Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Hemorrhagic and nonhemorrhagic brain lesions: evaluation with 0.35-T fast MR imaging

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.     

The INVITTOX Data Bank of in-vitro techniques in toxicology.

The dissemination of information about methods in in-vitro toxicology is subject to a number of constraints which are identified and discussed, as are the ways in which INVITTOX seeks to address these problems. The continued interest of scientists in INVITTOX suggests that a real gap in information provision is being filled.     

Parietal cell surface reactive autoantibody in pernicious anaemia demonstrated by indirect membrane immunofluorescence.

We examined, in a 'double blind' study, 60 sera from patients with pernicious anaemia for immunofluorescence reactivity with the surface membranes of viable parietal cells isolated from dog stomachs. Fifty-three sera (88%) gave an IgG autoantibody reaction with the surface membranes of parietal cells. Surface staining was also seen with parietal cells from monkey, pig, rat and mouse. The parietal cell surface reactive autoantibody was not found in any of 14 sera from patients with chronic active hepatitis, 10 from patients with systemic lupus erythematosus and 50 from healthy persons. The surface reactivity autoantibody was present in 13 of 14 sera without parietal cell microsomal antibody, 28 of 31 sera without intrinsic factor antibody and in four of four sera without microsomal and intrinsic factor antibodies. Absorption with parietal cell enriched gastric mucosal cells neutralized the activity of the surface reactive but not the microsomal antibody and cross absorption with gastric microsomes neutralized the activity of the microsomal but not the surface reactive antibody. Surface staining of parietal cells was not abolished by absorption with dog or rat hepatocytes, dog or rat kidney cells, human fibroblasts or human AB red blood cells. The results suggest that the parietal cell surface reactive antibody is probably different from the microsomal antibody. Immune reactions of the cell surface reactive antibody with parietal cell surface antigens may play a role in the pathogenesis of the gastric lesion in pernicious anaemia.     

Quantification of specific antibody response to Cryptosporidium antigens by laser densitometry.

Cryptosporidium spp. is a protozoan parasite with worldwide distribution associated with diarrhea in immunocompromised patients (particularly those with acquired immunodeficiency syndrome [AIDS]) and in immunocompetent humans. Immunoglobulin M (IgM) and IgG antibody responses are readily detected by an enzyme-linked immunosorbent assay. To determine which Cryptosporidium antigens invoke antibody responses in humans, we performed polyacrylamide gel electrophoresis using purified oocysts, followed by Western blots with human sera from various populations. Of 40 sera from persons with cryptosporidiosis (24 AIDS and 16 non-AIDS patients), in 37 (93%) a 23,000-dalton antigen measured quantitatively by laser densitometry was recognized. Of 63 sera from IgM- or IgG-positive individuals, as determined by enzyme-linked immunosorbent assay, in 58 (92%) this same antigen was recognized. Up to three additional bands between 125,000 and 175,000 daltons were identified by some of these sera. These results suggest that most persons infected with Cryptosporidium spp. produce antibodies which recognize at least one common low-molecular-weight antigen. Isolation of this antigen will be useful in development of diagnostic tests and may be important in the study of immunity.     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

A Cross-Country Network Analysis of Adolescent Resilience

PurposeIn situations of adversity, young people draw on individual, relational, and contextual (community and cultural) resources to foster their resilience. Recent literature defines resilience as a capacity that is underpinned by a network of interrelated resources. Although empirical studies show evidence of the value of a network approach, little is known regarding how different country contexts influence which resources are most critical within a resource network and how resources interact for adolescent resilience.MethodsNetwork analysis was conducted with data from studies that had used the Child and Youth Resilience Measure. Regularized partial correlation networks of 17 resources were estimated for 14 countries (Botswana, Canada, China, Colombia, Equatorial Guinea, India, Indonesia, Italy, Jordan, New Zealand, the Philippines, Romania, South Africa, and Syrian refugees living in Jordan). The sample size was 18,914 (mean age = 15.70 years, 48.8% female).ResultsWe observed mostly positive associations between the resources of interest. The salience and strength of associations between resources varied by country. The most central resource across countries was having supportive caregivers during stressful times because this resource had the most and strongest positive associations with other resources.ConclusionsThis study gives first empirical evidence from multiple countries that an interplay of social–ecological resources (such as individual skills, peer, caregiver and community support, and educational aspirations and opportunities) matter for adolescent resilience. Across countries, caregiver support appears to be most central for adolescent resilience. Future resilience interventions might apply this network approach to identify important, contextually relevant resources that likely foster additional resources.