[Does infusion therapy in trained patients with intermittent claudication have advantages?].
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Alprostadil↗
Biomedical subjects
E Hsu
Publications and source records attributed to E Hsu.
IgH enhancer-mediated deregulation of N-myc gene expression in transgenic mice: generation of lymphoid neoplasias that lack c-myc expression.
We have generated transgenic mouse lines that carry one of three different constructs in which the murine N-myc gene is expressed under the control of the immunoglobulin heavy chain transcriptional enhancer element (E mu-N-myc genes). High-level expression of the E mu-N-myc transgenes occurred in lymphoid tissues; correspondingly, many of these E mu-N-myc lines reproducibly developed pre-B- and B-lymphoid malignancies. The E mu-N-myc transgene also appeared to participate in the generation of a T cell malignancy that developed in one E mu-N-myc mouse. These tumors and cell lines adapted from them expressed exceptionally high levels of the E mu-N-myc transgene; the levels were comparable to those observed in human neuroblastomas with highly amplified N-myc genes. In contrast, all of the E mu-N-myc cell lines had exceptionally low or undetectable levels of the c-myc RNA sequences, consistent with the possibility that high-level N-myc expression can participate in the negative 'cross-regulation' of c-myc gene expression. Our findings demonstrate that deregulated expression of the N-myc gene has potent oncogenic potential within the B-lymphoid lineage despite the fact that the N-myc gene has never been implicated in naturally occurring B-lymphoid malignancies. Our results also are discussed in the context of differential myc gene activity in normal and transformed cells.
Animals↗
Evolution of immunoglobulin genes: VH families in the amphibian Xenopus.
We have isolated multiple independent cDNA clones that represent mRNA sequences of immunoglobulin heavy chains from the spleen of adult Xenopus laevis. These cDNA clones contained constant (C) region sequences that were either Cmu or a separate C region sequence believed to be Cnu. In individual cDNA clones the C region sequences were associated with independent heavy-chain variable region (VH) sequences that were classifiable into five distinct families. Genomic Southern blotting analyses with family-specific probes indicated that the haploid genome contains a minimum of 80 VH gene segments, a number similar to that found in various mammalian species. Multiple JH and putative DH segments were also identified (J, joining; D, diversity). Analyses of 13 independent VHDJH junctions suggest that combinatorial and junctional diversification mechanisms probably arose early in vertebrate evolution. Finally, comparison of Xenopus VH sequences to those from other vertebrates indicated conservation of V region framework residues that are responsible for the tertiary structure of the Fv throughout evolution.
Amino Acid Sequence↗
Prevalence and significance of mild bleeding disorders in children with recurrent epistaxis.
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Adolescent↗
Hemoglobin E: a common hemoglobinopathy among children of Southeast Asian origin.
With the recent immigration of Southeast Asians to Canada, hemoglobin E has become a frequent diagnosis. The clinical and hematologic findings in 42 children (mean age 4.3 years) with hemoglobin E are presented. There were 33 heterozygotes (having hemoglobin E trait), 6 homozygotes (having hemoglobin EE) and 3 double heterozygotes (having hemoglobin E-beta-thalassemia). The heterozygotes had low-normal hemoglobin levels and mean corpuscular volumes; coexisting iron deficiency, present in 62% of these children, resulted in substantially lower hemoglobin levels, very low mean corpuscular volumes and lower than expected levels of hemoglobin E on electrophoresis. The children with hemoglobin EE were only slightly anemic, but those with hemoglobin E-beta-thalassemia had severe anemia and required long-term transfusion therapy. Nutritional factors and parasitic infestations were the main causes of iron depletion, which was common, particularly in children less than 2 years old (87%). Physicians of patients of Southeast Asian origin should be aware of the clinical and hematologic presentation of these hemoglobinopathies.
Adolescent↗
Aspergillus-related aortic thrombosis.
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Aorta, Thoracic↗
Systemic lupus erythematosus and sickle hemoglobinopathies: a report of two cases and review of the literature.
Two adolescent black females with sickle cell disease who developed systemic lupus erythematosus (SLE) are presented. The recognition of SLE was delayed because all new symptoms were initially attributed to their underlying sickle cell disease. Nine similar cases have been previously reported. The hypothesis that a deficiency of the alternative complement pathway in some patients with sickle hemoglobinopathies predisposes them toward immune complex disorders was not confirmed in our study. Our first patient had normal and our second increased activity of the alternative pathway of complement activation.
Adolescent↗
Neutrophilic eccrine hidradenitis in acute myelomonocytic leukemia.
Neutrophilic eccrine hidradenitis is a rare but distinct dermatosis that has recently been described in adults with acute myelogenous leukemia. We report the first pediatric case in an 11-year-old girl with acute myelomonocytic leukemia who developed this eruption following her first and second course of VAPA-10 induction chemotherapy. Skin biopsy revealed selective neutrophilic infiltration around the eccrine coils, which is characteristic of this dermatosis. The clinical and biopsy findings of our patient are presented and compared with the previous three reported cases.
Antineoplastic Combined Chemotherapy Protocols↗
Major histocompatibility complex-encoded class I molecules are absent in immunologically competent Xenopus before metamorphosis.
The expression of class I and class II major histocompatibility complex (MHC)-encoded antigens has been examined at various stages of the development of the clawed frog, Xenopus. By immunoprecipitation with alloantisera or xenoantisera from radio-labeled spleen and thymus lysates, and by mixed lymphocyte reaction analysis, it was determined that the same class II molecules are expressed throughout ontogeny. In contrast, by fluorescence on frozen sections of tadpoles and by immunoprecipitation, the class I molecule is not detected in tadpoles, but appears on all tissues at the climax of metamorphosis. Animals maintained as tadpoles for long periods of time by chemical treatment do express class I antigens; thus, their expression can be independent of other biochemical and morphological changes that occur at metamorphosis. Immunofluorescence detects an otherwise uncharacterized MHC-linked alloantigen on tadpole thymic epithelium from the earliest stages of thymus differentiation.
Animals↗
Regulation of renal sulfoglycolipid biosynthesis.
The in vitro activity of the renal galactolipid sulfotransferase and the level of sulfated glycolipids in the rat kidney have been correlated as a function of age. The galactolipid sulfotransferase was found to be greatly reduced in the young as compared with the adult animal. The relatively minor changes in the sulfated glycolipid content of the kidney with age suggests that an increase in sulfoglycolipid turnover occurs during growth. An inhibitory activity was detected in the homogenate supernate of the young animal capable of reducing the in vitro sulfotransferase activity of the adult. Assay of the human renal galactolipid sulfotransferase showed that this enzyme activity is deleted in samples of the blastematous form of Wilm's renal tumor. The results suggest that the rate of synthesis of renal sulfoglycolipids may prove a marker of renal development, perhaps by post translational regulation.
Aging↗
Anti-IgM treatment influences immunoglobulin heavy and light chain mRNA levels in mitogen-stimulated B lymphocytes.
The mechanism by which soluble anti-IgM inhibits plaque formation by lipopolysaccharide-stimulated B cells was investigated. Since lower amounts of immunoprecipitable mu heavy and kappa light chains were found in cell lysates, this indicated that soluble anti-IgM was inhibiting not only secretion. Subsequently, Northern blot analysis of poly(A+) RNA showed that the steady state levels of mRNA for immunoglobulin heavy and light chain from B cells stimulated with lipopolysaccharide were reduced if the cultures were treated with soluble anti-IgM. The steady-state levels of class I major histocompatibility complex antigen RNA were unaffected by anti-IgM treatment. Addition of supernatants from mouse spleen cells stimulated with concanavalin A at day 2 of culture partially reversed the effect of soluble anti-IgM on immunoglobulin expression.
Animals↗
A third immunoglobulin class in amphibians.
A new class of immunoglobulin (IgX) has been found in the South African frog, Xenopus laevis, and other related species. IgX can be immunoprecipitated by monoclonal antibodies directed against determinants found on Xenopus light chain, or on variable regions of heavy chains. Reagents specific for the heavy chain of IgM or the amphibian IgG equivalent, IgY, failed to react with IgX. IgX, which exists in serum as a polymer, is composed of subunits of disulfide-bonded heavy chains of 80,000 daltons and light chains of 25,000 to 29,000 daltons. Like mu, the heavy chain of IgX carries a large amount of asparagine-linked carbohydrate, but the partial peptide maps of the two are different. Although the concentration of IgX varies greatly in the serum of individual frogs, it is always secreted in cultures of cells from the spleen and intestinal mucosae.
Animals↗
Evaluation of a simple immunodiffusion technique for quantitation of platelet-associated immunoglobulin G in childhood immune thrombocytopenias.
Platelet-associated IgG (PAIgG) was quantitated in 33 children with immune thrombocytopenia and platelet counts less than 100 X 10(9)/liter using a simple radial immunodiffusion (RID) assay. Elevated PAIgG levels were found in 76% (16/21) of children with acute idiopathic thrombocytopenic purpura (ITP), 88% (7/8) of children with chronic ITP, and all four children studied with systemic lupus erythematosus and thrombocytopenia. Normal PAIgG values were found in children with the following disorders: malignancy and chemotherapy-related thrombocytopenia; ITP in remission (platelet counts greater than 150 X 10(9)/liter); various nonimmune hematologic disorders and juvenile rheumatoid arthritis, these children having normal platelet counts. In children with acute ITP, elevated PAIgG values at initial presentation fell to within the normal range when clinical remission occurred. The RID assay can be easily established in most hematology laboratories and has the advantage that solubilized "test" platelets used in the assay can be stored frozen prior to analysis. We conclude that this simple technique is of value in the evaluation of childhood thrombocytopenic states and yields results comparable to those reported using more complex antiplatelet antibody assays.
Adolescent↗
Studies on Xenopus immunoglobulins using monoclonal antibodies.
Monoclonal antibodies raised against Xenopus Ig recognize antigenic determinants on IgM and low mol. wt Ig (LMW Ig or IgY ). On SDS-PAGE two forms of mu were distinguished in the supernatant and cell lysate of tunicamycin-treated spleen cell culture. The two bands of v observed in serum appear to be the result of carbohydrate heterogeneity. The light chains resolved into two distinct bands which differed in peptide maps; the more slowly migrating band of light chain was preferentially associated with v. Patterns of cross-reactivity between the immunoglobulins of 11 species of Xenopus and three subspecies of Xenopus laevis were obtained; the polymorphism of mu and v antigenic determinants and its implications for species divergence are discussed.
Animals↗
Immunoglobulin expression in diploid and polyploid interspecies hybrid of Xenopus: evidence for allelic exclusion.
The expression of species-specific surface IgM was studied in various Xenopus species hybrids. Whether the hybrids are diploid or polyploid, a lymphocyte does not produce all of the immunoglobulins (Ig) encloded by the Ig genes present in its genome. This suggests that the selection pressure to make a lymphocyte synthesize only one antibody is high and that allelic exclusion already existed in the ancestors of amphibians which appeared 300 million years ago. The apparent lack of cells producing multiple Ig in polyploid hybrids having more than one pair of functional Ig genes suggests that if a stochastic model for allelic exclusion is correct, the frequency of multiple successful rearrangements has to be very low, resulting in a huge waste of lymphocyte precursors. Given the particularity of frog development it is argued that this is not likely to be the case.
Alleles↗
Clinical and laboratory diagnosis of hemostatic disorders in newborn infants.
We describe a microtechnology for the study of the coagulation system in newborn infants. Interpretation of results demands an understanding of the techniques used and the nature of the control population from which normal values are drawn. We have examined two syndromes which represent the majority of hemostatic disorders of sick newborn infants. The first is thrombocytopenia resulting from bacterial infections in which there are minimal changes in the levels of blood coagulation factors and little tendency to bleed. The second is a syndrome of disseminated intravascular coagulation in which there is a profound disturbance in the coagulation mechanism, relatively little change in platelet counts, a severe hemorrhagic diathesis, and widespread ischemic necrosis.
Bacterial Infections↗
Effector and regulator functions of splenic and thymic lymphocytes in the clawed toad Xenopus.
B cells in Xenopus, as characterized by surface immunoglobulin, nylon-wool adherence and ability to produce antibody in vitro, were found in both major lymphoid organs: 10-25% Ig-positive cells for spleen and 0.5-4% for thymus. The splenic and thymic B cells were able to produce specific antibody of both isotypes, IgM and low molecular weight (LMW) Ig (IgG equivalent). While for a T-cell-dependent antigen, DNP-KLH, both required T-cell help, thymic B cells for a specific antigen produced far more LMW Ig than splenic B cells. Thymic T cells had the same ability as splenic T cells to elicit an allogenic GvH, but with much less efficiency, probably as a result of fewer mature cells. In contrast to splenic T cells, thymic T cells provided little or no help for B cells and, in certain instances, demonstrated suppressor activity.
Animals↗
Mitogenic effects of phorbol myristate acetate (PMA) on amphibian cells.
Tumour promoter phorbol myristate acetate (PMA) stimulates and causes proliferation of cells from the spleen, thymus and peripheral blood of Xenopus laevis, the clawed toad. Phagocytic cells become activated and from foci of clustered cells. B cells blast and change membrane immunoglobulin (Ig) expression; a small portion go on to secrete Ig. The surface Ig-negative splenocyte population, which contains T cells, responds to PMA by active proliferation. Splenocytes, once stimulated by PMA, become refractory to further addition of PMA but respond instead to ConA. These results are discussed in the general context of the effect of PMA lymphocytes.
Animals↗