Prokaryote or eukaryote? A unique microorganism from the deep sea.

There are only two kinds of organisms on the Earth: prokaryotes and eukaryotes. Although eukaryotes are considered to have evolved from prokaryotes, there were no previously known intermediate forms between them. The differences in their cellular structures are so vast that the problem of how eukaryotes could have evolved from prokaryotes is one of the greatest enigmas in biology.

Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia.

Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia.

Serum levels of TNF, IL-6 and sCD23 correlate with changes in lymphocyte count in patients with B-cell chronic lymphocytic leukaemia receiving interferon-alpha therapy.

The control of cell growth and differentiation in B-cell malignancies may be regulated by the autocrine production of cytokines, several of which have been implicated in the growth and survival of B-cells. The effect of interferon-alpha (IFN) therapy in these disorders may be to disrupt autocrine growth or survival loops. We have measured levels of circulating IL-1b, IL-6, TNF-a and soluble CD23 (sCD23) in 8 patients with Binet stage A B-cell chronic lymphocytic leukaemia (B-CLL) receiving IFN therapy, and compared these with changes in the lymphocyte count following IFN therapy.

Growth factors can protect B-chronic lymphocytic leukaemia cells against programmed cell death without stimulating proliferation.

The proliferation and survival of B-chronic lymphocytic leukaemia (B-CLL) cells may be regulated by autocrine growth factor loops. Furthermore, it has been suggested the reduction in lymphocytosis following therapy with interferon-alpha may be associated with the interruption of autocrine growth factor production. We have therefore examined the effects of a number of cytokines on the proliferation of B-CLL cells, and also on the regulation of programmed cell death, and the role of interferon-alpha in these systems.

BLT-esterase in infectious mononucleosis.

Peripheral blood lymphocytes of three patients suffering from infectious mononucleosis due to Epstein-Barr virus (EBV) infection were analysed for BLT-esterase expression in peripheral blood lymphocytes by a well established cytochemical staining method. During the acute phase of disease with presence of clinical symptoms a very high level of up to 90% BLT-esterase-expressing lymphocytes were detected. The increased percentage of lymphocytes expressing BLT-esterase coincided with the time of greatest symptoms and the peak elevation of hepatocellular enzymes.

Changes in maternal plasma macrophage-colony stimulating factor levels during normal pregnancy.

An enzyme-like immunosorbent assay and a blood autoanalyser were used to determine macrophage-colony stimulating factor (M-CSF) levels and the absolute number and percentage of circulating monocytes in 80 normal women with singleton pregnancies at 12-40 weeks' gestation, and ten healthy non-pregnant volunteers. The mean values of M-CSF and absolute number and percentage of circulating monocytes of the control group were 367 U/ml (SD 43) and 389 x 10(6)/l (SD 180) and 5.3% (SD 1.

Myeloperoxidase activity and nuclear segmentation of maternal neutrophils during normal pregnancy.

Myeloperoxidase (MPO) activity and nuclear segmentation of neutrophils were measured in peripheral blood samples from 90 normal pregnant women, arranged in nine groups of ten each, every four weeks at 8-40 weeks gestation and from 25 non-pregnant healthy female controls. A blood autoanalyser (Technicon H*1) was used to determine the mean peroxidase index (MPXI) and the lobularity index (LI) of circulating neutrophils. Mean MPXI levels in pregnancy decreased with gestation to a minimum at 20 weeks' gestation and increased thereafter to reach non-pregnant levels at 36 weeks.

Interferon-alpha up-regulates bcl-2 expression and protects B-CLL cells from apoptosis in vitro and in vivo.

The bcl-2 oncoprotein, which is involved in the t(14,18) translocation, protects cells against apoptosis. We examined the effects of interferon-alpha (IFN-alpha) on bcl-2 protein expression and apoptosis in B-chronic lymphocytic leukaemia (B-CLL) cells. None of 12 patients with B-CLL examined expressed the t(14,18) translocation; however, all these, and seven other patients, expressed significant levels of bcl-2 protein.

Serum macrophage colony-stimulating factor (M-CSF) levels correlate with clinical response to interferon-alpha in patients with early-stage B-CLL.

Interferon-alpha (IFN-alpha) reduces peripheral lymphocyte counts in B-CLL (CLL). In eight patients with stage 0 CLL on IFN-alpha therapy, peripheral lymphocyte counts fell to 61.7 +/- 19.

Recombinant interferon alfa 2a in the treatment of patients with early stage B chronic lymphocytic leukaemia.

18 patients with early stage, previously untreated B-CLL were given interferon alfa (IFN alpha) 2a. 3 MU thrice weekly, subcutaneously. The peripheral lymphocyte count decreased in all patients.

In vivo and in vitro primed lymphocytes. Correlation of cytochemically detected BLT-specific lymphoid serine protease with cytotoxic activity.

We describe the validation of a cytochemical method to detect a cytolytic cell-specific lymphoid serine protease which can be upregulated during viral infection and allogeneic stimulation. The cytolytic cell specificity was ascertained by demonstrating a high correlation between BLT substrate-specific serine protease (SP) activity and cytotoxicity of in vivo and in vitro stimulated lymphocytes. The presence of SP in peripheral blood lymphocytes was compared with their capacity to kill K562 targets in a lectin-dependent cytotoxicity assay.

Low-dose recombinant alfa-2a-interferon: a feasible maintenance therapy in acute myeloid leukaemia in the older patient.

Eleven patients with acute myeloid leukaemia (AML) in first complete remission (CR) were treated with alfa-2a-interferon (for short 'interferon') maintenance therapy, at a dose of 3 MU twice to thrice weekly subcutaneously. Adjustments were made to maintain neutrophil counts > 1 x 10(9)/l and platelet counts > 100 x 10(9)/l. A transient fall in haemoglobin, neutrophil and platelet counts was noted in all 9 evaluable patients.

Resistance of chronic lymphocytic leukaemia cells to interferon-alpha generated lymphokine activated killer cells.

Recent studies have shown that, when used in early stage disease, interferon-alpha (IFN-alpha) can produce a fall in the number of malignant cells in the peripheral blood of patients with B-CLL. In this study, we investigated the effect of IFN-alpha on natural killer (NK) cell and lymphokine-activated cell (LAK) activity in patients with B-CLL. In vitro, IFN-alpha (500 U/ml for 18 hours) induced LAK activity in patients with B-CLL (27.

In vitro sensitized autologous tumorocidal lymphocytes to colonic adenocarcinoma.

We report a method of developing a population of tumorocidal lymphocytes by culturing peripheral blood mononuclear cells (PBMC) with live isogenic colorectal tumour cells in a mixed cell culture. When the proportion of PBMC to tumour cells is 100:1, eradication of the tumour cell population results. The proportion of activated lymphocytes in culture increases with cytotoxic activity as demonstrated by the presence of the cytotoxic enzyme serine esterase in the lymphocyte granules.

Cytokine induction of leucocyte adhesion molecule-1 (LAM- 1) expression on chronic lymphocytic leukaemia cells.

Leucocyte adhesion molecule 1 (LAM-1) participates in the binding of human leucocytes to high endothelial venules in peripheral lymph nodes. Other adhesion receptors which are involved include CD44 and the integrin family, CD11/CD18. In this study, B-cell chronic lymphocytic leukemia (B-CLL) cells were examined for the expression of these adhesion molecules, and for the way in which cytokines are able to modulate the levels of these receptors.

Detection of BLT substrate-specific proteases in individual human peripheral blood leucocytes and bone marrow cells. Application of the method to the classification of leukaemia.

A trypsin-like serine esterase (SE) is known to be present in cultured cells with cytolytic potential. The distribution pattern of this enzyme in haematological cells and body tissues has been assessed using a method which permits rapid identification of individual cells. Cells and tissue sections were fixed and immersed in the substrate N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT)/Fast Blue BB chromogen solution.

Lymphocyte activation and serine-esterase induction following recombinant interleukin-2 infusion for lymphomas and acute leukaemias.

In this study we investigated the pattern of T lymphocyte changes in 16 adult patients with acute myeloid leukaemia (8), non-Hodgkin's lymphoma (4) and Hodgkin's disease (4) treated with continuous infusion of recombinant interleukin-2 (rIL-2). Effects indicative of lymphocyte activation occurred even prior to any rIL-2 therapy in these patients, being most prominent in patients with active diseases. Following each course of cytokine therapy, there were further changes in these parameters.

Production of tumour-derived suppressor factor in patients with acute myeloid leukaemia.

In an attempt to investigate the underlying cause of impaired cellular cytotoxic functions in patients with acute myeloid leukaemia and the relative ineffectiveness of immunotherapy with recombinant interleukin 2 (IL-2), normal donor lymphocytes were incubated in AML sera and in supernatant of myeloblasts. There was significant inhibition of both the natural killer activity and the lectin dependent cellular cytotoxicity of the normal donor lymphocytes compared to when incubation took place in autologous or normal allogeneic sera or marrow supernatant. This inhibition was time-related and partially reversible by washing of the normal lymphocytes immediately before the cytotoxicity assay.

Recombinant alpha-interferons, thyroid irradiation and thyroid disease.

Recombinant alpha-interferons are used as therapeutic agents in an increasing number of benign and malignant disorders. Long-term administration of recombinant alpha-interferon as a maintenance agent is associated with a small number of adverse side-effects which are responsible for patient intolerance of this drug. These include weight loss, alopecia and chronic fatigue, anorexia and depression syndrome.

Lymphocyte activation in patients with acute myeloid leukaemia. Evidence for the presence of myeloblast antigen?

A group of 27 patients with acute myeloid leukaemia (AML), 15 with active disease and 12 in complete remission, were investigated for evidence of T cell activation. The parameters of T cell activation measured were the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules and the proportions of T cells expressing the cytotoxicity-linked cytoplasmic serine esterase. All patients studied with active disease had elevated sIL-2R and sCD8 molecules and an elevated proportion of T cells expressing serine esterase.

Cellular cytotoxic function and potential in acute myelogenous leukaemia.

Twenty-seven adult AML patients (13 with active disease and 14 in complete remission) were investigated for their cellular cytotoxic potential and function. All AML patients, whether with active disease or in complete remission, showed increased percentage of CD3+ lymphocytes expressing the cytotoxicity-linked cytoplasmic serine esterase, suggesting a higher than normal cytotoxic potential. However, when the cytotoxic function in these patients were analysed in terms of the natural killer and lectin-dependent cellular cytotoxicity, all AML patients, whether with active disease or in complete remission, had impaired target cell lytic activity.

Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study.

The prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease.

T gamma delta cells and their subsets in blood and synovial tissue from rheumatoid arthritis patients.

We have examined the frequencies of T gamma delta cells in blood, synovial fluids, and synovial membranes of patients with rheumatoid arthritis (RA) and in blood from age-matched controls. Immunocytochemical and immunohistochemical techniques were used with monoclonal antibodies BB3 and A13 to define a major and minor blood subset of T gamma delta cells respectively. Together, these antibodies identify the majority (if not all) of the peripheral blood T gamma delta cells.

T gamma delta-cell subsets in cord and adult blood.

A minor population of T cells expresses a heterodimeric antigen receptor composed of gamma and delta chains (TcR-1). In blood from adults, two subsets of T gamma delta cells can be identified by the monoclonal antibodies (MoAb) BB3 and A13. Little is known about the distribution and markers of these subsets early in life.