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.     

Family Functioning and Social Support in the Adaptation of Caregivers of Children With Sickle Cell Syndromes

Objective: To examine moderating effects of family functioningand social support on the relationship of child-related stressorsto caregivers' psychological adaptation in a sample of caregiversof children with a chronic illness. Method: Participants were 67 caregivers of children and adolescentswith sickle cell syndromes. We conducted MANOVAs and subsequenteffect size calculations to determine if family functioningwould buffer the effects of caring for difficult-to-manage childrenwith this illness. Results: Findings supported a moderator effect of family functioningon the association of children's externalizing behavioral problemsto caregivers symptoms of hostility. Greater levels of cohesiveand adaptive family functioning buffered the potential detrimentaleffects of caring for children perceived as hard to manage.No significant associations were obtained between measures ofcaregivers' psychological adaptation and the severity of theirchildren's disease. Conclusions: We make recommendations for family systems interventions,particularly for caregivers of children with behavior problems.     

Comparison of fetal cerebellar measurements by two different techniques.

We examined 53 fetuses between 15 and 40 weeks of gestation with transverse and coronal sections of the head in order to evaluate the accuracy and reproducibility of the coronal cerebellar diameter. Intraobserver coefficient of variation was less than or equal to 2.2% and the mean interobserver difference was 2.2% (range, 0 to 6%). A positive linear correlation exists between transverse and coronal measurements (coronal diameter = 1.02 x transverse diameter - 0.48; R2 = 0.99; P less than 0.0001). We conclude that the coronal cerebellar diameter is reproducible and accurate and when indicated clinically can be used instead of the transverse cerebellar diameter when the latter is not obtainable because of fetal position.     

Comparison of iohexol 300 and diatrizoate meglumine 60 for body CT: image quality, adverse reactions, and aborted/repeated examinations.

Six hundred patients were prospectively randomized and given either diatrizoate meglumine 60 or iohexol 300 during dynamic contrast-enhanced body CT in order to compare image quality, contrast reactions, and the number of aborted studies or studies in which images had to be repeated. Three hundred two patients received iohexol 300, and 298 patients received diatrizoate meglumine 60. Thirty-nine percent (119/302) of the patients given iohexol 300 and 63% (188/298) of the patients given diatrizoate meglumine 60 had at least one adverse reaction thought to be related to contrast material during, or within 24 hr of, the body CT scan. When reactions of discomfort (heat or warmth, flushing, bad taste) were excluded, 16% (48/302) of the patients who received iohexol and 33% (99/298) of the patients who were given diatrizoate meglumine 60 had at least one adverse reaction. The differences in both types of reactions between the two agents were significant (p less than .001). Among scans evaluated for study quality, 71% (214/302) of the iohexol 300 group and 62% (184/298) of the diatrizoate meglumine 60 group had optimal enhancement (p = .02). However, when the optimal and adequate categories were combined, 301 of 302 patients given iohexol 300 and 292 of 298 patients given diatrizoate meglumine 60 had diagnostic-quality studies (no statistical difference). Studies were not terminated nor were images repeated in 97% (292/302) of the patients given iohexol 300 and in 94% (280/298) of those given diatrizoate meglumine 60. The CT study was repeated because of movement during the contrast injection or aborted because of contrast-related reactions in 0.7% of the patients given iohexol 300 and in 3.0% of the patients given diatrizoate meglumine 60. This difference was statistically significant (p = .04). Our results suggest that the difference in image quality, number of adverse reactions, and number of aborted/repeated CT scans performed with iohexol 300 or diatrizoate meglumine 60 are not sufficiently different to warrant conversion to nonionic agents for body CT scans.     

Setting targets: a three-stage model for determining priorities for health promotion

This paper describes a three-stage model for setting targets for health promotion. The model was developed in 1992 in response to the need to identify priority areas for health promotion for women in the Hunter Region of New South Wales. The approach enabled epidemiological data and views from the community to be synthesised and integrated with those of experts from health and social services (key informants), using a nominal group process. The reliability of the method was investigated by replicating the process with two groups of key informants. There was considerable commonality in the targets generated by the two groups. The process resulted in the identification of seven targets that reflected the concerns of the community and local experts as well as the health priorities suggested by local epidemiological data. The model used could be adapted for determining priorities in a wide range of health and health care settings, where available resources restrict the range of services or activities which can be offered. (Aust J Public Health 1995; 19: 263–9)     

Genetic differentiation between and within strains of the saw-toothed grain beetle, Oryzaephilus surinamensis (Coleoptera: Silvanidae) at RAPD loci

Nine strains of Oryzaephilus surinamensis have been kept in laboratory culture for periods ranging from 5 to 30 years (30–180 generations). Two RAPD primers provided sufficient information to separate the strains reliably and unambiguously. The strains are maintained at a population size of 200 breeding adults. The marked divergence between strains is consistent with the small population size, which for the older strains, according to population genetics theory, implies that roughly half the original genetic variation should now be lost from within strains. However, there is no indication that the older strains have less inter-strain variation. The results demonstrate RAPD loci can reliably detect population subdivision, which in field populations of pest species is of fundamental importance in understanding the population genetics of insecticide resistance.     

Single breath-holding scans of the abdomen using FISP and FLASH at 1.5 T

Single breath-holding gradient echo techniques fast imaging with steady-state free precession (FISP) and fast low angle shot (FLASH) images were evaluated in the study of the abdomen in 16 patients (13 liver, two kidney, and one pancreas examinations). Gradient echo images were compared retrospectively with conventional spin echo images for image quality (depiction of pathology and representation of anatomic detail), and contrast characteristics were evaluated. All lesions were shown on gradient echo images, and in three of 16 cases gradient echo images were more diagnostic than spin echo images. On both FISP and FLASH images, most hepatic metastases were hyperintense relative to normal liver. The predicted flip angles for maximal contrast for the liver were modeled from signal intensity equations for FISP and FLASH and yielded predicted flip angles of approximately 40-55 degrees for FISP and 15-25 degrees for FLASH. Peak signal-to-noise ratio in liver of normal volunteers occurred at approximately 30 degrees for both FISP and FLASH. Single breath-holding gradient echo images are useful in the evaluation of abdominal structures and this study provides a framework for future work.     

Practical problems of diagnosing trichomoniasis in women.

Analysis of eight groups of data collected at varying intervals during a period of seven years showed fluctuations in the sensitivity of tests to diagnose trichomoniasis in women. The best results were obtained from fresh, correctly prepared Diamond's medium, Feinberg-Whittington's medium, and modified Squires and McFadzean's medium (which showed 82% to 94% relative sensitivity). Poor results were identified consistently in commercially prepared Bushby medium from one source (40% relative sensitivity) and in a batch of commercially prepared Squires and McFadzean's medium from which chloramphenicol had been omitted (23% relative sensitivity). Examination of wet film, culture, and exfoliative cytology stained by Papanicolaou's method were shown to be indispensable for auditing the performance of each test and to maintain the quality of a diagnostic service.     

The effects of chondroitinase ABC on the rabbit intervertebral disc. A roentgenographic and histologic study

A series of intradiscal injections of chondroitinase ABC was performed in 31 young adult rabbits. Roentgenograms were taken immediately postinjection and were repeated at two, three, five, six, seven, or nine days after injection. All had roentgenographic evidence of disc space narrowing at all stages after the injection. Histologic evaluation of safranin-O fast green-stained sections indicated degradation of proteoglycans in the annulus fibrosus of chondroitinase ABC-injected discs. The cells of the chondroitinase ABC-injected discs, the end plates, and the growth-plate areas of adjacent vertebral bodies appeared unaffected.