Growth-inhibitory effect of 2-CdA on myeloid CFU-GM progenitors in normal human long-term bone marrow cultures and its compensation by G-CSF or IL-3.

As neutropenia is a common side effect of treatment with 2-chlorodeoxyadenosine (2-CdA), we investigated the myelosuppressive action of 2-CdA in Dexter-type human long-term bone marrow cultures (LTBMCs). LTBMCs were incubated with varying doses of 2-CdA (5 to 20 nM/L) during the first week. At 20 and 10 nM/L 2-CdA, we found a marked reduction in colony-forming unit-granulocyte/macrophage (CFU-GM) production throughout the culture period of 7 weeks (maximum reduction to 3.

Prevalence of hepatocellular carcinoma in alpha-1-antitrypsin deficiency.

The aim of the present study was to determine the prevalence of hepatocellular carcinoma in adults with heterozygous alpha 1-antitrypsin deficiency and to assess the presence of possible co-risk factors for the development of hepatocellular carcinoma. Two hundred and forty patients with cirrhosis of different aetiologies and 130 patients with alpha 1-antitrypsin deficiency without evidence of chronic liver disease were investigated. Out of the 240 patients with cirrhosis, 61 patients (25%) were found to have alpha 1-antitrypsin deficiency, 36 patients (15%) had chronic hepatitis C infection, 50 (21%) had chronic hepatitis B and 24 (10%) had hepatitis C and hepatitis B infection.

Alpha-1-antitrypsin deficiency and liver disease.

Alpha-1-antitrypsin deficiency is a common autosomal recessive disorder associated with premature development of emphysema, liver cirrhosis and hepatocellular carcinoma. This article reviews the existing literature on alpha-1-antitrypsin deficiency, with an emphasis on recent developments. A description of the protein, gene structure and function of alpha-1-antitrypsin as well as clinical aspects are presented.

[Prognosis and life expectancy in primary biliary cirrhosis].

The aim of the present study was to investigate prognosis and life expectancy in patients with primary biliary cirrhosis. We retrospectively analysed 59 patients from western Austria over 15 years (mean 6 years). The results of the present study were compared with the average life expectancy of the population of western Austria and with the results of the Mayo study published in 1989.

The acute-phase protein alpha 1-antitrypsin inhibits growth and proliferation of human early erythroid progenitor cells (burst-forming units-erythroid) and of human erythroleukemic cells (K562) in vitro by interfering with transferrin iron uptake.

We have previously shown that the hepatic acute-phase protein alpha 1-antitrypsin (alpha 1-AT) inhibits transferrin (tf) binding to its receptor (tfR) of human placental membranes. To evaluate the possibility that this interaction can explain the pathophysiology of the changes in iron metabolism in the course of chronic disease, subsequently leading to anemia in chronic disease (ACD), we examined the effect of alpha 1-AT on cells of the erythroid cell line. alpha 1-AT completely prevented tf binding to tfR on K562 human erythroleukemic cells and on reticulocytes.

Increased levels of serum neopterin and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha.

Objectives: The purpose of this study was to examine the role of tumor necrosis factor-alpha and tetrahydrobiopterin and superoxide anion release from neutrophils in severe chronic heart failure.

Background: Previous studies have demonstrated elevated production of tumor necrosis factor-alpha and free radical-induced endothelial cell damage in severe heart failure.

Methods: Plasma and serum levels of immunoreactive interleukin-1, interleukin-6, interferon-gamma, neopterin and tumor necrosis factor-alpha and the release of superoxide anions from circulating neutrophils both at basal conditions and after triggering with f-Met-Leu-Phe or phorbol 12-myristate 13-acetate were measured in 16 patients with severe heart failure and in 11 healthy control subjects.

Inhibition of superoxide anion release from circulating neutrophils by L-arginine in man.

In animal studies of myocardial ischemia/reperfusion L-arginine reduces necrotic injury by preservation of endothelial function and attenuation of neutrophil accumulation in ischemic cardiac tissue. Because release of oxygen radical species by circulating neutrophils is important in endothelial function and ischemia-reperfusion injury, this study investigated the effect of intravenous administration of L-arginine on the in vitro release of superoxide anion of neutrophils in healthy young adults. Neutrophils were obtained at various time points before, during, and after infusion of L-arginine (17 mg kg-1 min-1 for 30 min) and analyzed for superoxide dismutase inhibitable reduction of ferricytochrome c.

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid.

We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels.

Stimulation of monocyte chemotaxis by human growth hormone and its deactivation by somatostatin.

Monocyte infiltration occurs early in the course of inflammation and is a prerequisite for optimal repair of tissue damage. In this study, human recombinant growth hormone was shown to be a potent chemoattractant for human monocytes, inducing migration at picomolar concentrations of recombinant human growth hormone. Chemotaxis of monocytes was measured in vitro by a modified Boyden chamber assay using nitrocellulose micropore filters and measuring microscopically the migration depth of the leading front of monocytes.

High-affinity substance P binding sites of neurokinin-1 receptor type autoradiographically associated with vascular sinuses and high endothelial venules of human lymphoid tissues.

Background: Factors that affect leukocyte-endothelial cell interaction in high endothelial postcapillary venules and vascular sinuses of lymphatic tissues indirectly regulate immune function. Studies in sheep demonstrated that acute infusion of substance P (SP) into cannulated popliteal lymph node afferent lymphathics produced a marked and prolonged increase in the output of lymphocytes into nodal efferent lymph. The proposed mechanism is an influence of SP on lymph vascular systems.

Inhibition of recombinant human growth hormone-induced and prolactin-induced activation of neutrophils by octreotide.

Growth hormone, prolactin and somatostatin are polypeptide hormones of the neuroendocrine and peripheral nervous systems. In vitro, these have opposing effects on cells of the immune system. We compared the effects of these peptides on activation of neutrophils using a recombinant preparation of human growth hormone, human prolactin and octreotide, a long acting analog of somatostatin.

The hepatic acute-phase proteins alpha 1-antitrypsin and alpha 2-macroglobulin inhibit binding of transferrin to its receptor.

Transferrin binding to human placental sites was inhibited by the acute-phase proteins alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-MG), whereas haptoglobin, C-reactive protein and ferritin displayed no such effect. In equilibrium saturation binding assays, the effective acute-phase proteins decreased the apparent affinity of the binding sites for transferrin, but the transferrin binding-site density Bmax. was not significantly changed.

[After-care by the internal medicine physician following liver transplantation].

Orthotopic liver transplantation offers the only therapeutic option for many patients with end-stage liver disease. In adults, the overall five-year survival following transplantation has increased dramatically from approximately 30% a decade ago to nearly 70% currently. Cyclosporine A became available in the 1970s and substantially improved immunosuppressive therapy.

[Trans-septo-sphenoidal operation for pituitary adenoma in 92 patients: results and follow-up endocrine studies].

The short- and long-term therapeutic results of transseptosphenoidal adenomectomy were studied retrospectively in 92 patients with pituitary tumors (42 nonsecreting adenomas, 21 GH-, 15 PRL-, 10 ACTH-, 2 TSH-, and 2 FSH-secreting adenomas). Severe surgically related complications were not observed. The early remission rate was 53.

Regulation of myeloid phagocyte development and function by growth hormone: a review.

Growth hormone (GH) has previously been implicated in T cell development and function, and here we review its efficacy in promoting development and function of myeloid cells. Evidence obtained from both in vitro and in vivo studies suggests that, in animals as well as in man, GH augments proliferation and differentiation of erythroid, megakaryocytic and myeloid progenitor cells. Mechanisms of hemopoietic actions probably involve induction of insulin-like growth factor-1, which is under GH control.

In vivo activation of circulating monocytes by exogenous growth hormone in man.

Animal studies have shown that administration of growth hormone improves wound healing. Monocyte activation is a prerequisite for optimal repair of damage. In vitro, human recombinant growth hormone was shown to be a potent human monocyte chemoattractant.

Regulation of human T lymphoblast growth by sensory neuropeptides: augmentation of cholecystokinin-induced inhibition of Molt-4 proliferation by somatostatin and vasoactive intestinal peptide in vitro.

The effects on proliferation of Molt-4 lymphoblasts of cholecystokinin (CCK-8), somatostatin-14 (SS), vasoactive intestinal peptide (VIP) and substance P (SP) were investigated using different combinations of the peptides, peptide analogs and their antagonists. In vitro proliferation of the cells was measured by a colorimetric assay for cell growth and survival. Results indicate that SP and SP (3-11) stimulated, whereas CCK-8, VIP and SS inhibited, proliferation in a dose-dependent manner (P < 0.

High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease.

Objective: To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients.

Design: Cross-sectional study.

Setting: A referral-based university hospital.