Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Muscle function after exercise-induced muscle damage and rapid adaptation.

This brief review focuses on the time course of changes in muscle function and other correlates of muscle damage following maximal effort eccentric actions of the forearm flexor muscles. Data on 109 subjects are presented to describe an accurate time course of these changes and attempt to establish relationships among the measures. Peak soreness is experienced 2-3 d postexercise while peak swelling occurs 5 d postexercise. Maximal strength and the ability to fully flex the arm show the greatest decrements immediately after exercise with a linear restoration of these functions over the next 10 d. Blood creatine kinase (CK) levels increase precipitously at 2 d after exercise which is also the time when spontaneous muscle shortening is most pronounced. Whether the similarity in the time courses of some of these responses implies that they are caused by similar factors remains to be determined. Performance of one bout of eccentric exercise produces an adaptation such that the muscle is more resistant to damage from a subsequent bout of exercise. The length of the adaptation differs among the measures such that when the exercise regimens are separated by 6 wk, all measures show a reduction in response on the second, compared with the first, bout. After 10 wk, only CK and muscle shortening show a reduction in response. After 6 months only the CK response is reduced. A combination of cellular factors and neurological factors may be involved in the adaptation process.     

Changes in plasma zinc following high force eccentric exercise.

This study was done to determine whether eccentric exercise that causes muscle damage will produce an increase in plasma levels of zinc. Changes in total plasma zinc concentration (Zn) were examined following an eccentric and concentric exercise of the forearm flexors. Eight female subjects performed 24 maximal concentric actions (CON) with one arm and 10-14 days later performed 24 maximal eccentric actions (ECC) with the other arm. Maximal isometric force, elbow joint angles at a relaxed (RANG) and flexed position (FANG), muscle soreness, and plasma creatine kinase activity (CK) were measured as indicators of muscle damage. Zn levels were determined at the same time as CK. Maximal isometric force, RANG, FANG, and muscle soreness showed large changes after ECC but little if any change after CON. CK increased significantly after ECC but did not change after CON. Neither ECC nor CON showed significant changes in Zn following exercise. It is concluded that exercise-induced muscle damage does not appear to produce an increase in plasma zinc levels.     

Effects of massage on delayed-onset muscle soreness, swelling, and recovery of muscle function

Context: Delayed-onset muscle soreness (DOMS) describes muscle pain and tenderness that typically develop several hours postexercise and consist of predominantly eccentric muscle actions, especially if the exercise is unfamiliar. Although DOMS is likely a symptom of eccentric-exercise–induced muscle damage, it does not necessarily reflect muscle damage. Some prophylactic or therapeutic modalities may be effective only for alleviating DOMS, whereas others may enhance recovery of muscle function without affecting DOMS.Objective: To test the hypothesis that massage applied after eccentric exercise would effectively alleviate DOMS without affecting muscle function.Design: We used an arm-to-arm comparison model with 2 independent variables (control and massage) and 6 dependent variables (maximal isometric and isokinetic voluntary strength, range of motion, upper arm circumference, plasma creatine kinase activity, and muscle soreness). A 2-way repeated-measures analysis of variance and paired t tests were used to examine differences in changes of the dependent variable over time (before, immediately and 30 minutes after exercise, and 1, 2, 3, 4, 7, 10, and 14 days postexercise) between control and massage conditions.Setting: University laboratory.Patients or Other Participants: Ten healthy subjects (5 men and 5 women) with no history of upper arm injury and no experience in resistance training.Intervention(s): Subjects performed 10 sets of 6 maximal isokinetic (90°·s⁻¹) eccentric actions of the elbow flexors with each arm on a dynamometer, separated by 2 weeks. One arm received 10 minutes of massage 3 hours after eccentric exercise; the contralateral arm received no treatment.Main Outcome Measure(s): Maximal voluntary isometric and isokinetic elbow flexor strength, range of motion, upper arm circumference, plasma creatine kinase activity, and muscle soreness.Results: Delayed-onset muscle soreness was significantly less for the massage condition for peak soreness in extending the elbow joint and palpating the brachioradialis muscle (P < .05). Soreness while flexing the elbow joint (P = .07) and palpating the brachialis muscle (P = .06) was also less with massage. Massage treatment had significant effects on plasma creatine kinase activity, with a significantly lower peak value at 4 days postexercise (P < .05), and upper arm circumference, with a significantly smaller increase than the control at 3 and 4 days postexercise (P < .05). However, no significant effects of massage on recovery of muscle strength and ROM were evident.Conclusions: Massage was effective in alleviating DOMS by approximately 30% and reducing swelling, but it had no effects on muscle function.     

Dependence of reactive responses in human bimanual finger movements on sensory feedback and auditory cues

We examined the effects of repetitive experience of feedback events and cue signals on adaptation of bimanual reactive response, both of which can be used to predict load forces on handheld objects. Normal human subjects used bimanual index fingers to hold two plates mounted on separate torque motors. Sensory-driven reactive forces from the fingers were measured during concurrent loading of both plates or isolated loading of the left plate. After repeated experiences of single load conditions, right and left fingers increased normal forces in a coordinated manner during concurrent loading, while the left finger responded almost exclusively during isolated loading of the left plate. However, after switching load conditions from concurrent to isolated load, or vice versa, several trials were needed to adapt to the new condition, as was clearly observed in the dynamic phase of responses from the right finger. Adaptation depends on the number of feedback experiences, and specifically on prediction error, showing intermediate predictions between the two conditions. Thus influences of the previous experiences show similar properties to those observed in self-generated movement, which were reported previously. In addition, auditory cues informing subjects of coming load conditions also partially adapted responses to these conditions. The neuronal center for reactive responses is therefore influenced by both previous experience and cue signals, inducing the appropriate responses for the predicted sensory inputs.     

Prototype heel effect compensation filter for cone-beam CT

The prototype cone-beam CT (CBCT) has a larger beam width than the conventional multi-detector row CT (MDCT). This causes a non-uniform angular distribution of the x-ray beam intensity known as the heel effect. Scan conditions for CBCT tube current are adjusted on the anode side to obtain an acceptable clinical image quality. However, as the dose is greater on the cathode side than on the anode side, the signal-to-noise ratio on the cathode side is excessively high, resulting in an unnecessary dose amount. To compensate for the heel effect, we developed a heel effect compensation (HEC) filter. The HEC filter rendered the dose distribution uniform and reduced the dose by an average of 25% for free air and by 20% for CTDI phantoms compared to doses with the conventional filter. In addition, its effect in rendering the effective energy uniform resulted in an improvement in image quality. This new HEC filter may be useful in cone-beam CT studies.     

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

Inhibition of nitric oxide synthase induction by 15-deoxyspergualin in a cultured macrophage cell line, J774A.1 [correction of J744A.1] activated with IFN-gamma and LPS.

Immunosuppressant 15-deoxyspergualin (DSG) inhibited induction of inducible nitric oxide synthase (iNOS) following stimulation with IFN-gamma and LPS in a cultured macrophage cell line, J774A.1 [corrected]. By DSG treatment NO2- accumulation in the medium was blocked, and cellular iNOS protein level decreased as shown by Western blotting. DSG didn't have any direct effect on iNOS activity. DSG was not used as a substrate of NOS in in vitro enzyme systems, and it was too weak an inhibitor of iNOS and cNOS to cause the inhibition of accumulation of NO2-. DSG did not scavenge NO spontaneously generated from NOR. Structure-activity relationships of analogs and decomposed elements showed that there is correlation between the inhibition of iNOS induction and immunosuppressive activity.     

Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro.

Adult T-cell leukemia (ATL) is a fatal neoplasm derived from CD4-positive T-lymphocytes, and regardless of intensive chemotherapy, its mean survival time is less than 1 year. Nuclear factor-kappaB (NF-kappaB) activation was reported in HTLV-I associated cells, and has been implicated in oncogenesis and resistance to anticancer agents and apoptosis. We studied the effect of a proteasome inhibitor, bortezomib (formerly known as PS-341), on ATL cells in vitro and in vivo. Bortezomib could inhibit the degradation of IkappaBalpha in ATL cells, resulting in suppression of NF-kappaB and induction of cell death in ATL cells in vitro. Susceptibilities to bortezomib were well correlated with NF-kappaB activation, suggesting that suppression of the NF-kappaB pathway was implicated in the cell death induced by bortezomib. Although the majority of the cell death was apoptosis, necrotic cell death was observed in the presence of a caspase inhibitor, z-VAD-fmk. When bortezomib was administered into SCID mice bearing tumors, it suppressed tumor growth in vivo, showing that bortezomib was effective against ATL cells in vivo. These studies revealed that bortezomib is highly effective against ATL cells in vitro and in vivo by induction of apoptosis, and its clinical application might improve the prognosis of patients with this fatal disease.