bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanisms involved in the adaptive regulation of human intestinal biotin uptake: a study of the hSMVT system
Authors: Reidling Jack C. , Nabokina Svetlana M. , Said Hamid M.
Published: September 2006

Biotin, a water-soluble micronutrient, is vital for cellular functions, including growth and development. The human intestine utilizes the human sodium-dependent multivitamin transporter (hSMVT) for biotin uptake. Evidence exists showing that the intestinal biotin uptake process is adaptively regulated during biotin deficiency. Nothing, however, is known about molecular mechanism(s) involved during this adaptive regulation. This study compared two human-derived intestinal epithelial cell lines (HuTu-80 and Caco-2) during biotin-deficient or biotin-sufficient states and with an approach that assessed carrier-mediated biotin uptake, hSMVT protein and RNA levels, RNA stability, and hSMVT promoter activity. The results showed that during biotin deficiency, a significant and specific upregulation in carrier-mediated biotin uptake occurred in both human intestinal epithelial cell lines and that this increase was associated with an induction in protein and mRNA levels of hSMVT. The increase in mRNA levels was not due to an increase in RNA stability but was associated with an increase in activity of the hSMVT promoter in transfected human intestinal cells. Using promoter deletion constructs and mutational analysis in transiently transfected HuTu-80 and Caco-2 cells, a biotin deficiency-responsive region was mapped to a 103-bp area within the hSMVT promoter that contains gut-enriched Kruppel-like factor (GKLF) sites that confer the response to biotin deficiency. These results confirm that human intestinal biotin uptake is adaptively regulated and provide novel evidence demonstrating that the upregulation is not mediated via changes in hSMVT RNA stability but rather is due to transcriptional regulatory mechanism(s) that likely involve GKLF sites in the hSMVT promoter.
IL-18 mediates the formation of stress-induced, histamine-dependent gastric lesions
Authors: Seino Hitomi , Ueda Haruyasu , Kokai Masahiro , Tsuji Noriko M. , Kashiwamura Shinichiro , Morita Yoshio , Okamura Haruki
Published: September 2006

A role of IL-18 in the induction of gastric lesions by water immersion and restraint stress (WRS) was investigated. When wild-type BALB/c mice were exposed to WRS, levels of IL-18 in the serum and stomach increased rapidly with the development of acute gastric lesions. In IL-18-deficient mice [IL-18 knockout (KO) mice] similarly exposed to WRS, no gastric lesions were observed, but the administration of IL-18 before exposure to WRS resulted in the induction of WRS-induced gastric lesions. WRS enhanced gastric histidine decarboxylase (HDC) activity with concomitant increases in gastric histamine content. In IL-18 KO mice, the WRS-induced elevation of gastric HDC activity and histamine levels was much less than that in wild-type mice, but it was augmented by prior administration of IL-18. Treatment of wild-type mice with cimetidine, a histamine H2 receptor antagonist, inhibited the formation of WRS-induced gastric lesions with no effect on the induction of gastric IL-18 by WRS. Levels of corticosterone, one of the stress indicators, were lower in IL-18 KO mice than in wild-type mice. The glucocorticoid receptor antagonist mifepristone had no effect on gastric IL-18 and histamine levels but aggravated the stress-induced gastric lesions, indicating that corticosterone was not involved in the IL-18-mediated formation of stress-induced gastric lesions. These results indicate that IL-18 is involved in the induction of gastric lesions by WRS through augmentation of HDC activity and production of histamine in the stomach.
Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans
Authors: Romer Lee M. , Haverkamp Hans C. , Amann Markus , Lovering Andrew T. , Pegelow David F. , Dempsey Jerome A.
Published: September 2006

We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean ± SE maximum O2uptake (V̇o2 max) = 56.5 ± 2.7 ml·kg−1·min−1] cycled at ≥90% V̇o2 maxto exhaustion in normoxia [NORM-EXH; inspired O2fraction (FiO2) = 0.21, arterial O2saturation (SpO2) = 93 ± 1%] and hypoxia (HYPOX-EXH; FiO2= 0.13, SpO2= 76 ± 1%). The subjects also exercised in normoxia for a time equal to that achieved in hypoxia (NORM-CTRL; SpO2= 96 ± 1%). Quadriceps twitch force, in response to supramaximal single (nonpotentiated and potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10–100 Hz), was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated exercise-induced peripheral fatigue, as evidenced by a greater decrease in potentiated twitch force in HYPOX-EXH vs. NORM-CTRL (−39 ± 4 vs. −24 ± 3%, P < 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs. NORM-EXH (4.2 ± 0.5 vs. 13.4 ± 0.8 min, P < 0.01); however, peripheral fatigue was not different in HYPOX-EXH vs. NORM-EXH (−34 ± 4 vs. −39 ± 4%, P > 0.05). Blood lactate concentration and perceptions of limb discomfort were higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise.
The dorsomedial hypothalamus: a new player in thermoregulation
Authors: DiMicco Joseph A. , Zaretsky Dmitry V.
Published: September 2006

Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological responses to exteroceptive (“emotional”) stress in rats, including tachycardia. Tachycardia evoked from the DMH or seen in experimental stress in rats is blocked by microinjection of the GABAAreceptor agonist muscimol into the rostral raphe pallidus (rRP), an important thermoregulatory site in the brain stem, where disinhibition elicits sympathetically mediated activation of brown adipose tissue (BAT) and cutaneous vasoconstriction in the tail. Disinhibition of neurons in the DMH also elevates core temperature in conscious rats and sympathetic activity to least significant difference interscapular BAT (IBAT) and IBAT temperature in anesthetized preparations. The latter effects are blocked by microinjection of muscimol into the rRP, while microinjection of muscimol into either the rRP or DMH suppresses increases in sympathetic nerve activity to IBAT, IBAT temperature, and core body temperature elicited either by microinjection of PGE2into the preoptic area (an experimental model for fever), or central administration of fentanyl. Neurons concentrated in the dorsal region of the DMH project directly to the rRP, a location corresponding to that of neurons transsynaptically labeled from IBAT. Thus these neurons control nonshivering thermogenesis in rats, and their activation signals its recruitment in diverse experimental paradigms. Evidence also points to a role for neurons in the DMH in thermoregulatory cutaneous vasoconstriction, shivering, and endocrine adjustments. These directions provide intriguing avenues for future exploration that may expand our understanding of the DMH as an important hypothalamic site for the integration of autonomic, endocrine, and behavioral responses to diverse challenges.
Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury
Authors: Syring Rebecca S. , Otto Cynthia M. , Spivack Rebecca E. , Markstaller Klaus , Baumgardner James E.
Published: September 2006

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O2 (FiO2) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH2O, and either 1) high RR ( 24 ) and low PEEPe (3.5) or 2) low RR ( 7 ) and high PEEPe ( 14 ). We assessed cyclical lung recruitment with a fast arterial Po2 probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group ( P < 0.001), and mixed venous saturation was consistently greater in the high RR group ( P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.
Modulation of motor unit firing rates during a complex sinusoidal force task in young and older adults
Authors: Knight Christopher A. , Kamen Gary
Published: September 2006

This study compared motor unit rate coding and muscular force control in the first dorsal interosseous muscle of older ( n = 11, mean 72.3 yr) and young ( n = 12, mean 18.7 yr) adults. Rate coding during a sinusoidal isometric force-matching task was evaluated using spectral analysis of the time-varying changes in firing rate. The task required force modulations to match a trajectory comprising the sum of 0.15- and 0.45-Hz sine waves. Based on the amplitude of spectral peaks at 0.15 and 0.45 Hz, the amplitude of force modulation was similar in young and older adults at both frequencies ( F = 1.9, P = 0.17). Force modulation gain (FMG) was computed as the ratio of the amplitude of force modulation to the amplitude of firing rate modulation. To account for rate coding differences related to the properties of the motoneuron, recruitment threshold force was used as a covariate in age-group comparisons. At both task frequencies, firing rate was modulated with less amplitude ( F = 0 14, P < 0.001) and FMG was greater ( F = 0 27, P < 0.001) in the older adults. In its transformation of neural input to mechanical output, muscle is known to act as a low-pass filter. Compared with modulation at 0.15 Hz, less change in force per change in firing rate at 0.45 Hz (lower FMG; F = 0 67, P < 0.001), independent of age group, is consistent with this filtering effect. Our conclusion is that there is a reduced amplitude of firing rate modulation in older adults.
Anticipatory responses of catecholamines on muscle force production
Authors: French Duncan N. , Kraemer William J. , Volek Jeff S. , Spiering Barry A. , Judelson Daniel A. , Hoffman Jay R. , Maresh Carl M.
Published: September 2006

Few data exist on the temporal relationship between catecholamines and muscle force production in vivo. The purpose of this study was to examine the influence of preexercise arousal on sympathoadrenal neurohormones on muscular force expression during resistance exercise. Ten resistance-trained men completed two experimental conditions separated by 7 days: 1) acute heavy resistance exercise protocol (AHREP; 6 × 10 repetitions parallel squats, 80% 1 repetition maximum) and 2) control (Cont; rest). Peak force (Fpeak) was recorded during a maximal isometric squat preceding each set and mean force (Fmean) was measured during each set. Serial venous blood samples were collected before the AHREP and immediately preceding each set. Blood collection times were matched during Cont. Preexercise epinephrine (Epi), norepinephrine (NE), and dopamine (DA) increased ( P ≤ 0.05) above Cont by 270, 255, and 164%, respectively. During exercise, Epi, NE, and DA continued to increase by 512, 271, and 38%, respectively, above preexercise values. Fpeak and Fmean decreased by ∼20–25% over the course of the AHREP. Post hoc data analysis revealed that five subjects (Fmaintainers) showed no decline ( P ≥ 0.05) in muscular performance (Fpeak, Fmean) during AHREP and that five subjects (Freducers) had significant reductions in Fpeak and Fmean. Integrated area under the curve for Epi, NE, and Fpeak were greater ( P < 0.02) for Fmaintainers than Freducers. In conclusion, an anticipatory rise in catecholamines existed, which may be essential for optimal force production at the onset of exercise.
The Solitary Pulmonary Nodule – Is It Malignant or Benign? Diagnostic Performance of 99mTc-Depreotide SPECT
Authors: Naalsund Anne , Maublant Jean
Published: September 2006

Background: The diagnosis of malignancy may be difficult to establish in solitary pulmonary nodules (SPNs). Objectives: It was the aim of this study to assess diagnostic performances of technetium-99m (99mTc)-depreotide in differentiating benign from malignant SPNs and compare its diagnostic accuracy with fluor-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) in a subgroup of patients. Methods: One hundred and eighteen patients presenting with an SPN ≤3 cm suspected of malignancy on CT were included in a prospective, open-label, European multicentre trial. Single photon emission computed tomography (SPECT) images were acquired 1.1–4.5 h after injection of 459–770 MBq of 99mTc-depreotide. A subset of 29 patients also underwent FDG-PET imaging. Images were interpreted blindly and correlated with histopathology. Results:99mTc-depreotide was positive in 65 of 73 patients with a malignant lesion and negative in 30 of 45 patients with a benign lesion, resulting in a sensitivity, specificity and diagnostic accuracy of 89, 67 and 81%, respectively. In 40 patients with SPN ≤1.5 cm, diagnostic accuracy was 88, sensitivity 75 and specificity 96%. In the subset of 29 patients who underwent both 99mTc-depreotide SPECT and FDG-PET imaging, sensitivity, specificity and diagnostic accuracy were identical for both modalities, i.e. 90, 67 and 83%, respectively. Conclusions: The diagnostic accuracy of 99mTc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.
Heart Fatty Acid Binding Protein in the Diagnosis of Myocardial Infarction: Where Do We Stand Today?
Authors: Colli Andrea , Josa Miguel , Pomar Jose Luis , Mestres Carlos Alberto , Gherli Tiziano
Published: September 2006

Heart fatty acid binding protein (hFABP) is a novel small cytosolic protein that is abundant in the heart. It is highly cardiac-specific (i.e. expressed primarily in cardiac tissue), but is also expressed at low concentrations in tissues outside the heart. After myocardial ischemic damage, hFABP can be detected in the blood as early as 1–3 h after onset of chest pain, with peak values reached at 6–8 h and plasma levels returning to normal within 24–30 h. hFABP’s clinical diagnostic value is very limited in the presence of renal failure and skeletal muscle diseases as it is completely renally eliminated. In these conditions, the diagnosis of acute myocardial infarction (AMI) may be overestimated. The combination of initial hFABP release after symptom onset, rapid kidney clearance from the circulation and high cardiac specificity suggests great potential for clinical use. Serial measurements of hFABP in the first 24 h after onset of symptoms in AMI patients can: (a) identify patients who are susceptible to reperfusion strategies, (b) detect perioperative AMIs, (c) distinguish patients who reperfuse their infarct-related artery from those who do not, as early as 30 min after starting thrombolytic treatment, (d) detect re-infarction if it occurs within 10 h after symptom onset, and (e) permit an accurate estimation of myocardial infarct size providing important prognosis information.
Non-Invasive Quantitation of Myocardial Fibrosis Using Combined Tissue Harmonic Imaging and Integrated Backscatter Analysis in Dilated Cardiomyopathy
Authors: Mizuno Reiko , Fujimoto Shinichi , Saito Yoshihiko , Nakamura Shinobu
Published: September 2006

Background: Echocardiographic modalities have challenged the myocardial tissue characterization, but this reliability has not reached to the clinical use. This study investigated whether combined tissue harmonic imaging (THI) and integrated backscatter analysis (IB) provide the reliable and quantitative information about myocardial fibrosis in idiopathic dilated cardiomyopathy (DCM) in comparison with myocardial biopsy findings. Methods: We studied 56 patients with DCM. All patients underwent left ventricular endomyocardial biopsy and IB with fundamental imaging (FI) and THI. Results: In patients with good echocardiographic image quality, excellent correlations between the percentage of area occupied by myocardial fibrosis (% fibrosis) and the mean of integrated backscatter during a cardiac cycle (m-IB) measured with FI or THI were seen, and the correlation was closer with THI compared with FI. While in patients with poor image quality the correlation between m-IB and % fibrosis was only modest with FI, but the correlation was excellent with THI. Four cut-off values of m-IB with THI obtained from receiver operating characteristic curve discriminated between % fibrosis of more and less than 25, 30, 35, and 40% with high sensitivity and specificity. Multivariate analysis revealed that m-IB with THI was an independent predictor for discrimination of the severity of myocardial fibrosis. Conclusion: Combined IB and THI are a clinically applicable method and may be an alternative to myocardial biopsy in evaluating quantitatively myocardial fibrosis in DCM.
Impact of Statin Therapy on Clinical Outcomes in Chronic Heart Failure Patients According to Beta-Blocker Use: Results of CIBIS II
Authors: Krum Henry , Bailey Michael , Meyer Wilfried , Verkenne Patricia , Dargie Henry , Lechat Phillipe , Anker Stefan
Published: September 2006

Background: HMG-CoA reductase inhibitors (statins) are widely prescribed in patients with established systolic chronic heart failure (CHF). However, there is considerable controversy regarding their benefit in this setting. We therefore conducted a post-hoc analysis of outcomes according to statin use within the Second Cardiac Insufficiency Bisoprolol Study of the beta-blocker, bisoprolol, in NYHA classes III–IV systolic CHF patients (left ventricular ejection fraction <35%), eceiving background ACE inhibitor and diuretics. Methods: Analysis of clinical outcomes was performed according to baseline use of statins and subsequent randomisation to placebo or bisoprolol. Cumulative incidence curves for clinical events were constructed using the Kaplan-Meier method and tested for significance by log-rank statistic. Multivariate analysis was performed using the Cox proportional hazards regression model. Results: Two hundred and twenty-six of 2,647 patients were receiving statins at baseline (8.5%). Patients were well-matched in the 4 study groups at baseline for gender, weight, NYHA class and LVEF, however statin/bisoprolol patients were significantly younger (p < 0.05). Statin use at baseline was associated with a significant survival benefit compared with no statin use (p < 0.005, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.39–0.94). This benefit remained after adjusting for other significant predictors of survival (p < 0.05, HR = 0.60, 95%CI = 0.39–0.94). A significant interaction effect was noted with bisoprolol, survival being greatest in the statin/bisoprolol group (p < 0.001, HR = 0.14, 95% CI = 0.03–0.60). Survival was 98.3% in the statin/bisoprolol group, 82.1% in the statin/placebo group, 87.2% in the no statin/bisoprolol group and 82.8% in the no statin/placebo group. The statin/bisoprolol group was also associated with fewer cardiovascular (p < 0.005) and sudden deaths (p < 0.0005) compared with other groups. Conclusions: Despite the post-hoc, non-randomised nature of this analysis, these observations suggest that statin use appears to be beneficial in CHF. Furthermore, there appears to be a favourable interaction between statins and beta-blockade within the Second Cardiac Insufficiency Bisoprolol Study cohort. Prospective studies of statins are required to definitively address the role of these agents in established CHF.
Bronchial Involvement in the Cramp-Fasciculation Syndrome
Authors: de Entrambasaguas Manuel , Ortega-Albás Juan-José , Martínez-Lozano María-Dolores , Díaz José-Ramón
Published: September 2006

Background/Aims: Cramp-fasciculation syndrome (CFS) is an acquired, chronic, usually benign and rather heterogeneous condition with isolated fasciculations and muscle cramps generally induced by physical exercise. They commonly involve calf and quadriceps muscles. The pathophysiology of CFS is related to peripheral nerve hyperexcitability, most often located at the motor nerve terminal or intramuscular arborization. Methods: A 21-year-old man presented with a progressive syndrome of bronchospasm, cramps and muscle twitches related to physical exercise. Spirography showed bronchial hyperresponsiveness, so he received inhaled corticosteroids and β2-agonists that improved respiratory symptoms. Electrodiagnostic studies were consistent with CFS. Gabapentin was then introduced. Results: Both respiratory and muscle symptoms improved. A new spirogram after all inhaled medication had been discontinued was normal. Conclusion: This picture suggests a concomitant involvement of the peripheral motor nerves of both skeletal and airway autonomic smooth muscle, a presentation not previously reported in CFS.
The Craniospinal Venous System
Authors: Pearce J.M.S.
Published: September 2006

The valveless craniospinal venous system consists of veins and plexuses that communicate freely and whose flow is bidirectional. It comprises (1) the intracranial-cortical veins, dural sinuses, cavernous sinuses and ophthalmic veins, and (2) the vertebral venous plexuses, which freely anastomose with the intracranial venous system. The vertebral venous plexuses anastamose with the sacral, pelvic and prostatic venous plexus. It is clinically important since it provides a route for the spread of tumours, infection or emboli. This route may go unrecognised.
Diagnostic Agreement of Schizophrenia Spectrum Disorders among Chronic Patients with Functional Psychoses
Authors: Jakobsen K.D. , Frederiksen J.N. , Parnas J. , Werge T.
Published: September 2006

Background: To investigate whether diagnostic agreement across different diagnostic systems improves in a sample of chronic patients suffering from functional psychosis compared to first-admitted patients. Sampling and Methods: Among 353 patients with a history of functional psychosis, a subset of 100 individuals (35 women and 65 men) were randomly sampled and assessed using the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT). Based on the OPCRIT diagnoses the subjects suffering from schizophrenia and schizophrenia spectrum disorders according to seven diagnostic systems were identified. Diagnostic agreement was assessed using unweighted ĸ-statistics and pairwise concordance rates (CR). Results: High diagnostic agreement of schizophrenia was observed across the ICD-10 and DSM systems (CR >0.70, ĸ >0.70), which all had a significantly lower concordance to the St. Louis Criteria (SLC), research diagnostic criteria and Schneider’s first rank symptoms (FRS) (0.32< CR <0.66; –0.10< ĸ <0.51). Agreement on schizophrenia across all systems was observed for one fourth of the subjects. Elimination of the diagnostic impact of ‘co-occurrence of psychotic and affective symptoms’ excluded FRS standalone individuals from the sample, increased overall homogeneity and resulted in a dichotomized sample according to SLC (46 positive vs. 47 negative). SLC status could be predicted in 78% of cases by four items relating to family history and psychosocial function previous to the onset of illness. Similarly high pairwise CR were observed for schizophrenia spectrum disorders across all diagnostic systems. Conclusions: This study demonstrates that diagnostic agreement is higher among chronic patients than that observed in subjects with a recent onset of psychosis, although considerable discordance is also observed in this chronic sample. However, the discordance among chronic patients with functional psychosis largely derives from the different emphasis that diagnostic systems place on co-occurrence of psychotic and affective symptoms. This may have serious epistemological consequences, thus underlining the conventional nature of the present schizophrenia diagnoses and the need for biologically founded diagnostic criteria.
Antiproteinuric Effect of Losartan in Non-Diabetic Renal Disease Is Not Dependent on ACE Insertion/Deletion Polymorphism
Authors: Park Hyeong Cheon , Choi Hoon Young , Kim Beom Seok , Kang Shin Wook , Choi Kyu Hun , Ha Sung Kyu , Lee Ho Yung , Han Dae Suk
Published: September 2006

Background: The antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors appears to vary depending on the ACE insertion (I)/deletion (D) genotype in non-diabetic nephropathy. This interaction may be overcome by using an angiotensin II receptor blocker. We evaluated the short-term antiproteinuric effect of losartan according to the ACE I/D genotype in patients with non-diabetic proteinuric renal diseases. Methods: Ninety-nine (II/ID/DD: 36/52/11) non-diabetic patients with overt proteinuria were enrolled. The patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters including proteinuria were measured at baseline and at the end of each period. Results: At baseline each genotype (II/ID/DD) had comparable mean arterial blood pressure (mean ± SD) 103.2 ± 11.1/102.7 ± 10.6/104.1 ± 15.3; proteinuria (geometric mean, 95% CI, mg/day) 1,839 (1,518–2,227)/1,998 (1,683–2,372)/1,613 (1,072–2,427), and creatinine clearance (ml/min/1.73 m2) 65.7 ± 28.4/63.2 ± 27.8/68.8 ± 25.3, respectively. Both doses of losartan significantly lowered blood pressure and proteinuria (p < 0.05 vs. baseline), and losartan 100 mg was more effective than 50 mg in reducing proteinuria (52.5 ± 29.0 vs. 40.5 ± 30.8%, respectively, p = 0.001). No differences in the antiproteinuric effect of losartan was observed among the ACE I/D genotype. Losartan 100 mg demonstrated a comparable degree of mean arterial pressure (mean ± SD, %) (II/ID/DD, 13.3 ± 7.6/10.8 ± 9.8/13.0 ± 11.6, respectively, p = NS) and proteinuria reduction (mean, 95% CI) among the three genotypes (51.4% (40.3–62.5%)/53.4% (45.5–61.4%)/51.4% (40.0–63.8%), respectively, p = NS). Conclusion: Our data suggest that losartan provides a similar short-term antiproteinuric response for all three genotypes of ACE I/D genotype in non-diabetic proteinuric chronic renal disease.
Regulation of Fibrinolysis by Thrombin Activatable Fibrinolysis Inhibitor, an Unstable Carboxypeptidase B That Unites the Pathways of Coagulation and Fibrinolysis
Authors: Mosnier Laurent O. , Bouma Bonno N.
Published: September 2006

The coagulation and fibrinolytic systems safeguard the patency of the vasculature and surrounding tissue. Cross regulation of coagulation and fibrinolysis plays an important role in preserving a balanced hemostatic process. Identification of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) as an inhibitor of fibrinolysis and one of the main intermediates between coagulation and fibrinolysis, greatly improved our understanding of cross regulation of coagulation and fibrinolysis. As TAFI is an enzyme that is activated by thrombin generated by the coagulation system, its activation is sensitive to the dynamics of the coagulation system. Defects in coagulation, such as in thrombosis or hemophilia, resonate in TAFI-mediated regulation of fibrinolysis and imply that clinical symptoms of coagulation defects are amplified by unbalanced fibrinolysis. Thrombomodulin promotes the generation of both antithrombotic activated protein C (APC) and prothrombotic (antifibrinolytic) activated TAFI, illustrating the paradoxical effects of thrombomodulin on the regulation of coagulation and fibrinolysis. This review will discuss the role of TAFI in the regulation of fibrinolysis and detail its regulation of activation and its potential therapeutic applications in thrombotic disease and bleeding disorders.
Vertebral Artery Dissection
Authors: Arnold Marcel , Bousser Marie Germaine , Fahrni Gregor , Fischer Urs , Georgiadis Dimitrios , Gandjour Joubin , Benninger David , Sturzenegger Matthias , Mattle Heinrich P. , Baumgartner Ralf W.
Published: September 2006

Background and Purpose—

Few data exist about clinical, radiologic findings, clinical outcome, and its predictors in patients with spontaneous vertebral artery dissection (sVAD).

Methods—

Clinical characteristics, imaging findings, 3-month outcomes, and its predictors were investigated in consecutive patients with sVAD.

Results—

One hundred sixty-nine patients with 195 sVAD were identified. Brain ischemia occurred in 131 patients (77%; ischemic stroke, n=114, 67%; transient ischemic attack, n=17, 10%). Three patients with ischemic stroke showed also signs of subarachnoid hemorrhage (SAH); 3 (2%) had SAH without ischemia. The 134 patients with brain ischemia or SAH had head and/or neck pain in 118 (88%) and pulsatile tinnitus in seven (5%) patients. The remaining 35 patients (21%) had isolated head and/or neck pain in 21 (12%) cases, asymptomatic sVAD in 13 (8%), and cervical radiculopathy in one case (1%). Location of sVAD was more often in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) than in the prevertebral (V1; 20%) or intracranial (V4; 11%) segment (
P
=0.0001). Outcome was favorable (modified Rankin scale score 0 or 1) in 88 (82%) of 107 ischemic stroke patients with follow up. Two (2%) patients died. Low baseline National Institutes of Health Stroke Scale score (
P
<0.0001) and younger age (
P
=0.007) were independent predictors of favorable outcome.

Conclusions—

sVAD is predominantly located in the pars transversaria (V2) or the atlas loop (V3). Most patients show posterior circulation ischemia. Favorable outcome is observed in most ischemic strokes and independently predicted by low National Institutes of Health Stroke Scale score and younger age.
Reduced Pretreatment Ipsilateral Middle Cerebral Artery Cerebral Blood Flow Is Predictive of Symptomatic Hemorrhage Post–Intra-Arterial Thrombolysis in Patients With Middle Cerebral Artery Occlusion
Authors: Gupta Rishi , Yonas Howard , Gebel James , Goldstein Steven , Horowitz Michael , Grahovac Stephen Z. , Wechsler Lawrence R. , Hammer Maxim D. , Uchino Ken , Jovin Tudor G.
Published: September 2006

Background and Purpose—

Intracerebral hemorrhage (ICH) can be a devastating complication associated with thrombolytic therapy for acute ischemic stroke. We hypothesized that patients with lower prethrombolysis cerebral blood flow (CBF) were at a higher risk of symptomatic ICH (sICH).

Methods—

Twenty-three patients who underwent quantitative CBF assessment with Xenon CT studies for acute stroke before intra-arterial (IA) thrombolysis for a middle cerebral artery (MCA) or internal carotid artery terminus occlusion within 6 hours of symptom onset were studied. Univariate and multivariate analysis were carried out to determine predictors of sICH post-IA thrombolysis. Receiver operating characteristic curves were generated to determine the association between mean ipsilateral CBF and the occurrence of sICH.

Results—

The mean age of our cohort was 68±12 years and a mean National Institutes of Health Stroke Scale (NIHSS) score of 18±3. In univariate analysis, patients with higher percent of core infarct, hyperglycemia, and reduced mean ipsilateral CBF were at risk of sICH. In multivariate analysis only mean ipsilateral CBF was associated with higher rates of sICH (odds ratio 1.58; 95% CI, 1.01 to 2.51;
P
<0.04). The area under the receiver operating characteristic curve was 0.87 (95% CI, 0.76 to 0.97;
P
<0.005).

Conclusions—

Patients with lower pre-IA thrombolysis mean ipsilateral MCA CBF are at significantly higher risk for sICH in the setting of a MCA or carotid terminus occlusion. The threshold identified in this study may be useful for selection of patients with acute MCA occlusions for acute stroke thrombolysis.
Humanin Is a Novel Neuroprotective Agent Against Stroke
Authors: Xu Xingshun , Chua Chu C. , Gao Jinping , Hamdy Ronald C. , Chua Balvin H.L.
Published: September 2006

Background and Purpose—

Humanin (HN) is a 24-amino acid peptide best known for its ability to protect neurons from damage caused by Alzheimer disease-related proteins. This study examines the neuroprotective effects of HNG (a potent form of HN) on focal cerebral ischemia/reperfusion injury in mice.

Methods—

Mice underwent middle cerebral artery occlusion for 75 minutes followed by 24-hour reperfusion. Mice were pretreated with 0.1 μg HNG (intracerebroventricularly) 30 minutes before ischemia; posttreated at 0, 2, 4, and 6 hours after ischemia; or pretreated with 1 μg HNG (intraperitoneally) 1 hour before ischemia. Neurological deficits and cerebral infarct volume were evaluated. Neuronal apoptosis and activated poly(ADP-ribose) polymerase expression were measured by TUNEL and Western blot analysis, respectively. Activated ERKs were examined by Western blot analysis.

Results—

Pretreatment with 0.1 μg HNG (intracerebroventricularly) 30 minutes before ischemia reduced cerebral infarct volume from 56.2±3.0% to 26.1±1.4% (
P
<0.01). HNG posttreatment after 4 hours of reperfusion reduced cerebral infarct volume to 45.6±2.6% (
P
<0.05). Pretreatment with 1 μg HNG (intraperitoneally) 1 hour before ischemia or posttreatment after 2 hours of reperfusion reduced cerebral infarct volume significantly. HNG also significantly improved neurological function and inhibited both neuronal apoptosis as well as poly(ADP-ribose) polymerase activation. A significant decrease of phospho-ERK was observed in mice treated with HNG, whereas phospho-JNK and phospho-p38 levels were not altered.

Conclusions—

Our results demonstrate that HNG protects against cerebral ischemia/reperfusion injury in mice. HNG offers neuroprotection in vivo at least in part by inhibiting ERK activation. These findings suggest a potential therapeutic role for HNG in the treatment of stroke.
The Biological Living Conditions of Nineteenth-Century Chinese Males in America
Authors: Carson Scott Alan
Published: September 2006

Anthropometric data from American prisons reveal that the stature of Chinese immigrants to the American West compared favorably to that of other Chinese of the period for whom documentation exists. Year of birth was more significant than socioeconomic status in explaining variations in Chinese immigrants' height, indicating that political and economic events were primary factors in the decline of their stature as the century progressed.
Spatial Presence and Emotions during Video Game Playing: Does It Matter with Whom You Play?
Authors: Ravaja Niklas , Saari Timo , Turpeinen Marko , Laarni Jari , Salminen Mikko , Kivikangas Matias
Published: September 2006

The authors examined whether the nature of the opponent (computer, friend, or stranger) influences spatial presence, emotional responses, and threat and challenge appraisals when playing video games. In a within-subjects design, participants played two different video games against a computer, a friend, and a stranger. In addition to self-report ratings, cardiac interbeat intervals (IBIs) and facial electromyography (EMG) were measured to index physiological arousal and emotional valence. When compared to playing against a computer, playing against another human elicited higher spatial presence, engagement, anticipated threat, post-game challenge appraisals, and physiological arousal, as well as more positively valenced emotional responses. In addition, playing against a friend elicited greater spatial presence, engagement, and self-reported and physiological arousal, as well as more positively valenced facial EMG responses, compared to playing against a stranger. The nature of the opponent influences spatial presence when playing video games, possibly through the mediating influence on arousal and attentional processes.
An Augmented Reality System for the Treatment of Acrophobia: The Sense of Presence Using Immersive Photography
Authors: Juan M. Carmen , Baños Rosa , Botella Cristina , Pérez David , Alcaníiz Mariano , Monserrat Carlos
Published: September 2006

This paper describes an augmented reality (AR) system for the treatment of acrophobia. First, the technical characteristics of the original prototype are described. Second, the capacity of the immersive photography used in the AR system to provoke sense of presence in users is tested.

Forty-one participants without fear of heights walked around a staircase in both a real environment and an immersive photography environment. Immediately after their experience, participants were given the SUS questionnaire to assess their subjective sense of presence. The users' scores in the immersive photography were very high. Results indicate that the acrophobic context can be useful for the treatment of acrophobia. However, statistically significant differences were found between real and immersive photography environments. Specifically, the immersive photography environment was not confused with reality since data showed that SUS distinguished between the real and immersive photography experiences.
Is This My Hand I See Before Me? The Rubber Hand Illusion in Reality, Virtual Reality, and Mixed Reality
Authors: IJsselsteijn Wijnand A , de Kort Yvonne A. W , Haans Antal
Published: September 2006

This paper presents a first study in which a recently reported intermodal perceptual illusion known as the rubber hand illusion is experimentally investigated under mediated conditions. When one's own hand is placed out of view and a visible fake hand is repeatedly stroked and tapped in synchrony with the unseen hand, subjects report a strong sense in which the fake hand is experienced as part of their own body. In our experiment, we investigated this illusion under three conditions: (i) unmediated condition, replicating the original paradigm, (ii) virtual reality (VR) condition, where both the fake hand and its stimulation were projected on the table in front of the participant, and (iii) mixed reality (MR) condition, where the fake hand was projected, but its stimulation was unmediated. Dependent measures included self-report (open-ended and questionnaire-based) and drift, that is, the offset between the felt position of the hidden hand and its actual position. As expected, the unmediated condition produced the strongest illusion, as indicated both by self-report and drift towards the rubber hand. The VR condition produced a more convincing subjective illusion than the MR condition, although no difference in drift was found between the mediated conditions. Results are discussed in terms of perceptual mechanisms underlying the rubber hand illusion, and the illusion's relevance to understanding telepresence.
On Consistency and Network Latency in Distributed Interactive Applications: A Survey—Part II
Authors: Delaney Declan , Ward Tomás , McLoone Seamus
Published: September 2006

This paper is the second part of a two part paper that documents a detailed survey of the research carried out on consistency and latency in distributed interactive applications (DIAs) in recent decades. Part I reviewed the terminology associated with DIAs and offered definitions for consistency and latency. A classification for consistency maintenance mechanisms was given and various mechanisms belonging to the first of three categories, time management, were described. Here, in the second part of the paper, the remaining two categories of mechanisms are examined—information management (such as predictive contract techniques, relevance filtering, packet bundling) and system architecture (such as QoS and protocols).
European Security and Defense Policy Demystified
Authors: Anderson Stephanie , Seitz Thomas R.
Published: September 2006

From a military standpoint, the European Union’s Security and Defense Policy (ESDP) defies logic. Why would the European allies seek to create a competing military force outside NATO when worried about American isolationism and when unable and unwilling to dedicate the necessary resources? This article suggests an alternative motive behind the European Union’s establishment of a defense program—the development and enhancement of a “European identity.” In short, the ESDP is designed in no small part to further the project of nation-building in a broadening European Union. This article proposes a social-constructivist framework for analyzing this development.
Civilian Monitoring of U.S. Military Operations in the Information Age
Authors: Coletta Damon , Feaver Peter D.
Published: September 2006

Recent research on U.S. civil-military relations has applied principal-agent logic to analyze the post-cold war friction between civilian authorities and top military commanders. This article proposes a greater emphasis on bargaining to focus on the effects of new monitoring technologies available to the civilian principal in the information age. As monitoring capabilities increase and military agents perceive their autonomy disappearing, tacit bargaining over the president’s level of resource commitment to a crisis should become more prevalent. This idea receives support from a comparison across case studies of the limited use of force taken from different technological eras. A new style of civil-military bargaining presents both challenges and opportunities to the traditional conception of military professionalism.
Israel’s Cultural Code of Captivity and the Personal Stories of Yom Kippur War Ex-POWs
Authors: Gavriely Dalia
Published: September 2006

Between 1973 and 1993, over 30 of the 591 American ex-POWs from the Vietnam War (1973) published autobiographies; on the Israeli side, a book was written by only 1 of the 314 ex-POWs from the Yom Kippur War (1973). In the United States, their return transformed the POWs into national heroes. Alternatively, in Israel, the ex-POWs put on a thick cover of silence, to disappear from the public eye and the public discourse for almost twenty-five years. This article attempts to delve into the meaning of the voluntary reticence of Yom Kippur War ex-POWs. An examination of the complex relationship between their personal stories and Israel’s cultural code of captivity helps explain that silence. The article contributes to our understanding of the influence of cultural codes in the construction of military history, military autobiography, and military values and myths.
From Foe to Friend
Authors: Tovy Tal
Published: September 2006

This article examines a generally unnoticed chapter of the Vietnam War: the use of former Vietcong combatants as scouts in the United States military forces during the war. The name of the program was the Kit Carson Scout Program. The article will deal with all the aspects of the program, including the training program, the process of stationing the scouts in the United States Army and Marines units, and the significance contribution to the war efforts.
The Effects of Military Affiliation, Gender, and Political Ideology on Attitudes toward the Wars in Afghanistan and Iraq
Authors: Rohall David E. , Ender Morten G. , Matthews Michael D.
Published: September 2006

The United States armed-forces-and-society intersection is explored comparing attitudes toward the wars in Iraq and Afghanistan among West Point, Reserve Officers’ Training Corps (ROTC), and civilian undergraduates. A survey was administered in January and February 2003 to determine if military affiliation is associated with attitudes toward sending troops into Afghanistan after the war started and Iraq before sending troops. Majorities of all students supported both war efforts, though United States Military Academy at West Point and ROTC cadets are somewhat more supportive of both wars compared to civilian students. However, most differences are explained by students’ gender and political affiliation, suggesting that differences between groups result from selection effects rather than cultural differences. The authors contend a fourth wave in civil-military affairs potentially has emerged in the immediate aftermath of 9/11 through a civil-military attitude fusion complicated by a gender-politics gap.
Why Do I Hate Thee? Conflict Misperceptions and Intergroup Mistrust
Authors: Chambers John R. , Melnyk Darya
Published: September 2006

Members of partisan social groups often exaggerate how much their own opinions differ from those of their rivals. In the present two studies, partisans estimated their own and their rivals' attitudes toward different issues related to the social conflict and also made a variety of evaluative judgments about their own and the rival group. The authors found that (a) partisans perceive more disagreement with their rivals about values that are central to their own sides' ideological position than those that are central to their rivals' position and (b) perceptions of disagreement about the partisans' own central values are what predicts partisans' global evaluations of members of the outgroup (e.g., disliking, trait stereotypes, perceived similarity). Furthermore, partisans believed their adversaries were motivated by an opposition to the partisans' own core values rather than by promotion of the adversaries' core values. Discussion concentrates on the theoretical and applied implications of these findings.
Gender Differences in Attitudes Toward Gay Men and Lesbians: The Role of Motivation to Respond Without Prejudice
Authors: Ratcliff Jennifer J. , Lassiter G. Daniel , Markman Keith D. , Snyder Celeste J.
Published: September 2006

Research has uncovered consistent gender differences in attitudes toward gay men, with women expressing less prejudice than men (Herek, 2003). Attitudes toward lesbians generally show a similar pattern, but to a weaker extent. The present work demonstrated that motivation to respond without prejudice importantly contributes to these divergent attitudes. Study 1 revealed that women evince higher internal motivation to respond without prejudice (IMS, Plant & Devine, 1998) than do men and that this difference partially mediates the relationship between gender and attitudes toward gay men. The second study replicated this finding and demonstrated that IMS mediates the relationship between gender and attitudes toward lesbians. Study 2 further revealed that gender-role variables contribute to the observed gender differences in motivation to respond without prejudice. These findings provide new insights into the nature of sexual prejudice and for the first time point to possible antecedents of variation in motivation to respond without prejudice.
Overcoming the Self-Promotion Dilemma: Interpersonal Attraction and Extra Help as a Consequence of Who Sings One's Praises
Authors: Pfeffer Jeffrey , Fong Christina T. , Cialdini Robert B. , Portnoy Rebecca R.
Published: September 2006

Prior research has shown that positive information presented by a third party shields people from the negative consequences of being perceived as self-promoting. But in many contexts, those third parties are intermediaries with a financial interest in the person being promoted rather than neutral parties. In three experimental studies, the authors demonstrate that even when intermediaries are not neutral, they can be helpful for overcoming the self-promotion dilemma—the need to assert one's competence but not be harmed by the fact that people who self-promote are viewed negatively. The authors find that hiring an agent to sing one's praises results in more favorable perceptions of the client, which contributes, in turn, to a greater willingness to offer that person assistance. It is also shown that even when the intermediary is physically present and seen to be complicit with the client, the positive effects of having someone else speak on one's behalf persist.