An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization.

Staphylococcus epidermidis releases factors that activate the HIV-1 long terminal repeat, induce cytokine release, and activate nuclear factor B in cells of macrophage lineage. The active material had a mass of 34,500 daltons, was inactivated by proteases and partitioned into the phenol layer on hot aqueous phenol extraction, and thus was termed phenol-soluble modulin (PSM). High performance liquid chromatography (HPLC) of crude PSM yielded two peaks of activity designated PSM peak 1 and peak 2. MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectroscopy indicated the presence of two components in peak 1, which were designated PSM and PSM. Peak 2 contained a single component, designated PSM. Separation of PSM and PSM in peak 1 could be achieved by a second HPLC procedure. The structure of each component was determined by amino acid sequence analysis and identification and sequencing of their genes. PSM, PSM, and PSM were 22-, 44-, and 25-amino acid, respectively, strongly hydrophobic polypeptides. PSM was identified as Staphylococcus epidermidis delta toxin, whereas PSM and PSM exhibited more distant homology to previously described staphylococcal toxins. They appeared to exist as a complex or aggregate with activity greater than the component parts. The properties of the S. epidermidis PSMs suggest that they may contribute to the systemic manifestations of Gram-positive sepsis.

Lactobacilli and vaginal host defense: activation of the human immunodeficiency virus type 1 long terminal repeat, cytokine production, and NF-kappaB.

Lactobacilli, a component of the normal vaginal flora, can activate the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR) in the Jurkat T lymphocyte and THP-1 macrophage cell lines. Activation of the LTR in Jurkat cells was strongly enhanced by vanadate and inhibited by catalase, implicating H2O2. In contrast, activation in THP-1 cells occurred in the absence of vanadate and was unaffected by catalase. The active material partitioned into the phenol layer on hot aqueous phenol extraction. Lactobacilli also increased tumor necrosis factor-alphaand interleukin-1betaproduction and activated NF-kappaB in THP-1 cells and increased tumor necrosis factor-alphaproduction by human monocytes. Human vaginal fluid specimens had comparable properties, which correlated with their bacterial content. These findings suggest the presence in vaginal fluid of agent(s) derived from indigenous bacteria that can activate the HIV-1 LTR, cytokine production, and NF-kappaB in cells of macrophage lineage, with possible influence on vaginal physiology and host defense.

Acquired cystic kidney disease in ESRD.

Acquired cystic kidney disease (ACKD) in patients undergoing dialysis has been associated with life-threatening complications. Potential malignant transformation of the cysts has prompted concern regarding the need to screen patients for ACKD. The assumed increased morbidity associated with malignant transformation has not been clearly documented in the literature and may require further long-term analysis to adequately assess. Many reports on ACKD refer to the risk for malignancy, but other complications associated with ACKD may also arise. The development of ACKD has been shown to increase with increasing time on dialysis. Patients on dialysis appear to have a longer life expectancy and, consequently, more will develop ACKD. Complications related to ACKD may increase, which bolster efforts to establish specific guidelines related to the screening and management of ACKD. Nephrology nurses should be aware of symptoms suggesting a complication related to ACKD and confer with the nephrologist regarding evaluation. This article will discuss implications and management related to an increasing incidence of ACKD.

Activation of the human immunodeficiency virus-1 long terminal repeat by respiratory burst oxidants of neutrophils.

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) introduced in association with the luciferase reporter gene into Jurkat T cells was strongly activated by a combination of human neutrophils and phorbol myristate acetate (PMA). Activation was not observed when normal neutrophils were replaced by neutrophils which lack a respiratory burst, ie, from a patient with chronic granulomatous disease (CGD), was strongly inhibited by catalase, was potentiated by vanadate, was stimulated by relatively low concentrations of azide, and was inhibited by selective inhibitors of protein kinase C (PKC). The PMA affected activation in three ways: (1) by directly activating the LTR in Jurkat LTRluc; (2) by inducing a respiratory burst in neutrophils with the formation of H2O2; and (3) by increasing the sensitivity of Jurkat LTRluc to the activating effect of H2O2. When PMA was replaced by opsonized zymosan as the neutrophil stimulus, activation of the LTR was low unless azide was added. Activation in the presence of azide was not seen when CGD neutrophils were used or when catalase was added, suggesting that azide acts by inhibiting the degradation of H2O2. These findings indicate that activation of the HIV-1 LTR in Jurkat T cells can be induced by H2O2 released by neutrophils, particularly when PKC is concomitantly activated.

Osteitis fibrosa: treatment trends.

Renal osteodystrophy is frequently seen in patients with end stage renal disease. Osteitis fibrosa associated with secondary hyperparathyroidism is often diagnosed. Treatment options vary based on disease severity. Individual patient considerations need to be addressed to determine the best therapeutic plan. Medical management with calcitriol, dietary modifications, and administration of phosphate binders continues to be the best treatment for most patients. Parathyroidectomy should be reserved for patients with complications related to severe irreversible hyperparathyroidism and/or failure of medical management. Total resection of all parathyroid tissue with or without autotransplant is the most common surgery for hyperparathyroid bone disease.

Activation of the HIV type 1 long terminal repeat and viral replication by dimethylsulfoxide and related solvents.

The HIV-1 long terminal repeat (LTR) introduced into the macrophage cell line THP-1 and the T lymphocyte cell line Jurkat in association with the luciferase reporter gene is activated by the polar, aprotic solvents dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), and dimethylformamide (DMF). These solvents also greatly potentiated the activation of the LTR in THP-1 cells by phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), H202, and a Staphylococcus epidermidis product. Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) at 1 microg/ml had no effect on the LTR in THP-1 cells unless the solvents were added. The aprotic solvents also greatly potentiated the activation of the LTR in Jurkat cells by PMA, TNF-alpha, and H202, whereas LPS, LTA, or the S. epidermidis product had no effect in the presence or absence of the solvents. DMSO, DMAC, and DMF also increased the production of intact virions by latently HIV-1-infected ACH-2, J1.1, U1, and OM10.1 cells under some experimental conditions. The use of the polar aprotic solvents DMSO, DMAC, and DMF, by amplification, may allow the better detection of a weak activator of the LTR and facilitate studies of the mechanism of activation.