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PubMed1971

Immunofluorescent evidence for cellular control of synthesis of variable regions of light and heavy chains of immunoglobulins G and M by the same gene.

Two distinct paraproteins (IgG(2)-K and IgM-K) from one patient shared identical light chains and significant portions of the variable regions of the heavy chains. Idiotypic determinants on the IgG and IgM molecules were shared. Earlier studies, using class-specific antisera, showed that these paraproteins were produced by two different populations of cells. The present study, using rhodamine and fluorescein conjugates of the anti-idiotype antisera, demonstrates that all plasma cells that contain immunoglobulin, whether IgG or IgM, stained with anti-idiotype antisera; this occurred irrespective of whether the antisera were made originally against the patient's IgG or IgM. This, plus previous data, indicates that both populations of cells share genetic information for the constant and variable regions of light chains and significant portions of the heavy-chain genes. These, and other cited data, strongly suggest the occurrence of a switch-over from IgM to IgG synthesis in the same cell during the course of the normal immune response.

Animals↗

PubMed1988

Structural features of Ly-5 glycoproteins of the mouse and counterparts in other mammals.

The Ly-5 system of the mouse defines a set of transmembrane glycoprotein isoforms (T200, B220, etc) that hallmark various lineages and stages of hematopoietic differentiation. These isoforms are the products of a single Ly-5 gene comprising 34 exons, 32 of them (Exs-3-34) protein-coding and three (Exs-5-7) selectively represented in different isoforms (e.g., all three in isoform B220 but none in isoform T200). Probable structural features of Ly-5 glycoproteins, largely inferred from Ly-5 gene composition, are presented and compared with the rat L-CA and human LCA/T200 systems, which are phylogenetic counterparts of Ly-5 as an index of the extent and nature of structural conservation. The outer (N-terminal) region of the Ly-5 T200 isoform comprises three broadly similar domains (Exs-4, 8, 9) with salient features that jointly favor free interaction with the aqueous environment and are shared by the L-CA and human LCA/T200 systems despite an overall interspecies protein sequence similarity in this region of only about 50%. In the larger B220 isoform this region includes epitopes dictated by the selective exons Exs-5, 6, 7, these being more conserved than the shared exons Exs-4, 8, 9 and no doubt sustaining the differential functions of the respective isoforms. Comparison of the genomic sequences of Ex-5 in the Ly-5 and human systems suggests that a shift in splice donor site accounts for an extra 23 amino acids in the human Ex-5-coding domain, which is the only salient structural difference between the mouse Ly-5 and human systems. The inner extracellular region (Exs-10-16) includes subregions of high variability, but again there are shared salient interspecies similarities such as sites and numbers of Cys residues that imply a conserved, tightly-folded conformation, in contrast to the more open conformation predicted for the outer extracellular region. The transmembrane region (Ex-17) is highly conserved, as is the very large cytoplasmic region (Exs-17-34) which may interact with the plasma membrane but probably does not traverse it.

Amino Acid Sequence↗

PubMed1998

Nucleotide sequence analysis of a human monoclonal antibody 22-13 reactive with lung tumor-associated antigen.

A human monoclonal antibody (HuMAb) 22-13 (IgG1, kappa) recognizes a cytoplasmic antigen associated primarily with human lung tumors. This study reports the primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the HuMAb 22-13. This HuMAb uses a VH gene member of the V(H)Ia gene family, 51P1 and is productively rearranged with a D-D fusion product of the D(LR)2 and D(XP)2 germ line DH genes and the germ line JH3 gene. HuMAb 22-13 Vkappa belongs to the kappa light chain variable subgroup IIIb family and appears to be derived from the Humkv325 germ line gene and is rearranged with a germ line Jkappa5 gene. The results reveal that production of a HuMAb 22-13 is achieved by rearrangement of the 51P1/Humkv325 germ line variable region gene combination, associated with the autoimmune repertoire and that HuMAb 22-13 has a striking sequence homology to rheumatoid factors (RFs) of the Wa idiotypic family. HuMAb 22-13 and Wa RFs have in common V(H)Ia and VkappaIIIb gene segments, but use different DH, JH and Jkappa gene segments. However, in spite of this structural similarity, HuMAb 22-13 does not display rheumatoid factor activity. Taken together with the reported findings, these data indicate the representation of the shared usage of highly homologous variable region genes in entirely different humoral immune responses in the human system.

Amino Acid Sequence↗

PubMed2002

Olfactory acuity and cognitive function converge in older adulthood: support for the common cause hypothesis.

Visual and auditory thresholds and cognitive variables have shown converging losses in old age, which might exist because standard cognitive tests rely on these modalities for assessment. The present study investigated the common cause hypothesis in another sensory modality. Structural equation modeling tested the fit of a model representing the common cause hypothesis for olfactory acuity and cognitive function data from 98 nondemented older adults and 103 younger adults. The model fit better the data from the older adults, consistent with the common cause hypothesis. In addition, unique influences of age beyond those shared between cognitive and sensory variables were also demonstrated. The results suggest that olfactory functioning may be a valid indicator of the integrity of the aging brain in older adults.

Adolescent↗

PubMed2003

The neural basis of predicate-argument structure.

Neural correlates exist for a basic component of logical formulae, PREDICATE(x). Vision and audition research in primates and humans shows two independent neural pathways; one locates objects in body-centered space, the other attributes properties, such as colour, to objects. In vision these are the dorsal and ventral pathways. In audition, similarly separable "where" and "what" pathways exist. PREDICATE(x) is a schematic representation of the brain's integration of the two processes of delivery by the senses of the location of an arbitrary referent object, mapped in parietal cortex, and analysis of the properties of the referent by perceptual subsystems. The brain computes actions using a few "deictic" variables pointing to objects. Parallels exist between such nonlinguistic variables and linguistic deictic devices. Indexicality and reference have linguistic and nonlinguistic (e.g., visual) versions, sharing the concept of attention. The individual variables of logical formulae are interpreted as corresponding to these mental variables. In computing action, the deictic variables are linked with "semantic" information about the objects, corresponding to logical predicates. Mental scene descriptions are necessary for practical tasks of primates, and preexist language phylogenetically. The type of scene descriptions used by nonhuman primates would be reused for more complex cognitive, ultimately linguistic, purposes. The provision by the brain's sensory/perceptual systems of about four variables for temporary assignment to objects, and the separate processes of perceptual categorization of the objects so identified, constitute a pre-adaptive platform on which an early system for the linguistic description of scenes developed.

Afferent Pathways↗

PubMed2004

The InDeVal insertion/deletion evaluation tool: a program for finding target regions in DNA sequences and for aiding in sequence comparison.

BACKGROUND: The program InDeVal was originally developed to help researchers find known regions of insertion/deletion activity (with the exception of isolated single-base indels) in newly determined Poaceae trnL-F sequences and compare them with 533 previously determined sequences. It is supplied with input files designed for this purpose. More broadly, the program is applicable for finding specific target regions (referred to as "variable regions") in DNA sequence. A variable region is any specific sequence fragment of interest, such as an indel region, a codon or codons, or sequence coding for a particular RNA secondary structure. RESULTS: InDeVal input is DNA sequence and a template file (sequence flanking each variable region). Additional files contain the variable regions and user-defined messages about the sequence found within them (e.g., taxa sharing each of the different indel patterns).Variable regions are found by determining the position of flanking sequence (referred to as "conserved regions") using the LPAM (Length-Preserving Alignment Method) algorithm. This algorithm was designed for InDeVal and is described here for the first time. InDeVal output is an interactive display of the analyzed sequence, broken into user-defined units. Once the user is satisfied with the organization of the display, the information can be exported to an annotated text file. CONCLUSIONS: InDeVal can find multiple variable regions simultaneously (28 indel regions in the Poaceae trnL-F files) and display user-selected messages specific to the sequence variants found. InDeVal output is designed to facilitate comparison between the analyzed sequence and previously evaluated sequence. The program's sensitivity to different levels of nucleotide and/or length variation in conserved regions can be adjusted. InDeVal is currently available for Windows in Additional file 1 or from http://www.sci.muni.cz/botany/elzdroje/indeval/.

Codon↗

PubMed2006

A variable region in the Crimean-Congo hemorrhagic fever virus L segment distinguishes between strains isolated from different geographic regions.

Alignment of Crimean-Congo hemorrhagic fever virus (CCHFV) L genome segment full-length sequences reveals an overall high level of conservation among strains, with greater than 90% of translated amino acid residues strictly conserved. However, a region of marked variability identified previously, corresponding to L polyprotein amino acid positions 760-810, shares only 40% overall identity between strains. The variable regions sequences of 16 laboratory-adapted CCHFV strains were determined, including 11 strains from European Russia, one strain from Bulgaria, and four strains from the Central Asian countries of Tajikistan, Turkmenistan, and Uzbekistan. Phylogenetic analysis demonstrates this L segment variable region sequence divides CCHFV strains into similar geographically-defined groupings observed for S segment-derived trees, but with higher bootstrap support and a much smaller character set required for analysis.

Africa↗

PubMed1998

A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families.

Tricho-dento-osseous syndrome (TDO) is characterised by a variable clinical phenotype primarily affecting the hair, teeth, and bone. Different clinical features are observed between and within TDO families. It is not known whether the variable clinical features are the result of genetic heterogeneity or clinical variability. A gene for TDO was localised recently to chromosome 17q21 in four North Carolina families, and a 4 bp deletion in the human distal-less 3 gene (DLX3) was identified in all affected members. A previous genetic linkage study in a large Virginia kindred with TDO indicated possible linkage to the ABO, Gc, and Kell blood group loci. To examine whether TDO exhibits genetic heterogeneity, we have performed molecular genetic analysis to determine whether affected members of this Virginia kindred have the DLX3 gene deletion identified in North Carolina families. Results show that affected subjects (n=3) from the Virginia family have the same four nucleotide deletion previously identified in the North Carolina families. A common haplotype for three genetic markers surrounding the DLX3 gene was identified in all affected subjects in the North Carolina and Virginia families. These findings suggest that all people with TDO who have been evaluated have inherited the same DLX3 gene deletion mutation from a common ancestor. The variable clinical phenotype observed in these North Carolina and Virginia families, which share a common gene mutation, suggests that clinical variability is not the result of genetic heterogeneity at the major locus, but may reflect genetic heterogeneity at other epigenetic loci or contributing environmental factors or both.

Abnormalities, Multiple↗

PubMedDate not supplied

Sociodemographic correlates of alexithymia.

The association between alexithymia and sociodemographic variables is not well understood. Previous studies using the current 20-item and previous 26-item versions of the Toronto Alexithymia Scale (TAS) have shown inconsistent associations with age, sex, socioeconomic status, and years of education. We tested 380 subjects from the community stratified equally across sex, five age groups, and three socioeconomic classes. In addition to the TAS-20, we also administered the Levels of Emotional Awareness Scale (LEAS), a behavioral measure of the ability to be aware of and represent emotions in words, a core component of alexithymia. The TAS-20 and LEAS were each correlated with age, sex, socioeconomic status (SES), and years of education (P < .01) in the same direction and to approximately the same degree. Alexithymia (or low emotional awareness) is associated with older age, male sex, lower SES, and fewer years of education. The TAS-20 and LEAS are only slightly correlated (r = -.19, n = 380, P < .001), but their correlation is largely accounted for by their shared variance with these demographic variables. The convergence of findings with these two quite different measures and the nature of their overlap support the validity of these associations between alexithymia and sociodemographic variables.

Adolescent↗

PubMedDate not supplied

[Prevalence of human immunodeficiency virus and risk behaviours among opioid users seen in an emergency room].

INTRODUCTION: As prevalence of HIV-1 among drug users in Spain is high and it is difficult to contact them because of their hidden behaviors, emergency rooms are one of the health facilities where they can be located. A cross-sectional interview study was planned. The aims of the study were to estimate prevalence of HIV-1 and to describe risk behaviors. METHODS: The sample included all patients that in spring 1992 were detected and referred by the doctor as being current opiate users, defined as any use in the 30 days prior the interview. Drug users who did not know their HIV status or were negative for more than six months were asked to provide a urine sample to test HIV serology. A descriptive analysis with simple stratification was carried out. Row and adjusted odds ratio were used to analyse association between different variables and HIV status. Logistic regression was used to examine variables associated with HIV infection and risk behaviors (injecting drug use, sharing needles, and no use of condom). RESULTS: Three hundred and eighty three opiate users were interviewed. It was possible to know HIV status of 94% of the subjects. Of them, 61% were positive (219). The best adjusted logistic model to predict associated variables with HIV included being female, primary school level, sickness absence, to attend because of organic pathology, and more years of parenteral use. Seventy five percent of the sample injected drugs during the past 30 days, and among them 30% shared syringes. The variables associated with a higher probability of having injected heroin or cocaine in the last 30 days were to have completed at least primary education, to be unemployed or reliant on illegal activities, not to be in drug treatment, and a larger number of drugs used in the last 30 days. A higher probability of sharing syringes was associated with a lower educational level, not to be in drug treatment, to live alone and a higher number of drugs used during last 30 days. Twenty one percent of the subjects who were sexually active always or nearly always used condom with regular partners and 56% with casual partners. Women were more likely to use condom than men with casual partners. Subjects who shared syringes during last 30 days were nearly three times more likely not to use condom with casual partners. CONCLUSIONS: Although a high prevalence of HIV-1 was estimated among opioid users seen in an emergency room, it is not higher than estimates for intravenous drug users recruited from treatment centres, prison or needles exchange programs. A high frequency of risk behavior was also observed indicating a need to develop specific prevention programs for drug users.

Adolescent↗

PubMed1998

The interleukin-4/interleukin-13 receptor of human synovial fibroblasts: overexpression of the nonsignaling interleukin-13 receptor alpha2.

Interleukin (IL)-4 and IL-13 are known to bind to shared heteromultimeric receptor complexes of variable composition. Given the many regulatory effects of IL-4 and IL-13 on synovial cells, we aimed to characterize their IL-4/IL-13 receptor (R). Cultivated synovial fibroblasts expressed transcripts for IL-4Ralpha and IL-13Ralpha1, the human homolog of the recently cloned mouse IL-13R, but not the common gamma-chain of the IL-2R. In particular, IL-13Ralpha2 mRNA, encoding a different IL-13R recently cloned from human renal carcinoma cells, was expressed at a strikingly high level. Correspondingly, a predominant protein migrating at 65 to 75 kd was cross-linked by iodinated IL-13 and was not cross-competed by an excess of unlabeled IL-4. However, by flow cytofluorometry, IL-13Ralpha1 (detected by the anti-lL-13Ralpha1 mAb 65) and IL-4Ralpha (detected by the mAb S697) were expressed at similar low density. Radioligand binding studies revealed for both cytokines approximately 300 receptors/cell with similar high affinity. An additional class of IL-13Rs was identified after occupation of the shared high-affinity receptors by the nonsignaling, double-mutant IL-4121R-->D, 124Y-->D (RY-IL-4). In these experiments, 1251-IL-13 bound to a single receptor population with a Kd of approximately 300 pM and approximately 5000 sites/cell, matching the published affinity of monomeric IL-13Ralpha2 when expressed in COS7 cells. RY-IL-4 blocked the IL-4- and IL-13-mediated vascular cell adhesion molecule (VCAM)-1 expression and Stat6 activation, suggesting that the large number of high-affinity IL-13Ralpha2 monomers are silent receptors, likely representing a decoy target for IL-13.

Carrier Proteins↗

PubMed1994

Migration and market wage risk.

The author presents an approach to the analysis of labor migration that incorporates the role of market wage variability as a source of information in individual migration decisions. "The focus...is on quantifying the effects of the origin market acting through amenities and the share of market-specific wage variability as it affects forecasts of alternative wages and forecast precision. A subsample of employed males...from the [U.S.] National Longitudinal Survey of Youth (NLS) age 16 to 22 years is used for estimation. The empirical results are consistent with the theoretically predicted relationship between migration propensities and regional differences in the information content of wages. In addition, the results provide evidence that risk aversion deters migration given uncertainty, measured by forecast precision, about alternative market wage levels."

Americas↗

PubMed2001

Geophysical variables and behavior: CIII. Days with sudden infant deaths and cardiac arrhythmias in adults share a factor with PC1 geomagnetic pulsations: implications for pursuing mechanism.

If geomagnetic-mediated stimuli trigger many sudden infant deaths, then the days in which they and hospital admissions for cardiac arrhythmias for adults occur should share a similar source of variance. Factor analyses of the days in which a sudden infant death occurred in Ontario or adults were admitted for one of eight categories of cardiac crisis in the Sudbury (Ontario) Region for the year 1984 supported the hypothesis. This factor, with which infant deaths and adult cardiac arrhythmias each shared about 40% of their variance, also shared about 40% of the variance with a factor with which about 35% of the variance in daily occurrence of geomagnetic pulsations (0.2 Hz to 5 Hz) was associated. These results are consistent with the important role of geomagnetic variables in the occurrence of transient electrical anomalies in brain function rather than cardiac blood flow.

Adult↗

PubMed1991

Age and depression: unique and shared effects.

The degree to which psychosocial variables associated with depression were also associated with age was examined in 3 samples of community residents 50 years of age or older (N = 4,617). Most of the expected concomitants of depression were found. With only a few exceptions, age was not correlated with depression-related psychosocial variables. Rather, age was most strongly associated with levels in neuropsychological and psychophysiological functioning. In addition, the magnitudes of the correlations in women compared with men and in young-old age groups compared with old-age groups were examined. A number of significant differences emerged, and their implications for theories of depression are noted.

Adaptation, Psychological↗

PubMed2001

Common germinal-center B-cell origin of the malignant cells in two composite lymphomas, involving classical Hodgkin's disease and either follicular lymphoma or B-CLL.

BACKGROUND: Classical Hodgkin's disease (HD) and B-cell non-Hodgkin lymphoma (NHL) occasionally occur in the same patient. Such composite lymphomas represent interesting models to study the pathogenesis of B-cell lymphomas and the relationship between HD and B-cell NHL. MATERIALS AND METHODS: We analyzed two composite lymphomas (a combination of classical HD with follicular lymphoma [FL] and a combination of classical HD with B-cell chronic lymphocytic leukemia [B-CLL]) by micromanipulation of single cells from tissue sections and amplification of immunoglobulin V region genes for the clonal relationship of the tumor cells. RESULTS: In both cases, clonally related variable (V) genes with both shared as well as distinct somatic mutations were obtained from the two lymphomas, showing that in each of the cases the distinct tumor cells were members of a common germinal center (GC) B-cell clone. FL cells from two different lymph nodes of patient 1 showed a similar mutation pattern, suggesting that infiltration of these lymph nodes by tumor cells was not restricted to a particular FL cell or subclone. In the FL, a single cell was identified with a mutation signature indicating that premalignant cells can persist in the tissue. CONCLUSIONS: The cases presented here further underline the close relationship between HD and B-cell NHL and the role of the GC in lymphomagenesis. Whereas the latter was already suggested for FL and HD, the present study indicates that also in the B-CLL subset characterized by mutated Ig genes, important steps in malignant transformation happen in the GC, and that HRS cells can derive from CD5-positive B cells.

Aged↗

PubMed2000

Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease.

In rare cases of B-cell chronic lymphocytic leukemia (B-CLL), large cells morphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) can be found in a background of otherwise typical B-CLL. To test these HRS-like cells for a potential clonal relationship to the B-CLL cells, single cells were micromanipulated from immunostained tissue sections, and rearranged immunoglobulin genes were amplified from HRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct somatic mutations were found in HRS-like and B-CLL cells from 1 patient, which indicates derivation of these cells from 2 distinct members of a germinal-center B-cell clone. Separate clonal V gene rearrangements were amplified from HRS-like and B-CLL cells from 2 other patients, showing concomitant presence of 2 distinct expanded B-cell clones. Epstein-Barr virus (EBV) was detected in the HRS-like cells of these 2 latter cases, indicating clonal expansion of an EBV-harboring B cell in the setting of B-CLL. There is evidence that HRS-like cells in B-CLL, like HRS cells in HD, derive from germinal-center B cells. In all cases, somatic mutations have been detected in the rearranged V genes of the HRS-like cells, and in 1 of the EBV-positive HRS-like cell clones, somatic mutations rendered an originally functional V gene rearrangement nonfunctional. We speculate that the HRS-like cells in B-CLL represent potential precursors for HRS cells causing HD.

Aged↗

PubMed1999

Emotional contagion, empathic concern and communicative responsiveness as variables affecting nurses' stress and occupational commitment.

Based on data gathered from registered nurses at two hospitals, this research examined the extent to which empathy variables contributed to nursing stress and occupational commitment. The empathy variables examined were emotional contagion (i.e. sharing the emotions of patients), empathic concern (i.e. being concerned for patients) and communicative effectiveness (i.e. effectively communicating with patients and their families). Nursing stress was explored through the variables of depersonalization, reduced personal accomplishment and emotional exhaustion. Multiple regression analyses revealed that the combination of the three emotional communication variables explained significant proportions of the variance in all three of the stress variables, as well as occupational commitment. The analyses further revealed that a lack of empathic concern and poor communicative responsiveness accounted for significant proportions of the variance in depersonalization. Lack of empathic concern, poor communicative responsiveness and high emotional contagion significantly contributed to reduced personal accomplishment. Emotional contagion explained a significant proportion of the variance in emotional exhaustion. Emotional contagion also significantly reduced occupational commitment. The findings are discussed in terms of nursing education and administration.

Achievement↗

PubMed1984

Complete heavy and light chain variable region sequence of anti-arsonate monoclonal antibodies from BALB/c and A/J mice sharing the 36-60 idiotype are highly homologous.

Structural and serologic studies on murine A/J monoclonal anti-arsonate antibodies resulted in the identification of a second idiotype family (Id36-60) in addition to the predominant idiotype family (IdCR). Id36-60, unlike IdCR, is a dominant idiotype in the BALB/c strain but is a "minor" idiotype in the A/J strain. The complete heavy and light chain variable region (VH and VL) amino acid sequences of a representative Id36-60 hybridoma protein from both the A/J and BALB/c strains have been determined. There are only four amino acid sequence differences between the VH of antibody 36-60 (A/J) and antibody 1210.7 (BALB/c). Two of these differences arise from single nucleotide changes in which the A/J and BALB/c Id36-60 VH germline gene sequences differ. The two other differences are the result of somatic mutation in hybridoma protein 36-60. In addition, Id36-60 heavy chains employ the same D and JH3 segments in both strains. The entire Vk2 VL of 36-60 and 1210.7 differ by only two amino acids, suggesting that like the heavy chains, they are derived from highly homologous VL genes. The same Jk segment is used in both antibodies. A comparison of the amino acid sequence data from Id36-60-bearing hybridomas suggests that a heavy chain amino acid difference accounts for the diminished arsonate binding by the 1210.7 hybridoma protein. Because the 1210.7 heavy chain is the unmutated product of the BALB/c VH gene, somatic mutation in VH may be required to enhance Ars affinity in this system.

Amino Acid Sequence↗