Showing papers by "Myron S. Cohen published in 1985"

Gonococcal infection: a model of molecular pathogenesis.

Abstract: Human beings are the only reservoir for the gonococcus. In spite of public health efforts to control this pathogen, and the availability of adequate antibiotic therapy for 40 years, close to a mill...

Phagocytic Cells in Periodontal Defense: Periodontal Status of Patients with Chronic Granulomatous Disease of Childhood

Abstract: Both qualitative and quantitative neutrophil abnormalities have been associated with severe forms of periodontitis. Defects in chemotaxis, phagocytosis and bacterial killing have been reported among both peripheral blood and gingival neutrophils harvested from patients with juvenile and rapidly progressive periodontitis. Chronic granulomatous disease of childhood (CGD) is a rare, inherited disorder associated with the occurrence of severe, life-threatening, suppurative infections of skin, liver, lymph nodes and other organs. Neutrophils and monocytes from individuals with CGD lack enzymes necessary for the production of oxygen reduction/products such as H2O2 and superoxide anion, and therefore are unable to kill many species of bacteria and fungi. However, no detailed study of the periodontium of these patients has been undertaken. Accordingly, five patients whose ages ranged from 17 to 32 years were included in this study. An additional (sixth) patient was included based on complete dental records. Neutrophils from all patients demonstrated defective O2 metabolism, and all patients had histories of chronic recurrent abscesses consistent with CGD. All patients were receiving antibiotic prophylaxis. Several patients had ulcerative lesions of the oral cavity of unknown etiology. Examination of the periodontium revealed that three patients had gingivitis, one had localized early periodontitis, and one had generalized early-to-moderate periodontitis. The severity of periodontal disease was consistent with patient age and local etiologic factors. No patients had evidence of juvenile, severe or rapidly-progressing disease in spite of their leukocyte defects. These findings suggest the following possibilities.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphokine-induced monocytic differentiation as a possible mechanism for hypercalcemia associated with adult T-cell lymphoma.

Abstract: Patients with adult T-cell lymphoma frequently have hypercalcemia. Bone biopsies from these patients show increased numbers of osteoclasts. We hypothesized that substances produced by the malignant T-cell caused these phenomena by increasing the formation and/or activity of osteoclasts. To test this hypothesis, we cultured U937 cells in conditioned media from a clonal T-cell line derived from a patient with adult T-cell lymphoma and hypercalcemia. This conditioned media produced maturational changes in the U937 cells as evidenced by decreased proliferation, increased adherence, increased expression of complement receptors, and formation of multinucleated giant cells. These changes were synergistically enhanced by the addition of 1α,25-dihydroxyvitamin D 3 which is known to promote monocyte differentiation. We also tested interleukin 2 and γ- and α-interferon to see if they were responsible for the maturational changes. Although some effects were seen, these lympokines could not account for all the changes induced by the T-cell conditioned media. These findings support the above hypothesis and suggest that other unidentified factors may promote the differentiation of osteoclast precursors and be involved in the pathogenesis of the hypercalcemia.

Vitamin D, phagocyte differentiation and immune function.

Abstract: The data reviewed in this paper supports the hypothesis that 1,25-(OH)2D3 influences the differentiation and function of mononuclear phagocytes and lymphocytes. A caveat is the concentrations of 1,25-(OH)2D3 required in vitro for expression of these effects. The relevance of these concentrations to the actions of 1,25-(OH)2D3 in vivo is speculative because the experimental conditions involve the presence of serum (and vitamin D-binding protein) which undoubtedly alters the concentration of 1,25-(OH)2D3 entering the incubated cells. Serum is a critical reagent in most cell culture systems and it is not yet possible to separate the effects of serum from the effect of the 1,25-(OH)2D3 contained in serum. Our current hypothesis is that 1,25-(OH)2D3 in normal serum plays a permissive role in the functions of normal mononuclear phagocytes and lymphocytes, which are exaggerated at higher concentrations of 1,25-(OH)2D3. These data also suggest that skeletal homeostasis has immunologic dimensions. Lymphokines appear to be important in the formation of osteoclast-like cells. Lymphokines are also believed to be involved in some forms of hypercalcemia associated with malignancy such as multiple myeloma [80] and the adult T-cell lymphoma syndrome [81]. It is clear that the interactions between vitamin D, mononuclear phagocytes, lymphocytes and their products, and skeletal homeostasis have introduced new perspectives and dimensions to areas previously perceived as being unrelated or, at least, distantly linked.

Effects of human serum on the growth and metabolism of Neisseria gonorrhoeae: an alternative view of serum.

Abstract: Humans are the sole reservoir of Neisseria gonorrhoeae, an organism which undergoes a marked increase in metabolic rate after exposure to a low-molecular-weight, heat-stable component(s) of human serum. Further studies on the effect of serum on gonococcal metabolism were undertaken. Gonococcal broth (GCB) is commonly used for in vitro cultivation of gonococci. Gonococci suspended in GCB plus 10% serum exhibited oxygen consumption rates of 139% (P less than 0.01) and 456% (P less than 0.01) of those suspended in GCB or Hanks balanced salt solution, respectively. A twofold increase in growth rate also resulted from the addition of 10% serum to GCB. Gonococcal 14C-labeled adenine incorporation increased threefold with 10% serum supplementation of Hanks balanced salt solution. Dialysis of serum in 1,000-molecular-weight exclusion tubing removed the stimulatory factor(s). Neither correction of anion-cation concentrations altered by dialysis nor addition of substances of known importance to the metabolism of gonococci (i.e., lactate, pyruvate, cysteine, ATP, AMP, NADPH, amino acids, malate, and glutathione) to dialyzed serum reconstituted stimulatory capacity. The effect of serum on gonococcal glucose-catabolic pathways was measured by modified radiospirometry. An apparent threefold increase in Entner-Doudoroff and pentose phosphate pathway activities was induced by 10% serum, as was the increased shunting of glucose-derived glyceraldehyde-3-phosphate into these pathways. These metabolic changes did not allow specific identification of the serum stimulatory factor(s). Acetate, the major by-product of gonococcal glucose catabolism, inhibited gonococcal oxygen consumption as previously reported. A high-molecular-weight serum component, probably albumin, reversed acetate-mediated inhibition of gonococcal oxygen consumption, identifying a second mechanism by which serum increases gonococcal metabolism. These results suggest that supplementation of growth media with serum should be considered to provide N. gonorrhoeae with conditions more consistent with its normal environment.

Phagocytic cells synthesize 19-nor-10-keto-25-hydroxyvitamin D3, a metabolite that may induce differentiation of the human monoblastic cell line U937.

Abstract: Phagocytic cells, including normal human blood neutrophils and monocytes, metabolize 25-hydroxyvitamin D3 in vitro to more polar metabolites. Cells of the human monoblastic cell line U937 produced three metabolites when incubated with 25-hydroxyvitamin D3. One of these metabolites, previously designated peak III, has its maximal absorbance at 310 nm. Mass spectral analysis of the trimethylsilylated derivatives of peak III revealed a spectral pattern very similar to that published for the trimethylsilylated derivatives of 19-nor-10-keto-25-hydroxyvitamin D3. The biosynthetic 19-nor-10-keto-25-hydroxyvitamin D3 was active in the induction of differentiation of U937 cells.

Effect of Growth in Serum on Uptake of Neisseria gonorrhoeae by Human Neutrophils

Abstract: Because serum exposure precedes interaction of invasive Neisseria gonorrhoeae with neutrophils, neutrophil association with gonococci grown in serum was assessed. Uptake of a nonpiliated serum-resistant strain grown in 20% serum was reduced to 63.5% of control values. Heated serum (20%) yielded similar results. Stimulation of hexose monophosphate shunt activity in neutrophils by heated serum-grown gonococci (a phenomenon reflecting phagocytosis) was 64.5% of control values. Because gonococcal outer membrane (OM) structures mediate interaction with neutrophils, lithium acetate-treated OM preparations of gonococci grown in heated serum were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Multiple new protein bands and a quantitative decrease in amounts of proteins I, II, and III were noted. However, a decrease in the amounts of these membrane proteins was not observed with alternative membrane extraction techniques. Gonococcal growth in 20% serum dialyzed in 3,500-molecular-weight exclusion tubing allowed normal neutrophil association and OM protein expression.