PubMed Health⌕ Search

Biomedical subjects

H A Messner

Publications and source records attributed to H A Messner.

At least 55 records · Page 3Linked to original sources
PubMed1994

Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma.

We derived the lymphoma cell lines OCI-Ly 13.1 and OCI-Ly 13.2 from a patient with non-Hodgkin's lymphoma at the time of presentation and during chemotherapy-resistant relapse. These lines were of T-cell phenotype and contained the identical T-cell receptor beta-chain rearrangement, indicating that both lines were members of the same malignant clone. The lines differed in their growth characteristics; OCI-Ly 13.1 grew slowly and required growth factors for colony formation, whereas OCI-Ly 13.2 grew rapidly and formed colonies without addition of growth factors. To test whether or not these biologic differences were associated with specific genetic changes, we evaluated the status of the c-myc and p53 genes of both cell lines. The p53 and c-myc genes of OCI-Ly 13.1 were in germline configuration and produced normal-sized transcripts. The p53 protein expressed in OCI-Ly 13.1 was recognized by the anti-p53 monoclonal antibody, PAb240, indicating a conformation typical of p53 proteins expressed by p53 alleles containing a missense mutation. However, sequencing studies of the entire p53 coding region did not reveal any point mutations. In contrast, the cell line OCI-Ly 13.2 contained structural abnormalities of both the c-myc and p53 genes. In addition, one of the p53 alleles was lost as determined by a cDNA probe for the p53 gene (17p 13.1) and the YNZ22.1 probe (17p 13.3). These changes resulted in the absence of p53 protein and mRNA in OCI-Ly 13.2 as detected by immunoprecipitation and Northern blot analysis, respectively. They may be a reflection of disease progression and may be associated with the altered behavior of the malignant cell population within the patient and in vitro.

Base Sequence↗
PubMed1994

Spontaneous remission of polycythemia vera: clinical and cell culture characteristics.

A 20-year-old woman presented with polycythemia vera and was treated with phlebotomy alone for eleven years, following which all clinical manifestations of the disease disappeared. The clinical remission with normal physical findings and normal peripheral blood counts has persisted for a further 11 years. Erythroid colony culture results have paralleled the clinical state. Initial bone marrow cultures revealed spontaneous growth of erythroid burst-forming units (BFU-E). Subsequent cultures of peripheral blood cells throughout most of the period of spontaneous clinical remission have revealed little or no spontaneous growth of BFU-E. This suggests a suppression of the abnormal stem cell clone during the period of remission.

Adult↗
PubMed1994

Intraoral pyogenic granuloma after allogeneic bone marrow transplant. Report of three cases.

Allogeneic bone marrow transplant patients commonly have oral complications related to their disease or its treatment. Those reported include: xerostomia, mucositis, caries, infection, gingival hyperplasia, periodontitis, and graft-versus-host disease. These complications may be responsible for significant morbidity. This article reviews commonly reported oral complications of bone marrow transplantation and presents three cases in which intraoral pyogenic granuloma occurred. The cause of these lesions in post-bone marrow transplant patients is discussed.

Adult↗
PubMed1994

Determination of IL6, IL1, and IL4 in the plasma of patients with multiple myeloma.

Interleukin 6 (IL6) plasma levels were measured in 63 patients with multiple myeloma and 8 individuals with benign monoclonal gammopathy. 15 of these 71 samples showed by an enzyme linked immunosorbent assay (ELISA) detectable levels that ranged from 5 to 107 pg of IL6/ml. The IL6 levels of patients with multiple myeloma did not differ significantly from those of normal individuals (N = 25, range 5-27 pg IL6/ml) (Student's t-test, p = 0.295). The samples were negative for IL4; 3 were found positive for IL1 beta. A correlation between IL6, IL4 and IL1 beta levels and disease status was not observed for this group of patients.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Allogeneic bone marrow transplantation from a related donor undergoing long-term immunosuppressive and cytotoxic therapy.

We report the case of a patient with acute myeloid leukemia in second remission who received an allogeneic bone marrow transplant from an immunosuppressed HLA-identical sibling donor. The donor was receiving prednisone, azathioprine and cyclosporine for a cadaveric renal allograft. Bone marrow growth in culture from the donor was normal. Engraftment was within normal limits. Moderate acute graft-versus-host disease (GVHD) developed. We suggest that transplants from immunosuppressed donors are feasible and that this does not preclude the development of GVHD.

Antineoplastic Agents↗
PubMed1994

Minimal residual disease in bone marrow transplant recipients with chronic myeloid leukemia.

Bone marrow samples of 70 transplant recipients with CML were studied by Southern blot analysis and RT-PCR using a two-step procedure with nested primers. Twenty-two patients were studied once and 48 were assessed on multiple occasions. All patients remained in a hematological remission during the study. The time of follow-up after the transplant ranged from 2 to 144 months with a median of 42 months. Thirty-nine patients (56%) were negative by RT-PCR and Southern blot studies at the time of their last evaluation. The proportion of RT-PCR negative patients increased with the duration of follow-up after the transplant; 36% of patients were RT-PCR negative after 1 year compared with 60% after 2 years and 78% after > or = 5 years. Patients maintained on immunosuppression had a higher probability of remaining RT-PCR positive. Age, sex, time from diagnosis to BMT, as well as acute and chronic GVHD did not influence the RT-PCR status. The majority of patients studied on multiple occasions demonstrated a stable RT-PCR and Southern blot pattern. Some showed uni- or multi-directional transitions. However, none of the patients studied progressed to a hematological relapse. RT-PCR studies on colonies grown from RT-PCR positive. Southern blot negative patients confirmed that some of the clonogenic progenitors are able to produce BCR/ABL transcripts.

Adolescent↗
PubMed1993

Cell culture assessment of hematopoietic progenitors in bone marrow transplantation.

A number of cell culture techniques are now available to evaluate clonogenic hematopoietic progenitors as well as cell populations that represent an interactive network of cells with regulatory capabilities. Although clonogenic cells in allografts do not appear to be correlated with the time to recovery, they seem to predict their time to engraftment in autografts. However, these cell populations are likely to be only surrogate measurements because a reduction by various purging techniques does not seem to alter the ability of autografts to reestablishing hematopoiesis. Currently, it is not known whether or not these differences may relate to differences in the preparative regimens, graft-versus-host disease prophylaxis, or other differences in the management, such as administration of high concentrations of various antiviral agents. It is also now possible to measure growth factor production following the transplant procedure and to correlate the availability of endogenous factors and recovery after a transplant. Under normal conditions, the activity levels appear to return to normal values within 20-30 days, whereas in patients with late engraftment one may observe prolonged elevation of growth factors. If confirmed, this would suggest that in bone marrow transplants a delayed return is more related to reduced progenitor cells rather than a deficiency of growth factors.

Bone Marrow Transplantation↗
PubMed1993

Clonogenic hematopoietic progenitors and endogenous cytokine production in allogeneic bone marrow transplantation.

The suboptimal return of hematopoietic precursors after bone marrow transplantation is suggestive of a limited bone marrow reserve in recipients of allografts. The problem does not appear to lie in the ability to produce some of the well-known hematopoietic growth factors such as G-CSF or activities considered to stimulate megakaryocytopoiesis. The persistence of factor production in patients with slow returning counts is suggestive of either a defect in the repopulating cells or in the function of the microenvironment that is not reflected in the production of factors that can be measured in the plasma. A defect in the graft may be overcome by altering the composition of engrafting cells. As seen in autologous transplants the addition of peripheral blood stem cells may be effective in reducing the period to engraftment. Putative defects in the microenvironment have to be addressed by further studies. Exogenously added stroma related factors such as kit ligand or IL-11 may be effective in correcting the deficiency.

Bone Marrow Transplantation↗
PubMed1993

Differential sensitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diphtheria toxin-interleukin 6 fusion protein.

The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed. Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL-6 were relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT. Flow cytometric analysis for IL-6 receptor expression using phycoerythrin-conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL-6 receptors are involved in killing by the fusion toxin. Despite evidence for a role of IL-6 in myeloid cell development, normal bone marrow was insensitive to the IL-6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6-responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.

Cells, Cultured↗
PubMed1993

Merocyanine 540-sensitized photoinactivation of high-grade non-Hodgkin's lymphoma cells: potential application in autologous BMT.

This paper reports on the preclinical evaluation of merocyanine 540 (MC540) as an agent for the inactivation of tumour cells in BM grafts from non-Hodgkin's lymphoma (NHL) patients. The three cell lines used for this study, OCI-LY13.1, OCI-LY13.2 and OCI-LY9, originate from two patients with high-grade NHL. The OCI-LY13.1 and OCI-LY13.2 lines are derived from the same patient. The OCI-LY13.1 line was established at the time of diagnosis while the OCI-LY13.2 line was established after the tumour had become refractory to therapy. When used under conditions that are known to preserve about 50% of normal human pluripotent hematopoietic progenitor cells (CFU-GEMM), MC540-sensitized photoirradiation reduced in vitro clonogenic OCI-LY9 cells by 4 orders of magnitude and OCI-LY13.1 and OCI-LY13.2 cells by > or = 5. Survival curves for OCI-LY13.1 and OCI-LY13.2 cells were similar and followed first order kinetics, while those for OCI-LY9 cells were distinctly biphasic. Suspension cultures established with photoinactivated lymphoma cells confirmed that MC540-sensitized photoirradiation was cytotoxic and capable of eliminating > or = 4 log of tumour cells. These results encourage the further exploration of MC540-sensitized photoirradiation as a means to purge autologous marrow grafts from NHL patients.

Bone Marrow↗
PubMed1993

Pregnancy after BMT: three case reports.

A case of successful pregnancy after BMT in a 24-year-old woman with ALL, conditioned with CY, L-asparaginase, methylprednisolone and total body irradiation (TBI) is reported. A second case of two spontaneously aborted pregnancies in a woman transplanted for ALL at the age of 29 years using CY and TBI conditioning and a third case, this time a successful pregnancy in a woman transplanted for AML at age 27 years using CY and TBI conditioning are also described. There are now 6 successful live births after TBI reports of, versus 16 following regimens in which no TBI is used. This is the first report of a successful pregnancy reported in a female transplanted when older than 25 years using any TBI-containing regimen.

Adult↗
PubMed1992

Differentiation profiles of normal blast cell colonies derived from mononucleated cells, T cell depleted nonadherent cells and CD33-negative, CD34-positive normal human bone marrow cells.

Blast cell colonies can be grown reproducibly in methylcellulose from normal human mononuclear bone marrow cells (MNC) in the presence of 30% human plasma, 1 U human recombinant erythropoietin and 10% of medium conditioned by phytohemagglutinin stimulated leukocytes as a source of growth factors. The colonies can be recognized by inverted microscopy by their display of highly refractile cytoplasmic structures that resemble small vacuoles. A proportion of cells within these colonies remains CD34-positive (CD34+). The blast-like morphology of these cells was sustained for at least 14 to 21 days. The frequency of blast cell colony forming units (CFU-BL) can be increased by a series of separation procedures to produce E-rosette depleted, nonadherent cells (E-NAC), CD34+ cells and CD33-CD34+ cells. The mean number of CFU-BL per 10(5) cells was 1.9 +/- 1.6 in MNC, 5.7 +/- 2.7 in E-NAC, 108 +/- 51 in CD34+ cells and 112 +/- 109 in CD33-CD34+ cells. The enrichment procedures were not specific for CFU-BL but also resulted in a similar increase of multilineage and single lineage progenitors. The relative proportions of CFU-BL and other progenitors remained unchanged among these subpopulations. The size of individual blast cell colonies on day 16 varied from 20 to 1,600 cells. After 14 to 21 days, cells within blast cell colonies acquired mature morphological features. The majority of blast cell colonies developed into multilineage colonies (62%); some (38%) were restricted to a single hemopoietic lineage. Larger blast cell colonies had a higher probability of developing into multilineage colonies than smaller blast cell colonies.

Antigens, CD↗
PubMed1992

Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation.

PURPOSE: To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor. PATIENTS AND METHODS: Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day. RESULTS: Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA-identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred. CONCLUSIONS: This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy.

Adolescent↗
PubMed1992

A human lymphoma cell line with multiple immunoglobulin rearrangements.

The development of a cell culture system efficient in the establishment of lymphoma cell lines has made it possible to dissect basic biological and molecular aspects of lymphoma cells. We have established a lymphoma cell line from a patient with B cell lymphoma. The cell line has a complex karyotype with translocations involving bands 8q24, 14q32, and 18q21. Molecular analysis revealed that the Myc gene was rearranged; we were unable to demonstrate rearrangement of the Bcl-2 gene. Evaluation of the structure of the heavy chain Ig genes revealed that the cell line carried the same rearrangements as the cells from which the cell line was derived. The pattern of rearrangement, however, was unusual in that there were at least four rearranged bands when DNA cut with HindIII was probed with a fragment of the heavy chain joining region. To further characterize the cell line, subclones were derived. Individual subclones had the same pattern of rearrangement as the parent cell line. The results of these studies provide evidence that multiple rearranged Ig genes may be present in a single clone of cells.

Gene Rearrangement↗
PubMed1992

Constitutive production of the interleukins IL-5 and IL-6 by the lymphoma cell line OCI-Ly 17 derived from a patient with malignant lymphoma and hypereosinophilia.

Peripheral blood cells of a patient with diffuse large cell non-Hodgkin's lymphoma presenting with hypereosinophilia were used to establish an EBV negative lymphoma cell line termed OCI-Ly17. Cells of the line stained positive for CD2 and CD5 determinants and demonstrated rearrangement of the T-cell receptor beta chain. The immunoglobulin heavy chain gene was found to be in germ line configuration. Northern blot studies using probes for IL-1 alpha, IL-3, IL-4, IL-5, IL-6, and GM-CSF showed message for IL-5 and IL-6. Supernatants of the cell line were evaluated on normal non-adherent, E-rosette depleted bone marrow cells to determine the presence of growth promoting activities for clonogenic eosinophilic progenitors. Eosinophilic colonies were observed. Their frequency depended upon the amount of supernatant added to the cultures. The growth promoting activity in the supernatant was reduced in a dose dependent manner by preincubation with increasing concentrations of anti-IL-5 antibodies. The supernatants of the cell line were also tested on the IL-6 sensitive human myeloma line OCI-My4 and myeloma colonies grew in response. This stimulatory activity within the supernatant was neutralized by addition of increasing concentrations of anti-IL-6 antibodies. Although producing IL-5 and IL-6 constitutively, the lymphoma line did not increase proliferation in response to either interleukin, nor did it show a reduced proliferative rate when antibodies to IL-5 or IL-6 were added to the cultures.

Aged↗