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Biomedical subjects

E Akalin

Publications and source records attributed to E Akalin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intrathymic tolerance in the Lewis-to-F344 chronic cardiac allograft rejection model.

Successful induction of donor-specific unresponsiveness by intrathymic inoculation of alloantigen in several experimental acute rejection models has led us to hypothesize that similar immune manipulations can prevent chronic rejection and development of graft arteriosclerosis in the Lewis-to-F344 rat chronic cardiac allograft rejection model. Recipient F344 rats were treated with donor (Lewis) splenocytes by intrathymic injection (i.t.) alone (10 x 10(6) cells/lobe); with donor splenocytes i.t. plus a one-time dose of ALS (1 mg) by intraperitoneal injection (i.p.); or with ALS i.p. (1 mg) alone 2 and 6 weeks prior to heterotopic Lewis heart transplantation. Control F344 recipients received saline i.t. Allografts were monitored by daily palpation, and long-term surviving grafts were harvested on day 90 for histopathologic analysis. Control allografts had 28.6% long-term survival (> 90 days) with mean graft survival of 46.7 +/- 12.2 days. At day 90 the surviving control allografts were enlarged and fibrotic with barely palpable heartbeat (mean heartbeat grade 0.29 +/- 0.18), and histologically showed diffuse moderate mononuclear cell infiltrates and advanced graft arteriosclerosis (mean vessel score 3.57 +/- 0.10 and 89 +/- 1% vessels diseased). Recipient treatment with intrathymic donor splenocytes alone significantly prolonged graft survival (89% long-term survival; mean 83.8 +/- 6.2 days, P < 0.04), but did not significantly inhibit the development of graft arteriosclerosis (score 2.98 +/- 0.53 and 79 +/- 8% diseased, P = NS). By contrast, treatment with i.t. donor splenocytes plus ALS 2 weeks prior to transplantation prolonged graft survival (100% long-term; mean 90.0 +/- 0.0 days, P < 0.04), and markedly inhibited graft arteriosclerosis (score 0.80 +/- 0.14, P < 0.05; 27 +/- 4% diseased, P < 0.05). ALS alone given two weeks prior to transplantation also prolonged graft survival (100% long-term; mean 90.0 +/- 0.0 days, P < 0.04), and inhibited graft arteriosclerosis (score 0.89 +/- 0.31, P < 0.05; 25 +/- 7% diseased, P < 0.05). However, when ALS was given 6 weeks prior to heart transplantation the beneficial effect of ALS alone was abolished, suggesting that lymphocyte depletion may have been responsible for the observed effects when ALS was administered at 2 weeks. Interestingly, intrathymic donor splenocytes plus ALS 6 weeks prior to transplantation, on the other hand, showed significant prolongation of allograft survival (100% long-term, mean 90.0 +/- 0.0 days, P < 0.04), and inhibited graft arteriosclerosis (score 0.41 +/- 0.02, P < 0.05; 16 +/- 2% diseased, P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2.

Blocking the CD28-B7 T cell costimulatory pathway with the fusion protein CTLA4Ig inhibits alloimmune responses in vitro and in vivo and induces tolerance to cardiac allografts in mice and rats, but the mechanisms mediating the tolerant state in vivo are unknown. Here, we report the effects and potential mechanisms of CTLA4Ig in the rat renal allograft model. LEW rats were nephrectomized and received renal allografts from major histocompatibility complex-incompatible WF rats. While all untreated and control immunoglobulin (Ig)-treated animals acutely rejected their allografts and died, 86% of rats that received a single injection of CTLA4Ig on day 2 after transplantation had prolonged survival (> 60-100 days) with preserved renal function. By contrast, only 29% of animals that received CTLA4Ig on the day of engraftment had prolonged survival. Long-term survivors (> 100 days) exhibited donor-specific tolerance, accepting donor-matched WF but acutely rejecting third-party BN cardiac allografts. Immunohistological analysis of grafts sampled at 1 week after transplantation showed that both control and CTLA4Ig-treated animals had mononuclear cell infiltrates, with a higher percentage of CD4+ cells in the CTLA4Ig-treated group. However, while this was associated with vasculitis and tubulitis in control grafts, there was no evidence of tissue injury in CTLA4Ig-treated animals. The immune response leading to graft rejection in control animals was characterized by expression of the T helper (Th) type 1 cytokines interleukin (IL)-2 and interferon-gamma. In contrast, the persistent CD4+ infiltrate without graft rejection in CTLA4Ig-treated animals was associated with increased staining for the Th2-related cytokines IL-4 and IL-10. Furthermore, grafts from CTLA4Ig-treated animals had marked upregulation of intragraft staining for IgG1, but not IgG2a or IgG2b. Administration of rIL-2 to CTLA4Ig-treated animals restored allograft rejection in 50% of animals tested. These results confirm that blockade of the CD28-B7 pathway after alloantigenic challenge induces donor-specific acceptance of vascularized organ allografts, and indicates in this model that CTLA4Ig inhibits Th1 but spares Th2 cytokines in vivo.

Abatacept↗
PubMed1995

The indirect pathway of allorecognition. The occurrence of self-restricted T cell recognition of allo-MHC peptides early in acute renal allograft rejection and its inhibition by conventional immunosuppression.

There is evidence that T cells can "directly" recognize intact allo-MHC molecules on the surface of allogeneic stimulator or target cells, and/or "indirectly" recognize processed allo-MHC peptides presented by self antigen-presenting cells (APCs). We and others have recently demonstrated that in vivo-primed rat CD4+ T cells recognize and proliferate to specific polymorphic amino acid sequences when presented as MHC allopeptides by self APCs. Studies on the mechanisms of indirect T cell recognition of alloantigen are now reported. First, we studied the immunogenicity of 4 synthetic polymorphic class II MHC allopeptides representing full-length sequences of the hypervariable domains of RT1.Du beta (DR or I-E-like) in several responder strains: LEW (RT1(l)), ACI (RT1a), BUF (RT1b), BN (RT1n), and control syngeneic WF (RT1u) strains. Immunogenicity of the individual 25mer allopeptides varied in the different responder strains, indicating that self-restricted T cell recognition of allo-MHC peptides is determined not only by polymorphisms, but also by the responder MHC genotype. Self-restricted CD4+ T cell recognition of processed allo-MHC peptides has been shown to occur during acute skin and cardiac allograft rejection, and there is evidence that this pathway may play an important role in initiating and amplifying the immune response to allografts. T cells from LEW animals primed in vivo by WF (RT1u) vascularized renal allografts were capable of proliferating to the RT1.Du beta peptides as early as 3 days postengraftment, when presented by self APCs. We then tested the effects of various immunosuppressive drugs on self-restricted primed T cell proliferative response to an immunogenic MHC allopeptide in vitro. Methylprednisolone, cyclosporine, and FK506 inhibited the proliferative response of RT1.Du beta 2-primed LEW T cells in a dose-dependent fashion. In addition, a single injection of cyclosporine (25 mg/kg i.m.) to LEW recipients of WF renal allografts on the day of transplantation completely abolished the proliferative response of in vivo-primed T cells to RT1.Du beta 2, indicating the susceptibility of the indirect pathway of allorecognition to conventional immunosuppressive drugs.

Amino Acid Sequence↗
PubMed1995

Blocking cell microtubule assembly inhibits the alloimmune response in vitro and prolongs renal allograft survival by inhibition of Th1 and sparing of Th2 cell function in vivo.

Colchicine inhibits cell microtubule assembly by binding to and preventing the polymerization of tubulin monomers. Although there are data to indicate that colchicine inhibits a variety of cell-mediated immune responses, the effects and mechanisms of inhibiting cell microtubule assembly on the alloimmune response have not been thoroughly investigated. It has recently been shown that colchicine prevents acute rejection and promotes the long-term survival of rat renal allografts. In this study, the effects and mechanisms of inhibiting cell microtubule assembly by colchicine on the alloimmune response in vitro and in vivo were examined. First, the effects of colchicine on T lymphocyte response to alloantigen in vitro were tested. In the standard one-way mixed lymphocyte response (MLR), responder Lewis rat lymph node cells were cultured with irradiated Brown-Norway stimulators. Colchicine inhibited the MLR in a dose-dependent manner, with 100% inhibition at a concentration of 25 ng/mL (6.25 x 10(-8) M) and 50% inhibition at a concentration of approximately 5 to 10 ng/mL. Colchicine also inhibited the generation of cytotoxic T lymphocytes as well as cytotoxic T cell effector function in vitro in a dose-dependent fashion. Second, detailed immunohistologic studies of renal allografts harvested from unmodified control (acutely rejecting) and colchicine-treated rats (Day 15 or 30) were performed. These studies showed that grafts from colchicine-treated animals had significantly fewer mononuclear cell infiltrates and less edema, and moderately decreased deposition of immunoglobulin M, C3, and fibrin, as compared with acutely rejecting control grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Brucellosis of the spine.

The spinal form of brucellosis is still a disabling disease in many countries outside North America and northern and central Europe. Fifteen consecutive cases of spinal brucellosis diagnosed and treated over a 20-year period were reviewed retrospectively. Six patients were farmers, while 10 patients had a history of ingestion of unpasteurized milk or other dairy products. A high index of suspicion is necessary for the diagnosis, since there are no pathognomonic signs or symptoms. Radiological assessment of the disease was reviewed and highlights in the differential diagnoses were stressed. The diagnosis was based on actual culture of Brucella bacilli in seven patients. The principal treatment of brucellosis of the spine is conservative, namely, immobilization and antimicrobial therapy. We have found both a combination of ofloxacin and rifampin and ofloxacin monotherapy efficient as the early regimens used in this series. Three patients had to undergo surgery, since a diagnosis could not be made in any other way.

Adolescent↗
PubMed1993

Restoration of bactericidal activity of peritoneal fluid by cimetidine but not ranitidine or famotidine in burned mice.

OBJECTIVE: To find out the effect of 20%, third degree burns and H2 receptor antagonists on peritoneal bactericidal activity. DESIGN: Animal experiment. SETTING: Research laboratory of university school of medicine. SUBJECTS: 52 mice in five groups. INTERVENTIONS: Sham burn (n = 5, group I), burned, and received subcutaneous injections of saline (0.3 ml/kg day, n = 14, group II); ranitidine (10 ml/kg/day, n = 15, group III); cimetidine (10 mg/kg/day, n = 8, group IV); or famotidine (0.7 mg/kg/day, n = 10, group V); for 14 days. MAIN OUTCOME MEASURE: Peritoneal bactericidal activity in all groups measured 15 days after the burn. RESULTS: There was a significant difference in peritoneal bactericidal activity between the control and burned mice, but no significant difference between the control group and the burned mice that were given cimetidine and famotidine. CONCLUSION: Peritoneal bactericidal activity is suppressed in mice after 20% third degree burns and this effect may be partly reversed by cimetidine and famotidine.

Animals↗
PubMed1991

[The invitro activity of teicoplanin and vancomycin against gram positive microorganisms (corrected)].

The in vitro activities of teicoplanin and vancomycin against 288 gram positive cocci were determined by broth macrodilution method. MIC 90 values for teicoplanin were lmcg/ml for coagulase positive staphylococci (n = 115), 4 mcg/ml for coagulase negative staphylococci (n = 93), 0.50 mcg/ml for S. faecalis (n = 50) and 0.125 mcg/ml for S. pyogenes (n = 30). MIC 90 values for vancomycin were lmcg/ml 1 mcg/ml, 1 mcg/ml and 0.25 mcg/ml respectively. We were not able to detect in vitro resistance against teicoplanin and vancomycin.

Anti-Bacterial Agents↗
PubMed1990

[Group B streptococcal endocarditis].

In this article, a case of group B streptococcal endocarditis in a diabetic patient, taking immunosuppressive therapy because of dermatomyositis is reported.

Dermatomyositis↗
PubMed1990

[A case of hemiballismus during cryptococcal meningitis].

We present a case of hemiballismus related to cryptococcal meningitis. A 23 year-old man was hospitalized because of involuntary movements of his left side, confusion, hyperpyrexia, neck stiffness, bilateral papilledema, right hemiparesis and bilateral pyramidal signs. Diagnosis was made by CSF examination demonstrating cryptococci by india ink. CT with contrast showed hyperdense lesions in the head of the right caudate nucleus, in the left internal capsule and in the frontal and occipital lobes. After treatment with amphotericin B, 5-fluorocytosine and haloperidol, he experienced rapid recovery with disappearance of hemiballismus. To our knowledge, this is the first report of hemiballismus caused by cryptococcal meningitis.

Adult↗
PubMed1987

[Comparison of the in vitro effectiveness of sulbactam/ampicillin and ampicillin].

In this study, we compared the effectiveness of Sulbactam + Ampicillin compound and Ampicillin against to 1168 clinical isolates by means of disk diffusion technic. We observed that Sulbactam + Ampicillin compound is enhanced and regained the antibacterial activity of Ampicillin against some bacteria such as S. aureus, S. epidermidis and some gram negative microorganisms.

Ampicillin↗
PubMed1987

[Fluoroquinolones].

We reviewed, the structure, pharmacokinetic properties, mode of actions, antibacterial spectrum, therapeutic dosage and side effects of fluoroquinolones in this article.

Bacteria↗
PubMed1986

Serum bactericidal and opsonic activities in chronic lymphocytic leukemia and multiple myeloma.

Susceptibility to infection is widely recognized as the major cause of morbidity and mortality in patients with CLL and MM. The present study was designed to investigate the serum bactericidal (SBA) and serum opsonic activities (SOA) in 12 CLL and 12 MM patients, and results were compared to 20 normals. SBA and SOA were measured by a new radiometric assay. SBA was found to be normal in 11 patients with CLL and in all 12 patients with MM. In contrast, SOA was significantly lower in 11 out of 12 patients with CLL. Ten of twelve patients with MM also had significantly lower SOA compared to those of controls. No correlation was detected between the serum immunoglobulin and complement levels of the patients or between the degree of the opsonic defect and the incidence of infection. In mixture experiments, untreated normal serum partially corrected the opsonic activity of CLL and MM serum. The results suggest the presence of a possible inhibitor in the serum of patients with two well-known B-lymphocyte-derived disorders.

Blood Bactericidal Activity↗
PubMed1986

[Lymphocyte population and T lymphocyte subsets in brucellosis analyzed by monoclonal antibodies].

In this study, T-lymphocyte subsets and HLA-DR antigen (+) cells in the peripheral blood of 19 patients with acute brucellosis were determined and the results were compared to 19 healthy control subjects. Our findings suggest that exposure of the immune system to brucella microorganism and related antigens results in an increase in the circulating "activated" cell numbers (HLA-DR+) without significant alterations in the subpopulations of peripheral blood lymphocytes.

Acute Disease↗