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Showing papers by "Rush University Medical Center published in 2001"


Journal ArticleDOI
TL;DR: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes, independent of the reduction in blood pressure it causes.
Abstract: Background It is unknown whether either the angiotensin-II–receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. Methods We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. Results The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo gro...

5,484 citations


Journal ArticleDOI
TL;DR: The limited longitudinal database indicates that the UHDRS may be useful for tracking changes in the clinical features of HD over time and there was an excellent degree of interrater reliability for the motor scores.
Abstract: The Unified Huntington's disease Rating Scale (UHDRS) was developed as a clinical rating scale to assess four domains of clinical performance and capacity in HD: motor function, cognitive function, behavioral abnormalities, and functional capacity. We assessed the internal consistency and the intercorrelations for the four domains and examined changes in ratings over time. We also performed an interrater reliability study of the motor assessment. We found there was a high degree of internal consistency within each of the domains of the UHDRS and that there were significant intercorrelations between the domains of the UHDRS, with the exception of the total behavioral score. There was an excellent degree of interrater reliability for the motor scores. Our limited longitudinal database indicates that the UHDRS may be useful for tracking changes in the clinical features of HD over time. The UHDRS assesses relevant clinical features of HD and appears to be appropriate for repeated administration during clinical studies.

1,786 citations


Journal ArticleDOI
TL;DR: Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal.
Abstract: All metals in contact with biological systems undergo corrosion. This electrochemical process leads to the formation of metal ions, which may activate the immune system by forming complexes with endogenous proteins. Implant degradation products have been shown to be associated with dermatitis, urticaria, and vasculitis. If cutaneous signs of an allergic response appear after implantation of a metal device, metal sensitivity should be considered. Currently, there is no generally accepted test for the clinical determination of metal hypersensitivity to implanted devices. The prevalence of dermal sensitivity in patients with a joint replacement device, particularly those with a failed implant, is substantially higher than that in the general population. Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal. It is currently unclear whether metal sensitivity is a contributing factor to implant failure. Implant-related metal sensitivity has been well documented in case and group studies; however, overall it remains a relatively unpredictable and poorly understood phenomenon in the context of orthopaedic implant materials1-3. Dermal hypersensitivity to metal is common, affecting about 10% to 15% of the population1,2,4,5. Dermal contact with and ingestion of metals have been reported to cause immune reactions, which most typically manifest as hives, eczema, redness, and itching1,6,7. Historically, the ability of implant materials to demonstrate appropriate host and material responses has resulted in the elimination of candidate materials based on observation of adverse host responses. However, some adverse responses are difficult to characterize in preclinical and clinical settings because of their infrequent or subtle nature. In vivo metal hypersensitivity or hypersensitivity-like reactivity to metallic biomaterials is one such response. Although little is known …

860 citations


Journal ArticleDOI
TL;DR: Recent findings on the cellular and molecular mechanisms by which ROS signal events leading to impairment of endothelial barrier function and promotion of leukocyte adhesion are discussed.
Abstract: Reactive oxygen species (ROS) are generated at sites of inflammation and injury, and at low levels, ROS can function as signaling molecules participating as signaling intermediates in regulation of fundamental cell activities such as cell growth and cell adaptation responses, whereas at higher concentrations, ROS can cause cellular injury and death. The vascular endothelium, which regulates the passage of macromolecules and circulating cells from blood to tissues, is a major target of oxidant stress, playing a critical role in the pathophysiology of several vascular diseases and disorders. Specifically, oxidant stress increases vascular endothelial permeability and promotes leukocyte adhesion, which are coupled with alterations in endothelial signal transduction and redox-regulated transcription factors such as activator protein-1 and nuclear factor-κB. This review discusses recent findings on the cellular and molecular mechanisms by which ROS signal events leading to impairment of endothelial barrier fun...

760 citations


Journal ArticleDOI
TL;DR: No signs of toxicity have been observed with the normal intake of hesperidin or related compounds.
Abstract: Hesperidin, a bioflavonoid, is an abundant and inexpensive by-product of Citrus cultivation. A deficiency of this substance in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cramps. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds. Both hesperidin and its aglycone hesperetin have been reported to possess a wide range of pharmacological properties. This paper reviews various aspects of hesperidin and its related compounds, including their occurrence, physical and chemical properties, analysis, pharmacokinetics, safety and toxicity and the marketed products available. A special emphasis has been laid on the pharmacological properties and medicinal uses of these compounds.

709 citations


Journal ArticleDOI
TL;DR: Surface energy may be a more important determinant of cellAdhesion and proliferation, and may be more useful than surface roughness for directing cell adhesion and cell colonization onto engineered tissue scaffoldings.
Abstract: Directed cell adhesion remains an important goal of implant and tissue engineering technology. In this study, surface energy and surface roughness were investigated to ascertain which of these properties show more overall influence on biomaterial–cell adhesion and colonization. Jet impingement was used to quantify cellular adhesion strength. Cellular proliferation and extracellular matrix secretion were used to characterize colonization of 3T3MC fibroblasts on: HS25 (a cobalt based implant alloy, ASTM F75), 316L stainless steel, Ti-6Al4V (a titanium implant alloy), commercially pure tantalum (Ta), polytetrafluoroethylene (PTFE), silicone rubber (SR), and high-density polyethylene (HDPE). The metals exhibited a nearly five-fold greater adhesion strength than the polymeric materials tested. Generally, surface energy was proportional to cellular adhesion strength. Only polymeric materials demonstrated significant increased adhesion strength associated with increased surface roughness. Cellular adhesion on me...

556 citations


Journal ArticleDOI
TL;DR: This 2-part review examines the current health economic literature for asthma and rhinitis and explores how comparative studies have contributed to understanding how to best diagnose and treat asthma and allergic Rhinitis.
Abstract: As new health care strategies compete with existing ones for limited resources, the health care system and its providers are beginning to turn to health economic analyses to help inform choices in the delivery of care. This 2-part review examines the current health economic literature for asthma and rhinitis. This first installment of the review focuses on studies that characterize the economic burden of asthma and rhinitis and examines how resources are allocated to the care of persons with asthma and rhinitis. In 1998, asthma in the United States accounted for an estimated 12.7 billion dollars annually. Similarly, in 1994, allergic rhinitis was estimated to cost 1.2 billion dollars. Most of the costs for these conditions are attributed to direct medical expenditures, with medications emerging as the single largest cost component. Indirect costs also represent an important social effect. While cost-of-illness studies help to characterize the economic burden, comparative health economic studies evaluate the value of new and existing strategies for clinical care. The second part of this review will explore how comparative studies have contributed to understanding how to best diagnose and treat asthma and allergic rhinitis.

551 citations


Journal ArticleDOI
TL;DR: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolics heart failure.
Abstract: Background—The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. Methods and Results—We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was .16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 2468 mm Hg). The time constant of LV relaxation (average, 51615 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 3496140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. Conclusions—Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function. (Circulation. 2001;104:779-782.)

494 citations


Journal ArticleDOI
TL;DR: Autopsy data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.
Abstract: Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the entorhinal cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II entorhinal cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 +/- 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p 0.33). There was also significant atrophy of layer II entorhinal cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II entorhinal cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.

434 citations


Journal ArticleDOI
TL;DR: The number of people with Alzheimer disease and the proportion of the total population affected will increase substantially and without progress in preventing or delaying onset of Alzheimer disease is expected to increase substantially.
Abstract: Alzheimer disease will affect increasing numbers of people as baby boomers (persons born between 1946 and 1964) age. This work reports projections of the incidence of Alzheimer disease(AD) that will occur among older Americans in the future. Education adjusted age-specific incidence rates of clinically diagnosed probable AD were obtained from stratified random samples of residents 65 years of age and older in a geographically defined community. These rates were applied to U.S. Census Bureau projections of the total U.S. population by age and sex to estimate the number of people newly affected each year. The annual number of incident cases is expected to more than double by the midpoint of the twenty-first century: from 377,000 (95% confidence interval = 159,000-595,000) in 1995 to 959,000 (95% confidence interval = 140,000-1,778,000) in 2050. The proportion of new onset cases who are age 85 or older will increase from 40% in 1995 to 62% in 2050 when the youngest of the baby boomers will attain that age. Without progress in preventing or delaying onset of Alzheimer disease, both the number of people with Alzheimer disease and the proportion of the total population affected will increase substantially.

433 citations



Journal ArticleDOI
TL;DR: Clinical aspects of the disorder and new insights with respect to pathophysiology are reviewed, and potential new therapeutics based on the disease mechanism are discussed, such as prostacyclin analogues, serotonin antagonists, and calcitonin gene-related peptides.

Journal ArticleDOI
TL;DR: The pH of the media is dependent on the cell mass and on all organic acids produced by Lactobacillus species, and not all strains of G vaginalis can be inhibited by lactobacilli-producing bacteriocin.

Journal ArticleDOI
TL;DR: Although initial animal studies are promising for possible pharmacologic treatment and prevention of osteolysis, well-controlled human trials are required before agents such as bisphosphonates can be recommended for general clinical use.
Abstract: Since the recognition of aseptic loosening by Charnley in the early 1960s, much information has been gained on the basic science of periprosthetic bone loss. Initially termed cement disease, it now generally is accepted that, in most instances, osteolysis is a manifestation of an adverse cellular response to phagocytosable particulate wear and corrosion debris, possibly facilitated by local hydrodynamic effects. Tissue explant, animal, and cell culture studies have allowed us to compile an appreciation of the complexity of cellular interactions and chemical mediators involved in osteolysis. Cellular participants have been shown to include the macrophage, osteoblast, fibroblast, and osteoclast. The plethora of chemical mediators that are responsible for the cellular responses and effects on bone include prostaglandin E 2 , tumor necrosis factor-alpha, interleukin-1, and interleukin 6. However, an increasing number of other proinflammatory and antiinflammatory cytokines, prostenoids, and enzymes have been shown to play important roles in this process. The ultimate goal of basic research is to develop novel strategies for evaluation and treatment of patients with osteolysis. Although initial animal studies are promising for possible pharmacologic treatment and prevention of osteolysis, well-controlled human trials are required before agents such as bisphosphonates can be recommended for general clinical use.

Journal ArticleDOI
15 Aug 2001-Blood
TL;DR: It was concluded that thalidomide, as a single agent, is effective in improving cytopenias of some MDS patients, especially those who present without excess blasts.

Journal ArticleDOI
TL;DR: A preliminary framework for accounting for certain surface F0 variations in speech, including carryover and anticipatory variations, downstep, declination, and F0 peak alignment is proposed.

Journal ArticleDOI
02 May 2001-JAMA
TL;DR: Test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants.
Abstract: ContextHome monitors designed to identify cardiorespiratory events are frequently used in infants at increased risk for sudden infant death syndrome (SIDS), but the efficacy of such devices for this use is unproven.ObjectiveTo test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants.DesignLongitudinal cohort study conducted from May 1994 through February 1998.SettingFive metropolitan medical centers in the United States.ParticipantsA total of 1079 infants (classified as healthy term infants and 6 groups of those at risk for SIDS) who, during the first 6 months after birth, were observed with home cardiorespiratory monitors using respiratory inductance plethysmography to detect apnea and obstructed breathing.Main Outcome MeasuresOccurrence of cardiorespiratory events that exceeded predefined conventional and extreme thresholds as recorded by the monitors.ResultsDuring 718 358 hours of home monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445 infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of those events with apnea, 70% included at least 3 obstructed breaths. The frequency of at least 1 extreme event was similar in term infants in all groups, but preterm infants were at increased risk of extreme events until 43 weeks' postconceptional age.ConclusionsIn this study, conventional events are quite common, even in healthy term infants. Extreme events were common only in preterm infants, and their timing suggests that they are not likely to be immediate precursors to SIDS. The high frequency of obstructed breathing in study participants would likely preclude detection of many events by conventional techniques. These data should be important for designing future monitors and determining if an infant is likely to be at risk for a cardiorespiratory event.

Journal ArticleDOI
01 Apr 2001-Chest
TL;DR: The interactions of the underlying critical illness and MV with the GI tract are complex and can manifest in a variety of clinical pictures.

Journal ArticleDOI
14 Nov 2001-JAMA
TL;DR: The data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-ONSet PD.
Abstract: ContextThe relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD.ObjectiveTo identify genetic risk factors for idiopathic PD.Design, Setting, and ParticipantsGenetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status.Main Outcome MeasuresLogarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis.ResultsTwo-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients.ConclusionsOur data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

Journal ArticleDOI
TL;DR: This work reports on generation of dopamine neurons from long-term cultures of human fetal mesencephalic precursor cells, which might serve as a useful source of human dopamine neurons for studying the development and degeneration ofhuman dopamine neurons and may further serve as an on-demand source of cells for therapeutic transplantation in patients with Parkinson's disease.

Journal ArticleDOI
TL;DR: Both PRC and scaphoid excision and 4-corner arthrodesis are motion-preserving options for the treatment of scapholunate advanced collapse arthritis with minimal subjective or objective differences in short-term follow-up evaluations.
Abstract: Two cohort populations of 19 patients from separate institutions performing exclusively either a scaphoid excision and 4-corner arthrodesis (lunate, capitate, hamate, and triquetrum) or proximal row carpectomy (PRC) for scapholunate advanced collapse arthritis were compared. There were no preoperative differences with respect to age, gender, dominance, stage of arthritis, or preoperative measures of pain and function. The length of the follow-up period averaged 28 months for the 4-corner arthrodesis group compared with 19 months for the PRC patients. At the follow-up examination wrist motion revealed no significant differences in the flexion-extension arc, averaging 81 degrees in the PRC patients and 80 degrees following 4-corner arthrodesis, which was 62% and 58%, respectively, of the opposite wrist. The 4-corner arthrodesis patients maintained greater radial deviation and total percent radial-ulnar deviation of the wrist. Grip strength averaged 71% for the PRC group compared with 79% for the 4-corner arthrodesis patients. Pain relief was similar using a variety of measures and patient satisfaction was equivalent. Function was similar except that the 4-corner arthrodesis patients scored significantly higher on the mental health component of the short form-36 health status survey. No differences were seen on the physical health component or an outcome scale specifically designed for the wrist. Both PRC and scaphoid excision and 4-corner arthrodesis are motion-preserving options for the treatment of scapholunate advanced collapse arthritis with minimal subjective or objective differences in short-term follow-up evaluations.

Journal ArticleDOI
TL;DR: This review focuses on the recent advances in investigations of the role of cell surface carbohydrates in tumor metastasis, and summarizes the results of extensive studies of endogenous lectins, their structure, carbohydrate specificity and biological functions with the major emphasis on the significance of lectin–cell surface carbohydrate interactions in a metastatic process.
Abstract: This review focuses on the recent advances in investigations of the role of cell surface carbohydrates in tumor metastasis. It also summarizes the results of extensive studies of endogenous lectins, their structure, carbohydrate specificity and biological functions with the major emphasis on the significance of lectin-cell surface carbohydrate interactions in a metastatic process. Numerous data demonstrate that malignant transformation is associated with various and complex alterations in the glycosylation process. Some of these changes might provide a selective advantage for tumor cells during their progression to more invasive and metastatic phenotype. Cell glycosylation depends on the expression and function of various glycosyltransferases and glycosidases. Recently, transfection of genes encoding various glysosyltransferases gene in sense and antisense orientation helped to bring direct evidence that changes in cell surface carbohydrates are important for the metastatic behavior of tumor cells. Cell surface carbohydrates affect tumor cell interactions with normal cells or with the extracellular matrix during metastatic spread and growth. These interactions can be mediated via tumor cell carbohydrates and their binding proteins known as endogenous lectins. The family of the discovered endogenous lectins is rapidly expanding. The number of C-type lectins has reached 50 and at least 10 galectins have been identified. The biological significance of the endogenous lectins and their possible role in tumor growth and metastasis formation has started to unravel. Some lectins recognize the 'foreign' patterns of cell surface carbohydrates expressed by microorganisms and tumor cells, and play a role in innate and adaptive immunity. It was shown that lectins affect tumor cell survival, adhesion to the endothelium or extracellular matrix, as well as tumor vascularization and other processes that are crucial for metastatic spread and growth.

Journal ArticleDOI
TL;DR: It is suggested that the excess number of women with Alzheimer's disease is due to the longer life expectancy of women rather than sex-specific risk factors for the disease.
Abstract: A large proportion of people with Alzheimer's disease (AD) are women; however, it is not clear whether this is due to higher risk of disease or solely to the larger number of women alive at ages when AD is common. Beginning in 1982, two stratified random samples of people aged > or =65 years in East Boston, Massachusetts underwent detailed, structured clinical evaluation for prevalent (467 people) and incident (642 people from a cohort previously ascertained to be disease-free) probable AD. The prevalence sample was followed for mortality for up to 11 years (through December 1992). The age-specific incidence of AD did not differ significantly by sex (for men vs. women, odds ratio = 0.92; 95% confidence interval (CI): 0.51, 1.67). Controlled for age, prevalence also did not differ significantly by sex (for men vs. women, odds ratio = 1.29; 95% CI: 0.67, 2.48). The increase in risk of mortality due to AD did not vary by sex. The odds ratio for women with AD compared with women without AD was 2.07 (95% CI: 1.21, 3.56). For men, the odds ratio was 2.22 (95% CI: 1.02, 4.81). These findings suggest that the excess number of women with AD is due to the longer life expectancy of women rather than sex-specific risk factors for the disease.

Journal ArticleDOI
TL;DR: It is found that the G protein enhances virion binding to target cells but plays no role in penetration after attachment, which is due in large part to the less efficient release of virions and the lower infectivity of the released virions.
Abstract: Respiratory syncytial virus (RSV) produces three envelope glycoproteins, the attachment glycoprotein (G), the fusion (F) protein, and the small hydrophobic (SH) protein. It had been assumed, by analogy with other paramyxoviruses, that the G and F proteins would be required for the first two steps of viral entry, attachment and fusion. However, following repeated passage in cell culture, a viable mutant RSV that lacked both the G and SH genes was isolated (R. A. Karron, D. A. Buonagurio, A. F. Georgiu, S. S. Whitehead, J. E. Adamus, M. L. Clements-Mann, D. O. Harris, V. B. Randolph, S. A. Udem, B. R. Murphy, and M. S. Sidhu, Proc. Natl. Acad. Sci. USA 94:13961–13966, 1997). To explore the roles of the G, F, and SH proteins in virion assembly, function, and cytopathology, we have modified the full-length RSV cDNA and used it to rescue infectious RSV lacking the G and/or SH genes. The three resulting viruses and the parental virus all contain the green fluorescent protein (GFP) gene that serves to identify infected cells. We have used purified, radiolabeled virions to examine virus production and function, in conjunction with GFP to quantify infected cells. We found that the G protein enhances virion binding to target cells but plays no role in penetration after attachment. The G protein also enhances cell-to-cell fusion, presumably via cell-to-cell binding, and enhances virion assembly or release. The presence or absence of the G protein in virions has no obvious effect on the content of F protein or host cell proteins in the virion. In growth curve experiments, the viruses lacking the G protein produced viral titers that were at least 10-fold lower than titers of viruses containing the G protein. This reduction is due in large part to the less efficient release of virions and the lower infectivity of the released virions. In the absence of the G protein, virus expressing both the F and SH proteins displayed somewhat smaller plaques, lower fusion activity, and slower viral entry than the virus expressing the F protein alone, suggesting that the SH protein has a negative effect on virus fusion in cell culture.

Journal ArticleDOI
05 Jan 2001-AIDS
TL;DR: The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.
Abstract: Objective: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. Design: Prospective, randomized, double-blind, multicenter. Methods: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ART378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). Results: Mean baseline HIV-1 RNA was 4.9 logic copies/ml in both groups and CD4 cell count was 398 X 10 6 /l and 310 X 10 6 /l in Groups I and II respectively, In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (<50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC 50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. Conclusions: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.

Journal ArticleDOI
TL;DR: In this paper, low-income urban parents of color enrolled in a parent training study were interviewed to understand what motivated their participation and what led 30% of them to subsequently drop out.
Abstract: What Motivates Participation and Dropout Among Low-Income Urban Families of Color in a Prevention Intervention?* Low-income urban parents of color enrolled in a parent training study were interviewed to understand what motivated their participation and what led 30% of them to subsequently drop out. Most enrolled because they wanted to be better parents. Most dropped out because of time and schedule constraints. Retention was higher when parents' motivations for participation matched program goals. Program location and qualities of the recruiter were cited most often as important; financial compensation was cited least often as important. Key Words: attrition, low-income families, minority, parent training, participation, prevention. Parent training during early childhood has been identified as a potentially powerful intervention for promoting positive parenting skills and reducing risk factors associated with antisocial behavior in children (Gross, Fogg, & Tucker, 1995; Kazdin, 1997; Webster-Stratton, 1998). However, parent training studies are plagued by methodological flaws that affect most prevention studies: low participation and attendance rates and high attrition rates (Coie et al., 1993; Given, Keilman, Collins, & Given, 1990; Motzer, Moseley, & Lewis, 1997; Siddiqui, Flay, Phil, & Hu, 1996). Poor participation and high attrition rates are particularly apparent in research using low-income families of color. For example, in a study of the effectiveness of the Effective Black Parenting Program for inner city African-American families, Myers et al. (1992) reported participation rates as low as 13% and attendance rates at parent group meetings as low as 33%. Study validity is further compromised by the fact that low participation and retention tend to be systematically related to those risk factors that also are associated with poor childhood outcomes including low socioeconomic status, single parenthood, and lower parent educational levels (Forehand, Middlebrook, Rogers, & Steffe, 1983; Haggerty et al., 2000; Spoth, Goldberg, & Redmond, 1999; Weinberger, Tublin, Ford, & Feldman, 1990). These biases in participation and drop-out rates make it difficult to interpret the effectiveness of parent training for low-income families. Further, these biases make it difficult to determine whether the successes reported for parent training among middle-- class European-American families can be generalized to low-- income families of color (Forehand & Kotchick, 1996). To increase enrollment among low-income populations, researchers have typically implemented a range of costly incentives, such as monetary rewards for attending parent groups, monetary rewards for completing research assessments, gifts and door prizes, free food and childcare, and transportation (Cipaldi & Patterson, 1987; Conduct Problems Prevention Research Group, 1999; Dumka, Garza, Roosa & Stoerzinger, 1997; Stoy et al., 1995). However, it is not clear the degree to which these incentives are, in fact, important to the members of the target population (Moore, 1997; Saylor, Elksnin, Farah, & Pope, 1990). For example, parents participating in the Fast Track prevention intervention were paid $15 for every 2-hour class they attended (Orrell-Valente, Pinderhughes, Valente, Laird, & Conduct Problems Research Groups, 1999). Although enrollment rates were high, parent attendance at these groups averaged 56.3% of sessions. In a study of parent skills training for parents of middleschool children, Irvine and others (Irvine, Biglan, Smolkowski, Metzler, & Ary, 1999) offered a series of payments to parents for varying levels of participation. These included $10 for allowing the recruiter to come to their home, another $10 for attending at least 4 of the first 6 parenting classes, $10 for attending at least 4 of the last 6 classes, and an additional $10 for attending a total of 10 of the 12 classes. …

Journal ArticleDOI
TL;DR: There were few racial differences in the association of social relationships with disability, with the possible exception of instrumental support, which may allude to possible sociocultural Differences in the experience of instrumentalSupport exchanges.
Abstract: Objectives. We examined the association of structural and functional aspects of social relationships with change in disability, and the degree to which race modifies these associations. Methods. Data are from a population-based sample of 4,136 African Americans and Whites aged ^ 65 living in North Carolina. Disability data were collected during seven consecutive yearly interviews and summarized in two outcome measures. Measures of social relationships included five measures representing network size, extent of social interaction, and specific type of relationships, as well as instrumental and emotional support. Weighted proportional odds models were fitted to model disability as a function of baseline social network and support variables, and the interaction of each variable with follow-up time. Results. Network size and social interaction showed significant negative associations with disability risks, which did not vary by race, or as a function of time. Social interaction with friends was associated with a reduced risk for disability, but social interaction with children or relatives was not related to disability. Instrumental support was associated with a significantly increased disability risk, with a greater adverse effect among Whites than African Americans. Emotional support was not associated with disability, but a protective effect for ADL disability was found after controlling for its intercorrelation with instrumental support. Discussion. The findings provide further evidence for the role of social relationships in the disablement process, although not all types of social relationships may be equally beneficial. Furthermore, these associations may be more complex than simple causal effects. There were few racial differences in the association of social relationships with disability, with the possible exception of instrumental support, which may allude to possible sociocultural differences in the experience of instrumental support exchanges.

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TL;DR: Mechanisms that may contribute to ANK cell activity are suggested, including modulation of receptor expression to favor activation, up-regulation of cytotoxic effector molecules, and acquisition of new cytolytic pathways.
Abstract: NK-92, a highly cytotoxic, interleukin-2 (IL-2)-dependent human natural killer (NK) cell line, has been of interest for basic and translational research. We report on a comprehensive analysis of NK-92 for factors implicated in NK cytotoxicity to elucidate factors underlying NK-92's high cytolytic activity and target range. Thus, we hope to develop a method to identify patients best suited to NK-92 immunotherapy. In addition, as a model system, we hope to increase understanding of the basis for the elevated activity exhibited by activated NK (ANK) cells. NK-92 exhibits an unusual receptor expression profile, expressing a relatively large number of activating (NKp30, NKp46, 2B4, NKGD, E, CD28) receptors. Conversely, it expresses few inhibitory receptors (NKGA/B, low levels of KIR2DL4, ILT-2), lacking most of the killer inhibitory receptors (KIRs) clonally expressed on normal NK cells. In addition, NK-92 expresses high levels of molecules involved in the perforin-granzyme cytolytic pathway as well as additio...

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TL;DR: Levels of the proinflammatory cytokine tumor necrosis factor α (TNFα) are increased in postmortem brain and cerebral spinal fluid from patients with Parkinson's disease and these data strongly suggest that TNFα mediates cell death in a sensitive population of DA neurons and support the potential involvement of pro inflammatory cytokines in the degeneration ofDA neurons in PD.

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TL;DR: High blood pressure was not associated with an increased risk of AD in logistic regression models adjusted for age, sex, and level of education.
Abstract: Background It is uncertain whether high blood pressure increases the risk of developing Alzheimer disease (AD). Objective To examine the association between incident AD and blood pressure measured up to 13 years before diagnosis. Design Longitudinal cohort study conducted from 1982 to 1988, with blood pressure measured every 3 years in home interviews, and in 1973 for a portion (60%) of the sample. Setting Community of East Boston, Mass. Participants Six hundred thirty-four subjects 65 years or older and without AD were selected as a stratified random sample of participants of the East Boston Established Populations for Epidemiologic Studies of the Elderly. Main Outcome Measure Alzheimer disease was diagnosed by a neurologist using a structured clinical evaluation. Results High blood pressure was not associated with an increased risk of AD in logistic regression models adjusted for age, sex, and level of education. There was no association with systolic pressure measured 13 years before diagnosis (odds ratio = 1.03/10 mm Hg; 95% confidence interval, 0.80-1.32) and an inverse association with systolic pressure measured 4 years before diagnosis (odds ratio = 0.82/10 mm Hg; 95% confidence interval, 0.72-0.95). Associations for diastolic pressure were in the same direction as those for systolic pressure except with wider confidence intervals. The odds ratios were not materially different with further adjustment for cardiovascular risk factors and diseases. Conclusion In this large community study, high blood pressure was not associated with an increased risk of AD.