MaxiK channel partners: physiological impact

The basic functional unit of the large-conductance, voltage- and Ca²⁺-activated K⁺ (MaxiK, BK, BK_Ca) channel is a tetramer of the pore-forming α-subunit (MaxiKα) encoded by a single gene, Slo , holding multiple alternative exons. Depending on the tissue, MaxiKα can associate with modulatory β-subunits (β1–β4) increasing its functional diversity. As MaxiK senses and regulates membrane voltage and intracellular Ca²⁺, it links cell excitability with cell signalling and metabolism. Thus, MaxiK is a key regulator of vital body functions, like blood flow, uresis, immunity and neurotransmission. Epilepsy with paroxysmal dyskinesia syndrome has been recognized as a MaxiKα-related disorder caused by a gain-of-function C-terminus mutation. This channel region is also emerging as a key recognition module containing sequences for MaxiKα interaction with its surrounding signalling partners, and its targeting to cell-specific microdomains. The growing list of interacting proteins highlights the possibility that associations with the C-terminus of MaxiKα are dynamic and depending on each cellular environment. We speculate that the molecular multiplicity of the C-terminus (and intracellular loops) dictated by alternative exons may modulate or create additional interacting sites in a tissue-specific manner. A challenge is the dissection of MaxiK macromolecular signalling complexes in different tissues and their temporal association/dissociation according to the stimulus.     

Novel X-linked mental retardation syndrome with short stature maps to Xq24

Microdeletions in the 22q11 region are associated with a wide range of overlapping phenotypes. The main manifestations of the syndrome include palatal anomalies such as cleft palate or velopharyngeal insufficiency, conotruncal heart defects, hypocalcemia, immune disorders, and minor facial anomalies. Because of the wide variability, facial changes appear to be the most constant manifestation of the syndrome and characteristic for informed physicians. The purpose of this study is to report the preliminary results of a detailed analysis of anthropometric data (35 measurements) in 15 patients (7 females and 8 males between 5 and 38 years of age, all white Europeans) with a 22q11 microdeletion. Objective anthropometric study showed that 19 measurements and 7 indexes were significantly different between 22q11 patients and normative database. The typical face showed a short forehead with an anterior vertical excess. Downslanting eyes and large binocular width were the most common anomalies in the orbital area. The nose showed anomalies with a large root, a short tip, and a narrow alar base. There was a narrowing of the mouth and thin lips. Ears were small and slightly disharmonic for the children. Statistical comparison between children (10 cases) and adults (5 cases) showed that craniofacial assessment was more demonstrative in children than in adults.     

The influence of the herpes simplex virus-1 DNA template environment on the regulation of gene expression

To determine the role of the HSV-1 genome structure and environment on the regulation of gene expression, we constructed recombinant viruses containing a heterologous gene inserted into either the immediate early ICP0 or late glycoprotein C (gC) genes of HSV-1. The heterologous gene consisted of the SV40 early promoter (without enhancer sequences) linked to the coding sequences for the bacterial chloramphenicol acetyl transferase (CAT). The expression of CAT was examined in Vero cells infected with either virus (named ICP0-CAT and Sph 6). For both recombinants, expression of CAT was not dependent upon prior viral protein synthesis. The kinetics of expression of CAT-specific mRNA resembled that of the HSV-1 genes into which CAT was inserted. Primer extension analysis revealed that the SV40 promoter is recognized and used when placed in cis in two different HSV-1 genome locations, and Northern hybridization experiments confirmed that the heterologous gene was expressed in the absence of prior viral protein synthesis. Therefore, this gene was not regulated as strictly as an HSV-1 gene, but was influenced by the environment into which it was placed, presumably by factors that are present when the normal viral gene is on.     

Computer analysis system of blood oxygen saturation in an animal hypoxia model

An experimental animal hypoxia model has been developed. It consists of two sensors (an in vitro and in vivo model), an experimental device and a computer signal processing system. This method can easily be applied to determine and analyse blood oxygen saturation at various hypoxia levels. It can also be used to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation levels. The DC and AC components of recorded red and infra-red signals, the dual-wavelength ratio R₁₂ and the reading of a pulse oximeter (SpO₂) can be automatically calculated and displayed on a computer screen. Preliminary results of the animal hypoxia test indicate that the measurements made by the instrument correlate well with the oxygen saturation readings of the automatic blood gas analyser AVL945. The computer analysis system is suitable for repeated estimations in the animal model.     

医学信息学的研究领域及人才培养

医学信息学(MedicalInformatics,又称医药信息学)是计算机科学、信息科学与医学科学结合,新近形成的前沿多学科交叉的科学,它以信息论、系统论、计算机科学技术为理论基础,几乎全方位地涉及所有的医药卫生领域,已成为现代和未来生物医学发展的基石。目前,医学信息学应用的领域,面临人才短缺的现象,本文论述了在生物医学工程学科中,建立医学信息本科专业方向,通过相关课程体系的设置,培养符合社会需要的医学信息人才。     

Longitudinal alteration of circulating dendritic cell subsets and its correlation with steroid treatment in patients with severe acute respiratory syndrome

In this study, we found that 74 patients with severe acute respiratory syndrome (SARS) exhibited a rapid, dramatic decrease in numbers of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs) during the first 2 weeks of illness (5.3- and 28.4-fold reductions for mDCs and pDCs compared with 25 healthy individuals, respectively), with slow return to normal cell numbers during convalescence (weeks 5–7 of illness on average). In addition, numbers of circulating CD4 and CD8 T cells exhibited milder reductions (2.1- and 1.8-fold at week 1) and earlier return to normal at a mean of weeks 3 and 4, respectively. A significant inverse correlation was found between numbers of DC and T-cell subsets and high-dose steroid treatment. Our novel findings thus suggest that the acute SARS-coronavirus infection probably contributes to the initial reduction of DC and T-cell subsets in blood, and that high-dose steroid administration may subsequently exacerbate and prolong low expression of the cell subsets. These findings will aid the framing of further studies of the immunopathogenesis of SARS.     

Kinetics of the phenotype and function of murine peritoneal macrophages following acute inflammation

This study was undertaken to have a better understand for the process and the underlying mechanisms to limitmacrophage activation and population of activated macrophages.A comprehensive kinetics of cytokineproduction was performed in murine peritoneal macrophages recovered from Balb/c mice at various timeduring the course of an intraperitoneal injection with thioglycollate (TG).The expression of cell surfacemolecules such as MHC-Ⅰ,MHC-Ⅱ,B7-1 and B7-2 of these macrophages were also determined by flowcytometry.The present findings of our research suggested that the population of activated macrophages and theactivation of macrophages (including cytokines production and expression of cell surface functional molecules)were strictly controlled during inflammation process.This is one of the important mechanisms to retain the hosthomeostasis.Cellular & Molecular Immunology.2004;1(1):57-62.