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PubMedDate not supplied

[Relese of Ca2+ from mitochondria after mitochondrial membrane depolarisation].

With the aid of specific inhibitors of Ca(2+)-uniporter (ruthenium red) and mitochondrial permeability transition pore, PTP (cyclosporine A) it is shown that PTP opening takes place after loading the rat liver mitochondria with calcium and depolarisation of mitochondrial membrane with protonophore (carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and the pore opening accounts for accelerated efflux of calcium from mitochondrial matrix as well as availability of "rapid" component of two-exponential kinetic curve of Ca(2+)-efflux. An analysis of kinetic data of Ca2+ transport after membrane depolarisation also confirms our earlier observations that time frame of the pore open state is restricted, and membrane integrity is restored before all the calcium load is delivered into incubation medium. The absence of additivity between the shares of Ca(2+)-uniporter and PTP in Ca(2+)-transport is observed, and conclusion is made that partial share of PTP in calcium transport is not a constant, but a variable constituent which is diminished to zero as soon as the Ca(2+)-uniporter activity reaches its maximum after the abolition of membrane potential with CCCP. Based on some observations, it is supposed also that PTP inactivation takes place during calcium translocation across the mitochondrial membrane, which could account for limited release of Ca2+ from mitochondrial matrix through the pore itself as well as relatively narrow limits of the pore open state in comparison with time scale of complete cation release from depolarised mitochondria.

Animals↗

PubMed1987

Malaneese of Malana glen: analysis of morphometric data and ethnic relationship with some neighbouring populations of Himachal Pradesh, India.

A morphometric study of the Malaneese - an isolated community living in the midst of Himalayas in district Kullu, Himachal Pradesh - is undertaken with a view to tracing their ethnic relationship with some neighbouring populations viz. Kinnauras, Kulwis and Lahulies, with whom they share some linguistic and cultural experiences. The data consist of 23 anthropometric variables which include 7 linear body measurements, 6 body diameters and circumferences and 10 head and face measurements. The Mahalanobis generalized distance statistics (D2) was used as the primary basis of analysis. The results show that Malaneese are a distinct population clearly distinguishable from the neighbouring populations of Himachal Pradesh. The distance statistics reveal closer morphometric affinity of Malaneese with the Kulwis and Kinnauras than with Lahulies. The lexicostatistical data together with historical records of the movement of people in this region lend support to the above findings.

Adult↗

PubMed1994

The urge to merge: linking vital statistics records and Medicaid claims.

This paper describes a procedure used to link Medicaid claims data to California vital statistics records for very low birthweight infants. The linkage involved about 53,000 infants born from 1980 to 1987 and 1.46 million claims for delivery/birth-related hospital admissions during the same period. Because the two data files did not share a unique identifier, record linkage required combining evidence across several linking variables: delivery hospital, delivery/birth date or hospitalization period, names, mother's age, and zip code. To combine the various pieces of evidence, we used record linkage theory to compute scores that measure the likelihood of a match, i.e., that two records correspond to the same delivery. These scores appropriately weight the various pieces of evidence for or against a match. Implementation required dealing with large amounts of missing data in one of the files, errors and variations in reported names, and the need to minimize the number of incorrect links. The approach applies to a wide range of linkage problems. The ability to combine existing datasets to form new datasets containing analysis variables from each facilitates analyses that would otherwise be impossible, or prohibitively expensive.

Bias↗

PubMed1994

Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas.

The (2;5)(p23;q35) translocation which results in the fusion of the NPM (nucleophosmin) gene on chromosome 5q35 with the novel ALK (anaplastic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et al., Science (Washington DC), 263: 1281-1284, 1994] is associated with Ki-1 (CD30)-positive anaplastic large cell lymphomas (ALCL); a group of morphologically and immunophenotypically heterogenous high grade large cell lymphomas (LCL), which share many characteristics with Hodgkin's disease (HD), including the presence of variable numbers of Reed-Sternberg-like cells and the expression of CD30 antigen. Using a DNA probe immediately 5' to the NPM coding sequences, we have examined NPM gene rearrangements by Southern blotting in 5 Ki-1-positive lymphoma cell lines carrying a translocation involving the 5q35 breakpoint and in 25 Ki-positive lymphoma tumors, including 9 HD. Using this method, we detected rearrangements in all cell lines with apparent clustering of the breakpoints. Analysis of 25 Ki-1-positive lymphomas indicated that only 4 neoplasms, including two HD, had NPM gene rearrangements. Thus, our findings suggest that only a subset of ALCL has detectable involvement of the NPM gene. In addition, the presence of NPM gene rearrangements in HD indicates the involvement of this gene in a fraction of HD. Thus, NPM gene rearrangements may identify a certain subtype in ALCL and HD which may be closely related.

Chromosomes, Human, Pair 2↗

PubMed2026

Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD): A collaborative platform for behavioral analysis across the lifespan.

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data from multiple laboratories. ID-CARD is designed to support large-scale, integrative analyses and to facilitate secondary use of existing behavioral data in alignment with emerging data-sharing and transparency initiatives. Rather than imposing retrospective harmonization of experimental protocols, we implemented a normalization and modeling framework that enables comparison of learning trajectories while preserving meaningful variation across studies. Behavioral data from > 5000 rats spanning common strains, both sexes, and multiple ages were normalized in training and performance domains and fit with a logarithmic function to derive an error accumulation rate coefficient (EARC) as a measure of spatial learning. Age was strongly associated with increased EARC, indicating attenuated learning, even after adjusting for non-spatial cue performance. Analyses of goodness of fit revealed systematic structure in learning dynamics, where age was associated with reduced learning-curve conformity after accounting for overall performance. Inter-individual variability in spatial learning also increased with age, with strain-specific interactions. These findings demonstrate that integrated analysis of heterogeneous behavioral datasets can yield robust, individual-level insights into cognitive aging. ID-CARD provides a scalable resource and analytic framework to advance discovery in behavioral neuroscience by enabling reuse, integration, and comparative analysis of existing data.

Cognitive aging↗

PubMed1996

Molecular analysis of antigen receptor variable region repertoires in T lymphocytes infiltrating the intrathyroidal and extrathyroidal manifestations in patients with Graves' disease.

To determine whether T cells infiltrating thyroid, orbital and pretibial tissue of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD) represent a primary immune response that is directed against certain antigenic determinants shared between these involved tissues, we characterized these T cells at the molecular level. T cell antigen receptor (TcR) variable (V) region gene usage in thyroid, orbital, pretibial tissue and peripheral blood mononuclear cells of patients with GD, GO and PTD was assessed using RT-PCR and 22 V alpha and 23 V beta gene-specific oligonucleotide primers, followed by Southern hybridization analysis using TcR C-region-specific, digoxigenin-labelled oligonucleotide probes. In some instances, CDR3- and junctional regions of TcR V beta genes were sequenced. Marked restriction and similarities of V alpha and V beta gene usage were detected in samples derived from patients with active GO and PTD of recent onset. Moreover, sequence analysis of junctional domains of V beta families revealed oligoclonality of some intrathyroidal, orbital and pretibial T cell populations as well as the presence of conserved junctional motifs shared by T cells derived the thyroid gland and the extrathyroidal sites. These data suggest that similar antigenic determinants may be responsible for the recruitment and oligoclonal expansion of T cells both within the thyroid gland and at the involved extrathyroidal sites in Graves' disease.

Eye Diseases↗

PubMed2006

Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13.

The human SIRT3 gene contains an intronic VNTR enhancer whose variability is correlated with life span. The SIRT3 5' flanking region encompasses the PSMD13 gene encoding the p40.5 regulator subunit of the 26S proteasome. Proteasome is a multicatalytic proteinase whose function declines with aging. SIRT3 and PSMD13 are linked in a head-to-head configuration (788-bp intergenic region). The molecular configuration of two genes that are both related to aging prompted us to search for shared regulatory mechanisms between them. Transfection experiments carried out in HeLa cells by deletion mutants of the PSMD13-SIRT3 intergenic region showed a complex pathway of coregulation acting in both directions. Furthermore, linkage disequilibrium (LD) analyses carried out in a sample of 710 subjects (18-108 years of age) screened for A21631G (marker of PSMD13), and for G477T and VNTR(intron5) (markers of SIRT3), revealed high LD, with significantly different PSMD13-SIRT3 haplotype pools between samples of centenarians and younger people.

Adolescent↗

PubMed1986

Generation of diversity of the beta chain of the human T-lymphocyte receptor for antigen.

Human T-cell receptor beta-chain (Ti beta) genes are formed by the rearrangement of variable (V), diversity (D), and joining (J) gene segments. A comparison of the nucleotide and deduced amino acid sequences of the variable regions of six human Ti beta cDNAs reveals that they display a level of homology similar to that shared by human immunoglobulin heavy chain V genes. In contrast to immunoglobulin V regions, which contain three discrete regions of hypervariability, the Ti beta V regions display a more widely distributed pattern of variability. Southern blot analyses show that most human Ti V beta gene families contain one to three members. However, a single family containing at least eight members is identified. This analysis allows the identification of at least 15 human Ti V beta germ-line genes. The sequence data show that at least one germ-line Ti beta J gene is used preferentially in Ti beta cDNAs. Moreover, they suggest the presence of at least four human germ-line Ti beta D genes. At least three mechanisms are involved in generating the diversity of human Ti beta genes: (i) the combinatorial rearrangement of different V, D, and J genes; (ii) imprecise V-D-J joining, including V-D joining in any of three translational reading frames; and (iii) the addition of extra nucleotides at the V-D-J joints (N-region diversity).

Base Sequence↗

PubMed2003

Determining resuscitation preferences of elderly inpatients: a review of the literature.

Studies have shown that discussions with elderly hospital patients about cardiopulmonary resuscitation (CPR) preferences occur infrequently and have variable content. Our objective was to identify themes in the existing literature that could be used to increase the frequency and improve the quality of such discussions. We found that patients and families are familiar with the concept of CPR but have limited understanding of the procedure and overestimate its benefit. Most patients are interested in being involved in discussions about CPR and in sharing responsibility for decisions with physicians; however, older patients who participate in these discussions may have variable decision-making capacity. Physicians do not routinely discuss CPR with older patients, and patients do not initiate such discussions. When discussions do occur, the information provided to patients or families about resuscitation and its outcomes is not always consistent. Physicians should initiate CPR discussions, consider patients' levels of understanding and decision-making capacity, share responsibility for decisions where appropriate and involve the family where possible. Documentation of discussions and patient preferences may help to minimize misunderstandings and increase the stability of the decision during subsequent admissions to hospital.

Aged↗

PubMed1987

Studies on species cross-reactivity of hemopexin by use of monoclonal and polyclonal antibodies.

The extent of immunological cross-reactivity between hemopexins of four species (rat, human, rabbit and chicken) was assessed with four affinity purified polyclonal antibodies and three monoclonal antibodies using RIA, Western blotting and rocket immunoelectrophoresis. Neither the two monoclonal antibodies to rabbit hemopexin (Rb3D11 and Rb3H9), the monoclonal antibody (R4B3) to rat hemopexin nor any of the polyclonal antibodies showed shared antigenic determinants between avian and mammalian hemopexins as judged by RIA or rocket immunoelectrophoresis. Western blotting with polyclonal antibodies revealed some reactivity raising the possibility of a few shared, though distantly related, epitopes. Polyclonal antibodies, raised to the mammalian hemopexins cross-reacted to variable extents with the respective antigens by RIA, results paralleled by data obtained by Western blotting. Anti-rat monoclonal antibodies reacted only with rat hemopexin in Western blots and minimally with rabbit hemopexin in RIA. The anti-rabbit monoclonal antibodies recognized two distinct epitopes one of which is shared with human hemopexin and presumably highly conserved.

Animals↗

PubMed1987

Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes.

The mRNA encoding heavy and light chains of a hybridoma-derived monoclonal IgM, kappa anti-immunoglobulin (rheumatoid factor) and an IgG3, kappa anti-histone autoantibody from systemic lupus erythematosus and arthritis-prone MRL/Mp-lpr/lpr mice have been molecularly cloned, and the nucleotide sequences corresponding to their variable regions have been determined. To investigate whether autoantibodies with specificities frequently observed in lupus disease might share common structural components, the sequences obtained in this study have been compared with those of a monoclonal MRL/Mp-lpr/lpr IgM, kappa anti-DNA autoantibody previously analyzed in our laboratory (J. Exp. Med. 1985. 161: 805). The 3 immunoglobulins employed different heavy chain variable region (VH) genes belonging to the large J588 VH gene family, kappa light chain variable region (V kappa) genes from 3 different V kappa groups, and different diversity and joining segments. Our findings suggest that murine lupus-associated autoantibodies of different specificities do not have genetic components in common to signal their self-reactive nature and are encoded by a large number of immunoglobulin gene elements.

Animals↗

PubMed1999

Hobnail hemangioma: a pseudomalignant vascular lesion with a reappraisal of targetoid hemosiderotic hemangioma.

The clinicopathologic features of 15 cutanous hemangiomas having a distinctive and frequently pseudomalignant morphologic appearance are presented. There were 5 male and 9 female patients, whose ages at diagnosis ranged from 11 to 58 years (median 30.5). An angiomatous/pigmented, nontargetoid, flat, or exophytic lesion of variable duration was the main presenting sign. The tumor sizes ranged from 0.4 cm to 2 cm (median 1 cm). The locations included the lower limb, particularly the thigh (8); the trunk, including the shoulder area (4); the head (1); the gingiva (1); and the tongue (1). One patient had two lesions; none had a concomitant vascular anomaly or was suspected to have HIV infection. Treatment consisted of excisional biopsy in all cases. Follow-up information on 10 patients (range 4-66 months; median 13 months) showed no recurrence. On microscopic examination, the lesion showed a biphasic pattern characterized by the presence of well-formed, dilated, vascular channels in superficial dermis and a collagen-dissecting, pseudoangiosarcomatous pattern as the lesion infiltrated deeper into the dermis. The lining endothelium consistently showed distinctive hobnail cytomorphology; although there were endoluminal stromal papillae, there was no endothelial multilayering or tufting. Cytologic atypia was minimal or absent, and there were no mitoses. In 3 cases, the morphologic features were reminiscent of retiform hemangioendothelioma. Immunohistochemistry performed in 8 cases showed variable reactivity of endothelial cells with CD31, CD34, Factor VIII-related antigen, and Ulex europaeus agglutinin-1 in all cases; smooth muscle actin-positive pericytes were observed focally around some of the abnormal vascular spaces. The above-described hemangiomatous lesions share many features with so-called targetoid hemosiderotic hemangioma (a clinically descriptive term), but show a variable, often minimal, amount of hemosiderin deposition. The histologically descriptive term hobnail hemangioma is proposed to designate these lesions. Hobnail hemangioma should be distinguished from well-differentiated angiosarcoma, patch-stage Kaposi's sarcoma, and retiform hemangioendothelioma, with which it may be confused.

Adolescent↗

PubMed2003

Allospecific T cell epitope sharing reveals extensive conservation of the antigenic features of peptide ligands among HLA-B27 subtypes differentially associated with spondyloarthritis.

HLA-B*2702, B*2704, and B*2705 are strongly associated with spondyloarthritis, whereas B*2706 is not. Subtypes differ among each other by a few amino acid changes and bind overlapping peptide repertoires. In this study we asked whether differential subtype association with disease is related to differentially bound peptides or to altered antigenicity of shared ligands. Alloreactive CTL raised against B*2704 were analyzed for cross-reaction with B*2705, B*2702, B*2706, and mutants mimicking subtype changes. These CTL are directed against many alloantigen-bound peptides and can be used to analyze the antigenicity of HLA-B27 ligands on different subtypes. Cross-reaction of anti-B*2704 CTL with B*2705 and B*2702 correlated with overlap of their peptidic anchor motifs, suggesting that many shared ligands have similar antigenic features on these three subtypes. Moreover, the percent of anti-B*2704 CTL cross-reacting with B*2706 was only slightly lower than the overlap between the corresponding peptide repertoires, suggesting that most shared ligands have similar antigenic features on these two subtypes. Cross-reaction with B*2705 or mutants mimicking changes between B*2704 and B*2705 was donor-dependent. In contrast, cross-reaction with B*2702 or B*2706 was less variable among individuals. Conservation of antigenic properties among subtypes has implications for allorecognition, as it suggests that shared peptides may determine cross-reaction across exposed amino acid differences in the MHC molecules and that the antigenic distinctness of closely related allotypes may differ among donors. Our results also suggest that differential association of HLA-B27 subtypes with spondyloarthritis is more likely related to differentially bound peptides than to altered antigenicity of shared ligands.

Amino Acid Substitution↗

PubMed2004

Clinical, psychopathological and personality correlates of interoceptive awareness in anorexia nervosa, bulimia nervosa and obesity.

OBJECTIVE: To determine the levels of interoceptive awareness (IA), which measures the ability of an individual to discriminate between sensations and feelings, and between the sensations of hunger and satiety, in eating disorder patients and to identify the clinical, psychopathological and personal variables correlated with IA. SAMPLING AND METHODS: Sixty-one restrictor anorectics, 61 binge-purging anorectics, 104 purging bulimics, 49 obese subjects with binge eating disorder (BED) and 47 obese subjects without BED were compared. They were assessed with the Eating Disorder Inventory-2, the Temperament and Character Inventory, and the Beck Depression Inventory, and their clinical and sociodemographic features were recorded. RESULTS: In all patients, the levels of IA were higher than the 'normal' ones; in bulimia nervosa, they were higher than in anorexia nervosa and obesity. Similar personal features and eating attitudes are shared by patients with bulimia nervosa and BED. In the total sample, the following variables independently correlate with IA: the Beck Depression Inventory, self- directedness and persistence. CONCLUSIONS: The importance of an altered IA in eating disorders is supported. Both depression and a perfectionist and poorly self-directive personality can lead to greater difficulties in discriminating hunger and satiety.

Adult↗

PubMed2001

[Patient choice for cancer treatment: towards a shared-decision model?].

The process of medical decision implies the elaboration of a choice between alternatives. Who has the choice? The doctor? The patient? Both? That depends on the particular characteristics of the patient and of the tumour, but also of the characteristics of the doctor and of his approach of medical discipline. For that reason, we planned first to remind some principles. In our analysis, the patient-doctor's relationship ties with environment, culture and habits. Philosophical principles, moral, and models of the relation between patient and doctor concern first part. In the second part, these ideas are compared with our routine practice: surveys about patients' needs, the obstacles for complete information and participation, studies on patients' preferences. The authors' analysis is that we are going inescapably towards shared decision-making taking into account the patients preferences. This evolution is not only tied with ethical principles, but with medical reason, i.e. the variability of patients' preferences led to tailor the treatment to the individual patient especially when benefit is limited. Of course, the applicability of a shared model depends on the particular situation of the patient and of his demand. It is all the easier as the consequences of the treatment are well known the riks tiny and distant. In the classical paternalistic model, there is no choice for the patient because the doctor(s) give the treatment. In the ideal model of the shared decision, doctor and patient progress together towards medical decision, in this case, the patient is not alone facing a choice, and in all cases, he is never alone.

Choice Behavior↗

PubMed2006

TACI mutation in common variable immunodeficiency and IgA deficiency.

Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disease. Immunoglobulin A deficiency (IGAD) shares some clinical, laboratory, and genetic features with CVID and occurs with relatively greater frequency in first-degree relatives of individuals with CVID. Recently, patients with CVID and IGAD have been found to have mutations of the gene TNFRSF13B encoding the TACI (transmembrane activator and calcium-modulator and cyclophilin-ligand interactor), a member of the tumor necrosis factor-receptor superfamily. In this article, we review the various TACI mutations that have been identified so far. Although six mutations have been reported, no clear genotype-phenotype association has been shown to date. This suggests that the phenotypic expression of TACI mutation is affected by additional genetic and environmental factors. Analysis of a larger sample of patients will be needed to determine if the specific mutations are associated with a particular phenotype or predisposition to the common features of CVID and IGAD: autoimmunity, lymphoproliferation, or malignancy.

Animals↗

PubMed1982

Map position of Igh-Oxa gene within the Igh region of the DBA/2 mouse strain.

Mice of 23 BXD recombinant inbred strains derived from the cross of C57BL/6J and DBA/2J were typed for the presence of a public idiotype found in the antibodies against the hapten phenyloxazolone (phOx) produced by DBA/2 mice. The marker is under the control of an immunoglobulin heavy-chain variable region gene, Igh-Ox. Eleven out of the 23 BXK strains shared the public idiotype with the DBA/2 progenitor, while 12 other BXD strains were negative, like the C57BL/6 progenitor. The Igh-Ox marker was inherited concordantly with allotype in all BXD strains except BXD-27, which carries the Igh-1c allotype of DBA/2 but lacks the Igh-Ox idiotype. The Igh-Ox marker was inherited concordantly with 4 other Igh-V markers (Igh-Np, Igh-Nb, Igh-Bgl, and Igh-Gte) in all BXD strains except BXD-20, which has the DBA/2 alleles at Igh-1 and Igh-Ox but resembles C57BL/6 at the other 4 markers. On the basis of these results the Igh-Ox marker is tentatively placed between Igh-C and the rest of the Igh-V markers.

Animals↗

PubMed1993

The use of RAPDs for the study of the genetic diversity of Schistosoma mansoni and Trypanosoma cruzi.

Arbitrary primers have been used for the production of complex, PCR generated DNA profiles in order to undertake a preliminary random amplified polymorphic DNA (RAPD) analysis of strains (and related species) of two parasitic organisms that are responsible for important diseases endemic in Brazil: Schistosoma mansoni that causes schistosomiasis, and Trypanosoma cruzi that causes Chagas' disease. A relatively low level of polymorphism was found in S. mansoni when strains isolated from different regions of Brazil were compared, with less than 10% of bands exhibiting polymorphism. Comparison of different schistosome species, on the other hand, showed them to be distantly related with very few bands shared by even the more closely related species. Trypanosome strains were found to be much more variable. When strains were compared between zymodemes (groups of parasite strains with the same isoenzyme profiles), a maximum of 7% of bands were found to be common whereas among strains in the same zymodeme a clear characteristic pattern was observed. In the zymodeme most thoroughly studied, it was found that 59% of bands were shared. Band sharing analysis showed that the relationships of strains within a zymodeme correlate with their geographical origin and that the relationship between zymodemes correlates closely with that previously determined by isoenzyme analysis. These preliminary data indicate the ready applicability of RAPD analysis to the study of parasites where largely unexplored genetic variations may have an important bearing on the complexity and diversity of diseases.

Animals↗