Fascin-1 expression in papillary and invasive urothelial carcinomas of the urinary bladder

Fascin-1 is an actin-bundling protein that plays an important role in cell motility and adhesion. The level of fascin-1 is low or undetectable in normal epithelial cells. However, overexpression is reported in transformed epithelial cells and in several common types of carcinomas [Bioessays. 2002;24:359-361]. Up-regulation of fascin-1 is associated with higher grades and with aggressive tumors with poorer prognoses. We found no report on the role or the protein expression of fascin-1 in urothelial carcinomas (UCs) of the urinary bladder. In this study, we examined by immunohistochemistry the expression of fascin-1 in the normal human transitional epithelium, benign vesical lesions, and different types of UCs. We found no detectable fascin-1 in the normal transitional epithelium. There was no increase of fascin-1 expression in cystitis cystica, cystitis glandularis, nephrogenic adenoma (n = 10), inverted papilloma (n = 5), and classic exophytic papilloma (n = 4) or in adjacent transitional epithelia associated with these conditions. Patchy or diffusely weak fascin-1 expression was observed in 42% (5/12) of superficial papillary UCs (Ta), and 95% (19/20) of invasive UCs (T2 or higher) demonstrated diffuse strong staining for fascin-1. The microinvasive foci in the lamina propria of UC (T1, n = 8) were also positive for fascin-1, although they were not as strongly stained as in the deeply invasive tumors. Interestingly, the neoplastic cells in the tips of microinvasive carcinomas were distinctly positive for fascin-1. There were significant numbers of fascin-1-positive cells (>50% of the neoplastic cells) in UCs in situ (n = 10). These findings suggest an association between increased fascin-1 expression and increased invasiveness of carcinomas in the urinary bladder.     

On the surviving fraction in irradiated multicellular tumour spheroids: calculation of overall radiosensitivity parameters, influence of hypoxia and volume effects

We model the heterogeneous response to radiation of multicellular tumour spheroids assuming position- and volume-dependent radiosensitivity. We propose a method to calculate the overall radiosensitivity parameters to obtain the surviving fraction of tumours. A mathematical model of a spherical tumour with a hypoxic core and a viable rim which is a caricature of a real tumour is constructed. The model is embedded in a two-compartment linear-quadratic (LQ) model, assuming a mixed bivariated Gaussian distribution to attain the radiosensitivity parameters. Ergodicity, i.e., the equivalence between ensemble and volumetric averages is used to obtain the overall radiosensitivities for the two compartments. We obtain expressions for the overall radiosensitivity parameters resulting from the use of both a linear and a nonlinear dependence of the local radiosensitivity with position. The model's results are compared with experimental data of surviving fraction (SF) for multicellular spheroids of different sizes. We make one fit using only the smallest spheroid data and we are able to predict the SF for the larger spheroids. These predictions are acceptable particularly using bounded sensitivities. We conclude with the importance of taking into account the contribution of clonogenic hypoxic cells to radiosensitivity and with the convenience of using bounded local sensitivities to predict overall radiosensitivity parameters.     

Dementia associated with alcohol and other drug use

The acute use of alcohol and several other licit and illicit drugs can affect mental state and cognitive function. The chronic use of certain drugs may also increase the risk of cognitive impairment and perhaps dementia in later life. This paper focuses on the long-term cognitive consequences of using alcohol, benzodiazepines, tobacco and cannabis. Currently available evidence indicates that mild to moderate alcohol consumption is not associated with increased risk of cognitive decline and may in fact have a protective effect against dementia, although heavy, long-term consumption is likely to have a negative impact on cognitive function. The degree that alcohol-related cognitive impairment must reach to be classified as dementia is currently obscure. Longer-term smoking is associated with increased risk of cognitive impairment and possibly dementia. The chronic use of benzodiazepines has been associated with increased risk of cognitive impairment but information relating to dementia remains inconclusive. The chronic use of cannabis may impair intellectual abilities but data on this topic remain sparse and difficult to interpret. In conclusion, there is evidence that some drugs contribute to the causal pathway that leads to the development of cognitive impairment but currently available data do not support the introduction of a separate diagnostic category of drug-induced dementia (such as alcohol-related dementia). Health promotion programs designed to decrease tobacco smoking and "harmful" alcohol use (and possibly other drug use) may decrease the burden of cognitive impairment and perhaps dementia in later life.     

Dementia associated with infectious diseases

At the turn of the last century, infectious diseases represented an important cause of health morbidity and behavioral changes. Neurosyphilis, for example, was relatively common at the time and often led to the development of cognitive impairment and dementia. With the advent of effective antibiotic treatment, the association between infectious diseases and dementia became increasingly less frequent, although a resurgence of interest in this area has taken place during the past 15 years with the emergence of acquired immunodeficiency syndrome (AIDS) and variant Creutzfeldt-Jakob disease (vCJD). This paper reviews the most frequent infectious causes of dementia, including prion diseases, as well as infections caused by herpes virus, human immunodeficiency virus (HIV), toxoplasmosis, cryptococcus, cytomegalovirus, syphilis, borrelia and cysticercosis.     

Motivational interviewing in community-based research: Experiences from the field

Motivational Interviewing (MI) has been established as an effective psychotherapeutic treatment for problem drinking in clinical settings. Consequently, there is a growing interest in applying MI to facilitate change across other health behaviors, such as tobacco use, eating habits, and physical activity in a variety of community-based research settings. These extended applications pose new challenges regarding implementation and evaluation. For instance, investigators must consider how best to train intervention counselors; implement strategies for preserving the MI spirit, despite limited client contact time; incorporate adjunctive strategies that support brief MI sessions; and develop a plan for monitoring and evaluating MI treatment fidelity. This article highlights specific examples of how several behavior change research projects applied MI across a variety of settings and populations, provides lessons learned from our experience as a collaborative workgroup, and offers strategies for consideration in future community-based research. Funding for this multisite project was provided by RO1 HL62165, 1AR01 45901, 5M01 RR00334, 1 R01 HD37368-01, 1 R01 DE13093-01, 1 R01 MH59594-01 We express our appreciation of the contributions made by the MI workgroup of the BCC, with specific assistance from Judy Salkeld. Special thanks go to Karen Emmons, Diane Elliot, Esther Moe, and Patricia Jordan who offered substantive comments and guidance on earlier drafts of this article.     

Influence of the dopamine D2 receptor knockout on pain-related behavior in the mouse

We studied the role of the dopamine D2 receptor in physiological regulation of pain-related behavior. The experiments were performed in dopamine D2 receptor knockout mice and in their wild-type controls. Baseline sensitivity to thermal nociception was determined by measuring the response latency in the hot plate at three different stimulus temperatures and by determining the radiant-heat-induced paw withdrawal. Mechanical sensitivity was assessed by determining paw withdrawal responses to stimulation with a calibrated series of monofilaments. Intracolonic capsaicin was used to produce sustained pain-related behavior and referred hypersensitivity to mechanical stimulation. The hot plate response latencies were not significantly different between the dopamine D2 receptor knockout and wild-type animals, although the stimulus temperature-dependent decrease in the response latency was steeper in the wild-type group. The radiant-heat-induced paw withdrawal latency was slightly longer in the knockout animals. The number of capsaicin-induced behavioral responses or the latency to the occurrence of the first capsaicin-induced response was not different between the experimental groups. Dopamine D2 receptor knockout animals were more sensitive to mechanical stimulation of the hindpaws than wild-type animals both in the baseline condition and following development of capsaicin-induced referred hypersensitivity in the hindpaws. The results indicate that dopamine D2 receptors influence baseline nociception in the mouse, although this effect is weak and submodality selective. Additionally, dopamine D2 receptors may contribute to attenuation of referred hypersensitivity caused by sustained nociception.     

Assessing the reliability and validity of the Bermond-Vorst Alexithymia Questionnaire among U.S. Anglo and U.S. Hispanic samples

OBJECTIVE: The aim of this paper is to assess the psychometric properties of the Bermond-Vorst Alexithymia Questionnaire (BVAQ) in U.S. Anglo and U.S. Hispanic samples of college students. METHOD: One hundred ninety-four U.S. Hispanics and 304 U.S. Anglos participated in the study. In addition to completing the BVAQ, participants completed the 20-item Toronto Alexithymia Scale (TAS-20), the Beck Depression Inventory (BDI), and the Eysenck Neuroticism Scale (ENS). RESULTS: BVAQ and TAS-20 subscales were correlated across groups. While the identifying and verbalizing composites of the BVAQ subscales were predictive of neuroticism and depression across groups in the expected direction, the fantasizing subscale of the BVAQ was negatively predictive of depression and neuroticism across groups. CONCLUSION: Given the unexpected findings associated with some of the BVAQ subscales, future research should explore the dimensionality of alexithymia.