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Biomedical subjects

James Brown

Publications and source records attributed to James Brown.

31 records · Page 2Linked to original sources
PubMed2004

Differential expression of cholesterol hydroxylases in Alzheimer's disease.

Cholesterol is eliminated from neurons by oxidization, which generates oxysterols. Cholesterol oxidation is mediated by the enzymes cholesterol 24-hydroxylase (CYP46A1) and cholesterol 27-hydroxylase (CYP27A1). Immunocytochemical studies show that CYP46A1 and CYP27A1 are expressed in neurons and some astrocytes in the normal brain, and CYP27A1 is present in oligodendrocytes. In Alzheimer's disease (AD), CYP46A1 shows prominent expression in astrocytes and around amyloid plaques, whereas CYP27A1 expression decreases in neurons and is not apparent around amyloid plaques but increases in oligodendrocytes. Although previous studies have examined the effects of synthetic oxysterols on the processing of amyloid precursor protein (APP), the actions of the naturally occurring oxysterols have yet to be examined. To understand the role of cholesterol oxidation in AD, we compared the effects of 24(S)- and 27-hydroxycholesterol on the processing of APP and analyzed the cell-specific expression patterns of the two cholesterol hydroxylases in the human brain. Both oxysterols inhibited production of Abeta in neurons, but 24(S)-hydroxycholesterol was approximately 1000-fold more potent than 27-hydroxycholesterol. The IC(50) of 24(S)-hydroxycholesterol for inhibiting Abeta secretion was approximately 1 nm. Both oxysterols induced ABCA1 expression with IC(50) values similar to that for inhibition of A beta secretion, suggesting the involvement of liver X receptor. Oxysterols also inhibited protein kinase C activity and APP secretion following stimulation of protein kinase C. The selective expression of CYP46A1 around neuritic plaques and the potent inhibition of APP processing in neurons by 24(S)-hydroxycholesterol suggests that CYP46A1 affects the pathophysiology of AD and provides insight into how polymorphisms in the CYP46A1 gene might influence the pathophysiology of this prevalent disease.

Adenoviridae↗
PubMed2004

A case-control study of syphilis among men who have sex with men in New York City: association With HIV infection.

OBJECTIVE: The objective of this study was to determine factors associated with syphilis among men who report sex with other men in New York City. DESIGN, SETTING AND STUDY SUBJECTS: We conducted a case-control study among 88 men who reported sex with men in the previous year, 18 to 55 years old and diagnosed with primary or secondary syphilis during 2001; and 176 control subjects frequently matched by age and type of health provider. RESULTS: HIV prevalence among syphilis cases was 48% compared with 15% among control subjects (P <0.001). Variables associated with syphilis in a multivariate model were HIV infection (odds ratio [OR], 7.3; 95% confidence interval [CI], 3.5-15.4), income >$30,000 per year (OR, 2.7; CI, 1.4-5.2), and barebacking (OR, 2.6; CI, 1.4-4.8). The median time since HIV diagnosis for HIV-positive was 6 years for cases and 7 years for control subjects (P = 0.70). Among HIV-infected participants, syphilis cases were more likely than control subjects to report being on antiretroviral therapy (69% vs. 44%, P = 0.05) and to report having undetectable viral load (58% vs. 24%, P = 0.02). CONCLUSION: HIV infection was strongly associated with syphilis in this study. High-risk behavior reported by both cases and control subjects indicates the potential for increased HIV transmission.

Adolescent↗
PubMed2004

The cellular biochemistry of cholesterol and statins: insights into the pathophysiology and therapy of Alzheimer's disease.

The causes of late onset Alzheimer disease (AD) are poorly understood. Although beta-amyloid (Abeta) is thought to play a critical role in the pathophysiology of AD, no genetic evidence directly ties Abeta to late onset AD. This suggests that the accumulation of Abeta and neurodegeneration associated with AD might result from an abnormality that indirectly affects Abeta production or accumulation. Increasing evidence suggests that abnormalities in the metabolism of cholesterol and related molecules, such as cholseterol esters and 24(S) hydroxycholesterol might contribute to the pathophysiology of late onset AD by increasing production of Abeta. 24(S) Hydroxycholesterol is a member of a family of oxidized cholesterol catabolites, termed oxysterols, which function to regulate export of cholesterol from the cell and transcription of genes related to cholesterol metabolism. Cholesterol esters are cholesterol derivatives used for cholesterol storage. Levels of 24(S) hydroxycholesterol increase with AD. Polymorphisms in several different genes important for cholesterol physiology are associated with an increased load or level of Abeta in AD. These genes include apolipoprotein E, cholesterol 24 hydroxylase (Cyp46), acyl-CoA:cholesterol acetyltransferase (ACAT), and the cholesterol transporter ABCA1. Other studies show that levels of cholesterol, or its precursors, are elevated in subjects early in the course of AD. Finally, studies of the processing of amyloid precursor protein show that cholesterol and its catabolites modulate amyloid precursor protein processing and Abeta production. These lines of evidence raise the possibility that genetic abnormalities in cholesterol metabolism might contribute to the pathophysiology of AD.

Alzheimer Disease↗
PubMed2004

A focus group study of factors influencing African-American men's prostate cancer screening behavior.

This study was conducted to identify the factors perceived by African-American men as influencing their behavior relative to prostate cancer screening. A total of 49 African-American men, age 40 and above, participated in 10 focus group discussions in Florida. Data collection was between October 12, 2001 and March 9, 2002 in Tallahassee, Tampa, and Miami. Data analysis was conducted using a comprehensive ethnographical analysis, including the use of an ethnographical retrieval program, Nonnumerical Unstructured Data Indexing Searching and Theorizing (QSR NUD*IST 4.0) software. Factors identified as influencing prostate cancer screening participation by African-American men were impediments to prostate cancer screening; positive outcome beliefs associated with prostate cancer screening; social influence; negative outcome beliefs associated with prostate cancer screening; resources or opportunities that facilitate prostate cancer screening; prostate cancer knowledge; perceived susceptibility to prostate cancer; perceived threat of prostate cancer; perceived severity of prostate cancer; positive health activities; illness experience; and prostate cancer screening intervention message concept, message source, and message channel. The results of this study may offer an excellent guide to designing effective, culturally sensitive, and relevant interventions, which would increase African-American men's participation in prostate cancer screening.

Adult↗
PubMed2003

Cleavage of fragments containing DNA mismatches by enzymic and chemical probes.

We prepared synthetic 50-mer DNA duplexes, each containing four mismatched base-pairs in similar positions. We examined their cleavage by DNases I and II, micrococcal nuclease (MNase), methidiumpropyl-EDTA-Fe(II) [MPE-Fe(II)] and hydroxyl radicals. We find that single mismatches only produce subtle changes in the DNase I-cleavage pattern, the most common of which is attenuated cleavage at locations 2-3 bases on the 3'-side of the mismatch. Subtle changes are also observed in most of the DNase II-cleavage patterns, although GT and GG inhibit the cleavage over longer regions and generate patterns that resemble footprints. MNase cleaves the heteroduplexes at the mismatches themselves (except for CC), and in some cases cleaves CpG and CpC steps. None of the mismatches causes any change in the cleavage patterns produced by hydroxyl radicals or MPE-Fe(II). We also examined the cleavage patterns of fragments containing tandem GA mismatches in the sequences RGAY/RGAY and YGAR/YGAR (R, purine; Y, pyrimidine). RGAY causes only subtle changes in the cleavage patterns, which are similar to those seen with single mismatches, except that there are no changes in MNase cleavage. However, YGAR inhibits DNases I and II cleavage over 4-6 bases, and attenuates MPE-Fe(II) and hydroxyl radical cleavage at 2 bases. These changes suggest that this mismatch has a more pronounced effect on the local DNA structure. These changes are discussed in terms of the structural and dynamic effects of each mismatch.

Base Pair Mismatch↗
PubMed2003

Mechanisms of cancer invasion of the mandible.

There is little evidence that the tumor enters the mandible preferentially through the occlusal surface, the periodontal membrane, or named foramina. Tumor enters the mandible at the point of contact, which is often at the junction of the attached and reflected mucosa, which lies below the crest of the ridge in all but grossly resorbed mandibles. Angulation of the bone cut in rim or marginal resection of the mandible is advised. The erosive pattern of disease is associated with shallow mandibular invasion and smaller tumors in the soft tissue. This finding supports the principle of marginal resection in such cases. There is little evidence to support the principle that the tumor spreads preferentially along the inferior alveolar nerve or the bone marrow. The inclusion of the neurovascular bundle in marginal resections of the mandible is not necessary. Preoperative assessment should include plain radiography combined with a sensitive scan (bone scintigraphy, single photon emission computerized tomography, or MRI) and inspection of the bone surface after periosteal stripping at the time of the resection.

Female↗
PubMed2002

Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects.

Mucociliary clearance is determined by ciliary activity and rheology of airway surface liquid. To test the hypothesis that mucociliary clearance would increase after inhalation of an osmotically active agent that would increase the volume of airway surface liquid, we measured mucociliary clearance in 16 normal subjects after inhalation of varying tonicities of saline alone, and after pretreatment with a Na+ channel blocker (amiloride). Subjects inhaled vehicle (0.12% saline) or amiloride, followed by inhalation of 0.12, 0.9, or 7% saline. Subsequently, mucociliary clearance rates were measured by gamma scintigraphy of inhaled 99mTc Fe2O3. Mucociliary clearance of whole and peripheral lung was increased (approximately twofold) after inhalation of increasing concentrations of saline (p < 0.04). Pretreatment with amiloride increased mucociliary clearance rates (approximately twofold) after inhalation of 0.12 and 0.9% saline (p < 0.05), but not 7% saline. The rates of mucociliary clearance by pretreatment with amiloride and 7% saline alone (approximately 1.4% per minute) approached the rapid mucociliary clearance rates (approximately 2.0% per minute) reported in systemic pseudohypoaldosteronism, which has loss-of-function mutations of the epithelial Na+ channel and an increased volume of airway surface liquid. We conclude that maneuvers that increase the volume of airway surface liquid are associated with increased rates of mucociliary clearance in normal subjects.

Administration, Inhalation↗
PubMed2002

Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur.

Insulin-like growth factor II receptor (IGF2R) is a multifunctional cell surface receptor implicated in tumour suppression. Its growth inhibitory activity has been associated with an ability to bind IGF-II. IGF2R contains 15 homologous extracellular domains, with domain 11 primarily responsible for IGF-II binding. We report a 1.4 A resolution crystal structure of domain 11, solved using the anomalous scattering signal of sulfur. The structure consists of two crossed beta-sheets forming a flattened beta-barrel. Structural analysis identifies the putative IGF-II binding site at one end of the beta-barrel whilst crystal lattice contacts suggest a model for the full-length IGF2R extracellular region. The structure factors and coordinates of IGF2R domain 11 have been deposited in the Protein Data Bank (accession codes 1GP0 and 1GP3).

Amino Acid Sequence↗
PubMed2002

Methods for data mining from large multinational surveillance studies.

Traditionally, large surveillance studies have been analyzed by the use of the MICs at which 90% of isolates tested are inhibited (MIC(90)s), MIC(50)s, frequency distributions, and percent susceptibility. In the past, these approaches have proved satisfactory for the monitoring of resistance. From these traditional uses, one can readily detect an increase in MICs for organism and drug combinations. Now that large surveillance studies have been conducted for a number of years and databases have grown to include a large number of datum points, new approaches to the extraction of useful information from these studies are needed. The present study proposes approaches, including the use of antibiotypes, principal components analysis, phylogenetics, and population genetic analysis, to the evaluation of data from large multinational surveillance studies. Application of these types of analyses can be used to describe genetic diversity, analyze changes in susceptibility patterns over time, and possibly, shed light on the origins and evolution of antimicrobial resistance. As global surveillance studies become more common and new questions concerning the evolution of resistance are raised, innovative approaches to analysis of the data will increase in importance.

Algorithms↗
PubMedDate not supplied

Comparison of laparoscopic pyeloplasty with and without robotic assistance.

OBJECTIVES: The benefits of laparoscopic surgery with robotic assistance (da Vinci Robotic Surgical System, Intuitive Surgical, Sunnyvale, CA) includes elimination of tremor, motion scaling, 3D laparoscopic vision, and instruments with 7 degrees of freedom. The benefit of robotic assistance could be most pronounced with reconstructive procedures, such as pyeloplasty. We aimed to compare laparoscopic pyeloplasty, with and without robotic assistance, during a surgeon's initial experience to determine whether robotic assistance has distinct advantages over the pure laparoscopic technique. METHODS: We retrospectively compared the first 7 laparoscopic pyeloplasties with the first 7 robotic pyeloplasties performed by a single surgeon. All patients were preoperatively evaluated with computed tomographic angiography with 3D reconstruction to image crossing vessels at the ureteropelvic junction. All patients were followed up by lasix renograms and routine clinic visits. RESULTS: Patients were similar with respect to mean age (34 in laparoscopic pyeloplasty group vs 32 in the robotic pyeloplasty group), operative time (5.2 hours vs 5.4 hours), estimated blood loss (40 mL vs 60 mL), and hospital stay (3 days vs 2.5 days). Two patients in the laparoscopic pyeloplasty group had small anastomotic leaks managed conservatively, and one patient in the robotic pyeloplasty group had a febrile urinary tract infection necessitating treatment with intravenous antibiotics. Another patient in the robotic pyeloplasty group was readmitted with hematuria that was treated conservatively without transfusion. No recurrences were detected in either group. CONCLUSIONS: Operating times and outcomes during the learning curve for laparoscopic pyeloplasty were similar to those for robotic pyeloplasty. Long-term data with greater experience is needed to make definitive conclusions about the superiority of either technique and to justify the expense of robotic pyeloplasty.

Adult↗