Bacterial toxins affect early events of T lymphocyte activation.

The effects of pertussis toxin and cholera toxin on early events of T lymphocyte activation were examined in the T lymphocyte cell line, Jurkat. Pertussis toxin treatment of these T cells increased inositol phosphates production and led to increases in intracellular free calcium concentration. These effects were produced by the isolated B (binding) subunit of pertussis toxin, alone.

A novel mechanism of soluble guanylate cyclase stimulation: time-dependent activation by bacterial lipopolysaccharide in rat fetal spleen cells.

Small amounts of bacterial lipopolysaccharide (LPS) greatly increase cGMP levels in short term cultures of rat fetal liver and spleen cells in a dose and time dependent manner. To determine the role of guanylate cyclase in this response, a series of experiments was undertaken using either intact or broken fetal spleen cells, the most sensitive tissue evaluated to date. The phosphodiesterase inhibitor, 1-methyl-3-isobutyl-xanthine, potentiated the LPS-cGMP effect in cultures of these cells even at maximal doses of LPS.

Effects of recombinant erythropoietin on the concentration and cycling status of human marrow hematopoietic progenitor cells in vivo.

The concentration of human marrow progenitors CFU-E, BFU-E, CFU-GM, and CFU-Mk and the percentage of these progenitor cells in DNA synthesis were studied in nine patients with transfusion-dependent anemia of end-stage renal failure before and 2 weeks after treatment with human recombinant erythropoietin (Epo) at a dose of 150 to 300 U/kg intravenously three times per week. The concentration of CFU-E in the posttreatment marrow increased by a mean of 4.15-fold, BFU-E by 3.

Treatment of the anemia of predialysis patients with recombinant human erythropoietin: a randomized, placebo-controlled trial.

Recombinant human erythropoietin (r-HuEPO) was administered in two phases to 12 patients with chronic renal insufficiency (creatinine clearances of 0.17-0.51 ml/second [10-30 ml/minute]) and uremic anemia.

Erythropoietin messenger RNA levels in developing mice and transfer of 125I-erythropoietin by the placenta.

Erythropoietin (EP) mRNA was measured in normal and anemic mice during fetal and postnatal development. Normal fetal livers at 14 d of gestation contained a low level of EP mRNA. By day 19 of gestation, no EP mRNA was detected in normal or anemic fetal livers or normal fetal kidneys, but anemic fetal kidneys had low levels of EP mRNA.

Factors affecting the extension of peritumoural brain oedema. A CT-study.

In human brain tumours the extension of peritumoural brain oedema may vary considerably. 37 brain tumours of various pathology and 2 abscesses were examined to identify the factors and mechanisms responsible for the oedema spreading. Peritumoural oedema profiles were determined towards the white matter and ventricle by measuring the CT-numbers of consecutive tissue blocks of 3.

T4+ (helper phenotype) chronic lymphocytic leukemia: case report with liver failure and literature review.

T-cell lymphomas and leukemias are a heterogeneous group of neoplasms found in each anatomic compartment of the T system (marrow, thymus, and various peripheral tissues) and that have varying phenotypic expressions. Histopathologic features of the thymic and peripheral T neoplasms do not fit into a clearly defined pattern, and clinical expressions of T neoplasms are likewise variable. This report describes a 60-year-old man with "chronic" lymphocytic leukemia of T4+ (helper) phenotype.

Attenuation of endotoxin-induced cytotoxicity and prostacyclin production in cultured bovine pulmonary artery endothelial cells by phosphodiesterase inhibition.

Exposure of cultured bovine pulmonary endothelial cells to endotoxin (lipopolysaccharide, LPS) causes cytotoxicity and increased prostacyclin production. Since cyclic nucleotides have been proposed as modulators of inflammation, we wondered whether they were involved in LPS-induced endothelial damage. Bovine pulmonary endothelial cells were exposed for 24 h to LPS and the effects of 1-methyl-3-isobutylxanthine (MIX), a phosphodiesterase inhibitor, dibutyryl cyclic AMP (db-cAMP), forskolin (an adenylate cyclase activator), and sodium nitroprusside (an agent known to stimulate intracellular cyclic GMP generation) on LPS-induced injury were determined.

Lymphocyte-depleted Hodgkin's disease. Clinicopathologic review of 25 patients.

Clinicopathologic material from 25 patients with lymphocyte-depleted Hodgkin's disease was reviewed. The median age of the patients was 57 years. The patients had no prior diagnosis of Hodgkin's disease and were divided according to pathologic subtype of lymphocyte-depleted Hodgkin's disease: 11 diffuse fibrosis, 10 reticular, and four not otherwise specified.

Myoglobin expression in L6 muscle cells. Role of differentiation and heme.

Analysis of myoglobin levels in L6 cells (derived from rat skeletal muscle) by radioimmunoassay shows that myoglobin is not synthesized until after the cells differentiate to form multinucleated myotubes. Thereafter, myoglobin accumulates in a linear fashion for up to 20 days, the longest time for which the cultures may be reliably maintained. Treatment of cultures with hemin increased myoglobin levels in a dose-dependent manner resulting in a 70% increase in myoglobin with 20 microM hemin.

Malignant plasmacytic ascites. A report of two cases and a review of the literature.

Two patients with ascites due to peritoneal involvement by multiple myeloma are reported and seven previously described cases of plasmacytic ascites are reviewed. In all nine cases, ascitic fluid contained large numbers of bizzare, immature plasma cells. Although the cells were often difficult to characterize by light microscopy, they could be rapidly identified as malignant plasma cells by immunofluorescent demonstration of monoclonal, intracellular immunoglobulin as performed in one of the patients.

Further characterization of the effect of bacterial lipopolysaccharide preparations on cyclic GMP levels: the importance of macromolecular synthesis.

Bacterial lipopolysaccharides (LPS) greatly increase cGMP levels in short term cultures of rat fetal liver cells without affecting the concentration of cAMP. This effect is produced by very small (1 ng) amounts of LPS and is both dose and time dependent. The time dependence is characterized by an initial lag period of 60-120 min followed by a rapid, persistent increase in cGMP levels.

Activation of adenylyl cyclase by preincubation of rat cerebral-cortical membranes under phosphorylating conditions: role of ATP, GTP, and divalent cations.

The effects of preincubation under phosphorylating conditions on adenylyl cyclase activity were studied in preparations containing synaptic membranes from rat cerebral cortex. Preincubation of the membranes with 2 mM ATP and 10 mM MgCl2 resulted in a 50% increase of adenylyl cyclase activity which withstood sedimentation and washing. This activation was maximal after 5 min of preincubation, was reversed after longer preincubations, and paralleled the time course of endogenous phosphorylation-dephosphorylation of proteins observed under these conditions.

Plasma cell iron--clinical and morphologic features.

In order to identify the major clinical features and laboratory findings in patients with plasma cell iron, the authors reviewed the medical records and marrow aspirates of 53 consecutive patients with plasma cell iron hospitalized at Nashville Veterans Administration Hospital over a seven-year period. Plasma cell iron was associated most commonly with alcoholism and occurred in marrows with increased, normal, and decreased iron stores. In patients with decreased marrow iron, plasma cells were the major site of stainable iron.

Effects of endotoxemia on cyclic nucleotides in the unanesthetized sheep.

The effects of endotoxemia on hemodynamics, pulmonary fluid, and solute exchange and cGMP and cAMP concentrations in lung lymph and pulmonary artery and left atrial blood were studied in six unanesthetized sheep. Cyclic AMP levels increased early in the endotoxin reaction, reaching peak concentration 1 hr after endotoxemia (during the period of pulmonary hypertension). Cyclic GMP levels increased gradually during the endotoxin reaction, reaching peak concentrations 5 hr after endotoxemia (during the period of "increased pulmonary vascular permeability").

Further characterization of the effect of bacterial lipopolysaccharide preparations in cyclic 3',5'-GMP levels: the importance of serum.

Bacterial lipopolysaccharides (LPS) greatly increase cGMP levels in rat fetal liver cells without affecting the concentration of cAMP. This elevation is due to the Lipid A moiety of the LPS molecule, is time and dose dependent, and is markedly potentiated by small amounts of serum. Because of the magnitude of the serum potentiation, a series of experiments was undertaken to further characterize this effect.

Evidence that changes in platelet cyclic AMP levels regulate the fibrinogen receptor on human platelets.

Fibrinogen binds to human platelets after specific receptor sites are exposed by thrombin, ADP, epinephrine, and other stimuli. Since prostaglandin I2 (PGI2), a potent activator of platelet adenylate cyclase, prevents mobilization of the fibrinogen receptor by aggregating agents, we investigated the relationship between platelet cAMP levels and fibrinogen receptor status in thrombin-stimulated human platelets. A dose-dependent rise in platelet cAMP in response to two adenylate cyclase agonists, PGI2 and forskolin, correlated with progressive inhibition of fibrinogen binding.

Direct evidence that bacterial lipopolysaccharides elevate cyclic GMP levels in rat fetal liver cells.

We have previously shown that crude bacterial lipopolysaccharide (LPS) preparations markedly increase cGMP levels in rat fetal liver cells in a time- and dose-dependent manner. To provide evidence that this effect was due to LPS and not an impurity in the preparations, three series of experiments were undertaken. First, LPS was prepared from Escherichia coli 055:B5 cells and its cGMP potency assessed at various stages of purification; second, the cGMP activity of three highly purified LPS preparations of known chemical structure was measured, and third, a well characterized LPS was broken into its lipid A and polysaccharide fractions and the cGMP activity of each fraction determined.

Beneficial effect of hepatitis in leukemic reticuloendotheliosis.

A patient with leukemic reticuloendotheliosis had splenomegaly, neutropenia, and a severe underproduction anemia. During a three-year period, the hematocrit was never in the normal range, and periodic transfusions were required. However, after an episode of hepatitis that was positive for B surface antigen, the spleen became smaller, the number of neutrophils increased, the transfusion requirement disappeared, and the hematocrit rose to normal.

Erythropoietin and the regulation of erythropoiesis.

Recent advances in experimental hematology have provided new insight into the physiology of erythropoiesis. Techniques are now available for cloning in vitro the various hematopoietic progenitor cells of both animals and man. Erythropoietin has been purified and a radioimmunoassay for the hormone has been described.