Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte

A human erythrocyte membrane glycoprotein of 205,000 mol wt (gp205) has been identified as the C3b receptor of the erythrocyte, polymorphonuclear leukocyte (PMN), B lymphocyte, and monocyte. Initially, gp205 was sought and characterized as a constituent of the human erythrocyte membrane that can impair activation of the alternative complement pathway by inducing loss of function of the properdin-stabilized amplification C3 convertase (C3b,Bb,P) through displacement of Bb from C3b and by promoting cleavage-inactivation of C3b by C3b inactivator. These inhibitory activities of gp205 suggested that this membrane glyeoprotein had an affinity for C3b and prompted an analysis of its possible identity as the C3b receptor of human peripheral blood cells. The F(ab’)2 fragment of rabbit IgG anti-gp205 inhibited the formation of rosettes with sheep EC3b of human erythroeytes, B lymphocytes, monocytes and PMN in a dose-response manner; the 50 percent inhibitory doses were 0.13/μg/ml, 0.90 μg/ml, 1.25 μg/ml, and 1.20 μg/ml of F(ab’)2, respectively. Anti-gp205 did not impair the formation of rosettes by monocytes and B lymphocytes with sheep EC3bi or with EC3d. Scatchard analysis of the number of specific (125)I-F(ab’)(2) anti-gp205 binding sites/cell revealed 950 sites/erythrocyte, 21,000 sites/cell of B lymphocyte preparation, 57,000 sites/PMN, and 48,000 sites/monocyte, indicating that the higher concentrations of antibody that had been required for inhibition of rosette formation by the nucleated cells reflected larger numbers of receptors on these cells. Direct evidence for the identity of gp205 as the C3b receptor of the four cell types was obtained when detergent-solubilized membrane proteins of the surface-radioiodinated cells were reacted with anti- gp205 and the immunoprecipitate was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. In each instance, the antigenic material reacting with anti-gp205 represented a single protein with an apparent 205,000 mol wt. Thus, gp205 is the C3b receptor of human erythrocytes, PMN, B lymphocytes, and monocytes.     

Planning for children whose parents are dying of HIV/AIDS. American Academy of Pediatrics. Committee on Pediatric AIDS, 1998-1999

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.     

Morphological and molecular characteristics of living human fetuses between Carnegie stages 7 and 23: immunolocalization of inhibin {alpha} and {beta}a subunits

Transforming growth factor (TGF) is known to have the abilityto modify mitogenic responses of tissues to other peptide growthfactors and therefore may contribute to the rapid growth rateof an embryo. Throughout the TGF superfamily there is a similarfundamental molecular architecture. Included in this superfamilyare inhibin A, activin A and activin B. It has been shown thatactivin is a powerful mesodermal inducing factor in the earlyembryo. The human embryo has shown localization of inhibin inthe gonads after 16 weeks gestation but it has not been previouslyidentified in earlier embryos. The inhibin-activin protein wasfound in a range of tissues including the liver stages 19-21() and stages 19-22 (ß); oesophagus stages 19-22 (and ß); stomach stages 21 and 22 ( and ß);gut stages 16-22 () and 21 and 22 (ß); pericardiumstages 12-22 ( and ß); gonad stages 21 and 22 (ß)stage 22 (); adrenal stages 19-22 ( and ß); urogenitalsystem states 21 and 22 ( and ß); yolk sac stage 12( and ß); mesenchyme stages 16-22 (); surface ectodermstages 13-22 () and stages 16-22 (ßa); notochord stages13-22 (ß) and stages 21 and 22 (); nasal, tracheaand bronchi stages 19-22 ( and ß) leading to speculationof the role of both subunits.     

Morphological and molecular characteristics of living human fetuses between Carnegi stages 7 and 23: localization of inhibin mRNA {alpha} and {beta}a subunits by in-situ hybridization

Localization of the mRNA and ßa subunits of inhibinhas previously been reported in the human gonads during thesecond trimester. Adrenal inhibin has also been reported inthe second trimester for the ßa and ßbsubunits. Investigations showing localization by in-situ hybridizationduring the first trimester have not been reported. The resultshave shown hybridization of the and ßa subunits,throughout the period of development studied, in a variety oftissues including the dorsal and thoracic aortas and pericardiumstages 13-22 (ßa subunit); liver stages 19-21 (ßa)and stages 21-22 (); mesonephros stages 21 and 22 (ßa);gonad stages ( and ßa); adrenal stages 19-22 (); surfaceectoderm stages 16-22 (ßa); mesenchyme stages 16-22(ßa); amnion stages 13-16 (ßa); yolk sacstage 12 ( and ßa); cartilage stages 19-22 (ßa);and nasal proliferation stages 21 and 22 (ßa). Whencompared with distribution of the protein subunits it was notedthat more immunostaining activity was found, suggesting thatprobes were not sufficiently sensitive enough to detect alllevels of mRNA expressed. It can be surmised, therefore, thatthe lack of visual hybridization of the mRNA cannot precludethe possibility that it is not being translated within the tissueeven though hybridization was not apparent.     

Progesterone receptor subtype B is differentially regulated in human endometrial stroma

Two anti-progesterone receptor (PgR) antibodies, a new one specific to PgRB, the other to PgR subtypes A + B, have been used to examine the cellular location of PgR subtypes A and B in normal endometrium throughout the menstrual cycle and in early human decidua by standard immunohistochemical techniques. PgR(A+B) is the receptor detected by the antibody recognizing both isoforms of the receptor. PgRB is the receptor detected by the new antibody specific to the B isoform. Since it is not possible to raise antibody specific to PgR subtype A, all immunohistochemical analysis of the PgRA subtype is by subtractive inference. Thus we refer to PgRA as the subtype responsible for positive immunoreactivity when the PgRB subtype cannot be specifically detected. Endometrial biopsies were collected from 40 women with regular menses (n = 5 each stage of cycle: menstrual; early, mid and late proliferative; ovulatory; early, mid, and late secretory). Decidual tissue was obtained from 10 women undergoing first trimester surgical termination of pregnancy. As previously reported, the PgR(A+B) antibody stained glandular and stromal nuclei during the proliferative phase but only stromal nuclei during the secretory phase and early pregnancy. The new PgRB antibody also stained both cell types intensely during the proliferative phase, but failed to stain either stromal or glandular nuclei strongly during the secretory phase and early pregnancy. We concluded that, while both PgR subtypes were present in glands and stroma in the proliferative phase, and both subtypes were dramatically reduced in the glands during the secretory phase, PgRA remained as the predominant type in the stroma during the secretory phase and early pregnancy. The profound effects of progesterone on endometrium during the secretory phase and early pregnancy appear to be mediated primarily by PgRA in the stroma.      

Linkage studies of non-syndromic recessive deafness (NSRD) in a family originating from the Mirpur region of Pakistan maps DFNB1 centromeric to D13S175 [published erratum appears in Hum Mol Genet 1996 May;5(5):710]

Autosomal recessive non-syndromal hearing impairment (NSRD) is genetically heterogeneous. Five loci have been identified to date which map to chromosomes 13 (DFNB1), 11 (DFNB2), 17 (DFNB3), 7 (DFNB4) and 14 (DFBN5). We report definite linkage of NSRD to the locus DFNB1 in a single family of 27 families studied of Pakistani origin. Haplotype analysis of markers in the pericentromeric region of chromosome 13q revealed a recombination event which maps DFNB1 proximal to the marker D13S175 and in the vicinity of D13S143.      

炎症性肠病的癌变预防及氨基水杨酸类制剂的潜在化学预防作用

虽然炎症性肠病(IBD)最终发展为结直肠癌的概率较低,但IBD相关性结直肠癌一直被认为是最令人担忧的并发症.近年来,该领域进展颇多,如确定了癌变的危险因素,癌症预防相关研究的证据日益增多.目前认为IBD发展为结直肠癌的最大危险因素是疾病持续时间,成功的预防策略应包括对这些远期结局进行早期干预.本文旨在综述该领域的最新进展,包括IBD相关性结直肠癌的流行病学特征、发病机制和化学预防,特别强调5-氨基水杨酸盐(5-ASA)疗法.     

Chimeric Receptors Containing CD137 Signal Transduction Domains Mediate Enhanced Survival of T Cells and Increased Antileukemic Efficacy In Vivo

Persistence of T cells engineered with chimeric antigen receptors (CARs) has been a major barrier to use of these cells for molecularly targeted adoptive immunotherapy. To address this issue, we created a series of CARs that contain the T cell receptor-ζ (TCR-ζ) signal transduction domain with the CD28 and/or CD137 (4-1BB) intracellular domains in tandem. After short-term expansion, primary human T cells were subjected to lentiviral gene transfer, resulting in large numbers of cells with >85% CAR expression. In an immunodeficient mouse xenograft model of primary human pre-B-cell acute lymphoblastic leukemia, human T cells expressing anti-CD19 CARs containing CD137 exhibited the greatest antileukemic efficacy and prolonged (>6 months) survival in vivo, and were significantly more effective than cells expressing CARs containing TCR-ζ alone or CD28-ζ signaling receptors. We uncovered a previously unrecognized, antigen-independent effect of CARs expressing the CD137 cytoplasmic domain that likely contributes to the enhanced antileukemic efficacy and survival in tumor bearing mice. Furthermore, our studies revealed significant discrepancies between in vitro and in vivo surrogate measures of CAR efficacy. Together these results suggest that incorporation of the CD137 signaling domain in CARs should improve the persistence of CARs in the hematologic malignancies and hence maximize their antitumor activity.