Abstract The photoexcitation dynamics of N 3 − ‐bound ferric myoglobin (MbN 3 ) were investigated after exciting MbN 3 in D 2 O at 283 K with a 575 nm pulse by probing the anti‐symmetric stretching mode of the azide. Global fitting of the overall time‐resolved spectra revealed that thermal relaxation of two stretching bands proceeded with a time constant of 6 ps, and that a new absorption band formed and decayed with time constants of 0.6 and 23 ps, respectively. The new absorption near 2040 cm −1 was attributed to the high‐spin species 2.4 kJ/mol above the low‐spin species, as the excited low‐spin relaxes thermally via the high‐spin species. However, this absorption could also arise from deligated N 3 ̄ remaining within the protein. The decay of this absorption can be interpreted as either spin transition of the high‐spin species into the low‐spin species or geminate recombination of the dissociated N 3 ̄. The implications of both interpretations are discussed.
Abstract Background A high proportion of pediatric patients with brain tumors (BTs) are known to experience a decline in neurocognitive function after treatment. We prospectively examined neuropsychological functioning of patients with BTs of varying tumor types at different time points before, during, and after proton beam therapy. Materials and methods A total of 98 patients with posterior fossa tumors (PFTs; n = 33), germ cell tumors (GCTs; n = 52), and other supratentorial tumors (STTs; n = 13) underwent baseline neuropsychological assessments and 57 patients underwent follow‐up assessments. Results All groups displayed significantly lower performance intelligence quotient (PIQ) and processing speed (PS) scores than the normative means at baseline. The PFT group exhibited significantly lower scores for full‐scale IQ, PIQ, PS, attention, and executive function. The GCT group displayed full‐scale IQ scores within the normal range, but a significantly high proportion had memory deficits. In the STT group, all functions except for the PIQ and PS were intact. Longitudinal evaluations demonstrated stable global IQ scores over time in all groups. In the PFT group, verbal comprehension, attention, and PS improved over time. However, in the GCT group, verbal IQ scores declined significantly and psychological problems worsened over time, which were correlated with poorer neurocognitive function at 3–5 years after treatment. In the STT group, no significant changes were observed. Conclusion Because patients with BTs exhibit various types of neurocognitive deficit before radiotherapy, early cognitive treatment tailored to the tumor type maybe beneficial. Interventions for psychological problems and memory function may be necessary, especially for patients with GCT.
Rebinding dynamics of CO photolyzed from GdnHCl-denatured HbCO and MbCO in D20 at 283K was probed by femtosecond mid-IR spectroscopy. The rebinding of CO to the denatured protein is much more efficient and faster than that to the native protein, suggesting that native structure is crucial for efficient expulsion of toxic CO.
Background and Objective
AMP-activated protein kinase (AMPK) functions as a sensor of the intracellular energy status that can be stimulated by a synthetic activator, 5-aminoimidazole–4–carboxamide–1–beta–D–ribofuranoside (AICAR), which is used to replicate the effect of physical exercise in hepatocyte embryoid bodies. This study investigated the effect of AICAR on the CYP3A1 mRNA expression in primary hepatocyte embryoid bodies derived from a rat liver.
Material and Methods
The primary hepatocytes were isolated from a male Sprague Dawley (SD) rat (215 g) and subjected to the following treatments: control without AICAR (CTL, n=3), 1 μM AICAR (n=3), 10 μM AICAR (n=3), and 100 μM AICAR (n=3). RNA was isolated and used as the template for synthesizing cDNA by reverse transcriptase to perform quantitative PCR (qPCR). The independent samples t-test was conducted to examine differences between groups. Statistical significance was set at p<0.05.
Results
The qPCR analysis demonstrated that CYP3A1 mRNA expression in primary hepatocyte embryoid bodies significantly increased in the presence of 10 μM (t=1.730, p<0.05) and 100 μM AICAR (t=3.207, p<0.05) as compared to that in the control group hepatocytes. However, the observed increase of CYP3A1 mRNA in hepatocyte embryoid bodies was not statistically significant in the presence of 1 μM AICAR as the lowest test concentration.
Conclusion
In this study, we demonstrated that AICAR, an AMPK activator, can increase the expression of CYP3A1 mRNA in primary hepatocytes. Future studies should assess the effect of AICAR treatment on CYP3A4 in human hepatocytes.
This study aimed to investigate the impact of percent body fat (%BF) on muscle damage after high-intensity eccentric exercise. Thirty healthy male undergraduates (mean age: 22.0 ± 2 years, height: 176.9 ± 5 cm, weight: 75.8 ± 11.6 kg) participated in this study, and they were classified according to their %BF into a high %fat group (HFG, ≥20%, n = 15) and a low %fat group (LFG, ≤15%, n = 15). For eccentric exercise, two sets of 25 reps were performed on a modified preacher curl machine using the elbow flexor muscle. Maximal isometric strength, muscle soreness (passive and active), creatine kinase (CK), and myoglobin (Mb) were measured as indices of muscle damage. The data were analyzed with repeated measures ANOVA. The results show that there is a significant group–time interaction for both CK and Mb after eccentric exercise (p = 0.007, p = 0.015, respectively), with a greater increase in the HFG than in the LFG. However, there was no significant group–time interaction for maximal isometric strength and muscle soreness (passive and active) (p > 0.05). These results suggest that %BF is a factor that alters the muscle damage indices CK and Mb, which indicate membrane disruption, after eccentric exercise.
We identified the predictive factors for locoregional failure after definitive chemoradiation in patients with locally advanced cervical cancer.Altogether, 397 patients with locally advanced cervical cancer (stage IB2-IVA) were treated with definitive chemoradiation between June 2001 and February 2010. Platinum-based concurrent chemotherapy was given to all patients with median radiation dose of external beam radiotherapy 50.4 Gy in 28 fractions and intracavitary radiotherapy 30 Gy in 6 fractions. Competing risk regression analysis was used to reveal the predictive factors for locoregional failure.During the median follow-up of 7.2 years, locoregional failure occurred in 51 (12.9%) patients. The estimated 3-year rate of locoregional control was 89%, whereas the overall survival rate was 82%. After univariate and multivariate analyses, large tumor size (>5 cm), young age (≤40 years), nonsquamous histology, positive lymph node on magnetic resonance imaging, and advanced stage (III-IV) were identified as risk factors for locoregional failure (P = 0.003, P = 0.075, P = 0.005, P = 0.055, and P < 0.001, respectively). After risk grouping according to the coefficients from the multivariate model, we identified a high-risk group for locoregional failure after treatment with definitive chemoradiation as follows: (1) tumor size larger than 5 cm, and at least 1 other risk factor or (2) tumor size 5 cm or less, and at least 3 other risk factors. The cumulated estimated 3-year rate of locoregional failure of the high-risk group was 26%, which was significantly higher than that of the low-risk group (7%, P < 0.001). The 3-year overall survival rates of the 2 groups were also significantly different (57% vs 86%, P < 0.001).Large tumor size (>5 cm), young age (≤40 years), nonsquamous histology, positive lymph node on magnetic resonance imaging, and advanced stage are all risk factors for locoregional failure after definitive platinum-based chemoradiation in patients with locally advanced cervical cancer. In the high-risk group, further clinical trials are warranted to improve the locoregional control rate.
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