bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in growth and apoptosis of insulin receptor substrate-1-deficient β-cells
Authors: Hennige Anita M. , Ozcan Umut , Okada Terumasa , Jhala Ulupi S. , Schubert Markus , White Morris F. , Kulkarni Rohit N.
Published: April 2005

Insulin and IGF-I activate antiapoptotic pathways via insulin receptor substrate (IRS) proteins in most mammalian cells, including β-cells. IRS-1 knockout (IRS-1KO) mice show growth retardation, hyperinsulinemia, and hyperplastic but dysfunctional islets without developing overt diabetes, whereas IRS-2KOs develop insulin resistance and islet hypoplasia leading to diabetes. Because both models display insulin resistance, it is difficult to differentiate islet response to insulin resistance from islet defects due to loss of proteins in the islets themselves. We used a transplantation approach, as a means of separating host insulin resistance from islet function, to examine alterations in proteins in insulin/IGF-I signaling pathways that may contribute to β-cell proliferation and/or apoptosis in IRS-1KO islets. Islets isolated from wild-type (WT) or IRS-1KO mice were transplanted into WT or insulin-resistant IRS-1KO males under the kidney capsule. The β-cell mitotic rate in transplanted islets in IRS-1KO recipients was increased 1.5-fold compared with WT recipients and was similar to that in endogenous pancreases of IRS-1KOs, whereas β-cell apoptosis was reduced by ∼80% in IRS-1KO grafts in IRS-1KO recipients compared with WT recipients. Immunohistochemistry showed a substantial increase in IRS-2 expression in IRS-1KO islets transplanted into IRS-1KO mice as well as in endogenous islets from IRS-1KOs. Furthermore, enhanced cytosolic forkhead transcription factor (FoxO1) staining in IRS-1KO grafts suggests intact Akt/PKB activity. Together, these data indicate that, even in the absence of insulin resistance, β-cells deficient in IRS-1 exhibit a compensatory increase in IRS-2, which is associated with islet growth and is characterized by both proliferative and antiapoptotic effects that likely occur via an insulin/IGF-I/IRS-2 pathway.
Passive mechanics of canine internal abdominal muscles
Authors: Hwang Willy , Carvalho Jason C. , Tarlovsky Isaac , Boriek Aladin M.
Published: April 2005

The internal abdominal muscles are biaxially loaded in vivo, and therefore length-tension relations along and transverse to the directions of the muscle fibers are important in understanding their mechanical properties. We hypothesized that 1) internal oblique and transversus abdominis form an internal abdominal composite muscle with altered compliance than that of either muscle individually, and 2) anisotropy, different compliances in orthogonal directions, of internal abdominal composite muscle is less pronounced than that of its individual muscles. To test these hypotheses, in vitro mechanical testing was performed on 5 × 5 cm squares of transversus abdominis, internal oblique, and the two muscles together as a composite. These tissues were harvested from the left lateral side of abdominal muscles of eleven mongrel dogs (15–23 kg) and placed in a bath of oxygenated Krebs solution. Each tissue strip was attached to a biaxial mechanical testing device. Each muscle was passively lengthened and shortened along muscle fibers, transverse to fibers, or simultaneously along and transverse to muscle fibers. Both transversus abdominis and internal oblique muscles demonstrated less extensibility in the direction transverse to muscle fibers than along fibers. Biaxial loading caused a stiffening effect that was greater in the direction along the fibers than transverse to the fibers. Furthermore, the abdominal muscle composite was less compliant than either muscle alone in the direction of the muscle fibers. Taken together, our data suggested that the internal abdominal composite tissue has complex mechanical properties that are dependent on the mechanical properties of internal oblique and transversus abdominis muscles.
Ventilatory acclimatization in response to very small changes in Po2 in humans
Authors: Donoghue Simon , Fatemian Marzieh , Balanos George M. , Crosby Alexi , Liu Chun , O'Connor David , Talbot Nick P. , Robbins Peter A.
Published: April 2005

Ventilatory acclimatization to hypoxia (VAH) consists of a progressive increase in ventilation and decrease in end-tidal Pco2 (PetCO2). Underlying VAH, there are also increases in the acute ventilatory sensitivities to hypoxia and hypercapnia. To investigate whether these changes could be induced with very mild alterations in end-tidal Po2 (PetO2), two 5-day exposures were compared: 1) mild hypoxia, with PetO2 held at 10 Torr below the subject's normal value; and 2) mild hyperoxia, with PetO2 held at 10 Torr above the subject's normal value. During both exposures, PetCO2 was uncontrolled. For each exposure, the entire protocol required measurements on 13 consecutive mornings: 3 mornings before the hypoxic or hyperoxic exposure, 5 mornings during the exposure, and 5 mornings postexposure. After the subjects breathed room air for at least 30 min, measurements were made of PetCO2, PetO2, and the acute ventilatory sensitivities to hypoxia and hypercapnia. Ten subjects completed both protocols. There was a significant increase in the acute ventilatory sensitivity to hypoxia (Gp) after exposure to mild hypoxia, and a significant decrease in Gp after exposure to mild hyperoxia ( P < 0.05, repeated-measures ANOVA). No other variables were affected by mild hypoxia or hyperoxia. The results, when combined with those from other studies, suggest that Gp varies linearly with PetO2, with a sensitivity of 3.5%/Torr (SE 1.0). This sensitivity is sufficient to suggest that Gp is continuously varying in response to normal physiological fluctuations in PetO2. We conclude that at least some of the mechanisms underlying VAH may have a physiological role at sea level.
Transduction of phosphorylated heat shock-related protein 20, HSP20, prevents vasospasm of human umbilical artery smooth muscle
Authors: Flynn Charles R. , Brophy Colleen M. , Furnish Elizabeth J. , Komalavilas Padmini , Tessier Deron , Thresher Jeffrey , Joshi Lokesh
Published: April 2005

Activation of cyclic nucleotide-dependent signaling pathways inhibits agonist-induced contraction of most vascular smooth muscles except human umbilical artery smooth muscle (HUASM). This impaired vasorelaxation may contribute to complications associated with preeclampsia, intrauterine growth restriction, and preterm delivery. Cyclic nucleotide-dependent signaling pathways converge at the phosphorylation of the small heat shock-related protein HSP20, causing relaxation of vascular smooth muscle. We produced recombinant proteins containing a protein transduction domain linked to HSP20 (rTAT-HSP20). Pretreatment of HUASM with in vitro phosphorylated rTAT-HSP20 (rTAT-pHSP20) significantly inhibited serotonin-induced contraction, without a decrease in myosin light chain phosphorylation. rTAT-pHSP20 remained phosphorylated upon transduction into isolated HUASM as demonstrated by two-dimensional gel electrophoresis. Transduction of peptide analogs of phospho-HSP20 containing the phosphorylation site on HSP20 and phosphatase-resistant mimics of the phosphorylation site (S16E) also inhibited HUASM contraction. These data suggest that impaired relaxation of HUASM may result from decreased levels of phosphorylated HSP20. Protein transduction can be used to restore intracellular expression levels and the associated physiological response. Transduction of posttranslationally modified substrate proteins represents a proteomic-based therapeutic approach that may be particularly useful when the expression of downstream substrate proteins is downregulated.
Maternal diet programs embryonic kidney gene expression
Authors: Welham Simon J. M. , Riley Paul R. , Wade Angie , Hubank Mike , Woolf Adrian S.
Published: April 2005

Human epidemiological data associating birth weight with adult disease suggest that organogenesis is “programmed” by maternal diet. In rats, protein restriction in pregnancy produces offspring with fewer renal glomeruli and higher systemic blood pressures than controls. We tested the hypothesis that maternal diet alters gene expression in the metanephros, the precursor of the definitive mammalian kidney. We demonstrated that maternal low-protein diet initiated when pregnancy starts and maintained to embryonic day 13, when the metanephros consists of mesenchyme surrounding a once-branched ureteric bud, is sufficient to significantly reduce glomerular numbers in offspring by about 20%. As assessed by representational difference analyses and real-time quantitative polymerase chain reactions, low-protein diet modulated gene expression in embryonic day 13 metanephroi. In particular, levels of prox-1, the ortholog of Drosophila transcription factor prospero, and cofilin-1, a regulator of the actin cytoskeleton, were reduced. During normal metanephrogenesis, prox-1 protein was first detected in mesenchymal cells around the ureteric tree and thereafter in nascent nephron epithelia, whereas cofilin-1 immunolocalized to bud derivatives and condensing mesenchyme. Previously, we reported that low-protein diets increased mesenchymal apoptosis cells when metanephrogenesis began and thereafter reduced numbers of precursor cells. Collectively, these studies prove that the maternal diet programs the embryonic kidney, altering cell turnover and gene expression at a time when nephrons and glomeruli have yet to form. The human implication is that the maternal diet ingested between conception and 5- 6-wk gestation contributes to the variation in glomerular numbers that are known to occur between healthy and hypertensive populations.
A potential role of YC-1 on the inhibition of cytokine release in peripheral blood mononuclear leukocytes and endotoxemic mouse models
Authors: Pan Shiow-Lin , Guh Jih-Hwa , Peng Chieh-Yu , Chang Ya-Ling , Cheng Fong-Chi , Chang Jau-Hsiang , Kuo Sheng-Chu , Lee Fang-Yu , Teng Che-Ming
Published: April 2005

To evaluate the anti-sepsis potential of YC-1, we have examined the effect of YC-1 on the regulation of cytokine production in human leukocytes and endotoxemic mice. The data demonstrated that YC-1 showed a preferential inhibition on proinflammatory cytokine production without inhibition of cell growth or induction of cytotoxicity in human leukocytes. On the other hand, in the septic mouse model, treatment with an intraperitoneal application of LPS caused a cumulative death within 27 hours. The post-treatment administration of YC-1 significantly increased the survival rate in endotoxemic mice. Furthermore, several mediators were detected and the data showed that YC-1 profoundly blocked LPS-induced NO as well as TNF-α production, and prevented lung damage by histological examination. Samples from the animal model showed that LPS-induced NF-κB/DNA binding activity and consequent up-regulation of iNOS expression in tissues were abolished by post-administration of YC-1. Furthermore, YC-1, by itself, did not modify cGMP content while significantly inhibit LPS-induced cGMP formation, suggesting that YC-1-mediated effect was not through a cGMP-elevating pathway. Taken together, it is evident that the post-treatment administration of YC-1 after LPS application significantly inhibits NF-κB activation, iNOS expression, NO over-production, and cytokine release reaction resulting in an improved survival rate in endotoxemic mice. It is suggested that YC-1 may be a potential agent for the therapeutic treatment of sepsis.
Extracellular fibrinogen binding protein, Efb, from Staphylococcus aureus as an antiplatelet agent in vivo
Authors: Shannon Oonagh , Uekötter Andreas , Flock Jan-Ingmar
Published: April 2005

Staphylococcus aureus produces and secretes a protein, extracellular fibrinogen binding protein (Efb), which contributes to virulence in wound infection. We have previously shown that Efb is a potent inhibitor of platelet function in vitro. We confirm here that this is also the case in vivo. Pre-treatment with Efb resulted in a significant prolongation of bleeding time in a mouse model. Furthermore, Efb was capable of rescuing animals from death caused by the administration of potent platelet agonists. This antiplatelet effect may explain the retardation of wound healing associated with Efb in S. aureus wound infections. These results are important not only in terms of understanding S. aureus pathogenesis, and consequently identifying new treatment strategies, but also with regard to the development of potential, novel antiplatelet agents for the prevention of thrombosis.
B-domain deleted factor VIII is aggregated and degraded through proteasomal and lysosomal pathways
Authors: Guillet Benoit , Ducasse Cécile , Enjolras Nathalie , Rodriguez Marie-Hélène , Rolli Véronique , Négrier Claude , Plantier Jean-Luc
Published: April 2005

Factor VIII (FVIII) processing within mammalian cells is demonstrated to be much less efficient than proteins of similar size. The deletion of the B-domain from FVIII improves the level of production, due partly to the increase in mRNA synthesis. We aimed to characterise the cellular fate and the intracellular processing of the FVIII molecule devoid of B-domain. A B-domain deleted factor VIII (BDD-FVIII) possessing a furin consensus cleavage site in the connecting segment between the heavy and the light chain, was produced in CHO cell line. In such cells, FVIII was retained as two single chain products from which a majority was aggregated. The two species were located in Triton X-100 soluble (for 60–80%) and insoluble fractions (for 20–40%). The incubation of the expressing cells with tunicamycin (5 μg/ml) and the treatment of the intracellular species with a mixture of Neuraminidase and N-glycosidase-F revealed that both intracellular species were N-glycosylated. Furin over-expression neither diminished the intracellular FVIII contents nor improved its extracellular production. Intracellular FVIII was degraded through both lysosomal and proteasomal pathways as evidenced by inhibitor treatments (e.g. NH4Cl, leupeptin, clasto-Lactacystin β-lactone and MG-132), pulse-chase analysis and confocal observations. This study demonstrates that a BDD-FVIII expressed in CHO cells is inefficiently processed consecutively to intracellular aggregation, proteasomal degradation, and routage to lysosomes.
P2Y12 ADP receptor-dependent tyrosine phosphorylation of proteins of 27 and 31 kDa in thrombin-stimulated human platelets
Authors: Fälker Knut , Lange Danica , Presek Peter
Published: April 2005

In thrombin-stimulated human platelets several proteins undergo rapid and transient changes in tyrosine phosphorylation. We demonstrate that a set of proteins of 27, 29, 31, 34, and 39 kDa is affected by released ADP and P2Y12 receptor signaling during platelet activation. AR-C69931MX, an antagonist of the Gi2-coupled P2Y12 ADP receptor, inhibits initial tyrosine phosphorylation of p27 and p31 and prevents subsequent dephosphorylation of p29, p34, and p39. Antagonists of the Gq-coupled P2Y1 ADP receptor have no effect. Precluding integrin αIIbβ3 outside-in signaling with RGDS or S1197 does not affect the increase in tyrosine phosphorylation of the set of proteins but inhibits their subsequent dephosphorylation. Besides the ADP analogue 2-MeS-ADP, other platelet agonists such as collagen and the TXA2-mimetic U46619 also induce p27 and p31 tyrosine phosphorylation in a P2Y12 receptor-dependent manner. Tyrosine phosphorylation of p27 and p31 in response to collagen, but not thrombin, is prevented by aspirin and the TXA2 receptor antagonist SQ29548, indicating that the effect of collagen strongly relies on TXA2 signaling. Furthermore, epinephrine, acting via inhibitory Gz-coupled α2A-adrenoceptors, bypasses the inhibitory effect of AR-C69931MX on thrombin-induced p27 and p31 tyrosine phosphorylation. Finally, we demonstrate that tyrosine phosphorylation of p27 and p31 downstream of P2Y12 receptors is due to the inhibition of adenylyl cyclase but not phosphoinositide 3-kinase (PI 3-K) activation. Elevating cAMP levels with PGI2 or forskolin precludes thrombin-induced p27 and p31 tyrosine phosphorylation. Moreover, direct inhibition of adenylyl cyclase by SQ22536 reverses the effect of AR-C69931MX. Our data indicate that the observed changes in tyrosine phosphorylation are the result of both primary Gq signaling, initiating the release of ADP, as well as subsequent P2Y12 receptor-mediated Gi coupling.
Non-invasive imaging of glycoprotein VI binding to injured arterial lesions
Authors: Konrad Ildiko , Hauser Andrea , Sauer Suzanne , Li Zhongyan , Wester Hans-Jürgen , Bengel Frank , Schwaiger Markus , Schömig Albert , Massberg Steffen , Haubner Roland , Gawaz Meinrad
Published: April 2005

Glycoprotein VI (GPVI) is the major platelet collagen receptor and plays a critical role in the process of thrombosis at sites of atherosclerotic lesions. This study evaluates the feasibility of radiolabeled soluble GPVI to identify injured arterial lesions. Radiolabeling was carried out using the iodogen method and resulted in the radioiodinated GPVI in radiochemical yields between 97–100%. The biodistribution of [125I]GPVI was determined in normal mice and demonstrated a blood clearance halftime of approximately 5.5 hours. Vascular lesions were induced in the carotid artery in wild type and ApoE -/- mice. Immediately after injury radioiodinated GPVI was injected intravenously. Binding of [123I]GPVI to carotid lesions was assessed by szinti-graphic in vivo imaging. Carotid arteries were explanted for ex vivo autoradiography and histological characterization of the lesion. In vivo and ex vivo imaging revealed substantial accumulation of radioiodinated GPVI in the injured artery wall, with a ratio of lesion to control vessel of 3:1 and 7:1, respectively. Because GPVI is the critical collagen receptor that mediates platelet adhesion to vascular lesions, soluble radiolabeled GPVI may be an agent for non-invasive imaging of thrombogenic thus, vulnerable atherosclerotic plaques.
A novel homozygous mutation (1619delC) in GPIIb gene associated with Glanzmann thrombasthenia, the decay of GPIIb-mRNA and the synthesis of a truncated GPIIb unable to form complex with GPIIIa
Authors: Losonczy Gergely , Rosenberg Nurit , Kiss Csongor , Kappelmayer János , Vereb György , Kerényi Adrienne , Balogh István , Muszbek László
Published: April 2005

The absence of agonist-induced platelet aggregation and the lack of fibrinogen receptor (GPIIb/IIIa) on the platelet surface demonstrated that the severe hemorrhagic complications of a child of Romany descent were caused by Glanzmann thrombasthenia. DNA sequencing revealed a novel homozygous deletion of a cytosine (1619delC) in the GPIIb gene causing a frameshift and predicting a novel stop codon at position 533 following 24 altered amino acids. Both parents possessed the same deletion in heterozygous form. The amount of GPIIb mRNA in the patient’s platelets was 0.06% of the amount measured in control platelets. Neither GPIIb nor its truncated form could be detected in the platelets of the patient by Western blotting, while a small amount of GPIIIa was demonstrated. Quantitative flow cytometric analysis showed an elevated number of vitronectin receptors, a component of which is GPIIIa, on the patient’s platelets. The surface expression of vitronectin receptor on thrombasthenic, but not on normal platelets was further increased by activation with thrombin receptor agonist peptide. BHK cells transfected with wild type GPIIIa and mutated GPIIb failed to express any mature GPIIb or pro-GPIIb. Immunoprecipitation with a polyclonal antibody recognizing both GPIIb and GPIIIa recovered a 60 kDa truncated form of GPIIb. This band was absent when immunoprecipitation was carried out with an antibody recognizing GPIIIa, suggesting that the truncated protein, lacking calf-1, calf-2 domains and major part of the thigh domain, is unable to form complex with GPIIIa.
Effect of plasminogen activator inhibitor-1 deficiency on nutritionally-induced obesity in mice
Authors: Lijnen Roger
Published: April 2005

Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator. Recent studies in murine models have yielded apparently conflicting data on a potential role of PAI-1 in adipose tissue development and obesity. To reinvestigate this issue, we have rederived PAI-1 deficient (PAI-1-/-) and wild-type (WT) mice and generated true littermates in a 81.25% C57Bl/6: 18.75% 129 SV genetic background. Male 5-week-old PAI-1-/- and WT mice were kept on a high fat diet (20.1 kJ/g) for 15 weeks. Body weight gain was comparable for both genotypes, and at the time of sacrifice total body weights (39 ± 1.1 versus 41 ± 1.2 g) as well as the weights of subcutaneous (SC, 1,520 ± 110 versus 1,480 ± 110 mg) adipose tissue were not significantly different. In contrast, the gonadal (GON, 1,900 ± 43 versus 1,510 ± 86 mg, p < 0.005) tissue mass was larger in PAI-1-/- mice. Plasma levels of insulin, leptin, glucose, triglycerides, total, HDL and LDL cholesterol were comparable for both genotypes. Immunohisto-chemical analysis of SC and GON adipose tissues did not reveal differences in adipocyte size or number between both genotypes, whereas blood vessel density was also comparable for GON fat but lower in SC fat of WT mice. Thus, this study in littermate mice on high fat diet did not reveal an effect of PAI-1 deficiency on body weight, and a differential effect on SC and GON adipose tissue.
Drift Characteristics of a Moored Conductivity–Temperature–Depth Sensor and Correction of Salinity Data
Authors: Ando Kentaro , Matsumoto Takeo , Nagahama Tetsuya , Ueki Iwao , Takatsuki Yasushi , Kuroda Yoshifumi
Published: April 2005

The temperature and conductivity drift (time change of the characteristics) of moored SBE37IM conductivity and temperature (CT) sensors was investigated by pre- and postdeployment calibration of the Triangle TransOcean Buoy Network (TRITON). This buoy network comprises the western portion of the basinwide (Tropical Atmosphere Ocean) TAO/TRITON buoy array, which monitors phenomena such as El Niño and contributes to forecasting climate change. Over the time of deployment the drift of the temperature sensors was very small, within 3 mK of the postdeployment calibration data. The drift of the conductivity sensors was more significant. After 1 yr of mooring, conductivity drift observed in the shallowest layer (1.5–100 m) was positive and 0.010 S m−1 [equivalent to 0.065 (PSS-78) at 30°C and 6 S m−1; here, 1 S is 1 Ω−1] at 6 S m −1 on average. Drift observed in the thermocline layer (125–200 m) was also positive and 0.0053 S m−1 [0.034 (PSS-78)] at 6 S m−1 on average. Conversely, the drift of conductivity in the deepest layer (250–750 m) was 0.00002 S m−1 with a standard deviation of 0.001 S m−1 [0.0065 (PSS-78)].

Assuming a linear trend of conductivity drift with time, the authors attempted to correct the conductivity data using the postdeployment calibration data. The corrected data for about 80% of the sensors exhibited smaller differences than the uncorrected data when compared with the in situ conductivity–temperature–depth (CTD) data. However, the corrected salinity data became worse than the uncorrected data for about 20% of the sensors. The reasons for these errors are also discussed in this paper.
Sport-Dependent Variations in arm Position during Single-Limb Landing Influence Knee Loading
Authors: Chaudhari Ajit M. , Hearn Brenna K. , Andriacchi Thomas P.
Published: April 2005

Background

Increased valgus loading at the knee has been previously identified as a possible risk factor for noncontact anterior cruciate ligament injuries, which are common in sports. Arm position variation may affect risk of injury by altering valgus knee loading.

Hypothesis

Sport-dependent variations in arm position increase valgus loading of the knee during run-to-cut maneuvers.

Study Design

Controlled laboratory study.

Methods

Eleven subjects performed a sidestep cutting maneuver, first with no arm constraints and then with 3 sports-related arm positions in random order (holding a lacrosse stick, holding a football on the plant side, and holding a football on the cut side). The analysis focused on the knee valgus moment relative to the arm positions during the landing phase of the activity.

Results

Arm position significantly influenced the valgus moment with an increase in the lacrosse trials and in the plant-side football trials but not in the cut-side football trials (α =. 05).

Conclusions

Constraining the plant-side arm results in increased valgus loading at the knee during run-to-cut maneuvers, which suggests the possibility of greater risk of anterior cruciate ligament injury during these conditions.

Clinical Relevance

These results suggest that training methods that consider arm position as a risk factor could help reduce the risk of anterior cruciate ligament noncontact injury.
Variations in Mortise Anatomy
Authors: LeBrun Christopher T. , Krause John O.
Published: April 2005

Background

Variations in ankle mortise anatomy may be a predisposing factor to ankle instability.

Hypothesis

A posteriorly positioned fibula associated with ankle instability may not be a true pathologic entity but rather the result of measuring off an internally rotated talus.

Study Design

Cohort study (diagnosis); Level of evidence, 2.

Methods

The authors reviewed 60 ankle computed tomography scans performed on patients from their institution for reasons unrelated to ankle instability. They also reviewed ankle computed tomography scans on 21 patients surgically treated for clinical ankle instability. The position of the fibula in relation to the talar articular surface was calculated and expressed as the axial malleolar index, as described by Scranton et al. They also calculated the intermalleolar index, a new method that references the medial malleolus, not the talus.

Results

Using the method of Scranton et al, the axial malleolar index in the control and instability patients was similar to values previously described, and there was a significant difference between control and instability patients (P <. 01). However, using the intermalleolar index method referencing the medial malleolus, there was not a significant difference between control and instability patients (P =. 43).

Conclusion

The new method of referencing the medial malleolus assesses fibular position independent of talar rotation. The data, when referencing the medial malleolus, do not show significant variation in fibular position in patients with and without ankle instability.
The Posterolateral Corner of the Knee
Authors: Stannard James P. , Brown Stephen L. , Farris Rory C. , McGwin Gerald , Volgas David A.
Published: April 2005

Background

Injuries to the posterolateral corner of the knee are disabling. Despite improved understanding of this group of tendons and ligaments, the best surgical treatment of an unstable corner is not clear.

Hypothesis

Surgical repair of acute tears of the posterolateral corner has outcomes that are as good as those from reconstruction combined with an early motion rehabilitation protocol.

Study Design

Cohort study; Level of evidence, 2.

Methods

Sixty-three patients with 64 posterolateral corner tears were included in this study, with 39 posterolateral corner repairs and 25 reconstructions using the modified 2-tailed technique. Patients were evaluated with clinical and KT-2000 arthrometer examinations, as well as with Lysholm, International Knee Documentation Committee, and Short Form-36 scores.

Results

Fifty-six patients with 57 corner tears had minimum clinical follow-up of 24 months (range, 24-59 months). Acute primary repairs were performed on 35 patients, with 22 successful outcomes and 13 (37%) failures. Primary reconstructions were performed on 22 patients, with 20 successful outcomes and 2 (9%) failures. The difference in stability on clinical examination between repairs and reconstructions was significant (P <. 05). Fourteen of 15 patients with failures of the primary posterolateral corner repair or reconstruction underwent successful revision reconstruction. The final patient with failure of the primary repair elected not to have a revision reconstruction. The final mean Lysholm knee score for both repair and reconstruction patients was 88.7 (range, 53-100). Final International Knee Documentation Committee objective scores yielded 14 (26%) normal, 28 (52%) near-normal, 9 (17%) abnormal, and 3 (6%) severely abnormal knees; the mean score was 60 at the most recent clinical evaluation.

Conclusion

Results with repair followed by early motion rehabilitation have been significantly inferior when compared with results from reconstruction using the modified 2-tailed technique. The authors now use reconstruction rather than repair in the majority of patients who sustain posterolateral corner tears after high-energy injuries.
Instruction of Jump-Landing Technique Using Videotape Feedback
Authors: Oñate James A. , Guskiewicz Kevin M. , Marshall Stephen W. , Giuliani Carol , Yu Bing , Garrett William E.
Published: April 2005

Background

Anterior cruciate ligament injury prevention programs have used videotapes of jump-landing technique as a key instructional component to improve landing performance.

Hypothesis

All videotape feedback model groups will increase knee flexion angles at initial contact and overall knee flexion motion and decrease peak vertical ground reaction forces and peak proximal anterior tibial shear forces to a greater extent than will a nonfeedback group. The secondary hypothesis is that the videotape feedback using the combination of the expert and self models will create the greatest change in each variable.

Study Design

Controlled laboratory study.

Methods

Knee kinematics and kinetics of college-aged recreational athletes randomly placed in 3 different videotape feedback model groups (expert only, self only, combination of expert and self) and a nonfeedback group were collected while participants performed a basketball jump-landing task on 3 testing occasions.

Results

All feedback groups significantly increased knee angular displacement flexion angles [F(6,70) = 8.03, P =. 001] and decreased peak vertical ground reaction forces [F(6,78) = 2.68, P =. 021] during performance and retention tests. The self and combination groups significantly increased knee angular displacement flexion angles more than the control group did; the expert model group did not change significantly more than the control group did. All feedback groups and the nonfeedback group significantly reduced peak vertical forces across performance and retention tests. There were no statistically significant changes in knee flexion angle at initial ground contact (P =. 111) and peak proximal anterior tibial shear forces (P =. 509) for both testing sessions for each group.

Conclusion

The use of self or combination videotape feedback is most useful for increasing knee angular displacement flexion angles and reducing peak vertical forces during landing.

Clinical Relevance

The use of self or combination modeling is more effective than is expert-only modeling for the implementation of instructional programs aimed at reducing the risk of jump-landing anterior cruciate ligament injuries.
Location of the Glenoid Defect in Shoulders with Recurrent Anterior Dislocation
Authors: Saito Hidetomo , Itoi Eiji , Sugaya Hiroyuki , Minagawa Hiroshi , Yamamoto Nobuyuki , Tuoheti Yilihamu
Published: April 2005

Background

In patients with recurrent anterior dislocations of the shoulder, it is well known that the glenoid rim is often deficient (8%-95%). However, little is known regarding the precise location of the bony defect of the glenoid.

Hypothesis

The bony defect is anterior rather than anteroinferior to the glenoid

Study Design

Cohort study (symptom prevalence); Level of evidence, 2.

Methods

The authors studied 3-dimensional images of the glenoid reconstructed from computed tomography to determine the location of the glenoid defect in 123 shoulders of 123 patients with recurrent anterior dislocations of the shoulder. They measured the location, extent, and orientation of the defect based on the clock face of the glenoid.

Results

The defects were located between 12:08 and 6:32, with the range between 2:30 and 4:20 being the most frequent. The extent of the glenoid defect was 106.7°± 27.1° (mean ± standard deviation). The mean orientation of the defect was pointing toward 3:01 on the clock face of the glenoid, at a mean angle of 90.5°± 10.4° from the 12-o'clock direction.

Conclusion

The glenoid defect is located almost anterior to the glenoid.
Structure and properties of carbon steel–aluminium dissimilar joints
Authors: El-Sayed M.H. , Naka M.
Published: April 2005

Carbon steel is joined to aluminium using the ultrasonic brazing method with Zn–Al filler at 663 K, employing different ultrasound application times. Different reaction layers could be observed at the interface, containing compounds such as FeAl3, Fe2Al5, Fe3Al, and FeAl, and solid solutions such as Fe–Zn and Zn–Al. For shorter ultrasound application times, formation of the aluminium rich Fe–Al compounds occurred; conversely, after longer ultrasound times formation of the iron rich Al–Fe compounds occurred, which improves the joint bond strength. The maximum bond shear strength of 127 MPa was obtained for an Al–steel joint brazed at 663 K with 3 s ultrasound application time. Extending the ultrasound time beyond 3 s caused the formation of FeAl compound, which decreased the joint bond strength; however, the strength of the joints remained at a higher level than that obtained with FeAl3 and Fe2Al5.
Pulsed gas metal arc welding of Al–Cu–Li alloy
Authors: Padmanabham G. , Pandey S. , Schaper M.
Published: April 2005

An experimental Al–Cu–Li–Mg–Ag–Zr type alloy in the form of 13.7 mm thick plates was studied for its fusion characteristics using gas metal arc welding (GMAW) and pulsed gas metal arc welding (P-GMAW). High copper 2319 filler of 1.6 mm diameter was used. The burn-off characteristics of 2319 filler wire in GMAW and P-GMAW were experimentally determined, including the relation between pulse current and pulse duration for the desired one-drop detachment per pulse (ODPP) condition and feasible range of pulse parameters. The effect of welding parameters on bead geometry and shape relationships was investigated through beadon-plate experiments in the welding current range above the spray transition current. Reasonably good weld beads were obtained in P-GMAW at currents as low as 194 A and welding speeds of 45 cm min–1. P-GMAW yielded significantly higher weld penetration compared to GMAW.
Residual stresses in spot welded new generation aluminium alloys Part A – thermophysical and thermomechanical properties of 6111 and 5754 aluminium alloys
Authors: Khanna Sanjeev K. , Long X. , Porter W.D. , Wang H. , Liu C.K. , Radovic M. , Lara-Curzio E.
Published: April 2005

Thermophysical and thermomechanical properties of 5754 and 6111 aluminium alloys were experimentally determined between room temperature and 500°C for use as input in the numerical simulation of residual stress generated during fusion welding processes of these materials. The thermophysical properties determined included specific heat, thermal diffusivity and thermal expansion using the differential scanning calorimeter, laser flash technique and the dilatometer, respectively. Thermal conductivity was also calculated from thermal diffusivity, specific heat and density. The thermomechanical properties determined included yield strength, elastic modulus and Poisson ratio. The yield strength was determined using tensile test specimens in a heated chamber. The Poisson ratio and elastic modulus were determined using resonant ultrasound spectroscopy.
Mutant-specific gene programs in the zebrafish
Authors: Weber Gerhard J. , Choe Sung E. , Dooley Kimberly A. , Paffett-Lugassy Noëlle N. , Zhou Yi , Zon Leonard I.
Published: April 2005

Hematopoiesis involves the production of stem cells, followed by the orchestrated differentiation of the blood lineages. Genetic screens in zebrafish have identified mutants with defects that disrupt specific stages of hematopoiesis and vasculogenesis, including the cloche, spadetail (tbx16), moonshine (tif1g), bloodless, and vlad tepes (gata1) mutants. To better characterize the blood program, gene expression profiling was carried out in these mutants and in scl-morphants (sclmo). Distinct gene clusters were demarcated by stage-specific and mutant-specific gene regulation. These were found to correlate with the transcriptional program of hematopoietic progenitor cells, as well as of the erythroid, myeloid, and vascular lineages. Among these, several novel hematopoietic and vascular genes were detected, for instance, the erythroid transcription factors znfl2 and ncoa4. A specific regulation was found for myeloid genes, as they were more strongly expressed in vlt mutants compared with other erythroid mutants. A unique gene expression pattern of up-regulated isoprenoid synthesis genes was found in cloche and sclmo, possibly in migrating cells. In conjunction with the high conservation of vertebrate hematopoiesis, the comparison of transcriptional profiles in zebrafish blood mutants represents a versatile and powerful tool to elucidate the genetic regulation of blood and blood vessel development.
Conservation of unique cell-surface CD antigen mosaics in HIV-1–infected individuals
Authors: Woolfson Adrian , Stebbing Justin , Tom Brian D. M. , Stoner Kerryn J. , Gilks Walter R. , Kreil David P. , Mulligan Stephen P. , Belov Larissa , Chrisp Jeremy S. , Errington Will , Wildfire Adrian , Erber Wendy N. , Bower Mark , Gazzard Brian , Christopherson Richard I. , Scott Mike A.
Published: April 2005

Cluster of differentiation (CD) antigens are expressed on cells of myeloid and lymphoid lineages. As most disease processes involve immune system activation or suppression, these antigens offer unique opportunities for monitoring host responses. Immunophenotyping using limited numbers of CD antigens enables differentiation states of immune system cells to be determined. Extended phenotyping involving parallel measurement of multiple CD antigens may help identify expression pattern signatures associated with specific disease states. To explore this possibility we have made a CD monoclonal antibody array and scanner, enabling the parallel immunophenotyping of leukocyte cell suspensions in a single and rapid analysis. To demonstrate this approach, we used the specific example of patients infected with human immunodeficiency virus type-1 (HIV-1). An invariant HIV-induced CD antigen signature has been defined that is both robust and independent of clinical outcome, composed of a unique profile of CD antigen expression levels that are both increased and decreased relative to internal controls. The results indicate that HIV-induced changes in CD antigen expression are disease specific and independent of outcome. Their invariant nature indicates an irreversible component to retroviral infection and suggests the utility of CD antigen expression patterns in other disease settings.
'PACLIMS': A component LIM system for high-throughput functional genomic analysis
Authors: Donofrio Nicole , Rajagopalon Ravi , Brown Douglas , Diener Stephen , Windham Donald , Nolin Shelly , Floyd Anna , Mitchell Thomas , Galadima Natalia , Tucker Sara , Orbach Marc J , Patel Gayatri , Farman Mark , Pampanwar Vishal , Soderlund Cari , Lee Yong-Hwan , Dean Ralph A
Published: April 2005

Background

Recent advances in sequencing techniques leading to cost reduction have resulted in the generation of a growing number of sequenced eukaryotic genomes. Computational tools greatly assist in defining open reading frames and assigning tentative annotations. However, gene functions cannot be asserted without biological support through, among other things, mutational analysis. In taking a genome-wide approach to functionally annotate an entire organism, in this application the ~11,000 predicted genes in the rice blast fungus (Magnaporthe grisea), an effective platform for tracking and storing both the biological materials created and the data produced across several participating institutions was required.

Results

The platform designed, named PACLIMS, was built to support our high throughput pipeline for generating 50,000 random insertion mutants of Magnaporthe grisea. To be a useful tool for materials and data tracking and storage, PACLIMS was designed to be simple to use, modifiable to accommodate refinement of research protocols, and cost-efficient. Data entry into PACLIMS was simplified through the use of barcodes and scanners, thus reducing the potential human error, time constraints, and labor. This platform was designed in concert with our experimental protocol so that it leads the researchers through each step of the process from mutant generation through phenotypic assays, thus ensuring that every mutant produced is handled in an identical manner and all necessary data is captured.

Conclusion

Many sequenced eukaryotes have reached the point where computational analyses are no longer sufficient and require biological support for their predicted genes. Consequently, there is an increasing need for platforms that support high throughput genome-wide mutational analyses. While PACLIMS was designed specifically for this project, the source and ideas present in its implementation can be used as a model for other high throughput mutational endeavors.
Statistical Viewer: a tool to upload and integrate linkage and association data as plots displayed within the Ensembl genome browser
Authors: Stenger Judith E , Xu Hong , Haynes Carol , Hauser Elizabeth R , Pericak-Vance Margaret , Goldschmidt-Clermont Pascal J , Vance Jeffery M
Published: April 2005

Background

To facilitate efficient selection and the prioritization of candidate complex disease susceptibility genes for association analysis, increasingly comprehensive annotation tools are essential to integrate, visualize and analyze vast quantities of disparate data generated by genomic screens, public human genome sequence annotation and ancillary biological databases. We have developed a plug-in package for Ensembl called "Statistical Viewer" that facilitates the analysis of genomic features and annotation in the regions of interest defined by linkage analysis.

Results

Statistical Viewer is an add-on package to the open-source Ensembl Genome Browser and Annotation System that displays disease study-specific linkage and/or association data as 2 dimensional plots in new panels in the context of Ensembl's Contig View and Cyto View pages. An enhanced upload server facilitates the upload of statistical data, as well as additional feature annotation to be displayed in DAS tracts, in the form of Excel Files. The Statistical View panel, drawn directly under the ideogram, illustrates lod score values for markers from a study of interest that are plotted against their position in base pairs. A module called "Get Map" easily converts the genetic locations of markers to genomic coordinates. The graph is placed under the corresponding ideogram features a synchronized vertical sliding selection box that is seamlessly integrated into Ensembl's Contig- and Cyto- View pages to choose the region to be displayed in Ensembl's "Overview" and "Detailed View" panels. To resolve Association and Fine mapping data plots, a "Detailed Statistic View" plot corresponding to the "Detailed View" may be displayed underneath.

Conclusion

Features mapping to regions of linkage are accentuated when Statistic View is used in conjunction with the Distributed Annotation System (DAS) to display supplemental laboratory information such as differentially expressed disease genes in private data tracks. Statistic View is a novel and powerful visual feature that enhances Ensembl's utility as valuable resource for integrative genomic-based approaches to the identification of candidate disease susceptibility genes. At present there are no other tools that provide for the visualization of 2-dimensional plots of quantitative data scores against genomic coordinates in the context of a primary public genome annotation browser.
Many accurate small-discriminatory feature subsets exist in microarray transcript data: biomarker discovery
Authors: Grate Leslie R
Published: April 2005

Background

Molecular profiling generates abundance measurements for thousands of gene transcripts in biological samples such as normal and tumor tissues (data points). Given such two-class high-dimensional data, many methods have been proposed for classifying data points into one of the two classes. However, finding very small sets of features able to correctly classify the data is problematic as the fundamental mathematical proposition is hard. Existing methods can find "small" feature sets, but give no hint how close this is to the true minimum size. Without fundamental mathematical advances, finding true minimum-size sets will remain elusive, and more importantly for the microarray community there will be no methods for finding them.

Results

We use the brute force approach of exhaustive search through all genes, gene pairs (and for some data sets gene triples). Each unique gene combination is analyzed with a few-parameter linear-hyperplane classification method looking for those combinations that form training error-free classifiers. All 10 published data sets studied are found to contain predictive small feature sets. Four contain thousands of gene pairs and 6 have single genes that perfectly discriminate.

Conclusion

This technique discovered small sets of genes (3 or less) in published data that form accurate classifiers, yet were not reported in the prior publications. This could be a common characteristic of microarray data, thus making looking for them worth the computational cost. Such small gene sets could indicate biomarkers and portend simple medical diagnostic tests. We recommend checking for small gene sets routinely. We find 4 gene pairs and many gene triples in the large hepatocellular carcinoma (HCC, Liver cancer) data set of Chen et al. The key component of these is the "placental gene of unknown function", PLAC8. Our HMM modeling indicates PLAC8 might have a domain like part of lP59's crystal structure (a Non-Covalent Endonuclease lii-Dna Complex). The previously identified HCC biomarker gene, glypican 3 (GPC3), is part of an accurate gene triple involving MT1E and ARHE. We also find small gene sets that distinguish leukemia subtypes in the large pediatric acute lymphoblastic leukemia cancer set of Yeoh et al.