Dynamic cell cycle kinetics in vitro and in vivo in myelodysplastic syndromes with special reference to the influence of hematopoietic growth factors

We have investigated the effect of HGF in vivo and in vitro in MDS using a recently developed FCM assay involving the simultaneous measurement of cell surface antigens, DNA content, and BrdUrd or IodUrd incorporation. This allows for the determination of the dynamic cell kinetic parameters: LI, T_s, and T_pot and we observed that in vitro HGF stimulation resulted in a significant decrease in mean T_pot values from 6.6 to 3.5 days. Importantly, we demonstrated that in vivo GM-CSF administration to patients with RAEB resulted in a shortening of T_pot within the 2 first weeks of GM-CSF treatment.     

模拟缺血缺氧对左心室心肌细胞钠电流跨壁异质性的影响

目的 :　研究左心室心肌细胞快钠通道的跨壁异质性及模拟缺血对其的影响。　方法 :采用全细胞膜片钳记录技术直接记录左心室三层心肌细胞的快钠通道电流 (INa) ,并观察模拟缺血缺氧对心肌细胞INa跨壁异质性的影响。　结果 :左心室三层心肌细胞的钠电流特性存在异质性 ,表现为中层 (M )细胞的电流密度 电压关系(I V)曲线最低 ,M细胞的峰值INa是心内膜层 (Endo)和心外膜层 (Epi)的 2倍多 ;M细胞的INa失活最快。模拟缺血后 ,三层心肌细胞的INaI V曲线呈时间依赖性下移 ,M细胞的变化最显著 ;INa稳态失活曲线呈时间依赖性左移 ,以Epi变化最显著 ;模拟缺血 30min时Endo的恢复明显慢于M和Epi。　 结论 :左心室心肌细胞的INa存在跨壁异质性 ;模拟缺血缺氧对INa的跨壁异质性有明显影响。     

Heterogeneity in 1H-MRS profiles of presymptomatic and early manifest Huntington's disease

OBJECTIVE: To evaluate (1)H-MRS profiles of the putamen in presymptomatic and manifest Huntington's disease (HD) patients for spectroscopic markers that are reliable, consistent signs of early pathology and to look for hemispheric differences as signs of use activation in an accelerated degradative process of the dominant hemisphere. METHODS: A short echo time Point RESolved Spectroscopy (PRESS) spectroscopic imaging study was performed at low field (0.5 Tesla, T) on 27 right-handed patients (17 presymptomatic gene carriers and 10 manifest patients of less than 3 years from clinical onset) and 10 right-handed normal volunteers. Spectra from individual voxels (0.56 cm(3)) in the putamen were selected for analysis. Resonance areas of peaks were normalized to water as a concentration standard. Interhemispheric comparisons were made in individuals in all three groups to look for hemispheric differences. RESULTS: Two presymptomatic patients showed normal spectra but all other HD patients displayed some combination of reduced N-acetylaspartate (NAA), enhanced glutamate/glutamine (Glx) activity, and lactate (Lac) elevations or reduced creatine (Cr). Rather than showing any one metabolite as pathognomonic of early change, spectroscopic profiles showed heterogeneity between HD patients. Low creatine was common in the presymptomatic but not in the manifest group. Hemispheric ratios of abnormal metabolites showed lower values of NAA and Glx in the dominant hemisphere in all three groups but values of creatine were selectively lower in the dominant hemisphere of only the presymptomatic patients. Lac was elevated in both hemispheres but less so in the dominant hemisphere in all HD patients. CONCLUSIONS: (1)H-MRS profiles from the putamen of presymptomatic and manifest patients reflect heterogeneity in pathophysiology. With the possible exception of low creatine in presymptomatic patients (1)H-MRS spectra are not suggestive of hemispheric differences supportive of an overall accelerated degradative process in the dominant hemisphere.     

Dimensions of intelligence in schizophrenia: evidence from patients with preserved, deteriorated and compromised intellect

There is a growing literature describing a subgroup of "high-functioning" people with schizophrenia who show preserved intellectual ability (IQ). A detailed characterisation of the cognitive abilities of this group may be important in targeting appropriate treatment, management and services for patients with schizophrenia. It is a widely held belief that variation in cognitive processing speed is the basis of individual differences in intelligence. The main objective of this study was to identify subgroups of schizophrenia patients with preserved (N=45), deteriorated (N=47) and compromised (N=17) intellect in order to study whether these subgroups differ in specific cognitive abilities (e.g. executive functions) or in general cognitive processing speed, as measured with an inspection time (IT) task. The patients who displayed an average estimated premorbid IQ, with no evidence of IQ decline (premorbid-current IQ difference <10 points), were found to show better performance on measures of executive function (continuous performance task, verbal fluency) compared with patients in the deteriorated and compromised subgroups. Nevertheless, this represented significantly impaired performance relative to healthy controls. In contrast, the average inspection times of patients with preserved IQ were as slow as those obtained in the deteriorated or compromised groups, indicating that high functioning patients are impaired in terms of cognitive processing speed. Furthermore, the average IT for all schizophrenia groups was significantly slower than that of healthy controls. These findings suggest that high functioning patients with schizophrenia exhibit enduring cognitive difficulties that may impact on their ability to benefit from rehabilitation interventions.     

Unevenness of ventilation assessed by the expired CO(2) gas volume versus V(T) curve in asthmatic patients

Recently, we have shown that the expired CO2 gas volume versus tidal volume (VCO2-VT) curve is a useful tool for assessing unevenness of ventilation because it allows the separation of tidal volume into three functional compartments: (a) the CO2-free expired air (V0), (b) the transitional volume (Vtr), (c) the alveolar volume (VA) and the measurement of alveolar FCO2 during resting breathing in normal subjects and patients with COPD. In this paper, we have investigated whether changes pertaining to unevenness of ventilation taking place immediately after the administration of methacholine can be assessed using the VCO2-VT curve in asthmatic patients. The VCO2-VT curve was obtained during tidal breathing from 16 stable asthmatic patients who underwent a methacholine challenge test. It has been found that the Vtr, and hence Bohr's dead space (VD,Bohr = V0 + Vtr), over tidal volume ratios were significantly increased immediately after the methacholine administration, whilst the V0 over tidal volume ratio was not affected. The change of the above ratios was not related to the percentage decrease of FEV1.0 following methacholine administration.     

Changes with age in the distribution of a frailty index

Models of human mortality include a factor that summarises intrinsic differences in individual rates of ageing, commonly called frailty. Frailty also describes a clinical syndrome of apparent vulnerability. In a representative, cross-sectional, Canadian survey (n = 66,589) we calculated a frailty index as the mean accumulation of deficits and previously showed it to increase exponentially with age. Here, its density function exhibited a monotonic change in shape, being least skewed at the oldest ages. Although the shape gradually changed, the frailty index was well fitted by a gamma distribution. Of note, the variation coefficient, initially high, decreased from middle age on. Being able to quantify frailty means that health risks can be summarised at both the individual and group levels.     

食管癌多部位DNA含量分析及其临床意义

目的;探讨食管癌多部位ＤＮＡ含量与临床及病理特性之间的关系。方法：流工细胞光度术检测１００例食管癌手术切除新鲜标本的癌、癌旁和断端组织的ＤＮＡ含量。结果：癌组织ＤＮＡ非整倍体（ＡＮ）、ＤＮＡ指数（ＤＩ）和细胞增殖活性指数（ＰＩ）都显著高于癌旁和断端（Ｐ〈０．０５）;食管癌ＡＮ与肿瘤细胞分化和局部洒巴结转移密切相关（Ｐ〈０．０１）。在癌体与癌旁或断端组织间存在ＤＮＡ倍体异质性（１４．８％）;切距〈５     

Clinical Heterogeneity of Interstitial Lung Disease in Polymyositis and Dermatomyositis Patients With or Without Specific Autoantibodies

Background

The aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type.

Exploration of the volumetric composition of human lung cancer nodules in correlated histopathology and computed tomography

Gaining a complete and comprehensive understanding of lung cancer nodule histological compositions and how these tissues are represented in radiological data is important not only for expanding the current knowledge base of cancer growth and development but also has potential implications for classification standards, radiological diagnosis methods and for the evaluation of treatment response. In this study we generate large scale histological segmentations of the cancerous and non-cancerous tissues within resected lung nodules. We have implemented a processing pipeline which allows for the direct correlation between histological data and spatially corresponding computed tomography data. Utilizing these correlated datasets we evaluated the statistical separation between Hounsfield Unit (HU) histogram values for each tissue type. The findings of this study revealed that lung cancer nodules contain a complex intermixing of cellular tissue types and that trends exist in the relationship between these tissue types. It was found that the mean Hounsfield Unit values for isolated lung cancer nodules imaged with computed tomography, had statistically significantly different values for non-solid bronchoalveolar carcinoma, solid cancerous tumor, blood, and inactive fibrotic stromal tissue.     

Value of QT dispersion in evaluating spatial dispersion of ventricular repolarization during acute myocardial ischemia

OBJECTIVES:

To study the value of epicardial QT interval dispersion in predicting ischemia-induced heterogeneity of ventricular repolarization.

ANIMALS AND METHODS:

Ischemia was produced by total occlusion of the obtuse branch of the circumflex coronary artery in seven open-chest sheep. A 64-channel electrocardiogram (ECG) was acquired from the epicardium before and after coronary artery occlusion. Wavelet transformation was used to determine the characteristic points of the epicardial ECGs, and to measure the QT interval and activation-recovery interval (ARI) and their dispersions.

RESULTS:

The average QT interval and ARI from the epicardial ECG were not changed by acute myocardial ischemia (P=0.07 and P=0.13, respectively). QT dispersion remained unchanged during ischemia (P=0.17), whereas ARI dispersion was significantly increased by acute ischemia (59.9±24.0 ms versus 126.3±32.1 ms, P<0.001).

CONCLUSIONS:

These findings indicate that epicardial QT dispersion is less sensitive than ARI dispersion in estimating repolarization heterogeneity induced by acute myocardial ischemia.