bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune hemolytic anemia due to cimetidine: the first example of a cimetidine antibody
Authors: Arndt Patricia A. , Garratty George , Brasfield Farah M. , Vemuri Swarajyal L. , Asuncion Devi J. 
Published: October 2009

BACKGROUND: Although there have been a few reports of immune hemolytic anemia (IHA) thought to be due to cimetidine, none of them provided proof (e.g., serologic detection of anti‐cimetidine and/or repeat of IHA upon drug rechallenge). One report used cimetidine as an example of how temporal associations of drug administration and hemolytic anemia are not proof of a cause‐effect relationship.STUDY DESIGN AND METHODS: A 63‐year‐old cancer patient developed IHA on two occasions after receiving cimetidine (with and without chemotherapy). Serologic methods included testing cimetidine‐treated red blood cells (RBCs) as well as testing untreated RBCs in the presence of cimetidine.RESULTS: The patient's direct antiglobulin test was positive (C3 only) and a serum antibody to cimetidine was detected by both testing methods. An eluate from the patient's RBCs was nonreactive. Cimetidine‐treated RBCs were optimally prepared at room temperature and needed to be tested on the day of preparation.CONCLUSIONS: This is the first reported case of IHA due to a cimetidine antibody where a drug‐dependent antibody was demonstrated. The patient had IHA after receiving cimetidine on two separate occasions.
Periods without agitation diminish platelet mitochondrial function during storage
Authors: Skripchenko Andrey , Myrup Andrew , Thompson‐Montgomery Dedeene , Awatefe Helen , Moroff Gary , Wagner Stephen J. 
Published: October 2009

BACKGROUND: Prolonged periods without agitation produce platelet (PLT) storage lesions that result in reduced in vitro assay parameters and an increase of apoptotic markers during storage. The aim of this study was to evaluate the influence of periods without agitation on PLT mitochondrial function, blood gases, and activation.STUDY DESIGN AND METHODS: Apheresis PLT units (n = 12) were collected using a cell separator and each was equally divided among five storage bags (50 mL of PLT suspension in 300‐mL nominal volume containers). Four bags were held without agitation for 24, 48, 72, and 96 hours in a standard shipping box at room temperature and the fifth bag was continuously agitated. PLTs were assayed for standard in vitro PLT assays as well as for mitochondrial membrane potential (MMP), accumulation of reactive oxygen species, Annexin V binding, mitochondrial mass, and activity of mitochondrial reduction power (MRP) immediately after removal of units from the shipping container on Days 1, 2, 3, 4, and 7.RESULTS: Increasing periods without agitation resulted in increased superoxide anion generation and PLT activation as well as reduced PLT MMP and MRP. Increasing periods without agitation resulted in increasing Annexin V binding. PLTs that had undergone periods without agitation showed increased oxygen and carbon dioxide levels immediately after storage without agitation. The superoxide anion generation was highly correlated with the loss of MMP, increasing Annexin V binding, and pH decline.CONCLUSIONS: PLTs, if stored without agitation, produce a lesion that leads PLTs to apoptosis. The severity of the lesion depends on the length of the period without agitation. Prolonged periods without agitation induce formation of superoxides and depolarization of MMP along with a presentation of apoptotic markers.
HIV Nef is Secreted in Exosomes and Triggers Apoptosis in Bystander CD4+ T Cells
Authors: Lenassi Metka , Cagney Gerard , Liao Maofu , Vaupotič Tomaž , Bartholomeeusen Koen , Cheng Yifan , Krogan Nevan J. , Plemenitaš Ana , Peterlin B. Matija 
Published: October 2009

Abstract The HIV accessory protein negative factor (Nef) is one of the earliest and most abundantly expressed viral proteins. It is also found in the serum of infected individuals (Caby MP, Lankar D, Vincendeau‐Scherrer C, Raposo G, Bonnerot C. Exosomal‐like vesicles are present in human blood plasma. Int Immunol 2005;17:879–887). Extracellular Nef protein has deleterious effects on CD4+ T cells (James CO, Huang MB, Khan M, Garcia‐Barrio M, Powell MD, Bond VC. Extracellular Nef protein targets CD4+ T cells for apoptosis by interacting with CXCR4 surface receptors. J Virol 2004;78:3099–3109), the primary targets of HIV, and can suppress immunoglobulin class switching in bystander B cells (Qiao X, He B, Chiu A, Knowles DM, Chadburn A, Cerutti A. Human immunodeficiency virus 1 Nef suppresses CD40‐dependent immunoglobulin class switching in bystander B cells. Nat Immunol 2006;7:302–310). Nevertheless, the mode of exit of Nef from infected cells remains a conundrum. We found that Nef stimulates its own export via the release of exosomes from all cells examined. Depending on its intracellular location, these Nef exosomes form at the plasma membrane, late endosomes or both compartments in Jurkat, SupT1 and primary T cells, respectively. Nef release through exosomes is conserved also during HIV‐1 infection of peripheral blood lymphocytes (PBLs). Released Nef exosomes cause activation‐induced cell death of resting PBLs in vitro. Thus, HIV‐infected cells export Nef in bioactive vesicles, which facilitate the depletion of CD4+ T cells that is a hallmark of acquired immunodeficiency syndrome (AIDS).
Design and statistical analysis of oral medicine studies: common pitfalls
Authors: Baccaglini L , Shuster JJ , Cheng J , Theriaque DW , Schoenbach VJ , Tomar SL , Poole C 
Published: October 2009

Oral Diseases (2010) 16, 233–241A growing number of articles are emerging in the medical and statistics literature that describe epidemiologic and statistical flaws of research studies. Many examples of these deficiencies are encountered in the oral, craniofacial, and dental literature. However, only a handful of methodologic articles have been published in the oral literature warning investigators of potential errors that may arise early in the study and that can irreparably bias the final results. In this study, we briefly review some of the most common pitfalls that our team of epidemiologists and statisticians has identified during the review of submitted or published manuscripts and research grant applications. We use practical examples from the oral medicine and dental literature to illustrate potential shortcomings in the design and analysis of research studies, and how these deficiencies may affect the results and their interpretation. A good study design is essential, because errors in the analysis can be corrected if the design was sound, but flaws in study design can lead to data that are not salvageable. We recommend consultation with an epidemiologist or a statistician during the planning phase of a research study to optimize study efficiency, minimize potential sources of bias, and document the analytic plan.
Comparison of the canal centring ability of K3, Liberator and EZ Fill Safesiders by using spiral computed tomography
Authors: Venkateshbabu Nagendrababu , Emmanuel Satish , Santosh Goud K. , Kandaswamy Deivanayagam 
Published: October 2009

AbstractThe purpose of the study was to compare the canal centring ability of K3, Liberator and EZ Fill Safesiders by using spiral computed tomography (SCT). Forty curved mandibular premolars were selected. Before and after instrumentation teeth were scanned by spiral computed tomography and nine cross‐sectional views of each tooth were obtained at 1.5 mm intervals from the apex. Canal centring ratio was calculated. Mean values were compared between different study groups by using one‐way anova followed by Tukey – HSD procedure. At 1st, 2nd and 3rd levels, there was no statistical difference between groups. From 4th to 9th levels Safesider showed higher centring ratio, followed by Liberator and K3. Safesider showed better canal centring ability followed by Liberator and K3.
Safety and immunogenicity of an inactivated thimerosal‐free influenza vaccine in infants and children
Authors: Nolan Terry , Richmond Peter C. , McVernon Jodie , Skeljo Maryanne V. , Hartel Gunter F. , Bennet Jillian , Basser Russell L. 
Published: October 2009

Objective  Few prospective studies of inactivated split virion influenza vaccine have been conducted in infants and children. Our objective was to evaluate the safety, reactogenicity and immunogenicity of a thimerosal‐free inactivated influenza vaccine (Fluvax®; CSL Limited, Parkville, Australia) in children aged 6 months to <9 years.Methods  A prospective, open‐label, phase III clinical trial was conducted in 298 healthy children previously unvaccinated with influenza, commencing in the Southern Hemisphere 2005 autumn. Participants were divided into two groups (Group A: ≥6 months to <3 years; Group B: ≥3 years to <9 years), and received two doses of the 2005 vaccine, and one dose of the 2006 vaccine one year later (Group A: 0·25 ml per dose; Group B: 0·5 ml per dose). Vaccine safety and reactogenicity was evaluated for 30 days after each dose. Immunogenicity was assessed using hemagglutination inhibition and single radial hemolysis assays.Results  There were no withdrawals due to adverse events (AEs). The majority of solicited local and systemic AEs were of mild severity. A maximum intensity of severe was reported for injection site pain and fever by only 3·0% and 3·4% of participants, respectively. The vaccine was immunogenic for all antigens, with ≥95% of both younger and older children achieving seroprotection after dose 2.Conclusions  This thimerosal‐free inactivated influenza vaccine had a favorable safety profile and was immunogenic in children aged ≥6 months and <9 years. Primary and booster vaccination produced consistently immunogenic responses including in children under 3 years of age receiving 0·25 ml doses of vaccine.
Genetic cardiovascular risk factors and age‐related macular degeneration
Authors: Haas Paulina , Aggermann Tina , Steindl Kerstin , Krugluger Walter , Pühringer Helene , Oberkanins Christian , Frantal Sophie , Binder Susanne 
Published: October 2009

Abstract.Purpose:  To investigate the association between genetic cardiovascular risk factors and exudative age‐related macular degeneration (AMD) in a White Austrian population.Methods:  Seventy‐five unrelated AMD patients and 75 unrelated healthy, sex‐ and age‐matched control patients were genotyped for the following 19 single nucleotide polymorphisms (SNPs) in 14 different genes: blood coagulation factor V (FV) R506Q, factor II (prothrombin) G20210A and factor XIII (FXIII) V34L; 5,10‐methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; plasminogen activator inhibitor 1 (PAI‐1) 4G/5G; endothelial protein C receptor (EPCR) 4600 A>G (A3 haplotype), 4678 G>C (A1 haplotype); apolipoprotein B (ApoB) R3500Q; apolipoprotein E (ApoE) E2/E3/E4; β‐fibrinogen −455 G>A; human platelet antigen 1 (HPA1) a/b; angiotensin‐converting enzyme (ACE) I/D; endothelial nitric oxide synthase (eNOS) 786 T>C, 894 G>T; lymphotoxin alpha (LTA) 804 C>A and 9p21 rs10757278. Genotyping was carried out by polymerase chain reaction (PCR) followed by reverse hybridization (CVD StripAssays; ViennaLab Diagnostics, Vienna, Austria).Results:  No statistically significant association could be observed between AMD and the investigated genetic risk factors for cardiovascular disease (CVD). All factors seem to be uniformly distributed in the two groups of AMD patients and healthy controls. Two variables –β‐fibrinogen: −455 G>A (p = 0.0786) and apolipoprotein E4 (p = 0.0636) – were not as far from association as the others.Conclusion:  Our data show that the 19 tested CVD risk markers do not play a significant role in AMD. β‐Fibrinogen and apolipoprotein E4 should be examined in a larger cohort.
Day 1 postoperative intraocular pressure spike in vitreoretinal surgery (VDOP1)
Authors: Wong Roger , Gupta Bhaskar , Williamson Thomas H. , Laidlaw D. Alistair H. 
Published: October 2009

Abstract.Purpose:  To classify the clinical characteristics that might identify patients who may not require next‐day follow‐up following routine vitreoretinal intervention.Methods:  Prospective case series.Results:  The only statistically significant factors for raised intraocular pressure (IOP) were gas tamponade and preoperative raised IOP. 44.7% (17/38) of patients with preoperative IOP ≥ 20 mmHg had postoperative IOP ≥ 30 mmHg while 8.6% (17/197) of patients with preoperative IOP < 20 mmHg had postoperative IOP ≥ 30 mmHg (p = 0.0001). Phacoemulsification did not increase risk for a postoperative IOP spike. There was a 20–21% risk of postoperative IOP > 30 mmHg for patients with gas tamponade. All patients with no tamponade with IOP > 30 mmHg had preoperative IOP ≥ 20 mmHg.Conclusion:  Uncomplicated vitreoretinal procedures with preoperative IOP of< 20 mmHg and no gas tamponade are unlikely to have uncontrolled IOP spike at day 1.
Experimental Infection of Reindeer with Cervid Herpesvirus 2
Authors: das Neves Carlos G. , Mørk Torill , Godfroid Jacques , Sørensen Karen K. , Breines Eva , Hareide Ellinor , Thiry Julien , Rimstad Espen , Thiry Etienne , Tryland Morten 
Published: October 2009

ABSTRACT

Cervid herpesvirus 2 (CvHV2) has been isolated from reindeer (
Rangifer tarandus tarandus
), and serological data indicate that in reindeer this virus is endemic in Fennoscandia, Alaska, Canada, and Greenland. CvHV2 has been described as a cause of subclinical genital infections in reindeer, but little information on primary infections exists. In this study, six seronegative and presumably pregnant reindeer were allocated to one of two groups. Two animals were inoculated with CvHV2 intratracheally, and two animals intravaginally, with one control animal in each group receiving sterile water. Mild hyperthermia and serous discharges from the vagina and nose were observed. No abortions were recorded, but one calf died shortly after birth. Inoculated animals seroconverted and had neutralizing antibodies after days 7 to 10 postinfection. CvHV2 was detected by PCR in nasal and vaginal swabs from animals in both groups but could be isolated only from nasal swabs in the respiratory group and from vaginal swabs in the genital group. CvHV2 was detected by PCR in various organs and tissues postmortem. In control animals, the virus could not be isolated in spite of PCR-positive nasal and vaginal swab samples and some degree of positive immunostaining. One of the animals that were inoculated intratracheally developed a hemorrhagic, necrotizing bronchopneumonia, which was CvHV2 positive by PCR and immunohistochemistry. We conclude that CvHV2 can cause systemic infection, that both genital and respiratory inoculations can lead to virus shedding, and that the virus can infect the fetus in utero.
Monocyte-Derived Interleukin-10 Depresses the
Bordetella pertussis
- Specific Gamma Interferon Response in Vaccinated Infants
Authors: Dirix V. , Verscheure V. , Goetghebuer T. , Hainaut M. , Debrie A. S. , Locht C. , Mascart F. 
Published: October 2009

ABSTRACT

Antigen-specific gamma interferon (IFN-γ) has been demonstrated to participate in protection against
Bordetella pertussis
infection. Circulating mononuclear cells from
B. pertussis
-infected and from pertussis-vaccinated infants secrete high amounts of IFN-γ after in vitro stimulation by
B. pertussis
antigens, but with a large variation in the secreted IFN-γ levels between individuals. We show here that the inhibition of the specific IFN-γ response can be at least partially attributed to IL-10 secretion by monocytes. This IL-10 secretion was not associated with polymorphisms at positions −1082, −819, and −592 of the IL-10 gene promoter, suggesting that other genetic or environmental factors affect IL-10 expression and secretion.
Immunologic Paradox in the Diagnosis of Tuberculous Meningitis
Authors: Kim Sung-Han , Kim Yang Soo 
Published: October 2009

ABSTRACT

We report a patient with microbiologically documented tuberculous meningitis showing that the therapeutic paradox, a therapy-induced switch to a neutrophil-predominant situation in the differential cell counts of cerebrospinal fluid specimens, had a correlation with an immunologic paradox, an increased
Mycobacterium tuberculosis
-specific gamma interferon-producing T-cell response.
Presence of Genes Encoding the Panton-Valentine Leukocidin Exotoxin Is Not the Primary Determinant of Outcome in Patients with Complicated Skin and Skin Structure Infections Due to Methicillin-Resistant
Staphylococcus aureus
: Results of a Multinational Trial
Authors: Bae In-Gyu , Tonthat Giang T. , Stryjewski Martin E. , Rude Thomas H. , Reilly Lindsay F. , Barriere Steven L. , Genter Fredric C. , Corey G. Ralph , Fowler Vance G. 
Published: October 2009

ABSTRACT

The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for
pvl
and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were
pvl
positive. Patients with
pvl
-positive MRSA were more likely than those with
pvl
-negative MRSA to be young, to be North American, and to present with major abscesses (
P
< 0.001 for each). Patients were significantly more likely to be cured if they were infected with
pvl
-positive MRSA than if they were infected with
pvl
-negative MRSA (91.6% versus 80.7%;
P
= 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The
fnbA
,
cna
,
sdrC
,
map-eap
,
sed
,
seg
,
sei
,
sej
, SCC
mec
type IV, and
agr
group II genes were also associated with clinical response (
P
< 0.05). This contemporary, international study demonstrates that
pvl
was not the primary determinant of outcome in patients with MRSA cSSSI.
MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus
Authors: Wang Jennifer P. , Cerny Anna , Asher Damon R. , Kurt-Jones Evelyn A. , Bronson Roderick T. , Finberg Robert W. 
Published: October 2009

ABSTRACT
Coxsackie B viruses (CVB) are enteroviruses that have been associated with a variety of human diseases, including myocarditis. In the present study, we found that MDA5 and its adaptor molecule MAVS are critical for type I interferon responses to CVB, since the absence of either MAVS or MDA5 leads to deficient type I interferon production and early mortality in mice infected with CVB. Pancreatic and hepatic necrosis were observed on histopathological examination of MAVS and MDA5 knockout mice infected with CVB. Inflammatory cytokine production in response to systemic CVB infection was independent of MAVS. Surprisingly, virus titers were not elevated in MAVS-deficient mice, despite significant reductions in type I interferon levels. These data highlight the importance of type I interferon in host defense and provide insight on the mechanisms of innate immune responses following coxsackievirus infection.
The Rubella Virus Capsid Protein Inhibits Mitochondrial Import
Authors: Ilkow Carolina S. , Weckbecker Daniel , Cho Woo Jung , Meier Stephan , Beatch Martin D. , Goping Ing Swie , Herrmann Johannes M. , Hobman Tom C. 
Published: October 2009

ABSTRACT
The rubella virus (RV) capsid is an RNA-binding protein that functions in nucleocapsid assembly at the Golgi complex, the site of virus budding. In addition to its role in virus assembly, pools of capsid associate with mitochondria, a localization that is not consistent with virus assembly. Here we examined the interaction of capsid with mitochondria and showed that this viral protein inhibits the import and processing of mitochondrial precursor proteins in vitro. Moreover, RV-infected cells were found to contain lower intramitochondrial levels of matrix protein p32. In addition to inhibiting the translocation of substrates into mammalian mitochondria, capsid efficiently blocked import into yeast mitochondria, thereby suggesting that it acts by targeting a highly conserved component of the translocation apparatus. Finally, mutation of a cluster of five arginine residues in the amino terminus of capsid, though not interfering with its binding to mitochondria, abrogated its ability to block protein import into mitochondria. This is the first report of a viral protein that affects the import of proteins into mitochondria.
Associations between HLA Class I Alleles and Escape Mutations in the Hepatitis B Virus Core Gene in New Zealand-Resident Tongans
Authors: Abbott William G. H. , Tsai Peter , Leung Euphemia , Trevarton Alex , Ofanoa Malakai , Hornell John , Gane Edward J. , Munn Stephen R. , Rodrigo Allen G. 
Published: October 2009

ABSTRACT

The full repertoire of hepatitis B virus (HBV) peptides that bind to the common HLA class I molecules found in areas with a high prevalence of chronic HBV infection has not been determined. This information may be useful for designing immunotherapies for chronic hepatitis B. We identified amino acid residues under positive selection pressure in the HBV core gene by phylogenetic analysis of cloned DNA sequences obtained from HBV DNA extracted from the sera of Tongan subjects with inactive, HBeAg-negative chronic HBV infections. The repertoires of positively selected sites in groups of subjects who were homozygous for either HLA-B*4001 (
n
= 10) or HLA-B*5602 (
n
= 7) were compared. We identified 13 amino acid sites under positive selection pressure. A significant association between an HLA class I allele and the presence of nonsynonymous mutations was found at five of these sites. HLA-B*4001 was associated with mutations at E77 (
P
= 0.05) and E113 (
P
= 0.002), and HLA-B*5602 was associated with mutations at S21 (
P
= 0.02). In addition, amino acid mutations at V13 (
P
= 0.03) and E14 (
P
= 0.01) were more common in the seven subjects with an HLA-A*02 allele. In summary, we have developed an assay that can identify associations between HLA class I alleles and HBV core gene amino acids that mutate in response to selection pressure. This is consistent with published evidence that CD8
+
T cells have a role in suppressing viral replication in inactive, HBeAg-negative chronic HBV infection. This assay may be useful for identifying the clinically significant HBV peptides that bind to common HLA class I molecules.