Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-mediated ARDS.

Objectives: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime pulmonary sequestration of neutrophils (PMNs) and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the PMNs, which serves as the first event in the ARDS. Summary of Background Data: Intracellular metabolites accumulate in the plasma of severely injured patients.

Whole blood thrombin generation is distinct from plasma thrombin generation in healthy volunteers and after severe injury.

Background: Plasma thrombin generation has been used to characterize trauma-induced coagulopathy, but description of whole blood thrombin generation is lacking. This study aimed to evaluate plasma and whole blood thrombin generation in healthy volunteers and trauma patients. We hypothesized that (1) plasma and whole blood thrombin generation are distinct, (2) whole blood thrombin generation is more pronounced in trauma patients than in healthy volunteers, and (3) thrombin generation correlates with clinical coagulation assays.

Maternal characteristics and obstetrical complications impact neonatal outcomes in Indonesia: a prospective study.

Background: We investigated associations between maternal characteristics, access to care, and obstetrical complications including near miss status on admission or during hospitalization on perinatal outcomes among Indonesian singletons.

Methods: We prospectively collected data on inborn singletons at two hospitals in East Java. Data included socio-demographics, reproductive, obstetric and neonatal variables.

Plasma Cytokines and Chemokines in Zambian Children With Measles: Innate Responses and Association With HIV-1 Coinfection and In-Hospital Mortality.

To identify immune factors present during the acute rash phase of measles and associations with outcome and human immunodeficiency virus type 1 (HIV-1) coinfection, we measured the plasma levels of 22 cytokines and chemokines in Zambian children hospitalized with measles (n = 148) and control children (n = 44). Children with measles had higher levels of innate cytokines tumor necrosis factor (TNF) α, interleukin 1β (IL-1β), interleukin 18, and interleukin 6; chemokines CCL2, CCL4, CCL11, CCL22, CXCL8, and CXCL10; and T-cell cytokines interferon γ, and interleukin 2, 10, and 17. Children who died in the hospital had higher levels of TNF-α, IL-1β, interleukin 12p70; CCL2, CCL4, CCL13, CCL17, CXCL8, CXCL10; and interleukin 2 and interferon γ than children who survived, and lower levels of interleukin 4.

Maternal characteristics and clinical diagnoses influence obstetrical outcomes in Indonesia.

This Indonesian study evaluates associations between near-miss status/death with maternal demographic, health care characteristics, and obstetrical complications, comparing results using retrospective and prospective data. The main outcome measures were obstetric conditions and socio-economic factors to predict near-miss/death. We abstracted all obstetric admissions (1,358 retrospective and 1,240 prospective) from two district hospitals in East Java, Indonesia between 4/1/2009 and 5/15/2010.

HIV-1 infection in Zambian children impairs the development and avidity maturation of measles virus-specific immunoglobulin G after vaccination and infection.

Background: Endemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects that HIV infection has on immune responses to measles and to measles vaccine can impact measles elimination efforts. Assays to measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) to all measles virus (MV) proteins, and the plaque reduction neutralization (PRN) assay, which measures antibody to the hemagglutinin and correlates with protection.

Isolation of mononuclear cells from tonsillar tissue.

Located on the inside of the throat, the paired palatine tonsils form part of the first major barrier protecting the digestive and respiratory tracts from potentially invading microorganisms. The tonsils have a surface of stratified squamous epithelium that extends into deep and branched crypts lined by reticulated epithelium, which in parts may only be one cell thick. Organized in the sub-epithelial space are B cell rich lymphoid follicles.

Isolation of mononuclear cells from tonsillar tissue.

This unit describes a protocol for the derivation of lymphoid cell populations from tonsillar tissue. The procedure can also be applied with little or no modification to spleen and lymph node tissue. Human tonsils are the most readily available lymphoid organs and are often used as a source of large numbers of cells characteristic of local lymphoid tissue.

HIV type 1 infection is a risk factor for mortality in hospitalized Zambian children with measles.

Background: Measles remains a significant cause of vaccine-preventable mortality in sub-Saharan Africa, yet few studies have investigated risk factors for measles mortality in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence.

Methods: Between January 1998 and July 2003, children with clinically diagnosed measles who were hospitalized at the University Teaching Hospital in Lusaka, Zambia, were enrolled in an observational study. Demographic and clinical information was recorded at enrollment and at discharge or death.

Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: an observational study.

Background: Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination.

Methods: We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia.

Results: From May 2000 to November 2002, 696 children aged 2-8 months were enrolled.

Effects of mouse and human lipocalin homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin on gastrointestinal mucosal integrity and repair.

Background & Aims: The lipocalin superfamily, including the mouse and human homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin, show great functional diversity including roles in olfaction, transportation, and prostaglandin synthesis in mammals. Their potential role in maintaining gastrointestinal mucosal integrity and repair is, however, unclear.

Methods: Changes in 24p3/lcn2 expression in the mouse gut in response to various noxious agents were examined using Northern blot, in situ hybridization, and immunohistochemistry.

HIV-1 infection as a risk factor for incomplete childhood immunization in Zambia.

Immunizations are of particular importance for human immunodeficiency virus type 1(HIV-1)-infected children as they are at increased risk of severe disease and death from several vaccine-preventable diseases. Outside the United States, however, research on the impact of the HIV-1 epidemic on childhood immunization coverage is sparse. We conducted a nested case-control study in hospitalized children with measles to assess whether HIV-1 infection was a risk factor for incomplete immunization with diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV).

Influence of HIV infection on changes in circulating leukocyte counts during measles in Zambian children.

Measles remains an important problem in Africa, where human immunodeficiency virus type 1 (HIV-1) infection is prevalent. To identify the consequences of coinfection, Zambian children hospitalized with measles were studied at entry, discharge, and 1 month after discharge. All children had low lymphocyte and eosinophil counts at entry and high leukocyte and monocyte counts during recovery.

CD4+ and CD8+ T-lymphocyte subsets in Zambian children.

Age-related changes in lymphocyte subsets in HIV-uninfected Zambian children are described. The total lymphocyte count and numbers of CD4+ and CD8+ T-lymphocytes declined with increasing age, while the percentage of CD4+ and CD8+ T-lymphocytes changed little during childhood. Girls between the ages of 12 and 71 months had a higher percentage of CD4+ T-lymphocytes and a higher CD4:CD8 ratio than did boys of a similar age.

Colorimetric microtitre plate hybridization assay for the detection of Mycobacterium leprae 16S rRNA in clinical specimens.

We have developed a colorimetric microtitre plate hybridization assay in order to simplify detection of Mycobacterium leprae in clinical specimens. This system detects the products amplified by a sensitive RT-PCR assay targeting a species-specific sequence of the bacterial 16S rRNA. The assay detected as few as 10 bacilli isolated from infected nude mouse lymph nodes or human skin biopsies.

Increased thymic output during acute measles virus infection.

Measles virus infects thymic epithelia, induces a transient lymphopenia, and impairs cell-mediated immunity, but thymic function during measles has not been well characterized. Thirty Zambian children hospitalized with measles were studied at entry, hospital discharge, and at 1-month follow-up and compared to 17 healthy children. During hospitalization, percentages of naïve (CD62L+, CD45RA+) CD4+ and CD8+ T lymphocytes decreased (P = 0.

Tissue involution and the acute phase response.

After their roles in reproduction are completed, the mass of the uterus and the mammary gland decrease rapidly by the process of involution that involves an ordered series of events including apoptosis, neutrophil entry, the release of degradative enzymes, and phagocytosis of cellular debris. The acute phase proteins are produced by the liver and other tissues in response to inflammation or a toxic challenge. Uterocalin (SIP24/24p3) is one of these proteins.

Differential regulation of interleukin (IL)-4, IL-5, and IL-10 during measles in Zambian children.

To determine the effect of measles virus infection on cytokine production in children from sub-Saharan Africa, temporal changes in cytokine production in vivo were analyzed and the T cell sources of type 1 and type 2 cytokines were identified in Zambian children with measles. The immune response during measles involved early type 1 responses, with production of interferon-gamma by CD8(+) T cells and of interleukin (IL)-2 by CD4(+) T cells. Subsequently, more-prolonged increases were observed in the type 2 cytokines IL-4 and IL-13, both produced by CD4(+) T cells.

Functional and phenotypic changes in circulating lymphocytes from hospitalized zambian children with measles.

Measles is associated with immunosuppression and increased susceptibility to secondary infections and is a particular problem in developing countries. Lymphocyte changes accompanying immune activation and regulation of the immune response may contribute to immunosuppression. To evaluate lymphocyte changes during measles, children (n = 274) hospitalized with measles in Lusaka, Zambia, were evaluated at entry, discharge, and 1-month follow-up and compared to healthy Zambian children (n = 98).

Prospective study of measles in hospitalized, human immunodeficiency virus (HIV)-infected and HIV-uninfected children in Zambia.

Measles in persons coinfected with human immunodeficiency virus (HIV) has been reported to be unusual in its presentation and frequently fatal. To determine the effect of HIV coinfection on the clinical features and outcome of measles, a prospective study of hospitalized children with measles was conducted between January 1998 and October 2000 in Lusaka, Zambia. One-sixth (17%) of 546 children hospitalized with laboratory-confirmed measles were coinfected with HIV.

High expression in involuting reproductive tissues of uterocalin/24p3, a lipocalin and acute phase protein.

During reproduction the mass and number of cells in the uterus and the mammary gland increase rapidly and then diminish more rapidly after their reproductive functions are completed. The diminishment of tissue mass, known as involution, involves an ordered series of events that includes apoptosis of resident cells, neutrophil invasion, the release of degradative enzymes and phagocytosis of cellular debris. Local signals are believed to regulate the progression of involution in each tissue.

Suppression of human immunodeficiency virus replication during acute measles.

To determine the effect of measles virus coinfection on plasma human immunodeficiency virus (HIV) RNA levels, a prospective study of hospitalized children with measles was conducted between January 1998 and October 2000 in Lusaka, Zambia. Plasma HIV RNA levels were measured during acute measles and 1 month after hospital discharge. The median plasma HIV RNA level in 33 children with measles who were followed longitudinally was 5339 copies/mL at study entry, 60,121 copies/mL at hospital discharge, and 387,148 copies/mL at 1-month follow-up.

Prolonged measles virus shedding in human immunodeficiency virus-infected children, detected by reverse transcriptase-polymerase chain reaction.

A reverse transcriptase-polymerase chain reaction assay was used to detect measles virus RNA in peripheral blood mononuclear cells, urine, and nasopharyngeal specimens from Zambian children during hospitalization and approximately 1-2 months after discharge. Of 47 children, 29 (61.7%) had prolonged measles virus shedding, as defined by detection of measles virus RNA in > or =1 specimen obtained 30-61 days after rash onset.

Reverse transcription-PCR detection of Mycobacterium leprae in clinical specimens.

A reverse transcription (RT)-PCR assay targeting the 16S rRNA of Mycobacterium leprae was developed to detect the organism in clinical specimens. A 171-bp fragment was amplified when M. leprae RNA was used as a template but not when a panel of RNAs from 28 potentially cross-reacting mycobacterial species, seven genera related to Mycobacterium, and three organisms normally found among skin or nose flora were tested.

Uterocalin: a mouse acute phase protein expressed in the uterus around birth.

Mouse SIP24/24p3 is a 24 kDa lipocalin expressed in the liver and secreted into the bloodstream during the acute phase response (APR). In this report we show that SIP24/24p3 mRNA and protein are expressed in the uterus around parturition at levels higher than are found in the liver during the APR. Because of the unique expression of this lipocalin in the uterus, we have named this protein uterocalin.