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Biomedical subjects

H A Messner

Publications and source records attributed to H A Messner.

At least 73 records · Page 4Linked to original sources
PubMed1992

Growth of human lymphoma cells in SCID mice.

Two EBV-negative human lymphoma cell lines raised in this laboratory and peripheral blood cells of a patient with large cell lymphoma in leukemic phase were injected intravenously or intraperitoneally into C.B.17 SCID mice. One line (OCI-LY18) was derived from the pleural fluid of a patient with a large cell, immunoblastic malignant lymphoma. Cells of this line are of B cell origin and characterized by multiple rearrangements of the JH locus. The second line (OCI-LY17) was grown from the peripheral blood of a patient with a large cell lymphoma of T-cell phenotype which has characteristic rearrangement of the T-cell receptor beta chain. The cells directly obtained from a patient with large cell non-cleaved malignant lymphoma were of B-cell origin. Animals carrying OCI-LY18 developed large tumor masses within 6-8 weeks of inoculation. The tumors were detected in the intestine, mesentery, retroperitoneum, lymph nodes, spleen, lung and kidney. The masses resembled the primary tumor with respect to histological appearance and immunological phenotype. It was possible to generate secondary cell lines from the tumors found in the inoculated SCID mice. Injection of one of these secondary cell lines into SCID mice resulted in the rapid development of lymphoma and as few as 10 cells were sufficient to establish the disease in the inoculated animals. In contrast cells of OCI-LY17 produced small tumor aggregates that did not appear to progress over time and did not cause death of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Interleukin-6 levels in the plasma of patients with lymphoma.

We have suggested a growth stimulatory role of lymphoma cells in culture by interleukin 6. To test the hypothesis that IL-6 may have a role in vivo, the plasma of lymphoma patients was assayed for the presence of IL-6 bioactivity. A significantly greater proportion of lymphoma patients had elevated IL-6 levels (23 of 40) compared to controls (3 of 35). In follow-up, eight of 15 patients with previously elevated levels returned with decreased or undetectable levels of IL-6 post radio- or chemotherapy. This response was seen primarily in those with intermediate or high grade lymphomas. In contrast no change in IL-6 levels was seen in patients with low grade lymphoma despite measurable reductions in tumor size in both groups.

Biological Assay↗
PubMed1992

High-dose cytosine arabinoside remission induction for acute myelogenous leukemia: comparison of two regimens of remission maintenance.

We report a single institution sequential trial of two maintenance treatment regimens for patients with acute myelogenous leukemia (AML). A total of 175 consecutive patients with AML received initial remission induction therapy with high-dose cytosine arabinoside (ara-C) and glucocorticoids. For the initial 63 patients (group A), the control population, planned maintenance treatment was with conventional-dose ara-C given over 4 days for up to 18 months. The subsequent 107 patients (group B) had planned maintenance therapy of up to 6 courses of daunorubicin, ara-C and prednisone and daily cis-retinoic acid for up to two years. The presenting features of group A and B patients were similar as were the response to remission induction, 60 and 52%, respectively. Severe neurological toxicity was encountered once after high-dose ara-C; no drug-related deaths occurred during maintenance treatment. Median duration of remission for group B patients was 9.9 months compared with 5.5 for group A (p = 0.0685). Median survival duration for the two groups was similar, 9.1 months for group A and 10.4 for group B. Survival of patients in group B who attained a complete remission was significantly better than that of patients in group A (p = 0.0439). The studies confirm our initial experience with remission induction using single agent high-dose ara-C and suggest a positive role for maintenance therapy in AML.

Acute Disease↗
PubMed1991

Role of interleukin-6 in the proliferation of human multiple myeloma cell lines OCI-My 1 to 7 established from patients with advanced stage of the disease.

Interleukin-6 (IL-6) has been shown to stimulate the proliferation of multiple myeloma cells purified to a high degree from human bone marrow. IL-6 production in multiple myeloma has been attributed to cells belonging to the myeloma clone, thus supporting a mechanism of autostimulation. In addition, it has been shown that IL-6 may be produced by auxiliary cell populations of the bone marrow that are not part of the myeloma clone. A definitive separation of both putative sources for IL-6 may be difficult to achieve in fresh patient IL-6 growth requirement and production by pure myeloma cell populations using seven human myeloma cell lines (OCI-My 1 to 7) that were established from patients with advanced disease. The proliferative response of each line to recombinant IL-6 was measured in a clonogenic assay providing human plasma and methylcellulose as a viscous support and by 3H-thymidine uptake in liquid suspension culture. We observed marked heterogeneity, ranging from IL-6-dependent colony formation by OCI-My 4, to IL-6-independent growth. All lines expressed mRNA for the IL-6 receptor. Expression of IL-6 mRNA was analyzed after amplification by polymerase chain reaction and was present in five of seven lines. IL-6 protein was detected by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants of two lines (OCI-My 3 and 2). Its functional activity was confirmed in a bioassay using the IL-6-dependent murine hybridoma line B 13.29. This activity was neutralized by anti-IL-6 antibody. Two lines did not express mRNA for IL-6. The remaining three lines expressed mRNA for IL-6, but did not secrete IL-6 protein. Immunoprecipitation experiments with lysates of one of these three lines did not detect the presence of IL-6 protein. These results suggest that autocrine stimulation by IL-6 may occur in some cell lines derived from patients with multiple myeloma. However, it does not represent a universal mechanism in myeloma cell growth.

Cell Division↗
PubMed1991

Regulation of interleukin-6 expression in the lymphoma cell line OCI-LY3.

Previously we described a cell line OCI-LY3 derived from a patient with non-Hodgkin's lymphoma. The cell line produced interleukin-6 (IL-6) mRNA and protein and demonstrated an autocrine pattern of growth for IL-6. Southern blot analysis of the IL-6 gene did not reveal any rearrangement. To determine whether the production of IL-6 by OCI-LY3 was due to subtle changes in the promoter of IL-6 or due to the expression of trans-acting factors chloramphenicol acetyltransferase (CAT) reporter constructs containing from -1,180 to +13 to -112 to +13 of a normal IL-6 gene were electroporated into the cell line. When these constructs are transferred into unstimulated fibroblasts, no CAT activity is seen; however, CAT activity is induced when the cells are stimulated with either IL-1 alpha, lipopolysaccharide (LPS), or cyclic adenosine monophosphate (cAMP) analogues. When the cell line OCI-LY3 was transfected with these constructs, CAT activity was observed; it was not necessary to stimulate the cells with exogenous factors to observe this activity. No CAT activity was observed in a second lymphoma cell line, OCI-LY13.1, that does not produce IL-6. These results suggest that the constitutive production of IL-6 by the cell line OCI-LY3 is due to the presence of trans-acting factors that stimulate the expression of IL-6 and not due to a cis-acting mutation of the IL-6 promoter.

Blotting, Southern↗
PubMed1991

Bone marrow transplantation in hemopoietic malignancies.

Several developments have improved disease-free survival after allogeneic bone marrow transplantation. They have mainly involved prophylactic and therapeutic interventions to reduce some of the transplant-related complications. It is now apparent that disease control is achieved by several mechanisms, including the preparative regimen as well as immunologic interactions between tumor cells and cells that are graft derived and belong to the immune surveillance system. Appropriate manipulations of the latter group of mechanisms may result in a better understanding of disease control and make the underlying therapeutic principle universally applicable. Chronic myeloid leukemia patients in the chronic phase appear to have the most optimal risk-to-benefit ratio of all patients transplanted for hemopoietic malignancies. More recent results in acute myeloid leukemia patients transplanted in first remission, however, suggested that allogeneic bone marrow transplantation might also be acknowledged as the treatment of choice in this disease. This conclusion cannot be drawn as yet for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and malignant lymphoma.

Bone Marrow Transplantation↗
PubMed1991

Intrathecal vancomycin in the treatment of Ommaya reservoir infection by Staphylococcus epidermidis.

Ommaya reservoirs are frequently used in the treatment of patients with meningeal involvement by malignant diseases. The reported infectious complications range between 5-50%. We describe a 35-year-old male patient with Staphylococcus epidermidis infection of an Ommaya reservoir in whom intravenous antibiotics and removal of the reservoir failed to eradicate the organism. The patient was treated successfully by intrathecal injections of vancomycin. Patients with Ommaya reservoir related infections that persist in spite of shunt removal may derive a therapeutic benefit from the intrathecal administration of appropriate antibiotics.

Adult↗
PubMed1991

Human hemopoietic progenitors and their signals.

A number of recent advances have resulted in the definition of human pluripotent hemopoietic progenitors that can be considered candidates for stem cells. These cells may be CD34 positive and HLA-DR negative. They are capable of producing colonies composed of cells with blast-like morphology and re-establish long term bone marrow cultures when placed on irradiated stromal layers. These cells appear to interact at short range with stromal cells and become responsive to signals that initiate their proliferation and differentiation. These signals can be provided by interleukins produced by various auxiliary hemopoietic cell populations and may act over long distances. In addition, these interleukins may be aberrantly produced by certain malignant hemopoietic cells. This may result in paramoplastic auto- or paracrine growth promotion of the underlying malignancy and occasionally in the development of paraneoplastic syndromes.

Antigens, CD↗
PubMed1991

Long-term results of bone marrow transplantation for patients with AML, ALL and CML prepared with single dose total body irradiation of 500 cGy delivered with a high dose rate.

One hundred and sixty-six patients between the ages of 12 and 48 years with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation following single fraction total body irradiation (TBI) of 500 cGy from a cobalt source. Patients also received one of three chemotherapeutic regimens according to their diagnosis or disease status at time of transplant. The median follow-up was 67 months with a range of 33-120 months. The actuarial 5-year event-free survival (EFS) for the subgroup of patients with good risk disease (first complete remission AML and ALL or first chronic phase CML) was 43% with an actuarial relapse rate at 5 years of 26%. Patients with poor risk disease (other than first remission AML and ALL or other than first chronic phase CML) had an EFS at 5 years of 15% with a relapse rate of 62%. Disease status at the time of transplantation was the most important factor predicting outcome in this patient population. We conclude that preparation of good risk patients with chemotherapy and single fraction TBI of 500 cGy at a dose rate of 42-91 cGy/min resulted in EFS and relapse rates similar to those observed by centers using fractionated radiotherapy schedules, without a concomitant increase in toxicity, in particular interstitial pneumonitis and cataracts.

Adolescent↗
PubMed1990

Growth and detection of human bone marrow B-lineage colonies.

A reproducible method for growing normal human bone marrow B-lineage colonies in agar is described. The clonogenic cells require a rich medium, Opti-MEM (GIBCO/BRL, Burlington, Ontario, Canada), and a source of T-cell-derived factors for growth. The conditions described appear to be limiting for the colony progenitor, suggesting assay clonality. Three novel methods that permit routine and rapid detection of these human B-cell colonies are also described. Colonies containing cells that secrete immunoglobulin are detected by plaquing and protein immunoblotting, while RNA transcripts can be detected by RNA colony blotting. The detection of more than one secreted immunoglobulin isotype or RNA species in a single colony can also be achieved. This B-cell colony assay and the associated detection methods will allow the further delineation of human B lymphopoiesis in both normal and disease states.

B-Lymphocytes↗
PubMed1990

Cutaneous and mucosal neoplasms in bone marrow transplant recipients.

Fifty-six long-term survivors of bone marrow allografts were followed for a minimum of 40 months after bone marrow transplantation (BMT) to determine the frequency of secondary malignancies. The 56 patients included ten with severe aplastic anemia (SAA), 16 with acute myeloblastic leukemia (AML), 11 with acute lymphoblastic leukemia (ALL), and 19 with chronic myelogenous leukemia (CML). All patients received a preparative regimen combining high-dose chemotherapy with total body irradiation (TBI). Three patients developed a malignancy of the skin or oral mucosa. Two were diagnosed as squamous cell carcinoma and one as a malignant melanoma. All three patients had chronic graft versus host disease (GvHD) and were treated for prolonged periods with immunosuppressive medications. The lesions of all patients developed in areas involved by chronic GvHD.

Adult↗
PubMed1990

Complications associated with Ommaya reservoirs in patients with cancer. The Princess Margaret Hospital experience and a review of the literature.

The complications associated with the use of Ommaya reservoirs in 106 patients with meningeal involvement due to malignant disease are reviewed. Twenty-seven patients had acute lymphoblastic leukemia, 12 acute myelogenous leukemia, 3 chronic lymphocytic leukemia, 34 lymphoma, 29 carcinoma, and 1 chronic myelocytic leukemia. There were 11 technical complications, including 1 death due to misplacement of the catheter, 2 mild intraventricular hemorrhages, and 5 malfunctioning reservoirs; 3 required craniotomies (1 for subdural hematoma and 2 for subdural hygroma); 13 cases of bacterial meningitis occurred in 10 patients. One patient died of Staphylococcus aureus meningitis. The organisms causing the other infections were mainly coagulase-negative staphylococci (8 cases) or Propionibacterium acnes (2 cases). The projected infection rate for all patients (by Kaplan-Meier analysis) during the first year following insertion of a reservoir was 15%. Successful use of Ommaya reservoirs requires expert surgical implantation and meticulous care during accessing to minimize complications.

Adult↗
PubMed1989

Production of growth factors by malignant lymphoma cell lines.

Fourteen Epstein-Barr virus (EBV)-negative cell lines were raised from bone marrow (BM), peripheral blood (PB), or lymph node samples of patients with intermediate- or high-grade malignant lymphoma. The cell lines were propagated in liquid suspension culture. They contain clonogenic progenitors capable of forming lymphoma colonies in semi-solid culture medium. Cells of these lines were used to examine the growth factor requirements of their clonogenic progenitors and to assess their ability to produce their own growth factors. Two of the cell lines (OCI-Ly9 and OCI-Ly13.1) required addition of exogenous factors for colony growth. These factors were routinely provided by media conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM). Three lines formed some and nine lines gave rise to optimal numbers of colonies without addition of growth factors. Eight of these factor-independent lines were able to function as feeder cells and promoted colony formation by both factor-dependent lines. Cell lines that displayed feeder cell function released activities into supernatants able to replace their cellular source. Some of these endogenously produced growth-promoting activities could be replaced by known hematopoietic growth factors. Both factor-dependent cell lines were cultured with recombinant IL-1 alpha, IL-2, IL-3, IL-6, and GM colony-stimulating factor (CSF) and semipurified B-cell growth factor (BCGF) interleukin-4 (IL-4). A heterogeneous response pattern was observed. Both lines formed colonies with IL-4. The colonies were comparable in frequency and size with colonies observed with (PHA-LCM). OCI-Ly9 responded to IL-6 but showed no growth with IL-2. In contrast, the TAC-positive line OCI-Ly13.1 gave rise to colonies with IL-2 while remaining unresponsive to IL-6. A moderate number of colonies was observed when cells of this line were cultured with GM-CSF. Colony formation of both lines was uninfluenced by IL1 alpha or IL-3.

Cell Division↗
PubMed1989

A possible autocrine role for interleukin-6 in two lymphoma cell lines.

Interleukin-6 (IL-6) is a growth factor with diverse biologic activity. Originally described as a T-cell product that enhances immunoglobulin (Ig) secretion in antigen-stimulated B cells, it also affects the growth of T cells, plasmacytomas, hybridomas, and hematopoietic stem cells. We report the expression and secretion of IL-6 by two lymphoma cell lines, OCI-LY3 and OCI-LY12. Addition of recombinant IL-6 stimulated their growth, whereas addition of polyclonal anti-recombinant IL-6 (anti-rIL-6) had a marked inhibitory effect on proliferation. These results suggest an autocrine role for IL-6 in the growth of these lymphoma cells in culture.

Blotting, Northern↗
PubMed1989

Rapid decline of clonogenic hemopoietic progenitors in semisolid cultures of bone marrow samples derived from patients with chronic myeloid leukemia.

Bone marrow samples, from newly diagnosed patients with chronic myeloid leukemia (CML) and normal individuals, were grown in methylcellulose and serially recultured under identical conditions. Specimens derived from normal individuals gave rise to multilineage and megakaryocyte colonies for one to two sequential cultures. Erythroid bursts and granulocyte-macrophage colonies were observed for three to five sequential cultures. Cultures initiated from samples of patients with CML showed a rapid decline of all types of colonies. Colonies were rarely seen for more than two sequential cultures. When pooled colonies and background cells were recloned separately, secondary colonies were mainly seen in cultures of background cells. This observation is consistent with the view that secondary colonies are more likely to arise from dormant clonogenic progenitors, rather than through cells that have formed primary colonies through a self-renewal process.

Bone Marrow↗
PubMed1989

Restriction fragment length polymorphism analysis of hematopoietic cells following successful treatment of relapsed acute lymphoblastic leukemia following bone marrow transplantation.

Despite aggressive therapy for leukemia in the form of bone marrow transplantation (BMT) relapse occurs in a significant number of cases. The origin of the leukemic relapse, whether it is of donor or recipient origin, and how best to treat the patients continue to pose problems for the clinician. In this paper we present a case in which the cytogenetics suggested that the relapse was of donor origin; however, molecular analysis revealed that the leukemic population was of host origin. The leukemic relapse following the BMT was treated with a second BMT. This resulted in a remission of 28 months after which leukemic relapse was again diagnosed. Using conventional chemotherapy it was possible to obtain another complete remission. This case illustrates a pitfall to cytogenetic analysis and two contrasting methods of dealing with leukemic relapse following BMT.

Adult↗