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PubMed1985

The association of various D elements with a single-immunoglobulin VH gene segment: influence on the expression of a major cross-reactive idiotype.

A large fraction of the anti-p-azophenylarsonate antibodies of strain A/J mice share a major cross-reactive idiotype (IdCR). Structural analysis of monoclonal antibodies expressing this idiotype (IdCR+) indicates that a particular combination of variable region gene segments (Vk, Jk, VH, D, and JH) encodes the variable regions of the light and heavy chains of these IdCR+ antibodies. With the use of serologic methods, hybridoma cell lines have been isolated that produce monoclonal antibodies lacking IdCR determinants (IdCR-), but that are derived from most of the same combination of variable region gene segments that encode IdCR+ monoclonal antibodies. Structural analysis of these IdCR- monoclonal antibodies demonstrates that they are very homologous to each other and to IdCR+ monoclonal antibodies with respect to VH and VL sequences, but are markedly different from IdCR+ monoclonal antibodies in their utilization of D region segments. Comparisons of antigen avidity of these IdCR+ and IdCR- antibodies indicates that conservation of D region structure is not crucial for effective antigen binding. These results indicate the importance of the D region in idiotypy in the IdCR system and demonstrate the variation permitted in D region structure while maintaining antigen recognition.

Amino Acid Sequence↗

PubMed1980

Hormone receptors and target cell responsiveness.

The present article deals with some basic principles in the mechanism of hormone action. All classes of hormones elicit the majority of their physiological effects via specific receptors which are located in three separate compartments of target cells: cell membranes (peptide and glycopeptide hormones), cytoplasm (steroid hormones) and nucleus (thyroid and steroid hormones). These receptors, although distinctively different in their subcellular localizations share some mutual chemical characteristics which play important roles in the regulation of hormone action. Target cell receptor concentration seems to be one variable by which the magnitude and duration of hormone action is regulated, and is subject to both homologous and heterologous hormonal control. In addition, ligand-receptor interaction and occupancy of the receptors by their respective hormones are important factors that are responsible for regulation of hormone action. A major step towards understanding the physiological role of hormone receptors in man are findings that altered receptor function is involved in pathogenesis of and therapeutic approaches to a variety of diseases.

Animals↗

PubMed1998

Clonally-related immunoglobulin VH domains and nonrandom use of DH gene segments in rheumatoid arthritis synovium.

BACKGROUND: Synovia of patients with long-standing rheumatoid arthritis (RA) are typically infiltrated with B lymphocytes and plasma cells that secrete large amounts of immunoglobulin. The CDR3 of an immunoglobulin heavy chain is composed of the VH-DH-JH join, with interposed N region addition, and thus defines clonal relatedness. Furthermore, the CDR3 lies at the center of the antigen binding site, so its length and composition influence antigen binding. We sought definitive evidence of an antigen-driven B cell response (i.e., clones derived from the same VH, DH, and JH gene segments with shared somatic mutations) in RA synovial mRNA transcripts, and to characterize CDR3 intervals at the target of inflammation in this autoimmune disease. MATERIALS AND METHODS: We screened a cDNA library generated from unselected cells from the knee joint of a 62-year-old white female with long-standing RA. This technique does not have the potential bias of selecting for antibodies that express a particular reactivity such as rheumatoid factor. C gamma recombinants were sequenced and progenitor VH, DH, and JH gene segments were assigned and somatic mutations determined by comparison to germline sequences. Analyses of DH reading frame utilization and hydropathy characteristics of CDR3s were performed. RESULTS: Two of 67 recombinants were derived from the same VH (V3-11) and JH gene segments, demonstrated shared mutations, and contained nearly identical VH-DH-JH joins, including N region addition. Three other recombinants contained identical sequence throughout the variable domain. We also found preferential utilization of a limited number of VH and DH gene segments and marked preference for a DH reading frame encoding predominantly hydrophilic residues. CONCLUSIONS: Analysis of expressed heavy chain variable domains strongly supports the hypothesis that the B cell response in RA synovium is at least in part antigen driven and oligoclonal.

Amino Acid Sequence↗

PubMed1998

Physical activity and health-related fitness in youth: a multivariate analysis.

PURPOSE: To evaluate the relationship between indicators of physical activity and health-related fitness in youth 9-18 yr. METHODS: A cross-sectional sample of 356 boys and 284 girls 9-18 yr of age from phase I of the Quebec Family Study was studied. The sample was divided into three age groups by gender, 9-12, 13-15, and 16-18 yr of age. Physical activity variables included two estimates of activity, estimated daily energy expenditure (EE) and estimated moderate-to-vigorous physical activity (MVPA), and one estimate of inactivity, time spent watching television per day (TVTIME). Health-related fitness variables were the sum of six skin folds (SUM), number of sit-ups in 1 min (SITUP), physical work capacity at 150 beats x min(-1) (PWC150), and static strength of the leg (LMS). Partial canonical correlation was used to quantify the relationship between standardized (z-transformed) activity variables and health-related fitness items, controlling for age. RESULTS: There is a weak to moderate association between physical activity and fitness in youth. The first activity canonical variate is a function of positive loadings for EE and MVPA, with a smaller, negative loading for TVTIME. The first fitness variate generally includes positive loadings for PWC150 and SITUP, with a small negative loading for the SUM and a small positive loading for LMS. The first canonical correlations indicate that the variance shared by the fitness and activity variates ranges from 11 to 21%. CONCLUSION: There is a significant relationship between activity and health-related physical fitness, but a large part of the variability (80-90%) in fitness is not accounted for by physical activity as measured in this study.

Adolescent↗

PubMedDate not supplied

Domain specificity and variability in cognitive development.

There are core-specific and noncore-specific domains of knowledge, but only the core-specific domains benefit from innate skeletal structures. Core skeletal domains are universally shared, even though their particular foci may vary; individuals vary extensively in terms of the noncore domains they acquire.

Child↗

PubMed1994

A class of tests for linkage using affected pedigree members.

We describe a class of nonparametric tests for linkage between a marker and a gene assumed to exist and to govern susceptibility to a disease. The tests are formed by assigning a score to each possible pattern of marker allele sharing (identity-by-descent) among affected pedigree members, and then averaging the scores over all patterns compatible with the observed marker genotype and genealogical relationship of the affected members. Different score functions give different tests. One function, which examines marker allele similarity across pairs of affected pedigree members, gives a test similar to that of Fimmers et al. (1989, in Multipoint Mapping and Linkage Based on Affected Pedigree Members: Genetic Analysis Workshop, R. C. Elston, M. A. Spence, S. E. Hodge, and J. W. MacCluer (eds), 123-128; City: Alan R. Liss). A second function examines allele similarity across arbitrary subsets, not just pairs, of affected members. The resulting test can be more powerful than the one based solely on pairs of affected members. The approach has several advantages: it does not require knowledge of the mode of disease inheritance; it does not require unambiguous determination of identity-by-descent at the marker; it does not suffer from variability due to chance allele similarity among affected members who are unrelated, such as spouses; it allows marker genotypes of unaffected members to contribute information on allele sharing among the affected; it permits calculation of exact P-values. Computational requirements limit the tests to many pedigrees with few (< 16) affected members.

Alleles↗

PubMed1997

Interleukin-1 receptor antagonist allele: is it a genetic link between Henoch-Schönlein nephritis and IgA nephropathy?

Henoch-Schönlein purpura nephritis (HSPN) is a multi-organ systemic vasculitis, which shares many clinical, histological and immunological features with IgA nephropathy (IgAN). To address whether these two diseases have a common genetic background, the polymorphism of the variable number tandem repeat (VNTR) of IL-1 receptor antagonist (IL-1ra) gene has been analyzed using PCR in patients diagnosed with HSPN (N = 43) and IgAN (N = 97), together with normal controls (N = 98) and patients with acute post-infectious glomerulonephritis (APGN), under the concept that IL-1 might play an important role in mediating pathogenesis of vasculitis and glomerulonephritis. It was found that the allele frequency and carriage rate of the interleukin-1 receptor antagonist allele (IL1RN*2) of the IL-1ra gene increased significantly in HSPN patients as compared to IgAN (P < 0.01), APGN (P < 0.05) and normal subjects (P < 0.01). Interestingly, varied carriage rates of IL1RN*2 were found among various groups of IgAN patients presenting with different clinical manifestations. The carriage rate of IL1RN*2 was significantly higher in patients with recurrent gross hematuria than other groups of IgAN patients (P < 0.01). Furthermore, although the carriage rate of IL1RN*2 was higher in HSPN (46.5%) than average IgAN patients (26.8%; P < 0.01), there was no significant difference in the carriage rate of IL1RN*2 between HSPN and those IgAN patients with recurrent gross hematuria (42.8%l P > 0.05). It suggested that the IL1RN*2 allele might be a genetic marker shared by HSPN and a special group of IgAN patients with recurrent gross hematuria. Our preliminary observation provided a genetic evidence to support the hypothesis that HSPN and certain subgroup of IgAN are closely related diseases. Such an association of the gene polymorphism of IL-1ra between HSPN and IgAN with recurrent gross hematuria might serve as a key to explore their pathogenesis and eventually a specific intervention.

Adolescent↗

PubMed1986

An analysis of congressional health policy voting in the 1970s.

This paper analyzes nine health policy votes in the U.S. House of Representatives. The votes all occurred between 1973 and 1980 and include such issues as health planning, health maintenance organizations, cost containment, and professional standards review organizations. The objective of this analysis is to examine the independent contribution of variables indigenous to health issues while controlling for party identification and ideology. The influence of health providers, measured by the effect of the number of state medical association members in each state, is significant in the findings. The state and local share of Medicaid expenses is also significant in explaining several votes. Contributions from political action committees were not important until 1979, when the rising costs of campaigns gave them more influence, and when our measures of their influence improved. By the time Congress voted in 1979 on hospital cost containment legislation, the PAC variable surpassed even the AMA variable in importance.

Cost Control↗

PubMed1986

Structure and diversity of the human T-cell receptor beta-chain variable region genes.

In order to characterize the variability of the expressed human T-cell receptor (TCR) beta-chain repertoire and contrast this variability to the known murine beta-chain repertoire, 15 independent complementary DNA (cDNA) clones containing TCR beta-chain variable region (V beta) genes were isolated from a human tonsil cDNA library. The nucleotide and derived amino acid sequences of these 15 V beta genes were analyzed together with 7 previously defined sequences. Fifteen different human V beta genes could be identified from 22 independent sequences. By means of DNA hybridization and sequence homology comparisons, it was possible to group these 15 genes into ten distinct V beta subfamilies, each containing from one to seven members. Minimal polymorphism was noted between individuals, except in multimember subfamilies. The amino acid sequences of these genes contain conserved amino acids that are also shared by murine TCR V beta genes and immunoglobulins; no features were found that distinguish human V beta genes from their murine counterparts. Evaluation of secondary structure showed that maximum variability coincides with generally hydrophilic portions of the amino acid sequence, while specific hydrophobic regions were conserved in all V beta genes examined.

Amino Acid Sequence↗

PubMed1980

An inherited restriction in the idiotypic variability as a possible explanation of a genetic predisposition for a monoclonal component.

Genetic factors have been proposed to play a role in the aetiology of a monoclonal proliferation of B lymphocytes. As an additional genetic factor we postulate that a restriction in the idiotypic variability of an individual contributes to a genetic predisposition to monoclonal gammopathy. To support our hypothesis, we have examined three families with multiple occurrence of M-components for sharing of idiotypic antigenicity between the related M-components and between the M-components and the sera of unaffected relatives. Idiotypic antisera against five isolated M-components were raised in guinea-pigs and used in a radiobinding inhibition assay. In none of the three families was idiotypic cross-reactivity observed between the familial M-components. However, in a family with three members with an M-component, sera of first-degree relatives showed a higher inhibitory capacity than sera of non-related individuals when an idiotypic antiserum, raised against the M-component of proposita, was employed. Within this particular family the observed restriction in the idiotypic variability could have contributed to the multiple occurrence of M-components.

Antibody Specificity↗

PubMed1998

HIV/AIDS knowledge and attitudes among alcohol and drug abusers in Egypt.

The aim of this study was to assess knowledge, attitudes and practice towards HIV/AIDS among alcohol and drug abusers and the effect of health education (HE) on their knowledge and attitudes. Participants were 265 substance abusers, recruited from 8 addiction rehabilitation centers. A base line study preceding HE was done using a questionnaire composed of five sections. Three scores were developed to assess HIV/AIDS related knowledge. The base line study indicates that addicts with good knowledge scores > or =75%) regarding modes of transmission were significantly higher among males than females. About 70% of the addicts had negative attitudes towards dealing with HIV/AIDS patients, while 55.5% felt sympathy for them. Eleven percent of the injection drug abusers were sharing needle with others, while 38% of the participating females were previously convicted of prostitution. Logistic analysis showed that high level of education was the best predictive variable for good knowledge scores (> or =75%). Evaluation of the health education program revealed a highly significant increase in the knowledge scores among both males and females compared to the pretest scores. An increase in the percentages of male and female addicts with improved attitudes towards HIV/AIDS patients was also noted after HE. So, HE was found to be a successful tool in improving the knowledge and attitudes of substance abusers towards HIV/AIDS.

Adult↗

PubMed2004

Demonstration of a quantum teleportation network for continuous variables.

Quantum teleportation involves the transportation of an unknown quantum state from one location to another, without physical transfer of the information carrier. Although quantum teleportation is a naturally bipartite process, it can be extended to a multipartite protocol known as a quantum teleportation network. In such a network, entanglement is shared between three or more parties. For the case of three parties (a tripartite network), teleportation of a quantum state can occur between any pair, but only with the assistance of the third party. Multipartite quantum protocols are expected to form fundamental components for larger-scale quantum communication and computation. Here we report the experimental realization of a tripartite quantum teleportation network for quantum states of continuous variables (electromagnetic field modes). We demonstrate teleportation of a coherent state between three different pairs in the network, unambiguously demonstrating its tripartite character.

Journal Article↗

PubMed2005

The effects of patient cost sharing on ambulatory utilization in South Korea.

This study focused mainly on the effects of patient cost sharing on the demand for physician service, especially in the low-income people. Patient cost sharing is one of the policies used extensively in the health care financing in Korea, which has been adopted to control the health care cost. It has raised the argument that cost sharing inhibits low-income patients' access to affordable medical care. Data from the National Health and Nutrition Survey conducted 1998 by the Korean Ministry of Health and Welfare was used for this analysis. Multiple regression was done with the dependent variable of the amount of ambulatory utilization and price elasticities are estimated. We obtained significant out-of-pocket price elasticities depending on patient income levels and types of care facilities in the range of -0.21 to -0.07, -0.20 to -0.10, respectively. We found out that low-income patients are more sensitive to cost sharing than high-income patients. Furthermore, we found out that the users of general hospitals are less sensitive to cost sharing than the users of clinics. These results shows that the cost sharing policy in Korea does not efficiently work. Patient cost sharing in Korea induces inequitable medical service utilization and also it does not decrease moral hazard in the sense that the higher cost-sharing sector is less sensitive to cost sharing.

Adult↗

PubMed2001

Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster.

An extensive, highly diversified multigene family of novel immune-type receptor (nitr) genes has been defined in Danio rerio (zebrafish). The genes are predicted to encode type I transmembrane glycoproteins consisting of extracellular variable (V) and V-like C2 (V/C2) domains, a transmembrane region and a cytoplasmic tail. All of the genes examined encode immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic tail. Radiation hybrid panel mapping and analysis of a deletion mutant line (b240) indicate that a minimum of approximately 40 nitr genes are contiguous in the genome and span approximately 0.6 Mb near the top of zebrafish linkage group 7. One flanking region of the nitr gene complex shares conserved synteny with a region of mouse chromosome 7, which shares conserved synteny with human 19q13.3-q13.4 that encodes the leukocyte receptor cluster. Antibody-induced crosslinking of Nitrs that have been introduced into a human natural killer cell line inhibits the phosphorylation of mitogen-activated protein kinase that is triggered by natural killer-sensitive tumor target cells. Nitrs likely represent intermediates in the evolution of the leukocyte receptor cluster.

Amino Acid Sequence↗

PubMed2001

Chaperone-like activity of alpha-crystallin and other small heat shock proteins.

Small heat shock proteins (sHsps) are a large family of proteins with monomeric molecular weight of 12-43 kDa, present within the prokaryotic and eukariotic cell as large oligomeric complexes, ranging in size from 200-800 kDa. Unlike the high molecular weight Hsps, which are involved in protein folding in vivo, under normal conditions, sHsps play an important role in protecting organism from stress. SHsps share an evolutionarily conserved sequence of 80-100 amino acids, located in the C-terminal region, and called "alpha-crystallin domain"; its role in subunits interactions has been recently underlined by site-directed spin labeling studies and by fluorescence resonance energy transfer data. The N-terminal region, preceding the alpha-crystallin domain, is variable in length and amino acid sequence, contributing to structural diversity between different sHsps and having a role in multimerization. The alpha-Crystallin domain is followed by C-terminal extension, a polar structure, involved in protein solubility, which share no sequence homology. Expression of sHsps is induced in response to various kinds of stress including heat shock, oxidative stress, osmostress, or ischemia, but some sHsps are expressed constitutively under physiological conditions. In vitro, sHsps selectively bind and stabilize proteins and prevent their aggregation at elevated temperatures in an ATP-independent way and protect enzymes against heat-induced inactivation. Our own studies focused on the chaperone-like activity of alpha-crystallin, the major protein component of vertebrate lens, using another system than heat-induced aggregation. Our data demonstrated that alpha-crystallin specifically protects enzymes against inactivation by different posttranslational modifications such as glycation, carbamylation and aldehyde binding, and also reactivates GuHCl-denatured enzymes. Complex formation between alpha-crystallin and the denatured enzymes, was suggested as a mechanism of protection.

Animals↗

PubMed1994

Novel structural features of autoantibodies in murine lupus: a possible superantigen binding site?

The stimulus for the production of anti-DNA autoantibodies in lupus remains unknown. Since double-stranded DNA (dsDNA) is a weak immunogen, other stimuli such as B cell superantigens or anti-idiotypic antibodies may provide an alternative mechanism for their production. The presence of regulatory determinants on autoantibodies might be revealed through their structural characterization, but they have eluded detection, perhaps because they may be three-dimensional and require closer analysis. In this report we cloned and sequenced the heavy chain variable region (VH) of a monoclonal anti-dsDNA antibody, mAb 3E10, derived from MRL/lpr mice with lupus nephritis previously shown to express an idiotype associated with nephritis in murine and human lupus. We now show that mAb 3E10 VH contains novel structural features unrelated to DNA binding which are shared only by a subset of autoantibodies expressed in murine lupus. These lupus autoantibodies can be distinguished from antibodies of non-autoimmune strains by the presence of a specific sequence at the junction of the diversity and joining genes combined with the use of variable region genes with conserved sequences in framework 1 (FR1) and FR3. The location of the novel sequences indicates the possibility of a three-dimensional solvent-exposed determinant located distant from the classical antigen binding site that could regulate their production, possibly through binding B cell superantigens or other infectious agents.

Amino Acid Sequence↗

PubMed2000

Predictors of survival after In vivo split liver transplantation: analysis of 110 consecutive patients.

OBJECTIVE: To determine the factors that influence patient survival after in vivo split liver transplantation (SLT). SUMMARY BACKGROUND DATA: Split liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. METHODS: During a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors' in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. RESULTS: Overall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables-UNOS status and number of transplants per patient-were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. CONCLUSIONS: Patient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.

Adolescent↗

PubMed2005

Effects of backward speech and speaker variability in language discrimination by rats.

Human infants use prosodic cues present in speech to extract language regularities, and it has been suggested that this capacity is anchored in more general mechanisms that are shared across mammals. This study explores the extent to which rats can generalize prosodic cues that have been extracted from a training corpus to new sentences and how this discrimination process is affected by the normalization of the sentences when multiple speakers are introduced. Conditions 1 and 2 show rats' abilities to use prosodic cues present in speech, allowing them to discriminate between sentences not previously heard. But this discrimination is not possible when sentences are played backward. Conditions 3 and 4 show that language discrimination by rats is also taxed by the process of speaker normalization. These findings have remarkable parallels with data from human adults, human newborns, and cotton-top tamarins. Implications for speech perception by humans are discussed.

Animals↗