24-hour motor activity in genetically nervous and normal pointer dogs.
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Animals↗
Biomedical subjects
E Klein
Publications and source records attributed to E Klein.
The elevated natural killer sensitivity of targets carrying surface-attached C3 fragments require the availability of the iC3b receptor (CR3) on the effectors.
Human serum-treated Raji and Daudi cells were shown to bind C3 fragments on their surface as a consequence of their capacity to activate C via the alternative pathway. C3 molecules were detectable on the cell surfaces up to 24 h after serum exposure. The C3 fragment-coated cells showed increased sensitivity to spontaneous lymphocyte-mediated cytotoxicity. The effector lymphocytes involved in the enhanced cytotoxicity were NK cells with low buoyant density, carrying both CR3 and FcR. Blocking of the FcR and CR3 with F(ab)2 fragments from Leu-11c or Leu-15 mAb, respectively, did not influence the lysis of targets that did not carry C3 fragments. In contrast, the accessibility of CR3 on the effector lymphocytes was essential for the C3 fragment-mediated enhancement of cytotoxicity. In addition to the Leu-15 antibody, N-acetyl-D-Glucosamine, a compound known to block iC3b binding to CR3, also abrogated the C3 fragment-imposed effect. Our previous experiments showed that the C3 fragments bind to acceptor sites on target cells. The present experiments show that the C3 fragments fixed onto the target bind to CR3 on effector cells. These data substantiate the hypothesis that the bivalent C3 fragments, which are fixed on the targets, promote their interaction with lytic lymphocytes by bridging the two cells.
Binding Sites↗
Resistance to growth of the Moloney lymphoma YAC in semi-syngeneic graft recipients.
The growth of the Moloney-virus-induced lymphoma YAC was examined in its strain of origin, A, as well as in 6 AF1 hybrids, ALF1, AB6F1, ACBF1, AABYF1, AACAF1 and AASWF1. "Hybrid resistance", i.e., lower frequency of incidence of tumor takes compared to simultaneous A controls, was observed in all of the tested hybrids. The results with the H-2-congeneic hybrids AABYF1, AACAF1 and AASWF1 indicated that H-2 heterozygosity in itself was sufficient to exhibit hybrid resistance against YAC grafts. The A strain and its H-2 congeneic AABYF1, AACAF1 and AASWF1 hybrids all had similarly low activity in NK assays. Thus, the elevated resistance detected in these H-2 congeneic hybrids did not correlate with NK activity. The rejection capacity of the ALF1, AB6F1 and ACBF1 hybrids correlated to their relatively higher NK activity, when compared to the NK low AABYF1, AACAF1 and AASWF1 hybrids. However, consideration of quantitative differences in between the hybrids which expressed elevated NK activity (i.e., ALF1, AB6F1 and ACBF1) shows that the rejection capacity did not correlate with NK status. The hybrid with the strongest NK effect (ACBF1) was the least resistant to YAC growth (27% palpable tumors), and the hybrid with the weakest NK effect (ALF1) was the most resistant to YAC growth (7.2% palpable tumors).
Animals↗
The effect of synthetic peptides corresponding to Fc sequences in human IgG1 on various steps in the B cell activation pathway.
The influence of synthetic peptides comprising sequences in the exposed positions of the Fc region of human IgG 1 was tested on B lymphocyte activation. CH 2 domain peptides having an inhibitory effect on antibody-dependent cellular cytotoxicity, as well as the whole Fc fragment, induced the appearance of the early signs of activation on resting B lymphocytes such as increase in cell volume and HLA-DR antigen expression or leukocyte migration inhibitory factor production. The peptides did not induce proliferation of resting B cells even when B cell growth factor (BCGF)-containing supernatants were added. Exposure to Fc fragment, however, induced a weak proliferation which was significantly enhanced by BCGF. On the other hand, both the Fc fragment and the CH 2 or CH 3 domain peptides enhanced the IgM synthesis of human blood mononuclear cells when a suboptimal dose of pokeweed mitogen was present. This effect was lost when Fc fragment or the peptides were added on the third day of culture. These results suggest that the early steps of B cell activation can be induced by Fc fragment and by small molecular weight Fc peptides, which are potential ligands of Fc receptors. The Fc fragment activates B cells to the state where they respond to BCGF, but the peptides do not possess this activity. Furthermore, both Fc fragment and Fc peptides are able to enhance the IgM synthesis, when accessory cells and the appropriate differentiating factors are present.
Amino Acid Sequence↗
Leiomyomas of the duodenum.
Leiomyoma is a neoplasm of smooth muscle relatively common in the stomach, but very rare in the duodenal location. Symptoms are gastrointestinal bleeding or abdominal pain resembling peptic disease. Three cases of duodenal leiomyomas are described, and the importance of endoscopy is emphasized as a diagnostic tool. Surgical resection of the tumor is the recommended therapeutic procedure, and the difficulty in deciding at the pathological examination whether the leiomyoma is benign or malignant demands prompt follow-up of patients after surgery.
Aged↗
Importance of MHC antigen expression on solid tumors in the in vitro interaction with autologous blood lymphocytes.
In 54 patients with lung and 14 with ovarian carcinomas the quantitative variations of the major histocompatibility complex (MHC)-determined class I and class II antigens of the tumor cells were related to their in vitro interaction with blood lymphocytes, to the lymphoid infiltration of the tumors, and to the metastatic state of the disease. The tumor cell-lymphocyte interaction was measured by the proliferative response in mixed lymphocyte tumor cell culture and by the cytotoxic activity of the lymphocytes. The results showed that (1) none of the 23 tumors from patients with disseminated disease were lysed; (2) class I-negative tumors were not damaged; (3) lymphoid infiltration was present in a higher proportion of class II-positive tumors; and (4) both MHC-positive and -negative tumors were found among the disseminated tumors. The requirement of class I expression in the lytic interaction substantiates our earlier conclusion concerning the cytotoxic T lymphocyte nature of lymphocyte-mediated auto-tumor lysis. The lack of auto-tumor lysis in patients with metastases suggests impairment of lymphocyte function in advanced stages of the disease.
Adenocarcinoma↗
Effect of pancreatitis on moxalactam excretion in pancreatic fluids of dogs and man.
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Adult↗
Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow.
The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.
Animals↗
Elevated NK sensitivity of Raji cells carrying acceptor-bound C3 fragments.
The majority of cell lines derived from Burkitt lymphomas carry CR2 on their plasma membrane cell lines of haematopoietic origin can activate C3 present in human serum through the alternative pathway. However, only the lines that carry CR2 were shown to bind C3 fragments. This bond can be either fixation to acceptor sites or attachment to the CR. Our studies with Raji cells showed that when the possibility for the covalent acceptor bond was eliminated by using methylamine (MA)- or zymosan-treated serum, considerably lower amounts of C3 were bound. In the zymosan-treated serum C3 fragments are present that can bind to receptors but their capacity for acceptor bond is absent. These results indicate that when Raji cell are incubated in human serum some of the generated C3 fragments are bound to acceptors and a lower proportion through the specific interaction with complement receptors. Pretreatment of the CR2 carrying cell lines with human serum elevated their sensitivity to the lytic effect of human blood lymphocytes. We showed in this work that MA-treated serum did not induce this elevation. Zymosan-treated serum under conditions that excluded activation of the residual native C3 molecules, i.e., in the presence of EDTA, did not have the enhancing effect either. These results suggest that the increased lytic efficiency imposed by human serum was due to cleavage of C3 molecules by Raji and fixation of the C3 fragments by acceptor sites. Natural killer cells carry CR3; therefore it is likely that the attached C3 fragments bind also to the effector cells. The C3 molecules could elevate thereby the avidity between the target and the lytic lymphocytes. The observation that C3 fragments are not bound to the surface of CR2 negative lines in spite of their capacity to activate C3 suggests that the receptor molecule is either involved in the activation and/or serves also as an acceptor.
Complement C3↗
Combined treatment with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha up-regulates the expression of HLA class I determinants in Burkitt lymphoma lines.
Cell lines derived from Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma (BL) have a low or defective expression of polymorphic HLA class I determinants compared to EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin and are resistant to lysis by cytotoxic T lymphocytes (CTL) specific for the corresponding determinants (M. G. Masucci, S. Torsteinsdottir, J. Colombani, C. Brautbar, E. Klein, and G. Klein, Proc. Natl. Acad. Sci. USA 84, 4567, 1987; S. Torsteinsdottir, C. Brautbar, E. Klein, G. Klein, and M. G. Masucci, Int. J. Cancer, 41, 913, 1988). In order to investigate whether this phenotypic trait of the tumor cells can be modulated by agents known to enhance HLA class I antigen expression, pairs of LCL and BL lines were cultured in the presence of recombinant human interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Three low HLA A11 expressor EBV-negative BL lines, DG 75, BL 28, and BL 41, reacted significantly stronger with the anti-HLA A11 monoclonal antibody (Mab) AUF 5.13 after combined treatment with 500 U/ml IFN-gamma and 500 U/ml TNF-alpha. Reactivity with the AUF 5.13 and with other anti-polymorphic class I Mab's was up-regulated also in in vitro EBV-converted sublines of BL 28 and BL 41. The increment of antigen expression depended on the baseline expression in untreated cells. It was largest for the low expressor lines and decreased proportionally to the level of up-regulation induced by EBV conversion. Up-regulation of HLA A11 was accompanied by induction of sensitivity to HLA A11-specific CTLs in BL 28 and its converted subline E95A BL28 while BL 41 and E95A BL 41 remained resistant. The treatment did not affect significantly HLA A11 expression of two EBV-carrying, low HLA A11 expressor BL lines, WW-1-BL and WW-2-BL, and of the EBV-carrying BL 72 line that had a high spontaneous expression. The results suggest that the down-regulation of class I antigen expression is reversible in some but not all BL lines.
Antibodies, Monoclonal↗
Alpha-2 adrenergic receptor binding in platelets and brains of nervous and normal pointer dogs.
Nervous pointer dogs have been suggested as an animal model for certain human pathological anxiety states. Work done in humans and in animals suggests a role for noradrenergic overactivity in the manifestations of anxiety. We studied alpha 2 adrenergic receptor binding as determined by [3H]-yohimbine in platelets and brains of the nervous and normal dogs in our colony. Our findings indicate that alpha 2 adrenergic receptor density and affinity are similar in platelets and frontal cortex, but we did not observe significant differences in binding between the two groups of dogs.
Animals↗
The relationship between genetic deafness and fear-related behaviors in nervous pointer dogs.
Nervous pointer dogs have been extensively characterized as an animal model for some human pathological anxiety states. During our work with these animals suspicion developed that some of these dogs had a hearing deficit. We decided to systematically evaluate this observation and to study the relation between hearing status and fear-related behaviors in the nervous pointer dogs. Our results revealed that a majority of the nervous dogs in our colony (75%) suffer from bilateral deafness as demonstrated by complete absence of brain stem auditory evoked response. Furthermore, behavioral ratings revealed that hearing and deaf dogs do not differ in their pathological response to the characteristic fear-provoking stimuli (e.g., human interaction) and that both hearing and deaf nervous dogs markedly differ from normal dogs in that respect. The relation between these abnormalities and their implications for research involving breeding of animals for selected traits are further discussed in this report.
Animals↗
Lysis of CR2-carrying cells by natural killer cells and by activated T-lymphocytes is enhanced by C3 fragments.
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Antigens, Differentiation, B-Lymphocyte↗
Immunomodulatory effect of synthetic peptides corresponding to sequences within the CH2 and CH3 domain of human IgG1.
The Fc region of IgG is known to be the source of small peptides possessing immunomodulatory function. Results are summarized showing the effect of synthetic peptides composed of surface exposed residues of C gamma 2 or C gamma 3 domains on different steps of human B lymphocyte activation cycle. Both the CH2 (289Thr-301Arg) and CH3 (407Tyr-416Arg) peptides as well as the whole Fc fragment enhanced the IgM synthesis of PWM or PMA + CaI activated lymphocytes. This effect was exerted at the early phase of B cell activation. The incubation of separated resting B cells with Fc fragments or CH2 peptides resulted in increase of cell volume and in expression of HLA-DR antigen. On the other hand, LIF production was induced both by CH2 and CH3 peptides. It was also shown that Fc peptides induce IL-1 release from monocytes. The results suggest that the CH2 and CH3 domain peptides exert their effect partly directly, by activating resting B cells, rendering the cells more susceptible to other stimuli; and moreover, by enhancing the humoral response by triggering the release of IL-1.
B-Lymphocytes↗
Antibodies in human sera against the Epstein-Barr virus encoded latent membrane protein (LMP).
Antibodies reactive with the Epstein-Barr (EBV)-encoded latent membrane protein, LMP, were detected in human sera. Membrane fractions of the EBV-carrying Raji cells and a fusion protein (LMFP), that represents the carboxy part of LMP, were used as antigens. These were assayed by the reduction of the leukocyte migration inhibition (LMI) reaction. Reactivity with LMFP was detected in 10 of 14 sera from patients with Burkitt's lymphoma (BL) and in 3 of 23 sera from healthy EBV-seropositive individuals. The antibody levels were higher in the BL sera. Since the tumor cells do not express LMP, this may be due to the high virus load in the patients.
Antibodies, Viral↗
Surface marker characterization of EBV-carrying cells in blood of healthy seropositive individuals.
We have determined the phenotype of EBV-carrying cells in human blood by establishing spontaneous LCLs from populations selected according to three B cell markers, B1, B2, and 35.1C5. LCLs grew from the B1-positive, B2-positive, B2-negative and 35.1C5-positive population. Thus, EBV-carrying cells in blood of seropositive individuals are restricted to the B cell lineage. These B cells may or may not express the B2 epitope, and they may be derived from the lymph node mantle zone or the splenic marginal zone. These in vivo EBV-carrying cells could enter the viral productive cycle and transform coresident B cells during the initial 3 days in vitro. The characteristic of the LCLs with regard to these 3 B cell markers did not correspond to the original B cell population from which they were derived.
Adult↗
Rapid measurement of dialyzer clearance as a function of molecular weight.
The relationship between solute clearance and molecular weight (MW) is an important performance characteristic of hemodialyzers. Traditionally, this relationship has been determined using a range of solutes of diverse properties that require a variety of analytical procedures. We describe a simple method for obtaining clearance as a function of MW using a homologous series of glucose oligomers, continuous from the monomer to the octamer. Using HPLC, single analyses of the inflow and outflow streams of the dialyzer allow the determination of clearances over a MW range of up to 1314 daltons.
Calibration↗
Controlled study of verapamil for treatment of panic disorder.
The authors conducted a 16-week double-blind, crossover study in 11 patients with panic disorder to study the effects of verapamil, a calcium channel blocker commonly used in the treatment of cardiovascular disorders, on the treatment of panic disorder. Their findings suggest that verapamil has modest antianxiety and antipanic properties.
Adult↗