Tumor necrosis factor accounts for the neutrophil emigration activity released by cultured malignant fibrous histiocytoma cells

Cultured malignant fibrous histiocytoma (MFH) cells obtained from a spontaneous and transplantable rat tumor were studied for their ability to release tumor necrosis factor (TNF) and a factor which induces neutrophil migration in vivo. MFH cells obtained from 7-day cultures spontaneously released both activities into the supernatant (TNF: 36 +/- 9 IU TNF/ml supernatant, N = 3; neutrophil chemoattractant factor: control, Medium ip: 6 +/- 1 x 10(6); MFH supernatant: 18 +/- 1 x 10(6) neutrophils/cavity, N = 5). These releases were enhanced by treating MFH cells with LPS (TNF: 61%; neutrophil chemoattractant factor: 46%) and were abolished by the glucocorticoid dexamethasone (TNF: 68%; neutrophil chemoattractant factor: 100%). Anti-TNF antiserum abolished the neutrophil chemoattractant activity of the supernatants (95%). The release of TNF or neutrophil chemoattractant activity was reduced in cells obtained from older cultures (14 and 21 days) (TNF: 7-day culture, 36 +/- 9; 14-day culture, 19 +/- 2; 21-day culture, 19 +/- 1 IU of TNF/ml; neutrophil chemoattractant activity: 7-day culture, 18 +/- 1.6; 14-day culture, 13 +/- 3; 28-day culture, 8 +/- 1 x 10(6) neutrophils/cavity). The predominant cells present in 7-day cultures of MFH were histiocyte-like cells as determined by nonspecific esterase methods. The number of these cells decreased as the cultures aged (7-day culture, 71%; 14-day culture, 5%; 21-day culture, 0%). In conclusion, our results show a strong association between the intensity of the neutrophil chemoattractant activity and TNF concentration in the supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of potassium channels in amyloid-induced cell death

Basal forebrain cholinergic neurons are severely depleted early in Alzheimer's disease and appear particularly susceptible to amyloid beta-peptide (A beta) toxicity in vivo. To model this effect in vitro, a cholinergic septal cell line (SN56) was exposed to A beta. SN56 cells exhibited a tetraethylammonium (TEA)-sensitive outward K+ current with delayed rectifier characteristics. Increases of 64% (+/-19; p < 0.02) and 44% (+/-12; p < 0.02) in K+ current density were noted 6-12 and 12-18 h following the addition of A beta to SN56 cell cultures, respectively. Morphological observation and staining for cell viability showed that 25 +/- 4 and 39 +/- 4% of SN56 cells were dead after 48- and 96-h exposures to A beta, respectively. Perfusion of SN56 cells with 10-20 mM TEA blocked 71 +/- 6 to 92 +/- 2% of the outward currents, widened action potentials, elevated [Ca2+]i, and inhibited 89 +/- 14 and 68 +/- 14% of the A beta toxicity. High [K+]o, which depolarizes cell membranes and increases [Ca2+]i, also protected SN56 cells from A beta toxicity. This effect appeared specific since glucose deprivation of SN56 cells did not alter K+ current density and TEA did not protect these cells from hypoglycemic cell death. Furthermore, A beta was toxic to a dopaminergic cell line (MES23.5) that expressed a K+ current with delayed rectifier characteristics; K+ current density was not altered by A beta and MES23.5 cells were not protected by TEA from A beta toxicity. In contrast, a noncholinergic septal cell line (SN48) that shows minimal outward K+ currents was resistant to the toxicity of A beta. These data suggest that a K+ channel with delayed rectifier characteristics may play an important role in A beta-mediated toxicity for septal cholinergic cells.     

One-week low-dose triple therapy is effective in treating Helicobacter pylori-infected patients with bleeding peptic ulcers

Although lead has been extensively studied in children, its sources and effects remain unclear in adolescents. This study examined the relation of blood and tibia bone lead levels to lead determinants. One hundred adolescents living in Mexico City and surrounding suburbs were studied. Blood lead was measured by atomic absorption spectroscopy, and tibia lead was measured by a K X-ray Fluorescence (KXRF) instrument. Blood lead ranged from 1.8 to 29.2 microgram/dl, with a mean of 7.4 microgram/dl. Bone lead ranged from <1 to 44.82 microgram Pb/g bone mineral, with a mean of 4.8 microgram Pb/g. Predictors of bone lead included higher traffic density near the home, mother's smoking history, and time spent outdoors. Predictors of log-transformed blood lead included bone lead levels, male sex, use of lead-glazed ceramics, and living in Mexico City. Bone lead remained a significant predictor of blood lead after adjusting for covariates in a final multivariate regression model. In our final model, a rise in bone lead from the middle of the lowest quintile to the middle of the highest quintile (a difference of 21.6 microgram Pb/g) was associated with an increase in blood lead of 1.2 microgram/dl. Our data suggest that in addition to current sources of environmental lead exposure, bone lead accumulated over time constitutes a moderate source of circulating lead during adolescence and may account for some of the adverse health effects documented in recent studies.     

Nonrandom association of IS6110 and Mycobacterium tuberculosis: implications for molecular epidemiological studies

IS6110 restriction fragment length polymorphism typing is now established as the primary typing method for Mycobacterium tuberculosis. It has been assumed that the position of bands is random. Thus, the discrimination of the technique increases in proportion to the copy number. Two collections of M. tuberculosis were investigated to test this hypothesis. We identified 33 positions in isolates from a Tanzanian collection and 25 positions in isolates from a London, United Kingdom, collection where bands were significantly more likely to be present than would be expected by chance. These data suggest that band position is not random, and this possibility may have an impact on the interpretation of molecular epidemiological studies of M. tuberculosis.     

Angiotensin-converting enzyme gene and atherosclerosis

Common variants of the angiotensin-converting enzyme (ACE) gene (ACE ie humans, Ace in mice) associated with changes in circulating ACE activities have been suggested to confer differential risks for atherosclerosis. Using a mouse model of atherosclerosis induced by heterozygosity for apolipoprotein E gene disruption and an atherogenic diet, we have studied the impact on atherogenesis of a mutation that changes the level of function of Ace. We find that this genetically determined change does not influence the size or complexity of atherosclerotic lesions. Ace genotype was not a significant determinant of lesion size in female (+/+ = 12.9 +/- 1.5 and +/- = 11.7 +/- 1.6 microns2 x 10(4)) or male (+/+ = 0.95 +/- 0.25 and +/- = 1.83 +/- 0.59 microns2 x 10(4)) mice; however, lesions were significantly larger (P < .001) in female than male mice. Ace genotype also did not affect lesion complexity; however, lesions in females showed significantly increased frequency of cholesterol clefts, acellular cores, fibrous caps, and calcifications compared with those in males. The hypothesis that genetic variation in the level of ACE gene expression affects the development of atherosclerosis is not supported by these findings.     

A review of functional neuroimaging in mood disorders: positron emission tomography and depression

OBJECTIVE: To examine the progress of positron emission tomography (PET) as a tool for understanding the psychobiology of mood disorders, particularly major depression and bipolar disorder. METHOD: Review of the literature on functional imaging of mood disorders. RESULTS: Functional imaging techniques have been used in psychiatric research as a noninvasive method to study the behaviour and function of the brain. Techniques used so far have involved the manipulation of emotion in healthy volunteers, the evaluation of depressed (unipolar and bipolar as well as secondary depression), manic, and normal subjects under resting and various activation conditions, such as cognitive activation, acute pharmacological challenge, and chronic thymoleptic treatments. As a result, functional imaging studies tend to support abnormalities in specific frontal and limbic regions. CONCLUSION: Different PET methods demonstrate consistent abnormalities in the prefrontal, cingulate, and amygdala regions. These findings are in agreement with past animal and clinical anatomical correlates of mood and emotions.     

Contrast-enhanced MRI of the breast: accuracy, value, controversies, solutions

OBJECTIVE: Contrast-enhanced MRI of the breast has been one of the most controversial areas of MRI. Even though most investigators have, in selected indications, been able to improve accuracy by the additional use of contrast-enhanced MRI, its abuse has been feared not only because of increased costs for imaging, but also because of increased biopsy rates caused by false positive calls and because of errors caused by insufficient standardisation. In this article an overview is given of the present knowledge about contrast-enhanced MRI of the breast. Factors that influence the accuracy and reproducibility of contrast-enhanced MRI are analysed. METHOD: Factors that influence accuracy include: (1) technical factors that influence accuracy, e.g. slice thickness (partial volume effect), motion reduction, reduction of (cardiac) artifacts, dosage of contrast agent, choice of pulse sequence and echotime, and choice of the method for elimination of fat signal. (2) Hormonal factors (timing of the examination with reference to the menstrual cycle, hormonal replacement therapy). They influence accuracy and must be taken into account. (3) Interpretation guidelines-their choice influences sensitivity and specificity mostly inversely and the use of information from conventional imaging appears necessary. (4) Patient selection influences accuracy for statistical and for biological reasons. RESULTS: Based on the present literature and on the experiences gathered in six German universities (> 12000 examinations) an excellent sensitivity (> 98%) can be achieved for the combination of mammography and MRI. However, specificity strongly varies with the indications. Recommended indications include examination of breasts with impaired evaluation due to severe scarring, after silicon implants and in the dense breast, exclusion of multicentricity and search for primary tumor. Indications under investigation include high risk patients and strictly selected problem cases. CONCLUSION: If appropriately applied and used for selected indications, contrast-enhanced MRI may allow a significant diagnostic gain. In order to take advantage of the full potentials of contrast-enhanced MRI the development of commercially available biopsy coils is essential.