Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by ...IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.
Osteomyelitis is a common and challenging condition for hospitalists to manage. The 3 main types of osteomyelitis that are commonly seen in the hospital setting are 1) contiguous spread from ...decubitus or diabetic ulcers, 2) hematogenous spread, such as in vertebral or long bone metaphyses, and 3) infections associated with a prosthetic joint. In patients with diabetes, osteomyelitis is the underlying cause of about 20% of foot infections, and greatly increases the chance that the patient will eventually need an amputation and be subject to perioperative risks. Osteomyelitis from hematogenous spread is increasing. The prevalence of vertebral osteomyelitis is also increasing, particularly in intravenous drug users and patients treated with immune-modulating agents. Prosthetic joint infections are perhaps the most challenging type to treat, and require hospitalists, orthopedic surgeons, and infectious disease specialists to work closely together to plan for effective treatment. Due to increasing antibiotic resistance, the microorganisms involved are also proving more difficult to treat. Emerging resistance to the commonly used antibiotics is resulting in changes in treatment choices. Community-acquired methicillin-resistant Staphylococcus aureus is commonly seen, and there is increasing concern about emerging vancomycin resistance. Treatment of osteomyelitis is still based largely on expert opinion rather than evidence from controlled studies.
Cervical and plasma samples obtained twice, at 2-week intervals, from 49 human immunodeficiency virus type 1 (HIV-1)-positive women were assayed for HIV-1 RNA. More than 100 copies of HIV-1 RNA were ...detected in cervical swab supernatants (CSS) from 24 (49%) of 49 women. HIV-1 RNA in CSS was detected in younger women with higher levels of plasma HIV-1 RNA (median, 31,984 vs. 2880 copies/mL; P = .0004), lower CD4 cell counts (median, 190 vs. 390 per mm3; P = .012), and lower CD4 cell percents (median, 16% vs. 25%; P = .03). In multiple logistic regression analysis, only plasma HIV-1 RNA was significantly associated with CSS HIV-1 RNA, with an odds ratio of 4.79/log10 increase in plasma HIV-1 RNA (95% confidence interval, 1.4–16; P = .01). Detection of HIV-1 RNA in cervical secretions is primarily associated with increased plasma HIV-1 RNA.
Cytomegalovirus (CMV) is an important pathogen after allogeneic transplantation. However, few studies have examined CMV reactivation after autologous peripheral blood stem cell transplantation ...(APBSCT) to treat multiple myeloma (MM), especially in the setting of the newer chemotherapeutic agents and/or 2 sequential APBSCTs (ie, tandem transplantation). A retrospective chart review of patients with MM who underwent either single APBSCT or tandem transplantation was conducted to evaluate the incidence, risk factors, and outcomes of CMV infection at a single institution. A total of 104 patients with MM underwent transplantation during the study period, including 66 patients who received tandem transplantation. The majority of patients (66 of 104; 63.5%) were CMV-seropositive, and CMV viremia was frequently detected in this subgroup (32 of 66; 48.5%). No primary CMV infections were identified. CMV reactivation was more common in recipients of tandem transplantation than in recipients of single APBSCT ( P < .001). In addition, patients who developed CMV viremia were more likely to have received conditioning therapy with melphalan, bortezomib, dexamethasone, and thalidomide compared with those without CMV reactivation ( P = .015). However, on multiple logistic regression analysis, only receipt of tandem transplantation was significantly associated with CMV reactivation (odds ratio, 5.112; 95% confidence interval, 1.27-20.60; P = .022). Febrile episodes of CMV viremia were observed in 17 patients (17 of 32; 53.1%), and invasive CMV disease was diagnosed in 1 patient. Our data suggest that CMV reactivation after APBSCT for MM is relatively common, and that viremia is often associated with fever. CMV surveillance should be considered, especially when tandem transplantation is performed using combination chemotherapy with high-dose melphalan.
Six human immunodeficiency virus (HIV)-positive women were studied weekly over 8 weeks to detect HIV RNA in plasma and cervical secretions and proviral DNA in cervical, vaginal, and cervicovaginal ...lavage samples by polymerase chain reaction (PCR) amplification techniques. In cervical swab samples, cell-free HIV RNA was detected more frequently than cell-associated HIV proviral DNA (22/48 vs. 7/48, respectively). Cervical HIV RNA was consistently detected in 2 women with plasma HIV RNA >100,000 copies/mL but was not detected in 2 women with plasma HIV RNA < 10,000 copies/mL, regardless of menstruation status. HIV-specific IgA was detected in the plasma of 2 women and in at least 1 cervicovaginal lavage sample from all 6 women. Thus, quantitation of cervical HIV RNA can be accomplished by PCR techniques and may be useful in evaluating genital viral shedding.
Local exposure of the sites of elicitation (ears) of contact hypersensitivity (CHS) in mice to relatively modest doses of ultraviolet radiation (FS40 sunlamps) daily for 4 days prior to challenge in ...previously immunized animals results in significant enhancement of the CHS response as measured by 24-h swelling. This effect was seen in both C3H/HeJ and A/J mice and with the use of both trinitrochlorobenzene and dinitrofluorobenzene as contact sensitizers. Doses of PUVA (parenteral administration of 8-methoxypsoralen followed by exposure to UVA, 320–400 nm, radiation) up to that which can systemically suppress the induction of CHS failed to affect the elicitation of CHS. Irritation of the sites of elicitation of CHS by applications of turpentine also failed to affect the CHS elicitation reaction. Enhancement of the CHS elicitation response by local ultraviolet radiation exposure prior to challenge appears to be a specific photobiologic event.
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