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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 235 records · Page 13Linked to original sources
PubMed1990

Functional characteristics of the intercellular adhesion molecule-1 (CD54) expressed on cytotoxic human blood lymphocytes.

We have shown that intercellular adhesion molecule-1 (ICAM-1) (CD54) positive cells are mainly responsible for the natural cytotoxic function of human blood lymphocytes. The evidences were the inhibition of cytotoxicity by anti-ICAM-1 (LB-2) monoclonal antibodies (mAb) and the loss of lytic activity after removal of the ICAM-1+ cells. In addition, the cytotoxic potential of the separated ICAM-1- lymphocyte population after activation appeared in parallel with the expression of this molecule. The ICAM-1+ lymphocytes lysed both LFA-1 (CD11a/CD18 or Leu-CAMa) positive and negative cell lines, and pretreatment of the effectors with the LB-2 mAb also inhibited the lysis of LFA-1- targets. The results point to a yet unrecognized role of ICAM-1 on the lymphocytes. Kinetics experiments suggested that pretreatment of lymphocytes with alpha-ICAM-1 (LB-2) mAb did not inhibit the promptly established lytic interactions but influenced later events, recycling and/or recruitment of effectors. It is possible that the cytotoxic potential is regulated by contacts between the members of the lymphocyte population and that these events occur via their ICAM-1 and LFA-1. Exposure of lymphocytes to NK-sensitive targets for 16 hr elevated their cytotoxic potential. The function of activated lymphocytes was not inhibited by the LB-2 mAb.

Antibodies, Monoclonal↗
PubMed1990

Inhibition by antibiotic tetracyclines of rat cortical noradrenergic adenylate cyclase and amphetamine-induced hyperactivity.

Two antibiotic tetracyclines, demeclocycline (DMC) and minocycline, share several biochemical and behavioral properties with lithium (Li). DMC inhibited both noradrenaline- and chloradenosine-sensitive cyclic AMP accumulation in rat cerebral cortical slices both in vitro and ex vivo following two weeks of chronic dietary treatment. Minocycline, a lipophilic tetracycline, produced similar results in vitro. Both DMC and minocycline reduced open-field activity levels in rats following acute treatment, four hours prior to testing. Moreover, both drugs inhibited amphetamine-induced hyperactivity in the open field. Chronic treatment with 0.4% and 0.8% dietary DMC for two weeks attenuated amphetamine hyperactivity without affecting baseline activity levels in the open field. Neither DMC nor minocycline attenuated apomorphine-induced stereotypy at doses that attenuated amphetamine hyperactivity, a profile which is similar to that of lithium. Unlike lithium, however, DMC did not reverse reserpine-induced hypoactivity.

2-Chloroadenosine↗
PubMed1990

Contribution of CR3, CD11b/CD18 to cytolysis by human NK cells.

The complement receptor CR3 molecule functions in direct intercellular contacts mediated by its beta chain, CD18. Similarly to the Fc receptor (CD16), CR3 is a marker of human natural killer cells. We have shown that opsonization of NK targets with iC3b leads to their increased lytic sensitivity. Opsonization could be achieved by incubating certain B and T cell lines in human serum. The expression of CR2 was a prerequisite for C3 fragment fixation. The CR2 negative cell line, P3HR1 could be opsonized by incubation in human serum when induced to express the EBV envelope glycoprotein gp350. C3b or iC3b could also be deposited artificially on cell surfaces by chemical coupling to surface reactive antibodies. Similarly to the function of macrophages and monocytes, contact with opsonized targets exclusively through the iC3b binding site of CR3 did not seem to trigger NK function. We attempted to clarify the functional role of other CR3 ligands. The beta chain of the molecule, CD18, was essential to the NK effect. The NK targets did not seem to interact with the beta-glucan binding epitope on the alpha chain of CR3, CD11b. On the other hand, the cytolytic function could be enhanced through this epitope with the appropriate ligand.

Antigens, CD↗
PubMed1990

C3d-mediated negative and positive signals on the proliferation of human B cells separated from blood.

Soluble C3d applied to human blood-derived B lymphocytes inhibited anti-mu, T cell-produced growth factor, and EBV-induced DNA synthesis in serum-free culture. C3d added to the B cell cultures 1 and 2 days after the stimulus, still exerted inhibition, though with gradually diminishing efficiency. C3d, fixed on zymosan or attached to the culture wells, induced [3H]thymidine incorporation of the B cells in serum-free medium. The concentration of C3d used to coat the wells was critical, with optimal stimulatory effect of 8.3 micrograms/ml. These C3d molecules were shown to be denatured. Our results are in line with earlier data on B cells derived from mouse spleen and human tonsils showing that depending on the way of presentation and its amounts, the natural ligand of CR2 can exert negative or positive signals. Moreover, we demonstrate that C3d can inhibit even the proliferative stimulus of EBV.

B-Lymphocytes↗
PubMed1990

Epstein-Barr virus-carrying B cells in the blood during acute infectious mononucleosis give rise to lymphoblastoid lines in vitro by release of transforming virus and by proliferation.

In accordance with earlier studies, we detected higher numbers of Epstein-Barr virus (EBV)-carrying lymphocytes (B-EBV) in the blood of acute infectious mononucleosis (IM) patients and higher amounts of transforming EBV particles in the saliva compared to healthy seropositive individuals. B cells grew in cultures seeded with the low and high density IM lymphocytes. The majority of B cells which grew acquired the infection in vitro (2-step outgrowth), because addition of virus neutralizing antibodies considerably reduced the emergence of lymphoblastoid cell lines (LCLs). Only the minority of the explanted B-EBV cells proliferated. The antiviral drug phosphonoformate (PFA) did not influence the frequency of 2-step LCLs in the IM cultures. This may indicate that a large proportion of EBV carrying B cells have already entered the viral productive cycle in vivo and passed the PFA-sensitive stage at the time of explantation. Earlier experiments with blood of healthy seropositive individuals showed an inhibitory effect of PFA on the generation of LCLs. One healthy individual who entered this study as a control, probably had a reactivated EBV infection as judged by the anti-EA activity in his serum and the high level of virus in his saliva. He had antibodies against EBV nuclear antigens (EBNA), and therefore he did not have a primary infection at the time of the test. Judged by the number of wells with B cell growth, the frequency of virus-carrying B cells in his blood was low. It seems that anti-EBV immunity can control the number of infected B cells in the blood, but does not influence the virus load in the epithelial cells.

Acute Disease↗
PubMed1990

Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi.

From June 1984 to September 1989, 43 patients with large vena caval tumor thrombi from retroperitoneal malignancies underwent surgical treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). The primary malignancies were renal cell carcinoma (RCC) (n = 39), renal pelvic transitional cell carcinoma (n = 1), adrenal pheochromocytoma (n = 1), and renal (n = 1) or retroperitoneal (n = 1) sarcoma. The level of the caval thrombus was either suprahepatic (n = 27), intrahepatic (n = 14), or subhepatic (n = 2). In all cases the primary tumor and caval thrombus were completely removed. Concomitant procedures included coronary artery bypass grafting (n = 5), pulmonary resection (n = 2), and hepatic lobectomy (n = 1). The time of circulatory arrest ranged from 10 to 44 minutes (mean, 23.5 minutes). There were two operative deaths (4.7%), neither of them due to to the use of DHCA. Major postoperative complications occurred in 13 patients (30.2%). There were no ischemic or neurologic complications and no cases of perioperative tumor embolization. The median postoperative hospital stay was 9 days. Twenty-two patients (51%) are alive and enjoying a good quality of life. The 3-year patient survival rates in patients with localized (n = 24) versus metastatic (n = 15) RCC are 63.9% and 10.9%, respectively (p = 0.02). We conclude that CPB with DHCA facilities excision of retroperitoneal malignancies with large caval thrombi and provides the potential for cure with low morbidity and mortality rates.

Adult↗
PubMed1990

A comparison between emergency and delayed endoscopic injection sclerotherapy of bleeding esophageal varices in nonalcoholic portal hypertension.

To study whether or not emergency sclerotherapy was more effective than a program of stabilization and elective sclerosis, we studied 84 patients with bleeding esophageal varices. They underwent 332 sessions of endoscopic injection sclerotherapy, 134 of which were performed for acute variceal bleeding. Most patients (90.5%) had nonalcoholic portal hypertension. Emergency sclerotherapy (1-6 h after presentation) was performed in 65 bleeding episodes in 43 patients, and delayed sclerotherapy (more than 24 h from presentation) was performed in 69 episodes in 41 patients. The selection of patients was randomized. Emergency sclerotherapy arrested active variceal bleeding in all patients and resulted in an earlier eradication of varices and for a longer period than delayed sclerotherapy. Larger volumes of sclerosant (a mean of 26 ml compared to 13 ml) were more effective in arrest of bleeding and in an early eradication of varices. We conclude that emergency sclerotherapy, mainly with a large sclerosant volume, is highly effective in arresting active variceal bleeding. Such earlier arrest of bleeding was associated with reduced morbidity and mortality.

Adolescent↗
PubMed1990

Microbial and endotoxin contamination in water and dialysate in the central United States.

The purified water supplies and randomly selected dialysates of 51 chronic and acute dialysis centers in the central United States were surveyed to assess the relative risks to dialysis patients from microbial and endotoxin contamination. A culture medium more sensitive than those generally employed in routine quality assurance assays was used for recovery of bacteria from water. With this medium, 35.3% of the water samples and 19% of the dialysate samples were out of compliance with the Association for the Advancement of Medical Instrumentation (AAMI) standards: 200 and 2,000 colony forming units (CFU)/ml, respectively. There was no correlation observed between the type of water purification system or the frequency of disinfection of the system and the bacterial and endotoxin contamination levels. There was also no correlation found between the bacterial and fungal CFU per ml and the endotoxin concentration per ml (EU/ml). It is recommended that more sensitive culturing methods be used to provide adequate bacterial monitoring of dialysate center water supplies. Dialysis centers should monitor endotoxin in dialysate on a regular schedule and immediately after any endotoxemic-like patient reactions. Yeast and fungi were observed in 10% and 64% of the water systems, respectively. Dialysate was contaminated by yeast and fungi in 30% and 70% of the centers, respectively. The concentrations of these microbes in both fluids were much lower than bacteria. However, they were observed often enough to warrant further investigation of their impact on the well-being of dialysis patients.

Bacteria↗
PubMed1990

Differential drug response of panic and agoraphobic avoidance in a case of panic disorder.

A case is presented of a patient with severe panic disorder and agoraphobia in whom initial treatment with clomipramine resulted in complete elimination of panic attacks, with no improvement in agoraphobic avoidance. The addition of phenelzine to the pre-existing clomipramine treatment resulted in rapid and complete disappearance of the agoraphobic avoidance. The possible implications of this case for our understanding of the neurobiological relationship between panic attacks and agoraphobia are discussed.

Adult↗
PubMed1990

Epstein-Barr virus (EBV) antigens processed and presented by B cells, B blasts, and macrophages trigger T-cell-mediated inhibition of EBV-induced B-cell transformation.

The ability of B cells, B blasts, and macrophages to present Epstein-Barr virion antigens to autologous T cells and trigger their capacity to inhibit Epstein-Barr virus-induced B-cell transformation was tested. Macrophages were as efficient as B cells and B blasts in presenting the virus to T lymphocytes. This function required antigen processing, because it was inhibited by chloroquine treatment and by fixation of the antigen-presenting cells immediately after viral exposure but not 18 h later. T cells exposed to the purified Epstein-Barr virus envelope antigen gp350 coupled to immunostimulating complexes also showed inhibitory function. These results suggest that recognition of processed virion antigens elicits the generation of T-cell-mediated inhibition of Epstein-Barr virus-induced B-cell transformation.

Antigens, Viral↗
PubMed1990

Biogenic amines distribution in the brain of nervous and normal pointer dogs. A genetic animal model of anxiety.

Nervous pointer dogs have been suggested as an animal model for pathological anxiety. In order to study possible disturbances in neurotransmitter functions in this animal model, we measured brain biogenic amines (norepinephrine, dopamine, and serotonin) and their metabolites in both nervous and normal dogs. Eight nervous and six normal dogs were behaviorally tested and later anesthetized and killed. Brains were removed and dissected while frozen using a punch technique. Samples were assayed using high-performance liquid chromatography (HPLC) with electrochemical detection. The nervous dogs had higher [NE] in the reticular formation and lower serotonin, and its metabolite 5-hydroxyindoleacetic acid, in the septal nuclei, indicating possible important differences in noradrenergic and serotonergic functions in the nervous dogs. There was a trend for lower [HVA] and [DOPAC] levels and a significantly lower [DOPAC]/[DA] ratio in the nervous dogs, suggesting decreased dopaminergic function.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Differences in the competitive capacity of monoclonal antibody sensitized human A and B erythrocytes in complement mediated cytotoxicity.

Lysis of group A and B erythrocytes by human complement was studied using 9 anti-A (IgM) and 10 anti-B (IgM) monoclonal antibodies in direct and cold target competition 51Cr-release assays. The relative concentration of membrane-bound immunoglobulins was detected by indirect immunofluorescence in flow cytometric analysis. The number of binding sites/cell and affinity of the monoclonal antibodies was measured in ELISA assays. Complete haemolysis was obtained at 2 micrograms.ml-1 antibody concentrations with the majority of reagents when only a small proportion of the antibody binding sites were occupied. The influence of membrane-bound antibody on complement binding was examined by the complement consumption capacity of sensitized erythrocytes at supra-haemolytic antibody concentration. We found that complement consumption correlated with the amount of membrane-bound immunoglobulins. To obtain equal level of target and competitor cell lysis group B erythrocytes had to be equipped with higher amounts of antibodies than group A erythrocytes. The different lytic activity of IgM anti-A and anti-B monoclonal antibodies could not be accounted for merely by differences in their surface density.

ABO Blood-Group System↗
PubMed1990

Endoscopic sphincterotomy in patients with gallbladder in situ: the influence of periampullary duodenal diverticula.

Forty-four elderly patients (mean age, 77.2 years; range, 65 to 95) with acute bile duct obstruction, with gallbladder in situ, underwent endoscopic sphincterotomy without subsequent cholecystectomy during the same hospitalization. Thirty patients had periampullary duodenal diverticula, and 14 had no diverticula. Because periampullary diverticula were associated with biliary and pancreatic complications, possibly as a result of stasis in the diverticula, the clinical course in patients with and without diverticula was compared. Endoscopic sphincterotomy was well tolerated and resulted in a rapid clinical improvement in all patients. There were four complications related to the procedure (pancreatitis, two, and cholangitis, two), all were treated conservatively, and there were no deaths. The clinical outcome was similar in both groups of patients. During a mean follow-up of 25 months (range, 6 to 58), only two patients (one of each group) underwent elective cholecystectomy 2 and 3 months after initial presentation. It is concluded that endoscopic sphincterotomy is a safe and effective alternative to surgery as an initial treatment in elderly patients with choledocholithiasis and gallbladder in situ. Periampullary duodenal diverticulum does not interfere with the favorable results of endoscopic sphincterotomy in patients with gallbladder in situ.

Aged↗
PubMed1990

Inefficacy of single-dose nifedipine in the treatment of phobic anxiety.

Single-dose nifedipine was given to 13 phobic patients with increased generalized anxiety. Nifedipine failed to demonstrate anxiety-reducing effects on baseline anxiety ratings. Furthermore, in a subset of four patients, the drug failed to show an anxiolytic effect in exposure-related anxiety.

Arousal↗
PubMed1990

Endotoxin and bacterial contamination of dialysis center water and dialysate; a cross sectional survey.

The bacterial and endotoxin levels of purified water and effluent dialysate were examined in a cross section of dialysis centers in the central United States. All samples were collected within a four-hour drive of the University of Louisville and were collected, processed and analyzed by our personnel, to eliminate variability in sample handling. A medium capable of higher bacteria recovery from aqueous environments than those ordinarily employed in clinical assays was used. Endotoxins were determined by a quantitative colorimetric assay. By the more sensitive bacterial assay 53% of the centers had bacterial counts above the AAMI standard of 200 colony-forming units per ml (CFU/ml) for water and 35% of the centers had bacterial counts above the 2000 CFU/ml standard for dialysate in at least one sampling period. The samples showed 35% and 19% of water and dialysate above the standards, respectively. While there are no standards for endotoxin concentrations in water used to prepare dialysate, 2% of the centers had endotoxin levels in their water above five endotoxin units per ml (5 EU/ml = 1 ng/ml in our assay kit), the limit set by the AAMI standards for reprocessor water. Both bacterial and endotoxin levels tended to be elevated in dialysate, with the highest levels of endotoxin in dialysates posing an obvious potential risk when high-flux dialyzers are used.

Bacteria↗
PubMed1989

Lysis of P3HR-1 cells induced to enter the viral cycle by antibody-dependent and independent immunological mechanisms.

The P3HR-1 Burkitt lymphoma line carries the Epstein-Barr virus (EBV) genome and a small proportion of the cells (1-3%) enter the lytic cycle spontaneously. Treatment with TPA and n-butyrate elevates considerably the number of virus-producing cells (25-35%). Cells which enter the lytic cycle express the EBV early antigen EA, the viral capsid antigen VCA, and the membrane antigen MA. Antibodies against these antigens are present in EBV-immune human sera. The expression of virus envelope protein on the plasma membrane renders the cells sensitive to immune effector mechanisms. These were shown to be initiated by the alternative complement pathway (ACP)-activating capacity of the cells and by their reactivity with antibodies directed to the MA. When incubated with EBV-immune or nonimmune human serum, the induced (P3HR-1-V) cells activated C3 through ACP and fixed the generated C3 fragments. The efficiency of opsonization was higher in immune serum. By varying the experimental conditions we showed the damage of the induced cells by the complement system and by blood lymphocytes, and analysed the involvement of antibodies and the activated C3 fragments in the lymphocyte-mediated lysis. P3HR-1-V cells were lysed by immune serum and also by nonimmune serum though with lower efficiency. The induced cells had elevated sensitivity to the NK effect which was potentiated if the conditions allowed their opsonization. In the presence of antibodies the lymphocyte-mediated lysis was considerably higher and the ADCC mechanism was also potentiated by opsonization. These experiments suggest that B cells which enter the virus-producing cycle may be eliminated in EBV nonimmune host by NK cells. After the antibody response against the virus develops, the attack on these cells is more efficient through complement and lymphocyte-mediated antibody-dependent mechanisms. These effector mechanisms are enhanced by opsonization which is the consequence of the C3-activating capacity of the cells. The multiple ways of the immune attack on the B cells prepared to produce EBV may explain the absence of EA and VCA positive B cells in tumor cell populations and during the acute phase of infectious mononucleosis.

Antibodies, Monoclonal↗