Publications

OBJECTIVE

Glucocorticoid (GC) excess induces alterations in bone metabolism that weaken bone structure and increase fracture risk. The aim of this study was to identify genes associated with bone metabolism in GC-treated mice, by performing a microarray analysis.

METHODS

Long bones from mice exposed to GC excess were collected after 0, 7, 28, and 56 days of treatment, to measure bone microarchitecture and extract RNA for microarray analyses.

RESULTS

Bone loss in this animal model was confirmed by changes in bone turnover markers as well as bone architecture, as measured by microfocal computed tomography. GC excess induced an early up-regulation of genes involved in osteoclast activation, function, and adipogenesis, which peaked on day 7. The expression of genes associated with osteoclast cytoskeletal reorganization and genes associated with matrix degradation peaked on day 28. On day 28 and day 56, the expression of genes associated with osteoblast activation and maturation was decreased from baseline, while the expression of Wnt antagonists was increased. In addition, the expression of genes expressed in osteocytes associated with bone mineralization was significantly higher at the later time points, day 28 and day 56. Reverse transcription-polymerase chain reaction confirmed the results of microarray analysis in selected genes.

CONCLUSION

GC excess is associated with early activation of genes associated with osteoclastogenesis and adipogenesis and a later suppression of genes associated with osteogenesis and mineralization. Novel interventions with agents that modulate either Wnt signaling or mineralization may be effective in GC-induced osteoporosis.

OBJECTIVES

To provide chlamydia and gonorrhea screening and treatment to adolescents presumed to be at high risk, school screening was conducted among the 11th and 12th graders in San Francisco.

STUDY DESIGN

Two schools in neighborhoods with high chlamydia and gonorrhea rates and student populations > or = 15% black were chosen. Students viewed a 10-minute presentation and received test kits. Students decided in a private bathroom stall whether to test. All students were encouraged to return a test kit (whether they returned a urine specimen).

RESULTS

Of 967 eligible students, 853 (88%) were in attendance. Of these, 21 (2%) declined to participate and 537 (63%) returned a specimen for testing. Students who tested were predominately heterosexual (93%) and nonwhite (99%). No students tested positive for gonorrhea; 7 (1.3%) tested positive for chlamydia. Positivity was 2.2% (5 of 227) for female students and 0.6% (2 of 310) for male students. Positivity by race/ethnicity was 5.4% (4 of 74) for blacks, 2.0% (2 of 98) for Hispanics, 0.3% (1 of 342) for Asian/Pacific Islanders, and 0% (0 of 4) for whites. The highest positivity was among black female students: 9.3% (4 of 43). Not including planning and follow-up, each case identified used 63 staff hours.

CONCLUSIONS

Despite high participation among students attending school in high morbidity neighborhoods, few infections were identified. This is likely because students have low rates of sexual activity and do not necessarily attend neighborhood schools. Screening used substantial resources. Sexually transmitted disease control programs considering school screening should consider local epidemiology and whether schools have substantial proportions of students likely at high risk for sexually transmitted diseases.

OBJECTIVE

Hepatic ischemia-reperfusion can be associated with acute lung injury. Alveolar epithelial type II cells (ATII) play an important role in maintaining lung homeostasis in acute lung injury.

DESIGN

To study potentially new mechanisms of hepatic ischemia-reperfusion-induced lung injury, we examined how liver ischemia-reperfusion altered the proteome of ATII.

SETTING

Laboratory investigation.

SUBJECTS

Spontaneously breathing male Zucker rats.

INTERVENTIONS

Rats were anesthetized with isoflurane. The vascular supply to the left and medial lobe of the liver was clamped for 75 mins and then reperfused. Sham-operated rats were used as controls. After 8 hrs, rats were killed.

MEASUREMENTS AND MAIN RESULTS

Bronchoalveolar lavage and differential cell counts were performed, and tumor necrosis factor-alpha and cytokine-induced neutrophil chemotactic factor-1 in plasma were determined by enzyme-linked immunosorbent assay. ATII were isolated, lysed, tryptically digested, and labeled using isobaric tags (iTRAQ). The samples were fractionated by cation exchange chromatography, separated by high-performance liquid-chromatography, and identified using electrospray tandem mass spectrometry. Spectra were interrogated and quantified using ProteinProspector. Quantitative proteomics provided quantitative data for 94 and 97 proteins in the two groups. Significant changes in ATII protein content included 30% to 40% increases in adenosine triphosphate synthases, adenosine triphosphate/adenosine diphosphate translocase, and catalase (all p < .001). Following liver ischemia-reperfusion, there was also a significant increase in the percentage of neutrophils in bronchoalveolar lavage (48% +/- 26%) compared with sham-operated controls (5% +/- 3%) (p < .01), and plasma tumor necrosis factor-alpha levels were also significantly increased.

CONCLUSIONS

The proteins identified by quantitative proteomics indicated significant changes in moderators of cell metabolism and host defense in ATII. These findings provide new insights into possible mechanisms responsible for hepatic ischemia-reperfusion-related acute lung injury and suggest that ATII cells in the lung sense and respond to hepatic injury.

BACKGROUND

Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects.

OBJECTIVE

We compared anthropometric and magnetic resonance imaging (MRI)-based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects.

DESIGN

The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors.

RESULTS

In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r

CONCLUSION

Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects.

OBJECTIVE

Inflammation is a potential mechanism to explain the accelerated atherosclerosis observed in HIV- and hepatitis C virus (HCV)-infected persons. We evaluated C-reactive protein (CRP) in HIV-infected and HIV/HCV-coinfected individuals in the era of effective antiretroviral (ARV) therapy.

DESIGN

Cross-sectional study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort and controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study.

METHODS

CRP levels were measured in 1135 HIV-infected participants from the FRAM cohort and 281 controls from the CARDIA study. The associations of HIV and HIV/HCV infection with CRP levels were estimated by multivariable linear regression.

RESULTS

Compared with controls, HIV monoinfection was associated with an 88% higher CRP level in men (P < 0.0001) but with no difference in women (5%; P = 0.80) in multivariate analysis. CRP levels were not associated with ARV therapy, HIV RNA level, or CD4 cell count. Compared with controls, HIV/HCV coinfection was associated with a 41% lower CRP level in women (P = 0.012) but with no difference in men (+4%; P = 0.90). Among HIV-infected participants, HCV coinfection was associated with 50% lower CRP levels after multivariable analysis (P < 0.0001) in men and women. Greater visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were strongly associated with CRP levels. Among HIV-infected participants, CRP levels were 17% (P < 0.001) and 21% (P = 0.002) higher per doubling of VAT and SAT; among controls, CRP levels were 34% (P < 0.001) and 61% (P = 0.009) higher, respectively.

CONCLUSIONS

In the absence of HCV coinfection, HIV infection is associated with higher CRP levels in men. HCV coinfection is associated with lower CRP levels in men and women.