in glucose broth. Expression of pel-1 and pel-2 was also affected by the initial pH of the medium. Expression of pel-2, but not pel-1, was detected during infection of the host, round-leaved mallow, Malva pusilla. Transcripts of pel-2 were first detectable during the necrotrophic phase of infection approx. 24h after the first detection of pectic lyase enzyme activity. A comparison of expression of pel-1 and pel-2 in culture and in planta with other pectinase genes of C. gloeosporioides f.sp. malvae, as well as with other plant pathogenic fungi, indicates that expression during necrotrophic infection correlates with the ability to be expressed in media containing glucose.

Amino Acid Sequence↗
PubMed2000

Myocardial bridging does not predict sudden death in children with hypertrophic cardiomyopathy but is associated with more severe cardiac disease.

OBJECTIVES: We sought to examine the association between systolic compression of sections of epicardial coronary vessels (myocardial bridging) with myocardial perfusion abnormalities and clinical outcome in children with hypertrophic cardiomyopathy (HCM). BACKGROUND: It has recently been suggested that myocardial bridging is an important cause of myocardial ischemia and sudden death in children with HCM. METHODS: Angiograms from 57 children with HCM were reviewed for the presence of bridging (50% or more maximum systolic arterial compression). QT interval indices, echocardiographic and cardiac catheterization findings, treadmill exercise tests, exercise thallium scintigraphy, Holter monitoring and electrophysiologic study findings were compared in children with and without bridging. The findings were also related to the presence or absence of compression of septal branches of the left anterior descending artery (LAD). RESULTS: Bridging was present in 23 (40%) of the children. Multiple coronary arteries were involved in four children. Bridging involved the LAD in 16 of 28 (57%) affected vessels. Myocardial perfusion abnormalities were present in 14 of 30 (47%) children without bridging and in 17 of 22 (94%) children with bridging, p = 0.002. However, bridging was associated with more severe septal hypertrophy (19+/-8 mm vs. 28+/-8 mm, p < 0.001), a higher septum:posterior wall thickness ratio (2.7+/-1.2 vs. 1.8+/-0.9, p < 0.001), and higher left ventricle (LV) outflow gradient (45+/-37 mm Hg vs. 16+/-28 mm Hg, p = 0.002). Compression of septal LAD branches was present in 37 (65%) of the children and was significantly associated with bridging, severity of LV hypertrophy and outflow obstruction. Multivariate analysis demonstrated that LV septal thickness and septal branch compression, and not bridging, were independent predictors of thallium perfusion abnormalities. There was a 90% power at 5% significance to detect an effect of bridging on thallium abnormalities at an odds ratio of 3. Bridging was also not associated with significantly greater symptoms, increased QT and QTc intervals and QTc dispersion, ventricular tachycardia on Holter or induced at EP study, or a worse prognosis. CONCLUSIONS: Bridging and compression of septal branches of the LAD are common in HCM children and are related to magnitude of LV hypertrophy. Left ventricular hypertrophy and compression of intramyocardial branches of the epicardial coronary arteries may contribute to myocardial perfusion abnormalities. Our findings suggest that bridging does not result in myocardial ischemia and may not cause arrhythmias or sudden death in HCM children.

Adolescent↗
PubMed1999

Baseline IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus and the risk for cardiovascular disease in women.

BACKGROUND: Results of cross-sectional and retrospective studies have suggested that chronic infection may be a risk factor for cardiovascular disease. However, prospective data evaluating the relation between baseline antibody titers against various plausible agents and risk for cardiovascular disease are sparse, particularly among women. OBJECTIVE: To determine whether previous exposure to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, or cytomegalovirus is associated with increased risk for cardiovascular events. DESIGN: Prospective, nested, case-control study. SETTING: Women's Health Study. PARTICIPANTS: Apparently healthy postmenopausal women. MEASUREMENTS: IgG antibody titers against C. pneumoniae, H. pylori, herpes simplex virus, and cytomegalovirus were measured in baseline blood samples obtained from 122 study participants who subsequently reported a first cardiovascular event (case-patients) and 244 participants matched for age and smoking status who did not report a cardiovascular event (controls) during 3 years of follow-up. RESULTS: Little evidence was found of an association between risk for cardiovascular events and baseline IgG seropositivity for antibodies against C. pneumoniae (rate ratio, 1.1 [95% CI, 0.7 to 1.8]), H. pylori (rate ratio, 0.90 [CI, 0.6 to 1.4]), herpes simplex virus (rate ratio, 1.2 [CI, 0.6 to 2.1]), and cytomegalovirus (rate ratio, 0.9 [CI, 0.6 to 1.5]). In addition, there was little evidence of an association between a participant's total number of infections and subsequent cardiovascular risk (P > 0.2). CONCLUSION: In apparently healthy postmenopausal women, little evidence was found that previous infection, as measured by IgG antibody titers to C. pneumoniae, H. pylori, herpes simplex virus, and cytomegalovirus, is associated with subsequent risk for cardiovascular disease.

Antibodies, Bacterial↗
PubMed1999

Relationship between I2 imidazoline binding sites and monoamine oxidase B in liver.

Biochemical and pharmacologic studies suggest that I2 imidazoline binding sites (I2BS) represent a heterogeneous family of membrane proteins. Indeed, the imidazoline binding sites located on monoamine oxidases (MAO) A and B display different pharmacologic properties. Recent results suggest that in liver and brain, I2BS may be located on proteins distinct from MAOs. The following observations indicate that in liver and brain, [3H]idazoxan binds exclusively to I2BS located on MAO-B: (1) size exclusion chromatography of digitonin-solubilized preparations from rabbit and human liver showed that [3H]idazoxan-specific binding eluted only in two peaks (approximately 175,000 and approximately 100,000 Da, corresponding to 90% and 10% of the recovered [3H]idazoxan binding) which also contained MAOs as determined by [14C]tyramine oxidation and Western blot analysis; (2) according to previous results obtained in various human and rat tissues, experiments performed in mice liver and brain showed that idazoxan was a potent inhibitor of [125I]-AZIPI photoincorporation to MAO-B but not to MAO-A; (3) in MAO-deficient transgenic mice, [3H]idazoxan binding to liver and brain membranes was completely abolished in MAO-B knockout mice and was not affected in MAO-A knockout mice. Together, these results show that in both liver and brain, I2BS are located exclusively on MAO-B. The imidazoline binding site on MAO-A, which photoincorporates [125I]-AZIPI and displays a low affinity for idazoxan, may not belong to the family of the I2 imidazoline binding sites.

Animals↗
PubMed1999

Homocysteine and risk of cardiovascular disease among postmenopausal women.

CONTEXT: Individuals with elevated levels of homocysteine tend to have higher prevalence of cardiovascular disease. However, prospective studies of homocysteine are inconsistent and data among women are limited. OBJECTIVE: To determine whether elevated homocysteine levels in healthy postmenopausal women predict risk of developing cardiovascular disease. DESIGN: Prospective, nested case-control study with a mean 3-year follow-up. SETTING: The Women's Health Study, an ongoing US primary prevention trial initiated in 1993. PARTICIPANTS: From a total cohort of 28,263 postmenopausal women with no history of cardiovascular disease or cancer at baseline, 122 women who subsequently experienced cardiovascular events were defined as cases, and 244 age- and smoking status-matched women who remained free of disease during follow-up were defined as controls. MAIN OUTCOME MEASURES: Incidence of death due to cardiovascular disease, nonfatal myocardial infarction (MI), stroke, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft by baseline homocysteine level. RESULTS: Of the 122 cases, there were 85 events of MI or stroke and 37 coronary revascularizations. Case subjects had significantly higher baseline homocysteine levels than controls (14.1 vs 12.4 micromol/L; P = .02). Subjects with homocysteine levels in the highest quartile had a 2-fold increase in risk of any cardiovascular event (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8). This effect was largely due to an excess of cases with high levels of homocysteine; the RR for those with homocysteine levels at or higher than the 95th percentile (20.7 micromol/L) was 2.6 (95% CI, 1.1-5.7). Risk estimates were independent of traditional risk factors and were greatest for the end points of MI and stroke (RR for those with baseline homocysteine levels in the top quartile, 2.2; 95% CI, 1.1-4.6). Self-reported multivitamin supplement use at study entry was associated with significantly reduced levels of homocysteine (P<.001). However, the association between increasing quartile of homocysteine level and risk of MI or stroke remained significant in analyses controlling for baseline multivitamin supplement use (P = .003 for trend), and subgroup analyses limited to women who were (P = .02 for trend) or were not (P = .04 for trend) taking multivitamin supplements. CONCLUSIONS: Among healthy postmenopausal US women, elevated levels of homocysteine moderately increased the risk of future cardiovascular disease. Whether lowering the homocysteine level reduces risk of cardiovascular events requires testing in randomized controlled trials.

Aged↗
PubMed1999

Fermentation production of keratinase from Bacillus licheniformisPWD-1 and a recombinant B. subtilis FDB-29.

Fermentation scale-up was studied for the production of keratinase by Bacillus licheniformis PWD-1, the parent strain, and B. subtilis FDB-29, a recombinant strain. In both strains, keratinase was induced by proteinaceous media, and repressed by carbohydrates. A seed culture of B. licheniformis PWD-1 at early age, 6-10 h, is crucial to keratinase production during fermentation, but B. subtilis FDB-29 is insensitive to the seed culture age. During the batch fermentation by both strains, the pH changed from 7.0 to 8.5 while the keratinase activity and productivity stayed at high levels. Control of pH, therefore, is not necessary. The temperature for maximum keratinase production is 37 degrees C for both strains, though B. licheniformis is thermophilic and grows best at 50 degrees C. Optimal levels of dissolved oxygen are 10% and 20% for B. licheniformis and B. subtilis respectively. A scale-up procedure using constant temperature at 37 degrees C was adopted for B. subtilis. On the other hand, a temperature-shift procedure by which an 8-h fermentation at 50 degrees C for growth followed by a shift to 37 degrees C for enzyme production was used for B. licheniformis to shorten the fermentation time and increase enzyme productivity. Production of keratinase by B. licheniformis increased by ten-fold following this new procedure. After respective optimization of fermentation conditions, keratinase production by B. licheniformis PWD-1 is approximately 40% higher than that by B. subtilis FDB-29.

Journal Article↗
PubMed1998

Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women.

BACKGROUND: C-reactive protein (CRP) predicts risk of myocardial infarction (MI) and stroke among apparently healthy men, but in women, virtually no data are available. METHODS AND RESULTS: CRP was measured in baseline blood samples from 122 apparently healthy participants in the Women's Health Study who subsequently suffered a first cardiovascular event and from 244 age- and smoking-matched control subjects who remained free of cardiovascular disease during a 3-year follow-up period. Women who developed cardiovascular events had higher baseline CRP levels than control subjects (P=0.0001), such that those with the highest levels at baseline had a 5-fold increase in risk of any vascular event (RR=4.8; 95% CI, 2.3 to 10.1; P=0.0001) and a 7-fold increase in risk of MI or stroke (RR=7.3; 95% CI, 2.7 to 19.9; P=0.0001). Risk estimates were independent of other risk factors, and prediction models that included CRP provided a better method to predict risk than models that excluded CRP (all P values <0.01). In stratified analyses, CRP was a predictor among subgroups of women with low as well as high risk as defined by other cardiovascular risk factors. CONCLUSIONS: In these prospective data among women, CRP is a strong independent risk factor for cardiovascular disease that adds to the predictive value of risk models based on usual factors alone. (Circulation. 1998;98:731-733.)

Aged↗
PubMed1998

Determination of deoxyribonucleoside triphosphate pool sizes in ribonucleotide reductase cDNA transfected human KB cells.

Ribonucleotide reductase (RR) is a rate-limiting enzyme in DNA synthesis, which is responsible for controlling deoxyribonucleoside triphosphate (dNTP) pool size. It has been shown that transfection of RR M2 cDNA in human KB cells (M2-D clone) results in overexpression for the M2 subunit and resistance to hydroxyurea (HU). In this study, dNTP pool assays were performed to measure the pool sizes in six cell lines: two controls, three transfectants, and drug-induced HU-resistant (HUR) cells. Total dNTP levels among the six cell lines rose in the following order: KB wild-type, KB vector-only transfectant, M1 cDNA transfectant, M2 cDNA transfectant, M1/M2 cDNA transfectant, and HU-induced resistant clone. The dCTP levels of the cells mimicked the total dNTP pools on a smaller scale. The significant increases in the dCTP pool sizes of the M2-D, X-D, and HUR clones were proportional to their respective increases in RR activity. Relative to all other transfectants, the M1-D clone demonstrated lower dCTP levels but increased dATP pools. The M1-D clone demonstrated a significant resistance to dNTP inhibition of RR activity compared with the control KB wild-type cells. In contrast, a profound inhibition of dCTP and a decreased sensitivity to dATP inhibition was observed in M2-D, X-D, and HUR clones. In summary, M2 cDNA transfectants and HUR clones had increased RR activity as well as expanded dNTP pools, particularly dCTP, when compared with wild-type KB cells. These data provide evidence for the intertwined relationship between RR activity and dNTP pools.

Clone Cells↗
PubMed1998

Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential.

The ribonucleotide reductase (RR) gene has been associated with malignant transformation and metastatic potential. In this report, the significance of the expression of RR mRNA and enzymatic activity to the invasive potential was examined by Boyden chamber invasion assay. Our results suggest that overexpression of RR M2 mRNA and RR enzymatic activity correlates to an increase in cell invasive potential. The drug-induced HURs clone expressed a higher level RR M2 mRNA and enzyme activity which contributes significantly to the 3-fold increase in invasive potential of the cells observed relative to the KB wild-type control. On the contrary, the HUr revertant clone decreased the RR M2 mRNA level and enzymatic activity, concomitantly decreasing their invasive potential. This phenomenon is most likely due to the return of RR to levels comparable to that of the KB wild-type cells. To confirm that this observation was not of a drug-resistance phenotype associated with multiple gene alterations, the panel of RR transfectants (M1-D transfected M1 subunit cDNA, M2-D transfected M2 subunit cDNA, X-D transfected M1/M2 cDNA) characterized in a previous study were also tested in the invasion assay. The M2-D clone expressed 6-fold higher RR M2 mRNA and RR activity and also demonstrated 6-fold higher invasive potential in vitro than either the parental or vector only transfected cell line (KB-V). The X-D clone demonstrated 3-fold higher M2 mRNA expression and revealed 4-fold higher invasive potential than control cells. The M1-D clone, in contrast, expressed a baseline level of RR M2 mRNA and higher M1 mRNA. In contrast to the X-D and M2-D cells, the invasive potential of M1-D reached an even lower level in the invasive assay than the control. These results, therefore, suggest that RR M2 overexpression plays an important role in a tumor's invasiveness.

Carcinoma↗
PubMed1998

Development and characterization of monoclonal antibodies specific to the serotonin 5-HT2A receptor.

Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT2A receptor. To generate MAbs against 5-HT2AR, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT2AR recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT2AR, rat and human brain lysate, and lysate from cell lines transfected with 5-HT2AR cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT2AR N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT2AR in lysates from rat brain and a 5-HT2AR-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT2AR but not with recombinant 5-HT2BR and 5-HT2CR. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies.

Aged↗
PubMed1998

Intensity and correlates of fear of falling and hurting oneself in the next year: baseline findings from a Roybal Center fear of falling intervention.

Fear of falling is highly prevalent and associated with restricted activity. To help inform design of interventions, the authors examined the correlates of this fear. Data came from baseline information on subjects in a community-based falls intervention study (N = 392). In a multivariate model, lower levels of fear of falling and hurting oneself in the next year were related to being younger, having higher levels of dysfunction, and having lower levels of perceived ability to manage falls, with the last two remaining significant even after controlling for generalized fearfulness. When analyzing specific domains of dysfunction, higher levels of fear of falling and hurting oneself in the next year were associated with higher levels of physical dysfunction. The findings lend support to the expanding awareness that fear of falling may imperil quality of life and suggest the importance of interventions aimed at enhancing ability to manage falls.

Accidental Falls↗