Cervicovaginal (Papanicolaou) smear findings in patients with malignant mixed Müllerian tumors

Malignant mixed Müllerian tumor is a rare neoplasm that occurs most frequently in elderly patients. It is characterized by a mixture of malignant epithelial and sarcomatous components. Little has been published about Papanicolaou smear findings pertaining to malignant mixed Müllerian tumors. We present our experience, with an emphasis on cytologic detail. Nine patients (median age, 65 yr) met our study criteria. All available smears and surgical specimens were reviewed. Four smears were positive for malignancy, with a sensitivity of 44% (3 adenocarcinoma, and 1 squamous-cell carcinoma, small-cell type). The results of our study showed that Papanicolaou smear findings pertaining to malignant mixed Müllerian tumors are seen in patients with advanced-stage disease with involvement of the lower uterine segment or cervix. The usual finding is large numbers of high-grade epithelial malignant cells in a necrotic background. The mesenchymal component rarely sheds cells visible on Papanicolaou smear.     

Haemophilus ducreyi Outer membrane determinants, including DsrA, define two clonal populations

The Haemophilus ducreyi outer membrane component DsrA (for ducreyi serum resistance A) is necessary for complete resistance to normal human serum (NHS). When DsrA expression in 19 temporally and geographically diverse clinical isolates of H. ducreyi was examined by Western blotting, 5 of the strains expressed a different immunotype of the DsrA protein (DsrA(II)) than the well-characterized prototypical strain 35000HP (DsrA(I)). The predicted DsrA proteins expressed by the DsrA(II) strains were 100% identical to each other but only 48% identical to that of strain 35000HP. In addition to the DsrA(II) protein, class II strains also expressed variant forms of other outer membrane proteins (OMPs) including NcaA (necessary for collagen adhesion A), DltA (ducreyi lectin A), Hlp (H. ducreyi lipoprotein), major OMP, and/or OmpA2 (for OMP A2) and synthesized a distinct, faster-migrating lipooligosaccharide. Based on these data, strains expressing DsrA(I) were termed class I, and those expressing DsrA(II) were termed class II. Expression of dsrA(II) from strain CIP 542 ATCC in the class I dsrA(I) mutant FX517 (35000HP background), which does not express a DsrA protein, rendered this strain resistant to 50% NHS. This demonstrates that DsrA(II) protein is also critical to serum resistance. Taken together, these results indicate that there are two clonal populations of H. ducreyi. The implications of two classes of H. ducreyi strains differing in important antigenic outer membrane components are discussed.     

Serum resistance in Haemophilus ducreyi requires outer membrane protein DsrA

Haemophilus ducreyi is resistant to killing by normal serum antibody and complement. We discovered an H. ducreyi outer membrane protein required for expression of serum resistance and termed it DsrA (for "ducreyi serum resistance A"). The dsrA locus was cloned, sequenced, and mutagenized. An isogenic mutant (FX517) of parent strain 35000 was constructed and characterized, and it was found to no longer express dsrA. FX517 was at least 10-fold more serum susceptible than 35000. DsrA was expressed by all strains of H. ducreyi tested, except three naturally occurring, avirulent, serum-sensitive strains. FX517 and the three naturally occurring dsrA-nonexpressing strains were complemented in trans with a plasmid expressing dsrA. All four strains were converted to a serum-resistant phenotype, including two that contained truncated lipooligosaccharide (LOS). Therefore, serum resistance in H. ducreyi does not require expression of full-length LOS but does require expression of dsrA. The dsrA locus from eight additional H. ducreyi strains was sequenced, and the deduced amino acid sequences were more than 85% identical. The major difference between the DsrA proteins was due to the presence of one, two, or three copies of the heptameric amino acid repeat NTHNINK. These repeats account for the variability in apparent molecular mass of the monomeric form of DsrA (28 to 35 kDa) observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since DsrA is present in virulent strains, is highly conserved, and is required for serum resistance, we speculate that it may be a virulence factor and a potential vaccine candidate.     

Isolation and characterization of a novel gene, xMADML, involved in Xenopus laevis eye development.

We have identified Xenopus MADM-like (xMADML), a Xenopus laevis gene related to the murine MADM and the human NRBP genes. xMADML is expressed throughout early development and is expressed most strongly in the developing lens and more weakly in the retina and other anterior tissues. We demonstrate that disruption of xMADML translation by means of morpholino injection results in impaired retina and lens development. Reciprocal transplantation of the presumptive lens ectoderm between morpholino-injected embryos and those injected solely with a dextran lineage tracer demonstrates that xMADML is necessary in both the lens and the retina for correct development of these eye tissues. Analysis of gene expression after knockdown of xMADML revealed significant alterations in the expression of some genes, including Pax6, xSix3, Sox2, and Sox3, suggesting that xMADML plays a role in regulating gene expression during development of the eye. This investigation is the first in vivo study examining the developmental role of this novel gene and reveals an important role of xMADML in eye tissue development and differentiation.     

Antibiotic susceptabilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 microg ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.     

Epidemiology of the most frequent diseases in the European a-symptomatic post-menopausal women. Is there any difference between Ireland and the rest of Europe?

Osteoporosis, cardiovascular disease, breast cancer and genitourinary diseases are some of the most frequently diagnosed diseases in a-symptomatic post-menopausal women. There is a marked European geographic distribution of osteoporosis. Rates are higher in Scandinavia than in the Southern European countries. The possible reasons for this higher incidence of osteoporotic fractures in the Northern European countries is associated with the climate, which limits physical activity and exposure to sunlight and increases the risk of falls. During the next two decades, the number of hip fractures for European women over 65 years is expected to nearly double. Despite these figures, osteoporosis prevention has not yet been adopted in many European countries. There is a devastating impact and a huge financial burden on the European economy and health care system. Breast cancer is the most common cancer in females in Europe. The regions of highest incidence are Western and Northern Europe, while Southern and Eastern Europe have lower incidence rates. The causes of differences in breast cancer incidences between Northern and Southern Europe are not known, but the average 5-year survival of women with breast cancer has increased in Europe in the last three decades. Studies have revealed marked differences in cardiovascular diseases across Europe, showing cardiovascular death rates as highest among the Eastern and Central European countries and lowest in the Mediterranean countries. Cardiovascular disease is the major cause of mortality in European women. However, in North European countries, there are more ischaemic heart diseases in women than in Mediterranean countries. In Mediterranean countries, on the other hand, there are more strokes than in Northern Europe. These strokes events occur 10 years later than the ischaemic heart attacks.     

Both Th1 and Th2 cells require P-selectin glycoprotein ligand-1 for optimal rolling on inflamed endothelium

The acquisition of homing receptors that redirect lymphocyte trafficking to nonlymphoid tissues after antigen encounter is a fundamental aspect of effector T-cell development. Although a role for selectins and their ligands has been well characterized for trafficking of Th1 cells to nonlymphoid sites, mechanisms responsible for Th2 trafficking are not well understood. Using a flow chamber system in which the endothelial interactions of two distinct T-cell populations could be examined simultaneously, we directly compared the requirements for Th1 and Th2 cell tethering and rolling. We found that although Th2 cells expressed significantly lower levels of selectin ligands than Th1 cells, activation of the endothelium by Th2-derived factors induced rolling interactions that were comparable for both Th1 and Th2 populations. Further, in the absence of PSGL-1, no other adhesion molecule could effectively compensate for lack of PSGL-1 to mediate rolling of either Th1 or Th2 cells. Thus, both Th1 and Th2 populations express functional PSGL-1-based selectin ligands for tethering and rolling on activated endothelium, and both effector populations can use PSGL-1 as the dominant scaffold for functional selectin ligand expression.     

Hormonal and metabolic response to three types of exercise of equal duration and external work output

Summary Five normal men, aged 20–30 years, participated in three types of exercise (I, II, III) of equal duration (20 min) and total external work output (120–180 kJ) separated by ten days of rest. Exercises consisted of seven sets of squats with barbells on the shoulders (I; Maximal Power Output _max=600−900 W), continuous cycling at 50 rev · min⁻¹ (II; _max=100−150 W) and seven bouts of intermittent cycling at 70 rev · min⁻¹ (III; _max=300−450 W). Plasma cortisol, glucagon and lactate increased significantly (P<0.05) during the exercise and recovery periods of the anaerobic, intermittent exercise (I and III) but not in the continuous, aerobic exercise (II). No consistent significant changes were found in plasma glucose. Plasma insulin levels decreased only during exercise II. The highest increase in cortisol and glucagon was not associated with the highest , , _max or HR; however it was associated with the anaerobic component of exercise (lactic acid). It is suggested that in exercises of equal duration and total external work output, the continuous, aerobic exercise (II) led to lowest levels of glucogenic hormones.     

Post-awakening cortisol secretion during basic military training.

Salivary free cortisol concentrations in the first 30 min after awakening were assessed in 12 healthy army recruits at the beginning, middle and end of an 11-week intensive physical training course. To ensure strict adherence to protocol saliva collection was supervised and collected on each sampling day immediately on waking and again 15 and 30 min later. Self-rated psychological assessments of state levels of stress, arousal and fatigue were performed in the evening of each sampling day. A within-subjects repeated-measures analysis of participants who completed the course (12 of the original 20) showed a significant main effect of cortisol concentration across all three sampling points after awakening (F((2,22))=54.516, p<0.0001) and a significant main effect of weeks into the training course (F((3,33))=4.390, p=0.010). Further analysis of this effect of measurement-week revealed that at weeks 3 and 6 total cortisol secretion estimated by area under the curve was lower (F((3,33))=4.602, p=0.008) compared to the beginning and end of the course. Surprisingly self-reported stress, arousal and fatigue did not differ significantly across weeks, despite the large dropout rate (40%) and self-evident pressures of the course. We conclude that when controlling for many confounding variables, including participant adherence, post-awakening cortisol levels are sensitive to stressful challenge over a period of weeks.