Time-course of the uterine response to estradiol-17beta in ovariectomized ewes: expression of angiogenic factors

Uterine expression of angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) was evaluated in ovariectomized ewes at 0, 2, 4, 8, 24, 48, or 72 h after estradiol (E2) treatment. Endometrial VEGF mRNA increased more than 5-fold from 0 to 4 h, remained elevated at 8 h, and then declined through 72 h after E2 treatment. In contrast, endometrial bFGF mRNA remained constant from 0 to 4 h, increased 2.2-fold from 4 to 8 h, remained elevated at 24 h, and then declined through 72 h. Immunostaining for VEGF was present in myometrial and endometrial microvessels (arterioles, venules, and/or capillaries) and also in myometrial smooth muscle; the pattern of VEGF immunostaining followed that of mRNA expression, being elevated at 4 and 8 h after E2 treatment. Immunostaining for bFGF was present exclusively in uterine glands; the pattern of bFGF immunostaining also followed that of its mRNA, being elevated at 8 and 24 h after E2. On the basis of these observations, we suggest that VEGF and bFGF are probably important factors responsible for the dramatic uterine microvascular response that occurs 8 to 24 h after E2 treatment in ovariectomized ewes.     

Using leg muscles as shock absorbers: theoretical predictions and experimental results of drop landing performance

The use of muscles as power dissipators is investigated in this study, both from the modellistic and the experimental points of view. Theoretical predictions of the drop landing manoeuvre for a range of initial conditions have been obtained by accounting for the mechanical characteristics of knee extensor muscles, the limb geometry and assuming maximum neural activation. Resulting dynamics have been represented in the phase plane (vertical displacement versus speed) to better classify the damping performance. Predictions of safe landing in sedentary subjects were associated to dropping from a maximum (feet) height of 1.6-2.0 m (about 11 m on the moon). Athletes can extend up to 2.6-3.0 m, while for obese males (m = 100 kg, standard stature) the limit should reduce to 0.9-1.3 m. These results have been calculated by including in the model the estimated stiffness of the 'global elastic elements' acting below the squat position. Experimental landings from a height of 0.4, 0.7, 1.1 m (sedentary males (SM) and male (AM) and female (AF) athletes from the alpine ski national team) showed dynamics similar to the model predictions. While the peak power (for a drop height of about 0.7 m) was similar in SM and AF (AM shows a +40% increase, about 33 W/kg), AF stopped the downward movement after a time interval (0.219 +/- 0.030 s) from touch-down 20% significantly shorter than SM. Landing strategy and the effect of anatomical constraints are discussed in the paper.     

Paravertebral muscles in experimental scoliosis: a light and electron microscopic study

Experimental structural dextroconvex scoliosis was produced in rabbits by costotransversolisis with transversectomy and releasing of paravertebral muscles between TVII and TX on the right side. Two compensatory curves developed on the upper dorsal and lumbar levels. Biopsies of paravertebral muscles in experimental animals included, besides areas of normal tissue, a considerable derangement of the cell contractile apparatus with sarcoplasmic dilation and eventual cell disintegration and necrosis. Histological changes varied along levels, the convexity being more affected. The severity of changes and reduction in body weight and length were correlated with the degree of scoliosis. A selective atrophy of slow-twitch fibers was observed in experimental animals, especially at the level of the main curve, whereas fast-twitch fiber atrophy was more important caudally. Control animal biopsies always appeared normal. Our experimental model shows an overt participation of paravertebral muscles in the establishment of compensatory processes following scoliosis, although the role that paravertebral muscles play in the etiopathogenesis of human idiopathic scoliosis requires further investigation.     

The effect of limited exposure to antimycotics on the relative cell-surface hydrophobicity and the adhesion of oral Candida albicans to buccal epithelial cells

Candida albicans is the major aetiological agent of oral candidosis. Adhesion to oral mucosal surfaces is considered a prerequisite for its successful colonization and subsequent infection, and its relative cell-surface hydrophobicity (CSH) is a contributory physical force. Thus, the main aim here was to determine the CSH of 10 isolates of oral C. albicans after a short exposure to sublethal concentrations of four antifungal agents and to correlate these findings with their adhesion to human buccal epithelial cells (BEC). The yeasts were exposed to sublethal concentrations of nystatin [x 6 minimal inhibitory concentration (MIC)], 5-fluorocytosine (x 8 MIC), ketoconazole (x 4 MIC) and fluconazole (x 4 MIC) for 1 h. The drug was then removed, and the CSH and BEC adhesion assessed by a biphasic aqueous-hydrocarbon assay and a microscopic method, respectively. The mean percentage reductions of CSH after exposure to nystatin, 5-fluorocytosine, ketoconazole and fluconazole were 27.14% (p = 0.01), 9.46% (p = 0.43), 19.47% (p = 0.04) and 6.16% (p = 0.59). Similarly, exposure to all the drugs except 5-fluorocytosine resulted in a significant inhibition of yeast adhesion to BEC, with nystatin eliciting the highest and fluconazole the least inhibition. Further, on regression analysis a strong positive correlation was observed between CSH and adhesion to BEC after limited exposure to 5-fluorocytosine (r = 0.48, p < 0.0001), ketoconazole (r = 0.48, p < 0.0001), fluconazole (r = 0.55, p < 0.0001) as well as in the unexposed controls (r = 0.41, p = 0.001), although nystatin was an exception (r = 0.09, p = 0.44). Taken together, these data elucidate further mechanisms by which antimycotics may operate in vivo to suppress candidal pathogenicity.     

Preoperative irradiation therapy and radical hysterectomy: prognostic value of tumor regression after initial irradiation of squamous cell carcinoma of the cervix

OBJECTIVE: To investigate the role of tumor persistence in patients submitted to irradiation therapy and radical hysterectomy. DESIGN: A retrospective analysis of prognostic factors. LOCATION: Hospital A.C. Camargo, S?o Paulo, Brazil, a private non-profitmaking foundation and tertiary referral centre. PATIENTS: A total of 629 cases of invasive squamous cell carcinoma of the cervix were studied. Criteria for inclusion in the study were: confirmed histological diagnosis of squamous cell carcinoma and no previous treatment (except for preoperative radiotherapy carried out at the Hospital A.C. Camargo itself). At the end of the follow-up period, 410 patients (65%) had no evidence of disease and 219 (34.8%) had died because of the tumor. INTERVENTION: The patients were submitted to radical surgery and radiation therapy, separately or in combination between 1953 and 1982. MAIN OUTCOMES MEASURES: Multivariate analysis of the different variables was performed according to the Cox regression method. RESULTS: The variables of prognostic value were, in decreasing order of importance: the decade of patient admission (p = 0.0001), the modality of therapy employed (p = 0.0005), the presence of residual tumor in the surgical specimens (p = 0.0055) and the clinical stage of the disease (p = 0.0575). CONCLUSION: Radiation therapy controlled a considerable number of local tumors and pelvic lymph nodes but not all of them in every patient. There is a specific group of patients for whom radical surgery is necessary to achieve control of the disease.     

Escherichia coli transformant expressing the glucose dehydrogenase gene from Bacillus megaterium as a cofactor regenerator in a chiral alcohol production system

Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertical transmission of hepatitis C virus from human immunodeficiency virus-negative mothers. Forty-five mothers were hepatitis C virus-RNA positive: 4 to 45 children were positive at birth and during follow-up. The level of viremia plays an important role in vertical transmission.     

Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases

The presence of epidermal-growth-factor receptors (EGFR) and of its ligands (TGFalpha and amphiregulin) in breast-cancer tissues suggests that they play a paracrine/autocrine role in tumor growth or progression. This hypothesis was tested on 3 cell lines, S2T2, NS2T2A and NS2T2A1. These epithelial cells are derived from a normal human breast-epithelial-cell culture transformed by SV40-T Ag, are of the same clonal origin, have respectively increasing levels of EGFR, TGFalpha, amphiregulin and of thymidine-kinase activity associated with increasing tumorigenic potential in nude mice (tumor intake and tumor volume). The monoclonal antibody MAb 425, which blocks ligands interaction with EGFR, reduced by more than 90% anchorage-independent growth of the most tumorigenic cells, NS2T2A1. Another anti-EGFR MAb, 528, reduced to 25% of controls the mean tumor mass after NS2T2A1 grafting in mice. Anti-sense RNA expression of EGFR in these cells confirmed the importance of this receptor in tumor progression, since it reduced significantly the tumor volume and tumor weight of NS2T2A1 cells to 16% of those in mock-transfected control cells.