民办医学院校专科教学改革的探讨

该研究以山东万杰医学院为例,针对目前招生规模越来越大,生源质量不断下滑,大面积学生逃学、厌学、考试成绩不及格的严峻现实,提出有关教学方法、教学内容和考核方式的教学三项改革,这三项改革举措顺应了当前高校教育(特别是民办高校教育)形势的发展趋势。通过改革实践,已初见成效,进一步验证了只有坚定不移地搞好教学三项改革,才能保证和提高教学质量,从而使广大学生及其家长的利益得到充分保障;也只有大张旗鼓地继续搞好教学三项改革,学校才有生存和可持续发展的空间。     

Up-regulation of endothelial stretch-activated cation channels by fluid shear stress.

OBJECTIVE: Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca(2+) influx through SAC could induce an intracellular Ca(2+) signal stimulating Ca(2+)-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested whether laminar shear stress (LSS) regulates SAC function. METHODS: Electrophysiological properties of SAC were investigated in human umbilical vein endothelial cells (HUVEC) subjected to defined levels of LSS in a flow-cone apparatus. RESULTS: In HUVEC, we identified a Ca(2+) permeable SAC that was activated by membrane stretch. Single-channel current densities of SAC in cell-attached patches were significantly increased in HUVEC exposed to an LSS of 5 dyn/cm(2) for 4 h (1.15+/-0.17 SAC/patch) compared to HUVEC kept in stationary culture (0.46+/-0.07 SAC/patch). Exposure of HUVEC to a higher LSS of 15 dyn/cm(2) for 4 h induced similar up-regulation of SAC (1.27+/-0.21 SAC/patch). After 24 h exposure to LSS of 15 dyn/cm(2), single-channel current densities of SAC remained up-regulated (1.07+/-0.18 SAC/patch) compared to controls. In addition, stretch-sensitivity of SAC (channel activity NP(o) at -30 mmHg) significantly increased after 2 h of exposure to LSS of 5 and 15 dyn/cm(2) and remained up-regulated after 24 h. Inhibition of protein kinases and tyrosine kinases by H7 and genistein, respectively, prevented LSS-induced alteration of SAC function. CONCLUSION: Single-channel current density and mechanosensitivity of SAC in HUVEC is up-regulated by LSS. Up-regulation of SAC function leads to enhanced mechanosensitive Ca(2+) influx, and represents a novel adaptive mechanism of the endothelium in the presence of altered hemodynamic forces.     

Terfenadine effect on the bronchoconstriction, dermal response, and leukopenia induced by platelet-activating factor

We have investigated the protective effect of oral terfenadine, a H1 antagonist, on the dermal and pulmonary response, and changes of circulating WBCs to injected and inhaled platelet activating factor. Nine men with mild asthma participated in a double-blind, crossover study using terfenadine, 120 mg, or placebo. Three hours after administration of study drug, pulmonary function was measured, and a PAF challenge was performed. Skin test to histamine and PAF was performed prior to study drug, and 2.5 hours after drug. Circulating WBC count was determined prior to PAF inhalation and during the PAF challenge. There was a significant improvement in pulmonary function on terfenadine. Terfenadine significantly inhibited the wheal and flare response to histamine and the flare response to injected PAF. Terfenadine did not have an effect on the change in circulating WBC count or the change in pulmonary function to inhaled PAF. These results suggest a limited role for endogenous histamine for the effects of PAF.     

Effect of platelet-activating factor inhalation on nonspecific bronchial reactivity in man

Bronchial hyperactivity is a recognized hallmark of asthma, characterized by an exaggerated bronchial response to numerous mediators, including histamine. It is also well recognized that bronchial hyperresponsiveness is increased following allergen exposure, although no particular mediator has been shown to induce this response. The recent observation that PAF can induce increased nonspecific bronchial reactivity in normal subjects emphasizes its importance as an inflammatory mediator. In this report we sought to further elucidate the role of PAF in airway hyperreactivity by comparing the effect of PAF on methacholine-induced airway responsiveness in six non-asthmatic subjects. Nonspecific airway responsiveness was not significantly increased following PAF inhalation at 6 hours nor was it increased at 1, 2, 7, or 14 days. Further elucidation of the potential role of PAF in explaining changes in airway reactivity is necessary.     

Prevalence and clinical importance of Entamoeba histolytica in two high-risk groups: travelers returning from the tropics and male homosexuals

This study was undertaken to learn the prevalence of amebiasis and to assess the clinical importance of Entamoeba histolytica in two high-risk groups: 2700 travelers returning from the tropics and 320 male homosexuals. Some 16.3% of the homosexual men and 4.0% of the travelers had E. histolytica infections. Only five travelers showed a pathogenic zymodeme of E. histolytica, which correlated closely with invasive amebiasis with positive amebic serology and clinical symptoms with diarrhea. The homosexual group had neither a pathogenic isoenzyme pattern nor positive amebic serology. Currently, travelers to the tropics have a risk of 0.3% (1:340) of acquiring invasive amebiasis; 92.5% of all E. histolytica infections in travelers remain asymptomatic and are confirmed by serology and zymodeme status. No homosexual presented with invasive amebiasis.     

Shear stress-induced up-regulation of the intermediate-conductance Ca(2+)-activated K(+) channel in human endothelium

OBJECTIVE: Wall shear stress associated with blood flow is a major stimuli for generation of endothelial vasodilating and antithrombotic factors and it also regulates endothelial gene expression. Activation of endothelial intermediate-conductance Ca(2+)-activated K(+) channels (IK(Ca)) is important for the control of endothelial function by inducing cell hyperpolarization and thus generation of the endothelium-derived hyperpolarizing factor. In the present study we tested whether the IK(Ca) encoding IKCa1 gene is regulated by laminar shear stress (LSS). METHODS: Human umbilical vein endothelial cells (HUVEC) were subjected to LSS with a magnitude of 0.5-15 dyn/cm(2) and time intervals of 2-24 h in a flow cone apparatus. Expression of the IKCa1 gene and IK(Ca)-functions were determined by using real time RT-PCR and patch-clamp techniques. RESULTS: A short 2-4 h-or long 24 h-exposure to a LSS with a low (venous) magnitude of 0.5 dyn/cm(2) had no effect on IKCa1 expression levels. An exposure for 2 and 4 h to LSS with an intermediate magnitude of 5 dyn/cm(2) was also ineffective, whereas an exposure for 24 h induced a significant threefold up-regulation of IKCa1 expression levels. An exposure to LSS with a higher (arterial) magnitude of 15 dyn/cm(2), resulted in an eightfold up-regulation of IKCa1 expression levels after a 4 h-exposure and a fourfold increase of IKCa1 expression levels at 24 h. The increased IKCa1 expression levels following exposure to high levels of LSS resulted in enhanced IK(Ca) whole-cell currents and in an increased hyperpolarization of the endothelium in response to ATP and the IK(Ca) opener 1-EBIO. Inhibition of the mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK) kinase 1/2 (MEK/ERK) pathway by PD98059 prevented the LSS-induced up-regulation of IKCa1 expression levels and IK(Ca) whole-cell currents indicating that augmentation of IKCa1 expression levels is mediated by the LSS-induced activation of the MEK/ERK pathway. CONCLUSION: Long term exposure to LSS up-regulates expression and function of endothelial IK(Ca). This increase might represent a new important mechanism in endothelial adaptation to altered hemodynamics.     

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.     

Evaluation of laser-speckle contrast image analysis techniques in the cortical microcirculation of piglets

A new laser speckle-contrast analysis (LASCA) technique based on multi-exposure imaging was employed to simultaneously study pial arteriolar responses with cerebrocortical perfusion changes to various vasodilator (5-10% CO(2) ventilation, bradykinin (1-10 μM), N-methyl-D-aspartate (100 μM)) vasoconstrictor (10-100 μM noradrenaline, 1M KCl), or neutral (2.1% H(2) ventilation) stimuli as well as to asphyxia in the newborn piglet. Anesthetized, ventilated animals (n=20) were fitted with closed cranial windows. Multiple exposure laser-speckle image series (1-100 ms) were obtained using a near infrared diode laser (λ=808 nm). The autocorrelation decay time (τ) of speckle fluctuations was determined over pial arterioles and parenchymal areas to express 1/τ being proportional to blood flow velocity by two different LASCA techniques: our novel multi-exposure or a single exposure (2 and 20 ms) approach. 1/τ values yielded by different LASCA techniques were not significantly different at most points. LASCA easily detected both increases and decreases in cortical blood flow (CoBF). Cortical 1/τ changes to hypercapnia closely matched quantitative CoBF data determined previously, and were also in accordance with increases of pial arteriolar blood flow, calculated from arteriolar flow velocity and cross sectional area changes. In summary, LASCA emerges as an appealing method to simultaneously study microvascular reactivity and cortical perfusion changes in the piglet.