bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocyte Count and Mortality Risk in Older Persons. The Leiden 85‐Plus Study
Authors: Izaks Gerbrand J. , Remarque Edmond J. , Becker Sander V. , Westendorp Rudi G. J. 
Published: September 2003

Objectives: To investigate whether a low peripheral blood lymphocyte count is associated with increased mortality risk in older persons and to determine whether this association could be ascribed to ill health.Design: A cohort study with a total follow‐up period of 1,602 person years.Setting: Leiden, the Netherlands.Participants: Four hundred thirty‐six community‐dwelling residents aged 85 and older.Measurements: Health status and leukocyte total and differential counts were assessed at baseline. Lymphocyte subsets were measured with a fluorescence‐activated cell sorter. Age‐ and sex‐adjusted mortality risks were estimated using Cox proportional hazard regression analysis.Results: There was no association between lymphocyte count and mortality in persons with ill health (mortality risk lowest vs highest quartile=1.16; 95% confidence interval (CI)=0.85–1.58, P=.35), but mortality was dependent on lymphocyte count if disease was excluded (mortality risk lowest vs highest quartile=2.14; 95% CI=1.08–4.23, P=.03). A similar increase in mortality risk was found when the cluster designation (CD)4+, CD8+, and CD16+ lymphocyte subsets were analyzed. Within individuals, low values of the lymphocyte subsets were related and there was no compensatory increase in CD16+ lymphocyte counts. A low lymphocyte count was not associated with specific causes of death.Conclusion: A low lymphocyte count was associated with an increased mortality risk in older persons without apparent disease. This association was not only found for the total lymphocyte count but also for the CD4+, CD8+, and CD16+ lymphocyte subset counts.
Longitudinal Driving Performance in Early‐Stage Dementia of the Alzheimer Type
Authors: Duchek Janet M. , Carr David B. , Hunt Linda , Roe Catherine M. , Xiong Chengjie , Shah Kamini , Morris John C. 
Published: September 2003

Objectives: To longitudinally assess on‐road driving performance in healthy older adults and those with early‐stage dementia of the Alzheimer type (DAT).Design: A prospective longitudinal study.Setting: Large urban medical center and surrounding area.Participants: A sample of 58 healthy controls, 21 participants with very mild DAT, and 29 participants with mild DAT participated. DAT was diagnosed using validated clinical diagnostic criteria and staged according to the Clinical Dementia Rating (CDR) Scale.Measurements: Healthy controls and individuals with very mild DAT and mild DAT were administered a standardized on‐road driving assessment over repeated times of testing.Results: Subjects in the CDR=1 group (mild DAT) had a faster rate of receiving a rating of not safe on the driving test than subjects in the CDR=0 group (healthy controls; log rank test, P=.006), and the survival function of the CDR=0.5 group (very mild DAT) fell between those of the CDR=0 and CDR=1 groups. A Cox proportional hazards model indicated a significant difference in survival functions between the CDR=0 and CDR=1 groups after baseline age was controlled for (P<.001). Cox regression analysis also indicated that baseline age was a significant risk factor for a rating of “not safe” (P=.002).Conclusion: This study provides longitudinal evidence for a decline in driving performance over time, primarily in early‐stage DAT, and supports the need not only for driving assessments, but also for reevaluation of individuals with very mild and mild DAT.
A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of
Mycobacterium smegmatis
and Presence of a Novel Transposon, IS
1623
Authors: Alexander David C. , Jones Joses R. W. , Liu Jun 
Published: September 2003

ABSTRACT

Rifampin is a front-line antibiotic for the treatment of tuberculosis. Infections caused by rifampin- and multidrug-resistant
Mycobacterium tuberculosis
strains are difficult to treat and contribute to a poor clinical outcome. Rifampin resistance most often results from mutations in
rpoB
. However, some drug-resistant strains have
rpoB
alleles that encode the phenotype for susceptibility. Similarly, non-
M. tuberculosis
mycobacteria exhibit higher levels of baseline resistance to rifampin, despite the presence of
rpoB
alleles that encode the phenotype for susceptibility. To identify other genes involved in rifampin resistance, we generated a library of
Mycobacterium smegmatis
mc
2
155 transposon insertion mutants. Upon screening this library, we identified one mutant that was hypersensitive to rifampin. The transposon insertion was localized to the
arr
gene, which encodes rifampin ADP ribosyltransferase, an enzyme able to inactivate rifampin. Sequence analysis revealed differences in the
arr
alleles of
M. smegmatis
strain mc
2
155 and previously described strain DSM 43756. The
arr
region of strain mc
2
155 contains a second, partial copy of the
arr
gene plus a novel insertion sequence, IS
1623
.
Pentamidine Is Active In Vitro againstFusariumSpecies
Authors: Lionakis Michail S. , Lewis Russell E. , Samonis George , Kontoyiannis Dimitrios P. 
Published: September 2003

ABSTRACTFusariosis is an emerging opportunistic mycosis against which currently used antifungals have limited activity. Here, we investigated the in vitro activities of pentamidine (PNT) against 10 clinical isolates ofFusariumspecies (fiveFusarium solaniisolates and five non-F. solaniisolates) by using the National Committee for Clinical Laboratory Standards microdilution method in three different media (RPMI, RPMI-2, and a yeast nitrogen base medium), disk diffusion testing, and viability dye staining. PNT had significant activities against all 10Fusariumisolates. Non-F. solaniisolates were more susceptible thanF. solaniisolates (P< 0.05). Additionally, PNT was fungicidal against all non-F. solaniisolates, whereas it had fungistatic effects against four of the fiveF. solaniisolates. PNT also exhibited greater activity against conidial than against hyphal development of the fungus. This fungicidal activity against non-F. solani Fusariumisolates was confirmed microscopically after staining of PNT-treatedFusarium oxysporumhyphae with the fluorescent viability dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC). The MICs at which 50% of the isolates were inhibited (2 μg/ml for non-F. solaniisolates and 4 μg/ml forF. solaniisolates) and the minimum fungicidal concentration at which 50% of the isolates were killed (8 μg/ml for non-F. solaniisolates) were much lower than the PNT tissue concentrations previously reported in humans using conventional daily intravenous PNT dosing. Finally, PNT was more active againstFusariumisolates in a hypoxic environment of in vitro growth (P< 0.05). This finding may be clinically significant, becauseFusarium, an angiotropic mold, causes tissue infarcts with resultant low tissue perfusion. Our findings suggest that PNT may have a role in the management ofFusariuminfections. Future in vivo studies are needed to verify these in vitro findings.
Fungal Cell Wall Septation and Cytokinesis Are Inhibited by Bleomycins
Authors: Moore Carol W. , McKoy Judith , Del Valle Robert , Armstrong Donald , Bernard Edward M. , Katz Norman , Gordon Ronald E. 
Published: September 2003

ABSTRACTWhen the essential and distinctive cell walls of either pathogenic or nonpathogenic fungi break, cytoplasmic membranes rupture and fungi die. This fungicidal activity was discovered previously on nonproliferatingSaccharomyces cerevisiaecells treated briefly with the oxidative tool and anticancer drug family of bleomycins. The present studies investigated effects of bleomycin on growing fungal organisms. These included the medically importantAspergillus fumigatusandCryptococcus neoformans, as well as the emerging human pathogen and fungal model,S. cerevisiae.Bleomycin had its highest potency againstA. fumigatus. Scanning electron microscopy and thin-section transmission electron microscopy were used to study morphological growth characteristics. Killing and growth inhibition were also measured. Long, thin, and segmented hyphae were observed whenA. fumigatuswas grown without bleomycin but were never observed when the mold was grown with the drug. Bleomycin arrested conidial germination, hyphal development, and the progression and completion of cell wall septation. Similarly, the drug inhibited the construction of yeast cell wall septa, preventing cytokinesis and progression in the cell division cycle ofS. cerevisiae. Even when cytoplasms of mother and daughter cells separated, septation and cell division did not necessarily occur. Bizarre cell configurations, abnormally thickened cell walls at mother-daughter necks, abnormal polarized growth, large undivided cells, fragmented cells, and empty cell ghosts were also produced. This is the first report of a fungicidal agent that arrests fungal growth and development, septum formation, and cytokinesis and that also preferentially localizes to cell walls and alters isolated cell walls as well as intact cell walls on nongrowing cells.
Recombination Proficiency Influences Frequency and Locus of Mutational Resistance to Linezolid in
Enterococcus faecalis
Authors: Lobritz Michael , Hutton-Thomas Rebecca , Marshall Steve , Rice Louis B. 
Published: September 2003

ABSTRACT

In vitro linezolid resistance was selected at a higher frequency in
Enterococcus faecalis
JH2-2 than in recombination-deficient
E. faecalis
UV202. Resistance in JH2-2 was related to accumulated G2576T mutations in 23S rRNA genes, with the least resistance conferred by mutations in two of four copies. UV202 resistance was associated with a G2505A mutation present in a single copy in mutants with different MICs.
Role of
Klebsiella pneumoniae
OmpK35 Porin in Antimicrobial Resistance
Authors: Doménech-Sánchez Antonio , Martínez-Martínez Luis , Hernández-Allés Santiago , del Carmen Conejo María , Pascual Álvaro , Tomás Juan M. , Albertí Sebastián , Benedí Vicente Javier 
Published: September 2003

ABSTRACT

OmpK35 from
Klebsiella pneumoniae
is the homologue of
Escherichia coli
OmpF porin. Expression of OmpK35 in
K. pneumoniae
strain CSUB10R (lacking both OmpK35 and OmpK36) decreased the MICs of cephalosporins and meropenem ≥128-fold and decreased the MICs of imipenem, ciprofloxacin, and chloramphenicol ≥8-fold. MIC reductions by OmpK35 were 4 times (cefepime), 8 times (cefotetan, cefotaxime, and cefpirome), or 128 times (ceftazidime) higher than those caused by OmpK36, but the MICs were similar or 1 dilution lower for other evaluated agents.
Teicoplanin-Containing Cement Spacers for Treatment of Experimental
Staphylococcus aureus
Joint Prosthesis Infection
Authors: Ismael Farid , Bléton Rémy , Saleh-Mghir Azzam , Dautrey Sophie , Massias Laurent , Crémieux Anne-Claude 
Published: September 2003

ABSTRACT

Using a rabbit model of methicillin-resistant
Staphylococcus aureus
knee-prosthesis infection, we studied the efficacy of teicoplanin cement alone or in combination with systemic intramuscular (i.m.) injections of teicoplanin. Seven days after infection, surgical debridement and removal of the infected prostheses were performed, and five rabbits were randomly assigned to one of five different treatment groups: untreated controls, prosthesis replacement by drug-free cement spacer, prosthesis replacement by teicoplanin-loaded cement spacer (1.2 g of teicoplanin/40 g of cement), i.m. injections of teicoplanin (20 mg/kg of body weight, twice a day for 7 days), or systemic antibiotic treatment combined with teicoplanin-loaded spacers. The most effective regimen combined systemic teicoplanin and antibiotic spacers.
Prevalence of respiratory symptoms in sheep breeders
Authors: Radon K , Winter C 
Published: September 2003

Background:The European Farmers’ Study has indicated that sheep farmers might be at risk for the development of respiratory symptoms.Aims:To assess the prevalence of respiratory symptoms in sheep breeders and potential work related risk factors.Methods:All sheep breeders listed in two regions of South Germany were asked to answer a mailed questionnaire on respiratory symptoms, work related respiratory symptoms (WRS), and details of farming. Overall, 325 sheep breeders keeping at least 10 sheep could be included in the survey (response rate 81.9%). The prevalences were compared to the results of the European Farmers’ Study.Results:Sheep breeders showed a significantly higher prevalence of asthma related symptoms (prevalence odds ratio (POR) 2.1, 95% CI 1.5 to 3.0), chronic phlegm (POR 4.0, 95% CI 2.8 to 5.9), and WRS (POR 1.7, 95% CI 1.3 to 2.2) after adjusting for age, gender, smoking habits, full time farming, and study centre. In the multiple logistic regression model the risk for asthma related symptoms was doubled in full time farmers (POR 2.3, 95% CI 1.2 to 4.3). The major predictor of WRS was full time farming (POR 1.6, 95% CI 0.93 to 2.7) and the use of chemical footbaths (POR 2.1, 95% CI 1.2 to 3.7).Conclusions:Sheep breeders might be at high risk for the development of respiratory symptoms. These symptoms may be associated with work intensity and chemical exposure during work. Studies including objective measurements should be performed.
A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia
Authors: Cathcart Kathleen , Pinilla-Ibarz Javier , Korontsvit Tatyana , Schwartz Joseph , Zakhaleva Victoriya , Papadopoulos Esperanza B. , Scheinberg David A. 
Published: September 2003

AbstractA tumor-specific, bcr-abl-derived fusion peptide vaccine can be safely administered to patients with chronic myelogenous leukemia (CML) and can elicit a bcr-abl peptide-specific T-cell immune response. In the present phase 2 trial, 14 patients with CML in chronic phase were vaccinated with 6 fusion peptides mixed with Quillaja saponaria (QS-21). No significant toxic effects were observed. In 14 of 14 patients, delayed-type hypersensitivity (DTH) and/or CD4 proliferative responses developed after beginning vaccinations, and 11 of 14 patients showed interferon-gamma (IFN-gamma) release by CD4 enzyme-linked immunospot (ELISPOT) at one or more time points. These responses were CD4+CD45RO+. A peptide-specific CD8+ interferon-gamma ELISPOT was found in 4 patients. Four patients in hematologic remission had a decrease in Philadelphia chromosome (Ph) percentage (3 concurrently receiving interferon-alpha and 1 on imatinib mesylate), and 3 patients in molecular relapse after allogenic transplantation became transiently polymerase chain reaction (PCR) negative after vaccination; 2 of these patients received concurrent donor lymphocyte infusion (DLI). All 5 patients on IFN-alpha ultimately reached a complete cytogenetic remission. In conclusion, a tumor-specific bcr-abl breakpoint peptide-derived vaccine can be safely administered and can reliably elicit measurable peptide-specific CD4 immune responses, including in patients after bone marrow transplantation, on interferon, or on imatinib mesylate. A relationship between the clinical responses and vaccination cannot be determined from this trial. (Blood. 2004;103:1037-1042)
Constitutive mutants of the GM-CSF receptor reveal multiple pathways leading to myeloid cell survival, proliferation, and granulocyte-macrophage differentiation
Authors: Brown Anna L. , Peters Michelle , D'Andrea Richard J. , Gonda Thomas J. 
Published: September 2003

AbstractActivation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) family of receptors promotes the survival, proliferation, and differentiation of cells of the myeloid compartment. Several signaling pathways are activated downstream of the receptor, however it is not clear how these induce specific biologic outcomes. We have previously identified 2 classes of constitutively active mutants of the shared signaling subunit, human (h) βc, of the human GM-CSF/interleukin-3 (IL-3)/IL-5 receptors that exhibit different modes of signaling. In a factor-dependent bipotential myeloid cell line, FDB1, an activated mutant containing a substitution in the transmembrane domain (V449E) induces factor-independent proliferation and survival, while mutants in the extracellular domain induce factor-independent granulocyte-macrophage differentiation. Here we have used further mutational analysis to demonstrate that there are nonredundant functions for several regions of the cytoplasmic domain with regard to mediating proliferation, viability, and differentiation, which have not been revealed by previous studies with the wild-type GM-CSF receptor. This unique lack of redundancy has revealed an association of a conserved membrane-proximal region with viability signaling and a critical but distinct role for tyrosine 577 in the activities of each class of mutant.
Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome
Authors: Klion Amy D. , Robyn Jamie , Akin Cem , Noel Pierre , Brown Margaret , Law Melissa , Metcalfe Dean D. , Dunbar Cynthia , Nutman Thomas B. 
Published: September 2003

AbstractWe recently described a subset of patients with a myeloproliferative variant of hypereosinophilic syndrome (MHES) characterized by elevated serum tryptase levels, increased atypical mast cells in the bone marrow, tissue fibrosis, and the presence of the fusion tyrosine kinase, FIP1L1-PDGFRα, which is a therapeutic target of imatinib mesylate. Seven patients with MHES were treated with imatinib mesylate (300-400 mg daily). Clinical improvement and resolution of eosinophilia was observed in all patients, although cardiac dysfunction, when present, was not altered by therapy. Reversal of bone marrow pathology, including increased cellularity, the presence of spindle-shaped mast cells, and myelofibrosis, was evident in all patients at 4 to 8 weeks following initiation of therapy. This was accompanied by a decrease in activated eosinophils and mast cells in the peripheral blood and bone marrow, respectively. Serum tryptase levels declined rapidly to normal levels in all patients and remained in the normal range throughout therapy. Molecular remission, with disappearance of detectable FIP1L1/PDGFRA (F/P) transcripts, was achieved in 5 of 6 patients tested. The lack of reversal of cardiac abnormalities and persistence of the F/P mutation in some patients suggests that early intervention with higher doses of imatinib mesylate may be desirable in the treatment of patients with MHES.
Transgenesis and reverse genetics of mosquito innate immunity
Authors: Shin Sang Woon , Kokoza Vladimir A. , Raikhel Alexander S. 
Published: September 2003

SUMMARYIn recent years, mosquito molecular biology has been a scene of astounding achievements, namely the development of genetic transformation,characterization of inducible tissue-specific promoters, and acquirement of mosquito genome sequences. However, the lack of a complete genetic tool box for mosquitoes remains a serious obstacle in our ability to study essential mosquito-specific mechanisms. Unlike Drosophila, very few null mutations for mosquito genes exist. The development of reverse-genetic analyses based on RNAi and transgenic techniques will help to compensate for these deficiencies and aid in identification of critical genes in important regulatory pathways. The study of mosquito innate immunity is one example and described here. In this study, we combine mosquito transgenesis with reverse genetics. The advantage of transgenesis is the ability to establish genetically stable, dominant-negative and overexpression phenotypes. Using the blood-meal-activated vitellogenin gene (Vg) promoter, we have generated transgenic mosquitoes with blood-meal-activated, overexpressed antimicrobial peptides, Defensin A and Cecropin A. Moreover, we have recently generated a transgenic dominant-negative Relish mosquito strain, which after taking a blood meal, becomes immune-deficient to infection by Gram-negative bacteria. The latter accomplishment has opened the door to a reverse-genetic approach in mosquitoes based on transgenesis.
The role of MRI and ultrasound imaging in Morton’s neuroma and the effect of size of lesion on symptoms
Authors: Sharp R. J. , Wade C. M. , Hennessy M. S. , Saxby T. S. 
Published: September 2003

We investigated 29 cases, diagnosed clinically as having Morton’s neuroma, who had undergone MRI and ultrasound before a neurectomy. The accuracy with which pre-operative clinical assessment, ultrasound and MRI had correctly diagnosed the presence of a neuroma were compared with one another based on the histology and the clinical outcome. Clinical assessment was the most sensitive and specific modality. The accuracy of the ultrasound and MRI was similar and dependent on size. Ultrasound was especially inaccurate for small lesions. There was no correlation between the size of the lesion and either the pre-operative pain score or the change in pain score following surgery. Reliance on single modality imaging would have led to inaccurate diagnosis in 18 cases and would have only benefited one patient. Even imaging with both modalities failed to meet the predictive values attained by clinical assessment. There is no requirement for ultrasound or MRI in patients who are thought to have a Morton’s neuroma. Small lesions, < 6 mm in size, are equally able to cause symptoms as larger lesions. Neurectomy provides an excellent clinical outcome in most cases.
Factors which affect the progression of osteoarthritis after rotational acetabular osteotomy
Authors: Koga H. , Matsubara M. , Suzuki K. , Morita S. , Muneta T. 
Published: September 2003

We have investigated the factors which affect the progression of osteoarthritis after rotational acetabular osteotomy (RAO). Between 1984 and 1998, we treated 60 dysplastic hips by RAO. The mean age at surgery was 31.6 years (13 to 51) and the mean period of follow-up was 4.6 years (2 to 9.5). The thickness of the articular cartilage on the weight-bearing area, pre- and postoperative acetabular cover, and the sphericity of the femoral head were used for radiological assessment. The osteoarthritis did not progress in 39 hips. Significant factors which affected the radiological grade included sphericity of the femoral head and the postoperative acetabular cover. The surgical approach and preoperative acetabular cover did not affect the progression of osteoarthritis. Patients were divided into two groups according to the surgical approach used, either conventional (23 hips) or modified (37 hips). Significant factors included the postoperative acetabular cover in the modified approach, and the sphericity of the femoral head in the conventional approach. It is critical that the postoperative cover is sufficient, especially when RAO is carried out using our modified technique.