Search PubMed⌕ Search

Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 613 records · Page 34Linked to original sources

Enrichment (and depletion) of human suppressor cells with monoclonal antibodies and immunoglobulin-coated plates.

A cell separation method using immunoglobulin (Ig)-coated plates, originally devised for murine spleen cells, was modified and adapted for enrichment (and depletion) of cellular subpopulations from human peripheral blood. For the direct separation of B and T cells, F(ab')2 fragments of anti-human Ig were used to coat the plates. For indirect separation, the cells were first incubated with monoclonal antibodies to cell surface antigens and then separated in plates coated with anti-mouse Ig. Plates were first coated with poly-L-lysine to facilitate the adherence of anti-Ig antibodies, and finally with bovine serum albumin to mask free poly-L-lysine. Cells which did not react with the anti-Ig antibodies or which were nonadherent to the plate were pipetted off; cells which reacted with the anti-Ig antibodies or which were adherent were eluted after incubation with excess serum. T, non-T, T4+, T4-, T8+, and T8- lymphocytes were separated with high viability, purity, and yield. The method was used to study suppressor activity of a patient who was treated by bone marrow transplantation for myelofibrosis. Strong suppressor activity was associated with unfractionated peripheral blood mononuclear leukocytes, monocytes, T, T8+, and T4- cells but not with B, T8-, and T4+ cells.

Antibodies, Monoclonal↗

Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation.

Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).

Adult↗

Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins.

Twelve patients in the chronic phase of Ph1 (Philadelphia)-positive chronic granulocytic leukemia (CGL) received chemoradiotherapy and marrow from their normal, identical twins. All had a complete remission, with disappearance of all Ph1-positive cells. One patient died of pneumonitis while in remission. Three had a cytogenetic relapse 22 to 30 months after grafting; only one of these three entered blast crisis and died. Eight remain in complete remission 21 to 65 months (median, 30) after transplantation. Thus, the Ph1-positive clone can be ablated and blast crisis delayed or prevented. Of 10 patients with CGL who received transplants during the terminal phase, eight died soon after, one is in complete remission 11 months after receiving a second graft, and one remains in complete remission 71 months after transplantation. This experience suggests to us that every patient with CGL and an identical twin should receive a marrow graft, preferably in the chronic phase. On the basis of our results, trials of allogeneic-marrow transplantation for CGL seem justified.

Adolescent↗

Stimulation of canine lymphocyte subpopulations separated nonlytically by monoclonal anti-T and polyclonal anti-B cell antibodies.

Canine blood lymphocytes were nonlytically separated on antibody-coated petri dishes into surface immunoglobulin-positive (SIg+) and -negative (SIg-) populations. SIg- cells were further separated into cells reactive or non-reactive with monoclonal antibody DT-2 recognizing canine T lymphocytes. The purity of the three enriched lymphocyte populations exceeded 90% as assessed by immunofluorescence. Mitogen stimulation showed a vigorous response of SIg+ cells to pokeweed mitogen and concanavalin A but only a weak response to phytohemagglutinin. In mixed DT-2- and DT-2+ cells responded to phytohemagglutinin, concanavalin A and pokeweed mitogen, and both populations were good responders in mixed leukocyte culture. Only DT-2- cells were potent stimulators; DT-2+ cells were not. Hence, canine blood T cells can be divided into two subsets, DT-2+ and DT-2-, both of which are responsive to mitogens and alloantigens.

Animals↗

Unusual distribution of Ia-like antigens on canine lymphocytes.

The murine monoclonal antibody 7.2, specific for a framework determinant of human Ia antigens, cross-reacts with canine cell membranes recognizing a bimolecular complex (29,000 and 34,000 daltons) similar to that described in man. We investigated the distribution of these Ia-like antigens on mononuclear cells in peripheral blood, thoracic-duct lymph, marrow, alveolar lavage fluids, lymph nodes, and thymuses from normal dogs. By complement-mediated cytotoxicity and indirect immunofluorescence, virtually all lymphocytes expressing surface immunoglobulin (B lymphocytes), monocytes/macrophages, dendritic cells, and many thymus-epithelial cells were Ia-positive. Furthermore, most non-B-lymphocytes in peripheral blood, thoracic-duct lymph, and lymph nodes expressed Ia antigens. Alveolar (T) lymphocytes and most thymocytes were Ia-negative. Generally, fluorescence intensity was higher on monocytes/macrophages and B lymphocytes than on non-B-lymphocytes. In mixed leukocyte cultures and concanavalin A-induced blastogenesis assays, treatment of responder cells with antibody 7.2 and complement abolished proliferation. Proliferative responses could not be restored by adding untreated accessory cells, indicating that cytolytic treatment had eliminated responder T-lymphocytes. However, addition of antibody alone to cultures had no significant effect. These studies indicate that most mature canine T-lymphocytes express Ia-like antigens. Whether this is an intrinsic property of canine cells or possibly related to continuous in vivo stimulation remains to be determined.

Animals↗

Marrow graft studies in dogs: factors influencing resistance to engraftment and graft-versus-host disease.

Our studies have provided further data to support the concept of resistance to engraftment in the dog. Resistance seems to be mediated by antigens coded for by loci different from but linked to DLA. Resistance can be abrogated by the addition of viable lymphoid cells to the marrow inoculum, by high-dose (fractionated) TBI of the recipient and by MTX given postgrafting. CyA has an adverse effect on engraftment probably by interfering with the graft-facilitating effect of donor lymphocytes. GVHD following allogeneic marrow transplantation appears to be mediated by DLA and non-DLA antigens. GVHD can be prevented or ameliorated in recipients of DLA identical littermate marrow by postgrafting CyA or MTX. With DLA nonidentical or unrelated grafts MTX or even more so a combination of MTX and CyA appear to be able to induce tolerance in some recipients.

Animals↗

Allogeneic marrow transplantation for acute leukemia in relapse.

The results of allogeneic marrow transplantation in 75 patients with acute lymphoblastic leukemia and 63 patients with acute non-lymphoblastic leukemia in relapse are reviewed. The effects of various chemotherapeutic regimens added to the basic regimen of cyclophosphamide (Cy) 60 mg/kg given on each of two successive days followed by 1000 rad of total body irradiation (TBI) were evaluated. The regimens tested were dimethylbusulphan (DMB), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and daunorubicin. Seventeen of 138 patients are alive between three and nine and a half years from transplantation. The addition of other chemotherapeutic agents to th basic Cy and TBI regimen did not decrease relapse frequency or prolong survival.

Adolescent↗

Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation.

Twenty-three patients with acute non-lymphoblastic leukemia in relapse were treated with cyclophosphamide, fractionated total body irradiation (200 rad/day for six days) and allogeneic marrow transplantation. Six patients are alive in remission 756-1306 days following transplantation. One patient died of infection on day 17 without evidence of engraftment; all others achieved sustained engraftment. Eight patients died of recurrent leukemia, four of interstitial pneumonitis, two of infection, one of veno-occlusive disease of the liver and one of cardiac failure. The median survival time was 181 days.

Adolescent↗

Allogeneic marrow transplantation for patients with acute non-lymphoblastic leukemia in second remission.

Twenty-four patients with acute non-lymphoblastic leukemia (ANL) in second remission were transplanted from HLA-matched siblings. Twelve patients died of non-leukemic causes and four of recurrent leukemia. One patient is alive after relapse and seven patients are alive and free of disease 114-1907 days after transplantation. The first seven patients received 1000 rad total body irradiation (TBI) in a single exposure. The last 17 were entered on a randomized study to receive 1000 rad TBI as a single dose (seven patients) or 1200 rad TBI fractionated over six days (10 patients). Only one of the 10 patients receiving the fractionated TBI is alive and free of disease 786 days after transplantation while three of the seven receiving single-dose TBI remain in remission 114-541 days after grafting. Even if larger numbers of patients were accrued to this study, it is unlikely that the use of fractionated TBI would prove superior to single-exposure TBI. The actuarial analysis showed that the relapse rate for all 24 patients transplanted in second remission was 50% which was equivalent to patients with ANL transplanted in relapse. The disease-free survival two years after transplant was 24% for patients transplanted in second remission as compared to 26% for patients transplanted in relapse.

Adolescent↗

Allogeneic marrow transplantation using fractionated total body irradiation in patients with acute lymphoblastic leukemia in relapse.

Six fractionated total body irradiation (TBI) regimens given over 2-7 days to a total midline dose of between 1200 and 1750 rads were evaluated in 41 patients with acute lymphoblastic leukemia in relapse. Cyclophosphamide 120 mg/kg was given prior to TBI in all cases, and dimethylbusulphan was added to cyclophosphamide and 1500 rad TBI in one regimen. Relapses occurred in all regimens. The overall disease-free survival of three of 41 patients was not different from previous studies with 1000 rad TBI given in a single dose. Graft-vs-host disease occurred in only 12 of 41 patients. Two of three disease-free survivors had significant graft-vs-host disease.

Adolescent↗

Allogeneic marrow transplantation for acute lymphoblastic leukemia in remission using fractionated total body irradiation.

Twelve patients with acute lymphoblastic leukemia in second to fourth remission received allogeneic marrow transplants following preparation with cyclophosphamide, 120 mg/kg and 1400 rad of fractionated total body irradiation. Two patients died of interstitial pneumonitis 32 and 62 days post-transplantation. Six patients relapsed between days 59 and 659 and four died of leukemia-related problems. Two patients who relapsed are currently alive, one in remission and one in relapse. Four patients are alive and free of disease 657 to 991 days following transplantation. This disease-free survival was not significantly better than the six of 22 disease-free survivors previously observed following cyclophosphamide and 1000 rad of total body irradiation given in a single exposure.

Adolescent↗