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OBJECTIVE: To describe the personality traits of temperament and character in patients with tinnitus and to identify differences in these traits associated with the severity of tinnitus. STUDY DESIGN: Case series with comparisons. SETTING: Tertiary referral centre. PARTICIPANTS: From January to December 2014, one hundred and thirty-four adult patients with chronic subjective tinnitus completed psychoacoustic measurements of tinnitus and the Temperament and Character Inventory (TCI). MEASUREMENTS: Personality traits were assessed by the TCI. The TCI assesses seven dimensions of personality traits and four temperaments 'novelty seeking, harm avoidance, reward dependence, persistence', as well as three characters 'self-directedness, cooperativeness, self-transcendence'. MAIN OUTCOME MEASURES: The values of the TCI parameters in the tinnitus patients were compared with reference data from a non-institutional adult population, and associations between TCI parameter values and tinnitus severity were evaluated. RESULTS: In terms of temperament, tinnitus patients had higher scores for 'harm avoidance', whereas scores for 'novelty seeking', 'reward dependence' and 'persistence' were significantly lower than the reference. In terms of character, lower 'cooperativeness' and 'self-transcendence' were identified in the subjects with tinnitus. The 'novelty seeking' score was inversely related to tinnitus severity (r = -0.285, P = 0.001), while other temperament and character traits did not show significant correlations. CONCLUSIONS: There may be a connection between tinnitus and personality traits, especially in the case of 'novelty seeking', which is relatively constant over a lifetime. The TCI questionnaire may be useful in facilitating the application of personality traits to tailored counselling for tinnitus.
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Inventário de Personalidade , Temperamento , Zumbido/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psicoacústica , Índice de Gravidade de DoençaRESUMO
Hot pepper (Capsicum annuum) cultivated in India has been identified as a host of geminiviruses causing leaf curl disease such as Chilli leaf curl virus and Pepper leaf curl virus, leading to serious crop losses (3). In June 2013, hot pepper plants growing in Bangalore showed stunting and upward leaf curling. Viral DNA was extracted from a hot pepper with a Viral Gene-spin Viral DNA/RNA Extraction Kit (iNtRON Biotechnology, Seongnam, Korea) and amplified by rolling circle amplification using the illustra TempliPhi 100 Amplification Kit (GE Healthcare, Uppsala, Sweden) (2). Amplified products were digested by restriction enzyme KpnI (Takara Bio, Shiga, Japan), cloned, and sequenced (Macrogen, Seoul, Korea). Based on a BLAST search, a 2.6-kb DNA obtained from one plant sample was identified as Chickpea chlorotic dwarf virus (CpCDV), belonging to the genus Mastrevirus (family Geminiviridae) (GenBank Accession No. KF632712). The CpCDV-Bangalore isolate is 2,585 bases in length and exhibits 85.9 to 98.5% identity to previously reported CpCDV isolates. To our knowledge, this is the first report of CpCDV infecting hot pepper in India. CpCDV was recently reported from pepper plants in Oman (KF111683) (1), but it shared the lowest sequence identity (85.9%) with CpCDV-Bangalore isolate. References: (1) S. Akhtar et al. Plant Dis. 98:286, 2014. (2) E.-J. Kil et al. Arch. Virol. 159:2387. (3) D. M. J. B. Senanayake et al. Plant Pathol. 56:343, 2007.
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Eustoma (Eustoma grandiflorum), also called lisianthus, belongs to the family Gentianaceae and is cultivated for flower production globally (1), including in Korea. At least 10 viruses can infect eustoma, including Cucumber mosaic virus (genus Cucumovirus), Tobacco mosaic virus (genus Tobamovirus), Tomato spotted wilt virus (genus Tospovirus), and Tomato yellow leaf curl virus (TYLCV, genus Begomovirus) (1,2). In December 2012, disease symptoms such as leaf curling and stunting were observed on eustoma plants grown in Gumi, Korea, where TYLCV outbreak was reported on tomato farms. In a eustoma greenhouse, about 5% of eustoma plants showed the leaf curling and stunting symptoms. Total DNA was isolated from 15 symptomatic eustoma plants with a Viral Gene-spin Viral DNA/RNA Extraction Kit (iNtRON Biotechnology, Seongnam, Korea) and viral DNA was amplified by rolling circle amplification (TempliPhi Amplification Kit, GE Healthcare Life Sciences, Uppsala, Sweden) following the manufacturer's instructions. All amplicons were digested with the restriction enzyme SacI (TaKaRa Bio, Shiga, Japan) and 2.8-kb DNA fragments were verified on an agarose gel. Fifteen digested DNA fragments were purified from the gel, ligated into pGEM-T easy vector (Promega, Madison, WI), and sequenced (Macrogen, Seoul, Korea, GenBank Accession No. KF225312.1). A BLAST search exhibited a 99% identity to TYLCV previously reported in Korea (GenBank HM856911.1). This is the first report of TYLCV in eustoma plants in Korea. To identify the movement and replication of TYLCV in infected eustoma plants, PCR and Southern hybridization analysis were performed with samples from four organs (flower, leaf, stem, and root) of three individual TYLCV-infected plants. TYLCV TYL DNA from each organ sample was amplified using 2× Taq PCR MasterMix (Bioneer, Daejeon, Korea) with TYLCV-specific primers (TYLCV-F: 5'-ATATTACCGGATGGCCGCGCCT-3', CV-R: 5'-TCCACGGGGAACATCAGGGCTT-3'). Single-stranded as well as double-stranded TYLCV DNA were identified from all organs of symptomatic eustoma, indicating TYLCV can replicate and move systemically in eustoma plants. Whitefly (Bemisia tabaci)-mediated plant-to-plant viral transmission was performed with one TYLCV-infected eustoma plant and five healthy eustoma plants and revealed that 80% (4 of 5) of the eustoma plants were infected by whitefly-mediated transmission. These results indicate that TYLCV-infected eustoma plants could act as virus reservoirs to healthy eustoma plants as well as other potential TYLCV hosts, such as tomatoes. In Korea, TYLCV has been the most notorious plant virus since 2008 (3), but, until now, TYLCV infection in eustoma plants has not been reported in Korea. References: (1) C. C. Chen et al. Plant Dis. 84:506, 2000. (2) A. Kritzman et al. Plant Dis. 84:1185, 2000. (3) H. Lee et al. Mol. Cells 30:467, 2010.
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Sweet potato (Ipomoea batatas) is one of the most important crops in eastern Asia, including Korea. Consumption of sweet potato is increasing gradually because of its growing reputation as a health food. Recently, outbreaks of viruses infecting sweet potatoes have increased all over the world, probably because sweet potatoes are produced via vegetative propagation (1,2). In Korea, most sweet potatoes in fields have been infected by a begomovirus, Sweet potato leaf curl virus (SPLCV), and other viruses such as Sweet potato feathery mottle virus, Sweet potato virus G, and Sweet potato latent virus (3). Many countries have monitored sweet potato virus infections in fields as well as in germplasm collections to select virus-free stocks. In 2013, 20 sweet potato plants showing leaf roll symptoms in Muan, South Korea, were collected and analyzed. Total DNA was isolated from sweet potato leaves (Viral Gene-spin Viral DNA/RNA Extraction Kit, iNtRON Biotechnology, Seongnam, Korea) and viral DNA was amplified by rolling circle amplification (RCA, TempliPhi Amplification Kit, GE Healthcare Life Sciences, Uppsala, Sweden) following the manufacturer's instructions. Amplicons were digested by restriction enzyme SacI (TaKaRa Bio, Shiga, Japan) and products were run on a 1.5% agarose gel. A 2.8-kb DNA fragment was purified from a gel, ligated into a pGEM-T easy vector (Promega, Madison, WI), and sequenced (Macrogen, Seoul, Korea). Based on a BLAST search, most of the sequences (36/38) were identified as SPLCV, but two independent clones 2,824 nt in length from sweet potato cv. Sincheonmi were similar to Sweet potato golden vein associated virus (SPGVaV) isolate US:MS:1B-3 (94.38%, GenBank Accession No. HQ333143). The complete genome sequence of the SPGVaV-Korea isolate contained six ORFs, as expected for a typical monopartite begomovirus. The sequence was deposited in GenBank under accession number KF803170. SPGVaV is a whitefly (Bemisia tabaci)-transmitted virus (genus Begomovirus, family Geminiviridae). A phylogenetic analysis that included other begomoviruses that infect sweet potato showed SPGVaV-Korea to segregate with other SPGVaV isolates. SPGVaV has previously only been reported in Brazil and the United States (1). This is the first report of SPGVaV in sweet potato outside of the Americas. References: (1) L. C. Albuquerque et al. Virol. J. 9:241, 2012. (2) E. Choi et al. Acta Virol. 56:187, 2012. (3) H. R. Kwak et al. Plant Pathol. J. 22:239, 2006.
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Rapid and sensitive detection methods for three species of Curtovirus were developed using a loop-mediated isothermal amplification (LAMP) technique. A universal primer set for detecting the three main species of Curtovirus at the same time, and three kinds of species-specific primer sets were designed and used for LAMP reactions. Results from the LAMP reactions were visualized both by color changes after adding SYBR Green I staining dye and by DNA laddering on agarose gel electrophoresis. The optimal conditions for the curtovirus LAMP reaction were confirmed at 60°C for the universal primers and at 62°C for the three species-specific primer sets. Amplification of curtoviruses by LAMP reaction was ten-fold more sensitive than that by polymerase chain reaction. Primers designed for curtovirus detection in this study did not anneal to or amplify DNA from other DNA or RNA viruses (tomato yellow leaf curl virus, tomato spotted wilt virus, and potato virus Y). Taken together, the primer sets and reaction conditions developed in this study show that the LAMP technique could be a useful tool to detect the three species of Curtovirus simultaneously and distinguish them in the laboratory and the field.
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Geminiviridae/isolamento & purificação , Nicotiana/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Doenças das Plantas/virologia , Primers do DNA/genética , Geminiviridae/classificação , Geminiviridae/genéticaRESUMO
The ancestral gamete fusion protein, HAP2, catalyzes sperm-egg fusion in a broad range of taxa dating to the last eukaryotic common ancestor. Remarkably, HAP2 orthologs are structurally related to the class II fusogens of modern-day viruses, and recent studies make clear that these proteins utilize similar mechanisms to achieve membrane merger. To identify factors that may regulate HAP2 activity, we screened mutants of the ciliate Tetrahymena thermophila for behaviors that mimic Δhap2 knockout phenotypes in this species. Using this approach, we identified two new genes, GFU1 and GFU2, whose products are necessary for the formation of membrane pores during fertilization and show that the product of a third gene, namely ZFR1, may be involved in pore maintenance and/or expansion. Finally, we propose a model that explains cooperativity between the fusion machinery on apposed membranes of mating cells and accounts for successful fertilization in T. thermophila's multiple mating type system.
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BACKGROUND: Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer patients have rarely been studied. PATIENTS AND METHODS: We conducted a survey of daily skin care habits and the presence of skin problems in 866 cancer patients. RESULTS: Hot water bath>1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total results, including that hot water bath>1 h significantly increased the risk of definite eruptions (OR 3.41). CONCLUSIONS: Being a cross-sectional study, our study could not prove causality. However, at the present stage of knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to prevent skin problems in cancer patients.
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Neoplasias/terapia , Higiene da Pele/métodos , Dermatopatias/prevenção & controle , Antineoplásicos/efeitos adversos , Banhos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Educação de Pacientes como Assunto/métodos , Dermatopatias/induzido quimicamente , Dermatopatias/etiologia , Inquéritos e QuestionáriosRESUMO
It is known that the level of interleukin-6 (IL-6) is higher in patients with active Behcet's disease (BD) than in those with inactive disease. Herpes simplex virus (HSV) type 1 inoculation of the earlobes of ICR mice resulted in the development of BD-like symptoms. To find out whether downregulation of IL-6 would affect the symptoms of BD, IL-6 small interfering RNA (siRNA) was administered to a BD mouse model. IL-6 siRNA was intraperitoneally injected into BD mice to downregulate IL-6 (n=9). IL-6 siRNA injection downregulated serum IL-6 level (118.9+/-114.4 pg ml(-1)) compared with scramble injection (439.4+/-378.0 pg ml(-1)) in BD mice (P=0.01). In seven out of nine IL-6 siRNA-injected BD mice, 77.8% improved and the severity score was decreased from 3.1+/-1.05 to 1.7+/-0.87 (P=0.005), whereas two out of six (33.3%) scramble-injected BD mice improved and the severity score changed from 2.5+/-0.84 to 2.0+/-1.41 (P=0.203). Foxp3, ROR gamma t, IL-17A, IL-17F and tumor necrosis factor-alpha were also influenced in IL-6 siRNA-injected BD mice compared with scramble-injected BD mice. Adoptive transfer of CD4+CD25+ cells to BD mice affected the decrease of IL-6 serum levels and were dependent on CD4+CD25+ cell numbers. These results showed that downregulation of IL-6 improved the inflammatory symptoms in BD mice through upregulation of regulatory T cells and inhibition of Th17 cells.
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Síndrome de Behçet/terapia , Terapia Genética/métodos , Herpes Simples/complicações , Interleucina-6/genética , RNA Interferente Pequeno/genética , Transferência Adotiva , Animais , Síndrome de Behçet/genética , Síndrome de Behçet/imunologia , Síndrome de Behçet/virologia , Modelos Animais de Doenças , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Herpesvirus Humano 1 , Interleucina-17/biossíntese , Interleucina-23/biossíntese , Interleucina-6/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos ICR , Interferência de RNA/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/sangue , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Regulação para Cima/genética , Regulação para Cima/imunologiaRESUMO
OBJECTIVE: Resveratrol is a naturally occurring polyphenol, which possesses chemotherapeutic potential through its ability to trigger apoptosis. The objective of this study was to investigate the major determinant for the apoptotic cell death induction by resveratrol in fibroblast-like synoviocytes (FLS) derived from patients with RA. METHODS: The effect of resveratrol on apoptotic cell death was quantified in a population of subG1 in RA FLS by flow cytometry. The underlying signalling mechanism for apoptotic death was examined by analysing mitochondrial membrane potential, activation of the caspase cascade and translocation of Bid. RESULTS: We show that activation of caspase-8 is essential for triggering resveratrol-induced apoptotic signalling via the involvement of the mitochondrial pathway in RA FLS. Our findings also suggest that this enhanced apoptosis caused by resveratrol occurred in RA FLS irrespective of p53 status. Exposure to resveratrol caused extensive apoptotic cell death, along with a caspase-dependent (activation of caspase-9 and -3, poly ADPribose polymerase (PARP) cleavage and mitochondrial cytochrome c release) or caspase-independent [translocation of apoptosis-inducing factor (AIF) to the nucleus] signalling pathway. Analysis of upstream signalling events affected by resveratrol revealed that the activated caspase-8 triggered mitochondrial apoptotic events by inducing Bid cleavage without any alteration in the levels of Bax, Bcl-xL or Bcl2. The caspase-8 inhibitor or over-expression of crmA abrogated cell death induced by resveratrol and prevented processing of the downstream cascade. CONCLUSION: The results suggest that resveratrol causes activation of caspase-8, which in turn results in modulation of mitochondrial apoptotic machinery to promote apoptosis of RA FLS.
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Fator de Indução de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Artrite Reumatoide/fisiopatologia , Caspase 8/metabolismo , Estilbenos/farmacologia , Fator de Indução de Apoptose/efeitos dos fármacos , Artrite Reumatoide/metabolismo , Caspase 8/efeitos dos fármacos , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Imunofluorescência , Humanos , Potenciais da Membrana , Mitocôndrias/fisiologia , Probabilidade , Resveratrol , Sensibilidade e Especificidade , Membrana Sinovial/citologia , Membrana Sinovial/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: Intracranial solitary fibrous tumors (ISFTs) are rare mesenchymal neoplasms originating in the meninges. The aim of this study was to describe the CT, MR imaging, and angiographic features of the solitary fibrous tumor and to identify imaging characteristics. MATERIALS AND METHODS: We retrospectively reviewed CT, MR, and angiographic findings in 6 cases of ISFT. We evaluated the size, shape, and location of the tumor; the internal content and margin of the lesion; the pattern of enhancement; and the change of the adjacent structures. Density on noncontrast CT scans, signal intensity on MR images, and angiographic features were also documented. RESULTS: Each lesion appeared as a discrete extra-axial mass (size, 3-7 cm; mean, 5 cm). Five lesions were entirely solid, and 1 had peritumoral cyst. All 5 of the noncontrast CT scans showed hyperattenuated masses, and the tumors exhibited marked heterogeneous enhancement. No lesion contained calcification, and 2 cases showed bone invasions. On the MR images, 4 lesions showed mixed signal intensity on T2-weighted imaging. All of the lesions revealed marked heterogeneous enhancement. All of the tumors had thickening of the meninges adjacent to the tumor. Angiography showed delayed tumor blushing in all, and 3 of them had dysplastic dilation of the tumor vessels. CONCLUSION: Although there are no pathognomonic imaging findings, some imaging features, such as the "black-and-white mixed" pattern on T2-weighted images and marked heterogeneous enhancement, might be helpful in the diagnosis of intracranial solitary fibrous tumor.
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Angiografia Digital , Neoplasias Encefálicas/diagnóstico , Angiografia Cerebral , Imageamento por Ressonância Magnética , Neoplasias de Tecido Fibroso/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Neoplasias de Tecido Fibroso/patologia , Estudos Retrospectivos , CrânioRESUMO
BACKGROUND AND PURPOSE: Rhabdoid meningioma (RM) is a recently described variant of malignant meningioma, with radiologic features currently not well characterized in the medical literature. The purpose of this study was to describe and characterize clinical features and imaging findings associated with RM. MATERIALS AND METHODS: CT (n = 8) and MR (n = 15) images of 15 patients (4 men and 11 women; mean age, 52 years; range, 22-75 years) with 16 pathologically proved RMs along with associated clinical records were retrospectively reviewed. All of the patients underwent surgical resection and had additional radiation therapy except for 1 patient. After surgery, the patients had follow-up brain MR imaging to evaluate for tumor recurrence. RESULTS: Nine lesions (56%) were located in the cerebral convexity, and 4 lesions (25%) were located in the parasagittal areas. The tumors were isointense (n = 15) to gray matter on T1-weighted images, whereas they were hyperintense (n = 14) on T2-weighted images. On gadolinium-enhanced T1-weighted images, homogeneous enhancement was seen in 10 lesions, and heterogeneous enhancement was seen in 6 lesions that had cysts. Cystic components were noted in 6 lesions (38%). Severe peritumoral edema was seen in 12 lesions (75%). Nine lesions (56%) had hyperostosis, and 5 of them also had bone destruction. Among the 8 cases with initial CT scans, only 1 had amorphous calcifications (13%). There was only 1 recurrence of RM found during the follow-up period after surgical resection. CONCLUSION: RMs tend to have prominent peritumoral edema, cystic components, and bone involvement.
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Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/fisiopatologia , Meningioma/diagnóstico , Meningioma/fisiopatologia , Adulto , Idoso , Cistos/diagnóstico , Edema/induzido quimicamente , Edema/etiologia , Feminino , Seguimentos , Humanos , Hiperostose/diagnóstico , Hiperostose/etiologia , Masculino , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/cirurgia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Radioterapia Adjuvante , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: It has become clear that obesity is associated with a variety of infectious diseases, including urinary tract infection (UTI) and renal scarring. OBJECTIVE: The aim of this study was to evaluate the association between obesity and the degree of febrile UTI (fUTI) and renal scarring in children with vesicoureteral reflux (VUR), and to stratify the results into obesity subcategories. STUDY DESIGN: A total of 186 patients were diagnosed with VUR between January 2002 and December 2008. This study retrospectively reviewed the medical records of 72 children with primary VUR who had recurrent fUTI (more than twice). Overweight or obese status of the patients aged <2 years was defined using weight-for-length (WFL) measurements. For 2-5 year old children, body mass index (BMI) percentile-for-age was used. They were divided into three groups as follows; standard (<85%), overweight (85-95%), and obese (≥95%). The following clinical variables were compared: age at diagnosis of primary VUR (months), sex, VUR grade, hydronephrosis grade, presence of renal scarring, surgical treatment, and degree of inflammation during fUTI. RESULTS: In the overweight and obese groups, VUR was diagnosed at a young age (P = 0.05), the degree of renal scarring was more severe (P = 0.006), and serum white blood cell count, C-reactive protein, and erythrocyte sedimentation rate (ESR) levels were significantly higher (P < 0.001, P < 0.001, and P < 0.001, respectively). Abnormal focal dimercaptosuccinic acid (DMSA) defects were present in 25 of the 72 children (35%). Cortical defects occurred more frequently in children with obesity, and they were associated with a higher grade of reflux and serum ESR levels (P = 0.007, P = 0.042, and P = 0.021, respectively). Among these risk factors, high-grade VUR (OR = 9.93, 95% CI = 1.13-86.71), and being overweight and obese (OR = 5.26, 95% CI = 1.75-15.82) were associated with increased renal scarring. However, ESR was not associated with renal scarring (OR = 1.01, 95% CI = 0.95-1.07). DISCUSSION: The relationships between obesity and UTI are controversial. Some studies have shown positive results; however, other studies have shown opposite results. The main limitations of this study were the retrospective data collection via electronic medical records, and the small number of subjects. CONCLUSIONS: This study showed that obesity in patients with VUR has an effect on fUTI and renal scar formation. If the patients with VUR have obesity, close follow-up should be performed, and VUR patients should be started on a weight-loss program, which could reduce the number of patients with chronic kidney disease in the future.
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Cicatriz/epidemiologia , Febre/fisiopatologia , Hidronefrose/epidemiologia , Obesidade/epidemiologia , Infecções Urinárias/epidemiologia , Refluxo Vesicoureteral/epidemiologia , Fatores Etários , Análise Química do Sangue , Proteína C-Reativa/análise , Criança , Pré-Escolar , Cicatriz/patologia , Comorbidade , Intervalos de Confiança , Bases de Dados Factuais , Feminino , Humanos , Hidronefrose/diagnóstico , Incidência , Contagem de Leucócitos , Masculino , Obesidade/diagnóstico , Razão de Chances , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Infecções Urinárias/diagnóstico , Refluxo Vesicoureteral/diagnósticoRESUMO
BACKGROUND: YH4808, a K+ -competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease. AIMS: To determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. METHODS: This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). RESULTS: Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered. CONCLUSION: This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases.
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Antiulcerosos/farmacologia , Esomeprazol/análogos & derivados , Esomeprazol/farmacologia , Ácido Gástrico/metabolismo , Adulto , Antiulcerosos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Esomeprazol/administração & dosagem , Esomeprazol/farmacocinética , Humanos , Concentração de Íons de Hidrogênio , Masculino , Adulto JovemRESUMO
PURPOSE: The aim of this study was to differentiate hemangioblastomas from metastatic brain tumors using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and compare the diagnostic performances with diffusion-weighted imaging (DWI) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). METHODS: We retrospectively reviewed 7 patients with hemangioblastoma and 15 patients with metastatic adenocarcinoma with magnetic resonance imaging (MRI) including DWI, DSC-MRI, and DCE-MRI. Apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), and DCE-MRI parameters (K trans, k ep, v e, and v p) were compared between the two groups. The diagnostic performance of each parameter was evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: v p, k ep, and rCBV were significantly different between patients with hemangioblastoma and those with metastatic brain tumor (p < 0.001, p = 0.005, and p = 0.017, respectively). A v p cutoff value of 0.012 and a rCBV cutoff value of 8.0 showed the highest accuracy for differentiating hemangioblastoma from metastasis. The area under the ROC curve for v p and rCBV was 0.99 and 0.89, respectively. A v p > 0.012 showed 100 % sensitivity, 93.3 % specificity, and 95.5 % accuracy and a rCBV > 8.0 showed 85.7 % sensitivity, 93.3 % specificity, and 90.9 % accuracy for differentiating hemangioblastoma from metastatic brain tumor. CONCLUSION: DCE-MRI was useful for differentiating hemangioblastoma from metastatic brain tumor.
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Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Hemangioblastoma/diagnóstico por imagem , Adulto , Idoso , Neoplasias Encefálicas/secundário , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Malonate decarboxylase from Acinetobacter calcoaceticus was isolated and characterized (Kim, Y.S., Byun, H.S., J. Biol. Chem. 269 (1994) 29636-29641), and its subunits were reanalyzed recently to be alpha, beta, gamma, and delta. The genes for the subunits, MdcA (548 a.a.), B (295 a.a.), C (238 a.a.), and D (102 a.a.), of the enzyme have been cloned by using oligonucleotide primers deduced from amino acid sequences of peptides isolated from the purified enzyme, and sequenced to be clustered in an operon in the order of A-D-B-C. The operon was found to encode more genes than mdcABCD. The Escherichia coli, transformed with the vector containing the insert mdcADBC and about 1.7 kb of an upstream region, expressed the four subunits of the enzyme but the proteins did not show enzyme activity. It indicates that, like the enzymes from Malonomonas rubra and Klebsiella pneumoniae, more genes are needed for the formation of the functional malonate decarboxylase.
Assuntos
Acinetobacter calcoaceticus/genética , Carboxiliases/genética , Acinetobacter calcoaceticus/enzimologia , Sequência de Aminoácidos , Sequência de Bases , Carboxiliases/metabolismo , Clonagem Molecular , DNA Bacteriano , Escherichia coli/genética , Dados de Sequência Molecular , Óperon , Homologia de Sequência de AminoácidosRESUMO
As an extension of recent results (Rhodes, Xu and Bittman (1992) Biochim. Biophys. Acta 1128, 93; Hui, Xu and Bittman (1992) Langmuir 8, 2724) with a C18 diacetylenic phosphatidylcholine, bilayers of 1,2-bis(pentacosa-4,6-diynoyl)-sn-glycero-3-phosphocholine (C25) were investigated using X-ray diffraction on multibilayers and electron diffraction on Langmuir-Blodgett deposited bilayers. Monolayers of this lipid form solid (gel phase) domains at pi > 14 mN/m. Electron diffraction data indicated that the chain spacing in these domains is 4.25 A and that the chains are tilted at angle of approximately 35 degrees relative to the bilayer plane. Wide angle data from X-ray diffraction experiments indicated a similar spacing and chain tilt. Small angle data showed that the lamellar repeat was 70 A at high humidity and < or = 60 A at low humidity. The bilayer electron density profiles indicated a bilayer structure with no interdigitation. High angle reflections indicate that the principal acyl chain repeat is preserved as a function of hydration but some rearrangement occurs for other reflections. The approximately 10 A reflection corresponding to the headgroup spacing previously observed with C18-diacetylenic phosphatidylcholine bilayers was not observed. The results are interpreted in terms of a packing model and possible limitations or constraints to the polymerization process.
Assuntos
Acetileno/análogos & derivados , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Polímeros/química , Acetileno/química , Varredura Diferencial de Calorimetria , Cromatografia em Camada Fina , Polímero Poliacetilênico , Poli-Inos , Difração de Raios XRESUMO
A lymphatic malformation (LM) is the most common form of congenital vascular malformation (CVM). The new Hamburg classification of CVM distinguishes the truncular (T) form from the extratruncular (ET) form of LMs. Both are consequences of a developmental arrest at the different stages of lymphangiogenesis as a result of defective genes. The purpose of this review was to evaluate the current management results of both forms of LMs. A retrospective review of the clinical data of 315 patients with a diagnosis of LMs treated between September 1994 and December 2001 was performed. Lymphoscintigraphy was the most frequent diagnostic test. The patients with the ET form were treated with sclerotherapy with OK-432 and/or ethanol. Combinations of CDP (complex decongestive physiotherapy) and/or compressotherapy were used to treat all the T-form patients. In addition, surgery, either reconstructive or ablative, was offered to patients with the T form who failed to respond to the proper CDP. A multidisciplinary team performed the management of LM, and the results were evaluated every 6 months. Among 797 patients with CVM, 315 were confirmed to have LMs, either as the T form (226) or the ET form (89). Another 66 LMs were diagnosed with hemolymphatic malformations (HLM). Most of the ET forms (89/315) were the cystic type (70/89), while the T forms included aplasia and/or an obstruction (204/226). The ET form was most frequent in the head, neck, and thorax (69/89). The T form was located most frequently to the extremities (202/226), mostly to the lower limb (180/202). Two hundred and twenty-six T forms belonged to the various clinical stages: stages I-32, II-104, III-48, IV-18, and an unclear stage-24. The ET form was treated with sclerotherapy using OK-432 (108/120) and absolute ethanol (12/120). Among the 11 patients with the multiple ET form, 7 patients underwent perioperative sclerotherapy with OK-432 and a subsequent surgical excision. The clinical response of the T form at the extremity to CDP was excellent to good in a majority of clinical stages I to II (121/136) but decreased to a good to fair degree in stages III to IV (31/66). The additional surgical therapy, either reconstructive (10/19) or ablative (9/19), provided limited success in improving CDP efficacy, owing mainly to poor compliance. The long-term outcome of the initial success through self-motivated home-maintenance care during the follow-up period of up to 48 months was totally dependent on patient compliance. OK-432 sclerotherapy to 51 ET forms has shown excellent results on 88.9% of the cystic type (40/45) and 50% (3/6) of the cavernous type (minimum follow-up for 24 months). Seventeen ET forms in 7 patients were treated with a preoperative OK-432 sclerotherapy and a subsequent surgical excision, which provided good to excellent results in 14 for a minimum of 24 months. Primary lymphedema, which is the T form of LMs, can be managed safely by a combination of CDP with compressotherapy. Patients with good compliance can benefit from additional surgical therapy, either reconstructive or ablative. The ET form, particularly the cystic type, can be treated with various scleroagents that are preferably less toxic as the primary therapy. A surgical excision with or without perioperative sclerotherapy provides good results for patients with the localized cavernous type of the ET form. A multidisciplinary team approach is essential for the proper care of LM.
Assuntos
Doenças Linfáticas/congênito , Doenças Linfáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Pré-Escolar , Etanol/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Doenças Linfáticas/classificação , Linfedema/congênito , Linfedema/terapia , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Modalidades de Fisioterapia , Picibanil/uso terapêutico , Estudos Retrospectivos , Soluções Esclerosantes/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The clinical presentation of frontotemporal dementia (FTD) is often asymmetrical in terms of both its clinical features and atrophy on MRI. Asymmetry in the lateral ventricle size on structural neuroimaging in FTD patients may have clinical significance. However, this has not been systematically investigated yet. This study compares the ventricular asymmetry seen on MRI with that of the asymmetric glucose metabolism using FDG-PET in patients with FTD. METHODS: Nineteen FTD patients who underwent both brain MRI and FDG-PET were retrospectively selected. As control groups, 23 and 11 age and sex-matched healthy normal subjects underwent either brain MRI or FDG-PET, respectively. The ventricular asymmetry index (VAI) was obtained in two ways: by visual rating (VAI-V) and by measuring the lateral ventricular volumes (VAI-ROI). The hemispheric asymmetry of the glucose metabolism on FDG-PET (MAI) was assessed in three ways: 1) by visual rating (MAI-V), 2) by counting the FDG activity of each hemisphere on normalized and smoothed PET images (MAI-ROI) and 3) by counting the number of voxels with significant hypometabolism based on statistical parametric mapping results (MAI-SPM). RESULTS: The VAIs on MRI (VAI-V and VAI-ROI) were highly correlated, as were the MAIs (MAI-V, MAI-ROI, and MAI-SPM) on FDG-PET. More importantly, the VAIs on MRI and the MAIs on FDG-PET showed high correlation. CONCLUSIONS: Ventricular asymmetry in FTD patients was common (78.9%) and there was a high correlation between the ventricular structural asymmetry and the hemispheric metabolic asymmetry. Therefore, it would be reasonable to interpret that the hemisphere with larger ventricle on MRI in FTD patients is undergoing a more active degenerative process.