179 research outputs found

    Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism

    Get PDF
    KIT is a tyrosine kinase receptor expressed by several tumours, which has for specific ligand the stem cell factor (SCF). KIT is the main oncogene in gastrointestinal stromal tumours (GISTs), and gain-of-function KIT mutations are present in 70% of these tumours. The aim of the study was to measure and investigate the mechanisms of KIT activation in 80 KIT-positive GIST patients. KIT activation was quantified by detecting phosphotyrosine residues in Western blotting. SCF production was determined by reverse transcriptase–PCR, ELISA and/or immunohistochemistry. Primary cultures established from three GISTs were also analysed. The results show that KIT activation was detected in all cases, even in absence of KIT mutations. The fraction of activated KIT was not correlated with the mutational status of GISTs. Membrane and soluble isoforms of SCF mRNA were present in all GISTs analysed. Additionally, SCF was also detected in up to 93% of GISTs, and seen to be present within GIST cells. Likewise, the two SCF mRNA isoforms were found to be expressed in GIST-derived primary cultures. Thus, KIT activation in GISTs may in part result from the presence of SCF within the tumours

    Characterization of human lymphocyte N -acetyltransferase and its relationship to the isoniazid acetylator polymorphism

    Full text link
    Characterization of human lymphocyte N -acetyltransferase (NAT) for specific activity, substrate specificity, inhibition, pH optimum, apparent K m , kinetic mechanism, trypsin stability, freezing stability, and heat stability was carried out in rapid and slow isoniazid (INH) acetylators. There is a statistically significant difference in the heat stability of lymphocyte NAT from rapid and slow INH phenotypes. The lymphocyte enzyme from rapid INH acetylators is less heat stable than the lymphocyte enzyme from slow INH acetylators. This is an indication of a structural, possibly polymorphic, difference in lymphocyte NAT from the two acetylator phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44137/1/10528_2004_Article_BF00500122.pd

    Диагностика и лечение заворота сигмовидной кишки как формы толстокишечной непроходимости

    Get PDF
    Relevance. Intestinal obstruction can occur in all age groups, but most often it occurs at the age of 40–70 years and one of the causes of colonic obstruction may be volvulus of the sigmoid or cecum. Volvulus of the sigmoid colon is most common and reaches 15% of all types of strangulation intestinal obstruction. The mortality rate in sigmoid colon volvulus reaches 14–16%. In cases of necrosis of the sigmoid colon, the mortality can reach 70–78%.Aim of study. To evaluate the results of diagnosis and treatment of patients with sigmoid volvulus.Material and methods. In 2015–2020 at the N.V. Sklifosovsky Research Institute for Emergency Medicine we treated 28 patients with volvulus of the sigmoid colon. Of these, there were 13 women (46.4%) and 15 men (53.6%). The average age of the patients was 69 years. Upon admission to the hospital, patients underwent a clinical examination, basic laboratory and instrumental methods of examination. If volvulus of the sigmoid colon was suspected, colonoscopy, irrigoscopy, computed tomography of the abdominal organs with contrast enhancement, and diagnostic laparoscopy were additionally performed. In the department, patients underwent fluid maintenance, antispasmodic and symptomatic therapy, cleansing enemas. According to the indications, an operative benefit was provided by open and laparoscopic accesses.Results. The sensitivity of the x-ray method was 88%, but the sensitivity of the plain x-ray examination, supplemented with a barium enema (irrigoscopy), was 100%. The sensitivity of the ultrasound method was 57%, however, when supplemented with a Doppler study, the sensitivity increases to 72%. The sensitivity of CT was 100%. The sensitivity of colonoscopy among those studied is 96%. Operations performed in patients with volvulus of the sigmoid colon: endoscopic detorsion in 15 patients (64.3%), video-laparoscopic elimination of volvulus of the sigmoid colon in 3 (10.7%) patients. Midline laparotomy in 17 patients (60.7%). Among patients after endoscopic bowel detorsion, no complications were observed in the early period. After laparotomy and elimination of volvulus of the sigmoid colon, postoperative complications were observed in 3 (17.7%) patients. There were 3 deaths (10.7%).Conclusion. High mortality does not allow us to call the results of treatment satisfactory, and a small number of observations does not allow us to obtain statistically significant results, which requires further case recruitment and data analysis.Актуальность. Кишечная непроходимость может возникать во всех возрастных группах, но наиболее часто она встречается в возрасте 40–70 лет и одной из причин толстокишечной непроходимости может явиться заворот сигмовидной (ЗСК) или слепой кишки. ЗСК является наиболее распространенной формой и достигает 15% от всех видов странгуляционной кишечной непроходимости. Летальность при ЗСК достигает 14–16%. В случаях некроза сигмовидной кишки летальность может достигать 70–78%.Цель. Оценка результатов диагностики и лечения пациентов с ЗСК.Материал и методы. За период 2015–2020 годов в ГБУЗ «НИИ скорой помощи им. Н.В. Склифосовского» пролечены 28 пациентов с ЗСК. Из них было 13 женщин (46,4%) и 15 мужчин (53,6%). Средний возраст пациентов составил 69 лет. При поступлении в стационар пациентам выполняли клинический осмотр, базовые лабораторные и инструментальные методы обследования. При подозрении на ЗСК дополнительно выполняли колоноскопию, ирригоскопию, компьютерную томографию (КТ) органов брюшной полости с контрастным усилением, диагностическую лапароскопию. В отделении пациентам проводили инфузионно-спазмолитическую, симптоматическую терапия, постановку очистительных клизм. По показаниям оказывалось оперативное пособие открытым и лапароскопическим доступами.Результаты. Чувствительность рентгенологического метода составила 88%, однако чувствительность обзорного рентгенологического исследования, дополненная бариевой клизмой (ирригоскопией), составила 100%. Чувствительность ультразвукового метода составила 57%, однако при дополнении к исследованию допплерографии чувствительность повышается до 72%. Чувствительность КТ составила 100%. Чувствительность колоноскопии среди исследуемых — 96%. Выполненные операции у пациентов с ЗСК: эндоскопическая деторсия у 15 пациентов (64,3%), видеолапароскопическое устранение ЗСК — у 3 больных (10,7%). Срединная лапаротомия у 17 пациентов (60,7%). Среди больных после эндоскопической деторсии кишки осложнений в раннем периоде не наблюдалось. После лапаротомии и устранения ЗСК послеоперационные осложнения наблюдались у 3 больных (17,7%). Было 3 смертельных исхода (10,7%).Выводы. Высокая летальность не позволяет назвать результаты лечения удовлетворительными, а небольшое число наблюдений не позволяет получить статистически значимые результаты, что требует дальнейшего набора случаев и анализа данных

    Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes

    Full text link

    Clinical correlates of grey matter pathology in multiple sclerosis

    Get PDF
    Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

    Get PDF
    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
    corecore