ПАРАНЕОПЛАСТИЧЕСКОЕ ПОРАЖЕНИЕ ЦЕНТРАЛЬНОЙ И ПЕРИФЕРИЧЕСКОЙ НЕРВНОЙ СИСТЕМЫ ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ. КЛИНИЧЕСКИЙ СЛУЧАЙ

Paraneoplastic neurological syndrome involves the concurrent development of cancer and neurologicaldiseases. Breast cancer is the second most common cancer associated with paraneoplastic damage to the central and peripheral nervous system. Autoimmune genesis of the disease is characterized by the presence of highly specific onconeural antibodies, which selectively affect neurons in the brain cord, spinal cord and spinal ganglia, and cause the onset of neurological symptoms within 2 years before cancer is detected. Six well-characterized onconeural antibodies detected in the blood serum of breast cancer patients can be used for the laboratory diagnosis of paraneoplastic neurological syndrome. Of them, anti-Hu, anti-CV2 and anti-amphiphysin antibodies cause polyneuropathy most often. Anti-Yo antibody is usually associated with cerebellar degeneration. Multiple neuronal autoantibodies can be simultaneously detected in a patient. Removal of the tumor may lead to stabilization and even partial regression of the neurological symptoms in 70 % of patients. Therefore, the surgical treatment of cancer should consider not only the tumor extension, but also the severity and progression of neurological deficit. We present a case of paraneoplastic cerebellar degeneration and paraneoplastic polyneuropathy in a 50-year-old woman with the neurological symptoms appeared 5 months before breast infiltrating ductal carcinoma was detected. The current approaches to the diagnosis of paraneoplastic neurological syndrome, as well as feasibility of radical removal of the tumor due to progression of neurological deficit were discussed.Паранеопластический неврологический синдром предполагает параллельное развитие рака и неврологической болезни. Рак молочной железы является второй по частоте встречаемости злокачественной опухолью после рака легкого, ассоциированной с паранеопластическим поражением центральной и периферической нервной системы. Аутоиммунный генез заболевания предполагает наличие в крови высокоспецифичных онконевральных антител, избирательно поражающих нейроны головного, спинного мозга, спинальных ганглиев и вызывающих дебют неврологических симптомов в среднем за 2 года до диагностики рака. Шесть хорошо охарактеризованных и используемых в настоящее время в лабораторной диагностике паранеопластического неврологического синдрома онконевральных антител детектируются в сыворотке крови пациентов, страдающих раком молочной железы. Из них полиневропатию чаще вызывают anti-Hu, anti-CV2 и anti-amphiphysin антитела, а при мозжечковой дегенерации встречаются еще и anti-Yo антитела. У одного пациента могут быть обнаружены одновременно несколько типов нейрональных аутоантител. С точки зрения выявления рака на более ранних стадиях очевидна целесообразность проведения направленного онкологического поиска у пациентов с неврологическими симптомами и обнаруженными в крови онконевральными антителами. После удаления злокачественной опухоли, являющейся прямым источником нейрональных антигенов, в 70 % случаев имеет место стабилизация неврологических симптомов и даже частичный их регресс. Поэтому вопрос, касающийся хирургического лечения рака, необходимо рассматривать не только с точки зрения распространенности опухолевого процесса, но и с учетом тяжести и темпов прогрессирования неврологического дефицита. В статье описан клинический случай паранеопластической мозжечковой дегенерации и паранеопластической полиневропатии у женщины 50 лет с возникновением неврологических симптомов за 5 мес до обнаружения инфильтрирующей протоковой карциномы молочной железы. Обсуждены современные подходы к диагностике паранеопластического неврологического синдрома, а также вопросы течения неврологического заболевания на фоне химиотерапии рака и целесообразности радикального удаления опухоли в связи с нарастанием неврологического дефицита

Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.

Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the 'active' state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the 'deactive' state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I

Three dimensional electron microscopy reveals changing axonal and myelin morphology along normal and partially injured optic nerves

Following injury to the central nervous system, axons and myelin distinct from the initial injury site undergo changes associated with compromised function. Quantifying such changes is important to understanding the pathophysiology of neurotrauma; however, most studies to date used 2 dimensional (D) electron microscopy to analyse single sections, thereby failing to capture changes along individual axons. We used serial block face scanning electron microscopy (SBF SEM) to undertake 3D reconstruction of axons and myelin, analysing optic nerves from normal uninjured female rats and following partial optic nerve transection. Measures of axon and myelin dimensions were generated by examining 2D images at 5 µm intervals along the 100 µm segments. In both normal and injured animals, changes in axonal diameter, myelin thickness, fiber diameter, G-ratio and percentage myelin decompaction were apparent along the lengths of axons to varying degrees. The range of values for axon diameter along individual reconstructed axons in 3D was similar to the range from 2D datasets, encompassing reported variation in axonal diameter attributed to retinal ganglion cell diversity. 3D electron microscopy analyses have provided the means to demonstrate substantial variability in ultrastructure along the length of individual axons and to improve understanding of the pathophysiology of neurotrauma

Waterbugs (Heteroptera: Nepomorpha and Gerromorpha) as sources of essential n-3 polyunsaturated fatty acids in Central Siberian ecoregions

1. Aquatic systems are considered to be a main source of essential long-chain n-3 polyunsaturated fatty acids (PUFA), which are preferentially synthesized by microalgae and transferred along food chains to terrestrial consumers. Emerging aquatic insects comprise a significant part of this transfer of the essential PUFA from water to land. Quantitative data on PUFA content and composition are available mainly for rheophilic insects while taxa that are characteristic of wetlands and stagnant water bodies, such as aquatic Heteroptera, remain relatively unstudied. 2. We investigated the role of various waterbug taxa (Heteroptera: Nepomorpha and Gerromorpha) inhabiting different ecoregions in temperate Central Siberia (Russia) as potential sources of PUFA. The ecoregions were steppe, forest-steppe, hemiboreal forest and montane coniferous forest. Although these waterbugs insects are aquatic in both larval and adult stages, they can disperse through the landscape and transfer essential PUFAs from water to land so making them potentially available to terrestrial consumers. 3. Species of Naucoridae, Notonectidae and Corixidae were generally dominant in all ecoregions, attaining maximum biomass in the steppe. We showed that habitat or ecoregion played a major role in the variability of fatty acid composition of Notonectidae and Gerridae but not Corixidae. In contrast, the biochemical composition of the only naucoridae, Ilyocoris cimicoides, was largely affected by life stage. 4. Both the dominant families and species within them differed with respect to their mass-specific contents of essential long-chain PUFA of the n-3 family, namely eicosapentaenoic and docosahexaenoic acids. Corixid species had the highest content of these two essential PUFAs among the waterbug studies, and relative to literature reports for other aquatic insects. Corixids thus appear to be a potentially important vector for transfer of the essential biochemical compounds from water to land, especially in steppe ecoregions with numerous ephemeral water bodies

Waterbugs (Heteroptera: Nepomorpha and Gerromorpha) as sources of essential n-3 polyunsaturated fatty acids in Central Siberian ecoregions

1. Aquatic systems are considered to be a main source of essential long-chain n-3 polyunsaturated fatty acids (PUFA), which are preferentially synthesized by microalgae and transferred along food chains to terrestrial consumers. Emerging aquatic insects comprise a significant part of this transfer of the essential PUFA from water to land. Quantitative data on PUFA content and composition are available mainly for rheophilic insects while taxa that are characteristic of wetlands and stagnant water bodies, such as aquatic Heteroptera, remain relatively unstudied. 2. We investigated the role of various waterbug taxa (Heteroptera: Nepomorpha and Gerromorpha) inhabiting different ecoregions in temperate Central Siberia (Russia) as potential sources of PUFA. The ecoregions were steppe, forest-steppe, hemiboreal forest and montane coniferous forest. Although these waterbugs insects are aquatic in both larval and adult stages, they can disperse through the landscape and transfer essential PUFAs from water to land so making them potentially available to terrestrial consumers. 3. Species of Naucoridae, Notonectidae and Corixidae were generally dominant in all ecoregions, attaining maximum biomass in the steppe. We showed that habitat or ecoregion played a major role in the variability of fatty acid composition of Notonectidae and Gerridae but not Corixidae. In contrast, the biochemical composition of the only naucoridae, Ilyocoris cimicoides, was largely affected by life stage. 4. Both the dominant families and species within them differed with respect to their mass-specific contents of essential long-chain PUFA of the n-3 family, namely eicosapentaenoic and docosahexaenoic acids. Corixid species had the highest content of these two essential PUFAs among the waterbug studies, and relative to literature reports for other aquatic insects. Corixids thus appear to be a potentially important vector for transfer of the essential biochemical compounds from water to land, especially in steppe ecoregions with numerous ephemeral water bodies

PARANEOPLASTIC DAMAGE TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM IN BREAST CANCER: A CASE REPORT

Paraneoplastic neurological syndrome involves the concurrent development of cancer and neurologicaldiseases. Breast cancer is the second most common cancer associated with paraneoplastic damage to the central and peripheral nervous system. Autoimmune genesis of the disease is characterized by the presence of highly specific onconeural antibodies, which selectively affect neurons in the brain cord, spinal cord and spinal ganglia, and cause the onset of neurological symptoms within 2 years before cancer is detected. Six well-characterized onconeural antibodies detected in the blood serum of breast cancer patients can be used for the laboratory diagnosis of paraneoplastic neurological syndrome. Of them, anti-Hu, anti-CV2 and anti-amphiphysin antibodies cause polyneuropathy most often. Anti-Yo antibody is usually associated with cerebellar degeneration. Multiple neuronal autoantibodies can be simultaneously detected in a patient. Removal of the tumor may lead to stabilization and even partial regression of the neurological symptoms in 70 % of patients. Therefore, the surgical treatment of cancer should consider not only the tumor extension, but also the severity and progression of neurological deficit. We present a case of paraneoplastic cerebellar degeneration and paraneoplastic polyneuropathy in a 50-year-old woman with the neurological symptoms appeared 5 months before breast infiltrating ductal carcinoma was detected. The current approaches to the diagnosis of paraneoplastic neurological syndrome, as well as feasibility of radical removal of the tumor due to progression of neurological deficit were discussed