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PubMed2000

Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies.

Although the idiotypic structures of immunoglobulin from malignant B cells were the first tumor-specific determinants recognized, and clinical vaccination trials have demonstrated induction of tumor-specific immunity, the function of immunoglobulin-specific CD8+ cytotoxic T lymphocytes in tumor rejection remains elusive. Here, we combined bioinformatics and a T cell-expansion system to identify human immunoglobulin-derived peptides capable of inducing cytotoxic T-lymphocyte responses. Immunogenic peptides were derived from framework regions of the variable regions of the immunoglobulin that were shared among patients. Human-leukocyte-antigen-matched and autologous cytotoxic T lymphocytes specific for these peptides killed primary malignant B cells, demonstrating that malignant B cells are capable of processing and presenting such peptides. Targeting shared peptides to induce T-cell responses might further improve current vaccination strategies in B-cell malignancies.

B-Lymphocytes↗

PubMed1985

Geophysical variables and behavior: XXI. Geomagnetic variation as possible enhancement stimuli for UFO reports preceding earthtremors.

The contribution of geomagnetic variation to the occurrence of UFORs (reports of UFOs) within the New Madrid States during the 6-mo. increments before increases in the numbers of IV-V or less intensity earthquakes within the central USA was determined. Although statistically significant zero-order correlations existed between measures of earthquakes, UFORs and geomagnetic variability, the association between the latter two deteriorated markedly when their shared variance with earthquakes was held constant. These outcomes are compatible with the hypothesis that geomagnetic variability (or phenomena associated with it) may enhance UFORs but only if tectonic stress and strain are increasing within the region.

Behavior↗

PubMed1997

Scoring of severity in patients admitted to a respiratory intensive care unit.

A number of attempts have been made to develop measures of severity of illness for patients in the intensive care unit (ICU), but the impact of these indices in a Respiratory Intensive Care Unit (RICU) has not really been studied. At present, outcome can be accurately predicted in approximately 85% of ICU patients, while no data are available for the RICU. These indices will be reviewed in the article. The sophisticated Mortality Probability Model (MPM) II is used to predict the outcome of ICU patients. This technique is based on statistically-derived weights for its variables. The "most popular" indices are the Acute Physiology and Chronic Health Education (APACHE), the Simplified Acute Physiological Score (SAPS) and the Therapeutic Intervention Scoring System (TISS). Overall, the predictive accuracy of the latest APACHE III equation and score is rather good, but there are important limitations concerning its use in the RICU. The SAPS includes 17 variables, and can be considered as a simplified version of APACHE sharing with it the same problems of application. The TISS requires data on approximately 70 treatment variables and assigns each a score ranging 1-4. A high score represents serious intervention, while a low score illness requires much less medical or nursing intervention. The sum of these scores indicates severity of illness because more critical patients are presumed to require higher levels of interventions. The RICU is also characterized by the use of noninvasive mechanical ventilation (NMV) in the treatment of acute respiratory failure. Some indices able to predict the success of NMV, have been developed recently during a brief trial of NMV, and included the level of acidosis and hypercapnia.

APACHE↗

PubMed2006

Importance of genetic influences on chronic widespread pain.

OBJECTIVE: To estimate the relative importance of genetic and environmental factors in chronic widespread pain, and to assess whether there are sex differences in the type or magnitude of these influences. METHODS: Data were collected from a national sample of twins > or = 42 years of age, all of whom were participants in the Swedish Twin Registry. The presence of chronic widespread pain was assessed via computer-assisted telephone interviews, which were conducted between 1998 and 2002, using the American College of Rheumatology criteria for fibromyalgia. No clinical examinations were performed. In preliminary analyses, probandwise concordance rates and tetrachoric correlations were calculated. Structural equation modeling was then performed to estimate additive genetic, shared environmental, and nonshared environmental sources of variability in susceptibility for the development of chronic widespread pain. RESULTS: Of 61,355 eligible twins, 44,897 individuals (73.2%) responded to the interview. Both members of 15,950 pairs responded to the items regarding pain symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same-sex dizygotic, and 5,755 were opposite-sex dizygotic. The prevalence of chronic widespread pain was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance rates and tetrachoric correlations suggested modest genetic influences for both women and men. Genetic and shared environmental influences explained approximately half of the total variance, with no indication of sex differences in either the type or magnitude of these influences. CONCLUSION: Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain.

Chronic Disease↗

PubMed2003

The effect of health plan characteristics on Medicare+ Choice enrollment.

OBJECTIVE: To provide national estimates of the effect of out-of-pocket premiums and benefits on Medicare beneficiaries' choice among managed care health plans. DATA SOURCES/STUDY SETTING: The data represent the population of all Medicare+ Choice (M+C) plans offered to Medicare beneficiaries in the United States in 1999. STUDY DESIGN: The dependent variable is the log of the ratio of the market share of the jth health plan to the lowest cost plan in the beneficiary's county of residence. The explanatory variables are measures of premiums and benefits in the jth health plan relative to the premiums and benefits in the lowest cost plan. DATA COLLECTION METHODS: The data are from the 1999 Medicare Compare database, and M+C enrollment data from the Centers for Medicare and Medicaid Services (CMS). PRINCIPAL FINDINGS: A $10 increase in an M+C plan's out-of-pocket premium, relative to its competitors, is associated with a decrease of four percentage points in the jth plan's market share (i.e., from 25 to 21 percent), holding the premiums of competing plans constant. CONCLUSIONS: Although our price elasticity estimates are low, the market share losses associated with small changes in a health plan's premium, relative to its competitors, may be sufficient to discipline premiums in a competitive market. Bidding behavior by plans in the Medicare Competitive Pricing Demonstration supports this conclusion.

Aged↗

PubMed1990

Synthetic peptide vaccine against mucosal colonization by group A streptococci. I. Protection against a heterologous M serotype with shared C repeat region epitopes.

M protein is an antigenically variable virulence determinant present on the surface of group A streptococci, and it provides the basis for the serologic typing scheme. Type-specific serum antibodies afford strong protection against infection by the homologous serotype. Non-type-specific antigenic epitopes also exist within the surface-exposed portion of M protein. Previous studies demonstrated that intranasal immunization with Ag corresponding to sequences within the non-type-specific pepsin-susceptible site and adjacent C repeat regions of M6 protein, evoke protective immunity against pharyngeal colonization by type 6 streptococci in a mouse model. Although the protective immunogens are not type-specific, the pepsin site region of M6 is shared among less than 20% of serotypes examined. Therefore it was necessary to determine whether more highly conserved M protein epitopes elicit mucosal protection against group A streptococci, and if protective immunity extends to heterologous serotypes. In this report, peptides were synthesized that correspond to sequences completely contained within the highly conserved C repeat region of M6 protein. Peptide Ag were covalently coupled to the mucosal adjuvant, cholera toxin B subunit (CTB), and mice immunized intranasally and orally with peptide-CTB conjugates were compared to control groups that received CTB only. Immunization with the peptide-CTB conjugates led to significant protection against pharyngeal colonization by group A streptococci. Furthermore, protection was observed against the heterologous M serotype, type 14. These findings suggest that protection against multiple serotypes of group A streptococci can be achieved with a vaccine consisting of the widely shared C repeat region of M6 protein.

Amino Acid Sequence↗

PubMed2003

Drosophila lola encodes a family of BTB-transcription regulators with highly variable C-terminal domains containing zinc finger motifs.

Alternative splicing is an important mechanism contributing to the increased proteome diversity in higher eukaryotes. We have explored the alternative splicing events in the Drosophila longitudinals lacking (lola) gene by means of 5' RACE, 3' RACE, genome sequence searches, and EST sequencing. We demonstrated that the lola locus is comprised of 32 exons spanning over 60 kb, and encodes a total of 80 alternatively spliced variants consisting of 5' and 3' variable sequences and constitutive common exons. All the variants shared a common sequence (exons 5-8) encoding the N-terminal region containing the BTB domain, but both the 5' and 3' ends were variable. There were four promoters responsible for the variation in the 5' end (exons 1-4). Alternative splicing was involved in the variation in the 3' end corresponding to the C-terminal variable region, which was encoded by one or two exons that were selected from 20 groups of exons in a mutually exclusive manner (exons 9-32). Seventeen of the 20 isoforms contained C(2)H(2)-like zinc finger motifs in the C-terminal variable region. Analyses of the 3' variant-specific cDNA pools revealed that all combinations of 5' and 3' variable sequences were expressed in both the embryonic and third instar larval stages. Since the BTB domain mediates dimerization, lola encodes a family of transcription regulators with a large variety of DNA- or protein-binding specificities, and could be involved in various developmental processes, including the embryonic neural pathfindings. We also showed that the structures of Lola isoforms were highly conserved in Drosophila pseudoobscura.

3' Untranslated Regions↗

PubMed1990

[Rehabilitation of psychiatrically handicapped patients at halfway houses: the effect of work performance and other variables on the duration of hospitalization. A catamnestic study].

We studied the influence of rehabilitation in flat-sharing communities, or communes, on the duration of hospitalisation of 158 chronic psychiatric patients. Variables that shorten the length of hospital stay most effectively, were also investigated. The study covered a period of 13.5 years. The average residence in a commune is four years (mean) or two years (median), respectively. The length of further hospitalisation was reduced by more than fourfold (mean) or by more than twelvefold (median) respectively in comparison to the duration of hospitalisation before entry into a commune. 11 of the 18 variables investigated had a shortening effect on the further duration of hospitalisation. The influence of work performance on the duration of hospitalisation is studied.

Adult↗

PubMed1998

Diversity in the variable region of Helicobacter pylori cagA gene involves more than simple repetition of a 102-nucleotide sequence.

CagA, a product of cytotoxin-associated gene A cagA, is an important virulence-related antigen of Helicobacter pylori (HP). CagA varies in size from 128 kDa to about 140 kDa and this variation is believed to be generated by a 102-nucleotide (NT) repeat sequence in the so-called variable region of cagA. However, this explanation has not previously been tested by comparing the NT sequences of cagA derived from a number of different isolates of HP. In this study we first compared the size of PCR products obtained from 54 different isolates of HP with oligonucleotide primers designed to amplify a cagA fragment predicted to be at least 1059 NT, including the variable region of the gene. As expected, the size of the PCR products varied considerable, from 1110 to 1822 NT, but the majority (50 of 54) measured 1335 NT or less. The deduced amino acid (AA) sequences of 9 representative amplicons and 4 other known sequences were compared with the following result: Within the variable region of cagA there are actually two adjacent variable regions, which we label as proximal and distal. The proximal-variable region of CagA extends from a motif of 4 to 6 asparagine residues to a 7-AA repeat sequence (KIDQLNQ); the distal-variable region is confined between KIDQLNQ and a well-conserved duplicate, KIDNLNQ. Despite these shared features CagA of every HP strain examined to date has a variable region with a unique AA sequence.

Amino Acid Sequence↗

PubMed1996

The effects of sample size and variability on the correlation coefficient.

The purpose of the study was to investigate the effects of variability as a function of sample size on the Pearson product-moment correlation coefficient (PCC) under the assumption of a perfect relationship between two variables. The effects of sample size (subjects/trials) and variability on the PCC were demonstrated using a computer model. The model was also used to evaluate selected examples taken from the literature. The results indicated that variability in excess of 10% of the range for each variable resulted in a mean reduction of the shared variance by 50% or greater. Although sample size did not affect the mean PCC, it did have a dramatic effect on extreme percentile values producing unreliable results. These results indicate that a small PCC value can be an artifact of variability. It is suggested, therefore, that one should be cautious when stating conclusions regarding the relationship between two variables without having knowledge of the associated variabilities.

Humans↗

PubMedDate not supplied

Predictors of sharing drugs among injection drug users in the South Bronx: implications for HIV transmission.

HIV may be transmitted in the process of sharing injected drugs, even if all participants have their own syringes. In an effort to gain understanding of the extent and predictors of drug sharing, data were obtained via personal interviews with 1,024 injection drug users from four neighborhoods in the South Bronx. The relationship between drug-sharing and demographic, sexual, and drug-related variables was first examined in a bivariate analysis, and then via multiple logistic regression. Individuals who split drugs were more likely to be female, have had sex with a casual partner, exchanged sex for drugs or other needs, recently smoked crack cocaine, and shared needles. They were less likely to live or inject at their own home or have used a new needle the last time they injected. In a final logistic model, correlates of drug sharing included trading sex, injecting outside one's home, and using borrowed, rented or shared needles. Despite the lack of significance for gender in the final logistic model, females were at high risk of drug sharing because they constituted the great majority of those who exchanged sex. Continuing research is needed to understand how drug-sharing contributes to the spread of HIV and other infections, as are studies of approaches to reducing drug sharing. Prevention strategists and outreach organizations should be aware of the HIV risks inherent in the widespread practice of drug sharing.

Adult↗

PubMed2002

Aging and time-sharing aspects of executive control.

A particularly important aspect of executive functioning involves the ability to coordinate two simultaneous activities. The role of this aspect of executive functioning in adult-age differences in cognitive performance was examined in a study involving 150 adults between 20 and 91 years of age who performed the same visual-motor tracking task with three different primary tasks. The participants also performed several additional cognitive tasks that allowed examination of the relation of time-sharing efficiency to other types of cognitive functioning The results were consistent with the existence of a distinct time-sharing ability because the time-sharing costs in the three dual-task combinations were significantly correlated with one another but only weakly correlated with other cognitive variables. Increased age was associated with reductions in time-sharing ability, and greater efficiency in performing two tasks at once was associated with better performance on tasks assessing spatial, reasoning, and memory abilities. Although this pattern is what one would expect if executive processes contribute to age differences in cognitive functioning, the effects were smaller than those associated with a perceptual speed construct.

Aging↗

PubMed2005

Receptive syringe sharing among injection drug users in Harlem and the Bronx during the New York State Expanded Syringe Access Demonstration Program.

BACKGROUND: Effective on January 1, 2001, New York State enacted the Expanded Syringe Access Demonstration Program (ESAP), which allows syringes to be sold in pharmacies without a prescription or dispensed through doctors, hospitals, and clinics to persons 18 years of age or older and permits the possession of those syringes for the purposes of injecting drugs. OBJECTIVE: To assess changes in receptive syringe sharing since the inception of the ESAP. METHODS: Sociodemographic characteristics and syringe use data regarding the last injection episode were combined from 3 projects (n = 1181) recruiting injection drug users in ongoing studies in Harlem and the Bronx in New York City from January 2001 through June 2003. These data were analyzed as serial cross sections by calendar quarter. RESULTS: Receptive sharing decreased significantly over time, from 13.4% in the first quarter to 3.6% in the last quarter. Obtaining the last injection syringe from an ESAP source (mostly pharmacies) increased significantly over time, from 7.5% in the first quarter to 25.0% in the last quarter. In multiple logistic regression analysis, variables that were significantly associated with less receptive sharing were syringe exchange and ESAP syringe source as well as time since ESAP inception. Female gender and white race/ethnicity were significantly associated with greater receptive sharing. CONCLUSIONS: The increase in the use of pharmacies and other ESAP syringe sources in this sample has been accompanied by a decline in receptive sharing.

Adult↗

PubMed2006

Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma.

Aberrant somatic hypermutation (SHM) has been identified as a mechanism for genomewide instability in diffuse large B-cell lymphoma (DLBCL). To assess whether aberrant SHM plays a role in the molecular pathogenesis of Hodgkin lymphoma (HL), we investigated microdissected neoplastic cells of nodular lymphocyte-predominant HL (NLPHL; n = 10) and classic HL (cHL; n = 9) for the presence of mutations in the 5' sequences of 4 previously identified aberrant SHM targets (PIM1, PAX5, RhoH/TTF, c-MYC). Mutations in one or more genes were detected in 80% of NLPHLs and 55% of cHLs, with 50% and 30% of patients carrying mutations in 2 or more genes, respectively. The most frequently involved protooncogene was PAX5, mutated in 7 of 9 patients with NLPHL and 2 of 9 patients with cHL. In total, 34 mutations were detected in NLPHL (frequency, 1.04/1,000 bp) and 35 were detected in patients with cHL (frequency, 1.92/1,000 bp). Mutations were of somatic origin because they were absent in control T cells and shared most of the features of the immunoglobulin variable (IGV) gene-associated SHM mechanism-ie, single nucleotide substitutions (n = 63) with rare deletions/insertions (n = 6) and a predominance of transitions over transversions with preferential targeting motifs. Our finding that NLPHL and cHL are targeted by aberrant SHM, as is DLBCL, suggests that these lymphomas may share common molecular pathogenetic events.

Adolescent↗

PubMed2000

Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F.

BACKGROUND: Incomplete X-linked congenital stationary night blindness (CSNB) is a clinically variable condition that has been shown to be caused by mutations in the calcium-channel CACNA1F gene. We assessed the clinical variability in the expression of the incomplete CSNB phenotype in a subgroup of patients of Mennonite ancestry with the same founder mutation. METHODS: Sixty-six male patients from 15 families were identified with a common mutation in exon 27 of CACNA1F (L1056insC). Clinical variability in night blindness, reduced visual acuity, myopia, nystagmus and strabismus was examined. RESULTS: At least one of the major features of CSNB (night blindness, myopia and nystagmus) was absent in 72% of the patients. All the examined features varied widely, both between and within families. INTERPRETATION: Although the patients shared a common CACNA1F mutation, there was considerable variability in the clinical expression of the incomplete CSNB phenotype. These findings suggest the presence of other genetic factors modifying the phenotype of this disorder.

Adolescent↗

PubMed2003

Caprine arthritis-encephalitis virus-infected goats can generate human immunodeficiency virus-gp120 cross-reactive antibodies(1).

Lentiviruses display surprisingly disparate clinical manifestations in their specific hosts, share complex genetic structures, and exhibit extensive diversity, particularly in their envelope genes. The envelope protein, gp135, of caprine arthritis-encephalitis virus (CAEV) has minimal primary sequence homology to gp120, the envelope protein of human immunodeficiency virus (HIV). Nevertheless, they bear certain similarities in that they both possess five variable regions, both are heavily glycosylated, and both share short sequence motifs. We establish a further relationship and demonstrate that some goats, infected with CAEV, possess gp135-specific antibodies which cross-react with gp120 from several HIV strains, provided the protein is expressed in insect cells. We show that, although the cross-reactivity of these immunoglobulins depends on the level of glycosylation, nevertheless, some antibodies recognize the protein epitopes on gp120, at least some of which are linear in character. Further characterization of this unexpected cross-reaction will define its potential therapeutic utility.

Animals↗

PubMedDate not supplied

[Sudden infant death syndrome (SIDS)].

Sudden Infant Death Syndrome (SIDS) is the term first proposed in 1969 for a distinctive subgroup of unexpected infant deaths occurring during the first months of life, with relatively consistent clinical, epidemiological and pathological features, which remain unexplained after a thorough case investigation, including a complete autopsy, examination of death scene and review of clinical history. Sudden infant death unnecessary means SIDS. According to definition, SIDS remains a diagnosis of exclusion, distinguished from others only by subjective and permissive variables. Despite the vague and permissive nature of the definition, epidemiological studies identified some risk factors as prematurity and social disadvantage. Nevertheless, the most interesting findings are those related to environmental and care features, as drug addiction and/or smoke exposition during pregnancy, sleep position of the infant, environmental temperature, parental bed sharing and breast feeding. Those factors play a variable role, but their correction reduced SIDS incidence. Sudden infant death is a diagnosis made by expert pathologists with pediatrician's and investigator's advice, based primarily on autopsy findings and death scene investigation performed through the severe application of investigative protocols.

Female↗

PubMed2002

Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus.

The organization and allelic recombination of the merozoite surface protein-1 gene of Plasmodium vivax (PvMsp-1), the most widely prevalent human malaria parasite, were evaluated in complete nucleotide sequences of 40 isolates from various geographic areas. Alignment of 31 distinct alleles revealed the mosaic organization of PvMsp-1, consisting of seven interallele conserved blocks flanked by six variable blocks. The variable blocks showed extensive variation in repeats and nonrepeat unique sequences. Numerous recombination sites were distributed throughout PvMsp-1, in both conserved blocks and variable block unique sequences, and the distribution was not uniform. Heterozygosity of PvMsp-1 alleles was higher in Asia (0.953 +/- 0.009) than in Brazil (0.813 +/- 0.047). No identical alleles were shared between Asia and Brazil, whereas all but one variable block nonrepeat sequence found in Brazil occurred in Asia. These observations suggest that P. vivax populations in Asia are ancestral to Brazilian populations, and that PvMsp-1 has heterogeneity in frequency of allelic recombination events. Recurrent origins of new PvMsp-1 alleles by repeated recombination events were supported by a rapid decline in linkage disequilibrium between pairs of synonymous sites with increasing nucleotide distance, with little linkage disequilibrium at a distance of over 3 kb in a P. vivax population from Thailand, evidence for an effectively high recombination rate of the parasite. Meanwhile, highly reduced nucleotide diversity was noted in a region encoding the 19-kDa C-terminal epidermal growth factor-like domain of merozoite surface protein-1, a vaccine candidate.

Alleles↗