Walking modality affects respiratory muscle action and contribution to respiratory effort

We hypothesized that walking at increased speed or increasing gradient might have different effects on chest wall kinematics and respiratory muscle power components, and contribute differently to respiratory effort sensation. We measured the volumes of chest wall compartments by optoelectronic plethysmography, esophageal, gastric and transdiaphragmatic (P _di) pressures, and the sensation of the respiratory effort by a Borg scale in five normal subjects walking both at ascending gradient with constant speed (AG) and at ascending speed with constant gradient (AS). Chest wall kinematics, evaluated by displacement of chest wall compartments, did not show any significant difference between AS and AG. Muscle power, calculated as the product of mean flow and mean pressure, increased similarly, but its partitioning into pressure and velocity of shortening differed in the two modes. A greater increase in the pressure developed by the abdominal muscles (P _abm) (4.06-fold), and in the velocity of shortening of both rib cage inspiratory muscles (v _rcm,i) (2.01-fold) and the diaphragm (v _di) (1.90-fold) was associated with a lower increase in the pressure developed by the rib cage inspiratory muscles (P _rcm,i) (1.24-fold) and P _di (0.99-fold) with AG. Instead, with AS, a lower increase in P _abm (2.12-fold), v _rcm,i (1.66-fold) and v _di (1.54-fold) was associated with a greater increase in P _rcm,i (1.56-fold) and P _di (1.97-fold). A combination of P _abm and v _di during AG (Wald ²=23.19, P<0.0000), with the addition of P _rcm,i during AS (Wald ²=29.46, P<0.0000), was the best predictor of Borg score. In conclusion, the general strategy adopted by respiratory centers during different walking modes does not differ in terms of ventilation, chest wall kinematics, and respiratory muscle power production, whereas it does in terms of partitioning of power into pressure and velocity of shortening, and respiratory muscle contribution to respiratory effort sensation. Combinations of different patterns of flow and pressure generation made the respiratory effort sensation similar during AS and AG modes.     

Stem cell therapy for neurodegenerative diseases: the issue of transdifferentiation

In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward.     

Cutaneous mucormycosis in a young, immunocompetent girl.

We report a case of cutaneous mucormycosis in a healthy, immunocompetent young girl (age 14 years). The patient had a 5-year history of a slowly enlarging, erythematous plaque with slight elevated, scaling, circinate borders on the right thigh. Histopathology showed a granulomatous infiltrate with broad, pale, non-septate hyphae. Mycological study identified Mucor hiemalis (Wehmer).     

利用神经网络构建超声多普勒栓子信号自动检测系统

对血液中栓子的早期检测有着重要的临床诊断意义.超声多普勒技术使栓子的无损检测成为可能,但是目前的检测尚依赖于医生的手动操作和临床经验,仍缺乏可靠的自动检测系统.本文基于小波包变换和主元分析提取对栓子敏感的特征参数,并利用神经网络构建超声多普勒栓子信号的自动检测系统.仿真研究和临床实验表明:该系统有效提高了栓子检测的准确性,有望应用于临床诊断.     

Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients

To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic steatohepatitis, in HCV-infected subjects IFN-alpha and -beta mRNA levels were significantly lower, whereas IFN-gamma, IFNAR-1, STAT1alpha IRF-1, and IL-18 mRNA were upregulated. Moreover, IFN-gamma mRNA steady state levels were correlated positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL-18-specific mRNA, viral load was not related to liver injury. IFN-gamma and IRF-1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN-alpha and -beta mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN-gamma system and a downregulated IFN-alpha and -beta system, probably due to a mixed effect exerted by HCV-specific and inflammatory non-specific factors.     

放线菌素D/TNF-α诱导大鼠肝干细胞凋亡及HGF的拮抗作用

目的 研究TNF-α、肝细胞生长因子(HGF)在肝干细胞的增殖、分化调控及凋亡中的作用。方法 用大鼠肝干细胞系WB F-344细胞进行实验，用MTT法检测细胞毒作用；用DNA凝胶电泳及流式细胞仪检测细胞凋亡；用Western blot方法检测磷酸化MAPK及PI3K蛋白的表达。结果 发现TNF-α单独对WB F-344细胞无明显作用；而TNF-α对放线菌素D(ActD)致敏的WB F-344细胞有明显细胞毒作用。进一步，发现TNF-α能够诱导ActD致敏的WB F-344细胞发生凋亡，在作用9h即出现细胞凋亡(13．60％)，48h达高峰(51％)，并且这种凋亡呈剂量效应关系。我们还发现，HGF可以明显拮抗ActD／TNF-α诱导的WB F-344细胞凋亡，并且呈剂量效应关系。Western blot结果显示，HGF刺激后，磷酸化MAPK蛋白高表达，表明HGF激活了MAPK途径。我们进一步用PI3K特异的抑制剂WT阻断PI3K途径，发现HGF的抗凋亡作用被阻断；然而，用MAPK特异抑制剂U0126阻断MAPK途径后，却并不影响HGF的抗凋亡作用。结论 TNF-α能诱导ActD致敏的肝干细胞发生凋亡，而HGF则对这种细胞凋亡有明显的拮抗作用；虽然HGF能够激活PI3K及MAPK 2条途径，但其抗凋亡作用是由PI3K途径传导的。     

The nature of high frequency sister chromatid exchange cells (HFCs)

We employed the three-way differential staining technique (TWD),which allows SCEs to be distinguished on a per generation basisby scoring third metaphases (M3), in order to study the spontaneouslevels of SCEs in normal and high frequency cells (HFCs) thatoccurred in the first (S1), second (S2) and third (S3) S phases.Fifty one of 900 lymphocytes from 37 healthy donors were definedas HFCs by calculating the 95th percentile of the distributionof SCEs in S1 + S2. ‘Normal’ cells presented almostthe same number of SCEs after the first, second and third cellcycles (SCE averages of 2.43, 2.04 and 3.53 respectively). Incontrast, HFCs showed a higher SCE count in SI, which decreasedrapidly through the cycles and reached baseline level at S3(SCE averages of 7.18, 4.29 and 3.45 respectively). This wouldsuggest that the lesions responsible for the higher SCE frequencyin HFCs were effectively removed after two cell cycles and stronglysupport the hypothesis that HFCs are lymphocytes which accumulatehigher levels of DNA lesions through time. ¹To whom correspondence should be addressed     

Presymptomatic diagnosis of SMA III by genotype analysis

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc.