PubMed Health⌕ Search

Biomedical subjects

R Mazaheri

Publications and source records attributed to R Mazaheri.

12 recordsLinked to original sources

Vascular hamartoma as the cause of hind limb lameness in a horse.

We report a 5-year-old gelding with a rare benign tumour of 2-month duration in the subcutis of the hind limb that presented with lameness. Physical examination revealed normal vital signs. Laboratory findings were within normal ranges. No bone abnormalities were detected on radiographic examination of the affected area. Bloody fluid was obtained by aspiration. Through an I-shape skin incision the tumour was excised en-block. Microscopic study showed a vascular hamartoma characterized by cavernous haemangiomatous tissue and proliferation of multiple vessels of variable diameter. This report highlights the importance of limb vascular hamartoma, as an infrequent lesion, in the differential diagnosis of lameness in the horse.

Animals↗

Typing of serum-soluble HLA-B27 antigen by ELISA.

An ELISA using serum as soluble HLA antigen source was developed for HLA-B27 typing. Two sandwich assays were run in parallel. The first assay utilized a monoclonal antibody (mAb) reacting with a determinant expressed by both HLA-B7 and B27 antigens; the other assay utilized a mAb reactive with HLA-B7 antigens but not with HLA-B27 antigens. After incubation with serum samples, bound HLA antigen was detected using an anti-beta 2m antibody conjugated to peroxidase and a chromogenic substrate. Absorbance of each well was measured at 490 nm. Based on analysis of absorbances obtained with panels of specimens of known HLA phenotypes, a mathematical algorithm was developed to derive the specimen HLA-B27 phenotype from its ELISA absorbance values. Despite the lack of monospecific mAb, an accurate HLA-B27 typing was possible. 362 specimens (including 151 HLA-B27-positive) were tested. Agreement between microlymphocytotoxicity and ELISA was 99.2%. No correlation between the level of HLA-B27 antigen reactivity and the amount of total HLA class I antigen in serum was observed. This report demonstrates the possibility of using serum-soluble HLA antigen and ELISA technology for histocompatibility testing. The assay offers several significant advantages over microlymphocytotoxicity: no need for cell preparation, batch testing capabilities and objective, reproducible interpretation of results.

Algorithms↗

Histological and immunopathological analysis of recovered encapsulated allogeneic islets from transplanted diabetic BB/W rats.

Allogeneic islets encapsulated in an alginate/poly-L-lysine membrane and transplanted into diabetic BB/W rats resulted in graft failure within 2 weeks of transplantation. Graft failure was associated with a dense pericapsular infiltrate (PCI) that resulted in necrosis of the encapsulated islets. The PCI could be inhibited by immunosuppressive agents, including cyclosporine and dexamethasone, and this resulted in a significant increase in graft survival. Immunopathological characterization of the PCI indicated that there was a predominance of macrophages. T helper cells also appeared to be present in this PCI. Empty capsules were also found to induce a similar PCI that was identical in composition to that found around encapsulated islets. Thus alginate/poly-L-lysine capsules do not appear to be biocompatible and may account for the variable results in islet graft survival found with these capsules.

Animals↗

Mechanisms of rejection during OKT3 therapy: propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft.

Allograft rejection remains the single largest impediment to success in the field of transplantation. While OKT3 therapy has proven to be a significant advancement, many grafts are still lost. Late treatment, subtherapeutic OKT3 levels, anti-OKT3 antibodies, and OKT3-induced class II antigen expression are possible explanations. To determine the mechanism of OKT3 resistant rejection we propagated and characterized infiltrating T cells from the biopsy of a liver transplant patient who was rejecting while on prophylactic OKT3. The T lymphocytes demonstrated allospecific proliferation and interleukin 2 (IL2) production and showed a high degree of cytolysis of donor splenocytes. CD3 epsilon monoclonal antibodies (Mab) in concentrations up to 100 micrograms/ml did not inhibit lysis. In contrast, T lymphocytes derived from rejecting allografts of patients receiving cyclosporine and prednisone were readily inhibited from killing by CD3 epsilon Mab at doses of 1 microgram/ml. Furthermore, allospecific proliferation and IL2 production were not inhibited in the OKT3-treated patient by the addition of CD3 epsilon MaB. Incomplete modulation of the CD3-TCR complex was noted after a 72-hr incubation with CD3 epsilon Mab. The T cells did demonstrate other intact CD3-mediated functions such as a rise in intracellular calcium and CD3-dependent cytotoxicity. These results should alert clinicians that CD3 resistant cytotoxic T cells can emerge during OKT3 therapy and may cause rejection. Immunotherapy that targets additional cell surface structures may be of benefit.

Antibodies, Monoclonal↗

Transplantation of encapsulated allogeneic islets into diabetic BB/W rats. Effects of immunosuppression.

Allogeneic islets obtained from Lewis rats were transplanted into diabetic BB/W rats with or without cyclosporine. In addition, these islets were encapsulated in alginate-poly L-lysine membranes and then transplanted into diabetic BB/W rats with or without immunosuppressive and/or antiinflammatory agents. The agents used were cyclosporine, dexamethasone, indomethacin (Ind), or a combination of these. Our results show that islets alone survived for 7 days, with or without CsA therapy. Encapsulated islets survived for 14.2 days, and this was extended by CsA, Dex, or CsA + Ind. Loss of encapsulated graft functions was associated with formation of a dense pericapsular infiltrate, which was inhibited by CsA, Dex, CsA + Ind, or CsA + Dex. In addition, the infiltrate was reduced in animals that had diabetes for long periods of time (greater than 5 months versus less than 1 month). Empty capsules also provoked this cellular response. Thus, encapsulation of islets resulted in slightly prolonged islet survival, which was further enhanced by immunosuppression.

Animals↗

Humoral and cellular immune abnormalities in adult hemophiliacs followed over a 2-year period.

Immune function was assessed in 93 adult hemophiliacs in the 2 years prior to HTLV-III antibody testing of blood donors and routine heat treatment of coagulation factor concentrates. Parameters of humoral and cellular immunity studied included serum complements, immunoglobulins, immune complexes, blood cell counts, lymphocyte subsets, lymphocyte transformation, 2-5A synthetase, serology for HTLV-III and hepatitis B, skin tests, and clinical status. HTLV-III seropositivity was significantly more prevalent in patients treated with factor VIII concentrate; seropositive patients had a higher proportion of abnormal test results and were more symptomatic. Although many subjects had abnormal test results, specific test results generally did not correlate with type of blood component received or time of preceding treatment. The proportion of tests abnormal in individual patients was correlated with the intensity of factor replacement therapy when the time interval from the last treatment was a covariate. While T8+ lymphocytes were increased and T4/T8 ratios were decreased in many patients, significantly reduced T4+ lymphocytes were seen only in seropositive patients and in those treated with factor VIII concentrate. Neither seropositivity nor presence of symptoms correlated with abnormal lymphocyte mitogenic response or 2-5A synthetase levels, but synthetase levels were increased in 65% of patients tested. Over the 2-year study period, no significant deterioration of clinical or laboratory variables was observed in the patients. Abnormalities of immune function were found to be common in hemophiliacs regardless of type of treatment or of evidence of HTLV-III infection.

Antibodies, Viral↗

Clinical leukocyte phenotyping by laser flow cytometry and monoclonal antibodies (immunocytometry) in renal transplantation.

Absolute levels of peripheral blood mononuclear cells were sequentially monitored by immunocytometry in 54 consecutive renal allograft recipients receiving azathioprine/prednisone (STD gp, N = 16) or cyclosporine with or without prednisone (CsA gp, N = 38), before and after transplantation. In the CsA group, but not in those receiving STD therapy, the mean absolute levels of all but OKT4+ cells increased significantly with the duration of therapy. In both treatment groups (STD + CsA), the mean % delta OKT4/8 ratio increased from a prerejection quiescent value of 80 +/- 6% SE to a rejection value of 120 +/- 6% (P less than .001) and fell back to 77 +/- 6% (P less than .0005) in postrejection quiescence. The sensitivity and specificity of such an elevated ratio for rejection were 84.4% and 88.6%, while positive and negative likelihood ratios were 7.40 and 0.15, respectively. In rejection, concomitant immunopathology showed a predominance of OKT8+ cells in the graft with a mean T cell subset ratio of 0.8 +/- 0.3 SE in renal biopsies compared to 2.0 +/- 0.3 for circulating cells (P less than .0125). Parallel donor-antigen-specific assay of lymphocyte-mediated cytotoxicity (LMC) became positive with graft rejection. Immunocytometry with normalization of sequential data in longitudinal analysis thus appears to be a valuable tool in immunologic laboratory monitoring of graft rejection.

Adolescent↗

Dysfunction of humoral immunity in anergic surgical patients: absence of anti-tetanus IgG antibody production.

The experiments described have shown that, whereas the injection of tetanus toxoid (tet) into 8 of 12 control individuals resulted in the appearance of specific anti-tet-IgG antibodies in their plasma, immunization of 14 anergic patients did not elicit an antibody response. This observation was extended to an in vitro system, where cells from four control subjects were shown to secrete anti-tet-IgG antibodies in response to polyclonal activators whereas cells from eight anergic patients did not. It is suggested that this failure of humoral immunity could account for the high risk of bacterial infections in anergy.

Adult↗

Circulating lymphocyte subpopulations in experimental allergic neuritis.

T-cell subsets in the peripheral blood were analyzed using monoclonal antibodies during the development of experimental allergic neuritis in Lewis rats. Percentages of helper and suppressor cells and ratios of helper/suppressor cells did not exceed normal limits during the development of the disease.

Animals↗

Cell-mediated immunity: correlation of mixed-leucocyte-macrophage migration inhibition with delayed-type hypersensitivity after immunization and donor-specific transfer of cell migration inhibition by dialyzable leucocyte extract.

Active and adoptive sensitization of rhesus monkeys (Macacca mulatta) as well as the development of a novel sensitive in vitro cell migration inhibition assay for cell-mediated immunity (CMI) in this species are described. First, the correlation of mixed leucocyte-macrophage migration tests (LMMI) with the whole blood lymphocyte transformation (LT) and the delayed hypersensitivity skin test (DH) in immunized animals are shown. Second, these tests are used to demonstrate adoptive transfer of specific/nonspecific cellular immunity (CMI) with dialyzable leucocyte extract (DLE) from immunized donor to unimmunized recipient monkeys. Seventeen animals were immunized with keyhole limpet haemocyanin (KLH) or hepatitis B surface antigen (HBsAg) in Freund's complete adjuvant (FCA) or with FCA alone. Acquisition of antigen-specific cell-mediated immunity was detected by all three tests within 5 weeks of immunization. Positive LMMI responses were associated with positive DH and LT. However, there was no correlation between the magnitude or time of development of the three responses. Therefore, the LMMI test, like the LT test, is an in vitro parameter of DH, but reflects the activity of different subpopulations of lymphocytes and is regulated by different mechanisms. In addition, 12 naive animals received DLE. Within 3 weeks, transfer of sensitivity was detected towards antigens to which the recipients had previously not been reactive but the donors had been. An enhancement of transformation response to phytohaemagglutinin was also seen. Thus, rhesus DLE contains both donor-specific transfer factor-like and nonspecific adjuvant-like activities. In DLE recipients, unlike immunized animals, LMMI responses were dissociated from DH or LT responses in that positive LMMI was mostly seen with negative DH or LT to antigens. Therefore, LMMI emerged as the most sensitive assay for detecting adoptive transfer of CMI by DLE in vivo, supporting the view that different mechanisms regulate LMMI, LT, and DH.

Animals↗