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Biomedical subjects

A D Hess

Publications and source records attributed to A D Hess.

At least 145 records · Page 8Linked to original sources
PubMed1981

Suppressor cells in transplantation tolerance. II. maturation of suppressor cells in the bone marrow chimera.

Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods.

Animals↗
PubMed1981

The effects of electrophoretically "slow" and "fast" alpha-2 macroglobulin on mixed lymphocyte cultures.

It has been determined that alpha-2 macroglobulin (alpha 2M) is more suppressive of a mixed lymphocyte response (MLR) when complexed with proteinase than in its "native" state. Other alpha 2M preparations showed a moderate level of MLR suppression, but it is unlikely that this is a result of interaction with cellular proteinases. A panel of other proteinase inhibitors (alpha 1 PI, SBTI, BPTI, TLCK) did not suppress the MLR to the same extent as alpha 2M either when bound with or free from trypsin. A dose-responsive pattern of MLR suppression similar to that observed with purified proteinase-complexed alpha 2M was seen with serum containing proteinase-complexed alpha 2M. The population of cells that apparently conveys the suppressive property is the adherent cells (putative monocytes), which can reduce the MLR almost as well as unfractionated cells when exposed to alpha 2M. Most of these properties of alpha 2M were demonstrable in "serumless" medium with qualitative similarity to the MLR obtained in cultures performed with conventional serum supplemented medium. It was found that alpha 2M-trypsin complexes must be presented at or near culture initiation and remain in contact with the cells for a minimum of approximately 4 hr to have its optimum effect.

Blood↗
PubMed1981

In vitro activation of human suppressor cells: relative quantitation and specificity of suppressor cells generated in primary and secondary mixed lymphocyte cultures.

Human suppressor cells activated in primary and secondary mixed lymphocyte cultures (MLC) were quantitatively assessed for their ability to suppress the proliferative response of fresh responding lymphocytes to the original sensitizing (specific suppression) and third party, unrelated (non-specific suppression) alloantigens. Maximal levels of both specific and non-specific suppressor cell activities generated in primary MLC were found in the population of cells harvested on day 7 which corresponded to the peak of proliferation in bulk culture and decayed upon further culture reaching a nadir concomitant with the end of proliferation in primary bulk MLC. Maximal reactivation of the suppressor cells was accomplished by restimulation in secondary MLC with the original sensitizing alloantigens. Assessment of suppressor cell activity revealed that specific rechallenge with the original stimulating alloantigens in secondary MLC resulted in significant increases in both the levels of suppressor cell activity and in the specificity of action of the suppressor cell population as compared to suppressor cells harvested from primary MLC on day 7. Both primary and secondary MLC activated suppressor cells were capable of suppressing the induction of cytolytic lymphocytes in primary MLC. Suppression was not simply the result of altered kinetics of the fresh micro MLC response.

Cytotoxicity, Immunologic↗
PubMed1980

Immunosuppressive effects of rabbit anti-canine brain serum.

Liver absorbed rabbit anticanine brain serum (ABS) was tested for its immunosuppressive capacities in dogs. Single intravenous injection of ABS led to significant decrease in lymphocyte counts and functions after 24 hours, as measured by phytohemagglutinin stimulation and mixed lymphocyte culture. The immunosuppressive effectiveness of ABS could further be documented by prolongation of skin graft survival in unrelated dogs which were treated daily for 12 days with intramuscular ABS injections. The ABS was generally well-tolerated. One dog died of pneumonia. All dogs showed moderate decrease in platelet counts after 10 days of ABS treatment. Autopsies showed normal cerebral histology, moderate lymphoid hypoplasia, and no changes in the bone marrow and liver. The results suggest that liver absorbed anti-canine brain serum is a potent immunosuppressant with limited toxicity.

Animals↗
PubMed1980

Plasmapheresis as immunotherapeutic modality in the treatment of the canine venereal tumor.

Plasmapheresis was evaluated as a treatment modality for the transmissible venereal tumor (TVT) of the dog. The TVT is a unique tumor because of its capability for transplantation as a homograft between untreated randomly bred dogs and is characterized by the presence of dog leukocyte antigen (DLA) determinants on its tumor cells and reactivity in the mixed leukocyte tumor cell culture (MLTC). In the progressing phase, high titers of blocking antibodies measurable in the MLTC were noted. The purpose of this study was to evaluate the influence of plasmapheresis on the growth of established TVT and to correlate tumor response with the removal of blocking factors. Six pairs of DLA-identical dogs were used as experimental and control animals. Plasmapheresis was performed by discontinuous centrifugation using the Hemonetics model 30. An average of 1100 +/- 120 ml of plasma was exchanged on consecutive days during the third week after tumor injection. Consistently lower growth rates were observed in 2 experimental dogs, but there was no early rejection. Sera taken at day 14 of tumor growth contained significant blocking activity in all 12 dogs. Sera obtained post-plasmapheresis showed a decrease of blocking activity in all 6 experimental dogs, P less than 0.001. The TVT appears to be a suitable model for preclinical studies of plasmapheresis alone and in combination with other modalities.

Animals↗
PubMed1980

Effect of cyclosporin A on human lymphocyte responses in vitro. I. CsA allows for the expression of alloantigen-activated suppressor cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR.

The effect of cyclosporin A (CsA) on in vitro human lymphocyte responses was assessed. CsA suppressed in a dose-dependent fashion, the lymphocyte response to stimulation with mitogens and with alloantigens in primary and secondary mixed lymphocyte reactions (MLR). In contrast, the action of cytolytic effector lymphocytes was not affected by this compound. Time-course kinetic studies indicated that the mitogen response was markedly dependent on the time of addition of CsA to the cultures. Inhibition of the lymphocyte response to alloantigens was less dependent upon the time of addition of CsA to the cultures. Preincubation with CsA did not markedly affect the ability of the lymphocytes to respond to mitogens and alloantigens, nor was there an overt cytotoxic action. In addition, CsA was shown to have a differential effect on the activation of cytotoxic and suppressor lymphocyte subpopulations in primary MLR. The induction of cytolytic lymphocytes was markedly suppressed by minimal amounts of CsA, whereas the induction of alloantigen-activated suppressor cells was much less inhibited by this agent. These results suggest that CsA treatment favors the induction of suppressor cell mechanisms as opposed to cytolytic effector cells in primary MLR. This may account for the ability of this drug to establish transplantation tolerance in vivo.

Cell Division↗
PubMed1980

Inhibition of human lymphoblastoid cell line proliferation by ascites fluids from ovarian cancer patients.

Ascitic fluids from ovarian cancer patients which contained a component (lymphocyte-inhibitory activity) that inhibited the blastogenic responses of normal lymphocytes were tested for their effect on established lymphoblastoid cell lines. These ascites fluids inhibited proliferation as measured by [3H]thymidine uptake and cell growth in vitro of two different B- (SB and IM-1) and two different T- (HSB and CEM) lymphoblastoid cell lines but were not cytotoxic. No difference in the sensitivity of T- and B-lymphoblastoid cell lines to the active component in the ascites fluids could be demonstrated. In contrast, established nonlymphoid cell lines (HEp-2, oligodendroglioma, and bladder tumor cell lines) were unaffected by the ascites fluids. Two different preparations of partially purified lymphocyte inhibitory activity from these ascites fluids also inhibited lymphoblastoid cell line proliferation. In addition, both B- and T-lymphoblastoid cell lines absorbed and/or metabolized the lymphocyte-inhibitory activity at 37 degrees but not at 4 degrees. These data suggest that the inhibition of lymphoblastoid cell line proliferation and the inhibition of the blastogenic responses of normal lymphocytes by the ascites fluids are attributable to the same or similar factors.

Ascites↗
PubMed1979

Isolation and characterization of canine venereal tumor-associated inhibitory and blocking factors.

Spontaneous regression of the canine venereal tumor is associated with the production of a serum factor which inhibits in vitro tumor colony-forming units in agar. Logarithmic or persistent tumor growth, on the other hand, is characterized by a serum factor which protects cells against in vitro inhibition (blocking factor). These factors have been characterized by immunochemical methods. Whole regressor and blocking sera were fractionated by Sephadex G-200 filtration and immunoabsorption with rabbit antiserum specific for canine immunoglobulin G2a. Fractions were characterized by immunoelectrophoresis, radial immunodiffusion, and disc gel electrophoresis. In vitro inhibitory and blocking activity of the whole serum was accounted for by the purified immunoglobulin G2a. Blocking activity was also found in protein eluted from logarithmically growing tumors. Preparative polyacrylamide electrophoresis revealed five major fractions with blocking activity only in the immunoglobulin G fraction. Tumor eluates and immunoglobulin G isolated from serially removed tumors demonstrated with the clinical course of the tumor. Using ultrafiltration and sodium dodecyl sulfate electrophoresis of tumor-associated immunoglobulin G at low pH, it was not possible to identify an antigen complexed to the blocking antibody.

Animals↗
PubMed1977

Intralesional Bacillus Calmette-Guérin immunotherapy of canine venereal tumors.

Canine transmissible venereal tumors were studied for response to intralesional Bacillus Calmette-Guérin (BCG) therapy. Six pairs of littermates, identical for the major histocompatibility complex, were evaluated. One member of each pair received intralesional BCG to one of two growing tumors. Lesions of control animals received 0.9% NaCl solution. Both injected and noninjected lesions of BCG-treated animals underwent regression within 63 days, as compared to an extended period of tumor growth (beyond 100 days) for controls (p less than 0.05). Serial in vitro assays during therapy included; (a) mixed lymphocyte-tumor culture, (b) phytohemagglutinin stimulation, and (c) assessment of lymphocyte surface markers. Lymphocytes from BCG-treated dogs were significantly more responsive to tumor cells in mixed lymphocyte-tumor culture assay than were those from controls (p less than 0.05). Maximal responses occurred during tumor regression. T- and B-lymphocyte levels as assayed by rosette formation and surface marker immunoglobulins were not influenced by BCG therapy. It was concluded that intralesional BCG therapy of canine venereal tumors was highly effective in causing regression of injected and noninjected lesions. This tumor model system may be useful for the evaluation of the effectiveness of new immunotherapeutic approaches on established neoplasms in large, randomly bred animals.

Animals↗