Programmed death 1 and B and T lymphocyte attenuator immunoreceptors and their association with malignant T‐lymphoproliferative disorders: brief review

Malignant T‐cell lymphoproliferative diseases are relatively rare. T cells are activated through the T‐cell receptor with the aid of costimulating molecules that can be either excitatory or inhibitory. Such pathways have been also implicated in mechanisms of malignant T‐cell lymphoproliferative diseases' persistence and relapse by circumventing immune responses. To date, three major immunoinhibitory molecules have been recognized, namely programmed cell death‐1 (PD‐1), B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen 4 (CTLA‐4). Although CTLA‐4 is considered the ‘gatekeeper’ of immune tolerance, PD‐1 negatively regulates immune responses broadly, whereas BTLA activation has been shown to inhibit CD8+ cancer‐specific T cells. Both PD‐1 and BTLA downregulate proximal T‐cell receptor signalling cascade and are involved in immune evasion of leukaemias and lymphomas, even after allogeneic stem cell transplantation. These immunoregulatory molecules can have seemingly a synergistic effect on weakening the immune response of patients with haematological malignancies, and their manipulation represents a very active field of preclinical as well as clinical interest. Copyright © 2013 John Wiley & Sons, Ltd.     

Epidemiology and molecular analysis of hepatitis A,B and C in a semi-urban and rural area of Crete

AimAn observational seroepidemiological study was carried out in a well-defined primary-care district on the island of Crete in order to determine the recent endemicity of viral hepatitis in Cretan-population.Setting and participantsThe setting consisted of a semi-urban group and a remote & rural group. Serum samples were collected from 876 subjects (437 males, 439 females) aged 15 years or above. Subjects were randomly selected from the permanent population of the area that consisted of 5705 individuals. The aim was to measure the prevalence of selected viral-hepatitis markers.ResultsHepatitis B surface-antigen (HBsAg) was found positive in twenty-nine individuals, (3.3%). Antibodies to hepatitis B virus core-antigen (HBcAb) were detected in 287 subjects (32.8%) and antibodies to hepatitis C virus (anti-HCV) were detected in nineteen subjects (2.2%). Seropositivities for the semi-urban group were: 3.4%, 19.1%, 2.1% and 3.2%, 48.8%, 2.2% in remote & rural group respectively. Virtually, all subjects > 45 years old were seropositive for antibodies to hepatitis A, whereas approximately 80% of those in the 15–44 age-group were found to be seropositive.ConclusionA threefold increase in the HBV exposure and carrier proportion was found in Cretan native-population and in rural-areas compared to older studies carried out in other rural-populations of the island. It is still unknown whether the recent economic crisis or the demographic changes in Cretan-population contributed to these findings. HCV endemicity remains relatively constant, however an alteration of hepatitis C genotypes was observed. Exposure to HAV was found to be higher in remote and rural areas compared to semi-urban areas.     

Cyclic neutropenia (CN): a clue to the control of granulopoiesis

A simple quantitative feedback model of granulopoiesis is presented and discussed within the framework of existing data on granulopoiesis in both normals and patients with cyclic neutropenia (CN). The model assumes that the controlled compartment is the bone marrow pool of mature neutrophils (PMNs), which sends a negative feedback signal to the mitotic pool of early granulocyte precursors (i.e., CFU-C, myeloblasts, etc.) thus controlling the granulocyte production rate. Three parameters are found to play important roles in determining the response of the system to perturbations. These are: TM, the granulocyte maturation time; a, a parameter reflecting the strength of the negative feedback exerted by mature PMNs on the granulocyte production rate; and b, a parameter describing the leakiness of the bone marrow for PMN egress. It is shown that depending on the relative magnitudes of a and b, the system will either respond to perturbations with a damped oscillation (a less than b: the normal state) or with a sustained oscillation (a greater than b: the CN state). In both cases, the oscillation period is found to approximately equal 2TM. Deductions of the values of a, b, and TM from experimental data are consistent with the predictions of the model and show an increased value of a in CN relative to the normal state. This suggests an overly active feedback mechanism as the pathophysiologic basis of CN. In addition, the model can explain how various therapeutic agent correct CN and also provides insight into why other hematologic cell lines and CSA oscillate in CN.     

Blood flow imaging with MR: spin-phase phenomena

Blood flow phenomena occurring when flow is within the magnetic resonance (MR) imaging plane were analyzed. In this situation, the signal intensity of vascular lumina is predominantly determined by spin-phase change phenomena, and section transition effects of moving spins can be neglected. In this paper, we develop the concepts of in-plane flow, with emphasis on the notion that the spatial variations in velocity and acceleration of blood, which mainly occur along vessel walls, are important determinants of intravascular signal loss in MR images. Flow patterns in the large mediastinal arteries were qualitatively and quantitatively analyzed in six healthy subjects and 14 patients with hemodynamic abnormalities using multiple electrocardiograph-gated image acquisition; ungated studies of 30 patients were analyzed for venous flow effects. Intraluminal signal was strongly dependent on the phase of the cardiac cycle and the echo number. Signal loss was found to occur along vessel walls, in vascular bends, and at bifurcations.     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

程序变温法确定药物降解反应级数

通过电子计算机模拟程序升温加速试验,从理论上阐明了常规的程序升温法不能确定药物降解反应级数的原因是因为同一组数据可由不同的反应级数和活化能的组合所拟合;解决这一问题的关键是在一个变温程序中包含升温和降温部分;据此提出了一种新的程序变温方法(程序升降温法)。利用这种方法,可以真正做到只通过一次程序变温加速试验,就获得包括反应级数在内的药物降解的动力学参数,且确定反应级数的能力与恒温法相近似。     

4-芳杂环单/双氨甲基酚衍生物的合成和量化计算

本文在前报的基础上,设计和合成了4-芳杂环取代的氨甲基酚衍生物28个。初步药理试验表明,多数显示不同程度的抗炎活性。用CNDO/2法计算所得数据提示,该类化合物分子中的氨甲基氮和酚羟基氧与受体正电荷中心的结合,可能对抗炎活性起着重要作用。     

Use of pulse oximetry for blood pressure measurement after cardiac surgery

Blood pressure measurement using pulse oximeter waveform change was compared with an oscillometric measurement and the gold standard, intra-arterial measurement, in children after cardiac surgery. Forty six patients were enrolled and divided into groups according to weight. Simultaneous blood pressure measurements were obtained from the arterial catheter, the oscillometric device, and the pulse oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff proximal to the oximeter probe. The blood pressure measurements from the pulse oximeter method correlated better with intra-arterial measurements than those from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences between the pulse oximeter and intra-arterial measurements were significantly smaller than between the oscillometric and intra-arterial measurements in children less than 15.0 kg. The pulse oximeter waveform change is an accurate and reliable way to measure blood pressure in children non-invasively, and is superior to the oscillometric method for small patients.     

A contrast correction method for dental images based on histogram registration

Contrast correction is often required in digital subtraction radiography when comparing medical data acquired over different time periods owing to dissimilarities in the acquisition process. This paper focuses on dental radiographs and introduces a novel approach for correcting the contrast in dental image pairs.The proposed method modifies the subject images by applying typical registration techniques on their histograms. The proposed histogram registration method reshapes the histograms of the two subject images in such a way that these images are matched in terms of their contrast deviation. The method was extensively tested over 4 sets of dental images, consisting of 72 registered dental image pairs with unknown contrast differences as well as 20 dental pairs with known contrast differences. The proposed method was directly compared against the well-known histogram-based contrast correction method.The two methods were qualitatively and quantitatively evaluated for all 92 available dental image pairs. The two methods were compared in terms of the contrast root mean square difference between the reference image and the corrected image in each case. The obtained results were also verified statistically using appropriate t-tests in each set.The proposed method exhibited superior performance compared with the well-established method, in terms of the contrast root mean square difference between the reference and the corrected images. After suitable statistical analysis, it was deduced that the performance advantage of the proposed approach was statistically significant.