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1.
BMC Infect Dis ; 21(1): 1077, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663259

RESUMO

BACKGROUND: Taenia solium, present in most developing countries, infects many individuals and may result in their death. Neurocysticercosis (NCC) develops after invasion of the brain by parasitic larvae. It is the most common parasitic disease of the human central nervous system. On imaging scans it can be similar to brain tumors. We report a patient with a metastatic brain tumor and NCC. The co-presence of NCC was diagnosed based on specific neuroimaging- and epidemiologic findings. CASE PRESENTATION: A 36-year-old non-smoking Japanese woman with a history of non-small-cell lung cancer had undergone resection of the lower lobe followed by cytotoxic chemotherapy 2 years before apparently suffering recurrence. A positron emission computed tomography (PET) scan incidentally revealed multiple intracranial cold spots exhibiting differences in their shape and size. On brain magnetic resonance imaging (MRI) scans we observed many different patterns of peripheral edema and gadolinium-enhancing effects. As she had often visited Latin America and Southeast Asia and had eaten raw pork and Kimchi, we suspected that the brain lesions were due to NCC rather than metastatic brain tumors. However, serum immunoblotting assay and DNA analysis were negative for T. solium. Rather than performing resection, we administered albendazole (ABZ) and dexamethasone because her earlier cytotoxic chemotherapy had elicited severe pancytopenia. Except for a single large lesion in the left frontal lobe, this treatment resulted in a significant reduction in the size of these lesions and a decrease in perilesional edema. She underwent resection of the residual lesion 10 months later. Histology revealed it to be a metastatic tumor. Polymerase chain reaction (PCR) assay for NCC was negative. In the course of 11-months follow-up there has been no recurrence. CONCLUSION: This is the first presentation of NCC in a Japanese woman with a metastatic brain tumor. NCC was incidentally discovered on PET scans and, based on her travel history and epidemiological findings; it was diagnosed and successfully treated with ABZ. NCC is endemic in most developing countries and as visits to such countries have increased, NCC must be ruled out in patients with multiple cystic nodular brain lesions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neurocisticercose , Adulto , Feminino , Humanos , Japão , Recidiva Local de Neoplasia , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/tratamento farmacológico
2.
Nature ; 501(7468): 551-5, 2013 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-23842494

RESUMO

Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission, and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively. In mice, Anhui/1 and Shanghai/1 were more pathogenic than a control avian H7N9 virus (A/duck/Gunma/466/2011 (H7N9); Dk/GM466) and a representative pandemic 2009 H1N1 virus (A/California/4/2009 (H1N1pdm09); CA04). Anhui/1, Shanghai/1 and Dk/GM466 replicated well in the nasal turbinates of ferrets. In nonhuman primates, Anhui/1 and Dk/GM466 replicated efficiently in the upper and lower respiratory tracts, whereas the replicative ability of conventional human influenza viruses is typically restricted to the upper respiratory tract of infected primates. By contrast, Anhui/1 did not replicate well in miniature pigs after intranasal inoculation. Critically, Anhui/1 transmitted through respiratory droplets in one of three pairs of ferrets. Glycan arrays showed that Anhui/1, Shanghai/1 and A/Hangzhou/1/2013 (H7N9) (a third human A(H7N9) virus tested in this assay) bind to human virus-type receptors, a property that may be critical for virus transmissibility in ferrets. Anhui/1 was found to be less sensitive in mice to neuraminidase inhibitors than a pandemic H1N1 2009 virus, although both viruses were equally susceptible to an experimental antiviral polymerase inhibitor. The robust replicative ability in mice, ferrets and nonhuman primates and the limited transmissibility in ferrets of Anhui/1 suggest that A(H7N9) viruses have pandemic potential.


Assuntos
Vírus da Influenza A , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Replicação Viral , Animais , Antivirais/farmacologia , Células Cultivadas , Galinhas/virologia , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Cães , Inibidores Enzimáticos/farmacologia , Feminino , Furões/virologia , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A/química , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Influenza Humana/tratamento farmacológico , Macaca fascicularis/virologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Doenças dos Macacos/patologia , Doenças dos Macacos/virologia , Neuraminidase/antagonistas & inibidores , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/transmissão , Codorniz/virologia , Suínos/virologia , Porco Miniatura/virologia , Replicação Viral/efeitos dos fármacos
3.
Neuropathology ; 37(1): 52-57, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27297614

RESUMO

Atypical teratoid/rhabdoid tumors (AT/RTs) are rare malignant neoplasms of the CNS that preferentially affect young children. We herein report an adult case of AT/RT surviving for more than 5 years with the residual tumor. The patient, a 24-year-old man at onset, presented with a contrast-enhancing mass lesion in the left occipital lobe, and underwent partial tumor resection. Histologically, the tumor was predominantly composed of long spindle cells exhibiting nuclear palisading and perivascular pseudorosettes, which appeared to mimic mesenchymal, ependymal and Schwann cell tumors. A small number of isolated rhabdoid cells did not initially attract attention, and a tentative pathological diagnosis of a malignant mesenchymal tumor was made. In a later examination focusing on the small areas of rhabdoid cells, the extensive loss of the nuclear expression of INI1 was detected in all areas. Diffuse staining with vimentin and focal immunoreactivity for epithelial membrane antigen and alpha smooth muscle actin were observed not only in AT/RT foci, but also in spindle cell areas. Thus, polyphenotypic immunoreactivity was evident. Fluorescence in situ hybridization revealed a homozygous deletion of chromosome 22q covering the INI1 locus. Histopathological differences between infant and adult AT/RTs currently remain unclear. In the case of a malignant adult brain tumor showing a hardly classifiable morphology and immunophenotypic diversity, an analysis of the INI1 status may contribute to an accurate diagnosis.


Assuntos
Neoplasias Encefálicas/patologia , Lobo Occipital/patologia , Tumor Rabdoide/patologia , Teratoma/patologia , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Terapia Combinada , Irradiação Craniana , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/cirurgia , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/terapia , Temozolomida , Teratoma/diagnóstico por imagem , Teratoma/terapia , Resultado do Tratamento , Adulto Jovem
4.
J Med Case Rep ; 15(1): 111, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653404

RESUMO

BACKGROUND: Most sudden-onset hearing loss is due to otolaryngologic- and very rarely to cerebrovascular disease. We report a woman with sudden bilateral sensorineural hearing loss. This case suggests that even in the absence of brainstem or cerebellar signs, magnetic resonance imaging (MRI) and MR angiography (MRA) should be performed since such studies may reveal signs of life-threatening vertebrobasilar artery occlusion. CASE PRESENTATION: A 73-year-old Japanese woman with a history of hypertension, hyperlipidemia, and atrial fibrillation who suffered bilateral deafness with vertigo and vomiting was transferred from a local hospital to our department. On admission her consciousness was clear and vertigo was absent. Neurological examination revealed only bilateral sensorineural hearing loss. Head computed tomography (CT) returned no significant findings. The next morning she gradually developed severe drowsiness. Diffusion-weighted MRI demonstrated acute cerebral infarction in the brainstem and bilateral cerebellum; MRA showed basilar artery occlusion due to a cardioembolic thrombus. Revascularization was obtained by endovascular treatment. However, her condition worsened progressively during the following hours. CT revealed new brainstem lesions, massive cerebellar swelling, and obstructive hydrocephalus. She died on the second day after her admission. CONCLUSIONS: When hearing loss is due to vertebrobasilar occlusive disease, the prognosis is very poor. We suggest that vertebrobasilar stroke be suspected in patients with bilateral sensorineural hearing loss who present with risk factors for stroke such as atrial fibrillation and other neurologic signs.


Assuntos
Infartos do Tronco Encefálico/complicações , Doenças Cerebelares/complicações , AVC Embólico/complicações , Perda Auditiva Bilateral/etiologia , Perda Auditiva Súbita/etiologia , Diagnóstico Ausente , Insuficiência Vertebrobasilar/complicações , Idoso , Fibrilação Atrial/complicações , Artéria Basilar/diagnóstico por imagem , Infartos do Tronco Encefálico/diagnóstico por imagem , Doenças Cerebelares/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , AVC Embólico/diagnóstico por imagem , Feminino , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico por imagem
5.
Brain Pathol ; 28(5): 684-694, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28990708

RESUMO

Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow-up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by "astroblastic" pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S-100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break-apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma.


Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos X , Neoplasias Neuroepiteliomatosas/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Biomarcadores Tumorais/genética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/metabolismo , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/terapia , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Transativadores , Adulto Jovem
6.
Intern Med ; 41(7): 549-54, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12132523

RESUMO

A 57-year-old man showed high serum cortisol, plasma adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) levels with a large pituitary tumor and a prostatic cancer. High dose dexamethasone did not suppress cortisol secretion and CRH administration did not stimulate cortisol secretion. After surgical removal of the pituitary tumor, plasma CRH, ACTH and serum cortisol levels were normalized. Histological examinations showed pituitary adenoma and prostatic adenocarcinoma, and pituitary adenoma was stained with both anti-CRH and anti-ACTH antibodies, but prostatic cancer was not stained. A CRH-producing pituitary adenoma is a new type of Cushing's syndrome.


Assuntos
Adenoma/diagnóstico , Adenoma/metabolismo , Hormônio Adrenocorticotrópico/biossíntese , Hormônio Liberador da Corticotropina/biossíntese , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , Adenocarcinoma/complicações , Adenoma/complicações , Adenoma/cirurgia , Hormônio Adrenocorticotrópico/sangue , Hormônio Liberador da Corticotropina/sangue , Síndrome de Cushing/cirurgia , Dexametasona , Glucocorticoides , Humanos , Hidrocortisona/sangue , Hipofisectomia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Testes de Função Adreno-Hipofisária , Neoplasias da Próstata/complicações
7.
Hum Mol Genet ; 14(5): 575-83, 2005 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-15649948

RESUMO

Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.


Assuntos
Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Mutação , Amelogênese/genética , Amelogênese Imperfeita/patologia , Sequência de Aminoácidos , Animais , Mapeamento Cromossômico , Proteínas do Esmalte Dentário/metabolismo , Modelos Animais de Doenças , Etilnitrosoureia , Humanos , Camundongos , Dados de Sequência Molecular , Fenótipo , RNA Mensageiro/metabolismo , Análise de Sequência de DNA
8.
Biochem Biophys Res Commun ; 336(2): 609-16, 2005 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-16139793

RESUMO

The large-scale mouse mutagenesis with ENU has provided forward-genetic resources for functional genomics. The frozen sperm archive of ENU-mutagenized generation-1 (G1) mice could also provide a "mutant mouse library" that allows us to conduct reverse genetics in any particular target genes. We have archived frozen sperm as well as genomic DNA from 9224 G1 mice. By genome-wide screening of 63 target loci covering a sum of 197 Mbp of the mouse genome, a total of 148 ENU-induced mutations have been directly identified. The sites of mutations were primarily identified by temperature gradient capillary electrophoresis method followed by direct sequencing. The molecular characterization revealed that all the identified mutations were point mutations and mostly independent events except a few cases of redundant mutations. The base-substitution spectra in this study were different from those of the phenotype-based mutagenesis. The ENU-based gene-driven mutagenesis in the mouse now becomes feasible and practical.


Assuntos
Mapeamento Cromossômico/métodos , Análise Mutacional de DNA/métodos , Etilnitrosoureia/farmacologia , Camundongos/genética , Espermatozoides/efeitos dos fármacos , Animais , Sequência de Bases , Masculino , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Mutagênicos/farmacologia
9.
Hum Mol Genet ; 13(11): 1147-57, 2004 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-15102714

RESUMO

Mutant mouse models are indispensable tools for clarifying the functions of genes and for elucidating the underlying pathogenic mechanisms of human diseases. Currently, several large-scale mutagenesis projects that employ the chemical mutagen N-ethyl-N-nitrosourea (ENU) are underway worldwide. One specific aim of our ENU mutagenesis project is to generate diabetic mouse models. We screened 9375 animals for dominant traits using a clinical biochemical test and thereby identified 11 mutations in the glucokinase (Gk) gene that were associated with hyperglycemia. GK is a key regulator of insulin secretion in the pancreatic beta-cell. Approximately 190 heterozygous mutations in the human GK gene have been reported to cause maturity onset diabetes of the young, type 2 (MODY2). In addition, five mutations have been reported to cause permanent neonatal diabetes mellitus (PNDM) when present on both alleles. The mutations in our 11 hyperglycemic mutants are located at different positions in Gk. Four have also been found in human MODY2 patients, and another mutant bears its mutation at the same location that is mutated in a PNDM patient. Thus, ENU mutagenesis is effective for developing mouse models for various human genetic diseases, including diabetes mellitus. Some of our Gk mutant lines displayed impaired glucose-responsive insulin secretion and the mutations had different effects on Gk mRNA levels and/or the stability of the GK protein. This collection of Gk mutants will be valuable for understanding GK gene function, for dissecting the function of the enzyme and as models of human MODY2 and PNDM.


Assuntos
Diabetes Mellitus Tipo 2/genética , Modelos Animais de Doenças , Glucoquinase/genética , Camundongos Mutantes , Sequência de Aminoácidos , Animais , Glicemia/análise , Etilnitrosoureia , Feminino , Expressão Gênica , Teste de Tolerância a Glucose , Homozigoto , Insulina/administração & dosagem , Insulina/metabolismo , Resistência à Insulina , Fígado/patologia , Masculino , Camundongos , Dados de Sequência Molecular , Mutagênese , Fenótipo , Mutação Puntual , RNA Mensageiro/análise
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