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PubMed2003

Early predictors of longterm outcome in patients with juvenile rheumatoid arthritis: subset-specific correlations.

OBJECTIVE: To determine early predictors of longterm outcome in juvenile rheumatoid arthritis (JRA) in a multicenter cohort. METHODS: Patients were selected if they were > or = 8 years of age; the onset of arthritis occurred > or = 5 years before study; and a diagnosis of JRA was made at a participating center. Outcome variables were scores on self-administered Childhood Health Assessment Questionnaires (CHAQ) and active disease duration. Possible explanatory variables assessed included characteristics present at onset, HLA alleles, in particular the rheumatoid arthritis associated shared epitope (RASE), and radiographic indicators of joint damage within 2 years of onset. Data for 393 patients were available. Multivariate analyses were performed for the total group and for each onset subtype. RESULTS: Male sex correlated with worse disability in systemic onset JRA but less disability in RF negative, and a shorter active disease duration in RF positive polyarticular onset JRA. Positive antinuclear antibody correlated with a longer active disease duration in patients with pauciarticular onset JRA. Younger age at onset predicted longer active disease duration in pauciarticular and RF negative polyarticular, and a shorter active disease duration in systemic onset JRA. Residence on a reserve, rather than native North American race, correlated with worse disability. The RASE correlated with less disability in systemic JRA; but no correlation with outcome was evident for patients with rheumatoid factor positive polyarticular JRA. CONCLUSION: Variables predictive of longterm outcome in JRA are specific for each onset subtype. The most important early predictors were age at onset and sex of the patient. Place of residence may have a greater effect on disability than race. RASE may associate with a more favorable outcome in systemic onset disease.

Adolescent↗

PubMed2004

A coding region in Diaporthe helianthi reveals genetic variability among isolates of different geographic origin.

A set of Diaporthe helianthi isolates collected in different geographic areas was studied in order to examine whether different genetic biotypes could be responsible for epidemiological differences shown by sunflower stem canker. D. helianthi causes serious losses in France and in former Yugoslavia, while the pathogen is only sporadically recorded in Italy in spite of conducive pedoclimatic conditions. Variability of a D. helianthi coding genomic region, evaluated by means of polymerase chain reaction (PCR), Southern blot hybridisation and restriction fragments length polymorphism (RFLP), showed a conserved homogeneous pattern shared by French and Yugoslavian isolates compared with the heterogeneous pattern of Italian isolates. These results are consistent with other investigations (IGS and ITS region variability) performed on the same set of isolates, allowing a correlation between D. helianthi biotypes, their geographic origin and sunflower stem canker epidemiology.

Ascomycota↗

PubMed1989

Reliability and construct validity of the needle sharing inventory.

The Needle Sharing Inventory (NSI) is a 59-item test developed to specify and assess behavior patterns associated with drug use and needle sharing. In order to determine its reliability and construct validity, the NSI was administered to 80 intravenous drug users (IVDUs) recruited from a methadone maintenance program in New York City. Patients were included in the study if they reported using intravenous drugs during the previous month. Factor analysis was performed indicating that 31 of the items loaded onto 6 factors similar to those hypothesized: four dealing with the social context of needle sharing - indiscriminate sharing, social sharing, intimate sharing, and use of shooting galleries; and two dealing with the emotional context of intravenous drug use negative affect states and positive affect states. These variables accounted for 71% of the total variance, suggesting internal consistency of these items. Factor scores significantly correlated to subjects' self-reported estimates of time using nonsterile needles and sharing needles. These data suggest that the NSI is both a reliable and a valid measure which may be used in future studies of intravenous drug use and needle sharing behavior patterns. The NSI may prove useful for the purpose of developing and evaluating interventions aimed at preventing or reducing the spread of HIV through needle sharing.

Adult↗

PubMed2006

Common and specific effects of couples treatment for alcoholism: a test of the generic model of psychotherapy.

The generic model of psychotherapy (Orlinsky & Howard, 1987) eschews the view that inputs, processes or outputs associated with treatment exert linear and independent effects on outcomes. Variables within these three clusters must be viewed both within the context of time and through their interactions with other variables within a class. This study illustrates the use of this model by identifying common (comprising both traditional relationship factors and shared therapy ingredients) and specific factors in cognitive-behavioural (CB) and family systems (FS) treatments for alcoholic couples and tracking their contributions over two treatment phases - the acute phase, and the follow-up phase. While four process variables (therapy type, intensity of treatment, common elements and FS-specific procedures) contributed to outcomes during the active treatment phase, these variables became more interactive during follow-up. Indeed, high levels of both specific interventions of both treatments were negatively associated with benefit, if common factors were also frequently used during the acute phase. The best effects were obtained when common and specific interventions were counterbalanced, one being frequently used and the other being infrequently used. Implications for future alcohol treatment and recommendations for research on common and specific factors are discussed.

Adult↗

PubMed2002

Mutations of the X-linked lymphoproliferative disease gene SH2D1A mimicking common variable immunodeficiency.

UNLABELLED: Common variable immunodeficiency (CVID) and X-linked lymphoproliferative (XLP) disease are two immunodeficiencies that may share a similar immunological phenotype making differential diagnosis difficult. We report two patients initially diagnosed as affected with CVID who, using molecular analysis, have been subsequently found to be affected with XLP disease. Distinguishing between these two diseases is essential since they have different prognosis, treatment and genetic counselling. CONCLUSION: current techniques, such as genetic analysis of the SH2D1A gene and expression of signalling lymphocyte activation molecule-associated protein, allow a definite diagnosis of X-linked lymphoproliferative disease.

Adult↗

PubMed1994

Germline-encoded IgG antibodies bind mouse cartilage in vivo: epitope- and idiotype-specific binding and inhibition.

Autoantibodies specific for type-II collagen (CII) occur in mice and rats with collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse monoclonal antibodies (MoAbs) specific for separate epitopes in CII have been investigated. Two-day-old mice were injected intraperitoneally (i.p.) with the anti-CII antibody CIID3 in both unlabelled and biotinylated form. It was found that antibodies binding to the same epitope in CII in vivo can inhibit others from binding in an epitope-specific fashion. The binding in vivo and in vitro of anti-CII antibodies could be inhibited also by an anti-idiotypic rat antiserum produced against the D3 antibody. The anti-idiotypic antiserum inhibited the binding of the antibody D3 and the idiotypically related antibody C2. The cDNA's of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain germline encoded V-genes, apparently without somatic mutations. The variable heavy chain of D3 and C2 both expressed the same VH rearrangement, confirming that they share idiotypes. This report demonstrates that CII-specific germline-encoded IgG autoantibodies bind specifically to normal cartilage in vivo via their combining site.

Amino Acid Sequence↗

PubMed2001

Structurally modulated magnetic properties in the A(3)MnRu(2)O(9) phases (A = Ba, Ca): the role of metal-metal bonding in perovskite-related oxides.

Ca(3)MnRu(2)O(9) and Ba(3)MnRu(2)O(9) were synthesized from transition metal dioxides and alkaline earth metal carbonates at 1100-1300 degrees C. Ca(3)MnRu(2)O(9) adopts the prototypical GdFeO(3)-type perovskite structure with Mn and Ru statistically disordered over the single metal atom site. The susceptibility shows Curie-Weiss behavior above 240 K with mu(eff) = 3.14 micro(B)/metal atom, which is in excellent agreement with the expected spin-only moment of 3.20 micro(B). Below 150 K, the compound shows spin-glass-like short-range ferrimagnetic correlations. The high-temperature region of the electrical resistivity reveals a small activation energy of 17(1) meV whereas the low-temperature region is nonlinear and does not fit a variable range hopping model. Ba(3)MnRu(2)O(9) crystallizes in the 9-layer BaRuO(3)-type structure containing M(3)O(12) face-shared trioctahedral clusters in which Mn and Ru are statistically disordered. Ba(3)MnRu(2)O(9) shows nonlinear reciprocal susceptibility at all temperatures and is described by a variable-spin cluster model with an S = (1)/(2) ground state with thermally populated excited states. The low spin value of this system (S = (1)/(2)) is attributed to direct metal-metal bonding. Below 30 K, the compound shows short-range magnetic correlations and spin-glass-like behavior. The high-temperature region of the electrical resistivity indicates a small activation energy of 8.8(1) meV whereas the low-temperature region is nonlinear. The importance of metal-metal bonding and the relationships to other related compounds are discussed.

Journal Article↗

PubMed1997

Quality assurance of stem cell enumeration by flow cytometry. Canadian QASE Study Group.

The enumeration of CD34+ cells by flow cytometry is commonly employed to assess progenitor/stem cell numbers in peripheral blood, cord blood, and apheresis products used for peripheral blood stem cell transplantation (PBSCT). Until recently, the enumeration of CD34+ cells has evolved in the absence of any procedural guidelines or quality assurance programs. We established a voluntary quality assurance for stem cell enumeration (QASE) program for Canadian laboratories involved in PBSCT. The goals of this study were 1) to survey current flow cytometric procedures for CD34 enumeration; 2) to evaluate inter-institutional reproducibility of currently employed assays; and 3) to evaluate the impact of adoption of a common method on inter-laboratory variability. Fourteen to nineteen laboratories participated in this program by enumerating CD34+ cells in shared cord blood samples. The survey showed a wide variation in flow cytometric methodology which in part contributed to the wide range in results obtained between different centres. Major differences in methodology included the number of events counted, use of isotype control and gating strategy. Participation in this program and adoption of a common methodology increased level of agreement for any given result although this trend did not reach statistical significance (P = 0.13). The results of this survey emphasize the need for a quality assurance program for stem cell enumeration by flow cytometry.

Antigens, CD34↗

PubMed1988

Heterogeneity and variability in the oral-facial-digital syndromes.

The oral-facial-digital syndromes are a heterogeneous group of conditions sharing oral, facial, and digital anomalies. Based on more or less subtle clinical differences, at least seven causally different entities can be identified in this group. These include 1) oral-facial-digital syndrome (OFDS) I; 2) Mohr syndrome (OFDS II); 3) OFDS III; 4) OFDS with tibial anomalies (OFDS IV); 5) Thurston syndrome; 6) Varadi syndrome; and 7) Whelan syndrome. However, since differentiation between these entities is based on clinical findings, this classification should be viewed as tentative until more definitive methods are available.

Abnormalities, Multiple↗

PubMed2006

AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders.

OBJECTIVE: Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain "molar tooth" sign, a finding shared by a group of Joubert syndrome-related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown. METHODS: We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign. RESULTS: We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity. INTERPRETATION: AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Shared 'features' in prices: income and price elasticities for health care expenditures.

The evidence found in most studies suggests a strong positive relationship between health care expenditure and gross domestic product. However, this evidence weakens with respect to the actual value of the income elasticity. There are two possible sources of these discrepancies, the use of arbitrary deflators and specification errors. We find that health PPP cannot be taken as a 'universal' price index. The problem is that its components do not move together. Nevertheless, we derive a 'universal' health price index from a dynamic system in which its components share both short and long run co-movements. The omission of relevant explanatory variables seems to be the main cause of the discrepancies. We confirm that there exists a strong positive relationship between per capita health care expenditure and per capita GDP. However we estimate a long run income elasticity at or around unity, although it is greater than unity for the countries with lower per capita income (Spain and Ireland). The results for income elasticity are the same regardless of whether health care expenditure is converted using the GDP PPP or the 'universal' health price index. The importance of non-income variables is also confirmed, in particular the relative price of health care. We find that relative price has a strong rationing effect on the quantity of health demanded and has no effect on the expenditures.

Data Interpretation, Statistical↗

PubMed2002

Microarray analysis of E-box binding-related gene expression in young and replicatively senescent human fibroblasts.

An E-box (CACGTG) designer microarray was developed to monitor a group of genes whose expressions share a particular regulatory mode. Sensitivity and specificity of microarray hybridization, as well as variability of microarray data, were evaluated. This designer microarray was used to generate expression profiles of E-box binding-related genes in WI-38 fibroblast cultures at three different growth states: low-passage replicating, low-passage contact-inhibited quiescent, and replicatively senescent. Microarray gene screening reveals that quiescent and senescent cells, in comparison with replicating ones, are characterized by downregulation of Pam, a protein associated with c-Myc, and upregulation of Mad family genes, Max dimerization proteins. Moreover, quiescence and senescence can be distinguished by increased expression of Irlb, c-Myc transcription factor, and Miz-1, c-Myc-interacting Zn finger protein 1, only in the former state. Senescence is characterized by downregulation of Id4, inhibitor of DNA binding 4, and Mitf, microphthalmia-associated transcription factor, in comparison with young replicating and quiescent states. Differential expression of genes detected by microarray hybridization was independently confirmed by reverse transcription polymerase chain reaction technique. Alterations in the expression of E-box-binding transcription factors and c-Myc-binding proteins demonstrate the importance of these genes in establishing the contact-inhibited quiescent or senescent phenotypes.

Cell Division↗

PubMed2002

Coordination and control of forces during multifingered grasping in Parkinson's disease.

In this study, we focused on how subjects with Parkinson's disease (PD) grasp and lift with five-digits of the hand. This task provided the opportunity to simultaneously examine (a) the coordination of multiple segments (i.e., digits), (b) the sequencing of multiple tasks (i.e., force development, object lift, and hold), and (c) the control of force output. We found that PD patients coordinated and controlled five-digit forces comparable to that of age-matched controls. Specifically, these groups developed and maintained similar force amplitudes and force sharing patterns across all grasping phases. In addition, PD patients demonstrated similar levels of variability both within and across trials. In the frequency domain, however, some differences were observed across groups, especially in PD patients exhibiting obvious action tremor (AT) at a single modal frequency. In these subjects (four of nine PD patients), there was a systematic disruption, i.e., a phase-shifting away from approximately 0 degrees, in-phase force synchronization patterns normally observed between digits. This disruption typically occurred at and around the AT frequency, while at many other frequencies synchronization patterns were maintained. The composite of these findings implies that although global features observed in five-digit grasping in PD patients are preserved, more subtle aspects of the coordination between digits, as revealed by frequency domain analysis, are not. These results are discussed in relation to the neural mechanisms that might underlie physiological synchronization of forces and its pathological disruption.

Aged↗

PubMed2002

BIVM, a novel gene widely distributed among deuterostomes, shares a core sequence with an unusual gene in Giardia lamblia.

A novel gene, BIVM (for basic, immunoglobulin-like variable motif-containing), has been identified using an electronic search based on the conservation of short sequence motifs within the variable region of immunoglobulin (Ig) genes. BIVM maps to human chromosome 13q32-q33 and is predicted to encode a 503-amino-acid protein with a pI of 9.1. The 5' untranslated region of BIVM is encoded in two exons; the coding portion is encoded in nine exons. BIVM is tightly linked (41 bp) and in the opposite transcriptional orientation to MGC5302 (also known as KDEL1 and EP58) in human. The ubiquitous expression of BIVM in normal tissues and the presence of a 5' CpG island suggest that BIVM is a housekeeping gene. Characterization of BIVM in representative species demonstrates significant conservation throughout deuterostomes; no sequence with significant identity to BIVM has been detected in proteostomes. However, an unusual gene has been identified in the protozoan pathogen Giardia lamblia that is similar to the core sequence of BIVM, suggesting the possibility of a horizontal gene transfer.

Animals↗

PubMed2006

Observational assessment of surgical teamwork: a feasibility study.

BACKGROUND: Teamwork is fundamental to effective surgery, yet there are currently no measures of teamwork to guide training, evaluate team interventions or assess the impact of teamwork on outcomes. We report the first steps in the development of an observational assessment of teamwork and preliminary findings. METHOD: We observed 50 operations in general surgery from a single operating theater using a measure of teamwork specifically developed for use in the operating theater. The OTAS (Observational Teamwork Assessment for Surgery) comprises a procedural task checklist centered on the patient, equipment and communications tasks and ratings on team behavior constructs, namely: communication, co-operation, co-ordination, shared-leadership and monitoring. RESULTS: Ratings of overall team performance were reasonably high, though variable, but there was evidence that clinically significant steps were being missed which at the very least eroded safety margins. There was, for instance, a frequent failure to check both surgical and anesthetic equipment and a failure to confirm the procedure verbally, patient notes were missing in about one-eighth of the cases and delays or changes occurred in over two-thirds of the cases. CONCLUSIONS: This study takes an initial step towards developing measures of team performance in surgery that are defined in relation to tasks and behaviors of the team. The observational method of assessment is feasible and can provide a wealth of potentially valuable research data. However, for these measures to be used for formal assessment, more research is needed to make them robust and standardized.

Adult↗

PubMed2006

Genome analysis of a severe and a mild isolate of Papaya ringspot virus-type W found in Brazil.

Papaya ringspot virus-type W (PRSV-W) is one of the most economically threatening viruses of cucurbits in Brazil. Premunization is one of the most effective PRSV control measures currently applied in squash and zucchini crops. PRSV-W-1, a mild and premunizing strain of PRSV has been successfully used to protect cucurbits against both the severe PRSV-W-C strain and other Brazilian PRSVs. To aid in understanding the mechanism by which PRSV-W-1 premunization operates, the complete genome sequences of PRSV-W-1 and PRSV-W-C were determined. PRSV-W-1 had a genome size of 10,332 nucleotides, whereas indels within the coat protein encoding gene meant that the genome size of PRSV-W-C was six nucleotides shorter than that of the mild strain. The genomes of the two strains shared 94.63% nucleotide sequence identity, with the 5' UTR and P1 being the most variable regions, and the coat protein and 3' UTR being the most conserved. Rigorous recombination analysis revealed that neither PRSV-W-1 nor PRSV-W-C was obviously recombinant, there was significant evidence that many other fully sequenced PRSV genomes were recombinant.

Brazil↗

PubMed1994

Nucleotide sequence comparison of the membrane protein genes of three enterotropic strains of mouse hepatitis virus.

The nucleotide sequences of the membrane (M) protein genes and their deduced amino acid sequences of three enterotropic strains of the coronavirus mouse hepatitis virus (MHV) -Y, -RI and -DVIM were determined and compared with the previously reported sequences of two respiratory MHV strains -A59 and -JHM. The five MHV strains shared extensive nucleotide (95.2-99.0%) as well as amino acid homology (95.6-98.7%). A variable region, including a 15 nucleotide deletion unique to MHV-RI, could be identified at the 5'-terminus of the gene. This region of the M protein may be immunogenic and may contribute to the antigenic diversity of the MHV strains. Sequence relationships between the strains showed no correspondence with the primary cell tropism. This may suggest that evolution of enterotropism was not a single occurrence among different MHV strains. No sequence unique to either tropism group could be identified, indicating that the M protein of MHV probably has no part in the determination of MHV tissue tropism.

Amino Acid Sequence↗

PubMed2005

Extremely low penetrance of hearing loss in four Chinese families with the mitochondrial 12S rRNA A1555G mutation.

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic, and molecular characterization of four Chinese pedigrees with aminoglycoside-induced and nonsyndromic hearing impairment. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects, although these subjects share some common features: bilateral and sensorineural hearing impairment. Strikingly, these Chinese pedigrees exhibited extremely low penetrance of hearing loss (5.2%, 4.8%, 4.2%, and 13.3%, respectively, and with an average 8% penetrance). In particular, four of all five affected matrilineal relatives of these pedigrees had aminoglycoside-induced hearing loss. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical homoplasmic A1555G mutation, associated with hearing impairment in many families from different genetic backgrounds. The fact that mtDNA of those pedigrees belonged to different haplogroups R9a, N9a, D4a, and D4 suggested that the A1555G mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in these Chinese families. These data imply that the nuclear background or/and mitochondrial haplotype may not play a significant role in the phenotypic expression of the A1555G mutation in these Chinese pedigrees. However, aminoglycoside appears to be a major modifier factor for the phenotypic manifestation of the A1555G mutation in these Chinese families.

Adult↗