频闪喉镜对声带病理情况观察的研究

对1997年以来423例病态喉的频闪喉镜表现进行分析,结果显示声带有病理改变者其粘膜波、振幅、闭合相、运动周期性、对称性均有不同程度的变化,这种变化能直接反映声带病变的深度及范围,对喉部疾病的诊断、鉴别诊断、治疗指导及预后评价具有重要意义.     

The effects of vandellia cordifolia on renal functions and arterial blood pressure

Vandellia cordifolia (COLSM) G. DON of Scrophulariaceae (V. cordifolia) is an annual wild herb indigenous to Taiwan. It can be found in plains, low altitudes, swampy places, and paddy fields. Taiwanese folk physicians use it in "nephritis, uremia, furnucle, carbuncle." The LD50 (95% confidence limit) of the crude extract of V. codifolia given by the oral route was more than 10 g/kg in rats. By the intraperitoneal route, it was 4.6 g/kg (4.35-4.93). The extraction rate was 16.6%. We studied its effects on renal functions and blood pressure and found that (1) it had diuretic effect on normal rats, (2) it decreased glomerular filtration rate and renal blood flow on normal kidneys in rabbits, (3) it had no effects on glomerular filtration rate and renal blood flow on glycerin-induced insufficient kidneys in rabbits, (4) it had diuretic effects on both normal and glycerin-induced insufficient kidneys in rabbits, (5) it could inhibit Na+ and K+ reabsorption on normal and glycerin-induced insufficient kidneys in rabbits, (6) it had hypertensive effect and this effect could be blocked by phenoxybenzamine. From the above facts, we conclude that V. cordifolia has diuretic effect and it may act on renal tubules to inhibit Na+ and K+ reabsorption.     

Effects of the NMDA antagonists CPP and MK-801 on delayed conditional discrimination

N-methyl-D-aspartate (NMDA) receptor/channel antagonists have previously been shown to impair spatial working memory and hippocampal long-term potentiation. The present experiment investigated the effects of a variety of doses of NMDA antagonists on a working memory task in rats involving an auditory delayed conditional discrimination. Signal detection analysis and an exponential memory decay model were used to extract independent measures of stimulus discriminability and rate of forgetting. A competitive NMDA antagonist, (CPP, 0.33, 1.0, 10.0 mg/kg, IP) produced a reduction in discriminability which was linearly related to log dose, but which was only clear at the 10 mg/kg dose. Rate of forgetting was not increased by any dose. Similar results were obtained with a non-competitive antagonist (MK-801, 0.1, 0.33 mg/kg, IP). These data suggest that doses of NMDA receptor channel antagonists sufficient to disrupt hippocampal long-term potentiation and radial arm maze performance will also disrupt delayed conditional discrimination. The effect on delayed conditional discrimination is due to a disruption of stimulus discriminability and not to an increased rate of forgetting. The extent to which these effects relate to the reported changes in hippocampal long-term potentiation and radial arm maze performance remains to be determined.     

Involvement of MMP-7 in invasion of pancreatic cancer cells through activation of the EGFR mediated MEK-ERK signal transduction pathway

AIMS: To clarify the involvement of matrix metalloproteinase-7 (MMP-7) in cell dissociation and the subsequent invasion of pancreatic cancer cells.METHODS: Western blotting, in vitro invasion assay, immunocytochemistry, and immunohistochemistry were performed in pancreatic cancer cell lines or pancreatic cancer tissue.RESULTS: The active form of the MMP-7 protein was expressed exclusively in the conditioned medium of dissociated (PC-1.0 and AsPC-1) pancreatic cancer cells, whereas proMMP-7 protein was only detected in the conditioned medium of non-dissociated (PC-1 and Capan-2) cells. Both intracellular and conditioned medium localised MMP-7 was greatly reduced by treatment with the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the mitogen activated protein kinase kinase (MEK) inhibitor U0126 in pancreatic cancer cells. MMP-7 treatment significantly induced the disruption of tight junction (TJ) structures and subsequent cell dissociation, and activation of the EGFR mediated MEK- ERK (extracellular signal regulated protein kinase) signalling pathway in the non-dissociated pancreatic cancer cells. Moreover, the strong in vitro invasiveness of dissociated cells was inhibited by AG1478 and U0126 treatment, whereas the weak invasiveness of non-dissociated cells was apparently induced by MMP-7 treatment. In addition, MMP-7 expression was stronger at the invasive front than at the centre of human pancreatic tumours.CONCLUSION: MMP-7 is involved in cell dissociation and the subsequent invasion of pancreatic cancer cells. It induces the disruption of TJ structures and forms a positive feedback loop with activation of the EGFR mediated MEK-ERK signalling pathway.     

Synergistic antiviral activity of human interferon combinations in the hepatitis C virus replicon system.

The use of type I interferon (IFN), in combination with ribvirin, to treat chronic hepatitis C virus (HCV) infection has many drawbacks that prevent widespread application, ultimately leading to a significant unmet clinical need. Potential improvements in IFN therapy through targeted delivery, molecular alteration, and combination with other agents are ongoing in an attempt to decrease adverse effects and increase efficacy. In this report, the HCV replicon cell culture system was used to assess potential synergistic antiviral effects of multiple IFN species when administered in combination. Quantitative analysis of HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and qualitative analysis of HCV protein expression were used to measure the antiviral efficacy of individual and combination IFN treatments, and synergistic responses of IFN combinations were determined through statistical analysis of the TaqMan results. We found that when administered simultaneously, type I/II IFN combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN-beta) demonstrated a slightly antagonistic profile. The synergistic effect is likely due to differential cell surface receptors and signaling pathways employed by types I and II IFNs. Conversely, all type I IFN species bind the same receptor and signal through similar pathways, possibly accounting for the nearly additive response observed. In support of this hypothesis, IFN treatment resulted in differential induction of Stat1 phosphorylation at Tyr 701. In conclusion, simultaneous type I/II IFN combination treatment may allow an overall decreased effective IFN dose, which may reduce the side effect profiles that hinder current therapy.     

Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer

AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The intervening material was used for MP-FCM. Cells were immunostained with MNF116, followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of the 98 patients with breast carcinoma showed evidence of metastatic disease in the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2 mm (macrometastasis) and in 14 these foci were smaller than 2 mm (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs, although this was not seen at first glance in the H&E or IHC sections. After revision of the slides, one of these three remained negative. However, MP-FCM analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which was almost identical to that of the primary breast tumour. Duplicate measurements, done in 41 cases, showed a 99% reproducibility. In five of 14 patients with micrometastasis, one or two metastatic foci were found in the non-SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have metastatic tumour. All micrometastases except for the remaining negative one mentioned above showed only diploid tumour cells, despite the fact that their primary tumours contained both diploid and aneuploid tumour cells. In primary tumours with more than 60% aneuploid cells, predominantly aneuploid macrometastasis were found, whereas diploid primary tumours only showed diploid micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases were associated with non-SLN metastases in five of seven patients, whereas diploid cases showed additional non-SLN metastases in only seven of 16 patients. CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour cells in a large volume of lymph node tissue from SLNs. In some cases it was superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are accompanied by additional non-SLN metastases. The size of the aneuploid fraction (> 60%) in the primary tumour may influence the risk of having both SLN and non-SLN metastases.     

Immunoglobulin production in vitro by peripheral blood lymphocytes in systemic lupus erythematosus: helper T cell defect and B cell hyperreactivity

Peripheral blood lymphocytes (PBL) from 16 patients with systemic lupus erythematosus (SLE) and 15 healthy control subjects were cultured and immunoglobulin (Ig) production in vitro was measured by immunofluorescent staining for intracytoplasmic Ig, a reverse haemolytic plaque assay to quantify cells secreting Ig and a solid-phase radioimmunoassay for Ig secreted into culture supernatants. Compared with normal PBL, lymphocytes from patients with SLE produced significantly fewer Ig-containing cells, Ig-secretion cells (ISC) and less Ig in supernatants in cultures stimulated by pokeweed mitogen (PWM). These differences were most pronounced during phases of disease activity. Culturing SLE PBL with a supernatant obtained from PWM-activated cultures of normal T lymphocytes partially restored their capacity to produce ISC. This observation suggests a helper T cell defect of SLE lymphocytes. In addition, PBL from patients with active SLE generated more ISC when cultured with Staphylococcus aureus bacteria (S aureus) than with PWM. S. aureus-stimulated cultures of SLE PBL also generated more ISC than PBL from normal individuals. The S. aureus response of SLE lymphocytes did not correlate with disease activity. As S. aureus is a T cell-independent mitogen, the latter observations suggest that in SLE an intrinsic B cell hyperreactivity may be a more persistent defect whereas T cell defects are transitory.     

单钉——沟槽柱翼钢板的生物力学实验研究

作者自行研究设计的单钉－沟槽柱翼钢板复位固定治疗腰椎滑脱症。预先采用６具成人尸体的Ｌ３－Ｓ３骨骼做成椎弓崩裂并滑脱模型，采用临床Ｉ型手术方法进行了复位固定，在每片钢板上粘贴６片电阻应变片，进行中心和偏心加载试验，同时进行了弯矩和扭矩试验，在５８６微机上进行了线性回归分析，求出了线性方程及线性相关系数ｒ，中心和偏心加载达到９００Ｎ未出现钢板松动，扭矩和弯矩在８３３Ｎ；ｃｍ和６６６．４Ｎ．ｃｍ以内左右     

Isolation and phenogenetics of a novel circadian rhythm mutant in zebrafish

Widespread use of zebrafish (Danio rerio) in genetic analysis of embryonic development has led to rapid advances in the technology required to generate, map and clone mutated genes. To identify genes involved in the generation and regulation of vertebrate circadian rhythmicity, we screened for dominant mutations that affect the circadian periodicity of larval zebrafish locomotor behavior. In a screen of 6,500 genomes, we recovered 8 homozygous viable, semi-dominant mutants, and describe one of them here. The circadian period of the lager and lime (lag(dg2)) mutant is shortened by 0.7 h in heterozygotes,and 1.3 h in homozygotes. This mutation also shortens the period of the melatonin production rhythm measured from cultured pineal glands, indicating that the mutant gene product affects circadian rhythmicity at the tissue level, as well as at the behavioral level. This mutation also alters the sensitivity of pineal circadian period to temperature, but does not affect phase shifting responses to light. Linkage mapping with microsatellite markers indicates that the lag mutation is on chromosome 7. A zebrafish homolog of period1(per1) is the only known clock gene homolog that maps near the lag locus. However, all sequence variants found in per1 cDNA from lag(dg2) mutants are also present in wild type lines, and we were unable to detect any defect in per1 mRNA splicing, so this mutation may identify a novel clock gene.