bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRECLINICAL STUDY: Differential effects of ethanol on IFN‐γ‐ and TNF‐α‐producing splenic T lymphocytes in a murine model of gram‐negative pneumonia
Authors: Lanzke Nadine , Kleinwächter Robin , Kerschischnik Saskia , Sargsyan Lilit , Groneberg David A. , Kamradt Thomas , Liesenfeld Oliver , Krenn Veit , Sander Michael , Spies Claudia 
Published: December 2006

ABSTRACTThe incidence of bacterial pneumonia is increased in alcoholic patients. Alcohol consumption has been shown to impair cytokine production. Tumor necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ) are critical for host defense against Klebsiella pneumoniae (K. pneumoniae). In order to examine the influence of alcohol on the immune response to infection, we investigated the frequency of TNF‐α and IFN‐γ produced by splenic T‐lymphocytes in a murine model of gram‐negative pneumonia initiated after 8 days of alcohol treatment. Thirty‐two Balb/c mice were pretreated with ethanol (3 mg/g body weight) or saline intraperitoneally over 8 days. On day 7 half of each group was administered K. pneumoniae. Mice were sacrificed 24 hours later to excise lungs and liver for histological assessment and spleens for cell isolation. IFN‐γ‐ and TNF‐α‐producing CD4+ and CD8+ lymphocytes were determined by FACS analysis. In mice with Klebsiella infection, the percentages of IFN‐γ‐producing CD4+ (P < 0.01) and CD8+ (P < 0.01) were significantly decreased, the percentages of TNF‐α‐producing CD4+ (P = 0.01) and CD8+ (P < 0.01) T cells were significantly elevated after alcohol treatment compared with mice with saline treatment. The histological assessment showed an aggravation of K. pneumoniae‐induced pneumonia in alcohol‐treated mice. Alcohol differentially affects IFN‐γ and TNF‐α production in Klebsiella‐infected mice. Both effects obviously led to a weakened immune response as seen by increased histological damage. This suggests a role of T cells in the increased susceptibility of the alcoholic host to nosocomial infection due to inadequate cytokine response.
IMAGING STUDY: Gray matter volume abnormalities and externalizing symptoms in subjects at high risk for alcohol dependence
Authors: Benegal Vivek , Antony George , Venkatasubramanian Ganesan , Jayakumar Peruvumba N. 
Published: December 2006

ABSTRACTReduced right amygdala volumes have been reported in young, alcohol‐naïve subjects at high risk (HR) for alcohol dependence. The differences in brain morphometry have been associated with an excess of externalizing behaviors in these subjects. This may reflect a neurobiological vulnerability to alcohol dependence. Existing Magnetic Resonance Imaging (MRI) studies on these subjects have examined only a few, pre‐selected brain regions using the manual regions of interest (ROI) approach. MRI of HR subjects (n = 20) and age, sex, and handedness‐matched low‐risk (LR) subjects (n = 21) were analyzed using optimized voxel‐based morphometry and ROI approach. The externalizing symptoms of these subjects and their fathers were measured using the Semi‐Structured Assessment for the Genetics of Alcoholism. HR subjects had significantly smaller volumes of superior frontal, cingulate and parahippocampal gyri, amygdala, thalamus and cerebellum. These gray matter volumes correlated negatively with externalizing symptoms scores. Subjects at HR for alcoholism have reduced volumes of critical areas of brain gray matter, which are associated with increased externalizing symptoms. These represent key endophenotypes of alcoholism.
PRECLINICAL STUDY: Difference in magnitude of psychostimulant‐induced extracellular norepinephrine in the ventral tegmental area contributes to discrepant prefrontal dopamine outflow
Authors: Pan Wynn H. T. , Hsieh Min‐Chien , Wu Hsiao‐Hua , Lin Shi‐Kwang 
Published: December 2006

ABSTRACTThe dopamine (DA) efflux in the medial prefrontal cortex (mPFC) can be modulated by the interaction between afferent norepinephrine (NE) and somatodendritic DA in the ventral tegmental area (VTA). However, it is unclear how locally administered amphetamine (AMPH) or cocaine in the VTA results in discrepant response of DA efflux in the mPFC. In this study, intra‐VTA infusion of AMPH (1000 µM) or cocaine (200 µM) in anesthetized rats was employed to study the concurrent profile of extracellular DA level in the VTA and mPFC. In addition, the extracellular NE levels during the intra‐VTA infusion of these two psychostimulants were analyzed to compare their effects on prefrontal DA efflux. During the intra‐VTA infusion of AMPH, both extracellular DA and NE increased significantly in the VTA (270 ± 12% and 819 ± 40%, respectively). Meanwhile, the DA efflux in the mPFC elevated significantly. During the intra‐VTA infusion of cocaine, the extracellular DA and NE in the VTA also increased (271 ± 21% and 150 ± 15%, respectively). However, the DA efflux decreased significantly in the mPFC. Noteworthy, the increase of extracellular NE in the VTA was much more robust via AMPH infusion, as compared with cocaine. It is suggested that AMPH and cocaine enhance the extracellular NE concentrations in the VTA in different magnitudes, which in turn contribute to discrepant profiles of distal DA efflux in the mPFC.
GENETIC STUDY: Significant impact of MTHFR C677T polymorphism on plasma homovanillic acid (HVA) levels among alcohol‐dependent patients
Authors: Lutz Ulrich C. , Batra Anil , Wiatr Gerlinde , Machicao Fausto , Kolb Werner , Maurer Sandra , Buchkremer Gerhard , Köhnke Michael D. 
Published: December 2006

ABSTRACTThe enzyme 5,10‐methylenetetrahydrofolate reductase (MTHFR) synthesizes 5‐methyltetrahydrofolate. It plays a critical role in homocysteine metabolism. A high impact of MTHFR C677T polymorphism on plasma homocysteine levels has been observed among alcoholics. Recent studies indicate that homocysteine has toxic effects on dopaminergic neurons. Thus it lowers levels of homovanillic acid (HVA) in the striatal region in rats. Alcoholics had significantly lower plasma HVA concentrations compared with healthy controls. Aim of this study is to elucidate whether HVA plasma levels in alcoholics are influenced by MTHFR C677T polymorphism. A total of 142 alcohol‐dependent patients and 101 healthy controls were examined regarding plasma HVA concentration and MTHFR C677T genotype. Blood samples of alcoholics were obtained after a minimum of 22 days of abstinence. Among alcohol‐dependent patients MTHFR C677T polymorphism was significantly associated with plasma HVA levels: carriers of MTHFR C677T T‐allele had significantly lower HVA plasma levels compared with homozygote carriers of C‐allele: 11.9 ng/ml versus 14.4 ng/ml (χ2: 5.39; P = 0.02). In healthy control subjects plasma HVA levels did not differ significantly between MTHFR C677T T‐allele carriers and homozygote carriers of C‐allele: 15.1 ng/ml versus 15.3 ng/ml (χ2: 0.04; P = 0.82). The data suggest an influence of MTHFR C677T polymorphism on plasma HVA among alcohol‐dependent patients. This might be due to neurotoxic effects of homocysteine on the dopaminergic system or direct impairment of monoamine metabolism. Future studies should try to elucidate whether this effect is reversible during alcohol abstinence.
Does the patient‐held record improve continuity and related outcomes in cancer care: a systematic review
Authors: Gysels Marjolein , Richardson Alison , Higginson Irene J. 
Published: December 2006

AbstractObjectives  To assess the effectiveness of the patient‐held record (PHR) in cancer care.Background  Patients with cancer may receive care from different services resulting in gaps. A PHR could provide continuity and patient involvement in care.Search strategy  Relevant literature was identified through five electronic databases (Medline, Embase, Cinahl, CCTR and CDSR) and hand searches.Inclusion criteria  Patient‐held records in cancer care with the purpose of improving communication and information exchange between and within different levels of care and to promote continuity of care and patients’ involvement in their own care.Data extraction and synthesis  Data extraction recorded characteristics of intervention, type of study and factors that contributed to methodological quality of individual studies. Data were then contrasted by setting, objectives, population, study design, outcome measures and changes in outcome, including knowledge, satisfaction, anxiety and depression. Methodological quality of randomized control trials and non‐experimental studies were assessed with separate standard grading scales.Main results and conclusions  Seven randomized control trials and six non‐experimental studies were identified. Evaluations of the PHR have reached equivocal findings. Randomized trials found an absence of effect, non‐experimental evaluations shed light on the conditions for its successful use. Most patients welcomed introduction of a PHR. Main problems related to its suitability for different patient groups and the lack of agreement between patients and health professionals regarding its function. Further research is required to determine the conditions under which the PHR can realize its potential as a tool to promote continuity of care and patient participation.
Depressed patients’ perceptions of depression treatment decision‐making
Authors: Simon Daniela , Loh Andreas , Wills Celia E. , Härter Martin 
Published: December 2006

AbstractObjective  Little is known about the feasibility and effects of patient‐clinician shared decision‐making (SDM) for depression treatment. Within a goal of informing the design of a SDM intervention, the objective of this study was to investigate depressed patients’ perceptions of the treatment decision‐making process with general practitioners (GPs).Setting and participants  Data were gathered from a convenience sample of 40 depressed patients to understand key aspects of treatment decision‐making from the patient perspective. The sample varied in depression severity and type of setting in which treatment was sought.Main variables studied  Semi‐structured interview questions focused on patients’ prior experiences with depression and treatment, perceptions of the treatment decision‐making process, and needs and expectations about treatment. Current depression severity was also assessed.Results  Patient lack of insight regarding depression severity substantially delayed patient engagement in treatment seeking and decision‐making. Patients expected their GPs to be a first and main source of objective information and discussion about depression and treatment and to provide emotional support for decision‐making. Patients also identified needs for additional information about depression and its treatment, as well as concerns about certain aspects of treatment.Conclusions  The depression treatment context has some aspects that differ from treatment decision‐making for other types of health conditions. SDM approaches for depression treatment should be adapted based on depression severity and patient‐identified needs.
A bird can't fly on one wing: patient views on waiting for hip and knee replacement surgery
Authors: Conner‐Spady Barbara L. , Johnston Geoffrey H. , Sanmartin Claudia , McGurran John J. , Noseworthy Tom W. ,   the Saskatchewan Surgical Care Network/Western Canada Waiting List Project Research and Evaluation Working Group Committee
Published: December 2006

AbstractObjectives  To obtain patients’ perspectives on acceptable waiting times for hip or knee replacement surgery.Methods  A questionnaire with both open‐ and close‐ended items was mailed to 432 consecutive patients who had hip or knee replacement surgery 3–12 months previously in Saskatchewan, Canada. A content analysis was used to analyse the text data from the open‐ended questions.Results  The sample of 303 (response rate 70%) was 59% female with a mean age of 70 years (SD 11). The median waiting time from the decision date to surgery was 17 weeks. Individuals who rated their waiting time very acceptable (48%) had a median waiting time of 13 weeks compared with a median waiting time of 22 weeks for those who rated it unacceptable (23%). The two most common determinants of acceptability were patient expectations and pain and its impact on patient quality of life. The median maximum acceptable waiting time was 13 weeks and median ideal waiting time, 8.6 weeks. Seventy‐nine per cent felt that those in greater need (higher severity) should go before them on the waiting list. Patient ratings of maximum acceptable waiting time were based on: pain and loss of mobility, time needed to prepare for surgery, and severity at the time of seeing the surgeon. In consideration of changing their surgeon to one with a shorter waiting list, 68% would not.Conclusions  Patient views on waiting times are not only related to quality of life issues, but also to prior expectations and notions of fairness and priority. Understanding patient views on waiting for surgery has implications for better management of waiting times and experiences for joint replacement.
T lymphocytes expressing CCR3 are increased in allergic rhinitis compared with non‐allergic controls and following allergen immunotherapy
Authors: Francis J. N. , Lloyd C. M. , Sabroe I. , Durham S. R. , Till S. J. 
Published: December 2006

Background:  In T cell‐associated allergic inflammation, homing of T‐helper 2 (Th2) effector cells to mucosal sites may be influenced by chemokine receptor expression. Previous studies have identified CCR3 and CCR4 as putative markers of Th2 cells and CCR5 and CXCR3 as markers of Th1 cells. The aim of this study was to assess differential chemokine receptor expression from symptomatic atopic grass pollen‐sensitive subjects, compared with patients on high‐dose allergen injection immunotherapy (IT) and healthy controls.Methods:  We examined chemokine receptor expression (CCR1–7 and CXCR1–4) by flow cytometry of peripheral blood CD4+ and CD8+ T cells. We also depleted peripheral blood mononuclear cell (PBMC) populations of CCR3+ CD4+ cells by magnetic bead separation and cells were stimulated with grass pollen allergen for 6 days. Cytokine production was measured by enzyme‐linked immunosorbent assay.Results:  On freshly isolated PBMC, atopic individuals exhibited increased numbers of CCR3+ CD4+ cells compared with normal controls (P < 0.01). CCR3 expression in IT patients was reduced compared with matched atopic rhinitic controls (P < 0.05) and comparable with that observed in normal subjects. Depletion of CCR3+ CD4+ cells from allergen‐stimulated PBMC cultures resulted in decreased interleukin (IL)‐5 production compared with whole CD4+ populations (P < 0.05). Freshly isolated CCR3+ CD4+ cells have significantly higher intracellular IL‐4 and lower IFN‐γ levels than CCR3− CD4+ cells. CD4+ T cells cultured from both peripheral cells and nasal biopsies demonstrated increased expression of CCR3 in the presence of IL‐4 (P < 0.05).Conclusion:  CCR3+ CD4+ T cells are increased in allergic rhinitis, are reduced by allergen IT, have a Th2 phenotype and contribute to allergen‐specific responses. Strategies against CCR3+ T cells may be effective in human allergic diseases.
Relationship between matrix metalloproteinases MMP‐2, MMP‐9, tissue inhibitor of matrix metalloproteinases‐1 and IL‐5, IL‐8 in nasal polyps
Authors: Chen Y.‐S. , Langhammer T. , Westhofen M. , Lorenzen J. 
Published: December 2006

Background:  Nasal polyps (NP), a subgroup of chronic rhinosinusitis, are characterized by interleukin 5 (IL‐5) mediated infiltration of eosinophils in sinus mucosa, leading to pseudostratified ciliated columnar epithelium, thickening of the epithelial basement membrane and tissue edema. Matrix metalloproteinases (MMP) constitute a large group of Zn2+ dependent endopeptidases with the ability to degrade extracellular matrix and are possibly responsible for the development of tissue edema in chronic sinusitis.Objective:  The aim of this study was to determine the expression of MMP‐2, MMP‐9 and tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) mRNA and to locate the distribution of MMP‐2, MMP‐9 and TIMP‐1 by immunohistochemistry in ethmoid sinus mucosa in NP. Furthermore the correlation between IL‐5 or IL‐8 and MMP‐2, MMP‐9 or TIMP‐1 is examined.Methods:  Nasal polyps of 33 patients and 18 specimens of inferior turbinate mucosa were examined by real time RT‐PCR for MMP‐2, MMP‐9, TIMP‐1, IL‐5 and IL‐8 mRNA expression. Immunohistochemical labeling for MMP‐2, MMP‐9 and TIMP‐1 was performed.Results:  Differences between both locations were detectable for MMP‐9 (P < 0.001) and IL‐5 (P = 0.003) but not for MMP‐2 (P = 0.278), TIMP‐1 (P = 0.515) and IL‐8 (P = 0.386). Correlation was detected only between TIMP‐1 and IL‐5 (r = 0.422, P = 0.014). Cytoplasmic staining of MMP‐2 was present in the apical part of the ciliated cells, submucosal glands and in smooth muscle cells. Matrix metalloproteinase‐9 was expressed in surface epithelium, in seromucous glands and in polymorphonuclear cells.Conclusions:  Expression of MMP‐9 and IL‐5 mRNA are associated with NP. The correlation between IL‐5 and TIMP‐1 indicates the role of TIMP‐1 in maintaining the homeostasis in NP.
Relevance of the determination of serum‐specific IgE antibodies in the diagnosis of immediate β‐lactam allergy
Authors: Fontaine C. , Mayorga C. , Bousquet P. J. , Arnoux B. , Torres M.‐J. , Blanca M. , Demoly P. 
Published: December 2006

Background:  Allergic reactions to β‐lactams are the most frequent cause of adverse drug reactions mediated by specific immunologic mechanisms. They can be explored by in vivo and/or in vitro tests. The measurement of serum‐specific immunoglobulin E (IgE) presents several advantages: safety, simplicity, and availability to nonallergologist physicians.Objectives:  To establish the diagnostic value of specific IgE determination in the diagnosis procedure of immediate β‐lactam allergy.Methods:  The in vitro determination of β‐lactam‐specific IgE antibodies was compared in three well‐defined groups of patients (n = 45): one with negative skin tests and a positive drug provocation test, another with positive skin tests, and a third control exposed population with good tolerance. Two techniques were used: the CAP‐FEIA system (Phadia®) commercially available and a homemade radioallergosorbent test (RAST).Results:  The specificity of CAP‐FEIA ranged from 83.3% to 100% and sensitivity from 0% to 25% depending on initial clinical manifestations. The specificity of RAST was between 66.7% and 83.3% and sensitivity 42.9% and 75%. In the subgroup of patients with an anaphylactic shock and negative skin tests, the sensitivity and specificity of RAST were 75%. Positive and negative predictive values were 45.5% and 77.1% with CAP‐FEIA and 38.5% and 81.5% with RAST, respectively.Conclusion:  These results indicate that, although the specificity of β‐lactam‐specific IgE measurement is good, sensitivity is low. Immunoglobulin E measurement should be limited to patients with a clinical history of anaphylactic shock and negative skin tests in order to avoid a drug provocation test. More sensitive assays should be developed.
Distinct expression and inhibitory function of B and T lymphocyte attenuator on human T cells
Authors: Wang X.‐F. , Chen Y.‐J. , Wang Q. , Ge Y. , Dai Q. , Yang K.‐F. , Fang‐Xie  , Zhou Y.‐H. , Hu Y.‐M. , Mao Y.‐X. , Zhang X.‐G. 
Published: December 2006

AbstractB and T lymphocyte attenuator (BTLA) has been recently identified as a new inhibitory receptor of the CD28 superfamily, with similarities to cytotoxic T lymphocyte activation antigen (CTLA)‐4 and programmed death (PD)‐1. Engagement of BTLA on T lymphocytes can profoundly reduce the T cell receptor (TCR)‐mediated activation. In this study, we generated four monoclonal antibodies (mAbs) against human BTLA. Using the produced mAb 8H9, the BTLA molecule was found to distinctly express on many subgroups of immunocytes and show a regulatory expression, which was in accordance with its unique ligand herpes virus entry mediator (HVEM) in the process of T cell activation. In addition, the expression of BTLA was increased in the CD4+ and CD8+ T cells of pleural fluid in lung cancer patients. Furthermore, we showed that the BTLA‐induced negative signals could be triggered by mAb 7D7. Cross‐linking of BTLA with mAb 7D7 suppressed T lymphocyte proliferation, downregulated the expression of T cell activation marker CD25, and inhibited the production of interferon (IFN)‐γ, interleukin (IL)‐2, IL‐4, and IL‐10.
CD31/PECAM‐1 genotyping and haplotype analyses show population diversity
Authors: Robbins F.‐M. , Hartzman R. J. 
Published: December 2006

AbstractUsing direct sequencing of complementary DNA products, the sequences of human CD31 from exon 1 through exon 16 of 179 individuals (139 unrelated) were systematically examined. Of the 14 biallelic single nucleotide polymorphic sites detected, 7 polymorphic sites involved amino acid substitution. These 14 polymorphic sites yielded 18 observed CD31 alleles and 9 predicted CD31 polypeptide sequences. Based on molecular haplotyping and family pedigree analysis, linkage disequilibrium among some single nucleotide polymorphic sites was observed. Single nucleotide polymorphism frequencies between populations were also measured using dot‐blot hybridization with DNA or peptide nucleic acid probes.
Expression of APOBEC3G in kidney cells
Authors: Komohara Y. , Suekane S. , Noguchi M. , Matsuoka K. , Yamada A. , Itoh K. 
Published: December 2006

AbstractThe apolipoprotein B mRNA‐editing enzyme, catalytic polypeptide‐like 3G (APOBEC3G), a member of the APOBEC family possessing DNA mutator activity through cytosine deamination, is reported to play an important role in host defense against infections such as those of hepatitis B virus and human immunodeficiency virus. Here, we examined the expression of APOBEC3G in human kidney cells to better understand its biological role against infection. APOBEC3G was immunohistochemically detectable in kidney mesangial cells and also to some extent in kidney epithelial tubular cells. In addition, overexpression of APOBEC3G was shown in renal carcinoma tissues and cell lines. APOBEC3G expression was upregulated by inflammatory cytokines, such as interferon, interleukin‐6, and tumor necrosis factor. These results may provide new insight into the role of APOBEC3G in host defense against viral infection and cancer.