bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia
Authors: Rassenti Laura Z. , Jain Sonia , Keating Michael J. , Wierda William G. , Grever Michael R. , Byrd John C. , Kay Neil E. , Brown Jennifer R. , Gribben John G. , Neuberg Donna S. , He Feng , Greaves Andrew W. , Rai Kanti R. , Kipps Thomas J.
Published: June 2008

Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor. Knowledge of the IGHV mutation status or CD38 did not improve our ability to predict the time to first treatment except for ZAP-70–negative cases, which could be segregated into 2 groups of intermediate-risk or low-risk disease based on whether they expressed unmutated or mutated IGHV. ZAP-70 maintained its high relative prognostic value for the subset of patients with early-stage, asymptomatic disease, including patients evaluated within 1 year of diagnosis. Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70–positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years.
STAT3- and STAT5-dependent pathways competitively regulate the pan-differentiation of CD34pos cells into tumor-competent dendritic cells
Authors: Cohen Peter A. , Koski Gary K. , Czerniecki Brian J. , Bunting Kevin D. , Fu Xin-Yuan , Wang Zhengqi , Zhang Wen-Jun , Carter Charles S. , Awad Mohamed , Distel Christopher A. , Nagem Hassan , Paustian Christopher C. , Johnson Terrence D. , Tisdale John F. , Shu Suyu
Published: June 2008

The clinical outcomes of dendritic cell (DC)–based immunotherapy remain disappointing, with DCs often displaying a tenuous capacity to complete maturation and DC1 polarization in the tumor host. Surprisingly, we observed that the capacity for successful DC1 polarization, including robust IL12p70 production, could be regulated by STAT-dependent events even prior to DC differentiation. Exposure of CD34pos cells to single-agent granulocyte-macrophage colony-stimulating factor (GMCSF) induced multilineage, STAT5-dependent differentiation, including DCs that failed to mature in the absence of further exogenous signals. In contrast, Flt3L induced nearly global differentiation of CD34pos cells into spontaneously maturing DCs. IL-6 synergized with Flt3L to produce explosive, STAT3-dependent proliferation of phenotypically undifferentiated cells that nevertheless functioned as committed DC1 precursors. Such precursors not only resisted many tumor-associated immunosuppressants, but also responded to tumor contact or TGFβ with facilitated DC maturation and IL12p70 production, and displayed a superior capacity to reverse tumor-induced T-cell tolerance. GMCSF preempted Flt3L or Flt3L plus IL-6 licensing by blocking STAT3 activation and promoting STAT5-dependent differentiation. Paradoxically, following overt DC differentiation, STAT5 enhanced whereas STAT3 inhibited DC1 polarization. Therefore, nonoverlapping, sequential activation of STAT3 and STAT5, achievable by sequenced exposure to Flt3L plus IL-6, then GMCSF, selects for multilog expansion, programming, and DC1 polarization of tumor-competent DCs from CD34pos cells.
The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-κB through its N-terminal fragment
Authors: Chae Jae Jin , Wood Geryl , Richard Katharina , Jaffe Howard , Colburn Nona T. , Masters Seth L. , Gumucio Deborah L. , Shoham Nitza G. , Kastner Daniel L.
Published: June 2008

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV, which encodes a 781–amino acid protein denoted pyrin. We have previously shown that pyrin regulates caspase-1 activation and IL-1β production through interaction of its N-terminal PYD motif with the ASC adapter protein, and also modulates IL-1β production by interaction of its C-terminal B30.2 domain with the catalytic domains of caspase-1. We now asked whether pyrin might itself be a caspase-1 substrate, and found that pyrin is cleaved by caspase-1 at Asp330, a site remote from the B30.2 domain. Pyrin variants harboring FMF-associated B30.2 mutations were cleaved more efficiently than wild-type pyrin. The N-terminal cleaved fragment interacted with the p65 subunit of NF-κB and with IκB-α through its 15-aa bZIP basic domain and adjacent sequences, respectively, and translocated to the nucleus. The interaction of the N-terminal fragment with p65 enhanced entrance of p65 into the nucleus. The interaction of N-terminal pyrin with IκB-α induced calpain-mediated degradation of IκB-α, thus potentiating NF-κB activation. Absolute and relative quantities of cleaved pyrin and IκB-α degradation products were substantially increased in leukocytes from FMF patients compared with healthy controls. Our data support a new pyrin/caspase-1 pathway for NF-κB activation.
Hydroxychloroquine directly reduces the binding of antiphospholipid antibody–β2-glycoprotein I complexes to phospholipid bilayers
Authors: Rand Jacob H. , Wu Xiao-Xuan , Quinn Anthony S. , Chen Pojen P. , Hathcock James J. , Taatjes Douglas J.
Published: June 2008

Treatment with the antimalarial drug hydroxychloroquine (HCQ) has been associated with reduced risk of thrombosis in the antiphospholipid (aPL) syndrome (APS) and, in an animal model of APS, with reduction of experimentally induced thrombosis. Recognition of β2-glycoprotein I (β2GPI) by aPL antibodies appears to play a major role in the disease process. We therefore used the techniques of ellipsometry and atomic force microscopy (AFM) to investigate whether HCQ directly affects the formation of aPL IgG–β2GPI complexes on phospholipid bilayers. HCQ, at concentrations of 1 μg/mL and greater, significantly reduced the binding of aPL-β2GPI complexes to phospholipid surfaces and THP-1 (human acute monocytic leukemia cell line) monocytes. The drug also reduced the binding of the individual proteins to bilayers. This HCQ-mediated reduction of binding was completely reversed when the HCQ-protein solutions were dialyzed against buffer. HCQ also caused modest, but statistically significant, reductions of clinical antiphospholipid assays. In conclusion, HCQ reduces the formation of aPL-β2GPI complexes to phospholipid bilayers and cells. This effect appears to be due to reversible interactions between HCQ and the proteins and may contribute to the observed reduction of thrombosis in human and experimental APS. These results support the possibility that HCQ, or analogous molecules, may offer novel nonanticoagulant therapeutic strategies for treating APS.
GATA4/FOG2 transcriptional complex regulates Lhx9 gene expression in murine heart development
Authors: Smagulova Fatima O , Manuylov Nikolay L , Leach Lyndsay L , Tevosian Sergei G
Published: June 2008

Background

GATA4 and FOG2 proteins are required for normal cardiac development in mice. It has been proposed that GATA4/FOG2 transcription complex exercises its function through gene activation as well as repression; however, targets of GATA4/FOG2 action in the heart remain elusive.

Results

Here we report identification of the Lhx9 gene as a direct target of the GATA4/FOG2 complex. We demonstrate that the developing mouse heart normally expresses truncated isoforms of Lhx9 – Lhx9α and Lhx9β, and not the Lhx9-HD isoform that encodes a protein with an intact homeodomain. At E9.5 Lhx9α/β expression is prominent in the epicardial primordium, septum transversum while Lhx9-HD is absent from this tissue; in the E11.5 heart LHX9α/β-positive cells are restricted to the epicardial mesothelium. Thereafter in the control hearts Lhx9α/β epicardial expression is promptly down-regulated; in contrast, mouse mutants with Fog2 gene loss fail to repress Lhx9α/β expression. Chromatin immunoprecipitation from the E11.5 hearts demonstrated that Lhx9 is a direct target for GATA4 and FOG2. In transient transfection studies the expression driven by the cis-regulatory regions of Lhx9 was repressed by FOG2 in the presence of intact GATA4, but not the GATA4ki mutant that is impaired in its ability to bind FOG2.

Conclusion

In summary, the Lhx9 gene represents the first direct target of the GATA4/FOG2 repressor complex in cardiac development.
Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions
Authors: Larsson Tomas A , Olsson Frida , Sundstrom Gorel , Lundin Lars-Gustav , Brenner Sydney , Venkatesh Byrappa , Larhammar Dan
Published: June 2008

Background

One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY) receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes) and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishesTetraodon nigroviridisandTakifugu rubripes. These correspond toHomo sapienschromosomes 4, 5, 8 and 10.

Results

Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses inH. sapiens, M. musculus, D. rerio, T. rubripesandT. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs) showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains) and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events). RT-PCR carried out with several tissues inT. rubripesrevealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs.

Conclusion

We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate tetraploidizations forming a paralogon comprising human chromosomes 4, 5, 8 and 10 and one teleost tetraploidization. The combination of positional and phylogenetic data further strengthens the identification of orthologs and paralogs in the NPY receptor family.
Performance comparison of two microarray platforms to assess differential gene expression in human monocyte and macrophage cells
Authors: Maouche Seraya , Poirier Odette , Godefroy Tiphaine , Olaso Robert , Gut Ivo , Collet Jean-Phillipe , Montalescot Gilles , Cambien François
Published: June 2008

Background

In this study we assessed the respective ability of Affymetrix and Illumina microarray methodologies to answer a relevant biological question, namely the change in gene expression between resting monocytes and macrophages derived from these monocytes. Five RNA samples for each type of cell were hybridized to the two platforms in parallel. In addition, a reference list of differentially expressed genes (DEG) was generated from a larger number of hybridizations (mRNA from 86 individuals) using the RNG/MRC two-color platform.

Results

Our results show an important overlap of the Illumina and Affymetrix DEG lists. In addition, more than 70% of the genes in these lists were also present in the reference list. Overall the two platforms had very similar performance in terms of biological significance, evaluated by the presence in the DEG lists of an excess of genes belonging to Gene Ontology (GO) categories relevant for the biology of monocytes and macrophages. Our results support the conclusion of the MicroArray Quality Control (MAQC) project that the criteria used to constitute the DEG lists strongly influence the degree of concordance among platforms. However the importance of prioritizing genes by magnitude of effect (fold change) rather than statistical significance (p-value) to enhance cross-platform reproducibility recommended by the MAQC authors was not supported by our data.

Conclusion

Functional analysis based on GO enrichment demonstrates that the 2 compared technologies delivered very similar results and identified most of the relevant GO categories enriched in the reference list.
Proteomic profile of dormant Trichophyton Rubrum conidia
Authors: Leng Wenchuan , Liu Tao , Li Rui , Yang Jian , Wei Candong , Zhang Wenliang , Jin Qi
Published: June 2008

Background

Trichophyton rubrum is the most common dermatophyte causing fungal skin infections in humans. Asexual sporulation is an important means of propagation for T. rubrum, and conidia produced by this way are thought to be the primary cause of human infections. Despite their importance in pathogenesis, the conidia of T. rubrum remain understudied. We intend to intensively investigate the proteome of dormant T. rubrum conidia to characterize its molecular and cellular features and to enhance the development of novel therapeutic strategies.

Results

The proteome of T. rubrum conidia was analyzed by combining shotgun proteomics with sample prefractionation and multiple enzyme digestion. In total, 1026 proteins were identified. All identified proteins were compared to those in the NCBI non-redundant protein database, the eukaryotic orthologous groups database, and the gene ontology database to obtain functional annotation information. Functional classification revealed that the identified proteins covered nearly all major biological processes. Some proteins were spore specific and related to the survival and dispersal of T. rubrum conidia, and many proteins were important to conidial germination and response to environmental conditions.

Conclusion

Our results suggest that the proteome of T. rubrum conidia is considerably complex, and that the maintenance of conidial dormancy is an intricate and elaborate process. This data set provides the first global framework for the dormant T. rubrum conidia proteome and is a stepping stone on the way to further study of the molecular mechanisms of T. rubrum conidial germination and the maintenance of conidial dormancy.
Health services research in the public healthcare system in Hong Kong: An analysis of over 1 million antihypertensive prescriptions between 2004–2007 as an example of the potential and pitfalls of using routinely collected electronic patient data
Authors: Wong Martin CS , Jiang Johnny Y , Tang Jin-ling , Lam Augustine , Fung Hong , Mercer Stewart W
Published: June 2008

Background

Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example.

Methods

Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients' demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes).

Results

1,096,282 visit episodes were accessed, representing 93,450 patients. Patients' demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age ≥ 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32–0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39).

In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension.

Conclusion

The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients.
Noisy: Identification of problematic columns in multiple sequence alignments
Authors: Dress Andreas WM , Flamm Christoph , Fritzsch Guido , Grünewald Stefan , Kruspe Matthias , Prohaska Sonja J , Stadler Peter F
Published: June 2008

Motivation

Sequence-based methods for phylogenetic reconstruction from (nucleic acid) sequence data are notoriously plagued by two effects: homoplasies and alignment errors. Large evolutionary distances imply a large number of homoplastic sites. As most protein-coding genes show dramatic variations in substitution rates that are not uncorrelated across the sequence, this often leads to a patchwork pattern of (i) phylogenetically informative and (ii) effectively randomized regions. In highly variable regions, furthermore, alignment errors accumulate resulting in sometimes misleading signals in phylogenetic reconstruction.

Results

We present here a method that, based on assessing the distribution of character states along a cyclic ordering of the taxa, allows the identification of phylogenetically uninformative homoplastic sites in a multiple sequence alignment. Removal of these sites appears to improve the performance of phylogenetic reconstruction algorithms as measured by various indices of "tree quality". In particular, we obtain more stable trees due to the exclusion of phylogenetically incompatible sites that most likely represent strongly randomized characters.

Software

The computer program noisy implements this approach. It can be employed to improving phylogenetic reconstruction capability with quite a considerable success rate whenever (1) the average bootstrap support obtained from the original alignment is low, and (2) there are sufficiently many taxa in the data set – at least, say, 12 to 15 taxa. The software can be obtained under the GNU Public License from http://www.bioinf.uni-leipzig.de/Software/noisy/.
Response of pulmonary artery intimal sarcoma to surgery, radiotherapy and chemotherapy: a case report
Authors: Long Hong-qing , Qin Qin , Xie Cong-hua
Published: June 2008

Introduction

Pulmonary artery intimal sarcoma is a rare disease with no characteristic symptoms. It is difficult to diagnose early and is frequently misdiagnosed as a pulmonary embolism.

Case presentation

Here we report a case of pulmonary artery intimal sarcoma in a 54-year-old woman presenting with complaints of shortness of breath on exertion. Echocardiography and a computed tomography scan showed that the right pulmonary artery trunk was blocked by a low-density mass. The patient was diagnosed with pulmonary artery intimal sarcoma by pathology and a complete mass resection was performed. After experiencing 10 months of disease-free survival, she was re-admitted because of the recurrence and metastasis of the tumor. Radiotherapy and chemotherapy were performed; however, only limited success was achieved. The patient died 15 months after the initial onset of symptoms.

Conclusion

Some patients with intimal sarcoma of the pulmonary artery can benefit from radiotherapy and chemotherapy as well as surgery.
Mucinous cystadenoma of the appendix misdiagnosed as cystic hydatid disease of the liver: a case report
Authors: Krieg Andreas , Esch Jan Schulte am , Poll Ludger W , Braunstein Stefan , Knoefel Wolfram T
Published: June 2008

Introduction

Primary neoplastic lesions presenting with a mucocele of the appendix are very rare and can be divided into benign variants of mucinous adenomas or cystadenomas, mucinous tumours of uncertain malignant potential or mucinous cystadenocarcinomas. Most of these tumourous mucoceles are asymptomatic and are found incidentally. The major complication of neoplastic mucinous appendiceal tumours is the development of a pseudomyxoma peritonei due to spreading of mucin-producing cells within the abdominal cavity.

Case presentation

A 44-year-old man presented with a history of non-specific symptoms of right upper abdominal pain. Abdominal ultrasound and computed tomography scan identified a cystic mass consistent with the morphological characteristics of an echinococcal hydatid cyst. After completing systemic albendazole therapy, an explorative laparotomy revealed a cystic tumour of the appendix. Ileocaecal resection was performed and pathology reports confirmed the diagnosis of a mucinous cystadenoma of the appendix. The postoperative course was uneventful.

Conclusion

Here we present the case of a man with a mucinous cystadenoma of the appendix mimicking cystic hydatid disease. We discuss the importance of re-evaluation and differential diagnostic reflections in cases of appendiceal mucocele.
Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling
Authors: Boileau Christelle , Tat Steeve Kwan , Pelletier Jean-Pierre , Cheng Saranette , Martel-Pelletier Johanne
Published: June 2008

Introduction

Subchondral bone alterations represent an essential component of osteoarthritis (OA). Modifying the abnormal subchondral bone metabolism may be indicated to treat OA. We investigated the effect of diacerein and rhein on the changes occurring in subchondral bone during OA. To this end, we determined the drugs' effects on metalloprotease-13 (MMP-13) synthesis on subchondral bone and on the osteoblast signalling pathways. In osteoclasts, we studied MMP-13 and cathepsin K production as well as cell differentiation, proliferation, and survival.

Methods

The effect of diacerein/rhein on the production of subchondral bone MMP-13 was determined by enzyme-linked immunosorbent assay. Signalling pathways were evaluated on osteoblasts by Western blot. Osteoclast experiments were performed using cells from the pre-osteoclastic murine cell line Raw 264.7. Osteoclast MMP-13 and cathepsin K activities were determined by specific bioassays and differentiation of these cells quantified by tartrate-resistant acid phosphatase staining.

Results

Diacerein and rhein reduced, in a dose-dependent manner, the interleukin-1-beta (IL-1β)-induced MMP-13 production in OA subchondral bone. This effect occurred through the inhibition of ERK1/2 (extracellular signal-regulated kinase-1/2) and p38. In osteoclasts, they significantly reduced the activity of MMP-13 and cathepsin K. Moreover, these drugs effectively blocked the IL-1β effect on the osteoclast differentiation process and the survival of mature osteoclasts.

Conclusion

Altogether, these data suggest that diacerein/rhein could impact the abnormal subchondral bone metabolism in OA by reducing the synthesis of resorptive factors and osteoclast formation.
Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study
Authors: Lasocki Sigismond , Piednoir Pascale , Ajzenberg Nadine , Geffroy Arnaud , Benbara Abdel , Montravers Philippe
Published: June 2008

Introduction

Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting.

Methods

We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive.

Results

During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.

Conclusion

Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.
Histoplasma capsulatummanifests preferential invasion of phagocytic subpopulations in murine lungs
Authors: Deepe George S , Gibbons Reta S , Smulian A George
Published: June 2008

Numerous in vitro studies have demonstrated that Histoplasma capsulatum is engulfed by the diverse populations of phagocytic cells including monocytes/macrophages (Mφ), immature dendritic cells (DC), and neutrophils. The in vivo distribution of H. capsulatum has yet to be examined following an intrapulmonary challenge. To accomplish this goal, we engineered GFP into two genetically dissimilar strains of H. capsulatum, G217B and186R. C57BL/6 mice were infected with each of these strains, and we analyzed the distribution of this fungus in the three major phagocytic populations on successive days. Yeast cells were found in all three populations of cells from Days 1 through 7. Proportionally, DC dominated at Day 1, whereas the majority of yeast cells was detected in neutrophils thereafter. Yeast cells were present in inflammatory and resident Mφ on Day 3, but on Day 7, they were chiefly in inflammatory Mφ. Yeast cells were predominantly in a CD11c+intermediate/high, F4/80−, CD11b+, Ly-6C+, CD205+ DC population. Neutralization of TNF-α or IFN-γ produced a significant redistribution of yeast cells. These results reveal the complex nature of intracellular residence of this fungus. Moreover, the findings demonstrate that there is a skewing in the subpopulations of cells that are infected, especially DC.
Hookworm and Poverty
Authors: Hotez Peter
Published: June 2008

Human hookworm infection is the leading cause of anemia and undernutrition and the second most important parasitic infection of humans. Hookworm occurs almost exclusively in the setting of rural poverty in the developing countries of the tropics. The rural dependency reflects the precise soil and temperature requirements of the environmental life history stages of the parasite, whereas the relationship between hookworm and poverty is based on multiple factors, including inadequate sanitation, the absence of concrete floors in home dwellings, and lack of access to essential medicines. Also, hookworm not only occurs in the setting of poverty but also promotes poverty because of its health and educational effects in children, its adverse effect on pregnancy outcome, and its effect on worker productivity. Since the middle of the 20th century, poverty reduction and urbanization have successfully reduced the prevalence of hookworm in the world's industrialized nations and some middle‐income countries. However, the control of hookworm in low‐income countries still relies heavily on the frequent and periodic use of anthelminthic drugs either through deworming programs targeting school‐aged children or through integrated control programs that simultaneously target the seven neglected tropical diseases, including hookworm. However, the high rates of hookworm reinfection and the possible emergence of drug resistance will ultimately require the development of new control tools—including the Human Hookworm Vaccine, one of several so‐called antipoverty vaccines that could undergo development and testing over the next decade.
Food Security, Poverty, and Human Development in the United States
Authors: Cook John T. , Frank Deborah A.
Published: June 2008

Access to food is essential to optimal development and function in children and adults. Food security, food insecurity, and hunger have been defined and a U.S. Food Security Scale was developed and is administered annually by the Census Bureau in its Current Population Survey. The eight child‐referenced items now make up a Children's Food Security Scale. This review summarizes the data on household and children's food insecurity and its relationship with children's health and development and with mothers' depressive symptoms. It is demonstrable that food insecurity is a prevalent risk to the growth, health, cognitive, and behavioral potential of America's poor and near‐poor children. Infants and toddlers in particular are at risk from food insecurity even at the lowest levels of severity, and the data indicate an “invisible epidemic” of a serious condition. Food insecurity is readily measured and rapidly remediable through policy changes, which a country like the United States, unlike many others, is fully capable of implementing. The food and distribution resources exist; the only constraint is political will.
Improving the Health and Lives of People Living in Slums
Authors: Sheuya Shaaban A.
Published: June 2008

Urban poverty, ill health, and living in slums are intrinsically interwoven. Poverty is multidimensional and there is no agreement on a universal definition. UN‐HABITAT has introduced an operational definition of slums that is restricted to legal aspects and excludes the more difficult social dimensions. The World Health Organization definition is more comprehensive and uses a health and social determinants approach that is strongly based on the social conditions in which people live and work. Health and improving the lives of people living in slums is at the top of international development agenda. Proactive strategies to contain new urban populations and slum upgrading are the two key approaches. Regarding the latter, participatory upgrading that most often involves the provision of basic infrastructure is currently the most acceptable intervention in developing countries. In urbanization of poverty, participatory slum upgrading is a necessary but not sufficient condition to reduce poverty and improve the lives of slum dwellers. Empowering interventions that target capacity development and skill transfer of both individuals and community groups—as well as meaningful negotiations with institutions, such as municipal governments, which can affect slum dwellers' lives—appear to be the most promising strategies to improve the slum dwellers' asset bases and health. Non‐governmental organizations, training institutions, and international development partners are best placed to facilitate horizontal relationships between individuals, community groups, and vertical relationships with more powerful institutions that affect the slum dwellers' lives. The main challenge appears to be lack of commitment from the key stakeholders to upgrade interventions citywide.
Psychological Costs of Growing Up Poor
Authors: Dearing Eric
Published: June 2008

This chapter provides a synopsis of the extensive empirical and theoretical literatures on the psychological development of youth growing up poor. Low family income has statistically and practically significant costs for children's psychological development in cognitive and social–emotional domains, as shown by high rates of academic failure and mental health problems among youth growing up poor. These psychological costs are incurred primarily because poverty limits children's access to developmental stimulation and heightens their exposure to stress in both their physical and psychosocial environments. Yet, convergent evidence from experimental and nonexperimental studies also indicates that improving the economic well‐being of poor families translates into improved psychological well‐being for poor youth.
Health Insurance and Access to Health Care in the United States
Authors: Hoffman Catherine , Paradise Julia
Published: June 2008

Health insurance, poverty, and health are all interconnected in the United States. This article synthesizes a large and compelling body of health services research, finding a strong association between health insurance coverage and access to primary and preventive care, the treatment of acute and traumatic conditions, and the medical management of chronic illness. Moreover, by improving access to care, health insurance coverage is also fundamentally important to better health care and health outcomes. Research connects being uninsured with adverse health outcomes, including declines in health and function, preventable health problems, severe disease at the time of diagnosis, and premature mortality.
Supporting the Mental Health of Mothers Raising Children in Poverty
Authors: Beeber Linda S. , Perreira Krista M. , Schwartz Todd
Published: June 2008

Poverty increases maternal stress by heightening exposure to negative life events, job loss, chronic strains, poor housing, dangerous neighborhoods, and conflict with partners, culminating in crippling depressive symptoms, the most prevalent mental health threat. Depressive symptoms interfere with the provision of the strong maternal support needed to counter the hardships of poverty, thus placing infants and toddlers at risk for delayed language, social, and emotional development. Initial clinical trials in high‐risk mothers have shown promise, and successive tests of interventions will be strengthened if mothers who have mental health risks can be accurately targeted for inclusion. This article reports on a sequential, data‐driven process by which high‐risk mothers were targeted for intervention in two trials currently in progress to reduce depressive symptoms. An iterative process of using data to identify at‐risk mothers and validate the presence of risk factors helped hone the recruitment and design of the intervention trials. This report also offers guidance for further study.
Treating Multidrug‐Resistant Tuberculosis in Tomsk, Russia
Authors: Keshavjee S. , Gelmanova I.Y. , Pasechnikov A.D. , Mishustin S.P. , Andreev Y.G. , Yedilbayev A. , Furin J.J. , Mukherjee J.S. , Rich M.L. , Nardell E.A. , Farmer P.E. , Kim J.Y. , Shin S.S.
Published: June 2008

Tuberculosis (TB) and multidrug‐resistant TB (MDR‐TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities—overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few—the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR‐TB is reflected both in terms of a rise in TB and MDR‐TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR‐TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR‐TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case‐holding for the most vulnerable patients. The model of MDR‐TB care in Tomsk is applicable for other resource‐poor settings facing challenges to TB and MDR‐TB control.
Delivery of Agricultural Technology to Resource‐poor Farmers in Africa
Authors: Mignouna Hodeba D. , Abang Mathew M. , Omanya Gospel , Nang'ayo Francis , Bokanga Mpoko , Boadi Richard , Muchiri Nancy , Terry Eugene
Published: June 2008

Recent developments in agricultural science and technology have the potential to transform the agricultural sector in the developing world. These technological advances constitute key drivers of economic growth and hold great promise for poverty reduction in sub‐Saharan Africa (SSA). Agricultural research and development in Africa is undergoing a major paradigm shift. Until recently, public‐sector institutions in Africa worked in isolation to create and disseminate agricultural technologies to smallholder farmers. However, they need access to improved proprietary technologies developed for the most part by the private sector in developed countries. These technologies are currently concentrated in the hands of a few large corporations and are protected by intellectual property rights. The African Agricultural Technology Foundation (AATF) is a new initiative addressing the challenges associated with the access, development, and deployment of agricultural technologies to smallholder farmers in SSA. This article describes the AATF model of facilitating the creation of partnership alliances dedicated to promote and support collaboration among a wide variety of public‐ and private‐sector organizations around shared agricultural research and development goals for the public good. It explains AATF's public–private partnership framework for technology delivery in the light of market failures, institutional constraints, and systemic weaknesses, which impede public‐sector organizations from accessing and delivering pro‐poor knowledge and technology to farmers. The article provides policy makers, research managers, and business decision makers with an understanding of how access to, and delivery of, proprietary technologies could contribute to food security and the improvement of farmers' livelihoods in Africa.
Poverty and Access to Health Care in Developing Countries
Authors: Peters David H. , Garg Anu , Bloom Gerry , Walker Damian G. , Brieger William R. , Hafizur Rahman M.
Published: June 2008

People in poor countries tend to have less access to health services than those in better‐off countries, and within countries, the poor have less access to health services. This article documents disparities in access to health services in low‐ and middle‐income countries (LMICs), using a framework incorporating quality, geographic accessibility, availability, financial accessibility, and acceptability of services. Whereas the poor in LMICs are consistently at a disadvantage in each of the dimensions of access and their determinants, this need not be the case. Many different approaches are shown to improve access to the poor, using targeted or universal approaches, engaging government, nongovernmental, or commercial organizations, and pursuing a wide variety of strategies to finance and organize services. Key ingredients of success include concerted efforts to reach the poor, engaging communities and disadvantaged people, encouraging local adaptation, and careful monitoring of effects on the poor. Yet governments in LMICs rarely focus on the poor in their policies or the implementation or monitoring of health service strategies. There are also new innovations in financing, delivery, and regulation of health services that hold promise for improving access to the poor, such as the use of health equity funds, conditional cash transfers, and coproduction and regulation of health services. The challenge remains to find ways to ensure that vulnerable populations have a say in how strategies are developed, implemented, and accounted for in ways that demonstrate improvements in access by the poor.
Poverty and Human Immunodeficiency Virus in Children
Authors: Marais Barend Jacobus , Esser Monika , Godwin Sarah , Rabie Helena , Cotton Mark Fredric
Published: June 2008

Sub‐Saharan Africa is the region affected worst by human immunodeficiency virus (HIV), with the most southern countries, including Botswana, Zimbabwe, Swaziland, and South Africa, carrying the highest disease burden. This geographic distribution represents a complex interaction among virological, political, social, cultural, and economic forces. In South Africa the HIV epidemic is seemingly unchecked, with 18% of the adult population infected. Although South Africa is a middeveloped country, there is a large chasm between the wealthy and the poor, with many living in moderate to extreme poverty. Poverty creates conditions that fuel the HIV epidemic while HIV exacerbates the multiple interlinking causes of poverty. Children are the most vulnerable members of society, severely affected by all components of the poverty cycle. Although improved health education and access to care will alleviate many problems, sustainable poverty alleviation should form an essential component of the response to AIDS. The formulation of the United Nations Millennium Developmental Goals is an important step in the right direction, but global and local political commitment is essential for success.
Sustainable Transfer of Biotechnology to Developing Countries
Authors: Coloma Josefina , Harris Eva
Published: June 2008

Poverty and social inequalities have powerfully sculpted not only the distribution of infectious and other diseases but also the course of disease in those affected. The lack of proper diagnosis and access to adequate health services only compounds the problem. In low‐resource settings, the burden of disease can be reduced if the basic human and material resources exist to support the use of low‐cost interventions by appropriately trained personnel. For 20 years, the Sustainable Sciences Institute has built scientific capacity in developing countries to recognize, prevent, and respond to the threats posed by disease.
Mandated Empowerment
Authors: Banerjee Abhijit V. , Duflo Esther
Published: June 2008

The current trend in antipoverty policy emphasizes mandated empowerment: the poor are being handed the responsibility for making things better for themselves, largely without being asked whether this is what they want. Beneficiary control is now being built into public service delivery, while microcredit and small business promotion are seen as better ways to help the poor. The clear presumption is that the poor are both able and happy to exercise these new powers. This essay uses two examples to raise questions about these strategies. The first example is about entrepreneurship among the poor. Using data from a number of countries, we argue that there is no evidence that the median poor entrepreneur is trying his best to expand his existing businesses, even if we take into account the many constraints he faces. While many poor people own businesses, this seems to be more a survival strategy than something they want to do. The second example comes from an evaluation of a program in India that aims to involve poor rural parents in improving local public schools. The data suggest that despite being informed that they now have both the right to intervene in the school and access to funds for that purpose, and despite being made aware of how little the children were learning, parents opt to not get involved. Both examples raise concerns about committing ourselves entirely to antipoverty strategies that rely on the poor doing a lot of the work.
Diet and Health Outcomes in Vulnerable Populations
Authors: Sharkey Joseph R.
Published: June 2008

Good nutritional health is essential to physical and cognitive function, prevention or management of chronic health conditions, and prevention of disability. Poor nutritional health describes dietary intakes of inadequate amounts of energy, protein, and individual or multiple micronutrients. Homebound older adults are considered the most vulnerable for poor nutritional health; many are poor and experience persistent food insufficiency. This chapter discusses the importance of dietary intakes, especially for homebound older adults, and presents resource‐related factors that influence food choice and food acquisition. These factors include limited household income, food insufficiency, and utilization of community nutrition assistance programs. Of importance is that low dietary intakes influence balance, gait speed, leg strength, and overall lower extremity physical performance (LEP). This is crucial since decreased LEP is associated with increased disability over time. It is time to review policies and programs that influence dietary intake of homebound older adults.
The Effect of Poverty on Child Development and Educational Outcomes
Authors: Engle Patrice L. , Black Maureen M.
Published: June 2008

Poverty affects a child's development and educational outcomes beginning in the earliest years of life, both directly and indirectly through mediated, moderated, and transactional processes. School readiness, or the child's ability to use and profit from school, has been recognized as playing a unique role in escape from poverty in the United States and increasingly in developing countries. It is a critical element but needs to be supported by many other components of a poverty‐alleviation strategy, such as improved opportunity structures and empowerment of families. The paper reviews evidence from interventions to improve school readiness of children in poverty, both in the United States and in developing countries, and provides recommendations for future research and action.