Cytotoxic and noncytotoxic mechanisms involved in the in vitro anti-leukaemia effects of T cell clones established from a chronic myelogenous leukaemia patient during treatment in vivo with interferon alpha.

T cell clones derived from a chronic myelogenous leukaemia (CML) patient during interferon alpha (IFN alpha, Wellferon) biotherapy preferentially lysed autologous rather than allogeneic CML target cells in an apparently MHC-unrestricted fashion, but also lysed bone marrow cells from certain normal donors regardless of whether or not they shared HLA antigens with the patient. Although T cell clones inhibited both CML and normal bone marrow in the colony-forming assay, they blocked proliferation of CML cells more efficiently than bone marrow cells. This inhibitory effect was mediated at least in part by the tumour necrosis factor alpha (TNF alpha) and IFN gamma secreted by the clones.

Long-term cultured adult human keratinocytes secrete granulocyte-macrophage colony-stimulating factor but not interleukin-3 after cytokine exposure in vitro.

To investigate the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and of interleukin-3 (IL-3) by human keratinocytes in vitro, adult human keratinocytes (aHKc) from 3 different donors and a spontaneously transformed keratinocytic line (HaCaT) were cultured and exposed to various cytokines and to the protein kinase C-activating agent phorbol-12-myristate-13-acetate (PMA). GM-CSF and IL-3 were measured by highly specific and sensitive immunoassays. Our findings showed that long-term cultured aHKc and HaCaT cells are capable of secreting GM-CSF but not IL-3 upon cytokine and PMA stimulation.

[Familial benign chronic neutropenia in a Danish family].

Familial benign chronic neutropenia is a rare anomaly which is transmitted as an autosomally dominant trait and is characterized by normal or somewhat low total leukocyte counts, consistent neutropenia, and, usually, relative monocytosis and lymphocytosis, sometimes with eosinophilia. Affected individuals have a normal life expectancy. Many are asymptomatic, but some have histories of tendency to develop furuncles and/or periodontal disease.

Toxicity of novel anthracycline derivatives towards normal myeloid bone marrow progenitor cells (CFU-GM) is not increased by verapamil.

Drug-induced myelotoxicity is usually the dose-limiting factor of treatment of malignant tumors with cytostatic drugs. Suppression of in vitro myelopoiesis (CFU-GM) by cytostatics may be a suitable model reflecting the in vivo situation. Thus the inhibitory effects of the anthracyclines doxorubicin, theprubicin, idarubicin and cytorhodin S on CFU-GM were compared.

Susceptibility of autologous target cells to lysis by lymphokine-activated effectors from interferon-alpha-treated chronic myelogenous leukaemia patients.

Chronic myelogenous leukemia (CML) patients in chronic phase display compromised lymphokine-activated killer (LAK) cell induction, which is partly restored after therapy with interferon alpha. However, the relative resistance of the leukemic cells from these patients to autologous or allogeneic LAK lysis is not affected by this treatment. In an attempt to render CML cells more susceptible to lysis or cytostasis, they were precultured in serum-free medium with or without recombinant growth factors.

A comparison of two adjunctive treatment strategies in acute mania.

A benzodiazepine-neuroleptic adjunctive treatment strategy in a cohort of acutely manic patients was compared with standard neuroleptic adjunctive treatment in a matched sample treated in the same hospital. Thirty newly hospitalized manic patients receiving low-dose neuroleptic (310 mg/day chlorpromazine equivalents) and benzodiazepines (1.6 mg/day lorazepam equivalents) were compared, retrospectively, with 30 statistically similar patients receiving standard dose neuroleptic adjunctive treatment (590 mg/day chlorpromazine equivalents; 0.

Regulation of normal myelopoiesis and chronic myelogenous leukaemia cell proliferation through a non-cytotoxic mechanism by a gamma/delta T cell clone.

Regulatory effects on myelopoiesis and myelogenous leukaemia cell proliferation mediated by a human T cell clone (TCC) carrying a gamma/delta receptor have been studied. MHC-unrestricted cytotoxicity could be induced in this clone by culture with IL-2 but not IL-4. Increasing concentrations of IL-2 resulted in increased lysis of natural killer (NK)-susceptible target cells but lysis of NK-resistant targets could not be induced.

IL-4-responsive human helper T cell clones are resistant to growth inhibition by tumor necrosis factor-alpha.

Positive and negative signals for clonal expansion of preactivated human CD4+ alloreactive Th cells have been examined. Fifteen T cell clones tested 3 days after Ag-specific stimulation proliferated with IL-2 but only five of these responded to IL-4. The remaining 10 also failed to respond to IL-4 in the presence of IL-1 and/or autologous B-LCL.

Frequencies of HLA-DP alleles in the four major types of leukaemia.

The frequencies of HLA-DP alleles in 50 acute lymphocytic, 43 acute non-lymphocytic, 50 chronic myelogenous and 51 chronic lymphocytic leukaemia patients were compared with 254 controls using primed lymphocyte typing. In CLL and ANLL there were significantly decreased frequencies of DPw1. Decreased DPw1 and DPw3 was observed in ALL, but after correction for the number of comparisons made this was no longer significant.

[Treatment and socioeconomic consequences of skiing injuries in the County of Vejle during the 1986/1987 season].

In a prospective study conducted in the County of Vejle in the skiing-season 1986/1987, the hospitals were contacted by 129 persons who had skiing-injuries. Forty-one patients were primarily treated abroad and 35 patients were primarily examined or treated in Denmark after their return. Fifty-three patients who were injured in Denmark were primarily examined or treated in the casualty ward.

Selective inhibition of interleukin 2 but not of interferon-gamma, tumour necrosis factor-alpha or granulocyte/macrophage colony stimulating factor secretion by human helper T cell clones after antigen-driven tolerisation.

Alloreactive human T-helper cell clones chronically exposed to specific antigen can become tolerised, i.e. lose their autocrine proliferative capacity and no longer undergo antigen-driven clonal expansion.

Sequential expression of CD34 and CD33 antigens on myeloid colony-forming cells.

The expression of CD33 and CD34 antigens on human bone marrow cells was examined by fluorescence-activated cell sorting and colony assays. A marked difference of antigen expression was observed on sorted progenitors of the granulocyte/macrophage lineage (CFU-GM) with respect to enrichment and maturation status. Single-color cell sorting revealed no difference of enrichment by anti-CD33 antibody between day-7 and d-14 progenitors, while anti-CD34 antibody preferentially enriched d-14 colony-forming units (CFU).

Drug abuse in schizophrenia and bipolar disorder.

The incidence and type of drug abuse for 50 male schizophrenic patients and 60 male and female bipolar, manic patients were determined. Fifty percent of schizophrenic patients and 25% of bipolar patients abused one or more drugs. Alcohol, cannabis, and cocaine accounted for 82% of the drug abuse.

Antitumor activity in vitro in chronic myelogenous leukaemia revealed after treating peripheral cells with cytosine arabinoside.

Cytosine arabinoside (Ara-C) treatment of peripheral blood mononuclear cells from 12/12 chronic-phase chronic myelogenous leukaemia (CML) patients revealed a proliferative response stimulated by their untreated leukaemic cells. Specific recognition of tumour cells by patients' normal lymphocytes was suggested by the finding that cells of siblings genotypically identical for human leukocyte antigen caused no stimulation. Lymphocytes thus stimulated by tumour cells from one of these patients were cloned by limiting dilution and tested for antileukaemic effects in cytotoxicity and proliferation assays.

Differential secretion of tumor necrosis factor-alpha and granulocyte/macrophage colony-stimulating factors but not interferon-gamma from CD4+ compared to CD8+ human T cell clones.

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic lymphokine which may have important regulatory effects on immune responses. It is shown here that eight alloreactive CD4+ T cell clones (TCC) secreted significant amounts of TNF-alpha after stimulation with either specific alloantigen or 12-O-tetradecanoylphorbol 13-acetate together with the calcium ionophore ionomycin (up to 50 ng/ml/24 h/10(6) cells) whereas CD8+ TCC failed to do so (max. 2 ng/ml/24 h/10(6) cells).

The compulsion to repeat in action: a developmental perspective.

The compulsion to repeat in action is seen as being a particular way of thinking that is characteristic of the time when neurosis is formed. This type of thinking has been abundantly studied by Piaget, and is seen as a consequence of the development of more complex thought from action roots. Piaget has labelled this thinking as pre-operational, and it is seen as occurring between the ages of eighteen months and 7 years.

Prevention of human helper T-cell clone activation by cyclosporin A also blocks secretion of granulocyte/macrophage colony stimulating activity.

Cyclosporin A (CsA) blocks stimulation and growth of alloreactive T helper cell clones (Th-TCC), even in the presence of exogenous Interleukin-2 (IL-2). To examine whether this might reflect a generalised inhibition of cytokine production by these cells, their production of granulocyte/macrophage colony-stimulating factors (GM-CSF), thought not to be involved in the autocrine proliferation of the clones themselves, was investigated. Contrary to the prediction that only pathways relevant to T cell clonal expansion would be blocked by CsA, it was found that this immunosuppressive substance exerted a profound inhibitory activity on GM-CSF secretion, even in the presence of exogenous IL-2.

Division of human helper T cells into two sets on the basis of the induction of anti-tumor cytotoxicity by phorbol ester and calcium ionophore.

Fourteen noncytotoxic human helper T cell clones were examined for autocrine proliferative responses and cytotoxicity to tumor cells after stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA) and ionomycin (Io). Although all clones responded to alloantigen, they could be divided into two groups based on their proliferative response or lack of it to TPA/Io. Nonresponders could not be converted to responder status by addition of interleukin (IL) 1 or indomethacin to the cultures.

Response-oriented therapy with CHOP and VIM-Bleo in high-grade malignant non-Hodgkin's lymphomas.

Twenty four patients with high grade malignant NHL (stage II 8, stage III 4, stage IV 12 patients respectively) were treated with a response-oriented regimen: Treatment was initiated according to the CHOP-protocol. Patients achieving at least a partial remission after 2 and a complete remission (CR) after 4 cycles were continued on CHOP to a total of 9 cycles. Patients not meeting these criteria were switched to a combination of Etoposide, Ifosfamide, Methotrexate, and Bleomycin (VIM-Bleo).

Different signals for stimulation of proliferation and lymphokine secretion by a CD3+ WT31- cloned cytotoxic lymphocyte.

CD3+ WT31- T cells were sorted from peripheral blood of a normal healthy donor by a FACS IV and cloned by limiting dilution in the presence of a phorbol ester (tetradecanoyl phorbol acetate, TPA), calcium ionophore (ionomycin, Io), interleukin-2 (IL-2), allogeneic cells, and phytohemagglutinin (PHA). One of the derived clones, 290-2, was investigated in detail. 290-2 mediated strong natural killer (NK) but not lymphokine-activated killer (LAK) activity.

Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host.

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation.

[Renal involvement in malignant lymphoma: significance of imaging technics for determining spread].

Large autopsy series show an incidence of 33 to 62% of renal involvement in all patients with malignant lymphoma; at the time of diagnosis, this is found only very rarely. The present paper describes three patients with renal involvement at the time of diagnosis. The value of sonography, CT and angiography in detecting renal involvement and its clinical significance in the management of malignant lymphoma is discussed.