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Results for “Concordance factor”

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PubMedDate not supplied

Immunologic observations on 9 sets of twins either concordant or discordant for SLE.

The influence of genetic and nongenetic factors on abnormalities of the immune response in systemic lupus erythematosus (SLE) was studied in 9 sets of twins in which one or both twins had SLE. Particular emphasis was placed on contrasting the results between the sibs of 3 monozygotic pairs discordant for clinical SLE. Depression of cell-mediated immunity, determined by lymphocyte blastogenic response to mitogens, was associated with the clinical expression of illness. In contrast, autoreactive antilymphocyte antibodies and lymphocyte tubuloreticular structures were found in both clinically affected and unaffected subjects and were more prominently associated with the presence of other serologic abnormalities. No evidence of antigens or cell surfaces determinants unique to affected sibs was encountered.

Adult↗
PubMed1979

Facial clefts in Danish twins.

A total of 74 Danish twin pairs with cleft lip +/- palate (CL(P)) and isolated cleft palate (CP) born in Denmark from 1941 to 1969 were studied. Eight pairs were of indeterminate zygosity status' and 26 pairs of unlike sex were dizygous (DZ). Of the remaining 42 like-sexed pairs, zygosity assignments were made from genotyping and physical resemblance data. Twelve pairs were given MZ status and thirty pairs DZ status. The following data was calculated: 1) in contrast to other reports, the incidence of either CL(P) or CP was not increased for either MZ or DZ twins; 2) using the pairwise method for concordance rate calculation, concordance rates for CL(P) twins were: MZ = 36 per cent; DZ = 1.5 per cent. For CP, MZ = 33 per cent; DZ = 0 per cent. The results support the concept that heredity is a prime factor in the etiology of clefting, but the low MZ concordance rates also suggest genetic heterogeneity in this cleft population.

Cleft Lip↗
PubMed1979

Mechanisms of regulation of cell-mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes.

T-cell derived suppressor factor(s) (SF) specific for azobenzenearsonate (ABA) were prepared by the mechanical disruption of suppressor cells. Such suppressor factors were adsorbed to and recovered from immunoadsorbents prepared from the F(ab')2 fragments of rabbit immunoglobulin directed against the cross-reactive idiotype of A/J anti-ABA antibodies. These ABA-suppressor factors were not retained on Sepharose 4B immunoadsorbent columns which had been coupled with F(ab')2 fragments or normal rabbit immunoglobulins prepared from prebleeds of rabbits used to make anti-idiotypic antiserum. The specificity of the F(ab')2 rabbit anti-idiotypic serum was established by direct idiotypic-binding assays and by affinity purification over an immunoadsorbent consisting of CRI+ anti-ABA immunoglobulin from A/J mice. ABA-suppressor factors were shown to be specifically absorbed and eluted from F(ab')2 anti-idiotypic columns. Futhermore, the eluted suppressor factor can be specifically reabsorbed and recovered from a second anti-idiotypic immunoadsorbent. The concordance between antigen-binding specificity and the presence of idiotypic determinants was demonstrated by adsorbing ABA SF to antigen columns and then fractionating the ABA-specific factor on anti-idiotypic immunoadsorbents. ABA-suppressor factors were shown to be specifically retained on immunoadsorbents directed against major histocompatibility complex (MHC) determinants. Factor eluted from anti-MHC columns could then be specifically adsorbed to anti-idiotypic immunoadsorbents. This suggests that the same molecular complex that is recognized by the H-2 alloantiserum is specifically adsorbed to an anti-idiotypic immunoadsorbent. Genetic analysis of the expression of CRI+ suppressor factor was performed using the C.AL-20 mouse strain which has the AL/N allotype and produces CRI+ anti-ABA immunoglobulins. The implication of these findings to the nature of T-cell-derived regulatory molecules is discussed.

Animals↗
PubMed2026

Baseline Computed Tomography Coronary Angiography and Polygenic Risk Profiles in Adults With Type 2 Diabetes: A Cross-Sectional Analysis From the VOLTAIRE Study.

AIMS: To characterise baseline clinical, anatomical, and genetic cardiovascular risk profiles in participants enrolled in the VOLTAIRE (Evaluation of Polygenic Scores and CT Imaging in Risk Factor Modification in Patients with Type 2 Diabetes) study and examine concordance across these domains. METHODS: This analysis included adults with T2D who completed baseline computed tomography coronary angiography (CTCA) and polygenic risk score (PRS) assessment prior to randomisation in the VOLTAIRE study. Coronary atherosclerosis was evaluated using coronary artery calcium (CAC) score and CTCA-derived stenosis severity. Clinical risk was assessed using the New Zealand Society for the Study of Diabetes 5-year cardiovascular risk calculator. Polygenic risk for coronary artery disease was assessed using a genome-wide PRS and categorised into tertiles. RESULTS: Among 126 participants with T2D (mean age 57.5 ± 8.7 years; 62.7% male), coronary atherosclerotic burden was highly heterogeneous: 34.9% had CAC = 0, whereas 19.8% had CAC ≥ 400. Moderate-to-severe coronary stenosis (≥ 50%) was present in 40.5% of participants overall, including 20.4% of those classified as low clinical risk. PRS distribution was variable (low 37.3%, intermediate 35.7%, high 27.0%). Overlap between anatomical, genetic, and clinical domains was limited, with only 8.7% of participants classified as high risk across all three. CONCLUSIONS: Substantial heterogeneity and limited overlap exist between anatomical, genetic, and clinical cardiovascular risk measures in T2D. These findings support a multimodal approach to risk assessment integrating imaging and genetic profiling. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov; ID: NCT07091162.

Aged↗
PubMedDate not supplied

Discordant distribution of IgM and IgG antibodies to DNA and RNA in monozygotic twins with systemic lupus erythematosus.

Sera from six sets of twins (five monozygotic and one dyzygotic) in whom one or both has systemic lupus erythematosus (SLE) were evaluated for antibodies to DNA and RNA. Sera from three monozygotic twin sets were further studied to determine the distribution of 19S and 7S antibodies to DNA and RNA. The presence of significant binding of polyriboadenylic acid and of native DNA correlated with the presence of clinical SLE in this study. Sucrose density gradient fractionation studies of the sera revealed that the clinically normal twins had some binding of Poly A and DNA limited to the 19S region, whereas the twins with SLE generally had significant levels of 19S and 7S antibodies to DNA and/or Poly A. On the other hand, concordance for presence or absence of antibodies to doublestranded RNA was demonstrated within each twin set irrespective of concordance or discordance for clinical SLE. These results suggest that genetic factors may be important in determining which nucleic acids antigens become immunogenic, but genetic factors alone do not determine the immunoglobulin class distribution of antibodies to nucleic acids.

Antibodies, Antinuclear↗
PubMed1977

A simple blood agar plate medium for demonstration of the streptococcal serum opacity reaction.

Blood agar plates for demonstration of the streptococcal serum opacity reaction were prepared by pouring into Petri discs four layers, one above the other, in the following sequence: 1. agar; 2. horse-sheep blood mixed with agar; 3. porcine serum in agarose; and 4. agarose. The strains to be tested were streaked with a loop on the plates and a control medium was prepared as described above, but without porcine serum. After incubation for 18 hours at 37 degrees C, the streptococci producing opacity factor showed greenish zones around the colonies or else no haemolysis at all on the plates containing porcine serum, in contrast to a clear betahaemolysis on the control plates. Opacity reaction negative steptococci showed the same clear beta-haemolysis on both plates. Concordant results were obtained by this method and a standard method for demonstration of opacity factor.

Agar↗
PubMed2026

Human biopsy-defined ischemia-reperfusion injury-selective reperfusion signature prioritizes reperfusion-timed mitogen-activated protein kinase kinase inhibition after donation after circulatory death liver transplantation.

Early post-liver transplant ischemia-reperfusion injury (IRI) in donation after circulatory death grafts lacks therapies targeted to the immediate postreperfusion window, in part because generic reperfusion transcription obscures IRI-selective amplification. We analyzed paired prereperfusion/postreperfusion liver biopsies from 2 cohorts (GSE151648 and GSE87487) using a difference-in-differences interaction estimand (&#x394;&#x394; = [Post-Pre]IRI+ - [Post-Pre]IRI-) to define an IRI-selective early reperfusion program. Genome-wide &#x394;&#x394; effects were summarized using pathway-responsive genes, and pathway concordance was tested using permutation (B = 5000). The reproducible &#x394;&#x394; footprint highlighted epidermal growth factor receptor-mitogen-activated protein kinase signaling (Spearman &#x3c1; = 0.811; P = .001). Directional &#x394;&#x394; gene sets (interaction P < .05) were submitted to the L1000 characteristic direction signature search engine2; cross-cohort overlap identified 8 shared perturbagens, including 3 mitogen-activated protein kinase kinase (MEK)1/2 inhibitors. In a hepatic ischemia/reperfusion time course (GSE117915), epidermal growth factor receptor and mitogen-activated protein kinase activities increased within 0.5 hours of reperfusion, and transplant single-cell RNA sequencing (GSE189539) localized MEK/extracellular signal-regulated kinase pathway engagement predominantly to parenchymal cells. A representative MEK inhibitor, PD-0325901, reduced hepatocyte oxygen-glucose deprivation/reoxygenation injury and, when administered at reperfusion in a rat donation after circulatory death liver transplantation model (5-20 mg/kg), attenuated histologic and biochemical injury, apoptosis, and redox-inflammatory readouts and improved 7-day survival. Collectively, this biopsy-anchored &#x394;&#x394; interaction-phenotype framework, with cross-cohort concordance as a prespecified robustness gate, nominates reperfusion-timed MEK inhibition as a mechanism- and window-aligned strategy to blunt early post-liver transplant IRI.

difference-in-differences (time &#xd7; IRI interac↗
PubMed1977

Soluble fibrin complexes: separation as a function of pH and characterization.

1. The influence of the pH on the separation of high molecular weight derivatives obtained by a limited action of thrombin on fibrinogen was studied by agarose gel chromatography. When the pH of the elution buffer was 8.5, non crosslinked associations were easily separated in two peaks eluted prior to the fibrinogen peak: one contained a dimer, the other several high polymers. At pH 6.5, only the fibrinogen peak appeared: the fibrinogen molecule proteolysed by thrombin formed no stable associations at this pH and was eluted with the intact fibrinogen molecule. In the presence of factor XIII and Ca++, numerous associations were obtained which are independant of the pH. 2. The polypeptide chain composition of the different species separated at pH 8.5 was studied by SDS-polyacrylamide gel electrophoresis. This technic showed Aalpha, Bbeta and gamma chains in the fibrinogen peak, whereas in the chromatographic fractions containing the dimer four bands corresponding to Aalpha, alpha, Bbeta and gamma chains were found. In the peak containing the high polymers, only the presence of alpha, Bbeta and gamma chains was demonstrated. 3. These experimental results concerning the effect of pH on the formation of soluble complexes showed that the presence of fibrin monomers in fibrinogen solution was not sufficient to promote any associations. The formation of such derivatives is strongly dependent on the pH of the solution. This obviously can be explained by an influence of the pH either on the ionization of polymerisation sites and the intermolecular bonds between the complex units or on the unmasking of the polymerisation sites by a hypothetical pH induced conformational change of the fibrinogen molecule.

Animals↗
PubMed2024

Multi-omic Biomarkers Distinguish Rheumatoid Arthritis in Discordant Monozygotic Twins.

BACKGROUND: Although genetic factors have been identified in the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other features contribute to disease development. Further, the relative contribution of such non-genetic elements in identical twins have not been characterized. Here, we aimed to measure differentiating host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multi-omics approach. METHODS: Eight pairs of MZ twins discordant for RA (n=16) were enrolled. Gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and other plasma proteins were measured in both plasma and feces. Levels of short and medium-chain fatty acids from serum and feces were quantified using gas chromatography mass spectrometry (GC-MS). RESULTS: While overall microbiome diversity and composition did not significantly differ between twins, we observed a decrease in Blautia faecis in affected twins. Affected twins had higher concentrations of both fecal and plasma citrullinated and non-citrullinated autoantibodies, as well as significantly lower concentrations of fecal butyrate and propionate. CONCLUSION: Multi-omics biomarkers differentiate MZ twins discordant for RA. Blautia faecis, which is associated with reduced inflammatory cytokine expression, was decreased in RA twins. Similarly, short-chain fatty acids, known to have immune modulatory effects, were decreased in affected twins, suggesting further bi-directional interactions between inflammation at the gut barrier and disease state. If confirmed in other cohorts, exhaustive multi-omics approaches may improve our understanding of RA pathogenesis and potentially contribute to novel diagnostics and co-adjuvant therapies.

Journal Article↗
PubMed1979

Idiopathic scoliosis in identical (monozygotic) twins.

The exact nature of the primary predisposing cause of idiopathic scoliosis is unknown. Hereditary and/or environmental factors may be responsible. Two sets of identical twins presenting in adolescence with concordant scoliotic curves were studied and lend support for a hereditary predisposition favoring a multifactorial inheritance.

Adolescent↗
PubMed1978

[Psychopathologic structure of protracted endogenous depressions].

The psychopathological structure of protracted endogenous depressions was studied. An attempt was made to eliminate the main components of the depressive syndrome (variants of the depressive affect - anguish, anxiety, apathy, ideator and motor inhibition and "supplementary" symptoms). The results of the study demonstrated some general psychopathological regularities in the interrelationship of components of the depressive triade and some nozological differences. The assumption is made of the heterogenity in the mechanisms of "delayed" depressions. The most significant appeared to be such factors as the character of the main affect, the degree of intensity and concord of the triade elements and the existence of "supplementary" psychopathological phenomens.

Adult↗
PubMed1979

Helical structure of the human umbilical cord.

The helical structure of the human umbilical cord has been studied on 528 full-term cords from normal deliveries, 18 cords from aborted and developmentally normal fetuses with a CR length of 1.2-19.5 cm, 10 cords from monozygotic twins. In order to resolve the discrepancy in the nomenclature of the twist direction, a method has been suggested which takes into account the direction to which the fetus must have rotated to produce the twist. The incidence of the right helical pattern was 64.58%, of the left helical pattern 15.15%, and of the mixed patterns 17.43%; the twists were indeterminate in 1.89% and absent in 0.95% of the cords. Details of the mixed patterns are listed. The number of the uniform right twists ranged from 1 to 29 (7.5) and that of the left twists from 1 to 19 (6.7). There exists an exponential relation between the number of the twists and the ratio between length and thickness of the cords. The twists begin to appear during the early part of the 8th week, and their final number is possibly attained soon after the 9th week of development. In view of the absence of concordance in monozygotic twins, the helical nature of the cord is possibly controlled by factors which may be partly genetic and partly environmental.

Female↗
PubMed2026

KRAS Expression Complements Genomic Profiling in Identifying Therapeutic Vulnerability in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains a major therapeutic challenge. Although alterations in the RAS pathway occur in over 50% of tumors, only a limited proportion are clinically actionable. We investigated whether KRAS expression complements genomic profiling for patient stratification and therapeutic vulnerability in GC. METHODS: Comprehensive genomic profiling was performed in 19 Taiwanese GC patients and compared with TCGA-STAD data (n = 434). KRAS mRNA expression and overall survival were evaluated by meta-analysis of 13 independent cohorts (n = 2,521). Protein-level validation was performed by immunohistochemistry in an independent cohort (n = 121). Functional KRAS dependency and response to combined MEK/SHP2 inhibition were assessed in eight GC cell lines. RESULTS: KRAS amplification was entirely contained within the KRAS-high population, whereas most KRAS-high tumors lacked detectable amplification. High KRAS expression was associated with poorer overall survival (HR 1.23, p = 0.001) and remained an independent prognostic factor after multivariable adjustment (adjusted HR 1.24, p = 0.003). Protein-level analysis showed a concordant trend. KRAS expression correlated strongly with functional dependency (R2 = 0.88, p = 0.005), was enriched in MSI and CIN subtypes, and identified cell lines with enhanced sensitivity to combined MEK/SHP2 inhibition. CONCLUSIONS: KRAS expression complements genomic profiling by identifying biologically relevant KRAS-dependent GCs beyond mutation or amplification alone. Integrating expression-based stratification with genomic profiling may improve patient selection for RAS pathway-directed combination therapies.

Biomarker↗
PubMed2025

Indel mutation in transcription factor PabHLH2 regulates amygdalin accumulation and kernel bitterness in apricot.

Amygdalin, the phytochemical responsible for the characteristic bitterness of apricot (Prunus armeniaca L.) kernels, also exhibits significant bioactive properties and therapeutic potential. Genetic regulation of amygdalin content is therefore a key objective in apricot breeding programs aimed at quality improvement. In this study, we conducted quantitative trait loci (QTL) mapping to uncover the genetic basis of sweet-bitter differentiation in apricot kernels. We identified a 15-bp insertion/deletion (indel) polymorphism strongly related to kernel bitterness, with marker validation achieving 100% concordance across 601 apricot germplasm accessions. Notably, this polymorphic site is located within the helix-loop-helix (HLH) domain of the basic HLH (bHLH) transcription factor PabHLH2. Protein interaction analyses revealed that the 15-bp deletion variant impaired dimerization capacity, reducing transcriptional activation of downstream targets. Using yeast one-hybrid screening and dual-luciferase reporter assays, we identified PaCYP71AN24 and PaCYP79D16 as direct transcriptional targets of PabHLH2. Functional characterization further indicated that the PabHLH2a variant (harboring the 15-bp insertion) significantly enhanced the promoter activity of these cytochrome P450 genes compared with the deletion variant. Transient overexpression and silencing experiments in apricot kernels further confirmed that the 15-bp insertion positively regulates both PaCYP71AN24/PaCYP79D16 expression and prunasin accumulation, the immediate biosynthetic precursor of amygdalin. Overall, these findings provide mechanistic insights into the allelic variation underlying kernel bitterness and delineate the molecular cascade of amygdalin biosynthesis. The identified molecular markers and functional characterization establish a basis for marker-assisted breeding of low-amygdalin apricot cultivars, supporting the dual-purpose utilization of kernels in food and pharmaceutical industries.

Amygdalin↗
PubMed1977

A male MZ twin pair, concordant for transsexualism, discordant for schizophrenia.

A pair of male monozygous twins of gynandromorphic habitus but normal male body hair and genitalia, who appear concordant for transsexualism and explosive personality disorder but discordant for schizophrenia, is presented. No evidence of specific family dynamic factors, imitative learning or folie a deux was found in the twins' history. A constitutional aetiology of their transsexualism and one twin's schizophrenia is suggested. The relationship between transsexualism and schizophrenia is briefly reviewed. No evidence can be found that the modal transsexual is suffering from a schizophrenic disorder, florid or attenuated. A more subtle relationship is possible of transsexualism occurring as a schizophrenic spectrum disorder. This twin pair appears to illustrate such a relationship.

Adult↗
PubMed2026

An integrated proteomics and transcriptomics analysis highlights concordance between protein turnover and carbohydrate transport and metabolism as key functional categories during the growth of Trichophyton rubrum.

Dermatophytes are a class of keratinophilic skin fungi that invade host skin, hair, and nails to acquire nutrients. An integrated multi-omics approach utilizing liquid chromatography-tandem mass spectrometry and RNA-seq after growth in a protein-rich soy medium was employed to capture the major subset of secreted protein families of Trichophyton rubrum. The secretome consisted mainly of proteases and cell wall-degrading enzymes, with subtilisins (Sub6 and Sub7), metallopeptidase (LAP2), and chitinase having the most abundant peptides. Transcriptional profiling indicated fungal adaptation in protein-rich media to process the protein nutrients through modulation of metabolism and general cellular function pathways. Correlation analysis between proteomics and transcriptomics data using functional KOG categories shows high concordance of KOG categories O (posttranslational modification, protein turnover, and chaperones), P (inorganic ion transport and metabolism), and G (carbohydrate transport and metabolism), as per cosine similarity analysis.IMPORTANCEDermatophytes are keratinophilic skin fungal pathogens that invade host skin, hair, and nails to acquire nutrients. There is an epidemic-like increase in infections, as well as an increase in antimicrobial resistance among dermatophytes, as witnessed over the last decade. There is hence a need to understand the key pathways and virulence factors required during growth and infection. We present an integrated multi-omics analysis (proteomics and transcriptomics data) using a vector-based similarity approach to show high concordance of KOG functional categories belonging to posttranslational modification, protein turnover, carbohydrate transport, and metabolism.

Proteomics↗