RESUMO
Objective: To analyze the Staphylococcal enterotoxins, Staphylococcal enterotoxin genes, drug resistance and molecular typing of 41 Staphylococcus aureus isolates from 2 food-borne illness outbreaks on 21 August and 27 September 2020 in Guangzhou. Methods: A total of 41 Staphylococcus aureus isolates from 2 outbreaks were analyzed by multilocus sequence typing (MLST) and spa typing. The Staphylococcal enterotoxins typing and the Staphylococcal enterotoxin genes of the isolates were analyzed by ELISA and PCR, respectively. The antimicrobial susceptibility of the isolates was performed by disc diffusion. 21 Staphylococcus aureus isolates were characterized using whole genome sequencing (WGS). Based on the whole genome single nucleotide polymorphism (SNP), the phylogenetic tree was constructed by Snippy. Results: 41 Staphylococcus aureus isolates were divided into 2 types by MLST and spa typing: ST6-t701 and ST7-t091. 2 ST7-t091 isolates were identified as methicillin-resistant Staphylococcus aureus (MRSA). 25 ST7-t091 isolates and 14 ST6-t701 isolates were methicillin-sensitive Staphylococcus aureus (MSSA), and were resistant to 7 and 6 antibiotics, respectively. All isolates were positive for sea by PCR. WGS revealed all 21 isolates carried scn, sak, sea, hla, hld, hlgA, hlgB, hlgC, lukD virulence genes. The results showed the isolates contained an immune evasion cluster type D which located in bacteriophage ÏSa3. The SNP phylogenetic tree showed 2 MRSA ST7-t091 were constituted a separate clade from the 12 MSSA ST7-t091 isolates and 7 ST6-t701 isolates showed high similarity to each other. Conclusion: Base on the results of phylogenetic analysis, the 2 food-borne illness outbreaks occurred on 21 August and 27 September 2020 are caused by the combination of the MRSA ST7-t091 strain and the MSSA ST7-t091 strain, and the MSSA ST6-t701 strain, respectively. All isolates have high level of antibiotic resistance and carry high virulent genes.
Assuntos
Doenças Transmitidas por Alimentos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Surtos de Doenças , Doenças Transmitidas por Alimentos/epidemiologia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus/métodos , Filogenia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/genéticaRESUMO
Using inelastic neutron scattering and molecular dynamics simulations on a model Zr-Cu-Al metallic glass, we show that transverse phonons persist well into the high-frequency regime, and can be detected at large momentum transfer. Furthermore, the apparent peak width of the transverse phonons was found to follow the static structure factor. The one-to-one correspondence, which was demonstrated for both Zr-Cu-Al metallic glass and a three-dimensional Lennard-Jones model glass, suggests a universal correlation between the phonon dynamics and the underlying disordered structure. This remarkable correlation, not found for longitudinal phonons, underscores the key role that transverse phonons hold for understanding the structure-dynamics relationship in disordered materials.
RESUMO
Objective: To investigate the principles of diagnosis and treatment of breast cancer during pregnancy. Methods: Clinical data of patients with breast cancer during pregnancy admitted to Obstetrics and Gynecology Hospital of Fudan University between January 2012 to July 2017 were analyzed retrospectively. A total of 17 patients were diagnosed with breast cancer in pregnancy, the median age was 32 years (range from 25 to 45 years old), pathological staging revealed 2 patient with stage 0, 1 with stage â ¡a, 7 with stage â ¡b, 1 with stage â ¢a, 2 with stage â ¢c, 4 with stage â £. Results: Thirteen patients received surgical treatment in pregnancy, the gestational age at surgery was (27.7±4.6) weeks; 2 patients with ductal carcinoma in situ received mastectomy, 11 patients with breast cancer underwent modified radical mastectomy. In patients undergoing surgery during pregnancy, no prophylactic contractions were used in 4 patients who had been treated earlier, there were 2 patients with frequent contractions within 24 hours after operation in these patients. Follow-up 9 patients were given oral nifedipine to prevent contractions, no obvious contractions occurred after the operation. Seven patients received chemotherapy during pregnancy; the chemotherapy of 4 cases of triple negative breast cancer was weekly paclitaxel sequential epirubicin and cyclophosphamide, the chemotherapy of the other three patients was docetaxel sequential epirubicin and cyclophosphamide. Fifteen patients underwent cesarean section to terminate pregnancy, 2 patients underwent spontaneous labor. The gestational age of birth was (36.9 ±1.3) weeks. Less than 35 weeks of termination of pregnancy occurred in one patient, the fetus was delivered to the neonatal intensive care unit due to neonatal respiratory distress syndrome, and suffered from congenital dysaudia. The prognosis of the other 16 survived infants was good. The median follow-up time was 10 months (range from 4 to 27) months, in 13 patients of stage 0 to â ¢c, one patient were diagnosed with bone metastasis at 12 months after surgery, the remaining 12 patients had no disease progression, the progression free survival rate was 12/13, the overall survival rate was 13/13. Among the 4 patients with stage â £, one died in 7 months after delivery, one had new liver metastasis in 8 months after delivery. The remaining 2 patients were in stable condition. Conclusions: Breast cancer in pregnancy can be treated effectively, multidisciplinary cooperation and detailed assessment of maternal-fetal risks and benefits are necessary. Chemotherapy during pregnancy is safe for maternal-fetal, but it needed a large sample of clinical studies and long-term follow-up. The neonatal outcome was associated with gestational age, and therefore premature delivery was avoided as much as possible during treatment.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Mastectomia Radical Modificada , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/cirurgia , Adulto , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/cirurgia , Morte , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Medicina , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/cirurgiaRESUMO
Objective: To explore the impact of weight management and related medication intervention based on body weight changes on cardiac function among patients with chronic congestive heart failure (CHF). Methods: Using prospective, randomized, controlled study methods, consecutive CHF patients, who hospitalized in our department from June 2014 to June 2016 (n=350), were randomly divided into intervention group (n=175) and control group (n=175). Patients in the intervention group received weight management guidance and the post discharge diuretic drugs regimen was adjusted based on body weight changes. The control group received routine medical care post discharge. Left ventricular ejection fraction (LVEF), B type natriuretic peptide precursor (NT-proBNP), 6 minutes walk distance and NYHA classification at one day before discharge and after 6 months were compared between the two groups respectively. Results: Follow-up visit data were not available from 6 patients in the control and intervention group respectively. NYHA classification, LVEF, NT-proBNP and 6 minutes walk distance were similar between the two groups at one day before discharge (all P>0.05). After 6 months, the LVEF and 6 minutes walk distance were significantly higher while NT-proBNP level was significantly lower in the intervention group compared to the control group (all P<0.01). Meanwhile, the LVEF and 6 minutes walk distance were significantly increased, while NT-proBNP was significantly reduced at 6 months post discharge compared to one day before discharge in the intervention group (all P<0.01). The LVEF was also significantly improved (P=0.035), but the NT-proBNP and 6 minutes walk distance were similar (P were 0.328 and 0.807 respectively) at 6 months after discharge compared to one day before discharge in the control group. The NYHA classification was significantly lower in intervention group and in control group at 6 months after discharge compared to one day before discharge (Z=5.154, P<0.01 and Z=10.497, P<0.01), and the NYHA classification improved more in the intervention group than in control group at 6 months after discharge (Z=9.235, P<0.01). The re-hospitalization rate of CHF patients in intervention group was 11.83% (20/169), which was significantly lower than the control group (33.14% (56/169), χ(2)=21.99, P<0.01). At 6 months follow up, body weight remained unchanged in the intervention group, while body weight tended to be higher in the control group compared to one day before discharge. Conclusion: The weight management and diuretic drug regimen adjudgment intervention based on body weight changes can improve cardiac function and reduced re-hospitalization rate in CHF patients.
Assuntos
Diuréticos/uso terapêutico , Insuficiência Cardíaca/terapia , Redução de Peso , Peso Corporal , Doença Crônica , Hospitalização , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Estudos Prospectivos , Função Ventricular EsquerdaRESUMO
Glycine betaine is an important quaternary ammonium compound that is produced in response to several abiotic stresses in many organisms. The synthesis of glycine betaine requires the catalysis of betaine aldehyde dehydrogenase (BADH), which can convert betaine aldehyde into glycine betaine in plants, especially in halotolerant plants. In this study, we isolated the full-length cDNA of BADH from Suaeda corniculata (ScBADH) using reverse transcriptase-polymerase chain reaction and rapid amplification of cDNA ends. Next, we analyzed the expression profile of ScBADH using real-time PCR. The results showed that ScBADH expression was induced in the roots, stems, and leaves of S. corniculata seedlings under salt and drought stress. Next, ScBADH was overexpressed in Arabidopsis, resulting in the transgenic plants exhibiting enhanced tolerance over wild-type plants under salt and drought stress. We then analyzed the levels of glycine betaine and proline, as well as superoxide dismutase (SOD) activity, during salt stress in WT and transgenic Arabidopsis. The results indicated that overexpression of ScBADH produced more glycine betaine and proline, and increased SOD activity under NaCl treatment. Our results suggest that ScBADH might be a positive regulator in plants during the response to NaCl.
Assuntos
Betaína-Aldeído Desidrogenase/genética , Chenopodiaceae/genética , Proteínas de Plantas/genética , Betaína/metabolismo , Betaína-Aldeído Desidrogenase/metabolismo , Chenopodiaceae/enzimologia , Clonagem Molecular , Secas , Regulação da Expressão Gênica de Plantas , Glicina/metabolismo , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Salinidade , Estresse Fisiológico , Superóxido Dismutase/metabolismoRESUMO
Recombinant human anti-tumor necrosis factor (TNF)-α scFv-Fc was expressed in TKO mutant Arabidopsis thaliana seeds using plant-specific codons. Immunoblotting using a human IgG1 antibody detected the expression of anti-TNF-α proteins in plants. Results from qRT-PCR analysis demonstrated that the time of harvest significantly affected the protein yield and quality. Our results indicate that the Phaseolus vulgaris ß-phaseolin promoter directed anti-TNF-α scFv-Fc expression in A. thaliana seeds, with a maximum yield obtained at 20-days of development. Although the yield of anti-TNF-α scFv-Fc protein was not very high, accumulation of recombinant proteins in seeds is an attractive and simple method that can be used to purify biologically active anti-TNF-α scFv-Fc.
Assuntos
Arabidopsis/genética , Fragmentos Fc das Imunoglobulinas/genética , Sementes/metabolismo , Anticorpos de Cadeia Única/genética , Transgenes , Fator de Necrose Tumoral alfa/imunologia , Arabidopsis/metabolismo , Fragmentos Fc das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/metabolismo , Proteínas Recombinantes , Sementes/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismoRESUMO
The regulatory region of the ribulose-1,5-bisphosphate carboxylase small subunit gene SRS4 from soybean (Glycine max) was cloned using TAIL-PCR and general PCR, and named the rbcS promoter. The promoter was fused with the GUS gene and introduced into Nicotiana tabacum via Agrobacterium-mediated leaf disk transformation. In 4-week-old transgenic tobacco plants, the highest GUS expression levels were observed in the leaves, GUS activity was 7.13- and 7.40-fold higher in leaves than in stems and roots, respectively. Moreover, GUS activity was stimulated by light. In conclusion, spatial and light regulation of the soybean rbcS promoter was observed in N. tabacum, thus illustrating a leaf-specific and light-induced promoter.
Assuntos
Glycine max/genética , Nicotiana/genética , Ribulose-Bifosfato Carboxilase/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Luz , Dados de Sequência Molecular , Folhas de Planta/genética , Plantas Geneticamente Modificadas/genética , Reação em Cadeia da Polimerase/métodos , Regiões Promotoras Genéticas , Glycine max/enzimologia , Nicotiana/enzimologiaRESUMO
BACKGROUND: Distant metastasis is the major cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) has a critical role in this process. Accumulating evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-29c has been implicated as a tumor suppressor in several human cancers. However, the role of miR-29c in the progression of colorectal cancer (CRC) metastasis remains largely unknown. PATIENTS AND METHODS: The expression of miR-29c was examined by qRT-PCR in a cohort of primary CRC (PC) and distant liver metastasis (LM) tissues. A series of in vivo and in vitro assays were carried out in order to elucidate the functions of miR-29c and the molecular mechanisms underlying the pathogenesis of metastatic CRC. RESULTS: miR-29c was markedly downregulated in PCs with distant metastasis and determined to be an independent predictor of shortened patient survival. But LM tissues showed higher levels of miR-29c than that in PC tissues. In CRC cells, miR-29c dramatically suppressed cell migration and invasion abilities in vitro and cancer metastasis in vivo. In addition, miR-29c inhibited EMT and negatively regulated Wnt/ß-catenin signaling pathway. Guanine nucleotide binding protein alpha13 (GNA13) and protein tyrosine phosphatase type IVA (PTP4A) were identified as direct targets of miR-29c, which acted through ERK/GSK3ß/ß-catenin and AKT/GSK3ß/ß-catenin pathways, respectively, to regulate EMT. Furthermore, significant associations between miR-29c, its target genes (GNA13 and PTP4A) and EMT markers were validated in both PC and LM tissues. CONCLUSION: Our findings highlight the important role of miR-29c in regulating CRC EMT via GSK-3ß/ß-catenin signaling by targeting GNA13 and PTP4A and provide new insights into the metastatic basis of CRC.
Assuntos
Proteínas de Ciclo Celular/biossíntese , Neoplasias Colorretais/genética , Proteínas de Membrana/biossíntese , MicroRNAs/genética , Proteínas Tirosina Fosfatases/biossíntese , beta Catenina/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Humanos , Proteínas de Membrana/genética , Metástase Neoplásica , Proteínas Tirosina Fosfatases/genética , Via de Sinalização WntRESUMO
This study aimed to investigate the clinical effects and safety review of self-expanding stent surgery in the treatment of extracranial carotid artery stenosis. Seventy-eight patients with carotid artery stenosis were applied with the self-expanding stent for endovascular interventional therapy. Eighty-one stents were implanted into 80 blood vessels of the 78 patients, in which protective umbrellas were used in 56 cases, and the success rate of stent implantation was 100%. The stenosis degree decreased from the preoperative (86.72 ± 9.5%) to the postoperative (13.43 ± 5.62%) stage, and the blood peak velocity of the stenosed vessels decreased from 189.58 ± 13.5 to 83.73 ± 5.61 cm/s. Transient blood pressure and heart rate decreases occurred in 21 cases, continuously low blood pressure and heart rate decreasing occurred in 29 cases, and acute occlusion of the ipsilateral middle cerebral artery occurred in 1 case, which was resolved through thrombolysis and thrombus breaking in time. Over-perfusion symptoms were observed in 13 cases, although without serious complications such as cerebral hemorrhage. The follow-up period continued for 6-32 months, and ultrasonography revealed that 77 cases had no stent-restenosis, while 1 case had restenosis. The application of self-expanding stents had good clinical effects, with fewer complications and higher safety for the treatment of extracranial carotid artery stenosis.
Assuntos
Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Procedimentos Endovasculares/instrumentação , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , UltrassonografiaRESUMO
The study was designed to examine the effects of calcitonin (CT) on the development of murine pre-implantation embryos and possible molecular mechanisms involved in the process. In the present study, the 2-cell embryos were treated with different concentration of CT in vitro for the indicated time and the results demonstrated that CT promoted the development of the pre-implantation embryos in a dosage-dependent manner by increasing the intracellular Ca(2+) level. Furthermore, the present study showed that CT significantly increased the expression of phospho-P38MAPK (Mitogen-Activated Protein Kinase) of the pre-implantation embryos by Western blots and pre-treatment of specific P38MAPK inhibitor significantly reduced the promotion effects of CT on the embryonic development in vitro culture. Moreover, the results of intrauterine horn injection showed that the average number of embryos implanted in CT-antibody or specific P38 MAPK inhibitor-treated uterus was significantly lower than that of the corresponding control, respectively. And the observation of tissue specimen suggested that some embryos were degenerated in CT-antibody or specific P38 MAPK inhibitor-treated uterus, and adipose vacuoles were present in the decidual cells. In conclusion, CT promoted the development of pre-implantation embryos and the intracellular Ca(2+) -dependent P38MAPK signal molecule was involved in the process.
Assuntos
Calcitonina/farmacologia , Cálcio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Cálcio/imunologia , Técnicas de Cultura Embrionária , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Imidazóis/farmacologia , Imunoglobulina G , Camundongos , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
To identify genes potentially implicated in atherogenesis, a cDNA library was constructed from human atherosclerotic aorta and differentially screened with 32P-labeled-cDNAs prepared from human normal and atherosclerotic aortas. Two cDNA clones exhibiting higher hybridization to the 32P-labeled cDNAs from atherosclerotic vessels were isolated and identified to be genes encoding L-ferritin and H-ferritin, respectively. Northern blot analysis confirmed that the expression of both ferritin genes was notably higher in human and rabbit atherosclerotic aortas than in their normal counterparts. A time-course study illustrated that both L- and H-ferritin mRNAs were markedly increased in aortas of rabbits after feeding with a high cholesterol diet for 6 wk, which was also the time period after which the formation of lesions became evident. In situ hybridization revealed that both L- and H-ferritin mRNAs were induced in endothelial cells and macrophages of human early lesions. The signals were also detected in the smooth muscle cells of advanced lesions. Immunostaining further identified the presence of ferritin protein in atherosclerotic lesions. On the other hand, Prussian blue stain revealed the presence of iron deposits in advanced lesions but not in early human or rabbit lesions. Further experiments with cultured human monocytic THP-1 cells and aortic smooth muscle cells demonstrated that ferritin mRNAs were subjected to up-regulation by treatment with IL-1 or TNF, while TGF, PDGF, and oxidized LDL did not affect the expression of either ferritin gene in both cell lines. Collectively, these results clearly demonstrate that ferritin genes are susceptible to induction in the course of plaque formation.
Assuntos
Arteriosclerose/metabolismo , Ferritinas/genética , Regulação da Expressão Gênica , Animais , Células Cultivadas , DNA Complementar/análise , Ferritinas/análise , Humanos , Hibridização In Situ , Interleucina-1/farmacologia , Ferro/análise , Lipoproteínas LDL/metabolismo , Masculino , Monócitos/metabolismo , Oxirredução , Coelhos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
We have recently identified and characterized a novel oncogene, maelstrom (MAEL) from 1q24, in the pathogenesis of hepatocellular carcinoma. In this study, MAEL was investigated for its oncogenic role in urothelial carcinoma of the bladder (UCB) tumorigenesis/aggressiveness and underlying molecular mechanisms. Here, we report that overexpression of MAEL in UCB is important in the acquisition of an aggressive and/or poor prognostic phenotype. In UCB cell lines, knockdown of MAEL by short hairpin RNA is sufficient to inhibit cell growth, invasiveness/metastasis and suppressed epithelial-mesenchymal transition (EMT), whereas ectopic overexpression of MAEL promoted cell growth, invasive and/or metastatic capacity and enhanced EMT both in vitro and in vivo. We further demonstrate that MAEL could induce UCB cell EMT by downregulating a critical downstream target, the metastasis suppressor 1 (MTSS1) gene, ultimately leading to an increased invasiveness of cancer cells. Notably, overexpression of MAEL in UCB cells substantially enhanced the enrichment of DNA methyltrans-ferase (DNMT)3B and histone deacetylase (HDAC)1/2 on the promoter of the MTSS1, and thereby epigenetically suppressing the MTSS1 transcription. Downregulation of MTSS1 by MAEL in UCB cells is partially dependent on DNMT3B. Furthermore, we identify that beside the gene amplification of MAEL, miR-186 is a key negative regulator of MAEL and downregulation of miR-186 is another important mechanism for MAEL overexpression in UCBs. These data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1, and MAEL could be used as a novel prognostic marker and/or effective therapeutic target for human UCB.
Assuntos
Proteínas de Transporte/genética , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas dos Microfilamentos/genética , Proteínas de Neoplasias/genética , Neoplasias da Bexiga Urinária/genética , Animais , Proteínas de Transporte/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA , Regulação para Baixo , Epigênese Genética , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , DNA Metiltransferase 3BRESUMO
UNLABELLED: Spleen enlargement is commonly associated with portal hypertension from cirrhosis and may cause thrombocytopenia. Thus, accurate assessment of spleen size may be helpful in the clinical evaluation. Spleen length is not a precise estimate of spleen size because of the variation in spleen configuration, and spleen volumes measured by edging techniques can be tedious. We present a new method of measuring the functional spleen volume by liver-spleen scan (LSSs), validation experiments and some clinical data. METHODS: The method involves measurement of the total spleen counts by SPECT and dividing by a representative voxel concentration on a single frame to obtain the organ volume. Validation included phantom studies and clinical evaluation in 443 consecutive patients, including 216 with histologic assessments of chronic liver disease (CLD) and 11 healthy volunteers. RESULTS: A calibration factor determined from phantoms was used to convert the calculated volume (CV) to the "true" volume (V): V = CV (0.956) - 66.5 (r = 0.9991; P < 0.001). The volume calculations were validated in a second group of phantoms (r= 0.981; P < 0.0001). Spleen volumes were expressed as volume (cm3) and as volume per pound ideal body weight (IBW) (cm3/lb) (the conversion factor to convert cm3/lb IBW to cm3/kg IBW is 2.2). Clinical studies of reproducibility included demonstration of a significant (P < 0.0001) linear correlation between volumes calculated from repeat LSSs within 9 mo of the initial LSS in 11 healthy volunteers and 32 patients with CLD: y = 1.02x - 25; r = 0.968. The correlation with spleen volumes from autopsy or splenectomy was significant: y = 0.766x + 57; r = 0.845; P < 0.001. The normal spleen volume in 11 patients was 201 +/- 77 cm3 and 1.43 +/- 0.68 cm3/lb IBW (upper limits of normal: 335 cm3 or 2.5 cm3/lb IBW). In 443 consecutive LSSs over 15 mo, half of the patients had spleen volumes above the upper limits of healthy volunteers, and CLD was present in 90.9% of these patients. In 216 patients with histologically proven liver disease, a progressive increase in the percentage of spleen volumes above the upper limits of normal was noted from no fibrosis (10%) to mild to moderate fibrosis (36.7%) to early cirrhosis (52%) to advanced liver disease (75%). The correlation of spleen volume with platelet count was excellent (r = 0.7635; P < 0.005). CONCLUSION: This novel spleen volume measurement detects serious liver disease and correlates with splenic hyperfunction.
Assuntos
Hepatopatias/diagnóstico por imagem , Baço/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Doença Crônica , Humanos , Técnicas de Diluição do Indicador , Hepatopatias/fisiopatologia , Tamanho do Órgão , Imagens de Fantasmas , Contagem de Plaquetas , Estudos Prospectivos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Baço/fisiopatologia , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Tomografia Computadorizada por Raios XRESUMO
Prior studies from our institution have shown that single photon emission computed tomography is sensitive (100%) in predicting patients at risk for serious arrhythmias. However, the positive predictive value is low (15% to 20%). The purpose of this study was to determine if quantitative analysis of single photon emission computed tomographic defects could improve predictive value. One hundred seventy-five patients with positive single photon emission computed tomographic scans were studied. One hundred two patients developed arrhythmias, 42 of which were ventricular. Arrhythmias were associated with all defect loci and all defect sizes. The incidence of arrhythmias did increase with increasing size. Patients were at risk for arrhythmias up to 72 hours after trauma. The value of single photon emission computed tomography is its ability to predict patients at risk for arrhythmias. This study shows that any single photon emission computed tomographic defect, regardless of location or size, is a significant predictor of arrhythmias.
Assuntos
Traumatismos Cardíacos/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Ferimentos não Penetrantes/diagnóstico por imagem , Adolescente , Adulto , Idoso , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Contusões/complicações , Contusões/diagnóstico por imagem , Feminino , Traumatismos Cardíacos/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Ferimentos não Penetrantes/complicaçõesRESUMO
Two antibacterial and xanthine oxidase inhibitory cerebrosides, one of which is chemically new, were characterized from the chloroform-methanol (1:1) extract of Fusarium sp. IFB-121, an endophytic fungus in Quercus variabilis. By means of chemical and spectral methods [IR, electrospray ionization MS (ESI-MS), tandem ESI-MS, 1H and 13C NMR, distortionless enhancement by polarization transfer, COSY, heteronuclear multiple-quantum coherence, heteronuclear multiple-bond correlation, and 2-D nuclear Overhauser effect correlation spectroscopy], the structure of the new metabolite named fusaruside was established as (2S,2'R,3R,3'E,4E,8E,10E)-1-O-beta-D-glucopyranosyl-2-N-(2'-hydroxy-3'-octadecenoyl)-3-hydroxy-9-methyl-4,8,10-sphingatrienine, and the structure of the other was identified as (2S,2'R,3R,3'E,4E,8E)-1-O-beta-D-glucopyranosyl-2-N-(2'-hydroxy-3'-octadecenoyl)-3-hydroxy-9-methyl-4,8-sphingadienine. Both new and known cerebrosides, although inactive to Trichophyton rubrum and Candida albicans, showed strong antibacterial activities against Bacillus subtilis, Escherichia coli, and Pseudomonas fluorescens, with their minimum inhibitory concentrations being 3.9, 3.9, and 1.9 microg/mL, and 7.8, 3.9, and 7.8 microg/mL, respectively. Furthermore, both metabolites were inhibitory to xanthine oxidase, with the IC50 value of fusaruside being 43.8 +/- 3.6 microM and the known cerebroside being 55.5 +/- 1.8 microM.
Assuntos
Antibacterianos/metabolismo , Cerebrosídeos/metabolismo , Inibidores Enzimáticos/metabolismo , Fusarium/química , Quercus/microbiologia , Xantina Oxidase/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/isolamento & purificação , Cerebrosídeos/química , Cerebrosídeos/isolamento & purificação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Xantina Oxidase/metabolismoRESUMO
OBJECTIVES: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes. Fibroblast growth factor 10 (FGF10) acts as a growth factor for keratinocyte proliferation. The aim of this study is to investigate whether FGF10 blockage, a new monoclonal antibody against FGF10 we generated, could mitigate topical propranolol-induced psoriasis-like lesions in guinea pigs. MATERIALS AND METHODS: The monoclonal anti-FGF10 was generated by a routine method and purified by affinity chromatography. The effect of FGF10 and anti-FGF10 on human keratinocyte HaCaT cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The back of the ears of individual guinea pigs was topically exposed to 5% propranolol emulsion to induce psoriasis-like lesions and randomly treated topically with phosphate buffered saline (PBS), hydrocortisone butyrate, or different doses of anti-FGF10. The pathologic changes and the degrees of inflammation in the auricular areas of individual animals were examined histologically. RESULTS: Characterization revealed that anti-FGF10 had a purity of 90% and a titer of 1:12800. We found that FGF10 stimulated HaCaT cell proliferation while treatment with different doses of anti-FGF10 inhibited FGF10-induced cell proliferation in a dose-dependent manner (100, 200 ng/ml, p < 0.05 vs. control; 400, 800, 1600 ng/ml, p < 0.01 vs. control). Compared to PBS-treated psoriatic animals, treatment with anti-FGF10, like hydrocortisone butyrate, greatly inhibited the severity of psoriasis-like lesions by reducing the Baker's scores, the thickness of epidermis, and the numbers of monocyte infiltrates in the dermis of animals. CONCLUSIONS: The newly generated anti-FGF10 monoclonal antibody inhibited the proliferation of human keratinocytes in vitro and mitigated inflammation and pathogenic changes in propranolol-induced psoriasis-like lesions in animals. Therefore, these findings may provide a proof of principle that blockage of FGF-10 may inhibit psoriasis-related inflammation.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Fator 10 de Crescimento de Fibroblastos/imunologia , Queratinócitos/efeitos dos fármacos , Psoríase/tratamento farmacológico , Administração Tópica , Animais , Anticorpos Monoclonais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Cobaias , Humanos , Masculino , Camundongos Endogâmicos BALB C , Propranolol , Psoríase/induzido quimicamente , Psoríase/patologia , Pele/patologiaRESUMO
Growing evidence has suggested that hydrogen sulfide (H2S) acts as a novel neuro-modulator and neuroprotective agent; however, it remains to be investigated whether H2S has a direct effect on neural stem cells (NSCs). We report here that NSCs expressed cystathionine ß synthase (CBS) and addition of exogenous H2S donor, L-cysteine, stimulated proliferation and increased the differentiation potential of NSCs to neurons and astroglia. Moreover, pre-treatment with aminooxyacetic acid, the inhibitor of CBS or knockdown of CBS in using siRNA, significantly attenuated the effects of L-cysteine on elevated H2S levels and the cell proliferation; it also effectively suppressed L-cysteine-induced neurogenesis and astrocytogenesis. Further analysis revealed that L-cysteine-induced proliferation was associated with phosphorylation of extracellular signal-regulated kinases 1/2 and differentiation with altered expression of differentiation-related genes. Taken together, the present data suggest that L-cysteine can enhance proliferation and differentiation of NSCs via the CBS/H2S pathway, which may serve as a useful inference for elucidating its role in regulating the fate of NSCs in physiological and pathological settings.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cistationina beta-Sintase/metabolismo , Cisteína/farmacologia , Sulfeto de Hidrogênio/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Análise de Variância , Animais , Bromodesoxiuridina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Embrião de Mamíferos , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tacrolimo/análogos & derivados , Tacrolimo/farmacologia , Telencéfalo/citologia , Fatores de Tempo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Cardiac PEComa is very rare. We reported two cases of epithelioid PEComas, one in an adult and one in a 2-year-old child. Both tumors were composed of sheets of epithelioid cells with coagulation necrosis. In addition, the adult case showed marked nuclear atypia and high mitotic activity with atypical mitosis and the pediatric case showed unusual clear cell features. Immunohistochemically, both tumors were positive for HMB-45 and SMA and negative for S100 and cytokeratin. Electron microscopy was performed in the pediatric case and showed premelanosomes. The adult patient developed extensive metastasis indicating malignant behavior. Prior to the two cases, only 5 other cases of cardiac PEComa were reported and the literatures are reviewed.
Assuntos
Articulação do Joelho/cirurgia , Osteotomia , Adolescente , Adulto , Feminino , Humanos , Artropatias/cirurgia , Masculino , Osteotomia/métodosRESUMO
Local microenvironment plays an important role in determining the fate choice of stem cells in the central nervous system (CNS). Astrocytes, a major component of local microenvironment in the CNS, have been demonstrated to influence the proliferation and neural differentiation of stem cells including neural stem/progenitor cells, embryonic stem cells and bone marrow stromal cells (BMSCs). However, it has remained to be ascertained if inflammation-activated astrocytes can affect the behavior of BMSCs. To this end, astrocyte-conditioned medium (ACM) was prepared in this study for treatment of BMSCs. The ACM derived from Wistar rat astrocytes stimulated by lipopolysaccharide for 12, 36 or 72 h, respectively, served as inflammatory ACM (12 h ACM, 36 h ACM and 72 h ACM), while that from unstimulated astrocytes was used as normal control astrocyte-conditioned medium (N-ACM). The results showed that the proliferation and neural differentiation of BMSCs grown in inflammatory ACM were significantly increased compared with those grown in N-ACM. The efficiency of BMSCs exposed to 36 h ACM was significantly greater than that of those exposed to 12 or 72 h ACM. Following neutralization of interleukin-6 (IL-6) of the ACM, both the proliferation and astrocytic differentiation of BMSCs were decreased; on the other hand, the neuronal differentiation was significantly increased. The present findings suggest that inflammation-activated astrocytes can facilitate the proliferation and neural differentiation of BMSCs and activated astrocytes at different phase after CNS injuries might have distinct effects on BMSCs. Moreover, astrocyte-derived IL-6 participates in the proliferation and neural differentiation of BMSCs.