bluuebunny/crossref_metadata_2025 huggingface dataset:
Results after radical surgical treatment for advanced carcinoma of hypopharynx
Authors: Hasdemir Oğuz , Çöl Cavit , Büyükaşık Oktay , Akçayöz Nihat
Published: February 2009

The aim of the study was to investigate patients with hypopharyngeal cancer. And this study focuses on a case series with hypopharynx cancer and cervical oesophageal cancer invading the hypopharynx. There were 13 cases over a period of 8 years, treated with pharyngo-laryngo-esophagectomy (PLE) and cervical lymph node dissection. In 10 of the patients, reconstruction was done with gastric pull-up (GP). In 3 of the 10 patients gastric reconstruction was added to aid in pyloric drainage (2 pyloromyotomy and 1 pyloroplasty) but the remaining 7 patients did not receive such procedures. The reconstruction of the digestive system after PLE is still a matter of debate. GP method is the most frequently preferred method for reconstruction. We believe that a more important problem than gastric drainage is the reflux of the gastric content and pyloric drainage which will not have a positive effect for solving this clinical situation. But we need bigger series for analyze of this specific condition.
CDK2 Phosphorylation of Smad2 Disrupts TGF-β Transcriptional Regulation in Resistant Primary Bone Marrow Myeloma Cells
Authors: Baughn Linda B. , Di Liberto Maurizio , Niesvizky Ruben , Cho Hearn J. , Jayabalan David , Lane Joseph , Liu Fang , Chen-Kiang Selina
Published: February 2009

Resistance to growth suppression by TGF-β1 is common in cancer; however, mutations in this pathway are rare in hematopoietic malignancies. In multiple myeloma, a fatal cancer of plasma cells, malignant cells accumulate in the TGF-β-rich bone marrow due to loss of both cell cycle and apoptotic controls. Herein we show that TGF-β activates Smad2 but fails to induce cell cycle arrest or apoptosis in primary bone marrow myeloma and human myeloma cell lines due to its inability to activate G1 cyclin-dependent kinase (CDK) inhibitors (p15INK4b, p21CIP1/WAF1, p27KIP1, p57KIP2) or to repress c-myc and Bcl-2 transcription. Correlating with aberrant activation of CDKs, CDK-dependent phosphorylation of Smad2 on Thr8 (pT8), a modification linked to impaired Smad activity, is elevated in primary bone marrow myeloma cells, even in asymptomatic monoclonal gammopathy of undetermined significance. Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2. Our findings provide the first direct evidence that pT8 Smad2 couples dysregulation of CDK2 to TGF-β resistance in primary cancer cells, and they suggest that disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-β resistance in multiple myeloma.
A Defect in Marco Expression Contributes to Systemic Lupus Erythematosus Development via Failure to Clear Apoptotic Cells
Authors: Rogers Nicola Jane , Lees Mark Jeffrey , Gabriel Luisa , Maniati Eleni , Rose Sarah Jane , Potter Paul Keith , Morley Bernard John
Published: February 2009

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of numerous antinuclear autoantibodies and inflammatory mediators. The BXSB mouse strain is an excellent model of the disease. Previous work has determined a number of important disease susceptibility intervals that have been isolated in separate congenic strains. Here, we have combined expression data from those strains with functional analyses to demonstrate that reduced expression of the innate scavenger receptor Marco (macrophage receptor with collagenous structure) is a primary event in BXSB mice, that reduced mRNA expression is mirrored at the protein level, and that this results in a significant alteration in function. We have confirmed a role for Marco in the clearance of apoptotic cells and a generalized defect in both endocytosis and phagocytosis. The failure to clear apoptotic cells has previously been linked to the development of systemic lupus erythematosus. However, the use of congenic mice with limited phenotypes in this study has enabled us to propose that in the case of Marco at least, disease results from the production of anti-dsDNA Abs.
IgE Influences the Number and Function of Mature Mast Cells, but Not Progenitor Recruitment in Allergic Pulmonary Inflammation
Authors: Mathias Clinton B. , Freyschmidt Eva-Jasmin , Caplan Benjamin , Jones Tatiana , Poddighe Dimitri , Xing Wei , Harrison Krista L. , Gurish Michael F. , Oettgen Hans C.
Published: February 2009

Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcεRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE−/− animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE−/− mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.
Human Basophils Express the Glycosylphosphatidylinositol-Anchored Low-Affinity IgG Receptor FcγRIIIB (CD16B)
Authors: Meknache Nihad , Jönsson Friederike , Laurent Jérôme , Guinnepain Marie-Thérèse , Daëron Marc
Published: February 2009

Basophils express not only high-affinity IgE receptors, but also low-affinity IgG receptors. Which, among these receptors, are expressed by human basophils is poorly known. Low-affinity IgG receptors comprise CD32 (FcγRIIA, FcγRIIB, and FcγRIIC) and CD16 (FcγRIIIA and FcγRIIIB). FcγRIIA, FcγRIIC, and FcγRIIIA are activating receptors, FcγRIIB are inhibitory receptors, FcγRIIIB are GPI-anchored receptors whose function is poorly understood. Basophils were reported to express FcγRII, but not FcγRIII. We aimed at further identifying basophil IgG receptors. Basophils from normal donors and from patients suffering from an allergic skin disease (atopic dermatitis), allergic respiratory diseases (allergic rhinitis and asthma), or a nonallergic skin disease (chronic urticaria) were examined. We found that normal basophils contain FcγRIII transcripts and express FcγRIIIB, but not FcγRIIIA, which were detected on 24–81% basophils from normal donors and on 12–100% basophils from patients. Noticeably, the proportion of FcγRIIIB+ basophils was significantly lower in atopic dermatitis patients than in other subjects. This decreased FcγRIII expression was not correlated with an activated phenotype of basophils in atopic dermatitis patients, although FcγRIIIB expression was down-regulated upon basophil activation by anti-IgE. Our results challenge the two dogmas 1) that basophils do not express FcγRIII and 2) that FcγRIIIB is exclusively expressed by neutrophils. They suggest that a proportion of basophils may be lost during enrichment procedures in which FcγRIII+ cells are discarded by negative sorting using anti-CD16 Abs. They unravel an unexpected complexity of IgG receptors susceptible to modulate basophil activation. They identify a novel systemic alteration in atopic dermatitis.
Herpesvirus Seropositivity in Childhood Associates with Decreased Monocyte-Induced NK Cell IFN-γ Production
Authors: Saghafian-Hedengren Shanie , Sundström Yvonne , Sohlberg Ebba , Nilsson Caroline , Linde Annika , Troye-Blomberg Marita , Berg Louise , Sverremark-Ekström Eva
Published: February 2009

EBV infection is inversely associated with IgE sensitization in children, and this association is further enhanced by CMV coinfection. In mice, herpesvirus latency causes systemic innate activation and protection from bacterial coinfection, implying the importance of herpesviruses in skewing immune responses during latent infection. Early control of viral infections depends on IFN-γ release by NK cells, which generally requires the presence of accessory cells. We investigated IFN-γ production by NK cells in PBMCs from children seropositive (SP) for EBV alone, for both EBV and CMV, or seronegative for both viruses. The ability of classical (CD14++CD16−) and proinflammatory (CD14+CD16+) monocytes to induce autologous NK cell IFN-γ was studied by coculture experiments with enriched CD3−CD56+ cells. Transwell experiments were used to evaluate how monocytes interact with NK cells to induce IFN-γ synthesis. SP children had a significantly reduced proportion of IFN-γ+ NK cells and cognate intracellular IFN-γ levels, which was more pronounced in CMV-coinfected subjects. Also, resting PBMCs of SP children displayed lower proportions of proinflammatory monocytes. IFN-γ production by NK cells was dependent on interactions with monocytes, with the proinflammatory subset inducing the highest IFN-γ. Finally, SP children had markedly lower levels of plasma IFN-γ, concurrent with in vitro findings. Herpesvirus infections could be one contributing factor for maturation toward balanced Th1-Th2 responses. Our data indicate that early infection by herpesviruses may affect NK cell and monocyte interactions and thereby also influence the development of allergies.
Evolution of Lipopolysaccharide (LPS) Recognition and Signaling: Fish TLR4 Does Not Recognize LPS and Negatively Regulates NF-κB Activation
Authors: Sepulcre María P. , Alcaraz-Pérez Francisca , López-Muñoz Azucena , Roca Francisco J. , Meseguer José , Cayuela María L. , Mulero Victoriano
Published: February 2009

It has long been established that lower vertebrates, most notably fish and amphibians, are resistant to the toxic effect of LPS. Furthermore, the lack of a TLR4 ortholog in some fish species and the lack of the essential costimulatory molecules for LPS activation via TLR4 (i.e., myeloid differentiation protein 2 (MD-2) and CD14) in all the fish genomes and expressed sequence tag databases available led us to hypothesize that the mechanism of LPS recognition in fish may be different from that of mammals. To shed light on the role of fish TLRs in LPS recognition, a dual-luciferase reporter assay to study NF-κB activation in whole zebrafish embryos was developed and three different bony fish models were studied: 1) the gilthead seabream (Sparus aurata, Perciformes), an immunological-tractable teleost model in which the presence of a TLR4 ortholog is unknown; 2) the spotted green pufferfish (Tetraodon nigroviridis, Tetraodontiformes), which lacks a TLR4 ortholog; and 3) the zebrafish (Danio rerio, Cypriniformes), which possesses two TLR4 orthologs. Our results show that LPS signaled via a TLR4- and MyD88-independent manner in fish, and, surprisingly, that the zebrafish TLR4 orthologs negatively regulated the MyD88-dependent signaling pathway. We think that the identification of TLR4 as a negative regulator of TLR signaling in the zebrafish, together with the absence of this receptor in most fish species, explains the resistance of fish to endotoxic shock and supports the idea that the TLR4 receptor complex for LPS recognition arose after the divergence of fish and tetrapods.
Innate Immunity Mediated by MyD88 Signal Is Not Essential for Induction of Lipopolysaccharide-Specific B Cell Responses but Is Indispensable for Protection against Salmonella enterica serovar Typhimurium infection
Authors: Ko Hyun-Jeong , Yang Jin-Young , Shim Doo-Hee , Yang Hyungjun , Park Sung-Moo , Curtiss Roy , Kweon Mi-Na
Published: February 2009

Salmonella organisms are Gram negative and facultative anaerobic bacteria that cause typhoid fever in humans. In this study, we evaluated LPS-specific adaptive immunity in innate immune-deficient mice after oral administration of attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) strains. Of interest, identical levels of LPS-specific IgG and IgA Abs were elicited in the systemic (i.e., serum and spleen) and mucosal (i.e., fecal extract and small intestine) compartments of wild-type, TLR4−/−, and MyD88−/− mice following oral vaccination with recombinant attenuated S. Typhimurium (RASV). Depletion of CD4+ T cells during RASV vaccination completely abrogated the generation of LPS-specific Abs in MyD88−/− mice. In addition, mRNA expression levels of a B cell-activating factor of the TNF family were significantly increased in the spleens of MyD88−/− mice after oral administration, implying that T cell-independent B cell switching might be also enhanced in the MyD88 signal-deficient condition. Of most interest, orally vaccinated MyD88−/− mice that possessed high levels of LPS-specific IgG and IgA, which had a neutralizing effect against Salmonella, died earlier than nonvaccinated wild-type mice following lethal oral challenge with virulent Salmonella species. These results suggest that innate immunity mediated by MyD88 signal is dispensable for induction of LPS-specific Ab responses following oral administration of attenuated Salmonella strains but indispensable for efficient protection.
Human B Cell Responses to TLR Ligands Are Differentially Modulated by Myeloid and Plasmacytoid Dendritic Cells
Authors: Douagi Iyadh , Gujer Cornelia , Sundling Christopher , Adams William C. , Smed-Sörensen Anna , Seder Robert A. , Karlsson Hedestam Gunilla B. , Loré Karin
Published: February 2009

Selected TLR ligands are under evaluation as vaccine adjuvants and are known to activate dendritic cells (DCs) and B cells to affect vaccine-induced Ab responses. However, the relative contribution of the two main human DC subsets, myeloid (MDCs) and plasmacytoid (PDCs), in supporting B cell responses to TLR ligands remains poorly understood. We found that PDCs but not MDCs markedly enhanced B cell proliferation in response to TLR7/8-L, an imidazoquinoline derivative, and to a lesser extent to TLR9 ligands (CpG ODN classes A, B, and C). PDCs strongly enhanced TLR7/8-L-induced proliferation of both memory and naive B cells but were only able to support memory cells to differentiate to CD27high plasmablasts. In response to TLR7/8 stimulation, PDCs mediated the up-regulation of transcription factors B lymphocyte-induced maturation protein 1 and X-box binding protein 1 and enhanced differentiation of B cells into IgM-, IgG-, and IgA-producing cells. Type I IFN produced to high levels by PDCs was the principal mediator of the effects on TLR7/8 stimulation. Although MDCs expressed higher levels of the known B cell growth factors IL-6, IL-10, and B cell-activating factor in response to TLR7/8 stimulation, they were unable to enhance B cell responses in this system. These data help decipher the different roles of PDCs and MDCs for modulating human B cell responses and can contribute to selection of specific TLR ligands as vaccine adjuvants.
Ignition of p53 Bomb Sensitizes Tumor Cells to Granzyme K-Mediated Cytolysis
Authors: Hua Guoqiang , Wang Shuo , Zhong Chao , Xue Peng , Fan Zusen
Published: February 2009

Inactivation of tumor suppressor p53 results in loss of the apoptosis-regulating function of the p53 protein in tumor cells. Restoration of wild-type p53 expression in p53 mutant tumor cells increases tumor susceptibility to CTL-mediated cytolysis. However, the direct role of p53 in regulating tumor sensitivity to NK cell-mediated lysis and the functional relationship between p53 and granzymes in the control of tumor killing are still poorly documented. In this study, we found that p53 can sensitize tumor-killing susceptibility to NK and granzyme K-mediated cytolysis. Granzyme K is constitutively expressed in high levels in NK cells and induces rapid caspase-independent cell death. Granzyme K may exert a critical role in NK cell-mediated tumor clearance. p53 associates with granzyme K and is a physiological substrate of granzyme K. p53 was processed to three cleavage products of p40, p35, and p13 fragments at Lys24 and Lys305. These three cleavage products harbor strong proapoptotic activities that amplify the proapoptotic action of p53 to potentiate tumor-killing sensitivity. Therefore, p53 is as a cytotoxic bomb that can be triggered by granzyme K, leading to potentiating killing efficacy.
Kinetic of RelA Activation Controls Magnitude of TLR-Mediated IL-12p40 Induction
Authors: Bode Konrad A. , Schmitz Frank , Vargas Leonardo , Heeg Klaus , Dalpke Alexander H.
Published: February 2009

IL-12 is a crucial cytokine for dendritic cell-mediated induction of Th 1 cell differentiation. TLR ligands induce IL-12 to differing extents. Stimulation of dendritic cells allowed for the differentiation of three groups of TLRs; potency to induce IL-12 decreased in the order of TLR7/9, TLR3/4, and TLR1/2/6 stimulation. The MAPK, PI3K, and IRF (IFN regulatory factor) signaling pathways could be ruled out to be the cause for the differences in IL-12p40 induction. However, we observed that stimulation of dendritic cells with different TLR ligands resulted in striking differences in the kinetics of NF-κB activation. LPS induced a rapid but short-lived activation of RelA, whereas CpG-DNA stimulation resulted in prolonged RelA activity at the IL-12p40 promoter. Only TLR2 and TLR4 ligands were capable of inducing S536 phosphorylation of RelA, which has been proposed to be responsible for early termination of NF-κB activation. It is suggested that differences in the kinetics of a common TLR signaling module affect the biological response patterns of various TLRs, with IL-12p40 being a gene that needs prolonged NF-κB activation.
Genetically Encoded Förster Resonance Energy Transfer Sensors for the Conformation of the Src Family Kinase Lck
Authors: Paster Wolfgang , Paar Christian , Eckerstorfer Paul , Jakober Andrea , Drbal Karel , Schütz Gerhard J. , Sonnleitner Alois , Stockinger Hannes
Published: February 2009

The current model for regulation of the Src family kinase member Lck postulates a strict correlation between structural condensation of the kinase backbone and catalytic activity. The key regulatory tyrosine 505, when phosphorylated, interacts with the Src homology 2 domain on the same molecule, effectively suppressing tyrosine kinase activity. Dephosphorylation of Tyr505 upon TCR engagement is supposed to lead to unfolding of the kinase structure and enhanced kinase activity. Studies on the conformation-activity relationship of Lck in living cells have not been possible to date because of the lack of tools providing spatiotemporal resolution of conformational changes. We designed a biochemically active, conformation-sensitive Förster resonance energy transfer biosensor of human Lck using the complete kinase backbone. Live cell imaging in Jurkat cells demonstrated that our biosensor performed according to Src family kinase literature. A Tyr505 to Phe mutation opened the structure of the Lck sensor, while changing the autophosphorylation site Tyr394 to Phe condensed the molecule. The tightly packed structure of a high-affinity YEEI tail mutant showed that under steady-state conditions the bulk of Lck molecules exist in a mean conformational configuration. Although T cell activation commenced normally, we could not detect a change in the conformational status of our Lck biosensor during T cell activation. Together with biochemical data we conclude that during T cell activation, Lck is accessible to very subtle regulatory mechanisms without the need for acute changes in Tyr505 and Tyr394 phosphorylation and conformational alterations.
Activation of Rho Kinase Isoforms in Lung Endothelial Cells during Inflammation
Authors: Mong Phyllus Y. , Wang Qin
Published: February 2009

Rho kinase (ROCK) is a downstream effector of Rho family GTPases, and two highly homologous isoforms, ROCK1 and ROCK2, are similarly inhibited by the widely used pharmacologic inhibitors. In endothelial cells (ECs), activation of ROCK regulates myosin L chain (MLC) phosphorylation, stress fiber formation and permeability increases during inflammation. This study examined isoform-specific ROCK activation in lung ECs in vitro using human pulmonary microvascular ECs and ex vivo using freshly isolated lung ECs from mice. In unstimulated human as well as mouse lung ECs, ROCK2 activity was greater than ROCK1 activity. TNF-α stimulation induced activation of both ROCK1 and ROCK2 in cultured human ECs. Studies using lung ECs freshly isolated from mice showed that intratracheal instillation of LPS induced ROCK activation in lung ECs that was inhibited by treating animals with fasudil, a pharmacologic ROCK inhibitor, and that both ROCK1 and ROCK2 were activated. Small interference RNA targeting ROCK1 or ROCK2 was used to examine their functions in regulating MLC phosphorylation and permeability increases induced by TNF-α in human ECs. TNF-α-induced MLC phosphorylation required ROCK activation. Inhibition of ROCK1 alone was not sufficient to prevent TNF-α-induced MLC phosphorylation, whereas inhibition of ROCK2 prevented TNF-α-induced late MLC phosphorylation at 24 h. Although ROCK1 was dispensable for TNF-α-induced MLC phosphorylation, ROCK1 was required for TNF-α-induced early permeability increases. Therefore, ROCK1 and ROCK2 are both activated by TNF-α and can be functionally separated in the signaling pathways leading to TNF-α-induced MLC phosphorylation and permeability increases.
Myosin-IIA and ICAM-1 Regulate the Interchange between Two Distinct Modes of T Cell Migration
Authors: Jacobelli Jordan , Bennett F. Chris , Pandurangi Priya , Tooley Aaron J. , Krummel Matthew F.
Published: February 2009

How T cells achieve rapid chemotactic motility under certain circumstances and efficient cell surface surveillance in others is not fully understood. We show that T lymphocytes are motile in two distinct modes: a fast “amoeboid-like” mode, which uses sequential discontinuous contacts to the substrate; and a slower mode using a single continuously translating adhesion, similar to mesenchymal motility. Myosin-IIA is necessary for fast amoeboid motility, and our data suggests that this occurs via cyclical rear-mediated compressions that eliminate existing adhesions while licensing subsequent ones at the front of the cell. Regulation of Myosin-IIA function in T cells is thus a key mechanism to regulate surface contact area and crawling velocity within different environments. This can provide T lymphocytes with motile and adhesive properties that are uniquely suited toward alternative requirements for immune surveillance and response.
Activation of Mammalian Target of Rapamycin Controls the Loss of TCRζ in Lupus T Cells through HRES-1/Rab4-Regulated Lysosomal Degradation
Authors: Fernandez David R. , Telarico Tiffany , Bonilla Eduardo , Li Qing , Banerjee Sanjay , Middleton Frank A. , Phillips Paul E. , Crow Mary K. , Oess Stefanie , Muller-Esterl Werner , Perl Andras
Published: February 2009

Persistent mitochondrial hyperpolarization (MHP) and enhanced calcium fluxing underlie aberrant T cell activation and death pathway selection in systemic lupus erythematosus. Treatment with rapamycin, which effectively controls disease activity, normalizes CD3/CD28-induced calcium fluxing but fails to influence MHP, suggesting that altered calcium fluxing is downstream or independent of mitochondrial dysfunction. In this article, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in lupus T cells. Activation of mTOR was inducible by NO, a key trigger of MHP, which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in CD4+ lupus T cells, and in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 overexpression was also inversely correlated with diminished TCRζ protein levels. Pull-down studies revealed a direct interaction of HRES-1/Rab4 with CD4 and TCRζ. Importantly, the deficiency of the TCRζ chain and of Lck and the compensatory up-regulation of FcεRIγ and Syk, which mediate enhanced calcium fluxing in lupus T cells, were reversed in patients treated with rapamcyin in vivo. Knockdown of HRES-1/Rab4 by small interfering RNA and inhibitors of lysosomal function augmented TCRζ protein levels in vitro. The results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.
Blocking Development of a CD8+ T Cell Response by Targeting Lymphatic Recruitment of APC
Authors: Teoh Denise , Johnson Louise A. , Hanke Tomas , McMichael Andrew J. , Jackson David G.
Published: February 2009

Generating a protective immune response to viral infection is known to depend upon the priming and clonal expansion of virus-specific CD8+ T cells by Ag-loaded dendritic cells (DC) within secondary lymphoid tissue. However, the actual initiation of the response involves critical upstream events that control the recruitment of mature Ag-charged DC from the periphery via afferent lymphatics, events that are still only partly understood. Recent evidence has revealed that transmigration of lymphatic endothelium by DC is regulated by the adhesion molecules ICAM-1 and VCAM-1 both in vitro and in vivo. These findings imply that lymphatic entry may be an important rate-limiting step in primary immunity and a possible target for immune intervention. In this study, we have explored such possibilities using an F5 TCR-transgenic mouse model to assess the contribution of lymphatic cell adhesion molecules in the CD8+ T cell response to influenza virus nucleoprotein (NP). We show for the first time that immunization with ICAM-1- and VCAM-1-blocking mAbs can impair the T cell response in lymph node-draining sites of dermally administered nucleoprotein vaccine (MVA.HIVA.NP) by targeting lymphatic uptake of Ag-loaded DC ahead of other cell adhesion molecule-dependent events. These results reveal lymphatic entry as an important step that may be rate limiting in the development of immunity and reconfirm its potential as a target for localized immunotherapy in inflammation and tissue rejection.
A Role of IgM Antibodies in Monosodium Urate Crystal Formation and Associated Adjuvanticity
Authors: Kanevets Uliana , Sharma Karan , Dresser Karen , Shi Yan
Published: February 2009

Uric acid is released from injured cells and can act as an adjuvant signal to the immune system. Uric acid crystals invoke strong inflammatory responses in tissues. Although their biological effects are evident and the associated signaling mechanisms are becoming clear, it remains unexplained as to why uric acid precipitates rapidly in vivo, in sharp contrast to the minimal crystallization in vitro. We report in this study that a group of IgM Abs is able to bind to these crystals, which is interesting in light that B cell-deficient mice do not sense the proinflammatory adjuvant effect of uric acid. The titers of these Abs increase upon immunization with uric acid crystals. We have produced large quantities of such mAbs. The purified IgM Abs can significantly facilitate uric acid precipitation to form the inflammatory crystals in vitro. Infusion of these Abs into B cell-deficient mice significantly increases the basal level of inflammation in these recipients and restores the host’s ability to sense uric acid’s adjuvanticity. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid-induced immune activation.
Detection of Rh antibodies using two low ionic diluents
Authors: Skaik YA
Published: February 2009

Background:

Low ionic strength solution (LISS) is used to increase the rate of association of antibody to the corresponding antigen during antibody detection tests. A number of LISSs are available on the market.

Aims:

The efficiency of two commercial low ionic diluents, DiaMed ID-CellStab and Inverclyde LISS were assessed using the DiaMed-ID LISS Coombs microtube column system and an incubation time varying from 15 to 35 min.

Materials and Methods:

One-hundred samples containing five Rh antibodies (anti-D, anti-C, anti-E, anti-c and anti-e) were tested against commercial red cells using the two low ionic diluents after 15, 25 and 35 min.

Results:

The Inverclyde LISS detected 91, 95 and 96% of the Rh antibodies compared to 78, 79 and 83% for ID-CellStab after 15, 25 and 35 min incubation time, respectively, for both methods.

Conclusions:

The Inverclyde LISS is a more suitable and efficient diluent than ID-CellStab for the detection of Rh antibodies. The sensitivity of Rh antibody detection increased for the both methods as the incubation time increased.
Immunophenotypic characterisation of peripheral T lymphocytes in pulmonary tuberculosis
Authors: Al Majid FM , Abba AA
Published: February 2009

Background:

The cellular immune response plays an important role in determining the outcome of infection and disease in Mycobacterium tuberculosis. Many studies of these disease interactions yield contradictory results.

Aim:

This study aims at determining the changes that take place in the subpopulations of T lymphocytes in the blood of patients with pulmonary tuberculosis (TB).

Settings and Design:

This cross-sectional study was done at King Khalid University Hospital, Riyadh, Saudi Arabia.

Materials and Methods:

Flow cytometry was used to determine the absolute numbers and percentages of T CD3, T CD4, T CD8, T CD19 and natural killer (NK) T cells in 54 patients with active pulmonary TB before the commencement of treatment and in 25 healthy PPD negative volunteers.

Statistical Analysis:

Statistical Package for Social Sciences (version 11.5) was used for analysis.

Results:

There were significant differences in the values of CD3, CD4 and NK T cells among the groups. The numbers of CD3 and CD4 cells were lower in subjects than in controls [1091.9 ± 321.4 vs. 1364.6 ± 251.2; P < 0.001 and 639.8 ± 285 vs. 822 ± 189.9; P < 0.004, respectively] while numbers of NK T cells were much higher in patients than in controls (410.7 ± 286 vs. 182.3 ± 140; P < 0.001). The numbers of CD8 cells were not significantly changed with disease (609 ± 233.5 in subjects and 613.4 ± 170.3 in controls P = 0.761).

Conclusion:

There are significant changes in the cellular immune response particularly affecting the CD3, CD4 and NK T cells with the development of pulmonary TB. Therefore, further studies of these changes may have important implications on the development of diagnostic tools, vaccines and treatment modalities.
Relative efficiency of polymerase chain reaction and enzyme-linked immunosorbant assay in determination of viral etiology in congenital cataract in infants
Authors: Shyamala G , Sowmya P , Madhavan HN , Malathi J
Published: February 2009

Background:

Perinatal viral infections of fetus are among the leading causes of congenital cataract and identifying the viral etiology is important. Objectives: To detect the presence of Rubella virus (RV), herpes simplex virus (HSV) and cytomegalovirus (CMV) in lens aspirate specimens obtained from patients with congenital cataract and relate the results with serology.

Setting and Design:

Prospective study carried out in tertiary care hospital.

Materials and Methods:

Fifty lens aspirates from 50 infants with congenital cataract were subjected to HSV, RV isolation and polymerase chain reaction (PCR) for detection of HSV and CMV. Reverse transcription polymerase chain reaction (RT-PCR) was applied for RV detection. Peripheral blood specimens were screened for anti-HSV, RV and CMV antibodies by enzyme-linked immunosorbant assay (ELISA).

Results:

Rubella virus was detected in nine (18%) lens aspirates, by nRT-PCR which includes six positive by culture. HSV-2 DNA was detected in nine other lens aspirates, while CMV was not detected by PCR. Serological results did not correlate with the presence of viruses in the lens aspirates. This is the first report of detection of HSV-2 DNA in cases of congenital cataract.

Conclusions:

Cytomegalovirus may not be playing a significant role in causation of congenital cataract. The role of serology in identifying causative viral infection for congenital cataract needs to be re-evaluated.
Stomaplasty-anterior advancement flap and lateral splaying of trachea, a simple and effective technique
Authors: Trivedi NP , Patel D , Thankappan K , Iyer S , Kuriakose MA
Published: February 2009

Background:

Stomal stenosis after laryngectomy is a common and distressing complication. Once sets in, it is generally progressive, causes problems and needs active intervention.

Aim:

To evaluate effectiveness of new simple method of stomaplasty in solving troublesome complication of stoma stenosis.

Settings and Design:

Charts of eight patients who underwent modified stomaplasty and completed 1 year were reviewed.

Materials and Methods:

A modified anterior advancement flap and lateral splaying of trachea for stoma plasty are described. This involves excision of scar tissue of the anterior two-third of trachea and interposition of the defect with an inferiorly based triangular skin flap. The tracheo-esophageal-prosthesis (TEP) site is left untouched.

Statistical Analysis:

Outcome were measured in relation with need for further stenting or any other revision procedure required and ability to use TEP for speech production.

Results:

Eight patients underwent stoma revision surgery. Median preprocedure stoma diameter was 10 mm vertically (range 8-12 mm) and 6 mm horizontally (range 5-10 mm). This could be improved to 25 mm (range 22-30 mm) vertically and 16 mm (range 14-20 mm) horizontally after stoma revision. At 1-year follow-up, the median measurements were 20 mm (range 16-26) vertically and 14 mm (range 12-18) horizontally. Postprocedure, one patient required intermittent stenting at nighttime. All patients could use the TEP effectively. One patient who underwent salvage laryngectomy following chemoradiotherapy developed flap dehiscence.

Conclusions:

This is a simple and effective technique for stomaplasty. All patients treated with this technique had adequately large stoma for breathing and use of TEP.
Recurrent respiratory papillomatosis complicated by aspergillosis
Authors: Kuruvilla S , Saldanha R , Joseph LD
Published: February 2009

Pulmonary extension of recurrent invasive papillomatosis often poses a diagnostic challenge to the examining bronchoscopist, pathologist, radiologist and surgeon, in distinguishing it as a benign lesion that is confined to the mucosa and extending along the branches of the tracheobronchial tree from true invasion of a malignant tumor. We document here a case of recurrent invasive respiratory papillomatosis which initially presented as a laryngeal papilloma. After multiple recurrences, the patient presented with bronchopulmonary involvement, complicated by invasive aspergillosis in a non-immunocompromised setting.
Patient-controlled epidural analgesia with fentanyl and bupivacaine provides better analgesia than intravenous morphine patient-controlled analgesia for early thoracotomy pain
Authors: Behera BK , Puri GD , Ghai B
Published: February 2009

Background:

Intravenous patient-controlled analgesia (IVPCA) and patient-controlled epidural analgesia (PCEA) were studied in terms of analgesic efficacy, respiratory function and side effects after thoracic surgery for 24h. PCEA using fentanyl and bupivacaine as compared to IVPCA using morphine provides better pain relief both at rest and during coughing and is associated with fewer side effects.

Aims:

To compare IVPCA and PCEA in terms of analgesic efficacy, respiratory function and side effects after thoracic surgery.

Settings and Design:

Tertiary care teaching hospital. Prospective, randomized and open study.

Materials and Methods:

Thirty ASA-I or II patients undergoing thoracotomy were assigned randomly to receive either IVPCA using morphine or PCEA using fentanyl and bupivacaine combination postoperatively. No background infusion was administered in either group. Postoperative evaluation included pain intensity both at rest and during coughing, degree of sedation, arterial blood gas, forced vital capacity (FVC), peak expiratory flow rate (PEFR), presence of side effects such as nausea/vomiting and pruritis at 0, 2, 8, 12 and 24h. The primary outcome of the study was the percentage of patients with analgesia failure defined as VAS>30 despite three consecutive PCA boluses requiring rescue analgesia with intravenous fentanyl.

Statistical Analysis:

Data were analyzed using t -test, χ2 test and Mann-Whitney test.

Results:

Significantly less number of patients required rescue analgesia in PCEA group (P<0.05). Pain relief was better both at rest and during coughing (P<0.05) in PCEA group as compared to IVPCA. Patients in the PCEA group were less sedated and had fewer incidences of side effects, i.e. nausea/vomiting and pruritis. Postoperative FVC and PEFR were reduced significantly compared to baseline only in IVPCA group (P<0.05). Conclusion: After thoracic surgery, PCEA using fentanyl and bupivacaine as compared to IVPCA using morphine provides better pain relief both at rest and during coughing and associated with fewer side effects.
Family burden, quality of life and disability in obsessive compulsive disorder
Authors: Gururaj GP , Math SB , Reddy JYC , Chandrashekar CR
Published: February 2009

Background:

Obsessive compulsive disorder (OCD) is a psychiatric disorder that often tends to run a chronic course. The lifetime prevalence of OCD is around 1-3%, which is twice as prevalent as schizophrenia and bipolar disorder.

Aim:

To asses the family burden, quality of life (QoL) and disability in patients suffering from at least moderately ill OCD and then to compare them with schizophrenia patients of comparable severity.

Settings and Design:

We recruited 70 consecutive subjects (OCD=35, schizophrenia=35) who met study criteria between March 2005 and March 2006 from the psychiatric services of the National Institute of Mental Health and Neuro Sciences, Bangalore, India.

Materials and Methods:

The severity of illness was rated using the Clinical Global Impression-Severity (CGI-S). Instruments used in the current study were the Family Burden Schedule, the World Health Organization (WHO) QoL (Bref) and the WHO - Disability Assessment Schedule (DAS).

Statistical Analysis:

The Fisher's exact test/chi-square test was used to compare categorical variables and the independent sample t test was used to analyze continuous variables. Analysis of covariance (ANCOVA) was used to compare the groups after controlling for potential confounding variables. Pearson's correlation was used for correlation analysis.

Results:

Overall family burden, financial burden and disruption of family routines were significantly higher in schizophrenia patients compared to OCD although the groups did not differ with respect to other domains of family burden. On the WHO QoL, OCD patients were comparable to schizophrenia patients with respect to the psychological and social domains. On the WHO - DAS, both the groups were similar in all the domains except getting around.

Conclusion:

Severe OCD is associated with significant disability, poor QoL and high family burden, often comparable to schizophrenia. Therefore, there is an urgent need to increase the sensitivity among healthcare professionals to recognize and treat OCD.
Pulmonary function profile in patients with benign goiters without symptoms of respiratory compromise and the early effect of thyroidectomy
Authors: Pradeep PV , Tiwari P , Mishra A , Agarwal G , Agarwal A , Verma AK , Mishra SK
Published: February 2009

Background:

A large number of patients in our country develop goiters which seem to be apparently asymptomatic. Conventional radiography does not address the abnormal air flow dynamics. Flow volume loop studies have shown characteristic dampening of both inspiratory and expiratory curves. Pulmonary function tests (PFT) can provide a simple noninvasive method of assessing airway compromise.

Aim:

To address the effect of longstanding asymptomatic, benign goiter by performing PFT on the preoperative airway dynamics and the early postoperative changes at six weeks.

Setting and Design:

Tertiary care center, Prospective study. Materials and Methods: Sixty-four patients with benign goiters were included after they satisfied the necessary exclusion and inclusion criteria. Pulmonary function tests were performed in the pre and postoperative period.

Statistical Analysis Used:

SPSS ver. 10 software, Pearson's Bivariate correlation and students T test. Results: The preoperative PFT showed significant reduction in the Vital capacity (VC), Forced Vital Capacity (FVC), Forced expiratory volume in one second (FEV1), mid expiratory flow (MEF 25) and MEF 50 in the females and VC, FVC and FEV1 in males. Postoperatively significant improvement was observed in the tidal volume (VT) and FEV1 in the females and airway resistance in males.

Conclusions:

Pulmonary function tests can demonstrate the unmanifested abnormal airflow dynamics in benign asymptomatic goiters, which would have otherwise taken years to manifest. This abnormality improved after thyroidectomy, especially the forced expiratory maneuvers. The duration and weight of the goiter correlated well with reduction in FEV1 and its subsequent improvement after surgery in females.
Fournier′s gangrene
Authors: Unalp HR , Kamer E , Derici H , Atahan K , Balci U , Demirdoven C , Nazli O , Onal MA
Published: February 2009

Context:

Fournier's gangrene (FG) is a rapidly progressing acute gangrenous infection of the anorectal and urogenital area.

Aims:

The objectives of this study were to investigate patients with FG and to determine risk factors that affect mortality.

Settings and Design:

Retrospective clinical study.

Materials and Methods:

Clinical presentations and outcomes of surgical treatments were evaluated in 68 patients with FG.

Statistical Analysis Used:

Chi-square, Student's t -test, and logistic regression test.

Results:

Mean age of patients was 54 and female-to-male ratio was 9:59. Among the predisposing factors, diabetes mellitus (DM) was the most common (n =24, 35.3%), and sepsis on admission was detected in 31 (45.6%) and 15 (22.1%) patients, respectively. Seven (10.3%) patients died. Using logistic regression test, Fournier's Gangrene Severity Index (FGSI) <9, DM and sepsis on admission were found as prognostic factors. Conclusions: FG has a high mortality rate, especially in patients with DM and sepsis. An FGSI value <9 indicates high mortality rate.
Fournier′s gangrene in Mansoura Egypt
Authors: Ghnnam WM
Published: February 2009

Background:

Fournier's gangrene (FG), caused by synergistic aerobic and anaerobic organisms, is a life-threatening disorder in which infection of the perineum and scrotum (can affect penis alone) spreads along fascial planes, leading to soft-tissue necrosis. Despite antibiotics and aggressive debridement, the mortality rate of FG remains high.

Materials and Methods:

We analyzed 74 patients admitted to our institution's emergency surgical unit presenting with FG between January 2002 and January 2007, considering the anatomical site of infective gangrene, predisposing factors, etiological agents, and outcomes.

Results:

All the 74 patients included in this study were males; their mean age was 51±10.8 years (21-72 years). The mean duration from the onset of symptoms to admission to the hospital was 3.74±2.09 days (1-8 days). The mean hospitalization time was 9.2± 6.6 days (1-31). Forty patients (54.05%) had FG secondary to anorectal conditions. No etiologic factors for FG were found in 27 patients (36.5%). Diabetes mellitus as a predisposing factor was found in 38 patients (51.35%). There was no definite predisposing factor in 24 patients (32.43%). The microbiological finding was polymicrobial in 48 patients (64.8%) and monomicrobial in 26 patients (35.1%). The most frequent bacterial organisms were Escherichia coli (75.6%). Simple sigmoid loop colostomy was done in one patient (1.4%). Unilateral orchidectomy was done in one case (1.4%). The overall mortality rate was 16 patients (21.6%).

Conclusion:

FG is a rapidly progressive, fulminant infection. Even with aggressive surgical and medical treatment, mortality of the disease is high. In the present cases, such a high ratio of 21.6% means that this disease is still serious and fatal in Egypt.
Characterization of adult onset growth hormone deficiency syndrome in patients with hypothalamopituitary diseases
Authors: Bandgar TR , Prashanth M , Joshi SR , Menon PS , Shah NS
Published: February 2009

Background:

Hardly any data is available on Adult onset growth hormone deficiency (AOGHD) in Patients with hypothalamopituitary diseases in India.

Aims:

To characterize Asian Indian AOGHD syndrome in hypothalamopituitary diseases.

Settings and Design:

Cross-sectional analysis of data from a tertiary care hospital.

Materials and Methods:

Thirty patients with AOGHD were compared with 30 age-, sex-, body mass index-matched controls with respect to endocrine evaluation, biochemistry, body composition (BC), bone mineral density (BMD), cardiovascular risk profile and quality of life (QoL).

Statistical Analysis Used:

Comparisons were performed using two-tailed Student's test (SPSS Software version 10.0).

Results:

Most of the patients had abnormal BC with central obesity [Truncal FM (%): males {33.9±4.4 (patient) vs. 29.31±6.2 (control); P -0.027}; females {39.87±5.93 (patient) vs. 35.76±3.16 (control); P - 0.025}] and poor QoL. Patients aged over 45 years did not show low bone mass or lipid abnormalities as compared to controls. Low BMD and abnormal lipid profile {Triglycerides [mg/dl]:170.55±72.5 (patient) vs101.24±31.0 (control); P -0.038}; {very low density lipoprotein cholesterol [mg/dl]: 33.54±14.9 (patient) vs. 20.25±6.18 (control); P - 0.05} was seen in female patients less than 45 years of age.

Conclusions:

Male and female (more than 45 years) AOGHD patients have increased cardiovascular risk factors and poor QoL while BMD is unaffected. Females less than 45 years of age have the major characteristics of AOGHD and would be the group to benefit maximally with recombinant human Growth Hormone treatment, which is similar to that in the western literature.