Play in two societies: pervasiveness of process, specificity of structure.

The present study compared Argentine (N = 39) and U.S. (N = 43) children and their mothers on exploratory, symbolic, and social play and interaction when children were 20 months of age. Patterns of cultural similarity and difference emerged. In both cultures, boys engaged in more exploratory play than girls, and girls engaged in more symbolic play than boys; mothers of boys engaged in more exploratory play than mothers of girls, and mothers of girls engaged in more symbolic play than mothers of boys. Moreover, in both cultures, individual variation in children's exploratory and symbolic play was specifically associated with individual variation in mothers' exploratory and symbolic play, respectively. Between cultures, U.S. children and their mothers engaged in more exploratory play, whereas Argentine children and their mothers engaged in more symbolic play. Moreover, Argentine mothers exceeded U.S. mothers in social play and verbal praise of their children. During an early period of mental and social growth, general developmental processes in play may be pervasive, but dyadic and cultural structures are apparently specific. Overall, Argentine and U.S. dyads utilized different modes of exploration, representation, and interaction--emphasizing "other-directed" acts of pretense versus "functional" and "combinatorial" exploration, for example--and these individual and dyadic allocentric versus idiocentric stresses accord with larger cultural concerns of collectivism versus individualism in the two societies.

Wegener's granulomatosis: role of environmental exposures.

OBJECTIVE: The etiology of Wegener's granulomatosis (WG) remains unknown. The predominant involvement of the airways and the presence of neutrophilic alveolitis at disease onset have led us to postulate that an inhaled agent may trigger the onset of WG. This study is designed to analyze differences in self-reported environmental exposures between patients with WG and various control populations. METHODS: We conducted a standard interviewer-administered questionnaire case controlled survey of 101 patients with WG, 54 healthy controls, 24 patients with sarcoidosis or idiopathic pulmonary fibrosis, and 45 patients with various inflammatory rheumatologic diseases. We assessed environmental exposures for one year prior to the onset of symptoms or prior to the interview date for healthy controls. RESULTS: Seasonal differences in the onset of WG were not apparent. More than 75% of the patients in all groups noted remarkable environmental exposure to inhaled substances (fumes or particulate matter), within one year prior to disease onset for WG and other diseases or prior to the interview date for healthy controls. Differences between WG and control groups were apparent in several categories of exposure. Statistically significant differences occurred in regard to a vocational exposure to fumes or particulate materials (WG > healthy controls and rheumatic disease controls), residential exposure to particulate materials from construction (WG > pulmonary disease controls) and occupational exposure to pesticides (WG > healthy, pulmonary and rheumatic disease controls). CONCLUSION: This study confirms the absence of seasonal differences in the onset of WG. It also demonstrates high rates of self-reported environmental exposures to inhaled substances in WG and all control populations. It is possible that more significant differences in the quality, quantity and intensity of exposure to inhaled potential precipitants of WG had occurred between groups, but were not detected by our survey. Alternatively, the absence of substantial differences in patients with WG and controls may reflect the more important role of host susceptibility factors.

A cross-national study of self-evaluations and attributions in parenting: Argentina, Belgium, France, Israel, Italy, Japan, and the United States.

This study investigated and compared ideas about parenting in Argentine, Belgian, French, Israeli, Italian, Japanese, and U.S. mothers of 20-month-olds. Mothers evaluated their competence, satisfaction, investment, and role balance in parenting and rated attributions of successes and failures in 7 parenting tasks to their own ability, effort, or mood, to difficulty of the task, or to child behavior. Few cross-cultural similarities emerged; rather, systematic culture effects for both self-evaluations and attributions were common, such as varying degrees of competence and satisfaction in parenting, and these effects are interpreted in terms of specific cultural proclivities and emphases. Child gender was not an influential factor. Parents' self-evaluations and attributions help to explain how and why parents parent and provide further insight into the broader cultural contexts of children's development.

Anti-mitochondrial M5 type antibody represents one of the serological markers for anti-phospholipid syndrome distinct from anti-cardiolipin and anti-beta2-glycoprotein I antibodies.

The aim of this study was to characterize the antigen specificity and to evaluate the diagnostic and prognostic value of anti-mitochondrial M5 type antibodies (AMA M5). Fifty-eight patients selected on the basis of their AMA M5 positivity were investigated in relationship to their clinical and serological profile. Cross-absorption studies, Western blotting and immunoprecipitation analysis were carried out for AMA M5 antigen specificity characterization. Most patients had a diagnosis of systemic lupus erythematosus (SLE) (65.5%) or of primary anti-phospholipid syndrome (PAPS) (24%); all the patients were positive for IgG or IgM anti-cardiolipin (anti-CL) antibodies and 49% of them also displayed lupus anticoagulant (LA) activity. Anti-beta2-glycoprotein I (beta2-GPI) IgG were detectable in 30/38 sera (78.9%) and IgM in 34/38 (89.4%). While anti-CL and anti-beta2-GPI IgG antibodies were significantly associated with history of thrombosis and fetal loss, AMA M5 displayed a statistical association only for thrombocytopenia and recurrent fetal loss. Absorption with human beta2-GPI both in free solution or in solid phase as well as with CL liposomes or CL/beta2-GPI liposome complexes did not affect AMA M5 fluorescence. While AMA M5 activity is absorbed by whole mitochondrial preparations, no specific reactivities against several human, bovine and rat mitochondrial proteins could be detected in Western blotting and immunoprecipitation studies. AMA M5 appear to be detectable in both primary and secondary APS, displaying a strong association with the presence of thrombocytopenia and fetal loss. Although strictly related to anti-phospholipid antibodies, AMA M5, anti-CL and anti-beta2-GPI antibodies represent distinct serological markers of the APS.

[Non-Hodgkin lymphoma in adults. Protein profile of CSF and serum in 25 patients]. / Linfoma não-Hodgkin em adultos. Perfil proteico do lcr e do soro de 25 doentes.

Twenty-five non-Hodgkin's adult patients of a cohort studied for detection of neurologic involvement were evaluated on the cerebrospinal fluid (CSF) protein profile. CSF and serum were collected in the same occasion. Blood-brain barrier and local synthesis of IgG were studied. There was an incidence of neurologic signs and symptoms in 48% of all patients. Samples analysis showed: increase of total protein in CSF in 52%; local synthesis of IgG in one HIV seropositive patient; IgG concentration increase in the CSF in the absence of malignant cells in the CSF in two patients that clinically improved after chemotherapy; oligoclonal bands only in the CSF in one HTLV-I seropositive patient. These data show that the study of CSF protein profile can contribute in the characterization of CNS involvement in non-Hodgkin lymphoma.

From cell lineage to developmental genetics.

One of the bases of developmental genetics resides in the alliance of clonal analysis and genetic analysis. But the study of cell lineage--cells which have their genealogical relationship--and the study of the cellular labelled progeny, have their own history. We have tried to follow it since its foundation with C.O. Whitman (1878) and E.B. Wilson (1892). A.H. Sturtevant (1929) and C. Stern (1936) the first tools to study the 'cell lineage' in Drosophila. We stress the contribution of the pioneer work realised around 1940. In the following period we witness the emergence of developmental genetics in Drosophila mainly with E. Hadorn (1949-1966), C. Stern (1954-1968) and E.B. Lewis (1963-1964). We conclude with A. Garcia-Bellido's view of compartments: supra-cellular units of development (1973). A postscript presents the most recent publications and some critical focuses.

Immunopathogenesis of gastrointestinal and hepatobiliary diseases.

The largest lymphoid organ in the body is the gut and the gut-associated lymphoid tissue. The mucosal immune system faces many challenges in protecting the body from microbial invasion. Its chief function is to maintain a diverse population of mature lymphocytes capable of responding to foreign antigens. This task is accomplished with a variety of unique features that distinguish the mucosal from the systemic immune system. In addition, the mucosal immune system plays a role in inflammatory bowel disease, Whipple disease, autoimmune gastritis, Helicobacter pylori infection, immunoproliferative small intestinal disease, hepatitis A, B, C, D, E, F, and G, autoimmune hepatitis, primary biliary cirrhosis, progressive sclerosing cholangitis, and vanishing bile duct syndrome.

Use of recombinant proteins in the diagnosis of autoimmune connective tissue diseases.

The use of recombinant proteins has been an invaluable tool for the study of the structure and function of cell components, and the analysis of autoimmune-mediated responses. Furthermore, it has also been instrumental in facilitating the development of reliable assays for the detection of a number of autoantibodies. This article discusses basic aspects of recombinant DNA technology, as well as its applications and limitations in the diagnosis of autoimmune connective tissue diseases such as systemic lupus erythematosus, Sjogren's syndrome, systemic scleroderma, mixed connective tissue disease, autoimmune inflammatory myopathies and primary vasculitides.

Inhibition of PDC-E2 human combinatorial autoantibodies by peptide mimotopes.

Immunohistochemical studies have shown that a unique immunoreactive molecule is present near the apical region of human biliary epithelial (BE) cells in patients with primary biliary cirrhosis (PBC). This can be visualized by confocal microscopy in PBC livers using a number of unique monoclonal antibodies to the E2 component of pyruvate dehydrogenase complex (PDC-E2), the autoantigen most commonly recognized by antimitochondrial antibodies (AMA). One such antibody, the murine mAb C355.1 was used to identify peptide mimotopes of PDC-E2 by screening a random dodecapeptide phage library ON 159.2 to identify the possible biochemical nature of this apical staining molecule. Out of 36 independent clones, 29 showed a common sequence and seven other sequences were singly represented. Three common amino acid motifs (SYP, TYVS and VRH) were found among these eight sequences. Similar to C355.1, the human combinatorial antibodies derived from a patient with PBC, SP1 and SP4, recognize the inner lipoyl domain of PDC-E2. However, when these antibodies are used to stain PBC BE cells, SP4 stains the apical region of PBC BE cells with high intensity whereas SP1 produces only cytoplasmic staining. Competitive inhibition of immunohistochemical staining using PDC-E2 specific human combinatorial antibodies SP1 and SP4 was performed using five of the above dodecapeptides. Interestingly, the peptides selected with C355.1 differentially inhibited the binding of SP1 and SP4 to PBC BE cells. Finally, rabbit sera raised against one such peptide (WMSYPDRTLRTS) stained BE cells from patients with PBC with a higher intensity than controls. Comparable data was obtained with immunoelectronmicroscopy. These data suggest that a molecular mimic of PDC-E2 is present at the external aspect of PBC BE cells.

Immunopathology of primary biliary cirrhosis.

Our understanding of the immunopathology of PBC has dramatically changed with the application of molecular biology techniques in clinical medicine. This has allowed, not only the possibility of characterizing mitochondrial autoantigens fully at the molecular level, but also the identification of specific sites on these molecules that are targetted by autoreactive B and T cells. In addition, the expression of cloned antigens has facilitated the development of the most reliable assays currently available for the detection of mitochondrial autoantibodies. The assessment of the pathogenic capacity of autoreactive T cells, as well as the characterization the PDC-E2 'look alike' molecule expressed on the cell membrane of PBC biliary epithelial cells, remain the major unsolved issues in this disease. Ideally, the continuous effort from both basic and clinical scientist in understanding the pathogenic mechanisms of PBC will lead to more specific, effective, and safer modalities of treatment.

Anti-neutrophil cytoplasmic antibodies in patients with chromomycosis.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are a family of antibodies that react to proteins within neutrophil granules and monocyte lysosomes, and occur prominently in sera from patients with systemic necrotizing vasculitis. The cytoplasmic staining pattern (c-ANCA) is very sensitive and specific for Wegener's granulomatosis (WG), and most commonly results from reactivity with proteinase 3 (PR3). The features of tissue damage in the fungal infection chromomycosis, in particular polymorphonuclear neutrophil (PMN) infiltration and granuloma formation, bear a resemblance to that seen in WG. METHODS: We tested sera from 25 patients with clinical and histologic diagnosis of chromomycosis for the presence of ANCA by indirect immunofluorescence. These same sera were analyzed for reactivity to neutrophil primary granule extracts and PR3 by ELISA. RESULTS: Five of the 25 patients (20%) had detectable c-ANCA, without central accentuation, at serum dilutions of at least 1:40. Three of these 5 ANCA-positive patients reacted with neutrophil primary granule extracts by ELISA; however, none of them reacted with PR3. CONCLUSIONS: These results demonstrate that fungal infection should be included among the conditions, unrelated to necrotizing vasculitis, that can trigger autoreactivity against myeloid lysosomal antigens.

Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex.

Five different target mitochondrial autoantigens recognized by sera from patients with primary biliary cirrhosis (PBC) have been identified as subunits of the following 2-oxo acid dehydrogenase complexes: the pyruvate dehydrogenase complex (PDC), the branched chain 2-oxo acid dehydrogenase complex (BCOADC), and the 2-oxoglutarate dehydrogenase complex (OGDC). Unlike the E2 subunits of PDC (PDC-E2) and BCOADC (BCOADC-E2), the E2 subunits of OGDC (OGDC-E2) reactivity of PBC sera and the reactive epitope of OGDC-D2 have not hitherto been studied in detail. In this report, we took advantage of a recombinant fusion protein for OGDC-E2 to address these issues. Eighty of 268 (29.9%) PBC patient sera but none of the 45 controls reacted with recombinant OGDC-E2. The recombinant OGDC-E2 was judged to express the immunodominant epitope, because when sera from patients with PBC were preabsorbed with the recombinant fusion protein, such sera were depleted of reactivity against 48 kD OGDC-E2 when probed on beef heart mitochondria (BHM) but retained reactivity toward PDC-E2 and/or BCOADC-E2. Furthermore, affinity-purified PBC sera against recombinant OGDC-E2 reacted only with native OGDC-E2 and not with any other enzyme components of the 2-oxo acid dehydrogenase complex. Antimitochondrial autoantibodies (AMA) against OGDC-E2 included immunoglobulin (Ig)G2, IgG3 and IgM and the relative titers were as follows: IgG2 > IgG3 > IgM. Finally, using overlapping recombinant polypeptides, it was determined that a minimum of 81 amino acids (residues 67-147) corresponding to the lipoyl domain of OGDC-E2 are necessary for reactivity, suggesting that a conformational autoepitope is recognized by AMA. These data suggest that each of the 2-oxo acid dehydrogenase enzymes has distinct antigenicity despite their similarities in structure and function. The availability of recombinant OGDC-E2 autoantigen will allow the design of additional studies to further our understanding of the role of mitochondrial autoantigens in the pathogenesis of PBC.

Immunoreactivity of antimitochondrial autoantibodies in Japanese patients with primary biliary cirrhosis.

The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined sera from 107 patients with primary biliary cirrhosis from three geographically different regions of Japan. The sera were assayed by immunofluorescence on frozen tissue sections, immunoblotting on bovine heart mitochondria and recombinant E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2), ELISA using recombinant E2 subunit of human pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxoglutarate dehydrogenase complex (OGDC), and enzyme inhibition assay using procine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofluorescence, 102 (95%) by immunoblotting with at least one of the M2 autoantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by ELISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immunoblotting and ELISA against 2-OADC enzymes other than PDC was relatively higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Japan. The different autoantibody profiles for Japanese and Caucasian patients with primary biliary cirrhosis point to immunogenetic and environmental determinants of this disease, which should provide new insights into its autoimmune origins.

Molecular biology of autoantigens in rheumatic diseases.

The advent of molecular biologic techniques has provided new approaches that are of great utility to the study of autoimmune-mediated responses. In the past few years, there has been a remarkable accumulation of knowledge concerning the molecular identity and function of autoantigens, and further consolidation for the use of autoantibodies as diagnostic markers in clinical rheumatology. The understanding of basis methodologies in molecular biology applied to the study of autoantigens, in particular, techniques for cloning and analyzing genes that are important in rheumatic diseases, is valuable for both basic scientists and clinicians interested in diagnostic and prognostic markers of various connective tissue diseases.

Wegener's granulomatosis.

To manage Wegener's granulomatosis (WG) effectively, the clinician must establish the diagnosis without delay, recognize variability in clinical course and severity, critically monitor disease activity, and anticipate disease-related and treatment-related morbidity. These issues represent the focus of approach to the diagnosis and treatment of WG.

Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis and other diseases: clinical issues.

BACKGROUND: An association between antineutrophil cytoplasmic antibodies (ANCA) and nonimmune complex-mediated glomerulonephritis was first reported over 10 years ago. In Wegener's granulomatosis, the antibody usually binds proteinase 3. Antibodies to a variety of other antigens have been identified in a broad range of diseases. SUMMARY: The typical coarse, granular cytoplasmic ANCA pattern on indirect immunofluorescence almost always indicates reactivity with proteinase 3, whereas the perinuclear ANCA pattern may reflect reactivity with a host of different antigens. Antibodies to proteinase 3 are overwhelmingly associated with Wegener's granulomatosis (specificity > or = 90%). In a significant number of patients, however, disease activity is not linked to an ANCA titer. ANCA may play a role in the pathogenesis of many types of inflammatory conditions. Antibodies to proteinase 3 may be important in predisposing to Wegener's granulomatosis, but definitive in vivo proof of their role is not yet available. KEY POINTS: The presence of cytoplasmic ANCA in a patient who is suspected to have Wegener's granulomatosis is strong circumstantial evidence in support of that diagnosis. However, it does not represent absolute proof and should be viewed with skepticism if the clinical presentation is atypical. Conversely, a negative ANCA in the setting of a typical presentation should not rule out Wegener's granulomatosis. Because ANCA titers may not always vary in tandem with disease activity, the decision to modify therapy for Wegener's granulomatosis should continue to be based on clinical judgment.

[Virus, provirus and cancer]. / Virus, provirus et cancer.

Our purpose here is to retrace the history of the concept of prophage, to show how it expands into that of the episome and provirus. Its prehistory is that of lysogeny. We stress the relations between heredity and infection, the discovery of a non infectioius phase of the phage. André Lwoff is responsible for the concept of prophage. We then examine the research, discoveries and interpretations of François Jacob, Elie Wollman, William Hayes and Joshua Lederberg.