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Physiopathological significance of distortion-product otoacoustic emissions at 2f1-f2 produced by high- versus low-level stimuli.

Distortion product otoacoustic emissions emitted by the cochlea at 2f1-f2 in response to pairs of pure tones at f1 and f2 (DPOAE) form a class of otoacoustic emissions and as such, are viewed as a reliable tool for screening outer hair cell (OHC) dysfunctions on a pass/fail basis. However, the persistence of residual DPOAEs from impaired cochleae at high stimulus levels has suggested that above 60-70 dB SPL, instead of reflecting "active" cochlear motion, DPOAEs might represent another "passive" modality: they would thus become unsuitable for analyzing cochlear function. The present work reports the consequences on high- vs low-level DPOAEs of three types of cochlear impairments involving OHCs: progressive OHC degeneration of genetic origin in CD1 mice, complete cochlear ischemia in gerbils, and furosemide injection vs ischemia-reperfusion in gerbils. An alternative to the "active-passive" model was used wherein regardless of stimulus level, cubic DPOAEs are produced by N (probably OHC-borne) nonlinear elements driven by input I and modulated by a function F3 of their operating point o; thus, DPOAE proportional to NI3F3(o). When OHCs degenerated, thereby implying a decrease of N, DPOAE levels also decreased regardless of the stimulus level up to 80 dB SPL, in line with the previous formula but at variance with the prediction of the active-passive concept. Instead of affecting N, the other two experiments impaired the efficiency of the cochlear feedback loop as a result of its electrical drive being decreased by strial dysfunction. As it is well accepted that the impaired basilar-membrane motion, although greatly reduced at low levels, tends to catch up with a normal one at higher levels, it was assumed the same was true with I so that DPOAE levels had to be, and indeed were little affected at high levels while plummeting at low levels, without any need for invoking two modalities for DPOAE generation. Finally, comparisons of furosemide vs ischemia effects revealed additional influences on DPOAEs, possibly accounted for by function F3(o). These results lead to the proposal that although high-level DPOAEs are expected to be poor audiometric indicators, they seem well adapted to assessing the functional integrity of nonlinear elements in OHCs, i.e., presumably their mechanoelectrical transduction channels.

Acoustic Stimulation↗

Screening for and genetic analysis on T-DNA-inserted mutant pool in rice.

T-DNA tagging technique has provided a powerful strategy for identifying new functional genes in plants, and the key for success is the discovery of T-DNA-inserted mutants with changed phenotype. In this study, we screened 4,416 rice T1 tagged lines generated by enhancer trap system integrated with GLL4/VP16-UAS elements from two transformed parents, ZH11 and ZH15. We found many lines showed obvious morphological mutations, including two types--fake-homozygous mutation and separating mutation. The mutation phenotype was related to 14 kinds of trait such as plant height, heading date, leaf shape, leaf color, tiller number, panicle shape, spikelet number, grain shape, disease-like mutation, male sterility, awn, and so on. Among them, plant height, heading date, leaf color and male sterility had a comparatively high mutation frequency (over 1%). The mutation frequency of plant height and leaf color had no significant change between different years or transformed parents, but the frequency of heading date and male sterility varied greatly, suggesting that environment had a great effect on the expression of latter two traits. By conducting continuously co-segregating analyses in T1 and T2 generation, we identified 3 T-DNA-inserted mutants with malformed panicle or spikelets, which would provide a base for cloning correlative functional genes. At the same time, we selected randomly 42 lines with mutation phenotype and obtained 40 flanking sequences from 39 tagged lines by plasmid rescue or TAIL-PCR, of which, 26 were vector backbone sequence, 14 had good identity to rice genome sequence. The BlastN result showed the T-DNA preferentially integrated into protein-coding region in plants.

DNA, Bacterial↗

Establishment and utilization of a tetracycline-controlled inducible RNA interfering system to repress gene expression in chronic myelogenous leukemia cells.

RNA interference (RNAi), a posttranscriptional gene silencing process mediated by small double-stranded RNA specifically complementary to the targeted transcript, has been used extensively in the development of novel therapeutic approaches against various human diseases including chronic myelogenous leukemia (CML). Here, we report the successful construction of a tetracycline-controlled siRNA in CML cell line K562. A K562 cell line stably expressing the reverse tetracycline-controlled transactivator (rtTA) was constructed. A tetracycline responsive element (TRE) was integrated into the RNA polymerase III promoter region of pBS/U6 that was used to drive specific siRNA to target the novel cytokine receptor-like factor 3 (CRLF3) gene. The results show that rtTA was able to recognize the TRE to prevent siRNA-mediated exogenous and endogenous CRLF3 gene repressions. Moreover, CRLF3-siRNA mediated gene repression could be induced in a dose-dependent manner in the presence of doxycycline. Thus, the inducible siRNAi system in K562 cells might be useful for the study of RNAi-mediated therapeutic approaches against CML.

Base Sequence↗

Hydroxyapatite laminar spacers and titanium miniplates in cervical laminoplasty.

OBJECTIVE: The authors describe a new surgical technique for cervical laminoplasty that was performed in 25 patients. The posterior elements along with the various ligaments are removed en bloc and are stabilized in a lift-up position by placing hydroxyapatite (HA) laminar spacers and titanium miniplates and screws. The procedure and clinical results are discussed. METHODS: The posterior spinal elements, including the lamina(e), spinous process(es), and various attached ligaments, are removed en bloc by incising the lamina in its lateral aspect. Trapezoid-shaped HA spacers are placed between the cut ends of the laminae or between the laminae and lateral masses bilaterally at each level. Malleable titanium miniplates and screws are used for fixation of the spacers. The fixation of transected laminae was judged to be successful. Postoperative care included application of a soft neck collar for 1 week but no further restriction of activity. Surgery-related outcome was assessed in the 21 patients who attended more than 6 months of follow up after laminoplasty. There were 18 men and three women who ranged in age from 27 to 81 years. Cervical stenotic myelopathy was demonstrated in 15 patients who underwent decompressive and expansive laminoplasty, and spinal tumors were documented in six patients who underwent a nonexpansive laminoplasty. Postoperative and follow-up computerized tomography scans demonstrated no hardware failure. Bone formation around the spacers was observed either at 6- or at 9-month follow-up examination in all 21 patients. Fusion of the reconstructed laminae was found to be completed at 12 months in all 18 patients able to attend follow up for this duration. Spinal alignment and the range of motion of the cervical spine were well preserved. In patients with stenotic cervical myelopathy, neurological and anatomical outcome of canal expansion were satisfactory. CONCLUSIONS: This technique enables rigid laminoplasty while maintaining anatomical and biomechanical integrity of posterior elements of cervical spine. Expansive and nonexpansive laminoplasty procedures are possible.

Adult↗

Cell-based bonding of articular cartilage: An extended study.

This study evaluated the biomechanical characteristics of newly formed cartilaginous tissue synthesized from isolated chondrocytes and seeded onto devitalized cartilage in an extended study in vivo. Cartilage from porcine articular joints was cut into regular discs and devitalized by multiple freeze-thaw cycles. Articular chondrocytes were enzymatically isolated and incubated in suspension culture in the presence of devitalized cartilage discs for 21 days. This procedure allowed the isolated chondrocytes to adhere to the devitalized matrix surfaces. Chondrocyte-matrix constructs were assembled with fibrin glue and implanted in dorsal subcutaneous pockets in nude mice for up to 8 months. Histological evaluation and biomechanical testing were performed to quantify the integration of cartilage pieces and the mechanical properties of the constructs over time. Histological analysis indicated that chondrocytes grown on devitalized cartilage discs produced new matrix that bonded and integrated individual cartilage elements with mechanically functional tissue. Biomechanical testing demonstrated a time dependent increase in tensile strength, failure strain, failure energy, and tensile modulus to values 5-30% of normal articular cartilage by 8 months in vivo. The values recorded at 4 months were not statistically different from those collected at the latest time point, indicating that the limits of the biomechanical property values were reached after four months from implantation.

Animals↗

Clinical reasoning of an experienced physiotherapist: insight into clinician decision-making regarding low back pain.

BACKGROUND AND PURPOSE: Investigation of the clinical reasoning skills of experienced clinicians provides insight into decision-making in the practice of physiotherapy. The purpose of the present study was to analyse the clinical reasoning skills of an experienced physiotherapist during her assessment and treatment of clients with low back pain. METHOD: Deconstruction of the physiotherapist's reasoning process was accomplished through observation of encounters between her and each of six patient subjects. Reconstruction and analysis of the physiotherapist's decision-making process was performed through retrospective interviews and reflective analysis of her clinical reasoning during each encounter. RESULTS: A working model of the physiotherapist's clinical reasoning was created from an integration of theoretical elements in the literature and the data. Through analysis of this framework, two core dimensions of her clinical reasoning were revealed: the influence of clinical experience and the influence of advanced training in a specific philosophy of treating the spine. CONCLUSIONS: The construction of these themes has contributed to the growing understanding of clinical reasoning strategies and skills used in orthopaedic physical therapy practice. Detailed description of the physiotherapist's reasoning process provides more meaningful understanding of physiotherapy treatments. In this case the physiotherapist employed a pattern recognition strategy and forward reasoning process in making a diagnosis. Further research is necessary to expand knowledge on the development of clinical reasoning skills.

Adult↗

An immune system switch at birth triggers a change in the lifespan of peripheral T cells.

Lymphocyte recirculation is an essential element in the integration of immune responses and is an absolute requirement for the development of systemic memory in postnatal animals. During foetal life a large pool of recirculating T cells develops and migration pathways of naive T cells to skin and peripheral tissues as well as LN are established. At birth a process is triggered whereby naive fetal T cells are rapidly lost from the circulating pool and are replaced by newly arriving T cells which have been formed since birth. At present our data suggest that the thymic export in the fetus creates a pool of long-lived naive T cells of wide diversity. The situation in neonatal lambs is more complex since the thymus is exporting large numbers of short-lived thymic emigrants which enter a peripheral T-cell population where many T cells are dividing.

Animals↗

[Transplacental oncogenic effect of ethylnitrosourea in rabbits (author's transl)].

50 mg/kg ethylnitrosourea (ENU) per dose, diluted in a 0.9%NaCl/1%NaH2PO4 solution (pH 6.2) were administered intravenously to three pregnant rabbits. The injections were carried out on the following days of gestation: 21., 26., and 30./21., 25., and 31./22., 25., and 30. From the total offspring (22), 16 rabbits could be raised. In 12 animals, kidney tumours were observed after a latent period of 2--2 1/2 years. The induced tumours are generally composed of both epithelial and mesenchymal tissue elements. Two tumours of the series are of a pure epithelial or a pure mesenchymal nature respectively. In most of the mixed tumours, classified as Adenocarcino-Sarcomas (10), the epithelial and mesenchymal elements are closely integrated, sometimes one component predominated over the other one. Histologically the ENU-induced mixed tumours of kidney in rabbits and the "dysontogenetic" kidney tumours of children (WILMS) show comparable structural characteristics.

Adenocarcinoma↗

Client outcome reporting: the status method.

This paper describes the development and results of a method for capturing client outcomes of community services for persons with severe mental illness. Through the use of status scales, two major elements of community integration, independence of living arrangement and vocational independence can be continuously monitored. The initial results of the method include: unifying previously disparate agendas of state and local officials, enhanced vocational and living arrangement outcomes for clients, instigating program improvements, and the increased exchange of staff rewards. In addition, the method is economical whereby data on a worker caseload of 30-40 can be collected in about 20 minutes.

Community Mental Health Centers↗

Spatial and temporal processing in patients with Turner's syndrome.

Thirteen females with Turner's syndrome were examined for spatial abilitles and serial processing, and their performance was compared with that of normal females matched by age, intellignece, and socioeconomic class. Patients with Turners's syndrome performed significantly poorer on tests of spatial ability than controls, but only on spatial tests requiring the integration of isolated elements as synthetic wholes or the remembering of spatial configurations which could not be verbally mediated. Patients also performed less well than controls on tasks of serial processing when the tasks could not be mediated verbally. 2t was concluded that patients with Turner's syndrome may have a selective deficit in cortical functions that are lateralized to the right cerebral hemisphere.

Adolescent↗

The virtual absence of stress-ulceration related bleeding in ICU patients receiving prolonged mechanical ventilation without any prophylaxis. A prospective cohort study.

OBJECTIVE: To study the incidence of stress-ulcer related bleeding in ICU patients receiving prolonged (> 2 days) mechanical ventilation without any stress ulceration prophylaxis. DESIGN: A prospective cohort study in 183 patients. INTERVENTIONS: All patients received clinical treatment including maintenance of adequate tissue perfusion (with low dose inotropes and vasodilators), infection prevention (by selective decontamination of the digestive tract) throughout ICU stay and suppression of generalized inflammatory reaction (by steroids). SETTING: Medical/surgical ICU of a major teaching hospital in Amsterdam (Onze Lieve Vrouwe Gasthuis). MEASUREMENTS AND RESULTS: 167 patients were evaluated during 2182 treatment days in the ICU and during 1753 days on mechanical ventilation without stress ulceration prophylaxis. The mean total risk score for stress ulceration related bleeding was 38 (Tryba score). Stress ulceration related bleeding developed in 1 patient (0.6%). CONCLUSIONS: The incidence of SURB was less then 1% in this cohort of ICU patients receiving longterm mechanical ventilation with a high risk for SURB (mean total risk score 38). All patients received agressive shock resuscitation, infection prevention with selective decontamination of the digestive tract (SDD) and suppression of inflammatory response with steroids. Further studies are needed to evaluate the contribution of each of these elements of the integral approach.

Aged↗

Early mortality of lambs in African traditional livestock production systems.

Early mortality of lambs is a major constraint on total productivity. In 6 different environments the early death rate varied from 12 to 30% of all lambs born. Cause of death differed among systems but only a proportion could definitely be ascribed to infectious disease: nutrition, management and other environmental factors also contribute to the mortality rate. Mortality can be reduced by isolating solutions due to any of these factors but best results (lowest death rates) would be obtained by an integrated package containing elements of all these aspects.

Africa↗

Carrying capacity as "Informed Judgment": the values of science and the science of values.

Contemporary park and wilderness carrying capacity frameworks rely on formulation of standards of quality, which are defined as minimum acceptable resource and social conditions. Formulation of standards of quality involves elements of both science and values, and both of these elements must be integrated into informed judgments on the part of park and wilderness managers. That is, managers must ultimately make value-based judgments about the maximum acceptable level of visitor-caused impacts to the resource base and the quality of the visitor experience. However, such judgments should be as informed as possible by scientific data on the relationships between visitor use and resulting impacts and the degree to which park and wilderness visitors and other interest groups judge such impacts to be acceptable. Such information represents the "values of science" to managing carrying capacity in parks and wilderness. A growing body of literature has begun to address the corresponding "science of values," and how this type of information might be integrated in park and wilderness management. Visitor-based research has employed normative theory and techniques to explore the acceptability of a range of resource and social impacts related to visitor use, and findings from these studies are being integrated into a body of knowledge and applied in management decision-making. Conceptual and methodological extensions of the normative approach are currently being explored in a variety of park and wilderness contexts, and new theoretical and empirical approaches are being adapted to address trade-offs inherent in carrying capacity. In these ways, the science of values is progressing to meet the opportunities and challenges of the values of science to park and wilderness management. The concept of carrying capacity, along with the theoretical and methodological approaches described in this paper, can be extended to a large number of natural resource and environmental issues.

Conservation of Natural Resources↗

Tobacco ribosomal DNA spacer element elevates Bowman-Birk inhibitor expression in tomato plants.

Amplification promoting sequence (aps), from tobacco rDNA, was found to induce amplification and enhances the expression of heterologous genes, consequently increasing the expression of transgenic proteins in tobacco. In this report we demonstrate that aps element also affects integration, transcription, and translation of a soybean protease inhibitor, Bowman-Birk inhibitor (BBI), in transgenic tomato plants and quantifies its effects in different expression vectors. A synthetic bbi gene was constructed, based on the wild-type gene containing two independent inhibition sites; trypsin and chymotrypsin. Transformation vectors were designed using two different promoters; the tomato fruit specific E8 promoter and the constitutively active 35S CaMV promoter. These vectors were transformed into 'Moneymaker' tomato plants. In tomato fruits and leaves, aps caused a 3-fold increase in bbi mRNA levels when compared to the lines without aps. Similar increases were obtained in plants expressing bbi controlled by E8 or 35S CaMV promoters. Also, the level of BBI protein expression in aps-transformed plants was 3 fold-higher than in plants without aps. This is the first report of aps effect on the enhanced gene expression and transgenic protein production in plant other than tobacco.

Chymotrypsin↗

Imaging in spinal trauma.

Because it may cause paralysis, injury to the spine is one of the most feared traumas, and spinal cord injury is a major cause of disability. In the USA approximately 10,000 traumatic cervical spine fractures and 4000 traumatic thoracolumbar fractures are diagnosed each year. Although the number of individuals sustaining paralysis is far less than those with moderate or severe brain injury, the socioeconomic costs are significant. Since most of the spinal trauma patients survive their injuries, almost one out of 1000 inhabitants in the USA are currently being cared for partial or complete paralysis. Little controversy exists regarding the need for accurate and emergent imaging assessment of the traumatized spine in order to evaluate spinal stability and integrity of neural elements. Because clinicians fear missing occult spine injuries, they obtain radiographs for nearly all patients who present with blunt trauma. We are influenced on one side by fear of litigation and the possible devastating medical, psychologic and financial consequences of cervical spine injury, and on the other side by pressure to reduce health care costs. A set of clinical and/or anamnestic criteria, however, can be very useful in identifying patients who have an extremely low probability of injury and who consequently have no need for imaging studies. Multidetector (or multislice) computed tomography (MDCT) is the preferred primary imaging modality in blunt spinal trauma patients who do need imaging. Not only is CT more accurate in diagnosing spinal injury, it also reduces imaging time and patient manipulation. Evidence-based research has established that MDCT improves patient outcome and saves money in comparison to plain film. This review discusses the use, advantages and disadvantages of the different imaging techniques used in spinal trauma patients and the criteria used in selecting patients who do not need imaging. Finally an overview of different types of spinal injuries is given.

Aged↗

Effect of high linear energy transfer radiation on biological membranes.

Cellular membranes are vital elements, and their integrity is extremely essential for the viability of the cells. We studied the effects of high linear energy transfer (LET) radiation on the membranes. Rabbit erythrocytes (1 x 10(7) cells/ml) and microsomes (0.6 mg protein/ml) prepared from liver of rats were irradiated with 7Li ions of energy 6.42 MeV/u and 16O ions of energy 4.25 MeV/u having maximum LET values of 354 keV/microm and 1130 keV/microm, respectively. 7Li- and 16O-induced microsomal lipid peroxidation was found to increase with fluence. The 16O ions were more effective than 7Li ions, which could be due to the denser energy distribution in the track and the yield of free radicals. These findings suggested that the biological membranes could be peroxidized on exposure to high-LET radiation. Inhibition of the lipid peroxidation was observed in the presence of a membrane-active drug, chlorpromazine (CPZ), which could be due to scavenging of free radicals (mainly HO* and ROO*), electron donation, and hydrogen transfer reactions. The 7Li and 16O ions also induced hemolysis in erythrocytes. The extent of hemolysis was found to be a function of time and fluence, and showed a characteristic sigmoidal pattern. The 16O ions were more effective in the lower fluence range than 7Li ions. These results were compared with lipid peroxidation and hemolysis induced by gamma-radiation.

Animals↗

Structure of the Chlorella Zepp retrotransposon: nested Zepp clusters in the genome.

Zepp elements found in the telomeric region of Chlorella chromosomes show the characteristic features of non-viral (LINE-like) retrotransposons, including a poly(A) tail, 5' truncations, a retroviral reverse transcriptase-like ORF and flanking target duplications. We have isolated and characterized a full-length Zepp element (8943 bp long) from Chlorella chromosome V. Some peculiar features of this element, including nested integration, two ORF structures, a long 3' noncoding region and a possible promoter region are compared with those of the Drosophila telomeric retrotransposons HeT-A and TART. The Chlorella chromosome-Zepp system appears to represent an intermediate stage between canonical telomerase-telomeres and Drosophila retrotransposon-telomeres.

Amino Acid Sequence↗

Numerical simulations of intra-voxel dephasing effects and signal voids in gradient echo MR imaging using different sub-grid sizes.

Signal void artifacts in gradient echo imaging are caused by the intra-voxel dephasing of the spins. Intra-voxel dephasing can be estimated by computing the field distribution on a sub-grid inside each picture element, followed by integration of all magnetization components. The strategy of computing the artifacts based on the integration of the sub-voxel signal components is presented here for different sub-grids. The coarseness of the sub-grid is directly related to computational effort. The possibility to save memory space and computing time for the dipole model by computing the field only on a sub-grid is addressed in the presented article. It is investigated as to how far computational time and memory space can be reduced by using an appropriate sub-grid. Numerical results for a model of a partially diamagnetically coated needle shaft are compared to experimental findings. In the case of a pure titanium needle, it is shown as being sufficient to compute the field distribution on a sub-grid that is at least four times coarser in each direction than the grid used to discretize the object in the related MR image. Due to three nested loops over the 3D grid, the need for memory space and time is saved by a factor 64. Deviations between measurements and simulations for the broad side of the artifact (uncompensated) and for the small side of the artifact (compensated) were 15.5%, respectively, 19.1% for orientation parallel to the exterior field, and 22.7%, respectively, 23.1% for orientation perpendicular to the exterior field.

Artifacts↗