bluuebunny/crossref_metadata_2025 huggingface dataset:
Caffeine increases exogenous carbohydrate oxidation during exercise
Authors: Yeo Sophie E. , Jentjens Roy L. P. G. , Wallis Gareth A. , Jeukendrup Asker E.
Published: April 2005

Both carbohydrate (CHO) and caffeine have been used as ergogenic aids during exercise. It has been suggested that caffeine increases intestinal glucose absorption, but there are also suggestions that it may decrease muscle glucose uptake. The purpose of the study was to investigate the effect of caffeine on exogenous CHO oxidation. In a randomized crossover design, eight male cyclists (age 27 ± 2 yr, body mass 71.2 ± 2.3 kg, maximal oxygen uptake 65.7 ± 2.2 ml·kg−1·min−1) exercised at 64 ± 3% of maximal oxygen uptake for 120 min on three occasions. During exercise subjects ingested either a 5.8% glucose solution (Glu; 48 g/h), glucose with caffeine (Glu+Caf, 48 g/h + 5 mg·kg−1·h−1), or plain water (Wat). The glucose solution contained trace amounts of [U-13C]glucose so that exogenous CHO oxidation could be calculated. CHO and fat oxidation were measured by indirect calorimetry, and13C appearance in the expired gases was measured by continuous-flow IRMS. Average exogenous CHO oxidation over the 90- to 120-min period was 26% higher ( P < 0.05) in Glu+Caf (0.72 ± 0.04 g/min) compared with Glu (0.57 ± 0.04 g/min). Total CHO oxidation rates were higher ( P < 0.05) in the CHO ingestion trials compared with Wat, but they were highest when Glu+Caf was ingested (1.21 ± 0.37, 1.84 ± 0.14, and 2.47 ± 0.23 g/min for Wat, Glu, and Glu+Caf, respectively; P < 0.05). There was also a trend ( P = 0.082) toward an increased endogenous CHO oxidation with Glu+Caf (1.81 ± 0.22 g/min vs. 1.27 ± 0.13 g/min for Glu and 1.12 ± 0.37 g/min for Wat). In conclusion, compared with glucose alone, 5 mg·kg−1·h−1of caffeine coingested with glucose increases exogenous CHO oxidation, possibly as a result of an enhanced intestinal absorption.
Effects of selective hypoglossal nerve stimulation on canine upper airway mechanics
Authors: Yoo Paul B. , Durand Dominique M.
Published: April 2005

Electrical stimulation of the hypoglossal (XII) nerve has been demonstrated as an effective approach to treating obstructive sleep apnea. The physiological effects of conventional modes of stimulation (i.e., genioglossus activation or whole XII nerve stimulation), however, have yielded inconsistent and only partial alleviations of hypopneic or apneic events. Although selective stimulation of the multifasciculated XII nerve offers many stimulus options, it is not clear how these will functionally affect the upper airway (UAW). To study these effects, animal experiments in eight beagles were performed to investigate changes in the UAW resistance and critical pressure during simulated expiration ( n = 4) and inspiration ( n = 4). During expiration, nonselective XII nerve stimulation yielded the greatest improvement in UAW resistance (−0.66 ± 0.11 cmH2O·l−1·min−1), compared with that for selective activation of the geniohyoid (−0.29 ± 0.09 cmH2O·l−1·min−1), genioglossus (−0.31 ± 0.12 cmH2O·l−1·min−1), and hyoglossus/styloglossus (0.37 ± 0.06 cmH2O·l−1·min−1) muscles. For simulated inspiration, on the other hand, only whole XII nerve stimulation (−0.9 ± 0.4 cmH2O) and coactivation of the genioglossus + hyoglossus/styloglossus muscles (−1.18 ± 0.6 cmH2O) produced significant ( P < 0.05) improvements in UAW stability (i.e., lowered critical pressure), compared with baseline (−0.52 ± 0.32 cmH2O). The results of this study suggest that a multicontact nerve electrode can be used to achieve both UAW dilation and patency, comparable to that obtained with nonselective stimulation, by selectively activating the various branches of the XII nerve.
Computational simulation of human upper airway collapse using a pressure-/state-dependent model of genioglossal muscle contraction under laminar flow conditions
Authors: Huang Yaqi , Malhotra Atul , White David P.
Published: April 2005

A three-element, pressure- and state (sleep and wake) -dependent contraction model of the genioglossal muscle was developed based on the microstructure of skeletal muscle and the cross-bridge theory. This model establishes a direct connection between the contractile forces generated in muscle fibers and the measured electromyogram signals during various upper airway conditions. This effectively avoids the difficulty of determining muscle shortening velocity during complex pharyngeal conditions when modeling the muscle's contractile behaviors. The activation of the genioglossal muscle under different conditions was then simulated. A sensitivity analysis was performed to determine the effects of varying each modeled parameter on the muscle's contractile behaviors. This muscle contraction model was then incorporated into our anatomically correct, two-dimensional computational model of the pharyngeal airway to perform a finite-element analysis of air flow, tissue deformation, and airway collapse. The model-predicted muscle deformations are consistent with previous observations regarding upper airway behavior in normal subjects.
Effects of a 6-mo endurance-training program on venous compliance and maximal lower body negative pressure in older men and women
Authors: Hernandez Juliane P. , Franke Warren D.
Published: April 2005

Aging and chronic exercise training influence leg venous compliance. Venous compliance affects responses to an orthostatic stress. The extent to which exercise training in a previously sedentary older population will affect venous compliance and tolerance to the simulated orthostatic stress of maximal lower body negative pressure (LBNP) is unknown. The purpose of this investigation is to determine the influence of a 6-mo endurance-training program on calf venous compliance and responses and tolerance to maximal LBNP in older men and women. Twenty participants (exercise group: n = 10, 5 men, 5 women; control group: n = 10, 6 men, 4 women; all >60 yr) underwent graded LBNP to presyncope or 4 min at −100 mmHg before and after a 6-mo endurance-training program. Utilizing venous occlusion plethysmography, calf venous compliance was determined in both groups using the first derivative of the pressure-volume relation during cuff pressure reduction before training, at 3 mo, and at the end of the training program. The exercise group improved their fitness with the 6-mo endurance-training program, whereas the control group did not change (14 ± 3 vs. <1 ± 2%; P < 0.05). LBNP tolerance did not differ between groups or across trials ( P = 0.47). Venous compliance was not different between groups or trials, either initially or after 3 mo of endurance training, but tended to be greater in the exercise group after 6 mo of training ( P = 0.08). These data suggest that a 6-mo endurance-training program may improve venous compliance without affecting tolerance to maximal LBNP in older participants.
Pulmonary impedance and alveolar instability during injurious ventilation in rats
Authors: Allen Gilman B. , Pavone Lucio A. , DiRocco Joseph D. , Bates Jason H. T. , Nieman Gary F.
Published: April 2005

The mechanical derangements in the acutely injured lung have long been ascribed, in large part, to altered mechanical function at the alveolar level. This has not been directly demonstrated, however, so we investigated the issue in a rat model of overinflation injury. After thoracotomy, rats were mechanically ventilated with either 1) high tidal volume (Vt) or 2) low Vt with periodic deep inflations (DIs). Forced oscillations were used to measure pulmonary impedance every minute, from which elastance ( H) and hysteresivity (η) were derived. Subpleural alveoli were imaged every 15 min using in vivo video microscopy. Cross-sectional areas of individual alveoli were measured at peak inspiration and end exhalation, and the percent change was used as an index of alveolar instability (%I-EΔ). Low Vt never led to an increase in %I-EΔ but did result in progressive atelectasis that coincided with an increase in H but not η. DI reversed atelectasis due to low Vt, returning H to baseline. %I-EΔ, H, and η all began to rise by 30 min of high Vt and were not reduced by DI. We conclude that simultaneous increases in both H and η are reflective of lung injury in the form of alveolar instability, whereas an isolated and reversible increase in H during low Vt reflects merely derecruitment of alveoli.
Toward a Life Span Theory of Close Relationships: The Affective Relationships Model
Authors: Takahashi Keiko
Published: April 2005

This article addresses how close relationships can be conceptualized so that they can be accurately understood over the life span. First, two typical clusters of theories of close relationships, the attachment theory and the social network theory, are compared and discussed with regard to their fundamental but controversial assumptions regarding the scope of lifelong development. Second, previous research into close relationships among mature adults is reviewed. Third, a new social network model, the affective relationships model, and its assessment instrument are proposed. This model describes the nature of individual close relationships consisting of multiple significant others, and condenses the complexity of each social network by typological classifications. Fourth, new evidence based on the model is reviewed. Finally, fundamental assumptions about close relationships and emerging topics for future studies are discussed.
Effects of a Long-Term Dietary Xylitol Supplementation on Collagen Content and Fluorescence of the Skin in Aged Rats
Authors: Mattila Pauli T. , Pelkonen Päivi , Knuuttila Matti L.E.
Published: April 2005

Background: Dietary xylitol has been shown to increase the amounts of newly synthesized collagen, and to decrease fluorescence of the collagenase-soluble fraction in the skin of both healthy and diabetic rats. As in diabetic rats, a decreased rate of collagen synthesis and increased collagen fluorescence has also been detected in the skin of aged rats. We hypothesize that dietary xylitol supplementation may protect against these changes during aging. Objective: The purpose of the present study was to investigate whether a long-term dietary supplementation can protect against the decrease in the amounts of newly synthesized collagen, and against the increase in fluorescence in the collagenase-soluble fraction in the skin of aged rats. Methods:Twenty-four male Sprague-Dawley rats were used in the study. After weaning, the rats were divided into 2 groups of 12 animals. The rats in the control group were fed a basal RM1 diet, while the rats in the experimental group were fed the same diet supplemented with 10% xylitol. After 20 months, the rats were killed and pieces of skin from their dorsal areas were excised. The thickness of the samples was measured with a micrometer screw gauge. The collagen contents of rat skin were measured as hydroxyproline, and glycosylation as fluorescent intensity of collagen. Statistical significances of the differences between the groups were determined using the unpaired t test. Results: No general side effects were detected in the rats during the experimental period. The skin of the xylitol-fed rats was a little thicker than that of the control rats. The hydroxyproline content of the acid-soluble fraction was significantly greater in the xylitol group as compared to the controls. However, there were no significant differences in the hydroxyproline content of the collagenase-soluble fraction between the groups. The fluorescence of the collagenase-soluble fraction was significantly smaller in the xylitol-fed aged rats than in the aged rats fed the basal diet. Conclusions: The results of this study indicate that xylitol caused an increase in the amount of newly synthesized collagen and a decrease in collagen fluorescence in the skin of aged rats.
Is It Possible to Predict One-Year Survival in Centenarians? A Neural Network Study
Authors: Tafaro Laura , Cicconetti Paolo , Piccirillo Gianfranco , Ettorre Evaristo , Marigliano Vincenzo , Cacciafesta Mauro
Published: April 2005

Background: Human life expectancy is constantly increasing: the challenge for modern geriatric medicine is to identify the means to reach successfully extreme longevity. Objective: To determine which are the survival determinants in centenarians using a neural network. Methods: Sample of 110 centenarians living in Rome, mean age 101.6 years (SD = 1.8) with a sex ratio males:females of 1:3. We administered an extensive health interview (lasting 1–2 h) to each subject. The questionnaire, carried out according to the Geriatric Multidimensional Assessment, is made up of 100 items including a comprehensive health and psychosocial assessment aimed at various topics of general health and well-being and some scales used in geriatric practice. We applied several three-layered feed-forward neural networks by mixing in different ways the most important of the 100 items. Results: The most predicting powered net is the one constructed with 23 variables regarding comorbidity, cardiovascular risk factors, cognitive status, mood, functional status and social interactions, which therefore are strictly related to survival in centenarians. Conclusion: Survival in longevity is a complex biological phenomenon, which is an ideal field for using the neural network as a statistic method. The net shows us that the maintenance of social relationships even in presence of disability is of major importance for survival in the oldest old.
Cognitive Behaviour Therapy for Schizophrenia – A Review of Development, Evidence and Implementation
Authors: Tarrier Nicholas
Published: April 2005

Background: Schizophrenia and other psychotic disorders were once thought to be impervious to psychological treatments; however, there is accumulating evidence that cognitive behaviour therapy (CBT) can result in significant clinical benefit to these patients. Aim: This paper aims to describe the development and adaptation of CBT in the treatment of schizophrenia, to summarise the evidence to support CBT as a viable treatment and to outline some of the issues in ‘rolling out’ this treatment into normal clinical settings. Results: A number of clinical models of CBT have been developed and these typically consist of a variety of clinical methods with different models providing differing emphasis. Twenty controlled trials of CBT in schizophrenia in which 739 patients were included are reviewed. These studies have a mean effect size for CBT of 0.37 (SD 0.39). There is consistent evidence that CBT reduces persistent positive symptoms in chronic patients and may have modest effects in speeding recovery in acutely ill patients. The evidence of CBT reducing relapse rates is equivocal, although targeted early intervention is promising. The available evidence suggests that CBT can be utilised effectively in routine clinical practice. However, the dissemination of novel psychological treatments into widespread clinical practice is not without difficulty, and issues pertaining to the ‘roll-out’ of CBT are discussed. Conclusions: CBT as an adjunct treatment shows considerable promise for the future treatment of schizophrenia.
Efficacy and Safety of Intravenous Iron Therapy for HCV-Positive Haemodialysis Patients
Authors: Kahraman Serkan , Yilmaz Rahmi , Genctoy Gultekin , Arici Mustafa , Altun Bulent , Erdem Yunus , Yasavul Unal , Turgan Cetin
Published: April 2005

Background: Iron supplementation is the cornerstone of anaemia management in haemodialysis (HD) patients. However, efficacy and safety of intravenous (IV) iron therapy in hepatitis C virus (HCV)-positive HD patients is yet to be elucidated. Methods: Sixty-six maintenance HD patients with suboptimal response to recombinant human erythropoietin (rh-EPO) were administered IV iron. Each patient received 100 mg/session IV iron sucrose for ten consecutive HD sessions and then the dose was decreased to 50–100 mg weekly or biweekly. Patients were followed for haemoglobin (Hb), ferritin, rh-EPO dose requirements, transaminase levels, and adverse drug reactions. Results: Baseline demographic and clinical characteristics, as well as Hb, ferritin, transaminase levels, rh-EPO and iron doses were similar between HCV-positive (n = 32) and HCV-negative patients (n = 29). After 5 months of follow-up, a significant increase in ferritin and Hb levels and decrease in rh-EPO doses were observed in both groups. The incidence of adverse drug reactions was not associated with HCV serology. Significant elevation in both alanine and aspartate aminotransferase levels were detected in HCV-positive patients. Conclusion: This study has shown that IV iron administration reverses suboptimal response to rh-EPO administration in HD patients regardless of HCV serology. There is however subtle increase of transaminase levels in HCV-positive patients. Further studies are warranted to reveal the impact of variation in serum transaminase levels during IV iron administration in HCV-positive HD patients.
Renal Involvement of Non-Hodgkin’s Lymphoma and Its Prognostic Effect in Childhood
Authors: Büyükpamukçu Münevver , Varan Ali , Aydın Burça , Kale Gülsev , Akata Deniz , Yalçın Bilgehan , Akyüz Canan , Kutluk Tezer
Published: April 2005

Objective: To evaluate renal involvement in childhood lymphoma and define its prognostic effects. Patients and Methods: One hundred and four patients with non-Hodgkin’s lymphoma and renal involvement on admission to a single center between 1972 and 2003 were evaluated retrospectively. Blood urea nitrogen, serum creatinine, uric acid, electrolytes, and lactate dehydrogenase levels, as well as urinalysis, were evaluated. One or more of the following imaging methods were performed: intravenous urogram, ultrasound, computed tomography, and magnetic resonance imaging. The χ2 test was used to compare the groups. The Kaplan-Meier survival method was used to calculate survival rates, and the log-rank test was used to compare groups with respect to survival. Survival rates were also compared in two different time periods (before 1991 and after 1991). Results: There were 76 boys and 28 girls with a median age of 6 (0.9–16) years. The renal infiltration pattern was nodular in 62 patients (59.6%) and diffuse in 40 patients (38.5%). Two patients had tumoral masses that originated from their kidneys (1.9%). Renal involvement was bilateral in 75 patients (72.1%); the remaining 29 patients had unilateral involvement. The overall survival rate was 42.5% with a median follow-up of 64 months. The factors that had a statistically significant impact on survival were high creatinine (p = 0.00001) and blood urea nitrogen levels (p = 0.0001), the onset of tumor lysis syndrome (p = 0.01), and the need for dialysis (p = 0.009). The survival rate was higher in the time period after 1991 (p = 0.01). Conclusion: Impaired renal function is a poor prognostic factor for non-Hodgkin’s lymphoma. Renal function should therefore be monitored closely. Renal dysfunction caused by direct tumoral involvement may complicate therapy and shorten survival.
STAT1-Independent Down-Regulation of Interferon-Gamma-Induced Class II Transactivator and HLA-DR Expression by Transforming Growth Factor Beta-1 in Human Glomerular Endothelial Cells
Authors: Yang Won Seok , Han Nam Jeong , Kim Choung-Soo , Ahn Hanjong , Lee Sang Koo , Lee Ki-Up , Park Su-Kil
Published: April 2005

Background: The competition between STAT1 and Smad3 for a limiting amount of the nuclear protein p300, a transcriptional coactivator, was suggested to be a mechanism for the antagonism between interferon-γ (IFN-γ) and transforming growth factor-β1 (TGF-β1). We investigated the effect of TGF-β1 on IFN-γ-induced HLA-DR production in cultured human glomerular endothelial cells (HGECs), and the involvement of p300 in this process. Methods: Cell surface expression of HLA-DR and mRNA levels of HLA-DR and class II transactivator (CIITA), the master regulator of HLA-DR gene transcription, were measured by cellular ELISA and Northern blot, respectively. The levels of STAT1 and Smad3 protein were analyzed by Western blot. Nuclear binding activity of STAT1 was assessed by electrophoretic mobility shift assay. Results: IFN-γ increased the cell surface expression of HLA-DR along with increases in the mRNA levels of CIITA and HLA-DR, while these stimulatory effects of IFN-γ were down-regulated by TGF-β1. IFN-γ increased phosphorylation of STAT1 and this activation was not inhibited by TGF-β1. IFN-γ increased binding of p-STAT1 to p300, while TGF-β1 increased binding of Smad3 to p300. TGF-β1-induced Smad3 binding to p300 was inhibited by IFN-γ, whereas IFN-γ-induced p-STAT1 binding to p300 was not inhibited by TGF-β1. IFN-γ increased DNA binding activity of STAT1. Inhibition of interaction between STAT1 and p300 by addition of anti-p300 antibody to nuclear extract down-regulated DNA binding activity of STAT1. In contrast, TGF-β1 did not inhibit IFN-γ-induced STAT1 binding to DNA. Conclusions: TGF-β1 down-regulated IFN-γ-induced CIITA and HLA-DR expression in HGECs. Though there was an antagonism between IFN-γ and TGF-β1, the competition for p300 between p-STAT1 and Smad3 was not the mechanism for it.
Evaluating Associations between 5-HTTLPR Polymorphism and Alzheimer’s Disease for Korean Patients
Authors: Ha Tae Min , Cho Deuk Man , Park Sung Woo , Joo Myung Jin , Lee Bong Ju , Kong Bo Geum , Kim Jae Min , Yoon Jin Sang , Kim Young Hoon
Published: April 2005

There has been growing evidence that the serotonin (5-HT) system is important in the regulation of memory and thus might be associated with Alzheimer’s disease (AD), while research results on this issue have been inconsistent. The 5-HT system has also been suggested to be responsible for a significant portion of the behavioural aspects of AD. This study aimed to investigate the associations of the 5-HT transporter gene linked polymorphic region (5-HTTLPR) polymorphism with AD and delusional/aggressive symptoms of AD in Korean samples of 65 patients and 43 controls. The 5-HTTLPR polymorphism was neither associated with AD nor with delusional/aggressive symptoms of AD. It was suggested that phenotypic expression of the 5-HTTLPR polymorphism might be varied according to ethnic differences.
Plasma Homocysteine Concentration and Its Relation to Symptoms of Vascular Disease in Psychogeriatric Patients
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: April 2005

Background: There is a high frequency of elevated plasma total homocysteine (tHcy) concentrations in elderly patients with mental disorders. Psychogeriatric patients with a history of vascular disease exhibit a significantly higher plasma tHcy concentration than patients without vascular disease. Method: The main reason for the present study is to further investigate the association between plasma tHcy concentration and vascular disease in psychogeriatric patients. We therefore investigated 152 psychogeriatric patients and determined plasma tHcy and its most important determinants (serum folate and serum cobalamin, serum cystatin C and serum creatinine). The patients were divided into two groups according to the presence of vascular disease. Eighty-seven patients had concomitant vascular disease. We also analysed the natriuretic peptide N-terminal pro brain natriuretic peptide (NT-proBNP) and protein S-100B in serum. NT-proBNP is a marker for congestive heart failure, whereas protein S-100B is a marker for brain damage. Results: The plasma tHcy concentration is elevated in the presence of dementia or vascular disease in psychogeriatric patients. The presence of dementia or vascular disease is also associated with higher age, renal impairment and lower serum folate concentration than in patients without dementia or vascular disease. Furthermore, we observed elevated serum concentrations of NT-proBNP in patients with dementia or vascular disease as a sign of poorer cardiovascular status. Likewise, protein S-100B concentrations were elevated in patients with dementia or vascular disease, possibly indicating brain damage in these groups of patients. Conclusion: The high frequency of comorbidity of vascular disease and mental illness indicates a possibility to prevent and treat psychogeriatric disease by actively counteracting vascular disease in patients with psychogeriatric symptoms. Routine determination of NT-proBNP is valuable for obtaining information about cardiovascular status.
Test-Retest Reliability of the Dementia Rating Scale-2: Alternate Form
Authors: Schmidt Kara S. , Mattis Paul J. , Adams Jane , Nestor Paul
Published: April 2005

The purpose of this study was to examine the test-retest reliability of the newly developed Dementia Rating Scale-2: Alternate Form (DRS-2:AF) in a community-dwelling sample of older adults. Participants were administered the DRS-2:AF during two separate testing sessions; the interval between sessions was between 12 and 28 days. The stability coefficient for the Total Score was quite high (0.93), and reliability coefficients for the subscale scores ranged from adequate to high. This project provides evidence for the test-retest reliability of the DRS-2:AF. Given the need for cognitive status measures with equivalent forms, the DRS-2:AF is recommended as a reliable tool in the assessment of dementia.
Supplemental Use of Antioxidant Vitamins and Subsequent Risk of Cognitive Decline and Dementia
Authors: Maxwell Colleen J. , Hicks Matthew S. , Hogan David B. , Basran Jenny , Ebly Erika M.
Published: April 2005

There are conflicting reports about the potential role of vitamin antioxidants in preventing and/or slowing the progression of various forms of cognitive impairment including Alzheimer’s disease (AD). We examined longitudinal data from the Canadian Study of Health and Aging, a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. Our primary objective was to examine the association between supplemental use of antioxidant vitamins and subsequent risk of significant cognitive decline (decrease in 3MS score of 10 points or more) among subjects with no evidence of dementia at baseline (n = 894). We also explored the relationship between vitamin supplement use and incident vascular cognitive impairment (VCI; including a diagnosis of vascular dementia, possible AD with vascular components and VCI but not dementia), dementia (all cases) and AD. After adjusting for potential confounding factors assessed at baseline, subjects reporting a combined use of vitamin E and C supplements and/or multivitamin consumption at baseline were significantly less likely (adjusted OR 0.51; 95% CI 0.29–0.90) to experience significant cognitive decline during a 5-year follow-up period. Subjects reporting any antioxidant vitamin use at baseline also showed a significantly lower risk for incident VCI (adjusted OR 0.34, 95% CI 0.13–0.89). A reduced risk for incident dementia or AD was not observed. Our findings suggest a possible protective effect for antioxidant vitamins in relation to cognitive decline but randomized controlled trials are required for confirmation.
Association between Angiotensin-Converting Enzyme Gene Polymorphism and Alzheimer’s Disease in a Chinese Population
Authors: Zhang Jun-Wu , Li Xiao-Qing , Zhang Zhen-Xin , Chen Deng , Zhao Hua-Lu , Wu Ya-Ning , Qu Qiu-Ming
Published: April 2005

Angiotensin-converting enzyme has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the DCP1 gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer’s disease (AD), but ambiguous results have also been presented. We conducted a case-control study in a sample composed of 192 sporadic AD patients and 195 age- and sex-matched controls from Chinese Han population in Beijing and Xi’an districts to investigate the possible effect of the polymorphism. Our data revealed no association between the DCP1 polymorphism and AD risk in the total sample. There was no significant difference in the DCP1 allele or genotype frequencies between cases and controls when stratified by gender and APOE ε4 status. However, the D allele and D/D genotype were more frequent among AD patients between 66 and 70 years compared with controls (D allele: OR = 2.8, 95% CI = 1.5–5.2, p = 0.001; D/D genotype: OR = 5.9, 95% CI = 1.7–19.9, p = 0.002). Our results provided new proof that the DCP1 D allele was a probable risk factor for late-onset AD. Its role was independent and was limited to the population at a certain age.
Epithelial Defence by γδ T Cells
Authors: Kabelitz Dieter , Marischen Lothar , Oberg Hans-Heinrich , Holtmeier Wolfgang , Wesch Daniela
Published: April 2005

γδ T cells constitute a separate lineage of T lymphocytes which differ from conventional αβ T cells with regard to T cell receptor (TCR) repertoire and tissue localization. In murine skin, γδ T cells expressing a canonical Vγ5 TCR are abundant and contribute as so-called dendritic epidermal T cells to local immune surveillance. In humans, major subsets of γδ T cells are recognized on the basis of their TCR Vδ usage. While Vδ2 cells dominate in the peripheral blood, Vδ1 cells are preferentially localized in mucosal tissue including the intestinal epithelia. In this article we summarize basic features of intraepithelial γδ T cells and discuss their possible role in epithelial defence.
Isolated Type 2 Diabetes mellitus Causes Myocardial Dysfunction That Becomes Worse in the Presence of Cardiovascular Diseases: Results of the Myocardial Doppler in Diabetes (MYDID) Study 1
Authors: Govind Satish , Brodin Lars-Åke , Nowak Jacek , Quintana Miguel , Raumina Simin , Ramesh S.S. , Keshava R. , Saha Samir
Published: April 2005

Aims: Patients with type 2 diabetes mellitus (DM) often suffer disproportionately and have a worse outcome when burdened with cardiovascular complications compared with those without DM. A specific heart muscle disease reportedly caused by DM per se may explain this. We sought to investigate whether an echo Doppler diagnosis of such a myocardial disease is clinically relevant in DM with or without coexistent coronary artery disease (CAD) and/or hypertension (HTN). Subjects andMethods: Two hundred subjects (127 males, 73 females, 56 ± 10 years) including controls (n = 23), patients with HTN (n = 20), CAD (n = 35), uncomplicated DM (n = 59), DM+HTN (n = 27), DM+CAD (n = 16) and DM+CAD+HTN (n = 20) underwent tissue Doppler-enhanced dobutamine stress echocardiography. Myocardial function was assessed by measuring left ventricular myocardial peak systolic velocity (PSV) and early diastolic velocity at rest and during peak stress, besides measurements of standard Doppler variables. Results: Average left ventricular PSV at rest was significantly lower in CAD (4.7 ± 1.5) compared with controls (5.7 ± 1.2) and in DM+CAD+HTN (4.6 ± 1.4) compared with DM (5.6 ± 1.3; all p < 0.05). During peak stress, lower PSV persisted in CAD (9.5 ± 3.1) and DM+CAD+HTN (8.1 ± 2.7), while appearing de novo in DM (11.3 ± 2.6) and HTN (11.0 ± 2.3) unlike in the controls (12.5 ± 2.5; all p < 0.001). When pooled together, DM subjects with CAD and/or HTN or both had significantly lower PSV (9.1 ± 2.7) than those without (10.0 ± 2.8; p < 0.001). Early diastolic velocity response was equally lower in both groups compared with the controls. Conclusion: The results suggest that dobutamine stress unmasks myocardial functional disturbances caused by uncomplicated DM. The discrete disturbances become quantitatively more pronounced in the presence of coexistent cardiovascular diseases.
Mortality from Human Transmissible Spongiform Encephalopathies: A Record Linkage Study
Authors: Conti Susanna , Masocco Maria , Toccaceli Virgilia , Vichi Monica , Ladogana Anna , Almonti Susanna , Puopolo Maria , Pocchiari Maurizio
Published: April 2005

To evaluate the ability of the Italian Creutzfeldt-Jakob (CJD) register to detect human transmissible spongiform encephalopathy (TSE) cases we compared mortality data from the CJD register with those obtained from death certificates collected by the Italian National Census Bureau (ISTAT) between 1993 and 1999. We used the method of record linkage to compare and integrate data from these two sources. The integrated estimate of TSE deaths was 457: 183 deaths recorded by the CJD register and ISTAT, 210 cases only by the CJD register, and 64 cases only by ISTAT. The average integrated estimated mortality rate was 1.58 deaths per million people per year over the study period and peaked in 1999 at 2.13. This figure is similar to that obtained from data from the CJD register alone in the years 2000–2002. The increase in mortality rates is likely due to an improvement in case ascertainment. The misclassification of cases by ISTAT was above 50% from 1996 onward, suggesting that using only death certificates is not a reliable way to monitor TSE cases in Italy.
Morphometric Analysis of Gray Matter Volume in Demented Older Adults: Exploratory Analysis of the Cardiovascular Health Study Brain MRI Database
Authors: Rosano C. , Becker J. , Lopez O. , Lopez-Garcia P. , Carter C.S. , Newman A. , Kuller L. , Aizenstein H.
Published: April 2005

We tested the feasibility of a fully automated brain MRI voxel count technique – automated labeling pathway (ALP) – in a sample of 15 demented and 13 cognitively normal women (age 75–85 years) participating to the Cardiovascular Health Study (CHS). We hypothesized that ALP would replicate well-established findings of the anatomical correlates of dementia. In particular, we hypothesized that ALP volumetric measures would: (1) significantly differ between cognitively normal and demented women in those brain areas that are established markers for diagnosis of dementia (temporal and medial temporal lobes, hippocampus, amygdala and parahippocampus) but not in other brain areas (e.g., occipital lobe, visual cortex, motor cortex) and (2) correlate with visual ratings of brain disease which have been previously collected as part of the CHS. ALP required minimal operator intervention (input of brain images and verification of misalignments) and employed computer time of about 1 h per brain. ALP detected significant focal volumetric differences in the limbic system (p values between groups for hippocampus and parahippocampus: 0.002 and 0.005, respectively), temporal lobe (p < 0.0001) and caudate (p = 0.009), but not in other brain areas (e.g. occipital lobe, visual or motor cortex). Furthermore, ALP measures of medial temporal lobe atrophy strongly correlated with CHS visual ratings of ventricular enlargement (r2 = 0.6, p = 0.002 for medial temporal lobe). In conclusion, ALP-detected focal brain atrophy was strongly associated with dementia. Because of its fully automated design, ALP technique is an ideal candidate to assess whether volumetric measures of specific areas can discriminate dementia better than currently available measures of global brain atrophy in large epidemiological studies.
Vascular Endothelial Growth Factor Expression, Vascularization and Proliferation in Paragangliomas
Authors: Brieger Jürgen , Bedavanija Anan , Gosepath Jan , Maurer Jan , Mann Wolf J.
Published: April 2005

Objective/Hypothesis: Paragangliomas are heavily vascularized tumors, and the expression of VEGF (vascular endothelial growth factor) has been reported. The aim of our study was to extend the available database of VEGF expression in paraganglioma, to add correlated data concerning vessel density and proliferative activity, and to draw conclusions concerning the mechanisms resulting in tumor vascularization and growth. Study Design: Semiquantitative histopathologic examination of paraganglioma specimens obtained from surgical cases. Methods: Paraffin-embedded paragangliomas were analyzed by immunohistochemistry. Fourteen consecutive samples were hybridized with VEGF-, CD31- and Ki67-specific antibodies, and visualized by diaminobenzidine staining. Vessel density was determined by counting CD31-positive vessels and proliferation by quantification of Ki67-positive cells. Results: Ten out of 14 samples were positive for VEGF. In this group, vessel density was up to 5 times as high and proliferative activity was about twice as high as in the VEGF-negative group. Conclusions: We observed higher CD31 and Ki67 counts in VEGF-positive tumors, but statistical significance could not be assessed due to low sample numbers. These data might suggest a contribution of VEGF secreted by paragangliomas to tumor vascularization and possibly proliferation. The clinical impact of VEGF expression analysis has to be proven in future studies.
Cerebral Ischemic Events in Patients with Advanced Lung or Prostate Cancer
Authors: Behrendt Carolyn E. , Ruiz Rolando B.
Published: April 2005

Conventional stroke risks are thought responsible for most cerebral ischemic events (CIE) in adult cancer patients. Also suspected as a risk is cisplatin chemotherapy, alone or in combination with tumor angiogenesis inhibitor. We investigated whether treatment or tumor characteristics, independently of conventional stroke risks, are associated with CIE in a retrospective cohort study of 1,559 patients with advanced non-small cell lung cancer or hormone-refractory prostate cancer followed during 3 clinical trials of matrix metalloprotease inhibitor (prinomastat) versus placebo, with chemotherapy (gemcitabine/cisplatin, paclitaxel/carboplatin or mitoxantrone/prednisone). During 11,907 patient-months, 28 CIE (17 cerebral infarction, 11 transient ischemic attack) were diagnosed in 24 patients, all but 1 over 55 years. Neither prinomastat, platinum-based chemotherapy nor their combination was associated with CIE after age 55. However, such events were predicted by the presence of distant metastases in the liver or lungs and not in distant lymph nodes (hazard estimate 4.6, 95% CI 2.0–10.5, adjusted for conventional stroke risks). Further studies are needed to verify this preliminary finding and determine its generalizability to advanced tumors other than lung or prostate cancer.
Intraluminal Application of Vascular Endothelial Growth Factor Enhances Healing of Microvascular Anastomosis in a Rat Model
Authors: Infanger Manfred , Shakibaei Mehdi , Kossmehl Peter , Hollenberg Siri M. , Grosse Jirka , Faramarzi Shideh , Schulze-Tanzil Gundula , Paul Martin , Grimm Daniela
Published: April 2005

Background: Early reconstitution after injury to the endothelium is an important feature for reducing a number of vessel wall pathologies. We investigated the effect of vascular endothelial growth factor (VEGF) and its impact on the vascular remodeling process and reendothelialization after microsurgery. Methods and Results: Microvascular anastomosis was performed in the rat femoral artery. One group was treated with intraluminal administration of VEGF and the other with vehicle. We investigated morphological, ultrastructural and immunohistochemical changes of the vascular wall and the reendothelialization process. After 10 days, reendothelialization was significantly faster in VEGF-treated rats. Transmission electron microscopy revealed a complete healing in contrast to vehicle-treated vessels. Moreover, extracellular matrix proteins, such as fibronectin, collagen types I, III and IV, were significantly increased. Furthermore, VEGF treatment significantly induced VEGF receptor 2, flk-1, osteopontin and TGF-β1 proteins. Conclusions: Our data clearly document for the first time that intraluminal treatment with VEGF is beneficial to the healing process in vascular microsurgery. Osteopontin and TGF-β1, both induced by VEGF, may play an important role in the vascular remodeling process. Our results provide clear evidence that VEGF application may represent a useful strategy in accelerating reendothelialization and improving vascular healing after microsurgery.
Vascular Endothelial Growth Factor–Expressing Mesenchymal Stem Cell Transplantation for the Treatment of Acute Myocardial Infarction
Authors: Matsumoto Ryo , Omura Takashi , Yoshiyama Minoru , Hayashi Tetsuya , Inamoto Sakiko , Koh Ki-Ryang , Ohta Kensuke , Izumi Yasukatsu , Nakamura Yasuhiro , Akioka Kaname , Kitaura Yasushi , Takeuchi Kazuhide , Yoshikawa Junichi
Published: April 2005

Objective—Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium.

Methods and Results—The human VEGF165gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, α-smooth muscle actin–positive cells were most increased in the VEGF group.

Conclusions—This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.
New Links Between Inflammation and Thrombosis
Authors: Wagner Denisa D.
Published: April 2005

This article is a summary of the Sol Sherry Lecture of the Council on Arteriosclerosis, Thrombosis, and Vascular Biology, which was presented at the Scientific Sessions of the American Heart Association in November 2004. It highlights work from our laboratory, focusing mainly on new aspects of P-selectin and CD40L (CD154) biology and on the interplay of platelets and leukocytes in thrombosis and inflammation.
Increased Cholesterol Deposition, Expression of Scavenger Receptors, and Response to Chemotactic Factors in
Abca1
-Deficient Macrophages
Authors: Francone Omar L. , Royer Lori , Boucher Germaine , Haghpassand Mehrdad , Freeman Ann , Brees Dominique , Aiello Robert J.
Published: April 2005

Objective—

Studies in bone marrow transplanted from ATP-binding cassette transporter A1 (ABCA1)–deficient mice into normal mice provides direct evidence that the absence of leukocyte ABCA1 exerts a marked proatherogenic effect independent of changes in plasma lipids, suggesting that ABCA1 plays a key role in the regulation of cholesterol homeostasis and function of macrophages. Therefore, we examined whether the absence of ABCA1 affects the morphology, properties, and functional activities of macrophages that could be related to the development of atherosclerosis.

Methods and Results—

We conducted a series of experiments in macrophages isolated from Abca1-deficient and wild-type mice and compared several of their properties that are thought to be related to the development of atherosclerosis. Macrophages isolated from Abca1-deficient mice have an increase in cholesterol content, expression of scavenger receptors, and secretion of chemokines, growth factors, and cytokines, resulting in an increased ability to respond to a variety of chemotactic factors.

Conclusion—

Our studies indicate that the absence of ABCA1 leads to significant changes in the morphology, properties, and functional activities of macrophages. These changes, together with the proinflammatory condition present in ABCA1-deficient mice and increased reactivity of macrophages to chemotactic factors, play a key role in the development and progression of atherosclerosis.
ACAT2 Is a Target for Treatment of Coronary Heart Disease Associated With Hypercholesterolemia
Authors: Rudel Lawrence L. , Lee Richard G. , Parini Paolo
Published: April 2005

The inhibition of intracellular cholesterol esterification as a means to prevent atherosclerosis has been considered to have potential for many years. Two different ACAT enzymes were discovered about 7 years ago, and it has become clear that the two enzymes provide separate physiologic functions. Much has been learned from mice with gene deletions for either ACAT1 or ACAT2. Deletion of ACAT2 has consistently been atheroprotective whereas deletion of ACAT1 has been varyingly problematic. ACAT1 functions in converting cellular cholesterol into cholesteryl ester in response to cholesterol abundance inside the cells. In atherosclerotic lesions, where macrophages ingest excess cholesterol, the ability to esterify the newly-acquired cholesterol seems important for cell survival. Inhibition of ACAT1 may bring undesired consequences with destabilization of cellular membrane function upon cholesterol accumulation leading to macrophage cell death. In contrast, ACAT2 is expressed only in hepatocytes and enterocytes, where ACAT1 is silent, and appears to provide cholesteryl esters for transport in lipoproteins. These two cell types have an abundance of additional mechanisms for disposing of cholesterol so that depletion of ACAT2 does not signal apoptosis. At the present time, the bulk of the available data suggest that the strategy seeming to bear the most potential for treatment of coronary heart disease associated with hypercholesterolemia would be to specifically inhibit ACAT2.
Relation of Body Mass Index and Insulin Resistance to Cardiovascular Risk Factors, Inflammatory Factors, and Oxidative Stress During Adolescence
Authors: Sinaiko Alan R. , Steinberger Julia , Moran Antoinette , Prineas Ronald J. , Vessby Bengt , Basu Samar , Tracy Russell , Jacobs David R.
Published: April 2005

Background—

This study assessed the relation of fatness and insulin resistance and their interaction with cardiovascular risk factors, inflammatory factors, and oxidative stress in thin and heavy adolescents.

Methods and Results—

Euglycemic insulin clamp studies were performed on 295 (169 male, 126 female) adolescents (mean±SE age, 15±0.1 years). Comparisons were made between (1) heavy and thin adolescents; (2) insulin-sensitive and insulin-resistant adolescents; and (3) thin insulin-sensitive (T-IS), thin insulin-resistant (T-IR), heavy insulin-sensitive (H-IS), and heavy insulin-resistant (H-IR) adolescents. Summed
z
scores were used to determine clustering of risk factors (fasting insulin, triglycerides, HDL-C, and systolic blood pressure [SBP]) among the groups. SBP, triglycerides, and fasting insulin were significantly higher and HDL-C significantly lower in the heavy adolescents. Fasting insulin and triglycerides were significantly higher and HDL-C significantly lower in the insulin-resistant adolescents. Among the 4 groups, the risk factors and cluster score followed a pattern of risk as follows: T-IS<T-IR<H-IS<H-IR, with H-IR significantly greater than the other groups and showing an interaction between fatness and insulin resistance.

Conclusions—

These results show the significant association of both fatness and insulin resistance and their significant interaction with cardiovascular risk factors in adolescence. The finding that insulin resistance may be acting interactively with fatness suggests that interventions directed at insulin resistance in addition to weight loss may be required to alter early development of cardiovascular risk.