bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of coronary vasospasm by detection of postischemic regional left ventricular delayed relaxation using echocardiographic evaluation with color kinesis
Authors: Ishii Katsuhisa , Miwa Kunihisa , Makita Toshinori , Okuda Nobuaki , Aoyama Takeshi
Published: June 2007

Background: Coronary vasospasm has been diagnosed by invasive provocative procedures during coronary arteriography. It would be useful to have a reliable, noninvasive, and safe diagnostic method for coronary vasospasm. Regional left ventricular (LV) diastolic dysfunction may persist without systolic dysfunction after an episode of coronary vasospasm. Color kinesis (CK) has been recently developed to facilitate the echocardiographic evaluation of regional wall motion.

Hypothesis: Color kinesis may be useful for diagnosis of coronary vasospasm by detection of postischemic regional LV diastolic wall motion abnormality.

Methods: Fifty‐one consecutive patients with the last chest symptom within 2 weeks (4 ± 3 days) were studied echocardiographically. Regional fractional area change during the first 30% of LV filling time in percentage of the segmental end‐diastolic area change (CK diastolic index) was used to identify diastolic endocardial motion asynchrony.

Results: After diagnostic coronary arteriography with spasm provocation, 26 patients were diagnosed with coronary spastic angina (CSA) and the other 25 with chest pain syndrome (CPS). Regional delayed relaxation (CK‐diastolic index ≤ 50%) or diastolic asynchrony had been observed in at least one region in 25 (96%) patients with CSA, whereas it had been noted in 2 (8%) patients with CPS. In 17 (65%) patients with CSA, it had been detected in multiple vascular territories, suggesting multivessel spasm. The diastolic asynchrony disappeared in CSA after a month of angina‐free period.

Conclusion: Analysis of CK images allows identification of regional LV delayed relaxation or diastolic asynchrony in patients with coronary vasospasm, differentiating them from patients with chest pain syndrome (sensitivity 96%, specificity 92%).
Practicability and limitations of enhanced external counterpulsation as an additional treatment for angina
Authors: Werner Dierk , Kropp Joachim , Schellong Sebastian , Friedel Chris , Voigt Jens‐Uwe , Ludwig Josef , Daniel Werner G. , Flachskampf Frank A.
Published: June 2007

Background: An increasing number of clinical studies indicates reduction of angina and myocardial ischemia by enhanced external counterpulsation (EECP) therapy. However, given the wide range of contraindications and the long duration of treatment, eligibility and practicality issues have not been addressed systematically.

Hypothesis: Of all candidates for EECP (patients with drug‐refractory angina without possibility of revascularization), the majority either have contraindications or have practical problems complying with the time demands that this therapy imposes. In the rest, EECP leads to satisfactory results.

Methods: During 18 months, every consecutive patient with angina despite medical and interventional therapy was evaluated for EECP at one center. Treated patients underwent a bicycle exercise test and perfusion imaging before and after the standard course of 35 h of EECP. In addition, patients were asked about frequency of angina and nitroglycerin usage before and after EECP, and all patients filled out a final questionnaire 1 year after the end of therapy.

Results: Overall, 48 patients were considered candidates for EECP. Of these, 24 were excluded for medical reasons: poor ejectionfraction (4), peripheral artery disease (4), anticoagulation (4), and atrial fibrillation (3). Eight further patients declined EECP for lack of time or accommodation. Another 3 of the 16 remaining patients dropped out because of side effects. In the 13 patients who finished the treatment course, weekly anginal episodes were reduced by 48% (p < 0.05), on‐demand nitroglycerin puffs were reduced by 51% (p<0.05), work capacity was improved by 22% (p <0.05), and the number of reversible perfusion defects in perfusion scans decreased non‐significantly (‐28%). However, 4 of 13 treated patients determined 1 year later that the detriment of loss of time exceeded the benefits of EECP.

Conclusion: Similar to previous reports, our study confirms the reduction of angina and improvement of work capacity after EECP. However, using established contraindications, approximately two‐thirds of patients considered to be candidates had to be excluded, and one‐third of the treated patients regarded EECP therapy retrospectively as too time consuming.
Autopsy findings in siblings with hypertrophic cardiomyopathy caused by Arg92Trp mutation in the cardiac troponin T gene showing dilated cardiomyopathy‐like features
Authors: Shimizu Masami , Ino Hidekazu , Yamaguchi Masato , Terai Hidenobu , Uchiyama Katsuharu , Inoue Masaru , Ikeda Masatoshi , Kawashima Atsuhiro , Mabuchi Hiroshi
Published: June 2007

Background: Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes that encode sarcomeric proteins. Although some patients with HCM have shown dilated cardiomyopathy (DCM)‐like features, the relationship between genotype and histologic findings is not well known.

Hypothesis: Family members with the same gene mutation may show the same histopathologic changes and clinical manifestations.

Methods: Siblings with HCM caused by an Arg92Trp mutation in the cardiac troponin T gene, showing DCM‐like features, were examined.

Results: The patients were a 69‐year‐old woman and her 57‐year‐old brother who both died from congestive heart failure. Their autopsies revealed the same histopathologic findings in the heart. The anterior walls and interventricular septa of their hearts were replaced with extensive fibrosis and showed thinning. Myocyte hypertrophy, disarray, and thickened medial walls of the intramural coronary arteries were found. On electron microscopy, the number of mitochondria was seen to be increased and they formed many clusters.

Conclusions: Patients with HCM caused by an Arg92Trp mutation in the cardiac troponin T gene may have the same histopathologic findings, whichmay result in DCM‐like features.
The association of homocysteine and coronary artery disease
Authors: Gauthier Gregory M. , Keevil Jon G. , McBride Patrick E.
Published: June 2007

Hyperhomocysteinemia has been associated with increased risk of atherosclerosis and myocardial infarction by a number of prospective case‐control studies. A variety of genetic mutations, nutritional deficiencies, disease states, and drugs can elevate homocysteine concentrations. Treatment with folic acid with or without B‐complex vitamins effectively lowers homocysteine levels. Whether therapy corresponds with decreased risk of coronary events is unknown, but may be promising. This article reviews the biochemistry of homocysteine metabolism, pathogeneisis, and etiology of hyperhomocysteinemia, along with its association with coronary artery disease, screening, and treatment.
Increased plasma thioredoxin in patients with acute myocardial infarction
Authors: Soejima Hirofumi , Suefuji Hisakazu , Miyamoto Shinzo , Kajiwaram Ichiro , Kojima Sunao , Hokamaki Jun , Sakamoto Tomohiro , Yoshimura Michihiro , Nakamura Hajime , Yodoi Junji , Ogawa Hisao
Published: June 2007

Background and hypothesis: Thioredoxin is an important biomarker for oxidative stress. We investigated whether thioredoxin levels were elevated in patients with acute myocardial infarction (AMI) and were associated with the results of coronary reperfusion.

Methods: The present study determined plasma thioredoxin levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA), and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after admission in patients with SEA and CPS.

Results: Plasma thioredoxin levels on admission were higher in patients with AMI than in those with SEA and CPS. Plasma thioredoxin levels in patients with AMI were decreased in 12 h without further change thereafter. However, thioredoxin levels in patients with AMI remained higher than in those with SEA. In multivariate analysis, higher levels of thioredoxin on admission were a risk factor for failure in emergent reperfusion therapy in patients with AMI independent of other factors.

Conclusion: Plasma thioredoxin levels are elevated in patients with AMI, and higher thioredoxin levels may predict subsequent failed coronary reperfusion therapy in patients with AMI.
Potential application of tissue doppler imaging to assess regional left ventricular diastolic function in patients with hypertrophic cardiomyopathy: Comparison with 123I‐β‐methyl iodophenyl pentadecanoic acid myocardial scintigraphy
Authors: Yamada Hirotsugu , Oki Takashi , Yamamoto Takashi , Tanaka Hideji , Tabata Tomotsugu , Wakatsuki Tetsuzo , Nomura Masahiro , Ito Susumu , Thomas James D.
Published: June 2007

Background: Tissue Doppler imaging (TDI) has been utilized to evaluate left ventricular myocardial dysfunction in patients with hypertrophic cardiomyopathy (HCM); however, no clear explanation for the abnormality of TDI variables has been forthcoming.

Hypothesis: Peak negative myocardial velocity gradient (MVG) derived from TDI may correlate with a disorder of fatty acid metabolism in patients with HCM.

Methods: Tissue Doppler imaging and 123I‐β‐methyl iodophenyl pentadecanoic acid (123I‐BMIPP) myocardial scintigraphy were performed in 15 patients with asymmetric septal hypertrophy (mean age 47 ± 18 years) and in 12 healthy controls (mean age 43 ± 10 years).

Results: In early 123I‐BMIPP images, accumulation defects were observed in the ventricular septum in 12 patients and in the posterior wall in 8 patients with HCM. Peak negative MVG in the ventricular septum (1.1 ± 0.5 vs. 2.8 ± 0.5, p<0.0001) and posterior wall (5.2 ± 1.4 vs. 6.7 ± 0.8, p< 0.01) was significantly lower in the HCM group than in the controls; also, these parameters were significantly lower in patients with than in those without a defect in the region in question. The peak negative MVG in the ventricular septum and posterior wall correlated inversely with the washout rate in all subjects.

Conclusions: Peak negative MVG according to TDI is related to disorder of fatty acid metabolism in the regional left ventricular myocardium of patients with HCM.
A population‐based evaluation of the thrombolysis in myocardial infarction risk score for unstable angina and non‐ST elevation myocardial infarction
Authors: Bartholomew Beth A. , Sheps David S. , Monroe Stephen , McGorray Susan , Smith Karen , Pepine Carl J.
Published: June 2007

Background: The Thrombolysis in Myocardial Infarction risk score (TIMI‐RS) for unstable angina/non‐ST elevation myocardial infarction (MI) was developed in patients presenting with unstable angina accompanied by high‐risk features or non‐ST elevation MI to determine early risk stratification.

Hypothesis: The validity in patients presenting for emergency care with symptoms suggestive of acute coronary syndrome (ACS) has not been well established, and the present study sought to do so by evaluating the TIMI‐RS in a prospective fashion.

Methods: A prospective TIMI‐RS using seven variables was calculated in 245 patients admitted to the hospital with symptoms suggestive of ACS: (1) age > 65, (2) three or more cardiac risk factors, (3) ST deviation, (4) aspirin use within 7 days, (5) two or more anginal events over 24 h, (6) history of coronary stenosis, and (7) elevated troponin. Patients were contacted at 30 days and data were collected concerning major adverse cardiac events.

Results: In patients presenting with chest pain, a higher TIMI‐RS was associated with an increase in major adverse cardiac events within 30 days. We found that the 30‐day event rate was 0% for a score of 1, 20% for a score of 2, 24% for a score of 3, 42% for a score of 4, 52% for a score of 5, and 70% for a score of 6 or 7 (p < 0.0001).

Conclusions: The TIMI‐RS successfully differentiates early risk for major adverse cardiac events in a general population presenting with symptoms suggestive of acute coronary syndrome. A simple bedside calculation of the TIMI‐RS provides rapid risk stratification, allowing facilitation of therapeutic decision making in patients with symptoms suggestive of ACS.
Evolving targets for risk reduction in diabetes
Authors: Caputo Gregory M. , Braunstein Joel B. , Blumenthal Roger S.
Published: June 2007

Recent evidence shows that target low‐density lipoprotein cholesterol should be less than 100 mg/dl in patients with diabetes, and that even those with initially low levels benefit from pharmacologic therapy. Recent studies document that blood pressures lower than the previous target of 140/90 mmHg are beneficial, in addition to providing observational evidence against a lower threshold of benefit. Evidence that addresses the effect of blood glucose on macrovascular disease risk in patients with diabetes is reviewed. Finally, recommendations are made regarding systematic changes in healthcare delivery that will facilitate risk reduction strategies in diabetes.
Electrocardiogram and clinical characteristics of patients referred for cardiac transplantation: Implications for pacing in heart failure
Authors: Freudenberger Ronald , Sikora Jo Ann , Fisher Michael , Wilson Alan , Gold Michael
Published: June 2007

Background: Permanent pacing for the treatment of heart failure (HF) has been the subject of intense research over the past decade. Those with conduction abnormalities may benefit most from pacing. The incidence of these conduction abnormalities in patients referred for cardiac transplantation and its relationship to outcome has not been well described.

Hypothesis: This study sought to determine the incidence of these abnormalities and to correlate these findings to outcome in this patient population.

Methods: A review of 100 patients referred for transplantation was performed. Data were analyzed in two groups: those with QRS duration < 120 ms and those with a QRS duration > 120 ms. Times to transplantation or death were analyzed in these two groups.

Results: Of these patients, 34% had QRS duration ≥ 120 ms and survival was inversely associated with QRS duration. Of those with QRS duration < 120 ms, 24% (16) went on to cardiac transplantation or died. Of those with a QRS duration ≥ 120 ms, 55% (17) went on to transplantation or died (p = 0.0134).

Conclusions: This suggests that in addition to a multi‐drug regimen for heart failure, 34% of patients referred for transplantation may benefit from additional therapy with biventricular pacing.
The effect of st resolution on QT dispersion after interventional treatment in acute myocardial infarction
Authors: Ilkay Erdoǧan , Yavuzkir Mustafa , Karaca Ilgin , Akbulut Mehmet , Pekdemir Murat , Aslan Nadi
Published: June 2007

Background: It has been reported that reperfusion treatment reduces QT dispersion (QTD) in cases of acute myocardial infarction (AMI). Successful myocardial perfusion is not synonymous with Thrombolysis in Myocardial Infarction (TIMI) III flow. It has been demonstrated that in AMI, the grade of ST‐resolution correlates strongly with left ventricular (LV) function, enzyme elevation, and mortality after primary angioplasty.

Hypothesis: This study investigated the relation between ST‐resolution grade and QTD and the feasibility of using QTD as a determinant of successful myocardial tissue perfusion in patients in whom TIMI III flow in the infarct‐related artery (IRA) is restored by interventional treatment for AMI.

Methods: The study included 57 patients (38 men, 19 women, average age 54.4 ± 11.6 years), whose IRA was perfused by primary angioplasty after the diagnosis of anterior AMI with ST elevation. Electrocardiograms of patients were taken 45 ± 12 min post procedure, and patients were divided into three groups depending on the grade of ST resolution: Group 1, full ST resolution; Group 2, partial ST resolution; and Group 3, unsuccessful ST resolution.

Results: Full ST resolution was seen in 19 cases (33%), partial resolution in 26 cases (47%), and unsuccessful resolution in 12 cases (20%). There were no differences among groups in terms of risk factors, stent diameters, symptom onset–balloon time, LV function, and preprocedure corrected QTD (QTcD) (p = 0.274). After the procedure, a signiFICAnt reduction in QTcD was found within the groups (p = 0.0001 in Group 1, p = 0.004 in Group 2, and p = 0.011 in Group 3). Reductions in QTcD post procedure were 24.21 ± 14.27, 11.85 ± 16.18, and 12.50 ± 11.58 ms in Groups 1, 2, and 3, respectively. There was a statistically signiFICAnt difference of p = 0.015 between Groups 1 and 2 and a difference of p = 0.028 between Groups 1 and 3. There was no statistically signiFICAnt difference between Groups 2 and 3 (p = 0.916).

Conclusion: In acute MI, TIMI III flow led to a reduction in QTcD, and full myocardial perfusion made an additional contribution to the electrical stability of the myocardium.
A case of paradoxical embolism “in situ” associated with massive pulmonary embolism: Role of echocardiography
Authors: Sumner Andrew D. , Henderson Rick , Martin Deena , Sorrell Vincent L.
Published: June 2007

A 49‐year‐old man was admitted in transfer for further management of a pulmonary embolism (PE) and possible mitral valve vegetation. Transthoracic echocardiography performed at our institution showed evidence of right ventricular (RV) enlargement and dysfunction. Within the right atrium was a serpentine mobile thrombus which traversed the interatrial septum at the level of the fossa ovalis and extended into the left atrium to the level of the anterior mitral valve leaflet. Because of the patient's dyspnea, RV dysfunction, and large clot burden, thrombolytic therapy was considered and would have been administered had the thrombus in situ not been identified. In light of the thrombus in situ and the concern about possible systemic embolization with thrombolytic therapy, the patient underwent successful surgical thrombectomy. This case highlights the importance of echocardiography in the management of patients with PE. We believe that all patients should undergo echocardiography prior to receiving thrombolytic therapy for pulmonary emboli. Careful interrogation of the interatrial septum for the presence of a thrombus in situ is warranted. Thrombectomy should be considered in individuals with PE who have a thrombus in situ.
Role of noninvasive studies in risk stratification for sudden cardiac death
Authors: Kunavarapu Chandra , Bloomfield Daniel M.
Published: June 2007

Sudden cardiac death (SCD) is one of the leading causes of mortality in developing countries. To prevent SCD, it is crucial to have effective tools for identifying patients at risk, given that there are now effective devices and medications that can prevent SCD. Two noninvasive electrocardio‐graphic tools have been approved by the Food and Drug Administration and are being used clinically for identifying patients at risk for SCD: the signal‐averaged electrocardiogram (SAECG) and T‐wave alternans (TWA). This article reviews each of these approaches and includes a discussion of the mechanisms and a summary of the clinical studies published to date.
Reduced quality of life after myocardial infarction in women compared with men
Authors: Agewall Stefan , Berglund Margareta , Henareh Loghman
Published: June 2007

Background: Psychosocial factors have been suggested as risk factors for atherosclerotic disease.

Hypothesis: The purpose of the present study was to examine whether there is a gender difference in quality of life after a myocardial infarction with modern treatment of acute ischemic heart disease.

Methods: In all, 123 men and women aged between 31 and 80 years, and with a hospital‐diagnosed myocardial infarction occurring 1‐‐12 months prior to inclusion, were studied. Minor symptoms evaluation profile (MSEP) was used to estimate quality of life at entry.

Results: Age, hemodynamic data, smoking habits, as well as laboratory data, concomitant cardiovascular disease, and revascularization rate did not differ between men and women. Women had significantly more negative feelings regarding all the estimated dimensions of quality of life (Contentment, Vitality, and Sleep) than did men.

Conclusion: Self‐assessed quality of life after a myocardial infarction was significantly lower among women than among men despite similar age, treatment, and hemodynamic and laboratory data. The causal relationship is however, not known. Further studies are needed to evaluate the underlying mechanism of this observation. This may lead to the development of novel treatment strategies in female patients after a myocardial infarction.
Gender‐specific association between preproendothelin‐1 genotype and reduction of systolic blood pressure during antihypertensive treatment‐‐‐results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA)
Authors: Hallberg P. , Karlsson J. , Lind L. , Michaëlsson K. , Kurland L. , Kahan T. , Malmqvist K. , Öhman K. P. , Nyström F. , Liljedahl U. , Syvänen A. C. , Melhus H.
Published: June 2007

Background: Studies suggest that endothelin‐1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin‐1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment.

Hypothesis: This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol.

Methods: We determined the preproendothelin‐1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double‐blind fashion to treatment with either the AT1‐receptor antagonist irbesartan or the beta1‐adrenoceptor antagonist atenolol.

Results: The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin‐1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T‐allele responded on average with a more than two‐fold greater reduction than those with the G/G genotype (‐21.9 mmHg [3.9] vs. ‐8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T‐allele were seen among women.

Conclusions: Our finding suggests a gender‐specific relationship between the G5665T preproendothelin‐1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.
Prospective validation of a quantitative method for differentiating ischemic versus nonischemic cardiomyopathy by technetium‐99m sestamibi myocardial perfusion single‐photon emission computed tomography
Authors: Yao Siu‐Sun , Qureshi Ehtasham , Nichols Kenneth , Diamond George A. , Depuey E. Gordon , Rozanski Alan
Published: June 2007

Background: Myocardial perfusion single‐photon emission computed tomography (SPECT) permits assessment of stress perfusion and resting left ventricular (LV) function. Quantitative analysis of perfusion patterns among patients with LV dysfunction offers an opportunity for developing criteria to differentiate ischemic from nonischemic cardiomyopathy.

Hypothesis: Quantitative assessment of SPECT may allow differentiation between ischemic and nonischemic cardiomyopathy.

Methods: We evaluated 144 patients with LV ejection fraction ≤40%, divided into 63 patients with nonischemic and 81 with ischemic cardiomyopathy. Mean relative myocardial counts were obtained for regions drawn over defect and normal zones on rest and stress polar perfusion maps.

Results: Multivariate logistic regression analysis of significant univariate SPECT predictors of ischemic cardiomyopathy revealed that the stress defect severity ratio (SDSR) was the best predictor of ischemic cardiomyopathy (p < 0.0001). By receiver operator characteristic (ROC) curve analysis, an SDSR of ≤ 45% optimized prediction of ischemic cardiomyopathy (sensitivity 81%, specificity 96%). An SDSR of ≤ 45% occurred in 65 of 81 (80%) patients with ischemic cardiomyopathy, but in only 3 of the 63 (4%) patients with nonischemic cardiomyopathy (p < 0.0001). Applying the ≤45% SDSR threshold to a prospective group of 89 patients yielded a somewhat lower sensitivity (60%), but retained high specificity (91%) for identifying ischemic cardiomyopathy (p = NS vs. retrospective group).

Conclusions: Presence of a severe and extensive stress perfusion defect is a hallmark of ischemic cardiomyopathy. By contrast, a mild stress perfusion defect (SDSR of > 45%) is commonly present among patients with ischemic and non‐ischemic cardiomyopathy. An SDSR of ≤45% is a reproducible specific marker for identifying the presence of ischemic cardiomyopathy.
Effort/gains dynamics in heterogeneous networks
Authors: Mamatas L. , Tsaoussidis V.
Published: June 2007

We investigate the behaviour of TCP(α, β) protocols in the presence of wireless networks. We seek an answer to strategic issues of maximizing energy and bandwidth exploitation, without damaging the dynamics of multiple‐flow equilibrium. We take a fresh perspective on protocol design: What is the return of the effort that a protocol expends? Can we achieve more gains with less effort? We study first the design assumptions of TCP(α, β) protocols and discuss the impact of equation‐based modulation of α and β on protocol efficiency. We introduce two new measures to capture protocol behaviour: the ‘Extra Energy Expenditure’ and the ‘Unexploited Available Resource Index’. We confirm experimentally that, in general, smoothness and responsiveness constitute a tradeoff; however, we show that this tradeoff does not graft its dynamics into a conservative/aggressive behaviour, as it is traditionally believed. We uncover patterns of unjustified tactics; our results suggest that an adaptive congestion control algorithm is needed to integrate the dynamics of heterogeneous networks into
protocol behaviour. Copyright © 2007 John Wiley & Sons, Ltd.
Homeostatic proliferation of intestinal intraepithelial lymphocytes precedes their migration to extra‐intestinal sites
Authors: Stankovic Sanda , Zhan Yifan , Harrison Leonard C.
Published: June 2007

Cells with the phenotype of intraepithelial lymphocytes (IEL) are present systemically and have been implicated in immune regulation. To determine whether IEL undergo homeostatic proliferation and migrate from the small intestine, we analysed the fate of congenic IEL transferred into lymphopenic mice. Donor IEL homed to the small intestinal epithelium, where they expanded in an IL‐15‐dependent manner and expressed CD69, CD44 and CD103; proliferation did not occur in the spleen, the main other site of IEL detection early after transfer. By 12 days after transfer, a small proportion of intestinal IEL had up‐regulated the trafficking molecule CD62L. Four weeks after transfer, donor IEL with a CD69–CD44hiCD103– phenotype similar to memory T cells were present in spleen and other extra‐intestinal sites. Treatment of mice with blocking antibody to CD62L reduced appearance of cells in mesenteric lymph nodes; treatment with FTY720, a sphingosine 1‐phosphate receptor agonist that blocks egress of T cells from lymph nodes, reduced appearance of cells in spleen. The distribution of TCR αβ and γδ IEL varied between organs, αβ IEL being predominant. IEL proliferation and emigration under lymphopenic conditions suggests similar IEL turnover, albeit at a lower level, under physiological conditions.
Two‐chiral component microemulsion EKC – chiral surfactant and chiral oil. Part 2: Diethyl tartrate
Authors: Kahle Kimberly A. , Foley Joe P.
Published: June 2007

In this second study on dual‐chirality microemulsions containing a chiral surfactant and a chiral oil, a less hydrophobic and lower interfacial tension chiral oil, diethyl tartrate, is employed (Part 1, Foley, J. P. et al.., Electrophoresis, DOI: 10.1002/elps.200600551). Six stereochemical combinations of dodecoxycarbonylvaline (DDCV: R, S, or racemic, 2.00% w/v), racemic 2‐hexanol (1.65% v/v), and diethyl tartrate (D, L, or racemic, 0.88% v/v) were examined as pseudostationary phases (PSPs) for the enantioseparation of six chiral pharmaceutical compounds: pseudoephedrine, ephedrine, N‐methyl ephedrine, metoprolol, synephrine, and atenolol. Average efficiencies increased with the addition of a chiral oil to R‐DDCV PSP formulations. Modest improvements in resolution and enantioselectivity (αenant) were achieved with two‐chiral‐component systems over the one‐chiral‐component microemulsion. Slight enantioselective synergies were confirmed using a thermodynamic model. Results obtained in this study are compared to those obtained in Part 1 as well as those obtained with chiral MEEKC using an achiral, low‐interfacial‐tension oil (ethyl acetate). Dual‐chirality microemulsions with the more hydrophobic oil dibutyl tartrate yielded, relative to diethyl tartrate, higher efficiencies (100 000–134 000 vs. 80 800–94 300), but lower resolution (1.64–1.91 vs. 2.08–2.21) due to lower enantioselectivities (1.060–1.067 vs. 1.078–1.081). Atenolol enantiomers could not be separated with the dibutyl tartrate‐based microemulsions but were partially resolved using diethyl tartrate microemulsions. A comparable single‐chirality microemulsion based on the achiral oil ethyl acetate yielded, relative to diethyl tartrate, lower efficiency (78 300 vs. 91 600), higher resolution (1.99 vs. 1.83), and similar enantioselectivities.
Holocene climatic change and human settlement between the central Sahara and the Nile Valley: Archaeological and geomorphological results
Authors: Bubenzer Olaf , Riemer Heiko
Published: June 2007

Supraregional investigations of the Holocene occupational history of the eastern Sahara west of the Nile combined with the study of climatic, environmental, and geomorphological archives were carried out in contrasting desert regions from the Mediterranean coast strip to Wadi Howar in Sudan. The research areas are located far away from groundwater influence and are therefore capable of indicating environmental changes. Climatic development in accordance with nearly 500 14C dates from archaeological sites indicates a Holocene optimum lasting from approximately 9500 B.P. till the beginning of the drying trend that set in about 6300 B.P. (9000–5300 cal. B.C.). Although the faunal and floral remains are arid types, they indicate slightly wetter conditions than today. Surface water was the key factor that influenced the adaptation strategies of the mobile hunter‐gatherers (and in some parts, the pastoralists) in the desert regions. Large episodic camp sites agglomerated at favorable drainage systems and water pools, and settlement patterns strongly correlate with the paleohydrological factors examined with remote sensing cartography, geomorphological work, and the analysis of digital elevation models. © 2007 Wiley Periodicals, Inc.
Impaired liver regeneration and increased oval cell numbers following T cell–mediated hepatitis
Authors: Hines Ian N. , Kremer Michael , Isayama Fuyumi , Perry Ashley W. , Milton Richard J. , Black April L. , Byrd Christy L. , Wheeler Michael D.
Published: June 2007

The regeneration of liver tissue following transplantation is often complicated by inflammation and tissue damage induced by a number of factors, including ischemia and reperfusion injury and immune reactions to the donor tissue. The purpose of the current study is to characterize the effects of T cell–mediated hepatitis induced by concanavalin A (ConA) on the regenerative response in vivo. Liver regeneration following a partial (70%) hepatectomy (pHx) was associated with elevations in serum enzymes and the induction of key cell cycle proteins (cyclin D, cyclin E, and Stat3) and hepatocyte proliferation. The induction of T cell–mediated hepatitis 4 days before pHx increased serum enzymes 48 hours after pHx, reduced early cyclin D expression and Stat3 activation, and suppressed hepatocyte proliferation. This inhibition of proliferation was also associated with increased expression of p21, the activation of Smad2, the induction of transforming growth factor beta and interferon gamma expression, and reduced hepatic interleukin 6 production. Moreover, the ConA pretreatment increased the numbers of separate oval cell-like CD117+ cells and hematopoietic-like Sca-1+ cell populations 48 hours following pHx. The depletion of natural killer (NK) cells, an important component of the innate immune response, did not affect liver injury or ConA-induced impairment of hepatocyte proliferation but did increase the numbers of both CD117-positive and Sca-1–positive cell populations. Finally, splenocytes isolated from ConA-pretreated mice exerted cytotoxicity toward autologous bone marrow cells in an NK cell–dependent manner.

Conclusion:

T cell–mediated hepatitis alters early cytokine responses, reduces hepatocellular regeneration, and induces NK cell–sensitive oval cell and hematopoietic-like cell expansion following pHx. (HEPATOLOGY 2007;46:229–241.)
Sodium retention and ascites formation in a cholestatic mice model
Authors: Ackermann Daniel , Mordasini David , Cheval Lydie , Imbert-Teboul Martine , Vogt Bruno , Doucet Alain
Published: June 2007

Renal sodium retention in experimental liver cirrhosis originates from the distal nephron sensitive to aldosterone. The aims of this study were to (1) determine the exact site of sodium retention along the aldosterone-sensitive distal nephron, and (2) to evaluate the role of aldosterone and mineralocorticoid receptor activation in this process. Liver cirrhosis was induced by bile duct ligation in either adrenal-intact or corticosteroid-clamped mice. Corticosteroid-clamp was achieved through adrenalectomy and corticosteroid supplementation with aldosterone and dexamethasone via osmotic minipumps. 24-hours renal sodium balance was evaluated in metabolic cages. Activity and expression of sodium- and potassium-dependent adenosine triphosphatase were determined in microdissected segments of nephron. Within 4-5 weeks, cirrhosis induced sodium retention in adrenal-intact mice and formation of ascites in 50% of mice. At that time, sodium- and potassium-dependent adenosine triphosphatase activity increased specifically in cortical collecting ducts. Hyperaldosteronemia was indicated by increases in urinary aldosterone excretion and in sgk1 (serum- and glucocorticoid-regulated kinase 1) mRNA expression in collecting ducts. Corticosteroid-clamp prevented induction of sgk1 but not cirrhosis-induced sodium retention, formation of ascites and stimulation of sodium- and potassium-dependent adenosine triphosphatase activity and expression (mRNA and protein) in collecting duct. These findings demonstrate that sodium retention in cirrhosis is independent of hyperaldosteronemia and of the activation of mineralocorticoid receptor.

Conclusion:

Bile duct ligation in mice induces cirrhosis which, within 4-5 weeks, leads to the induction of sodium- and potassium-dependent adenosine triphosphatase in cortical collecting ducts, to renal sodium retention and to the formation of ascites. Sodium retention, ascites formation and induction of sodium- and potassium-dependent adenosine triphosphatase are independent of the activation of mineralocorticoid receptors by either aldosterone or glucocorticoids. (HEPATOLOGY 2007;46:173–179.)
Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process
Authors: Narayanaswamy Bommayya , Gonde Christopher , Tredger Michael J. , Hussain Munther , Vergani Diego , Davenport Mark
Published: June 2007

Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intra- and extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4+ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measurable inflammatory component longitudinally by studying a panel of cellular adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]) and soluble proinflammatory mediators (T helper 1 [interleukin {IL}-2 and interferonγ] and T helper 2 [IL-4 and IL-10]) cytokines and macrophage markers (tumor necrosis factor [TNF] α and IL-18) in 21 consecutive infants with BA post-Kasai portoenterostomy (KP). The levels of all adhesion molecules and cytokines (except IL-10) increased progressively by 6 months post-portoenterostomy. The response was non-polarized but with 100-fold increases in IL-2, TNFα and IL-18 particularly but only modest elevations in IL-10. When proinflammatory profiles were related to outcome, we found poor discrimination if assessed as clearance of jaundice but markedly higher values for IL-2, interferonγ, IL-4, IL-10, TNFα and sICAM-1 for those who would be transplanted by 1 year. Using ROC curve analysis for sICAM-1 levels at 1 month post-KP, a cutoff level of 1,779 ng/ml was determined to predict the need for transplantation at 1 year with 92% specificity and 87% sensitivity.

Conclusion:

The early circulating inflammatory process in BA is persistent, progressive and involves a non-polarized T cell, macrophage and cell adhesion molecule response only partially ameliorated by KP. (HEPATOLOGY 2007;46:180–187.)
Hippocampus modulates the behaviorally‐sensitizing effects of nicotine in a rat model of novelty‐seeking: Potential role for mossy fibers
Authors: Bhatti Amrinder S. , Hall Penny , Ma Zhiyuan , Tao Rui , Isgor Ceylan
Published: June 2007

Present experiments investigate interactions between a rat model of the novelty‐seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally‐sensitizing effects of NIC. Outbred rats were phenotype‐screened as high‐responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low‐responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3‐d intervals on postnatal days 33–44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra‐pyramidal mossy fiber (SP‐MF) terminal field. The increase in the SP‐MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC‐induced locomotion and the SP‐MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC. © 2007 Wiley‐Liss, Inc.
Consistent expression of the stem cell renewal factor BMI‐1 in primary and metastatic melanoma
Authors: Mihic‐Probst Daniela , Kuster Ariana , Kilgus Sandra , Bode‐Lesniewska Beata , Ingold‐Heppner Barbara , Leung Carly , Storz Martina , Seifert Burkhardt , Marino Silvia , Schraml Peter , Dummer Reinhard , Moch Holger
Published: June 2007

Stem cell‐like cells have recently been identified in melanoma cell lines, but their relevance for melanoma pathogenesis is controversial. To characterize the stem cell signature of melanoma, expression of stem cell markers BMI‐1 and nestin was studied in 64 cutaneous melanomas, 165 melanoma metastases as well as 53 melanoma cell lines. Stem cell renewal factor BMI‐1 is a transcriptional repressor of the Ink4a/Arf locus encoding p16ink4a and p14Arf. Increased nuclear BMI‐1 expression was detectable in 41 of 64 (64%) primary melanomas, 117 of 165 melanoma metastases (71%) and 15 of 53 (28%) melanoma cell lines. High nestin expression was observed in 14 of 56 primary melanomas (25%), 84 of 165 melanoma metastases (50%) and 21 of 53 melanoma cell lines (40%). There was a significant correlation between BMI‐1 and nestin expression in cell lines (p = 0.001) and metastases (p = 0.02). These data indicate that cells in primary melanomas and their metastases may have stem cell properties. Cell lines obtained from melanoma metastases showed a significant higher BMI‐1 expression compared to cell lines from primary melanoma (p = 0.001). Further, primary melanoma lacking lymphatic metastases at presentation (pN0, n = 40) was less frequently BMI‐1 positive than melanomas presenting with lymphatic metastases (pN1; n = 24; 52% versus 83%; p = 0.01). Therefore, BMI‐1 expression appears to induce a metastatic tendency. Because BMI‐1 functions as a transcriptional repressor of the Ink4a/Arf locus, p16ink4a and p14Arf expression was also analyzed. A high BMI‐1/low p16ink4a expression pattern was a significant predictor of metastasis by means of logistic regression analysis (p = 0.005). This suggests that BMI‐1 mediated repression of p16ink4a may contribute to an increased aggressive behavior of stem cell‐like melanoma cells. © 2007 Wiley‐Liss, Inc.
Gossypol reduction of tumor growth through ROS‐dependent mitochondria pathway in human colorectal carcinoma cells
Authors: Ko Ching‐Huai , Shen Shing‐Chuan , Yang Liang‐Yo , Lin Cheng‐Wei , Chen Yen‐Chou
Published: June 2007

Among 13 different cell lines, gossypol (GOS) showed the most potent cytotoxic effect against human colorectal carcinoma cells including HT29, COLO205, COLO320HSR and COLO320DM cells according to an MTT assay. The cytotoxic effect of GOS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in both COLO205 and HT29 cells. Activation of caspase 3, 6, 8 and 9, but not caspase 1, accompanied by the appearance of cleaved fragments of PARP (85 kDa), and caspase 3 (p17/p15), was identified in GOS‐treated cells. Decreases in Bcl‐xL and phosphorylated Bad proteins were found in GOS‐treated cells. GOS induction of ROS production was detected by in vitro plasmid digestion, and an increase in the intracellular peroxide level was observed in GOS‐treated COLO205 cells by the DCHF‐DA assay. Antioxidants including N‐acetyl‐L‐cysteine (NAC), catalase (CAT), tempol (TEM) and melatonin (MEL), but not allopurinol (ALL), pyrrolidine dithiocarbamate (PDTC) or diphenylene iodonium (DPI), significantly inhibited GOS‐induced Reactive oxygen species (ROS) production through blocking the occurrence of apoptosis. GOS induced mitochondrial dysfunction characterized by a loss of the mitochondria membrane potential via DiOC6 staining, and the release of cytochrome c (Cyt c) and apoptosis‐inducing factor (AIF) from mitochondria to the cytoplasm was observed. Removing mitochondria by ethidium bromide (EtBr) treatment significantly reduced the apoptotic effect of GOS in COLO205 cells. Furthermore, an intraperitoneal injection of GOS or gossypol acetic acid (GAA) significantly reduced the growth of colorectal carcinoma induced by a subcutaneous injection of COLO205 cells in nude mice. Results of the present study provide the first evidences demonstrating the in vitro and in vivo antitumor effects of GOS via an ROS‐dependent mitochondrial apoptosis in colorectal carcinoma. © 2007 Wiley‐Liss, Inc.
In vitro and in vivo evaluation of intrinsic immunogenicity of reporter and insulin gene therapy plasmids
Authors: Ratanamart Jarupa , Huggins Christopher G. , Kirby John A. , Shaw James A. M.
Published: June 2007

Background

Plasmid DNA vectors offer the potential of safe gene therapy avoiding viral vector‐mediated toxicity and immunogenicity. As plasmid DNA is bacterial in origin, presence of bacterial lipopolysaccharide (LPS) or unmethylated CpG dinucleotides may stimulate host innate immunity.

Methods

Primary cultures of mouse and rat dendritic cells were established and incubated with bacterial lipopolysaccaride; immunostimulatory CpG oligodeoxynucleotide; control GpC oligodeoxynucleotide; and a range of (pVR1012) plasmids encoding transgenes with increasing CpG content (wild‐type and mutant human preproinsulin; non‐mammalian eukaryotic eGFP reporter gene; and bacterial β‐galactosidase reporter gene). IL‐12 secretion was assayed to determine in vitro plasmid immunogenicity. Local inflammatory response following intramuscular injection of these plasmids, with or without a non‐ionic carrier SP1017, was characterised in vivo.

Results

Dose‐responsive LPS and CpG stimulation of IL‐12 secretion from dendritic cells was demonstrated. All plasmids induced significant IL‐12 secretion in comparison to control unstimulated cells. The β‐galactosidase plasmid had highest CpG content and induced significantly higher IL‐12 secretion than constructs containing a eukaryotic transgene. Injection of rat muscle with the β‐galactosidase construct induced greater inflammatory response than human preproinsulin constructs. This was further enhanced by SP1017. At 2 days post‐injection, monocyte/macrophage injection site infiltration predominated with CD8‐positive lymphocytes predominating at 7 days. There was no evidence of transgene expression in infiltrating immune cells.

Conclusions

Dendritic cell immunostimulation may be employed as an in vitro bioassay of innate immune response to plasmid DNA vectors during evaluation for clinical gene therapy. Copyright © 2007 John Wiley & Sons, Ltd.
Hepatitis C virus infection and genotypes in Antananarivo, Madagascar
Authors: Razafindratsimandresy Richter , Dubot Audrey , Ramarokoto Charles‐Emile , Iehlé Catherine , Soares Jean‐Louis , Rousset Dominique
Published: June 2007

The prevalence of hepatitis C virus (HCV) genotypes in Madagascar is not well known. Serum samples were obtained from 2,169 individuals selected by random sampling in the population living in Antananarivo city. Using HCV antibody test (Monolisa anti‐HCV Plus version 2), 36 (1.7%) of the 2,169 samples were positive. The presence of HCV RNA was determined by using reverse transcription polymerase chain reaction amplifying the 5′‐untranslated region (UTR): HCV RNA was detected in 17 of the 36 HCV antibodies positive samples. The genotype was determined using BLAST tool with another 5′‐UTR fragment. The phylogenetic analysis of the polymerase (NS5b) and envelope (E1/E2) fragment sequences showed a low level of diversity compared to the high diversity in other African countries: subtype 1b (nine cases, 52.9%) and genotype 2 (eight cases, 47.1%) including subtype 2b (six cases), subtype 2k (one case), and one unclassified subtype. BLAST search with the 5′‐UTR fragment sequence of this unclassified subtype identified that strain as subtype 2a. J. Med. Virol. 79: 1082–1088, 2007. © 2007 Wiley‐Liss, Inc.