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1.
Braz. j. biol ; 83: e244311, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285616

RESUMO

Abstract Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.


Resumo A tuberculose é uma doença transmissível com altas taxas de morbimortalidade nos países em desenvolvimento. O objetivo principal do estudo é comparar métodos convencionais, como cultura de bacilo álcool-ácido resistente (BAAR) e microscopia, com métodos de diagnóstico rápido. O objetivo secundário é comparar os achados histopatológicos e microbiológicos em pacientes com suspeita de linfadenite tubercular. Um total de 111 amostras (agosto de 2018 a setembro de 2019) de gânglios linfáticos foi processado ​​para microscopia de AFB, culturas de AFB, teste de susceptibilidade a drogas (DST), histopatologia e Xpert Mycobacterium tuberculosis (MTB)/ensaios de resistência à rifampicina (RIF). Das 111 amostras de linfonodos, 6 (5,4%) foram positivas para baciloscopia de AFB, 84 (75,6%) foram positivas para cultura de AFB, 80 (70,7%) foram positivas para o GeneXpert e 102 (91,8%) foram indicativas de tuberculose para estudos histopatológicos. A positividade da cultura do tubo indicador de crescimento de micobactérias (MGIT) foi 84 (75,6%), maior que a cultura sólida de Lowenstein-Jensen (LJ), 74 (66,6%). As culturas positivas foram submetidas a DST fenotípico. Dois casos eram multirresistentes (MDR) ao DST, enquanto três casos eram resistentes à rifampicina no GeneXpert. A sensibilidade do GeneXpert foi 62% contra o método convencional de cultura AFB. O fraco desempenho dos métodos convencionais de diagnóstico de linfadenite requer metodologia de diagnóstico precoce e precisa. O teste Xpert MTB/RIF pode ajudar no tratamento de casos de tuberculose multirresistente. No entanto, métodos rápidos e convencionais devem ser usados ​​para o isolamento completo do Mycobacterium tuberculosis.

2.
Braz. j. biol ; 83: e247018, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285617

RESUMO

Abstract The Rufous treepie (Dendrocitta vagabunda) belongs to family corvidae, order Passeriformes which includes about 100 species. The current study was conducted to gather information about the Population distribution and habitat analysis of D. vagabunda at District Abbottabad, Pakistan. The data were collected on monthly basis both morning and evening times (2018-2019). "The ''Point count Method" was used for population estimation and ''Quadrates Method" for habitat analysis of study area. The result shows an average month-wise population density of D. vagabunda was maximum at Jhangra 0.14±0.039/ha, whereas minimum at Havelian 0.11±0.022/ha. There was no significant difference (p>0.05) among monthly population densities of D. vagabunda, however, a significant difference (p<0.05) was found between morning and evening times population of the specie. The present study revealed that importance value index (IVI) of plants species at Sherwan, Bakot, Havelian, Langra and Jhangra were 59.6±12.6, 50.1±6.9, 53.4±6.3, 66.8±10 and 60.1±7.7. Likewise, the frequency of shrubs at Sherwan, Bakot, Havelian, Langra and Jhangra were 33.3±4.2, 45±9.4, 46.7±8.2, 55.6±22.2 and 37.5±8.5. Similarly, the frequency of herbs at Sherwan, Bakot, Havelian, Langra and Jhangra were 40.4±6.0, 37.5±5.6, 53.3±7.4, 48.5±5.2 and 46.9±7.4 respectively. Our results show the study area as suitable habitat for D. vagabunda.


Resumo A trepadeira Rufous (Dendrocitta vagabunda) pertence à família corvidae, ordem Passeriformes que inclui cerca de 100 espécies. O estudo atual foi realizado para reunir informações sobre a distribuição da população e análise do habitat de D. vagabunda no distrito de Abbottabad, Paquistão. Os dados foram coletados mensalmente pela manhã e à noite (2018-2019). O "método de contagem de pontos" foi usado para estimativa da população e o "método dos quadrados" para análise de habitat da área de estudo. O resultado mostra que uma densidade populacional média mensal de D. vagabunda foi máxima em Jhangra 0,14 ± 0,039 / ha, enquanto a mínima em Havelian 0,11 ± 0,022/ha. Não houve diferença significativa (p> 0,05) entre as densidades populacionais mensais de D. vagabunda, entretanto foi encontrada diferença significativa (p <0,05) entre os períodos matutino e noturno da população da espécie. O presente estudo revelou que o índice de valor de importância (IVI) das espécies de plantas em Sherwan, Bakot, Havelian, Langra e Jhangra foi de: 59,6 ± 12,6, 50,1 ± 6,9, 53,4 ± 6,3, 66,8 ± 10 e 60,1 ± 7,7. Da mesma forma, a frequência de arbustos em Sherwan, Bakot, Havelian, Langra e Jhangra foi de: 33,3 ± 4,2, 45 ± 9,4, 46,7 ± 8,2, 55,6 ± 22,2 e 37,5 ± 8,5. Da mesma forma, a frequência de ervas em Sherwan, Bakot, Havelian, Langra e Jhangra foi: 40,4 ± 6,0, 37,5 ± 5,6, 53,3 ± 7,4, 48,5 ± 5,2 e 46,9 ± 7,4, respectivamente. Nossos resultados mostram a área de estudo como habitat adequado para D. vagabunda.

3.
Braz J Biol ; 83: e244311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34431905

RESUMO

Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose dos Linfonodos/diagnóstico
4.
Braz J Biol ; 83: e247018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34431914

RESUMO

The Rufous treepie (Dendrocitta vagabunda) belongs to family corvidae, order Passeriformes which includes about 100 species. The current study was conducted to gather information about the Population distribution and habitat analysis of D. vagabunda at District Abbottabad, Pakistan. The data were collected on monthly basis both morning and evening times (2018-2019). "The ''Point count Method" was used for population estimation and ''Quadrates Method" for habitat analysis of study area. The result shows an average month-wise population density of D. vagabunda was maximum at Jhangra 0.14±0.039/ha, whereas minimum at Havelian 0.11±0.022/ha. There was no significant difference (p>0.05) among monthly population densities of D. vagabunda, however, a significant difference (p<0.05) was found between morning and evening times population of the specie. The present study revealed that importance value index (IVI) of plants species at Sherwan, Bakot, Havelian, Langra and Jhangra were 59.6±12.6, 50.1±6.9, 53.4±6.3, 66.8±10 and 60.1±7.7. Likewise, the frequency of shrubs at Sherwan, Bakot, Havelian, Langra and Jhangra were 33.3±4.2, 45±9.4, 46.7±8.2, 55.6±22.2 and 37.5±8.5. Similarly, the frequency of herbs at Sherwan, Bakot, Havelian, Langra and Jhangra were 40.4±6.0, 37.5±5.6, 53.3±7.4, 48.5±5.2 and 46.9±7.4 respectively. Our results show the study area as suitable habitat for D. vagabunda.


Assuntos
Ecossistema , Animais , Paquistão , Densidade Demográfica
5.
New Microbes New Infect ; 36: 100716, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32637123

RESUMO

Globally, urinary tract infection (UTI) is considered a major public health concern and the second most common bacterial infection affecting individuals of different ages. Bacteria are responsible for about 95% of UTIs. The emergence of antimicrobial resistance in uropathogens may lead to poor treatment outcomes in individuals with UTIs. The knowledge of the microorganism involves and antibiograms are important for the empirical treatment of UTIs. A cross-sectional study was carried out over 7 months (January to July 2019) with a focus on the identification of bacterial pathogens causing UTI and the evaluation of their antibiogram. In total, 804 urine samples were collected from individuals with suspected UTIs and inoculated on recommended media. Isolation and identification of the bacterial strains were performed using standard microbiological protocols. Antibiotic susceptibility was carried out following CLSI recommended guidelines. Among the tested specimens, 290 (36.1%) had significant bacterial growth and 147 (50.7%) of the strains were isolated from female patients. The frequently identified isolates were Escherichia coli (68.9%), followed by Klebsiella pneumoniae (8.9%) and Staphylococcus aureus (6.7%). The highest percentages of resistance have been observed against tested antibiotics. The majority of the isolates were extended-spectrum ß-lactamase producers (85.2%) and multidrug-resistant (98.3%). We observed that Gram-negative bacteria were the main cause of UTIs where the predominant microorganism was E. coli.

7.
Trop Biomed ; 37(4): 1000-1007, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33612752

RESUMO

Hemophilia is a rare bleeding disorder that needs plasma or clotting factor concentrate transfusion. Therefore chances of blood-borne pathogens like HCV transmission increase due to high prevalence in healthy donors. This study was aimed to determine the prevalence of HCV genotypes and associated risk factors in hemophilia patients of Khyber Pakhtunkhwa, Pakistan. Blood samples and data were collected from 672 hemophiliacs after proper consent obtained from each patient. Samples were analyzed for anti-HCV, HCV RNA and HCV genotype/s detection. Of the total, 22.32% (150) were anti-HCV positive, of which HCV RNA was detected in 18.45% (124) individuals. HCV genotype 3a was found with significantly higher prevalence (p<0.05) (19.35%) as compared to 2a (16.13%) and 1a (12.90%). HCV-3b and HCV-4 were found each in 3.22% samples. Dual infection of genotypes was found in 22.58% of individuals and 22.58% HCV RNA positive sampels were not typed. A total of 572 (85.12%) subjects had hemophilia A and 100 (14.88%) had hemophilia B. In hemophiliacs A the most dominant genotype was 3a (19.27%) while in hemophilia B, genotype 1a was prevalent (26.67%). Whole blood and plasma transfusion were observed as the main risk factors of HCV. It is concluded that HCV genotype 3a and 2a are prevalent in hemophilia patients of Khyber Pakhtunkhwa Pakistan and the main risk factor observed was an unscreened whole blood transfusion.


Assuntos
Hemofilia A/epidemiologia , Hemofilia B/epidemiologia , Hepacivirus/genética , Hepatite C/epidemiologia , Adolescente , Adulto , Transfusão de Componentes Sanguíneos , Criança , Pré-Escolar , Genótipo , Hemofilia A/virologia , Hemofilia B/virologia , Hepatite C/virologia , Humanos , Pessoa de Meia-Idade , Paquistão/epidemiologia , Prevalência , Fatores de Risco , Adulto Jovem
8.
Bone Joint J ; 101-B(5): 547-551, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31039000

RESUMO

AIMS: The aim of this study was to investigate the differences in 30-day outcomes between patients undergoing revision for an infected total hip arthroplasty (THA) compared with an aseptic revision THA. PATIENTS AND METHODS: This was a retrospective review of prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, between 2012 and 2017, using Current Procedural Terminology (CPT) codes for patients undergoing a revision THA (27134, 27137, 27138). International Classification of Diseases Ninth Revision/Tenth Revision (ICD-9-CM, ICD-10-CM) diagnosis codes for infection of an implant or device were used to identify patients undergoing an infected revision THA. CPT-27132 coupled with ICD-9-CM/ICD-10-CM codes for infection were used to identify patients undergoing a two-stage revision. A total of 13 556 patients were included; 1606 (11.8%) underwent a revision THA due to infection and there were 11 951 (88.2%) aseptic revisions. RESULTS: Patients undergoing an infected revision had a significantly greater length of stay of more than three days (p < 0.001), higher odds of any 30-day complication (p < 0.001), readmission within 30 days (p < 0.001), 30-day reoperations (p < 0.001), and discharge to a destination other than the patient's home (p < 0.001). CONCLUSION: The findings suggest the need for enhanced risk adjustment based on the indication of revision THA prior to setting prices in bundled payment models of total joint arthroplasty. This risk adjustment should be used to reduce the chance of financial disincentives in clinical practice. Cite this article: Bone Joint J 2019;101-B:547-551.


Assuntos
Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/cirurgia , Reoperação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Gastos em Saúde , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Reoperação/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
9.
Cardiovasc Intervent Radiol ; 41(12): 1826-1839, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30039506

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially lethal outcome of pulmonary embolism. Balloon pulmonary angioplasty (BPA) is aimed at improving pulmonary perfusion and pulmonary hemodynamics and has gained a lot of interest recently in patients either unsuitable for or refractory to surgical pulmonary endarterectomy. This article outlines the clinical features and diagnostic criteria, imaging evaluation, current medical and surgical treatment options for CTEPH. BPA is discussed in detail, focusing on the rationale, patient selection, technical details, post-procedural care and outcomes.


Assuntos
Angioplastia com Balão/métodos , Hipertensão Pulmonar/terapia , Embolia Pulmonar/terapia , Doença Crônica , Hemodinâmica , Humanos , Hipertensão Pulmonar/etiologia , Seleção de Pacientes , Artéria Pulmonar , Embolia Pulmonar/complicações
10.
Clin Genet ; 91(2): 328-332, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27629923

RESUMO

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.


Assuntos
Proteínas de Ciclo Celular/genética , Claudinas/genética , Disgenesia Gonadal 46 XX/genética , Perda Auditiva Neurossensorial/genética , Animais , Consanguinidade , Exoma/genética , Feminino , Disgenesia Gonadal 46 XX/patologia , Perda Auditiva Neurossensorial/patologia , Homozigoto , Humanos , Masculino , Camundongos , Mutação , Linhagem
11.
Osteoarthritis Cartilage ; 25(2): 321-331, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27693502

RESUMO

OBJECTIVE: Oxidative stress is a major obstacle against cartilage repair in osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this issue. We evaluated the effect of Vitamin E preconditioning in improving the potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative stress prevailing during OA. METHODS: Vitamin E pretreated MSCs were exposed to oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in surgically-induced rat model of OA. Analysis was done in terms of cell proliferation, apoptosis, cytotoxicity, chondrogenesis and repair of cartilage tissue. RESULTS: Vitamin E pretreatment enabled MSCs to counteract H2O2-induced oxidative stress in vitro. Proliferative markers, proliferating cell nuclear antigen (PCNA) and Ki67 were up-regulated, along with the increase in the viability of MSCs. Expression of transforming growth factor-beta (TGFß) was also increased. Reduction of apoptosis, expression of vascular endothelial growth factor (VEGF) and caspase 3 (Casp3) genes, and lactate dehydrogenase (LDH) release were also observed. Transplantation of Vitamin E pretreated MSCs resulted in increased proteoglycan contents of cartilage matrix. Increased expression of chondrogenic markers, Aggrecan (Acan) and collagen type-II alpha (Col2a1) accompanied by decreased expression of collagen type-I alpha (Col1a1) resulted in increased differentiation index that signifies the formation of hyaline cartilage. Further, there was an increased expression of PCNA and TGFß genes along with a decreased expression of Casp3 and VEGF genes with increased histological score. CONCLUSION: Taken together results of this study demonstrated that Vitamin E pretreated MSCs have an improved ability to impede the progression of OA and thus increased potential to treat OA.


Assuntos
Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Vitamina E/uso terapêutico
12.
Mol Psychiatry ; 22(11): 1604-1614, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-27457812

RESUMO

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.


Assuntos
Deficiência Intelectual/genética , Alelos , Consanguinidade , Exoma/genética , Família , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Humanos , Mutação , Paquistão , Linhagem , Sequenciamento Completo do Exoma/métodos
13.
Osteoarthritis Cartilage ; 22(11): 1894-901, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25128628

RESUMO

OBJECTIVE: To evaluate the therapeutic efficacy of Adipose derived MSCs (ADMSCs) in combination with chondrocytes in counteracting oxidative stress in chondrocytes in vitro and in rat model of osteoarthritis (OA). METHOD: Cultured chondrocytes were exposed to oxidative stress with 200 µM Hydrogen peroxide (H2O2), followed by co-culture with ADMSCs or chondrocytes or combination of both cell types in a transwell culture system for 36 h. The cytoprotective effect was assessed by immunocytochemistry and gene expression analysis. In vivo study evaluated therapeutic effect of the above mentioned three treatments after transplantation in OA rats. RESULTS: The Combination of ADMSCs + Chondrocytes decreased the extent of oxidative stress-induced damage of chondrocytes. Enhanced expression level of Acan and Collagen type-II alpha (Col2a1) with a correspondingly decreased expression of Collagen type-I alpha (Col1a1) and Matrix metallopeptidase 13 (Mmp13) was maximally observed in this group. Moreover, reduced count of annexin-V positive cells, Caspase (Casp3) gene expression and Lactate dehydrogenase (LDH) release with concomitantly enhanced viability and expression of proliferating cell nuclear antigen (PCNA) gene was observed. In vivo study showed that homing of cells and proteoglycan contents of knee joints were significantly better in ADMSCs + Chondrocytes transplanted rats. Increased expression of Acan and Col2a1 along with decreased expression of Col1a1 and Mmp13 indicated formation of hyaline cartilage in this group. These rats also demonstrated significantly reduced expression of Casp3 while increased expression of PCNA genes than the other cell transplanted groups. CONCLUSIONS: Our results demonstrated that a combination of ADMSCs and chondrocytes may be a more effective therapeutic strategy against OA than the use of ADMSCs or chondrocytes separately.


Assuntos
Condrócitos/transplante , Colágeno Tipo I/genética , Regulação da Expressão Gênica , Metaloproteinase 13 da Matriz/genética , Osteoartrite do Joelho/genética , Amplitude de Movimento Articular/efeitos dos fármacos , Fatores de Transcrição/uso terapêutico , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Western Blotting , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Colágeno Tipo I/biossíntese , Modelos Animais de Doenças , Imuno-Histoquímica , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/fisiopatologia , Masculino , Metaloproteinase 13 da Matriz/biossíntese , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/metabolismo , Reação em Cadeia da Polimerase , RNA/genética , Amplitude de Movimento Articular/fisiologia , Ratos , Ratos Sprague-Dawley
14.
Genomics ; 103(2-3): 169-76, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24603341

RESUMO

Exome and whole-genome analyses powered by next-generation sequencing (NGS) have become invaluable tools in identifying causal mutations responsible for Mendelian disorders. Given that individual exomes contain several thousand single nucleotide variants and insertions/deletions, it remains a challenge to analyze large numbers of variants from multiple exomes to identify causal alleles associated with inherited conditions. To this end, we have developed user-friendly software that analyzes variant calls from multiple individuals to facilitate identification of causal mutations. The software, termed exomeSuite, filters for putative causative variants of monogenic diseases inherited in one of three forms: dominant, recessive caused by a homozygous variant, or recessive caused by two compound heterozygous variants. In addition, exomeSuite can perform homozygosity mapping and analyze the variant data of multiple unrelated individuals. Here we demonstrate that filtering of variants with exomeSuite reduces datasets to a fraction of a percent of their original size. To the best of our knowledge this is the first freely available software developed to analyze variant data from multiple individuals that rapidly assimilates and filters large data sets based on pattern of inheritance.


Assuntos
Conjuntos de Dados como Assunto , Exoma , Doenças Genéticas Inatas/genética , Mutação INDEL , Polimorfismo de Nucleotídeo Único , Software , Alelos , Análise Mutacional de DNA/métodos , Feminino , Estudo de Associação Genômica Ampla/métodos , Heterozigoto , Homozigoto , Humanos , Masculino , Linhagem
15.
Leukemia ; 27(6): 1301-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23486531

RESUMO

Polycomb repressive complex 2 (PRC2) is involved in trimethylation of histone H3 lysine 27 (H3K27), chromatin condensation and transcriptional repression. The silencing function of PRC2 complex is mostly attributed to its intrinsic activity for methylating H3K27. Unlike in B-cell lymphomas, enhancer of zeste homolog 2 (EZH2) mutations in myeloid malignancies are inactivating/hypomorphic. When we assessed the mutational status in myeloid malignancies (N=469 cases examined), we found EZH2 and EED/SUZ12 mutations in 8% and 3.3% of cases, respectively. In addition to mutant cases, reduced EZH2 expression was also found in 78% cases with hemizygous deletion (-7/del7q cases involving EZH2 locus) and 41% of cases with diploid chromosome 7, most interestingly cases with spliceosomal mutations (U2AF1/SRSF2 mutations; 63% of cases). EZH2 mutations were characterized by decreased H3K27 trimethylation and increased chromatin relaxation at specific gene loci accompanied by higher transcriptional activity. One of the major downstream target is HOX gene family, involved in the regulation of stem cell self-renewal. HOXA9 was found to be overexpressed in cases with decreased EZH2 expression either by EZH2/spliceosomal mutations or because of -7/del7q. In summary, our results suggest that loss of gene repression through a variety of mutations resulting in reduced H3K27 trimethylation may contribute to leukemogenesis.


Assuntos
Epigênese Genética , Neoplasias Hematológicas/genética , Histonas/genética , Complexo Repressor Polycomb 2/metabolismo , Western Blotting , Cromossomos Humanos Par 7 , Proteína Potenciadora do Homólogo 2 de Zeste , Humanos , Mutação , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
16.
Phys Rev Lett ; 109(16): 167003, 2012 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-23215117

RESUMO

The spin fluctuation spectra from nonsuperconducting Cu-substituted, and superconducting Co-substituted, BaFe(2)As(2) are compared quantitatively by inelastic neutron scattering measurements and are found to be indistinguishable. Whereas diffraction studies show the appearance of incommensurate spin-density wave order in Co and Ni substituted samples, the magnetic phase diagram for Cu substitution does not display incommensurate order, demonstrating that simple electron counting based on rigid-band concepts is invalid. These results, supported by theoretical calculations, suggest that substitutional impurity effects in the Fe plane play a significant role in controlling magnetism and the appearance of superconductivity, with Cu distinguished by enhanced impurity scattering and split-band behavior.

18.
Emerg Med J ; 26(6): 452-5, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19465626

RESUMO

INTRODUCTION: Prehospital thrombolysis has been shown to improve patient outcomes in clinical trials and this has been confirmed in the ongoing large national myocardial infarction registry (Myocardial Infarction National Audit Project; MINAP) reports. This paper describes a system to improve the delivery of prehospital thrombolysis and the associated governance requirements to gain maximum patient benefit. METHODS: Demographic data were prospectively collected on all patients treated by the East Anglian Ambulance Trust with bolus thrombolytics for a presumed diagnosis of ST elevation myocardial infarction between November 2003 and February 2007. Survival status was determined from the NHS strategic tracing service. RESULTS: 1062 patients (mean age 64.0 years (SD 10.6), 795 men) were treated in this time period. There were 71 deaths in this group, with actuarial survival of 93.9% (SE 0.9%) at 30 days, 91.7% (SE 1.0%) at 6 months and 90.8% (SE 1.1%) at 12 months after treatment. Age and cardiac arrest were most strongly associated with mortality (both p<0.001). Twelve (1.2%) patients received thrombolysis that on review was considered inappropriate. There were no deaths in this subgroup. CONCLUSIONS: Prehospital thrombolysis can be administered safely by ambulance staff supported by a Trust clinical support system with excellent clinical outcomes.


Assuntos
Atenção à Saúde/normas , Serviços Médicos de Emergência/normas , Auxiliares de Emergência , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Terapia Trombolítica/normas , Fatores de Tempo , Resultado do Tratamento
19.
J Appl Microbiol ; 106(5): 1682-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19226385

RESUMO

AIMS: Dental caries is caused by the disturbance in oral homeostasis, marked by a notable increase in the population of Streptococcus mutans. Lectins are a group of plant proteins that are capable of recognizing the glycoconjugates present on the bacterial surface. The aim of this study was to evaluate the effect of seven plant lectins on the growth and initial adhesion of S. mutans. METHODS AND RESULTS: Lectins of different carbohydrate specificities were isolated from plant sources by conventional methods of protein purification. The effect on growth of S. mutans was evaluated following CLSI guidelines. None of the lectins used in this study inhibited the bacterial growth and multiplication. The adherence and biofilm formation of bacteria to saliva-coated polystyrene plates was tested in the presence of plant lectins. All the plant lectins tested, inhibited both the adherence and biofilm in a concentration dependent manner. Confocal microscopy and scanning electron microscopy were employed to assess the biofilm formation in the presence of plant lectin (glucose/mannose-specific) at sub-minimal inhibitory concentrations. These evaluations revealed that lectins inhibited the clumping and attachment of S. mutans. CONCLUSIONS: Lectins tested here inhibited initial biofilm formation by S. mutans. Glucose/Mannose-specific lectin altered the adhesion arrangement of the bacteria on the saliva-coated surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: The plant lectins used in this study may offer a novel strategy to reduce development of dental caries by inhibiting the initial adhesion and subsequent biofilm formation of S. mutans.


Assuntos
Biofilmes/crescimento & desenvolvimento , Lectinas/farmacologia , Saliva , Streptococcus mutans/fisiologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Microscopia Confocal , Microscopia Eletrônica de Varredura , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/ultraestrutura
20.
Clin Genet ; 75(1): 86-91, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18505454

RESUMO

Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date, six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage of USH to the 11 known USH loci and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.


Assuntos
Cromossomos Humanos Par 15/genética , Síndromes de Usher/genética , Adolescente , Adulto , Idoso , Criança , Mapeamento Cromossômico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Adulto Jovem
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