Search PubMed⌕ Search

Biomedical subjects

M Symann

Publications and source records attributed to M Symann.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Efficiency of high-dose FEC chemotherapy for the mobilization of hematopoietic stem cells into peripheral blood].

The best regimen for mobilizing hematopoietic stem cells (HSC) into peripheral blood is not yet defined. The efficiency of FEC chemotherapy in the treatment of breast cancer is well established and the effects of FEC on HSC mobilization have been characterized. We tested the feasibility and the toxicity of a high-dose FEC regimen which may improve the mobilizing capacity of conventional FEC. Twenty patients with poor prognosis breast cancer received high-dose FEC and filgrastim 5 micrograms/kg. Three leukaphereses were performed on each patient for 3 consecutive days. Total numbers of CFU-GM and CD34+ cells were assessed, and a retrospective analysis was made. The numbers of CFU-GM/kg and CD34+ cells/kg collected (mean +/- standard error) were respectively 12.2 x 10(5) (+/- 2.4) and 14.6 x 10(6) (+/- 2.5). Extra-hematologic toxicity was negligible. Hematologic recovery after CTCb high-dose chemotherapy and HSC infusion was rapid. High-dose FEC is efficient for collecting HSC in peripheral blood. Extra-hematologic toxicity is weak and hematologic recovery after autograft is normal. Increased dosage of epirubicin and cyclophosphamide could allow a single leukapheresis collection of sufficient HSC from peripheral blood.

Adult↗
PubMed1996

Peripheral blood mononuclear cells from autologous hematopoietic stem cell transplantation recipients produce and respond to IL-12.

Autologous hematopoietic stem cell transplantation effectively results in restoration of hematopoiesis, but induces an often prolonged period of T cell dysfunction including redistribution of T cell subsets and defective T cell proliferation. Because IL-2 production is markedly decreased following autologous stem cell engraftment, and because IL-12 has direct stimulatory effects on TH1 cells, a major source of IL-2, we investigated the production and responsiveness of IL-12 of peripheral blood mononuclear cells (PBMC) of autologous stem cell recipients in the first 6 months following engraftment. When stimulated with S. aureus Cowan I (SAC), PBMC from autologous hematopoietic transplant recipients in the early months following engraftment show no decrease in production of IL-12 as compared to control PBMC. Furthermore, transplant-derived PBMC appear to be functionally responsive to exogenously provided IL-12 as indicated by several criteria. In vitro proliferation of total PBMC and of isolated CD4+ T cells from transplanted recipients to PHA (1 microgram/ml) + IL-12 (20 U/ml) was comparable to controls, excluding the possibility that only NK or CD8+ cells respond to IL-12. Culture of both control and transplant-derived PBMC in PHA + IL-12 (20 U/ml) or IL-2 (100 U/ml) + IL-12 (20 U/ml) combinations yielded comparable production of IFN-gamma, one of the major biological effects of IL-12 in vivo, as well as equal production of TNF-alpha, a costimulatory factor of IL-12-mediated induction of IFN-gamma by NK cells. Taken together, this in vitro evidence suggests that following autologous transplantation, PBMC do not appear to have either decreased production of endogenous IL-12 or defective functional responsiveness to exogenously provided IL-12.

CD4-Positive T-Lymphocytes↗
PubMed1995

Digital necrosis associated with chronic myeloid leukemia: a rare paraneoplastic phenomenon.

We describe the case of a 72-year-old man who developed unilateral digital necrosis, four years after diagnosis of chronic myeloid leukemia (CML). The etiology of this paraneoplastic phenomenon appears multiple. The digital necrosis responded well to an aggressive varied treatment. The unusual association of CML with digital necrosis and the etiology of this rare paraneoplastic complication are discussed.

Aged↗
PubMed1994

Tolerance of sequential or simultaneous administration of IL-3 and G-CSF in improving peripheral blood stem cells harvesting following multi-agent chemotherapy: a pilot study.

A pilot study was devised to assess tolerance of combined administration of interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) given after chemotherapy to mobilize peripheral blood progenitors cells (PBPC). Eight patients with advanced malignancies received 1 week courses of both IL-3 and G-CSF in one of three schedules: simultaneous 7 days administration (3 patients), sequential administration (3 patients) or partial (3 days) overlap of the two growth factors (2 patients). IL-3 (7.5 micrograms/kg/day) and G-CSF (5 micrograms/kg/day for the simultaneous schedule and 12 micrograms/kg/day for the partial overlapping and sequential schedules) were administered subcutaneously. Side-effects during cytokine administration included WHO grade I-II fever in 6 of 8 patients, flu-like symptoms (including myalgias and arthralgias) in 4 of 8, WHO grade I-II headache in 2 of 8 and WHO grade II nausea and vomiting in 1 of 8. Overall, side-effects appeared similar during combined administration of IL-3 and G-CSF to those observed during administration of IL-3 alone. No fever was observed when G-CSF was administered alone. Two leukaphereses were performed following the treatment with cytokines. Only the seven patients who received cytokines following chemotherapy were analyzed for PBPC mobilization. The median collection of CFU-GM/kg per patient in the seven analyzed patients was 1.3 x 10(5) (range 5.7 x 10(2)-3.6 x 10(5)). In two patients, a second cycle of mobilization with either granulocyte macrophage-colony stimulating factor (GM-CSF) or G-CSF was administered to allow safe engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

IL-3 and peripheral blood stem cell harvesting.

Transplantation of blood-derived stem cells is increasingly performed because when used alone or when combined with autologous bone marrow grafting, it can demonstrably shorten myelosuppression following multi-agent chemotherapy. Hematopoietic growth factors can mobilize peripheral blood stem cells from the bone marrow to therapeutically intervene in accelerating hematologic recovery. Interleukin 3 (IL-3), whose hematopoietic activities were first described some ten years ago, is one of several candidate growth factors that may prove useful in enhancing this mobilization in order to obtain adequate yields of circulating stem cells for transplantation. IL-3 used in conjunction with synergistically acting cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte CSF (G-CSF) have already yielded interesting results, while new factors like stem cell factor are in the process of clinical evaluations and appear promising. However, further issues remain to be clarified to confirm the general applicability of cytokine-augmented peripheral blood stem cells in improving on-schedule delivery of high-dose myelosuppressive chemotherapy in patients with malignancies.

Animals↗
PubMed1993

Restriction fragment length polymorphisms and single germline coding region sequence in VH18/2, a duplicated gene encoding autoantibody.

In this study, we analyze the restriction fragment length polymorphisms of VH18/2, a gene encoding the heavy chain of an anti-DNA antibody, and correlate that with the germline sequence of the gene's coding region. Oligonucleotides probes complementary to the CDR1 and to both the 5' and 3' halves of the CDR2 gene segments were hybridized under stringent conditions to genomic DNA digested with XbaI, and yielded polymorphic bands of 26, 24 and 18 kb with all three probes. Individuals had either one, two, or three bands in common in their genomic DNA, indicating duplication of VH18/2 genes at two sites within the IgH locus. While it is difficult to say which of the three polymorphic gene segments constitute an allelic pair, the 26 and 24 kb fragments were the most commonly seen (97% of individuals had one or both). VH18/2 is known to be over-represented in the expressed repertoire with very little nucleotide divergence from the germline sequence. In order to determine whether the observed RFLPs are due to sequence polymorphism of the VH18/2 coding region, and whether differences in the expressed genes arise from somatic mutation, size-selected genomic DNA containing the gene was cloned and sequenced. A single coding region sequence was found in the germline. The results of this study suggest that overexpression of VH18/2 may in part be due to its duplication. Like other genes encoding autoantibody, which are well conserved, nonpolymorphic and expressed early in programmed immunologic development, VH18/2 may be instrumental in the establishment or regulation of the immune repertoire.

Antibodies, Antinuclear↗
PubMed1993

Oligonucleotide probes to the 5' end of the framework 3 (FR3) gene segment detect polymorphisms of VH gene sequences encoding biologically important amino acid residues.

In this study, we demonstrate the use of oligonucleotide probes to the most VH family-specific framework, the Framework 3 (FR3) gene segment, in the analysis of germline DNA. Compared with the hybridization of restriction enzyme-digested genomic DNA to large, cloned human VH family probes, hybridization with oligonucleotides derived from nucleotides 199 to 258 of the FR3 gene segments both yields less complex patterns and highlights polymorphic variations between individuals. The potentially important role played by amino acid residues encoded by the FR3 gene segment in influencing conformation, antigen binding and affinity of the physically proximal complementarity determining regions (CDRs) suggests FR3 sequence conservation to be biologically significant. Genomic studies combining information from both CDR and framework restriction fragment polymorphisms can prove useful in detecting specific genes and in identifying haplotypes of interest.

Genes, Immunoglobulin↗
PubMed1992

Effects of escalating doses of recombinant human interleukin-2 in correcting functional T-cell defects following autologous bone marrow transplantation for lymphomas and solid tumors.

High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-unrestricted cytotoxicity in vitro, can be applied in vivo as immunotherapy to reduce these potential complications. Recombinant human IL-2 (rIL-2) was administered by continuous i.v. infusion for four courses in 19 patients following ABMT for lymphomas and solid tumors. The patients were assigned to five groups of escalating doses of rIL-2 ranging from 3 to 30 x 10(6) IU/m2/day. The immunological effects and toxicity were monitored. After a transient reduction of lymphocytes in the peripheral blood, a significant lymphocytosis was observed during the rIL-2 infusion with an augmentation of CD2+, CD25+, and CD8(+)-Ia+ T cells and a dose-related increase of CD56+ lymphocytes. Natural killer (NK) activity appeared enhanced in patients treated with as little as 6 x 10(6) IU/m2/day. No statistically significant increase in lymphokine-activated killer (LAK) activity was seen after rIL-2, when compared to LAK activity following ABMT prior to rIL-2 administration. Administration of exogenous rIL-2 to patients who have undergone ablative chemotherapy and ABMT has a role in restoring defective T-cell function. Further trials defining those patients most likely to benefit from rIL-2 integrated with ablative chemotherapy and ABMT are now warranted.

Adult↗
PubMed1991

Recombinant interleukin-2 in metastatic renal cell carcinoma--a European multicentre phase II study.

This multinational, multicentre study represents the introduction of recombinant interleukin-2 (rIL-2) in Europe. From December 1987 to June 1989, 57 eligible patients with metastatic renal cell cancer were treated with rIL-2 administered as continuous intravenous infusion. 8 out of 51 evaluable patients responded (16%), 2 complete remission (CR) and 6 partial remission (PR). 10 patients had no change (20%). The response duration for CR was 209 and 394+ days. The median response duration for PR was 371 (range 140-506+) days. Dose-limiting grade 3-4 toxicities were hypotension in 52% of the patients, arrhythmia (4%), dyspnoea (8%), creatinine rise (4%), peripheral neurotoxicity (10%) and central neurotoxicity (10%). Toxicities most often recovered solely on interrupted therapy. 2 patients died due to catheter-related septicaemia and one patient died of rIL-2 induced renal failure. The study confirmed the antitumour efficacy of rIL-2 in renal cell cancer. Toxicities were numerous, but manageable by close observation in a normal oncology ward without routine use of an intensive care unit.

Adult↗
PubMed1991

Hematopoietic growth factors as supportive therapy for cancer- and chemotherapy-induced conditions.

A number of human hematopoietic growth factors have been genetically cloned and recombinant proteins produced. Several phase I and II clinical trials have already been published and results from phase III studies are becoming available. The use of erythropoietin to alleviate chemotherapy-induced myelosuppression is being tested. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have been extensively studied in patients receiving chemotherapy at standard or escalated doses and after bone marrow transplantation and appear to ameliorate chemotherapy-induced neutropenia and to speed bone marrow engraftment after high-dose cancer therapy. Interleukin-3 and interleukin-6 are quite early in their clinical development, but appear able to alleviate post-chemotherapy thrombocytopenia.

Anemia↗
PubMed1990

Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC).

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.

Adenocarcinoma↗
PubMed1990

In vivo elaboration of CSF in acute inflammation: proportionality to the intensity of the inflammatory stimulus and requirement of T lymphocytes.

The colony-stimulating factor(s) (CSF) that stimulates the in vitro growth of bone marrow granulocyte-monocyte progenitors (CFU-GM) increases in the serum of mice challenged by an aseptic abscess induced by copper rod insertion. The effect of the inflammation on the increase of serum CSF is dose-related. The creation of 3 aseptic abscesses indeed results in a higher and longer elevation of serum CSF than 1 abscess. Serum CSF also increases in parallel with the rise in bone marrow CFU-GM; this is consistent with the CSF playing a role in regulation of haematopoiesis in vivo. From previous studies, it appears that T lymphocytes play a central role in the regulation of haematopoiesis. In order to determine the role of T lymphocytes in the inflammation response, cyclosporin A (CyA), an inhibitor of T lymphocyte function, was given in vivo, 2 days before inflammation induction. CyA abrogates the increase in both serum CSF and CFU-GM. Furthermore, a lower increase in serum CSF was observed in copper-implanted nude mice. These results suggest that the CSF production induced by inflammation requires the functional integrity of T lymphocytes.

Abscess↗
PubMed1990

Biology of small cell lung cancer: an overview.

Despite disappointing results in the treatment of small cell lung cancer (SCLC), major progress in our understanding of SCLC biology has occurred in the past decade. Advances in the technique for culturing SCLC tumours in vitro have greatly facilitated the study of the biological properties of this tumour. The major progress in our understanding of SCLC includes: 1) the availability of nonspecific biological tumour markers such as neuron-specific enolase (NSE), the BB isoenzyme of creatine phosphokinase (CPKBB), bombesin/gastrin releasing peptide (GRP) and chromogranin A; 2) the generation of monoclonal antibodies raised against the neural and epithelial features of SCLC tumours; 3) the identification of several autocrine growth factors such as bombesin/GRP, insulin-like growth factor (IGF), transferrin and physalaemin; 4) the close study of cytogenetic abnormalities leading to the discovery of a unique chromosomal deletion of the short arm of chromosome 3 (del 3p 14-21), and to changes in oncogenic expression, e.g. c-myc, L-myc and N-myc, accounting for known biological and treatment results. These data suggest that all lung cancers arise from a common stem cell of endodermal origin. The information derived from these biological studies represents the most promising avenue towards new treatment strategies in SCLC.

Antibodies, Monoclonal↗
PubMed1990

Interleukin-2 after autologous bone marrow transplantation as consolidative immunotherapy against minimal residual disease.

Recipients of autologous BMT demonstrate clinically significant immune deficiency, particularly involving the T lymphocytes. While quantitatively the immune system generally returns to normal during the first 3 months, there is a prolonged delay in the recovery of qualitative immune functions. T cell proliferation is impaired immediately after transplantation and slowly recovers over a period of more than 1 year. In addition, a defect has been documented in IL-2 producing cells and may be of major importance in the pathophysiology of this immunodeficiency. However, post-ABMT, PHA-stimulated T cells are TAC+ and are able to respond to exogenous IL-2 in vitro. Very early after ABMT, NK and LAK activities of PBMC normalize but are significantly increased in vitro by IL-2. On this basis, a clinical assessment of rIL-2 administration on the immunological reconstitution of ABMT patients and as consolidation immunotherapy against minimal disease has been initiated in a phase I/II study.

Bone Marrow Transplantation↗
PubMed1989

Diffusion chamber colony-forming unit (CFU-d): a primitive stem cell.

Assay of hematopoietic precursor cells in diffusion chambers (DCs) implanted intraperitoneally in experimental animals provides a powerful tool for studying stem cell kinetics in vivo. In this system, the effect of cell migration (which complicates whole animal studies) is eliminated because the membranes utilized in the construction of the chambers are impermeable for cells, while permitting free passage of molecules present in the humoral phase of the host. As judged by light microscopy, conditions in the DC cultures primarily favor macrophage and granulocyte growth. However, the use of in vitro and in vivo subculture to further analyze chamber contents has demonstrated that the system supports proliferation of early hematopoietic progenitors. Additionally, cells capable of rescuing lethally irradiated mice proliferate in DC cultures. Development of the plasma clot DC technique has revealed that most of the growth occurs in colonies which are derived from single cells (CFU-d). Characterization of these cells indicates that they are at least as primitive as other colony-forming cells and, also based on subculture studies, can differentiate along several hematopoietic lineages. In addition to normal CFU-d, both embryonal and leukemic cells can give rise to granulocytes, macrophages, megakaryocytes and erythroid cells in the DC cultures. Evaluation of the effects of humoral factors on hematopoietic cell proliferation and differentiation in the system has led to the identification of both stimulators and inhibitors that may be different from the well-characterized cytokines. Thus, the system seems to be useful for detecting molecules controlling the most primitive stages of hematopoiesis. We believe that the DC culture technique holds enormous potential in the study of stem cell proliferation and differentiation in vivo.

Animals↗