Nonhemolytic antibody-induced loss of erythrocyte surface antigen

Transfusion of red blood cells (RBCs) into patients with anti-donor RBC antibodies (crossmatch-incompatible transfusion) can result in lethal antibody-mediated hemolysis. Less well appreciated is the ability of anti-RBC antibodies to specifically remove their target antigen from donor RBCs without compromising cell survival or adversely affecting the transfusion recipient. In an effort to elucidate the mechanistic details of this process, we describe the first animal model of nonhemolytic antibody-induced RBC antigen loss. RBCs from transgenic mHEL mice express surface hen egg lysozyme (HEL) as a transmembrane protein. Transfusion of mHEL RBCs into mice immunized with HEL results in selective loss of HEL antigen from donor RBCs without affecting other blood group antigens or reducing the circulatory life span of the transfused RBCs. While this process does not require the presence of a spleen, it requires both anti-RBC immunoglobulin G (IgG) antibodies and the FcgammaIII receptor. These studies provide mechanistic insight into the phenomenon of antigen loss during incompatible transfusion in humans.     

Busulfan,cyclophosphamide, and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma

Autologous stem cell transplantation (ASCT) has enabled the use of high-dose alkylating agents either as a single agent or in combination with other cytotoxic agents and/or total body irradiation (TBI) for the treatment of multiple myeloma. Despite improved complete remission rates, relapse and regimen-related toxicities remain challenging. In an effort to increase event-free survival and decrease the high incidence of regimen-related toxicity, we have studied the use of etoposide in combination with reduced-dose busulfan and cyclophosphamide as a conditioning regimen for ASCT in a group of 26 patients with advanced multiple myeloma. Median follow-up for the group was 30 months. There was no early treatment-related mortality. The main toxicity was mucositis. Otherwise, there was 1 case of reversible, clinically diagnosed hepatic veno-occlusive disease. Post-engraftment, 10 patients (38%) achieved CR, 15 (58%) patients achieved PR or SD, and 1 patient developed progressive disease (4%). Five patients in PR and 1 with progressive disease before transplant attained a CR post-transplant. The median times for event-free survival and overall survival after transplantation were 24 and 43 months, respectively. In conclusion, conditioning with busulfan, cyclophosphamide, and etoposide followed by ASCT is a safe regimen with comparable effectiveness to other previously used preparative regimens, thus providing another approach of non-TBI containing high-dose chemotherapy for patients with multiple myeloma.     

Prevalence and correlates of snoring in adolescents

Snoring can occur alone or it may be the presenting feature of Obstructive Sleep Apnea and other common chronic conditions. In our study, we aimed to estimate the prevalence and correlates of snoring in adolescent students in Tehran, Iran. A cross-sectional study was designed and students were selected from 20 secondary and high schools, in 5 different zones in Tehran in order to have a representative sample of the adolescent population. A total of 2900 students (1200 male and 1700 female students) 11-17 year-old who were attending secondary and high schools were investigated. Information was collected via a structured face-to-face interview, based on a questionnaire. In addition to snoring, nocturnal cough, asthma-related symptoms, and daytime symptoms were also questioned. BMI was measured by two trained physicians. The prevalence of snoring was 7.9% (4.8% in girls and 12.4% in boys). The prevalence of snoring was significantly higher among males (P< 0.05). Snoring was positively associated with asthma and nocturnal cough. Overweight/obese adolescents had significantly higher rates of snoring and asthma symptoms. Prevalence of daytime symptoms increased significantly in the snoring group.These results suggest that snoring is associated with multiple factors in adolescents. We conclude that the prevalence of snoring is relatively high in children of this region. This highlights the need for awareness among physicians about the problem of sleep-disordered breathing, especially in children with asthma and obesity, and also the need for further studies to measure the prevalence of sleep breathing disorders among Iranians.     

An office-based serological test for detection of current Helicobacter pylori infection: is it useful?

OBJECTIVE: To compare the accuracy of a new office-based serological test for the detection of current Helicobacter pylori infection with gastric histopathology. METHODS: An office-based serological test for detection of current H. pylori infection was performed in 92 consecutive patients with dyspeptic symptoms. The result of this test was compared blindly with the rapid urease test and histopathology for H. pylori on gastric biopsies. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this test were calculated against the histopathology. RESULTS: Among 92 patients, H. pylori was detected by histopathology and rapid urease test in 61 (66%) and 56 (60%) patients, respectively. Meanwhile the serological test diagnosed current H. pylori infection in 55 patients (59%). On comparison against the histology, the sensitivity and specificity of this new serological test was 85 and 90%, respectively. The positive predictive value and negative predictive value of this test were 94 and 76%, and the accuracy was 87% in this study. CONCLUSION: The specificity and sensitivity of the serological test was found comparable with histopathology in the diagnosis of current H. pylori infection. This test is a useful tool for rapid diagnosis of H. pylori in out patients' setting.     

Central lipoprivation-induced suppression of luteinizing hormone pulses is mediated by paraventricular catecholaminergic inputs in female rats

The present study aims to clarify the role of fatty acids in regulating pulsatile LH secretion in rats. To produce an acute central lipoprivic condition, mercaptoacetate (MA), an inhibitor of fatty acids oxidation, was administered into the fourth cerebroventricle (4V) in ad libitum fed ovariectomized (OVX) rats (0.4, 2, and 10 micromol/rat) with or without an estradiol (E2) implant producing diestrus plasma E2 levels. Pulsatile LH secretion was suppressed by 4V MA administration in a dose-dependent manner in both OVX and OVX plus E2 rats. Mean LH levels and LH pulse frequency and amplitude were significantly reduced by the highest dose of MA in OVX rats, and by the middle and highest dose of MA in E2-treated rats, suggesting that estrogen enhanced LH suppression. Blood glucose levels increased immediately after the highest dose of MA in both groups. Fourth ventricular injection of trimetazidine (2 and 3 micromol/rat), another inhibitor of fatty acids oxidation, also inhibited pulsatile LH release, resulting in significant and dose-dependent suppression of LH pulse frequency and an increase in blood glucose levels in OVX plus E2 rats. In contrast, peripheral injection of the highest 4V dose of MA (10 micromol/rat) did not alter LH release or blood glucose levels. Microdialysis of the hypothalamic paraventricular nucleus (PVN) revealed that norepinephrine release in the region was increased by 4V MA administration. Preinjection of alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, into the PVN completely blocked the lipoprivic inhibition of LH and the counter-regulatory increase in blood glucose levels in OVX plus E2 rats. Together, these studies indicate that fatty acid availability may be sensed by a central detector, located in the lower brainstem to maintain reproduction, and that noradrenergic inputs to the PVN mediate this lipoprivic-induced suppression of LH release.     

Minority and foreign-born representation among US blood donors: demographics and donation frequency for 2006

BACKGROUND: Historically, minority populations have represented only a small proportion of US blood donors, but recent trends in immigration and potential blood shortages emphasize the need for recruitment strategies to increase minority donations.
STUDY DESIGN AND METHODS: Donation data from a network of six US blood centers for 2006 were analyzed. Race/ethnicity, country of birth, and educational attainment data were collected specifically for the study and assessed for their influence on donation behavior. Logistic regression was used to determine independent associations with repeat donors status and annual donation frequency.
RESULTS: A total of 1,288,998 donations from 729,068 donors were studied; most donors had data on race/ethnicity (97.1%) and country of birth (93.1%). The proportion of minority donors differed by blood center, with African American donors (16%) most common at the Southeastern blood center and Asian (12%), Hispanic (13%), and foreign-born donors (13%) most common at the Northern California blood center. Minority donors and those born in Mexico or Latin America were younger than white donors. Minority and non–US-born donors were less likely than white and US-born donors to be repeat donors (odds ratio [OR], 0.60-0.78), and most were less likely to give two or more annual donations (OR, 0.82-1.11).
CONCLUSION: Minority and Mexico/Latin America–born donors represent a younger and often first-time donor population compared to white and US-born donors, but their annual donation frequency was only slightly lower than white and US-born donors. Increasing the retention and donation frequency of minorities will be important for supplementing the blood supply.     

Hepatitis C virus core protein modulates several signaling pathways involved in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth most common cancer, and hepatitis C virus(HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β(TGF-β), vascular endothelial growth factor(VEGF), Wnt/β-catenin(WNT), cyclooxygenase-2(COX-2) and peroxisome proliferator-activated receptor α(PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.     

In vitro and in vivo responses to interleukin 12 are maintained until the late SIV infection stage but lost during AIDS

The in vitro proliferative responses of macaque peripheral blood mononuclear cells (PBMCs) to IL-12 appeared similar before and early after SIV infection, whereas macaque PBMCs sampled during symptomatic stages of SIV infection showed markedly decreased responses. IL-12 was administered to SIVmac239-infected rhesus macaques either during the asymptomatic or the AIDS stage of infection in efforts to evaluate the effect of this cytokine on immune responses, viral loads, and hematopoietic functions in vivo. IFN-gamma secretion levels induced during the asymptomatic or early symptomatic phase were similar to preinfection induced levels, whereas in later AIDS stages this response was lost. The constitutive levels of other measured cytokines were not affected by IL-12 administration in vivo. The frequency and activity of circulating NK cells were markedly enhanced at early stages but not at symptomatic stages of SIV infection. pCTL frequencies were enhanced at early symptomatic stages but not at late AIDS stages. Despite its immunomodulatory effect, IL-12 did not seem to exacerbate or inhibit the replication of SIV in vivo, or the frequency of circulating infected lymphocytes. IL-12 administration was associated with a significant yet subclinical and transient decrease in hematocrit and hemoglobin levels without evidence of hemolysis, hemodilution, or reduction in the frequency of colony-forming unit potential of bone marrow CD34+ cells. This phenomenon may be explained by a functional inhibition of differentiation rather than an altered generation of bone marrow precursors. Thus, these results suggest that IL-12 may benefit HIV-1-infected patients only as long as their immune system retains its capability to respond to cytokine stimulation.