The expression of surface tissue factor apoprotein by blood monocytes in the course of infections in early infancy.

The expression of surface tissue factor procoagulant activity and its shedding by blood monocytes can be induced by several stimuli. Few of these defined situations, other than the presence of bacteria and their toxins, are commonly present in the young human infant. In this study, measurements were made of the percentage of monocytes expressing surface tissue factor apoprotein (TFA) in blood taken from babies in the early weeks of life. Mononuclear cells were separated from blood in an environment free of detectable endotoxin. After exposure to a polyclonal rabbit antibody raised to purified brain TFA and subsequent exposure to a fluorescin-labeled murine anti-rabbit IgG, the cell fluorescent activity was analyzed by flow cytometry. The percentage of monocytes showing strong fluorescence was determined. In every instance when systemic bacterial infection was present, more than 60% of the monocytes examined showed fluorescence indicative of the presence of surface TFA. In a single case of fungal Candida septicemia, none of the monocytes was positive. More than 60% of cells were found to be positive in certain instances where infection was highly probable but not proven. Positive cells were found in three cases of isoimmune hemolytic disease of the newborn, as had been anticipated from previous studies, whereas less than 25% of monocytes derived from babies in the absence of discernible infection or isoimmune hemolytic disease expressed surface TFA (p less than 0.001). These findings provide insight into a possible mechanism of coagulation activation in sepsis and may prove to be a useful predictor of the presence of infection or endotoxemia in young infants.     

Prosthetic practice in the National Health Service: 2. Partial dentures.

This two-part series on the making of dentures in the National Health Service includes useful practical advice for the general practitioner. Part 1 discussed complete denture, whilst part 2 covers partial dentures.     

Low Serum Retinol Is Associated with Increased Severity of Measles in New York City Children

Children with no known prior vitamin A deficiency exhibited a significant decline in their serum retinol levels during the acute phase of measles. This decline in circulating retinol was associated with increased duration of fever, higher hospitalization rates, and decreased antibody titers.     

Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologues

BACKGROUND: The mucosal mast cell (MMC) granule-specific beta-chymase, mouse mast cell protease-1 (mMCP-1), is released systemically into the bloodstream early in nematode infection before parasite-specific IgE responses develop and TGF-beta1 induces constitutive release of mMCP-1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein-1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated. OBJECTIVE: To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP-1, and the chemokine, CCL2. METHODS: MMC homologues were generated by culturing bone marrow cells in the presence of TGF-beta1, IL-3, IL-9 and stem cell factor (SCF). The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP-1 and CCL2 was investigated using the Golgi-disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA. RESULTS: mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP-1 was significantly inhibited ( approximately 40%) by cycloheximide and by the Golgi-disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP-1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2. CONCLUSION: The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators.     

Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

Epidermal growth factor receptor and other oncogenes as prognostic markers.

Analysis of epidermal growth factor receptor (EGFr) and estrogen receptor (ER) was performed on tumor samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumors greater than 10 fmol/mg of 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than .00001). EGFr was second only to axillary-node status as a prognostic marker for all patients in terms of both relapse-free and overall survival in univariate analysis (P less than .001, log-rank EGFr + v EGFr-). For patients with histologically negative axillary nodes, EGFr was superior to ER in predicting relapse and survival (P less than .01 and P less than .005, respectively, compared to P less than .1 and P less than .1, log-rank). In a multivariate (Cox model) analysis, only EGFr--out of EGFr, ER, size, and grade--was predictive for either relapse-free or overall survival for patients with node-negative disease (P = .052 and P = .026, respectively). One hundred eighty-seven case patients in the series were assessed for neu expression immunochemically, and 31 were positive. There was a highly significant increased risk of relapse and death in the positive group. In patients with otherwise good prognostic markers (ER+, node-negative, well-differentiated tumors), neu expression predicted for significantly worsened overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)