bluuebunny/crossref_metadata_2025 huggingface dataset:
AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo
Authors: Shearer Jane , Fueger Patrick T. , Rottman Jeffrey N. , Bracy Deanna P. , Martin Paul H. , Wasserman David H.
Published: July 2004

AMP-activated protein kinase (AMPK) independently increases glucose and long-chain fatty acid (LCFA) utilization in isolated cardiac muscle preparations. Recent studies indicate this may be due to AMPK-induced phosphorylation and activation of nitric oxide synthase (NOS). Given this, the aim of the present study was to assess the effects of AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; 10 mg·kg−1·min−1) on glucose and LCFA utilization in cardiac muscle and to determine the NOS dependence of any observed effects. Catheters were chronically implanted in a carotid artery and jugular vein of Sprague-Dawley rats. After 4 days of recovery, conscious, unrestrained rats were given either water or water containing 1 mg/ml nitro-l-arginine methyl ester (l-NAME) for 2.5 days. After an overnight fast, rats underwent one of four protocols: saline, AICAR, AICAR + l-NAME, or AICAR + Intralipid (20%, 0.02 ml·kg−1·min−1). Glucose was clamped at ∼6.5 mM in all groups, and an intravenous bolus of 2-deoxy-[3H]glucose and [125I]-15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid was administered to obtain indexes of glucose and LCFA uptake and clearance. Despite AMPK activation, as evidenced by acetyl-CoA carboxylase (Ser221) and AMPK phosphorylation (Thr172), AICAR increased cardiac LCFA but not glucose clearance. l-NAME + AICAR established that this effect was not due to NOS activation, and AICAR + Intralipid showed that increased cardiac LCFA clearance was not LCFA-concentration dependent. These results demonstrate that, in vivo, AMPK stimulation increases LCFA but not glucose clearance by a NOS-independent mechanism.
Time course of nitric oxide production after endotoxin challenge in mice
Authors: Braulio Valeria B. , Ten Have Gabrie A. M. , Vissers Yvonne L. J. , Deutz Nicolaas E. P.
Published: July 2004

Nitric oxide (NO) regulates numerous processes during endotoxemia and inflammation. However, the sequential changes in whole body (Wb) nitric oxide (NO) production during endotoxemia in vivo remain to be clarified. Male Swiss mice were injected intraperitoneally with saline (control group) or lipopolysaccharide (LPS group). After 0, 2, 4, 6, 9, 12, and 24 h, animals received a primed constant infusion of l-[guanidino-15N2-2H2]arginine, l-[ureido-15N]citrulline, l-[5-15N]glutamine, and l-[ ring-2H5]phenylalanine in the jugular vein. Arterial blood was collected for plasma arginine (Arg), citrulline (Cit), glutamine (Gln), and phenylalanine (Phe) concentrations and tracer-to-tracee ratios. NO production was calculated as plasma Arg-to-Cit flux, Wb de novo Arg synthesis as plasma Cit-to-Arg flux, and Wb protein breakdown as plasma Phe flux. LPS reduced plasma Arg and Cit and increased Gln and Phe concentrations. Two peaks of NO production were observed at 4 and 12 h after LPS. Although LPS did not affect total Arg production, de novo Arg production decreased after 12 h. The second peak of NO production coincided with increased Wb Cit, Gln, and Phe production. In conclusion, the curve of NO production in both early and late phases of endotoxemia is not related to plasma Arg kinetics. However, because Wb Cit, Gln, and Phe fluxes increased concomitantly with the second peak of NO production, NO production is probably related to the catabolic phase of endotoxemia.
Phosphoinositides in Constitutive Membrane Traffic
Authors: Roth Michael G.
Published: July 2004

Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.
Nitric Oxide in Health and Disease of the Respiratory System
Authors: Ricciardolo Fabio L. M. , Sterk Peter J. , Gaston Benjamin , Folkerts Gert
Published: July 2004

During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.
Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease
Authors: Owens Gary K. , Kumar Meena S. , Wamhoff Brian R.
Published: July 2004

The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/processes are altered in vascular injury or disease. A major challenge in understanding differentiation of the vascular SMC is that this cell can exhibit a wide range of different phenotypes at different stages of development, and even in adult organisms the cell is not terminally differentiated. Indeed, the SMC is capable of major changes in its phenotype in response to changes in local environmental cues including growth factors/inhibitors, mechanical influences, cell-cell and cell-matrix interactions, and various inflammatory mediators. There has been much progress in recent years to identify mechanisms that control expression of the repertoire of genes that are specific or selective for the vascular SMC and required for its differentiated function. One of the most exciting recent discoveries was the identification of the serum response factor (SRF) coactivator gene myocardin that appears to be required for expression of many SMC differentiation marker genes, and for initial differentiation of SMC during development. However, it is critical to recognize that overall control of SMC differentiation/maturation, and regulation of its responses to changing environmental cues, is extremely complex and involves the cooperative interaction of many factors and signaling pathways that are just beginning to be understood. There is also relatively recent evidence that circulating stem cell populations can give rise to smooth muscle-like cells in association with vascular injury and atherosclerotic lesion development, although the exact role and properties of these cells remain to be clearly elucidated. The goal of this review is to summarize the current state of our knowledge in this area and to attempt to identify some of the key unresolved challenges and questions that require further study.
Stochastic processes and antiderivational equations on non‐Archimedean manifolds
Authors: Ludkovsky S. V.
Published: July 2004

Stochastic processes on manifolds over non‐Archimedean
fields and with transition measures having values in the
field ℂ of complex numbers are studied.
Stochastic antiderivational equations (with the
non‐Archimedean time parameter) on manifolds are
investigated.
On the class of square Petrie matrices induced by cyclic permutations
Authors: Du Bau-Sen
Published: July 2004

Let n ≥ 2 be an integer and let P = {1, 2, …, n, n + 1}. Let
Zp denote the finite field {0, 1, 2, …, p − 1},
where p ≥ 2 is a prime. Then every map σ on P

determines a real n × n Petrie matrix Aσ which is
known to contain information on the dynamical properties such as
topological entropy and the Artin‐Mazur zeta function of the
linearization of σ. In this paper, we show that if
σ is a cyclic permutation on P, then all such
matrices Aσ are similar to one another over Z2 (but
not over Zp for any prime p ≥ 3) and their characteristic
polynomials over Z2 are all equal to . As a
consequence, we obtain that if σ is a cyclic
permutation on P, then the coefficients of the characteristic
polynomial of Aσ are all odd integers and hence nonzero.
Nonoperative Management for In-Season Athletes with Anterior Shoulder Instability
Authors: Buss Daniel D. , Lynch Gregory P. , Meyer Christopher P. , Huber Shane M. , Freehill Michael Q.
Published: July 2004

Background

Acute or recurrent anterior shoulder instability is a frequent injury for in-season athletes. Treatment options for this injury include shoulder immobilization, rehabilitation, and shoulder stabilization surgery.

Purpose

To determine if in-season athletes can be returned to their sports quickly and effectively after nonoperative treatment for an anterior instability episode.

Methods

Over a 2-year period, 30 athletes matched the inclusion criteria for this study. Nineteen athletes had experienced anterior dislocations, and 11 had experienced subluxations. All were treated with physical therapy and fitted, if appropriate, with a brace. These athletes were followed for the number of recurrent instability episodes, additional injuries, subjective ability to compete, and ability to complete their season or seasons of choice.

Results

Twenty-six of 30 athletes were able to return to their sports for the complete season at an average time missed of 10.2 days (range, 0-30 years). Ten athletes suffered sport-related recurrent instability episodes (range, 0-8 years). An average of 1.4 recurrent instability episodes per season per athlete occurred. There were no further injuries attributable to the shoulder instability. Sixteen athletes underwent surgical stabilization for their shoulders during the subsequent off-season.

Conclusions

Most of the athletes were able to return to their sport and complete their seasons after an episode of anterior shoulder instability, although 37% experienced at least 1 additional episode of instability during the season.
Effects of Patellar Tendon Width and Preoperative Quadriceps Strength on Strength Return after Anterior Cruciate Ligament Reconstruction with Ipsilateral Bone–Patellar Tendon–Bone Autograft
Authors: Shelbourne K. Donald , Johnson Brent C.
Published: July 2004

Background

Strength return after anterior cruciate ligament reconstruction varies greatly.

Hypothesis

Patients with small patellar tendons and weak preoperative quadriceps muscle strength would not be able to regain full strength.

Study Design

Retrospective review of prospectively collected data.

Methods

Patellar tendon widths for 540 patients were measured intraoperatively and grouped according to size (small, 20-26 mm; medium, 27-30 mm; large, 31-36 mm). Strength measured preoperatively was determined by dividing the torque value of the injured leg by the torque value of the noninjured leg. Strength after surgery was determined by dividing the postoperative value in the anterior cruciate ligament–reconstructed leg by the preoperative value of the uninjured leg.

Results

At 1, 2, and 3 months after surgery, patients with large tendons had statistically significantly better strength than patients with small and medium tendons (P < .01), but this difference was not significant 2 years after operation. At all times after surgery, patients with preoperative strength >90% had statistically significantly better strength than patients with preoperative strength <75% (P < .01). At 3 months after surgery, patients with good preoperative strength and large tendons had a mean postoperative strength of 79% compared with 62% for patients who had poor preoperative strength and small tendons (P < .001).

Conclusions

If patients undergoing anterior cruciate ligament reconstruction have a weak leg before surgery and small patellar tendons, their ability to regain full strength after surgery may be compromised, especially in the first year after surgery.
In Vivo Elongation of the Anterior Cruciate Ligament and Posterior Cruciate Ligament during Knee Flexion
Authors: Li Guoan , DeFrate Louis E. , Sun Hao , Gill Thomas J.
Published: July 2004

Background

Most knowledge regarding cruciate ligament function is based on in vitro experiments.

Purpose

To investigate the in vivo elongation of the functional bundles of the anterior cruciate ligament and posterior cruciate ligament during weightbearing flexion.

Hypothesis

The biomechanical role of functional bundles of the anterior cruciate ligament and posterior cruciate ligament under in vivo loading is different from that measured in cadavers.

Study Design

In vivo biomechanical study.

Methods

Elongation of the anterior cruciate ligament and posterior cruciate ligament was measured during a quasi-static lunge using imaging and 3-dimensional computer-modeling techniques.

Results

The anterior-medial bundle of the anterior cruciate ligament had a relatively constant length from full extension to 90° of flexion. The posterior-lateral bundle of the anterior cruciate ligament decreased in length with flexion. Both bundles of the posterior cruciate ligament had increased lengths with flexion.

Conclusion

The data did not demonstrate the reciprocal function of the 2 bundles of the anterior cruciate ligament or the posterior cruciate ligament with flexion observed in previous studies. Instead, the data suggest that there is a reciprocal function between the anterior cruciate ligament and posterior cruciate ligament with flexion. The anterior cruciate ligament plays a more important role in low-flexion angles, whereas the posterior cruciate ligament plays a more important role in high flexion.

Clinical Relevance

Understanding the biomechanical role of the knee ligaments in vivo is essential to reproduce the structural behavior of the ligament after injury (especially for 2-bundle reconstructions) and thus improve surgical outcomes.
A New Operative Approach in the Correction of External Coxa Saltans
Authors: White Richard A. , Hughes Mike S. , Burd Timothy , Hamann Joshua , Allen William C.
Published: July 2004

Background

External snapping hip is an entity that describes a snap that is felt on the lateral aspect of the hip. Several surgical interventions are described.

Hypothesis

The external snapping hip can be corrected with a simple procedure that is minimally invasive and less demanding than other techniques.

Study Design

This is a retrospective review from June 1994 until January 2002 looking at released external snapping hips.

Methods

There were 16 patients with 17 hips; follow-up was in 15 patients with 16 snapping hips. Twelve patients with 13 hips were contacted by telephone interview, and 3 were followed up by their most recent chart note. All underwent the same procedure performed by the senior author. The questionnaire was conducted at an average of 32.5 months after surgery (range, 9-74 months). For 3 patients, chart-only follow-up was at 6 weeks, 3 months, and 6 months, respectively.

Results

Fourteen of 16 hips remained asymptomatic after final surgical release (2 hips needed a second release). All patients contacted by telephone would undergo the same procedure again if faced with the same symptoms.

Conclusions

This technique is simpler than most of those previously described with the benefit of no formal postoperative regimen and comparable results.
Sports Massage after Eccentric Exercise
Authors: Jönhagen Sven , Ackermann Paul , Eriksson Tommy , Saartok Tönu , Renström Per A. F. H.
Published: July 2004

Background

The use of sports massage is very common in the athletic community. However, only a few studies have shown any therapeutic effect of massage.

Hypothesis

Sports massage can improve the recovery after eccentric exercise.

Study Design

Prospective randomized clinical trial.

Methods

Sixteen subjects performed 300 maximal eccentric contractions of the quadriceps muscle bilaterally. Massage was given to 1 leg, whereas the other leg served as a control. Subjects were treated once daily for 3 days. Maximal strength was tested on a Kin-Com dynamometer, and functional tests were based on 1-leg long jumps. Pain was evaluated using a visual analog scale.

Results

There was a marked loss of strength and function of the quadriceps directly after exercise and on the third day after exercise. The massage treatment did not affect the level or duration of pain or the loss of strength or function following exercise.

Conclusion

Sports massage could not improve the recovery after eccentric exercise.
Anchor Design and Bone Mineral Density Affect the Pull-Out Strength of Suture Anchors in Rotator Cuff Repair
Authors: Tingart Markus J. , Apreleva Maria , Lehtinen Janne , Zurakowski David , Warner Jon J. P.
Published: July 2004

Background

Different metal and biodegradable suture anchors are available for rotator cuff repair. Poor bone quality may result in anchor loosening and tendon rerupture.

Hypotheses

Higher bone mineral density is associated with higher pull-out strength of suture anchors. Depending on anchor placement, pull-out strengths of anchors are different within the greater tuberosity.

Study Design

Cadaveric biomechanical study.

Methods

Trabecular and cortical bone mineral densities were determined for different regions within the greater tuberosity. Metal screw-type and biodegradable hook-type anchors were cyclically loaded.

Results

Mean failure load of metal and biodegradable anchors was 273 N and 162 N, respectively, for the proximal part (P < .01) and 184 N and 112 N, respectively, for the distal part (P < .01). Both types of anchors showed higher failure loads in the proximal-anterior and -middle parts of the greater tuberosity than in the distal part (P < .01). A significant positive correlation was found between cortical bone mineral density and failure load of metal anchors (P < .01).

Conclusion

Bone quality, anchor type, and anchor placement have a significant impact on anchor failure loads.

Clinical Relevance

Suture anchors should be placed in the proximal-anterior and -middle parts of the greater tuberosity. In the distal parts, biodegradable hook-like anchors should be used with caution.
An Analysis of an Anatomical Posterolateral Knee Reconstruction
Authors: LaPrade Robert F. , Johansen Steinar , Wentorf Fred A. , Engebretsen Lars , Esterberg Justin L. , Tso Andy
Published: July 2004

Background

To date, no surgical technique to treat posterolateral knee instability anatomically reconstructs the 3 major static stabilizing structures of the posterolateral knee: the fibular collateral ligament, the popliteus tendon, and the popliteofibular ligament.

Hypothesis

Static varus and external rotatory stability would be restored to the reconstructed knee with a posterolateral knee injury.

Methods

The anatomical locations of the original fibular collateral ligament, popliteus tendon, and popliteofibular ligament were reconstructed using a 2-graft technique. Ten cadaveric specimens were tested in 3 states: intact knee, knee with the 3 structures cut to simulate a grade III injury, and the reconstructed knee.

Results

For the varus loading tests, joint stability was significantly improved by the posterolateral reconstruction compared to the cut state at 0°, 30°, 60°, and 90° of flexion. There were no significant differences between the intact and reconstructed knees at 0°, 60°, and 90° for varus translation. For the external rotation torque tests, external rotation was significantly higher for the cut state than for the intact or reconstructed posterolateral knee. There was no significant difference in external rotation between the intact and reconstructed posterolateral knees at any flexion angle.

Conclusions

This 2-graft technique to reconstruct the primary static stabilizers of the posterolateral knee restored static stability, as measured by joint translation in response to varus loading and external rotation torque, to knees with grade III posterolateral injuries.
The Effect of Posterior Knee Capsulotomy on Posterior Tibial Translation during Posterior Cruciate Ligament Tibial Inlay Reconstruction
Authors: Park Sang Eun , Stamos Bruce D. , DeFrate Louis E. , Gill Thomas J. , Li Guoan
Published: July 2004

Purpose

To measure the biomechanical effect of the surgical capsulotomy made during a posterior cruciate ligament reconstruction using the tibial inlay technique.

Hypothesis

The posterior capsule contributes to posterior tibial stability.

Study Design

Controlled laboratory experiment.

Methods

Six knee specimens were tested on a robotic testing system from 0° to 120° of flexion with the posterior cruciate ligament intact and resected and with a posterior capsulotomy identical to that performed during tibial inlay reconstruction (sham surgery). A longitudinal incision with medial and lateral soft tissue stripping sufficient to mount an inlay bone block and pass an Achilles tendon graft into the knee was made in the oblique popliteal ligament, muscle belly of the popliteus, and posterior capsule. The posterior tibial translation was measured under a posterior tibial load of 130 N at multiple flexion angles.

Results

Capsulotomy increased the posterior laxity compared with the posterior cruciate ligament–resected knee at every flexion angle. An additional 0.97 ± 0.48 mm, 0.65 ± 0.47 mm, 0.56 ± 0.33 mm, 0.48 ± 0.38 mm, and 0.94 ± 0.60 mm of posterior laxity was recorded at 0°, 30°, 60°, 90°, and 120° of flexion, respectively. These values were all statistically significant (P≤ .001).

Conclusions

A posterior capsulotomy alone, without associated posteromedial or posterolateral disruption, produces additional posterior tibial translation in vitro compared with posterior cruciate ligament–deficient knee with intact capsule.

Clinical Relevance

Damage to the posterior capsule may contribute to the residual posterior laxity noted clinically after posterior cruciate ligament reconstruction.
Ability of Plasmodium falciparum to invade Southeast Asian ovalocytes varies between parasite lines
Authors: Cortés Alfred , Benet Ariadna , Cooke Brian M. , Barnwell John W. , Reeder John C.
Published: July 2004

Plasmodium falciparum, the causative agent of the most lethal form of human malaria, uses multiple ligand-receptor interactions to invade host red blood cells (RBCs). We studied the invasion of P falciparum into abnormal RBCs from humans carrying the Southeast Asian ovalocytosis (SAO) trait. One particular parasite line, 3D7-A, invaded these cells efficiently, whereas all other lines studied invaded SAO RBCs to only about 20% of the extent of normal (non-SAO) cells. This result is consistent with the clinical observation that SAO individuals can experience high-density P falciparum infections and provides an explanation for previous discrepant results on invasion of SAO RBCs. Characterization of the invasion phenotype of 3D7-A revealed that efficient invasion of SAO RBCs was paralleled by relatively efficient invasion of normal RBCs treated with either neuraminidase, trypsin, or chymotrypsin and a novel capacity to invade normal RBCs treated sequentially with both neuraminidase and trypsin. Our results suggest that only parasites able to use some particular invasion pathways can invade SAO RBCs efficiently in culture. A similar situation might occur in the field.
Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells
Authors: Reed James , McNamee Christine , Rackstraw Stephen , Jenkins John , Moss Diana
Published: July 2004

IgLONs are a family of four cell adhesion molecules belonging to the Ig superfamily that are thought to play a role in cell-cell recognition and growth-cone migration. One member of the family, opioid-binding cell-adhesion molecule (OBCAM), might act as a tumour suppressor. Previous work has shown that limbic-system-associated protein (LAMP), CEPU-1/Neurotrimin and OBCAM interact homophilically and heterophilically within the family. Here, we show that, based on their relative affinities, CEPU-1 might be both a homo- and a heterophilic cell adhesion molecule, whereas LAMP and OBCAM act only as heterophilic cell adhesion molecules. A binding assay using recombinant IgLONs fused to human Fc showed that IgLONs are organized in the plane of the membrane as heterodimers, and we propose that IgLONs function predominantly as subunits of heterodimeric proteins (Diglons). Thus, the four IgLONs can form six Diglons. Furthermore, although singly transfected cell lines have little effect on neurite outgrowth, CHO cell lines expressing both CEPU-1 and OBCAM (Diglon-CO) inhibit neurite outgrowth from cerebellar granule cells.
Synthesis of K–β-Al2O3 Powder by Hydrothermal Multicomponent Coprecipitation Method
Authors: Zhang Xiangfeng , Wen Zhaoyin , Lin Zuxiang , Gu Zhonghua , Xu Xiaohe
Published: July 2004

A precursor for K–β-Al2O3 powder has been synthesized by hydrothermal multicomponent coprecipitation method. The precursor for the synthesis was composed of the solid solution of KxNH4(1−x)Al(OH)2CO3(x = 0.1885). The effect of calcination temperature on the formation of K–β-Al2O3 phase was investigated. It is the first attempt to prepare K–β-Al2O3 powder by a kind of low-cost wet chemical process.
Preparation of Silver Nanorods by Rapid Microwave Heating
Authors: Liu Fu-Ken , Chang Yu-Cheng , Huang Pei-Wen , Ko Fu-Hsiang , Chu Tieh-Chi
Published: July 2004

We report a method for preparing silver nanorods by a rapid heating process. The procedure we use is one in which a silver salt is reduced to silver metal by sodium citrate under the influence of microwave irradiation. The silver products were characterized by UV–vis absorption spectroscopy, transmission electron microscopy, energy-dispersive X-ray analysis, and X-ray diffractometry. Key aspects for the production of nanorods having high aspect ratios are rapid microwave heating and adequate reaction times.
Ischemia-Modified Albumin Concentrations in Patients with Peripheral Vascular Disease and Exercise-Induced Skeletal Muscle Ischemia
Authors: Roy Debashis , Quiles Juan , Sharma Rajan , Sinha Manas , Avanzas Pablo , Gaze David , Kaski Juan Carlos
Published: July 2004

Background: Ischemia-modified albumin (IMA) is a new marker of myocardial ischemia, there is concern that IMA concentrations may be affected by ischemia occurring in tissues other than the myocardium.

Methods: We assessed 23 consecutive patients (15 males; mean age, 67 years) with typical leg claudication and documented peripheral vascular disease (PVD). All patients underwent both treadmill-exercise stress testing to induce leg ischemia and dobutamine stress echocardiography 1 week apart for the assessment of myocardial ischemia. Blood samples for IMA measurements were obtained at baseline, immediately after peak exercise/stress, and 1 h after exercise/stress. Statistical analysis was performed with the ANOVA repeated-measures test.

Results: Compared with baseline, mean (SD) IMA was significantly lower after the induction of skeletal muscle ischemia and returned to baseline values at 1 h: baseline, 74.6 (15.6) kilounits/L; peak stress, 69.5 (14.0) kilounits/L (P <0.0001 vs baseline); 1 h after stress, 75.9 (15.7) kilounits/L (P <0.0001 vs peak stress; P = 0.3 vs baseline). Baseline, peak stress, and 1-h poststress IMA concentrations were inversely correlated with the ankle-brachial index after exercise (r = −0.4; P <0.05). None of the patients showed regional wall motion abnormalities during dobutamine stress echocardiography, and IMA concentrations remained unchanged from baseline. There were no differences in baseline [74.6 (15.6) vs 72.7 (11.5) kilounits/L; P = 0.6], peak stress, or poststress IMA concentrations when exercise testing and dobutamine stress echocardiography values were compared.

Conclusions: The relationship between disease severity (of a noncardiac origin) and baseline IMA values is an important and novel finding. IMA is significantly lower immediately after exercise-induced leg ischemia in patients with PVD and is related to disease severity. IMA concentrations can therefore be affected by the development of skeletal muscle ischemia, and this may have implications regarding the ability of IMA to detect myocardial ischemia in PVD patients.
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
Authors: Fonseca Maria Isabel , Zhou Jun , Botto Marina , Tenner Andrea J.
Published: July 2004

C1q, the recognition component of the classical complement activation pathway, is a multifunctional protein known to be expressed in brain of Alzheimer's disease (AD) patients. To experimentally address the role of C1q in AD, a mouse model lacking C1q (APPQ-/-) was generated by crossing Tg2576 animals (APP) with C1q-deficient mice. The pathology of APPQ-/- was compared with that of APP mice and B6SJL controls at 3-16 months of age by immunohistochemistry and Western blot analysis. At younger ages (3-6 months), when no plaque pathology was present, no significant differences were seen in any of the neuronal or glial markers tested. At older ages (9-16 months), the APP and APPQ-/- mice developed comparable total amyloid and fibrillar β-amyloid in frontal cortex and hippocampus; however, the level of activated glia surrounding the plaques was significantly lower in the APPQ-/- mice at 12 and 16 months. In addition, although Tg2576 mice showed a progressive decrease in synaptophysin and MAP2 in the CA3 area of hippocampus compared with control B6SJL at 9, 12, and 16 months, the APPQ-/- mice had significantly less of a decrease in these markers at 12 and 16 months. In a second murine model for AD containing transgenes for both APP and mutant presenilin 1 (APP/PS1), a similar reduction of pathology was seen in the APPPS1Q-/- mice. These data suggest that at ages when the fibrillar plaque pathology is present, C1q exerts a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation.
The Retinitis Pigmentosa 1 Protein Is a Photoreceptor Microtubule-Associated Protein
Authors: Liu Qin , Zuo Jian , Pierce Eric A.
Published: July 2004

The outer segments of rod and cone photoreceptor cells are highly specialized sensory cilia made up of hundreds of membrane discs stacked into an orderly array along the photoreceptor axoneme. It is not known how the alignment of the outer segment discs is controlled, although it has been suggested that the axoneme may play a role in this process. Mutations in the retinitis pigmentosa 1 (RP1) gene are a common cause of retinitis pigmentosa (RP). Disruption of theRp1gene in mice causes misorientation of outer segment discs, suggesting a role for RP1 in outer segment organization. Here, we show that the RP1 protein is part of the photoreceptor axoneme. Amino acids 28-228 of RP1, which share limited homology with the microtubule-binding domains of the neuronal microtubule-associated protein (MAP) doublecortin, mediate the interaction between RP1 and microtubules, indicating that the putative doublecortin (DCX) domains in RP1 are functional. The N-terminal portion of RP1 stimulates the formation of microtubulesin vitroand stabilizes cytoplasmic microtubules in heterologous cells. Evaluation of photoreceptor axonemes from mice with targeted disruptions of theRp1gene shows that Rp1 proteins that contain the DCX domains also help control axoneme length and stabilityin vivo. These results demonstrate that RP1 is a MAP. Given the specific expression of RP1 in photoreceptors, RP1 is thus the first photoreceptor-specific MAP to be identified. Furthermore, these findings indicate that the RP1 form of inherited retinal degeneration is part of the larger class of neurodegenerative diseases caused by MAP dysfunction.
Alteration of Neuronal Firing Properties afterIn VivoExperience in a FosGFP Transgenic Mouse
Authors: Barth Alison L. , Gerkin Richard C. , Dean Kathleen L.
Published: July 2004

Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, functional magnetic resonance imaging, 2-deoxyglucose studies, and induction of gene expression have been helpful in determining the brain areas responsible for particular functions, these methods are technically limited. Currently, there is no method that allows for the identification and electrophysiological characterization of individual neurons that are associated with a particular function in living tissue. We developed a strain of transgenic mice in which the expression of the green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. These mice enable anin vivoorex vivocharacterization of the cells and synapses that are activated by particular pharmacological and behavioral manipulations. Cortical and subcortical fosGFP expression could be induced in a regionally restricted manner after specific activation of neuronal ensembles. Using the fosGFP mice to identify discrete cortical areas, we found that neurons in sensory-spared areas rapidly regulate action potential threshold and spike frequency to decrease excitability. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations. In addition, because activated neurons can be functionally characterized, this tool may enable the development of better pharmaceuticals that directly affect the neurons involved in disease states.
Corticotropin-Releasing Factor Receptors CRF1and CRF2Exert Both Additive and Opposing Influences on Defensive Startle Behavior
Authors: Risbrough Victoria B. , Hauger Richard L. , Roberts Amanda L. , Vale Wylie W. , Geyer Mark A.
Published: July 2004

The corticotropin-releasing factor (CRF) receptors (CRF1and CRF2) are crucial mediators of physiological and behavioral responses to stress. In animals, CRF1appears to primarily mediate CRF-induced anxiety-like responses, but the role of CRF2during stress is still unclear. Here we report the effects of CRF1and CRF2on the magnitude and plasticity of defensive startle responses in mice. Startle plasticity is measured by inhibition of startle by sensory stimuli, i.e., prepulse inhibition (PPI), and is disrupted in patients with panic or posttraumatic stress disorders in which CRF neurotransmission may be overactive. Pharmacological blockade of CRF1reversed both CRF-induced increases in startle and CRF-induced deficits in PPI. CRF2blockade attenuated high-dose but not low-dose CRF-induced increases in startle and reduced PPI. Conversely, activation of CRF2enhanced PPI. CRF had no effect on startle and increased PPI in CRF1knock-out mice. These data indicate that CRF receptors act in concert to increase the magnitude of defensive startle yet in opposition to regulate the flexibility of startle. These data support a new model of respective CRF receptor roles in stress-related behavior such that, although both receptors enhance the magnitude of defensive responses, CRF1receptors contravene, whereas CRF2receptors enhance, the impact of sensory information on defensive behavior. We hypothesize that excessive CRF1activation combined with reduced CRF2signaling may contribute to information processing deficits seen in panic and posttraumatic stress disorder patients and support CRF1-specific pharmacotherapy.
Modellbasierter Ansatz zur Anwendungsintegration (A Model-based Approach for Enterprise Application Integration)
Authors: Dorda Clemens , Steiert Hans-Peter , Sellentin Jürgen
Published: July 2004

Moderne Produkte zur Anwendungsintegration in Unternehmen (EAI) bieten Werkzeuge, um Integrationsszenarien zu modellieren. Allerdings lassen sich damit heterogene IT-Umgebungen bisher immer nur ausschnittsweise darstellen, da die Modelle unterschiedlicher EAI-Produkte nicht ausgetauscht oder integriert werden können. Unser Ziel ist es, die Bildung solcher ‘Integrationsinseln’ zu vermeiden. Dazu präsentieren wir einen Ansatz, der durch technologie- und herstellerunabhängige Modellierung eine integrierte Sicht erlaubt. Unser Vorgehensmodell schlägt vor, diese integrierte Sicht werkzeuggestützt auf der Basis von Repositories zu verfeinern, um die Realisierung mit konkreten Produkten und das Deployment auf konkreten Plattformen zu automatisieren.
Techniken der XML-Familie zur Systemintegration (Deploying XML Technology for System's Integration)
Authors: Jeckle Mario
Published: July 2004

Anwendungen der Extensible Markup Language (XML) haben sich seit ihrem Erscheinen in vielfältiger Weise etablieren können. Die breite Basis verfügbarer Standards und deren Umsetzung, gepaart mit dem vergleichsweise einfachen Einsatz dieser Technikfamilie, lassen auf XML gründende Anwendungen auch für verschiedene Aspekte der Systemintegration interessant werden.
Dagstuhl-Seminar “Dynamically and Partially Reconfigurable Architectures” (Dynamisch und partiell rekonfigurierbare Architekturen)
Authors: Becker Jürgen
Published: July 2004

The paper addresses people from information technology, electrical engineering, computer science, and related areas. It gives an introduction and classification to fine-, coarse-, as well as multi-grain reconfigurable architectures. This data-stream-based and transport-triggered parallel computing technique in combination with dynamical and partial reconfiguration features demonstrates promising perspectives for future CMOS-based microelectronic solutions in multimedia and infotainment, mobile communication, as well as automotive application domains, among others.
Split-step Wavelet-Kollokationsmethoden zur Simulation linearer und nichtlinearer optischer Wellenausbreitung (Split-step Wavelet Collocation Methods for Linear and Nonlinear Optical Wave Propagation)
Authors: Kremp Tristan
Published: July 2004

Optische Wellenlängen-Multiplex-Übertragungs-Systeme (WDM) sind eine Schlüsseltechnologie zur Bewältigung des ständig wachsenden Internet-Datenverkehrs. Um WDM-Systeme mit großen Bandbreiten und Propagationsdistanzen innerhalb praktikabler Rechenzeiten simulieren zu können, sind numerische Algorithmen mit optimaler Komplexität erforderlich. Die in dieser Dissertation entwickelten Verfahren erfüllen diese Anforderungen und erlauben erstmals Simulationen mit erheblichen Rechenzeitvorteilen gegenüber dem etablierten Standardverfahren. Die gezielte Optimierung von WDM-Systemparametern wie zum Beispiel der optischen Kanalleistung wird dadurch wesentlich vereinfacht.
Elucidation of a cryptic interstitial 7q31.3 deletion in a patient with a language disorder and mild mental retardation by array‐CGH
Authors: Tyson Christine , McGillivray Barbara , Chijiwa Chieko , Rajcan‐Separovic Evica
Published: July 2004

We report on a 14‐year‐old boy who presented with bilateral cleft lip and palate, hearing loss, a language processing disorder, and mild mental retardation (MR). G‐banded chromosome analysis of the patient and his family revealed he carried an apparently balanced de novo complex translocation involving chromosomes 5, 6, and 7. Chromosomal comparative genomic hybridization (CGH) was performed to investigate the possibility of any genomic imbalance as a result of the complex rearrangement. No abnormality was detected at any of the translocation breakpoint regions (5p13.2, 6p24, 7q21.1, and 7q21.3), nor was there any other imbalance which fell inside our significance level of 0.8–1.2. Array‐CGH analysis was initiated to perform a higher resolution search for gains and losses, and revealed a deletion of two adjacent clones, CTB‐133K23 and RP11‐112P4, mapping to 7q31.3, which are 4.4 Mb apart. Fluorescence in situ hybridization (FISH) using these two clones confirmed the deletion. 7q31 has frequently been implicated in the search for genes involved in speech and language disorders. The specific 7q31.3 region deleted in our patient has significant overlap with some such areas of the genome. These findings are, therefore, of value in identifying genes involved in the speech and language phenotypes. This study has shown the importance of array‐CGH in investigating patients who have clinical features suggestive of a chromosome abnormality, but with apparently balanced chromosome rearrangements. It has demonstrated that the array‐CGH technique provides a much greater insight into submicroscopic chromosome imbalances than conventional cytogenetic techniques. © 2004 Wiley‐Liss, Inc.
Determining β‐sheet stability by Fourier transform infrared difference spectra
Authors: Wang Ting , Xu Yao , Du Deguo , Gai Feng
Published: July 2004

We describe here a new method for determining the conformational stability of antiparallel β‐sheets. Due to coupling between the transition dipoles, β‐sheet conformations typically exhibit a characteristic high‐frequency amide I component centered at ∼ 1680 cm−1. Using one β‐sheet protein and two small β‐hairpins, we demonstrate that this high‐frequency component, which is fairly narrow (∼ 8–10 cm−1), can be quantitatively resolved and used in thermal stability determination. Compared with the commonly used CD and fluorescence techniques, this ir method offers advantages. Since the area of this high‐frequency component is only proportional to the folded population, it eliminates the need for a priori information of the folded and unfolded baselines encountered in other methods. Thus, it is applicable to a variety of β‐sheet systems. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
The Mycobacterium tuberculosis chaperonin 10 monomer exhibits structural plasticity
Authors: Fossati Gianluca , Cremonesi Pietro , Izzo Gaetano , Rizzi Emanuele , Sandrone Giovanni , Harding Stephen , Errington Neil , Walters Christopher , Henderson Brian , Roberts Michael M. , Coates Anthony R.M. , Mascagni Paolo
Published: July 2004

The conditions which favor dissociation of oligomeric Mycobacterium tuberculosis chaperonin 10 and the solution structure of the monomer were studied by analytical ultracentrifugation, size exclusion chromatography, fluorescence, and circular dichroism spectroscopies. At neutral pH and in the absence of divalent cations, the protein is fully monomeric below approximately a 4.7 μM concentration. Under these conditions the monomer forms completely unfolded and partially folded conformers which are in equilibrium with each other. One conformer accumulates over the others which is stable within a very narrow range of temperatures. It contains a β‐sheet‐structured C‐terminal half and a mostly disordered N‐terminal half. Other components of the equilibrium include partially helical structures which do not completely unfold at high temperature or under strong acidic conditions. Complete unfolding of the monomer occurs in the presence of denaturants or below 14°C. Cold‐denaturation is detected at an unusually high temperature and this may be due to the concentration of hydrophobic residues, which is larger in chaperonins than in other globular proteins. Finally, the monomer self‐associates in the pH range 5.8–2.9, where it forms small oligomers. A structure–activity relationship was investigated with the sequences known to be involved in the various biological activities of the monomer. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Titration of poly(dA‐dT) · poly(dA‐dT) in solution at variable NaCl concentration
Authors: Airoldi Marta , Boicelli C. Andrea , Cadoni Fabio , Gennaro Giuseppe , Giomini Marcello , Giuliani Anna M. , Giustini Mauro
Published: July 2004

CD and uv absorption data showed that high molecular weight poly(dA‐dT) · poly(dA‐dT), at 298 K, undergoes an acid‐induced transition from B‐double helix to random coil in NaCl solutions of different concentrations, ranging from 0.005 to 0.600M. Similarly, titration of the polynucleotide with a strong base causes duplex‐to‐single strands transition. The base‐ and acid‐induced transitions were both reversible by back‐titration (with an acid or, respectively, with a base): the apparent pKa were the same in both directions. However, the number of protons per titratable site (adenine N1) required to reach half‐denaturation was in great excess over the stoichiometric value; to a much larger extent, the same effect was observed also for the deprotonation of the N3H sites of thymine. Moreover, in the basic denaturation experiments, at low salt concentrations ([NaCl]≤0.300M) less acid than calculated was needed to back‐titrate the base excess to half‐denaturation. Both effects could be qualitatively justified on the basis of the counterion condensation theory of polyelectrolytes and considering the energy barrier created by the negatively charged phosphodiester groups to the penetration of the OH− ions inside the double helix and the screening effect of the Na+ ions on such charges, in the deprotonation experiments. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
The influence of biomass on the hydrodynamic behavior and stability of expanded beds
Authors: Lin Dong‐Qiang , Thömmes Jörg , Kula Maria‐Regina , Hubbuch Jürgen J.
Published: July 2004

Expanded bed adsorption is an innovative chromatographic technology that allows the introduction of particle‐containing feedstock without the risk of blocking the bed. Provided a perfectly classified fluidized bed (termed expanded bed) is formed in the crude feedstock and the biomass is not influencing protein transport towards the adsorbent surface, a sorption performance comparable to packed beds is found. The influence of biomass on the hydrodynamic stability of expanded beds is essential and was investigated systematically in this article. Residence‐time distribution analyses were performed using model systems and a yeast suspension under various fluid‐phase conditions. It is demonstrated that three factors (biomass/adsorbent interactions, biomass concentration, and flow rate) play an interdependent role disturbing the classified fluidization of an expanded bed. A clear correlation between the degree of aggregative fluidization—obtained by PDE modeling of RTD data—and the expansion behavior of the fluidized bed has been found. Thus, combining three analytical methods, namely cell transmission index analysis, expansion analysis, and RTD analysis provides a solid base for understanding and control of the fluidization behavior and thus further process design during the initial phase of process development. © 2004 Wiley Periodicals, Inc.