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Biomedical subjects

S Ferris

Publications and source records attributed to S Ferris.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of the promoters and 5'-UTR of mouse Cd59 genes, and of their functional activity in erythrocytes.

The complement regulatory protein CD59 inhibits formation of the membrane attack complex (MAC), the terminal effector of the complement system. There are two mouse Cd59 genes in mice but only one in humans. In the work reported here we (a) mapped the promoter regions of both mCd59a and mCd59b genes, (b) identified two different promoters for each mCd59 gene, (c) defined a previously unrecognized additional exon 1 in each mCd59 gene, (d) identified that each mCd59 gene expresses two different tissue-specific transcripts that differ in their 5'-UTR, and (e) confirmed the presence of mCd59b mRNA in multiple tissues. At the functional level, comparison of the sensitivity of mCd59ab(-/-) and mCd59a(-/-) red blood cells to MAC-mediated lysis revealed that mCd59b protects RBC from MAC-mediated lysis, at least in the setting of mCd59a deficiency. Together these findings indicate that the mCd59 genes may have complex and perhaps different regulatory mechanisms in different tissues.

5' Untranslated Regions↗
PubMed2004

Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). METHODS: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. RESULTS: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. CONCLUSION: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

Aged↗
PubMed2004

Behavioral symptoms in mild cognitive impairment.

The authors investigated neuropsychiatric symptoms in mild cognitive impairment (MCI) from baseline data of the Investigation in the Delay to Diagnosis of AD with Exelon (InDDEx) study (n = 1,010). Neuropsychiatric symptoms were reported in 59% of subjects (Neuropsychiatric Inventory [NPI]). NPI+ subjects had significantly greater impairment on global, cognitive, and functional scores than NPI- subjects. The presence of neuropsychiatric symptoms appears to be a marker of MCI severity.

Aged↗
PubMed2002

Measuring cognition in advanced Alzheimer's disease for clinical trials.

Measurement of cognitive dysfunction and treatment response in the early stages of Alzheimer's disease (AD) has used such scales as the Mini-Mental State Examination (MMSE) and the AD Assessment Scale (ADAS). With the exception of clinical rating scales, however, there are only a few objective measures of cognition for tracking progression in advanced AD. Given renewed interest in potential therapies for advanced AD, objective measures of cognition are important for the adequate evaluation of change due to AD progression or therapy. Several cognitive measures for advanced AD are reviewed. One measure, the Severe Impairment Battery (SIB) is reviewed in detail. Preliminary analyses from a trial of memantine show significant change on the SIB in memory (p < 0.001) and visuospatial functions (p < 0.02) over six-months with a trend for language and praxis. Data from a donepezil trial also highlight the importance of accurate assessment in advanced AD.

Aged↗
PubMed2001

The complete genome sequence of the murine respiratory pathogen Mycoplasma pulmonis.

Mycoplasma pulmonis is a wall-less eubacterium belonging to the Mollicutes (trivial name, mycoplasmas) and responsible for murine respiratory diseases. The genome of strain UAB CTIP is composed of a single circular 963 879 bp chromosome with a G + C content of 26.6 mol%, i.e. the lowest reported among bacteria, Ureaplasma urealyticum apart. This genome contains 782 putative coding sequences (CDSs) covering 91.4% of its length and a function could be assigned to 486 CDSs whilst 92 matched the gene sequences of hypothetical proteins, leaving 204 CDSs without significant database match. The genome contains a single set of rRNA genes and only 29 tRNAs genes. The replication origin oriC was localized by sequence analysis and by using the G + C skew method. Sequence polymorphisms within stretches of repeated nucleotides generate phase-variable protein antigens whilst a recombinase gene is likely to catalyse the site-specific DNA inversions in major M.pulmonis surface antigens. Furthermore, a hemolysin, secreted nucleases and a glyco-protease are predicted virulence factors. Surprisingly, several of the genes previously reported to be essential for a self-replicating minimal cell are missing in the M.pulmonis genome although this one is larger than the other mycoplasma genomes fully sequenced until now.

Animals↗
PubMed2001

Description and evaluation of a Newton-based electronic appetite rating system for temporal tracking of appetite in human subjects.

This study assessed the reliability and validity of a palm-top-based electronic appetite rating system (EARS) in relation to the traditional paper and pen method. Twenty healthy subjects [10 male (M) and 10 female (F)] - mean age M=31 years (S.D.=8), F=27 years (S.D.=5); mean BMI M=24 (S.D.=2), F=21 (S.D.=5) - participated in a 4-day protocol. Measurements were made on days 1 and 4. Subjects were given paper and an EARS to log hourly subjective motivation to eat during waking hours. Food intake and meal times were fixed. Subjects were given a maintenance diet (comprising 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6xResting Metabolic Rate (RMR), as three isoenergetic meals. Bland and Altman's test for bias between two measurement techniques found significant differences between EARS and paper and pen for two of eight responses (hunger and fullness). Regression analysis confirmed that there were no day, sex or order effects between ratings obtained using either technique. For 15 subjects, there was no significant difference between results, with a linear relationship between the two methods that explained most of the variance (r(2) ranged from 62.6 to 98.6). The slope for all subjects was less than 1, which was partly explained by a tendency for bias at the extreme end of results on the EARS technique. These data suggest that the EARS is a useful and reliable technique for real-time data collection in appetite research but that it should not be used interchangeably with paper and pen techniques.

Adult↗
PubMed2001

Effect of altering the variety of sensorially distinct foods, of the same macronutrient content, on food intake and body weight in men.

OBJECTIVE: To examine the effect of increasing the variety of sensorially distinct but nutritionally identical foods on appetite, food intake and body weight, over 7 days, in men. DESIGN: Six younger, lean men (mean (s.d.) age 27.0 (2.9) y; weight 74.7 (3.9) kg; height 1.78 (0.03) m; body mass index (BMI) 23.6 (1.1) kg/m2) and six older, overweight men (mean (s.d.) age 39.7 (2.9) y; weight 89.2 (4.4) kg; height 1.78 (0.04) m; BMI 28.1 (0.5) kg/m2) were each studied three times during a 9 day protocol, whilst resident in the Human Nutrition Unit. On days 1-2, subjects consumed a medium fat (MF) maintenance diet (40% fat, 13% protein and 47% carbohydrate by energy) calculated at 1.6 x resting metabolic rate (RMR). On days 3-9 subjects had ad libitum access to MF foods (550 kJ/100 g) with every item the same macronutrient composition and energy density. Subjects had continuous ad libitum access to 5, 10 or 15 food items per day on the low-variety (LV), medium-variety (MV) and high-variety (HV) treatments, respectively. The order of treatments was randomized across subjects. Subjective hunger was tracked hourly during waking hours using visual analogue scales (VAS). Body weight (as a proxy of changes in energy balance) was measured before eating and after voiding, each morning. RESULTS: Food and energy intake of the 12 men increased as the variety of foods increased, giving mean energy intakes of 10.13, 11.00 and 11.89 MJ/day on the LV, MV and HV treatments, respectively (F(2,20) = 10.32; P < 0.001). This effect was ascribable almost entirely to the lean men. Energy intake amounted to 1.57, 1.76 and 1.97 x RMR in the lean men and 1.33, 1.40 and 1.45 x RMR, for the overweight men on the LV, MV and HV diets, respectively. Weight changes amounted to -0.16, -0.28 and + 0.43 kg (lean) -1.03 and -1.52 kg and -0.66 kg (overweight), on the LV, MV and HV diets, respectively. The overweight men may have constrained their energy intake relative to expected requirements. This may have been due to a congnitive effect or an age effect. There was no significant group or diet effect on subjectively rated hunger. CONCLUSIONS: These data suggest that increasing the variety of sensorially distinct foods that are virtually identical in composition can increase food and energy intake and in the short to medium term can alter energy balance.

Adult↗
PubMed2001

Outcome measures for probable vascular dementia and Alzheimer's disease with cerebrovascular disease.

Vascular dementia (VaD) can be defined as dementia associated with cerebrovascular disease (CVD), and accounts for a large proportion of all dementia cases. There is substantial overlap in the clinical symptomatology, pathophysiology and neurochemical mechanisms in VaD compared with Alzheimer's disease, suggesting that an effective treatment for Alzheimer's disease may also offer benefit as a symptomatic treatment in VaD. However, there are currently no explicit guidelines for conducting clinical pharmacotherapy trials in VaD patients. Two important requirements for assessing therapeutic benefits in such trials are 1) the inclusion of appropriate patients and 2) the use of appropriate outcome measures. Debate on the precise definition of VaD in relation to patient selection criteria continues, but many of the recommendations for outcome measures in Alzheimer's disease are already applicable to VaD. There is consensus that cognitive and global function measures, and assessments of abilities to perform activities of daily living (ADL) must be included as part of the optimal assessment battery in VaD trials. A measure of reduced behavioural symptoms with associated reductions in demands on caregivers would also be desirable. However, care must be taken in extrapolating Alzheimer's disease-specific evaluations to VaD, in that important differences in specific domains affected and characteristics of disease course must be taken into account. Between them, measures such as the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog; perhaps with supplemental tests of attention and other frontal lobe functions), evaluations of clinical global impression of change and a functional assessment addressing instrumental as well as basic ADL, e.g. Disability Assessment in Dementia (DAD) scale, should provide a good overall description of VaD-related deficits and sufficient appraisal of treatment effects. The Neuropsychiatric Inventory has also been shown to have good potential utility for measuring behavioural alterations in VaD. These and other assessments are reviewed to provide a balanced and realistic view of the type of treatment outcomes that can be expected in VaD pharmacotherapy trials, and to address the best ways of measuring these outcomes.

Alzheimer Disease↗
PubMed2000

Detection of Ureaplasma diversum in cattle using a newly developed PCR-based detection assay.

Ureaplasma diversum has been associated with different clinical manifestations including bovine vulvitis, endometritis, salpingitis, spontaneous abortion and infertility. Because the isolation of this ureaplasma from clinical samples is difficult, there is a need for improved detection methods. We developed a PCR assay based on amplification of a region of the gene encoding 16S rRNA. The specificity of the amplification was verified by sequence analysis. Female bovine vaginal swabs (n=168) were collected and the presence of U. diversum evaluated by both culture methods and by the PCR assay. Culture was positive for 60 samples (35.7%), and PCR-specific amplification was obtained for 89 samples (52.9%). These results indicated a high prevalence of U. diversum in the selected animals and the higher sensitivity of this PCR assay as compared to culture.

Animals↗
PubMed2000

Quantitating physical activity in COPD using a triaxial accelerometer.

STUDY OBJECTIVE: To determine the reliability, validity, and stability of a triaxial accelerometer for walking and daily activity measurement in a COPD sample. DESIGN: Cross-sectional, correlational, descriptive design. SETTING: Outpatient pulmonary rehabilitation program in a university-affiliated Veterans Affairs medical center. PARTICIPANTS: Forty-seven outpatients (44 men and 3 women) with stable COPD (FEV(1), 37% predicted; SD, 16%) prior to entry into a pulmonary rehabilitation program. MEASUREMENTS AND RESULTS: Test-retest reliability of a triaxial movement sensor (Tritrac R3D Research Ergometer; Professional Products; Madison, WI) was evaluated in 35 of the 47 subjects during three standardized 6-min walks (intraclass correlation coefficient [rICC] = 0.84). Pearson correlations evaluated accelerometer concurrent validity as a measure of walking (in vector magnitude units), compared to walking distance in all 47 subjects during three sequential 6-min walks (0. 84, 0.85, and 0.95, respectively; p < 0.001). The validity of the accelerometer as a measure of daily activity over 3 full days at home was evaluated in all subjects using Pearson correlations with other indicators of functional capacity. The accelerometer correlated with exercise capacity (maximal 6-min walk, r = 0.74; p < 0.001); level of obstructive disease (FEV(1) percent predicted, r = 0.62; p < 0.001); dyspnea (Functional Status and Dyspnea Questionnaire, dyspnea over the past 30 days, r = - 0.29; p < 0.05); and activity self-efficacy (Activity Self-Efficacy Questionnaire, r = 0.43; p < 0.01); but not with self-report of daily activity (Modified Activity Recall Questionnaire, r = 0.14; not significant). Stability of the accelerometer to measure 3 full days of activity at home was determined by an rICC of 0.69. CONCLUSIONS: This study provides preliminary data suggesting that a triaxial movement sensor is a reliable, valid, and stable measure of walking and daily physical activity in COPD patients. It has the potential to provide more precise measurement of everyday physical functioning in this population than self-report measures currently in use, and measures an important dimension of functional status not previously well-described.

Activities of Daily Living↗
PubMed1999

Phase variations of the Mycoplasma penetrans main surface lipoprotein increase antigenic diversity.

Mycoplasma penetrans is a recently identified mycoplasma, isolated from urine samples collected from human immunodeficiency virus (HIV)-infected patients. Its presence is significantly associated with HIV infection. The major antigen recognized during natural and experimental infections is an abundant P35 lipoprotein which, upon extraction, segregates in the Triton X-114 detergent phase and is the basis of M. penetrans-specific serological assays. We report here that the P35 antigen undergoes spontaneous and reversible phase variation at high frequency, leading to heterogeneous populations of mycoplasmas, even when derived from a clonal lineage. This variation was found to be determined at the transcription level, and although this property is not unique among the members of the class Mollicutes, the mechanism by which it occurs in M. penetrans differs from those previously described for other Mycoplasma species. Indeed, the P35 phase variation was due neither to a p35 gene rearrangement nor to point mutations within the gene itself or its promoter. The P35 phase variation in the different variants obtained was concomitant with modifications in the pattern of other expressed lipoproteins, probably due to regulated expression of selected members of a gene family which was found to potentially encode similar lipoproteins. M. penetrans variants could be selected on the basis of their lack of colony immunoreactivity with a polyclonal antiserum against a Triton X-114 extract, strongly suggesting that the mechanisms involved in altering surface antigen expression might allow evasion of the humoral immune response of the infected host.

Amino Acid Sequence↗
PubMed1999

Decreased lactic acidosis and anemia after transfusion of o-raffinose cross-linked and polymerized hemoglobin in severe murine malaria.

Severe anemia is a major cause of death in falciparum malaria. Blood transfusion increases survival in humans and in animal models of this disease. Because of logistic constraints and viral contamination of the blood supply, transfusions are frequently not practical in endemic regions. Modified hemoglobin is an effective O2 carrier in hemorrhagic shock. It is free of infectious contamination, may not require refrigeration, and because of its nitric oxide scavenging and small size, may have pharmacologic benefits in malaria. The effects of transfusions of modified hemoglobin in rats with high-grade parasitemia were evaluated. Modified hemoglobin decreased lactic acidosis and corrected anemia as well as transfusions with red blood cells; these findings may correlate with improved survival and suggest a possible proerythropoietic effect. Further study of this novel therapy is warranted.

Acidosis, Lactic↗
PubMed1998

Molecular evidence for nosocomial transmission of human immunodeficiency virus from a surgeon to one of his patients.

We have investigated the molecular evidence in favor of the transmission of human immunodeficiency virus (HIV) from an HIV-infected surgeon to one of his patients. After PCR amplification, the env and gag sequences from the viral genome were cloned and sequenced. Phylogenetic analysis revealed that the viral sequences derived from the surgeon and his patient are closely related, which strongly suggests that nosocomial transmission occurred. In addition, these viral sequences belong to group M of HIV type 1 but are divergent from the reference sequences of the known subtypes.

Base Sequence↗
PubMed1997

An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

We developed a set of informant-based items describing performance of activities of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which ADL are useful for assessment of patients in clinical trials. Evaluation of ADL is an important outcome measure in AD clinical trials. For clinical trial measurement, ADL should have broad applicability, good test-retest reliability, scaling to cover a range of performance, and sensitivity to detect change in disease progression. A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months. Controls performed virtually all ADL items optimally at baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely applicable, i.e., performed at baseline or premorbidly by > 90% of subjects; showed good test-retest reliability between baseline and 1 and 2 months; correlated with MMSE scores of AD patients cross-sectionally; and showed a decline in performance from baseline to 12 months in at least 20% of AD patients. ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE. The remaining 18 ADL included several that may be useful for trials that target specific populations, e.g., women with AD. Because change on specific items depends on baseline MMSE, ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial.

Activities of Daily Living↗
PubMed1996

Organization of Ureaplasma urealyticum urease gene cluster and expression in a suppressor strain of Escherichia coli.

Ureaplasma urealyticum is a pathogenic ureolytic mollicute which colonizes the urogenital tracts of humans. A genetic polymorphism between the two biotypes of U. urealyticum at the level of the urease genes was found. The urease gene cluster from a biotype 1 representative of U. urealyticum (serotype I) was cloned and sequenced. Seven genes were found, with ureA, ureB, and ureC encoding the structural subunits and ureE, ureF, ureG, and a truncated ureI) gene encoding accessory proteins. Urease expression was not obtained when the plasmid containing these genes was incorporated into an opal suppressor strain of Escherichia coli, although this enzymatic activity was found in the same E. coli strain transformed with pC6b, a plasmid with previously cloned urease genes from the U. urealyticum T960 strain of biotype 2 (serotype 8). Although there are 12 TGA triplets encoding tryptophan within urease genes, the level of expression obtained was comparable to the levels reported for other bacterial genes expressed in E. coli. Nested deletion experiments allowed us to demonstrate that ureD is necessary for urease activity whereas another open reading frame located downstream is not. The promoter for ureA and possibly other urease genes was identified for both serotypes.

Amino Acid Sequence↗