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Biomedical subjects

R Billing

Publications and source records attributed to R Billing.

At least 19 recordsLinked to original sources
PubMed2001

Photoinduced chain reactions of alcohols in the presence of diphenyliodonium ion pairs with cyanometallates--steady state UV/visible spectroscopic and pulse radiolysis studies.

Diphenyliodonium ions (Ph2I+) form donor-acceptor ion pairs with suitable cyanometallates such as [Mo(CN)8]4-, [W(CN)8]4-, [Ru(CN)6]4- and [Os(CN)6]4-. Such ion pairs are characterized by new spectroscopic transitions due to second-sphere interactions between donor ([M(CN)x]4-, x=6, 8) and acceptor (Ph2I+) ions. Photochemical excitation of these ion-pair charge-transfer (IPCT) states leads to efficient electron transfer reactions that yield short-lived diphenyliodyl radicals (Ph2I*) and oxidized cyanometallates ([M(CN)x]3-). Diphenyliodyl radicals decay to iodobenzene and phenyl radicals. This very convenient source for generating phenyl radicals was applied to the photoinduced chain oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones, respectively. However, unexpected side reactions led to undesired chain-terminating reactions. Adduct formation of diphenyliodonium ions with alpha-hydroxyalkyl radicals was verified by pulse radiolysis studies. These relatively longlived adducts give rise to chain-terminating reactions because of interactions with [M(CN)x]4- complexes that lead to oxidized cyanometallates [M(CN)x]3- upon regeneration of the starting alcohols.

Journal Article↗
PubMed1995

Response of steroid-resistant graft-versus-host disease to lymphoblast antibody CBL1.

Therapy of steroid-resistant graft-versus-host disease (GVHD) with antibodies to T cells or cytokines is of limited value because GVHD is mediated by a pleomorphic group of effective cells and cytokines. CBL-1, a murine monoclonal antibody, recognises an antigen on activated T cells, B cells, and natural killer cells. We administered CBL-1 to ten patients with grade III or IV steroid-resistant GVHD. Complete remissions occurred in five cases and partial remissions in four. The organ system(s) affected by GVHD was not a predictor of response. CBL-1 was well tolerated and did not exacerbate post-transplant immunodeficiency. Our findings support the use of CBL-1 in primary prophylaxis for GVHD.

Adolescent↗
PubMed1987

Immunologic reconstitution after haploidentical bone marrow transplantation for immune deficiency disorders: treatment of bone marrow cells with monoclonal antibody CT-2 and complement.

Patients with congenital T lymphocyte deficiency disorders received transplants with parental bone marrow depleted of mature T cells by the use of an anti-T cell monoclonal antibody (CT-2) and complement. Our results with 16 consecutive patients (20 transplants) showed rapid engraftment of donor cells; cytoreduction (busulfan, cytosine arabinoside [ara-C], cyclophosphamide) was used in six transplants, and marrow ablation was used in six (ara-C, cyclophosphamide, 1,365-cGy total body irradiation). No patient received prophylactic anti-graft-v-host disease (GVHD) therapy posttransplant, and only one patient developed significant GVHD, which involved the skin, liver, and gastrointestinal tract. Seven others showed some manifestations of GVHD, but these were of minimal clinical significance and required only occasional steroid therapy. Overall, eight patients are alive and well; eight did not survive. Polyclonal immunoglobulin synthesis by donor memory B cells was seen shortly after transplantation, with peak donor-derived serum levels seen approximately 2 months after transplantation. After this initial immunoglobulin synthesis waned, another wave of B cell responses developed. This immunoglobulin response appears to be permanent. T cell functions appeared as soon as 3 weeks after transplantation. This experience in a variety of patients with combined immunodeficiency who received transplants with monoclonal antibody T cell-depleted marrow shows gratifying results with a consistent T and B cell benefit.

Adult↗
PubMed1987

Thymus and B cell reconstitution in severe combined immunodeficiency after transplantation of monoclonal antibody depleted parental mismatched bone marrow.

Two brothers were transplanted with bone marrow which was depleted of mature T cells with monoclonal antibody CT-2 plus complement. One child died of sepsis due to candida present prior to transplant. The other is alive and well with full T and B cell reconstitution over 36 months after transplant. Thymus biopsy taken after transplant demonstrated normal morphology and cellularity. Portions of the marrow that were radiolabeled permitted an assessment of traffic patterns of aliquots that were injected intravenously and directly into the marrow space. The studies reported here document that a one haplotype mismatch is not a sufficient disparity to preclude both B and T cell reconstitution, and that monoclonal antibody plus complement is an effective method for T cell depletion.

Antibodies, Monoclonal↗
PubMed1986

Depletion of T cells from bone marrow for allogeneic transplantation: method for treatment of bone marrow in bulk.

T lymphocytes were depleted from donor marrow for 23 patients undergoing allogeneic bone marrow transplantation using an anti-T-cell antibody, CT-2, and complement. The methodology is described in detail for in vitro depletion of large quantities of bone marrow. The extent of T-lymphocyte depletion using various T-cell markers, the percent of marrow lost in the processing and quantity of antibody, and complement needed are presented. These techniques for in vitro T-lymphocyte depletion were reproducible and did result in an average final yield of 47% of the harvested donor marrow.

Antibodies, Monoclonal↗
PubMed1986

In vitro analysis of donor bone marrow following monoclonal antibody treatment for the prevention of acute graft versus host disease.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this. CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained. Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III-IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.

Acute Disease↗
PubMed1985

Clinical trial depleting T lymphocytes from donor marrow for matched and mismatched allogeneic bone marrow transplants.

Nine patients received T-lymphocyte-depleted histocompatible bone marrow and 28 patients received T-lymphocyte-depleted histoincompatible bone marrow. Eight of nine patients receiving matched bone marrow quickly engrafted without severe graft-versus-host disease (GvHD). None of the eight patients received anti-GvHD prophylaxis medications. Two of these eight patients are currently alive. Nonengraftment and severe GvHD were problems seen in some of the patients given the histoincompatible bone marrow. Additional cytarabine pretransplant permitted engraftment in those patients undergoing histoincompatible transplants for treatment of malignancy, and prednisone and cyclosporine posttransplant reduced the incidence of acute GvHD in those given T-lymphocyte-depleted grafts. Seven of these 28 patients are currently alive. T-lymphocyte-depleted marrow can reduce the occurrence or prevent severe acute GvHD, especially when combined with additional prednisone and cyclosporine; however, the impact on relapse patterns and survival remains to be determined. The occurrence of nonengraftment and treatment-related lymphomas are formidable problems to overcome.

Adolescent↗
PubMed1985

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection.

A total of 41 patients with hematologic malignancies (other than acute leukemia in relapse) received allogeneic bone marrow transplants at the University of Wisconsin from 1 April 1980 through 31 March 1984. In an effort to minimize graft-versus-host disease, marrow was depleted of T-lymphocytes in vitro with monoclonal anti-T-cell antibody and complement prior to infusion for seven of 19 recipients of marrow from HLA-identical, MLC-nonreactive siblings, and for all 22 recipients of marrow from MLC-reactive HLA-haploidentical donors. The recipients of HLA-identical T-depleted marrow all showed excellent engraftment following standard pre-BMT conditioning with cyclophosphamide and total body irradiation. In contrast, five of five recipients of T-depleted haploidentical marrow failed to engraft following this same conditioning regimen. The addition of cytosine arabinoside to the pretransplant conditioning appeared to correct this problem, allowing engraftment in 14 of 17 subsequent patients. These clinical results, coupled with prior in vitro data, demonstrate the need to adequately suppress residual host-versus-graft immunity in order to prevent the rejection of T-cell-depleted HLA-haploidentical bone marrow.

Adolescent↗
PubMed1985

Mismatched bone marrow transplantation in children with hematologic malignancy using T lymphocyte depleted bone marrow.

Twenty children with hematologic malignancies were treated with bone marrow transplantation using histoincompatible donor marrow depleted of T lymphocytes. CT-2 and complement were used to deplete the T lymphocytes. Engraftment was not a major problem in those receiving increased pre- and posttransplant immunosuppression. Five of the 20 children are currently alive and disease-free. Complications in the other children included engraftment problems, cyclosporin toxicity, infections, and bleeding. However, for most children, durable engraftment was seen. Thus, the nonavailability of histocompatible donors is no longer a contraindication to allogeneic bone marrow transplantation for those at high risk of relapse.

Adolescent↗
PubMed1984

Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells.

Gamma-Interferon (IFN-gamma) is a lymphokine produced by T lymphocytes. We find that recombinant human IFN-gamma induces expression of HLA-D antigens on human promyelocytic leukemia cells (HL-60) and enhances expression of HLA-D antigens on normal human monocytes and macrophages. Induction of both HLA-D antigen expression and HLA-D mRNA accumulation occurs within 1 day of exposure of HL-60 to IFN-gamma and is maximal by day 5. Maximal antigen expression occurs in the presence of 100-500 units of IFN-gamma per ml. IFN-gamma induces expression of DR but not DC antigens on HL-60, as confirmed by using four different murine monoclonal antibodies or one rabbit heterologous antibody. RNA blot data show that IFN-gamma-exposed HL-60 cells contain mRNA for DR alpha and DR beta polypeptides but not for DC alpha and DC beta polypeptides, which also suggests that HLA-DR and HLA-DC gene regions can be independently regulated. IFN-gamma induces 20% of HL-60 cells to differentiate to macrophage-like cells. However, IFN-gamma dose-response studies using both HL-60 cells and a nondifferentiation variant of HL-60 cells (HL-60 blast) clearly show that induction of transcription and expression of HLA-D gene products by IFN-gamma can be uncoupled from expression of other monocyte-macrophage characteristics. Further studies show that IFN-gamma enhances expression of HLA-D antigens on normal human monocytes and macrophages. Expression of the HLA-D antigens is necessary for the interaction of macrophages and T lymphocytes; IFN-gamma may play a fundamental role in this interaction.

B-Lymphocytes↗
PubMed1984

Depletion of T cells from human bone marrow with monoclonal antibody CT-2 and complement.

CT-2 mouse monoclonal antibody to the E-rosette receptor was used with complement to deplete bone marrow of E-rosette-positive cells (T cells). Depletion of E-rosette-positive cells was complete and nontoxic to hematopoietic progenitor cells. Depletion of E-rosette-positive cells with CT-2 may decrease the severity of graft-versus-host disease following bone marrow transplantation and extend the application of bone marrow transplantation to those without HLA-identical donors.

Antibodies, Monoclonal↗
PubMed1984

A cytotoxic monoclonal antibody detecting a novel B cell membrane antigen expressed predominantly on cells bearing surface membrane immunoglobulin.

A new human B lymphocyte membrane antigen, CB2, has been detected by a mouse monoclonal IgM antibody. CB2 appears to be predominantly expressed on normal and malignant cells expressing surface membrane immunoglobulin (SmIg). By indirect immunofluorescence, the number of CB2-positive cells in normal peripheral blood correlated well with the number of SmIg-positive cells. Cytotoxicity studies on isolated cell populations showed that CB2 was present on normal B cells isolated from the spleens of 52 donors and on peripheral blood B cells from 8 donors. Monocytes, T cells, granulocytes, platelets, and red cells were CB2 negative. Only malignant cells expressing SmIg were positive. These included B-CLL, B lymphoma, prolymphocytic leukemia, and B lymphoma cell lines Daudi, Raji, and Conception. SmIg-negative leukemia cells, such as common acute lymphoblastic leukemia, acute and chronic myelogenous leukemia, and T cell leukemias, were negative. Blocking studies with human immunoglobulin suggests that the CB2 antigen is not directed against immunoglobulin determinants. Immunoperoxidase studies on normal lymph node sections show that CB2-positive cells are predominantly present in the mantle region of the follicle, whereas B1-positive cells are mainly in the germinal center.

Animals↗
PubMed1983

Crossreactivity between human and canine Ia antigens using a mouse monoclonal antibody (CIA).

A mouse monoclonal antibody (CIA) produced against human Ia antigens that reacts with 20-30% of human peripheral blood lymphocytes was found to react with more than 90% of dog lymphocytes. Less than 41% of the Ia-positive dog lymphocytes expressed surface immunoglobulins. Immunoprecipitation studies with 125I-labeled cells precipitated heavily labeled Ia bands at 28K and 35K from human cells, but from dog cells the 29K beta chain of Ia was much more heavily labeled than the alpha chain.

Animals↗
PubMed1983

A monoclonal antibody cross-reactive with human platelets, megakaryocytes, and common acute lymphocytic leukemia cells.

A cytotoxic monoclonal antibody, CALL1, produced against a human schwannoma tumor was found to react with human platelets, common acute lymphocytic cells (cALL), and lymphoblasts from lymphoid blast crisis of chronic myelocytic leukemia (CML). The hybridoma was repeatedly cloned, and the antibody was considered reactive to a single antigen by absorption tests demonstrating that platelets remove cALL activity and cALL cells absorb platelet activity from the antibody. In addition, chromatofocusing showed that the antibody against platelets and cALL had the same isoelectric point. The CALL1 antibody bound to megakaryocytes but inhibited neither myeloid (CFU-C) nor erythroid (BFU-E) colony formation from bone marrow stem cells. Immunoprecipitation and SDS-gel electrophoresis indicated that CALL1 reacts with a polypeptide of 26,000 daltons.

Antibodies, Monoclonal↗
PubMed1983

Analysis of B-cell antigens in normal reactive lymphoid tissue using four B-cell monoclonal antibodies.

Lymph nodes from 13 cases of reactive hyperplasia were examined with four different monoclonal antibodies to B cells. B-1 recognizes an antigen of 30,000 daltons on B cells. CB-2 was prepared with normal spleen and binds to a glycolipid. BA-1 labels surface immunoglobulin-positive cells, but not T lymphocytes or monocytes. B-532 recognizes an antigenic determinant of 45,000 daltons. Using the immunoperoxidase method on frozen sections of reactive lymph nodes, the staining patterns of these four unique antibodies showed dramatic differences. B-1 labeled 80%-90% of the germinal center cells and 10%-50% of the mantle region. Few interfollicular cells were positive. CB-2 stained predominantly in the mantle area (50%-90% positive cells), with moderate staining in the germinal center as well and less than 1% positive cells in the diffuse cortex. BA-1 exhibited predominant labeling in the mantle (50%-90%), with little staining in the germinal center. A large number of cells in the interfollicular, subcapsular, and medullary regions expressed the BA-1 antigen. The B-5 antibody demonstrated intense staining in the follicle (50%-95%). This staining often appeared to be polarized within the germinal center. The mantle zone demonstrated staining of 30%-50% of the cells. The different staining patterns of the B-cell antibodies, as demonstrated by the in situ distribution of positive cells within the lymph node, may reflect stages of development or activation of the B-cell population.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibody specific for human T acute lymphoblastic leukaemia.

A cytotoxic mouse monoclonal antibody (CALL2) was produced against a cultured T acute lymphocytic leukaemia (T ALL) cell line 8402. Ascites fluid containing the antibody was cytotoxic to a titre of up to 1:100 000 against 4 of 6 cultured T ALL cell lines and against leukaemia cells from 7 of 8 T ALL patients and 1 of 5 T chronic lymphatic leukaemia patients. The antibody did not react with normal peripheral-blood T and B lymphocytes, monocytes, granulocytes, spleen cells, thymocytes, platelets, and other acute and chronic leukaemia cells. The CALL2 antibody did not react with bone marrow stem cells of the myeloid series (CFU-C). This antibody may be useful for passive immunotherapy trials since it does not react with normal cells and is highly cytotoxic to T ALL cells.

Antibodies, Monoclonal↗
PubMed1982

A monoclonal antibody against an epitope common to HLA-b locus antigens.

A monoclonal antibody G4 that appears to be directed against a determinant common to all HLA-B locus antigens is described. This antibody reacted with a large panel of B and T lymphocyte and cell lines, but it did not react with two lines that do not serologically express HLA antigens (Daudi and K562) and two lines that expressed A-locus but not B-locus antigens (8402 and HPBMLT). The F(ab')2 fragment of G4 blocked B-locus but not A-locus HLA alloantisera. By immunoprecipitation and SDS-polyacrylamide gel electrophoresis G4 reacted with a dimer consisting of a heavy chain of 44,000 daltons and a light chain of 12,7000 daltons.

Animals↗