bluuebunny/crossref_metadata_2025 huggingface dataset:
Palmitoylation-Dependent Plasma Membrane Transport but Lipid Raft-Independent Signaling by Linker for Activation of T Cells
Authors: Hundt Matthias , Harada Yohsuke , De Giorgio Lauren , Tanimura Natsuko , Zhang Weiguo , Altman Amnon
Published: July 2009

Linker for activation of T cells (LAT) is a dually palmitoylated transmembrane adaptor protein essential for T cell development and activation. However, whether LAT palmitoylation and/or lipid raft localization are required for its function is controversial. To address this question, we used a combination of biochemical, imaging, and genetic approaches, including LAT retrovirus-transduced mouse T cells and bone marrow chimeric mice. A nonpalmitoylated, non-lipid raft-residing mutant of transmembrane LAT could not reconstitute T cell development in bone marrow chimeric mice. This mutant was absent from the plasma membrane (PM) and was restricted mainly to the Golgi apparatus. A chimeric, nonpalmitoylated LAT protein consisting of the PM-targeting N-terminal sequence of Src kinase and the LAT cytoplasmic domain (Src-LAT) localized as a peripheral membrane protein in the PM, but outside lipid rafts. Nevertheless, Src-LAT restored T cell development and activation. Lastly, monopalmitoylation of LAT on Cys26 (but not Cys29) was required and sufficient for its PM transport and function. Thus, the function of LAT in T cells requires its PM, but not raft, localization, even when expressed as a peripheral membrane protein. Furthermore, LAT palmitoylation functions primarily as a sorting signal required for its PM transport.
Mast Cell-Dependent Contraction of Human Airway Smooth Muscle Cell-Containing Collagen Gels: Influence of Cytokines, Matrix Metalloproteases, and Serine Proteases
Authors: Margulis Alexander , Nocka Karl H. , Brennan Agnes M. , Deng Bijia , Fleming Margaret , Goldman Samuel J. , Kasaian Marion T.
Published: July 2009

In asthma, mast cells infiltrate the airway smooth muscle cell layer and secrete proinflammatory and profibrotic agents that contribute to airway remodeling. To study the effects of mast cell activation on smooth muscle cell-dependent matrix contraction, we developed coculture systems of human airway smooth muscle cells (HASM) with primary human mast cells derived from circulating progenitors or with the HMC-1 human mast cell line. Activation of primary human mast cells by IgE receptor cross-linking or activation of HMC-1 cells with C5a stimulated contraction of HASM-embedded collagen gels. Contractile activity could be transferred with conditioned medium from activated mast cells, implicating involvement of soluble factors. Cytokines and proteases are among the agents released by activated mast cells that may promote a contractile response. Both IL-13 and IL-6 enhanced contraction in this model and the activity of IL-13 was ablated under conditions leading to expression of the inhibitory receptor IL-13Rα2 on HASM. In addition to cytokines, matrix metalloproteinases (MMPs), and serine proteases induced matrix contraction. Inhibitor studies suggested that, although IL-13 could contribute to contraction driven by mast cell activation, MMPs were critical mediators of the response. Both MMP-1 and MMP-2 were strongly expressed in this system. Serine proteases also contributed to contraction induced by mast cell-activating agents and IL-13, most likely by mediating the proteolytic activation of MMPs. Hypercontractility is a hallmark of smooth muscle cells in the asthmatic lung. Our findings define novel mechanisms whereby mast cells may modulate HASM-driven contractile responses.
SLP-76 Couples Syk to the Osteoclast Cytoskeleton
Authors: Reeve Jennifer L. , Zou Wei , Liu Yuli , Maltzman Jonathan S. , Ross F. Patrick , Teitelbaum Steven L.
Published: July 2009

The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the αvβ3 integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited ∼40% in either SLP-76−/− or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.
MicroRNA-98 and let-7 Confer Cholangiocyte Expression of Cytokine-Inducible Src Homology 2-Containing Protein in Response to Microbial Challenge
Authors: Hu Guoku , Zhou Rui , Liu Jun , Gong Ai-Yu , Eischeid Alex N. , Dittman Jared W. , Chen Xian-Ming
Published: July 2009

Posttranscriptional gene regulation by microRNAs (miRNAs) has been implicated in the fine-tuning of TLR-mediated inflammatory response. The cytokine-inducible Src homology 2-containing protein (CIS), one member of the suppressors of cytokine signaling family of proteins, is an important negative regulator for inflammatory cytokine signaling. Using in vitro models using normal human biliary epithelial cells (cholangiocytes), we demonstrated that LPS stimulation or infection with the parasitic protozoan Cryptosporidium parvum induced expression of CIS protein without a change in CIS mRNA levels by activating the TLR signaling pathway. Of those miRNAs expressed in cholangiocytes, we found that targeting of the 3′-untranslated region of CIS by microRNA-98 (miR-98) or let-7 resulted in translational repression, but not CIS mRNA degradation. LPS stimulation or C. parvum infection decreased cholangiocyte expression of miR-98 and let-7. Down-regulation of miR-98 and let-7 relieved miRNA-mediated translational suppression of CIS and contributed to LPS- and C. parvum-stimulated CIS protein expression. Moreover, gain-of-function (by overexpression of CIS) and loss-of-function (by siRNA interference) studies revealed that CIS could enhance IκBα degradation and regulate NF-κB activation in cholangiocytes in response to LPS stimulation or C. parvum infection. Our data suggest that miR-98 and let-7 confer cholangiocyte expression of CIS in response to microbial challenge, a process that may be relevant to the regulation of TLR-mediated epithelial innate immune response.
Human CD14+ Macrophages in Intestinal Lamina Propria Exhibit Potent Antigen-Presenting Ability
Authors: Kamada Nobuhiko , Hisamatsu Tadakazu , Honda Haruki , Kobayashi Taku , Chinen Hiroshi , Kitazume Mina Tokutake , Takayama Tetsuro , Okamoto Susumu , Koganei Kazutaka , Sugita Akira , Kanai Takanori , Hibi Toshifumi
Published: July 2009

Intestinal APCs are considered critical in maintaining the balance between the response against harmful pathogens and the induction of tolerance to commensal bacteria and food Ags. Recently, several studies indicated the presence of gut-specific APC subsets, which possess both macrophage and dendritic cell (DC) markers. These unique APC subsets play important roles in gut immunity, especially for immune regulation against commensal bacteria. Herein, we examined a unique macrophage subset, which coexpressed the macrophage (Mφ) marker CD14 and the DC marker CD209 in human intestinal lamina propria (LP). The LP Mφ subset in both normal control subjects or Crohn’s disease (CD) patients induced proliferation of naive CD4+ T cells as well as monocyte-derived DCs, and it expressed retinoic acid synthetic enzyme retinaldehyde dehydrogenase 2 and retinol dehydrogenase 10, which induced expression of gut homing receptors on T cells in a retinoic acid-dependent manner. Moreover, the LP Mφ subset strongly evoked differentiation of Th1 cells and slightly induced Th17 cells in both normal control subjects and CD patients; the inducing potential was highest in CD patients. In CD patients, Th17, but not Th1, induction by the LP Mφ subset was enhanced in the presence of commensal bacteria Ags. This enhancement was not observed in normal control subjects. The Th17 induction by the LP Mφ subset was inhibited by neutralization of IL-6 and IL-1β, but it was enhanced by blockade of retinoic acid signaling. These observations highlight a role for LP Mφ in the enhanced Th1, and potentially in Th17 differentiation, at the inflammatory site of inflammatory bowel diseases.
Fas Apoptosis Inhibitory Molecule Enhances CD40 Signaling in B Cells and Augments the Plasma Cell Compartment
Authors: Kaku Hiroaki , Rothstein Thomas L.
Published: July 2009

Fas apoptosis inhibitory molecule (FAIM) was cloned as a mediator of Fas resistance that is highly evolutionarily conserved but contains no known effector motifs. In this study, we report entirely new functions of FAIM that regulate B cell signaling and differentiation. FAIM acts to specifically enhance CD40 signaling for NF-κB activation, IRF-4 expression, and BCL-6 down-regulation in vitro, but has no effect on its own or in conjunction with LPS or anti-Ig stimulation. In keeping with its effects on IRF-4 and BCL-6, FAIM overexpression augments the plasma cell compartment in vivo. These results indicate that FAIM is a new player on the field of B cell differentiation and acts as a force multiplier for a series of events that begins with CD40 engagement and ends with plasma cell differentiation.
A Central Role for Transcription Factor C/EBP-β in Regulating CD1d Gene Expression in Human Keratinocytes
Authors: Sikder Hashmat , Zhao Yuming , Balato Anna , Chapoval Andre , Fishelevich Rita , Gade Padmaja , Singh Ishwar S. , Kalvakolanu Dhananjaya V. , Johnson Peter F. , Gaspari Anthony A.
Published: July 2009

CD1d is a nonclassical Ag-presenting molecule that presents glycolipid Ags to NKT cells that are involved in immune defense and tumor rejection. It also plays a role in immunoregulatory functions in the epidermis. The mechanisms controlling the expression of CD1d are not well understood. Therefore, we cloned the CD1d gene promoter and characterized its activities in primary human keratinocytes and other cell lines of epithelial origin. We found that a CCAAT box in the CD1d promoter is required for its expression in keratinocytes. We show here that transcription factor C/EBP-β binds to the CCAAT box in the CD1d promoter in vitro and in vivo. Consistent with these observations, deletion of the gene encoding for C/EBP-β caused a loss of CD1d expression. The in vivo regulation of CD1d has significant implications for the pathologic mechanisms of certain immunologic skin diseases in which NKT cells play a role, such as allergic contact dermatitis and psoriasis. Together, these data show a central role for C/EBP-β in regulating CD1d transcription.
Expression of a CD200 Transgene Is Necessary for Induction but Not Maintenance of Tolerance to Cardiac and Skin Allografts
Authors: Gorczynski Reginald M. , Chen Zhiqi , He William , Khatri Ismat , Sun Yang , Yu Kai , Boudakov Ivo
Published: July 2009

CD200, a type 2 transmembrane molecule of the Ig supergene family, can induce immunosuppression in a number of biological systems, as well as promote increased graft acceptance, following binding to its receptors (CD200Rs). Skin and cardiac allograft acceptance are readily induced in transgenic mice overexpressing CD200 under control of a doxycycline-inducible promoter, both of which are associated with increased intragraft expression of mRNAs for a number of genes associated with altered T cell subset differentiation, including GATA-3, type 2 cytokines (IL-4, IL-13), GITR, and Foxp3. Interestingly, some 12–15 days after grafting, induction of transgenic CD200 expression can be stopped (by doxycycline withdrawal), without obvious significant effect on graft survival. However, neutralization of all CD200 expression (including endogenous CD200 expression) by anti-CD200 mAb caused graft loss, as did introduction of an acute inflammatory stimulus (LPS, 10 μg/mouse, delivered by i.p. injection). We conclude that even with apparently stably accepted tissue allografts, disruption of the immunoregulatory balance by an intense inflammatory stimulus can cause graft loss.
Intracellular Replication-Deficient Leishmania donovani Induces Long Lasting Protective Immunity against Visceral Leishmaniasis
Authors: Selvapandiyan Angamuthu , Dey Ranadhir , Nylen Susanne , Duncan Robert , Sacks David , Nakhasi Hira L.
Published: July 2009

No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1−/−) parasite can persist and be both safe and protective in animals. LdCen1−/− has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1−/− showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4+ T cell population a significant increase of single and multiple cytokine (IFN-γ, IL-2, and TNF) producing cells and IFN-γ/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1−/− also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1−/− can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.
Antigen Specificity Is not Required for Modulation of Lung Allergic Responses by Naturally Occurring Regulatory T Cells
Authors: Joetham Anthony , Takeda Katsuyuki , Okamoto Masakazu , Taube Christian , Matsuda Hiroyuki , Dakhama Azzeddine , Gelfand Erwin W.
Published: July 2009

Naturally occurring Foxp3+CD4+CD25+ T cells isolated from lungs of naive mice regulate lung allergic airway hyperresponsiveness, inflammation, levels of Th2 cytokines, and mucus production. OVA-specific (αβTCR+) CD4+CD25+ T cells suppressed ragweed-induced airway hyperresponsiveness and inflammation as did anti-TCR-treated OVA-specific CD4+CD25+ T cells, suggesting that Ag-specificity was not required for expression of regulatory activities. Suppression was associated with increased levels of IL-10 and TGF-β; decreased levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid; and reduced recruitment and activation of CD8+ T cells in the airways. Following intratracheal administration, OVA-specific CD4+CD25+ T cells were identified in both the airway lumens and lung parenchyma, and in some instances in close proximity to host CD8+ T cells. These results demonstrate that the regulatory activities of naturally occurring Foxp3+CD4+CD25+ T cells on lung allergic responses are Ag-nonspecific and thus, independent of Ag-specific recognition.
Anti-CD40 Monoclonal Antibody Synergizes with CTLA4-Ig in Promoting Long-Term Graft Survival in Murine Models of Transplantation
Authors: Gilson Christopher R. , Milas Zvonimir , Gangappa Shivaprakash , Hollenbaugh Diane , Pearson Thomas C. , Ford Mandy L. , Larsen Christian P.
Published: July 2009

Blockade of the CD40/CD154 signaling pathway using anti-CD154 Abs has shown promise in attenuating the alloimmune response and promoting long-term graft survival in murine model systems, although side effects observed in humans have hampered its progression through clinical trials. Appropriately designed anti-CD40 Abs may provide a suitable alternative. We investigated two isoforms of a novel monoclonal rat anti-mouse CD40 Ab (7E1) for characteristics and effects mirroring those of anti-CD154: 7E1-G1 (an IgG1 isotype); and 7E1-G2b (an IgG2b isotype). In vitro proliferation assays to measure the agonist properties of the two anti-CD40 Abs revealed similar responses when plate bound. However, when present as a soluble stimulus, 7E1-G1 but not 7E1-G2b led to proliferation. 7E1-G2b was as effective as anti-CD154 when administered in vivo in concert with CTLA4-Ig in promoting both allogeneic bone marrow chimerism and skin graft survival, whereas 7E1-G1 was not. The protection observed with 7E1-G2b was not due to depletion of CD40-bearing APCs. These data suggest that an appropriately designed anti-CD40 Ab can promote graft survival as well as anti-CD154, making 7E1-G2b an attractive substitute in mouse models of costimulation blockade-based tolerance regimens.
Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice
Authors: Hamilton-Williams Emma E. , Martinez Xavier , Clark Jan , Howlett Sarah , Hunter Kara M. , Rainbow Daniel B. , Wen Li , Shlomchik Mark J. , Katz Jonathan D. , Beilhack Georg F. , Wicker Linda S. , Sherman Linda A.
Published: July 2009

In humans and NOD mice, defects in immune tolerance result in the spontaneous development of type-1-diabetes. Recent studies have ascribed a breakdown in tolerance to dysfunction in regulatory T cells that is secondary to reduced IL-2 production by T cells having the NOD diabetes susceptibility region insulin-dependent diabetes 3 (Idd3). In this study, we demonstrate a peripheral tolerance defect in the dendritic cells of NOD mice that is independent of regulatory T cells. NOD CD8 T cells specific for islet Ags fail to undergo deletion in the pancreatic lymph nodes. Deletion was promoted by expression of the protective alleles of both Idd3 (Il2) and Idd5 in dendritic cells. We further identify a second tolerance defect that involves endogenous CD4 T cell expression of the disease-promoting NOD alleles of these genetic regions. Pervasive insulitis can be reduced by expression of the Idd3 and Idd5 protective alleles by either the Ag-presenting cell or lymphocytes.
An Engineered GM-CSF-CCL2 Fusokine Is a Potent Inhibitor of CCR2-Driven Inflammation As Demonstrated in a Murine Model of Inflammatory Arthritis
Authors: Rafei Moutih , Berchiche Yamina A. , Birman Elena , Boivin Marie-Noëlle , Young Yoon Kow , Wu Jian Hui , Heveker Nikolaus , Galipeau Jacques
Published: July 2009

CCR2 is a chemokine receptor widely expressed by lymphomyeloid cells involved in maladaptive autoimmune ailments. Therefore CCR2 is of great interest as a biological target for immune suppression due to its direct implication in autoimmune diseases such as rheumatoid arthritis. We have generated a novel fusion protein using GM-CSF and an N-terminal truncated version of MCP-1/CCL2 (6–76, GMME1) and investigated its utility as a CCR2-specific immune suppressor. Using BRET studies, we found that distinct to CCL2, GMME1 binding to CCR2 led to altered conformational changes in the CCR2 homodimer and did not induce the recruitment of β-arrestin 2 to the receptor. However, CCR2-dependent calcium mobilization, BAX induction and caspase-3 activation followed by cell death was observed. Using Th17 cells harvested from DBA/1 mice ill with bovine collagen-induced arthritis, we demonstrate that GMME1 is capable of blocking their production of IL-17 in vitro. Upon its delivery to mice symptomatic with inflammatory arthritis, a robust clinical recovery occurred with decreased paw thickness to normal levels and a significant reduction in anti-collagen Ab titer and rheumatoid factor titer, as well as reduction of proinflammatory cytokines levels both intraarticular and systemic. Our data demonstrate that GMME1 is a powerful synthetic suppressor cytokine that coopts CCR2-dependent cellular signaling and blunts the effects of CCR2-expressing lymphomyeloid cells causative of autoimmune arthritis.
Gene Regulation and Chromatin Remodeling by IL-12 and Type I IFN in Programming for CD8 T Cell Effector Function and Memory
Authors: Agarwal Pujya , Raghavan Arvind , Nandiwada Sarada L. , Curtsinger Julie M. , Bohjanen Paul R. , Mueller Daniel L. , Mescher Matthew F.
Published: July 2009

A third signal that can be provided by IL-12 or type I IFN is required for differentiation of naive CD8 T cells responding to Ag and costimulation. The cytokines program development of function and memory within 3 days of initial stimulation, and we show here that programming involves regulation of a common set of ∼355 genes including T-bet and eomesodermin. Much of the gene regulation program is initiated in response to Ag and costimulation within 24 h but is then extinguished unless a cytokine signal is available. Histone deacetylase inhibitors mimic the effects of IL-12 or type I IFN signaling, indicating that the cytokines relieve repression and allow continued gene expression by promoting increased histone acetylation. In support of this, increased association of acetylated histones with the promoter loci of granzyme B and eomesodermin is shown to occur in response to IL-12, IFN-α, or histone deacetylase inhibitors. Thus, IL-12 and IFN-α/β enforce in common a complex gene regulation program that involves, at least in part, chromatin remodeling to allow sustained expression of a large number of genes critical for CD8 T cell function and memory.
Uncoordinated 119 Protein Controls Trafficking of Lck via the Rab11 Endosome and Is Critical for Immunological Synapse Formation
Authors: Gorska Magdalena M. , Liang Qiaoling , Karim Zunayet , Alam Rafeul
Published: July 2009

The activation of T cells through the TCR is essential for development of the adaptive immune response. TCR does not have any enzymatic activity and relies on the plasma membrane-associated lymphocyte-specific protein tyrosine kinase (Lck) for initiation of signaling. Here we uncover a mechanism that is responsible for plasma membrane targeting of Lck. We show that Lck is transported to the membrane via a specific endosomal compartment. The transport depends on the adaptor protein Uncoordinated 119 (Unc119), on the GTPase rat brain 11 (Rab11), and on the actin cytoskeleton. Unc119 regulates the activation of Rab11. Consequently, Unc119 orchestrates the recruitment of the actin-based motor protein, myosin 5B, and the organization of multiprotein complexes on endosomes. The Unc119-regulated pathway is essential for immunological synapse formation and T cell activation.
Human B Cells Secrete Granzyme B When Recognizing Viral Antigens in the Context of the Acute Phase Cytokine IL-21
Authors: Hagn Magdalena , Schwesinger Elisabeth , Ebel Verena , Sontheimer Kai , Maier Julia , Beyer Thamara , Syrovets Tatiana , Laumonnier Yves , Fabricius Dorit , Simmet Thomas , Jahrsdörfer Bernd
Published: July 2009

Human B cells are currently not known to produce the proapoptotic protease granzyme B (GrB) in physiological settings. We have discovered that BCR stimulation with either viral Ags or activating Abs in the context of the acute phase cytokine IL-21 can induce the secretion of substantial amounts of GrB by human B cells. Importantly, GrB response to viral Ags was significantly stronger in B cells from subjects recently vaccinated against the corresponding viruses as compared with unvaccinated subjects. GrB-secreting B cells featured a homogeneous CD19+CD20+CD27−CD38−IgD− phenotype, improved survival, and enhanced expression of costimulatory, Ag-presenting and cell-adhesion molecules. B cell-derived GrB was enzymatically active and its induction required the activation of similar signaling pathways as those in CTLs. Our findings suggest that GrB-secreting B cells support the early antiviral immune response against viruses with endosomal entry pathways, thereby counteracting overwhelming viral replication at the beginning of an infection until virus-specific T cells from draining lymph nodes arrive at the site of infection. Our data may also explain the elevated serum GrB levels found in the early phase of various viral diseases.
Atypical Memory B Cells Are Greatly Expanded in Individuals Living in a Malaria-Endemic Area
Authors: Weiss Greta E. , Crompton Peter D. , Li Shanping , Walsh Laura A. , Moir Susan , Traore Boubacar , Kayentao Kassoum , Ongoiba Aissata , Doumbo Ogobara K. , Pierce Susan K.
Published: July 2009

Epidemiological observations in malaria endemic areas have long suggested a deficiency in the generation and maintenance of B cell memory to Plasmodium falciparum (Pf) in individuals chronically reinfected with the parasite. Recently, a functionally and phenotypically distinct population of FCRL4+ hyporesponsive memory B cells (MBCs) was reported to be expanded in HIV-infected individuals with high viral loads. In this study, we provide evidence that a phenotypically similar atypical MBC population is significantly expanded in Pf-exposed Malian adults and children as young as 2 years of age as compared with healthy U.S. adult controls. The number of these atypical MBCs was higher in children with chronic asymptomatic Pf infections compared with uninfected children, suggesting that the chronic presence of the parasite may drive expansion of these distinct MBCs. This is the first description of an atypical MBC phenotype associated with malaria. Understanding the origin and function of these MBCs could be important in informing the design of malaria vaccines.
Assessment of quality of data provided on Pap test requisitions: Implications for quality of care and patient safety
Authors: Naryshkin Sonya , Schultz Brenda L.
Published: July 2009

Background:

The reliability of patient history and clinical information on Pap test requisitions has been questioned but not previously objectively determined. The effect of incomplete/inaccurate information on quality of patient care has not been previously quantified. Our objectives were (1) to find out how clinicians and their assistants viewed the requisition slip, and whether they understood the reasons for supplying the information requested, (2) to measure the completeness and accuracy of information on the requisition slips, and (3) to determine whether the clinical information and patient history provided on Pap test requisitions could be relied upon to accurately assign a Pap test to the laboratory's “high-risk rescreen” pool.

Methods:

Clinicians and their assistants were surveyed. A total of 899 consecutive Pap test requisition slips were reviewed. Patient history and clinical information from the slips were compared to data from our laboratory information system and/or electronic patient medical records.

Results:

Most survey respondents felt that proper completion of requisitions was important, but only 17% of clinicians and less staff realized that negative high-risk Pap tests underwent a quality assurance rescreen. Clinicians and/or staff recorded the last menstrual period, specimen source, and clinical information on the requisition slips 96%, 97%, and 88% of the time, respectively. Of 695 Pap tests with applicable computerized records, 172 (25%) qualified for high-risk rescreen based upon information provided on the requisition slip alone. An additional 52 Pap tests (7%), or 23% of the total high-risk Pap tests were discovered to be of high risk only after review of the electronic records.

Conclusions:

Clinicians and staff were receptive to discussions concerning the completion of requisition slips, but laboratory expectations could be better communicated. Requisition slips were properly completed with a high frequency, but the check boxes did not elicit all the information expected, so revision was necessary. The high accuracy of the completion of requisition slips permitted 77% of high-risk Pap tests to be identified via the requisition slip alone. Our findings challenge the conventional anecdotal impressions of “notoriously unreliable” information on Pap test requisition slips, but our experience may not be applicable to other settings.
Immediate Oxidation of Sulfides to Sulfoxides with Zinc Dichromate Trihydrate under Solvent Free Condition
Authors: HASSANI H.
Published: July 2009

Various types of sulfides were converted to sulfoxide by zinc dichromate trihydrate in high yields and rates under solvent‐free conditions.
Theoretical Evaluation of the Global and Local Electrophilicity Patterns to Characterize Hetero Diels‐Alder Cycloaddition in the Synthesis of Isoxazolo[4,5‐e](1,2,3,4‐tetrazine)
Authors: SHARMA Pratibha , KUMAR Ashok , SINGH Jitendra , SAHU Vinita
Published: July 2009

A series of substituted dienophiles 1–10 and three 1,2‐diazadienes namely D‐1, D‐2, D‐3 were chosen to understand the reactivity and selectivity of Diels‐Alder cycloaddition. The global and local electrophilicity patterns have been evaluated on a series of cycloaddition reactions to assess the reaction pathways (NDAC/IEDDAC) using the absolute scale of electrophilicity proposed by Parr et al. Regional electrophilicity at the active sites of the reagents involved in Diels‐Alder processes has been described on a quantitative basis using local or regional electrophilicity index i.e. Fukui function. Good qualitative/quantitative comparison was found between molecular energy gaps and global electronic parameters, which has been employed to assess the cycloaddition pathways successfully.
Synthesis and Crystal Structures of Four Metal(II) Complexes with 1‐(4‐Hydroxyphenyl)‐5‐mercaptotetrazole Ligand
Authors: ZHANG Shuguang , FENG Yunlong
Published: July 2009

Tetrazolic acid, CN4H, has similar acidity to carboxylic acid group, COOH. 1‐(4‐Hydroxyphenyl)‐5‐mercaptotetrazole (H2L) can act as a monodentate (S or N) or a bidentate (N, N or N, S) ligand, forming coordination compounds with metal ions. Four new M(II) complexes with HL− ligands, Co(HL)2(Py)2(H2O)2 (1), [Mn(HL)2(H2O)4]·2H2O (2), Mn(HL)2(Phen)2 (3), and [Zn(HL)2(Phen)2]·0.5H2O·1.5CH3OH (4) have been synthesized and structurally determined by X‐ray structure analyses. Among these complexes, the M(II) centers are all six‐coordinated in an octahedral coordination geometry, and HL− ligands bond to M(II) centers via nitrogen atoms in 1 and 2, while via sulfur atoms in 3 and 4, respectively.
Electrochemical Sensor for Oxidation of NO Based on Au‐Pt Nanoparticles Self‐assembly Film
Authors: XIE Jia , YU Zhihui , XIA Dingguo
Published: July 2009

Au‐Pt bimetallic nanoparticles film used as an efficient electrochemical sensor was prepared by self‐assembled Au‐Pt bimetallic nanoparticles on a glassy carbon (GC) substrate using thioglycolic acid as a linker. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the Au‐Pt nanoparticles self‐assembly film was dense and uniform. Electrochemical experiments revealed that Au‐Pt bimetallic nanoparticles film/GC electrode showed high electrocatalytic activity to the oxidation of nitric oxide.
Theoretical Study on Structures and Properties of N2O···HOCl Complexes
Authors: YUAN Ku , LIU Yanzhi , MA Weichao , TANG Huian , ZHU Yuancheng , ZHANG Ji
Published: July 2009

B3LYP/6‐311++G∗︁∗︁ and MP2/6‐311++G∗︁∗︁ calculations were used to analyze the interaction between hypochlorous acid (HOCl) and nitrous oxide (N2O). The results showed that there are six and four equilibrium geometries at the B3LYP/6‐311++G∗︁∗︁ and MP2/6‐311++G∗︁∗︁ computational levels, respectively. The equilibrium geometries of S1 and S3 were confirmed to be transition states by analytical frequency computations, and the other equilibrium geometries as minima. Complexes of S3, S5 and S6 use the H(6) atom of HOCl as a proton donor and the terminal O(3) atom of N2O as an acceptor. However, S2 uses the terminal N(1) atom of N2O as an acceptor. As for S1 and S4, S1 uses the Cl(4) atom of HOCl as a proton donor and the terminal N(1) atom of N2O as an acceptor; S4 uses the terminal O(3) atom of N2O as an acceptor. Interaction energy of the complexes corrected with basis set superposition error (BSSE) lies in the range of −1.56–−8.73 kJ·mol−1 at the B3LYP/6‐311++G∗︁∗︁ levels. The natural bond orbit (NBO) and atoms in molecules (AIM) theory were also applied to explain the structures and the properties of the complexes.
Classification of Rat FTIR Colon Cancer Data Using Wavelets and BPNN
Authors: CHENG Cungui , XIONG Wei , TIAN Yumei
Published: July 2009

A feature extracting method based on wavelets for horizontal attenuated total reflectance Fourier transform infrared spectroscopy (HATR‐FTIR) and the cancer classification using artificial neural network trained with back‐propagation algorithm is presented. The FTIR data collected from 36 normal Sprague‐dawley (SD) rats, 60 1,2‐DMH‐induced SD rats, and 44 second generation rats of those induced rats were first preprocessed. Then, 12 feature variants were extracted using continuous wavelet analysis. Based on BPNN classification, all spectra were classified into two categories: normal and abnormal ones. The accuracy values of identifying normal, dysplastic, early carcinoma, and advanced carcinoma were 100%, 94%, 97.5%, and 100%, respectively. This result indicated that FTIR with continuous wavelet transform (CWT) and the back‐propagation neural network (BPNN) could effectively and easily diagnose colon cancer in its early stages.
Three‐component Synthesis of Homoallylic Amines Catalyzed by Phosphomolybdic Acid in Water
Authors: XIE Zhengfeng , LI Guilong , ZHAO Gang , WANG Jide
Published: July 2009

The three‐component reactions of aromatic aldehydes, amines and allyltributylstannane in water catalyzed by phosphomolybdic acid (PMA), underwent smoothly to afford the corresponding homoallylic amines in high yields at room temperature.
Enantioselective Direct Aldol Reactions Catalyzed by Cinchonine‐derived Prolinamides
Authors: ZHAO Jing , CHEN Aijun , LIU Quanzhong
Published: July 2009

Highly enantioselective aldol reactions catalyzed by cinchonine‐derived prolinamides are reported. Both cyclic and acyclic ketones were reacted with various aldehydes furnishing the desired aldol products in up to 90% yield with excellent enantioselectivities (up to 95%) and moderate diastereoselectivities (up to 3.6/1) in the case of cyclic ketones. A possible mechanism that elucidates the excellent observed enantioselectivities is presented.
Effect of Electronic Factor in Ru‐phosphine‐diamine Complexes on Selective Hydrogenation of CC and CO Bonds
Authors: ZHANG Yu , YU Xiaojun , YU Changbin , XIA Yuqing , LI Ruixiang , CHEN Hua , LI Xianjun
Published: July 2009

A series of ruthenium complexes bearing different phosphines and diamines were synthesized and their components and structures were characterized by NMR spectra and elemental analyses. The catalytic properties of these complexes for the hydrogenation of benzylideneacetone and the mixture of acetophenone and styrene were investigated. The results showed that the basicity increase of phosphine or diamine dramatically facilitates the hydrogenation activity and selectivity to CO double bond. On the contrary, the basicity decrease of phosphine or diamine not only slows down the catalytic activity, but also significantly suppresses the hydrogenation selectivity to CO double bond. Based on the effect of electron factors of these complexes on the hydrogenation activity and selectivity of benzylideneacetone and the mixture of styrene and acetophenone, the activation mechanism of dihydrogen in ruthenium‐phosphine‐diamine system was proposed.
One‐step Preparation and Antibacterial Property of Poly(N‐iso‐propyl‐acrylamide) Grafted Poly(acrylonitrile/styrene) Microspheres Immobilized with Silver Nanoparticles
Authors: FENG Jiao , FAN Liheng , CHU Hong , XIONG Wanbin , JIANG Jinqiang , CHEN Mingqing
Published: July 2009

Monodispersed silver nanoparticles were immobilized onto the surface of poly(N‐isopropylacrylamide) grafted poly(acrylonitrile/styrene) (PNIPAAm‐g‐PAN/PSt) microspheres by a one‐step method using AgNO3 as a silver source. This process was performed via the coordination interaction between Ag+ ions and amide groups on PNIPAAm‐g‐PAN/PSt microsphere surfaces with the reduction of the corresponding ions by ethanol taking place simultaneously. Fourier transform infrared (FTIR) spectroscopy and ultraviolet (UV)‐visible spectra illustrated that the silver nanoparticles were successfully immobilized onto the PNIPAAm‐g‐PAN/PSt microspheres. The size and morphology of silvered microspheres were characterized by transmission electron microscopy (TEM). The weight percent of silver nanoparticles immobilized onto the microspheres was 12% based on the determination of thermogravimetric analysis (TGA). The antibacterial tests demonstrated that the as‐prepared silvered microspheres showed activity against Gram‐negative bacteria.
Design, Synthesis and Anti‐HIV Integrase Evaluation of 1,2,3‐ Triazol‐4‐yl‐substituted 1,4‐Dihydro‐4‐oxo‐1,5‐napthyridine‐ 3‐carboxylic Acids
Authors: ZENG Jia , LÜ Xiuhua , ZENG Chengchu , HU Liming , ZHONG Rugang
Published: July 2009

Copper(I)‐catalyzed terminal alkyne‐azide 1,3‐cycloaddition reaction has emerged as one of the main strategies for the rapid creation and screening of a small molecular library. The present work describes the design and synthesis of a series of 1,2,3‐triazol‐4‐yl‐substituted 1,4‐dihydro‐4‐oxo‐1,5‐napthyridine‐3‐carboxylic acids in which the hydrophobic and hydrophilic domains were efficiently incorporated by a click reaction. The structures of the desired products 8 and 12 were characterized by spectroscopic methods and their HIV integrase inhibitory activities were also screened.
A quantitative relationship of electrocardiographic criteria of left ventricular hypertrophy with echocardiographic left ventricular mass: A multivariate approach
Authors: Kansal S. , Roitman D. I. , Sheffield L. T.
Published: July 2009

The purpose of this study was to evaluate the sensitivity of various electrocardiographic (EKG) criteria of left ventricular hypertrophy (LVH) in relation to echocardiographic left ventricular mass (LVME) and to assess the relative strength of various EKG variables used in the diagnosis of LVH by multivariate analysis. An attempt was also made to determine if a new combination of precordial and T‐wave voltage could improve the sensitivity of EKG. In 89 patients, M‐mode echocardiograms and standard EKGs were studied. Correlation of Romhilt‐Estes point‐score system with LVME was r = 0.621, sensitivity and specificity was 57 and 81%, respectively. Other voltage criteria had lower sensitivity. Various combinations of precordial and T‐wave voltage were not superior. The quantitative relationship of individual EKG variable, QRS duration, SV1‐3, R V4‐6, strain T wave, left atrial abnormality, intrinsicoid deflection and axis, with LVM was, r = 0.661,0.595,0.429, 0.42, 0.347, and 0.225, respectively. By multivariate analysis, QRS duration, S V1‐3, T‐wave and R V4‐6 voltage had F‐value (relative strength) of 27.95, 27.15, 22.02, and 4.03, respectively, other variables were statistically insignificant. In conclusion, the most important EKG variables predictive of LVH are QRS duration, S V1‐3, strain T‐wave and lateral voltage in decreasing value. Rescoring these variables in accordance to their correlation to LVM may improve EKG sensitivity for the diagnosis of LVH.
The effect of radiographic contrast agents on bleeding time and platelet aggregation
Authors: Verdirame J. D. , Davis J. W. , Phillips P. E.
Published: July 2009

The purpose of this study was to determine whether the use of relatively small amounts of radio‐graphic contrast agents may impair hemostasis. Before and after injection of contrast agents, we measured the template bleeding time, platelet count in whole blood and platelet‐rich plasma, platelet aggregation induced by epinephrine and adenosine diphosphate (ADP), and percent disaggregation of ADP‐induced platelet aggregates in platelet‐rich plasma of 18 patients. Ten patients received 50–100 ml of sodium iothalamate (66.8%) for intravenous urography and 8 patients received 125–200 ml of a combination of meglumine diatrizoate (66%) and sodium diatrizoate (10%) for coronary an‐giography and left ventriculography. Neither group demonstrated a statistically significant mean difference (p >0.05) for any parameter measured before and after administration of the contrast agents. However, 2 patients who received diatrizoate had lengthening of their bleeding times to greater than twice the baseline value without any change in in vitro platelet aggregation. Physicians should be aware of this potential cause of bleeding which could be of particular danger to patients undergoing cardiopulmonary bypass with its inherent hemostatic defects.
Detection of a diurnal rhythm in arterial blood pressure in the evaluation of 24‐hour antihypertensive therapy
Authors: Germanó G. , Ciavarella M. , Appolloni A. , Ferrucci A. , Corsi V. , Damiani S.
Published: July 2009

Uncertainty in defining hypertensive disease makes a prolonged study of blood pressure pattern necessary, using continuous or semicontinuous blood pressure recordings. Its pathophysiological meaning involves data sufficiently indicative of blood pressure profile with reference to the continuous stimulations of different intensity and duration, which are met by subjects both in their daily activities and in the passage from an active life to sleep. Such a parameter is, in fact, an indispensable premise for a correct course of therapy. The aim of our work was at first the detection of a diurnal rhythm in blood pressure, using data obtained in a 24‐h ambulatory monitoring away from the conditioning of different activities and daily routine. We have employed three groups of 34 males each. The first group consisted of hypertensive outpatients, while hospitalized subjects comprised the second group. Thtrthird group was composed of normal subjects. Furthermore, after finding this system productive, we started studying whether this rhythm of blood pressure could be modified under the influence of a single administered drug dose, and whether information obtained could be easily interpreted. We studied 12 male patients with essential hypertension, which had been untreated. Each patient underwent three 24‐h blood pressure ambulatory monitorings. Two different doses of nifedipine (10 and 20 mg) were randomly administered to each of the patients at the beginning of the second and third readings. We observed a significant fall in systolic blood pressure and a minor decrease in diastolic blood pressure after administration of a single 10 mg nifedipine tablet.
Abnormal left ventricular filling in patients with sustained myocardial relaxation: Assessment of diastolic parameters using radionuclide angiography and echocardiography
Authors: Bryhn M.
Published: July 2009

Parameters of left ventricular filling obtained from time‐activity curves of radionuclide angiograms were compared with parameters of myocardial relaxation from digitized M‐mode curves of the free wall endocardium in 25 consecutive patients. Eight patients had normal left ventricular systolic and diastolic function. Five patients with low ejection fraction (EF < 50%) also had abnormal values of peak filling rate (PFR), time to peak filling rate (Tr), and/or time constant of endocardial retraction (Te). Twelve patients with normal EF had three (40%), two (40%), or one (20%) of the diastolic parameters within the pathological range. Tr correlated significantly with Te (r=0.88, p<0.001), and patients with Te prolongation always had high values of Tr. One of the diastolic parameters (PFR) correlated significantly with EF (r=0.60, p<0.01). Parameters of left ventricular filling and myocardial relaxation are thus abnormal in many patients with normal systolic function, indicating that diastolic parameters may be more sensitive to myocardial deterioration.
Noninvasive index of cardiac contractility during stress testing: A collaborative study
Authors: Luisada A. A. , Singhal A. , Portaluppi F. , Strozzi C.
Published: July 2009

The present study was conducted in parallel in three different institutions with a similar purpose but using different technical setups. Based on the experimental demonstration that the external phonocardiogram is similar to the rate of acceleration (d3P/d3t) of the left ventricular pressure, and that catecholamines in a similar way increase the early positive wave of the left ventricular pressure and the first heart sound (S1) of the external phonocardiogram; knowing that exercise causes secretion of catecholamines and sympathetic reflexes, we have studied the S1 changes as a result of exertion in 34 normal young subjects. Blood pressure, heart rate, electrocardiograph, and phonocardiograph recordings of each subject were taken. In 10 subjects, cardiac output was also recorded by impedance cardiography. The result of the study was that the first heart sound increased routinely 4–5 times the normal amplitude; in a few subjects the increase was up to 15 times greater. While the extent of increase of S1 was proportional to the severity and duration of the effort and was usually proportional to the increase of other parameters, exceptions were noted as having marked increase of S1 with moderate increase of either blood pressure or heart rate. This was explained by the different receptors activated by the catecholamines and by the complexity of hormonal and neural influences acting on various organs in a stress test. The amplitude of S1 was found to be a reasonably reliable index for following changes of cardiac contractility during exercise, and the suggestion was made that this parameter should be studied in parallel with the others in routine stress tests.
Ochronotic cardiovascular disease
Authors: Ptacin M. , Sebastian J. , Bamrah V. S.
Published: July 2009

Ochronosis is a disease of tyrosine metabolism. Although most commonly associated with alcaptonuria and spondyloarthropathy, cardiovascular abnormalities have been associated. We describe a case which exemplifies the cardiovascular findings in this entity.
Right ventricular subendocardial infarction in a patient with pulmonary hypertension, right ventricular hypertrophy, and normal coronary arteries
Authors: Carlson E. B. , Reimer K. A. , Rankin J. S. , Peter R. H. , Mccormack K. M. , Alexander L. G.
Published: July 2009

Right ventricular infarction is usually associated with coronary artery disease and concomitant left ventricular infarction. Isolated right ventricular subendocardial necrosis was discovered at autopsy in a 52‐year‐old woman with pulmonary hypertension, right ventricular hypertrophy, and normal coronary arteries, who died with septicemia 41 days after mitral valve replacement. This represents the first well‐documented report of isolated right ventricular subendocardial infarction associated with normal coronary arteries.
Dissection of the left main coronary artery: A complication of ptc a to the anterior descending artery
Authors: Lotan C. , Gotsman M. , Milgalter E.
Published: July 2009

This case report describes a patient with severe discrete left anterior descending coronary artery atheroma who underwent percutaneous transluminal coronary angioplasty. During the procedure, dissection occurred in a superior atheromatous plaque of the left main coronary artery and needed immediate surgery. Special care should be taken in the selection and angioplasty of patients with concomitant left main artery disease.