bluuebunny/crossref_metadata_2025 huggingface dataset:
Substrate polypeptide presents a load on the apical domains of the chaperonin GroEL
Authors: Motojima Fumihiro , Chaudhry Charu , Fenton Wayne A. , Farr George W. , Horwich Arthur L.
Published: October 2004

A conundrum has arisen in the study of the structural states of the GroEL–GroES chaperonin machine: When either ATP or ADP is added along with GroES to GroEL, the same asymmetric complex, with one ring in a GroES-domed state, is observed by either x-ray crystallographic study or cryoelectron microscopy. Yet only ATP/GroES can trigger productive folding inside the GroES-encapsulated cis cavity by ejecting bound polypeptide from hydrophobic apical binding sites during attendant rigid body elevation and twisting of these domains. Here, we show that this difference occurs because polypeptide substrate in fact presents a load on the apical domains, and, although ATP can counter this load effectively, ADP cannot. We monitored apical domain movement in real time by fluorescence resonance energy transfer (FRET) between a fixed equatorial fluorophore and one attached to the mobile apical domain. In the absence of bound polypeptide, addition of either ATP/GroES or ADP/GroES to GroEL produced the same rapid rate and extent of decrease of FRET (
t
1/2
< 1 sec), reflecting similarly rapid apical movement to the same end-state and explaining the results of the structural studies, which were all carried out in the absence of substrate polypeptide. But in the presence of bound malate dehydrogenase or rhodanese, whereas similar rapid and extensive FRET changes were observed with ATP/GroES, the rate of FRET change with ADP/GroES was slowed by >100-fold and the extent of change was reduced, indicating that the apical domains opened in a slow and partial fashion. These results indicate that the free energy of γ-phosphate binding, measured earlier as 43 kcal per mol (1 cal = 4.184 J) of rings, is required for driving the forceful excursion or “power stroke” of the apical domains needed to trigger release of the polypeptide load into the central cavity.
Food, youth and the Mediterranean diet in Spain. Development of KIDMED, Mediterranean Diet Quality Index in children and adolescents
Authors: Serra-Majem Lluís , Ribas Lourdes , Ngo Joy , Ortega Rosa M , García Alicia , Pérez-Rodrigo Carmen , Aranceta Javier
Published: October 2004

Objective:

To evaluate dietary habits in Spanish children and adolescents based on a Mediterranean Diet Quality Index tool, which considers certain principles sustaining and challenging traditional healthy Mediterranean dietary patterns.

Design:

Observational population-based cross-sectional study. A 16-item Mediterranean Diet Quality Index was included in data gathered for the EnKid study (in which two 24-hour recalls, a quantitative 169-item food-frequency questionnaire and a general questionnaire about socio-economic, demographic and lifestyle items were administered).

Setting:

Spain.

Subjects:

In total, 3850 children and youths aged 2–24 years residing in Spain.

Results:

Of the sample, 4.2% showed very low KIDMED index results, 49.4% had intermediate values and 46.4% had high index results. Important geographical differences were seen, with subjects from the Northeast showing the most favourable outcomes (52% with elevated scores vs. 37.5% of those from the North). Lower percentages of high diet quality were observed in low socio-economic groups, compared with middle and upper income cohorts (42.8%, 47.6% and 54.9%, respectively). Large cities had more positive results and only slight variations were seen for gender and age.

Conclusions:

The KIDMED index, the first to evaluate the adequacy of Mediterranean dietary patterns in children and youth, confirms that this collective is undergoing important changes, which makes them a priority target for nutrition interventions. Results challenge certain commonly perceived notions tied to income level, population size and diet quality.
Mediterranean Adequacy Index of Italian diets
Authors: Alberti-Fidanza Adalberta , Fidanza Flaminio
Published: October 2004

Objective:

To assess, particularly in longitudinal studies, how close or far the food intakes of population groups are from a reference dietary pattern.

Design:

Computation of an index, called the Mediterranean Adequacy Index (MAI), by dividing the sum of the percentage of total energy from typical Mediterranean food groups by the sum of the percentage of total energy from non-typical Mediterranean food groups. The reference Italian–Mediterranean diet utilised was that of subjects from Nicotera in 1960.

Setting:

Different areas in Italy.

Subjects:

Men aged 45–65 years at the start of the study from rural areas of Italy in the Seven Countries Study followed for 26 years (Crevalcore and Montegiorgio), elderly men and women from Perugia followed for 11 years, men and women from Pollica (Salerno) followed for 32 years, and families from Rofrano (Salerno) followed for 41 years.

Results:

The median value of MAI among 40–59-year-old men from Nicotera in 1960 was 7.2; in Crevalcore it was 2.9 in 1965 and 2.2 in 1991; and in Montegiorgio, 5.6 in 1965 and 3.9 in 1991. In Pollica, the values in men ranged from 5.6 to 6.3 in 1967 and from 2.4 to 4.5 in 1999; for women, the corresponding ranges were 4.2–7.2 and 2.7–4.1. In elderly men of Perugia, median MAI value was 4.9 in 1976 and 3.2 in 1987; for women, the corresponding values were 3.1 and 2.6.

Conclusions:

The diet of these Italian population groups has changed over the last four decades, progressively abandoning the nutritional characteristics of the reference Italian–Mediterranean diet. The MAI proposed is simple to compute; it has satisfactory discriminating power particularly for longitudinal dietary data with only a few limitations.
Ageing and the Mediterranean diet: a review of the role of dietary fats
Authors: Battino Maurizio , Ferreiro Maria Soledad
Published: October 2004

Consumers are becoming increasingly aware of the relationship between food and health. Concerns have been raised about dietary fats and their relative nutritional advantages or disadvantages. In investigations of the associations between health and fat intake, special emphasis has been placed on the benefits of virgin olive oil for counteracting certain neurodegenerative diseases and ageing. With respect to ageing, accumulating evidence indicates that an improvement in quality of life can be reached by modulation of the extrinsic factors that influence many ageing processes. Of the modifiable factors, nutrition appears to be one of the strongest elements known to influence the rate of ageing as well as the incidence of age-associated diseases such as atherosclerosis and neurodegenerative pathologies.

This paper reviews the theory of ageing and the role of fatty acids in the mechanisms affecting its evolution. It also confirms that virgin olive oil, an essential component of the Mediterranean diet, provides large amounts of stable and not easily oxidisable fatty acids as well as remarkable quantities of powerful antioxidant molecules.
Mediterranean diet and cognitive decline
Authors: Panza F , Solfrizzi V , Colacicco AM , D'Introno A , Capurso C , Torres F , Del Parigi A , Capurso S , Capurso A
Published: October 2004

Objective:

To investigate the possible role of diet in age-related cognitive decline (ARCD) and cognitive impairment of both degenerative (Alzheimer's disease, AD) and vascular (vascular dementia, VaD) origin.

Design:

Literature review.

Results:

In an elderly population of southern Italy with a typical Mediterranean diet, high energy intake of monounsaturated fatty acids (MUFA) appeared to be associated with a high level of protection against ARCD. In addition, dietary fat and energy in the elderly seem to be risk factors, while fish consumption and cereals are found to reduce the prevalence of AD in European and North American countries. Finally, the relative risk of dementia (AD and VaD) was lower in the subjects of a French cohort who drank three or four glasses of red wine each day compared with total abstainers.

Conclusion:

Essential components of the Mediterranean diet – MUFA, cereals and wine – seem to be protective against cognitive decline. As such, dietary antioxidants and supplements, specific macronutrients of the Mediterranean diet, oestrogens and anti-inflammatory drugs may act synergistically with other protective factors, opening up new therapeutic interventions for cognitive decline.
Nutrition education and Mediterranean diet: exploring the teaching process of a school-based nutrition and media education project in Cretan primary schools
Authors: Kafatos Irene , Peponaras Antonis , Linardakis Manolis , Kafatos Anthony
Published: October 2004

Background:

During the past few decades there has been a gradual abandoning of the traditional Mediterranean diet by the population of Crete and especially among the younger generations. Since this is related to the rapidly increasing morbidity and mortality rates from chronic diseases, the need for educating young people on the principles of good nutrition becomes increasingly important. It is also acknowledged that the epidemiological field needs to focus on studying the implementation process, since this will allow for a deeper understanding of the outcomes.

Objectives:

The aims of the present study were to explore the process of implementing an innovation in Cretan primary schools and to identify best teaching practices and principles.

Design:

In three state primary schools on the island of Crete, 107 children took part in a 30-h nutrition and media education programme. Classroom observations were used to define attitudes towards the programme and teaching methods. Besides baseline and post evaluation, the pupils were also interviewed about 11 months after the end of the programme.

Implementation:

During observation of the teaching process, emerging issues were the teacher's motivation and interest in the course, his/her preparation before each class, teaching ability and communication skills, the respect and discipline he/she kept and the innovative teaching methods used. In some cases researcher intervention in the classroom could not be avoided.

Findings and conclusions:

Overall, individual teacher willingness and teaching skills were mainly responsible for the quality of teaching, the variety of educational methods used in classrooms and pupils' interest in the course. Changes in pupils' knowledge and recall of the course were related to teacher enthusiasm but also to researcher intervention. Exploring the teaching and learning process allowed a deeper understanding of the data. It is concluded that attempts to introduce the principles of a Mediterranean diet to children through nutrition education require innovative, enthusiastic and highly motivated teachers.
Globalisation and income growth promote the Mediterranean diet
Authors: Regmi Anita , Ballenger Nicole , Putnam Judy
Published: October 2004

Objective:

To examine global food demand patterns and how changing diets may stimulate demand for and trade of Mediterranean diet products.

Design:

Literature review. Trends in global and US food consumption patterns are examined and trade data are reviewed to evaluate the impact of changing diets on trade of Mediterranean diet products. Market access issues are also addressed briefly to highlight the role of policy in the trade of Mediterranean diet products.

Results:

Diets are shifting towards higher-value products such as meats, fruits and vegetables, and a wider array of packaged food products. Trade in these products has also grown in the past two decades, with several non-traditional importers and exporters becoming increasingly active in the global market.

Conclusions:

Income-driven demands for quality and variety are likely to increase the demand for Mediterranean diet products globally. While the middle-income countries appear to be the best growth prospects, the USA remains a potential growth market if these products can meet the growing consumer demand for variety, quality and convenience. Although consumer trends globally indicate growth in demand for Mediterranean diet products, the additional demand may not be reflected by a corresponding growth in trade. Trade in Mediterranean diet products continues to be hampered by higher than average trade barriers and high transportation costs for perishables.
A Monte Carlo simulation to validate the EAR cut-point method for assessing the prevalence of nutrient inadequacy at the population level
Authors: de Lauzon B , Volatier JL , Martin A
Published: October 2004

Objective:

The aim of this study was to validate the EAR cut-point method for assessing the prevalence of nutrient inadequacy at the population level.

Design and subjects:

Different methods for estimating the prevalence of inadequate intake were compared: the cut-off point method, with cut-off points at the Recommended Dietary Allowance (RDA), 0.66 RDA, 0.50 RDA and the Estimated Average Requirement (EAR); the probability approach; and a Monte Carlo simulation. In total, 591 men and 674 women, aged 20–55 years, were included in the analyses.

Results:

The prevalence of inadequate intake as estimated by the EAR cut-point method was similar to the prevalence of inadequacy estimated by both probabilistic methods. The cut-point method with RDA, 0.66 RDA and 0.50 RDA as cut-off limits induced an over- or an underestimation of the real prevalence of inadequacy.

Conclusions:

Probabilistic methods consider both the intake variability and the requirement variability, and, as a result, their estimation should be closer to the real prevalence of inadequacy. The use of the EAR cut-point method yields a good estimation of the prevalence of inadequate intake, comparable to the probability approach, and limits over- and underestimation of the prevalence induced by other cut-off points.
Dietary intake and body mass index in HIV-positive and HIV-negative drug abusers of Hispanic ethnicity
Authors: Forrester Janet E , Tucker Katherine L , Gorbach Sherwood L
Published: October 2004

Objective:

Malnutrition in drug abusers has been attributed to poor diet. However, previous studies are conflicting. Many studies have not considered possible concurrent HIV disease. The purpose of this study was to determine the relationship between drug abuse and dietary intake in Hispanic Americans with and without HIV infection.

Design:

Dietary intake was measured using 3-day food records and 24-hour dietary recalls in three groups: HIV-positive drug abusers, HIV-negative drug abusers and HIV-positive persons who do not use drugs (‘non-drug abusers’).

Setting:

The baseline data from a prospective cohort study of the role of drug abuse in HIV/AIDS weight loss and malnutrition conducted in Boston, Massachusetts, USA.

Subjects:

The first 284 participants to enrol in the study.

Results:

HIV-positive drug abusers had a body mass index (BMI) that was significantly lower than that of HIV-positive non-drug abusers. Reported energy, fat and fibre intakes did not differ between groups. All groups had median reported intakes of vitamin A, vitamin B6, vitamin B12, selenium and zinc that were in excess of the dietary reference values (DRI). Intakes of α-tocopherol were below the DRI, but did not differ from intakes of the general US population. However, increasing levels of drug abuse were associated with lower reported intakes of vitamin B6, vitamin B12, selenium and zinc.

Conclusions:

Overall, this study does not support the notion that dietary intake can explain the lower BMI of HIV-positive drug abusers. Further studies examining non-dietary determinants of nutritional status in drug abusers are warranted.
The UK Women's Cohort Study: comparison of vegetarians, fish-eaters and meat-eaters
Authors: Cade JE , Burley VJ , Greenwood DC ,   UK Women's Cohort Study Steering Group
Published: October 2004

Background:

This paper describes the development of the UK Women's Cohort Study and presents cohort baseline characteristics.

Methods:

In total, 35 372 women, aged 35–69 years at recruitment, were selected to ensure a wide range of dietary intakes. Diet was assessed by a 217-item food-frequency questionnaire (FFQ). Detailed lifestyle information was collected by postal questionnaire. Vegetarians, fish-eaters and meat-eaters were compared.

Results:

The cohort women are mainly white, well-educated, middle-class and married with children. They are health-conscious with only 11% current smokers and 58% taking dietary supplements. Twenty-eight per cent of subjects self-report as being vegetarian and 1% as vegan. However, only 18% are defined as 'vegetarian' from the FFQ. Fat provides 32% of energy; vitamin and mineral intakes are high, with a broad range of intakes. Meat-eaters are older, with a higher body mass index (BMI) and the lowest intakes of carbohydrate, fibre, vitamin C, folate, iron and calcium. Other fish-eaters are similar to vegetarians. Vegetarians have the lowest intakes of protein, fat and saturated fat. Oily fish-eaters have the lowest BMI; are the least likely to smoke or use full-fat milk; and are the most likely to use dietary supplements and consume the most fruit and vegetables. Oily fish-eaters have the highest total energy intake and vegetarians the lowest. Semi-skimmed milk, bread, potatoes, wine, bananas and muesli are important contributors to energy for all groups.

Conclusion:

A large cohort of middle-aged women has been created encompassing a wide range of different eating patterns, including diets currently of interest to research into protection against cancer and coronary heart disease. Participants will be followed up to study the effects of different food and nutrient intakes on long-term health outcomes.
The association of diet and other lifestyle factors with the onset of overactive bladder: a longitudinal study in men
Authors: Dallosso Helen M , Matthews Ruth J , McGrother Catherine W , Donaldson Madeleine MK , Shaw Chris ,   Leicestershire MRC Incontinence Study Group
Published: October 2004

Objective:

To investigate associations between diet and non-dietary lifestyle factors and the onset of overactive bladder (OAB) in men.

Subjects:

Random sample of community-dwelling men aged 40 years plus.

Design and methods: Baseline data on urinary symptoms and diet were collected from 5454 men using a postal questionnaire and a food-frequency questionnaire. Follow-up data on urinary symptoms were collected from 4887 men in a postal survey one year later. Logistic regression analysis was used to investigate diet and lifestyle factors associated with onset of OAB in the men without OAB at baseline.

Results:

There was a highly significant negative association between beer intake at baseline and subsequent OAB onset (P = 0.001), with reduced risk at all levels of intake compared with those who seldom/never drank beer. Adjustment for total alcohol intake (g ethanol day−1) reduced the significance of the association (P = 0.02). None of the food groups studied was associated with OAB onset, with the possible exception of potatoes (P = 0.05), which showed an increased risk of onset at the highest level of consumption. Physical activity, smoking and obesity were not significantly associated.

Conclusions:

While most diet and lifestyle factors were not associated with OAB onset, the evidence from this prospective longitudinal study suggests that beer may have a protective role in the development of OAB. This could be due to a non-alcoholic ingredient as well as the alcohol content.
High alcohol consumption in Germany: results of the German National Health Interview and Examination Survey 1998
Authors: Burger Martina , Mensink Gert BM
Published: October 2004

Objective:

To analyse the alcohol consumption behaviour of the German adult population, with a focus on the characteristics of persons drinking more than the tolerable upper alcohol intake level (TUAL) of 10–12 g day−1 for healthy adult women and 20–24 g day−1 for healthy adult men.

Design and setting: For the German National Health Interview and Examination Survey 1998, a representative sample of free-living adults was drawn. A total of 7124 participants were interviewed comprehensively about their sociodemographic background, lifestyle and eating habits including alcohol consumption.

Subjects:

A sub-sample of 4030 women and men, 18–79 years old, who were involved in the integrated German Nutrition Survey.

Results:

About 16% of women and 31% of men had mean alcohol consumption above the TUAL. Among other factors, the inclination to exceed the TUAL was related to middle-age, high socio-economic status, smoking and use of soft drugs. Among both women and men, a high proportion of persons drinking above the TUAL was observed among those consuming low amounts of soft drinks, fruit, poultry, milk products, bread and cake/biscuits. Women preferred to drink wine, whereas men preferred to drink beer.

Conclusions:

Many Germans have an alcohol consumption level above the TUAL and thus are supposed to be at increased risk for alcohol-associated diseases.
Factors associated with the initiation of breast-feeding by Aboriginal mothers in Perth
Authors: Binns C , Gilchrist D , Gracey M , Zhang M , Scott J , Lee A
Published: October 2004

Objectives:

To identify the prevalence of breast-feeding at discharge and the determinants of breast-feeding initiation amongst Aboriginal women.

Design:

A prospective cohort study using a self-administered baseline questionnaire and telephone-administered follow-up interviews.

Setting:

Six hospitals with maternity wards in Perth, Western Australia.

Subjects:

Four hundred and twenty-five Aboriginal mothers of newborn infants.

Results:

At discharge, 89.4% of Aboriginal mothers were breast-feeding. Breast-feeding at discharge was most positively associated with perceived paternal support of breast-feeding, with an adjusted odds ratio (OR) of 6.65 (95% confidence interval (CI) 2.81–15.74), and with maternal age (OR 1.12, 95% CI 1.03–1.22), but negatively associated with parity and having delivered vaginally.

Conclusion:

The factors independently associated with breast-feeding at discharge were similar to those previously identified for a group of non-Aboriginal Perth women, suggesting that separate breast-feeding interventions specially targeted at Aboriginal women are not warranted. The findings do, however, highlight the importance of including the father in the breast-feeding discussions.
Secular and socio-economic trends in compliance with dietary targets in the north Glasgow MONICA population surveys 1986–1995: did social gradients widen?
Authors: Wrieden Wendy Louise , Connaghan John , Morrison Caroline , Tunstall-Pedoe Hugh
Published: October 2004

Objective:

To compare trends in the consumption of key foods over 10 years in the most deprived and least deprived quarters in north Glasgow, Scotland as defined by the Carstairs deprivation index for their postcode of domicile.

Design:

Four random, cross-sectional, age- and gender-stratified population surveys carried out in 1986, 1989, 1992 and 1995. After assigning a deprivation score, food-frequency questionnaires from 2883 men and 3127 women were examined for compliance with dietary targets, examining trends by gender and within the most and least deprived quarters of the population.

Setting:

North Glasgow, Scotland.

Subjects:

Over 600 men and 600 women (aged 25–64 years) in each of the four survey years who completed a lifestyle questionnaire including a food frequency section.

Results:

Increasing trends in the reported consumption of fruit and vegetables and oil-rich fish were observed over the 10-year period. However, the trend to increased fruit and vegetable consumption in the most deprived groups was not significant, and in 1995 only 8% of men and 12% of women in this group claimed consumption of these foods 4 or more times a day. In general, a higher percentage of those in the least deprived group met the targets for the key foods.

Conclusions:

Trends to increasing consumption of fruit and vegetables and fish were in the right direction, but the targets for consumption of certain key foods were met by a minority of the population. The progress towards the target for fruit and vegetables showed widening social gradients with time.
Flow Visualization Tools for Image Analysis of Capillary Networks
Authors: JAPEE SHRUTI A. , ELLIS CHRISTOPHER G. , PITTMAN ROLAND N.
Published: October 2004

Objective: Video recordings of red blood cell (RBC) flow through capillary networks contain a considerable amount of information pertaining to oxygen transport through the microcirculation. Image analysis of these video recordings has been widely used to determine RBC dynamics (velocity, lineal density and supply rate) and oxygenation (Brunner et al., 2000; Ellis et al., 1990, 1992; Ellsworth et al., 1987; Klyscz et al., 1997; Pries 1988). However, not all capillaries in a given field of view are suitable for image analysis. Typically, capillary segments that are relatively straight and in sharp focus, and exhibit flow of individual RBCs that are well separated by plasma gaps, are good candidates for analysis. We have developed several image processing tools to aid in the selection of such capillaries for analysis and to obtain quick overviews of RBC flow through the microcirculation.

Methods: Burgess et al. (Microcirc. 2:75, 1995) and Burkell et al. (Annals Biomed. Eng. 24:1, 1996; J. Vasc. Res. 35:2, 1998) have previously introduced mean and variance images to aid in the selection of capillaries for analysis. We have extended their concept and developed similar two dimensional visualization techniques for studies of RBC flow through capillary networks.

Results: Five new methods of processing video data were developed. The minimum image highlights all capillaries containing RBCs in a given field of view. The maximum image identifies capillaries that exhibit high lineal density or stopped flow. The range image represents the difference between the maximum and minimum light intensity values that occur at a given pixel over a given time period, and helps to identify capillary segments that are in good focus and are perfused by RBCs and plasma. The difference image represents the cumulative sum of the square of differences in intensity values between consecutive frames and gives an indication of the frequency of passage of RBCs separated by plasma gaps. The transition image represents the number of times the intensity at a given pixel crosses a predefined threshold and indicates the number of RBCs (or trains of RBCs) that passes a given location during the observation period.

Conclusions: The above flow visualization techniques are valuable tools to aid in the study of image focus, network geometry, RBC flow paths and dynamics, that can then be used in identifying capillaries for subsequent (separate) detailed analysis to provide quantitative information about RBC flow.
Enhancement of Glucocorticoid and Mineralocorticoid Receptor Density in the Microcirculation of the Spontaneously Hypertensive Rat
Authors: DE LANO FRANK A. , SCHMID‐SCHöNBEIN GEERT W.
Published: October 2004

Objective: Elevated blood pressure and abnormal physiological parameters in the microcirculation of the spontaneously hypertensive rat (SHR) can be normalized by adrenalectomy. Thus glucocorticoids and mineralocorticoids may have major control over blood pressure status and organ injury mechanisms in SHRs. As background, this study was designed to examine the distribution of the glucocorticoid and mineralocorticoid receptors in a microvascular network.

Methods: Mature SHR and their normotensive controls, the Wistar‐Kyoto (WKY) rat, were studied. An immunohistochemical method was developed that provides a comprehensive display of the receptors in all segments of the mesentery microcirculation and the surrounding tissue parenchyma.

Results: All cells in the mesentery exhibit immunolabeling of the glucocorticoid receptor with predominant expression in the nuclei of parenchymal and endothelial cells. The mineralocorticoid receptor is expressed also in most cells of the microcirculation and adjacent parenchymal tissue. Both receptors exhibit the highest levels of immunolabel in the wall of the arterioles and venules, with lower levels in capillaries. Compared with WKY rats, the SHRs exhibit significantly enhanced density of glucocorticoid and mineralocorticoid receptors in endothelial cells of arterioles and venules as well as in parenchymal cells.

Conclusions: These results suggest that the enhanced sensitivity of the SHR to glucocorticoids and aldosterone may be in part associated with enhanced glucocorticoid and mineralocorticoid receptor densities in the microcirculation.
Gene Combination Transfer to Block Autoimmune Damage in Transplanted Islets of Langerhans
Authors: Bertera Suzanne , Alexander Angela M. , Crawford Megan L. , Papworth Glenn , Watkins Simon C. , Robbins Paul D. , Trucco Massimo
Published: October 2004

Islet transplantation therapy would be applicable to a
wider range of diabetic patients if donor islet acceptance
and protection were possible without systemic immunosuppression
of the recipient. To this aim, gene transfer
to isolated donor islets ex vivo is one method that has
shown promise. This study examines the combined effect of
selected immunomodulatory and anti‐inflammatory genes
known to extend the functional viability of pancreatic islet
grafts in an autoimmune system. These genes, indoleamine
2,3‐dioxygenase (IDO), manganese superoxide dismutase
(MnSOD), and interleukin (IL)‐1 receptor antagonist protein
(IRAP), were transferred to isolated NOD donor islets
ex vivo then transplanted to NODscid recipients and evaluated
in vivo after diabetogenic T‐cell challenge. The length
of time the recipient remained euglycemic was used to measure
the ability of the transgenes to protect the graft from
autoimmune destruction. Although the results of these cotransfections
gave little evidence of a synergistic relationship,
they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic
T cells.
Noninvasive Orthogonal Polarization Spectral Imaging as Applied to Microvascular Studies in Mice
Authors: Nivoit P. , Chevrier A. M. , Lagarde M. , Renaudin C. , Wiernsperger N.
Published: October 2004

In vivo observations of the mouse microcirculation can
hardly be performed due to technical difficulties, limiting
the knowledge that could be obtained from gene manipulated
mice models. The aim of the present study was to
check the applicability of a novel optical system, the orthogonal
polarization spectral technology, to study the mouse
microcirculation. In anaesthetized mice, the spinotrapezius
muscle microcirculation was observed in situ. The diameter
of precapillary arterioles was measured before and after
a pharmacological or hormonal stimulation. High‐contrast
images of the muscle microcirculation were obtained and
significant vasodilatation of arterioles was observed after
topical applications of acetylcholine, sodium nitroprusside,
and insulin. As compared to conventional techniques, orthogonal
polarization spectral imaging makes it possible to
assess and study microvascular beds in mice, which were inaccessible
until now, allowing the use of gene manipulated
mice to investigate, for example, the mechanisms involved
in the development of diabetic microangiopathy.
Effect of High Glucose Concentration on Collagen Synthesis and Cholesterol Level in the Phenotypic Modulation of Aortic Cultured Smooth Muscle Cells of Sand Rat (Psammomys obesus)
Authors: Bouguerra S. Aouichat , Benazzoug Y. , Bekkhoucha F. , Bourdillon M. C.
Published: October 2004

To simulate diabetic conditions, the effects of high glucose
concentration on collagen synthesis and cholesterol
level in cultured aortic smooth muscle cells of Psammomys
were investigated. For collagen biosynthesis, smooth muscle
cells (SMCs) were incubated in synthetic proliferative
phase and in postconfluent phase with  3H‐proline. Cellular
cholesterol was determined by enzymatic method. Under
high glucose concentration, the results showed morphological
modifications characterized by morphometric cellular,
nuclear, and nucleolar changes. In biochemical studies, the
authors observed an increase of free and esterified cellular
cholesterol as well as of total proteins, collagen biosynthesis,
and α1 (I+III) and α2 (I) chains of collagen contained
in the SMCs and in the extracellular matrix. These results
showed the sensitivity of Psammomys aortic SMCs to high
glucose concentration and would constitute an interesting
cellular model to study atherosclerosis pathogeny in experimental
diabetes.
Database driven test case generation for protein–protein docking
Authors: Zöllner Frank , Neumann Steffen , Kummert Franz , Sagerer Gerhard
Published: October 2004

Summary: We present a method for automatic test case generation for protein–protein docking. A consensus-type approach is proposed processing the whole PDB and classifying protein structures into complexes and unbound proteins by combining information from three different approaches (current PDB-at-a-glance classification, search of complexes by sequence identical unbound structures and chain naming). Out of this classification test cases are generated automatically. All calculations were run on the database. The information stored is available via a web interface. The user can choose several criteria for generating his own subset out of our test cases, e.g. for testing docking algorithms.

Availability:  http://bibiserv.techfak.uni-bielefeld.de/agt-sdp/

Contact:  fzoellne@techfak.uni-bielefeld.de
A simple procedure for estimating the false discovery rate
Authors: Dalmasso Cyril , Broët Philippe , Moreau Thierry
Published: October 2004

Motivation: The most used criterion in microarray data analysis is nowadays the false discovery rate (FDR). In the framework of estimating procedures based on the marginal distribution of the P-values without any assumption on gene expression changes, estimators of the FDR are necessarily conservatively biased. Indeed, only an upper bound estimate can be obtained for the key quantity π0, which is the probability for a gene to be unmodified. In this paper, we propose a novel family of estimators for π0 that allows the calculation of FDR.

Results: The very simple method for estimating π0 called LBE (Location Based Estimator) is presented together with results on its variability. Simulation results indicate that the proposed estimator performs well in finite sample and has the best mean square error in most of the cases as compared with the procedures QVALUE, BUM and SPLOSH. The different procedures are then applied to real datasets.

Availability: The R function LBE is available at http://ifr69.vjf.inserm.fr/lbe

Contact:  broet@vjf.inserm.fr
Image‐Guided Endoscopic Surgery: Results of Accuracy and Performance in a Multicenter Clinical Study Using an Electromagnetic Tracking System
Authors: Fried Marvin P. , Kleefield Jonathan , Gopal Harsha , Reardon Edward , Ho Bryan T. , Kuhn Frederick A.
Published: October 2004

Image‐guided surgery has recently been described in the literature as a useful technology for improved functional endoscopic sinus surgery localization. Image‐guided surgery yields accurate knowledge of the surgical field boundaries, allowing safer and more thorough sinus surgery. We have previously reviewed our initial experience with The InstaTrak System. This article presents a multicenter clinical study (n=55) that assesses the system's capability for localizing structures in critical surgical sites. The purpose of this paper is to present quantitative data on accuracy and performance. We describe several new advances including an automated registration technique that eliminates the redundant computed tomography scan, compensation for head movement, and the ability to use interchangeable instruments.
Interferon Gamma Expression in Human Nasal Polyps
Authors: Dellacono Frank R. , Eisma Roselle , Lafreniere Denis , Leonard Gerald , Kreutzer Donald
Published: October 2004

One feature among nasal polyps (NPs) is the predominance of lymphocytes and eosinophils. We hypothesize that elevated levels of interferon gamma (IFN‐γ) activate lymphocytes and eosinophils within the NP microenvironment. Nasal polyps were evaluated for distribution and levels of IFN‐γ specimens from 27 patients with nasal polyposis and 4 controls. Immunohistochemical study revealed IFN‐γ staining of eosinophils, glandular cells, and epithelium (27 of 27 patients). ELISA analysis indicated elevated IFN‐γ levels in total NP tissues (25.6 ± 7.23 pg/mg total protein [TP]) compared with controls (16.27 ± 6.54 pg/mg TP).

Three subpopulations were identified based on IFN‐γ levels: low IFN‐γ group (10.7 ± 5.51 pg/mg TP); medium IFN‐γ group (25.70 ± 5.90 pg/mg TP); and high IFN‐γ group(52.58 ± 10.29 pg/mg TP). The latter levels were approximately 3.5 times the control levels (P < 0.0025). Patients with previous polypectomy surgery showed higher levels of IFN‐γ compared with controls(P < 0.0423). A trend was found with increased IFN‐γ levels and allergy, asthma, and topical steroid use.
Intracellular Reservoir of Streptococcus pyogenes In Vivo: A Possible Explanation for Recurrent Pharyngotonsillitis
Authors: Österlund Anders , Popa Raul , Nikkilä Tapio , Scheynius Annika , Engstrand Lars
Published: October 2004

Numerous theories have been presented that attempt to explain the frequent recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these recurrences occur after seemingly adequate antibiotic treatment. We previously have demonstrated that S pyogenes can survive for up to 7 days intracellularly in immortalized human respiratory epithelial cells grown in an antibiotic supplemented medium. Viable S pyogenes were externalized and established an extracellular infection, whenever the extracellular antibiotic was removed. We have investigated the presence of intracellular S pyogenes in two in vivo studies using respiratory epithelial cells collected from patients with tonsillitis and the tonsils of asymptomatic carriers. Electron microscopy and immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore, intracellular S pyogenes were found in macrophage‐like cells in eight (73%) and in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes carriers. These in vivo data strongly support the hypothesis that intracellular S pyogenes can constitute a reservoir of bacteria with the potential to cause reinfections
Final Results of a Randomized Trial Comparing Chemotherapy Plus Radiotherapy With Chemotherapy Plus Surgery Plus Radiotherapy in Locally Advanced Resectable Hypopharyngeal Carcinomas
Authors: Beauvillain C. , Mahé M. , Bourdin S. , Peuvrel P. , Bergerot P. , Rivière A. , Vignoud J. , Deraucourt D. , Wesoluch M.
Published: October 2004

After neoadjuvant chemotherapy, a routine conservative approach followed by salvage surgery was evaluated in terms of local control and survival in cases of advanced potentially resectable hypopharyngeal carcinoma. Between 1985 and 1989, 92 patients with T3 or T4‐N0,N3 operable squamous cell hypopharyngeal carcinomas received three courses of neoadjuvant chemotherapy every 2 weeks involving a combination of cisplatin, 100 mg/m2, on day 1 and fluoruracil, 1 g/m2, on days 2 to 5, followed by total laryngopharyngectomy plus postoperative radiotherapy in 47 patients (arm A) or radiotherapy alone in 45 patients (arm B). Randomization was always performed prior to chemotherapy. The response rates of tumor and node to chemotherapy were, respectively, 67% in arm A versus 79% in arm B (P > 0.05) and 54% in arm A versus 73% in arm B (P > 0.05). Grade III or IV toxicity was similar, affecting 15% of patients and 7% of cycles in arm A versus 16% of patients and 6% of cycles in arm B. After a mean follow‐up of 92 months, survival was statistically better (P = 0.04) in arm A (5‐year overall survival, 37%; median survival, 40 months) than in arm B (19% and 20 months) because of a better local control rate (63% versus 39%; P < 0.01). Better results were obtained for mutilant surgery in terms of local control and overall survival, regardless of response to neoadjuvant chemotherapy.
Characterization of Novel Cell Lines From Pleomorphic Adenomas of the Parotid Gland Established in a Collagen Gel System
Authors: Steiner Melissa G. , Kuhel William I. , Carew John F. , Huo Jerry , Hoda Syed A. , Staiano‐Coico Lisa , Schley W. Shain
Published: October 2004

The pathobiology of salivary neoplasms can best be studied in a model system that reflects the native state of the tumor. The present study describes the use of a three‐dimensional collagen gel (organoid) system in which pleomorphic adenomas of the parotid gland were propagated in vitro. Five pleomorphic adenoma cultures were established as organoid gels and compared with touch‐preparations or cryopreserved specimens of native tumor. The organoid cultures demonstrated normal DNA content, the expression of myoepithelial cell proteins, and the production of sulfated acid mucins; these cellular and secretory features mimicked those found in the archival specimens. Further, organoid cultures of pleomorphic adenoma could be initiated after monolayer culture, demonstrating that culture on a plastic support does not alter the nature of the cells. Development of an in vitro culture system that maintains the native state of pleomorphic adenoma is an important tool for studying the pathobiology of these tumors.
Carotid Resection and Reconstruction for Advanced Cervical Cancer
Authors: Katsuno Satoshi , Ishiyama Tetsuya , Sakaguchi Masanori , Takemae Hiroki
Published: October 2004

Patients with advanced cervical cancers often have direct invasion of their carotid arteries. The prognosis for these patients with nonsurgical therapy is extremely poor. Because complete tumor removal is the only therapy that can offer these patients a chance for cure, carotid resection should be performed. We performed carotid resection and reconstruction on nine patients with advanced cervical cancers. Of these patients, none suffered from severe neurologic postoperative complications such as permanent hemiplegia. Three of the nine patients have been disease free for more than 24 months. These three patients would not have survived without carotid resection. Further study will show the usefulness of carotid resection and reconstruction in decreasing the morbidity and mortality in patients with cervical cancer involving the carotid artery.
An Increase in Laryngeal Aerosol Deposition by Ultrasonic Nebulizer Therapy With Intermittent Vocalization
Authors: Kumazawa Hirobumi , Asako Mikiya , Yamashita Toshio , Ha‐Kawa SanG Kil
Published: October 2004

In acute or chronic laryngitis as well as pharyngitis, nebulization with steroid and antibiotics is considered to be a safe and effective treatment. However, the optimal dose, frequency, duration, and method of administration by ultrasonic nebulization is not known. To evaluate whether there is continual improvement using ultrasonic nebulizer therapy, the deposition rate of aerosol particles into the upper airway was studied. We analyzed the deposition rate in the upper airway by a counting system of radioactive isotope (99mTc‐diethylene triaminepentaacetic acid; 99mTc DTPA). Volunteers in good health inhaled an aerosol containing 99mTc DTPA under various conditions of inhalation. Deep and slow inhalation at a respiratory rate of 12 breaths/minute resulted in a high deposition rate of 99mTc DTPA in the lung and a low deposition rate in the larynx. In contrast, faster inhalation at a respiratory rate of 36 breaths/minute resulted in an increase in the isotope deposition rate in the larynx. Furthermore, when the volunteers vocalized intermittently during the fast inhalation at a respiratory rate of 36 breaths/minute, the isotope deposition rate in the volunteer's larynx was higher than in all other inhalation conditions. These results suggest that fast inhalation with intermittent vocalization is one of the important inhalation methods used to improve the deposition rate of aerosol particles into the upper airway with an ultrasonic nebulizer.
Posterior Glottic Stenosis Mechanism and Surgical Management
Authors: Hoasjoe Denis K. , Franklin Scott W. , Aarstad Robert F. , Day Terry A. , Stucker Fred J.
Published: October 2004

Posterior glottic stenosis with arytenoid fixation is an uncommon complication of laryngeal injury. Though etiologies vary; the most common is prolonged intubation. Patients with this problem are tracheotomy dependent and have compromised voice production. There has been no acceptable approach to reconstruction of the larynx, the majority of patients being treated with some type of vocal fold lateralization. The success rate with this approach varies, and this procedure does not take advantage of the intact neuromuscular status of the larynx. Over the past 3 years we have utilized an alternative approach, to repair the stenosis and mobilize the arytenoids in 10 patients. Our surgical technique involves laryngeal exposure via a laryngofissure, the removal of posterior glottic cicatricial tissues, and the application of an autologous graft. Subsequently, all but one of the patients were able to be decannulated. Subjective postoperative voice analysis showed improved voice production. The pathophysiology for this disorder and a review of different treatment modalities are discussed.
Compositional Differences Between Bilateral Middle Ear Effusions in Otitis Media With Effusion: Evidence for a Different Etiology?
Authors: Johnson I. J.M. , Brooks T. , Hutton D. A. , Birchall J. P. , Pearson J. P.
Published: October 2004

The aim of this study was to clarify the site of primary pathology in otitis media with effusion. Effusions were collected from 64 children with bilateral effusions at the time of myringotomy. The rheological properties and biochemical compositions of effusions were measured for 23 pairs of effusions, and the levels of the inflammatory mediators TNFα, IL‐1β, and IL‐8 were measured in 41 pairs using specific enzyme‐linked immunosorbent assays(ELISAs). Measurements from paired ears were compared using analysis of variance (ANOVA) tests and significant differences were found for reduced specific viscosity, mucin content, protein content, and levels of IL‐8. The results demonstrate that the two ears have different immunological processes or rates of processes which might explain the significantly different rheological properties of effusions. This suggests that each ear undergoes pathological changes independently and has implications for using the opposite ear as a control in clinical trials.
Inhibition of foot-and-mouth disease virus replication by small interfering RNA
Authors: Kahana Ronen , Kuznetzova Larisa , Rogel Arie , Shemesh Mordechai , Hai Dalia , Yadin Hagai , Stram Yehuda
Published: October 2004

Foot-and-mouth disease, caused by foot-and-mouth disease virus (FMDV), is one of the most dangerous diseases of cloven-hoofed animals and is a constant threat to the dairy and beef industries in the Middle East and other regions of the world, despite intensive vaccination programmes. In this work, the ability of specific small interfering (si)RNAs to inhibit virus replication in BHK-21 cells was examined. By using bioinformatic computer programs, all FMDV sequences in public-domain databases were analysed. The analysis revealed three regions of at least 22 bp with 100 % identity in all FMDV entries. From these sequences, three specific siRNA molecules were prepared and used to test the ability of siRNAs to inhibit virus replication. By using real-time quantitative PCR to measure the amount of viral RNA in infected cells, it was shown that virus replication was inhibited in cells that were transfected with siRNAs. When viral titres were examined, 100 % inhibition of growth could be demonstrated in cells transfected with a mixture of all three anti-FMDV siRNAs, compared with control cells transfected with anti-LacZ siRNA.