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急性非淋巴细胞白血病合并中枢神经系统浸润21例分析

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中国误诊学杂志 2004年第5期4卷 779-779页

作者：刘峥嵘郑州大学医学院一附院血液科河南郑州450052

我院1984-08～2001-l2确诊的急性非淋巴细胞白血病316例中,符合白血病中枢神经系统浸润(CNSL)诊断标准[1]21例,分析如下.

关键词：自血病非淋巴细胞急性/病理学中枢神经系统/病理学自血病浸润误诊

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The invasion routes of neurovirulent A Hong Kong 483/97 (H5N1) influenza virus into the central nervous system after respiratory infection in mice

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ARCHIVES OF VIROLOGY 2002年第7期147卷 1425-1436页

作者： Park, CH Ishinaka, M Takada, A Kida, H Kimura, T Ochiai, K Umemura, T Hokkaido Univ Lab Comparat Pathol Sapporo Hokkaido Japan Hokkaido Univ Grad Sch Vet Med Microbiol Lab Sapporo Hokkaido Japan Univ Tokyo Inst Med Sci Div Virol Tokyo Japan

A/Hong Kong/483/97 (H5N1) influenza virus (HK483) isolated from the third patient during the outbreak of chicken and human influenza in Hong Kong in 1997 was shown to be neurovirulent in mice. HK483 was inoculated intranasally to mice, and the invasion routes of the virus in the central nervous system (CNS) were investigated by immunohistochemical and in situ hybridization. The pathological changes consisted of bronchopneumonia, ganglionitis, and nonpurulent encephalomyelitis of the brain stem and the anterior part of the thoracic cord. Viral antigens and viral nucleic acids (RNA and mRNA) were demonstrated in the pterygopalatine, trigeminal and superior ganglions prior to or simultaneously with their detection in the CNS. The antigens and nucleic acids were also observed in the olfactory bulb from an early stage of the infection. In the spinal cord, virus-infected cells were first demonstrated in the grey matter of the thoracic cord. The virus, which primarily replicated in the lungs, was considered to invade the thoracic cord via cardiopulmonary splanchnic nerves and sympathetic nerves. These findings indicate that the virus reached the CNS through afferent fibers of the olfactory, vagal, trigeminal, and sympathetic nerves following replication in the respiratory mucosa.

关键词：抗原病毒/分析脑干/病毒学支气管肺炎/病理学支气管肺炎/病毒学中枢神经系统/病理学中枢神经系统/病毒学疾病模型动物脑脊髓炎/病理学脑脊髓炎/病毒学神经节交感/病毒学免疫组织化学原位杂交肺/病理学肺/病毒学小鼠近交BALBC 嗅球/病毒学正黏病毒科/遗传学正黏病毒科/免疫学正黏病毒科/分离和提纯正黏病毒科感染/病理学正黏病毒科感染/病毒学 RNA 信使/分析 RNA 病毒/分析脊髓/病毒学时间因素动物人类男(雄)性小鼠

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Nipah virus infection - Pathology and pathogenesis of an emerging paramyxoviral zoonosis

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AMERICAN JOURNAL OF PATHOLOGY 2002年第6期161卷 2153-2167页

作者： Wong, KT Shieh, WJ Kumar, S Norain, K Abdullah, W Guarner, J Goldsmith, CS Chua, KB Lam, SK Tan, CT Goh, KJ Chong, HT Jusoh, R Rollin, PE Ksiazek, TG Zaki, SR Ctr Dis Control & Prevent Infect Dis Pathol Act Natl Ctr Infect Dis Atlanta GA 30333 USA Minist Hlth Kuala Lumpur Malaysia Univ Malaya Kuala Lumpur Malaysia

In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological. findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.

关键词：亚洲东南部/流行病学血管/病理学血管/病毒学中枢神经系统/病理学中枢神经系统/病毒学中枢神经系统病毒感染/诊断中枢神经系统病毒感染/流行病学中枢神经系统病毒感染/病理学中枢神经系统病毒感染/病毒学传染病新出现/诊断传染病新出现/流行病学传染病新出现/病理学传染病新出现/病毒学疾病暴发流行神经元/病毒学副黏病毒科感染/诊断副黏病毒科感染/流行病学副黏病毒科感染/病理学副黏病毒科感染/病毒学副黏病毒亚科/生理学猪动物传染病青少年成年人老年人动物女(雌)性人类男(雄)性中年人

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Early detection of central nervous system relapse by polymerase chain reaction in children with B-precursor acute lymphoblastic leukemia

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ANNALS OF HEMATOLOGY 2002年第1期81卷 59-61页

作者： de Haas, V Vet, RJWM Verhagen, OJHM Kroes, W van den Berg, H van der Schoot, CE Univ Amsterdam Acad Med Ctr Emma Kinderziekenhuis NL-1105 AZ Amsterdam Netherlands Univ Amsterdam Acad Med Ctr Cent Lab Blood Transfus Serv NL-1105 AZ Amsterdam Netherlands Univ Amsterdam Acad Med Ctr Expt & Clin Immunol Lab NL-1105 AZ Amsterdam Netherlands Univ Amsterdam Acad Med Ctr Dept Cytogenet NL-1105 AZ Amsterdam Netherlands Blood Transfus Serv Cent Lab Dept Expt Immunohematol NL-1066 CX Amsterdam Netherlands

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Pivotal role of interleukin-12 and interferon-γ axis in controlling tissue parasitism and inflammation in the heart and central nervous system during Trypanosoma cruzi infection

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AMERICAN JOURNAL OF PATHOLOGY 2001年第5期159卷 1723-1733页

作者： Michailowsky, V Silva, NM Rocha, CD Vieira, LQ Lannes-Vieira, J Gazzinelli, RT Fundacao Oswaldo Cruz Inst Oswaldo Cruz Dept Immunol Rio De Janeiro Brazil Fundacao Oswaldo Cruz Rene Rachov Res Ctr Immunopathol Lab Belo Horizonte MG Brazil Univ Fed Minas Gerais Inst Biol Sci Dept Biochem & Immunol Belo Horizonte MG Brazil

The role of cytokines in the control of tissue parasitism and pathogenesis of experimental Chagas' disease was investigated. Wild-type and different cytokine as well as inducible nitric oxide synthase (iNOS) knockout mice were infected with the Colombian strain of Trypanosoma cruzi, and the kinetics of tissue parasitism, inflammatory reaction, parasitemia, and mortality were determined. We demonstrate the pivotal role of the interleukin (IL)-12/interferon (IFN)-gamma /iNOS axis and the antagonistic effect of IL-4 in controlling heart tissue parasitism, inflammation, and host resistance to acute infection with T. cruzi. Further, the heart and central nervous system were shown the main sites of reactivation of T. cruzi infection in mice lacking functional genes for IFN-gamma, and IL-12, respectively. Our results also show that in contrast to IFN-gamma knockout (KO) mice, splenocytes from IL-12 KO mice infected with T. cruzi produced low levels of IFN-gamma upon stimulation with antigen. Consistently, high levels of anti-T. cruzi IgG2a antibodies were detected in the sera from IL-12 KO, but not from IFN-gamma KO mice, infected with the Colombian strain of T. cruzi. Thus, our results suggest that the level of IFN-gamma deficiency is a major determinant of the site of reactivation of T. cruzi infection in immunocompromised-host.

关键词：中枢神经系统/寄生虫学中枢神经系统/病理学中枢神经系统疾病/寄生虫学中枢神经系统疾病/病理学 Chagas心肌病/寄生虫学 Chagas心肌病/病理学 Chagas病/寄生虫学 Chagas病/病理学疾病易感性心脏/寄生虫学干扰素γ/缺乏干扰素γ/遗传学干扰素γ/生理学白细胞介素12/缺乏白细胞介素12/遗传学白细胞介素12/生理学白细胞介素4/缺乏白细胞介素4/遗传学白细胞介素4/生理学小鼠近交BALBC 小鼠近交C57BL 小鼠基因敲除/遗传学心肌炎/寄生虫学心肌炎/病理学心肌/病理学一氧化氮合酶/缺乏一氧化氮合酶/遗传学一氧化氮合酶/生理学一氧化氮合酶Ⅱ型复发动物女(雌)性小鼠

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Experimental Elaphostrongylus cervi infection in sheep and goats

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JOURNAL OF COMPARATIVE PATHOLOGY 2000年第4期123卷 248-257页

作者： Handeland, K Gibbons, LM Skorping, A Natl Vet Inst Sect Wildlife Dis N-0033 Oslo Norway Univ London Royal Vet Coll Dept Pathol & Infect Dis Hatfield AL9 7TA Herts England Univ Bergen Dept Zool N-5007 Bergen Norway

The pathogenesis and migratory life cycle of Elaphostrongylus cervi were studied in four sheep and sir;goats killed and examined 6 days to 5 months after inoculation with infective third-stage larvae (L3). Detailed histological studies demonstrated that the L3 followed a porto-hepatic, and probably also a secondary lymphatic, migratory route from the abomasum and small intestine to the lungs, with subsequent spread via the general circulation to the central nervous system (CNS) and other tissues. In addition, the results suggested that haematogenously spread L3, arrested in arterial vessels outside the spinal card, migrated into the cord along the spinal nerves. During migration, the L3 caused focal inflammation and necrosis in the organs and along the spinal nerve roots, and infarcts occurred in the myocardium, kidneys and CNS. Nematode development took place in the CNS. During development, there was a gradual die-off of nematodes and patent infections were not observed. However, in one animal many mature nematodes were demonstrated in the CNS. In the nervous system, the nematodes caused encephalomyelitis, focal traumatic encephalomalacia, gliosis, meningitis, choroiditis, radiculitis and perineuritis. Two goats and one sheep displayed long-lasting paraparesis starting 6 weeks after inoculation. The signs apparently resulted from nematode-induced spinal nerve root lesions. From 19 weeks after inoculation the sheep also showed signs of severe brain disturbances due to traumatic and inflammatory lesions caused by adult E. cervi in the cerebral parenchyma. We conclude that E. cervi represents a potential cause of neurological disease in small ruminants grazing areas inhabited by red deer. This is the first report confirming the infectivity of E. cervi for domestic ruminants. (C) 2000 Harcourt Publishers Ltd.

关键词：中枢神经系统/寄生虫学中枢神经系统/病理学消化系统/寄生虫学消化系统/病理学山羊疾病/寄生虫学山羊疾病/病理学山羊肾/寄生虫学肾/病理学肝/寄生虫学肝/病理学肺/寄生虫学肺/病理学淋巴结/寄生虫学淋巴结/病理学后圆线虫总科/致病力心肌/病理学绵羊绵羊疾病/寄生虫学绵羊疾病/病理学圆线目感染/寄生虫学圆线目感染/病理学圆线目感染/兽医学动物女(雌)性男(雄)性

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Pathology of Madras type of motor neuron disease (MMND) - a histological and immunohistochemical study

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ACTA NEUROPATHOLOGICA 2000年第4期99卷 428-434页

作者： Shankar, SK Gourie-Devi, M Shankar, L Yasha, TC Santosh, V Das, S Natl Inst Mental Hlth & Neurosci Dept Neuropathol Bangalore 560029 Karnataka India Natl Inst Mental Hlth & Neurosci Dept Neurol Bangalore 560029 Karnataka India

A neuropathological report of Madras type of motor neuron disease (MMND) is presented and the differences from other forms of MND are discussed. An 18-year-old girl presented with nerve deafness and slow ly progressive bulbo-spinal muscular atrophy, characteristic of MMND. Post-mortem examination of the spinal cord showed a severe loss of anterior horn cells, prominent dilatation of vessels, diffuse, but sparse sprinkling of microglial cells and lymphocytes, and demyelination and sclerosis of the ventrolateral columns. Neuronal depletion and marked gliosis was noted in the cochlear nucleus on both sides, while other bulbar motor nuclei were also involved. The cochlear nerve showed demyelination and axonal loss. Trigeminal and vestibular ganglia revealed features of ganglionitis. The possibility of an inflammatory aetiology for MMND needs to be considered.

关键词：中枢神经系统/病理学致命性结局免疫组织化学印度运动神经元病/病理学青少年女(雌)性人类

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Zic2 regulates the kinetics of neurulation

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第4期97卷 1618-1623页

作者： Nagai, T Aruga, J Minowa, O Sugimoto, T Ohno, Y Noda, T Mikoshiba, K RIKEN Brain Sci Inst Dev Neurobiol Lab Wako Saitama 3510198 Japan RIKEN Tsukuba Life Sci Ctr Mol Neurobiol Lab Tsukuba Ibaraki 3050074 Japan Japanese Fdn Canc Res Inst Canc Dept Cell Biol Toshima Ku Tokyo 1708455 Japan Univ Tsukuba Div Res Facilitat Tsukuba Ibaraki 3058577 Japan Univ Tokyo Inst Med Sci Dept Mol Neurobiol Minato Ku Tokyo 1088639 Japan

Mutation in human ZIC2, a zinc finger protein homologous to Drosophila odd-paired, causes holoprosencephaly (HPE), which is a common, severe malformation of the brain in humans. However, the pathogenesis is largely unknown. Here we show that reduced expression (knockdown) of mouse Zic2 causes neurulation delay, resulting in HPE and spina bifida. Differentiation of the most dorsal neural plate, which gives rise to both roof plate and neural crest cells, also was delayed as indicated by the expression lag of a roof plate marker, Wnt3a, In addition the development of neural crest derivatives such as dorsal root ganglion was impaired. These results suggest that the Zic2 expression level is crucial for the timing of neurulation, Because the Zic2 knockdown mouse is the first mutant with HPE and spina bifida to survive to the perinatal period, the mouse will promote analyses of not only the neurulation but also the pathogenesis of human HPE.

关键词：骨和骨组织/胚胎学骨和骨组织/病理学细胞分化中枢神经系统/胚胎学中枢神经系统/病理学疾病模型动物胚胎和胎儿发育基因表达调控发育期基因打靶前脑无裂畸形/胚胎学原位杂交原位缺口末端标记小鼠基因敲除突变神经管缺损/遗传学核蛋白质类蛋白质类/遗传学椎管闭合不全/胚胎学转录因子/遗传学转录因子/药理学 Wnt蛋白质类 Wnt3蛋白质 Wnt3A蛋白质锌指动物人类小鼠

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A comparative study of pseudorabies virus (PRV) strains with defects in thymidine kinase and glycoprotein genes

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JOURNAL OF COMPARATIVE PATHOLOGY 2000年第2-3期123卷 152-163页

作者： Ferrari, M Mettenleiter, TC Romanelli, MG Cabassi, E Corradi, A Dal Mas, N Silini, R Ist Zooprofilatt Sperimentale Lombardia & Emilia I-25125 Brescia Italy Friedrich Loeffler Inst Fed Res Ctr Virus Dis Anim Insel Riems Germany Univ Verona Fac Med & Chirurg Ist Biol & Genet I-37100 Verona Italy Univ Parma Fac Med Vet Ist Anat Patol I-43100 Parma Italy Azienda Sanit Locale Brescia Italy

In the course of two experiments, an examination was made of the virulence and neuroinvasiveness for pigs of two pseudorabies virus mutants (strain 6C2TK(-), with a defect in thymidine kinase (TK) function;and strain 6C2TK(-), gI(-)/gE(-), with defects in TK and glycoproteins I and E) and of the wild-type parent strain (86/27V). At various times after intranasal inoculation, pigs were killed and samples of tonsil, lung and different levels of the trigeminal and olfactory nervous pathways were examined by methods that included viral isolation, polymerase chain reaction assay and immunohistochemistry. Both mutant viruses were of reduced virulence, as indicated by no more than moderate clinical signs and lesions, and only sporadic isolation of virus;moreover, unlike the wild-type parent strain, the mutant viruses were not reactivated from the latent state by corticosteroid treatment. In addition, migration of the mutant strains to the central nervous system (olfactory and trigeminal nervous pathways) was reduced as compared with that of the wild-type strain. Thus, mutations in the genes encoding the TK enzyme and the gI/gE complex were associated with reduced virulence, reduced replication in peripheral target tissues, and reduced migration to the olfactory and trigeminal pathways. (C) 2000 Harcourt Publishers Ltd.

关键词：抗体病毒/血液抗体病毒/药物作用抗原病毒/分析细胞系中枢神经系统/病理学中枢神经系统/病毒学 DNA 病毒/遗传学地塞米松/治疗应用疱疹病毒1型猪/遗传学疱疹病毒1型猪/免疫学疱疹病毒1型猪/致病力免疫组织化学突变嗅球/病理学嗅球/病毒学聚合酶链反应假性狂犬病/病理学假性狂犬病/预防和控制假性狂犬病/病毒学猪胸苷激酶/遗传学时间因素三叉神经节/病理学三叉神经节/病毒学病毒包膜蛋白质类/遗传学毒力/遗传学病毒激活/遗传学病毒潜伏期/遗传学动物

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Paradoxical influence of acid β-galactosidase gene dosage on phenotype of the twitcher mouse (genetic galactosylceramidase deficiency)

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HUMAN MOLECULAR GENETICS 2000年第11期9卷 1699-1707页

作者： Tohyama, J Vanier, MT Suzuki, K Ezoe, T Matsuda, J Suzuki, K Univ N Carolina Sch Med Ctr Neurosci Chapel Hill NC 27599 USA Univ N Carolina Sch Med Dept Neurol Chapel Hill NC 27599 USA Univ N Carolina Sch Med Dept Psychiat Chapel Hill NC 27599 USA Univ N Carolina Sch Med Dept Pathol & Lab Med Chapel Hill NC 27599 USA Lyon Sud Hosp Lyon Sud Sch Med & Fdn Gillet Merieux INSERM U189 F-69921 Oullins France

We have cross-bred twitcher mice (galactosylceramidase deficiency) and acid beta-galactosidase knockout mice (G(M1) gangliosidosis) and found that the acid beta-galactosidase gene dosage exerts an unexpected and paradoxical influence on the twitcher phenotype, Twitcher mice with an additional complete deficiency of acid beta-gatactosidase have the mildest phenotype with the longest lifespan and nearly rescued CNS pathology. In contrast, twitcher mice with a single functional acid beta-galactosidase gene have the most severe disease with the shortest lifespan, despite the fact that G(M1) gangliosidosis carrier mice with an otherwise normal genetic background are phenotypically normal. A significant proportion of these galc(-/-), bgal(+/-) mice clinically develop additional extreme hyper-reactivity and generalized seizures not seen in any other genotypes, Consistent with the clinical seizures, widespread neuronal degeneration is present in the galc(-/-), bgal(+/-) mice, most prominently in the CA3 region of the hippocampus. The double knockout mice show a massive accumulation of lactosylceramide in ail tissues. The brain inexplicably contains only a half-normal amount of galactosylceramide, which may account for the mild clinical and pathological phenotype, On the other hand, brain psychosine level is increased in all twitcher mice, but galc(-/-), bgal(+/-) mice show a significantly higher level than other genotypes, The reduced galactosylceramide in the brain of the double knockout mice and the significantly higher psychosine in the brain of the galc(-/-), bgal(+/-) mice cannot readily be explained from the genotypes of these mice. These observations are contrary to the expected outcome of Mendelian autosomal recessive single gene disorders and may also be interpreted as that the acid beta-galactosidase gene functions as a modifier gene for the phenotypic expression of genetic galactosylceramidase deficiency.

关键词：中枢神经系统/酶学中枢神经系统/代谢中枢神经系统/病理学半乳糖神经酰胺酶/缺乏半乳糖神经酰胺酶/遗传学基因型生长障碍/酶学生长障碍/遗传学生长障碍/死亡率肝/酶学肝/代谢肝/病理学小鼠近交C57BL 小鼠基因敲除小鼠突变型神经变性/酶学神经变性/遗传学神经变性/病理学表型存活率时间因素 β半乳糖苷酶类/遗传学 β半乳糖苷酶类/代谢动物女(雌)性男(雄)性小鼠

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