Home About us Contact
|
Home About us Contact | ||
|
|
||
Pattern Suggestive (pattern + suggestive)
Selected AbstractsAnalysis of N-cadherin function in limb mesenchymal chondrogenesis in vitro,DEVELOPMENTAL DYNAMICS, Issue 2 2002Anthony M. Delise Abstract During embryonic limb development, cartilage formation is presaged by a crucial mesenchymal cell condensation phase. N-Cadherin, a Ca2+ -dependent cell,cell adhesion molecule, is expressed in embryonic chick limb buds in a spatiotemporal pattern suggestive of its involvement during cellular condensation; functional blocking of N-cadherin homotypic binding, by using a neutralizing monoclonal antibody, results in perturbed chondrogenesis in vitro and in vivo. In high-density micromass cultures of embryonic limb mesenchymal cells, N-cadherin expression level is high during days 1 and 2, coincident with active cellular condensation, and decreases upon overt chondrogenic differentiation from day 3 on. In this study, we have used a transfection approach to evaluate the effects of gain- and loss-of-function expression of N-cadherin constructs on mesenchymal condensation and chondrogenesis in vitro. Chick limb mesenchymal cells were transfected by electroporation with recombinant expression plasmids encoding wild-type or two mutant extracellular/cytoplasmic deletion forms of N-cadherin. Expression of the transfected N-cadherin forms showed a transient profile, being high on days 1,2 of culture, and decreasing by day 3, fortuitously coincident with the temporal profile of endogenous N-cadherin gene expression. Examined by means of peanut agglutinin (PNA) staining for condensing precartilage mesenchymal cells, cultures overexpressing wild-type N-cadherin showed enhanced cellular condensation on culture days 2 and 3, whereas expression of the deletion mutant forms (extracellular/cytoplasmic) of N-cadherin resulted in a decrease in PNA staining, suggesting that a complete N-cadherin protein is required for normal cellular condensation to occur. Subsequent chondrogenesis was also affected. Cultures overexpressing the wild-type N-cadherin protein showed enhanced chondrogenesis, indicated by increased production of cartilage matrix (sulfated proteoglycans, collagen type II, and cartilage proteoglycan link protein), as well as increased cartilage nodule number and size of individual nodules, compared with control cultures and cultures transfected with either of the two mutant N-cadherin constructs. These results demonstrate that complete N-cadherin function, at the levels of both extracellular homotypic binding and cytoplasmic linkage to the cytoskeleton by means of the catenin complex, is required for chondrogenesis by mediating functional mesenchymal cell condensation. © 2002 Wiley-Liss, Inc. [source] Decreased activities of mitochondrial respiratory chain complexes in non-mitochondrial respiratory chain diseasesDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2006Joannie Hui MBBS The aim of this study was to illustrate the difficulties in establishing a diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical grounds in combination with intermediate activities of the MRC enzyme complexes. We reviewed retrospectively all medical and laboratory records of patients initially considered likely to have MRC disorders on clinical grounds, and subsequently diagnosed with other disorders (n=20; 11 males, 9 females). Data were retrieved from hospital records, referral letters, and results of enzymatic analysis at a reference laboratory. Clinical symptoms included developmental delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany, microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss, muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively. One or more MRC complex activities (expressed as ratios relative to citrate synthase and/or complex II activity) were less than 50% of control mean activity in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl-CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One patient had a pattern suggestive of mitochondrial proliferation. We conclude that intermediate results of MRC enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses. [source] Evaluation of PG-M3 antibody in the diagnosis of acute promyelocytic leukaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2010Sanjeev Kumar Gupta Eur J Clin Invest 2010; 40 (10): 960,962 Abstract Background & objectives, Acute promyelocytic leukaemia (APL) is a distinct subtype of acute myeloid leukaemia (AML) characterized by a reciprocal translocation, t(15;17) and a high incidence of life-threatening coagulopathy. APL diagnosis is considered a medical emergency. As reverse transcription-polymerase chain reaction (RT-PCR) for PML-RAR, fusion oncoprotein is time consuming, there is a need for a rapid and accurate diagnostic test for APL. This study evaluates the role of PG-M3 monoclonal antibody using immunofluorescence (IF) in the early diagnosis of APL. Materials and Methods, Thirty-six new untreated APL cases diagnosed with RT-PCR for PML-RAR, as the gold standard and 38 non-APL controls (28 non-APL AMLs and 10 non-leukaemic samples) were evaluated by routine morphology and cytochemistry, RT-PCR and IF using PG-M3 monoclonal antibody. Results, Using IF, 34 of 36 (94·4%) APL cases showed a microgranular pattern suggestive of APL and two cases (5·6%) showed a speckled pattern typical of wild-type PML protein (False negative). By comparison, two of 28 (7·1%) non-APL AMLs showed microgranular pattern (false positive). Hence, IF as a diagnostic test for APL resulted in a sensitivity of 94·4%, specificity of 92·9% and positive and negative predictive values of 94·4% and 92·9% respectively. All 10 non-leukaemic samples showed a speckled pattern. Conclusions, IF using PG-M3 antibodies can be used as a rapid (takes 2 h), cheap, sensitive and specific method to identify APL. It can be a useful adjunct for diagnosis of APL especially if facilities for RT-PCR are not available, particularly in resource-limited settings. [source] Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinizationHISTOPATHOLOGY, Issue 6 2006D E Burstein Aims :,To examine invasive head and neck squamous carcinomas for expression of GLUT1, a glucose transporter and marker of increased glucose uptake, glycolytic metabolism and response to tissue hypoxia; p63, a p53 homologue that is a marker of the undifferentiated proliferative basaloid phenotype; and phospho-histone H1, a marker of activation of the cell cycle-promoting cyclin-dependent kinases 1 and 2. Methods :,Routinely processed slides from 34 invasive squamous carcinomas, including 25 with intraepithelial components, were immunostained with anti-GLUT1 (Chemicon), anti-p63 (4A4, Santa Cruz), and antiphospho-histone H1 (monoclonal 12D11). Results :,In keratinizing carcinomas, all three markers were most commonly immunodetected peripherally, with loss of expression in central keratinized zones. In contrast, in non-keratinizing carcinomas, p63 and phospho-histone H1 expression was most commonly observed throughout tumour nests and anti-GLUT1 stained in a pattern suggestive of hypoxia-induced expression (,antistromal' staining), in which cells at the tumour,stromal interface were GLUT1, and cells in central, perinecrotic zones showed progressive induction of GLUT1. Intraepithelial components also displayed basal and ,antibasal' GLUT1 staining patterns, homologous to the pro- and antistromal patterns in invasive carcinoma; basal patterns in intraepithelial lesions appeared to be more predictive of keratinizing invasive carcinoma and antibasal intraepithelial staining more predictive of non-keratinizing poorly differentiated carcinomas. Conclusions :,Keratinizing and non-keratinizing squamous carcinomas differ in expression patterns of GLUT1, p63 and phospho-histone H1. In the former, all three markers were typically suppressed in conjunction with keratinization; in the latter, GLUT1 expression was more likely to occur in a hypoxia-inducible pattern and expression of p63 and phospho-histone H1 was unsuppressed. GLUT1 expression patterns in intraepithelial lesions may be predictive of the differentiation status of the associated invasive carcinoma. [source] Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomasINTERNATIONAL JOURNAL OF CANCER, Issue 6 2002Pu Yan Abstract In a previous study, we showed that telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA expression were undetectable in benign mesenchymal lesions and low-grade soft tissue sarcomas (STSs), but detectable in about 50% of intermediate-/high-grade STSs. We wondered if this lack of TA or hTERT mRNA expression could be related to the tumor sample examined and if there was a relationship between the former 2 parameters and telomere length. Two separate tumor samples from 37 STSs were examined for telomerase activity, using the telomerase repeat amplification protocol (TRAP) assay and for hTERT mRNA expression, using RT-PCR. Telomere length was determined in each tumor sample, using the terminal restriction fragments (TRF) technique. Significant variations in telomere length, TA and hTERT mRNA expression between 2 samples of the same tumor were observed in 27%, 11% and 27% of STSs, respectively. Telomere length did not correlate with TA or hTERT mRNA expression. Despite great intratumoral heterogeneity in telomere length, short and long telomeres were more often seen in the low/intermediate-grade and high-grade STS categories, respectively. Few STSs that showed a TRF pattern suggestive of alternative lengthening of telomeres (ALT) may contain ALT subpopulations. © 2002 Wiley-Liss, Inc. [source] Current HIV-2 diagnostic strategy overestimates HIV-2 prevalence in China,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2009Maofeng Qiu Abstract A significant number of HIV-2 infections have been reported in China using Western blot as per current guidelines for HIV-2 diagnosis in China. However, most specimens were also positive on HIV-1 Western blot suggesting cross-reactivity and possible overestimation. We carried out the current study to evaluate a strategy to diagnose the HIV-2 infections in China. A total of 119 specimens received from 16 provinces were likely to be HIV-2 when tested according to current guidelines in China using the Genelabs Western blot (HIV Blot 2.2 WB). Further testing by HIV-2 WB (Bio-Rad New LAV Blot II or Genelabs HIV Blot 1.2 WB) scored 56 (47.1%) of 119 samples with banding pattern suggestive of HIV-2 infection, and 63 (52.9%) were HIV-2 indeterminate. A peptide-based HIV-1 and HIV-2 enzyme immunoassay for differential diagnosis of HIV-1 and HIV-2 infections was validated and used. This in-house EIA demonstrated that only 1 (0.8%) of 119 specimens had HIV-2 specific antibodies, while 2 (1.7%) were dually reactive. These results were highly concordant (>99%) with those by Inno-LIA HIV-I/II (Innogenetics, Belgium), which also use specific peptides for type-specific diagnosis. Our data demonstrates that HIV-2 infection is rare in China, and HIV-2 Western blot may overestimate the prevalence of HIV-2 in the population with HIV-1. The HIV-2 diagnostic strategy in China needs to be revised to include more specific peptide-based immunoassays. J. Med. Virol. 81:790,797, 2009. © 2009 Wiley-Liss, Inc. [source] A Brief Motivational Interview in a Pediatric Emergency Department, Plus 10-day Telephone Follow-up, Increases Attempts to Quit Drinking Among Youth and Young Adults Who Screen Positive for Problematic DrinkingACADEMIC EMERGENCY MEDICINE, Issue 8 2010Judith Bernstein RNC ACADEMIC EMERGENCY MEDICINE 2010; 17:890,902 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Adolescents in their late teens and early 20s have the highest alcohol consumption in the United States; binge drinking peaks at age 21-25 years. Underage drinking is associated with many negative consequences, including academic problems and risk of intentional and unintentional injuries. This study tested the effectiveness of pediatric emergency department (PED) screening and brief intervention to reduce alcohol consumption and associated risks. Methods:, A three-group randomized assignment trial was structured to test differences between intervention (I) and standard assessed control (AC) groups in alcohol consumption and alcohol-related behaviors from baseline to 12 months and to compare the AC group with a minimally assessed control (MAC) group to adjust for the effect of assessment reactivity on control group behavior. Patients aged 14,21 years were eligible if they screened positive on the Alcohol Use Disorders Identification Test (AUDIT) or for binge drinking or high-risk behaviors. The MAC group received a resource handout, written advice about alcohol-related risks, and a 12-month follow-up appointment. Patients in the AC group were assessed using standardized instruments in addition to the MAC protocol. The I group received a peer-conducted motivational intervention, referral to community resources and treatment if indicated, and a 10-day booster in addition to assessment. Measurements included 30-day self-report of alcohol consumption and alcohol-related behaviors, screens for depression and posttraumatic stress disorder, and self-report of attempts to quit, cut back, or change conditions of use, all repeated at follow-up. Motor vehicle records and medical records were also analyzed for changes from baseline to 1-year follow-up. Results:, Among 7,807 PED patients screened, 1,202 were eligible; 853 enrolled (I, n = 283; AC, n = 284; MAC, n = 286), with a 12-month follow-up rate of 72%. At 12 months, more than half of enrollees in Reaching Adolescents for Prevention (RAP) attempted to cut back on drinking, and over a third tried to quit. A significantly larger proportion of the I group made efforts to quit drinking and to be careful about situations when drinking compared to AC enrollees, and there was a numerically but not significantly greater likelihood (p = 0.065) among the I group for efforts to cut back on drinking. At 3 months, the likelihood of the I group making attempts to cut back was almost triple that of ACs. For efforts to quit, it was double, and for trying to be careful about situations when drinking, there was a 72% increase in the odds ratio (OR) for the I group. Three-month results for attempts were sustained at 12 months for quit attempts and efforts to be careful. Consumption declined in both groups from baseline to 3 months to 12 months, but there were no significant between-group differences in alcohol-related consequences at 12 months or in alcohol-related risk behaviors. We found a pattern suggestive of assessment reactivity in only one variable at 12 months: the attempt to cut back (73.3% for the I group vs. 64.9% among the AC group and 54.8% among the MAC group). Conclusions:, Brief motivational intervention resulted in significant efforts to change behavior (quit drinking and be careful about situations while drinking) but did not alter between-group consumption or consequences. [source] Characterization and peripheral blood biomarker assessment of anti,Jo-1 antibody,positive interstitial lung diseaseARTHRITIS & RHEUMATISM, Issue 7 2009Thomas J. Richards Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti,Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti,Jo-1 antibody,positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti,Jo-1 antibody,positive ILD. Results Among the 90 anti,Jo-1 antibody,positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti,Jo-1 antibody,positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti,signal recognition particle antibody,positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti,Jo-1 antibody,positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti,Jo-1 antibody,positive ILD and serum levels of CRP as well as the interferon-,,inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD. [source] | |||||||||||||