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PubMed2025

The Arabidopsis TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins.

The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small molecule immune signals. Plant genomes can encode hundreds of TIR-domain containing proteins-many of which confer important agricultural disease resistance as TIR-NLR (nucleotide-binding, leucine-rich repeat) immune receptors. Despite their importance, how natural variation influences TIR enzymatic output and immunity-associated cell death is largely unexplored. We assayed a complete collection of the TIR domains of Arabidopsis thaliana Col-0 (the "AtTIRome") to explore variation in TIR metabolite production and cell death signaling. Roughly half of the AtTIRome triggered cell death in transient assays. Artificial TIR proteins designed based on consensus sequences of the AtTIRome's cell death phenotypic classes revealed polymorphisms controlling variation in TIR cell death elicitation and metabolite production. Structure-function analyses of artificial TIRs revealed that natural variation in the "BB-loop", a flexible region overlying the catalytic pocket, determines differences in function across Arabidopsis TIR-containing proteins. We further demonstrate that artificial TIRs are functional on an NLR chassis and that BB-loop variation can tune the activity of a natural TIR-NLR protein. These findings shed light on the diversity of TIR outputs and reveal methods to design and engineer TIR-based immune receptors.

Arabidopsis↗

PubMed2005

In vivo RNA localization of I factor, a non-LTR retrotransposon, requires a cis-acting signal in ORF2 and ORF1 protein.

According to the current model of non-LTR retrotransposon (NLR) mobilization, co-expression of the RNA transposition intermediate, and the proteins it encodes (ORF1p and ORF2p), is a requisite for the formation of cytoplasmic ribonucleoprotein complexes which contain necessary elements to complete a retrotransposition cycle later in the nucleus. To understand these early processes of NLR mobilization, here we analyzed in vivo the protein and RNA expression patterns of the I factor, a model NLR in Drosophila. We show that ORF1p and I factor RNA, specifically produced during transposition, are co-expressed and tightly co-localize with a specific pattern (Loc+) exclusively in the cytoplasm of germ cells permissive for retrotransposition. Using an ORF2 mutated I factor, we show that ORF2p plays no role in the Loc+ patterning. With deletion derivatives of an I factor we define an RNA localization signal required to display the Loc+ pattern. Finally, by complementation experiments we show that ORF1p is necessary for the efficient localization of I factor RNA. Our data suggest that ORF1p is involved in proper folding and stabilization of I factor RNA for efficient targeting, through Loc+ patterning, to the nuclear neighborhood where downstream steps of the retrotransposition process occur.

Animals↗

PubMed1982

Differences in performance impairment due to brompheniramine maleate as a function of the sustained-release system.

1 study examined whether different sustained release systems would cause variation in the effect of an antihistamine, brompheniramine maleate 10 mg, upon mood and psychomotor performance. Two commercial preparations were examined, one giving linear release (LR) of the drug over time, the other releasing the drug in a non-linear fashion (NLR). 2 Thirty-six males were allocated to four separate groups receiving either the drug with LR, drug with NLR, placebo or drug-free control. Single dosage of the drug occurred at 08.30 h and subjects completed mood inventories and performed serial choice reaction time and visual search tasks at 1 h, 2.75 h, 5.5 h and 7.25 h post dosage. 3 The NLR system significantly increased feelings of unco-ordination at 2.75 h and significantly slowed reaction time at both 2.75 and 5.5 h post dosage. The LR system significantly slowed reaction time only at 5.5 h but increased pausing in serial choice performance at that time. Neither system impaired visual search. 4 Results suggest that two preparations having identical active constituents may vary in their effects on psychomotor performance and mood as a function of their sustained release systems. A system giving linear release of the drug can reduce the early post-dosage performance decrement associated with a non-linear release system.

Adult↗

PubMed2005

Prestorage leukoreduction and low-temperature filtration reduce hemolysis of stored red cell concentrates.

BACKGROUND: Universal prestorage leukoreduction in Canada created the perception that stored red cells (RBCs) are more hemolyzed than their unfiltered predecessors. A pool-split design tested the effects of leukoreduction on hemolysis of stored RBCs. STUDY DESIGN AND METHODS: Two ABO-matched units were pooled, divided, and then processed into leukoreduced (LR) and nonleukoreduced (NLR) units with the Pall LT-WB or RC-PL systems and sampled during standard processing and storage for testing of sterility, counts, hemolysis, and osmotic fragility. RESULTS: Room temperature (RT) filtration of 10 pairs of LT-WB-LR and -NLR units showed significantly different percentage of hemolysis (0.39%) and osmotic fragility (0.643%) at 42 days. Cold-stored and -filtered units (2 days at 4 degrees C before processing) were less hemolyzed, but showed a similar proportional decrease of hemolysis in LR units (0.13% vs. 0.25% at 42 days). RBCs from RC-PL systems showed the lowest hemolysis although there was a filtration effect (0.05% vs. 0.12%, 42 days). Osmotic fragility paralleled hemolysis. Segment samples gave inaccurate results. Two-day prefiltration cold storage reduced hemolysis from 0.36 to 0.07 percent (42 days, p < 0.001). RT-LR hemolysis became significantly higher by Day 10 and 4 degrees C LR by Day 12. NLR units showed hemolysis by Day 7. LR units filtered cold were less hemolyzed (p < 0.05) than RT-LR but osmotic fragility was unchanged. CONCLUSIONS: LR-RBCs prepared by any of three methods (LT-WB, RT or cold; RC-PL), filtered at 4 degrees C, were less hemolyzed during storage than nonfiltered concentrates: 4 degrees C leukoreduction is beneficial for RBCs and does not cause hemolysis or enhance fragility.

Blood Preservation↗

PubMedDate not supplied

An assessment of methods to combine published survival curves.

PURPOSE: To assess the accuracies of different techniques for combining published survival curves, for use in disease modeling applications. METHODS: Five methods were identified: 1) iterative generalized least-squares (IGLS), 2) meta-analysis of failure-time data with adjustment for covariates (MFD), 3) nonlinear regression (NLR), 4) log relative risk (LRR), and 5) weighted LRR (w-LRR). Each method was used to combine the survival curves from eight single-arm Phase II trials of chemotherapy in 918 patients with advanced non-small-cell lung cancer (NSCLC). The resulting summary curves were compared with the curve calculated from the corresponding individual patient data (IPD). RESULTS: All methods were able to produce accurate summary survival curves statistically similar to the IPD-derived curve. Maximum discrepancies ranged from 1.8% to 4.7%. MFD appeared to be the most accurate when censoring information was complete. Characteristics of the component trials that adversely affected the accuracies of the different techniques were 1) a high proportion of censored observations (MFD); 2) variability in the length of follow-up (IGLS, NLR, LRR, w-LRR); and 3) the heterogeneity of the treatment results (NLR, w-LRR). CONCLUSIONS: All methods were able to accurately reproduce summary survival curves from the published literature. The best method depends on characteristics of the data and the purpose of the analysis.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

[Estimation of adverse drug reactions by the evaluation scores of subjective symptoms (complaints) and background of patients--VI. Drug-induced metabolic disorders].

OBJECTIVES: The purpose of this study was to develop, implement, and assess estimation procedures to prevent adverse drug reactions (ADRs), especially drug-induced metabolic disorders, based on the subjective symptoms (complaints) of patients. METHODS: Our own database called CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information System) was started in 1987 and now contains ca. 23,000 case reports of ADRs. We extracted 264 cases of drug-induced metabolic disorders from CARPIS, such as hyperglycemia, hypoglycemia, and hypokalemia. Evaluation scores were created based on the subjective symptoms and the backgrounds of these patients. The scores were applied to the 264 cases to demonstrate their efficiency in estimation of ADRs. RESULTS: The evaluation scores estimated ADRs as follows: 39.6% of the 96 hyperglycemia cases, 53.6% of the 84 hypoglycemia cases, and 59.5% of the 84 hypokalemia cases. The validity measures of the evaluation scores were estimated to be as follows: for hyperglycemia sensitivity (SE) = 39.6%, specificity (SP) = 99.0%, predictive value of positive test (PVP) = 97.4%, positive likelihood ratio (PLR) = 39.6, and negative likelihood ratio (NLR) = 0.61; for hypoglycemia, SE = 53.6%, SP = 93.0%, PVP = 86.5%, PLR = 7.7 and NLR = 0.50; and for hypokalemia, SE = 59.5%, SP = 99.0%, PVP = 98.0%, PLR = 59.5, and NLR = 0.41. CONCLUSIONS: The proposed evaluation scores are a reliable estimation method to detect ADRs related to drug-induced metabolic disorders. The scores should be incorporated into the integrated ADR estimation system available at a Web site our institution is developing, along with other evaluation scores of drug-induced liver disorders, extrapyramidal symptoms, and leakopenia, and druy eruptions.

Adverse Drug Reaction Reporting Systems↗

PubMed2026

Tobamoviruses: Advances in Molecular Biology, Host Interactions and Integrated Disease Management.

Tobamoviruses (viruses in the genus Tobamovirus, family Virgaviridae) lead to major yield losses in economically important crops around the world. In this review, we go beyond the canonical gene expression framework by integrating recent discoveries of reverse open reading frames (rORFs) on the negative-strand RNA. These rORFs have only been experimentally validated in cucumber green mottle mosaic virus (CGMMV), with predicted sequence-conserved homologs across a subset of the genus, including TMV, ToBRFV, and PMMoV. However, they are not universally present in all tobamoviruses. We systematically dissect the infection cycle-from disassembly and replication to cell-to-cell and systemic movement-with an emphasis on the host factors hijacked at each stage. We synthesize current understanding of plant antiviral immunity, focusing on RNA silencing and NLR receptor-mediated resistance as two pillars of defense, along with the transcription factors and microRNAs that orchestrate these responses. We critically evaluate the experimental evidence for both plant defenses and viral counter-strategies, noting that many mechanistic models derive from limited model systems. We further characterize host genetic resistance and susceptibility factors applicable to crop breeding. These resources include dominant NLR and non-NLR resistance, as well as recessive resistance derived from modified host susceptibility genes. We address how viral mutations, recombination and fitness trade-offs undermine resistance durability. We then evaluate their practical deployment through conventional breeding, the exploitation of quantitative resistance, and genome editing, and outline associated agronomic drawbacks and regulatory constraints. Using ToBRFV as a case study, we analyze its epidemiological traits and assess the current arsenal of surveillance tools, from field diagnostics to remote sensing. Finally, we survey management strategies across a spectrum of maturity. Some approaches, including sanitation protocols and conventionally bred resistant cultivars, have proven effective under field conditions. The first dsRNA-based biopesticide has recently been registered in China, while other biological control agents and low-risk chemical approaches remain largely at the experimental stage. We also discuss the bottlenecks that impede lab-to-field transition and highlight promising solutions such as precision breeding and evolution-oriented cultivar deployment. By bridging molecular virology, epidemiology, and integrated disease management, this review provides a critical, bench-to-field framework for the sustainable control of tobamoviruses.

TMV↗

PubMed2002

Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET.

UNLABELLED: PET using 18F-FDG is a promising technique to monitor response in oncology. Unfortunately, a multitude of analytic methods is in use. To date, it is not clear whether simplified methods could replace complex quantitative methods in routine clinical practice. The aim of this study was to select those methods that would qualify for further assessment in a future prospective response-monitoring study by comparing results with patient outcome. METHODS: Dynamic 18F-FDG PET scans were obtained on 2 groups of patients. First, 10 patients with advanced non-small cell lung cancer (NSCLC) were scanned on consecutive days before treatment to assess test-retest variability. Second, 30 scans were obtained on 19 patients with locally advanced NSCLC as part of an ongoing response-monitoring study. These scans were analyzed by 2 observers to assess observer variability. In addition, these studies were used to compare various methods with the gold standard, full kinetic analysis (nonlinear regression [NLR]). RESULTS: Using an image-derived input function, NLR showed excellent test-retest and observer agreement confirming that it could be used as a gold standard method. From a total of 34 analytic methods, 10 showed good correlation with NLR. Taking into account the degree of complexity of the methods, 4 remain for further evaluation. CONCLUSION: The optimal method for analysis of 18F-FDG PET data was determined for several levels of complexity. Four methods need to be evaluated further to determine the optimal trade-off between simplicity and accuracy for routine clinical practice.

Antineoplastic Agents↗

PubMed2002

[Integral indices of peripheral blood leukogram in the estimation of non-specific immunological reactivity in patients with ischemic heart disease].

With the help of differential blood count analysis and velocity of erythrocyte sedimentation (VES), 30 healthy persons (donors), 30 patients with chronic ischemic hearty disease (IHD) and 34 patients with acute myocardial infarction (AMI) underwent the procedure of calculation for leukocyte index (LI), leukocyte intoxication index (LII), leukocyte shift index (LSI), leukocyte and VES ratio (LVESR), leukocytic and granulocytic index (LGI), general index (GI), neurophil-lymphocyte ratio (NLR), neurophil-monocyte ratio (NMR), lymphocyte-monocyte ratio (LMR) and lymphocyte-eosinophil ratio (LER). Unlike healthy people, patients with chronic IHD had higher indices of LVESR, GI and LER while patients with AMI had increasing indices of LII, LSI, NLR, LER and decreasing indices of LI, LGI, GI, LMI. In case of AMI compared with chronic IHD, average indices of LII, LSI, NLR were higher and indices of LI, LGI, LVESR, GI, LMR were lower. The obtained results show expansion of possibilities to get information about the state of non-specific immunologic reactivity in patients with various IHD forms with the help of integral indices in blood leukogram.

Chronic Disease↗

PubMed2004

Comparison of different quantitative approaches to 18F-fluoride PET scans.

UNLABELLED: The aim of this study was to evaluate the relationship between 18F-fluoride bone metabolic measures obtained by nonlinear regression (NLR), Patlak analysis, and standardized uptake value (SUV) for a wide range of normal and pathologic bone conditions. In patients imaged twice, changes in metabolic rates were determined using the different quantitation methods. METHODS: In 33 patients 2-51 mo after resection of a bone tumor of the limbs, a total of 42 dynamic PET scans were performed after injection of 250-350 MBq 18F-fluoride. SUV, fluoride bone influx rate obtained by Patlak analysis (KPat), and fluoride bone influx rate obtained by NLR (KNLR) were calculated in each patient for the bone graft, the contralateral normal side, and the spine, if within the field of view. RESULTS: SUV ranged from 0.4 to 9.9, KPat from 0.0035 to 0.0742 mL/min/mL, and KNLR from 0.0027 to 0.0737 mL/min/mL. Significant linear correlations were found between KPat and KNLR (r = 0.99), KPat and SUV (r = 0.95), and KNLR and SUV (r = 0.93). Eight patients have been imaged twice within 6 mo. Changes in metabolic values of the grafts were significantly correlated for KPat and KNLR (r = 0.96), KPat and SUV (r = 0.88), and KNLR and SUV (r = 0.79). The 95% ranges of normal change in limb bones were +/-58.0% for SUV, +/-23.0% for KPat, and +/-20.2% for KNLR; the corresponding 95% ranges in the spine were +/-8.6%, +/-7.6%, and +/-19.6%. CONCLUSION: The results of this study show that 18F-fluoride metabolic values as well as changes in bone metabolism measured by SUV and Patlak analysis were strongly correlated with NLR findings. The high 95% range of normal change of SUV in limb bones, however, indicates that this parameter is of limited value in areas with low metabolic activity. The range of spontaneous bone metabolic rate fluctuations presented in this study may be used as an estimate for assessing changes in bone metabolic activity, and the normal values for limb bones provide a basis for further studies on 18F-fluoride bone metabolism.

Adolescent↗

PubMed2025

Pan-analysis of intra- and inter-species diversity reveals a group of highly variable immune receptor genes in rice.

Plant immune receptors and their natural variations play a central role in combating disease-causing pathogens. These immune receptors include intracellular nucleotide-binding leucine-rich repeat (LRR) receptors (NLRs) and cell-surface pattern recognition receptors (PRRs) that can be further classified as receptor-like proteins (RLPs) and receptor-like kinases (RLKs). Although the NLRome has been characterized, the repertoire and extent of diversity of PRRome remain undetermined in rice. In this study, we examined the diversity of immune receptor genes using high-quality genomes of 309 rice accessions from 8 species within the genus Oryza. A total of 376 310 immune receptor genes were identified, including 149 592 NLR-coding genes and 226 718 PRR coding genes. Shannon entropy analysis revealed a set of immune receptors that display significant intra-species and inter-species diversity in rice. In general, RLPs are more variable than RLKs, while NLRs and LRR-RLPs are more variable than LRR-RLKs. Additionally, NLR and PRR genes exhibit contrasting shoot/root expression patterns, with NLRs generally skewed towards root expression. Furthermore, we found that the size of the LRR-RLK gene families correlates with local annual precipitation, suggesting a stronger selection pressure on LRR-RLK genes in rice accessions grown under wet conditions than dry conditions. In sum, this pan-genomic analysis not only reveals the extensive diversity of the immune receptor repertoires in rice but also provides potential target genes for improving disease resistance in rice.

Oryza↗

PubMed2006

Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf.

Legionella pneumophila is an intracellular bacterium that causes an acute form of pneumonia called Legionnaires' disease. After infection of human macrophages, the Legionella-containing phagosome (LCP) avoids fusion with the lysosome allowing intracellular replication of the bacterium. In macrophages derived from most mouse strains, the LCP is delivered to the lysosome resulting in Legionella degradation and restricted bacterial growth. Mouse macrophages lacking the NLR protein Ipaf or its downstream effector caspase-1 are permissive to intracellular Legionella replication. However, the mechanism by which Ipaf restricts Legionella replication is not well understood. Here we demonstrate that the presence of flagellin and a competent type IV secretion system are critical for Legionella to activate caspase-1 in macrophages. Activation of caspase-1 in response to Legionella infection also required host Ipaf, but not TLR5. In the absence of Ipaf or caspase-1 activation, the LCP acquired endoplasmic reticulum-derived vesicles, avoided fusion with the lysosome, and allowed Legionella replication. Accordingly a Legionella mutant lacking flagellin did not activate caspase-1, avoided degradation, and replicated in wild-type macrophages. The regulation of phagosome maturation by Ipaf occurred within 2 h after infection and was independent of macrophage cell death. In vivo studies confirmed that flagellin and Ipaf play an important role in the control of Legionella clearance. These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation.

Pyrin domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity against intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors, known as PYD-Nod-like receptors (NLR), PAN, PYPAF, NALP, Nod, and Caterpiller proteins, to the activation of downstream effectors, including activation of caspase-1 and NF-kappaB. Activation of these effectors occurs when specific protein complexes, known as inflammasomes, are formed. PYD signal transduction leads to inflammasome assembly and activation of specific effector proteins. It is modulated by a cellular PYD-only protein (cPOP1), which binds to ASC and interferes with the recruitment of ASC to activated PYD-NLRs. Here we describe the identification and characterization of a second cellular POP (cPOP2), which shows highest homology to the PYD of PAN1. cPOP2 binds to ASC and PAN1, thereby blocking formation of cryopyrin and PAN1-containing inflammasomes, activation of caspase-1, and subsequent processing and secretion of bioactive interleukin-1beta. Existence of a second cPOP provides additional insights into inflammasome formation and suggests that POPs might be a common regulatory mechanism to "fine-tune" the activity of specific PYD-NLR family protein-containing inflammasomes.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Bioengineering Functional Copolymers. IX. Poly[(maleic anhydride-co-hexene-1)-g-poly(ethylene oxide)].

Amphiphilic bioengineering copolymers having a combination of hydrophilic/hydrophobic linkages and polyelectrolyte behavior, along with an ability to interact with biomacromolecules, in particular with the invertase enzyme, have been synthesized by (a) complex-radical copolymerization of maleic anhydride (MA, the acceptor) and hexene-1 (H-1, the donor) monomers with benzoyl peroxide as the initiator in 1,4-dioxane at 65 degrees C under high-conversion conditions and (b) subsequent grafting (polyesterification) of synthesized poly(MA-alt-H-1) with alpha-methoxy-omega-hydroxy-poly(ethylene oxide) (PEO). Copolymerizations were also carried out in the steady state, in order to essentially reduce the effect of copolymer composition drift. The values of the monomer reactivity ratios (r(1) and r(2)) determined by using the known terminal models of Fineman-Ross (FR) and Kelen-Tüdös (KT), as well as by nonlinear regression (NLR) analysis, are: r(1) = 0.16 and r(2) = 0.30 (FR), r(1) = 0.14 and r(2) = 0.27 (KT), and r(1) = 0.15 and r(2) = 0.29 (NLR), respectively. All the copolymers and graft copolymers were characterized by FTIR spectroscopy, (1)H{(13)C} NMR spectroscopy, viscometric measurements, and chemical (acid number), thermal (DSC and TGA), and X-ray diffraction analyses. Unlike poly(MA-alt-H-1)s, PEO macrobranched graft copolymers exhibit expressed polyelectrolyte and swelling behavior in diluted and concentrated dioxane solutions, respectively. The copolymer and its PEO hyperbranched derivatives can be used as carriers for enzyme immobilization.

Enzymes, Immobilized↗

PubMed1991

Gene expression and metastasis of somatic cell hybrids between murine fibroblast cell lines of different malignant potential.

We have used somatic cell hybrids to study the relationship between ras sensitivity, metastasis, and the expression of ras-responsive or "metastasis-associated" genes. We have previously shown that NIH 3T3 cells are nontumorigenic, but are made metastatic by transfection and expression of activated ras (i.e., they are ras-sensitive). LTA cells, however, are initially tumorigenic, but nonmetastatic, and are not altered in malignancy by ras (i.e., they are ras-resistant). We also have shown that patterns of expression of ras-responsive and "metastasis-associated" genes differ markedly between these two cell types. In the present work, we have constructed three sets of somatic cell hybrids: NIH 3T3 X LTA cells (designated NL), NIH 3T3 X ras-transfected LTA cells (designated NLR), and LTA X ras-transfected NIH 3T3 cells (designated LNR). In all three sets of cell hybrids, pooled clones were found to be highly metastatic in the chick embryo assay, suggesting complementation had occurred. Those cell hybrids that contained ras (NLR and LNR hybrids) were significantly more metastatic than those that did not (NL hybrids). Selected clones of low and high metastatic ability from both NL and LNR fusions were examined for tumorigenicity and "experimental" metastatic ability in nude mice, as well as for expression of several genes thought to be involved in ras-induced progression and malignancy. Patterns of expression of these genes showed a relationship to level of malignancy of the hybrids and demonstrated a responsiveness to the expression of activated ras. These results suggest that the complementation of phenotype observed in the hybrids may arise through a gene regulatory factor(s) supplied by the NIH 3T3- to the LTA-derived parent.

Animals↗

PubMed2003

Reliability of perception of fever by touch.

OBJECTIVE: To assess the reliability of touch to predict fever in children. METHODS: 200 children who reported with fever formed the study material. Group I consisted of 100 children between 0-1 year of age and Group II consisted of 100 children between 6-12 years of age. Preterm, neonates under warming device, tachypnoeic and hypothermic were excluded from the study. The caregiver (CG) and the medical staffs (MS) response regarding presence or absence of fever by touch was noted in each child. Both were blinded to each other's response. Immediately temperature was recorded by calibrated rectal thermometer in Group I and calibrated axillary thermometer in Group II. RESULTS: The CG's touch had a sensitivity of 70.5% specificity of 40.9%, PPV of 38% NPV of 72.9%, PLR was 1.16 and NLR was 0.75. The MS's touch had a sensitivity of 78.0%, specificity of 63.6%, PPV of 38.0% NPV 84.8%, PLR of 2.08 and NLR of 0.36. There is over and under diagnosis of fever by both, the former being more by the CG reflecting the parental anxiety. The MS's touch is better to affirm or negative fever as compared to CG. The best site to palpate for presence of fever was abdomen, neck and forehead. CONCLUSION: Touch is not a valid screening test for fever. It is recommended that a thermometer must always be used by the MS to record fever and CG must be motivated for the same.

Child↗

PubMed1991

Skeletal muscle function after ischemia: "no reflow" versus reperfusion injury.

The isometric contraction (supramaximal tetanic stimulation) of anterior tibialis muscle was studied in 32 New Zealand white rabbits after 5 hr of ischemia. Reperfusion was achieved after systemic heparinization (100 U/kg) by removal of vascular clamps (normal reperfusion, NR, N = 10); isolated pump perfusion at 15 cc/min for 30 min followed by normal reperfusion (controlled reperfusion, CR, N = 8); CR with a Sepacell 500 filter in the circuit (leukopenic, thrombocytopenic, controlled reperfusion, L/TR, N = 9); or adding 25,000 U of urokinase to the initial reperfusate (UKR, N = 5). Experimental muscle is compared to control nonischemic contralateral muscle in each animal and expressed as percentage of control function. Specimens were studied by light microscopy. No significant difference in mean function at 2 hr was seen between the four groups, with NLR having 53% of control function, CR 55% of control function, L/TR 61% of control function, and UKR 48% of control function. "No reflow," as defined by the absence of Doppler flow signals over the muscle pedicle with no recovery of function during reperfusion and continued incidence of persistent ischemia, was seen in NLR 4/10, CR 5/8, and L/TR 6/9 preparations with arteriolar, capillary, and venule thrombi documented by light microscopy. In contrast, "no reflow" was not seen in UKR (0/5, P less than 0.05). Peak function at any interval (potential maximal recovery) in muscles that adequately reperfused was best in CR (73%) and L/TR (73%). No difference in the degree of injury in adequately reperfused muscles was seen between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Laboratory screening of connective tissue diseases by a new automated ENA screening assay (EliA Symphony) in clinically defined patients.

BACKGROUND: The measurement of antinuclear antibodies (ANA) is used in the autoimmune laboratory for the screening of connective tissue diseases (CTD). ANA measurements are mainly performed by indirect immunofluorescence (IIF) on HEp-2 cells or by enzyme immunoassay (EIA). The objective of this study was to clinically evaluate an automated EIA for extractable nuclear antigens (ENA) which lacks anti-dsDNA for the screening of CTD. METHODS: The study involved a total of 170 serum samples, 54 from patients with CTD, 26 from patients with other autoimmune diseases, and 90 from patients with non-autoimmune diseases. For all sera, ANA detection was performed by IIF and by EliA Symphony (Pharmacia Diagnostics, Freiburg, Germany), an ENA screening which detects the following autoantibodies: SSA/Ro, SSB/La, U1RNP (70 kDa, A, C), Scl-70, JO-1, centromere B and Sm. Also, anti-dsDNA (EliA dsDNA, Pharmacia Diagnostics, Freiburg, Germany) was measured on all samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), efficiency, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. RESULTS: Diagnostic efficiency was similar for IIF (82.6%) and EliA Symphony (82.3%), as well as PLR (6.5 for IIF, and 7.3 for Eli Symphony), and NLR (0.35 for IIF, and 0.41 for EliA Symphony). The combined measurement of EliA Symphony and dsDNA increased sensitivity but not PLR. Area under receiver operator characteristic (ROC) curve was similar for IIF (0.847) and EliA Symphony (0.823). CONCLUSIONS: The results of the study demonstrate that EliA Symphony solely or combined with anti-dsDNA detection has an efficiency similar to HEp-2 cells IIF with a cut-off of 1:160 for the diagnosis of CTD.

Antibodies, Antinuclear↗