麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.     

General primer polymerase chain reaction in combination with sequence analysis for identification of potentially novel human papillomavirus genotypes in cervical lesions.

We recently described the detection of potentially novel human papillomaviruses (HPV) genotypes (HPV types X [HPV X]) in cervical smears (A. J. C. van den Brule, C. J. L. M. Meijer, V. Bakels, P. Kenemans, and J. M. M. Walboomers, J. Clin. Microbiol. 28:2739-2743, 1990) by using the general primer-mediated polymerase chain reaction method (GP-PCR). In this study, the HPV specificities of GP-PCR products were determined by sequence analyses. M13 bacteriophage clones of PCR products derived from cloned unsequenced HPV genotypes 13, 32, 35, 43, 44, 45, 51, and 56 were subjected to dideoxy sequencing. Analyses of the putative amino acid sequences of these HPV types in addition to published HPV sequence data revealed stretches of highly conserved amino acid residues present in all HPV types, resulting in an HPV amino acid consensus sequence. Subsequently, HPV X-specific PCR products found in premalignant cervical lesions (n = 3), carcinomas in situ (n = 6), and invasive cancer (n = 6) were analyzed for their nucleotide sequences. Comparison of these sequences with published HPV nucleotide sequences and data obtained in this study revealed three HPV type 35, two HPV type 45, one HPV type 51, two HPV type 56, and six unique HPV X sequences, of which three types were present in four cases of carcinomas (in situ). The nucleotide sequences determined appeared to be unique after a data bank search. Furthermore, the sequences of all HPV X isolates matched the HPV amino acid consensus sequence, thus confirming HPV specificity. This study illustrates the power of GP-PCR in combination with sequence analysis to determine HPV specificity and genotyping of PCR products derived from sequenced as well as unsequenced HPVs, including novel, not yet identified HPV types.     

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

Distinct expression patterns of polycomb oncoproteins and their binding partners during the germinal center reaction

Polycomb group (PcG) genes encode two chromatin-binding protein complexes, the PRC1 and the PRC2 PcG complexes, which are essential for the maintenance of cell identity and play a role in oncogenesis. PcG complexes were recently identified as novel regulators of hematopoiesis, and appear to be expressed in a non-overlapping pattern in resting and mature follicular B cells. Using highly specific antisera in combination with immunohistochemistry and triple immunofluorescence, we investigated the expression pattern of nine human PcG genes in germinal center (GC) B cells and highly purified germinal center B cell subpopulations. PcG proteins were detected in characteristic binding patterns that were not necessarily related to mutually exclusive expression of the two PcG complexes. We conclude that the two PcG complexes are expressed throughout GC development, and that the fine composition of each complex is determined by the differentiation status of the cell. In addition, a subset of dividing cells with a centrocyte CD marker profile was identified that co-expresses core components of the PRC1 and PRC2 complex. We propose that these cells reflect a transitional stage between resting and dividing follicular B lymphocytes, and that they possibly represent the healthy precursors of nodal large B cell lymphomas.     

Cultured chinese-hamster ovary cells lack a transferable x-radiation resistance factor

We determined if we could transfer X-radiation resistance from CHO AA8 cells to their radiosensitive, mutant V3 cells by several methods. These methods include co-incubating the two cell lines for three days before irradiation, adding heavily-irradiated AA8 to V3 cells following irradiation of the latter and then co-incubating these cells for at least eight days during the colony-forming assay and lastly, adding conditioned medium from unirradiated, subconfluent AA8 cells to V3 cultures and incubating for two days before irradiation. None of these procedures enhanced the clonogenic survival of the V3 cells to a single dose of 4 Gy X-radiation. Adding heavily-irradiated V3, instead of AA8, cells did not increase the clonogenic survival of the 4 Gy-irradiated V3 cells either, indicating that there was no autocrine mode of action. Moreover, adding conditioned medium from a related CHO cell line, K1, to its own radiosensitive, mutant 5-11 and incubating for two days before irradiation did not enhance clonogenic survival of the latter to a single dose of 3 Gy X-radiation. We therefore conclude that it is unlikely that CHO cells have the X-radiation resistance factor that has been reported in some mouse melanoma cell lines by other investigators.     

Active vs. passive resistance, dose-response relationships, high dose chemotherapy, and resistance modulation: a hypothesis

Summary With chemotherapy, the in vitro and clinical dose-response curve is steep in some situations, but is relatively flat in others, possibly due to the mechanism by which tumors are resistant to chemotherapy. For tumors with resistance due to factors that actively decrease chemotherapy efficacy (e.g., p-glycoprotein, glutathione, etc.), one would predict that high dose chemotherapy and therapy with some resistance modulating agents would increase therapeutic efficacy. Such active resistance would most likely generally arise from gene amplification or over expression, and would be characterized by a shoulder on the log response vs. dose curve, with eventual saturation of the protective mechanism. On the other hand, one would expect that high dose chemotherapy and most resistance modulating agents would be of little value for rumors with resistance due to defective apoptosis or due to a deficiency in or decreased drug affinity for a drug target, drug activating enzyme, drug active uptake system, or essential cofactor. Such passive resistance would most likely generally arise from gene down regulation, deletion, or mutation, and would probably be characterized by a relatively flat log response vs. dose curve, or by a curve in which a steep initial section is followed by a plateau, as target, etc., is saturated. (If response were plotted vs. log dose, then compared to the curve for a sensitive cell line, the curve for active resistance would be analogous to the pharmacodynamic curve seen with competitive antagonism [i.e., a sigmoid curve shifted to the right], and the curve for most types of passive resistance would be analogous to the pharmacodynamic curve seen with noncompetitive antagonism [i.e., a sigmoid curve with reduced maximal efficacy]. As such, one might also refer to active vs. passive resistance as competitive vs. noncompetitive resistance, respectively.) Many tumor types probably possess a combination of active and passive mechanisms of resistance. New in vivo strategies could be helpful in defining dose-response relationships, mechanisms of resistance, and targets for resistance modulation. Such in vivo studies would be conducted initially in animals, but might also be tested clinically if animal studies demonstrated them to be feasible and useful. These in vivo studies would be conducted by randomizing 5–25 subjects to one of 10–20 dose levels over a potentially useful therapeutic range. Nonlinear regression analysis would then be used to define the characteristics of a curve generated by plotting against dose the log percent tumor remaining after the first course of therapy. While this might offer insight into the nature of resistance mechanisms present initially, plotting further tumor shrinkage vs. dose-intensity vs. course number for each later treatment course (or plotting dose-intensity vs. time to tumor progression) might provide information on how tumors become increasingly resistant to drugs following treatment.