Expression of macrophage markers by a population of T cells obtained from synovial fluid of a subgroup of patients with juvenile rheumatoid arthritis

OBJECTIVE: To characterize distinctive lymphoid cell populations in the synovial fluid (SF) of patients with juvenile rheumatoid arthritis (JRA) that have the specific ability to display monocytic markers when cultured in vitro. METHODS: Mononuclear cells obtained from SF of patients with JRA and depleted of adherent macrophages were cultured in vitro in RPMI 1640 medium supplemented with only fetal calf serum (FCS). Phenotypic evaluation of these cells was by flow cytometry and immunohistochemical analysis was by specific fluorochrome labeled antibodies. RESULTS: T cells from a JRA subgroup displayed some typical macrophage attributes, i.e., abundant cytoplasm, adherence to plastic, and phagocytosis of latex beads when cultured in vitro. These cells have the ability to survive in culture for several weeks in RPMI 1640 medium containing only 10% FCS. The macrophage-like T cells rosetted with sheep red blood cells and proliferated when stimulated with phytohemagglutinin or anti-CD3, indicating functional T cell responses. CONCLUSION: Our data indicate that a population of T cells obtained from the SF of a subgroup of patients with JRA exhibited characteristics of macrophages, yet retained their CD3 and T cell receptor expression. Whether this promiscuous behavior is caused by malignant transformation of lymphoid precursor cells or is induced by the concerted effect of a myriad of cytokines and growth factors present in the SF remains unknown. The presence of these cells in the SF of 2 patients with JRA with different onset types raises the question of their function and significance in an autoimmune disorder such as JRA.     

Regulation of cytokine-induced neutrophil chemoattractant in rat bone marrow-derived macrophages by inflammatory mediators

During the course of inflammation, macrophages are highly influenced by their local environment and changes in the cytokine milieu. Exposure of macrophages to various factors during different phases of the inflammatory response may have a strong influence on the pattern of gene expression, which a macrophage exhibits. We examined how these mediators affect the regulation of the expression and production of cytokine-induced neutrophil chemoattractant (CINC). Our study demonstrates that CINC can be induced in bone marrow-derived macrophages by lipopolysaccharide, interleukin-1 beta, tumor necrosis factor-alpha (TNFalpha), and interferon-gamma/TNF alpha. These mediators are factors which a macrophage would be expected to encounter early in an inflammatory process. In contrast, transforming growth factor-beta (TGFbeta), which is expressed late in the inflammatory process during mesenchymal cell proliferation and tissue repair, did not induce detectable amounts of CINC and functioned to suppress CINC production stimulated by early inflammatory mediators. Suppression of CINC production occurred whether TGF beta was added simultaneously, 12 or 24 h prior to the stimulus.     

Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases

Breast cancer cell lines vary in invasive behavior and one highly invasive cell line (MDA-MB-231) proteolytically degrades extracellular matrix with invadopodia (Thompson et al. 1992, J Cell Physiol, 150, 534-44; Chen et al 1994, Breast Cancer Res Treat, 31, 217-26). Invadopodial proteolysis of extracellular matrix is thought to be necessary for invasion; however, this has not been demonstrated directly. To obtain such evidence, normal (HBL-100) and malignant (MCF-7, MDA-MB-231) breast cells were evaluated for invadopodial proteolysis of extracellular matrix and invasive behavior. We report that invadopodial proteolysis of immobilized fibronectin is positively correlated with invasion of cells into type I collagen gels. Moreover, reducing the proteolytic activity of invadopodia with the metalloproteinase inhibitor, batimastat (BB-94), also decreases invasion indicating that breast cancer cell invasion is dependent upon proteolytically active invadopodia.     

Bioelectromagnetic applications for multiple sclerosis

There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.     

Effect of follicular or oviductal fluids on movement characteristics of bovine sperm during capacitation in vitro

Mammalian sperm exhibit characteristic motility changes associated with capacitation. Movement characteristics of bovine sperm incubated in noncapacitating (control, medium alone), capacitating (oviduct fluid, nonluteal, and luteal), or capacitating, acrosome reaction inducing (follicular fluid) conditions were investigated using a computer-assisted automated semen analysis system. Sperm were incubated up to 4 hours in a modified Tyrode's medium (control), 20 and 60% nonluteal (NL) or luteal (L) oviduct fluid (ODF), or 20 and 60% follicular fluid (FF). Relative to sperm incubated in control medium, motility of sperm treated with ODF or FF had increased linearity and vigorous motility. Sperm incubated in 60% ODF or FF showed a small decrease in mean trajectory/path straightness and velocity over time compared to 20% fluid treatments and control. Frequency distribution graphs were symmetric for 20% NL- and L-ODF treated sperm. However, 20% FF and 60% ODF and FF treatments had distributions skewed to the left, indicating smaller values for lateral head displacement (ALH) and curvilinear velocity (VCL). Median values for ALH and VCL were determined for control-treated sperm, and subtracted from individual sperm values for all treatments to estimate deviation from control, designated ALHc and VCLc. Three-dimensional plots of ALHc, VCLc and corresponding frequency indicated shifts in peak patterns for fluid-treated sperm compared to control sperm. Incubation in 20% ODF and FF resulted in peak shift for ALH and VCL values; yet, little change in peak position was observed in sperm incubated in 60% ODF and FF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Care and care alike

If family and friends were paid for their care of the chronically ill, the U.S. health care tab would take a $194 billion hit--exceeding home health spending. What do they get for giving so much? Harm to their own health.     

Transdermal absorption of clindamycin and tretinoin from topically applied anti-acne formulations in man

The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL(-1)) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake.     

Characterization of the flow in the molten metal sump during direct chill aluminum casting

A recent analytical model for the liquid aluminum flow in a direct chill (DC) casting sump has been investigated and the scaling coefficients evaluated. The magnitudes of flow-field features, such as the depth of the temperature stratification in the sump and the velocity of the metal in the thermal boundary layer close to the solidification front, have been calculated. The results broadly agree with recent full numerical calculations of the flow in the sump. The variation of these essential flow features has been investigated across a range of typical ingot sizes, casting speeds, and superheats, and critical macro-casting-parameter combinations have been identified. The limitations of the model are discussed and the possible effects the identified structure has on macrosegregation are briefly explored. Finally, the influence on the flow field of the method of feeding the ingot is investigated, and it is concluded that the model and these results are not invalidated if the feeding is nonuniform over the top surface of the sump.