Miracle-dz/UniFAR-FTUs huggingface dataset:
Lumbosacral spinal fusion. A biomechanical study.

The effects of spinal fusion on fused segment and the adjacent, unfused segments play a significant role in the clinical effectiveness of spinal fusion for low-back pain with or without sciatica. Much of the information on this important subject is derived from clinical impressions. The purpose of this biomechanical study is to investigate the altered kinematics and biomechanics of the three different types of spinal fusion (posterior, bilateral-lateral, and anterior) on the adjacent, unfused segment as well as within the fused segment and to investigate their clinical implications. Sixteen fresh human cadaver lumbosacral spines were tested under a simulated physiologic loading condition. The test specimens included three motion segments, L3-4, L4-5, and L5-S1. To study the mechanics of the lumbar spine under combined compression and bending loads, a special apparatus was designed. These loads were applied by an MTS machine through two sets of pulley systems. The loads, as well as displacement data from both actuators, were recorded. A video camera system was utilized to record the kinematics of the spinal motion segment. The unfused specimen was tested first, and the fused specimen then was retested under the identical loading conditions. A total of 16 spine specimens were tested and evaluated--five posterior, four bilateral-lateral, and seven anterior fusions. All types of fusion resulted in increased bending and axial stiffnesses. Overall, anterior fusion provided the largest increase in stiffness, followed by bilateral-lateral fusion and posterior fusion. (ABSTRACT TRUNCATED AT 250 WORDS)
Nalbuphine by PCA‐pump for analgesia following hysterectomy: bolus application versus continuous infusion with bolus application

The analgesic properties of the partial agonist–antagonist nalbuphine in the postoperative period are well known. When used for patient‐controlled analgesia (PCA) the effectiveness of this substance is comparable to that of morphine or tramadol. However, the optimal programme for administration of nalbuphine in PCA‐pumps has not been investigated. In particular, the combination of bolus administration vs bolus administration plus continuous basal administration is disputable.
Non‐alcoholic steatohepatitis in the Asia–Pacific region: Future shock?

Clinicians in both the developed and also the newer industrial economies in the Asia–Pacific region will encounter non‐alcoholic fatty liver disease (NAFLD) with increasing frequency. Although the region has been a significant contributor to the current state of knowledge, the spectrum of NAFLD, its severity and the potential for significant future morbidity and health costs are not widely recognized. Lifestyle changes, the epidemic of childhood and adult obesity and type 2 diabetes sweeping the Asia–Pacific represent the key substrates for the rising prevalence of NAFLD. Physicians in all disciplines need to be aware of clinical clues to the presence of NAFLD in the absence of other liver disease and in those with chronic viral hepatitis and they should be able to identify subsets at risk for liver‐related morbidity. Given the scope of the problem, efforts should focus primarily on preventing or ameliorating the impact of risk factors; the key one is insulin resistance and its associates of diabetes and central obesity. Pharmacotherapy may play a role in selected individuals. A regional agenda for case definition, future study and public health initiatives is urgently required.
Respiratory compliance in infants—a preliminary evaluation of the multiple interrupter technique

Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end‐expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is a linearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume‐pressure data, from one expiration, which relate to a single end‐expiratory level.
Differentiating Overreporting and Extreme Distress: MMPI-2 Use With Compensation-Seeking Veterans With PTSD

This purpose of this study was to examine overreporting on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) in compensation-seeking veterans with posttraumatic stress disorder (PTSD). A sample of veterans tested during a V.A. hospital compensation and pension exam were given the MMPI-2 and measures of PTSD, depression, and combat exposure. Veteran's MMPI-2s were only included in the analyses if their profile was extremely exaggerated, as measured by an F scale T score above 80, did not elevate the MMPI-2 VRIN and TRIN scales, and had a primary diagnosis of PTSD (n = 127). Using the Infrequency-Psychopathology, F(p), scale to distinguish overreporting from distress, it was found that 98 veterans elevated profiles due to distress, whereas 29 elevated due to overreporting, F(p) below and above 7, respectively. Differences between groups on MMPI-2 clinical scales and the other measures were assessed. Implications of these findings for assessing veteran response style and using the MMPI-2 with a PTSD population are discussed.
The role of slow-reacting substance of anaphylaxis in the late bronchial response after antigen challenge in allergic sheep.

Allergic sheep respond to inhalation challenge with Ascaris suum antigen with an immediate bronchoconstriction that resolves within 2 to 4 h, followed by a second bronchial obstruction occurring 6.5 to 8 h after challenge. The purpose of this study was to determine if the antigen-induced late bronchial response in allergic sheep is mediator dependent and to determine the extent to which histamine and/or slow-reacting substance of anaphylaxis (SRS-A) are involved in this response. To do this, 10 conscious sheep with Ascaris suum hypersensitivity underwent an inhalation challenge with antigen, and the average increase in specific lung resistance (SRL = mean pulmonary flow resistance times thoracic gas volume) was determined for each animal between 6.5 and 8 h after challenge, i.e., the time of late bronchial response. On another occasion, separated by at least 14 days, the animals were rechallenged with antigen, but prior to the onset of the late response (5.5 h) the animals were treated with either the mast cell stabilizer cromolyn (1 mg/kg), the SRS-A antagonist FPL-55712 (3 ml of a 1% wt/vol solution), or the histamine H1. receptor antagonist chlorpheniramine (2 mg/kg). Compared with the control response, inhaled aerosols of cromolyn or FPL-55712 blocked the late increase in SRL (p less than 0.01). Intravenously administered chlorpheniramine alone, or in conjunction with atropine, had no effect on the late response. Finally, the late response was partially reversed by FPL-55712 inhalation. These results suggest that the late bronchial response after inhalation challenge in allergic sheep is mediator dependent, and that SRS-A is a principal mediator of this response.
Endothelin‐1 and heme oxygenase‐1 as modulators of sinusoidal tone in the stress‐exposed rat liver

Heme oxygenase (HO)‐1 is up‐regulated after ischemia/reperfusion and contributes to maintenance of hepatic perfusion and integrity. Blockade of HO‐1 leads to an increased portal pressor response in the stress‐exposed liver. We tested whether the increase in portal pressure reflects unmasking of a concomitant up‐regulation of the vasoconstrictor endothelin (ET)‐1. Hemorrhagic shock induced messenger RNAs encoding HO‐1 (16‐fold) and ET‐1 (9‐fold) with a similar time course in the liver. At maximum induction of both mediators, rats received either vehicle or the endothelin ETA/B antagonist bosentan (10 mg/kg intravenously). Subsequently, the HO pathway was blocked in all animals by tin‐protoporphyrin (SnPP)‐IX (50 μmol/kg intravenously). Portal and sinusoidal hemodynamics were measured using microflow probes and intravital microscopy, respectively. Blockade of the HO pathway led to a significant increase in portal resistance (sham/SnPP‐IX, 0.17 ± 0.046 mm Hg · min · mL−1; shock/vehicle/SnPP‐IX, 0.57 ± 0.148 mm Hg · min · mL−1; P < 0.05) and a decrease in sinusoids conducting flow (shock/vehicle/SnPP‐IX: baseline, 28.3 ± 0.85 sinusoids/mm; 10 minutes after SnPP‐IX, 23.1 ± 1.09 sinusoids/mm; P < 0.05). Intravital microscopy showed narrowing of failing sinusoids colocalizing with stellate cells after blockade of the HO pathway. Blockade of ETA/B receptors attenuated the increase in portal resistance (shock/bosentan/SnPP‐IX, 0.29 ± 0.051 mm Hg · min · mL−1) and prevented sinusoidal perfusion failure (shock/bosentan/SnPP‐IX: baseline, 28.2 ± 0.97 sinusoids/mm; 10 minutes after SnPP‐IX, 28.8 ± 1.18 sinusoids/mm) as well as sinusoidal narrowing. In conclusion, a functional interaction of the up‐regulated vasodilatory HO system and the vasoconstrictor ET‐1 on the sinusoidal level exists under stress conditions. Both mediator systems affect sinusoidal diameter via direct action on hepatic stellate cells in vivo. (HEPATOLOGY2002;36:1453–1465).
Differential Expression of T- and L-Type Voltage-Dependent Calcium Channels in Renal Resistance Vessels

Abstract— The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells showed coexpression of mRNAs for T-type subunits (CaV3.1, CaV3.2) and for an L-type subunit (CaV1.2). The same expression pattern was observed in juxtamedullary efferent arterioles and outer medullary vasa recta. No calcium channel messages were detected in cortical efferent arterioles. CaV1.2 protein was demonstrated by immunochemical labeling of rat preglomerular vasculature and juxtamedullary efferent arterioles and vasa recta. Cortical efferent arterioles were not immunopositive. Recordings of intracellular calcium concentration with digital fluorescence imaging microscopy showed a significant increase of calcium in response to K+ (100 mmol/L) in isolated afferent arterioles (140±25%) and in juxtamedullary efferent arterioles (118±21%). These calcium responses were attenuated by the L-type antagonist calciseptine and by the T-type antagonist mibefradil. Intracellular calcium increased in response to K+ in cortical efferent arterioles (21±9%). Mibefradil and nickel concentration dependently blocked K+-induced contraction of perfused rabbit afferent arterioles. Calciseptine blocked the contraction mediated by K+ (EC50 8×10−14). S-(-)-Bay K 8644 had no effect on vascular diameter in the afferent arteriole. We conclude that voltage-dependent L- and T-type calcium channels are expressed and of functional significance in renal cortical preglomerular vessels, in juxtamedullary efferent arterioles, and in outer medullary vasa recta, but not in cortical efferent arterioles.
Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study.

AIMS Identification of risk factors for ventricular tachycardia/ventricular fibrillation (VT/VF) occurrence in patients with implantable cardioverter-defibrillators (ICD) is reasonable, because ICD patients with multiple risk factors might benefit from more aggressive anti-arrhythmic therapy for the prevention of arrhythmic events. Furthermore, in the era of prophylactic ICD therapy and limited healthcare resources, additional markers are needed for improved patient selection. METHODS AND RESULTS Thus, in Prospective Analysis of Risk Factor for Appropriate ICD Therapy (PROFIT), we prospectively analyzed the role of ejection fraction (EF), N-terminal probrain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) class, atrial fibrillation, and QRS-duration as independent predictors for VT/VF occurrence in 250 ICD patients. Kaplan-Meier analysis showed that EF<40% (log-rank P=0.001), NT-proBNP levels higher than median (>or=405 ng/L; log-rank P=0.04), QRS-duration >or=150 ms (log-rank P=0.016), permanent atrial fibrillation (log-rank P=0.008), and higher NYHA class (log-rank P=0.029) were associated with VT/VF occurrence. By multivariate Cox regression analysis EF, QRS-duration and atrial fibrillation remained significantly associated with appropriate VT/VF therapy, whereas there was no relationship among NT-proBNP, NYHA class, and VT/VF occurrence. Stratifying patients according to the number of their independent risk factors (EF<40%, AF, QRS-width>or=150 ms) showed that patients with greater than or equal to two risk factors had a 100% 2-year risk of VT/VF occurrence, whereas patients with no or one risk factor had a 19.3 and 25% 2-year risk, respectively. CONCLUSIONS EF<40%, permanent atrial fibrillation, and QRS>or=150 ms are independent predictors for VT/VF occurrence in predominantly secondary prophylactic ICD patients. Combining all independent predictors, we developed a risk score for VT/VF occurrence identifying a subgroup of patients with two or more risk factors who had a 100% 2-year risk. Future studies will reveal if this risk score helps to identify ICD patients suitable for empirical anti-arrhythmic therapy and to improve patient selection for prophylactic ICD therapy.
CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication

The CDC45 gene of Saccharomyces cerevisiae was isolated by complementation of the cold-sensitive cdc45-1 mutant and shown to be essential for cell viability. Although CDC45 genetically interacts with a group of MCM genes (CDC46, CDC47, and CDC54), the predicted sequence of its protein product reveals no significant sequence similarity to any known Mcm family member. Further genetic characterization of the cdc45-1 mutant demonstrated that it is synthetically lethal with orc2-1, mcm2-1, and mcm3-1. These results not only reveal a functional connection between the origin recognition complex (ORC) and Cdc45p but also extend the CDC45-MCM genetic interaction to all known MCM family members that were shown to be involved in replication initiation. Initiation of DNA replication in cdc45-1 cells was defective, causing a delayed entry into S phase at the nonpermissive temperature, as well as a high plasmid loss rate which could be suppressed by tandem copies of replication origins. Furthermore, two-dimensional gels directly showed that chromosomal origins fired less frequently in cdc45-1 cells at the nonpermissive temperature. These findings suggest that Cdc45p, ORC, and Mcm proteins act in concert for replication initiation throughout the genome.
The Acute Cardiac Effects of Dialysis

It is well recognized that the procedure of hemodialysis is associated with significant changes in blood pressure and systemic hemodynamics; 20–30% of treatments are complicated by intradialytic hypotension (IDH). There are now an increasing number of studies using electrocardiographic, isotopic and echocardiographic techniques that show that subclinical myocardial ischemia occurs during dialysis. This concept is supported by some studies showing that dialysis can induce acute rises in troponins and creatinine kinase MB, although this has not been found by all authors. Some of this controversy may at least in part be due to the collection of blood samples immediately postdialysis, which is likely to be too early to reliably detect dialysis‐induced elevations of cardiac enzymes. Cardiovascular death is the biggest single cause of mortality in dialysis patients and of this sudden death comprises the largest proportion. As such, there is a large body of evidence examining whether dialysis is pro‐arrhythmogenic. It is clear that dialysis can increase QTc interval and QT dispersion and is capable of inducing arrhythmias on Holter monitoring, likely due to the interaction of multiple factors, some of which prime for the development of arrhythmias (particularly the presence of preexisting cardiac disease), and some of which act as triggers. However, the link between these electrocardiographic alterations and sudden death is relatively poorly studied. This review summarizes the available literature regarding the acute cardiac effects of dialysis in relation to the above, and discusses how these acute changes may contribute to the genesis of uremic cardiomyopathy and longer term cardiac outcomes.
Homologous Recombination Contributes to the Repair of DNA Double-Strand Breaks Induced by High-Energy Iron Ions

Abstract To test the contribution of homologous recombinational repair (HRR) in repairing DNA damage sites induced by high-energy iron ions, we used (1) HRR-deficient rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We found that in response to exposure to iron ions, HRR contributed to cell survival in rodent cells and that HRR deficiency abrogated RAD51 focus formation. Complementation of the HRR defect by human RAD51D rescues both enhanced cytotoxicity and RAD51 focus formation. For human cells irradiated with iron ions, cell survival was decreased, and in p53 mutant cells, the levels of mutagenesis were increased when HRR was impaired. Human cells synchronized in S phase exhibited a more pronounced resistance to iron ions compared with cells in G1 phase, and this increase in radioresistance was diminished by RAD51 knockdown. These results indicate a role for RAD51-mediated DNA repair (i.e. HRR) in removing a fraction of clustered lesions induced by charged-particle radiation. Our results are the first to directly show the requirement for an intact HRR pathway in human cells in ensuring DNA repair and cell survival after exposure to high-energy high-LET radiation.
Slow depolarizing and hyperpolarizing currents which mediate bursting in Aplysia neurone R15.

Interruption of normal bursting activity by application of a voltage clamp reveals that action potentials in Aplysia neurone R15 are followed by two slow currents that long outlast the currents produced during the action potentials. Similar currents are seen following simulation of an action potential with a brief depolarizing pulse delivered under continuous voltage clamp. One of these currents, herein called ID, is an inward, or depolarizing current 0.5‐5 nA in amplitude that reaches a peak 300‐500 ms after the action potential. It produces the depolarizing after‐potential that follows action potentials in this cell and is responsible also for the grouping together of action potentials into bursts. The second current, herein called IH, is an outward, or hyperpolarizing current 0.1‐2 nA in amplitude that reaches a peak in 2‐10 s and is still present for many tens of seconds following the action potential. IH mediates the interburst hyperpolarization. Both currents summate temporally during the burst. Despite changes in the amplitude and duration of action potentials during the burst, each action potential adds nearly constant increments to the summated amplitudes of ID and IH. The summated amplitude of ID grows during the first few action potentials and gives rise to the increased rate of depolarization and the increased firing rate seen during the first half of the burst. Due to its slower kinetics, IH summates throughout the burst until its summated amplitude is large enough to cause the cell to hyperpolarize, thereby bringing the burst to an end. When the normal burst is interrupted by application of the voltage clamp, the ID and IH current peaks are followed by a current which approaches a more negative steady‐state level with a time course that consists of at least two phases. The first phase is exponential with a time constant of 15‐30 s. Under continuous voltage clamp, the current following a train of depolarizing pulses returns to the holding current with a similar time course. These observations, together with time constants for IH that are longer than the interburst interval, suggest that IH is always partially activated during normal bursting. A computer simulation demonstrates that opposing inward and outward currents with different kinetics, i.e. ID and IH, are sufficient to give rise to bursting activity, in the absence of non‐linear voltage‐dependent conductances. Such voltage‐dependent conductances, which are present in the normal cell, contribute to but are not necessary for bursting activity.
Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration

Primary effusion lymphoma (PEL) is associated with Kaposi sarcoma herpesvirus (KSHV) but its pathogenesis is poorly understood. Many KSHV‐associated products can deregulate cellular pathways commonly targeted in cancer. However, KSHV infection alone is insufficient for malignant transformation. PEL also lacks the chromosomal translocations seen in other lymphoma subtypes. We investigated 28 PELs and ten PEL cell lines by 1 Mb resolution array comparative genomic hybridization (CGH) and found frequent gains of 1q21–41 (47%), 4q28.3‐35 (29%), 7q (58%), 8q (63%), 11 (32%), 12 (61%), 17q (29%), 19p (34%), and 20q (34%), and losses of 4q (32%), 11q25 (29%), and 14q32 (63%). Recurrent focal amplification was seen at several regions on chromosomes 7, 8, and 12. High‐resolution chromosome‐specific tile‐path array CGH confirmed these findings, and identified selectin‐P ligand (SELPLG) and coronin‐1C (CORO1C) as the targets of a cryptic amplification at 12q24.11. Interphase FISH and quantitative PCR showed SELPLG/CORO1C amplification (>4 extra copies) and low levels of copy number gain (1–4 extra copies) in 23% of PELs, respectively. Immunohistochemistry revealed strong expression of both SELPLG and coronin‐1C in the majority of PELs, irrespective of their gene dosage. SELPLG is critical for cell migration and chemotaxis, while CORO1C regulates actin‐dependent processes, thus important for cell motility. Their overexpression in PEL is expected to play an important role in its pathogenesis. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cycloheximide-induced T-cell Death Is Mediated by a Fas-associated Death Domain-dependent Mechanism*

Cycloheximide (CHX) can contribute to apoptotic processes, either in conjunction with another agent (e.g. tumor necrosis factor-α) or on its own. However, the basis of this CHX-induced apoptosis has not been clearly established. In this study, the molecular mechanisms of CHX-induced cell death were examined in two different human T-cell lines. In T-cells undergoing CHX-induced apoptosis (Jurkat), but not in T-cells resistant to the effects of CHX (CEM C7), caspase-8 and caspase-3 were activated. However, the Fas ligand was not expressed in Jurkat cells either before or after treatment with CHX, suggesting that the activation of these caspases does not involve the Fas receptor. To determine whether CHX-induced apoptosis was mediated by a Fas-associated death domain (FADD)-dependent mechanism, a FADD-DN protein was expressed in cells prior to CHX treatment. Its expression effectively inhibited CHX-induced cell death, suggesting that CHX-mediated apoptosis primarily involves a FADD-dependent mechanism. Since CHX treatment did not result in the induction of Fas or FasL, and neutralizing anti-Fas and anti-tumor necrosis factor receptor-1 antibodies did not block CHX-mediated apoptosis, these results may also indicate that FADD functions in a receptor-independent manner. Surprisingly, death effector filaments containing FADD and caspase-8 were observed during CHX treatment of Jurkat, Jurkat-FADD-DN, and CEM C7 cells, suggesting that their formation may be necessary, but not sufficient, for cell death.