bluuebunny/crossref_metadata_2025 huggingface dataset:
New Diagnostic Approaches for Early Detection of Gastric Cancer
Authors: Sugano Kentaro , Sato Kiichi , Yao Kenshi
Published: April 2005

Detection of gastric cancer in early stages is vitally important for ascertaining better prognosis and quality of life for the patients. Therefore, every endoscopist should be trained to master enough diagnostic skills to identify early gastric cancer that often shows minimal alteration from the surrounding mucosa, easily evading detection. For the first step, it is essential that endoscopists understand the normal gastric mucosa as well as the mucosal changes caused by chronic H. pylori infection, a high-risk condition for the development of gastric cancer. Once a suspicious lesion is identified, use of a dye-spraying method may be useful to clarify structural alteration caused by neoplastic changes and facilitate the biopsy sampling. Development of zoom (magnifying) endoscopy enabling 80× magnification with a one-touch switch from conventional endoscopic observation helps to identify the detailed surface structure as well as the vascular architecture of the mucosa without tissue biopsy. Combined with chromoendoscopy, this powerful endoscopic method can be used to identify small cancer foci or delineate the margin of early gastric cancer that can be treatable by mucosal dissection. Other new modalities using a variety of optical devices have been developed but the real value of their utility still remains to be proven in the actual clinical settings.
Gene Therapy and Virotherapy of Gastric Cancer: Preclinical Results and Clinical Developments
Authors: Heideman Daniëlle A.M.
Published: April 2005

Despite advances in current treatment modalities, the clinical outcome of gastric cancer remains dismal. New treatment modalities are urgently required to improve the prognosis of patients with gastric cancer. Cancer gene therapy and virotherapy comprise a potential category of new therapeutics and will be discussed in this review. To date, various gene therapy strategies have been developed, but first clinical trials reported only limited therapeutic efficacy as a result of limited gene transfer efficiency. Consequently, targeted viral vectors for enhanced delivery of transgenes to tumor cells and replicative viral systems designed to replicate selectivelyin malignant tissue were developed. Replication-selective oncolytic viral vectors have the advantage over non-replicative systems to cause pronounced bystander effect via self-perpetuating infection of adjacent cells after cytolysis of primary targeted cells. So far, clinical studies on virotherapy showed encouraging results; especially promising are combinations of virotherapy with current modes of treatment like chemo- and radiotherapy, or insertion of therapeutic genes in the viral genome such as combination with enzyme-prodrug therapy. Further research aiming to enhance anti-tumor efficacy and to improve selectivity of infection and replication, will eventually lead to full realization of the therapeutic potential of (replicating) viral vector systems for gastric cancer.
Down-Regulation of Secretory Leukocyte Protease Inhibitor Expression in Gastric Mucosa Is a General Phenomenon in Helicobacter pylori-Related Gastroduodenal Diseases
Authors: Wex Thomas , Sokic-Milutinovic Aleksandra , Todorovic Vera , Bjelovic Milos , Milosavljevic Tomica , Pesko Predrag , Malfertheiner Peter
Published: April 2005

Background: Secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein of the gastric mucosa exerting anti-microbial and anti-inflammatory effects. Recently, a local down-regulation of antral SLPI expression in Helicobacter pylori (Hp)-infected healthy volunteers was demonstrated. Aim: To analyze mucosal SLPI expression in patients with various gastroduodenal disorders. Methods: The prospective study included 90 patients with following gastroduodenal disorders diagnosed: gastric cancer (GC, n = 22), duodenal ulcer (DU, n = 17), Hp-positive dyspeptic patients (NUD, n = 31) and Hp-negative NUD (n = 20). During esophagogastroduodenoscopy, biopsies were taken each from antrum, corpus and tumor. SLPI expression was analyzed by quantitative RT-PCR and ELISA. Results: Antral SLPI levels were reduced in all Hp-infected patients (NUD, DU, GC) by about 75% (1,494–1,826 pg/50 µg protein) compared to Hp-negative NUD (6,563 pg/50 µg protein, p < 0.001, ANOVA). Tumor tissue had twofold higher SLPI levels than surrounding tumor-free gastric mucosa (3,900 vs. 1,826 pg/50 µg protein, p = 0.013), but revealed reduced SLPI levels compared to Hp-negative NUD patients (p = 0.067). No differences were found between SLPI expression of intestinal and diffuse GC. SLPI transcript levels were unchanged throughout all groups and locations implying that transcriptional regulation of SLPI is not involved. Conclusion: Local down-regulation of SLPI in antral mucosa is a general phenomenon of Hp-related diseases.
Subtotal Esophageal Resection in Motility Disorders of the Esophagus
Authors: Gockel Ines , Kneist Werner , Eckardt Volker F. , Oberholzer Katja , Junginger Theodor
Published: April 2005

Background: Esophagectomy for motility disorders is performed infrequently. It is indicated after failed medical therapy, pneumatic dilation, non-resecting surgical and redo procedures. Patient selection in this group is challenging and the operative risk has to be weighted carefully against the poor quality of life with persistent or recurrent dysphagia. Patients and Methods: Between September 1985 and April 2004, subtotal esophageal resections for advanced esophageal motility disorders of the esophagus not responding to previous therapy were carried out in 8 patients (6 females, 2 males). The median age of these patients was 59.5 (43–78) years. Six patients had a megaesophagus secondary to achalasia; 1 patient had a non-specific esophageal motility disorder with a stenosis of the distal esophagus, and a further patient displayed a recurrent huge epiphrenic diverticulum, which occurred in the context of a collagen disease. A transhiatal esophageal resection was performed in 6, a transthoracic procedure in 2 patients. Results: Outcome assessment was done after a follow-up of 43.5 (3–92) months in median. The resection and reconstruction of the esophagus in advanced and decompensated esophageal motility disorders led to a marked functional improvement with disappearance of dysphagia. Despite previous therapeutic failures, alimentation could be restored in all patients. Conclusion: Favourable long-term results with significant improvement of symptoms can be achieved by esophageal resection even if endoscopic therapy or non-resecting surgical measures are unsuccessful. Transhiatal esophagectomy with gastric pull-up should be the preferred procedure and can be performed with low morbidity.
Geometric and Elastic Properties of in vivo Human Achilles Tendon in Young Adults
Authors: Muraoka Tetsuro , Muramatsu Tadashi , Fukunaga Tetsuo , Kanehisa Hiroaki
Published: April 2005

The purpose of this study was to clarify whether the major determinant of the extendibility of the Achilles tendon in young adults was the geometric properties of the tendon. The subjects were 38 healthy young adults (26 male, 12 female; 26 ± 5 years). The subjects developed maximum voluntary isometric plantar flexion (MVIP) torque while the displacement of the distal myotendinous junction of the medial gastrocnemius and ankle joint rotation was determined using a B-mode ultrasonograph and a goniometer, respectively. The tendon force (F) was calculated from MVIP torque and the moment arm of Achilles tendon. The elongation of the Achilles tendon (ΔX) was obtained from the tendon displacements and ankle joint rotation. Achilles tendon stiffness (k) was calculated by dividing F by ΔX. The specific stiffness of the Achilles tendon (ks) was obtained from k normalized to the Achilles tendon length at rest. The cross-sectional area of the Achilles tendon (CSA) was measured at 5, 10, and 15% of the lower leg length proximal to the insertion of the Achilles tendon using a B-mode ultrasonography. The results showed that more distal portion of the Achilles tendon had a larger CSA, and that there was a strong correlation between the average and minimum Achilles tendon CSA. ΔX was 9.9 ± 2.5 mm. k and ks were 330 ± 77 N/mm and 63 ± 20 kN, respectively. No significant correlation was seen between CSA and ks (r = 0.15, p > 0.05). It was suggested that a stiffer Achilles tendon did not necessarily have a thicker shape, which might indicate that the major determinant of the extendibility of the Achilles tendon was not its geometric properties in young adults.
Localization and Characterization of Specific Cornification Proteins in Avian Epidermis
Authors: Alibardi Lorenzo , Toni Mattia
Published: April 2005

Little is known about proteins involved in the formation of the stratum corneum in the avian apteric epidermis. The present immunocytochemical, autoradiographic and electrophoretic study shows that antibodies against characteristic proteins of mammalian cornification (α-keratins, loricrin, sciellin, filaggrin, transglutaminase) recognize avian epidermal proteins. This suggests the presence of avian protein with epitopes common to related mammalian proteins. These proteins may also be involved in the formation of the cornified core and cell envelope of mature avian corneocytes. The immunoblotting study suggests that protein bands, cross-reactive for antibodies against loricrin (45, 52–57 kDa), sciellin (54, 84 kDa), filaggrin (32, 38, 45–48 kDa), and transglutaminase (40, 50, 58 kDa), are present in the avian epidermis. Immunocytochemistry shows that immunoreactivity for the above proteins is localized in the transitional and lowermost corneous layer of apteric epidermis. Their epitopes are rapidly masked/altered in cornifying cells and are no longer detectable in mature corneocytes. In scaled epidermis a thick layer made of β-keratins of 14–18, 20–22, and 33 kDa is formed. Only in feathered epidermis (not in scale epidermis), an antifeather chicken β-keratin antibody recognized a protein band at 8–12 kDa. This small β-keratin is probably suitable for the formation of long, axial filaments in elongated barb, barbule and calamus cells. Conversely, the larger β-keratins in scales are irregularly deposited forming flat plates. Tritiated histidine coupled to autoradiography show an absence of both keratohyalin and histidine-rich proteins in adult feathered and scaled epidermis. Most of the labeling appears in proteins within the range of β- and α-keratins. These data on apteric epidermis support the hypothesis of an evolution of the apteric and interfollicular epidermis from the expansion of hinge regions of protoavian archosaurians.
The Tenth Vascular Component in a Rare Form of the Cerebral Arterial Circle of Fetuses
Authors: Vasović Ljiljana P.
Published: April 2005

The ancient knowledge of the cerebral arterial circle (CAC) angioarchitecture could be supplemented by either a new or a forgotten old fact about it. Therefore, 7 cases of a rare form of the CAC of fetuses were described, where the so-called intermediate communicating artery, as an excess vessel into the posterior part, represented either its new vascular component or the developmental segment of this part. The paper aims at revealing the fetal history and morphological features of this ‘underdeveloped’ posterior part of the CAC during the 2nd and 3rd gestational trimesters, which could be of anatomical and clinical meaning in similar prenatal and/or postnatal cases.
The Problematic Slit Ventricle Syndrome
Authors: Olson Sarah
Published: April 2005

This review discusses the clinical difficulties with the so-called slit ventricle syndrome. It discusses why this terminology makes it difficult to formulate treatment algorithms. Slit ventricle syndrome should probably be known as the non-compliant ventricle syndrome to avoid confusion of radiological ‘slit ventricles’ with the syndrome. Therapeutic measures should ideally focus on the underlying pathology related to the syndrome. For those patients with iatrogenic small calvaria and synostosis, subtemporal decompression would appear a low-risk and quick procedure. Calvarial expansion would be a second-line treatment. For those patients with a normal-sized calvarium and non-compliant ventricle syndrome, valve upgrade, adding an antisiphon device or programmable valve would appear a good first step. For patients in whom the diagnosis is unclear, a potential management plan is discussed.
Lumbar CSF Shunting Preferentially Drains the Cerebral Subarachnoid over the Ventricular Spaces: Implications for the Treatment of Slit Ventricle Syndrome
Authors: Khorasani Leila , Sikorski Christian W. , Frim David M.
Published: April 2005

Based on a proposed pathophysiology of slit ventricle syndrome (SVS), we have hypothesized that lumboperitoneal shunting exerts effects in SVS patients by increasing the buffering capacity for raised intracranial pressure (ICP) via an increase in cerebrospinal fluid drainage from the cerebral subarachnoid space (SAS). We describe 3 SVS patients with patent lumbar subarachnoid drainage but under-functioning ventriculoperitoneal shunts (VPS) who presented with ventriculomegaly (not SVS), and persistence of shunt malfunction like symptoms. Revision of the VPS resulted in complete resolution of symptoms despite a finding of low pressure in the ventricular space. This supports the hypothesis that lumboperitoneal shunting preferentially drains the SAS over the intraventricular space and in these cases allows the ‘SVS’ ventricles to enlarge by creating a pressure gradient from ventricles to SAS through the cortical mantle.
Choroid Plexus and Aquaporin-1: A Novel Explanation of Cerebrospinal Fluid Production
Authors: Longatti P.L. , Basaldella L. , Orvieto E. , Fiorindi A. , Carteri A.
Published: April 2005

Aquaporins are selective water channel proteins that play a central role in the homeostasis of human body water. The choroid plexus (CP) is considered to be the main cerebrospinal fluid (CSF)-producing structure. In this study, six specimens of normal human CP obtained during surgery were analyzed by immunohistochemistry techniques for aquaporin-1 (AQP1) expression and distribution. Intense, uniformly distributed AQP1 immunostaining was observable in the apical but not the basolateral side of cuboid cells of the CP. Moreover, this polarized expression of AQP1 was weakly detectable in the endothelial cells of choroid microvessels and, with a different pattern, in the cells lining the tubules shaped into crypts. Selective AQP1 expression on the surface of the normal human CP might explain the role of CSF production by this complex structure.
Congenital Peripheral Facial Palsy Associated with Cerebellopontine Angle Arachnoid Cyst
Authors: Erman Tahsin , Demirhindi Hakan , Göçer A. İskender , Akgül Erol , İldan Faruk , Boyar Bülent
Published: April 2005

Objects: A rare case of cerebellopontine angle arachnoid cyst leading to congenital peripheral facial palsy was presented. Clinical Presentation: A 1-year-old girl presented with peripheral facial paralysis since birth. Computed tomography and magnetic resonance imaging revealed left cerebellopontine angle arachnoid cyst causing moderate displacement of the brain stem. Intervention: Retrosigmoid suboccipital craniotomy was performed and microsurgical resection of the cyst wall and fenestration of the cyst to the basal cisterns were achieved. Conclusions: Cerebellopontine angle arachnoid cyst should be considered as a potential cause of congenital peripheral facial palsy.
Spontaneous Pneumocephalus Presenting with Apnea Attacks in a Newborn with Open Myelomeningocele
Authors: Erol Fatih Serhat , Kaplan Metin
Published: April 2005

We report a case who had an open myelomeningocele and developed respiratory arrest associated with spontaneous pneumocephalus. Spontaneous respiration resumed after closing of the defect and ventriculoperitoneal shunting. We conclude that repairment of the defect in the early period is very useful both to minimize the infection risk and to prevent the complication of pneumocephalus in these cases.
Anosognosia in Very Mild Alzheimer’s Disease but Not in Mild Cognitive Impairment
Authors: Kalbe E. , Salmon E. , Perani D. , Holthoff V. , Sorbi S. , Elsner A. , Weisenbach S. , Brand M. , Lenz O. , Kessler J. , Luedecke S. , Ortelli P. , Herholz K.
Published: April 2005

Objective: To study awareness of cognitive dysfunction in patients with very mild Alzheimer’s disease (AD) and subjects with mild cognitive impairment (MCI). Methods: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were ≧24 in all cases. The discrepancy between the patients’ and caregivers’ estimations of impairments was taken as a measure of anosognosia. Results: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). Conclusions: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver’s assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE ≧24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.
The Effect of Different Diagnostic Criteria on the Prevalence and Incidence of Post-Stroke Dementia
Authors: Rasquin S.M.C. , Lodder J. , Verhey F.R.J.
Published: April 2005

There is little agreement about the prevalence and incidence of vascular dementia (VaD) mainly because investigators have used different diagnostic criteria. The aim of this study was to examine the influence of different diagnostic criteria on the prevalence and cumulative incidence of VaD in first-ever stroke patients (n = 194) clinically evaluated at 1, 6, 12, and 24 months after stroke. Post-stroke VaD was diagnosed using the DSM-III, DSM-III-R, DSM-IV, ICD-10-NA, NINDS-AIREN, and ADDTC criteria. The prevalence of dementia was highest at 1 month; ranging from 11.3% with the NINDS-AIREN to 20.1% with the ICD-10-NA. The incidence was highest at 6 months, ranging from 2.6% with the ADDTC to 5.2% with the ICD-10-NA. Agreement among diagnostic criteria was high, with the exception of the ADDTC. In conclusion, both the prevalence and incidence of dementia are highest directly after stroke, but exact rates are influenced by the diagnostic criteria used.
The Use of the 12-Item Short-Form Health Status Instrument in a Longitudinal Study of Patients with Stroke and Transient Ischaemic Attack
Authors: Müller-Nordhorn Jacqueline , Nolte Christian H. , Rossnagel Karin , Jungehülsing Gerhard J. , Reich Andreas , Roll Stephanie , Villringer Arno , Willich Stefan N.
Published: April 2005

The 36-item short-form health survey (SF-36) is one of the most commonly used health status instruments in patients with cerebrovascular disease. However, responsiveness to change in health-related quality of life (HRQoL) has not yet been assessed for the SF-36 and its shortened version, the SF-12. The main objective of the present study was to determine responsiveness to change of the SF-12 in patients with cerebrovascular disease. Patients with stroke/transient ischaemic attack (TIA) were included at admission to one of four participating hospitals. HRQoL was assessed with the Physical (PCS-12) and Mental (MCS-12) Component Summary scales at baseline (referring to the status prior to the event) and after 12 months. Responsiveness to change was determined with the standardized response mean (SRM) and classified as small (SRM 0.20–0.49), moderate (0.50–0.79) or large (≧0.80). A total of 558 patients were included [55% men, mean age 65 (SD, 13) years; 45% women, mean age 69 (SD, 14) years]. Indications for admission were stroke (74%) and TIA (26%). In patients with stroke, SRMs were small for the PCS-12 [SRM 0.49; absolute change –5.9 (SD, 12)] and moderate for the MCS-12 [SRM 0.52; absolute change –6.6 (SD, 13)]. In patients with TIA, SRMs were below 0.2 for the PCS-12 [absolute change –0.7 (SD, 11)] and small for the MCS-12 [SRM 0.34; absolute change –3.7 (SD, 11)]. SRMs increased with stroke severity as indicated by the NIHSS score. The SF-12 summary scales showed a small to moderate responsiveness to change in patients after stroke. Responsiveness to change was higher in patients with increased symptom severity.
Case-Control Study of Nutritional Antioxidant Intake in Essential Tremor
Authors: Louis Elan D. , Jurewicz Eva C. , Parides Michael K.
Published: April 2005

The theory that oxidative stress is involved in the pathogenesis of neurodegenerative diseases has received considerable attention and studies have linked these diseases to the diminished use of antioxidant vitamins (vitamins E and C) and other dietary antioxidants. Essential tremor (ET) is a chronic, progressive disease. One possible disease mechanism is neurodegenerative. Whether nutritional antioxidant use differs between ET cases and controls is not known. Using a case-control design, we conducted detailed dietary assessments and tested the hypothesis that diminished use of nutritional antioxidants is associated with ET. Data on diet were collected on 156 ET cases and 220 controls using a semi-quantitative food-frequency questionnaire. There was no evidence that current nutritional antioxidant exposure differs in ET cases and controls. This does not exclude the possibility that nutritional antioxidant exposure was lower in ET cases prior to their disease onset.
Higher Burden of Hemorrhagic Stroke among Women
Authors: Aikawa Vânia N. , Bambirra Alberto P. , Seoane Luciana A. , Bensenor Isabela M. , Lotufo Paulo A.
Published: April 2005

The aim of this study was to verify the gender difference in sudden cardiovascular death, mainly comparing brain infarction and hemorrhagic stroke. We analyzed 970 autopsy cases from a total of 3,802 nonviolent deaths (448 considered as sudden deaths, 296 undetermined, and 226 non-sudden deaths) including patients aged 30–69 years. All cardiovascular diseases were responsible for 69% of sudden deaths, and all types of stroke for only 14%. The proportions of sudden death for all cardiovascular diseases, coronary heart disease and ischemic stroke deaths were similar for both sexes. However, sudden deaths due to all types of stroke (women 20.0%; men 11.1%; p = 0.012) and hemorrhagic stroke (women 15.6%; men 7.9%; p = 0.019) were significantly more frequent among women when compared to men, the main cause being subarachnoid hemorrhage (women 5.6%; men 1.0%; p = 0.011). Hemorrhagic stroke deaths were usually sudden deaths among women.
Parametric Approach to Genomic Imprinting Analysis with Applications to Angelman’s Syndrome
Authors: Shete Sanjay , Zhou Xiaojun
Published: April 2005

Genomic imprinting is a mechanism by which only one copy of a gene pair is expressed, and this expression is determined by the parental origin of the copy. The deregulation of imprinted genes has been implicated in a number of human diseases. The Imprinted Gene Catalogue now has more than 200 genes listed, and estimates based on mouse models suggest many more may exist in humans. Therefore, the development of methods to identify such genes is important. In this communication, we present a parametric model-based approach to analyzing arbitrary-sized pedigree data for genomic imprinting. We have modified widely used LINKAGE program to incorporate our proposed approach. In addition, our approach allows for the use of sex-specific recombinations in the analysis, which is of particular importance in a genome-wide analysis for imprinted genes. We compared our imprinting analysis approach to that implemented in the GENEHUNTER-IMPRINT program using simulation studies as well as by analyzing causal genes in Angelman’s syndrome families, which are known to be imprinted. These analyses showed that the proposed approach is very powerful for detecting imprinted genes in large pedigrees.
Defining the Mechanisms of Borderline Personality Disorder
Authors: Clarkin John F. , Posner Michael
Published: April 2005

Understanding the biological connections to mental processes was one of the original goals of psychoanalysis, and the development of cognitive and affective neuroscience and its methods might contribute to actualizing this goal. Personality disorders provide an opportunity to examine the complex mental structures of individuals experiencing extreme difficulties in interacting with their social environment. We provide initial information on a collaboration exploring an approach to one of the most serious personality disorders, borderline personality disorder, based upon the study of normal attention, individual differences in temperament, self definition and attachment organization, with the potential to illuminate the psychology and psychobiology of the disorder and to contribute to psychotherapeutic intervention. This developing model of borderline personality disorder can relate the symptoms to more enduring temperamental aspects of the patients. The goal is to understand the development of neural networks that underlie the abnormalities of adults, and eventually work out the interaction between temperament, genes, and experience that produce the disorder, and potentially inform intervention.
The Association between Attentional and Executive Controls in the Expression of Borderline Personality Disorder Features: A Preliminary Study
Authors: Fertuck Eric A. , Lenzenweger Mark F. , Clarkin John F.
Published: April 2005

Background: Basic neurocognitive functions such as attention and executive cognitive control represent promising endophenotypes that may improve understanding of the development and expression of borderline personality disorders (BPD). We evaluated the association between performance on the Attention Network Task (ANT) and the Wisconsin Card Sorting Test (WCST), two neurocognitive laboratory instruments, and the extent of BPD psychopathology. Sampling and Methods: We studied 22 BPD-diagnosed individuals who were independently administered these two laboratory assays. Performance on these tests was used as a predictor of the extent of BPD psychopathology. Results: Indexes of the ANT and the WCST were correlated with one another in this sample. Further, the extent of impairment in attention networks, specifically the orienting network, was associated with a greater spectrum of BPD psychopathology, independent of the effects of age and medication status. Finally, ANT and WCST performance were uncorrelated with general psychosocial functioning in this sample, implicating relative specificity to the extent, as contrasted with functional severity, of BPD psychopathology. Conclusions: Attentional and executive functions are promising endophenotypic markers of BPD psychopathology. The implications of these findings are considered from developmental, experimental, and clinical perspectives.
The Construct of Effortful Control: An Approach to Borderline Personality Disorder Heterogeneity
Authors: Hoermann Simone , Clarkin John F. , Hull James W. , Levy Kenneth N.
Published: April 2005

Background: The present study investigated the heterogeneity of DSM-IV borderline personality disorder (BPD) diagnosis as a function of the construct of effortful control. We hypothesized 3 subgroups of BPD patients based on effortful control, that would also differ in other areas of functioning, such as symptoms, interpersonal relations and personality organization. Sampling and Methods: Forty-seven clinically referred individuals were reliably diagnosed as meeting DSM-IV criteria for BPD using semistructured interviews. Effortful control, symptomatology, interpersonal functioning and personality organization were assessed using self-report questionnaires. Results: Cluster and profile analyses were performed and identified 3 subgroups. Subgroup 1, with high effortful control, exhibited the fewest problems in symptoms, interpersonal functioning and personality organization. Subgroup 3, with low ratings of effortful control, had the most problems in these areas, and subgroup 2, a group high in some aspects of effortful control but low in others, ranged midway between groups 1 and 3. Discussion: The findings indicate a relationship between attentional mechanisms and the clinical expression of borderline personality pathology. Effortful control is a valuable construct for identifying subgroups of BPD patients, thus helping to understand the heterogeneity in BPD. Limitations of the study include the exclusive use on self-report of effortful control, as well as the small sample size. Future research should further investigate the associations of neurocognition and borderline pathology, as well as different approaches to treatment of the different BPD subgroups.
Association of Regular Aspirin Use and Breast Cancer Risk
Authors: Swede Helen , Mirand Amy L. , Menezes Ravi J. , Moysich Kirsten B.
Published: April 2005

Of the limited number of epidemiological investigations on aspirin (and other nonsteroidal anti-inflammatory drugs) and breast cancer, the majority observe a protective role, yet only a few report dose-response effects for frequency or duration of use. We studied aspirin use among 1,478 breast cancer patients diagnosed from 1982 to 1998, and 3,383 cancer-free hospital controls at the Roswell Park Cancer Institute. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Compared to never use,both regular (≧1 tablet per week for ≧1 year) and occasional use were inversely associated with breast cancer (adjusted OR = 0.84, 95% CI 0.64–0.97; adjusted OR = 0.80, 95% CI 0.67–0.96, respectively). Among regular users, an inverse trend was found for number of tablets consumed per week (1, 2–6, or ≧7) with corresponding ORs of 0.95, 0.80, and 0.74 (Ptrend = 0.01). Daily use spanning 10 or more years was associated with a more pronounced reduction in risk (Ptrend = 0.005). Our findings corroborate the growing body of observational evidence that regular aspirin use may be associated with reduced risk of breast cancer.
Beta-Endorphin Ameliorates Synovial Cell Hyperfunction in the Collagen-Induced Arthritis Rat Model by Specific Downregulation of NF-kappa B Activity
Authors: Yin Hongen , Zhang Fengchun , Yu Mengxue , Cheng Hong , Lin Jiayou , Gao Yang , Han Bing , Zhu Liping
Published: April 2005

Objectives: To observe the multiple immunoregulating effects of β-endorphin (β-END) on synovium cells of collagen-induced arthritis (CIA) in rats and to determine whether the regulation involves the transcriptional factor-ĸB (NF-ĸB) signal pathway. Methods: CIA was induced in female Wistar rats by immunization with native bovine type-II collagen emulsified with complete Freund’s adjuvant. Synovial cells in the knees of the CIA rats were cultivated, and the effects of β-END, β-END receptor inhibitor (naloxone, Nal) in proliferation and apoptosis of the synovial cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, flow cytometry, and DNA integrity, respectively. The effects of β-END and Nal on mRNA expression of several cytokines in the synovial cells, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, regulated upon activation normal T-cell expressed and secreted (RANTES), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 were estimated by quantitative reverse transcription-polymerase chain reaction. Effects of β-END and Nal on NF-ĸB activity were analyzed using luciferase gene reporter assays. The effects of β-END and Nal on p65NF-ĸB expression of the synovial cells were examined using Western blot. Results: 75% of the rats were demonstrated to have established the CIA model successfully. β-END was shown to exert multiple effects on synovial cells of CIA rats including decreased proliferation, induced apoptosis, and downregulation of TNF-α, IL-1β, IL-6, RANTES, iNOS, MMP-2 and MMP-9 mRNA expression. β-END seemed to play an immunoregulating role by downregulating the activity and expression of NF-ĸB. It was found that the β-END receptor blockage could counteract all the effects. Conclusions: β-END ameliorates synovial cell functions of CIA rats through binding with receptors and downregulating the NF-ĸB signal pathway. This suggests that β-END, by blocking the activity and expression of NF-ĸB, is a potential anti-inflammatory and anti-rheumatic agent against CIA.
Angiographic Characteristics of Renal Arterial Disease over the Spectrum of Coronary Artery Disease
Authors: Rigatelli Gianluca , Roncon Loris , Rinuncini Massimo , Giordan Massimo , Bedendo Emiliano , Panin Stefano , Rigatelli Giorgio , Zonzin Pietro
Published: April 2005

Background/Aim: The angiographic characteristics of renal artery stenoses (RAS) in patients with coronary artery disease (CAD) have not been yet fully investigated. We sought to evaluate the angiographic characteristics of RAS in patients with CAD. Methods: The medical records of consecutive patients who underwentcoronary angiography in a single public institution over a 12-month period were evaluated. The patients who underwent coincident diagnostic renal angiography to evaluate renal vessels on the basis of clinical criteria and who had at least one-vessel CAD were analyzed. Moderate (50–70%) to severe (70–100%) arterial stenoses were noted as significant angiographic findings. The types of stenosis (ostial, true renal, mixed) and presence and location of calcium were recorded. Results: Angiographically significant RAS were reported in 40 (19.5%) of 205 consecutive patients (mean age 67.1 ± 12.8 years, mean serum creatinine concentration 2.1 ± 0.5 mg/dl, mean glomerular filtration rate 52 ± 13 ml/min) for a total of 55 lesions. The RAS severity was moderate in 30.9% (17/55), severe in 69.1% (38/55), ostial in 27.2% (15/55), true renal in 10.9% (6/55), and mixed in 61.8% (34/55) of the patients. The mean lesion length was 16 ± 1.8 mm. Patients with ≧3-vessel CAD had a statistically significantly higher prevalence of mixed calcified RAS (18/24, 75%). Logistic regression analyses revealed ≧3-vessel CAD (odds ratio 9.917, p = 0.002), age >65 years (odds ratio 3.817, p = 0.036), and ≧3 risk factors (odds ratio 2.8, p = 0.048) as independent predictors of RAS. Conclusion: RAS in multivessel CAD patients seems to have a peculiar angiographic pattern, such as a higher prevalence of mixed calcified lesions and poststenotic enlargement, that should be taken in account when dealing with RAS.
Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells
Authors: Jaulmes Amandine , Janvier Brigitte , Andreani Marise , Raymondjean Michel
Published: April 2005

Objective—

The inflammation that occurs during the development of atherosclerosis is characterized by a massive release of sPLA2-IIA (group IIA secretory phospholipase A2) from vascular smooth muscle cells (VSMCs). We have investigated the autocrine function of sPLA2-IIA in rat aortic and human VSMCs.

Methods and Results—

We found that the transcription of the endogenous sPLA2-IIA gene increased by adding a cell supernatant containing human sPLA2-IIA proteins. We show that this effect was independent of the sPLA2 activity using sPLA2-IIA proteins lacking enzyme activity. Transient transfections with various sPLA2-IIA rat promoter-luciferase constructs demonstrated that the C/EBP, NK-κB, and Ets transcription factors are involved in the increase in sPLA2-IIA gene transcription. We also found the M-type sPLA2 receptor mRNA in VSMCs, and we showed that the sPLA2-luciferase reporter gene was induced by the specific agonist of the sPLA2 receptor, aminophenylmannopyranoside (APMP), and that this induction was mediated by the same transcription factor-binding sites. Finally, we used a sPLA2-IIA mutant unable to bind heparan-sulfate proteoglycans to show that the binding of wild-type sPLA2-IIA to proteoglycans is essential for the induction of an autocrine loop.

Conclusions—

We have thus identified new autocrine and paracrine pathways activating sPLA2-IIA gene expression in rat and human VSMCs.
Extracellular Proteases in Atherosclerosis and Restenosis
Authors: Garcia-Touchard Arturo , Henry Timothy D. , Sangiorgi Giuseppe , Spagnoli Luigi Giusto , Mauriello Alessandro , Conover Cheryl , Schwartz Robert S.
Published: April 2005

Extracellular proteolysis plays a key role in many pathophysiologic processes including cancer, inflammatory diseases, and cardiovascular conditions such as atherosclerosis and restenosis. Whereas matrix metalloproteinases are their best known member, many others are becoming better known. The extracellular proteases are a complex and heterogeneous superfamily of enzymes. They include metalloproteinases (matrix metalloproteinases, adamalysins, or pappalysins), serine proteases (elastase, coagulation factors, plasmin, tissue plasminogen activator, urokinase plasminogen activator), and the cysteine proteases (such cathepsins). In addition to their matrix degradation capabilities, they have other less well known biologic functions that include angiogenesis, growth factor bioavailability, cytokine modulation, receptor shedding, enhancing cell migration, proliferation, invasion, and apoptosis. This review discusses extracellular proteases relevant to the vasculature, their classification and function, and how protease disorders contribute to arterial plaque growth, including chronic atherosclerosis, acute coronary syndromes, restenosis, and vascular remodeling. These broad extracellular protease functions make them potentially interesting therapeutic targets.
C-Reactive Protein–Induced In Vitro Endothelial Cell Activation Is an Artefact Caused by Azide and Lipopolysaccharide
Authors: Taylor Karolina E. , Giddings John C. , van den Berg Carmen W.
Published: April 2005

Objective—

C-reactive protein (CRP) has been proposed to be an independent risk factor for cardiovascular disease. In vitro studies investigating the mechanism behind this have used purified commercial CRP (cCRP) and endothelial cells. We investigated the role of contaminants in cCRP preparations.

Methods and Results—

Human umbilical vein endothelial cells and the human endothelial cell line EA.hy926 were incubated with
Escherichia coli
–derived cCRP, in-house–generated azide-free recombinant, and ascites-purified CRP, azide, or lipopolysaccharide (LPS) equivalent to the concentration present in cCRP preparations. Cells were investigated for change in cell proliferation, morphology, apoptosis, and expression of endothelial NO synthase and intercellular adhesion molecule-1. Cell supernatants were assessed for monocyte chemoattractant protein-1 (MCP-1), interleukin-8, von Willebrand factor secretion, and pH change. Only cCRP was able to induce all activation events analyzed; however, this ability was lost on extensive dialysis, suggesting that low molecular weight contaminants were responsible for these events. Indeed, the effects of cCRP were mirrored by azide or LPS.

Conclusions—

We investigated a wide range of effects on endothelial cells ascribed to CRP; however, azide and LPS, but never CRP itself, were responsible for the cell activation events. We conclude that CRP, per se, does not activate endothelial cells.
A New Cellular Signaling Mechanism for Angiotensin II Activation of NF-κB
Authors: Zhang Liping , Ma Yewei , Zhang Jiqiang , Cheng Jizhong , Du Jie
Published: April 2005

Objective—

Angiotensin II (Ang II) promotes vascular inflammation and remodeling via activation of nuclear factor κB (NF-κB)–mediated transcription of proinflammatory genes such as interleukin-6 (IL-6). We examined the signaling mechanism whereby Ang II activates NF-κB in vascular smooth muscle cells (VSMCs).

Methods and Results—

Ang II treatment did not increase phosphorylation of inhibitor of κBα (IκBα) or IκBβ or decrease their levels. In contrast, mitogen-activated protein kinase kinase-1 (MEK1) inhibition (dominant-negative MEK1 adenovirus or inhibitor U0126) suppressed Ang II–induced NF-κB promoter activity, NF-κB DNA-binding activity, p65 phosphorylation, and led to 70% reduction in IL-6 transcription/production. The mechanism involved Ang II activation of Ras and MEK1. Signaling distal to MEK1 involved extracellular signal-regulated kinase (ERK) because inhibition of MEK1 suppressed the Ang II–induced activation of ribosomal S6 kinase (RSK), a substrate of ERK. Downregulation of RSK by small interfering RNA (SiRNA) in VSMCs was found to suppress Ang II–induced activation of NF-κB and p65 phosphorylation. Immunopurified RSK from Ang II–treated VSMCs phosphorylated recombinant glutathione
S
-transferase–p65 in vitro.

Conclusion—

We uncovered a nonclassical signaling pathway (Ras/MEK1/ERK/RSK) from Ang II to activation of NF-κB, a mechanism by which Ang II stimulates RSK-mediated phosphorylation of p65 to participate in vascular inflammation.
Elevated Serum C-Reactive Protein Levels and Advanced Atherosclerosis in Youth
Authors: Zieske Arthur W. , Tracy Russell P. , McMahan C. Alex , Herderick Edward E. , Homma Satoki , Malcom Gray T. , McGill Henry C. , Strong Jack P.
Published: April 2005

Objective—

To determine the associations among serum C-reactive protein (CRP) concentration, age, sex, risk factors for coronary heart disease (CHD), and atherosclerosis in young people.

Methods and Results—

In 1244 subjects 15 to 34 years of age, we measured gross atherosclerotic lesions in the right coronary artery (RCA) and abdominal aorta (AA) and American Heart Association (AHA) lesion grade in the left anterior descending (LAD) coronary artery; serum CRP, lipoprotein cholesterol, and thiocyanate (for smoking) concentrations; intimal thickness of renal arteries (for hypertension); glycohemoglobin (for hyperglycemia); and body mass index (for obesity). Serum CRP levels increased with age, were higher in women than in men, and were positively related to obesity and hyperglycemia. Serum CRP ≥10 mg/L was associated with more extensive gross raised lesions in the RCA after age 25 and in the AA after age 30. Serum CRP ≥3 was associated with a greater prevalence of AHA grade 5 lesions in the proximal LAD coronary artery after age 25. The associations of CRP with lesions were independent of the traditional CHD risk factors.

Conclusion—

Serum CRP level is independently associated with advanced atherosclerosis in young persons.
Immunomodulator FTY720 Induces eNOS-Dependent Arterial Vasodilatation via the Lysophospholipid Receptor S1P
3
Authors: Tölle Markus , Levkau Bodo , Keul Petra , Brinkmann Volker , Giebing Günter , Schönfelder Gilbert , Schäfers Michael , Lipinski Karin von Wnuck , Jankowski Joachim , Jankowski Vera , Chun Jerold , Zidek Walter , Giet Markus Van der
Published: April 2005

The novel immunomodulator FTY720 is effective in experimental models of transplantation and autoimmunity, and is currently undergoing Phase III clinical trials for prevention of kidney graft rejection. FTY720 is a structural analogue of sphingosine-1-phosphate (S1P) and activates several of the S1P receptors. We show that FTY720 induces endothelium-dependent arterial vasodilation in phenylephrine precontracted mouse aortae. Vasodilation did not occur in thoracic aortic rings from eNOS-deficient mice, implicating and effect dependent of activation of the eNOS/NO pathway. Accordingly, FTY720 induced NO release, Akt-dependent eNOS phosphorylation and activation in human endothelial cells. For biological efficacy, FTY720 required endogenous phosphorylation, since addition of the sphingosine kinase antagonist
N
′,
N
-dimethylsphingosine (DMS) prevented activation of eNOS in vitro and inhibited vasodilation in isolated arteries. The endothelial phosphorylation of FTY720 was extremely rapid with almost complete conversion after 10 minutes as determined by mass spectrometry. Finally, we identified the lysophospholipid receptor S1P
3
as the S1P receptor responsible for arterial vasodilation by FTY720, as the effect was completely abolished in arteries from S1P
3
-deficient mice. In summary, we have identified FTY720 as the first immunomodulator for prevention of organ graft rejection in clinical development that, in addition, positively affects the endothelium by stimulating NO production, and thus potentially displaying beneficial effects on transplant survival beyond classical T cell immunosuppression.
Adenosine-Dependent Induction of Glutathione Peroxidase 1 in Human Primary Endothelial Cells and Protection Against Oxidative Stress
Authors: Zhang Yufeng , Handy Diane E. , Loscalzo Joseph
Published: April 2005

Cellular glutathione peroxidase (GPx-1), a selenocysteine-containing enzyme, plays a central role in protecting cells from oxidative injury. GPx-1 is ubiquitously expressed in eukaryotic cells where it reduces hydrogen and lipid peroxides to alcohols. Adenosine, which is released from stressed or injured cells, protects against ischemia/reperfusion injury and apoptosis. In this study, we hypothesize that the cytoprotective effect of adenosine involves an increase in the activity of GPx-1. Treatment of human primary pulmonary artery endothelial cells (HPAECs) with 50 μmol/L adenosine in the presence of 10 μmol/L erytho-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, for 48 hours increased GPx-1 mRNA levels 2-fold. GPx-1 protein and enzyme activity also increased ≈2-fold after treatment. The induction of GPx-1 expression was found to be a consequence of increased mRNA stability and not an increase in transcription. Bisindolylmaleimide I (BIM), a protein kinase C signaling pathway inhibitor, significantly attenuated the induction of GPx-1 mRNA by ≈36%. The adenosine/EHNA-treated cells were more resistant to hydrogen peroxide stress. Both pharmacological inhibition and siRNA knockdown of GPx-1 attenuated the protective affect of adenosine/EHNA treatment, indicating that the adenosine-induced increase in GPx-1 contributes to an increase in cellular protection against oxidative stress. These data suggest that adenosine may protect the cardiovascular system from ischemia/reperfusion injury, in part, by enhancing the expression of the central intracellular antioxidant enzyme, GPx-1.
Autonomic Function Is Impaired in Elderly Stroke Survivors
Authors: McLaren Andrew , Kerr Simon , Allan Louise , Steen I. Nicholas , Ballard Clive , Allen John , Murray Alan , Kenny Rose Anne
Published: April 2005

Background and Purpose—

Impaired autonomic function is common in the acute poststroke phase but little is known about the longer term effects, particularly in older people. We sought to determine if autonomic function is impaired after stroke recovery in older patients.

Methods—

A cross-sectional case-control study comparing autonomic function in 76 nondemented stroke patients with 70 community-living controls aged older than 75 years.

Results—

Cases were assessed on average 9 months after stroke. From power spectral analysis of heart rate variability, stroke patients had lower total (
P
=0.032) and low-frequency (
P
=0.014) spectral densities and impaired baroreflex sensitivity (α low-frequency baroreflex sensitivity,
P
=0.006). From a series of cardiovascular autonomic reflex tests, heart rate variation during forced respiration, Valsalva ratio, and blood pressure overshoot during Valsalva maneuver were significantly lower in stroke patients (
P
=0.003, <0.001, and 0.027, respectively). Blood pressure response to isometric exercise was significantly exaggerated in stroke patients (
P
=0.007).

Conclusions—

Cardiovascular autonomic function is impaired long after the index event in stroke survivors. Impaired autonomic function may increase the risk of all-cause mortality and cardiovascular mortality in older stroke survivors.