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Biomedical subjects

J A Hansen

Publications and source records attributed to J A Hansen.

At least 19 recordsLinked to original sources

Cell surface antigens of human melanoma identified by monoclonal antibody.

Mouse NS-1 myeloma cells were fused with spleen cells from mice that had been immunized with cells from a human melanoma, M1804. Hybrid cells were grown in selective medium and tested for production of antibody to surface antigens of M1804 cells. Three hybrids that produced antibodies that bound to the melanoma cells but not to autologous skin fibroblasts were cloned. Antibodies produced by two of the clones were cytotoxic to M1804 cells in the presence of rabbit complement. Extensive specificity tests showed that the antibodies produced by the clones bound strongly only to M1804 cells; significant, although weaker, binding occurred with 2 of 11 allogeneic melanomas. Apart from weak binding of the antibody produced by one of the clones to a breast carcinoma, binding assays of five carcinomas, one sarcoma, and fibroblasts from 17 individuals were negative, as were cytotoxic tests of 10 lymphoblastoid cell lines and peripheral blood lymphocytes from 68 normal donors and 12 chronic lymphocytic leukemia patients. This suggests that we have identified one or more determinants of a melanoma-associated antigen(s), whose expression is limited to a small proportion of melanomas.

Animals

Human blood T lymphocytes that suppress the mixed leukocyte culture reactivity of lymphocytes from HLA-B14 bearing individuals.

A nontransfused male patient with recurrent bladder carcinomata has been demonstrated to have blood T lymphocytes that suppress the MLC responsiveness of lymphocytes only from normal individuals positive for HLA-B14. Unexpectedly, this T-suppressor cell differs from three other reported blood T-suppressor cells arising in man in that it apparently does not require HLA-D locus compatibility between the suppressor cell and the lymphocyte being suppressed.

Epitopes

Intralesional injection of the methanol extraction residue of Bacillus Calmette-Guerin (MER) into cutaneous metastases of malignant melanoma.

Twenty-two patients with cutaneous metastases of malignant melanoma were treated with intralesional injections of the methanol extraction residue of bacillus Calmette-Guerin (MER). The local reaction consisted of erythema and pustule formation followed by ulceration and tumor necrosis. Side effects included fever, chills, headache and malaise in the majority of patients; nausea, vomiting, cyanosis and hypotension occurred infrequently. Hypersensitivity reactions were not observed. Temporary abnormalities in liver function were seen in 11 of 19 patients tested. Reversible lymphopenia and thrombocytopenia developed in 7 of 17 and 7 of 18 patients, respectively. Immune function, as measured by skin tests for delayed hypersensitivity and the in vitro response of isolated lymphocytes to mitogens and microbial antigens, was not influenced by treatment with MER. Transient increases were observed in total hemolytic complement, complement components and the reduction of nitroblue-tetrazolium by neutrophils. Eight of eighteen evaluable patients showed a complete disappearance of all injected lesions. We conclude that intratumoral injection of MER is effective treatment for cutaneous metastases of malignant melanoma, with a complete response rate comparable to that observed after intralesional injection of BCG.

Adult

The indirect assay for leukocyte migration inhibitory factor (LIF)--standardization and the effect of pH.

In the indirect assay for leukocyte migration inhibitory factor (LIF), lymphokine-rich supernatants were obtained by culture of stimulated lymphocytes and then tested for LIF activity in agarose plates using purified granulocytes as target cells. Studies on the standardization of the conditions under which LIF acts on the target cells are described, with emphasis on the use of "standard" supernatants of known LIF activity and the influence of pH on the action of LIF and the sensitivity of the assay. The observation that LIF activity is reduced when the ambient pH falls below 7.2 is suggested as an explanation firstly for the "escape" phenomenon seen particularly in capillary tube assays for LIF, and secondly for the reduced sensitivity of the capillarly tube assay in comparison with the corresponding agarose plate assay.

Granulocytes

Pretransplant lymphocytotoxins do not predict bone marrow graft rejection.

Ninety multitransfused patients with severe aplastic anemia were conditioned with cyclophosphamide and given marrow transplants from HLA-identical siblings. Thirty patients had complement-dependent lymphocytotoxins against a panel of cells from unrelated individuals immediately before transplantation while 60 did not. Lymphocytotoxins were more frequent among patients who had received more blood product transfusions, and these patients were more likely to be refractory to random platelet support. Twenty-seven patients rejected the marrow transplant while 63 had sustained engraftment. The present of pretransplant lymphocytotoxins did not correlate with graft rejection and hence does not appear to be useful as a test for identification of patients at high risk of rejection.

Anemia, Aplastic

Effects of transfer factor in patients with advanced cancer.

Eighteen patients with advanced cancer were given subcutaneous injections of pooled dialyzable transfer factor (TFd) from normal donors for periods of from 9 days to 6.5 months. Minor tumor regression was observed in only two patients, an effect of no therapeutic significance. However, treatment with TFd was associated with at least a temporary increase in delayed hypersensitivity reactions in 12 of 17 patients tested, including four patients who became responsive to 2,4-dinitrochlorobenzene. In general, in vitro tests of immune function were not changed after treatment with TFd except for levels of C1q, and/or C3, which were increased in 6 of 10 patients tested. We conclude that TFd may augment delayed hypersensitivity in patients with advanced cancer, and that its effects are, at least in part, immunologically nonsepcific.

Adolescent

Successful transplantation of marrow from an HLA-A, -B, -D mismatched heterozygous sibling donor into an HLA-D-homozygous patient with aplastic anemia.

A patient with aplastic anemia who was found to be homozygous for an HLA-D determinant shared by her unrelated parents achieved sustained engraftment and full restoration of hematopoietic and lymphoid function following a transplant from an HLA-A and -B nonidentical, ABO incompatible sibling who was heterozygous for the shared HLA-D specificity. Transplantation was complicated by transient graft-versus-host disease of moderate severity, which resolved completely following treatment with antithymocyte globulin and prednisone. The case indicates that patients found to be HLA-D-homozygous may be successfully transplanted from HLA-D-heterozygous sibling donors despite HLA-A and HLA-B incompatibilities, and thus further demonstrates the importance of the HLA-D region as a marker of donor-host histocompatibility.

Anemia, Aplastic

In vitro responses of peripheral blood and spleen lymphoid cells to mitogens and antigens in childhood Hodgkin's disease.

Over the past 5 years, parameters of immunological function have been determined in all children with biopsy-proven Hodgkin's disease in the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center. This report summarizes the in vitro responses of lymphocytes to stimulation by mitogens and antigens (between January 1975 and December 1976) in 33 of these previously untreated patients. In nine of these patients, responses of the splenic lymphocytes were studied concomitantly with the responses of peripheral blood lymphocytes. Peripheral blood from normal children and adults was used as the control. Our results have demonstrated no significant differences between the responses of normal children and adult controls. The absolute necessity for concomitant studies of the controls and the patients was shown. The value of examining multiple concentrations of a single mitogen was also well defined. In the children with Hodgkin's disease, there was a consistent failure of the peripheral blood lymphocytes to respond to the lower concentration dose of phytohemagglutinin. However, this abnormality was not found in the splenic lymphocytes.

Adolescent

Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor.

A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.

Bone Marrow Transplantation

Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex.

In an attempt to map the gene (or genes) controlling the synthesis fo the fourth component of complement (C4), we performed linkage studies in a family with hereditary C4 deficiency. The proband, a seven-year-old boy with lupus erythematosus, consistently lacked deteftable serum C4 by both functional and protein measurements. The complement defect was transmitted as an autosomal recessive disorder. Eight of 15 family members were considered to be heterozygotes, seven because of low C4 levels and one because of genetic data (obligate heterozygote). The gene (or genes) coding for C4 deficiency appeared to be linked to the major histocompatibility complex (A2,B12,DW2 on the maternal side and A2,BW15,LD108 on the paternal side) and to other markers known to be in close proximity to the histocompatibility complex on chromosome 6 (phosphoglucomutase-3, glyoxalase-1 and properdin factor B).

Child, Preschool

HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases.

Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.

Adult