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Increased Proportion (increased + proportion)

Distribution by Scientific Domains

Medical Sciences	73%
Life Sciences	16%
Chemistry	6%

Distribution within Medical Sciences

Immunology	17%
12 Other Subdomains	66%

Selected Abstracts

Fat as a fuel: emerging understanding of the adipose tissue,skeletal muscle axis

ACTA PHYSIOLOGICA, Issue 4 2010
K. N. Frayn
Abstract The early pioneers in the field of metabolism during exercise such as Lindhard and Krogh understood the importance of fat as a fuel for muscle contraction. But they could not have understood the details of the pathways involved, as neither the metabolic role of adipose tissue nor the transport role of non-esterified fatty acids (NEFA) in the plasma was clearly understood at the time. We now recognize that the onset of muscular contraction coincides with an increase in the delivery of NEFA from adipose tissue, probably coordinated by the sympatho-adrenal system. During light exercise, adipose tissue-derived NEFA make up the majority of the oxidative fuel used by muscle. As exercise is prolonged, the importance of NEFA increases. The onset of exercise is marked by an increased proportion of NEFAs entering ,-oxidation rather than re-esterification and recycling. At moderate intensities of exercise, other sources of fat, potentially plasma- and intramyocellular-triacylglycerol, supplement the supply of plasma NEFA. The delivery of NEFA is augmented by increased adipose tissue blood flow and by other stimuli such as atrial natriuretic peptide. Only during high-intensity exercise is there a failure of adipose tissue to deliver sufficient fatty acids for muscle (which is coupled with an inability of muscle to use them, even when fatty acids are supplied artificially). This limitation of adipose tissue NEFA delivery may reflect some feedback inhibition of lipolysis, perhaps via lactate, or possibly ,-adrenergic inhibition of lipolysis at very high catecholamine concentrations. [source]

The relationship between major depression and marital disruption is bidirectional

DEPRESSION AND ANXIETY, Issue 12 2009
Andrew G. Bulloch Ph.D.
Abstract Background: Marital status is important to the epidemiology of psychiatric disorders. In particular, the high prevalence of major depression in individuals with separated, divorced, or widowed status has been well documented. However, the literature is divided as to whether marital disruption results in major depression and/or vise versa. We examined whether major depression influences changes of marital status, and, conversely, whether marital status influences the incidence of this disorder. Methods: We employed data from the longitudinal Canadian National Population Health Survey (1994,2004), and proportional hazards models with time-varying covariates. Results: Major depression had no effect on the proportion of individuals who changed from single to common-law, single to married, or common-law to married status. In contrast, exposure to depression doubled the proportion of transitions from common-law or married to separated or divorced status (HR=2.0; 95% CI 1.4,2.9 P<0.001). Conversely an increased proportion of nondepressed individuals with separated or divorced status subsequently experienced major depression (hazard ratio, HR=1.3; 95% CI 1.0,1.5 P=0.04). Conclusion: The high prevalence of major depression in separated or divorced individuals is due to both an increased risk of marital disruption in those with major depression, and also to the higher risk of this disorder in those with divorced or separated marital status. Thus a clinically significant interplay exists between major depression and marital status. Clinicians should be aware of the deleterious impact of major depression on marital relationships. Proactive management of marital problems in clinical settings may help minimize the psycho-social "scar" that is sometimes associated with this disorder. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc. [source]

An increased proportion of inflammatory cells express tumor necrosis factor alpha in idiopathic achalasia of the esophagus

DISEASES OF THE ESOPHAGUS, Issue 5 2009
A. Kilic
SUMMARY Achalasia is a motility disorder characterized by the absence of coordinated peristalsis and incomplete relaxation of the lower esophageal sphincter. The etiology remains unclear although dense inflammatory infiltrates within the myenteric plexus have been described. The nature of these infiltrating cells is unknown. The aim of this study was to evaluate the expression of proinflammatory cytokines , namely, tumor necrosis factor alpha and interleukin-2 , in the distal esophageal muscle in patients with achalasia. Lower esophageal sphincter muscle from eight patients undergoing myotomy or esophagectomy for achalasia of the esophagus were obtained at the time of surgery. Control specimens consisted of similar muscle taken from eight patients undergoing operation for cancer or Barrett's esophagus. The expression of tumor necrosis factor alpha and interleukin-2 were assessed by immunohistochemistry. The total number of inflammatory cells within the myenteric plexus were counted in five high power fields. The percentage of infiltrating cells expressing tumor necrosis factor alpha or interleukin-2 was calculated. Clinical data including demographics, preoperative lower esophageal sphincter pressure, duration of symptoms, and dysphagia score (1 = no dysphagia to 5 = dysphagia to saliva) were obtained through electronic medical records. Statistical comparisons between the groups were made using the unpaired t -test, Fisher's exact test, or Mann,Whitney U test, with a two-tailed P -value less than 0.05 being considered significant. The total number of inflammatory cells was found to be similar between the groups. A significantly higher proportion of inflammatory cells expressed tumor necrosis factor alpha in achalasia as compared with controls (22 vs. 11%; P= 0.02). A similar percentage of infiltrating cells expressed interleukin-2 (40 vs. 41%; P= 0.87). Age, gender, preoperative lower esophageal sphincter pressure, or dysphagia score were not correlated to expression of these cytokines. There was, however, a significant inverse correlation between duration of symptoms and the proportion of inflammatory cells expressing tumor necrosis factor alpha in achalasia (P= 0.007). In conclusion, a higher proportion of infiltrating inflammatory cells expressed tumor necrosis factor alpha in achalasia. Furthermore, this proportion appears to be highest early in the disease process. Further studies are required to more clearly delineate the role of tumor necrosis factor alpha in the pathogenesis of this idiopathic disease. [source]

Involvement of mitochondrial signaling pathways in the mechanism of Fas-mediated apoptosis after spinal cord injury

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009
Wen Ru Yu
Abstract Activation of the Fas receptor has been recently linked to apoptotic cell death after spinal cord injury (SCI). Although it is generally considered that Fas activation mediates apoptosis predominantly through the extrinsic pathway, we hypothesized that intrinsic mitochondrial signaling could be involved in the underlying mechanism of Fas-induced apoptosis after SCI. In the present study, we utilized the FejotaTM clip compression model of SCI at T5,6 in C57BL/6 Fas-deficient (lpr) and wild-type mice. Complementary studies were conducted using an in vitro model of trauma or a Fas-activating antibody to induce apoptosis in primary neuronal,glial mixed spinal cord cultures. After in vivo SCI, lpr mice, in comparison with wild-type mice, exhibited reduced numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells at the lesion, reduced expression of truncation of Bid (tBid), apoptosis-inducing factor, activated caspase-9 and activated caspase-3, and increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL. After in vitro neurotrauma or the induction of Fas signaling by the Jo2 activating antibody, lpr spinal cord cultures showed an increased proportion of cells retaining mitochondrial membrane integrity and a reduction of tBid expression, caspase-9 and caspase-3 activation, and TUNEL-positive cells as compared to wild-type spinal cord cultures. The neutralization of Fas ligand (FasL) protected against traumatically induced or Fas-mediated caspase-3 activation and the loss of mitochondrial membrane potential and tBid expression in wild-type spinal cord cultures. However, in lpr spinal cord cultures, FasL neutralization had no protective effects. In summary, these data provide direct evidence for the induction of intrinsic mitochondrial signaling pathways following Fas activation after SCI. [source]

UXT interacts with the transcriptional repressor protein EVI1 and suppresses cell transformation

FEBS JOURNAL, Issue 15 2007
Roger McGilvray
The EVI1 transcriptional repressor is critical to the normal development of a variety of tissues and participates in the progression of acute myeloid leukaemias. The repressor domain (Rp) was used to screen an adult human kidney yeast two-hybrid library and a novel binding partner designated ubiquitously expressed transcript (UXT) was isolated. Enforced expression of UXT in Evi1-expressing Rat1 fibroblasts suppresses cell transformation and UXT may therefore be a negative regulator of Evi1 biological activity. The Rp-binding site for UXT was determined and non-UXT-binding Evi1 mutants (Evi1,706,707) were developed which retain the ability to bind the corepressor mCtBP2. Evi1,706,707 transforms Rat1 fibroblasts, showing that the interaction is not essential for Evi1-mediated cell transformation. However, Evi1,706,707 produces an increased proportion of large colonies relative to wild-type, showing that endogenous UXT has an inhibitory effect on Evi1 biological activity. Exogenous UXT still suppresses Evi1,706,707-mediated cell transformation, indicating that it inhibits cell proliferation and/or survival by both Evi1-dependent and Evi1-independent mechanisms. These observations are consistent with the growth-suppressive function attributed to UXT in human prostate cancer. Our results show that UXT suppresses cell transformation and might mediate this function by interaction and inhibition of the biological activity of cell proliferation and survival stimulatory factors like Evi1. [source]

Dietary prevention of malignant glioma aggressiveness, implications in oxidant stress and apoptosis

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2008
Daniel Pouliquen
Abstract Our study explored the influence of diet on gliomagenesis and associated systemic effects (SE) in rats. The experimental diet contained various ingredients supposed to interfere with carcinogenesis, mainly phytochemicals (PtcD for phytochemical diet) and its effects were compared to those of the same diet without the phytochemicals (BD for basal diet). Glioma was induced by ethylnitrosourea to pregnant females fed the diets from the start of gestation until the moment of sacrifice of the offpsrings. In male rats fed the PtcD or the BD the incidence of gliomas was markedly reduced compared to rats fed a standard diet (StD). In females this effect was weaker and was limited to the PtcD. A significant proportion of rats with brain tumors and fed the StD exhibited SE evidenced by weight loss, a shorter survival, reduction in liver weight and an increased proportion of liver mitochondria, effects that were not observed in their counterpart fed PtcD. Comparison of the expression of genes involved in the balance proliferation/apoptosis and in the response to oxidative stress in male brain tumors showed that the prevention of SE was associated with an increase in bcl-2 and catalase and a decrease in ki-67, sod-1 and sod- 2 transcripts. These results show that the degree of agressiveness of gliomas can be modulated by dietary interventions and suggest that some phytochemicals with antioxidant properties could participate to the mechanism. © 2008 Wiley-Liss, Inc. [source]

Epstein-Barr virus infection and risk of lymphoma: Immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controls

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2007
Silvia de Sanjosé
Abstract Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case,control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab_EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15,1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22,3.95). Lower levels of ab_EBV were observed for follicular lymphoma (OR = 0.38, 95%CI = 0.15,0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful tool to explore EBV imbalances preceeding or paralleling possible EBV associated oncogenic events. © 2007 Wiley-Liss, Inc. [source]

Suppression of generation and replication of acyclovir-resistant herpes simplex virus by a sensitive virus

JOURNAL OF MEDICAL VIROLOGY, Issue 1 2004
Tomoko Okuda
Abstract The role of acyclovir-sensitive herpes simplex virus (HSV) was analyzed in the process of its replacement by a resistant virus in vitro and in vivo in the aspect of acyclovir therapy. The mode of replacement of acyclovir-sensitive HSV with acyclovir-resistant HSV was examined by the passages of acyclovir-sensitive wild type HSV in Vero cells under acyclovir-treatment. The development of resistance was monitored more adequately by counting the number of acyclovir-resistant viruses in 10,000 plaque forming units than by the conventional susceptibility assay. The resistance increased with the proportion of thymidine kinase-deficient (TK,) viruses, when the susceptibilities of acyclovir-treated HSV population to 5,-iodo-2,deoxyuridine and phosphonoacetic acid were examined. The increased resistance was due to the increased proportion of acyclovir-resistant virus but not intermediately resistant virus. Infection with mixtures of TK, and acyclovir-sensitive strains rendered TK, sensitive to acyclovir, and virus yields were reduced to the levels of acyclovir-sensitive virus in Vero cells. Their yield reduction depended on the proportion of acyclovir-sensitive viruses and induction of TK activity. This reduction in virus yields of the mixture of TK, and acyclovir-sensitive strains was confirmed by acyclovir treatment in the skin of mice with cutaneous infection. Acyclovir treatment combined with superinfection of acyclovir-sensitive virus delayed the development of herpetic skin lesions due to acyclovir-resistant virus and reduced virus yields in the infected skin. Acyclovir-sensitive virus plays an important role in suppressing the generation and replication of acyclovir-resistant virus during acyclovir therapy. J. Med. Virol. 72:112,120, 2004. © 2004 Wiley-Liss, Inc. [source]

The characterization of versican and its message in human articular cartilage and intervertebral disc

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2002
Robert Sztrolovics
Splicing variation of the versican message and size heterogeneity of the versican core protein were analyzed in human articular cartilage and intervertebral disc. Splicing variation of the message was studied by PCR analysis to detect the presence or absence of exons 7 and 8, which encode large chondroitin sulfate attachment regions. At all ages in normal cartilage from the third trimester fetus to the mature adult, the presence of the versican isoform possessing exon 8 but not exon 7 (V1) could be readily detected. The message isoforms possessing neither exon 7 nor 8 (V3) or both exons 7 and 8 (V0) were only detectable in the fetus, and the isoform possessing only exon 7 (V2) was never detected. In osteoarthritic cartilage and in adult intervertebral disc the versican message pattern was the same as that observed in the normal adult with only the isoform possessing exon 8 being detected. Core protein heterogeneity was studied by immunoblotting following enzymic removal of the glycosaminoglycan chains from the proteoglycan, using an antibody recognizing the globular G1 region of versican. All articular cartilage extracts from the fetus to the mature adult contained multiple core protein sizes of greater than 200 kDa. The adult cartilage extracts tended to have an increased proportion of the smaller sized core proteins and osteoarthritic cartilage possessed similar core protein sizes to the normal adult. In contrast, intervertebral disc at all post-natal ages showed a greater range of size heterogeneity with a prominent component of about 50 kDa. The abundance of this component increased if the samples were treated with keratanase prior to analysis, suggesting that the G1 region of versican in disc can be substituted with keratan sulfate. The increased presence of versican in the disc relative to articular cartilage may suggest a more pronounced functional role for this proteoglycan, particularly in the nucleus pulposus. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]

Spousal Concordance for Alcohol Dependence: Evidence for Assortative Mating or Spousal Interaction Effects?

ALCOHOLISM, Issue 5 2007
Julia D. Grant
Background: Alcohol dependence (AD) is among the most common psychiatric disorders, and impacts the health and well-being of problem drinkers, their family members, and society as a whole. Although previous research has consistently indicated that genetic factors contribute to variance in risk for AD, little attention has been paid to nonrandom mating for AD. When assortative mating occurs for a heritable trait, spouses are genetically correlated and offspring are at increased risk of receiving high-risk genes from both parents. The primary goal of the present analyses is to test hypotheses about the source(s) and magnitude of spousal associations for AD using a twin-spouse design. Methods: DSM-IV AD (without the clustering criterion) was assessed via telephone interview for 5,974 twin members of an older cohort of the Australian Twin Register (born 1902,1964) and 3,814 spouses of the twins. Quantitative genetic modeling was used to determine the extent to which variability in risk for AD was influenced by genetic factors, the extent of spousal association for AD, and whether the association was attributable to assortative mating, reciprocal spousal interaction, or both processes. Results: Genetic factors explained 49% of the variance in risk for AD. There was no evidence of gender differences in the spousal interaction effect, the degree of rater bias, or the association between the twin's report of spouse AD and the spouse's AD phenotype. Either the assortative mating parameter or the spousal interaction parameter could be removed from the model without a significant decrement in fit, but both could not be dropped simultaneously, suggesting a lack of power to differentiate between these 2 causes of spousal correlation. When both effects were included in the model, the spousal correlation was 0.29, the assortative mating coefficient was 0.45 (i.e., "like marries like"), and the reciprocal spousal interaction coefficient was ,0.10 (i.e., after controlling for assortative mating, the additional impact of spousal interactions is slightly protective). Conclusions: These analyses provide evidence of significant spousal associations for AD, with assortative mating increasing spouse similarity and spousal interaction effects decreasing it after controlling for assortative mating. Although the genetic impact is modest, assortative mating results in an increased proportion of offspring exposed to 2 alcoholic parents and the associated detrimental environmental sequelae, and increases the likelihood of offspring inheriting high-risk genes from both parents. [source]

Quality of Reporting of Clinical Trials of Dogs and Cats and Associations with Treatment Effects

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010
J.M. Sargeant
Background: To address concerns about the quality of reporting of randomized controlled trials, and the potential for biased treatment effects in poorly reported trials, medical journals have adopted a common set of reporting guidelines, the Consolidated Standards of Reporting Trials (CONSORT) statement, to improve the reporting of randomized controlled trials. Hypothesis: The reporting of clinical trials involving dogs and cats might not be ideal, and this might be associated with biased treatment effects. Animals: Dogs and cats used in 100 randomly selected reports of clinical trials. Methods: Data related to methodological quality and completeness of reporting were extracted from each trial. Associations between reporting of trial features and the proportion of positive treatment effects within trials were evaluated by generalized linear models. Results: There were substantive deficiencies in reporting of key trial features. An increased proportion of positive treatment effects within a trial was associated with not reporting: the method used to generate the random allocation sequence (P < .001), the use of double blinding (P < .001), the inclusion criteria for study subjects (P= .003), baseline differences between treatment groups (P= .006), the measurement used for all outcomes (P= .002), and possible study limitations (P= .03). Conclusions and Clinical Importance: Many clinical trials involving dogs and cats in the literature do not report details related to methodological quality and aspects necessary to evaluate external validity. There is some evidence that these deficiencies are associated with treatment effects. There is a need to improve reporting of clinical trials, and guidelines, such as the CONSORT statement, can provide a valuable tool for meeting this need. [source]

Proteomic analysis of plasma from patients with systemic lupus erythematosus: Increased presence of haptoglobin ,2 polypeptide chains over the ,1 isoforms

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue S1 2006
Esther J. Pavón
Abstract In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hp, polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2,2, or Hp 2,1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0,625 (Hp2), 0.281 (Hp1S), and 0.093 (Hp1F) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp2), 0.233 (Hp1S), and 0.033 (Hp11F), which clearly indicated an increased frequency of Hp2, a similar proportion of Hp1S and a diminished proportion of Hp1F in SLE patients compared with that in healthy controls. Preferential Hp,2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders. [source]

Heart Transplantation in the United States, 1999,2008

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4p2 2010
M. R. Johnson
This article features 1999,2008 trends in heart transplantation, as seen in data from the Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR). Despite a 32% decline in actively listed candidates over the decade, there was a 20% increase from 2007 to 2008. There continues to be an increase in listed candidates diagnosed with congenital heart disease or retransplantation. The proportion of patients listed as Status 1A and 1B continues to increase, with a decrease in Status 2 listings. Waiting list mortality decreased from 2000 through 2007, but increased 18% from 2007 to 2008; despite the increase in waiting list death rates in 2008, waiting list mortality for Status 1A and Status 1B continues to decrease. Recipient numbers have varied by 10% over the past decade, with an increased proportion of transplants performed in infants and patients above 65 years of age. Despite the increase in Status 1A and Status 1B recipients at transplant, posttransplant survival has continued to improve. With the rise in infant candidates for transplantation and their high waiting list mortality, better means of supporting infants in need of transplant and allocation of organs to infant candidates is clearly needed. [source]

Harm and Benefits of Primary Liver Resection and Salvage Transplantation for Hepatocellular Carcinoma

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010
A. Cucchetti
Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm. [source]

NK Cells Mediate Costimulation Blockade-Resistant Rejection of Allogeneic Stem Cells During Nonmyeloablative Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2006
L. S. Kean
Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 × 108/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation. [source]

Increased expression of CD40 on bone marrow CD34+ hematopoietic progenitor cells in patients with systemic lupus erythematosus: Contribution to Fas-mediated apoptosis

ARTHRITIS & RHEUMATISM, Issue 2 2009
Katerina Pyrovolaki
Objective Patients with systemic lupus erythematosus (SLE) display increased apoptosis of bone marrow (BM) CD34+ hematopoietic progenitor cells. This study was undertaken to evaluate the expression of CD40 and CD40L in the BM of SLE patients, and to explore the possible involvement of these molecules in apoptosis of CD34+ cells. Methods The proportion and survival characteristics of CD40+ cells within the BM CD34+ fraction from SLE patients and healthy controls were evaluated by flow cytometry. The production of CD40L by BM stromal cells was assessed using long-term BM cultures, and the effect of CD40L on the survival characteristics and clonogenic potential of CD34+ cells was evaluated ex vivo by flow cytometry and clonogenic assays. Results SLE patients displayed an increased proportion of CD40+ cells within the CD34+ fraction as compared with controls. The CD34+CD40+ subpopulation contained an increased proportion of apoptotic cells compared with the CD34+CD40, fraction in patients and controls, suggesting that CD40 is involved in the apoptosis of CD34+ cells. Stimulation of patients' CD34+ cells with CD40L increased the proportion of apoptotic cells and decreased the proportion of colony-forming cells as compared with untreated cultures. The CD40L-mediated effects were amplified following treatment with recombinant Fas ligand, suggesting that the effects of these ligands are synergistic. CD40L levels were significantly increased in long-term BM culture supernatants and adherent layers of BM cells from SLE patients as compared with controls. Conclusion These data reveal a novel role for the CD40/CD40L dyad in SLE by demonstrating that up-regulation and induction of CD40 on BM CD34+ cells from patients with SLE contribute to the amplification of Fas-mediated apoptosis of progenitor cells. [source]

Synergic effect of retinoic acid and extremely low frequency magnetic field exposure on human neuroblastoma cell line BE(2)C

BIOELECTROMAGNETICS, Issue 6 2010
Pamela Marcantonio
Abstract The aim of the present study was to assess whether exposure to a sinusoidal extremely low frequency magnetic field (ELF-MF; 50,Hz, 1,mT) can affect proliferation and differentiation in the human neuroblastoma cell line BE(2)C, which is representative of high risk neuroblastomas. Cells were subjected to ELF-MF exposure in the presence or absence of a neuronal differentiating agent (all-trans-retinoic acid, ATRA) for 24,72,h. In each experiment, ELF-MF-exposed samples were compared to sham-exposed samples. Cells exposed to ELF-MF combined with retinoic treatment showed a decreased cellular proliferation and an increased proportion of G0/G1 phase cells compared to cells exposed to either treatment alone. Moreover, ELF-MF- and ATRA-treated cells showed more differentiated morphological traits (a higher neurite number/cell, an increased neurite length), together with a significant increase of mRNA levels of p21WAF1/CIP1 and cdk5 genes, both involved in neuronal differentiation. In addition, the expression of cyp19 gene, which is involved both in neuronal differentiation and stress response, was evaluated; cyp19 gene expression was enhanced by ATRA treatment and significantly enhanced further by ELF-MF exposure combined with ATRA. In conclusion, our data suggest that ELF-MF exposure can strengthen ATRA effects on neuroblastoma cells. Bioelectromagnetics 31:425,433, 2010. © 2010 Wiley-Liss, Inc. [source]

Maternal carriership of factor V Leiden associated with pathological uterine artery Doppler measurements during pregnancy

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2001
Pelle G. Lindqvist
To determine whether increased vascular resistance in the uterine artery is associated with carriership of factor V Leiden, a retrospective study was undertaken of 231 pregnant women who were monitored with Doppler velocimetry of the uterine arteries. These women had been part of a prospective study of 2480 pregnant women in whom factor V Leiden had been analysed. When compared with non-carriers of factor V Leiden, carriers had a tendency towards an increased proportion of pathological Doppler measurements, including a significant increase in bilateral uterine artery notches (7/33 vs 16/198, relative risk 3.1; 95% CI 1.2,8.1). This suggests an increased vascular resistance in the uteroplacental circulation among carriers of factor V Leiden. [source]

Is head and neck melanoma a distinct entity?

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2006
A clinical registry-based comparative study in 5702 patients with melanoma
Summary Background, The head and neck region is more heavily exposed to ultraviolet (UV) radiation than any other body site. Therefore, cutaneous malignant melanoma (CMM) of the head and neck area is proposed to have notable differences from melanoma at other body sites regarding clinicopathological features and survival of patients. Objectives, The present retrospective study based on clinical registry data aims to compare clinical features and prognostic factors of head and neck melanoma (HNM) vs. melanoma at other anatomical regions (MOR) in order to detect differences which may be associated to the mode of sun exposure. Methods, The clinical records and histopathological findings of 844 patients with clinical stage I and II invasive HNM were compared with the data of 4858 patients with MOR. Survival analysis was performed using the Kaplan,Meier estimate, and the multivariate Cox proportional hazard model was used to evaluate independent prognostic factors. Results, Melanoma density was clearly higher for HNM than for MOR: this was particularly true for the face, where it was elevated by a factor of 2·6. There was a higher male/female ratio in patients with HNM and they were significantly older than patients with MOR (P < 0·0001). Breslow tumour thickness did not differ between HNM and MOR. However, CMMs at the scalp were significantly thicker and to a higher degree ulcerated. Concerning clinicopathological CMM subtypes, there was an increased proportion of lentigo maligna melanoma among HNM and of nodular melanoma in the scalp and neck regions. Excision margins were narrower and the rate of complete primary excision was lower in HNM than in MOR. Overall, there was no significant statistical difference in cumulative 10-year survival rates according to Kaplan,Meier estimates among patients with HNM (84·6%) and MOR (87·8%). Tumour thickness turned out to be the variable with the highest prognostic impact followed by ulceration in both HNM and MOR. Conclusions, In relation to the skin surface significantly more CMMs were found in the head and neck area than in other anatomical regions. This might indicate, but does not prove, that UV exposure promotes the development of CMM. Although HNM showed specific clinicopathological features, prognosis remained unaffected. Thus HNM seems not to be a distinct subtype of CMM. [source]

Impact of BCR/ABL gene expression on the proliferative rate of different subpopulations of haematopoietic cells in chronic myeloid leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006
Daniel Primo
Summary Despite the effects of BCR ABL on cell proliferation, no study has compared the proliferative rate of different haematopoietic cell compartments from chronic myeloid leukaemia (CML) with those of normal bone marrow (NBM). We comparatively analysed the cell cycle distribution and BCR/ABL expression in different compartments of BM cells from 15 CML and 11 NBM. Overall, our results showed similar proliferative indices in CML patients and NBM. However, CD34+ myeloid precursors from CML patients displayed an increased proportion of S + G2/M-phase cells (P = 0·04), while no significant differences were found between CML and NBM for other BM cell subsets analysed. In BM cells separated by fluorescence-activated cell sorting, decreasing levels of BCR/ABL mRNA were found from CD34+/CD38+ myeloid precursors to myeloblasts; BCR/ABL expression increased afterwards with a peak at the myelocyte/metamyelocyte stage, decreasing in the more mature band/neutrophil compartment. Unexpectedly, BCR/ABL gene expression showed an inverse correlation with the proportion of S + G2/M-phase cells (R = ,0·33; P = 0·04). These results suggest that in CML, BCR/ABL expression is associated with an increased proliferation of CD34+ myeloid haematopoietic progenitor cells but not of other more mature myeloid precursors, as confirmed by the observation of an inverse correlation between the amount of BCR/ABL transcripts and the proportion of S + G2/M-phase cells. [source]

The impact of retroviral suicide gene transduction procedures on T cells

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003
Waseem Qasim
Summary., Retroviral vectors encoding the herpes simplex thymidine kinase gene have been used to render T cells sensitive to the prodrug ganciclovir. Such genetically modified T cells have been used in clinical trials for their graft-versus-leukaemia effects following allogeneic haematopoietic stem cell transplantation. In the event of graft-versus-host disease (GVHD) the cells were susceptible to elimination through exposure to ganciclovir. We have investigated the impact of T-cell activation, required for successful retrovirus-mediated gene transfer, on T-cell receptor repertoire profile, subset distribution and antiviral potential. Using a combination of antibodies against CD3 and CD28, T cells were transduced at high efficiency when exposed to retrovirus between 48 and 72 h later. Lymphocytes had undergone up to seven cycles of cell division by the end of the procedure. Although the T-cell receptor V, repertoire was not altered after retroviral transduction, there were notable shifts in subset profiles with an increased proportion of CD45RO cells in transduced populations. T cells continued to proliferate for several days after transduction and were difficult to sustain under the extended culture conditions required to generate virus-specific T cells. These observations may explain the lower than expected levels of GVHD and poor antiviral immunity reported in recent trials. [source]

Androgen ablation therapy for prostate carcinoma suppresses the immunoreactive telomerase subunit hTERT

CANCER, Issue 2 2004
Kenneth A. Iczkowski M.D.
Abstract BACKGROUND Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain. METHODS hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups. RESULTS The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score , 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score , 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score , 8: 46% (P < 0.005) (from a mean 63% to 17%). CONCLUSIONS CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors. Cancer 2004;100:294,9. © 2003 American Cancer Society. [source]

Decreased expression of germinal center,associated nuclear protein is involved in chromosomal instability in malignant gliomas

CANCER SCIENCE, Issue 11 2009
Kazutaka Ohta
Malignant glioma (MG) is highly proliferative and invasive, with the malignant characteristics associated with aneuploidy and chromosomal instability (CIN). Here, we found that the level of germinal center,associated nuclear protein (GANP), a mammalian homologue of yeast Sac3, was markedly decreased in MGs with a poor prognosis; and thus we explored the effect of its decrease on cell-cycle progression of MG cell lines. Glioblastomas showed a significantly lower level of ganp mRNA than anaplastic astrocytomas, as measured by real-time reverse transcription-PCR, in 101 cases of adult MG. MGs of ganpLow expression displayed more malignant characteristics, with loss of heterozygosity on chromosome 10, epidermal growth factor receptor gene amplification, and significantly poorer prognosis than the ganpHigh group. Human diploid fibroblasts depleted of ganp mRNA by the RNA interference (RNAi) method showed a decreased percentage of S-phase cells and a cellular-senescence phenotype. MG cell lines harboring abnormalities of various cell-cycle checkpoint molecules displayed slippage of mitotic checkpoints and an increased proportion of hyperploid cells after ganp RNAi-treatment. These results suggest that GANP protects cells from cellular senescence caused by DNA damage and that a significant decrease in GANP expression leads to malignancy by generating hyperploidy and CIN. (Cancer Sci 2009); 00: 000,000) [source]

Comparative therapeutic effects of orally administered 1,25-dihydroxyvitamin D3 and 1alpha-hydroxyvitamin D3 on type-1 diabetes in non-obese diabetic mice fed a normal-calcaemic diet

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2008
J. P. Driver
Summary Frequent injections of the hormonal form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25D3) reportedly inhibits autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by correcting some of the abnormalities in antigen-presenting cells which contribute the development of pathogenic T cell responses. This route of administration greatly elevates the levels of these compounds in the bloodstream for hours after treatment, which requires mice to be fed diets formulated to contain much reduced levels of Ca to avoid the toxic effects of hypercalcaemia. In the current work, we demonstrate that feeding 1,25D3 or its synthetic precursor, 1alpha(OH) vitamin D3 (1alphaD3), as part of a T1D supportive chow diet containing normal levels of Ca, is an effective means of reducing the incidence of disease in NOD mice, but the doses required for protection elicited hypercalcaemia. However, T1D protection elicited by D3 analogue feeding appears, at least partially, to have an immunological basis, as splenic T cells from treated mice had a decreased capacity to adoptively transfer disease. Protection is associated with an increased proportion of T cells with CD4+ forkhead box P3+ regulatory phenotype within the islet infiltrate of treated animals. The 1alphaD3 precursor is converted rapidly to the active 1,25D3 isoform in vivo. However, feeding the 1alphaD3 analogue elicited stronger T1D protection than the 1,25D3 compound, but also induced more severe hypercalcaemia. In future, the dietary supplementation of novel low-calcaemic D3 analogues may enable their continuous delivery at levels that inhibit T1D development in susceptible humans consuming normal levels of Ca. [source]

Chemokines in human periodontal disease tissues

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2001
E. Gemmell
An immunoperoxidase technique was used to examine IP-10 (interferon-gamma inducible protein 10), RANTES (regulated on activation normal T cell expressed and secreted), MCP-1 (monocyte chemoattractant protein-1), and MIP-1alpha (macrophage inflammatory protein-1alpha) in gingival biopsies from 21 healthy/gingivitis and 26 periodontitis subjects. The samples were placed into 3 groups according to the size of infiltrate. MIP-1alpha+ cells were more abundant than the other chemokines with few MCP-1+ cells. The mean percent MIP-1alpha+ cells was higher than the percent MCP-1+ cells (P = 0·02) in group 2 (intermediate size infiltrates) lesions from periodontitis subjects, other differences not being significant due to the large variations between tissue samples. Analysis of positive cells in relation to CD4/CD8 ratios showed that with an increased proportion of CD8+ cells, the mean percent MIP-1alpha+ cells was significantly higher in comparison with the mean percent RANTES+ and MCP-1+ cells (P < 0·015). Endothelial cells were MCP-1+ although positive capillaries were found on the periphery of infiltrates only. Keratinocyte expression of chemokines was weak and while the numbers of healthy/gingivitis and periodontitis tissue sections positive for IP-10, RANTES and MCP-1 reduced with increasing inflammation, those positive for MIP-1alpha remained constant for all groups. In conclusion, fewer leucocytes expressed MCP-1 in gingival tissue sections, however, the percent MIP-1alpha+ cells was increased particularly in tissues with increased proportions of CD8 cells and B cells with increasing inflammation and also in tissues with higher numbers of macrophages with little inflammation. Further studies are required to determine the significance of MIP-1alpha in periodontal disease. [source]

Inflammatory airway disease, nasal discharge and respiratory infections in young British racehorses

EQUINE VETERINARY JOURNAL, Issue 3 2005
J. L. N. WOOD
Summary Reasons for performing study: Respiratory disease is important in young Thoroughbred racehorses, but the variation in the rates of occurrence between different ages and training groups has not been characterised. Objectives: To determine the rates of respiratory disease, particularly inflammatory airway disease (IAD), as well as evidence of infection, and their variation between age and group. Methods: Horses were examined monthly in 7 British flat training yards over a 3 year period. IAD was defined as increased mucus in the trachea with increased proportions of neutrophils in tracheal wash samples. Frequencies of disease outcomes were estimated from the data. Results: The prevalence of IAD was 13.8% and the incidence was 8.9 cases/100 horses/month. Rates varied with training and age groups, decreasing in older animals. The prevalence of nasal discharge (ND) was 4.1%. Rates of bacterial isolation were more common than viral infections. The incidence and prevalence of several bacterial species decreased with age. Conclusions: IAD and ND were common in young racehorses, varying significantly between training groups and decreasing with age, consistent with infection playing a role in aetiology. Potential relevance: The high prevalence of IAD in 2-year-old horses in Britain suggests that routine endoscopic examination may be helpful in providing early diagnosis and appropriate therapy. The transmission of bacteria and viruses within and between groups of young animals and the role of infection, stable environment and factors inherent to each horse, including their genetic make-up, in the multifactorial aetiology of the disease all merit further study. [source]

Hypertension in Minority Populations

JOURNAL OF CLINICAL HYPERTENSION, Issue 5 2006
Keith C. Ferdinand MD
The US population, by percentage, shows a trend toward increased proportions of citizens identified as minorities. Whereas in 2000, according to the US Census Bureau, 71.4% of the population was self-identified as white; this group is expected to decrease to 61.9% by 2025. The proportion of blacks and African Americans from 2000 vs. 2025 is expected to increase from 12.2% to 12.9%. Also, in the smaller population of American-Indian, Eskimo, and Aleutian natives, growth is projected from 0.7% to 0.8%. Asians and Pacific Islanders as a category will become a larger proportion, from 3.9% to 6.2%. The largest increase in proportion will be seen in those identified as Hispanic (of any race), from 11.8% in 2002 to 18.2% in 2025. [source]

REVIEW ARTICLE: Immunological Modes of Pregnancy Loss

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010
Joanne Kwak-Kim
Citation Kwak-Kim J, Park JC, Ahn HK, Kim JW, Gilman-Sachs A. Immunological modes of pregnancy loss. Am J Reprod Immunol 2010 During the implantation period, a significant portion of embryos are lost and eventually less than half of clinically established pregnancies end as full-term pregnancies without obstetrical complications. A significant portion of these pregnancy losses is associated with immune etiologies, including autoimmune and cellular immune abnormalities. Although an autoimmune etiology such as anti-phospholipid antibodies (APAs) has been reported to induce placental infarct and thrombosis at maternal,fetal interface, APAs induce inflammatory immune responses as well. Inflammatory immune responses, such as increased proportions of NK cells and Th1/Th2 cell ratios in peripheral blood are related to recurrent pregnancy losses and multiple implantation failures. Systemic and local inflammatory immune responses seem to be induced by activation of Toll-like receptors with infectious agents, fetal cell debris, or gonadotropin-releasing hormone agonist, etc. Cellular activation of T and NK cells leads to pro-inflammatory cytokine storm and consequently, placental infarction and thrombosis. Potential application of anti-inflammatory therapeutic agents for the prevention of pregnancy losses should be explored further. [source]

Influence of dietary palm oil on growth, tissue fatty acid compositions, and fatty acid metabolism in liver and intestine in rainbow trout (Oncorhynchus mykiss)

AQUACULTURE NUTRITION, Issue 4 2005
J. FONSECA-MADRIGAL
Abstract This study aimed to investigate the effects of dietary crude palm oil (CPO) on fatty acid metabolism in liver and intestine of rainbow trout. Triplicate groups of rainbow trout for 10 weeks at 13 °C were fed on diets in which CPO replaced fish oil (FO) in a graded manner (0,100%). At the end of the trial, fatty acid compositions of flesh, liver and pyloric caeca were determined and highly unsaturated fatty acid (HUFA) synthesis and fatty acid oxidation were estimated in isolated hepatocytes and caecal enterocytes using [1- 14C]18:3n-3 as substrate. Growth performance and feed efficiency were unaffected by dietary CPO. Fatty acid compositions of selected tissues reflected the dietary fatty acid composition with increasing CPO resulting in increased proportions of 18:1n-9 and 18:2n-6 and decreased proportions of n-3HUFA, 20:5n-3 and 22:6n-3. Palmitic acid, 16:0, was also increased in flesh and pyloric caeca, but not in liver. The capacity of HUFA synthesis from 18:3n-3 increased by up to threefold in both hepatocytes and enterocytes in response to graded increases in dietary CPO. In contrast, oxidation of 18:3n-3 was unaffected by dietary CPO in hepatocytes and reduced by high levels of dietary CPO in enterocytes. The results of this study suggest that CPO can be used at least to partially replace FO in diets for rainbow trout in terms of permitting similar growth and feed conversion, and having no major detrimental effects on lipid and fatty acid metabolism, although flesh fatty acid compositions are significantly affected at an inclusion level above 50%, with n-3HUFA reduced by up to 40%. [source]