Presumptive BSE cases with an aberrant prion protein phenotype in Switzerland, 2011: Lack of prion disease in experimentally inoculated cattle and bovine prion protein transgenic mice.

Bovine spongiform encephalopathy (BSE) is caused by different prion strains that are discriminated by the molecular characteristics of the pathological prion protein. In 2011, Switzerland reported two presumptive cases of BSE in cattle with a prion protein phenotype different from previously described strains, and it was unclear whether these findings were related to a transmissible disease and have implications on animal and public health. In this study, brain tissues of these cases were inoculated into transgenic mice expressing the bovine prion protein (BoPrP-Tg110) and into cattle. Clinical and pathological investigations as well as molecular testing did not provide evidence for the presence of BSE in the Swiss cases after two passages in BoPrP-Tg110 mice and a challenge period of 3.5 years in cattle. This lack of disease transmission suggests that the Swiss 2011 cases were not affected by a prion disease and were unrelated to the feed-born BSE epidemic.

Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma.

Glioblastoma multiforme (GBM) tumors display extensive histomorphological heterogeneity, with great variability in the extent of invasiveness, angiogenesis, and necrosis. The identification of genes associated with these phenotypes should further the molecular characterization, permitting better definition of glioma subsets that may ultimately lead to better treatment strategies. Therefore, we performed a differential mRNA display analysis comparing six GBM-derived primary cell cultures from patients having tumors with varied histomorphological features. We identified stromal cell-derived factor 1 (SDF1) as a gene with varied expression. SDF1 (cytokine) and CXC chemokine receptor 4 (CXCR4) interactions are implicated in modulating cell migration. They are also implicated in modulating the immune response in AIDS patients by macrophage-mediated T-cell apoptosis. GBM patients also fail to mount an immune response, although their tumors are seemingly exposed to immune cells in regions of angiogenesis, where the blood-brain barrier is absent, or in areas of necrosis. To determine whether the expression and localization of SDF1 and CXCR4 are consistent with such a role in these brain tumors, immunohistochemical analyses of these proteins were performed on normal brain and astrocytomas (grades II-IV). In normal brain tissue, low levels of SDF1 (0.5+) were observed in astrocytic processes, in neurons, and in the occasional phagocytic cells around vessels. CXCR4 expression was negative in brain tissue but was observed in phagocytic cells within the vessel lumen. In tumors, SDF1 and CXCR4 expression was colocalized when both were expressed, and SDF1 and CXCR4 expression increased with increasing tumor grade (from 0.5+ to 6+). Additionally, CXCR4 was expressed in neovessel endothelial cells. The proteins were expressed in regions of angiogenesis and degenerative, necrotic, and microcystic changes. Those tumors displaying greater amounts of these features had greater staining intensity of the proteins. The expression of SDF1 and CXCR4 did not colocalize with the proliferation marker MIB-1. Thus, our data suggest that SDF1 and CXCR4 expressions: (a) increase with increasing grade; (b) colocalize to regions within these tumors where their interaction may contribute to angiogenesis and/or modulation of the immune response; and (c) may serve to characterize subsets of GBMs.

Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis.

BACKGROUND & AIMS: Alterations in the production of epithelial mucins have been correlated with advanced tumor stage in the colon, but direct evidence for a role of specific mucin genes in liver metastasis is lacking. The current study was designed to establish more directly the role of MUC2 in colon cancer metastasis. METHODS: MUC2 levels were manipulated in highly metastatic human colon cancer cells using eukaryotic expression constructs designed to express a portion of MUC2 complementary DNA in antisense orientation. To assess the effect of MUC2 levels on metastatic potential, liver colonization was assessed in athymic mice after splenic-portal inoculation. RESULTS: Stable integration of the MUC2 antisense construct into metastatic colon cancer cells (LS LiM6) resulted in an 80% reduction in MUC2-specific messenger RNA and a concomitant decrease in MUC2 apomucin protein. This reduction was associated with a 50% reduction in synthesis of mature glucosamine-labeled mucin, almost complete inhibition of secretion of sialyl-LeX and sialyl-Tn antigens, and a 40% decrease in binding of colon cancer cells to E-selectin. Reduction in MUC2 levels was associated with a marked decrease in liver colonization. CONCLUSIONS: This study provides direct evidence that MUC2 plays an important role in colon cancer metastasis.

Tobacco-related instruction in undergraduate nursing education in Illinois.

Tobacco use is responsible for more deaths in the United States than any other factor. Nurses are in a unique position to convey life-saving messages to clients regarding tobacco use. To gauge the type and extent of tobacco-related background knowledge acquired by nurses in the course of their education, the Nurses' Committee of the Illinois Division of the American Cancer Society (ACS) surveyed 70 nursing programs in the state of Illinois. The number of lecture hours spent on tobacco-related issues was greater in LPN programs than in either associate or baccalaureate degree programs, and instruction was scattered throughout the curriculum of each program. Most schools reported heavy reliance on adult medical-surgical textbooks to convey tobacco-related content. The most recent editions of the textbooks used by the schools were reviewed, and they also were found to adopt a scattered approach, with a disappointing lack of depth regarding the hazards of tobacco. It is recommended a single course be identified as responsible for relaying tobacco-related content and information supplied by general medical-surgical textbooks be supplemented by materials drawn from other sources.

Factors contributing to the plasticity of the extended longevity phenotypes of Drosophila.

A number of laboratories have constructed independently derived long-lived strains of Drosophila, each of which have similar but not identical patterns of variability in their adult longevity. Given the observed plasticity of longevity within each of these strains, it would be useful to review the operational and environmental factors that give rise to this phenotypic plasticity and ascertain whether they are common or strain specific. Our review of the more extensively analyzed strains suggests that the allelic composition of the initial genomes and the selection/transgene strategy employed yield extended longevity strains with superficially similar phenotypes but which are probably each the result of different proximal genetic mechanisms. This then offers a plausible explanation for the differential effects of various environmental factors on each strain's particular pattern of phenotypic plasticity. It also illustrates that the species has the potential to employ any one of a number of different proximal mechanisms, each of which give rise to a similar longevity phenotype.

A coordinate upregulation of antioxidant gene activities is associated with the delayed onset of senescence in a long-lived strain of Drosophila.

The extended longevity phenotype (ELP) characteristic of our selected long-lived strain of Drosophila is brought about by a delayed onset of senescence which occurs in the young (5-7 day) adult. Genetically competent animals will not express the resistance to exogenous paraquat characteristic of the ELP as adults unless they develop in a particular larval environment. This induction leads to a series of coordinated increases in their antioxidant defense system mRNA levels and in their enzyme activities. Not all genes show such changes. These increases in antioxidant gene product levels appear to be functional, as witnessed by the fact that the long-lived animals show an increase in their resistance to exogenous paraquat at that same time. Aminotriazole-induced destruction of catalase activity in the long-lived animals results in the loss of their increased resistance to paraquat. The non-induced control animals do not show such elevations in antioxidant defense system elevations, and shortly thereafter show a significant decline in their paraquat resistance followed by the subsequent loss of certain behavioral traits diagnostic of senescence.

The expression of the EF1 alpha genes of Drosophila is not associated with the extended longevity phenotype in a selected long-lived strain.

A quantitative dot blot analysis was performed to determine whether the expression of the EF-1 alpha genes of Drosophila melanogaster are associated with the extended longevity phenotype characteristic of our genetically selected long-lived strain. These data were compared to that obtained from two normal-lived strains and from two iso-chromosomal strains with an intermediate life span. The relative mRNA levels of both EF-1 alpha genes (EF-1 alpha F1 and EF-1 alpha F2) for all five strains were measured through the larval, pupal, and early adult stages, and statistically analyzed. Our findings from these studies indicate that the F2 mRNA tracks with the extended longevity; however, the F1 mRNA is the major component and, thus, the relative total expression of these genes at the mRNA level is approximately equivalent for all five strains. These conclusions suggest that the expression of the EF-1 alpha genes is not associated with the extended longevity phenotype.

Chromosomal localization and regulation of the longevity determinant genes in a selected strain of Drosophila melanogaster.

A controlled chromosome substitution experiment was performed on a strain (NDC-L) selected for long life to determine if the genes responsible for the extended-longevity phenotype could be localized to any particular chromosome(s). All 27 different possible combinations of the three major chromosomes of Drosophila melanogaster were constructed and longevities were determined on 3875 individual animals of both sexes and analysed. The results are statistically significant and demonstrate that mean longevity is specified primarily by recessive genes on the third chromosome (c3). The extended longevity phenotype (ELP) is only expressed in those lines which are homozygous for the NDC-L type c3. Loci on the first (c1) and second (c2) chromosomes interact, both positively (c1) and negatively (c2), respectively, such that c1 represses c2 which in turn represses c3. The ELP is fully expressed in the mutual presence and mutual absence of c1 and c2. The significance of these results is discussed in the context of broader categories of molecular genetic mechanisms suggested previously to be involved in the modulation of longevity in Drosophila.

Larval regulation of adult longevity in a genetically-selected long-lived strain of Drosophila.

Our previous work has shown that the major genes involved in the expression of the extended-longevity phenotype are located on the third chromosome. Furthermore, their expression is negatively and positively influenced by chromosomes 2 and 1, respectively. In this report we show that the expression of the extended-longevity phenotype is dependent on the larval environment. A controlled chromosome substitution experiment was carried out using a strain selected for long life (L) and its parent (R) strain. Twenty different combinations of the three major chromosomes were conducted and their longevities were determined under both high (HD) and low (LD) larval density conditions. The extended-longevity phenotype was only expressed under HD conditions. The chromosome interactions were not apparent under LD conditions. Density-shift experiments delineate a critical period for expression of the extended-longevity phenotype, extending from 60 h after egg laying (AEL) to 96 h AEL, during which the developing animal must be exposed to HD conditions if the extended-longevity phenotype is to be expressed. The change from HD to LD conditions is accompanied by statistically significant increases in body weight. The possible role of a dietary restriction phenomenon is examined and the implications of these findings discussed. It is now apparent, however, that the extended-longevity phenotype in Drosophila is a developmental genetic process.

Genetic and environmental factors regulating the expression of an extended longevity phenotype in a long lived strain of Drosophila.

We have demonstrated that the expression of the ELP in our strains is the outcome of a genetically determined, environmentally modulated, event dependent, developmental process. Given the appropriate genetic and environmental conditions, we observe an early acting temporal progression of alterations in specific gene activity patterns which appear to give rise to functional phenotypic changes. The observed patterns are consistent with the interpretations drawn from our chromosome substitution and biomarker experiments. The interaction of specific environmental and genetic factors is sufficient to explain the observed plasticity of longevity in our L strain. Independently derived long lived strains may have altered different combinations of physiological mechanisms so as to give rise to a statistically equivalent ELP. Theoretically based conclusions obtained from only one set of sister strains may be difficult to extrapolate to other strains. Future work will involve the experimental verification of the genetic-environmental circuitry discussed here, using novel molecular genetic techniques to define, characterize, and isolate the genes involved in the expression of the ELP.

Quality of life of patients with sarcoma postchemotherapy.

This study was designed to describe the effects of a 96-hour doxorubicin hydrochloride/dacarbazine chemotherapy protocol for soft-tissue sarcoma on patients' functioning, life-style, and quality of life (QOL). Patients from the surgical oncology clinic of a large, midwestern university completed the Quality of Life Index--Cancer Version (QLI) and Functional Living Index: Cancer (FLIC). Additional information obtained regarded response to chemotherapy and demographic data. Patients were most satisfied with faith in God, family health, health care, long life, and their spouse. Patients were least satisfied with sex life, stress or worries, unemployment, financial independence, and government influence. QOL in the family domain was found to be significantly higher than QOL in the health, functioning, and socioeconomic domains (p less than 0.05). Functional living assessment indicated that patients were confident in their prescribed course of treatment, optimistic about the future, generally felt well, and felt that their QOL had improved since treatment. Aspects of chemotherapy that most interfered with patients' lives were the length of treatment and the financial burden. The patients reported a high confidence level in the medical and nursing care that they received.

Review of genetic investigations into the aging processes of Drosophila.

The field has progressed to the point where a genetic investigation of the aging processes in Drosophila can be viewed as constituting both a serious and a feasible research program. There now exists at least one single gene mutant which yields an accelerated aging phenotype, at least two single gene null mutants affecting enzymes implicated in regulating the aging process and resulting in premature death, and at least two strains created by artificial selection which produce extended-longevity phenotypes. In addition, genes such as adh have an indirect and interactive effect upon the animal's longevity and might also play an important role in the genetic regulation of this process. Although far from complete, some essential tools are now in place and are being used to answer some of the questions posed by Martin. Of the several theories put forth to explain aging in Drosophila, it appears as if the data best uphold the free radical and the protein synthesis/gene expression theories. It is entirely possible that these two theories are complementary aspects of a broader underlying process. The genetic mechanisms controlling these physiological processes clearly do so in concert with certain environmental factors. The net effect of their interactions may be the decreased synthetic and repair ability of the cell as suggested by Lamb and by Webster. It is probably true that aging and longevity are multicausal phenotypes. Our only hope of understanding such a complex phenotype is to dissect it genetically, one (or a few) genes at a time under rigidly controlled conditions. Thorough genetic description of each system will be the prerequisite to their molecular analysis. This will likely result in multiple explanations, ideally one for each system. Yet these multiple molecular genetic explanations may well enable us to see some commonality underlying the aging process in this organism. The fact that several different lines of evidence appear to be converging on a small number of theoretical explanations is an encouraging sign. We should also be heartened by the extraordinary increase in our knowledge of embryonic development in Drosophila as a result of just such a strategy. And we should not forget that the homeotic mutants which now play such a large role in the deciphering of embryogenesis were once classified as "complex loci" and that the then-accepted explanations gave no hint of the underlying molecular relationships. For now it is fair to conclude that aging in Drosophila may be viewed as a genetically-determined, environmentally-modulated, event-dependent process.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of personal pain experience on pain assessment.

The purpose of this study was to determine the effect of nurses' personal pain experiences on the assessment of their patients' pain. The sample consisted of 134 registered nurses employed in three Midwestern hospitals. In response to a personal pain history questionnaire, pain with headache, menstrual distress and dental events were cited most frequently. Most also reported that a family member had experienced pain in their presence (cancer, surgery, orthopedic injuries). Responses to the Standard Measure of Inferences of Suffering (Davitz & Davitz, 1981) showed significant differences between intensity of pain experienced by the nurse and overall perceived patient psychological distress. Furthermore, the intensity of pain experienced by the nurse was the only variable that predicted significantly perceptions of patients' physical suffering and psychological distress. While additional study is warranted, the findings support the notion that nurses who have experienced intense pain are more sympathetic to the patient in pain.