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Biomedical subjects

E Zeller

Publications and source records attributed to E Zeller.

17 recordsLinked to original sources

Transgenic mice expressing a truncated Peromyscus leucopus TNF-alpha gene manifest an arthritis resembling ankylosing spondylitis.

Several studies have implicated tumor necrosis factor-alpha (TNF-alpha) in autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the role of TNF-alpha in inflammatory arthritis, we generated transgenic mice harboring a truncated Peromyscus leucopus TNF-alpha (Pe-TNF) gene. An arthritic phenotype closely resembling human ankylosing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic phenotype in detail by radiographic and histologic techniques. It consisted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus TNF-alpha gene, in contrast to the RA-like phenotype described in transgenic mice expressing a truncated human TNF-alpha gene. The Pe-TNF transgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-alpha may initiate an autoimmune arthritis resembling ankylosing spondylitis.

Animals↗

A human-human hybridoma secreting anti-HLA class II antibody.

In this report, we describe the production and characterization of the first human-human hybridoma secreting antibody to HLA Class II determinants. The hybridoma (GMEC101), which has been stable in tissue culture for greater than 20 mo, secretes 10 to 50 micrograms/ml of IgM-kappa antibody. This antibody binds to a wide range of human cell lines, but not to the HLA-A,B,C, and DR-negative K562 cell line. Functionally, GMEC101 strongly inhibits a unidirectional mixed lymphocyte reaction (MLR) at the level of the stimulator cell. Neither the cellular ELISA binding nor the MLR inhibition is lost after a triple platelet absorption (which removes Class I but not Class II activity). Because the binding and MLR blocking show no correlation with the known DR or DQ specificities, we suggest that GMEC101 may be detecting a novel HLA Class II determinant.

Antibody Specificity↗

Detection of antibodies to cell surface antigens by a simplified cellular ELISA (CELISA).

An improved method for screening human hybridoma antibodies to cell surface antigens is described. The following modifications have been developed: rapid expansion of desired screening cell types by EBV transformation; use of only 5 X 10(4) cells/well; elimination of the need for glutaraldehyde fixation; elimination of the requirement for PLL to attach cells to microplates; preparation of a large number of plates which can be stored at 4 degrees for 3 months; Protein A-peroxidase ELISA assay yielding excellent replicates, low background "noise", and high OD readings for positive wells. The techniques we have developed should greatly simplify and shorten the assay procedures for detecting human antibodies to a variety of cell surface antigens.

Antibodies, Monoclonal↗

Tetrabenazine (Nitoman) therapy of chronic spontaneous oral dyskinesia. A video- and EMG-controlled study.

Therapeutic results achieved with tetrabenazine in six patients with spontaneous oral dyskinesia were evaluated by clinical rating as well as time-blind video and EMG assessment. Dramatic improvement of symptoms was observed in five of our six patients and good to satisfactory improvement in the remaining patient. The correspondence among clinical findings, EMG data, and video analysis was good. Medication was started at low doses and slowly increased. Adverse reactions (i.e., rigidity, akinesia, vasodepression) were minimal.

Aged↗

Results of a phase II study of the antidepressant effect of rolipram.

The antidepressant effect of rolipram, believed to be based on a new mechanism of action, was investigated in an open phase II study in 10 depressive patients, most of whom had been refractory to previous antidepressant therapy. Five patients displayed a good to very good improvement of their depressive condition. Four patients failed to show any substantial improvement, and therapy had to be withdrawn in one case due to deterioration of the condition. In most cases, the antidepressant effect of the trial preparation became noticeable after 2-4 days of treatment only. Basing on the presented cases, the tolerance can be described as excellent compared to other antidepressants. Although, on the whole the trial yielded very encouraging results, only double-blind trials can determine the true antidepressant efficacy of rolipram.

Adult↗

Strong HLA-DR expression in T cell cultures after activation is necessary for IL-2-dependent proliferation.

We have examined the appearance of DR antigens on human T cells activated by PHA, using a monoclonal anti-DR framework antibody and a large panel of human HLA typing sera. Strong DR expression within the culture by day 8 was associated with the ability of cells to grow for long periods in IL-2 containing medium, whereas weak or absent DR expression was predictive of poor in vitro growth. All the cells responded equivalently to initial stimulation with PHA. These data support the hypothesis proposed by Moretta et al. to explain blocking of IL-2-dependent proliferation by an anti-DR antibody--that DR molecules may be involved in the transmission of signals by IL-2.

Cells, Cultured↗

[Spontaneous oral dyskinesia. Successful treatment with tetrabenazine (author's transl)].

Tetrabenazine (50-150 mg/day) was a moderate to excellent efficacy in each of six patients with severe spontaneous oral dyskinesia. Slight akinesia, rigidity, and transient disorientation were occasional side effects that could easily be controlled and were tolerated by the patient in view of the lasting amelioration of this debilitating symptom. When tetrabenazine was administered for blepharospasm, only two of six cases showed partial improvement with more severe side effects.

Aged↗

Activation of classical complement pathway by naturally occurring heteroantibodies in normal rabbit serum. Effect on subpopulations of human lymphoid cells.

Heteroantibodies present in normal rabbit serum (NRS) are toxic to human B lymphocytes, T lymphocytes, and monocytes. Even NRS, which exhibits little back ground cytotoxicity for human lymphoid cells in conventional HLA or B-cell lymphocytotoxic assays, can be shown to contain considerable activity by making two modifications in usual procedures: by washing cells in saline or balanced salt solutions devoid of protein or sugar substances, and by increasing incubation time for 1 h to 3--4 h. Using such modifications, the cytotoxic activity of NRS towards human lymphoid cells was investigated and was found to involve activation of the classical complement pathway rather than activation of the alternate complement pathway. Residual unwanted background cytotoxicity of NRS toward human lymphoid cells can be decreased without loss of desired complement activity either by heating NRS for 15 min at 50 degrees C or by mixing NRS with small amounts of normal human serum.

Animals↗

Association of HLA-B8, DRw3, and anti-acetylcholine receptor antibodies in myasthenia gravis.

Twenty-eight patients with myasthenia gravis (MG), five with and 23 without thymoma, and 47 normal controls were typed for serologically defined HLA-A, B, C, and DRw antigens. Sera from all patients were titered for antibodies to acetylcholine receptors (AChR). The frequency of HLA-B8 and DRw3 in the non-thymoma MG patients was significantly higher than in the normal population. Most of the non-thymoma patients with AChR titers higher than the average level were positive for HLA-B8 and/or DRw3, while the majority of the HLA-B8(-) and/or DRw3(-) non-thymoma patients demonstrated AChR titers below average. These findings support the possibility of the existence of immune response genes in the HLA-B, DRw segment of the major histocompatibility complex which are concerned in the response to or recognition of autoantigens.

Acetylcholine↗

The merrit alloantigenic system of human B lymphocytes: evidence for thirteen possible factors including one six-member segregant series.

An analysis of the typing results of a 70-member chronic lymphatic leukemia B cell panel revealed evidence for 13 possible groups of the Merrit alloantigenic system. Six of these appeared possibly allelic and may represent a segregant series. The CLL panel was also fully typed for HLA and some degree of linkage dysequilibrium between Merrit and HLA seemed apparent from the data. Merrit antibodies can be absorbed out with selected surface membrane immunoglobulin (SMIG)-positive normal lymphocytes and less so or not at all with E rosette-forming T cells or Fc-positive SMIG-negative lymphocytes.

Absorption↗

A new alloantigenic system on human lymphocytes.

Certain otherwise well-definedHL-Atyping sera contain extra antibodies which do not appear to be closely related to known HL-A specificites and which react in the cytotoxic test with chronic lymphaticleukemia lymphocytes but not with normal lymphocytes. Despite nonreactivity in thecytotoxic test, absorption studies show that the antigenic factors are well represented onnormal lymphocytes. Based on cross-absorption experiments using both normal andleukemic cells, followed by back-testing with the cytotoxic test against a leukemiccell panel, evidence is presented suggesting the existence of a complex, probablymultiple allelic system on human lymphoid cells which appears distinct from the, HL-Asystem, and is definable by serologic techniques.

Cross Reactions↗