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Armen A Galoyan,Josef Krieglstein,Susanne Klumpp,Kristina E Danielian,Karine A Galoian,Wolfram Kremers,Kristina B Bezirganyan,Tigran K Davtyan The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. It has been shown that PRP-1 has many potentially beneficial biological effects including immunoregulatory, hematopoi... ( view more )etic, antimicrobial and anti-neurodegenerative properties. Here we investigated the influence of PRP-1 on staurosporine-induced apoptosis of postnatal hippocampal cells and on doxorubicin-induced bone marrow granulocyte- and monocyte apoptosis. The intention was to further characterize the effect of PRP-1 on the survival rate of neurons and in context with myelopoiesis. We demonstrate that PRP-1 significantly reduced apoptosis of postnatal hippocampal cells induced by staurosporine. The protective effect of PRP-1 against apoptotic cell death was shown to be both time- and dose-dependent. Neuroprotection was more pronounced after prolonged pretreatment of the cells with PRP-1 before the induction of apoptosis with staurosporine. The related peptide [arg(8)]vasopressin did not reveal neuroprotection. PRP-1 also significantly reduced apoptosis of bone marrow monocytes and granulocytes induced by doxorubicin. This protective effect lasted for 2-4 h and was not detectable anymore after 24 h when PRP-1 and doxorubicin were added simultaneously. Previously obtained data and results of the current studies suggested that the hypothalamic PRP-1 possibly represents an endogenous peptide whose primary functions are to regulate myelopoiesis and neuron survival as we provide evidence that PRP can differentially reduce both staurosporine- and doxorubicin-induced hippocampal and bone marrow cell apoptosis. ( view less ) Kristina Karrman,Erik Forestier,Mette K Andersen,Kirsi Autio,Georg Borgström,Sverre Heim,Kristina Heinonen,Randi Hovland,Gitte Kerndrup,Bertil Johansson,Nordic Society of Paediatric Haematology and Oncology (NOPHO) and the NOPHO Leukaemia Cytogenetic Study Group (NLCSG) Trisomy 21 is common in ETV6/RUNX1-positive acute lymphoblastic leukaemia (ALL); both these aberrations are associated with a favourable outcome. The prognostic impact of +21 as a sole cytogenetic change could be due to a cryptic t(12;21)(p13;q22). The occurrence of ETV6/RUNX1 was determined in 66 ... ( view more )childhood ALLs with an acquired +21 and a chromosome number <51. ETV6/RUNX1 was found in 45% of cases and in the majority (10/18; 56%) of ALLs with sole +21. Event-free survival did not differ between the t(12;21)-positive and -negative cases. Thus, the prognostic impact of +21 is not attributable to cryptic ETV6/RUNX1. ( view less ) Jack A Elias,Min Jong Kang,Kristina Crothers,Kristina Crouthers,Robert Homer,Chun Geun Lee Alveolar destruction is a cardinal feature of emphysema but is not traditionally believed to contribute to the pathogenesis of "classical" asthma. However, the relationship between chronic obstructive pulmonary disease (COPD) and asthma is controversial and the variety of mechanisms that can mediat... ( view more )e the alveolar destruction in emphysema have not been adequately defined. To address these issues, we used overexpression transgenic approaches to define the effects of Th1/Tc1 and Th2/Tc2 cytokines in the mature murine lung and compared findings in these transgenic systems to the effects of similar interventions after cigarette smoke (CS) exposure. In these experiments, the Th1/Tc1 and Th2/Tc2 cytokines IFN-gamma and interleukin (IL)-13, respectively, both caused emphysema. The IFN-gamma response was associated with neutrophilia but was not associated with mucus metaplasia or a major fibrotic response. In this setting, IFN-gamma was a potent stimulator of matrix metalloproteinases (MMPs), cathepsins, and CXC and other chemokines while inhibiting secretory leukocyte proteinase inhibitor (SLPI). Interestingly, IFN-gamma induced its destructive effects via at least two mechanisms, a CCR5/cathepsin-dependent and apoptosis-mediated pathway and an MMP-12-dependent/apoptosis-independent pathway. CS-induced inflammation, apoptosis, and emphysema were also induced by IFN-gamma- and CCR5-dependent mechanisms. In contrast, IL-13-induced emphysema was associated with eosinophilia, mucus metaplasia, and pulmonary fibrosis. In this setting, IL-13 stimulated MMPs, cathepsins, and a variety of CC chemokines while inhibiting alpha(1)-antitrypsin. A cathepsin-dependent apoptosis pathway also contributed to this remodeling response. Interestingly, abnormalities in vascular endothelial growth factor (VEGF) were also appreciated with VEGF(165) excess producing an asthmalike pulmonary response and IFN-gamma abrogating this response while inducing emphysematous alveolar destruction. These findings provide molecular support for both points of view in the British/Dutch hypothesis controversy regarding the relationship between asthma and COPD. They also highlight the complexity of the pathways that can induce alveolar destruction and suggest that there is a continuum, based on VEGF, between asthma and COPD. ( view less ) Taryn Vian,Kristina Gryboski,Kristina Grybosk,Zamira Sinoimeri,Rachel Hall As governments seek to expand access to quality health care services, policy makers in many countries are confronting the problem of informal payments to medical personnel. The aim of this study was to help health planners in Albania understand informal payments occurring in government health facil... ( view more )ities. Researchers used in-depth interviews and focus groups with 131 general public and provider informants in three districts. The results suggest that factors promoting informal payments in Albania include perceived low salaries of health staff; a belief that good health is worth any price; the desire to get better service; the fear of being denied treatment; and the tradition of giving a gift to express gratitude. Members of the general public also believe informal payments create uncertainties and anxiety during the care-seeking process, while providers perceive that informal payments harm their professional reputation, induce unnecessary medical interventions, and create discontinuity of care. The study showed that focusing on the most harmful effects and targeting the most vulnerable populations may be one way to gain consensus for policy reform. Understanding citizens' and caregivers' viewpoints is an important step in designing regulatory and bureaucratic interventions. ( view less ) Mathias Uhlén,Erik Björling,Charlotta Agaton,Cristina Al-Khalili Szigyarto,Bahram Amini,Elisabet Andersen,Ann-Catrin Andersson,Pia Angelidou,Anna Asplund,Caroline Asplund,Lisa Berglund,Kristina Bergström,Harry Brumer,Dijana Cerjan,Marica Ekström,Adila Elobeid,Cecilia Eriksson,Linn Fagerberg,Ronny Falk,Jenny Fall,Mattias Forsberg,Marcus Gry Björklund,Kristoffer Gumbel,Asif Halimi,Inga Hallin,Carl Hamsten,Marianne Hansson,My Hedhammar,Görel Hercules,Caroline Kampf,Karin Larsson,Mats Lindskog,Wald Lodewyckx,Jan Lund,Joakim Lundeberg,Kristina Magnusson,Erik Malm,Peter Nilsson,Jenny Odling,Per Oksvold,Ingmarie Olsson,Emma Oster,Jenny Ottosson,Linda Paavilainen,Anja Persson,Rebecca Rimini,Johan Rockberg,Marcus Runeson,Asa Sivertsson,Anna Sköllermo,Johanna Steen,Maria Stenvall,Fredrik Sterky,Sara Strömberg,Mårten Sundberg,Hanna Tegel,Samuel Tourle,Eva Wahlund,Annelie Waldén,Jinghong Wan,Henrik Wernérus,Joakim Westberg,Kenneth Wester,Ulla Wrethagen,Lan Lan Xu,Sophia Hober,Fredrik Pontén Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles ... ( view more )in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, approximately 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research. ( view less ) Linda Mathsson,Andreas Tejde,Kristina Carlson,Martin Höglund,Bo Nilsson,Kristina Nilsson-Ekdahl,Johan Rönnelid Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance... ( view more ) with our findings of IC-induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or FcgammaRIIa, FcgammaRIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme-linked immunosorbent assay. CG-induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via FcgammaRIIa- and complement-dependent mechanisms. Complement blockade resulted in increased IgG CG-induced interleukin (IL)-10 production that was inversely correlated with decreased production of tumour necrosis factor-alpha. CG-induced IL-10 might be a growth factor for malignant B-lymphocytes in CG-associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG-induced cytokine production can be useful for designing treatments for type I CG-associated pathology in lymphoproliferative diseases. ( view less ) Kristina Chen,Eunice Y Chang,Kent H Summers,Robert L Obenchain,Kristina S Yu-Isenberg,Peter Sun OBJECTIVE: To compare medical and pharmacy costs and utilization between patients with diabetes who received insulin lispro versus regular human insulin. METHODS: A retrospective analysis of medical and pharmacy claims was conducted among continuously enrolled users of insulin lispro or regular ins... ( view more )ulin during the identification period, March 1, 2000, through February 28, 2001, within a large managed care organization. This study improved upon the methodology used in previous studies by (a) stratifying (rather than 1:1 matching) individuals by their likelihood to use insulin lispro using the propensity score binning technique, and (b) refining the study inclusion criteria to include only patients with 3 or more fills of the insulin under study (lispro or regular) to exclude individuals who may have been on either product for a short time. Because the propensity score binning technique groups patients with similar baseline characteristics within strata (bins) and not among individual patients, almost the entire available sample is retained in the analysis, unlike propensity score matching, where large numbers of patients can be excluded depending on the matching scheme. Therefore, the propensity score binning technique, because it uses more complete information, is less likely to produce biased results. Patients were grouped into 5 bins (quintiles) based on their estimated likelihood to receive insulin lispro rather than regular insulin. The propensity score model used baseline characteristics of age, gender, comorbidities, use of oral antidiabetic medications, prescription copayment, and diabetes-related costs and utilization. Overall cost and utilization differences (lispro minus regular insulin) during the 12-month follow-up period were calculated using weights inversely proportional to variances of within-bin differences. RESULTS: Of 6,436 patients, 1,972 (30.6%) received insulin lispro and 4,464 (69.4%) received regular insulin. The propensity score estimation produced 5 bins, each containing between 1,287 and 1,288 patients, utilizing all patients in the analysis. Patients in the lower-numbered propensity score quintiles were older, more likely to use oral antidiabetic medications, and had more comorbidities than those in the higher-numbered quintiles. As quintile number increased, the percentage of insulin lispro users also increased. The weighted mean annual cost difference (lispro minus regular insulin) per patient was + USD 79 (P < 0.001) for diabetes-related pharmacy cost, + USD 212 (P < 0.001) for total pharmacy cost, USD 75 (P < 0.857) for diabetes-related medical cost, USD 2,286 (P <0.011) for nondiabetes medical cost, and USD 2,327 (P = 0.072) for total medical cost. CONCLUSIONS: Compared with regular insulin users, insulin lispro users incurred higher diabetes-related and total pharmacy costs but lower nondiabetes medical costs and similar total medical costs. Fewer hospitalizations among insulin lispro as compared with regular insulin users contributed to lower nondiabetes medical costs and similar total medical costs. ( view less ) Kristina Eriksson,Lars Bellner,Staffan Görander,Gun-Britt Löwhagen,Petra Tunbäck,Kristina Rydberg,Jan-Ake Liljeqvist T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoprote... ( view more )ins C and E (gC-1 and gE-1) were compared. CD4(+) T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals responded in vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4(+) T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4(+) T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular. ( view less ) Kristina Mårdberg,Kristina Nyström,Mads Agervig Tarp,Edward Trybala,Henrik Clausen,Tomas Bergström,Sigvard Olofsson The herpes simplex virus type 1 (HSV-1) glycoprotein gC-1 is engaged both in viral attachment and viral immune evasion mechanisms in the infected host. Besides several N-linked glycans, gC-1 contains numerous O-linked glycans, mainly localized in two pronase-resistant clusters in the N-terminal dom... ( view more )ain of gC-1. In the present study we construct and characterize one gC-1 mutant virus, in which two basic amino acids (114K and 117R) in a putative O-glycosylation sequon were changed to alanine. We found that this modification did not modify the N-linked glycosylation but increased the content of O-linked glycans considerably. Analysis of the O-glycosylation capacity of wild-type and mutant gC-1 was performed by in vitro glycosylation assays with synthetic peptides derived from the mutant region predicted to present new O-glycosylation sites. Thus the mutant peptide region served as a better substrate for polypeptide GalNAc-transferase 2 than the wild-type peptide, resulting in increased rate and number of O-glycan attachment sites. The predicted increase in O-linked glycosylation resulted in two modifications of the biological properties of mutant virus-that is, an impaired binding to cells expressing chondroitin sulfate but not heparan sulfate on the cell surface and a significantly reduced plaque size in cultured cells. The results suggested that basic amino acids present within O-glycosylation signals may down-regulate the amount of O-linked glycans attached to a protein and that substitution of such amino acid residues may have functional consequences for a viral glycoprotein involving virus attachment to permissive cells as well as viral cell-to-cell spread. ( view less ) Lisa LaFranco-Scheuch,Kristina Abel,Norbert Makori,Kristina Rothaeusler,Christopher J Miller Viral suppression by noncytolytic CD8+ T cells, in addition to that by classic antiviral CD8+ cytotoxic T lymphocytes, has been described for human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. However, the role of soluble effector molecules, especially beta-chemokines,... ( view more ) in antiviral immunity is still controversial. In an attenuated vaccine model, approximately 60% of animals immunized with simian/human immunodeficiency virus (SHIV) 89.6 and then challenged intravaginally with SIVmac239 controlled viral replication (viral RNA level in plasma, <10(4) copies/ml) and were considered protected (K. Abel, L. Compton, T. Rourke, D. Montefiori, D. Lu, K. Rothaeusler, L. Fritts, K. Bost, and C. J. Miller, J. Virol. 77:3099-3118, 2003). To determine the in vivo importance of beta-chemokine secretion and CD8+-T-cell proliferation in the control of viral replication in this vaccine model, we examined the relationship between viral RNA levels in the axillary and genital lymph nodes of vaccinated, protected (n = 20) and vaccinated, unprotected (n = 11) monkeys by measuring beta-chemokine mRNA levels and protein expression, the frequency of CD8+ T cells expressing beta-chemokines, and the extent of CD8+-T-cell proliferation. Tissues from uninfected (n = 3) and unvaccinated, SIVmac239-infected (n = 9) monkeys served as controls. Axillary and genital lymph nodes from unvaccinated and vaccinated, unprotected monkeys had significantly higher beta-chemokine mRNA expression levels and increased numbers of beta-chemokine-positive cells than did vaccinated, protected animals. Furthermore, the lymph nodes of vaccinated, unprotected monkeys had significantly higher numbers of beta-chemokine(+) CD8+ T cells than did vaccinated, protected monkeys. Lymph nodes from vaccinated, unprotected animals also had significantly more CD8+-T-cell proliferation and marked lymph node hyperplasia than the lymph nodes of vaccinated, protected monkeys. Thus, higher levels of virus replication were associated with increased beta-chemokine secretion and there is no evidence that beta-chemokines contributed to the SHIV89.6-mediated control of viral replication after intravaginal challenge with SIVmac239. ( view less ) Henry E Young,Cecile Duplaa,Michael J Yost,Nicholas L Henson,Julie A Floyd,Kristina Detmer,Angela J Thompson,Steven W Powell,T Clark Gamblin,Kirk Kizziah,Benjamin J Holland,Angel Boev,J M Van De Water,Dan C Godbee,Stephanie Jackson,Marylen Rimando,Chad R Edwards,Eveline Wu,Chris Cawley,Pamela D Edwards,Anna Macgregor,Ryan Bozof,T Michele Thompson,George J Petro,Heather M Shelton,Beth L McCampbell,Jared C Mills,Frederick L Flynt,Timothy A Steele,Marianne Kearney,Amy Kirincich-Greathead,Wade Hardy,Paul R Young,Aman V Amin,R Steve Williams,Miranda M Horton,Shaun McGuinn,Kristina C Hawkins,Kurt Ericson,Louis Terracio,Catherine Moreau,Douglas Hixson,Brian W Tobin,John Hudson,Frank P Bowyer,Asa C Black Undifferentiated cells have been identified in the prenatal blastocyst, inner cell mass, and gonadal ridges of rodents and primates, including humans. After isolation these cells express molecular and immunological markers for embryonic cells, capabilities for extended self-renewal, and telomerase ... ( view more )activity. When allowed to differentiate, embryonic stem cells express phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. When implanted in vivo, undifferentiated noninduced embryonic stem cells formed teratomas. In this report we describe a cell clone isolated from postnatal rat skeletal muscle and derived by repetitive single-cell clonogenic analysis. In the undifferentiated state it consists of very small cells having a high ratio of nucleus to cytoplasm. The clone expresses molecular and immunological markers for embryonic stem cells. It exhibits telomerase activity, which is consistent with its extended capability for self-renewal. When induced to differentiate, it expressed phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. The clone was designated as a postnatal pluripotent epiblastic-like stem cell (PPELSC). The undifferentiated clone was transfected with a genomic marker and assayed for alterations in stem cell characteristics. No alterations were noted. The labeled clone, when implanted into heart after injury, incorporated into myocardial tissues undergoing repair. The labeled clone was subjected to directed lineage induction in vitro, resulting in the formation of islet-like structures (ILSs) that secreted insulin in response to a glucose challenge. This study suggests that embryonic-like stem cells are retained within postnatal mammals and have the potential for use in gene therapy and tissue engineering. ( view less ) Vivian B Faden,Nancy L Day,Michael Windle,Rebecca Windle,Joel W Grube,Brooke S G Molina,William E Pelham,Elizabeth M Gnagy,Tracey K Wilson,Kristina M Jackson,Kenneth J SherThis article presents the proceedings of a workshop at the 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida. The organizers and chairs were Vivian Faden and Nancy Day. The presentations were (1) Lessons Learned From the Lives Across Time Longitudinal Study, by Michael Windle ... ( view more )and Rebecca Windle; (2) Methodological Issues in Longitudinal Surveys With Children and Adolescents, by Joel Grube; (3) The Pittsburgh ADHD Longitudinal Study: Methodological and Conceptual Challenges, by Brooke Molina, William Pelham, Elizabeth Gnagy, and Tracey Wilson; and (4) Lessons learned in Conducting Longitudinal Research on Alcohol Involvement: If Only I Had Known Before Hand! by Kristina Jackson and Kenneth Sher. ( view less ) Henry E Young,Cecile Duplaa,Marina Romero-Ramos,Marie-Francoise Chesselet,Patrick Vourc'h,Michael J Yost,Kurt Ericson,Louis Terracio,Takayuki Asahara,Haruchika Masuda,Sayaka Tamura-Ninomiya,Kristina Detmer,Robert A Bray,Timothy A Steele,Douglas Hixson,Mohammad el-Kalay,Brian W Tobin,Roy D Russ,Michael N Horst,Julie A Floyd,Nicholas L Henson,Kristina C Hawkins,Jaime Groom,Amar Parikh,Lisa Blake,Laura J Bland,Angela J Thompson,Amy Kirincich,Catherine Moreau,John Hudson,Frank P Bowyer,T J Lin,Asa C Black Tissue restoration is the process whereby multiple damaged cell types are replaced to restore the histoarchitecture and function to the tissue. Several theories have been proposed to explain the phenomenon of tissue restoration in amphibians and in animals belonging to higher orders. These theories... ( view more ) include dedifferentiation of damaged tissues, transdifferentiation of lineage-committed progenitor cells, and activation of reserve precursor cells. Studies by Young et al. and others demonstrated that connective tissue compartments throughout postnatal individuals contain reserve precursor cells. Subsequent repetitive single cell-cloning and cell-sorting studies revealed that these reserve precursor cells consisted of multiple populations of cells, including tissue-specific progenitor cells, germ-layer lineage stem cells, and pluripotent stem cells. Tissue-specific progenitor cells display various capacities for differentiation, ranging from unipotency (forming a single cell type) to multipotency (forming multiple cell types). However, all progenitor cells demonstrate a finite life span of 50 to 70 population doublings before programmed cell senescence and cell death occurs. Germ-layer lineage stem cells can form a wider range of cell types than a progenitor cell. An individual germ-layer lineage stem cell can form all cells types within its respective germ-layer lineage (i.e., ectoderm, mesoderm, or endoderm). Pluripotent stem cells can form a wider range of cell types than a single germ-layer lineage stem cell. A single pluripotent stem cell can form cells belonging to all three germ layer lineages. Both germ-layer lineage stem cells and pluripotent stem cells exhibit extended capabilities for self-renewal, far surpassing the limited life span of progenitor cells (50-70 population doublings). The authors propose that the activation of quiescent tissue-specific progenitor cells, germ-layer lineage stem cells, and/or pluripotent stem cells may be a potential explanation, along with dedifferentiation and transdifferentiation, for the process of tissue restoration. Several model systems are currently being investigated to determine the possibilities of using these adult quiescent reserve precursor cells for tissue engineering. ( view less ) Wanhong Ding,Stefan Beissert,Liang Deng,Edward Miranda,Christopher Cassetty,Kristina Seiffert,Kristina L Campton,Zhengmin Yan,George F Murphy,Jeffrey A Bluestone,Richard D Granstein IL-10 is a pleiotropic cytokine that inhibits several immune parameters, including Th1 cell-mediated immune responses, antigen presentation, and antigen-specific T cell proliferation. Recent data implicate IL-10 as a mediator of suppression of cell-mediated immunity induced by exposure to UVB radia... ( view more )tion (280-320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A(+) epidermal and dermal cells and fewer I-A(+) hapten-bearing cells in regional lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression by I-A(+) epidermal cells was also observed. vIL-10 transgenic mice demonstrated a smaller delayed-type hypersensitivity response to allogeneic cells upon challenge but had normal contact hypersensitivity to an epicutaneously applied hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased ability to stimulate allogeneic T cell proliferation, as did splenocytes. Additionally, chronic exposure of mice to UVB radiation led to the development of fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice had increased splenic NK cell activity against YAC-1targets. These findings support the concept that IL-10 is an important regulator of cutaneous immune function. ( view less ) Kristina Abel,Lara Compton,Tracy Rourke,David Montefiori,Ding Lu,Kristina Rothaeusler,Linda Fritts,Kristen Bost,Christopher J Miller Attenuated primate lentivirus vaccines provide the most consistent protection against challenge with pathogenic simian immunodeficiency virus (SIV). Thus, they provide an excellent model to examine the influence of the route of immunization on challenge outcome and to study vaccine-induced protecti... ( view more )ve anti-SIV immune responses. In the present study, rhesus macaques were immunized with live nonpathogenic simian-human immunodeficiency virus (SHIV) 89.6 either intravenously or mucosally (intranasally or intravaginally) and then challenged intravaginally with pathogenic SIVmac239. The route of immunization did not affect mucosal challenge outcome after a prolonged period of systemic infection with the nonpathogenic vaccine virus. Further, protection from the SIV challenge was associated with the induction of multiple host immune effector mechanisms. A comparison of immune responses in vaccinated-protected and vaccinated-unprotected animals revealed that vaccinated-protected animals had higher frequencies of SIV Gag-specific cytotoxic T lymphocytes and gamma interferon (IFN-gamma)-secreting cells during the acute phase postchallenge. Vaccinated-protected animals also had a more pronounced increase in peripheral blood mononuclear cell IFN-alpha mRNA levels than did the vaccinated-unprotected animals in the first few weeks after challenge. Thus, innate as well as cellular anti-SIV immune responses appeared to contribute to the SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239. ( view less ) Stanislava Domarkiene,Abdonas Tamosi?nas,Regina Reklaitiene,Doma Sidlauskiene,Kristina Jureniene,Lile Margeviciene,Kristina Buivydaite,Migle Kazlauskaite OBJECTIVE OF THE STUDY: To evaluate dynamics in prevalence of main risk factors of cardiovascular diseases among middle-aged Kaunas population between 1993 and 2002. MATERIAL AND METHODS: Four independent surveys in 1983-1984, 1986-1987, 1992-1993, and 2001-2002 were carried out in random samples o... ( view more )f men and women aged 35-64 involving 2413, 1762, 1231 and 1403 persons respectively. The risk factors were defined within the framework of the WHO MONICA study (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease). RESULTS: During the 19 years the mean values of systolic blood pressure decreased among men. Among women decreased both mean values of systolic and diastolic blood pressure, however the prevalence of hypertension has decreased only among women by 11.9%, with no significant changes among men. The prevalence of overweight decreased among men, and the prevalence of obesity declined among women. Among women the body mass index decreased as well. No changes in the prevalence of hypercholesterolemia among men (80.7%) as well as among women (82.7%) have been detected, meanwhile the mean of total cholesterol among men increased from 5.9 mmol/l to 6.1 mmol/l and among women - from 6.09 mmol/l to 6.31 mmol/l (p<0.001). The prevalence of smoking has increased by 7.2% among women and didn't change among men. IN CONCLUSION: The decreasing trends in the prevalence of some risk factors have been estimated in Kaunas middle-aged population during 1983-2002 years. However the profile of cardiovascular disease risk factors is still rather high. Programs or strategies targeted to control levels of main cardiovascular disease risk factors are urgently needed. ( view less ) Kristina Abel,Michelle J Alegria-Hartman,Kristina Rothaeusler,Marta Marthas,Christopher J Miller To define the role of alpha/beta interferons (IFN-alpha/beta) in simian immunodeficiency virus (SIV) infection, IFN-alpha and IFN-beta mRNA levels and mRNA levels of Mx, an antiviral effector molecule, were determined in lymphoid tissues of rhesus macaques infected with pathogenic SIV. IFN-alpha/be... ( view more )ta responses were induced during the acute phase and persisted in various lymphoid tissues throughout the chronic phase of infection. IFN-alpha/beta responses were most consistent in tissues with high viral RNA levels; thus, IFN-alpha/beta responses were not generally associated with effective control of SIV replication. IFN-alpha/beta responses were differentially regulated in different lymphoid tissues and at different stages of infection. The most consistent IFN-alpha/beta responses in acute and chronic SIV infection were observed in peripheral lymph nodes. In the spleen, only a transient increase in IFN-alpha/beta mRNA levels during acute SIV infection was observed. Further, IFN-alpha and IFN-beta mRNA levels showed a tissue-specific expression pattern during the chronic, but not the acute, phase of infection. In the acute phase of infection, SIV RNA levels in lymphoid tissues of rhesus macaques correlated with mRNA levels of both IFN-alpha and IFN-beta, whereas during chronic SIV infection only increased IFN-alpha mRNA levels correlated with the level of virus replication in the same tissues. In lymphoid tissues of all SIV-infected monkeys, higher viral RNA levels were associated with increased Mx mRNA levels. We found no evidence that monkeys with increased Mx mRNA levels in lymphoid tissues had enhanced control of virus replication. In fact, Mx mRNA levels were associated with high viral RNA levels in lymphoid tissues of chronically infected animals. ( view less ) Kristina Seiffert,Junichi Hosoi,Hideshi Torii,Hiroaki Ozawa,Wanhong Ding,Kristina Campton,John A Wagner,Richard D Granstein The sympathetic nervous system modulates immune function at a number of levels. Within the epidermis, APCs (Langerhans cells (LC)) are frequently anatomically associated with peripheral nerves. Furthermore, some neuropeptides have been shown to regulate LC Ag-presenting function. We explored the ex... ( view more )pression of adrenergic receptors (AR) in murine LC and assessed their functional role on Ag presentation and modulation of cutaneous immune responses. Both purified LC and the LC-like cell lines XS52-4D and XS106 expressed mRNA for the ARs alpha(1A) and beta(2). XS106 cells and purified LC also expressed beta(1)-AR mRNA. Treatment of murine epidermal cell preparations with epinephrine (EPI) or norepinephrine inhibited Ag presentation in vitro. Furthermore, pretreatment of epidermal cells with EPI or norepinephrine in vitro suppressed the ability of these cells to present Ag for elicitation of delayed-type hypersensitivity in previously immunized mice. This effect was blocked by use of the beta(2)-adrenergic antagonist ICI 118,551 but not by the alpha-antagonist phentolamine. Local intradermal injection of EPI inhibited the induction of contact hypersensitivity to epicutaneously administered haptens. Surprisingly, injection of EPI at a distant site also suppressed induction of contact hypersensitivity. Thus, catecholamines may have both local and systemic effects. We conclude that specific ARs are expressed on LC and that signaling through these receptors can decrease epidermal immune reactions. ( view less ) Somer Bekiroglu,Olle Myrberg,Kristina Ostman,Marianne Ek,Torbjörn Arvidsson,Torgny Rundlöf,Birgit Hakkarainen A (1)H-nuclear magnetic resonance (NMR) spectroscopy method for quantitative determination of benzethonium chloride (BTC) as a constituent of grapefruit seed extract was developed. The method was validated, assessing its specificity, linearity, range, and precision, as well as accuracy, limit of qu... ( view more )antification and robustness. The method includes quantification using an internal reference standard, 1,3,5-trimethoxybenzene, and regarded as simple, rapid, and easy to implement. A commercial grapefruit seed extract was studied and the experiments were performed on spectrometers operating at two different fields, 300 and 600MHz for proton frequencies, the former with a broad band (BB) probe and the latter equipped with both a BB probe and a CryoProbetrade mark. The concentration average for the product sample was 78.0, 77.8 and 78.4mg/ml using the 300 BB probe, the 600MHz BB probe and CryoProbetrade mark, respectively. The standard deviation and relative standard deviation (R.S.D., in parenthesis) for the average concentrations was 0.2 (0.3%), 0.3 (0.4%) and 0.3mg/ml (0.4%), respectively. ( view less ) Anita Mehner,Ulf Lindblad,Lennart Råstam,Kristina Bengtsson Boström OBJECTIVE: To assess the use of lipid-lowering therapy in patients with known coronary heart disease (CHD), cerebrovascular disease or diabetes in a community-based population in Sweden considering expert recommendations. METHODS: A random sample of individuals aged >/=40 years who were surveyed in... ( view more ) 1993-1994 were revisited 10 years later during 2003-2004 (n = 724). A clinical investigation focused on cardiovascular risk including serum total cholesterol. Information on medical history and current medication was collected in structured interviews. RESULTS: Eighty-two patients (11.3%) reported a history of CHD, including 51 men and 31 women. Fifty-three patients fulfilled criteria for treatment and most of them (85%) were on lipid-lowering therapy. A higher fraction of women were treated; however only 13% of them reached target cholesterol levels compared to 37% of the men (P < 0.001). Sixty-five subjects (9.0%) had diabetes and/or a previous stroke (29 men, 36 women) but no previous CHD. Patients with CHD were more likely to be treated compared to patients with diabetes and/or stroke but no CHD (85.0 vs. 28.5%, OR 6.0, 95% CI 2.2-16.9, P = 0.01). In a total of 79 participants (10.9%) who were on lipid-lowering therapy, women reached a total serum cholesterol level below 5.0 mmol/L less often than men (26.3 vs. 63.4%, P < 0.001). CONCLUSIONS: A considerable proportion of patients in primary care were untreated despite current guidelines on lipid-lowering therapy. Treatment outcome in women was less efficient compared with men. Strategies to improve pharmacological treatment in these patients should be developed. ( view less ) Jenny-Anne S Lie,Kristina Kjaerheim,Tore Tynes The influence of occupational exposure to ionizing radiation on risk of radiation-related cancers was studied among Norwegian nurses. A cohort of 43 316 nurses who graduated between 1914 and 1984, and were registered by the Norwegian Board of Health's registry of nurses, was followed up from 1953 t... ( view more )hrough 2002 by linkage to the Norwegian Cancer Registry by unique personal identification numbers. Indicators of radiation exposure were developed from data on work history. Internal analyses were performed with Poisson regression, according to time since first potential radiation exposure, duration of exposure, and period of first exposure, using unexposed nurses as reference group. No clear association was found between exposure to ionizing radiation and cancers of the breast, thyroid, ovary, or leukemia, malignant melanoma or other skin cancer. Increased risk of lung cancer was found in the subgroups of nurses first exposed after 1950 (rate ratio=1.47, 95% confidence interval: 0.97-2.23, 26 cases), and in nurses with less than 20 years since first exposure (rate ratio=3.41, 95% confidence interval: 1.67-6.99, 9 cases), but the most likely explanation was confounding by smoking.No firm evidence that nurses potentially exposed to ionizing radiation had increased risk of radiation-related cancer was found. ( view less ) Parvinder Kaur,Kristina Schulz,Ingrid Heggland,Michael Aschner,Tore Syversen The effect of methylmercury (MeHg) on reactive oxygen species (ROS) induction in neural cell lines was measured by the fluorescent probe, chloro methyl derivative of di-chloro di-hydro fluoresceindiacetate (CMH(2)DCFDA). Three different MeHg concentrations (5, 10 and 25muM) and time periods (30, 50... ( view more ) and 90min) were studied in C6-glial and B35-neuronal cell lines. In addition, the relationship between MeHg-induced ROS and cell density (day3 vs. day4) was also explored. The (14)C-labelled MeHg measurements were done to determine the cell associated-MeHg content. At 30 and 50min exposure, a significant increase (p<0.05) in MeHg-induced ROS was observed at 10 and 25muM MeHg for C6 cells and at 25muM MeHg for B35 cells. However, the amount of ROS produced with 25muM MeHg varied significantly (p<0.001) at different time periods. For both the cell lines, significant cell density dependent differences (p<0.05) were observed at 10muM MeHg treatment for 50min. MeHg treatments were associated with a concentration as well as cell-density dependent increase in cell associated-MeHg. These findings provide experimental evidence that special attention should be focused upon concentration, exposure time and cell density when assessing MeHg-induced ROS via fluorescence. ( view less ) Kristina Elfhag,Lesley C Morey Personality traits can give a fuller understanding for eating behaviors in obesity. The objective was to describe eating behavior (Dutch Eating Behaviour Questionnaire) in terms of the Big Five personality traits (NEO Personality Inventory-Revised) in obesity patients (n=442). Emotional eating was ... ( view more )strongly positively associated to Neuroticism, in particular impulsiveness and depression, and further linked to lower Conscientiousness mainly seen in lower self-discipline, and lower Extraversion. External eating was likewise mainly associated to the facets impulsiveness and lower self-discipline. Restrained eating was on the other hand related to higher Conscientiousness, Extraversion and Openness, and lower Neuroticism. These results imply that poor self-control seen in impulsiveness and lower self-discipline was most important for eating due to negative emotions as well as in response to external food stimuli, suggesting that the inhibition of eating and difficulties to govern ones behavior are major aspects of these eating behaviors. Attempts to control food intake and body weight seen in restrained eating were associated with more character strengths and ambitions, and also a more outgoing personality style with more stable emotions. ( view less ) Xinjun Li,Jan Sundquist,Kristina Sundquist OBJECTIVE: Familial risks of depression have been assessed in small case-control studies, usually based on reported, but not medically verified, depressions in family members; thus the degree of familial clustering of these diseases remains to be established. METHODS: The Multigeneration Register, ... ( view more )in which all men and women born in Sweden from 1932 onward are registered together with their parents, was linked to hospital admission data. Standardized incidence ratios (SIRs) were calculated as the ratio of the observed to the expected number of cases in men and women with mothers or fathers affected by depression, compared with men and women whose mothers or fathers were not affected by depression. RESULTS: A total of respectively 60,477 and 79,969 depressions were recorded in offspring and parents. In 6.44% of all families, an offspring and a parent were affected, giving a population-attributable proportion of 4.04% and a familial SIR of 2.68. The parental transmission of depression was similar for both men and women (2.72 and 2.66). CONCLUSIONS: This study has provided the first data on age-specific familial clustering of depressions, based on medically confirmed records. The risks were so high that hereditary factors were considered to be likely to contribute to depression, possibly modified by environmental factors. Age-specific risk tables would be helpful for clinical counseling. ( view less ) Kristina Reimhult,Keiichi Yoshimatsu,Klas Risveden,Si Chen,Lei Ye,Anatol Krozer Molecularly imprinted polymers (MIPs) are gaining great interest as tailor-made recognition materials for the development of biomimetic sensors. Various approaches have been adopted to interface MIPs with different transducers, including the use of pre-made imprinted particles and the in situ prepa... ( view more )ration of thin polymer layers directly on transducer surfaces. In this work we functionalized quartz crystal microbalance (QCM) sensor crystals by coating the sensing surfaces with pre-made molecularly imprinted nanoparticles. The nanoparticles were immobilized on the QCM transducers by physical entrapment in a thin poly(ethylene terephthalate) (PET) layer that was spin-coated on the transducer surface. By controlling the deposition conditions, it was possible to gain a high nanoparticle loading in a stable PET layer, allowing the recognition sites in nanoparticles to be easily accessed by the test analytes. In this work, different sensor surfaces were studied by micro-profilometry and atomic force microscopy and the functionality was evaluated using quartz crystal microbalance with dissipation (QCM-D). The molecular recognition capability of the sensors were also confirmed using radioligand binding analysis by testing their response to the presence of the test compounds, (R)- and (S)-propranolol in aqueous buffer. ( view less )
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