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D Roth

Publications and source records attributed to D Roth.

At least 37 records · Page 2Linked to original sources
PubMed1991

The effects of tissue-associated and MHC class II antigen presentation on in vitro lymphoproliferative responses against canine liver and kidney cell subpopulations.

Purified hepatocytes (LH), Kupffer cells (LKu), and intrahepatic biliary duct cells (LD) were isolated from canine livers, as well as tubular cells from canine kidneys, by enzymatic digestion, gradient centrifugation, and tissue culture techniques. Incubation of LH, LKu, and LD for 48 hr in a two-compartment diffusion chamber opposite two-way mixed lymphocyte cultures, or with canine gamma interferon purified and standardized in our laboratory, resulted in a significant increase in class II expression. This was detected in the cell analyzer with directly fluoresceinated B1F6, a monoclonal antibody (mab) generated in our laboratory vs. a canine class II monomorphic epitope. An amplification of the allogeneic mixed lymphocyte liver cell cultures (MLLC) of at least 2-fold was observed by preinduction of canine class II expression with IFN-gamma on LKu and LD cells, but an autologous reaction could not be elicited. However, an autologous as well as allogeneic lymphoproliferation against kidney tubular cells (MLKC) could be easily observed without IFN-gamma and amplified with IFN-gamma to stimulation indices of at least 3 times that of noninduced cultures. Dependence of the allogeneic MLLC and allogeneic and autologous MLKC on class II gene expression was also evidenced by blocking of 3H-thymidine uptake seen by incubation with 5 micrograms of B1F6. Another mab, I1F6, generated against tubular cells and inhibiting the autologous and allogeneic MLKC, had no blocking effect on lymphoproliferation with any of the liver cell preparations. No such tissue-specific mab (analogous to I1F6) has thus far been found in response to mouse immunization with LH, LKu, or LD. In the absence of accepted defined molecular probes in the dog as yet, we conclude that, in contrast to kidney tubular cells, cells of the normal canine liver do not readily stimulate a primary lymphoproliferative autoimmune reaction in vitro despite class II amplification. Thus autoreactivity (as opposed to alloreactivity) is much less prominent in immune recognition of purified cellular components of nondiseased liver tissue than of kidney tissue in which tissue-associated epitopes are more operative.

Animals↗
PubMed1991

Evidence that antibodies to cytomegalovirus and the T cell receptor (TCR)/CD3 complex may have common ligands.

Immunoglobulins derived from sera containing anti-antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, alpha F1, another MAb recognizing the framework of the TCR alpha chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, alpha F1 showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a approximately 50 KD band of TCML and several bands (approximately 34, approximately 40, and approximately 50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, alpha F1 immunoprecipitated a approximately 96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipitable with LAb. Both LAb and alpha F1 also showed positive binding to paraformaldehyde-fixed and Triton X-100-permeabilized PBT in flow cytometry. Sera containing Ab2 blocked alpha F1 binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both alpha F1 and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.

Antibodies, Monoclonal↗
PubMed1991

Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies.

Individuals with anti-phospholipid antibodies are at increased risk for the development of thrombosis and fetal loss. The pathogenesis of these syndromes is unknown, but may involve antibody-mediated alterations in endothelial cell coagulant activity. To address this possibility, we determined the incidence of endothelial cell-reactive antibodies in 76 patients whose plasma contained anti-phospholipid antibodies, but who had no clinically-evident immune disorder. Plasma from 47 patients deposited significantly more immunoglobulin on cultured endothelial cells than control plasma. Positive tests were more frequent in patients with a history of thrombosis than in those without (17/19 v 23/48; P = 0.004). However, we observed no correlation between immunoglobulin deposition on cardiolipin and endothelial cells by individual plasmas. Furthermore, endothelial cell reactivity was not diminished by adsorption of anti-cardiolipin antibodies from patient sera using liposomes. Immunoglobulin fractions prepared from 5/6 patient sera immunoprecipitated a approximately 70 kDa endothelial cell surface protein; 4/5 of these fractions also induced the release of von Willebrand factor from endothelial cells. These results demonstrate that plasma from many patients with anti-phospholipid antibodies, but no clinically-evident autoimmune disease, also contains endothelial cell-reactive antibodies. Detection of such antibodies might help identify individuals in this patient population at greatest risk for thrombosis.

Antibodies↗
PubMed1991

[The transfilter culture system as a model for the study of proliferation and migration of smooth muscle cells of the rabbit and human].

By cultivating smooth muscle cells, isolated from media-pieces of rabbit and human aorta, on microporous filter membranes (transfilter-culture-system), it is possible to examine proliferation and migration of smooth muscle cells at the same time. After addition of Epinephrine to the cultures, an increase in proliferation and migration was observed.

Animals↗
PubMed1991

[Cell culture as a prescreening system for drug prevention of restenosis?].

Migration and proliferation of smooth muscle cells (SMC) from the media into the subendothelial space are important steps in the development of restenosing events after angioplasty; therefore a medical inhibition of this activity seems to be of clinical interest. Primary stenosing plaque material of 20 patients and restenosing plaque material of 6 patients was removed by atherectomy (Prof. Höfling, Dr. Bauriedel, Munich). For the isolation of plaque cells a mixture of Collagenase/Elastase was used. The vast majority of plaque cells was identified as smooth muscle cells by positive reaction with monoclonal antibodies against smooth muscle alpha-Actin. Propranolol (10(-4) mol/l to 10(-9) mol/l), Prednisolone (10(-3) mol/l to 10(-8) mol/l) and Etoposide (10(-4) mol/l to 10(-9) mol/l) were added to the cultures one day after seeding. After 3 days cell number and cell size distribution were analysed in a cell counter (Casy I, Schärfe System, Reutlingen). While Propranolol didn't change proliferative activity of SMC, Prednisolone caused a slight, but dose dependent inhibition of SMC-proliferation. Etoposid inhibited SMC-proliferation even below clinical concentrations to 50%. The local application of steroid or cytostatic agents might improve long term results after angioplasty. The clinical relevance of this 'Prescreening System' has to be evaluated by experimental and clinical studies.

Angioplasty, Balloon↗
PubMed1990

A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression.

1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated. 3. Studies of major depression ought to be designed to last 8-10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.

Adult↗
PubMed1990

OKT3 induction via idiotypic networks of mirror-image immunosuppressive antiimmunoglobulins in renal transplant recipients.

Four of 21 renal transplant recipients treated with OKT3 for rejection episodes developed a second sustained (approximately 2 weeks) depression in CD3 peripheral blood lymphocyte cell-surface-marker expression. This occurred after OKT3 therapy had ceased, subsequent to a return toward baseline CD3 levels seen before OKT3 therapy was instituted. The second decrease in CD3 T cell counts was dissociated from CD2 marker T cell counts using flow cytometry and coincided with transient cytomegaloviral infections. Three phases of immunosuppression were defined in these 4 patients: phase I (during OKT3 treatment); phase II (after treatment when CD3 counts were reconstituted); and phase III (when CD3 counts again were depressed). During phase III, serum of the 4 affected patients could transfer a blocking effect on the expression of the CD3 marker of peripheral blood T cells of "normal" laboratory volunteers. Contained in these sera were human IgG antibodies that bound on Western blot analysis and by radioautography after immunoprecipitation to a protein band of a T cell membrane lysate with an m.w. of 23 kD. The reaction was identical to that seen with OKT3 (immunoprecipitation). Moreover, this Western blot binding could be virtually (but not completely) eliminated by multiple absorptions of the T cell membrane lysate with OKT3. By using an affinity-purified human anti-OKT3 IgG from one of the 4 patients, it was possible to immunoabsorb from phase III sera the CD3 blocking activity as well as the binding to the 23 KD protein band. A reverse immune absorption by the phase III sera with the anti-OKT3 IgG after ultracentrifugation prevented the anti-OKT3 IgG from binding to OKT3 coated plates in solid-phase radioimmunoassay. These data support the notion that autoimmune human anti-anti-id (Ab2) antibodies can occasionally be generated by treatment with OKT3, which are directed against CD3 complex epitopes similar to the ligand of OKT3.

Adolescent↗
PubMed1990

Symptom anticipation and the learned visceral response: a major neglected determinant of morbidity in functional and organic disorders.

This article explores the idea that symptoms in certain functional and organic disorders may be precipitated by a patient's anxiety in anticipation of that symptom's recurrence (symptom anticipation). Furthermore, through a process of learning from earlier experience, the induction of symptoms may be a highly directed process mediated by the nervous system and driven by the patient's apprehension or anxiety. In some patients this anticipation may be a major factor in causing a seemingly deteriorating clinical situation, which is often poorly responsive or unresponsive to conventional and perhaps previously effective medication. This situation tends to evoke a response from the treating physician that may lead to a course of action potentially dangerous to the patient through the use of more invasive diagnostic procedures, second-line drugs with more hazardous side effects, or even surgery. This article attempts to demonstrate that psychosomatic processes may be of considerable importance in mediating suffering through a defined mechanism in patients with established organic disease states.

Anxiety↗
PubMed1990

How "mild" is mild Munchausen syndrome by proxy?

This paper describes four cases of Munchausen Syndrome by Proxy (MSbP), in each of whom the disorder could be considered mild from the physical viewpoint. However, in all cases a severe emotional disturbance was evident in the mother-child relationship, and certain significant features were common to each case, including the dynamics of the development of the disorder. In all, maternal anxiety resulted in the mother perceiving the child as sick, leading to her insistence that he/she receive medical attention. A follow-up over several years showed severe disturbances in the emotional development of all the children. It is thus suggested that mild cases of MSbP may be indicators of severely disturbed mother-child relationships, raising important questions about their proper management.

Adolescent↗
PubMed1990

HIV-1 and HTLV-I infection in renal transplant recipients.

The prevalence of retroviral infection in renal transplantation remains poorly defined. We tested retrospectively sera from 224 of 331 patients undergoing renal transplantation between 1979 and 1985. Viral antigen based EIA was used for screening IgG antibodies to human immunodeficiency virus (HIV-I) and human T-cell leukemia virus type I (HTLV-I). Positive EIAs were confirmed by Western blot. Six patients (2.7%) were found to have retroviral infection, four with HIV-1 and two with HTLV-I. The four patients with HIV-1 infection were negative before and became EIA and Western blot positive following transplantation. All patients had transient HIV-1 antigenemia documented before antibody was detected. One patient died of Kaposi's sarcoma 2 years posttransplantion with a functioning graft. One is alive and asymptomatic 4 years posttransplant, and two rejected their grafts and are asymptomatic on maintenance hemodialysis. Six patients tested positive for HTLV-I by EIA. Only two patients, however, were also positive for HTLV-I by Western blot, RIPA, and p24 antigen RIA, one prior to and one after transplantation. Both had HTLV-I-positive lymphocyte cultures and remain asymptomatic of retroviral infection 3 years after renal transplantation. A third patient, positive for HTLV-I by EIA, had indeterminate Western blot and negative RIPA, RIA, and lymphocyte culture. Intravenous drug use was not a risk factor for retroviral infection in this patient population. It is likely that patients became infected peritransplantation from blood transfusions. Contamination by donor kidneys, however, cannot be excluded.

Acquired Immunodeficiency Syndrome↗