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E Akalin

Publications and source records attributed to E Akalin.

At least 19 recordsLinked to original sources
PubMed2003

Glomerular infiltration by CXCR3+ ICOS+ activated T cells in chronic allograft nephropathy with transplant glomerulopathy.

The pathogeneses of chronic allograft nephropathy (CAN), a leading cause of allograft failure, and one of its complications, transplant glomerulopathy (TGP), are unknown. Immunohistologic analysis of human renal transplant biopsies showed expression of inducible costimulator (ICOS), the chemokine receptor CXCR3, and its ligands, Mig and IP-10, by intraglomerular and periglomerular leukocytes in biopsies with CAN and TGP but not CAN alone. ICOS and CXCR3 are both characteristics of activated, effector T cells, suggesting different pathogenetic mechanisms underlying TGP vs. CAN. We conclude that targeting of specific chemokine and chemokine receptor pathways and/or ICOS may have clinical application in the prevention and treatment of TGP.

Adult↗
PubMed2001

Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology.

BACKGROUND: High-density oligoarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. Oligoarray analysis of genes expressed during human renal allograft rejection has not been reported previously. METHODS: Seven human renal allograft biopsies with histologic evidence of acute cellular rejection and three renal allograft biopsies without evidence of rejection (control) were analyzed for the expression of 6800 human genes using high-density oligoarrays (GeneChip, Affymetrix, Santa Clara, CA). Quantitative expression of gene transcripts was determined and a comparison analysis between acute rejection and control biopsy samples was performed. Up-regulation of a specific gene transcript during acute rejection was considered to be significant if transcript abundance increased fourfold or more relative to control biopsy samples. RESULTS: Comparison analysis revealed that between 32 and 219 gene transcripts are up-regulated (>fourfold) during acute rejection. Of these transcripts, only four (human monokine induced by interferon-gamma, T-cell receptor active beta-chain protein, interleukin-2 stimulated phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were consistently up-regulated in each acute rejection sample relative to at least two of three control biopsy samples. Six other genes were up-regulated in six of seven acute rejection samples. These were interferon-stimulated growth factor-3, complement factor 3, nicotinamide N-methyltransferase, macrophage inflammatory protein-3beta, myeloid differentiation protein, and CD18. Only two gene transcripts were down-regulated in five of seven acute rejection samples. Significant up-regulation of cytotoxic T-cell effector molecules, previously reported as markers of acute renal rejection in humans, was not detected. CONCLUSIONS: High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The droopy shoulder syndrome.

Droopy shoulder syndrome (DSS) is characterized by a depression of the shoulders that stretches the brachial plexus, thus causing pain without any signs of neurological impairment. We describe ten patients with DSS; all had been treated for different diagnoses before. Contrary to previous reports, three patients had unilateral involvement, and five had accompanying disease of the cervical-shoulder region. All patients responded well to conservative treatment in 2-10 weeks. DSS must be kept in mind in the differential diagnosis of pain in the cervical-shoulder region, to prevent unnecessary medication.

Adolescent↗
PubMed2001

Normouricemia in the syndrome of inappropriate antidiuretic hormone secretion.

Hyponatremia is seen in 40% to 60% of hospitalized acquired immune deficiency syndrome (AIDS) patients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) and volume contraction are the most common causes. The serum uric acid level can be used to distinguish between these two causes of hyponatremia. Hypouricemia is the rule in SIADH, whereas hyperuricemia commonly accompanies volume contraction. This report presents an AIDS patient with SIADH and normouricemia secondary to pyrazinamide and ethambutol.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Gene polymorphisms and transplantation.

The influence of gene polymorphisms in key immunoregulatory molecules on the clinical course post-transplant has become an area of active research, since it offers a possible explanation for the heterogeneity in outcomes between individuals. Several groups have now investigated the association of polymorphisms in molecules--including cytokines, cytokine receptors, adhesion molecules and costimulatory molecules--that participate in the immune response to an allograft. Several interesting observations have been made that would suggest that genetic variability influencing allograft survival reaches beyond that of the MHC molecules.

Gene Expression Regulation↗
PubMed1998

Dermatomal and mixed nerve somatosensory evoked potentials in the diagnosis of neurogenic thoracic outlet syndrome.

To evaluate the diagnostic utility of dermatomal and mixed nerve somatosensory evoked potentials (SEPs) in patients with thoracic outlet syndrome (TOS) and to compare their value with routine electrodiagnostic methods, we studied a group of 44 patients with neurogenic TOS and 30 healthy controls. In addition to bilateral median and ulnar SEPs, evoked potentials were recorded after stimulation of C6 and C8 dermatomes from the first and fifth digits, respectively. The patients were classified into 3 groups according to the nature of their clinical condition. The abnormality rate for both ulnar and C8 dermatomal SEPs was 100% in a small group of patients with severe neurological signs like atrophy. In groups of patients with lesser degrees of neurogenic damage, abnormality rates for ulnar and C8 dermatomal SEPs on affected limb(s) were 67 and 50%, respectively. Same abnormality rates were 25 and 18% in patients with only subjective symptoms. In patients with objective neurological signs, the major increase in sensitivity was with electromyography (EMG). Abnormalities of routine nerve conduction studies and F-wave latency were observed in patients with severe neurogenic damage. We concluded that the most useful tests in the diagnosis of neurogenic TOS are needle EMG and ulnar SEPs.

Adult↗
PubMed1998

Susceptibility testing of Klebsiella spp.--an international collaborative study in quality assessment.

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure agreement between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment was performed to investigate the performance of susceptibility testing of Klebsiella spp. Ninety-five strains of klebsiellae were selected from clinical isolates at the London Hospital Medical College (LHMC). These included strains with a diversity of susceptibility profiles to amoxycillin/clavulanate, piperacillin, ceftazidime, cefuroxime, ciprofloxacin, gentamicin and trimethoprim. The strains were sent to 13 participating laboratories in Europe and the USA and laboratories were asked to test the susceptibility of these strains to these antibiotics by their usual methods. They were also asked to provide details of the method used to test susceptibility. Several different standard recommended testing methods were used. Reporting of susceptibilities was generally accurate, but a number of anomalies were noted. Discrepancies of reporting between the LHMC and the participating laboratories was more marked for resistant strains, particularly in the detection of resistance to cefuroxime and ciprofloxacin, as well as the assignment of susceptibility and resistance to piperacillin and amoxycillin/clavulanate. Some discrepancies could be attributed to the use of different breakpoints, leading to differing assignment of susceptibility. Methodological variations including disc content, inoculum and failure to measure and interpret zone sizes consistently also led to anomalies. This quality assessment programme has helped to identify problems in susceptibility testing which should be investigated further.

Anti-Bacterial Agents↗
PubMed1996

CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model: inhibition of cell-mediated and humoral immune responses in vivo.

Blocking CD28-B7 T-cell costimulation by CTLA4Ig induces tolerance to rat renal allografts and inhibits Th1, but spares Th2, cytokines. We now report on the mechanisms of CD28-B7 blockade in this model. Lymphocytes from CTLA4Ig-treated animals showed significant reduction of mixed lymphocyte response, as well as antidonor cytotoxic T-cell effector function, as compared with rejecting controls. Flow cytometry studies on sera of renal allograft recipients showed complete inhibition of antidonor humoral responses by CTLA4Ig. Analysis by reverse transcriptase-polymerase chain reaction and immunohistology showed that intragraft macrophage products, monocyte chemoattractant protein-1 and inducible nitric oxide synthase, were reduced by CTLA4Ig therapy. Immunohistologic studies also showed reduced intragraft macrophage infiltration and decreased staining for the fibrogenic and mitogenic growth factor, transforming growth factor-beta. These results indicate that CD28-B7 blockade inhibits cell-mediated and humoral immune responses, and suggest that strategies targeting T-cell costimulation may provide a novel approach to prevent chronic allograft rejection.

Abatacept↗
PubMed1996

Emphysematous cystitis and pyelitis in a diabetic renal transplant recipient.

Emphysematous cystitis is a rare complication of urinary tract infection. Patients with diabetes mellitus, neurogenic bladder, bladder outlet obstruction, and recurrent urinary tract infection are at increased risk for the disease. We present a case of emphysematous cystitis and pyelitis in a diabetic renal transplant recipient. He was treated with antibiotics alone with complete clinical and radiologic resolution. The clinical course was benign, as described in most patients. The prognosis of emphysematous cystitis is good after early diagnosis and prompt treatment with appropriate antibiotics, blood glucose control, and adequate urinary drainage.

Cystitis↗
PubMed1996

Induction of "infectious" tolerance to MHC-incompatible cardiac allografts in CD4 monoclonal antibody-treated sensitized rat recipients.

LBNF1 heart grafts are rejected in an accelerated manner within 36 h by LEW rats that have been sensitized with Brown Norway rat skin grafts on day -7. Treatment with RIB-5/2, a CD4-nondepleting mAb (10 doses of 5 mg/rat/day, i.v., from day -7 to day +21) abrogated rejection at <36 h and produced indefinite (>200 days) cardiac allograft survival. Transplantation tolerance in this model developed within several weeks, and during the maintenance phase (>100 days) it was associated with diminished host circulating allo-Ab responses and induction of peripheral allospecific T cell unresponsiveness both in vitro and in vivo. Tolerant cells in mAb-treated hosts could disable naive or alloimmune cells, so that they failed to trigger graft rejection. Moreover, donor-specific and organ-nonspecific tolerance could be adoptively transferred by spleen cells alone into new sets of primary (100%) and secondary (>40%) test recipients. CD4+ T cells were instrumental for the induction of such readily transferable tolerance. The first and second generation suppressive regulatory cells were also critical for the inhibition of allograft recognition by normal or even alloimmune cells. Hence, the features of an "infectious" tolerance pathway to minor histocompatibility-mismatched skin grafts, originally described in thymectomized mice, may be applied to the euthymic primed rats rendered tolerant to fully MHC-incompatible vascularized organ allografts. Such reprogramming of host cell-mediated regulatory mechanisms following CD4-targeted therapy adds to our appreciation of the potential utility and applicability of infectious tolerance in transplant recipients treated with a perioperative course of CD4-targeted monotherapy.

Adoptive Transfer↗
PubMed1996

Chronic cardiac rejection in the LEW to F344 rat model. Blockade of CD28-B7 costimulation by CTLA4Ig modulates T cell and macrophage activation and attenuates arteriosclerosis.

CTLA4Ig, a fusion protein that blocks CD28-B7 costimulation, was studied in a LEW to F344 rat model of chronic cardiac rejection. In rats treated with a single dose of CTLA4Ig (0.5 mg intraperitoneally) 2 d after transplantation, allografts survived significantly longer ( > 70 d in 64%) than in untreated controls or rats treated with control Ig (all rejected within 25 d). Only 25% of grafts from rats treated with a single, high dose of cyclosporine A (25 mg/kg, 2 d after transplantation) survived longer than 70 d. Reverse transcriptase PCR and immunostaining analyses of tissue from 75-d, CTLA4Ig-treated allografts showed reduced expression of the T cell factor IFN-gamma and macrophage activation factors monocyte chemoattractant protein-1, inducible nitric oxide synthase, and galactose/N-acetylgalactosamine macrophage lectin, as well as TGF-beta. Grafts from longterm survivors ( > 120 d) treated with CTLA4Ig showed significant reductions in the frequency and severity of arteriosclerosis in comparison with cyclosporine A-treated rats. Thus, T cell activation is a proximal event in the cascade that culminates in the arteriosclerosis of chronic rejection. Strategies for blocking T cell costimulation may help prevent chronic rejection in clinical transplantation.

Abatacept↗
PubMed1996

Susceptibility testing of Haemophilus influenzae--an international collaborative study in quality assessment.

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure that agreement is achieved between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment study, involving 15 laboratories in eight countries, was performed to investigate the standard of performance of the susceptibility testing of Haemophilus influenzae. One hundred and fifty strains of H. influenzae were distributed from the London Hospital Medical College (LHMC) to all laboratories who were asked to test the susceptibility of the strains to ampicillin, chloramphenicol, tetracycline, trimethoprim, cephalosporins and ciprofloxacin. Laboratories were also asked to provide the details of methodology to test the susceptibility. Significant discrepancy between the LHMC and the participating laboratories appeared in the detection of resistance to ampicillin (especially beta-lactamase-negative strains resistant to ampicillin) as well as the assignment of susceptibility and resistance to chloramphenicol, tetracycline and trimethoprim. Often these reflected the use of inappropriate breakpoints which led to erroneous assignment of susceptibility. Other variations including disc content, medium and supplement, inoculum as well as failure to measure zone sizes properly also led to some repeating anomalies.

Ampicillin↗
PubMed1996

Characterization of beta-lactamase gene blaPER-2, which encodes an extended-spectrum class A beta-lactamase.

Plasmidic extended-spectrum beta-lactamases of Ambler class A are mostly inactive against ceftibuten. Salmonella typhimurium JMC isolated in Argentina harbors a bla gene located on a plasmid (pMVP-5) which confers transferable resistance to oxyiminocephalosporins, aztreonam, and ceftibuten. The beta-lactamase PER-2 (formerly ceftibutenase-1; CTI-1) is highly susceptible to inhibition by clavulanate and is located at a pI of 5.4 after isoelectric focusing. The blaPER-2 gene was cloned and sequenced. The nucleotide sequence of a 2.2-kb insert in vector pBluescript includes an open reading frame of 927 bp. Comparison of the deduced amino acid sequence of PER-2 with those of other beta-lactamases indicates that PER-2 is not closely related to TEM or SHV enzymes (25 to 26% homology). PER-2 is most closely related to PER-1 (86.4% homology), an Ambler class A enzyme first detected in Pseudomonas aeruginosa. An enzyme with an amino acid sequence identical to that of PER-1, meanwhile, was found in various members of the family Enterobacteriaceae isolated from patients in Turkey. Our data indicate that PER-2 and PER-1 represent a new group of Ambler class A extended-spectrum beta-lactamases. PER-2 so far has been detected only in pathogens (S. typhimurium, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis) isolated from patients in South America, while the incidence of PER-1-producing strains so far has been restricted to Turkey, where it occurs both in members of the family Enterobacteriaceae and in P. aeruginosa.

Amino Acid Sequence↗
PubMed1996

Colchicine interferes with L-selectin and leukocyte function-associated antigen-1 expression on human T lymphocytes and inhibits T cell activation.

Colchicine, which inhibits cell microtubule assembly by preventing polymerization of tubulin monomers, inhibits cell-mediated immune responses and promotes long-term survival of major histocompatibility complex-incompatible renal allografts in rats. Here we evaluated the effect of blocking cell microtubule assembly by colchicine on T cell and endothelial cell adhesion receptors involved in transducing signals for T cell activation. By using immunofluorescence flow cytometry analysis, evidence is presented that colchicine, in a dose-dependent fashion, downregulated L-selectin and leukocyte function-associated antigen-1, but not CD2 and CD44 on the surface of naive human peripheral blood lymphocytes. This effect was confirmed in two subsets of T lymphocytes, namely, CD45RA- and CD45RO-positive cells. However, colchicine did not influence the rapid shedding of L-selectin from T lymphocytes exposed to activating stimuli. Colchicine inhibited expression of interleukin-2 receptor on activated T lymphocytes. This effect was observed when T lymphocytes were stimulated with both anti-CD3 and anti L-selectin monoclonal antibodies. Colchicine also inhibited lymphocyte function in vitro as documented by inhibition of the human mixed lymphocyte response in a dose-dependent fashion. Moreover, colchicine downregulated surface expression of intercellular adhesion molecule-1 and E-selectin on activated human umbilical vein endothelial cells. These results indicate that blocking cell microfubule assembly inhibits surface expression of adhesion molecules on T cells and endothelial cells, and provides insights into the complex mechanisms of the action of colchicine in vivo.

Antibodies, Monoclonal↗
PubMed1995

Binding of activated protein C to a specific receptor on human mononuclear phagocytes inhibits intracellular calcium signaling and monocyte-dependent proliferative responses.

Upon activation, mononuclear phagocytes (Mphi) play key roles in the development of septic shock and multiple host immune responses, but details of the regulation of Mphi activation are little understood. We recently showed that the physiologic anticoagulant molecule, activated protein C (APC), blocks responses of human blood Mphi, alveolar Mphi, or THP-1 cells induced by LPS, IFN-gamma, or PMA, including TNF-alpha production and down-regulation of several LPS binding-related proteins. We now report a possible mechanism of action through inhibition of the rapid intracellular calcium signaling that occurs at the onset of Mphi activation, and characterization of a specific Mphi receptor for APC. Flow cytometry studies using Fluo-3 showed that Mph activation by Fc-receptor cross-linking or rIFN-gamma caused a rapid increase in free intracellular calcium, a primary event in multiple signal transduction pathways, which was blocked by pretreatment with APC. Consistent with this, addition of APC inhibited PHA-induced T cell proliferation in a dose- and time-dependent manner. Peak suppression (> 70%) required addition of APC within the first hour of 72 hr cocultures of Mphi and lymphocytes, and proliferative responses were not restored by addition of IL-2 or TNF-alpha. Biochemical studies showed that 125I-labeled APC bound specifically to M phi in a time-dependent and saturable manner. Scatchard analysis indicated there were 180,690 binding sites for APC per cell, which were of high affinity (Kd value of 12.9 mM). Binding of 125I-APC was doubled by activation of Mphi with LPS, and bound APC was not displaced by the zymogen, protein C (PC), or by enzymatically inactive (diisopropyl fluorophosphate- or PPACK-treated) APC, indicating an absolute requirement for the active site of APC in its binding to Mphi. APC binding was blocked by a polyclonal Ab to human PC/APC, but not by protein S, factor Va or Xa, or a polyclonal antithrombomodulin antibody. When 125I-APC was crosslinked to its receptor, immunoprecipitated and analyzed by SDS-PAGE under reducing conditions, a covalent complex (110-115 kD) of 125I-APC (62 kD) and its receptor was seen. In addition, a Mphi membrane protein of 50-55 kD, as determined by SDS-PAGE, was affinity-purified using an APC-Affigel column, and confirmed by ligand binding. Taken together, our findings document the presence of a M phi surface receptor for APC, which appears distinct from a recently described endothelial receptor for PC and APC, and which may be involved in the inhibitory effects of APC on activation of human Mphi, including Mphi-dependent T cell proliferation.

Calcium↗
PubMed1995

CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Th1 but spares Th2 cytokines in the central nervous system.

We studied the contribution of the CD28-B7 costimulatory T cell activation pathway to the pathogenesis of experimental autoimmune encephalomyelitis in the Lewis rat model. Systemic administration of CTLA4Ig suppressed clinical disease and was effective even when CTLA4Ig was delayed until day 10 postimmunization, a time when pathologic disease is evident. This protection was not reversible by systemic administration of high doses of IL-2. Detailed immunohistologic studies showed that CTLA4Ig therapy resulted in suppression of the inflammatory response with inhibition of Th1 (IL-2 and IFN-gamma) and sparing of Th2 (IL-4, IL-10, and IL-13) cytokines in the central nervous system. These results indicate that the CD28-B7 T cell costimulatory pathway plays an important role in experimental autoimmune encephalomyelitis, a Th1-mediated disease, and suggest that blockade of this costimulatory pathway protects against active disease by causing a state of immune deviation towards Th2 function. The ability of CTLA4Ig to treat animals with pathologically established disease may have important clinical implications for patients with multiple sclerosis.

Abatacept↗