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Aplasia cutis congenita (ACC) is one of several congenital malformations associated with antithyroid/thiourylene drug use in pregnancy. While uncommon among the general population (1-3/100 000 cases), the risk among those on thiourylenes is between 1.6% and 3%. The scalp is the most common site for this congenital anomaly. We present the case of a male infant with multifocal ACC of the scalp discovered at birth and born to a mother with Graves disease that was controlled during pregnancy using carbimazole. Thyroid function tests were normal throughout the pregnancy. There was no involvement of underlying subcutaneous tissue or structures. At age 18 months, the single largest lesion remained with only partial coverage. Prospective management involved periodic surveillance with planned 2-stage repair. This case reinforces the association between the antithyroid drugs carbimazole (CMZ) and methimazole (MMI) and supports the proposition of an MMI/CMZ embryopathy. It adds to a literature of case reports in which malformations arise in offspring of such mothers whose thyrotoxicosis is controlled antenatally, thereby challenging the suggestion that ACC is attributable to poorly controlled disease rather than thiourylenes. As yet the underlying mechanism is not understood, nor is it known why MMI and CMZ may cause potentially significant embryopathy while congenital defects attributable to the structurally similar propylthiouracil are typically less severe. [ABSTRACT FROM AUTHOR]

Why does the United States seek to export its own political and economic system as part of an intervention? We argue that the United States has an ideologically inflected strategic culture which has yielded two "ways" of intervention over time. The limited model is cost-conscious and cedes control over the future of the state to local actors provided that they guarantee open markets and good government. The vindicationist model involves the United States paying costs to remake another society in its own image. We argue that the vindicationist way of intervention is activated by specific types of strategic surprises, which cause policymakers to react by gambling on interventions to remake another society. To empirically investigate this claim, we examine the record of America's major interventions from 1946 to 2005 and present two contrasting case studies of Cold War interventions in Lebanon and the Dominican Republic. [ABSTRACT FROM AUTHOR]

Explanations for the third-person phenomenon generally hinge on either self-favoring biases or cognitive mechanisms. While controlling for common perceptual factors, we demonstrate an additional cognitive component: exemplar availability, using a 2-study design. The first considers the third-person perception in the context of media-generated stereotypes. The second considers 3 distinct types of advertisements meant to evoke varied third- and first-person perceptions. Results of both studies showed that the ability to think of examples serves as the most consistent predictor, even after accounting for the influence of perceived exposure and similarity. [ABSTRACT FROM AUTHOR]

Feline McDonough Sarcoma-like tyrosine kinase 3 (FLT3), a tyrosine-protein kinase involved in hematopoiesis, is detectable on the cell surface of approximately 80% of leukemia isolates from adult patients with acute myeloid leukemia (AML). AMG 553 is an investigational chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of AML. FLT3 expression analysis and in vitro and in vivo studies were leveraged to evaluate the nonclinical safety of AMG 553. Cynomolgus monkeys administered autologous anti-FLT3 CAR T cells demonstrated no evidence of CAR T-cell-mediated toxicity, expansion, or persistence, likely due to restricted cell surface FLT3 protein expression in healthy animals. This highlights the limited value of such in vivo studies for safety assessment of the CAR T-cell modality when directed against a target with restricted expression. To complement these studies and directly evaluate the potential toxicities of eliciting T-cell-mediated cytotoxicity against cells with surface expression of FLT3 protein in vivo , data from cynomolgus monkey toxicology studies with 2 bispecific T-cell engager molecules targeting FLT3 were leveraged; findings were consistent with the targeted killing of bone marrow cells expressing cell surface FLT3. Potential AMG 553-induced cytotoxicity was assessed against a wide range of normal human primary cells and cell lines; cytotoxicity was observed against FLT3-positive AML cell lines and a percentage of primary bone marrow CD34+ cells. In conclusion, the nonclinical safety data suggest that AMG 553 can target FLT3 protein on AML cells, whereas only affecting a percentage of normal hematopoietic stem and progenitor cells, supporting clinical development. [ABSTRACT FROM AUTHOR]

An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the association between autoantibodies and atherosclerosis, amongst individuals without clinical autoimmune disease. An electronic search of five databases to June 2016 was performed by two independent reviewers. Inclusion criteria were analytical studies of adults, with at least two studies per autoantibody. Quality analysis was carried out using the Newcastle-Ottawa scale and the Cochrane Risk of Bias Quality Assessment Tool where appropriate. Where possible, studies were pooled using random effects models. Raised levels of anti-cardiolipin (odds ratio [OR] = 1.30; 95% CI: 1.15-1.49) and anti-oxidized low-density lipoprotein Immunoglobulin (Ig) G (OR = 1.25; 95% CI: 1.11-1.41), unspecified anti-cyclic citrullinated protein (OR = 3.09; 95% CI: 1.49-6.41) and anti-human heat shock protein 60 IgA (OR = 1.57; 95% CI: 1.15-2.16) were observed to increase the risk of cardiovascular outcomes. Alternatively, Anti-phosphorylcholine IgM (OR = 1.31; 95% CI: 1.14-1.50) conferred protection against CVD. Our results support an important role for autoantibodies in mediating cardiovascular events, independent of therapeutic treatments. Future research may focus on the presence of autoantibodies as markers of immune dysregulation and CVD risk. [ABSTRACT FROM AUTHOR]

Objective This study examined the measurement invariance of the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) DSM-oriented scales between extremely low birth weight (ELBW) and normal birth weight (NBW) youth. Methods The sample included 158 ELBW survivors and 145 matched, NBW controls at 8 and 12-16 years of age. Results Strict invariance was established at 8 years for parent-reported CBCL attention-deficit hyperactivity, conduct, and oppositional defiant scales, though invariance could not be established for affective problems at 8 or 12-16 years. Strict invariance was observed between 12-16-year-old ELBW and NBW groups on attention-deficit hyperactivity, anxiety, and oppositional defiant CBCL and YSR scales. Invariance could not be established for youth-reported conduct problems. Conclusions While the majority of CBCL/YSR DSM-oriented subscales assess the same concepts in both ELBW and NBW children and adolescents across parent and youth reports, this may not be the case for affective and conduct problems. [ABSTRACT FROM AUTHOR]

Objective The objectives of this study were to determine whether a measure of global self-concept demonstrated longitudinal measurement invariance between adolescents aged 10-19 years with and without chronic illness and to document differences in their global self-concept trajectories over time. Methods Data were obtained from the National Longitudinal Survey of Children and Youth (N = 10,064). Global self-concept was measured using a scale based on the Self-Determination Questionnaire. Results 16 percent of adolescents had chronic illness. There was evidence of partial longitudinal invariance in global self-concept between adolescents with and without chronic illness. Controlling for sociodemographic characteristics, adolescents with a chronic illness exhibited lower levels of global self-concept and more precipitous declines over time. Conclusions The results from this study suggest that comparisons of global self-concept between adolescents with and without chronic illness are meaningful and, compared to healthy controls, adolescents with chronic illness are at risk for low global self-concept. [ABSTRACT FROM AUTHOR]

One of the distinctive elements of President Barack Obama's approach to counterterrorism has been his embrace of Unmanned Aerial Vehicles (UAVs), or drones, to target terrorist operatives abroad. The Obama administration has used drones in active theatres of war, such as Afghanistan, but it has also dramatically increased the number of drone attacks launched by the CIA in other countries, such as Pakistan, Yemen and Somalia. The conventional wisdom on drone warfare holds that these weapons are highly effective in killing terrorist operatives and disabling terrorist organizations, while killing fewer civilians than other means of attack. This article argues that much of the existing debate on drones operates with an attenuated notion of effectiveness that discounts the political and strategic dynamics-such as the corrosion of the perceptions of competence and legitimacy of governments where drone strikes take place, growing anti-Americanism and fresh recruitment of militant networks-that reveal the costs of drone warfare. Focusing particularly on drone use in Pakistan, Yemen and Somalia, the article suggests that the Obama administration's counterterrorism policy operates at cross-purposes because it provides a steady flow of arms and financial resources to build up governments whose legitimacy it systematically undermines by conducting unilateral strikes on their territory. It concludes that the US embrace of drone technology is a losing proposition over the long term as it will usher in a new arms race and lay the foundations for an international system that is increasingly violent, destabilized and polarized between those who have drones and those who are victims of them. [ABSTRACT FROM AUTHOR]

Objective To critically assess the research quality of studies examining self-concept in adolescents with epilepsy (AWE) and, based on the evidence of these studies, to determine whether AWE have compromised self-concept, to identify correlates of self-concept, and to evaluate interventions aimed at improving self-concept. Method MEDLINE and EMBASE were searched for relevant publications. The modified Quality Index was used to evaluate study quality. Results 20 studies were reviewed and 8 studies were included in a meta-analysis. There was no significant difference in self-concept between AWE versus healthy control subjects. Self-concept was associated with a number of sociodemographic, clinical, and behavioral variables. Conclusion The limited number and modest quality of the studies available for review suggest that the negative findings should be interpreted with caution. In addition to addressing the limitations of existing studies, future research should focus on exploring the potential role of self-concept in the development of mental health problems in AWE. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated the third-person perception, but many aspects of its origin and consequences remain unaddressed. In this study, we examine how potential positive and negative video game effects are perceived differently based on the extent to which respondents actually play video games. Although video games exhibit clear third-person perceptions and subsequent support for censorship, these patterns are greatly diminished for heavy players. [ABSTRACT FROM AUTHOR]

Objective To examine the contribution of adolescents’ sleep problems and tiredness to psychological symptoms after accounting for shared risk and psychological co-morbidity. Methods Secondary analyses of cross-sectional data on 12–16-year-old (N = 980) adolescents without chronic illness, functional limitation, or developmental delay. Adolescents rated sleep problems, tiredness, and psychological symptoms. Parents provided information about risk factors, adolescent tiredness, and psychological symptoms. Results Prior to accounting for psychological co-morbidity, most sleep variables were significant correlates of adolescent-, but not parent-rated, psychological symptoms. After accounting for psychological co-morbidity: nightmares were associated with adolescent-rated anxiety/depression; sleeping more than others was associated with adolescent-rated aggression; trouble sleeping was associated with adolescent-rated attention problems, anxiety/depression, and withdrawal; and adolescent-rated tiredness was associated with adolescent-rated aggression and withdrawal. Conclusions Studies examining sleep and psychopathology should control for psychological co-morbidity. [ABSTRACT FROM AUTHOR]

Objectives Examine the contribution of sleep problems and indicators of inadequate sleep to psychopathology among children after accounting for shared risk and comorbid psychopathology. Methods Secondary analyses of cross-sectional data on 4- to 11-year-old (N = 1,550) children without chronic illness or developmental delay or disability. Parents provided information about sleep problems, indicators of inadequate sleep, symptoms of psychopathology, and risk factors for psychopathology. Teachers provided information about indicators of inadequate sleep and symptoms of psychopathology. Results Adjusting for risk factors and comorbid psychopathology, sleeping more than other children was related to parent-rated aggression. Nightmares and trouble sleeping were related to parent-rated anxious/depressed mood. Sleep problems were not related to attention problems. Being overtired was related to parent- and teacher-rated psychopathology. Conclusions Relations among sleep problems, indicators of inadequate sleep, and psychopathology are complex; accounting for potential confounding variables and considering sleep variables separately may clarify these relations. [ABSTRACT FROM AUTHOR]

One of the underlying assumptions of the contemporary debate over Afghanistan is that counterterrorism objectives can be achieved through counterinsurgency methods. The recent decision by President Barack Obama to deploy 30,000 extra troops to Afghanistan is premised on the idea that to disrupt Al Qaeda and prevent it from forming training camps in Afghanistan it will be necessary to first reverse the momentum of the Taleban insurgency. This approach—which places the US and UK on the offensive to disrupt terrorist plots before they arrive on their shores—assumes that the threats from Al Qaeda and the Taleban are intertwined and thus the strategy of response must seamlessly comprise elements of counterterrorism and counterinsurgency. In fact, counterterrorism and counterinsurgency are very different—often contradictory—models of warfare, each with its own associated assumptions regarding the role of force, the importance of winning support among the local population, and the necessity of building strong and representative government. Rather than being mutually reinforcing, they may impose tradeoffs on each other, as counterterrorism activities may blunt the effectiveness of counterinsurgency approaches and vice versa. The last four years in Afghanistan provide evidence that when employed in the same theatre counterterrorism and counterinsurgency strategies can offset one another. To be in a position to begin the withdrawal of US troops before July 2011, the Obama administration will need to find a way to manage the tradeoffs between its counterterrorism and counterinsurgency strategies in Afghanistan. [ABSTRACT FROM AUTHOR]

Background Children are at high risk of exposure to environmental tobacco smoke and biofuel smoke at home in developing countries. This study examines whether exposure to cigarette and biofuel smoke is associated with height-for-age of children (0–59 months) in seven developing countries. [ABSTRACT FROM PUBLISHER]

The 9/11 attacks made the war on terror the central plank of American grand strategy. Yet despite its importance in shaping US policy choices, there has been considerable confusion over how the war on terror relates to foreign policy goals. This article attempts to locate the war on terror within American grand strategy and makes three claims. First, it argues that the Bush administration's approach to the war on terror rests on a false analogy between terrorism and fascism or communism. This has led to misinterpretations of the goals of the war on terror and to a persistent misuse of American power. Second, it suggests that the central purpose of the war on terror should be to de-legitimize terror as a tactic and to induce states to assume responsibility for controlling terrorists within their borders. American grand strategy should be focused on creating a normative anti-terror regime with costly commitments by linchpin states—defined as great powers and crucial but endangered allies such as Pakistan and Saudi Arabia—rather than on conducting regime change against rogue states on the margins of the international system. Success in the war on terror should be measured not by the perceived legitimacy of discrete US policy choices, but by the number of these crucial states who accept the de-legitimation of terrorism as a core foreign policy principle and act accordingly. Third, it argues that bilateral enforcement of an anti-terror regime imposes high costs for US power and puts other elements of American grand strategy— including the promotion of democracy and the promotion of human rights—at risk. To reduce these costs and to preserve American power over the long-term, the US should attempt to institutionalize cooperation in the war on terror and to scale back ambitious policy choices (such as achieving a democratic revolution in the Middle East) which increase the risks of state defection from the anti-terror regime. [ABSTRACT FROM AUTHOR]

The recent publication of State of denial, by veteran Washington journalist Bob Woodward, created firestorm of controversy over its central claim that the Bush administration is in denial over the severity of the unfolding crisis in Iraq. But one of the most revealing aspects of the book is its portrayal of the American policymaking process as dysfunctional, incompetent and beset by personal rivalries and ambitions. Woodward's account of the Bush administration's handling of Iraq reveals that bureaucratic necrosis, cronyism and internecine warfare between the Pentagon and the State Department are now the signature features of the American government. Thus an alternative reading of Woodward's book suggests that American people are no longer in denial about Iraq, but have yet to reckon with the deeper problem: the deterioration of their foreign policy establishment. [ABSTRACT FROM AUTHOR]

Objectives: CNS infections due to multiresistant Acinetobacter baumannii (MRAB) are an emerging problem in neurosurgical patients. Colistin remains one of the few remaining treatment options for MRAB but has poor CNS penetration. We describe our experience with intraventricular or intrathecal colistin for this infection.Methods: Cases known to have received intraventricular or intrathecal colistin for CNS infections due to MRAB were retrospectively reviewed regarding colistin treatment, colistin efficacy and adverse events.Results: Five patients were identified. All were admissions to the neurosurgical ICU and all were cured of their CNS infections. Three cases were complicated by drug-induced aseptic meningitis or ventriculitis.Conclusions: This largest case series to date shows that direct instillation of colistin into the CNS may cause chemical meningitis or ventriculitis but it is an effective treatment option for MRAB CNS infection. Further study of dosing regimens is needed. [ABSTRACT FROM PUBLISHER]

With the tension between national security and civil liberties as a backdrop, this study examines responses to news coverage of activist groups. This 2 × 2 experiment presented participants with news stories about government efforts to restrict the civil liberties of an “extremist” individual or group (news frame) advocating for a cause supported or opposed by the respondent (cause predisposition). Willingness to take expressive action was greatest for individual-framed stories about a cause opposed by the respondent and for group-framed stories about a cause supported by the respondent. We contend that when reporters frame stories about extremist groups around individuals, fewer people will speak out in favor of causes they agree with and more will rally against causes they oppose. [ABSTRACT FROM AUTHOR]

Protein H is an immunoglobulin-binding protein expressed by certain M1 serotypes of Streptococcus pyogenes. In a recent study of invasive group A isolates, it was found that none of the 16 M1 serotype isolates analyzed expressed protein H on their surface despite the presence of the protein H gene (sph) in approximately one-third of the isolates. Selection of stable protein H-expressing variants could be achieved by infection of prtH+ non-expressing strains into a mouse skin and recovering bacteria from the spleen. This effect was independent of the transcription regulator Mga, since a similar effect was noted in an mga− mutant. Thus, host passage of S. pyogenes can lead to stable high level expression of Protein H. [Copyright &y& Elsevier]

Determines the role of interferon-alpha in the observed protection and in the natural immunity to group A streptococcal infection. Role of interleukin-12 in survival after infections caused by extracellular bacterial pathogens; Effect of the neutralization of interferon-alpha; Relationship between interleukin-12 pretreatment dosage and protection against lethal infection with group A streptococci.

This study estimates the effects of place on the distribution of health problems, health-related quality of life, general well-being, and family functioning for youths and adults aged 12 years and older. Data come from the Ontario Health Survey, a cross-sectional study done in 1990 to provide baseline statistical data on population health within 42 public health units throughout the province. Place effects were generally small and were influenced by both the size of the geographic area used to define place and the health indicator selected for study. Variations in health explainable at the public health region level were less than 1%. Variations in health explainable within smaller geographic boundaries (enumeration areas) ranged from 4.7% for health problems to 0.2% for family functioning. Adjustment for area differences in the age, gender, education, marital slatus, income, and birthplace of inhabitants reduced these place effects at the enumeration area level to 3.7% for health problems and to less than 0.1% for family functioning. The lack of evidence for place effects within large jurisdictional boundaries raises questions about both the usefulness of carrying out health needs assessment surveys within these areas and the informativeness of these geographic boundaries for studying place effects. Am J Epidemiol 1999;149:577–85. [ABSTRACT FROM AUTHOR]

This review highlighted several problems associated with the use of antibody and complement in the elimination of tumor cells from bone marrow that was to be used for transplantation, and it discussed some of the difficulties encountered in developing this approach in model systems. These problems should be seriously considered by any clinician contemplating this method for bone marrow purging. [J Natl Cancer Inst 1988;80:154-159] [ABSTRACT FROM PUBLISHER]

The virulence of group A streptococcal isolate 64/14 and paired isogenic mutants in which either the emm or mrp gene had been insertionally inactivated was compared in mice. Loss of expression of the emm gene product resulted in a significant loss of virulence when the isolate was injected into the skin but had no significant difference when injected intraperitoneally. By contrast, inactivation of the mrp gene caused the organism to be more virulent in the skin, while having no significant effect intraperitoneally. An isogenic mutant, in which the mga gene was inactivated and neither the emm gene nor the mrp gene was expressed, demonstrated no significant difference in virulence from the wild type organism. Organisms recovered from the spleen of mice lethally infected with the mga mutant expressed all Mga-regulated IgG-binding gene products despite the presence of the spectinomycin-resistance cassette, which was used to inactivate the mga gene, in its original position. [ABSTRACT FROM PUBLISHER]

Group A streptococci incubated in human plasma can acquire a plasmin-like enzymatic activity. This process involves at least two bacterial proteins and two human protein cofactors. In this study, the key bacterial proteins were identified by using a series of isogenic mutants of group A isolate, CS101. These studies confirm a key role for the secreted plasminogen activator, streptokinase, and identify the major surface fibrinogen-binding protein as the product of the mrp gene. The requirement for human fibrinogen and plasminogen as key cofactors was also confirmed. [ABSTRACT FROM PUBLISHER]

Recent clinical Streptococcus pyogenes isolates of the Ml serotype can be grouped according to the IgG-binding properties of their M proteins. One group expressed an IgG-binding M1 protein reactive with human IgG1, IgG2, IgG3, and IgG4 (type IIo); the other expressed a protein with predominant reactivity with human IgG3 alone (type IIb). Both IgG-binding protein phenotypes were equally resistant to phagocytosis in human blood; however, when they were injected into a skin air sac on outbred CD1 mice, all mice injected with Ml isolates of the type IIo phenotype were dead within 70 h, while only 40% of those injected with M1 isolates of the type IIb phenotype died within the same period. Bacteria recovered from the spleens of animals that died after injection with type IIb phenotype isolates demonstrated a change in their IgG-binding profile and were indistinguishable, in vitro or in vivo, from isolates displaying the type IIo phenotype. [ABSTRACT FROM PUBLISHER]

In this study, the role of the staphylococcal plasminogen activator, staphylokinase (SAK), was analyzed for its ability to mediate acquisition of cell-associated plasmin-like activity by staphylococci in the presence of a source of human plasminogen. A panel of staphylococcal strains isolated from humans was tested for the presence of the SAK gene, secretion of the plasminogen activator, and the ability to acquire enzymatic activity when incubated with purified human plasminogen or serum. When SAK was compared with the eukaryotic plasminogen activators, urokinase and tissue plasminogen activator, only SAK could mediate acquisition of cell-associated enzymatic activity by staphylococci without first generating significant fluid-phase plasmin. These studies provide evidence for a novel mechanism by which SAK-producing S. aureus can acquire an unregulatable host plasmin-like activity that might contribute to their invasive potential. [ABSTRACT FROM AUTHOR]

Acquisition of plasmin(ogen) by group A streptococci occurs by two distinct pathways. In addition to the well-characterized direct interaction of plasmin with cell-surface receptors on group A streptococci, a second pathway dependent on streptokinase and a nonplasminogen factor(s) present in human plasma was identified. The role of streptokinase in the second pathway was not merely as a plasminogen activator, since substitution of the plasminogen activator urokinase did not result in the capture of plasmin(ogen) by bacteria in the presence of plasminogen-depleted plasma. However, if streptokinase was added to plasmin that had been generated by treatment of plasminogen with urokinase, the ability of the bacteria to capture plasmin in the presence of plasminogen-depleted plasma was restored. Fibrinogen present in human plasma was identified as the major factor required for streptokinase-dependent uptake of plasmin(ogen) by group A streptococci. [ABSTRACT FROM AUTHOR]

Group A streptococci isolated from throat swabs or blood cultures were compared for the expression of plasmin(ogen) receptors. The majority of isolates bound 125I-labeled Lys-plasmin and 12SI-labeled Lys-plasminogen while displaying minimal reactivity with 125I-labeled Glu-plasminogen. All streptococcal isolates could acquire surface enzymatic activity when incubated in human plasma but not if the plasma had been depleted of plasminogen. The ability to acquire surface enzymatic activity was limited by the quantity of streptokinase in the reaction mixture. There was no statistically significant difference between group A streptococci isolated from throat swabs and those from blood cultures with respect to their interaction with components of the fibrinolytic system in human plasma. However, these isolates could be divided into two groups based on their ability to acquire surface enzymatic activity when incubated in plasma with exogenous streptokinase. Surprisingly, the acquisition of surface enzymatic activity when incubated in plasma containing streptokinase was not always correlated with the plasmin(ogen) binding capacity determined by direct binding of radio labeled ligands. Analysis of this phenomenon suggests that group A streptococci can use diverse mechanisms to acquire plasmin(ogen)-dependent enzymatic activity. [ABSTRACT FROM PUBLISHER]

Group A streptococci grown in the presence of human plasma generated plasmin from plasminogen and captured the functional enzyme to a specific cell-surface receptor. Bacteria-bound plasmin was not regulated by α2-antiplasmin present in the medium. The ability of the bacteria to acquire cell-associated plasmin activity was dependent on both the presence of plasminogen in the culture medium and the production of a bacterial plasminogen activator, streptokinase. The ability of group A streptococci to produce a plasminogen activator and capture resulting plasmin in an unregulatable form could provide the organism with a mechanism for invasion of normal tissue barriers. [ABSTRACT FROM PUBLISHER]

The c protein (Ibc) of group B streptococci (GBS) is associated with at least four antigens (a, β, γ, δ). To assess the virulence potential of these antigens, 255 GBS isolates recovered from septic neonates, healthy neonates, and pregnant women were serotyped and surveyed for reactivity with sera to c protein and the four associated antigens. A radioimmunoassay using intact bacteria was used to detect the GBS antigens. In contrast to earlier reports, most (66%) of the type III strains expressed the c protein. Except for the 'Y antigen, none of the other c protein- associated antigens showed an increased association with pathogenic strains independent of the polysaccharide antigens. The γ antigen was expressed by 15 of 41 c protein-positive earlyonset strains and by 4 of 38 c protein-positive late-onset strains (P = .007). This association was independent of the type-specific antigen, suggesting a potential role for the 'Y antigen as a virulence factor in GBS strains causing early-onset sepsis. [ABSTRACT FROM PUBLISHER]

A two-stage radioimmunoassay (RIA) has been developed that identifies type-specific antigens on the surfaces of group B streptococci. In addition to detecting the type-specific carbohydrate antigens Ia, Ib, II, and III, the RIA identified four unique antigens reactive with the Centers for Disease Control's c-protein typing antiserum. Analysis of hot-acid extracts by immunoelectrophoresis confirmed that two of these reactivities corresponded to the reported α and β antigens of the c-protein marker. In addition, the identification of two heretofore unidentified antigens, γ and δ, by the two-stage RIA is detailed in this report. The assay uses intact bacteria and does not require hot-acid extraction, a procedure thus enabling detection of acid-labile antigens in their native unmodified form. The semiquantitative RIA requires less typing reagent than does precipitin testing and is more objective, reproducible, and rapid. The assay described here could be applied to the detection of any cell surface antigen for which a monospecific antiserum is available. [ABSTRACT FROM PUBLISHER]

It has been shown that interleukin (IL)-12 induces cell-mediated immunity and provides significant protection against intracellular organisms. The ability of this cytokine to enhance immunity in a mouse model of group A streptococcal skin infection was studied. Outbred CD1 mice were injected for 3 consecutive days with 0.1 µg of recombinant murine IL-12 before or after challenge with strain 64/14 group A streptococci. In both cases, in vivo IL-12 treatment significantly decreased the rate of death after infection and increased survival over the period of experimental observation. Thus, IL-12 may be useful for treatment of gram-positive bacterial infections. The time course of the experiments suggests that IL-12 is acting in this model system to enhance natural, rather than acquired, immunity. [ABSTRACT FROM PUBLISHER]

Corticosteroids are the mainstay of therapy for immune reconstitution inflammatory syndrome (IRIS). However, little is known about how to treat IRIS unresponsive to steroids. We report a patient with HIV-TB coinfection who was unresponsive to first prednisolone and then infliximab but whose IRIS resolved with adalimumab. [ABSTRACT FROM AUTHOR]

Examines the effect of the enzymatic activity of group A streptococci on its virulence in a mouse skin infection model. Enhancement of virulence for bacteria preincubated in human plasma; Correlation between surface-associated enzymatic activity and virulence; Association of the assembly of a surface-associated plasmogen activator with virulence.