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Biomedical subjects

S Small

Publications and source records attributed to S Small.

At least 19 recordsLinked to original sources
PubMed2005

The use of rhodamine 6G and fluorescence microscopy in the evaluation of phospholipid-based polymeric biomaterials.

A technique is described that allows the staining and subsequent visualization of polymers that contain the phosphorylcholine (PC) group. These materials are useful as bulk materials or coatings for the fabrication of medical devices. The staining method employs rhodamine 6G, which can be simply and rapidly applied to the polymer coating and imaged using fluorescence microscopy. The specificity of the staining for the PC polymers makes this technique suitable for the evaluation of a wide range of substrates and provides qualitative information on coating uniformity, coverage and morphology. It can be used to examine the durability of, and defects in, the coating. Statistical analysis of the fluorescent intensity by measuring the pixel value during imaging can allow for the method to be used as a quality control tool.

Biocompatible Materials↗
PubMed2002

Long-term stability of a coronary stent coating post-implantation.

A coronary stent possessing a phosphorylcholine-based polymer coating was removed from a human patient 6 months after implantation and analyzed for the presence of the coating. An atomic force microscopy (AFM) technique has been employed to scrape away several 10- micro m(2) areas on the struts of the explanted stent. Scanning-electron microscopy (SEM) and tapping-mode AFM confirmed a surface coating had been removed in each case. Cross-sectional analysis and force-of-removal measurements showed that both coating depth and hardness were characteristic of that for the phosphorylcholine- (PC-) based coating prior to implantation. AFM amplitude-phase and distance curves from the explanted stent were comparable to those obtained when an unused stent was analyzed. Furthermore, laser ablation high-resolution inductively coupled-plasma mass spectometery (LA-HR-ICP-MS) was used to detect the low level of silicon present in the PC coating after explantation. The results from these techniques confirm that the stent coating is the original PC polymer and is not of biological origin, and support the long-term stability of the coating in vivo.

Aged↗
PubMed2001

Thoracic patterning by the Drosophila gap gene hunchback.

Localized gene expression patterns are critical for establishing body plans in all multicellular animals. In Drosophila, the gap gene hunchback (hb) is expressed in a dynamic pattern in anterior regions of the embryo. Hb protein is first detected as a shallow maternal gradient that prevents expression of posterior gap genes in anterior regions. hb mRNA is also expressed zygotically, first as a broad anterior domain controlled by the Bicoid (Bcd) morphogen, and then in a stripe at the position of parasegment 4 (PS4). Here, we show that the PS4-hb stripe changes the profile of the anterior Hb gradient by generating a localized peak of protein that persists until after the broad domain has started to decline. This peak is required specifically for the formation of the mesothoracic (T2) segment. At the molecular level, the PS4-hb stripe is critical for activation of the homeotic gene Antennapedia, but does not affect a gradient of Hb repressive activity formed by the combination of maternal and Bcd-dependent Hb. The repressive gradient is critical for establishing the positions of several target genes, including the gap genes Kruppel (Kr), knirps (kni), and giant (gt), and the homeotic gene Ultrabithorax (Ubx). Different Hb concentrations are sufficient for repression of gt, kni, and Ubx, but a very high level of Hb, or a combinatorial mechanism, is required for repression of Kr. These results suggest that the individual phases of hb transcription, which overlap temporally and spatially, contribute specific patterning functions in early embryogenesis.

Animals↗
PubMed2001

Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan.

OBJECTIVE: To compare the incidence rates for AD among elderly African-American, Caribbean Hispanic, and white individuals and to determine whether coincident cerebrovascular disease contributes to the inconsistency in reported differences among ethnic groups. METHODS: This was a population-based, longitudinal study over a 7-year period in the Washington Heights and Inwood communities of New York City. Annual incidence rates for AD were calculated and compared by ethnic group, and cumulative incidence adjusted for differences in education, diabetes, cardiovascular risk factors, and stroke was calculated. RESULTS: The age-specific incidence rate for probable and possible AD was 1.3% (95% CI, 0.8 to 1.7) per person-year between the ages of 65 and 74 years, 4.0% (95% CI, 3.2 to 4.8) per person-year between ages 75 and 84 years, and 7.9% (95% CI, 5.5 to 10.5) per person-year for ages 85 and older. Compared to white individuals, the cumulative incidence of AD to age 90 years was increased twofold among African-American and Caribbean Hispanic individuals. Adjustment for differences in number of years of education, illiteracy, or a history of stroke, hypertension, heart disease, or diabetes did not change the disproportionate risks among the three ethnic groups. CONCLUSION: The incidence rate for AD was significantly higher among African-American and Caribbean Hispanic elderly individuals compared white individuals. The presence of clinically apparent cardiovascular or cerebrovascular disease did not contribute to the increased risk of disease. Because the proportion of African-American and Caribbean Hispanic individuals reaching ages 65 and older in the United States is increasing more rapidly than the proportion of white individuals, it is imperative that this disparity in health among the elderly be understood.

Aged↗
PubMed1999

Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium.

OBJECTIVE: To assess the safety and tolerability of lexipafant in HIV-associated cognitive impairment. BACKGROUND: Cognitive impairment is the most common neurologic complication of advanced HIV-1 infection. There is evidence that a variety of inflammatory mediators, including platelet-activating factor (PAF), may contribute to neuronal injury. We hypothesized that lexipafant, a PAF antagonist, might improve cognitive dysfunction in HIV-infected people. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the safety and tolerability of lexipafant 500 mg/day. The primary outcome measure for tolerability was the ability to complete the study on the originally assigned dosage of medication. Thirty patients with cognitive impairment were enrolled. RESULTS: Lexipafant was safe and well tolerated. Ninety-three percent in the placebo group and 88% in the lexipafant group completed the study at the originally assigned dosage. Trends toward improvement were seen in neuropsychological performance, especially verbal memory, in the lexipafant treatment group. CONCLUSIONS: This study shows that lexipafant, the first PAF antagonist used in HIV-associated cognitive impairment, is a safe and well tolerated compound. The observed trends toward improvement in neuropsychological test scores warrant the pursuit of a larger and longer efficacy trial to assess the impact of lexipafant on cognitive performance.

Adult↗
PubMed1999

Low-density lipoprotein cholesterol and the risk of dementia with stroke.

CONTEXT: Next to Alzheimer disease, vascular dementia is the second most common form of dementia in the elderly, yet few specific risk factors have been identified. OBJECTIVE: To investigate the relationship of plasma lipids and lipoproteins to dementia with stroke. DESIGN AND SETTING: Prospective longitudinal community-based study over a 7-year period (1991-1998). PARTICIPANTS: A total of 1111 nondemented participants (mean [SD] age, 75.0 [5.9] years) were followed up for an average of 2.1 years (range, 1-7.8 years). MAIN OUTCOME MEASURE: Incident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype. RESULTS: Two hundred eighty-six (25.7%) of the 1111 subjects developed dementia during follow-up; 61 (21.3%) were classified as having dementia with stroke and 225 (78.7%) as having probable Alzheimer disease. Levels of LDL cholesterol were significantly associated with an increased risk of dementia with stroke. Compared with the lowest quartile, the highest quartile of LDL cholesterol was associated with an approximately 3-fold increase in risk of dementia with stroke, adjusting for vascular risk factors and demographic variables (relative risk [RR], 3.1; 95% confidence interval [CI], 1.5-6.1). Levels of LDL corrected for lipoprotein(a) were an even stronger predictor of dementia with stroke in the adjusted multivariate analysis. Compared with the lowest quartile, the RR of dementia with stroke for the highest quartile of lipoprotein(a)-corrected LDL cholesterol was 4.1 (95% CI, 1.8-9.6) after adjusting for vascular factors and demographic variables. Lipid or lipoprotein levels were not associated with the development of Alzheimer disease in our cohort. CONCLUSIONS: Elevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke.

Aged↗
PubMed1999

Fatigue in chronic illness: the experience of individuals with chronic obstructive pulmonary disease and with asthma.

Although fatigue has been identified as a major problem for individuals with chronic obstructive pulmonary disease and with asthma, no research was found in which the symptom was directly studied in persons with these conditions. From studies carried out on various patient populations, it appears that fatigue has some specificity to disease state. Thus, it is important to describe the experience of fatigue within patient populations. To expand theoretical understanding of fatigue, qualitative research methods need to be applied. The purpose of this study therefore was to describe and compare the fatigue experiences of persons with chronic obstructive pulmonary disease (n=17) and with asthma (n=19). Data were obtained by use of a semi-structured questionnaire and were content analysed for categories and themes. There were many similarities between the fatigue experiences of the two groups. Fatigue is inextricably linked to laboured breathing. Although it interferes with their ability to carry out meaningful activities, the majority of individuals with chronic obstructive pulmonary disease or asthma cope well with it. The informants identified two types of coping strategies they use to manage their situation, which may be categorized as: problem-focused, including energy conservation, utilization and restoration; and emotion-focused, including being positive, accepting the physical limitations, distracting and normalizing.

Activities of Daily Living↗
PubMed1999

Hospitalization and Alzheimer's disease: results from a community-based study.

BACKGROUND: Prior studies offer conflicting findings on whether Alzheimer's disease (AD) is associated with an increased risk of hospitalization. METHODS: We investigated AD and hospitalization in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a community-based study of 2,334 elders in New York City. In 1996, an electronic medical records system was established that allows an e-mail alert to be sent to the research team whenever WHICAP subjects are admitted to Columbia-Presbyterian Medical Center (CPMC), the site of hospital care for the majority of subjects. RESULTS: Of the WHICAP cohort, 13.1% was admitted to CPMC in 21 months of follow-up; 17.5% of AD patients and 11.9% of unaffected subjects were admitted (p<.01). Multivariate logistic regression models showed that more advanced AD (Clinical Dementia Rating scale 3+) was a significant risk factor for hospitalization independently of age, gender, education, comorbid medical conditions, and death in the follow-up period (OR 2.3; 95% CI: 1.1, 4.6); subjects with mild or moderate AD did not show a significantly elevated risk. The prevalence of psychiatric symptoms did not differ between AD subjects who were hospitalized in the reporting period and AD subjects who were not hospitalized. Infectious disease was a more common discharge diagnosis for subjects with AD (p<.05). CONCLUSIONS: In this community-based cohort, subjects with severe AD were more likely to be hospitalized than unaffected subjects. The increased use of hospital care by these AD patients appears to be specific to AD but is not a result of psychiatric morbidity or end-of-life care. Rather, a greater risk of medical complications that require hospital care, especially infections, appears to be characteristic of severe AD.

Age Factors↗
PubMed1998

dCtBP mediates transcriptional repression by Knirps, Krüppel and Snail in the Drosophila embryo.

The pre-cellular Drosophila embryo contains 10 well characterized sequence-specific transcriptional repressors, which represent a broad spectrum of DNA-binding proteins. Previous studies have shown that two of the repressors, Hairy and Dorsal, recruit a common co-repressor protein, Groucho. Here we present evidence that three different repressors, Knirps, Krüppel and Snail, recruit a different co-repressor, dCtBP. Mutant embryos containing diminished levels of maternal dCtBP products exhibit both segmentation and dorsoventral patterning defects, which can be attributed to loss of Krüppel, Knirps and Snail activity. In contrast, the Dorsal and Hairy repressors retain at least some activity in dCtBP mutant embryos. dCtBP interacts with Krüppel, Knirps and Snail through a related sequence motif, PXDLSXK/H. This motif is essential for the repression activity of these proteins in transgenic embryos. We propose that dCtBP represents a major form of transcriptional repression in development, and that the Groucho and dCtBP co-repressors mediate separate pathways of repression.

Alcohol Oxidoreductases↗
PubMed1998

Rapid preparation of a panel of polyclonal antibodies to Drosophila segmentation proteins.

We describe a method for rapidly raising a panel of high quality polyclonal antibodies from bacterially expressed proteins. Approximately 1(2)/3 days of preparation is required per protein. One step that speeds up the procedure is the visualization of purified bands by precipitated sodium dodecyl sulfate (SDS). Antigenicity of the purified recombinant proteins may be increased by precipitation in double-distilled water. The results of using the serums obtained for fluorescent staining of Drosophila embryos are shown.

Animals↗
PubMed1998

Hourly care received by people with Alzheimer's disease: results from an urban, community survey.

People with Alzheimer's disease living in a defined community in New York City were identified and assessed on two occasions to determine the number of hours of activities of daily living (ADL) care they received. Nearly half received all care hours from informal sources; however, a quarter received all ADL care hours from formal sources. The mean number of daily ADL hours in the sample was 9.7, of which 4.2 came from formal sources. This reflects the extensive use of Medicaid-based home care services in New York City. As dementia worsened, substitution of formal for informal care was rare, but formal care assumed a greater proportion of total care hours.

Activities of Daily Living↗
PubMed1998

Two distinct mechanisms for differential positioning of gene expression borders involving the Drosophila gap protein giant.

We have combined genetic experiments and a targeted misexpression approach to examine the role of the gap gene giant (gt) in patterning anterior regions of the Drosophila embryo. Our results suggest that gt functions in the repression of three target genes, the gap genes Krüppel (Kr) and hunchback (hb), and the pair-rule gene even-skipped (eve). The anterior border of Kr, which lies 4-5 nucleus diameters posterior to nuclei that express gt mRNA, is set by a threshold repression mechanism involving very low levels of gt protein. In contrast, gt activity is required, but not sufficient for formation of the anterior border of eve stripe 2, which lies adjacent to nuclei that express gt mRNA. We propose that gt's role in forming this border is to potentiate repressive interaction(s) mediated by other factor(s) that are also localized to anterior regions of the early embryo. Finally, gt is required for repression of zygotic hb expression in more anterior regions of the embryo. The differential responses of these target genes to gt repression are critical for the correct positioning and maintenance of segmentation stripes, and normal anterior development.

Amino Acid Sequence↗
PubMed1997

Concentration-dependent patterning by an ectopic expression domain of the Drosophila gap gene knirps.

The asymmetric distribution of the gap gene knirps (kni) in discrete expression domains is critical for striped patterns of pair-rule gene expression in the Drosophila embryo. To test whether these domains function as sources of morphogenetic activity, the stripe 2 enhancer of the pair-rule gene even-skipped (eve) was used to express kni in an ectopic position. Manipulating the stripe 2-kni expression constructs and examining transgenic lines with different insertion sites led to the establishment of a series of independent lines that displayed consistently different levels and developmental profiles of expression. Individual lines showed specific disruptions in pair-rule patterning that were correlated with the level and timing of ectopic expression. These results suggest that the ectopic domain acts as a source for morphogenetic activity that specifies regions in the embryo where pair-rule genes can be activated or repressed. Evidence is presented that the level and timing of expression, as well as protein diffusion, are important for determining the specific responses of target genes.

Animals↗
PubMed1996

Regulation of two pair-rule stripes by a single enhancer in the Drosophila embryo.

Previous studies on the regulation of the segmentation gene even-skipped (eve) have centered on the transcription of stripe 2. Here, we characterize another enhancer module contained within the complex eve promoter that directs expression of stripes 3 and 7. This enhancer is approximately 500 bp in length and maps approximately 3.3 kb upstream of the transcription start site. The stripe 3 + 7 enhancer appears to be regulated by one or more ubiquitously distributed activators, including components of a JAK-Stat pathway. The two-stripe pattern results via multiple tiers of repressors which delimit this ubiquitous activation. The zinc finger repressor hunchback appears to be responsible for establishing the anterior border of stripe 3 and the posterior border of stripe 7. knirps, a member of the nuclear receptor family of transcription factors, appears to establish the posterior border of stripe 3 and the anterior border of stripe 7. Activator and repressor proteins bind in vitro to several sites within the enhancer. These findings suggest a general model for the regulation of segmentation stripes, whereby enhancers integrate positional information provided by broadly distributed activators and spatially restricted repressors.

Alleles↗
PubMed1996

Identification of a Stat gene that functions in Drosophila development.

A Drosophila Stat gene (D-Stat) with a zygotic segmental expression pattern was identified. This protein becomes phosphorylated on Tyr-704 when coexpressed in Schneider cells with a Drosophila janus kinase (JAK), Hopscotch (HOP). The phosphorylated protein binds specifically to the consensus sequence TTCCCGGAA. Suppressor mutations of hopTum-I, a dominant hyperactive allele of hop whose phenotype is hematocyte overproduction and tumor formation, were selected. One of these mutants, statHJ, mapped to the same chromosomal region (92E) as does D-Stat, had an incompletely penetrant pair rule phenotype, and exhibited aberrant expression of the pair rule gene even skipped (eve) at the cellular blastoderm stage. Two D-STAT-binding sites were identified within the eve stripe 3 enhancer region. Mutations in either of the STAT-binding sites greatly decreased the stripe 3 expression in transgenic flies. Clearly, the JAK-STAT pathway is connected to Drosophila early development.

Amino Acid Sequence↗