Assuntos
Síndrome Nefrótica , Humanos , Criança , Síndrome Nefrótica/tratamento farmacológico , HormôniosRESUMO
OBJECTIVE: High-risk (HR) human papillomavirus (HPV) is one of the major causes for most anal and penile cancers and oropharyngeal cancers in men, and vaccination against HPV is recommended for the prevention of these cancers. Data on HPV infection in Chinese men is still limited, which requires further investigation to guide vaccine development and assess the effectiveness of HPV vaccines. We thus studied the HR-HPV genotype distribution in HPV-infected men in Northern China. PATIENTS AND METHODS: Genital specimens were obtained from male patients (≥18 years old) at the clinic for sexually transmitted infections of the Shandong Provincial Hospital between January 2016 and December 2018. Samples were analyzed for 15 HR-HPV genotypes, and 2 low-risk HPV (LR-HPV) genotypes using a multiplex real-time quantitive polymerase chain reaction (qPCR) assay. RESULTS: Of 1,163 participants enrolled, 426 patients were diagnosed as verruca acuminata (CA) and 737 were asymptomatic men. The overall prevalence of HPV infection was 42% (489/1,163), and 27.4% (319/1,163) were positive for HR-HPV. HPV 16 (5.2%, 61/1,163) was the most common HR genotype overall, followed by HPV 52 (4.6%, 54/1,163), 51 (4.3%, 50/1,163), 18 (4.1%, 48/1,163), and 39 (4.0%, 47/1,163). Genotypes 16, 52, 39, 51, and 18 were most prevalent in CA patients, and 16, 51, 18, 59, and 39 in asymptomatic men. Prevalence of genotypes 31, 33, and 45 covered by the 9-valent HPV prophylactic vaccine was low in the assessed region. CONCLUSIONS: HPV 16, 52, 51, 18, 39, and 59 were the most common HR genotypes detected in men in Northern China. Importantly, HPV 39, 51, and 59 are not currently covered by either the 4-valent or 9-valent HPV vaccines.
Assuntos
Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/virologia , China , Estudos Transversais , Genótipo , Humanos , MasculinoRESUMO
Objective: To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). Methods: A retrospective analysis was performed on the clinical data, laboratory tests and genetic test results of three children with hematuria and the probands in three families with hematuria. The families were ascertained at the Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command from August 2014 to May 2018. Results: The proband of Family One, an 8-year-old boy, manifested gross hematuria. His renal biopsy pathology revealed IgAN. His father also manifested hematuria. Genetic testing showed that the proband and his father carried a heterozygous variant of the CFHR5 gene,533A>G (Asn178Ser). The child of Family Two, a 4-year-old girl, manifested hematuria. Her father, the proband of the family, was 36 years old, and manifested hematuria, proteinuria, high-frequency sensorineural deafness and renal insufficiency. He was diagnosed as IgAN according to clinical manifestations, renal pathology and routine immunohistochemistry without renal biopsy electron microscopy, renal tissue type â £ collagen α3, α4, α5 chains immunofluorescence and skin type â £ collagen α5 chain immunofluorescence. Genetic testing showed that the girl carried a heterozygous variant of the COL4A5 gene,566G>T (Gly189Val), and her father carried the hemizygous variant. The child of Family Three, a 7-year-old girl, manifested hematuria and proteinuria. Her mother, the proband of the family, was 34 years old, and manifested hematuria and proteinuria as well. The proband was diagnosed as IgAN by the same method used for Family Two. The girl's grandfather died of uremia at the age of 44. Genetic testing showed that the girl and her mother carried a heterozygous variant 539G>A (Gly180Glu)in COL4A5 gene. Conclusions: The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.
Assuntos
Variação Genética/genética , Hematúria/diagnóstico , Nefrite Hereditária/diagnóstico , Adulto , Criança , Pré-Escolar , Feminino , Testes Genéticos/métodos , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/patologia , Hematúria/genética , Humanos , Rim , Masculino , Nefrite Hereditária/genética , Estudos Retrospectivos , Sequenciamento do ExomaRESUMO
Objective: To investigate the prevalence and characteristics of pathogenic variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome (aHUS). Method: Eleven Han Chinese children with aHUS, including 9 boys and 2 girls aged between 1 year and 4 months and 13 years, were investigated in Department of Pediatrics, Fuzhou General Hospital, from November 1998 to February 2014. Analysis of variants of all the exons of 10 complement genes (CFH, MCP, CFI, C3, CFB, CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5), including 25 bases from 3' end and 25 bases from 5' end, was performed in the 11 cases by targeted sequence capture and next generation sequencing. Significant variants detected by next generation sequencing were confirmed by Sanger sequencing. To understand pathogenicity of variants found in the captured genes, we investigated genetic conservation by multiple protein sequence alignment among different species, and analyzed whether the variants were located in protein domains or not, and investigated functional significance by functional computational prediction methods. Result: Twenty-seven percent of Han Chinese children with aHUS carried pathogenic variants in the 10 complement genes. Pathogenic variant CFB 221G>A (R74H) was detected in Patient 3 and Patient 9, which was not found in parents of Patient 3' , and was found in healthy father of patient 9. Pathogenic variant CFHR5 242C>T (P81L) was found in Patient 2, and was found in healthy father of patient 2. However, no pathogenic variants in genes CFH, MCP, CFI, C3, CFHR1, CFHR2, CFHR3 and CFHR4 were identified. Conclusion: Pathogenic variants in the 10 complement genes were identified in 3/11 of Han Chinese children with aHUS in our study and CFB was the most frequently mutated gene.
Assuntos
Síndrome Hemolítico-Urêmica Atípica , Proteínas do Sistema Complemento , Adolescente , Sequência de Aminoácidos , Povo Asiático , Síndrome Hemolítico-Urêmica Atípica/genética , Criança , Pré-Escolar , Proteínas do Sistema Complemento/genética , Éxons , Feminino , Variação Genética , Humanos , Lactente , MasculinoRESUMO
The aim of this study was to investigate the selection of plasma exchange (PE) parameters and the safety of children with severe ricinism. The PE parameters and heparin dosage in 7 children with severe ricinism were recorded, and changes in the patients' vital signs and coagulation function were monitored before and after PE. All patients successfully completed PE. The speed of blood flow was 50-80 mL/min, speed of exchange flow was 600-800 mL/h, and isolating rate of blood plasma was 12.5-19.05%. Transmembrane pressure was stable at approximately 100 mmHg, and venous pressure was stable at approximately 95 mmHg. The first dose of heparin was 0.39 ± 0.04 mg/kg, and the maintaining heparin dose was 0.40 ± 0.05 to 0.22 ± 0.03 mg·kg(-1)·h(-1). During the PE process, mean arterial pressure, heart rate, respiratory rate, and pulse oxygen saturation were steady. After PE, the activated partial thromboplastin time and thrombin time prolonged to 2-3 times greater than that before PE. However, no bleeding tendency was seen. For children with severe ricinism, the choice of PE to eliminate the toxin from blood, tissues, and organs was safe and effective.
Assuntos
Troca Plasmática/métodos , Ricina/intoxicação , Ricinus communis/intoxicação , Coagulação Sanguínea/efeitos dos fármacos , Criança , Feminino , Humanos , Masculino , Tempo de Tromboplastina Parcial , Troca Plasmática/efeitos adversos , Tempo de TrombinaRESUMO
Mutations in the Wilms' tumor suppressor gene (WT1) can lead to syndromic forms of steroid-resistant nephrotic syndrome (SRNS) such as Denys-Drash or Frasier syndrome and can cause isolated SRNS. A mutation within WT1 is a frequent cause of sporadic isolated SRNS in girls. In a worldwide cohort of girls, the rate of occurrence was 10.8%. Previous reports have indicated that in Chinese girls, the detection rate of WT1 mutations is 16.7% for early onset isolated nephrotic syndrome. The detection rate of WT1 mutations in Chinese girls with sporadic isolated SRNS is unknown. We examined WT1 mutations in 14 Chinese girls with sporadic isolated SRNS using polymerase chain reaction and direct sequencing and studied a control group of 38 boys with sporadic isolated SRNS. We identified a WT1 mutation in 1 of 14 (7.1% detection rate) Chinese girls with sporadic isolated SRNS. No mutations occurred in WT1 in the remaining 13 girls or the control group. Our investigation supports the necessity of genetic examination for mutations in WT1 in girls with sporadic isolated SRNS.
Assuntos
Síndrome Nefrótica/genética , Mutação Puntual , Esteroides/farmacologia , Proteínas WT1/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Análise Mutacional de DNA , Resistência a Medicamentos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Cariótipo , Masculino , Síndrome Nefrótica/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
Since the identification of the NPHS1 gene, which encodes nephrin, various investigators have demonstrated that the NPHS1 mutation is a frequent cause of congenital nephrotic syndrome (CNS); it is found in 98% of Finnish children with this syndrome and in 39-80% of non-Finnish cases. In China, compound heterozygous mutations in the NPHS1 gene have been identified in two Chinese families with CNS. To our knowledge, however, whether or not NPHS1 is the causative gene in sporadic Chinese CNS cases has not been established. We identified a homozygous mutation of NPHS1, 3250insG (V1084fsX1095), in a Chinese child with sporadic CNS. This finding leads us to suggest that NPHS1 mutations are also present in sporadic Chinese CNS cases. This gives additional support for the necessity for genetic examination of mutations in the NPHS1 gene in Chinese children with sporadic CNS.
Assuntos
Proteínas de Membrana/genética , Síndrome Nefrótica/genética , Povo Asiático/genética , Humanos , Lactente , Masculino , MutaçãoRESUMO
Recently, scientists interested in diseases of the human brain have paid much attention to the endothelin group of peptides. Under normal conditions they are found in some types of neurons and in endothelial cells of microvessels but not in glial cells. This review focuses on the endothelin peptides and their involvement in various brain diseases. Particular attention is paid to their expression in reactive astrocytes seen in many pathological conditions of the human brain. Endothelin-1 is a very potent vasoconstrictor which may be involved in the vasospasm occurring in subarachnoid haemorrhage. Intracerebral injection or application to cerebral arteries in animals will cause a focal necrosis, apparently due to severe vasoconstriction. Reactive astrocytes occurring in cases with infarcts, lacunae, Alzheimer's disease, progressive multifocal leukoencephalopathy (PML) and subacute sclerosing panencephalitis (SSPE) express endothelin-like immunoreactivity. Astrocytes in vitro may produce, store and release endothelins. To some extent astrocytes grown in vitro mimic reactive astrocytes in vivo since in cultures astrocytes are removed from their natural environment which may trigger reactive responses. Therefore, in vivo reactive astrocytes may produce, store and release endothelins just as in vitro. If endothelins are released from reactive astrocytes they may act as mitogens and may influence microcirculation by inducing vasoconstriction of intracerebral arterioles. In such ways endothelins may contribute to the final lesions seen in cases with infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain.
Assuntos
Astrócitos/metabolismo , Encefalopatias/fisiopatologia , Endotelinas/fisiologia , Neuropeptídeos/fisiologia , Animais , Barreira Hematoencefálica/fisiologia , Encefalopatias/metabolismo , Transtornos Cerebrovasculares/fisiopatologia , Endotelinas/metabolismo , Humanos , Neuropeptídeos/metabolismo , Hemorragia Subaracnóidea/fisiopatologia , Vasoconstrição/fisiologiaRESUMO
In order to investigate the expression of endothelin-like immunoreactivity in astrocytes of viral infections of the human brain the avidin-biotin peroxidase complex method and a polyclonal antiserum were used. Autopsy material was obtained from 5 cases of herpes simplex encephalitis, two of progressive multifocal leukoencephalopathy (PML) and two of subacute sclerosing panencephalitis (SSPE). All the 5 herpes simplex encephalitis cases presented groups of immunoreactive astrocytes around necrotic, inflammatory lesions. The PML cases exhibited a large number of immunoreactive astrocytes in and around lesions of the white matter. The cases of SSPE disclosed numerous, markedly stained fibrillary immunoreactive astrocytes; they were most abundant in degenerated regions of the white matter. The processes and peripheral cytoplasm of giant astrocytes in the PML cases contained immunoreactive material but the perinuclear region was devoid of such material. In the herpes simplex and the SSPE cases immunoreactivity was present throughout the cytoplasm and processes of reactive fibrillary astrocytes. Many nerve cells in the cerebral cortex, hippocampus, cerebellum and pons of control cases exhibited endothelin-like immunoreactivity but this occurred in only exceptional astrocytes of control cases. Endothelin-like immunoreactivity was not present in the oligodendrocytes and vascular endothelial cells of controls and cases of virus infection. The expression of endothelin-like immunoreactivity in astrocytes in human viral diseases reflects probably an increased intracellular content of endothelin. If this peptide is released from such astrocytes, it may act as a mitogen and by inducing constriction of arterioles it may influence the microcirculation.
Assuntos
Astrócitos/metabolismo , Encefalite Viral/metabolismo , Endotelinas/metabolismo , Herpes Simples/metabolismo , Leucoencefalopatia Multifocal Progressiva/metabolismo , Panencefalite Esclerosante Subaguda/metabolismo , Adolescente , Adulto , Idoso , Criança , Encefalite Viral/patologia , Feminino , Herpes Simples/patologia , Humanos , Imuno-Histoquímica/métodos , Leucoencefalopatia Multifocal Progressiva/patologia , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem , Panencefalite Esclerosante Subaguda/patologiaRESUMO
The avidin-biotin peroxidase complex method and a polyclonal antiserum were used to investigate the distribution of endothelin-1-like immunoreactivity of cerebral astrocytes in autopsy cases of Alzheimer's disease compared with controls. The cases of Alzheimer's disease presented numerous astrocytes with intense endothelin-1-like immunoreactivity of the cell body often extending into the finest ramifications of the cell processes. Absorption of the antiserum by the corresponding antigen eliminated this immunostaining. The immunoreactive astrocytes were most consistently present in the subcortical white matter of the cerebral hemispheres and the folia of the cerebellum. The immunoreactive cells were often located in small clusters close to blood vessels. Five of the seven cases showed immunoreactive astrocytes in the molecular layer of the cerebral cortex and three of the seven cases presented regions in which immunoreactive astrocytes appeared to be located in the periphery of plaques. The pons contained small groups of immunoreactive astrocytes in five of the cases. The cerebellum had such cells in six of the seven investigated patients. Immunoreactive astrocytes were very rare in control cases without cerebral disease. Many nerve cells in the cerebral neocortex, hippocampus, cerebellum and pons of Alzheimer cases and controls exhibited endothelin-1-like immunoreactivity. Oligodendrocytes and endothelial cells of blood vessels of controls and Alzheimer cases did not show such immunoreactivity. The expression of endothelin-1-like immunoreactivity in astrocytes of Alzheimer's disease probably reflects an increased content of endothelin-1. If endothelin-1 is released from such astrocytes it may reach smooth muscle cells of the intracerebral blood vessels and disturb micro-circulation since this compound is a most powerful vasoconstrictor peptide.
Assuntos
Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Endotelinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Astrócitos/imunologia , Avidina , Biotina , Encéfalo/patologia , Endotelinas/imunologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
The avidin-biotin peroxidase complex method and a polyclonal antiserum were used to investigate the expression of endothelin-like immunoreactivity in human autopsy cases presenting cerebral infarcts and lacunes. Cases with recent infarcts showed loss of immunoreactivity in neurons of the infarcts. Immunoreactive granules started to appear in astrocytic endfeet of microvessels of the border zones. Later on, numerous reactive astrocytes presented immunoreactivity in the entire cell body. Cases with old infarcts had a more widespread presence of astrocytes with endothelin-like immunoreactivity around the lesions. Macrophages particularly of old infarcts showed a strong immunoreactivity. Cases with old lacunes presented numerous reactive fibrillary astrocytes with endothelin-like immunoreactivity in the cell body and the processes. Astrocytes of controls showing endothelin-like immunoreactivity were very rare and such cells were usually confined to the molecular layer of the cerebral cortex. The endothelin-like immunoreactivity in astrocytes and macrophages of cases with cerebrovascular diseases probably reflects an increased intracellular content of endothelin. If this compound is released from such cells it may act as a mitogen and influence microcirculation by inducing vasoconstriction of intracerebral arterioles.-
RESUMO
The expression of endothelin-1-like immunoreactivity in astrocytes of the human brain was investigated by the avidin-biotin-peroxidase complex method in post mortem material. A marked immunoreaction was present in reactive astrocytes around infarcts, lacunes, traumatic injuries, the lesions of progressive multifocal leuco-encephalopathy and in the cerebral cortex and white matter of Alzheimer's disease. The brains of patients who had neither history nor signs of cerebral disease exhibited only occasional immunoreactive astrocytes. A hypothesis is presented that endothelin-1 may be released from reactive astrocytes in many organic diseases of the human brain with considerable pathogenic consequences. It is known from experimental investigations that endothelin-1 may for instance cause severe vasoconstriction resulting in cell injury and that it may act as a growth factor for glial cells.