Changes in knee joint muscle activation patterns during walking associated with increased structural severity in knee osteoarthritis

PurposeTo determine whether alterations in knee joint muscle activation patterns during gait were related to structural severity determined by Kellgren–Lawrence (KL) radiographic grades, for those with a moderate knee OA classification.ScopeEighty-two individuals with knee OA, classified as moderate using a functional and clinical criterion were stratified on KL-grade (KL II, KL III and KL IV). Thirty-five asymptomatic individuals were matched for age and walking velocity. Lower limb motion and surface electromyograms from rectus femoris plus lateral and medial sites for the gastrocnemii, vastii and hamstring muscles were recorded during self-selected walking. Gait velocity and characteristics from sagittal plane knee angular displacement waveforms were calculated. Principal component analysis extracted amplitude and temporal features from electromyographic waveform. Analysis of variance models tested for main effects (group, muscle) and interactions (α = 0.05) for these features. No differences in anthropometrics, velocity, knee muscle strength and symptoms were found among the three OA groups (p > 0.05). Specific features from medial gastrocnemius, lateral hamstring and quadriceps amplitude and temporal patterns were significantly different among OA groups (p < 0.05).ConclusionsSystematic alterations in specific knee joint muscle activation patterns were associated with increasing structural severity based on KL-grades whereas other alterations were associated with the presence of OA.     

Changes in ion channel expression and function associated with cardiac arrhythmogenic remodeling by Sorbs2

The Sorbin and SH3 domain-containing protein 2 (Sorbs2) is an important component of cardiomyocyte sarcomere. It has been recently reported that loss of Sorbs2 is causally associated with arrhythmogenic cardiomyopathy in human. However, the ionic mechanisms leading to cardiac arrhythmogenesis by Sorbs2 deficiency are unknown. In this study, we hypothesized that Sorbs2 plays an important role in regulating cardiac ion channel expression and function. Using electrophysiological and molecular biological approaches, we found that the Sorbs2 knockout (KO) mice progressively developed cardiac structural and electrical remodeling as early as 1 to 2 months of age and died prematurely at 5 to 7 months of age. Electrocardiographic recordings showed that Sorbs2 KO mice had conduction delays, spontaneous ventricular extrasystoles and polymorphic ventricular tachyarrhythmia. Intracellular recordings revealed abnormal action potentials with depolarized resting potential, reduced upstroke velocity, prolonged repolarization, and effective refractory period in the ventricular preparations of Sorbs2 KO mice. Patch clamp experiments demonstrated that Sorbs2 KO mice displayed distinct abnormalities in the expression and function of cardiac ion channels, including those of the voltage-gated Na⁺ channels, L-type Ca²⁺ channels, the voltage-gated K⁺ channels and the inward-rectifier K⁺ channels. Moreover, Sorbs2 physically interacted with the RNAs and/or proteins of important cardiac ion channels and directly regulated their expression in vitro. Our results indicate that Sorbs2 plays a pivotal role in the regulation of cardiac channel physiology. Loss of Sorbs2 promotes cardiac ion channelopathies and life-threatening arrhythmias.     

恶性血液病患者化疗前后肠道免疫功能及微生态改变状况研究

目的 探讨恶性血液病患者化疗后肠道免疫功能及微生态改变状况。方法 采用前瞻性队列研究。入选初发恶性血液病并需要化疗的患者,留取化疗前后粪便标本。根据患者化疗后是否出现发热,分为粒细胞减少伴发热组及粒细胞减少不伴发热组。采用光冈法对粪便需氧菌及厌氧菌进行定量培养,分析肠道菌群变化。同时检测患者化疗前后粪便IgA值变化。结果 共纳入24例患者,化疗后出现粒细胞减少症伴发热的患者10例,占41.7%;未发热患者14例,占58.3%。24例患者化疗后粪便IgA水平及B/E值显著性下降,肠道微生态发生改变,具体表现为肠杆菌、假单胞菌及真菌显著增多。化疗后,粒细胞减少伴发热组与未发热组相比肠杆菌及真菌显著增多,两组患者粪便IgA水平、B/E值变化无明显差异。结论恶性血液病患者化疗后肠道免疫功能、微生物定植抗力下降,侵袭性细菌增多。化疗后粒细胞减少伴发热患者肠杆菌显著增多,可能成为粒细胞减少症伴发热患者的潜在致病菌。     

Membrane Changes associated with Malignancy

The specific structural and metabolic changes on the surface membrane which result in agglutinability of transformed cells by concanavalin A are associated with cell malignancy in vivo.     

Factors predicting knee function in patients with meniscal lesions

The relationships between the magnitude of strength and muscle activation (EMG activity) deficits during maximal isokinetic knee movements and clinical and anthropometric factors (pain, effusion, type of meniscal lesion, degenerative changes, duration of symptoms and age) were studied in a group of 34 patients 5 days (5.3 ± 6.2 days) before arthroscopic meniscectomy. Moderate correlations were found between deficits in the area under the torque-angle curve (work) and the activation level in the agonist muscles during both the extension and flexion tests at 30° s⁻¹ and 180° s⁻¹ suggesting that the decrease in the isokinetic mechanical output is dependent on the reduced muscle activation. The severity of pain during tests was the best predictive clinical factor for the size of the work and EMG deficits but each of the tollowing factors: the presence of knee effusion and thigh atrophy, the type of meniscal lesion and the age of the patients, also had some predictive value for the magnitude of the deficits. In contrast, the duration of symptoms and the presence of osteo-articular degenerative changes were not related to the preoperative isokinetic knee performance. These results suggest that older patients (especially over 45 yr) with bucket-handle meniscal tears, knee effusion, thigh atrophy and severe pain on exertion, are most likely to have poor preoperative knee isokinetic performance. Since the magnitude of the pre- and postoperative knee deficits are correlated, it is important to identify patients at risk preoperatively so that optimal rehabilitation can be instituted.     

Changes in wireworm population associated with cropping

Data are given to show that the rate of decline of the wireworm population associated with a root crop is not significantly greater than that associated with a cereal crop. Data are given on the wireworm populations of adjoining ley plots over 3-5 successive years, and indicate a slow rate of increase during the early years.     

Changes in the macrophage function with aging

Changes in the adherence, opsonization, phagocytosis, nitroblue tetrazolium reduction and antibody-dependent cell cytotoxicity of peritoneal macrophages were observed with aging in BALB/C mice. A decrease in all the parameters studied, except for the reduction capacity of nitroblue tetrazolium, which increased with aging, was found in the long-lived mice. The role of the macrophage in immune hyporesponsiveness with aging is discussed.     

Changes in ventilation in response to ramp changes in treadmill exercise load

These experiments examined the changes in ventilation during a 40-s ramp increase in exercise load, produced by increasing either the speed of the treadmill or the grade, to equivalent end-points of oxygen uptake. Six subjects underwent five trials each for grade and speed, while ventilation was monitored breath-by-breath. For each subject, ventilation versus time for all five of the speed trials was plotted on a single graph and fitted by linear regression. The data for the grade trials were similarly treated. For all subjects, the slope of the regression line for the speed plots was found to be significantly (P < 0.05) greater than that for the grade plots. We concluded that these experimental results support the hypothesis that the neural drive to ventilation persists as exercise continues and is proportionately related to the frequency of limb movement.     

Changes in ribosome function induced by protein kinase associated with ribosomes of Streptomyces collinus producing kirromycin.

Protein kinase associated with ribosomes of streptomycetes phosphorylates 11 ribosomal proteins. Phosphorylation activity of protein kinase reaches its maximum at the end of exponential phase of growth. When (32)P-labeled cells from the end of exponential phase of growth were transferred to a fresh medium, after 2 h of cultivation ribosomal proteins lost more than 90% of (32)P and rate of polypeptide synthesis increases twice. Protein kinase cross-reacting with antibody raised against protein kinase C was partially purified from 1 M NH(4)Cl wash of ribosomes and used to phosphorylation of ribosomes. Phosphorylation of 50S subunits (L2, L3, L7, L16, L21, L23, and L27) had no effect on the integrity of subunits but affects association with 30 to 70S monosomes. In vitro system derived from ribosomal subunits was used to examine the activity of phosphorylated 50S at poly(U) translation. Replacement unphosphorylated 50S with 50S possessed of phosphorylated r-proteins leads to the reduction of polypeptide synthesis of about 52%. The binding of N-Ac[(14)C]Phe-tRNA to A-site of phosphorylated ribosomes is not affected but the rate of peptidyl transferase is more than twice lower than that in unphosphorylated ribosomes. These results provide evidence that phosphorylation of ribosomal proteins is involved in mechanisms regulating the translational system of Streptomyces collinus.     

Changes in gene expression associated with loss of function of the NSDHL sterol dehydrogenase in mouse embryonic fibroblasts

Seven human disorders of postsqualene cholesterol biosynthesis have been described. One of these, congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome, results from mutations in the X-linked gene NADH sterol dehydrogenase-like (NSDHL) encoding a sterol dehydrogenase. A series of mutant alleles of the murine Nsdhl gene are carried by bare patches (Bpa) mice, with Bpa(1H) representing a null allele. Heterozygous Bpa(1H) females display skin and skeletal abnormalities in a distribution reflecting random X inactivation, whereas hemizygous male embryos die before embryonic day 10.5. To investigate the molecular basis of defects associated with perturbations in cholesterol biosynthesis, microarray analysis was performed comparing gene expression in embryonic fibroblasts expressing the Bpa(1H) allele versus wild-type (wt) cells. Labeled cDNAs from cells grown in normal serum or lipid-depleted serum (LDS) were hybridized to microarrays containing 22,000 mouse genes. Among 44 genes that showed higher expression in the Bpa(1H) versus wt cells grown in LDS, 11 function in cholesterol biosynthesis, 7 are involved in fatty acid synthesis, 3 (Srebp2, Insig1, and Orf11) encode sterol-regulatory proteins, and 2 (Ldlr and StarD4) are lipid transporters. Of the 21 remaining genes, 16 are known genes, some of which have been implicated previously in cholesterol homeostasis or lipid-mediated signaling, and 5 are uncharacterized cDNA clones.     

Changes in cell wall polysaccharides associated with growth

Changes in the polysaccharide composition of Phaseolus vulgaris, P. aureus, and Zea mays cell walls were studied during the first 28 days of seedling development using a gas chromatographic method for the analysis of neutral sugars. Acid hydrolysis of cell wall material from young tissues liberates rhamnose, fucose, arabinose, xylose, mannose, galactose, and glucose which collectively can account for as much as 70% of the dry weight of the wall. Mature walls in fully expanded tissues of these same plants contain less of these constituents (10%-20% of dry wt). Gross differences are observed between developmental patterns of the cell wall in the various parts of a seedling, such as root, stem, and leaf. The general patterns of wall polysaccharide composition change, however, are similar for analogous organs among the varieties of a species. Small but significant differences in the rates of change in sugar composition were detected between varieties of the same species which exhibited different growth patterns. The cell walls of species which are further removed phylogenetically exhibit even more dissimilar developmental patterns. The results demonstrate the dynamic nature of the cell wall during growth as well as the quantitative and qualitative exactness with which the biosynthesis of plant cell walls is regulated.     

Changes in articular eminence morphology with dental function

Measurements of mandibular fossa depth and slope of the articular eminence were obtained for human skeletal samples chosen to represent a wide spectrum of subsistence strategies and oral function: hunter-gatherers (Eskimos, Australians), American Indians dependent to a variable extent on maize agriculture, and early twentieth century American whites and blacks. In the Eskimo and Australian samples, a generalized and steady increase in fossa depth and slope was observed with increasing functional age (tooth wear) through wear level 5 (of 8), followed by a levelling off or slight decrease in fossa depth in later wear levels on the anterior teeth and a sharp decrease in fossa depth in later wear levels on the molars. Although much less consistent due in part to extensive and early molar loss, patterns of variation in the remaining samples were characterized overall by a decrease in fossa depth and slope with increasing wear, especially on the molars. Further, in those samples with high incidences of posterior tooth loss, fossa depth was routinely less and the eminence more gently sloped in subsamples having experienced molar loss than in subsamples retaining all their molars. These data provide evidence that the temporomandibular joint (TMJ) undergoes continuous morphological alteration throughout adult life, and that these alterations are probably mediated by dental function. Moreover, they suggest that differences in patterning of such alterations may exist among human groups with contrasting patterns of tooth use.     

Changes in gene expression associated with IFN-beta and IL-2-induced augmentation of human natural killer cell function

NK function can be augmented by a variety of agents, including the cytokines IL-2 and IFN. The mechanisms associated with IL-2- and IFN-mediated augmentation of NK function are largely unknown. In order to learn more about the regulation of NK activity, we have studied changes in gene expression that occur upon treatment of a cloned line of NK cells (NK 3.3) with rIL-2 and rIFN-beta. Both IL-2 and IFN-beta induced rapid augmentation of lysis mediated by NK 3.3, which was significant within 1 h, peaked at 6 h of treatment, and declined by 12 h. This enhancement of lytic function was independent of proliferation and associated with a corresponding increase in steady state levels of RNA coding for both the nuclear proto-oncogene c-myb and for the IL-2R. These changes were specific in that RNA levels of another nuclear proto-oncogene, c-myc, were increased by IL-2 but not by IFN-beta, whereas HLA class I RNA levels were relatively unchanged by either IL-2 or IFN-beta treatment. Treatment of NK 3.3 with the combination of IL-2 and IFN enhanced both lysis and c-myb expression in an additive fashion. These findings suggest that c-myb may play a regulatory role in the cytolytic activity of NK cells.     

Changes in plasma glucose and lipid concentrations during treadmill exercise in domestic fowl

• 1.1. Plasma glucose, non-esterified fatty acid, triglyceride, cholesterol and lactate concentrations were measured during 90 min treadmill exercise at a work intensity of 55–60% maximum.
• 2.2. After 90 min exercise plasma glucose fell by 35% whilst the non-esterified fatty acid concentration rose to as much as 3–4 times resting.
• 3.3. Exercise had no significant effect on plasma cholesterol, triglyceride or lactate concentrations.
• 4.4. The findings indicate a progressive increase in fat utilization during prolonged exercise. Possible hormonal mechanisms underlying exercise-induced changes in lipid and carbohydrate metabolism are discussed.

     

Changes in Epstein-Barr virus antibody titers associated with aging

Antibody titers to the Epstein-Barr virus (EBV), early antigen (EA) IgG, and virus capsid antigen (VCA) IgG and IgA, were measured in 44 geriatric subjects to determine if the depression in cellular immunity known to be associated with aging affects the expression of latent EBV. Similar assays were performed on plasma obtained from a young adult (medical student) population as a control group. We found that 89% of the geriatric samples were positive for EA IgG, and 83% of the plasma obtained from medical students were positive for EA IgG. One hundred percent of the geriatric subjects were positive for VCA IgG, and 87% of the medical students were positive for VCA IgG. Seven percent of the medical student blood samples were positive for VCA IgA; in contrast, 36% of the blood samples obtained from the geriatrics subjects were positive. Significant differences were also found in the geometric mean titers (GMT) of antibodies to EBV antigens; the GMT to EBV EA and VCA were significantly higher in the geriatric group. The data suggest that there may be some loss of control over latent EBV by the cellular immune response in geriatric individuals.     

Monitoring changes in body surface temperature associated with treadmill exercise in dogs by use of infrared methodology

The aim of this study was to evaluate the influence of moderate treadmill exercise session on body surface and core temperature in dog measured by means of two infrared instruments. Ten Jack Russell Terrier/Miniature Pinscher mixed-breed dogs were subjected to 15 min of walking, 10 min of trotting and 10 min of gallop. At every step, body surface temperature (T_surface) was measured on seven regions (neck, shoulder, ribs, flank, back, internal thigh and eye) using two different methods, a digital infrared camera (ThermaCam P25) and a non-contact infrared thermometer (Infrared Thermometer THM010-VT001). Rectal temperature (T_rectal) and blood samples were collected before (T0) and after exercise (T3). Blood samples were tested for red blood cell (RBC), hemoglobin concentration (Hb) and hematocrit (Hct). A significant effect of exercise in all body surface regions was found, as measured by both infrared methods. The temperature obtained in the eye and the thigh area were higher with respect to the other studied regions throughout the experimental period (P<0.0001). RBC, Hb, Hct and T_rectal values were higher at T3 (P<0.05). Statistically significant higher temperature values measured by infrared thermometer was found in neck, shoulder, ribs, flank, back regions respect to the values obtained by digital infrared camera (P<0.0001). The results obtained in this study showed that both internal and surface temperatures are influenced by physical exercise probably due to muscle activity and changes in blood flow in dogs. Both infrared instruments used in this study have proven to be useful in detecting surface temperature variations of specific body regions, however factors including type and color of animal hair coat must be taken into account in the interpretation of data obtained by thermography methodology.     

Changes in the fibrinolytic system associated with physical conditioning

The effects of physical conditioning on plasma fibrinolytic activity were studied in two groups of subjects. Volunteers not engaged in any sport were compared with individuals having been subjected to aerobic conditioning (middle-distance runners, defined as men running more than 80 km per week). Plasma concentrations of the different components of the fibrinolytic system were evaluated before and immediately after a maximal effort treadmill protocol. Comparison of the resting parameters revealed that under basal conditions for plasma concentrations of plasminogen, fibrinogen, alpha 2-antiplasmin, protein C and protein S there were no differences between the two groups. Concentrations of the fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were significantly higher in the runners than in the control group, indicating an increased fibrinolytic potential that seemed to be a consequence of the reduced formation of tissue plasminogen activator-plasminogen activator inhibitor (t-PA-PAI) complexes. Acute maximal exercise resulted in pronounced fibrinolysis, evidenced by the elevation of FbDP and FgDP concentrations, in both groups of subjects. The acceleration of the fibrinolytic activity was larger in conditioned individuals, which could be accounted for by a higher t-PA release and reduced formation of t-PA-PAI complexes when compared to the untrained subjects.