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To evaluate the results of preventive endovascular hemostasis in patients with high risk of recurrent bleeding from the upper gastrointestinal tract.We analyzed treatment outcomes in 158 patients with ulcerative gastroduodenal bleeding and high risk of recurrence (≥17 scores), Forrest 1-2 A/B and mortality (SAPS II score ≥30). Endovascular embolization of the left gastric or gastroduodenal artery was performed to prevent recurrent bleeding.Endovascular hemostasis was technically successful in 94.4% of cases (153 patients). Embolization could not be performed due to technical reasons in 5 patients. One patient developed retroperitoneal hematoma as a complication after transcatheter angiography and embolization that required surgical intervention. Recurrent bleeding after technically successful embolization occurred in 11 (7%) patients. The PVA microemboli and spirals were used for embolization of the left gastric and gastroduodenal arteries, respectively. Additional PVA microemboli were also used in gastroduodenal artery in some cases. Twenty-six (16.5%) patients died.Endovascular hemostasis in patients with severe comorbidities (SAPS II score ≥30) and high risk of recurrent bleeding (≥17 scores) reduced the incidence of recurrent bleeding to 6.96% and mortality to 17%.Оценка результатов применения профилактического эндоваскулярного гемостаза у больных с высоким риском рецидива кровотечения из желудка и двенадцатиперстной кишки.Работа основана на изучении результатов лечения 158 пациентов с язвенным гастродуоденальным кровотечением и высоким риском его рецидива (17 баллов и более по системе прогноза рецидива кровотечения), Forrest 1—2 A/B и летального исхода (30 баллов и более по SAPS II). Для профилактики рецидива кровотечения выполняли эндоваскулярную эмболизацию левой желудочной либо гастродуоденальной артерий.Технический успех эндоваскулярного гемостаза достигнут у 153 (94,4%) пациентов. У 5 пациентов эмболизацию выполнить не удалось по техническим причинам. Осложнение после транскатетерной ангиографии и эмболизации — забрюшинная гематома, потребовавшая хирургического вмешательства, отмечено в одном случае. Рецидив кровотечения после технически успешной эмболизации зафиксирован у 11 (7%) пациентов. Для эмболизации левой желудочной артерии использовали микроэмболы PVA, гастродуоденальной артерии — спирали и в некоторых случаях дополнительно микроэмболы PVA. Умерли 26 (16,5%) пациентов.Использование эндоваскулярного гемостаза у пациентов с тяжелыми соматическими заболеваниями (30 баллов и более по SAPS II) и высоким риском рецидива кровотечения (17 баллов и более по системе прогноза рецидива кровотечения) позволило снизить частоту повторных кровотечений до 7%, а летальность до 16,5%.

We present a rare clinical observation of a patient with an early reoperation performed up to 2 weeks after a recurrent stroke. Carotid endarterectomy with removal of previously installed stents for critical stenoses of the internal carotid arteries after the first stroke was performed. Early bilateral restenosis up to 80-90% of the lumen in the stents of both internal carotid arteries was observed 6 months after stenting. Open interventions were performed in the acute period of recurrent ischemic stroke in two stages with a favorable outcome. No data on the increase of neurological symptoms were obtained for 2 years of observation. Treatment and application of early rehabilitation methods, improved the patient's general condition, strength in the left extremities increased up to 4.5 points, left-sided hemihypesthesia decreased, speech disorders regressed. The patient walks and serves himself independently.Представлено клиническое наблюдение пациента с выполнением ранней повторной операции в период до 2 недель после повторного инсульта. Выполнена каротидная эндартерэктомия с удалением стентов, установленных ранее по поводу критических стенозов внутренних сонных артерий после первого инсульта. Наблюдался ранний двусторонний рестеноз до 80—90% просвета в стентах обеих внутренних сонных артерий в сроки через 6 мес после стентирования. Открытые вмешательства выполнены в остром периоде повторного ишемического инсульта в два этапа с благоприятным исходом. Наблюдается в течение 2 лет, данных за нарастание неврологической симптоматики не получено. На фоне проводимого лечения, применения методов ранней реабилитации улучшилось общее состояние пациента, отмечено нарастание силы в левых конечностях до 4,5 баллов, уменьшилась левосторонняя гемигипестезия, регрессировали речевые нарушения. Пациент ходит и обслуживает себя самостоятельно.

Mortality rates in acute mesenteric ischemia remain at an extremely high level for many decades. Early diagnosis and selection of the optimal method of revascularization are among the ways to optimize tactics. The diagnostic study of choice is CT angiography. Its active and systemic use can help to detect ischemia at the reversible stage. The article examines in detail the indications for the application of this diagnostic study. The question of preference for the revascularization method remains debatable. The arguments of proponents of open and endovascular interventions on mesenteric vessels are presented. Other, still unresolved tactical issues are also considered, such as indications for re-operations and application of the principles of damage control tactics.Показатели летальности при острой мезентериальной ишемии остаются на экстремально высоком уровне в течение многих десятилетий. Среди путей оптимизации тактики называются ранняя диагностика и выбор оптимального способа реваскуляризации. Методом выбора в диагностике заболевания является КТ-ангиография, активное и системное применение которой может способствовать выявлению ишемии на стадии обратимых изменений кишечной стенки. В статье подробно рассматриваются показания к выполнению этого исследования. Вопрос предпочтения метода реваскуляризации остается дискуссионным. Приводятся доводы сторонников открытых и эндоваскулярных вмешательств на мезентериальных сосудах. Рассматриваются и другие, до конца не решенные тактические вопросы, такие как показания к повторным операциям, применение принципов тактики damage control.

Key points Epidural electrical stimulation (ES) of the spinal cord restores/improves locomotion in patients. ES-evoked locomotor movements differ to some extent from the normal ones. Operation of the locomotor network during ES is unknown. We compared the activity of individual spinal neurons during locomotion initiated by signals from the brainstem and by ES. We demonstrated that the spinal network generating locomotion under each of the two conditions is formed by the same neurons. A part of this network operates similarly under the two conditions, suggesting that it is essential for generation of locomotion under both conditions. Another part of this network operates differently under the two conditions, suggesting that it is responsible for differences in the movement kinematics observed under the two conditions. Abstract Locomotion is a vital motor function for both animals and humans. Epidural electrical stimulation (ES) of the spinal cord is used to restore/improve locomotor movements in patients. However, operation of locomotor networks during ES has never been studied. Here we compared the activity of individual spinal neurons recorded in decerebrate cats of either sex during locomotion initiated by supraspinal commands (caused by stimulation of the mesencephalic locomotor region, MLR) and by ES. We found that under both conditions, the same neurons had modulation of their activity related to the locomotor rhythm, suggesting that the network generating locomotion under the two conditions is formed by the same neurons. About 40% of these neurons had stable modulation (i.e. small dispersion of their activity phase in sequential cycles), as well as a similar phase and shape of activity burst in MLR- and ES-evoked locomotor cycles. We suggest that these neurons form a part of the locomotor network that operates similarly under the two conditions, and are critical for generation of locomotion. About 23% of the modulated neurons had stable modulation only during MLR-evoked locomotion. We suggest that these neurons are responsible for some differences in kinematics of MLR- and ES-evoked locomotor movements. Finally, 25% of the modulated neurons had unstable modulation during both MLR- and ES-evoked locomotion. One can assume that these neurons contribute to maintenance of the excitability level of locomotor networks necessary for generation of stepping, or belong to postural networks, activated simultaneously with locomotor networks by both MLR stimulation and ES.

To evaluate the effectiveness of hybrid interventions, i.e. endovascular mechanical thrombectomy from intracranial arteries combined with open thrombectomy or carotid endarterectomy from extracranial internal carotid artery.We analyzed 16 patients who underwent mechanical thrombectomy/thrombaspiration combined with open surgery between January 2014 and March 2021. All patients had occlusion of extracranial and intracranial segments internal carotid artery or initial segments of the middle cerebral artery. Baseline data, diagnostic algorithm, timing and results of treatment were analyzed. Study endpoints were technical success of revascularization, clinically significant hemorrhagic transformation, NIHSS and modified Rankin score of neurological impairment, as well as outcome of disease within 90 days.We restored patency of ICA and intracranial arteries in 13 out of 16 patients. In 9 patients, we obtained a positive effect with significant regression of neurological symptoms (mRS2). In 3 patients, severe neurological deficit persisted throughout the entire follow-up period. Four patients died. Thus, effectiveness of technique was 56.2% (Hybrid interventions for tandem occlusions of carotid arteries can significantly increase efficiency and accelerate recanalization of great extracranial vessels in patients with tandem lesions in acute phase of ischemic stroke. Moreover, hybrid interventions significantly reduce the cost of reperfusion procedure. In case of severe atherosclerotic stenosis, simultaneous open endarterectomy from common and internal carotid arteries has a significant advantage over stenting due to no need for antithrombotic therapy.Оценить эффективность гибридных вмешательств: эндоваскулярная механическая тромбэктомия/тромбаспирация из внутричерепных артерий в сочетании с «открытой» тромбэктомией или каротидной эндартерэктомией из экстракраниальных отделов ВСА.Проведен анализ лечения 16 пациентов, которым выполняли механическую тромбэктомию/тромбаспирация в сочетании с открытым хирургическим вмешательством с января 2014 по март 2021 г. У всех пациентов имелась полная окклюзия экстракраниальных отделов ВСА и окклюзия внутричерепного отдела ВСА или начальных сегментов средней мозговой артерии (СМА). Были проанализированы исходные данные пациентов, диагностический алгоритм, сроки и результаты лечения. Критериями оценки результатов — технический успех реваскуляризации, наличие клинически значимой геморрагической трансформации, динамика неврологического дефицита по шкале NIHSS и модифицированной шкале Рэнкин, и исход заболевания в течение 90 дней.Из 16 оперированных пациентов у 13 удалось добиться технического успеха в виде восстановления проходимости ВСА и внутричерепных артерий. У 9 пациентов удалось добиться положительного эффекта в виде значительного регресса неврологической симптоматики (mRS2). У троих пациентов тяжелый неврологический дефицит сохранялся на всем периоде наблюдения, 4 больных скончались. Таким образом, эффективность методики составила 56,2% (Применение гибридных вмешательств при тандемных окклюзиях каротидных артерий позволяет существенно повысить эффективность и сократить время восстановления кровотока по крупным экстракраниальным сосудам у больных с тандемными поражениями в острейшей фазе ишемического инсульта, а также значительно снизить стоимость процедуры реперфузии. При наличии значимых атеросклеротических стенозов, одномоментная открытая эндартерэктомия из ОСА и ВСА имеет значительное преимущество в сравнении со стентированием, за счет отсутствия необходимости назначения антитромботической терапии.

To optimize the treatment strategy for acute mesenteric ischemia (AMI).The study included 43 patients aged 76.4±10.3 years. CT angiography and endovascular repair of mesenteric vessels underlie the new treatment approach.CT angiography according to the established criteria was performed in 31 patients with suspected AMI throughout 1 year. Sensitivity was 90.0%, specificity - 100%, accuracy - 95%. Endovascular interventions were applied in 13 patients (successful in 8 cases and unsuccessful in 5 patients). Mortality rate was 37.5%. Fifteen patients with clinical signs of peritonitis or after previous unsuccessful interventional revascularization underwent open surgery. Mortality rate was 86.7%.CT angiography is valuable to diagnose AMI at the stage of reversible changes in bowel wall in some cases. Endovascular revascularization as the first-line treatment has certain prospects.Оптимизация тактики при острой мезентериальной ишемии (ОМИ).В исследование включены 43 пациента. В основу нового подхода положено активное применение КТ-ангиографии (КТ-АГ) и эндоваскулярных вмешательств на мезентериальных сосудах.За год применения КТ-АГ по предложенным критериям исследование выполнено у 31 пациента с подозрением на ОМИ. Чувствительность составила 90%, специфичность — 100%, точность — 95%. Эндоваскулярные вмешательства применены у 13 больных: в 8 случаях успешно, в 5 случаях безуспешно. Уровень летальности составил 37,5%. У 15 больных с клиникой перитонита либо после безуспешных попыток реваскуляризации интервенционным способом выполнены полостные вмешательства с уровнем летальности 86,7%.Активное использование КТ-АГ позволяет в определенных случаях диагностировать ОМИ на стадии обратимых изменений кишечной стенки. Применение эндоваскулярных вмешательств первым этапом лечения имеет перспективы.

A literature review of the publications of foreign authors on the treatment of non-varicose bleeding from the upper gastrointestinal tract of elderly and senile patients is presented. The authors showed a modern view of the possibilities of endovascular hemostasis in comparison with a surgical operation with inefficiency of endoscopic hemostasis and characterized patients in whom it is possible this will be most effective.Представлен литературный обзор публикаций иностранных авторов по лечению неварикозного кровотечения из верхнего отдела ЖКТ у больных пожилого и старческого возраста. Авторы отобразили современный взгляд на возможности эндоваскулярного гемостаза в сравнении с хирургической операцией при неэффективности эндоскопического гемостаза и охарактеризовали пациентов, у которых, возможно, это будет максимально эффективно.

Background Bloodstream infections (BSI) remain a major challenge with high mortality rate, with an incidence that is increasing worldwide. Early treatment with appropriate therapy can reduce BSI-related morbidity and mortality. However, despite recent progress in molecular based assays, complex sample preparation steps have become critical roadblock for a greater expansion of molecular assays. Here, we report a size based, label-free, bacteria separation from whole blood using elasto-inertial microfluidics. Results In elasto-inertial microfluidics, the viscoelastic flow enables size based migration of blood cells into a non-Newtonian solution, while smaller bacteria remain in the streamline of the blood sample entrance and can be separated. We first optimized the flow conditions using particles, and show continuous separation of 5 μm particles from 2 μm at a yield of 95% for 5 µm particle and 93% for 2 µm particles at respective outlets. Next, bacteria were continuously separated at an efficiency of 76% from undiluted whole blood sample. Conclusion We demonstrate separation of bacteria from undiluted while blood using elasto-inertial microfluidics. The label-free, passive bacteria preparation method has a great potential for downstream phenotypic and molecular analysis of bacteria. Electronic supplementary material The online version of this article (doi:10.1186/s12951-016-0235-4) contains supplementary material, which is available to authorized users.

Signaling through both angiotensin AT1 receptors (AT1R) and dopamine D1 receptors (D1R) modulates renal sodium excretion and arterial BP. AT1R and D1R form heterodimers, but whether treatment with AT1R antagonists functionally modifies D1R via allosterism is unknown. In this study, the AT1R antagonist losartan strengthened the interaction between AT1R and D1R and increased expression of D1R on the plasma membrane in vitro. In rat proximal tubule cells that express endogenous AT1R and D1R, losartan increased cAMP generation. Losartan increased cAMP in HEK 293a cells transfected with both AT1R and D1R, but it did not increase cAMP in cells transfected with either receptor alone, suggesting that losartan induces D1R activation. Furthermore, losartan did not increase cAMP in HEK 293a cells expressing AT1R and mutant S397/S398A D1R, which disrupts the physical interaction between AT1R and D1R. In vivo, administration of a D1R antagonist significantly attenuated the antihypertensive effect of losartan in rats with renal hypertension. Taken together, these data imply that losartan might exert its antihypertensive effect both by inhibiting AT1R signaling and by enhancing D1R signaling.

Calcyon is a brain-specific protein, implicated in clathrin-mediated endocytosis. In this descriptive study we show that calcyon is exclusively expressed in neurons, and localized in moving vesicles. The movement of calcyon-containing vesicles was dependent on temperature and on intact microtubules, in addition these vesicles were colocalized with a marker for endocytosed plasma membrane proteins, suggesting that calcyon vesicles follow the endocytic recycling pathway. We also show using evanescent wave microscopy that there is a pool of ready releasable calcyon vesiclesaccumulated beneath the plasma membrane. We conclude that the mobility and storage properties of calcyon-containing vesicles imply that they play a role in brain plasticity.

Introduction of transvesical extraurethral adenomectomy into clinical practice was preceded by the clinical and morphological study of the prostate, prostatic urethra, bladder, upper urinary tract and renal function. It was found that at any volume of adenomatous (hyperplastic) tissue in the prostate, front semicircle around the prostatic urethra remains intact, and changes occur only in the proximal part of its back semicircle. Front semicircle adherent to the anterior commissure of the prostate has no adenomatous tissue. Extraurethral method enables you to perform a prostatectomy at any size of adenomatous tissue (fragmentarily) with preservation of the prostatic urethra, urethral vascular plexus and, if necessary, to carry out the vesico-urethral segment correction without blood loss. Free independent urination is recovered at days 10-12 after the healing of the suprapubic surgical wound and removal of drainage tube. Since the introduction of transvesical extraurethral prostatectomy into clinical practice, more than 3,000 radical adenomectomies at different stages in patients with co-morbidities were performed only at Burdenko Central Military Clinical Hospital and the 2nd Mandryka CMCH.

The body posture during standing and walking is maintained due to the activity of a closed-loop control system. In the review, we consider different aspects of postural control: its functional organization, the distribution of postural functions in different parts of the central nervous system, and the activity of neuronal networks controlling posture.

Birth is a transition from an underwater life in the uterus to a terrestrial life in a milieu where supply of water is limited. Rapid adaptation to the new environment is crucial for survival and health of infants. The discovery of a family of molecules-aquaporin (AQP) water channels-that are responsible for regulated water transport across cell membranes has made it possible to identify the molecular mechanisms behind the postnatal homeostatic adaptation and to better understand water imbalance-related disorders in infancy and childhood. Thirteen mammalian AQP isoforms have been identified, most of them having a unique tissue-specific pattern of expression. Most mammalian AQPs can be dynamically regulated, which makes them potential targets for the development of new drugs for diseases associated with disturbances in water homeostasis. This review deals with AQP in kidney, lung, and brain. Evidence is presented that AQPs are expressed in a specific age-dependent manner and that the timed expression of AQPs may have a crucial role during the early postnatal period.

Chromosome 3p21.3 region is frequently (>90%) deleted in lung and other major human carcinomas. We subdivided 3p21.3 into LUCA and AP20 subregions and discovered frequent homozygous deletions (10-18%) in both subregions. This finding strongly implies that they harbor multiple tumor suppressor genes involved in the origin and/or development of major epithelial cancers. In this study, we performed an initial analysis of RBSP3/HYA22 , a candidate tumor suppressor genes located in the AP20 region. Two sequence splice variants of RBSP3/HYA22 (A and B) were identified, and we provide evidence for their tumor suppressor function. By sequence analysis RBSP3/HYA22 belongs to a gene family of small C-terminal domain phosphatases that may control the RNA polymerase II transcription machinery. Expression of the gene was drastically (>20-fold) decreased in 11 of 12 analyzed carcinoma cell lines and in three of eight tumor biopsies. We report missense and nonsense mutations in tumors where RBSP3/HYA22 was expressed, growth suppression with regulated transgenes in culture, suppression of tumor formation in severe combined immunodeficient mice, and dephosphorylation of ppRB by RBSP3/HYA22, presumably leading to a block of the cell cycle at the G 1 /S boundary.

A quantitative approach was applied to the study of in vivo expression of foreign genes introduced into mice by ballistic transfection. Because in some cases one must take into account both the level of synthesized protein and that of antibodies to it, we derived the equation which allows to calculate the exact quantity of both proteins. This formula was applied to in vivo expression of a chimeric (human/mice) immunoglobulin E gene. The immunochemical analysis using this equation showed that the Ig concentration succeeded 4, 6, 12 IU/ml and undetectable level, respectively, upon transfection in mouse liver, spleen, foot pad and ear cartilage.

We have examined the genetic aberrations in two near-diploid glioblastoma multiforme cell lines that appear to have arisen from different glial lineages. One cell line, Hu-O-2A/Gb1, expresses antigens and metabolic profiles characteristic of the oligodendrocyte-type-2 astrocyte (0-2A) lineage of the rat central nervous system. This line generates, in vitro, cells with characteristics of 0-2A progenitor cells, oligodendrocytes and astrocytes. The second cell line, IN1434, is derived from an astrocyte or a precursor cell restricted to astrocytic differentiation. In Hu-O-2A/Gb1 the sole homologue of chromosome 10 is disrupted at band 10p11–12.1 by translocation with chromosomes X and 15. The translocation breakpoint is localized between genetic markers D10S2103 and [D10S637, D10S1962, D10S355]. Other aberrations include a 5;14 translocation, deletion of the long and short arms of chromosome 16 and loss of one copy of the CDKN2 gene. IN1434 cells share some cytogenetic abnormalities with Hu-O-2A/Gb1 cells, despite their apparent derivation from a different biological origin, but also have translocations involving the long and short arms of chromosome 1 and the long arm of chromosome 7, and deletion of chromosome 13 at bands 13q12–21. © 1999 Cancer Research Campaign

B-cell chronic lymphocytic leukemia (B-CLL) is a human hematological neoplastic disease often associated with the toss of a chromosome 13 region between RB1 gene and locus D13S25, A new tumor suppressor gene (TSG) may be located in the region. A cosmid contig has been constructed between the Loci D13S1168 (W19598) and D13S25 (H2-42), which corresponds to the minimal region shared by B-CLL associated deletions. The contig includes more than 200 LANL and ICRF cosmid clones covering 620 kb, Three cDNAs likely corresponding to three different genes hare been found in the minimally deleted region, sequenced and mapped against the contigged cosmids, cDNA clone 10k4 as well as a chimeric clone 13g3, codes for a zinc-finger domain of the RING type and shares homology to some known genes involved in tumorigenesis (RET finger protein, BRCA1) and embryogenesis (MID1). We have termed the gene corresponding to 10k4/13g3 clones LEU5, This is the first gene with homology to known TSGs which has been found in the region of B-CLL rearrangements. (C) 1998 Federation of European Biochemical Societies.

Despite the development of endourology, issues of open surgical treatment of prostate adenoma remain relevant. It is not always possible to perform transurethral electro-resection of prostate or other minimally invasive surgery. Urologists performing the transvesical adenomectomy still often face serious complications in both early and late in the postoperative period. This article presents a 15-year experience of performing the extraurethral transvesical adenomectomy according to N.F. Sergienko procedure in 308 patients with BPH. Assessment of functional results was performed using uroflowmetry and IPSS score. The effectiveness of extraurethral transvesical adenomectomy (EUTA) was statistically confirmed. The use of EUTA technique allows minimizing intraoperative injury, maintaining the integrity of the front semicircumference and lateral sides of the vesico-urethral segment, which provides early rehabilitation of damaged tissues and contributes to a significant reduction in the number of early and late postoperative complications.

The article considers the results of studying the aggregation function of thrombocytes including indicators of homeostasis system and routine biochemical markers in patients with chronic kidneys disease receiving hemodialysis sessions. It is demonstrated that plasma hemostasis is activated in all patients. The relationship is established between aggregation degree and level of fibrinolitic activity of plasma and concentration of calcium and phosphorus in blood serum.

True non-parasitic splenic cysts are a rare pathology represented by some 800 cases recorded worldwide. The method of choice for the treatment of this condition is surgical intervention. To-day, open surgery is substituted by low-invasive methods, such as laparoscopic splenectomy. A clinical case is described illustrating approaches to diagnostics and stages of surgical management of this pathology.

Surgeons of the clinic of P.V. Mandryka Central Military Hospital have rich 10-year experience in creation of neobladders after cystectomy. So, from 2000 to 2009 a total of 90 cystectomies were made for different diseases of the urinary bladder and prostatic gland as well as in cancer of the other pelvic organs. Vesicoplasty, both heterotopic and orthotopic, was performed from an iliac segment by an original technique with creation of antireflux bypass with the ureters. The examination of the patients in different terms after operation (up to 10 years later) provided information about changes in the neobladder under the influence of urine and systemic changes in the body. The analysis of the results show that creation of the iliac neobladder in our modification is perspective, while side effects are rare. Further long-term follow-up will give new arguments for and against this procedure.

The postural system maintains a specific body orientation and equilibrium during standing and during locomotion in the presence of many destabilizing factors (external and internal). Numerous studies in humans have revealed essential features of the functional organization of this system. Recent studies on different animal models have significantly supplemented human studies. They have greatly expanded our knowledge of how the control system operates, how the postural functions are distributed within different parts of CNS, and how these parts interact with each other to produce postural corrections and adjustments. This review outlines recent advances in the studies of postural control in quadrupeds, with special attention given the neuronal postural mechanisms.

Lung monitoring and visualization in intensive care unit (ICU) patients is a difficult task. Chest X-ray and auscultation are the most commonly used methods today. The new technique vibration response imaging (VRI) based on the vibration that is generated by airflow in the lung and that is its surrogate manifestation allows visualization of lung function. This method provides clinicians with an easy-to-use, non-radiation, non-invasive acoustic-based imaging technique of visual and quantitative evaluation of the lung. VRI objective dynamic image is a clinical addition to the existing static visual modalities used in the ICU.

The authors effectuated a retrospective analyze of operative treatment of 108 patients with carcinoma of urocyst in urological unit of the 2nd CMCH by Mandryka P. V. for the period of 1995-2007.

To keep balance when standing or walking on a surface inclined in the roll plane, the cat modifies its body configuration so that the functional length of its right and left limbs becomes different. The aim of the present study was to assess the motor cortex participation in the generation of this left/right asymmetry. We recorded the activity of fore- and hindlimb-related pyramidal tract neurons (PTNs) during standing and walking on a treadmill. A difference in PTN activity at two tilted positions of the treadmill (± 15 deg) was considered a positional response to surface inclination. During standing, 47% of PTNs exhibited a positional response, increasing their activity with either the contra-tilt (20%) or the ipsi-tilt (27%). During walking, PTNs were modulated in the rhythm of stepping, and tilts of the supporting surface evoked positional responses in the form of changes to the magnitude of modulation in 58% of PTNs. The contra-tilt increased activity in 28% of PTNs, and ipsi-tilt increased activity in 30% of PTNs. We suggest that PTNs with positional responses contribute to the modifications of limb configuration that are necessary for adaptation to the inclined surface. By comparing the responses to tilts in individual PTNs during standing and walking, four groups of PTNs were revealed: responding in both tasks (30%); responding only during standing (16%); responding only during walking (30%); responding in none of the tasks (24%). This diversity suggests that common and separate cortical mechanisms are used for postural adaptation to tilts during standing and walking.

New comparative genome hybridization technology on NotI-microarrays is presented (Karolinska Institute International Patent WO02/086163). The method is based on comparative genome hybridization of NotI-probes from tumor and normal genomic DNA with the principle of new DNA NotI-microarrays. Using this method 181 NotI linking loci from human chromosome 3 were analyzed in 200 malignant tumor samples from different organs: kidney, lung, breast, ovary, cervical, prostate. Most frequently (more than in 30%) aberrations--deletions, methylation,--were identified in NotI-sites located in MINT24, BHLHB2, RPL15, RARbeta1, ITGA9, RBSP3, VHL, ZIC4 genes, that suggests they probably are involved in cancer development. Methylation of these genomic loci was confirmed by methylation-specific PCR and bisulfite sequencing. The results demonstrate perspective of using this method to solve some oncogenomic problems.

Water channels AQP7 and AQP8 may be involved in transcellular water movement in the small intestine. We show that both AQP7 and AQP8 mRNA are expressed in rat small intestine. Immunoblot and immunohistochemistry experiments demonstrate that AQP7 and AQP8 proteins are present in the apical brush border membrane of intestinal epithelial cells. We investigated the effect of several metals and pH on the osmotic water permeability (Pf) of brush border membrane vesicles (BBMVs) and of AQP7 and AQP8 expressed in a cell line. Hg2+, Cu2+, and Zn2+caused a significant decrease in the BBMV Pf, whereas Ni2+and Li+had no effect. AQP8-transfected cells showed a reduction in Pfin the presence of Hg2+and Cu2+, whereas AQP7-transfected cells were insensitive to all tested metals. The Pfof both BBMVs and cells transfected with AQP7 and AQP8 was not affected by pH changes within the physiological range, and the Pfof BBMVs alone was not affected by phlorizin or amiloride. Our results indicate that AQP7 and AQP8 may play a role in water movement via the apical domain of small intestine epithelial cells. AQP8 may contribute to the water-imbalance-related clinical symptoms apparent after ingestion of high doses of Hg2+and Cu2+.

Different species maintain a particular body orientation in space (upright in humans, dorsal-side-up in quadrupeds, fish and lamprey) due to the activity of a closed-loop postural control system. We will discuss operation of spinal and supraspinal postural networks studied in a lower vertebrate (lamprey) and in two mammals (rabbit and cat). In the lamprey, the postural control system is driven by vestibular input. The key role in the postural network belongs to the reticulospinal (RS) neurons. Due to vestibular input, deviation from the stabilized body orientation in any (roll, pitch, yaw) plane leads to generation of RS commands, which are sent to the spinal cord and cause postural correction. For each of the planes, there are two groups of RS neurons responding to rotation in the opposite directions; they cause a turn opposite to the initial one. The command transmitted by an individual RS neuron causes the motor response, which contributes to the correction of posture. In each plane, the postural system stabilizes the orientation at which the antagonistic vestibular reflexes compensate for each other. Thus, in lamprey the supraspinal networks play a crucial role in stabilization of body orientation, and the function of the spinal networks is transformation of supraspinal commands into the motor pattern of postural corrections. In terrestrial quadrupeds, the postural system stabilizing the trunk orientation in the transversal plane was analyzed. It consists of two relatively independent sub-systems stabilizing orientation of the anterior and posterior parts of the trunk. They are driven by somatosensory input from limb mechanoreceptors. Each sub-system consists of two closed-loop mechanisms - spinal and spino-supraspinal. Operation of the supraspinal networks was studied by recording the posture-related activity of corticospinal neurons. The postural capacity of spinal networks was evaluated in animals with lesions to the spinal cord. Relative contribution of spinal and supraspinal mechanisms to the stabilization of trunk orientation is discussed.

Results of treatment of 61 patients with "mallet finger" injuries have been analyzed. After discontinuation of permanent immobilization the patients of the main group (n = 20) underwent "splint dishabituation" consequentially and bit by bit during 8 weeks, according to an original protocol developed with special reference to the stages of biological process of union of the damaged tendon. Following permanent immobilization patients of the group of comparison (n = 35) were recommended to use a removable splint at night during two weeks. The proposed protocol of "splint dishabituation" improved the results of treatment of injuries of the "mallet finger" type.

The aim is to study influence of short-term episodes ischemic of myocardium in a combination with intravenous introduction of creatine phosphate on current of ischemic heart disease at the patients with distal stenoses of coronary arteries. We survey 86 patients, which were divided into two groups: basic, which are receiving neoton in a combination with ischemic training and control who are receiving standard antianginal therapy. The research proceeded within 5 years. The authentic improvement of tolerance to physical effort, quality of life, decrease anginal attacks and normalization systolic and diastolic cardiac function of the basic group is marked.

Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several other tissues. Erythrocytes are, together with kidney and liver, the main targets for copper toxicity. Here we report that both water and glycerol permeability of human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the natural buffer system in our body, doses in the range of those observed in Wilson disease and in copper poisoning caused significant inhibition. AQP7, another aquaglyceroporin, was insensitive to copper. Three extracellular amino acid residues, Trp128, Ser152, and His241, were identified as responsible for the effect of copper on AQP3. We have previously shown that Ser152 is involved in regulation of AQP3 by pH. The fact that Ser152 mediates regulation of AQP3 by copper may explain the phenomenon of exquisite sensitivity of human erythrocytes to copper at acidic pH. When AQP3 was co-expressed with another AQP, only glycerol but not water permeability was inhibited by copper. Our results provide a better understanding of processes that occur in severe copper metabolism defects such as Wilson disease and in copper poisoning.

Physical chromosome mapping by fluorescence in situ hybridization (FISH) is among the major lines of research on the human genome (as well as genomes of numerous other organisms). To localize particular genes or anonymous DNA sequences on individual chromosomes or chromosome regions, FISH was developed in the late 1980s and early 1990s, when the International Human Genome Project and the Russian program Human Genome were launched. Now FISH continues to play a prominent part in studies of the human genome. The review considers the major steps of FISH development in Russia with special emphasis on the key roles of the Institute of Cytology and Genetics (Novosibirsk) and Engelhardt Institute of Molecular Biology (Moscow). Physical mapping of human chromosomes 3 and 13 by FISH is described in detail. The promotion of FISH in Russia contributed to the progress in the related fields such as comparative animal genomics (ZOO-FISH) and studies of plant chromosomes.

Hybridization of a loach (Misgurnus fossilis) oocyte 5S rRNA gene repeat with human chromosomes was carried out to refine the localization of the 5S RNA gene in the human genome. Preliminary in situ hybridization analysis showed that this repeat hybridized with human chromosome region 1q42→q43, the same location previously reported for the human 5S rRNA gene. High-resolution banding revealed the presence of two sites of hybridization, with a main peak in chromosome region 1q42.1 and a second peak in 1q43. These results are consistent with our data on the existence in the human genome of different 5S rRNA gene clusters specified by BamHl and Hindlll restriction sites in spacer DNA (Timofeeva et al., 1993) and suggest a multicluster organization of the human 5S rRNA genes.

Most human somatic cells have no telomerase activity. This leads to terminal underreplication of chromosomes and, hence, proliferative ageing of cells. We studied the consequences of introduction of the gene of the catalytic component of human telomerase hTERT in the normal fibroblasts of adult human skin. The expression of this gene led to the appearance of telomerase activity in the fibroblasts, elongation of telomeres (to the size characteristic of the embryonic cells), and immortalization. The cells retained their normal karyotype. The activity of ribosomal genes remained unchanged: the degree of their methylation, abundance, and transcriptional activity (two clones were studied). The cells did not undergo significant changes after transition over the Hayflick's limit, retained the constant rate of proliferation (one of the clones was followed to the level of 200 duplications of the population), and resembled, in appearance, young diploid human fibroblasts. The initial cells and cells transfected by an empty vector could pass through no more than 68 duplications, their proliferation slowed down and they acquired the morphology characteristic for the ageing cells. The telomerized cells retained the normal capacity of entering the proliferative rest as a result of serum starvation. Telomerization did not eliminate the contact inhibition of proliferation but led to an increased saturating density of cells, which reached the levels characteristic for the early embryonic cells. The long-term suppression of the telomerase function by azidothymidine led to a shortening of telomeres and significantly slowed down cell proliferation. The cells that did not divided for a long time were enlarged, preserved their viability, and resembled, in appearance, the ageing cells. In the test on heterokaryons (index of telomerase activity on the chromosomes inside the cell), the telomerized cells behaved as other immortal cells. All these data suggest that the telomerized cells preserved the normal mechanisms of regulation of cell proliferation.

Nickel is a common cause of pneumoconiosis. Here, we show that nickel inactivates aquaporin (AQP)-3, the water channel expressed apically in epithelial cells of human terminal airways. Human AQP3 was transiently transfected into human lung cells, and water permeability was measured in transfected and neighboring untransfected cells. Incubation with NiCl2 rapidly, dose-dependently, and reversibly decreased water permeability in AQP3-expressing cells. Acidification of the extracellular medium also caused rapid, dose-dependent, and reversible inhibition of AQP3. Sensitivity of AQP3 to nickel was lower at alkaline pH than at neutral and acidic pH. Cells transfected with human AQP4 and AQP5, which are also expressed in airway epithelia, were insensitive to nickel and extracellular acidification. Zinc and cadmium, other common causes of pneumoconiosis, had no effect on the water permeability of AQP3. Three extracellular residues, Trp128, Ser152, and His241, were responsible for the blocking effect of nickel on human AQP3. Ser152 was identified as a common site for nickel and pH sensitivity. His53, Tyr124, and His154 were also involved in regulation of AQP3 by extracellular pH. In addition, the aromatic side chain of His154 was shown to be important for the water permeability of AQP3. Our results imply that nickel and extracellular pH may modulate lung water clearance and that defective water clearance may be an early component of nickel-induced lung disease.

Forty-five patients (32 with open arterial duct and 13 with aortic coarctation) were examined. Forty-nine intravascular ultrasonic examinations were performed, qualitative and quantitative analysis of 139 vascular segments was carried out. Despite the fact that mean morphometric indices of open arterial duct and aorta in angiography and intravascular ultrasonic examination had no significant difference, real confidence of the o data was seen only in 13.3% cases for open arterial duct an in 16.7% cases--for aortic coarctation. In 37.5 and 50% patients, respectively, difference in the dimensions was so significant that dictated choice of instruments with difference size. Roentgenoendovascular surgeries were performed in 23 patients with open arterial duct and in 12--with aortic coarctation. Choice of instruments parameters based on data of intravascular ultrasonic examination provided safer and more efficient procedures.

Owing to a great progress in studying the human genome, its euchromatic portion is almost completely sequenced; the complete sequence is still unknown only for pericentric and telomeric regions and short arms of acrocentric chromosomes. Extended satellite blocks and segment duplications located in these regions substantially hinder the joining of the sequenced fragments and construction of the full-length genome map. The sequence was established for a 1.5-kb human chromosome 13 subtelomeric region, which is about 10 kb away from the rDNA cluster, and deposited in GenBank under accession no. AF478540. The region showed 83-84% homology to the pericentric region of human chromosome 19, and contained short fragments homologous to the pericentric region of human chromosome 13. The results may contribute to the current revision of genome evolution concepts in view of numerous segment duplications revealed.

Background Successful automated chromosome analysis requires the development of new techniques to increase and standardize chromosome length and improve banding patterns. Methods Human and plant cells were pretreated with the DNA intercalator 9-aminoacridine (9-AMA), and chromosomes were stained with GTG and aceto-orcein banding techniques and investigated by an image analysis system. Results The human optimal chromosome spreads with the 850 G-band resolution level, suitable for image analysis, were obtained by 9-AMA pretreatment for 1 h at a final concentration of 0.5–1 μg/ml, as compared with 600–700 bands after ethidium bromide treatment and about 400 bands without pretreatment. The best results for plant chromosomes were obtained after pretreatment with 1–2 μg/ml of 9-AMA for 12–24 h. The chromosomes elongated approximately 1.5-fold, and the resolution of chromosome banding patterns increased, reaching approximately 140 bands per haploid set in the case of camomile. Conclusions 9-AMA is an efficient reagent for the standardization and increasing the resolution of chromosome banding patterns in human and plant chromosomes. It is extremely important for chromosome investigation in small plants. Cytometry Part A 51A:52–57, 2003. © 2002 Wiley-Liss, Inc.

In previous work we demonstrated that various types of cultured cells with a limited life span could not reactivate DNA synthesis in the nuclei of mouse peritoneal macrophages in heterokaryons. We now investigate the role of telomerase in the process of the macrophage nucleus reactivation in heterokaryons with immortal telomerase-positive 3T3 Swiss mouse fibroblasts and human fibroblasts with introduced hTERT gene. We report that introduction of the hTERT gene into human diploid fibroblasts results in emergence of telomerase activity in these cells and the ability to induce the reactivation of DNA synthesis in the macrophage nuclei in heterokaryons. Inhibition of telomerase activity in heterokaryons by reverse transcriptase inhibitors (azidothymidine and guanosine polyphosphonate analogues) and by a 2′-O-methyl-RNA oligonucleotide anti-sense to the template region of telomerase RNA, block reactivation of DNA synthesis in macrophage nuclei without inhibiting DNA synthesis in the nuclei of fibroblasts. Our results suggest alterations (shortening or damage) in the macrophage telomere structure. As far as we know, heterokaryons with macrophages are the first cellular model for rapid investigation of the effects of telomerase inhibitors.

Sequence tagged sites generated for 60 NotI clones (NotI-STSs) from human chromosome 3-specific NotI-jumping and NotI-linking libraries were physically located using PCR screening of a radiation hybrid (RH) GeneBridge4 panel. The NotI map of chromosome 3 was generated using these RH-mapping data and those obtained earlier by FISH and sequencing of the corresponding NotI clones. The sequences of the NotI clones showed significant homologies with known genes and/or ESTs for 58 NotI-STSs (97%). These 58 NotI clones displayed 91-100% identity to 54 genes and 23 cDNA/EST clones. One known and two hypothetical protein-coding genes were localized for the first time and nine cDNA clones (unknown genes) were also carefully mapped only in this work. Three newly mapped genes are histone gene H1X (NR1-BK20C) and genes for hypothetical proteins THC1032178 and THC1024604 (NL1-243).

Summary Macrophage-like development of myeloid leukemia cells which can be induced by agents such as phorbol esters (TPA) is accompanied by integrin expression and cell adhesion. Thus, in differentiating myeloid leukemia cells CD11b is predominantly expressed which can associate with CD18 to form the functional heterodimeric integrin Mac-1. To elucidate the role of cell adhesion during macrophage-like differentiation, we transfected human U937 myeloid leukemia cells with a vector containing the CD11b gene in antisense orientation. Expression of the CD11b antisense gene in stably transfected U937 cells (as-CD11b cells) resulted in an attenuated response to TPA. As-CD11b cells demonstrated poor adhesion to solid substrate upon TPA treatment in contrast to U937 control cells. Constitutive expression of c-myc in as-CD11b transfectants was higher than in control cells and failed to be repressed by TPA treatment. Moreover, unlike control cells, antisense transfectants failed to induce expression of early response genes such as c-jun and the redox factor ref-1 upon TPA stimulation. Consequently, the induction of monocytic differentiation markers such as the activity of α-naphthyl acetate esterase, the capacity to reduce nitroblue tetrazolium and the expression of the vimentin gene was much lower in antisense transfectants than in control U937 cells. According to the failure to undergo a monocytic differentiation program, TPA treatment of as-CD11b cells resulted in a progressively increasing amount of apoptotic cells whereas the differentiated population of U937 control cells remained alive. Taken together, these data suggest that the integrin-mediated (particularly CD11b – mediated) adhesion of myeloid leukemia cells in the course of induced monocytic differentiation is crucial for cell attachment, development of a monocytic phenotype and subsequent survival.

Results of roentgenendovascular treatment of arterial thrombosis by rheolytic thrombectomy with "Angiojet" are presented. 18 patients (1 woman, 17 men) underwent 19 rheolytic thrombectomies from peripheral arteries. Mean age of patients was 53.3 +/- 3.0 years, time of thrombosis--from 20-30 min to 60 days (mean 121 +/- 17 hours). Thrombectomy was performed from superficial femoral, popliteal or tibial arteries, or from all these vessels simultaneously. In one case thrombus was removed from femoro-popliteal graft. Rheolytic thrombectomy was combined with balloon angioplasty of hemodynamicaly important stenosis, 5 patients underwent implantation of 9 stents. Good and satisfactory results were achieved in 77.8% patients; thrombectomy as the stage of operation was ineffective in one case only. Rheolytic thrombectomy from coronary arteries was performed 3 times, with complete effect in 1 and with partial--also in 1 patient.

Failure of drug therapy of Duchenne muscular dystrophy (DMD) stimulated intense search for adequate methods of gene therapy (GT) which would ensure effective delivery of the dystrophin (D) gene, its long-term persistence in transfected cells, and its expression in muscle fibers. The main results of the experimental GT of DMD with the use of viral and nonviral delivery of the D gene into muscles of biological models are discussed. Delivery of a mini-gene of D with a specific muscle promoter using a modified adenoassociated virus is currently the most promising method, which will soon be available for clinical trials. The main results of the studies on the DMD GT in Russia are summarized. The results of experiments on genetic transfection of mdx mice with marker genes and various constructions with the D gene are outlined. The genes are delivered into muscles by means of gene gun, electroporation, viral oligopeptides, liposomes, microspheres, lactoferine, and other nonviral vehicles. It is emphasized that consolidation of funds and efforts of all Russian laboratories dealing with gene and cell therapy of DMD are necessary to complete the experiments and start clinical trials.

We used the method of particle bombardment (ballistic transfection) to introduce beta-galactosidase and human dystrophin genes into mouse embryos and skeletal muscles of adult mice. We examined the mechanisms of DNA transfer into skeletal muscle cells, the biological processes accompanying and following this transfer, the susceptibility of various types of muscle cells to transfection, and the duration of expression of and conditions affecting the introduced genes. We have also developed an effective, convenient, and practical methods of skeletal muscles transfection.