Nuclear distribution of human DNA topoisomerase IIbeta: a nuclear targeting signal resides in the 116-residue C-terminal tail

Surgery is considered to be a standard therapy for stage III or the earlier stage of esophageal cancer. However, the standard therapy is changing because of the recent advances in the non-surgical approach, especially chemoradiotherapy. Various obstacles remain to estimate the outcomes of combined modality therapy, while the consensus of the treatment for such stage excluding T4 diseases are as follows: 1) Concurrent chemoradiotherapy has a superior outcome to radiation alone in patients with squamous cell carcinoma. 2) Recent chemoradiotherapy without surgery achieves results comparable to surgery alone. 3) Preoperative chemoradiotherapy can achieve better results than surgery alone in patients with adenocarcinoma. 4) Preoperative chemotherapy is still experimental. Our preliminary results of chemoradiotherapy for esophageal cancer also showed comparable data to extended surgery in terms of survival. Some significant points to be elucidated regarding combined modalities in stage III or earlier are: 1) the comparison of definitive chemoradiotherapy with Japanese extended surgery, and 2) evaluation of efficacy of surgery after chemoradiotherapy. However, these studies require randomized trials comparing surgery with non-surgical treatment, which appears to present significant obstacles. Critical estimation for each study should be recommended based on accurate clinical staging, biological behavior, and intention-to-treat.     

Correlation of the enzyme activities of Bacillus stearothermophilus lactate dehydrogenase on three substrates with the results of molecular dynamics/energy minimization conformational searching

Current methods for reengineering enzyme substrate specificities rely heavily on the use of static x-ray crystallographic models. In this article we detail the use of a molecular mechanics approach for suggesting regions of Bacillus stearothermophilus L-lactate dehydrogenase (EC 1.1.1.27) involved in substrate specificity, and hence areas of interest for protein engineers. The approach combines molecular dynamics with energy minimization (MD/EM) to search the conformational space available to a 15-A sphere of the ternary complex centered on the catalytic histidine. The search is carried out by calculating a 30-ps dynamics trajectory at 300 K and minimizing structures at 1-ps intervals. The protocol has been performed on 14 systems containing different combinations of substrate and mutant/wt LDH. In order to discover which interactions are important in defining substrate specificity, eight conformational parameters representing substrate-active site interactions were measured in each of the 420 minimized structures. These parameters were then compared to the measured catalytic activity of the protein-substrate combinations. These comparisons show that arginine 109 orientation is a major determining factor in LDH specificity. Using this methodology it is possible to estimate the catalytic activity of proteins of varied sequence by computer simulation before synthesis.     

Parasites of South African wildlife. XIV. Helminths of nyalas (Tragelaphus angasii) in the Mkuzi Game Reserve, KwaZulu-Natal

Reliability of event-related P3 parameters. Various parameters of the P3 wave were tested for reliability and test-retest stability. To this end, event-related P3 waves were evoked in 21 subjects during visual and auditory oddball tasks. The protocol was repeated one to two weeks later. Amplitude, latency and area between P3 and baseline were estimated by different procedures. The stability within and between sessions was assessed with the split-half method and a measure of test-retest reliability, respectively. A literature review revealed that latency estimation is most commonly done by computer-aided peak measurement, but determining peak parameters visually after interpellating superimposed artifacts turned out to be significantly more reliable. Interrater reliability for this visual inspection was very high if preestablished rules were employed. Amplitude and area were measured reliably by both computer-aided procedures and visual inspection. The area was quite stable both within and between sessions. Area can serve as a measure of cerebral activation and should therefore be determined. Based on the results recommendations are made about analyzing components of event-related potentials. The need to control for error variance is emphasized. This is the only way to improve methods enough that they will be suitable for use in single case diagnosis.     

Development of a competitive enzyme linked immunosorbent assay to measure alpha 2-macroglobulin in irradiated rat serum

A competitive enzyme linked immunosorbent assay with antigen immobilized on the solid phase was developed to measure alpha 2-macroglobulin in rat serum. The cross reactivity with albumin and hemoglobin was eliminated by use of IgG fractions that were isolated after chromatography on Cibacron Blue F3-GA Sepharose immobilized rat whole serum and hemoglobin Sepharose. Blocking materials and pH of the coating buffer had no effect on the amount of alpha 2-macroglobulin that binds to the plate. When the coating amount of alpha 2-macroglobulin was 100 ng/well, at pH 7.4, 10 mM Tris-HCl containing 150 mM sodium chloride and the IgG amount added was 60 ng/well, then albumin and hemoglobin did not affect the assay at concentrations of 150 micrograms/ml or 200 micrograms/ml. This assay is useful for measuring the concentration of alpha 2-macroglobulin in normal and irradiated rat serum.     

The use of combined methods of magnetoelectrotherapy in treating polyneuropathies

A comparative evaluation by such parameters as alleviation of pain syndrome, improvement of peripheral resistance and vegetotrophic processes, a decline in pareses and sensory disorders has been performed in 3 groups of patients: group 1 underwent benzohexonium electrophoresis, group 2 benzohexonium electrophoresis in the magnetic field produced by the unit "Polyus-I" followed by low-frequency electrotherapy with bipolar impulse current, group 3 benzohexonium electrophoresis in the magnetic field from the unit "ADMT-Magnipuls" followed by low-frequency electrotherapy with bipolar impulse current. The best clinical and physiological results were reported in group 3 patients.     

Thermal model validation of plate heat exchangers with generalized configurations

Thermal models of plate heat exchangers rely on correlations for the evaluation of the convective heat transfer coefficients inside the channels. It is usual to configure the exchanger with one countercurrent single-pass arrangement for acquiring heat transfer experimental data. This type of configuration approaches the ideal case of pure countercurrent flow conditions, and therefore a simplified mathematical model can be used for parameter estimation. However, it is known that the results of parameter estimation depend on the selected exchanger configuration because the effects of flow maldistribution inside its channels are incorporated into the heat transfer coefficients. This work presents a parameter estimation procedure for plate heat exchangers that handles experimental data from multiple configurations. The procedure is tested with an Armfield FT-43 heat exchanger with flat plates and the parameter estimation results are compared to those obtained from the usual method of single-pass arrangements. It can be observed that the heat transfer correlations obtained for plate heat exchangers are intimately associated with the configuration(s) experimentally tested and the corresponding flow distribution pattern(s).     

Phenotypic variation in leukoencephalopathy with vanishing white matter

OBJECTIVE: The objective of this study is to describe milder and later onset variants of a recently described leukoencephalopathy with vanishing white matter. BACKGROUND: The diagnostic criteria used currently for this disease include an early-childhood onset of neurologic deterioration. METHODS: Clinical, MRI, and spectroscopic findings of five patients were reviewed who fulfilled all inclusion criteria for the disease of vanishing white matter, apart from the age at onset. In one patient histopathologic findings were documented. RESULTS: Onset of the disease was in late childhood or adolescence in four patients, and one patient was still presymptomatic in his early twenties. The course of the disease tended to be milder than in the patients with early-childhood onset. MRI revealed a diffuse cerebral hemispheric leukoencephalopathy with evidence of white matter rarefaction. MRS of the abnormal white matter showed a serious decrease but not complete disappearance of all "normal" signals and, in some patients, the presence of extra signals from lactate and glucose. Changes in relative spectral peak heights were compatible with axonal damage or loss, but not with active demyelination or substantial gliosis. Autopsy in one patient confirmed the extensive rarefaction of the cerebral white matter. There was a commensurate loss of axons and myelin sheaths. Within the brainstem, pontine lesions were present, also involving the central tegmental tracts--a phenomenon previously described in early-onset patients. CONCLUSION: Later onset does occur in the disease of vanishing white matter, and both MRS and histopathology are compatible with a primary axonopathy rather than primary demyelination.     

Displacement of leisure reinforcers by food during preference assessments

Identification of reinforcers for individuals with developmental disabilities is often based on the outcome of preference assessments in which participants make selections from among a variety of items. We determined the extent to which individuals might show a general preference for food items over leisure items during such assessments and whether leisure items that are "displaced" by food items might nevertheless function as reinforcers. Arrays consisting of food items only and then nonfood items only were presented separately to 14 participants and then were ranked to determined preference. The top selections from these initial assessments were subsequently combined in a third assessment, and preferences were again established. All but 2 participants showed a general preference for food items, such that selection of nonfood items in the combined arrays was displaced downward relative to selection of nonfood in the nonfood-only arrays. Two of the participants were exposed to a condition in which a nonfood item was delivered contingent on the occurrence of an adaptive response, and increased rates of responding by both individuals were observed. Results are discussed in terms of limitations posed by using only food items as reinforcers and the resulting need to take precautionary measures when attempting to identify nonfood reinforcers.     

The phantom ligand effect: allosteric control of transcription by the retinoid X receptor

OBJECTIVE: This two-part study investigated the cognitive processing of food- and threat-related information in a non-eating-disordered population, particularly exploring the mechanisms that might explain the process of cognitive avoidance among women with bulimic attitudes. METHOD: In the first study, 30 female students solved anagrams of neutral, food, and threat words. In the second study, 50 male and female students solved anagrams of words reflecting physical threat, self-directed ego threat, and ego threat directed from others. RESULTS: In this task, there was no association between slower processing of threats and eating characteristics, but there were associations with Eating Disorders Inventory (EDI) scales that reflect "ego development." DISCUSSION: The most reliable evidence of cognitive avoidance was among those participants who show the ego development characteristics that have been identified as important in the development and etiology of eating psychopathology. The implications for models of eating psychopathology and their treatment are discussed.