Anti-angiogenic effects of Hypericin-photodynamic therapy in combination with Celebrex in the treatment of human nasopharyngeal carcinoma

Photodynamic therapy (PDT) is being investigated as an alternative treatment modality in cancer treatment. It has been shown to induce tumor hypoxia and upregulation of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). The objective of this study was to improve in vivo tumor growth control of nasopharyngeal carcinoma (NPC), treated at a subcurative dosage by using a combination of Hypericin-PDT and COX-2 inhibitor, Celebrex (CX). The effect of an initial CX dose at 6- and 24-h post-PDT was investigated simultaneously. It was observed that hypoxic NPC/CNE2 cells upregulate both COX-2 and VEGF A genes in vitro. In vivo studies, down-regulation of COX-2 and hypoxia inducible factor-1alpha (HIF-1alpha) genes at 24-h post-PDT and bulk tumor ablation at 48-h post-PDT was observed. However, 24-28 days later regrowth was observed. In a combination treatment, 1st CX dose at 6-h post-PDT had the highest tumor control in which tumors were 相似文献   

Acrocentric prophasing in bromodeoxyuridine-incorporated chromosomes

Chromosomes that appear to be incompletely condensed [pulverized, prematurely condensed chromosomes (PCCs), prophasing] are known to occur in metaphase spreads of cells from normal individuals and more frequently in cells from individuals with malignant disease or in cells exposed in vitro or in vivo to various agents such as viruses, chemicals, and radiation. In this study involving bromodeoxyuridine (BrdU)-treated lymphocytes, a selective prophasing of acrocentrics appeared to be occurring. The acrocentrics involved were generally in interconnected groups.     

Rapid detection and identification of human adenovirus species by adenoplex, a multiplex PCR-enzyme hybridization assay

Human adenoviruses (AdV) have been implicated in a wide variety of diseases and are ubiquitous in populations worldwide. These agents are of concern particularly in immunocompromised patients, children, and military recruits, resulting in severe disease or death. Clinical diagnosis of AdV is usually achieved through routine viral cell culture, which can take weeks for results. Immunofluorescence and enzyme-linked immunosorbent assay-based techniques are more timely but lack sensitivity. The ability to distinguish between the six different AdV species (A to F) is diagnostically relevant, as infections with specific AdV species are often associated with unique clinical outcomes and epidemiological features. Therefore, we developed a multiplex PCR-enzyme hybridization assay, the Adenoplex, using primers to the fiber gene that can simultaneously detect all six AdV species A through F in a single test. The limit of detection (LOD) based on the viral 50% tissue culture infective dose/ml for AdV A, B, C, D, E, and F was 10(-2), 10(-1), 10(-1), 10(-2), 10(-1), and 10(-2), respectively. Similarly, the LOD for the six DNA controls ranged from 10(2) to 10(3) copies/ml. Twelve common respiratory pathogens were tested with the Adenoplex, and no cross-reactivity was observed. We also validated our assay using clinical specimens spiked with different concentrations of AdV strains of each species type and tested by multiplex PCR and culture. The results demonstrated an overall sensitivity and specificity of Adenoplex of 100%. This assay can be completed in as few as 5 h and provides a rapid, specific, and sensitive method to detect and subtype AdV species A through F.     

Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau

Neurofibrillary pathology was produced in the brains of adult rats after localized gene transfer of human tau carrying the P301L mutation, which is associated with frontotemporal dementia with parkinsonism. Within 1 month of in situ transfection of the basal forebrain region of normal rats, tau-immunoreactive and argyrophilic neuronal lesions formed. The fibrillar lesions had features of neurofibrillary tangles and tau immunoreactivity at light and electron microscopic levels. In addition to neurofibrillary tangles, other tau pathology, including pretangles and neuropil threads, was abundant and widespread. Tau gene transfer to the hippocampal region of amyloid-depositing transgenic mice produced pretangles and threads, as well as intensely tau-immunoreactive neurites in amyloid plaques. The ability to produce neurofibrillary pathology in adult rodents makes this a useful method to study tau-related neurodegeneration.     

Molecular identification of pathogenetic IdLNF+1 autoantibody idiotypes derived from the NZBxSWR F1 model for systemic lupus erythematosus

The acceleration of nephritis in SNF(1) mice by CD4(+) T-cell clones reactive with a nephritogenic idiotype, Id(LN)F(1) [1], as well as the ability of anti-Id(LN)F(1) antisera to down-regulate the production of Id(LN)F(+)(1) immunoglobulin (Ig) in vivo and delay nephritis [2], suggests that dysregulation of this idiotype may contribute to the development of SNF(1) nephritis. Herein, we show that a monoclonal Id(LN)F(1)-expressing antibody, 540, significantly (P< or = 0.01) stimulated Id(LN)F(1)-reactive T-cell clones B6 and D2 to proliferate, while other Id(LN)F+1 antibodies did not. Further, injection of 540-producing hybridoma cells into nonautoimmune (SWRxBalb/c)F(1) mice resulted in the deposition of Id(LN)F(+)(1) Ig in the kidneys, in a pattern indicative of early nephritis. To identify the pathogenetic Id(LN)F(1) epitope(s) at the molecular level, we compared the deduced amino acid sequences of the heavy and light chain variable regions of pathogenetic and non-pathogenetic Id(LN)F(1)-expressing Igs 540, 317, and 533. Two overlapping peptides derived from the V(H) sequence of 540 (aa 54-66 and 62-73), which both contain the triple basic amino acid motif K(X)K(X)K, stimulated SNF(1) T cells and T-cell clones B6 and D2. These results further support the involvement of a subset of Id(LN)F(1)-expressing Ig in SNF(1) nephritis.     

Hemodynamic and hormonal responses to lower body negative pressure in men with varying profiles of strength and aerobic power

Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake ( O_2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6°) head-down tilt (HDT), each subject underwent graded LBNP to –6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither O_2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.     

Psychometric qualities of the rand 36-item health survey 1.0: A multidimensional measure of general health status

The reliability and validity of the RAND 36-Item Health Survey 1.0 were investigated in a population sample of 1,063 inhabitants of a Dutch township, all age 17or older. Confirmatory factor analysisonly partly supported the internal structure of the RAND 36-Item Health Survey 1.0. The internal consistency of the instrument was high. Pointing to high convergent validity, a multitrait-multimelhod matrix revealed that the RAND-36 scales showed higher correlations with corresponding scales from other instruments than with noncorresponding scales. However, indicating low discriminant validity, some of these correlations did not exceed the intercorrelations among the RAND-36 scales. Multivariate analysis of variance (MANOVA) showed significant effects of age for physical functioning, role limitations (physical problem), general health perception and pain, and significant effects of education on physical functioning and general health perception. Significant sex differences were found for mental health only. The results of this study on the psychometric properties of the RAND 36-Item Health Survey 1.0 seem promising. There is a need for further studies investigating its factor structure and cross-cultural equivalence.     

Acrocentric interconnections and NOR variants in human lymphocytes

Acrocentric interconnections and NOR (nucleolus organizer region) variants are frequently observed in silver-stained metaphase preparations from lymphocytes of phenotypically normal individuals. The types of interconnections and of NOR variants are outlined. It is speculated that the satellite acrocentrics (both normal and variant) are the consequence of breakage and recoiling of these interconnections. Awareness of these two features of the human genome may facilitate understanding of the NOR/nucleolus interaction(s) in such important processes as nucleolus formation and in development and/or diagnosis of disease states (i.e., malignancy).     

Lung development and the pulmonary surfactant system: Hormonal influences

The effect of hormones on developmental events is not a new area of scientific investigation. However, in the last decade, the developing lung has been the focus of an increasing amount of basic and applied research. Inadequate development of the newborn's respiratory system precludes extrauterine existence; indeed, such respiratory inadequacy has been a leading cause of death in premature infants. Tremendous strides have been made in understanding the basic cell biology of the developing lung. Much has been learned about the source, composition, and function of pulmonary surfactant, a surface-active material produced by the lung and essential to alveolar stability. Deficient stores of this material is a major etiologic factor in the respiratory distress syndrome of the newborn (RDS). This fact, coupled with observations that certain hormones can accelerate lung development and the consequent availability of adequate stores of pulmonary surfactant, has led to a large body of literature dealing with the effects of hormones (and other agents) on lung development. It is the purpose of this literature review (1) to discuss the various kinds of investigations which have linked surfactant synthesis to the type II pulmonary epithelial cell; and (2) to review the current status of research dealing with the effects of glucocorticoids and thyroid hormons on lung maturation.