Blood system responses in inflammation and mechanisms of their development]

A model of acute infectious peritonitis in mice demonstrated that the inflammation is attended by marked biphasic activation of bone-marrow granulomonocytopoiesis and that the activation is due in many respects to increased functional activity of elements forming the hemopoiesis-inducing microenvironment. This was suggested by increased colony-stimulating activity of the marrow mononuclear cells and the content of hemopoietic islets in the marrow. The colony-stimulating activity of peripheral blood also increased. It was established that inflammation is also characterized by activation of bone-marrow erythropoiesis, which is linked with increased erythropoietic activity of the hemopoiesis-inducing microenvironment and blood. There was a relation between the hemopoietic changes and the kinetics of leukocytes in the focus of inflammation.     

Interleukin-2 and granulocyte-macrophage colony-stimulating factor stimulate growth of a virulent strain of Escherichia coli.

The effect of human recombinant interleukin-2 (IL-2) and human recombinant granulocyte-macrophage colony-stimulating factor on the growth of a virulent strain of Escherichia coli in tissue culture medium and in untreated, normal mouse serum was investigated. Both of these cytokines enhanced the growth of the microorganism two- to threefold in tissue culture medium with or without additional fetal calf serum and in untreated mouse serum. IL-4 did not have any effect on the growth of this microbe under the conditions tested. That the enhancement of growth seen with recombinant IL-2 was due to the active cytokine was shown by the following data: (i) addition of an antibody to IL-2 abrogated the growth-promoting effect; (ii) the excipient buffer, which contained everything except the active cytokine, was inactive in modifying bacterial growth; and (iii) heat-inactivated recombinant IL-2 did not promote enhanced microbial growth. The enhancement of growth with IL-2 was significant with concentrations as low as 1 U/ml. Growth of an avirulent strain of E. coli was not stimulated by IL-2. Moreover, addition of IL-2 to growth virulent E. coli in tissue culture medium led to rapid removal of the cytokine from the medium. Collectively, these data suggest that cytokines may act as growth factors for some virulent bacteria.     

A method to differentiate between anti-C1q antibodies and C1q-binding immune complexes using collagenase-digested solid phase C1q.

A method for the detection of circulating immune complexes in the presence of autoantibodies to C1q is described. Solid phase C1q-digestion with bacterial collagenase results in the elimination of the collagen-like region of C1q. Binding of model immune complexes to this modified solid phase C1q is practically unaltered, while reactivity of anti-C1q antibodies is abolished by this procedure. In conjunction with an ELISA using the collagen-like region of C1q as antigen this modified C1q solid phase assay may be used to determine immune complexes and anti-C1q antibodies in the sera of patients with autoimmune rheumatic diseases.     

Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells

The authors studied the effects of 4-hydroxyandrostene-3,17-dione (4-OHA) on progesterone (P), 17 beta-estradiol (E2), and 20 alpha-hydroxy-4-pregnen-3-one synthesis and pregnenolone accumulation in cultured human midluteal cells. A dose-dependent inhibition with and without human chorionic gonadotropin (hCG) of E2 and P production was observed. The accumulation of pregnenolone was significantly enhanced three to fourfold by 4-OHA in this culture system, as compared with control value. In addition, a sevenfold increase on pregnenolone accumulation was observed in the presence of 4-OHA plus 10 IU of hCG as compared with control values and 2.2-fold as compared with the 4-OHA treatments. These in vitro findings indicate a direct effect of 4-OHA on luteal steroidogenesis. Nevertheless, the suppressive effect of 4-OHA on P and E2 production is located at different sites of the steroidogenic pathway. In addition, the results demonstrate that hCG in the presence of 4-OHA stimulated pregnenolone accumulation, suggesting that the inhibition of P synthesis is in some steps after the formation of pregnenolone. These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms.     

Pneumocandins from Zalerion arboricola. III. Structure elucidation.

Pneumocandin B0 (6) and six related lipopeptides are antifungal and anti-Pneumocystis carinii agents from mutants of Zalerion arboricola, whose structures were determined mainly on the basis of spectroscopic analysis. They belong, along with pneumocandin A0 (L-671,329) previously isolated from these laboratories, to the echinocandin class of antifungal agents. The product from base-catalyzed ring opening involving the hemiaminal position of the dihydroxyornithine residue of B0, has been clearly defined as 6b. Modifications were limited to the 3-hydroxy-4-methylproline, 3,4-dihydroxyhomotyrosine and 4,5-dihydroxyornithine residues of pneumocandin A0.     

Neuropsychological efficiency measures in male and female alcoholics.

The role of time in performance on many neuropsychological tests has been relatively neglected in the literature to date. Neuropsychological functioning in 90 male and female alcoholics and 65 peer controls was examined using both accuracy and time measures for four basic types of neuropsychological functioning: verbal skills, learning and memory, problem-solving and abstracting, and perceptual-motor skills. Alcoholics had significantly lower efficiency ratios (accuracy/time) than controls in each of the four areas, and had significantly lower overall accuracy and time scores. There were no significant Group x Gender interactions for efficiency, speed or accuracy scores, indicating that male and female alcoholics have similar deficits as a result of chronic alcoholism. The study is the first to apply systematically an empirical measure of neuropsychological efficiency to different areas of cognitive function; the results have implications for neuropsychological testing procedures.     

Widenings of the myelin lamellae in a typical Guillain–Barré syndrome

The so-called “widenings of the myelin lamellae” are thought to be specific ultrastructural features of peripheral nerve myelin in patients with peripheral neuropathy associated with a monoclonal dysglobulinemia of IgM type and antiglycolipid activity. We report here a case of Guillain–Barré syndrome with no evidence of serum monoclonal dysglobulinemia, presenting the typical widenings of the myelin lamellae in small-diameter myelinated fibers from a sural nerve biopsy. In view of the positive reaction with anti-C3d complement on direct immunofluorescence, an immunological mechanism may be involved in the widenings of the myelin lamellae. © 1994 John Wiley & Sons, Inc.     

Dioxin concentrations in the blood of workers at municipal waste incinerators.

OBJECTIVES--Increased concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs) in pooled blood samples from workers at municipal waste incinerators have been reported. This study was undertaken to confirm these results in individual blood samples from potentially exposed and unexposed workers at municipal waste incinerators compared with matched unexposed controls and compared with concentrations in the slag and fly ash from the municipal waste incinerators. METHODS--Concentrations of PCDDs and PCDFs were determined in the blood of 10 workers from an old municipal waste incinerator without adequate pollution controls, 11 workers from a newer incinerator with modern pollution controls, and 25 controls from the general population group matched for age (+/- 10 years), sex, and race, and in the slag and fly ash from the older incinerator. RESULTS--Significant increases of certain PCDDs and PCDFs were found in the blood of the workers from the older incinerator compared with the controls as follows: octaCDD (1051 (438) v 637 (344), P < 0.001), hexaCDF (52.3 (28.7) v 30.2 (18.2), P < 0.01), heptaCDF (43.9 (30.4) v 22.7 (12.4), P < 0.001), total PCDDs (1262 (484) v 825 (454), P < 0.001), total PCDFs (133.0 (68.1) v 93.7 (36.7), P < 0.05), and total PCDD/Fs (1395 (537) v 918 (437), P < 0.001). The workers from the older incinerator with the greatest exposure were found to have the most significant increases of the blood PCDDs and PCDFs, and the pattern of increased PCDD and PCDF congeners in the blood corresponded to the pattern in the incinerator slag and ash. No significant differences were found between the blood concentrations of the workers at the newer incinerator and the controls. CONCLUSION--Occupational exposure to slag and fly ash from municipal waste incinerators may increase the blood concentrations of PCDDs and PCDFs. Modern pollution control technology in new incinerators may be able to minimise potential exposure to slag and fly ash and thus the absorption of PCDDs and PCDFs from this source.