Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Rupture of the posterior tibial tendon: CT and surgical findings

Computed tomography (CT) was performed in 42 patients with 49 clinically suspected tears of the posterior tibial tendon. Twenty-eight of the 49 suspected tears were subsequently surgically explored and repaired. Three patterns of tendon abnormalities were recognized on CT scans: type I-intact, hypertrophied, heterogeneous tendon; type II-attenuated tendon; and type III-absence of a portion of a tendon. Types I and II correlated with partial rupture seen during surgery, and type III correlated with complete rupture of the tendon. CT findings were accurate in 96% of the patients who underwent surgery. In four cases (14%), tendon rupture was seen on CT scans, but the extent of the injury was underestimated and the rupture was misclassified. Reactive periostitis of the distal tibia was seen in 71% of diseased tendons and may represent an important factor in the diagnosis of tendon rupture.     

Associations between body morphology and bone mineral density in premenopausal women

To investigate whether body morphology, obesity and its long time evolution were associated with lumbar and femoral bone mineral density (BMD) in premenopausal women of the same age. Design: Cross-sectional study. Subjects: 72 healthy premenopausal women born in 1950 (42 years) with a regular physical activity. Measurements: BMD measured by dual-X-ray absorptiometry (DEXA) at lumbar spine and proximal femur; body weight, body mass index (BMI), BMI at 20 years (BMI-20), increase in BMI since age of 20 (BMI->20), body circumferences (breast, waist, hip) and their ratios (WHR, BHR, WBR), smoking and alcohol intake. Results: Lumbar spine BMD did not correlate with any anthropometric measurement. Femoral BMDs correlated positively with weight, BMI, BMI-20, breast, waist, WHR and BHR. The BMI-20 explained the 5% and the current BMI the 13% of variance of total femur BMD. After adjustment for weight or BMI, breast circumference and BHR remained significantly correlated with all femoral BMDs sites except neck. Weight was the best predictor for neck BMD (R² = 0.08; p < 0.02), and BHR for Ward's triangle (R² = 0.12; p < 0.01) and trochanter (R² = 0.10; p < 0.001). Alcohol intake, cigarette smoking, and age of menarche were not related to BMDs. Conclusion: In premenopausal women of the same age, lumbar spine BMD was not associated with any anthropometric measurement. Greater BHR and its long time of evolution may be determinants of greater femoral BMD (trabecular), whereas body weight may be determinant of femoral neck BMD (cortical). Further studies are needed to determine whether large breast to hip ratio may be considered as a protective factor for femoral osteoporosis.     

Solid phase C1q microassay for the rapid detection of circulating immune complexes

A C1q solid phase microassay was designed for the rapid detection of circulating immune complexes. Its level of sensitivity is comparable to that of the Raji cell and greater than the C1q binding assay; furthermore, it is faster and low in cost. These conditions make it more practical and applicable in the clinical setting.     

Non-pathogenic Entamoeba histolytica: functional and biochemical characterization of a monoxenic strain

We have cultured under monoxenic conditions and characterized an Entamoeba histolytica clone, MAV-I CINVESTAV (MAV-I), obtained from feces from an asymptomatic carrier. The clone shows the non-pathogenic E. histolytica zymodeme type I, which did not change through the process of monoxenization. Clone MAV-I was non-pathogenic in both in vivo and in vitro tests, and it did not have a functional 112-kDa adhesin. As far as we know, this is the first non-pathogenic monoxenic strain reported. Clone A (strain HM1:IMSS), a highly virulent clone with pathogenic zymodeme type II, and which has the 112-kDa adhesin, was used as a control. Protein patterns from both clones were almost identical in one-dimensional gels. In two-dimensional gels, differences in high-molecular-weight proteins were detected. Clone MAV-I adhered and phagocytosed only 12% of the red blood cells adhered and phagocytosed by clone A. MAV-I trophozoites did not destroy cell culture monolayers and did not produce hepatic abscesses in hamsters. They also showed deficiency in protease activity. The absence of virulence in clone MAV-I correlated directly with the absence of a functional 112-kDa adhesin, supporting the role that this protein plays in virulence.