bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the human germinal center–associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival
Authors: Natkunam Yasodha , Hsi Eric D. , Aoun Patricia , Zhao Shuchun , Elson Paul , Pohlman Brad , Naushad Hina , Bast Martin , Levy Ronald , Lossos Izidore S. 
Published: September 2006

AbstractThe human germinal-center–associated lymphoma (HGAL) gene and its cognate protein are expressed in a germinal center (GC)–specific manner. Its expression in classic Hodgkin lymphoma (cHL) prompted us to address whether HGAL expression could distinguish biologically distinct subgroups of cHL. Tissue microarrays from 145 patients treated with curative intent showed HGAL staining in 75% and was closely correlated with MUM1/IRF4 (92%) expression. BCL6 (26%), CD10 (0%), BCL2 (31%), Blimp1 (0.02%), and Epstein-Barr virus (EBV) (20%) showed no specific correlation; neither did phospho-STAT6, a key mediator of IL-4 and IL-13 signaling that induces HGAL and is implicated in cHL pathogenesis. In our study cohort, the 5-year overall survival (OS) correlated with young age (less than 45 years, P < .001), low stage (stage I and II, P = .04), and low International Prognostic Score (P = .002). In univariate analysis, HGAL expression was associated with improved OS (P = .01) and failure-free survival (FFS) (P = .05) but was not independent of other factors in multivariate analysis of OS or FFS. The expression of the GC-specific marker HGAL in a subset of cHL suggests that these cHLs retain characteristics of GC-derived lymphomas. The association with improved OS in univariate but not multivariate analysis suggests that HGAL expression is related to known clinical parameters of improved survival.
Reduced expression of inducible gelatinase B/matrix metalloproteinase-9 in monocytes from patients with myelodysplastic syndrome: correlation of inducible levels with the percentage of cytogenetically marked cells and with marrow cellularity
Authors: Iwata Mineo , Pillai Manoj , Ramakrishnan Aravind , Hackman Robert C. , Deeg H. Joachim , Opdenakker Ghislain , Torok-Storb Beverly 
Published: September 2006

AbstractRegulatory molecules produced by stromal cells are often membrane bound until cleaved by matrix metalloproteinases (MMPs); cleavage can either activate or inactivate regulatory functions. We report here that marrow stromal cells induce the expression of MMP-9 in monocytes. Induction was contact independent and could be reproduced with recombinant MCP-1/CCL2, whereas IL-6, M-CSF, G-CSF, GM-CSF, IL-8/CXCL8, SDF-1/CXCL12, and MGSA/CXCL1 did not have this effect. Stroma-induced levels of MMP-9 in the monocyte population from healthy donors were relatively consistent, whereas induced levels varied significantly (P < .001) in the CD14+ population from 27 patients with myelodysplastic syndrome (MDS). In patients with a clonal chromosomal marker, the level of inducible MMP-9 expression in the monocyte population was inversely correlated with the percentage of marker-positive cells (n = 11, P = .01), suggesting that the ability to induce MMP-9 may be compromised in clonally derived monocytes. The inducible levels of MMP-9 were also inversely correlated with marrow cellularity observed in biopsies from MDS patients (P < .001). We conclude that monocytes can express MMP-9 in response to stromal factors and that this response may be significantly decreased in MDS-derived monocytes.
Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic leukemia lymphocytes by suppressing interstrand DNA crosslink removal
Authors: Moufarij Mazin A. , Sampath Deepa , Keating Michael J. , Plunkett William 
Published: September 2006

AbstractOxaliplatin and fludarabine have different but potentially complementary mechanisms of action. Previous studies have shown that DNA repair is a major target for fludarabine. We postulate that potentiation of oxaliplatin toxicity by fludarabine may be due to the inhibition by fludarabine of the activity of the DNA excision repair pathways activated by oxaliplatin adducts. To test this, we investigated the cytotoxic interactions between the 2 drugs in normal and chronic lymphocytic leukemia (CLL) lymphocytes. In each population, the combination resulted in greater than additive killing. Analysis of oxaliplatin damage revealed that fludarabine enhanced accumulation of interstrand crosslinks (ICLs) in specific regions of the genome in both populations, but to a lesser extent in normal lymphocytes. The action of fludarabine on the removal of oxaliplatin ICLs was explored to investigate the mechanism by which oxaliplatin toxicity was increased by fludarabine. Lymphocytes from patients with CLL have a greater capacity for ICL unhooking compared with normal lymphocytes. In the presence of fludarabine the extent of repair was significantly reduced in both populations, more so in CLL. Our findings support a role of fludarabine-mediated DNA repair inhibition as a mechanism critical for the cytotoxic synergy of the 2 drugs.
An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study
Authors: Mallia Patrick , Message Simon D , Kebadze Tatiana , Parker Hayley L , Kon Onn M , Johnston Sebastian L 
Published: September 2006

Abstract

Background
Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.

Methods
We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II). Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.

Results
All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events.

Conclusion
Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.
HIV-2 Protease resistance defined in yeast cells
Authors: M'Barek Najoua Ben , Audoly Gilles , Raoult Didier , Gluschankof Pablo 
Published: September 2006

Abstract

Background
Inhibitors of the HIV-1 Protease currently used in therapeutic protocols, have been found to inhibit, although at higher concentrations, the HIV-2 encoded enzyme homologue. Similar to observations in HIV-1 infected individuals, therapeutic failure has also been observed for some patients infected with HIV-2 as a consequence of the emergence of viral strains resistant to the anti-retroviral molecules. In order to be able to define the specific mutations in the Protease that confer loss of susceptibility to Protease Inhibitors, we set up an experimental model system based in the expression of the viral protein in yeast.

Results
Our results show that the HIV-2 Protease activity kills the yeast cell, and this process can be abolished by inhibiting the viral enzyme activity. Since this inhibition is dose dependent, IC50 values can be assessed for each anti-retroviral molecule tested. We then defined the susceptibility of HIV-2 Proteases to Protease Inhibitors by comparing the IC50 values of Proteases from 7 infected individuals to those of a sensitive wild type laboratory adapted strain.

Conclusion
This functional assay allowed us to show for the first time that the L90M substitution, present in a primary HIV-2 isolate, modifies the HIV-2 Protease susceptibility to Saquinavir but not Lopinavir. Developing a strategy based on the proposed yeast expressing system will contribute to define amino acid substitutions conferring HIV-2 Protease resistance.
Caveolin-1 interacts with the Gag precursor of murine leukaemia virus and modulates virus production
Authors: Yu Zheng , Beer Christiane , Koester Mario , Wirth Manfred 
Published: September 2006

Abstract

Background
Retroviral Gag determines virus assembly at the plasma membrane and the formation of virus-like particles in intracellular multivesicular bodies. Thereby, retroviruses exploit by interaction with cellular partners the cellular machineries for vesicular transport in various ways.

Results
The retroviral Gag precursor protein drives assembly of murine leukaemia viruses (MLV) at the plasma membrane (PM) and the formation of virus like particles in multivesicular bodies (MVBs). In our study we show that caveolin-1 (Cav-1), a multifunctional membrane-associated protein, co-localizes with Gag in a punctate pattern at the PM of infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix protein (MA) of the Gag precursor. This interaction is mediated by a Cav-1 binding domain (CBD) within the N-terminus of MA. Interestingly, the CBD motif identified within MA is highly conserved among most other γ-retroviruses. Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells. Overexpression of a GFP fusion protein containing the putative CBD of the retroviral MA resulted in a considerable decrease in production of infectious retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected retroviral titres significantly.

Conclusion
This study demonstrates that Cav-1 interacts with MLV Gag, co-localizes with Gag at the PM and affects the production of infectious virus. The results strongly suggest a role for Cav-1 in the process of virus assembly.
Prospective randomized study comparing the Teleflex Medical SaphLITE Retractor to the Ethicon CardioVations Clearglide Endoscopic System
Authors: Schultz Scot C , Stapleton Dennis , D'Ambra Paula , Loftis Cynthia , Wahrmann Christine , Ebra George 
Published: September 2006

Abstract

Background
Several minimally invasive saphenous vein harvesting techniques have been developed to reduce morbidities associated with coronary artery bypass grafting. This prospective, randomized study was designed to compare two commonly used minimally invasive saphenous vein harvesting techniques, the SaphLITE Retractor System (Teleflex Medical) and the Clearglide Endoscopic Vessel Harvesting System (Ethicon CardioVations, Inc.).

Methods
Between January 2003 and March 2004, a total of 200 patients scheduled for primary, nonemergent coronary artery bypass grafting, with or without concomitant procedures were randomized into two groups: SaphLITE (n = 100) and Clearglide (n = 100). Pre-, intra- and postoperative data was collected and subjected to statistical analysis. Randomization provided homogenous groups with respect to preoperative risk factors.

Results
Harvest location for the SaphLITE group was thigh (n = 40), lower leg (n = 5) and both lower leg and thigh (n = 55). The location of harvest for the Clearglide group was thigh (n = 3), lower leg (n = 16) and both lower leg and thigh (n = 81). The mean incision length was 3.6 cm (range, 2–6) in the SaphLITE group versus 2.1 cm (range, 1–4) in the Clearglide group (p < 0.05). The total incision length was 12.9 cm versus 8.9 (p < 0.05) in the SaphLITE and Clearglide groups. Conversion to the open technique occurred in 5 SaphLITE patients and 7 Clearglide patients. Intraoperative leg exploration for bleeding occurred in two of the Clearglide patients and none of the SaphLITE patients. Post-operative complications specifically related to minimally invasive harvesting technique, including a two-week post-discharge visit, were not statistically different between the groups.

Conclusion
The saphenous vein can be safely harvested utilizing the SaphLITE and Clearglide systems. While the Clearglide system allows for fewer incisions (number and length) and less harvest time, these benefits may be outweighed by the increased cost of the Clearglide system compared to the SaphLITE retractor.
Genomic features of Bordetella parapertussisclades with distinct host species specificity
Authors: Brinig Mary M , Register Karen B , Ackermann Mark R , Relman David A 
Published: September 2006

Abstract
Background
The respiratory pathogen Bordetella parapertussis is a valuable model in which to study the complex phenotype of host specificity because of its unique two-species host range. One subset of strains, including the sequenced representative, causes whooping cough in humans, while other strains infect only sheep. The disease process in sheep is not well understood, nor are the genetic and transcriptional differences that might provide the basis for host specificity among ovine and human strains.

Results
We found 40 previously unknown genomic regions in an ovine strain of B. parapertussis using subtractive hybridization, including unique lipopolysaccharide genes. A microarray survey of the gene contents of 71 human and ovine strains revealed further differences, with 47 regions of difference distinguishing the host-restricted subgroups. In addition, sheep and human strains displayed distinct whole-genome transcript abundance profiles. We developed an animal model in which sheep were inoculated with a sheep strain, human strain, or mixture of the two. We found that the ovine strain persisted in the nasal cavity for 12 to 14 days, while the human strain colonized at lower levels and was no longer detected by 7 days post-inoculation. The ovine strain induced less granulocyte infiltration of the nasal mucosa.

Conclusion
Several factors may play a role in determining host range of B. parapertussis. Human- and ovine-associated strains have differences in content and sequence of genes encoding proteins that mediate host-pathogen contact, such as lipopolysaccharide and fimbriae, as well as variation in regulation of toxins, type III secretion genes, and other virulence-associated genes.
Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors
Authors: Heinrich Michael C. , Corless Christopher L. , Blanke Charles D. , Demetri George D. , Joensuu Heikki , Roberts Peter J. , Eisenberg Burton L. , von Mehren Margaret , Fletcher Christopher D.M. , Sandau Katrin , McDougall Karen , Ou Wen-bin , Chen Chang-Jie , Fletcher Jonathan A. 
Published: September 2006

PurposeGastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem.Patients and MethodsOne hundred forty-seven patients with advanced, unresectable GISTs were enrolled onto a randomized, phase II clinical study of imatinib. Specimens from pretreatment and/or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity.ResultsMolecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance. Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance (10% v 67%; P = .002). Evidence for clonal evolution and/or polyclonal secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary kinase mutations were nonrandomly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon 11 mutations. Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways.ConclusionDifferent molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs.
Internal and external trauma to the larynx
Authors: Holinger Paul H. , Schild Joyce A. , Maurizi Dino G. 
Published: September 2006

AbstractTrauma affects the larynx internally through vocal misuse, chemical and thermal burns, and intralaryngeal instrumentation; externally through physical violence, industrial accidents and automobile collisions. Occupational laryngeal trauma is that seen in the larynges of professional voice users such as singers, preachers, lawyers, school teachers, politicians, telephone operators, sales people, credit managers and auctioneers. Particularly common are the nodules on the vocal cords of housewives with several small children! In industry, voice changes and laryngeal pathology are common in voice abusers such as foremen, women assembly line workers, men working near a steam jack and engineers and firemen in cabs of diesel locomotives.1 Bridging these two categories of white collars and blue shirts are representatives in management‐labor relations who have additional reason to develop laryngeal trauma.
Sound evoked frequency‐following responses in the central auditory pathway
Authors: Marsh James T. , Worden Frederic G. 
Published: September 2006

AbstractAn acoustically evoked response is described which reproduces the frequency and waveform of the stimulus. This frequency following response (FFR.) is recordable from gross electrodes in the central auditory pathway.The FFR. differs from an acoustic stimulus of graded onset, and the CM., in that it has a sharp onset and a latency appropriate to the locus from which it is recorded. It is less resistant to anoxia than CM., and disappears before CM. is seriously affected.The frequency range of FFR. increases with stimulus intensity. At 80 db SPL., the range is approximately 500 Hz. to 5 KHz.The waveform and amplitude of FFR. vary with stimulus frequency. Amplitude becomes smaller, and waveform becomes more variable.The contrast to the auditory evoked potential, which can be recorded widely in the brain, FFR. is recordable only within, or close to, the auditory pathway. We have observed it only at and below the level of the inferior colliculus.FFR. has implications for the neurophysiology of hearing which are different from those of the auditory evoked potential. Some of these are discussed.
Injury and repair of the recurrent laryngeal nerves in dogs.
Authors: Boles Roger , Fritzell Bjorn 
Published: September 2006

AbstractSurgical repair of recurrent laryngeal nerve injuries has received renewed experimental attention in recent years.1,2,3 This work has been motivated by the considerable disability which vocal cord paralysis continues to cause, particularly regarding phonation, aspiration on swallowing, and difficulty in breathing. Interest in direct nerve repair has also evolved out of the frequent failure to achieve complete rehabilitation of the laryngeal functions with the usual surgical procedures of tracheostomy, arytenoidectomy and arytenopexy, and vocal fold injection and displacement techniques.
Wound healing.
Authors: Schiff Maurice 
Published: September 2006

AbstractWound healing is like a diamond with many facets. Newer techniques and methods are available to study some of the problems of wound healing. This is a highly complex subject with so many ramifications that only a few will be presented. Throughout the world, many laboratories are investigating the fundamental aspects of repair and regeneration. This starts at the cell level and terminates with the healed wound. In 1968, at a Centennial Symposium on Repair and Regeneration, at the University of California in San Francisco, there was assembled a group of pathologists, biochemists, bioengineers, enzymologists, and surgeons. All attempted to contribute something to the advancement of the new frontiers of study of wound healing. These proceedings will be published early in 1969. A study in wound repair requires consideration of the activity of the epithelium and the connective tissue beneath it. These two systems interact and inform each other of their status and the requirements of each other.
Cytotoxic reactions in the diagnosis of food allergy.
Authors: Bryan William T. K. , Bryan Marian P. 
Published: September 2006

AbstractThe diagnosis of food allergy remains one of the infrequently solved problems in medicine; furthermore, its importance is only occasionally recognized, and I emphasize the statement of Dr. William Kaufman in 195514 that no physician can estimate with any degree of accuracy how much ill health and human misery result from ailments caused by undiagnosed food allergy. From the large and varied sampling of patients who consulted him in his practice of internal medicine during the preceding 12 years, he could say with confidence that most practicing physicians see many patients almost daily who present themselves with a wide variety of complaints, which are caused by unrecognized food allergies.
Results of tympanoplasty and mastoidectomy at the massachusetts eye and ear infirmary
Authors: Lee Keatjin , Schuknecht Harold F. 
Published: September 2006

AbstractThe primary objectives of surgery for chronic suppurative disease of the ear are the elimination or arrest of disease and the preservation or improvement of auditory function. The concept is not new, for even the earliest otologists1 performed temporal bone surgery with the hope of preserving the sound transmitting mechanism of the middle ear. Before the availability of antibiotic drugs for the control of bacterial infection, it was not always prudent to compromise the removal of diseased tissues for the sake of preserving function. It was observed, however, that good thresholds of hearing sometimes occurred even though the ossicles and tympanic membrane were partly or completely destroyed by disease or surgery. These cases were the result of fortuitous patterns of healing in which the function of the ossicular system or the phase difference at the oval and round windows was preserved. Tympanoplasty tries to achieve these goals without compromising the desired end result of a safe, dry, and asymptomatic ear.