bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Age-Related Cerebral White Matter Changes on the Transition to Disability – The LADIS Study: Rationale, Design and Methodology
Authors: Pantoni Leonardo , Basile Anna Maria , Pracucci Giovanni , Asplund Kjell , Bogousslavsky Julien , Chabriat Hugues , Erkinjuntti Timo , Fazekas Franz , Ferro José M. , Hennerici Michael , O’Brien John , Scheltens Philip , Visser Marieke C. , Wahlund Lars-Olof , Waldemar Gunhild , Wallin Anders , Inzitari Domenico
Published: September 2004

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65–84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.
Family History of Stroke among Mexican-American and Non-Hispanic White Patients with Stroke and TIA: Implications for the Feasibility and Design of Stroke Genetics Research
Authors: Lisabeth Lynda D. , Kardia Sharon L.R. , Smith Melinda A. , Fornage Myriam , Morgenstern Lewis B.
Published: September 2004

Family history of stroke may differ by ethnicity. This study examined the associations of ethnicity and stroke risk factors with family history of stroke using data from the Brain Attack Surveillance in Corpus Christi Project. A random sample of stroke/transient ischemic attack cases was interviewed about family history of stroke (n = 524). Thirty-six percent of the cases reported a family history of stroke, with 26% reporting a parental and 13% a sibling history. Compared to non-Hispanic whites (NHWs), Mexican-Americans (MAs) were two times (OR = 2.07; 95% CI: 1.09–3.95) more likely to have a sibling with stroke. More MAs (8.1%; 95% CI: 4.6–11.6) had living siblings with stroke compared to NHWs (1.9%; 95% CI: 0.1–3.8). Since MAs are more likely to have living siblings with stroke compared with NHWs, MAs may be a more feasible population for family stroke studies than predominantly white populations.
Familial Prion Diseases in the Basque Country (Spain)
Authors: Zarranz Juan J. , Digon Anton , Atarés Begoña , Arteagoitia José M. , Carrera Nieves , Fernández-Manchola Iñaki , Fernández-Martínez Manuel , Fernández-Maiztegui Covadonga , Forcadas Isabel , Galdos Luis , Ibáñez Agustín , Lezcano Elena , Martí-Massó José F. , Mendibe María M. , Urtasun Miguel , Uterga Juan M. , Saracibar Nieves , Velasco Fernando , González de Galdeano Luis
Published: September 2004

In 1995, a surveillance system for prion diseases was set up in the Basque Country, an autonomous region in northern Spain (2.1 million inhabitants). In the period from January 1993 to December 2003, we diagnosed 21 patients with familial prion diseases prospectively and another 4 patients retrospectively. They represent 35% of all the cases referred to the epidemiological registry. Two main possible explanations for this unusual high incidence of familial prion diseases are proposed: first, comprehensive case ascertainment by public health neurologists; second, a probable cluster of the D178N mutation within families of Basque origin related to a still unconfirmed common ancestor. Further genetic and genealogical studies should resolve this issue.
Anemia and Diabetes
Authors: Deray G. , Heurtier A. , Grimaldi A. , Launay Vacher V. , Isnard Bagnis C.
Published: September 2004

World Health Organization statistics identify 150 million people with diabetes mellitus worldwide and suggest that this figure may double by 2025. In countries with a western lifestyle, the number of patients admitted for renal replacement therapy with diabetes as a co-morbid condition has increased significantly up to three to four times in a period of 10 years. Diabetes and renal failure are thus tightly linked diseases, and so is anemia. However, whether anemia may be worsened and/or directly, at least in part, caused by diabetes is not clearly elucidated yet. In this article, we review the prevalence, pathophysiology and consequences of anemia in diabetic patients.
A Tale of Medical Shopping or the Hazards of Repetitious Cytological Screening of the Cervix
Authors: Bourgain Claire , Amy Jean-Jacques , Wallon Joëlle , Vanderlinden Sonia , van der Stehen Kris , Peeters Tony
Published: September 2004

A 65-year-old woman had on her own initiative three cervical smears taken at very short intervals. The second smear was taken only 1 day after the first one. It contained necrotic cellular material with atypia due to the scraping on the day before; it was at first mistakenly interpreted as showing malignant features. This led to the performance of various diagnostic procedures, and a considerably greater cost for the medical insurance system.
Physiological and Chronobiological Changes during Ramadan Intermittent Fasting
Authors: Roky Rachida , Houti Imad , Moussamih Samya , Qotbi Souad , Aadil Nadia
Published: September 2004

Background and Aims: During the month of Ramadan, Moslems refrain from drinking and eating between sunrise and sunset. This review aimed to analyze the effects of Ramadan fasting on physiological and behavioral variables in healthy subjects. Methods: Articles included in this paper were taken from Medline, three international congresses on health and Ramadan, and in several cases from local journals. Results: Ramadan fasting did not dramatically affect the metabolism of lipids, carbohydrates and proteins, or the daily mean of hormonal serum levels. An increase in serum urea and uric acid was frequently reported and this could be attributed to dehydration during this month. Some changes, such as the increase of HDL and apoprotein A1, and the decrease in LDL, could be beneficial for the cardiovascular system. However, the chronobiological studies have shown that Ramadan fasting affects the circadian distribution of body temperature, cortisol, melatonin and glycemia. The amplitude of most of these rhythms decreased and the acrophase shifted. Nocturnal sleep, daytime alertness and psychomotor performance were decreased. Conclusion: The major changes during Ramadan fasting are chronobiological and behavioral. They could be responsible for the high incidence of road traffic accidents and the reduction of working hours during the month of Ramadan.
Differential Gene Expression of Blood-Derived Cell Lines in Familial Combined Hyperlipidemia
Authors: Morello Fulvio , de Bruin Tjerk W.A. , Rotter Jerome I. , Pratt Richard E. , van der Kallen Carla J.H. , Hladik Gary A. , Dzau Victor J. , Liew Choong-Chin , Chen Yii-Der I.
Published: September 2004

Objectives—

The genetic background of familial combined hyperlipidemia (FCHL) is currently unclear. We propose transcriptional profiling as a complementary tool for its understanding. Two hypotheses were tested: the existence of a disease-specific modification of gene expression in FCHL and the detectability of such a transcriptional profile in blood derived cell lines.

Methods and Results—

We established lymphoblastic cell lines from FCHL patients and controls. The cells were cultured in fixed conditions and their basal expression profile was compared using microarrays; 166 genes were differentially expressed in FCHL-derived cell lines compared with controls, with enrichment in metabolism-related genes. Of note was the upregulation of EGR-1, previously found to be upregulated in the adipose tissue of FCHL patients, the upregulation of DCHR-7, the downregulation of LYPLA2, and the differential expression of several genes previously unrelated to FCHL. A cluster of potential EGR-1–regulated transcripts was also differentially expressed in FCHL cells.

Conclusion—

Our data indicate that in FCHL, a disease-specific transcription profile is detectable in immortalized cell lines easily obtained from peripheral blood and provide complementary information to classical genetic approaches to FCHL and/or the metabolic syndrome.
Sarcoplasmic Reticulum Ca
2+
Refilling Controls Recovery From Ca
2+
-Induced Ca
2+
Release Refractoriness in Heart Muscle
Authors: Szentesi Peter , Pignier Christophe , Egger Marcel , Kranias Evangelia G. , Niggli Ernst
Published: September 2004

In cardiac muscle Ca
2+
-induced Ca
2+
release (CICR) from the sarcoplasmic reticulum (SR) is initiated by Ca
2+
influx via L-type Ca
2+
channels. At present, the mechanisms underlying termination of SR Ca
2+
release, which are required to ensure stable excitation-contraction coupling cycles, are not precisely known. However, the same mechanism leading to refractoriness of SR Ca
2+
release could also be responsible for the termination of CICR. To examine the refractoriness of SR Ca
2+
release, we analyzed Na
+
-Ca
2+
exchange currents reflecting cytosolic Ca
2+
signals induced by UV-laser flash-photolysis of caged Ca
2+
. Pairs of UV flashes were applied at various intervals to examine the time course of recovery from CICR refractoriness. In cardiomyocytes isolated from guinea-pigs and mice, β-adrenergic stimulation with isoproterenol-accelerated recovery from refractoriness by ≈2-fold. Application of cyclopiazonic acid at moderate concentrations (<10 μmol/L) slowed down recovery from refractoriness in a dose-dependent manner. Compared with cells from wild-type littermates, those from phospholamban knockout (PLB-KO) mice exhibited almost 5-fold accelerated recovery from refractoriness. Our results suggest that SR Ca
2+
refilling mediated by the SR Ca
2+
-pump corresponds to the rate-limiting step for recovery from CICR refractoriness. Thus, the Ca
2+
sensitivity of CICR appears to be regulated by SR Ca
2+
content, possibly resulting from a change in the steady-state Ca
2+
sensitivity and in the gating kinetics of the SR Ca
2+
release channels (ryanodine receptors). During Ca
2+
release, the concomitant reduction in Ca
2+
sensitivity of the ryanodine receptors might also underlie Ca
2+
spark termination by deactivation.
Role for Sterol Regulatory Element-Binding Protein in Activation of Endothelial Cells by Phospholipid Oxidation Products
Authors: Yeh Michael , Cole Amy L. , Choi Jenny , Liu Yi , Tulchinsky Dmitry , Qiao Jian-Hua , Fishbein Michael C. , Dooley Alek N. , Hovnanian Talin , Mouilleseaux Kevin , Vora Devendra K. , Yang Wen-Pin , Gargalovic Peter , Kirchgessner Todd , Shyy John Y.-J. , Berliner Judith A.
Published: September 2004

Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atherosclerotic lesions, paradoxically depletes endothelial cholesterol, causing caveolin-1 internalization from the plasma membrane to the endoplasmic reticulum and Golgi, and activates sterol regulatory element-binding protein (SREBP). Cholesterol loading reversed these effects. SREBP activation resulted in increased transcription of the low-density lipoprotein receptor, a target gene of SREBP. We also provide evidence that cholesterol depletion and SREBP activation are signals for OxPAPC induction of IL-8. Cholesterol depletion by methyl-β-cyclodextrin induced IL-8 synthesis in a dose-dependent manner. Furthermore, cholesterol loading of ECs by either the cholesterol–cyclodextrin complex or caveolin-1 overexpression inhibited OxPAPC induction of IL-8. These observations suggest that changes in cholesterol level can modulate IL-8 synthesis in ECs. The OxPAPC induction of IL-8 was mediated through the increased binding of SREBP to the IL-8 promoter region, as revealed by mobility shift assays. Overexpression of either dominant-negative SREBP cleavage-activating protein or 25-hydroxycholesterol significantly suppressed the effect of OxPAPC on IL-8 transcription. A role for SREBP activation in atherosclerosis is suggested by the observation that EC nuclei showed strong SREBP staining in human atherosclerotic lesions. The current studies suggest a novel role for endothelial cholesterol depletion and subsequent SREBP activation in inflammatory processes in which phospholipid oxidation products accumulate.
Structure of Cerebral Arterioles in Mice Deficient in Expression of the Gene for Endothelial Nitric Oxide Synthase
Authors: Baumbach Gary L. , Sigmund Curt D. , Faraci Frank M.
Published: September 2004

We examined effects of pharmacological inhibition of nitric oxide synthase (NOS) and genetic deficiency of the endothelial isoform of NOS (eNOS) on structure and mechanics of cerebral arterioles. We measured pressure, diameter, and cross-sectional area (CSA) of the vessel wall (histologically) in maximally dilated cerebral arterioles in mice that were untreated or treated for 3 months with the NOS inhibitor,
N
G
-nitro-
l
-arginine methyl ester (
l
-NAME; 10 mg/kg per day in drinking water). Treatment with
l
-NAME increased systemic arterial mean pressure (SAP; 143±4 versus 121±4 mm Hg,
P
<0.05) and CSA (437±27 versus 310±34 μm
2
,
P
<0.05). These findings suggest that hypertension induced in mice by NOS inhibition is accompanied by hypertrophy of cerebral arterioles. To determine the role of the eNOS isoform in regulation of cerebral vascular growth, we examined mice with targeted disruption of one (heterozygous) or both (homozygous) genes encoding eNOS. Wild-type littermates served as controls. SAP and CSA were significantly increased in homozygous (SAP, 141±5 versus 122±3 mm Hg in wild-type mice,
P
<0.05; CSA, 410±18 versus 306±15 μm
2
in wild-type mice,
P
<0.05), but not in heterozygous (SAP, 135±4 mm Hg; CSA, 316±32 μm
2
) eNOS-deficient mice. Carotid ligation normalized cerebral arteriolar pulse pressure did not prevent increases in CSA in homozygous eNOS-deficient mice. Thus, cerebral arterioles undergo hypertrophy in homozygous eNOS-deficient mice, even in the absence of increases in arteriolar pulse pressure. These findings suggest that eNOS plays a major role in regulation of cerebral vascular growth.
Ischemic Preconditioning From Transient Ischemic Attacks?
Authors: Johnston S. Claiborne
Published: September 2004

Reduced impact of ischemia after an initial ischemic insult—ischemic preconditioning—has been demonstrated in a number of animal models. Transient ischemic attack (TIA) may produce ischemic preconditioning in people who have a subsequent stroke within days of an initial ischemic insult. We performed a cohort study of all 1707 patients given a diagnosis of TIA by an emergency department physician in 1 of 16 hospitals in a managed care plan in Northern California from March 1997 to February 1998. We evaluated the impact of the timing and duration of TIA on disability in a cohort of 180 patients with TIA and subsequent ischemic stroke within 90 days of the TIA. There was no association between duration of TIA, used as a surrogate for degree of ischemia, and likelihood of disability from a subsequent stroke. Furthermore, there was no difference in rates of disability among patients with strokes occurring within 1 day, 1 to <7 days, and 7 to 90 days after the TIA. We cannot confirm results of several other studies showing an association of prior TIA with lesser stroke severity. Whether differences in underlying pathophysiology and treatment of those with prior TIA could account for differences in outcome of subsequent strokes in prior studies is unknown. Evaluating whether ischemic preconditioning occurs after TIA is extremely difficult in observational studies in humans. Given the potential hazards of inducing therapeutic transient brain ischemia in humans, a trial may not be advisable, and proof may require testing of agents that safely mimic the effects of ischemia.
UGT1A1 variation and gallstone formation in sickle cell disease
Authors: Haverfield Eden V. , McKenzie Colin A. , Forrester Terrence , Bouzekri Nourdine , Harding Rosalind , Serjeant Graham , Walker Thomas , Peto Tim E. A. , Ward Ryk , Weatherall David J.
Published: September 2004

Pigment gallstones are a common clinical complication of sickle cell (SS) disease. Genetic variation in the promoter of uridine diphosphate (UDP)–glucuronosyltransferase 1A1 (UGT1A1) underlies Gilbert syndrome, a chronic form of unconjugated hyperbilirubinemia, and appears to be a risk factor for gallstone formation. We investigated the association between UGT1A1 (TA)n genotype, hyperbilirubinemia, and gallstones in a sample of Jamaicans with SS disease. Subjects were from the Jamaican Sickle Cell Cohort Study (cohort sample, n = 209) and the Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica (clinic sample, n = 357). The UGT1A1 (TA)n promoter region was sequenced in 541 SS disease subjects and 111 healthy controls (control sample). Indirect bilirubin levels for (TA)7/(TA)7 and (TA)7/(TA)8 genotypes were elevated compared with (TA)6/(TA)6 (clinic sample, P < 10–5; cohort sample, P < 10–3). The (TA)7/(TA)7 genotype was also associated with symptomatic presentation and gallstones in the clinic sample (odds ratio [OR] = 11.3; P = 7.0 × 10–4) but not in the younger cohort sample. These unexpected findings indicate that the temporal evolution of symptomatic gallstones may involve factors other than the bilirubin level. Although further studies of the pathogenesis of gallstones in SS disease are required, the (TA)7/(TA)7 genotype may be a risk factor for symptomatic gallstones in older people with SS disease.
Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow–derived cells
Authors: Tepper Oren M. , Capla Jennifer M. , Galiano Robert D. , Ceradini Daniel J. , Callaghan Matthew J. , Kleinman Mark E. , Gurtner Geoffrey C.
Published: September 2004

Ischemia is a known stimulus for vascular growth. Bone marrow (BM)–derived endothelial progenitor cells (EPCs) are believed to contribute to new blood vessel growth, but the mechanism for this contribution is unknown. To elucidate how BM cells are able to form new blood vessels, a novel murine model of soft tissue ischemia was developed in lethally irradiated mice with BM reconstituted from either tie2/lacZ or ROSA/green fluorescent protein (GFP) mice (n = 24). BM-derived EPCs were recruited to ischemic tissue within 72 hours, and the extent of recruitment was directly proportional to the degree of tissue ischemia. At 7 days, there were persistently elevated levels of vascular endothelial growth factor (VEGF) (2.5-fold) and circulating VEGF receptor-2/CD11– (flk-1+/CD11–) cells (18-fold) which correlated with increased numbers of BM-derived EPCs within ischemic tissue. The cells were initially located extravascularly as proliferative clusters. By day 14, these clusters coalesced into vascular cords, which became functional vessels by day 21. In vitro examination of human EPCs from healthy volunteers (n = 10) confirmed that EPC proliferation, adhesion, and chemotaxis were all significantly stimulated in hypoxic conditions. We conclude that BM-derived cells produce new blood vessels via localized recruitment, proliferation, and differentiation of circulating cells in a sequence of events markedly different from existing paradigms of angiogenesis.
Endothelial dysfunction and type of cigarette smoked: the impact of ‘light’ versus regular cigarette smoking
Authors: Papamichael Christos M , Aznaouridis Konstantinos A , Stamatelopoulos Kimon S , Karatzis Emmanouil N , Protogerou Athanassios D , Papaioannou Theodoros G , Lekakis John P , Mavrikakis Myron E
Published: September 2004

Acute cigarette smoking leads to temporary endothelial dysfunction, which is an early event in atherogenesis. Sufficient data concerning the effect of cigarettes with low tar and nicotine yield are lacking. Seventeen healthy individuals (nine women, eight men, aged 27.8 3.6 years) were subjected to evaluation of endothelial function by means of endothelium-dependent, flow-mediated dilatation (FMD) of the brachial artery, before, immediately after and 30, 60 and 90 min after smoking a regular cigarette (nicotine 0.9 mg, tar 12 mg) or the corresponding ‘light’ cigarette (nicotine 0.6 mg, tar 8 mg). The following day, measurements were repeated after smoking the opposite kind of cigarette. Baseline FMD was 6.1 1.6% and 7.2 2.0% in the light and regular cigarette groups, respectively (p 1/4 NS). The overall effect of the regular cigarette over time on FMD compared with the light cigarette was significantly different (F 1/4 3.039, p 1/4 0.023). FMD was significantly depressed after smoking both types (light: F 1/4 8.192, p < 0.001; regular: F 1/4 16.698, p < 0.001). Immediately after smoking, FMD declined in both groups (light: 3.0 2.4% and regular: 1.6 3.2%, p < 0.001 and p < 0.001, respectively), and it remained significantly depressed in the regular cigarette group at 30 min (0.75 1.5%, p < 0.001) and 60 min (3.5 3.1%, p 1/4 0.024), while in the light cigarette group FMD differences were abolished at 30, 60 and 90 min after smoking. In conclusion, acute smoking of both regular and light cigarettes leads to temporary vasomotor dysfunction; its duration is shorter after smoking a ‘light’ cigarette.
The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the ‘ATTICA’ study
Authors: Chrysohoou Christina , Panagiotakos Demosthenes B , Pitsavos Christos , Zeimbekis Akis , Zampelas Antonis , Papademetriou Lambros , Masoura Constantina , Stefanadis Christodoulos
Published: September 2004

Homocysteine levels are considered, by some investigators, as an independent factor of cardiovascular disease; however, others suggest that there is not a causal relationship. The aim of this work was to investigate the associations between homocysteine levels and several lifestyle-related factors. The ATTICA study is a population-based cohort that has randomly enrolled 1128 adult men and 1154 women, stratified by age and gender, from the greater area of Athens, during 2001 2002. Among several demographic, lifestyle, clinical and biochemical characteristics, we measured total plasma homocysteine levels. For the present analysis, we excluded people who had a history of cardiovascular disease. The factors that showed the strongest relationship with homocysteine levels, in both genders, even after adjusting for several potential confounders were: cigarette smoking (p=0.03), endurance exercise (inverse, p<0.05), fruit (inverse, p=0.01) and vegetable intake (inverse, p=0.04), and alcohol (p=0.04) and coffee intake (p=0.04). In conclusion, several lifestyle-related factors seem to be associated with homocysteine levels. However, the vast majority of the associations were weak when we adjusted for other co-factors. The latter may indicate the mutual confounding effect of various socio-demographic, anthropometric and other clinical characteristics on the relationship between homocysteine and cardiovascular risk.
Mother Ireland and the revolutionary sisters
Authors: Kearns Gerry
Published: September 2004

The symbolic role of women in Irish nationalism has to some extent obscured their practical involvements. By studying some of the most prominent female nationalists, this paper shows how women often read representations of women as icons of nationhood very much against the grain of the passive interpretations favoured by later historians. The paper also shows how heavily contested was the ultimate exclusion of women from public and political spaces.
Pharmacological Inhibition of Phosphodiesterase 4 Triggers Ovulation in Follicle-Stimulating Hormone-Primed Rats
Authors: McKenna Sean D. , Pietropaolo Michael , Tos Enrico Gillio , Clark Ann , Fischer David , Kagan David , Bao Bagna , Chedrese P. Jorge , Palmer Stephen
Published: September 2004

Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides to render them biologically inactive. As such, these enzymes are critical regulators of signal transduction pathways that use cyclic nucleotides as second messengers. PDE4 is one such member that has been identified in ovarian tissue and purported to have a role in the regulation of gonadotropin action. In the present study, selective PDE4 inhibitors enhanced intracellular signaling in a human LH receptor-expressing granulosa cell line. In vivo, PDE4 inhibition in FSH-primed rats resulted in ovulation, indicating that the PDE4 inhibitors can substitute for LH and human chorionic gonadotropin (hCG) in this process. Moreover, when coadministered with a subeffective dose of hCG, PDE4 inhibitors acted synergistically to enhance the ovulation response. Inhibitors of PDE3 or PDE5 had no ovulatory effect under similar conditions. Oocytes that were ovulated after PDE4 inhibition could be fertilized in vitro at a rate similar to that of oocytes from hCG-induced ovulation. Moreover, such oocytes were fully capable of being fertilized in vivo and developing into normal live pups. These results indicate that small molecule PDE4 inhibitors may be orally active alternatives to hCG as part of a fertility treatment regimen.
Molecular Cloning and Developmental Expression of Corticotropin-Releasing Factor in the Chicken
Authors: Vandenborne Kristien , De Groef Bert , Geelissen Sofie M. E. , Boorse Graham C. , Denver Robert J. , Kühn Eduard R. , Darras Veerle M. , Van der Geyten Serge
Published: September 2004

We have characterized the structure of the chicken corticotropin-releasing factor (CRF) gene through cDNA cloning and genomic sequence analysis, and we analyzed the expression of CRF mRNA and peptide in the diencephalon of the chick throughout embryonic development. The structure of the chicken CRF gene is similar to other vertebrate CRF genes and contains two exons and a single intron. The primary structure of the mature chicken CRF peptide is identical to human and rat CRF. This is the first archosaurian CRF gene to be characterized. We used RIAs to analyze CRF peptide content in the diencephalon and the median eminence and plasma corticosterone during the last week of embryonic development. We also developed a semiquantitative RT-PCR method to analyze the expression of CRF mRNA during the same period. CRF peptide content in the diencephalon increased, whereas peptide content in the ME decreased just before hatching, suggesting that release and biosynthesis are coupled. Plasma corticosterone concentration significantly increased between embryonic d 20 and the first day post hatch. By contrast, CRF mRNA levels in the diencephalon decreased just before hatching. Changes in CRF production just before hatching may be causally related to the regulation of the thyroid and interrenal axes at this stage of chicken development.
Macrophage Migration Inhibitory Factor Is Released from Pituitary Folliculo-Stellate-Like Cells by Endotoxin and Dexamethasone and Attenuates the Steroid-Induced Inhibition of Interleukin 6 Release
Authors: Tierney Tanya , Patel Reshma , Stead Caroline A. S. , Leng Lin , Bucala Richard , Buckingham Julia C.
Published: September 2004

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by peripheral immune cells and also by endocrine cells in the anterior pituitary gland. MIF exerts its proinflammatory actions in the host-defense system by blocking the inhibitory effects of glucocorticoids on the release of other proinflammatory cytokines (e.g. IL-1, IL-6, TNFα). Reports that pituitary folliculo-stellate (FS) cells share many characteristics with immune cells led us to propose that these cells may serve as an additional source of MIF in the pituitary and that pituitary-derived MIF may act in an autocrine or paracrine manner to modulate endotoxin-induced cytokine release from FS cells. In the present study we addressed this hypothesis by using 1) immunohistochemistry to localize MIF in primary pituitary tissue and 2) well-characterized FS (TtT/GF), corticotroph (AtT20), and macrophage/monocyte (RAW 264.7) cell lines to explore the effects of CRH, endotoxin, and dexamethasone on MIF release and to examine the effects of MIF on IL-6 release. Our immunohistochemical study showed that MIF is expressed in abundance in S100-positive FS cells and also in other pituitary cell types. All three cell lines expressed MIF protein and responded to endotoxin (10–1000 ng/ml, 24 h) and dexamethasone (100 pm to 10 nm, 24 h) with concentration-dependent increases in MIF release. CRH (10–100 nm) also stimulated MIF release from AtT20 cells but, unlike endotoxin and dexamethasone, it had no effect on MIF release from TtT/GF or RAW cells. Recombinant MIF did not affect the basal release of IL-6 from TtT/GF cells; however, it effectively reversed the inhibitory effects of dexamethasone (1 nm) on the endotoxin-induced release of IL-6 from these cells. The results suggest that the FS cells are both a source of and a target for MIF and raise the possibility that MIF serves as a paracrine/autocrine factor in the pituitary gland that contributes to the protective neuroendocrine response to endotoxin.
Special Issue on Engineering Plasticity: Prediction of spring-back in anisotropic sheet metals
Authors: Nguyen V T , Chen Z , Thomson P F
Published: September 2004

Constitutive equations for plane stress problems based on the modified form of a non-quadratic yield criterion suitable for aluminium alloy sheet were derived to account for the Bauschinger effect (BE). Numerical predictions of spring-back based on the original yield function and its modified form were performed and compared with the results of draw-bending tests. The results show the necessity of including the BE in the constitutive equations to enhance the accuracy in predicting spring-back.
Design of a multi-punching system based on a locking mechanism
Authors: Nandi A K
Published: September 2004

In the jacquard weaving system, more than 10 000 cards having multiple holes thereon in a particular way are required to produce a pattern on woven cloth. To make these kinds of selective hole, which are based on the type of pattern, is cumbersome and time consuming. In order to solve this problem, in this paper, a locking mechanism is presented on the basis of which a multi-punching system is designed to create selective holes. Fundamentally, a locking mechanism is used to lock or unlock a component (tool) in order to perform a specific operation. Based on the concept of a locking mechanism, it is possible to integrate a mechanical system with computer in conjunction with electronic/pneumatic devices. In the present study, a locking pin with two springs is used to perform the locking operation. The basic advantage of the proposed locking mechanism is simple in structure and more rigid. A multi-punching system is developed here, incorporating the concept of proposed locking mechanism, which is finally integrated with a computer. The developed technology is successfully implemented in the jacquard weaving system for making punched cards that may be used in different forms for other applications such as turnpike toll receipts and automatic voting systems.
On the State-Space Representation of Local Affine Models in Takagi–Sugeno–Kang Fuzzy Systems (Zur Zustandsdarstellung von Takagi–Sugeno–Kang-Fuzzy-Systemen mit Lokal Affinen Modellen)
Authors: Kroll Andreas
Published: September 2004

Considering the constant terms in the local models of dynamic Takagi–Sugeno–Kang fuzzy models can provide for improved prediction quality. However, the constant terms have typically not been treated analytically in analysis and controller design. In this paper, minimal state-space representations are derived from local affine input/output models for usage in TSK fuzzy models. Transformation algorithms for structure, parameters and initial values are proposed.
Taiwan's National Identity Politics and the Prospect of Cross-Strait Relations
Authors: Chu Yun-han
Published: September 2004

Neither principled believers in independence nor principled believers in unification are numerous enough to give any elected Taiwanese leader a clear mandate for imposing a solution on the question of national identity anytime soon. The existence of a large number of non-committed rationalists would, in the short run, mitigate the polarized conflict and could, over the long run, shift the political equilibrium in either direction, depending on changing external conditions.
Taiwan's Political Parties and National Identity: The Rise of an Overarching Consensus
Authors: Schubert Gunter
Published: September 2004

National identity is still one of the most contentious issues in present-day Taiwan. At the surface level, the confrontation between the “pan-blue” and “pan-green” party camps suggests the existence of competing and irreconcilable national identities. However, the overall quest for Taiwanese sovereignty against Beijing's insistence on the “one country, two systems” formula suggests the rise of an overarching consensus between all political parties that reflects the fact that a Taiwanese nation already exists. Although civic in nature, this nation may soon close ranks against the idea of “one China” if Beijing does not compromise on the issue of sovereignty.
THE NEW ERA AND THE NEW WOMAN
Authors: CLEMENTS K. A.
Published: September 2004

Lou Henry Hoover, wife of Herbert Hoover, demonstrated the strengths and limitations of the expanded social de�nition of womanhood that had been won by reformers during the Progressive Era and World War I. As a leader of several business and women's social welfare organizations, she urged young women to follow her example in seeking professional education and careers as well as upholding traditional domestic roles. Protected by wealth and social status from the most burdensome aspects of domesticity, her public position emphasized the opportunities but understated problems faced by the "new women" in the 1920s and later generations.
SING SHEN VS. SOUTHWOOD
Authors: BROOKS C.
Published: September 2004

In 1952 Chinese immigrant Sing Sheng encountered racial discrimination when he tried to purchase a home in the all-white South San Francisco housing tract of Southwood. Sheng, believing that racism could not be the majority sentiment in a democracy, asked white Southwood residents to vote to accept or reject his family. The Shengs lost the unof�cial referendum, but it became national news and created immense sympathy for the family. Many white Americans claimed that housing discrimination against Asian Americans could in�uence Asian nations to reject democracy and embrace communism. The Sheng affair and similar incidents demonstrate that the Cold War improved housing opportunities for California's Asian Americans, even though many whites perceived them as foreign and continued to discriminate against blacks and Mexican Americans.
About \( L^{p} \) estimates for the spatially homogeneous Boltzmann equation
Authors: Desvillettes Laurent , Mouhot Clément
Published: September 2004

For the homogeneous Boltzmann equation with (cutoff or noncutoff) hard potentials, we prove estimates of propagation of

L^{p}

norms with a weight

(1 + |x|^{2})^{q/ 2}

(

1 < p < + \infty

,

q \in \mathbb{R}_{ + }

large enough), as well as appearance of such weights. The proof is based on some new functional inequalities for the collision operator, proven by elementary means.

On prouve la propagation de normes

L^{p}

avec poids

(1 + |x|^{2})^{q/ 2}

et l'apparition de tels poids pour l'équation de Boltzmann homogène dans le cas des potentiels durs (avec ou sans troncature angulaire). La démonstration est basée sur de nouvelles inégalités fonctionnelles pour l'opérateur de collision, que l'on prouve par des moyens élémentaires.
Routine outcome monitoring in clinical practice: service and non-service costs of psychiatric patients attending a Community Mental Health Centre in Italy
Authors: Percudani Mauro , Barbui Corrado , Beecham Jennifer , Knapp Martin
Published: September 2004

Objective.

– This study estimated service and non-service costs in a random sample of patients attending a community psychiatric mental health centre in Italy.

Methods

– A randomly selected sample of patients identified during 1 week of routine clinical activity was enrolled. Information was collected using the Italian-language checklistQuestionario Economico per l’attività clinica dei Servizi Psichiatrici(QESP). Costs were classified in two categories: service costs (from the provision of services) and non-service costs (loss of productivity and informal care).

Results.

– One hundred and twenty patients were included. Patients suffering from schizophrenia and related disorders (n = 50) had a mean age of 44.5 years (S.D. 12.9), and patients with other diagnoses (n = 70) had a mean age of 44.9 years (S.D. 14.8). More patients in the schizophrenia group were single, living alone, had a low educational level and a higher unemployment rate. In patients suffering from schizophrenia, the monthly service cost per patient was nearly double that for patients with other diagnoses. Non-service costs associated with patients’ lack of job opportunities were more than three times higher for patients with schizophrenia. Non-service costs associated with patients’ and care-givers’ time off work were similar in the two groups. In the multivariate analysis, being unemployed was associated with higher service costs. Younger age, length of illness and diagnosis of schizophrenia were determinants of higher non-service costs. The latter three independent variables were also associated with overall (service and non-service) costs.

Conclusion.

– The present study estimated service and non-service costs under routine circumstances to provide information on costs that community psychiatric services, patients and care-givers sustain when dealing with psychiatric problems.
Seasonal variability of epibenthic communities in different areas of the southern North Sea
Authors: Reiss Henning , Kröncke Ingrid
Published: September 2004

Between November 2000 and May 2002, epibenthos was sampled monthly with a 2-m beam trawl at three stations along a transect from the southern German Bight towards the northeastern part of the Dogger Bank (North Sea) in order to investigate the seasonal variability of the epibenthic communities. The stations were chosen to reflect a gradient in the hydrigraphic regime, organic matter supply, and fishing effort. The epibenthic community of the southern German Bight was characterized by high biomass and abundance, dominated by Asterias rubens and Ophiura albida. In contrast, at the northern stations in the Oyster Ground and at the Dogger Bank, epibenthic biomass and abundance were substantially lower and the dominant species were mainly crustaceans such as Corystes cassivelaunus, Liocarcinus holsatus, and Pagurus bernhardus. In terms of seasonal variability, mean abundance and biomass in the southern German Bight showed highest values in the summer months and lowest values in the winter months. A similar pattern, but less distinct, was observed in the Oyster Ground. But at the Dogger Bank the pattern was different, with highest abundance and biomass values in the winter months. The differences in spatial and temporal patterns are discussed in relation to differences in temperature, thermal stratification and fishing effort at the three study sites.
Stock structure of Atlantic cod (Gadus morhua) in West Greenland waters: implications of transport and migration
Authors: Storr-Paulsen Marie , Wieland Kai , Hovgård Holger , Rätz Hans-Joachim
Published: September 2004

Atlantic cod in West Greenland waters have varied greatly in abundance and distribution in the past decades. Strong year classes yielded good catches inshore and offshore in the late 1980s, but since then cod have been nearly absent offshore and the inshore fishery has been depressed, though there has been a small increase inshore over the past few years. Different components contribute to the Greenland cod stock, and re-analysed tagging experiments indicate that migration behaviour differs between them. Inshore cod are sedentary, with almost no migration between different fjord systems. In contrast, there are many cases of alongshore migration of cod tagged on the offshore fishing banks. Further, observations have been made of occasional migrations from offshore to inshore, notably so in years of good recruitment originating from Icelandic waters.
The effect of neonatal handling on adult feeding behavior is not an anxiety‐like behavior
Authors: Silveira P.P. , Portella A.K. , Clemente Z. , Gamaro G.D. , Dalmaz C.
Published: September 2004

Brief periods of handling during the neonatal period have been shown to have profound and long‐lasting physiological consequences. Previous studies performed in our laboratory have demonstrated that handling the pups during the neonatal period leads to increased sweet food ingestion in adult life. The objective of this study is to verify if this effect could be explained by the enhanced anxiety levels in these animals. Litters were divided in: (1) intact; (2) handled (10 min in an incubater/day) and (3) handled + tactile stimulation (10 min/day). Procedures were performed on days 1–10 after birth. When adults, rats were tested in the elevated plus maze apparatus, light dark exploration test and open field test. They were also tested for sweet food ingestion, being injected with 2 mg/kg diazepam or vehicle 60 min before the test. Handling and handling + tactile stimulation do not alter performance in the plus maze test, but handled rats presented more crossings in the light/dark exploration test and open field (two‐way ANOVA). Females also spent more % time in the open arms in the plus maze and more time in the lit compartment in the light/dark test, presenting more crossings in both tests. Both treated rats (handled and handled + tactile stimulation groups) consumed more sweet food than intact ones (two‐way ANOVA). When diazepam was injected prior to the measurement of sweet food ingestion, there was no effect of the drug. We suggest that handling during the neonatal period leads to plastic alterations in the central nervous system of these animals, causing an increased ingestion of palatable food in adult life, and this alteration does not express an anxiety‐like behavior.
LEAPT: Lectin-directed enzyme-activated prodrug therapy
Authors: Robinson Mark A. , Charlton Stuart T. , Garnier Philippe , Wang Xiang-tao , Davis Stanley S. , Perkins Alan C. , Frier Malcolm , Duncan Ruth , Savage Tony J. , Wyatt David A. , Watson Susan A. , Davis Benjamin G.
Published: September 2004

Targeted drug delivery to selected sites allows reduced toxicity, enhanced efficiency and interchangeable target potential [Langer, R. (2001)Science293, 58-59 and Molema, G. & Meijer, D. K. F., eds. (2001)Drug Targeting(Wiley-VCH, Weinheim, Germany)]. We describe a bipartite drug-delivery system that exploits (i) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme conjugates to specific, predetermined cell types followed by (ii) administration of a prodrug activated by that predelivered enzyme at the desired site. The carbohydrate structure of an α-l-rhamnopyranosidase enzyme was specifically engineered through enzymatic deglycosylation and chemical reglycosylation. Combinedin vivoandin vitrotechniques (gamma scintigraphy, microautoradiography and confocal microscopy) determined organ and cellular localization and demonstrated successful activation of α-l-rhamnopyranoside prodrug. Ligand competition experiments revealed enhanced, specific localization by endocytosis and a strongly carbohydrate-dependent, 60-fold increase in selectivity toward target cell hepatocytes that generated a >30-fold increase (from 0.02 to 0.66 mg) in protein delivered. Furthermore, glycosylation engineering enhanced the serum-uptake rate and enzyme stability. This created enzyme activity (0.2 units in hepatocytes) for prodrug therapy, the target of which was switched simply by sugar-type alteration. The therapeutic effectiveness of lectin-directed enzyme-activated prodrug therapy was shown through the construction of the prodrug of doxorubicin, Rha-DOX, and its application to reduce tumor burden in a hepatocellular carcinoma (HepG2) disease model.
Local graph alignment and motif search in biological networks
Authors: Berg Johannes , Lässig Michael
Published: September 2004

Interaction networks are of central importance in postgenomic molecular biology, with increasing amounts of data becoming available by high-throughput methods. Examples are gene regulatory networks or protein interaction maps. The main challenge in the analysis of these data is to read off biological functions from the topology of the network. Topological
motifs
, i.e., patterns occurring repeatedly at different positions in the network, have recently been identified as basic modules of molecular information processing. In this article, we discuss motifs derived from families of mutually similar but not necessarily identical patterns. We establish a statistical model for the occurrence of such motifs, from which we derive a scoring function for their statistical significance. Based on this scoring function, we develop a search algorithm for topological motifs called
graph alignment
, a procedure with some analogies to sequence alignment. The algorithm is applied to the gene regulation network of
Escherichia coli
.