Spontaneous gastric perforation.
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Female↗
Biomedical subjects
E Zisman
Publications and source records attributed to E Zisman.
A computational fluid dynamic model of antigen-antibody surface adsorption on a piezoelectric immunosensor.
A novel computational fluid dynamic model describing the antigen-antibody binding on an electrode surface is presented. It was assumed that the adsorption rate of the antibody sample is dependent upon the flow field in the vicinity of the electrode. Numerical solution of the steady flow in a two-dimensional triangular cell using the Navier-Stokes equations was carried out for predicting mass adsorption on the surface of the crystal. The relationships between the mass adsorbed over the area surface of the electrode, the kinetics of the binding process, and the flow field were determined. The effect of the inlet conditions (location, velocity magnitude, and direction) on the time constant of the mass adsorption process was investigated. It was found that the time constant was decreased by moving the inlet near the edge of the crystal or increasing the normal to the boundary component of the velocity. These changes may significantly reduce the time needed to conduct the test.
Adsorption↗
Prostate-specific antigen induces proliferation of peripheral blood lymphocytes and cytokine secretion in benign prostate hypertrophy patients.
PURPOSE: The etiology of benign prostatic hypertrophy (BPH) is still obscure. Data supporting an interaction connecting prostate hyperplasia and immune dysregulation is accumulating lately. The aim of the study was to assess the cellular immune responses to PSA by measuring the in vitro potential of PSA to induce proliferation and cytokine secretion in peripheral blood lymphocytes (PBLs) of BPH patients. MATERIALS AND METHODS: PBLs were extracted from fresh blood of 36 BPH patients and 11 age-matched controls. The PBLs were incubated with PSA. Proliferation of the cultured PBLs was determined by thymidine incorporation. Secretion of cytokines to the culture medium was measured either by biological assay (IL-2) or by ELISA (IL-4, IL-10, IFNgamma, TNFalpha). RESULTS: Twelve of the 36 BPH patients responded to PSA, whereas none of the 11 controls responded (p = 0.04). The proliferative response of PBLs from BPH patients was significantly higher as compared to PBLs of controls (p = 0.03). The mean total prostate volume and the transition zone volume were 51% and 54% bigger, respectively, among the responders to PSA as compared to the nonresponders (p < 0.05), whereas the mean serum PSA level did not differ significantly. PBLs of BPH patients secreted significantly higher levels of TNFalpha, both spontaneously and in response to PSA, as compared to controls (p = 0.003). CONCLUSIONS: These findings show that PSA is able to induce proliferation of PBLs in vitro in BPH patients. Moreover, the higher spontaneous and PSA-induced secretion of TNFalpha in BPH patients may reflect a role for this proinflammatory cytokine in vivo. Based on these observations, we suggest that autoimmune dysregulation might have a role in BPH.
Aged↗
Piezoelectric immunosensors for urine specimens of Chlamydia trachomatis employing quartz crystal microbalance microgravimetric analyses.
The assembly of a biosensor for Chlamydia trachomatis based on the microgravimetric quartz crystal microbalance (QCM) analysis of the bacteria association to an antibody-functionalized electrode is described. The sensing interfaces consist of a primary cystamine monolayer assembled onto Au electrodes associated with the quartz crystal. The monolayer is further modified with sulfosuccinylimidyl 4-(p-maleimidophenyl)butyrate (sulfo-SMPB) and the goat IgG-anti-mouse IgG Fc-specific Ab or the fragmented F(ab')2 anti-mouse IgG Ab that act as sublayers for the association of the sensor-active anti-C. trachomatis LPS-Ab. Bacteria in the concentration range from 260 ng.mL-1 to 7.8 micrograms.mL-1 are sensed by the functionalized crystals. The association of C. trachomatis to the sensing interface can be confirmed and amplified via interaction of the crystal with various anti-C. trachomatis antibodies. Urine-pretreated functionalized quartz crystals are applied in the analysis of C. trachomatis in urine samples. The sensitivity limits of the electrodes for sensing the bacteria in urine samples corresponds to approximately 260 ng.mL-1. The functionalized crystals assembled via association of anti-C. trachomatis LPS-Ab to the fragmented F(ab')2 anti-mouse IgG Ab reveal long-term stability upon storage at 4 degrees C.
Antibodies, Bacterial↗
T cell receptor expression and differential proliferative responses by T cells specific to a myasthenogenic peptide.
Myasthenia gravis (MG) is a T-cell-regulated autoimmune disease in which a pathological autoantibody response is mounted against the nicotinic acetylcholine receptor of the neuromuscular junction. Our laboratory previously identified a T cell epitope, p195-212, derived from the human acetylcholine receptor alpha subunit, which triggered PBL to proliferate from about 70% of MG patients tested. p195-212 was also found to be an immunodominant T cell epitope in SJL mice and a cryptic epitope in C3H.SW mice. Inoculation of naive SJL mice with cells from a p195-212-specific syngeneic T cell line caused MG-related autoimmune manifestations in those mice. In these studies we analyzed TCR alpha and beta chain sequences used by T cell lines and clones from both high- and low-responder mouse strains in response to p195-212. T cell lines generated from either strain expressed single TCR V beta gene segments (V beta 17 in SJL mice and V beta 8 in C3H.SW mice). By deleting V beta 17-expressing T cells in p195-212-immunized SJL mice we established a T cell line that expressed the V beta 6 gene product, suggesting that SJL mice are not limited to using a single V beta gene segment in response to p195-212. In addition, we found that N- and/or C-terminal-truncated peptides of p195-212, presented under the same culture conditions to different clones bearing the same TCR alpha beta chain, could elicit very different proliferative responses from the clones. Thus, even within a constrained system, factors other than TCR sequence contribute to the differential stimulation of T cell responses.
Amino Acid Sequence↗
A peptide composed of tandem analogs of two myasthenogenic T cell epitopes interferes with specific autoimmune responses.
Myasthenia gravis (MG) is a T cell-regulated, antibody-mediated autoimmune disease. Two peptides representing sequences of the human acetylcholine receptor alpha-subunit, p195-212 and p259-271, were previously shown to stimulate peripheral blood lymphocytes of patients with MG and were found to be immunodominant T cell epitopes in SJL and BALB/c mice, respectively. Single amino acid substituted analogs of p195-212 (analog Ala-207) and p259-271 (analog Lys-262) were synthesized. We showed that analogs Ala-207 and Lys-262 inhibited, in vitro and in vivo, the proliferative responses of T cell lines specific to the relevant peptide and lymph node cells of mice immunized to p195-212 and p259-271, respectively. To inhibit T cell responses to both peptides (p195-212 and p259-271), we synthesized dual analogs composed of the tandemly arranged two single (Ala-207 and Lys-262) analogs (dual analog) either sequentially (Ala-207-Lys-262) or reciprocally (Lys-262-Ala-207). In the present study, we report that both dual analogs could bind to major histocompatibility complex class II molecules on antigen-presenting cells of SJL and BALB/c mice. Analog Lys-262-Ala-207, which bound more efficiently to major histocompatibility complex class II molecules, was found to inhibit the proliferative responses of both p195-212- and p259-271-specific T cell lines. Furthermore, the analog inhibited the in vivo priming of lymph node cells of both SJL and BALB/c mice when administered i.v., i.p., or per os. The dual analog Lys-262-Ala-207 could also immunomodulate myasthenogenic manifestations in mice with experimental autoimmune MG induced by inoculation of a pathogenic T cell line. Thus, a single peptide that is composed of analogs to two epitope specificities can be used to regulate T cell responses and disease associated with each epitope.
Amino Acid Sequence↗
Photochemically-activated electrodes: application in design of reversible immunosensors and antibody patterned interfaces.
Antigen monolayers assembled onto Au electrodes associated with a quartz crystal act as electrochemical or microgravimetric quartz-crystal-microbalance (QCM) sensing interfaces for the complementary antibody. Electrochemical analysis of the antibody (Ab) is based on the insulation of the antigen monolayer electrode by the associated Ab towards a redox probe in the electrolyte solution. Ferrocene-modified glucose oxidase (Fc-GOx) and glucose are employed as redox probes for the amperometric transduction of the Ab association to the electrode. Bioelectrocatalyzed oxidation of glucose provides an electrochemical route to amplify the antigen-Ab complex formation. Electrochemical analysis of the dinitrophenyl antibody, DNP-Ab, by a dinitrophenyl-lysine monolayer electrode is presented. QCM analysis of the Ab is based on the frequency changes of the quartz crystal resulting from the association of the Ab to the crystal assembly. This method is discussed with the analysis of the fluorescein antibody, Flc-Ab, using a fluorescein monolayer-modified quartz crystal. A novel method to tailor reversible immunosensor devices by the application of photoisomerizable antigen monolayers on electrodes is presented. The antigen is modified by photoactive units exhibiting reversible photoisomerizable properties. In one photoisomer state, the antigen exhibits affinity for the Ab and enables its electrochemical or QCM analysis. Photoisomerization to the complementary state perturbs the antigen structure and the monolayer lacks affinity for the Ab. This enables the washing-off of the Ab and the regeneration of the actively sensing interface by a second illumination process that restores the antigen monolayer-modified surface. This method is exemplified by the development of a reversible DNP-Ab sensing electrode. N-Mercaptobutyl dinitrospiropyran was assembled as a photoisomerizable monolayer on a Au electrode. The dinitrospiropyran monolayer, SP-state, exhibits affinity for the DNP-Ab and enables the amperometric detection of the Ab using Fc-GOx and glucose as redox probe. The complementary photoisomerized protonated dinitromerocyanine monolayer, MRH(+)-state, lacks affinity for the DNP-Ab. By photoisomerization of the DNP-Ab associated with the SP-monolayer electrode to the MRH(+)-monolayer state, the DNP-Ab is washed-off, and by a second illumination process, the MRH(+)-monolayer is re-isomerized to the SP-monolayer assembly, which is the active interface for further analysis of the DNP-Ab. Cyclic amperometric detection of the DNP-Ab by the photoisomerizable dinitrospiropyran monolayer is demonstrated. The association of the DNP-Ab to the SP-monolayer electrode and the dissociation of the Ab from the MRH(+)-monolayer electrode are confirmed by QCM experiments using a dinitrospiropyran monolayer-modified quartz crystal. The insulating features of an antigen-Ab complex on a conductive surface and the photochemically controlled association of an antibody to a photoisomerizable monolayer assembled onto the surface were used to develop means for micropatterning of surfaces by the antibody. A dinitrospiropyran antigen monolayer was assembled onto conductive ITO glass. A DNP-Ab solution was used as 'ink solution' to pattern the surface. The Ab-pattern was imaged by electrochemical copper deposition onto the Ab-lacking surface domains. The dinitrospiropyran monolayer assembled onto ITO or Pyrex glass surfaces was employed as an active interface for the photolithographic patterning of the surface with the DNP-Ab. (ABSTRACT TRUNCATED)
Antigen-Antibody Reactions↗
Different roles of D-amino acids in immune phenomena.
Peptides and polypeptides either fully or partially built of D-amino acids interest researchers because of their advantages over all L peptides and polypeptides. In exploiting these characteristics, one should realize that the resulting molecules are nonetheless not inert, but rather may induce a unique immune response, which is hardly cross-reactive with the L-enantiomer. Moreover, cross-reaction between the L- and the D-sequences is limited also at the T cell level, probably due to different sterical conformations of the MHC-antigen-T cell receptor complexes formed. Polypeptides built exclusively of D-amino acids lead to antibody formation only at a relatively low concentration, otherwise they provoke immunological paralysis. The specificity of the immune response toward peptides containing D-amino acid residues is exquisite, and often D-amino acids play a dominant role in defining the specificity. Polypeptides composed exclusively of D-amino acids are thymus-independent antigens. Nevertheless, it is possible to prepare against them highly specific T cell hybridomas. In future plans for synthetic vaccines against infectious or autoimmune diseases, the inclusion of D-amino acids may be an advantage in terms of both specificity and efficacy, the latter because of longer persistence in an undigested form because they resist enzymatic degradation.
Amino Acids↗
Reactivity of T cells from seronegative patients with myasthenia gravis to T cell epitopes of the human acetylcholine receptor.
Seronegative (SN) patients with myasthenia gravis (MG) have clinical and electrophysiologic features similar to those of seropositive (SP) patients, and they respond to the same therapeutic measures. However, because SN patients lack detectable (by standard radioimmunoassays) serum antibodies to acetylcholine receptor (AChR), which are considered to have a crucial role in MG, the pathophysiologic basis for the disease is not clear. We therefore compared the ability of peripheral blood lymphocytes (PBL) of SN patients (11) and SP patients (39) to respond to myasthenogenic T cell epitopes of human AChR. We tested two aspects that relate to T-cell immunity: 1) T cell responses to myasthenogenic peptides by proliferation and IL-2 production, and 2) the ability of antigen-presenting cells to bind these T-cell epitopes. T cells of SN patients did not differ from those of SP patients in their ability to respond and to bind the two human AChR-derived myasthenogenic peptides. This supports the belief that most SN patients indeed suffer from an autoimmune disease directed against the AChR. The presence of T-cell immunity in the absence of antibodies may emphasize the importance of AChR-specific T cells in MG.
Adult↗
A comparison between arterial- and venous-sampled activated clotting time measurements.
In order to compare activated clotting time (ACT) sampled from an arterial (heparin-flushed) line with the control, a venous (heparin-free) line, arterial and venous ACT values were assessed before and after cardiopulmonary bypass in 150 patients while undergoing open-heart surgery. ACT was measured by Hemochron 801 automatic analyzer. Baseline arterial ACT was significantly higher than baseline venous ACT (14%; p < 0.001, using one-way analysis of variance and Bonferroni multiple comparisons test). The differences between the values of arterial and venous ACT after protamine reversal, between arterial ACT at baseline and after protamine reversal, and between venous ACT at baseline and after protamine reversal were not statistically significant. We conclude that arterial-sampled ACT measurement is suitable and reliable for monitoring heparin reversal by protamine after cardiopulmonary bypass.
Adult↗
MHC class II-mediated T cell response to DNA.
Anti-DNA antibodies are elevated in several autoimmune diseases, including systemic lupus erythematosus. Yet, DNA was not shown to be presented by molecules of the major histocompatibility complex (MHC), nor was it reported to specifically stimulate T cells in vivo, although these steps are essential for antibody production. We now demonstrate DNA-specific T cell activation, which involves presentation of DNA by MHC class II molecules. T cells, isolated from lymph nodes of mice immunized with a murine monoclonal anti-anti-DNA antibody, proliferated in response to DNA. Moreover, presentation of DNA by murine antigen-presenting cells could be inhibited with an isotype-specific anti-Ia antibody, and with peptides restricted by the same H-2 haplotype, suggesting that it is MHC class II-mediated. These results indicate that DNA can play a direct role in the regulation of T cells and in autoimmune processes.
Animals↗
Peptide analogs to pathogenic epitopes of the human acetylcholine receptor alpha subunit as potential modulators of myasthenia gravis.
Myasthenia gravis is an autoimmune disease in which T cells specific to epitopes of the autoantigen, the human acetylcholine receptor, play a role. We identified two peptides, p195-212 and p259-271, from the alpha subunit of the receptor, which bound to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APCs) from peripheral blood lymphocytes of myasthenia gravis patients and stimulated lymphocytes of >80% of the patients. We have prepared analogs of these myasthenogenic peptides and tested their ability to bind to MHC class II determinants and to interfere specifically with T-cell stimulation. We first determined relative binding efficiency of the myasthenogenic peptides and their analogs to APCs of patients. We found that single substituted analogs of p195-212 (Ala-207) and p259-271 (Lys-262) could bind to human MHC molecules on APCs as efficiently as the original peptides. Moreover, dual analogs containing the two single substituted analogs in one stretch (either sequentially, Ala-207/Lys-262, or reciprocally, Lys-262/Ala-207) could also bind to APCs of patients, including those that failed to bind one of the single substituted analogs. The single substituted analogs significantly inhibited T-cell stimulation induced by their respective myasthenogenic peptides in >95% of the patients. The dual analogs were capable of inhibiting stimulation induced by either of the peptides: They inhibited the response to p195-212 and p259-271 in >95% and >90% of the patients, respectively. Thus, the dual analogs are good candidates for inhibition of T-cell responses of myasthenia gravis patients and might have therapeutic potential.
Adult↗
Is male gender a risk factor for conversion of laparoscopic into open cholecystectomy?
BACKGROUND: Based on a clinical observation that the conversion rate of laparoscopic cholecystectomy (LC) to open cholecystectomy (OC) is higher in males, we decided to review our records and to verify whether a significant difference in conversion rates exists between sexes. METHODS: A retrospective study on conversion rates of elective laparoscopic cholecystectomy (LC) into open cholecystectomy (LC) in relation to gender was carried out in 329 patients: 267 females and 62 males. RESULTS: Our data revealed that the probability of conversion is fivefold greater in males than females, 21% vs 4.5%, respectively (p = 0.0001). We attribute this striking difference to significantly more adhesions p = 0.0002) and anatomical difficulties (p = 0.003) in males during LC, leading to conversion. CONCLUSIONS: We conclude that conversion of LC to OC is more prevalent among males and is probably attributable to a greater incidence of anatomical difficulties.
Cholecystectomy↗
Left, but not right, one-lung ventilation causes hypoxemia during endoscopic transthoracic sympathectomy.
OBJECTIVE: To describe the respiratory and cardiovascular effects of one-lung ventilation, using a double-lumen tube, during endoscopic transthoracic sympathectomy. DESIGN: A prospective clinical study. SETTING: A university-affiliated medical center. PARTICIPANTS: Nineteen adult patients (10 men, 1 woman) between 16 and 35 years of age, ASA (American Society of Anesthesiologists) physical status I and II, participated in the study. INTERVENTIONS: Endoscopic transthoracic sympathectomy was performed under general anesthesia, using a double-lumen endobronchial tube, after induction of artificial pneumothorax plus insufflation of CO2 into the operated chest. Via radial artery cannulae, one to three arterial blood gas samples were taken during two-lung ventilation before surgery, at each one-lung ventilation, in most cases during the period of two-lung ventilation when switching between the operated sides, and after surgery. MEASUREMENTS AND MAIN RESULTS: Comparisons were performed using the Wilcoxon matched-pairs single-ranks test. Left-lung ventilation and right-chest operation caused profound decrease of arterial oxygen partial pressure (PaO2), compared with two-lung ventilation before surgery (70.7%, P > 0.0003) and compared with PaO2 at two-lung ventilation during and after surgery (decrease of 80.1% and 75.3%, respectively; P > 0.001 and < 0.005, respectively). Right-lung ventilation and left-chest operation did not cause hypoxemia. Arterial CO2 partial pressure, pH, and bicarbonate, as well as hemodynamic parameters, did not change from baseline values throughout surgery. CONCLUSIONS: Pulse oximetry and repeated blood gas measurements are needed during endoscopic transthoracic sympathectomy in order to detect and treat hypoxemic events, which may jeopardize the patient's life.
Adolescent↗
Altered peptide ligands of a myasthenogenic epitope as modulators of specific T-cell responses.
Myasthenia gravis (MG) is a T-cell regulated autoimmune disease. A peptide representing a sequence of the human acetylcholine receptor alpha-subunit (p195-212) was previously shown to stimulate proliferative responses of peripheral blood lymphocytes from MG patients and to be an immunodominant and myasthenogenic T-cell epitope in SJL mice. The authors generated a panel of analogues of p195-212 that contain single amino acid substitutions. Three of the analogues (203PHE, 204GLY and 207ALA) triggered low to no proliferative responses of a p195-212-specific T-cell line designated TCSJL195-212. Two of these analogues were able to stimulate the line to produce interleukin-2 (IL-2) and IL-4 (203PHE and 204GLY), whereas one analogue, 207ALA, did not stimulate the line to produce these cytokines. Binding assays revealed that the binding affinity of an altered peptide for a given major histocompatibility complex (MHC) molecule is not sufficient to determine whether it will be stimulatory or inhibitory to a native peptide-specific T-cell line. Two of the analogues, 204GLY and 207ALA, inhibited proliferative responses of cells of the TCSJL195-212 line when co-cultured with p195-212 and syngeneic antigen presenting cells (APC). The two inhibitory analogues were also able to inhibit proliferative responses of the TCSJL195-212 line when APC were pre-pulsed with p195-212, indicating that MHC blockade is not the only mechanism of action of these peptides. Moreover, both analogues inhibited the ability of p195-212 to prime lymph node cells for proliferative responses even when the analogues were administered in a soluble form. Thus the altered peptide ligands 207ALA and 204GLY can modulate T-cell responses both in vitro and in vivo and may have therapeutic potential for the treatment of MG.
Amino Acid Sequence↗
Down-regulation of hepatic peripheral-type benzodiazepine receptors caused by acute lead intoxication.
In the present study we investigated the influence of acute lead poisoning upon the expression of benzodiazepine receptors. In addition, we examined if administration of PK 11195, an isoquinoline carboxamide derivative, to lead-poisoned rats could modulate the changes in receptor binding properties achieved by lead alone. Lead poisoning was ascertained by determination of urine delta-aminolevulinic acid levels and lead levels in rat livers. Scatchard analysis of saturation curves of [3H]PK 11195 binding to liver membranes of rats treated with lead alone or with both lead and PK 11195 showed and approximately two-fold decrease in receptor density in comparison with control groups. Peripheral benzodiazepine receptor density in kidneys and adrenals of poisoned rats was not changed by lead intoxication per se or by coadministration of PK 11195. Scatchard analysis of saturation curves of [3H]Ro 15-1788 binding in rat cerebral cortex tissue showed no difference in the receptor density between the various groups. The Kd values of all organs were in the nanomolar range (1-4 nM). We conclude that PK 11195 is not a protective agent of hepatic peripheral benzodiazepine receptors in lead intoxication. Moreover, it causes over-accumulation of lead in hepatocytes in an unknown mechanism of action.
Adrenal Glands↗
Beneficial effects of bone marrow transplantation on the serological manifestations and kidney pathology of experimental systemic lupus erythematosus.
We have recently shown, using allogeneic bone marrow transplantation (BMT), that susceptibility of mice to the induction of experimental systemic lupus erythematosus (SLE) is determined by bone marrow (BM)-derived cells. In the present study we investigated the ability of BMT to cure mice already afflicted with this disease. We found that transplantation of SLE-diseased mice, with T-cell-depleted BM cells either from an SLE-resistant or from an SLE-susceptible donor, caused a significant reduction in the levels of anti-16/6 Id, 16/6 Id+, anti-ssDNA, and anti-dsDNA autoantibodies, compared to untreated SLE-afflicted mice. Interestingly, the reduction caused by the BMT of SLE-susceptible donor cells in the levels of the two former antibodies was significantly milder than the reduction caused by BMT of SLE-resistant cells. In contrast, the reduction in the levels of anti-ssDNA and anti-dsDNA antibodies, following BMT of cells from SLE-susceptible donors, did not differ from that caused by transplantation of BM cells from SLE-resistant donors. Following the transplantation of SLE-resistant but not of SLE-susceptible BM cells, a significant reduction was observed in the frequency of mice suffering from SLE-related immune complex deposits in their kidneys. If performed at advanced stages of the disease, transplantation of SLE-resistant BM cells into experimental SLE-diseased mice still led to a reduction in the levels of SLE-related autoantibodies, although to a lesser extent, but failed in improving kidney pathology. In conclusion, our data demonstrate that bone marrow transplantation has a beneficial effect on mice afflicted with experimental SLE.
Animals↗
Binding of peptides of the human acetylcholine receptor alpha-subunit to HLA class II of patients with myasthenia gravis.
MG is an autoimmune disease in which T cells specific to T-cell epitopes of the human acetylcholine receptor play a role. We have identified two peptides, p195-212 and p259-271, of the human acetylcholine receptor alpha-subunit, to which PBLs of MG patients responded by proliferation. Nevertheless, proliferation assays are relatively complicated to perform and might be affected by medications taken by the patients. Therefore, we tested the possibility of using a different assay to determine recognition of these peptides by MG patients. Thus, we performed a direct binding assay using biotinylated peptides and APCs from peripheral blood of MG patients and healthy controls. With this assay we detected the binding of the two peptides to the surface of intact APCs of both MG patients and control donors. Moreover, the presentation of peptide p259-271 by individuals with MG was significantly higher than that observed in healthy subjects. The peptides were specifically bound to HLA class II determinants on the APCs, as shown by inhibition with antibodies to the HLA class II haplotypes of the individuals investigated. Moreover, the binding of these peptides was in correlation with their ability to induce specific proliferative responses of peripheral blood T cells of these patients. The ability to screen for potentially pathogenic epitopes in each patient is of importance for the future design of specific inhibitory analogues that might be used to treat MG.
Amino Acid Sequence↗