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The nuclear factor of activated T cell 1 (Nfatc1) locus is a common insertion site for murine tumorigenic retroviruses, suggesting a role of transcription factor NFATc1 in lymphomagenesis. Although NFATc1 is expressed in most human primary lymphocytes and mature human T- and B-cell neoplasms, we show by histochemical stainings that NFATc1 expression is suppressed in anaplastic large cell lymphomas and classical Hodgkin's lymphomas (HLs). In HL cell lines, NFATc1 silencing correlated with a decrease in histone H3 acetylation, H3-K4 trimethylation, and Sp1 factor binding but with an increase in HP1 binding to the NFATC1 P1 promoter. Together with DNA hypermethylation of the NFATC1 P1 promoter, which we detected in all anaplastic large cell lymphoma and many HL lines, these observations reflect typical signs of transcriptional silencing. In several lymphoma lines, methylation of NFATC1 promoter DNA resulted in a "window of hypomethylation," which is flanked by Sp1-binding sites. Together with the under-representation of Sp1 at the NFATC1 P1 promoter in HL cells, this suggests that Sp1 factors can protect P1 DNA methylation in a directional manner. Blocking immunoreceptor signaling led to NFATC1 P1 promoter silencing and to a decrease in H3 acetylation and H3-K4 methylation but not DNA methylation. This shows that histone modifications precede the DNA methylation in NFATC1 promoter silencing.

beta-Barrel-shaped channels of the Omp85 family are involved in the translocation or assembly of proteins of bacterial, mitochondrial, and plastidic outer membranes. We have compared these proteins to understand the evolutionary development of the translocators. We have demonstrated that the proteins from proteobacteria and mitochondria have a pore diameter that is at least five times smaller than found for the Omp85 in cyanobacteria and plastids. This finding can explain why Omp85 from cyanobacteria (but not the homologous protein from proteobacteria) was remodeled to become the protein translocation pore after endosymbiosis. Further, the pore-forming region of the Omp85 proteins is restricted to the C terminus. Based on a phylogenetic analysis we have shown that the pore-forming domain displays a different evolutionary relationship than the N-terminal domain. In line with this, the affinity of the N-terminal domain to the C-terminal region of the Omp85 from plastids and cyanobacteria differs, even though the N-terminal domain is involved in gating of the pore in both groups. We have further shown that the N-terminal domain of nOmp85 takes part in homo-oligomerization. Thereby, the differences in the phylogeny of the two domains are explained by different functional constraints acting on the regions. The pore-forming domain, however, is further divided into two functional regions, where the distal C terminus itself forms a dimeric pore. Based on functional and phylogenetic analysis, we suggest an evolutionary scenario that explains the origin of the contemporary translocon.

We prospectively studied the natural history of untreated acute grade III acromioclavicular separations. Twenty-five patients were treated nonoperatively with a sling for comfort through progressive early range of motion as tolerated. Ten additional uninjured subjects underwent strength testing to evaluate the difference between the dominant and nondominant sides so that patient data could be standardized. The patients were examined at intervals of 6, 12, 24, 36, and 52 weeks after injury, at which time they completed a subjective questionnaire and underwent isometric dynamometer testing as well as military press and bench press strength testing. One patient underwent a surgical procedure at 2 weeks after injury because of cosmetic concerns. Twenty of the 25 patients completed the 1-year evaluation and strength-testing protocol. Subjectively, 4 of the 20 patients (20%) thought that their long-term outcome was suboptimal, although for 3 of them it was not enough to warrant surgery. Objective examination and strength testing of the 20 patients revealed no limitation of shoulder motion in the injured extremity and no difference between sides in rotational shoulder muscle strength. The bench press was the only strength test that showed a significant short-term difference, with the injured extremity being an average of 17% weaker. This study documents the natural history of patients with an untreated acute grade III acromioclavicular separation and provides a reference with which to judge all other proposed methods of treatment.

The purpose of this study was to investigate kinematic and kinetic changes as a result of extended play in baseball pitching. Seven major league baseball pitchers were videotaped with high-speed (120 Hz) cameras during multiple innings of the same game. For each athlete, two fastballs (one thrown during the initial inning of play and one from the final inning) were chosen for analysis. Twenty-one physical landmarks were manually digitized from the video data. Kinematic and kinetic parameters were subsequently calculated relative to four phases of the pitching motion: windup, cocking, acceleration, and follow-through. Paired t-tests revealed that seven parameters changed significantly between early and late innings. These included decreases in maximum external rotation of the shoulder, knee angle at ball release, ball velocity, maximum distraction force at both the shoulder and elbow, and horizontal adduction torque at both release and its maximum value. Ultimately, a decline in performance was evident by a 2 m/s (5 mph) drop in ball speed. It is unclear whether the kinematic and kinetic changes occurred because of fatigue or if protective mechanisms were adopted.

Long-term biomechanical integrity of the surgical site is crucial to the outcome of rotator cuff repair. Usually after rotator-cuff surgery, the arm is immobilized for 6-12 weeks to minimize disruption at the healing site. Unfortunately, currently there is very little clinical data on the effects of immobilization after rotator cuff surgery. This study analyzed the effect of immobilization on rotator cuff healing by comparing the healing strength of the tendon in a bone trough using a sheep model. In sixteen (16) female adult sheep, the right infraspinatus tendons were reattached into a bone trough using a modified Mason-Allen suture pattern. After surgery, each sheep was randomly assigned into either an immobilized or non-immobilized treatment group. The immobilized group was fitted with a softball taped under the foot to restrict limb movement for 6 weeks. The non-immobilized treatment group was allowed to fully bear weight on the treated shoulder. At 26 weeks, the animals were sacrificed and the surgical shoulders were harvested and stored in a -30 degrees C freezer. Biomechanical testing was performed using a MTS 809 Axial/Torsional Servohydraulic System. Special cryo-grips were used to test the infraspinatus tendon-bone interface in anatomical alignment. All samples were preloaded with 10 +/- 5 N, and then force was measured during a crosshead displacement of 500 mm/min until failure. Force and displacement were acquired at 100 Hz and used to calculate load-to-failure and stiffness of the bone-tendon interface. The load-to-failure (N) and stiffness (N/cm) were determined for both treatment groups. For the non-immobilized group, the loads to failure and stiffness means were 2571.95 +/- 329.9 N and 2319.09 +/- 457.72 N/cm. The immobilized group means were 2954.42 +/- 473.52 N (load-to-failure) and 2579.13 +/- 383.51 N/cm (stiffness). A two-tailed two-samples unequal variance student t-test with significance set at 0.05, found no significant difference between the treatment groups for load-to-failure (p = 0.2174) and stiffness (p = 0.8286).

Hot electrons generated upon interaction of p-polarized 130 fs laser pulses with copper and penetrating into the target material are characterized with respect to their energy distribution and directionality. "Experimental" data are obtained by comparing the rear-side x-ray emission from layered targets with Monte Carlo electron-photon transport simulations. Theoretical electron energy distributions are derived by means of a one and a half-dimensional particle-in-cell code. Both sets of data consist of a two-temperature distribution of electrons propagating in a direction almost perpendicular to the target surface. The "experimental" data contain a considerably higher population of the lower temperature electrons. The discrepancy is explained by the intensity distribution of the laser spot. The results are used to design an experiment for demonstrating photopumping of cobalt with copper Kalpha radiation. A 10 &mgr;m copper foil is backed with 1 mm of polyethylene (PE) followed by 10 &mgr;m of cobalt, the rear-side Kalpha emission of which is measured. The PE layer prevents fast electrons from reaching the cobalt. Comparing the cobalt Kalpha emission with that of nickel, which is not photopumped by copper Kalpha shows enhancement by almost a factor of 2.

We have studied the distribution function of the hot electrons produced during the interaction of a 120-fs, 60-mJ, 800-nm wavelength and a p-polarized laser pulse with bilayered Al/Fe targets. The main pulse interacts with a preformed plasma, obtained with a controlled prepulse, whose density gradient scale length has been measured. The electron distribution function is characterized by means of the Kalpha emission of the two materials of the target as a function of the Al-layer thickness. The low-energy region (<50 keV) of the hot-electron distribution function shows no dependency in shape on the gradient scale length, but only a variation in the total number of the generated electrons. The comparison between the experimental results and the particle-in-cell and Monte Carlo calculations of the electron distribution function and the Kalpha emission is gratifying.

Ultrashort pulse laser-solid interaction experiments with 4x10(16) W/cm(2),120 fs, 45 degrees incidence angle, p-polarized pulses are theoretically analyzed with the help of 1(1/2)-dimensional (1(1/2) D) particle-in-cell (PIC) simulations. The laser impinges upon preformed plasmas with a precisely controlled density-gradient scale-length. PIC electron distribution functions are used as an input to 3D Monte Carlo simulations to interpret measured electron distributions and Kalpha radiation emission. Satisfactory agreement between the experimental and simulation results is obtained for the measured absorption coefficient, the energy distribution of the back-scattered hot electrons, the hot-electron temperature in the bulk of the target, and the Kalpha yield, when the preplasma scale-length is varied.

The effects of changes in blood volume on arterial pressure patterns during the Valsalva maneuver are incompletely understood. In the present study we measured beat-to-beat arterial pressure and heart rate responses to supine Valsalva maneuvers during normovolemia, hypovolemia induced with intravenous furosemide, and hypervolemia induced with ingestion of isotonic saline. Valsalva responses were analyzed according to the four phases as previously described (W. F. Hamilton, R. A. Woodbury, and H. T. Harper, Jr. JAMA 107: 853-856, 1936; W. F. Hamilton, R. A. Woodbury, and H. T. Harper, Jr. Am. J. Physiol. 141: 42-50, 1944). Phase I is the initial onset of straining, which elicits a rise in arterial pressure; phase II is the period of straining, during which venous return is impeded and pressure falls (early) and then partially recovers (late); phase III is the initial release of straining; and phase IV consists of a rapid "overshoot" of arterial pressure after the release. During hypervolemia, early phase II arterial pressure decreases were significantly less than those during hypovolemia, thus making the response more "square." Systolic pressure hypervolemic vs. hypovolemic falls were -7.4 +/- 2.1 vs. -30.7 +/- 7 mmHg (P = 0.005). Diastolic pressure hypervolemic vs. hypovolemic falls were -2.4 +/- 1.6 vs. -15.2 +/- 2.6 mmHg (P = 0.05). A significant direct correlation was found between plasma volume and phase II systolic pressure falls, and a significant inverse correlation was found between plasma volume and phase III-IV systolic pressure overshoots. Heart rate responses to systolic pressure falls during phase II were significantly less during hypovolemia than during hypervolemia (0.7 +/- 0.2 vs. 2.82 +/- 0.2 beats. min-1. mmHg-1; P = 0.05) but were not different during phase III-IV overshoots. We conclude that acute changes in intravascular volume from hypovolemia to hypervolemia affect cardiovascular responses, particularly arterial pressure changes, to the Valsalva maneuver and should be considered in both clinical and research applications of this maneuver.

This article discusses the effectiveness of MR imaging in evaluating the injuries of both upper and lower extremities in the professional football player. Topics include bone, joint and soft tissue disorders, and injuries resulting from overuse or trauma of the shoulder, elbow, forearm, and wrist; the pelvis and hip, lower extremity muscle and tendon, knee, and ankle.

There is little quantitative information available on the required healing time after a rotator cuff surgery. This study evaluated two surgical procedures by comparing the healing strength as a function of time of the tendon in a bone trough using a sheep model. The two surgical procedures compared were bioabsorbable suture anchors and bone tunnel suture technique. The infraspinatus tendon was split in half and procedure (suture anchor/tunnel suture) locations were randomly allocated to the proximal or distal half of the tendon at the healing time points of 0, 3, 6, 9, and 12 weeks with n = 6 at t = 0 and n = 8 in all other groups. At each time point, the surgical (right) and normal (left) shoulders were harvested and stored in a -30 degrees C freezer until testing. Biomechanical testing was performed using a MTS 809 Axial/Torsional Servohydraulic System. Special cryo-grips designed and built to test the infraspinatus tendon-bone interface in anatomical alignment were used. All samples were preloaded with 5 Newtons, and then force was measured during a crosshead displacement of 50 cm/min until failure. Force and displacement data were recorded to calculate load to failure and stiffness of the bone-tendon construct. There was only significant difference (95% CI) in mean tensile force at week 0, with the bone tunnel suture technique tensile force greater than the suture anchor method tensile force (p = 0.0261). There was no significant difference between stiffness means at any of the survival times.

We investigated the integrated cardiovascular responses of 15 human subjects to the acute gravitational changes (micro- and hypergravity portions) of parabolic flight. Measurements were made with subjects quietly seated and while subjects performed controlled Valsalva maneuvers. During quiet, seated, parabolic flight, mean arterial pressure increased during the transition into microgravity but decreased as microgravity was sustained. The decrease in mean arterial pressure was accompanied by immediate reflexive increases in heart rate but by absent (or later-than-expected) reflexive increases in total vascular resistance. Mean arterial pressure responses in Valsalva phases IIl, III, and IV were accentuated in hypergravity relative to microgravity (P < 0.01, P < 0.01, and P < 0. 05, respectively), but accentuations differed qualitatively and quantitatively from those induced by a supine-to-seated postural change in 1 G. This study is the first systematic evaluation of temporal and Valsalva-related changes in cardiovascular parameters during parabolic flight. Results suggest that arterial baroreflex control of vascular resistance may be modified by alterations of cardiopulmonary, vestibular, and/or other receptor activity.

Muscle activity, joints, angles, and heart rate during uphill walking were compared for application in knee rehabilitation. The objectives of this study were to quantify muscle activation levels at different treadmill grades and to determine the grade(s) at which knee range of motion would not further compromise the joint. Average and peak electromyographic activity of the quadriceps (vastus medialis oblique and vastus lateralis) and hamstrings (biceps femoris and medial hamstrings (semimembranosus/semitendinosus)] was recorded during walking at 0, 12, and 24% grade. Six subjects (age = 28.5 +/- 3.7 years, stature = 1.79 +/- .05 m, and mass = 74.7 +/- 7.9 kg) walked at self-selected speeds at each grade while ankle, knee and hip angles, heart rate, and electromyographic activity (surface electrodes) were recorded. Maximum voluntary contractions provided a relative reference for the electromyographic activity during walking. Average and peak electromyographic activity increased significantly across grades for the vastus medialis oblique (125 and 154%), vastus lateralis (109 and 139%), and biceps femoris (53 and 46%), but remained similar for the medial hamstrings. Maximum knee flexion at heel strike increased significantly with grade. Despite decreased self-selected speeds with increasing grade, there were significant increases in heart rate across grades. The results of this study provide a basic understanding of the quadriceps and hamstrings activity levels, lower extremity joint range of motion, and cardiovascular requirements of graded treadmill walking in normal subjects. The results also suggest that a grade just greater than 12% may be most beneficial for knee rehabilitation to minimize patellofemoral discomfort or potential strain on the anterior cruciate ligament. The benefits achieved through this functional activity encourage its implementation in rehabilitation and provide a basis for comparison with injured patients.

Arthritis of the glenohumeral joint can cause pain, weakness, and limit motion. Preoperative treatment consists of physical therapy to manage pain, increase shoulder motion, and increase rotator cuff and scapulothoracic muscle strength. The postoperative three-phase rehabilitation program described is structured, supervised, and involves the cooperation of the patient, surgeon, and physical therapist. Rate of progression and ultimate outcome is based on underlying pathology, surgical technique, and patient tolerance to exercise. Patients with an intact rotator cuff should be expected to tolerate a more aggressive rehabilitation program and expect a higher functional outcome. Those with a deficient cuff mechanism can expect more modest gains oriented toward restoring pain-free functional activity.

The presented automatic sleep analysis is based on the time courses of the mean amplitudes of EEG (delta, beta and alpha bands), EMG and motility and specific patterns (spindles, REMs, delta waves greater than 40 microV) detected automatically. The interindividual variability of the parameters is taken into consideration by interactively determining the threshold levels. Sleep stages are classified for every epoch using context free decision rules according to the manual of Rechtschaffen and Kales. The resulting cyclograms are smoothed and corrected using context sensitive rules which considers the successive epochs and the probability of stage transitions.

EEG, EOG, EMG and motility are recorded and preprocessed by hardware filtering of EEG and hardware detection of sigma spindles, rapid eye movements (REMs) and delta-waves (greater than 45 microV). After AD-conversion calculation of mean values and smoothing, the sleep-wake-process can be represented by the time-curves of 8 parameters: mean amplitudes per epoch (30 s) of EMG, motility and EEG (in the delta- alpha- and beta-band), delta-time (time/epoch of counted delta-waves) and presence or absence of spindles and REMs per epoch. These parameters can be presented graphically or stored for further analysis of sleep stages, sleep structure or sleep periodicity.

Male adult albino rats living from the 6th week of their lives under conditions of artificial light-dark cycle (16 hrs light, 8 hrs dark) were used to study possible relationships between circadian sensitivity cycles and synchronization of dynamics and the frequency variability of periodicities of reaction times of conditional-reflectory processes with wavelengths in the minute range. The experiments have revealed differences at the time of the activity maximum and minimum of a circadian cycle in the studied parameters of the minute rhythm (mean level of oscillation, mean amplitude, length of period and coupling). In the dark phase (activity maximum) there prevailed an increased level of central-nervous excitation and a tendency towards a higher frequency and diminished coupling of minute periods. In the light phase (activity minumum) the animals showed a balanced level of excitation, reduced frequency and a rigid coupling of periodicities of conditional-reflectory events involved in the process. Relations are shown to exist between central-nervous processes and circadian sensitivity cycles. For the experimental practice it is concluded that the different times of the day should be accounted for in assessing the criteria of minute rhythm and in conditional-reflectory studies in pharmacology and toxicology.

Forty male albino rats were used to study the relationship between experimentally (concentrated hydrochloric acid) produced local structural changes of the coronary artery wall and central nervous information processing and chronobiological events, respectively. The alterations of the coronary arteries caused by this treatment did not produce infarction but initiated on the whole length of the arterial branch proliferative processes that are complete within 12 weeks following the intervention. Central nervous information processing and chronoregulatory processes showed, immediately after exposure to hydrochloric acid, pronounced malfunctions followed by a stage of hyperreactivity (4 weeks following the damage). At 8 weeks from the intervention, the parameters of information processing and chronobiological events of the CNS again equalled the control values. Since the central nervous functions were back to normal earlier than the structural alterations, the results are interpreted as reflecting CNS-controlled interactions between the complex of visceral afference and efference, the regulation of which is determined by the CNS after coronary damage in such a way as to restore the adaptational capacity of the organism by a predominance of sanogenetic processes.

Periodicities of conditional-reflectory processes in the minute range were measured in albino rats kept under various conditions (emotional stress, exercise, normal stall maintenance) and analyzed by different statistical procedures. It was possible in this way to judge by selected parameters of periodical processes the intensity of loads and effects of exercise. The additional use of cluster analysis for scaling the biological effectiveness of different communicative relations of the organisms proved useful.