Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature.

The CD4(+)CD25(+) lineage of regulatory T (Treg) cells plays a key role in controlling immune and autoimmune responses and is characterized by a unique transcriptional signature. The transcription factor Foxp3 had been thought to determine the Treg cell lineage, a hypothesis challenged by recent observations. We have performed a cross-sectional analysis of the Treg cell signature in Treg-like cells generated under a number of conditions, with or without Foxp3, to delineate the elements that can be ascribed to T cell activation, interleukin-2, transforming growth factor-beta (TGF-beta) signaling, or Foxp3 itself. These influences synergized to determine many of the signature's components. Much of the Treg cell signature was not ascribable to Foxp3 because it contained gene clusters that are coregulated with, but not transactivated by, Foxp3. Thus, a higher level of regulation upstream of Foxp3 determines the lineage, distinct from elements downstream of Foxp3 that are essential for its regulatory properties.

Rahnella aquatilis bacteremia from a suspected urinary source.

A 76-year-old male with prostatic hyperplasia presented with acute pyelonephritis. Blood cultures yielded Rahnella aquatilis. Treatment with intravenous followed by oral levofloxacin resulted in cure. Important characteristics of this organism include its biochemical similarities to Enterobacter agglomerans, its apparent ability to cause bacteremia from a renal focus, and its response to quinolone therapy.

Lipodystrophy and dyslipidemia among patients taking first-line, World Health Organization-recommended highly active antiretroviral therapy regimens in Western India.

OBJECTIVE: To determine the prevalence of lipodystrophy, dyslipidemia, and hyperglycemia among HIV-infected patients taking long-term, first-line, World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens in India. DESIGN: : Cross-sectional study. METHODS: Asymptomatic, antiretroviral-naive patients and those treated for > 1 year with zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) and stavudine (d4T)/3TC/NVP were subjectively assessed for lipodystrophy (lipoatrophy, lipohypertrophy, and mixed patterns), and lipid profiles were determined after an overnight fast. The US National Cholesterol Education Program III guidelines were used to define dyslipidemia (total cholesterol > or = 200 mg/dL, low-density lipoprotein cholesterol > or = 130 mg/dL, triglycerides > or = 150 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, and total cholesterol/high-density lipoprotein cholesterol ratio > or = 6.5). Prevalence and risk factors associated with these complications were determined. RESULTS: Of the 306 patients (126 controls, 30 on ZDV/3TC/NVP, and 150 on d4T/3TC/NVP), the prevalence of lipodystrophy was 46.1%, and lipoatrophy was significantly associated with d4T use. The prevalence of dyslipidemia and fasting hyperglycemia was significantly higher in the treatment groups. Proportion of patients with high-density lipoprotein > or = 60 mg/dL was significantly higher in the treatment groups; however, this had little impact on the total cholesterol/high-density lipoprotein ratio. CONCLUSION: There is a high prevalence of lipodystrophy, dyslipidemia, and hyperglycemia in patients taking long-term WHO-recommended generic HAART in western India. Interventions to address these complications need to be incorporated into antiretroviral scale-up programs, including improving access to alternative less-offending drugs like tenofovir and abacavir.