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A A Czitrom

Publications and source records attributed to A A Czitrom.

At least 19 recordsLinked to original sources

Analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft-tissue sarcomas.

We examined 43 sporadic bone and soft-tissue sarcomas for molecular genetic alterations affecting the retinoblastoma susceptibility gene Rb-1 (also known as RB1). The gene was altered in 6 of 14 sporadic osteosarcomas and in 5 of 29 other bone and soft-tissue sarcomas. Rb-1 messenger RNA (mRNA) transcripts were detected in normal tissues and benign lipomas, but they were absent or altered in each of the 19 sarcomas we examined. To examine the association of deletions in the Rb-1 gene with tumor grade, we correlated the DNA alterations in the Rb-1 gene with clinical data for 36 patients. The Rb-1 gene was altered in 40% of high-grade bone and soft-tissue tumors, but not in low-grade bone tumors and in only one low-grade, soft-tissue sarcoma. Overall, 10 of 25 high-grade sarcomas had detectable alterations of the Rb-1 gene compared with only 1 of 11 low-grade tumors.

Bone Neoplasms

Class I (H-2Kb) gene transfection reduces susceptibility of YAC-1 lymphoma targets to natural killer cells.

A "hybrid gene" (MTKb) comprised of the human metallothionein IIA promoter ligated to the genomic sequence of the major histocompatibility complex class I (H-2Kb) gene was subcloned into the expression vector pSV2neo and transfected into the natural killer (NK) cell-sensitive YAC-1 lymphoma. The Kb gene product was readily detectable on the cell surface of G418-resistant transfectants using both Kb-specific monoclonal antibodies and H-2b-specific cytolytic T cells. Unlike control pSV2neo transfectants, MTKb-pSV2neo transfectants were relatively resistant to lysis by NK cells from H-2a, H-2b, H-2k or H-2 (a x b)F1 haplotype mice. These data strongly suggest that the effects of MHC expression on susceptibility to NK cells can be mediated by a single and well-defined class I molecule, Kb.

Animals

The viability of articular cartilage in fresh osteochondral allografts after clinical transplantation.

The articular cartilage of four fresh osteochondral allografts was biopsied after transplantation, and its viability was studied by autoradiography. The biopsy specimens were labeled with both 3H-cytidine, for newly synthesized ribonucleic acid, and 35S-sulphate, for newly synthesized proteoglycans. The cartilage of a lateral humeral condylar graft at twelve months had 96 to 99 per cent labeled chondrocytes, the articular cartilage of a medial femoral condylar graft at twenty-four months showed 69 to 78 per cent labeled chondrocytes, and the cartilage of a medial tibial-plateau graft at forty-one months had 90 per cent labeled cells. At six years, a lateral tibial-plateau graft had 37 per cent labeled chondrocytes.

Adult

Measurement of grip strength in the diagnosis of wrist pain.

Grip strength was assessed in patients with chronic wrist pain and correlated with the results of subsequent bone scans and pathology. The results showed a highly significant decrease of grip strength in patients with positive bone scans or confirmed wrist pathology compared with those with negative bone scans (p less than 0.01). We conclude that the detection of weakness of grip is a simple indicator of true pathology in "obscure" wrist pain.

Adolescent

Bone banks and allografts in community practice.

The increasing volume of orthopaedic reconstructive procedures requiring replacement of bone stock justifies the initiation of programs of bone banking in community hospitals. Provided that strict criteria are followed to assure rigorous screening of donor bone and the reliable preservation of bone graft material, community banking is safe and cost-effective. Banked allograft bone can be used successfully in a wide variety of orthopaedic procedures performed in community hospitals. In general, the best uses are filling bone cavities, buttressing, and augmenting the quantity of autograft bone. In revision reconstructive surgery of the hip, bank bone is used to replace bone stock in protrusio, acetabular dysplasia, and proximal femoral deficiency. The best and most common indication for the use of bank bone in tumor surgery is after curettage or excision of benign lesions. Allografts may be used to reconstruct bony defects after excision of malignant tumors and in the surgical treatment of metastatic disease. These instances require larger bone bank facilities than those commonly available in a community hospital setting. Medicolegal considerations related to bone banking and the use of allografts in community practice include the regulatory requirements outlined in the UAGA, questions concerning negligence liability, and theories of strict product liability. Overall, good medical practice and obtaining informed consents will minimize legal risks related to bone banking and transplantation in a community setting.

Bone Transplantation

Granulocyte precursors are the principal cells in bone marrow that stimulate allospecific cytolytic T-lymphocyte responses.

Mouse bone marrow cells were fractionated and enriched for functional activity as stimulators of allospecific cytolytic T-lymphocyte (CTL) responses in vitro. The relevant stimulator cells were enriched sequentially in the low-density fraction of bone marrow, its 2-hr adherent and 18-hr non-adherent fractions and in the FcR-negative fraction of 18-hr non-adherent cells. The functionally enriched cell population contained over 90% granulocyte precursors by ultrastructural analysis. The results indicate that granulocyte precursors are the principal cells in bone marrow that stimulate alloreactive T-cell responses.

Animals

Ulnar variance in carpal instability.

Ulnar variance was measured in wrist conditions of patients with carpal instability and compared to values obtained from the assessment of normal wrist x-ray films. The results showed a significantly greater amount of negative ulnar variance in patients with scapholunate dissociations than in normal controls (t-test, p less than 0.0005; chi-square test, p less than 0.02). Ulnar variance in lunotriquetral dissociations and old scapholunate dissociations with arthrosis did not differ significantly from controls (p greater than 0.6). Posttraumatic scapholunate dissociations do correlate with negative ulnar variance.

Carpal Bones

Ontogeny of priming of cytotoxic T cells to minor alloantigens: the development of direct priming precedes that of cross-priming.

Cytotoxic T lymphocytes of heterozygous adult mice primed in vivo with minor alloantigens on cells of one parental H-2 genotype can be boosted in vitro to respond to minor alloantigens on cells of both the immunizing parental H-2 genotype (direct priming) and of the H-2 genotype of the other parent (cross-priming). We studied the ontogeny of this phenomenon and show that during early postnatal life the development of direct priming precedes that of cross-priming. The delayed maturation of cross-primed responses parallels the known development time sequence of functional antigen-presenting cells and provides evidence for the explanation of cross-priming in terms of antigen processing.

Aging

Case report 398.

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Adult

Analysis of HLA B27 in ankylosing spondylitis with human alloreactive cytolytic T lymphocyte clones: failure to detect disease-related T cell epitopes.

We have generated several human alloreactive cytolytic T lymphocyte (CTL) clones specific for HLA B27 expressed on cells of normals or of patients with ankylosing spondylitis (AS). These clonal T cell reagents were used to test the recognition of panels of target cells from B27+AS+, B27+AS- and B27- individuals. None of these CTL clones distinguished differences between B27+AS+ and B27+AS- cells. Three clones recognized subtypes of HLA B27 and two of these were cytolytic with group-reactive epitopes of other HLA antigens. The results suggest that there are no immunogenic disease-specific epitopes of HLA B27 in B27-linked spondyloarthropathy.

Clone Cells

Bone and cartilage allotransplantation. A review of 14 years of research and clinical studies.

The authors review their experience of over 14 years in the field of osteochondral allotransplantation. Experimental studies demonstrated the immunogenicity of bone and cartilage, immunosuppression in skeletal transplantation models, and a subset of myeloid cells within bone marrow with strong immunogenic properties. Clinical results of knee joint resurfacing with fresh small-fragment osteochondral allografts have been best in posttraumatic joints. Experience with allograft reconstructions of skeletal defects after tumor surgery has been gratifying as a limb salvage procedure. Microvascular fibular autografts have been an important adjunct in massive reconstructive osteochondral transplantation.

Animals

Stimulator requirements for primed alloreactive T cells: macrophages and dendritic cells activate T cells across all genetic disparities.

The cellular requirements for stimulating primed alloreactive T cells have been investigated. In vitro-primed secondary alloreactive cells, long-term lines, and Ly 1+2- noncytolytic clones which reacted with allo-H-2K, D, or Mls (M locus) antigens were tested. The data indicated that a specialized antigen-presenting cell such as a macrophage or a dendritic cell was required for stimulating primed alloreactive cells across all the genetic disparities tested. B and T lymphocytes were ineffective stimulators. The stimulator requirement for secondary and Ly 1+2- clone responses was heterogeneous, since both macrophages and dendritic cells were effective stimulators. Thus, the allostimulator requirement for inducing proliferation and mediator secretion by the primed T-cell populations closely paralleled the requirement for stimulating unprimed populations. The only exception found was the peritoneal washout population, which did not stimulate a primary response but did stimulate secondary responses. The failure of peritoneal macrophages to stimulate a primary response was shown to be due to an inhibitory pathway which did not occur when the responding population was alloantigen primed.

Animals

Characterization of stimulator cells for alloreactive cytotoxic-T-lymphocyte responses in vivo.

Mouse spleen cells were fractionated and tested for their ability to induce alloreactive cytotoxic-T-lymphocyte responses in vivo. The cells with allostimulatory potential are enriched maximally in a population of low density, Ig-negative, Thy 1-negative cells. This fraction has the cytochemical and ultrastructural characteristics of cells of the early myeloid series and not those of typical dendritic cells or macrophages. These myeloid cells represent a new subset of accessory cells which could be a potential source of allostimulation in organ grafts. They should be considered along with other accessory cell types as potential elements which induce transplantation responses.

Acid Phosphatase

The function of antigen-presenting cells in mice with severe combined immunodeficiency.

We have examined the antigen-presenting function of spleen cells in the C.B-17 scid mouse, a mutation that severely impairs the development of T and B lymphocytes. We show that antigen-presenting cells (APC) of SCID mice function normally in antigen-specific proliferative responses of primed T cells and in the antigen-specific activation of IL 2-producing T cell hybridomas. In both quantitative and qualitative terms, APC of SCID mice are equivalent to those of normal mice. These results indicate that the development and differentiation of APC function in vivo is independent of signals from mature, functional T or B lymphocytes.

Animals

Induction of minor alloantigen-specific T cell subsets in vivo: recognition of processed antigen by helper but not by cytotoxic T cell precursors.

Primary cytotoxic T lymphocyte (CTL) and helper T (Th) cell responses were generated from regional lymph nodes of heterozygous mice sensitized in the footpad with spleen cells of parental H-2 genotype but differing for multiple minor alloantigens of the B10 background. Cytotoxic and helper responses were read after a short in vitro culture period, which did not influence the restriction specificities of in vivo sensitized T cells. We show that under these conditions, Th cell responses appear unrestricted, whereas CTL responses are restricted to the immunizing parental H-2 genotype. Furthermore, we present evidence that these two functions are mediated by distinct T cell subsets and that the in vivo induction of Lyt-2- Th cells has the appearance of being unrestricted whereas that of Lyt-2+ CTL is restricted by H-2. These findings suggest that in a primary immune response, in vivo precursors of Th cells recognize processed antigen on F1 antigen-presenting cells (clones restricted to each parental H-2 genotype are cross-sensitized) under conditions in which those of CTL only respond directly to foreign minor alloantigens on the injected stimulator cells (clones restricted to parental H-2 genotypes are not cross-immunized). This dichotomy is taken to suggest the possibility that processing of cell membrane-bound antigens is controlled at their association step with products of the major histocompatibility complex.

Animals