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1.
J Appl Microbiol ; 126(1): 68-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30153380

RESUMO

AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml-1 ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml-1 ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability. CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.


Assuntos
Amaranthus/química , Antibacterianos/farmacologia , Betacianinas/farmacologia , Biofilmes/efeitos dos fármacos , Cactaceae/química , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Betacianinas/isolamento & purificação , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificação , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologia
2.
Skin Res Technol ; 22(3): 370-4, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26452436

RESUMO

BACKGROUND: Hypohidrosis is defined as diminished sweating in response to an appropriate thermal or sympathetic stimulus. When encountered in a clinical setting, it necessitates an accurate documentation of its pattern and extent to prognosticate the risk of associated heat-related illnesses. This can be achieved by thermoregulatory sweat testing which includes a starch-iodine sweat test that can be administered via various methods. OBJECTIVE: To describe and evaluate the effectiveness and safety of a novel method of using an atomizer spray gun in administering the starch-iodine test. METHODS: We describe the administration of the starch-iodine test via an atomizer spray gun (Series 700 Lab Model; Mitsuba Systems, Mumbai, India). The method was utilized for the evaluation of 30 individuals who presented with symptoms of hypohidrosis. RESULTS: Application of iodinated starch powder prepared in-house with the atomizer spray gun achieved a lightweight and homogeneous coat on our patients' skin which allowed for clear visualization of the sweating pattern in areas of anhidrosis. The sharp demarcation of the pathological regions enabled the precise calculation of the affected body surface area of impaired sweating. Unlike the starch-iodine tests using the Minor and Wada methods, neither staining of the skin nor irritation was detected in this method. CONCLUSION: We report a novel method of using an atomizer spray gun to perform the starch-iodine test in a rapid, reproducible, effective, and safe manner suitable for use in the clinical evaluation of hypohidrosis.


Assuntos
Dermoscopia/métodos , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/patologia , Nebulizadores e Vaporizadores , Pele/efeitos dos fármacos , Amido/análogos & derivados , Administração Cutânea , Adulto , Aerossóis/administração & dosagem , Aerossóis/síntese química , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pós , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Amido/administração & dosagem , Amido/síntese química
3.
Med J Malaysia ; 71(Suppl 1): 87-99, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27801391

RESUMO

The aim of this review was to summarise published literature on child abuse and neglect and its consequences in Malaysia, to discuss the implications of the research findings and to identify gaps in the local literature on child abuse and neglect. Medical and social literature in the English language published between the year 2000 to 2015 were searched for, resulting in forty four papers to be reviewed inclusive of a few key papers in the earlier years to provide some background information. The literature shows that child abuse and neglect is an important impact factor on mental health outcomes, involvement in substance abuse and delinquency due to the slant of the research interest from social studies. At least 70% of perpetrators are known to the affected children according to school-based prevalence studies. Safety programs and rehabilitation outcome studies involve small cohort groups. Studies on childhood mortality from child abuse or neglect are very limited. Overall, there are a few comprehensive studies involving school children but overall available studies are too patchy in to advocate for resource allocation, change in statutory procedures or training requirements. More extensive studies looking at the complex interaction of social environment, parenting skills, societal attitudes and responses, resilience factors and child safety nets and statutory response and their impact on different types of abuse or neglect are required.


Assuntos
Maus-Tratos Infantis , Pesquisa/tendências , Criança , Emprego , Humanos , Malásia
4.
Med J Malaysia ; 71(5): 244-249, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-28064289

RESUMO

BACKGROUND: Little is known about the views of faculty members who train medical students concerning open disclosure. OBJECTIVES: The objectives of this study were to determine the views of faculty in a medical school on: 1 what constitutes a medical error and the severity of such an error in relation to medication use or diagnosis; 2 information giving following such an adverse event, based on severity; and 3 acknowledgement of responsibility, remedial action, compensation, disciplinary action, legal action, and reporting to a higher body in relation to such adverse event. METHODS: We adapted and contextualized a questionnaire developed from a previous study. The questionnaire had 4 case vignettes that described 1 clear medication error with lifelong disability; 2 possible diagnostic error with lifelong disability; 3 possible diagnostic error without harm; and 4 clear medication error without harm. We invited all faculty members attached to the medical school at the International Medical University to participate in the study. RESULTS: Seventy faculty members took part. Faculty members viewed a medical error as having taken place depending on how clearly an error had occurred (94% and 73% versus 53% and 27%). They viewed cases as more severe based on the severity of complications (85% and 46% versus 5% and 10%). With increasing severity, they tended to attribute responsibility for the event and the duty to disclose towards more senior clinicians. They were also more agreeable with remedial action, compensation, disciplinary action, and reporting to a higher agency. There was no strong evidence of association between these areas and the demographics of faculty members. CONCLUSIONS: Faculty members are more likely to perceive an error had occurred depending on the clarity of the circumstances. They viewed severity based on the presence of complications. Severity determined how they attributed responsibility, duty to disclose, and other areas related to open disclosure.


Assuntos
Docentes de Medicina , Erros Médicos , Faculdades de Medicina , Revelação da Verdade , Humanos , Pais
5.
Anaesthesia ; 70(4): 393-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25311146

RESUMO

Emergence delirium is a significant problem in children regaining consciousness following general anaesthesia. We compared the emergence characteristics of 120 patients randomly assigned to receive a single intravenous dose of dexmedetomidine 0.3 µg.kg(-1) , propofol 1 mg.kg(-1) , or 10 ml saline 0.9% before emerging from general anaesthesia following a magnetic resonance imaging scan. Emergence delirium was diagnosed as a score of 10 or more on the Paediatric Anaesthesia Emergence Delirium scale. The incidence of emergence delirium was 42.5% in the dexmedetomidine group, 33.3% in the propofol group and 41.5% in the saline group (p = 0.671). Three patients in the dexmedetomidine group, none in the propofol group and two in the saline group required pharmacological intervention for emergence delirium (p = 0.202). Administration of neither dexmedetomidine nor propofol significantly reduced the incidence, or severity, of emergence delirium. The only significant predictor for emergence delirium was the time taken to awaken from general anaesthesia, with every minute increase in wake-up time reducing the odds of emergence delirium by 7%.


Assuntos
Anestesia Geral/efeitos adversos , Delírio/prevenção & controle , Dexmedetomidina/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Propofol/uso terapêutico , Período de Recuperação da Anestesia , Criança , Pré-Escolar , Delírio/induzido quimicamente , Dexmedetomidina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Injeções Intravenosas , Masculino , Propofol/administração & dosagem , Fatores de Tempo
6.
J Nutr Health Aging ; 26(2): 243-246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35297466

RESUMO

BACKGROUND: A growing body of evidence has demonstrated the prognostic value of skeletal muscle area and quality measured by computed tomography (CT) as biomarkers of sarcopenia and frailty. However, there exists little data in normal healthy subjects to inform reference values and determine the effects of advancing age and sex on CT muscle parameters. METHODS: Abdominal CT images of patients (20-80 years of age) presenting to the emergency department with benign abdominal symptoms and no significant medical comorbidities were retrospectively collected from 2014 to 2017. Psoas and abdominal wall muscle area (PMA, WMA) and density (PMD, WMD) at the level of the L4 vertebrae were measured with the CoreSlicer.com web app. The normal reference range was computed by non-parameteric 2.5th and 97.5th percentiles stratified by sex and restricted by age to the younger subgroup (20-39 years of age). RESULTS: The cohort consisted of 390 otherwise healthy patients (162 males, 228 females). The lower reference range for PMA was <22.0 cm2 in males and <11.1 cm2 in females, and for WMA was <112.2 cm2 in males and <75.6 cm2 in females. There was a graded decline observed in PMA and WMA among older compared to younger adults (especially ≥60 years of age) (P<0.001) and among females compared to males (P<0.001). There was also a graded decline observed in PMD and WMD among older compared to younger adults (P<0.001), irrespective of sex. CONCLUSION: This study has defined the normal reference values and age-associated down-trend for CT muscle parameters at L4 in a healthy population using an accessible web-based software, which help contextualize and interpret these imaging biomarkers of sarcopenia in clinical care.


Assuntos
Sarcopenia , Envelhecimento , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Músculos Psoas/patologia , Valores de Referência , Estudos Retrospectivos , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios X
7.
Artigo em Inglês | MEDLINE | ID: mdl-35457592

RESUMO

Sarcopenia is a condition that is highly prevalent among older adults. This condition is linked to numerous adverse health outcomes, including cognitive impairment that impairs healthy ageing. While sarcopenia and cognitive impairment may share a common pathway, limited longitudinal studies exist to show the relationship between these two conditions. Therefore, this study aimed to examine the longitudinal association between sarcopenia and cognitive impairment. This is a cohort study among older adults residing in Kuala Pilah District, Negeri Sembilan, Malaysia. There were 2404 respondents at the baseline and 1946 respondents at one-year follow-up. Cognitive impairment was determined using Mini-mental State Examination scores. Sarcopenia was identified using the Asian Working Group for Sarcopenia 2019 criteria, gait speed was measured using a 4-meter gait test, handgrip strength was assessed using Jamar handheld dynamometer, and appendicular skeletal muscle mass was measured using bioelectrical impedance analysis. Generalized estimating equation (GEE) was used to determine the longitudinal association between sarcopenia and cognitive impairment, presented as relative risk (RR) and its 95% confidence interval. The prevalence of sarcopenia was 5.0% (95% CI 4.00-5.90), and severe sarcopenia was 3.60% (95% CI 2.84-4.31). Upon adjusting for covariates, older adults with sarcopenia have an 80 per cent increased risk of cognitive impairment compared to those without (RR 1.80; 95% CI 1.18-2.75). Similarly, severe sarcopenia was found to significantly increase the risk of cognitive impairment by 101 per cent in the adjusted model (RR 2.01; 95% CI 1.24-3.27). Our study showed that sarcopenia, severe sarcopenia, low physical activity, depressive symptoms, hearing impairment and chronic pain were associated with a higher risk of cognitive impairment among community-dwelling older adults. Therefore, early intervention to prevent sarcopenia, depressive symptoms, hearing impairment, chronic pain, and higher physical activity among older adults is recommended.


Assuntos
Dor Crônica , Disfunção Cognitiva , Sarcopenia , Idoso , Dor Crônica/complicações , Disfunção Cognitiva/etiologia , Estudos de Coortes , Força da Mão/fisiologia , Humanos , Malásia/epidemiologia , Prevalência , Sarcopenia/diagnóstico
8.
Med J Malaysia ; 66(4): 350-2, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22299556

RESUMO

The concept of diastolic heart failure (DHF) is not new. However awareness and understanding on this subject may remains uncertain among medical practitioners. We wished to examine the extent of awareness of such entity among doctors in Malaysia. A questionnaire was designed and distributed randomly during hospital Continuous Professional Development (CPD/CME) sessions and also in the respective outpatient departments (OPD) between July to October 2008. This cross-sectional survey in three urban-based general hospitals showed that there are a significant proportion of doctors who are lack of understanding and awareness of diastolic heart failure.


Assuntos
Insuficiência Cardíaca Diastólica/diagnóstico , Estudos Transversais , Hospitais Gerais , Humanos , Malásia , Inquéritos e Questionários
9.
World J Surg ; 33(10): 2077-81, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19649760

RESUMO

BACKGROUND: Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population. METHODS: We conducted a retrospective review of the medical records of 152 women with breast cancer who underwent genetic testing for BRCA mutations. The patients self-reported ethnicity, age at onset, and clinical stage at diagnosis and tumor pathology were reviewed. RESULTS: A total of 31 patients carried germline deleterious mutations (16 BRCA1, 15 BRCA2). We found that tumors in BRCA1 carriers were more likely to be estrogen receptor (ER)-negative and progesterone receptor (PR)-negative. HER2 was more likely to be negative in both BRCA1 and BRCA2 subjects compared with non-BRCA subjects. We found a strong association between triple-negative status and BRCA1 carriers. In addition, tumors in BRCA1 carriers were more likely to be higher grade than those in BRCA2 and non-BRCA carriers; but the difference was not statistically significant. CONCLUSIONS: These results suggest that tumors associated with BRCA1 mutations are distinct from those of BRCA2-associated and non-BRCA-associated breast cancers, and that the tumors associated with BRCA2 mutations are similar to the non-BRCA-associated breast cancers. Further studies are required to determine if the prognosis is different in each of these groups and the best management strategy for each group.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Países em Desenvolvimento , Genes BRCA1 , Genes BRCA2 , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Malásia , Pessoa de Meia-Idade , Grupos Raciais , Estudos Retrospectivos
10.
Emerg Med J ; 26(9): 681-2, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19700598

RESUMO

Ventricular ectopics can potentially lead to ventricular fibrillation (VF). A case of idiopathic VF that began as ventricular bigeminy is presented. A 30-year-old man lost consciousness transiently while driving but made a complete recovery soon after. He was pale and sweaty at the onset of the event. There was neither a history of ill health nor a family history of sudden cardiac death. He was asymptomatic on arrival at the emergency department (ED) with sinus tachycardia. Two hours later ventricular bigeminy was observed. This subtle presentation did not qualify him for being high risk according to the American College of Physician's recommendations or the San Francisco syncope rule, which almost led to his discharge from the ED. Despite this, he was admitted for observation. The patient had four VF arrests overnight, which were eventually terminated by emergency radiofrequency ablation. Upon further investigation, he was found to be normal on cardiac magnetic resonance imaging, echocardiogram and 24-h Holter monitoring. His serum biochemistry was normal, ruling out electrolyte disturbances. He eventually received an implantable cardioverter and remained free of recurrences in the subsequent months. This case serves as a reminder not to ignore ventricular ectopics or bigeminy.


Assuntos
Síncope/etiologia , Fibrilação Ventricular/complicações , Adulto , Eletrocardiografia , Humanos , Masculino , Fibrilação Ventricular/diagnóstico
11.
Med J Malaysia ; 64(1): 34-6, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19852318

RESUMO

This is a prospective study to determine the severity of disability and prognosis of acute stroke patients related to their Body Mass index (BMI). A total of 79 consecutive CT-scan-proven acute stroke patients who were admitted to Hospital Tuanku Ja'afar, Seremban between November 2006 and April 2007 were recruited (male:female 49:30; mean age 62.7 years; ischemic stroke 70, intracerebral bleed 9). The patients were divided according to BMI less than 25 (Group A) and equal or greater than 25 (Group B). Severity of disability was measured between 24-48 hours by modified Rankin's score. Patients were followed up after one month. Thirty-seven patients had severe disability (Rankin Score 5). Twenty-nine patients had adverse outcomes including 11 deaths and 18 rehospitalizations or prolonged hospital/nursing home stay. 34.3% of Group B had severe disability compared to 56.8% of Group A (chi2 P = 0.046). Conversely 42.9% of Group B had adverse events at one month compared to 31.8% of Group A (chi2 P = 0.312). There were no statistical differences between high- and low-BMI groups for gender ratio, smoking, hypertension, diabetes, prior cardiovascular disease, mean age, mean lipid profile and blood pressure. When comparing patients with Rankin Score 1-4 versus 5, age and BMI were statistically significant between the two groups. By multivariate analysis only age is independent predictor for severe disability (P < 0.05). The results of this pilot study should be confirmed in larger prospective multicentre trial.


Assuntos
Índice de Massa Corporal , Pessoas com Deficiência , Acidente Vascular Cerebral/complicações , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
12.
Malays Fam Physician ; 11(1): 7-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28461842

RESUMO

INTRODUCTION: Fall is a major cause of injuries and can increase the risk of early mortality among elderly. The objective of this study was to determine the prevalence of falls among community-dwelling elderly in rural Malaysia and its associated factors. METHODS: Data were obtained from a cross-sectional survey in five randomly selected districts in the state of Perak, Malaysia. A total of 250 households were randomly selected. A total of 811 individuals aged 60 years or more were recruited and interviewed using a structured questionnaire. Information about socio-demographic, history of falls in the past 1 year, medical history, drug history and physical activity level were enquired. RESULTS: The prevalence of falls in the past 1 year among community-dwelling elderly was reported to be 4.07%. Indigenous elderly (Adjusted odd ratio, AOR = 6.06, 95% CI = 1.10-33.55, p = 0.039) and living alone (AOR = 2.60, 95% CI = 1.04-6.50, p = 0.042) were shown to be factors associated with falls. Physical activity level, number of co-morbidities and number of medications used were not associated with falls. CONCLUSION: Elderly of indigenous ethnicity and living alone are the main factors associated with falls in this population. Indigenous people may be at higher risk, which warrant further investigation with a larger sample to improve the precision of estimates.

13.
Biochim Biophys Acta ; 975(2): 222-30, 1989 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-2525929

RESUMO

Mutants of Saccharomyces cerevisiae carrying defined lesions in the mitochondrial aap1 gene, coding for membrane subunit 8 of the H+-ATPase, have been investigated to examine the consequence of the mutations on the function and assembly of the enzyme complex. These include three mit- mutants, which cannot grow by oxidative metabolism due to their inability to synthesize full-length subunit 8, and three partial revertants of one of the mutants. The mutations in these strains have been previously characterized by DNA sequencing. The use of a monoclonal antibody to the beta subunit of the H+-ATPase as a probe of assembly defect revealed that the presence of subunit 8 is essential for the assembly of subunit 6 to the enzyme complex. Mitochondria isolated from the mit- mutants have negligible [32Pi]ATP exchange activity and they exhibited ATPase activity which is not sensitive to inhibition by oligomycin, indicating a defective membrane F0 sector. Normal assembly of subunit 8 (and subunit 6) was observed in the revertant strains, despite 8-9 amino-acid substitutions in the membrane-spanning region of the H+-ATPase subunit 8 in two of the strains. The assembled complex, however, exhibited reduced [32Pi]ATP exchange activity and low sensitivity to oligomycin, indicating that the product of the aap1 gene is a functional subunit of the mitochondrial H+-ATPase.


Assuntos
Mitocôndrias/enzimologia , Mutação , ATPases Translocadoras de Prótons/metabolismo , Saccharomyces cerevisiae/enzimologia , Sequência de Aminoácidos , Cinética , Substâncias Macromoleculares , Modelos Teóricos , Dados de Sequência Molecular , Consumo de Oxigênio , Biossíntese de Proteínas , ATPases Translocadoras de Prótons/genética , Saccharomyces cerevisiae/genética
14.
Biochim Biophys Acta ; 806(2): 290-304, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-2413888

RESUMO

mit- Mutants carrying genetically defined mutations in the oli2 region of the mitochondrial DNA were analysed. Most of these mutants demonstrated either the absence of subunit 6 or its replacement by shorter mitochondrial translation products which could be shown to be structurally related to subunit 6 by using a rabbit anti F1F0-antiserum, and by limited proteolytic mapping of the new mitochondrial translation products. Three representative oli2 mit- strains were analysed for the effects of a grossly altered subunit 6 or of a complete absence of this subunit on the activity and assembly of the H+-ATPase. Our results suggest that this subunit is not required for the assembly of the proton channel of the enzyme complex. Thus, in the absence of subunit 6, the mitochondrial respiratory activities in the oli2 mutants were found to be still sensitive to oligomycin, a specific inhibitor of the H+-ATPase proton channel. Immunoprecipitation of the assembled H+-ATPase subunits from these mutant strains using a monoclonal anti-beta-subunit antibody indicates that subunit 6 is also not essential for the assembly of most F1 subunits to components of the F0 sector.


Assuntos
Mitocôndrias/enzimologia , ATPases Translocadoras de Prótons/genética , Saccharomyces cerevisiae/enzimologia , DNA Fúngico/genética , DNA Mitocondrial/genética , Membranas Intracelulares/enzimologia , Canais Iônicos/metabolismo , Complexos Multienzimáticos/genética , Mutação , Oligomicinas/farmacologia , Fosforilação Oxidativa , ATPases Translocadoras de Prótons/biossíntese , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética
15.
Biochim Biophys Acta ; 592(3): 431-44, 1980 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-6251866

RESUMO

1. Two oligomycin-resistant strains of Saccharomyces cerevisiae have been isolated and shown to have mutations in the oli2 region of the mitochondrial DNA. On solid media containing a non-fermentable energy source, the mutant strains were able to grow only slowly at 28 degrees C and not at all at 18 degrees C or 36 degrees C. 2. When grown in a glucose-limited chemostat at 28 degrees C, the mutant strains were almost completely defective in oxidative metabolism. The mutant mitochondria contained significant levels of all respiratory enzymes, and an active, oligomycin-sensitive ATPase, but the ATP-32Pi exchange activity and P : O ratio were very low. 3. The mutations in these strains are genetically closely linked to mit mutations which have been shown to affect a 20 000-dalton ATPase subunit (Roberts, H., Choo, W.M., Murphy, M., Marzuki, S., Lukins, H.B. and Linnane, A.W. (1979) FEBS Lett. 108, 501-504). Since the mitochondrial ATPase in these mutant strains appears to be fully assembled, the defect in the coupling mechanism is probably a result of a small alteration in the structure of the 20 000-dalton ATPase subunit. 4. When the mutant strains were grown at 18 degrees C, the mitochondria had very low cytochrome oxidase activities, and reduced levels of cytochrome aa3. The largest subunit (Mr 40 000) of this enzyme was not synthesized.


Assuntos
DNA Fúngico/genética , Mitocôndrias/metabolismo , Mutação , Fosforilação Oxidativa , Saccharomyces cerevisiae/metabolismo , Adenosina Trifosfatases/metabolismo , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Fenômenos Químicos , Química , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Saccharomyces cerevisiae/genética
16.
Biochim Biophys Acta ; 933(1): 212-22, 1988 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-2894858

RESUMO

mit- mutants with genetically defined mutations in the mitochondrial structural genes of the H+-ATPase membrane subunits 6, 8 and 9 were analysed to determine the H+-ATPase assembly defects that resulted as a consequence of the mutations. These include mutants which do not synthesize one of the membrane subunits and mutants which can synthesize these subunits, but in an altered form. Protein subunits which can still be assembled to the defective H+-ATPase in these mutants were determined by immunoprecipitation using a monoclonal antibody to the beta-subunit of the enzyme complex. The results suggest that the assembly pathway of the mitochondrially synthesized H+-ATPase subunits involves the sequential addition of subunits 9, 8 and 6 to a membrane-bound F1-sector. In addition to subunits of the F0- and F1-sectors, two other polypeptides (Mr = 18,000 and Mr = 25,000) are associated with the yeast H+-ATPase. These polypeptides were not observed in the immunoprecipitates obtained from mutants in which the F0-sector is not properly assembled.


Assuntos
Anticorpos Antifúngicos/imunologia , Anticorpos Monoclonais/imunologia , Proteínas Fúngicas/genética , Complexos Multienzimáticos/genética , ATPases Translocadoras de Prótons/genética , Saccharomyces cerevisiae/enzimologia , Proteínas Fúngicas/imunologia , Genes , Genes Fúngicos , Mitocôndrias/enzimologia , Mutação , ATPases Translocadoras de Prótons/imunologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/imunologia
17.
Cell Death Discov ; 1: 15032, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27551463

RESUMO

Hepatocellular carcinoma (HCC) is a deadly cancer because of its commonly late diagnosis and limited treatment options. SAG (sensitive to apoptosis gene)-dependent UPS (ubiquitin-proteasome system) is a key switch between immune-mediated apoptosis and overactivation-mediated protumorigenesis, prompting us to hypothesize that SAG-UPS modulates chronic inflammation-induced tumorigenesis. Here, we investigated the molecular mechanism by which SAG-UPS regulates death/survival of liver cancer cells. By retrospective studies, we found reciprocal expressions of anti-/proapoptotic factors: SAG/SARM and SAG/Noxa in human primary HCC tissues - the antiapoptotic SAG was significantly upregulated whereas the proapoptotic SARM and Noxa were markedly downregulated, suggesting their involvement in hepatocarcinogenesis. Upregulated SAG-UPS effectively manipulates the levels of high-molecular-weight ubiquitinated SARM and Noxa in carcinoma tissues compared with corresponding normal tissues. SAG-overexpressing HCC cell lines display reduced SARM and Noxa (but not Bcl-2, Bax and Bcl-xL), suggesting that SARM and Noxa are specific substrates of SAG-dependent ubiquitination. SARM overexpression activated caspase-3 and caspase-9, reducing cell viability. SAG knockdown significantly elevated apoptosis with increased cytosolic cytochrome c, confirming SAG-mediated antiapoptosis in HCC. SAG overexpression stimulated protumorigenic cytokines, IL-1ß, IL-6 and TNF, but not antitumorigenic IL-12p40 and anti-inflammatory IL-10. This is consistent with higher proinflammatory cytokines (IL-1ß, IL-6 and TNF) in hepatoma compared with healthy tissues. Altogether, early stage-upregulated SAG-UPS exacerbates hepatocarcinogenesis progression, through: (1) ubiquitination-mediated degradation of proapoptotic SARM and Noxa; and (2) production of protumorigenic cytokines that induce a protumorigenic microenvironment, conferring survival advantage to HCC cells. Thus, we propose SAG-UPS to be an early diagnostic marker for HCC, and a potential target for therapeutics development.

18.
J Virol Methods ; 39(1-2): 125-38, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1331144

RESUMO

The types of Kunjin virus-specified proteins present in purified Vero cell plasma membrane were studied. Immunofluorescence of unfixed Kunjin virus-infected whole cell monolayers, indicated that two structural proteins (envelope and prM) and three non-structural proteins (NS1, 3 and 5) were found at the plasma membrane. There was no obvious progressive accumulation of the observed antigens over the time periods between 8 to 24 h p.i. Thus SDS-PAGE analysis was performed using purified radiolabelled Vero cell plasma membranes. From the protein profiles, all five antigens detected by immunofluorescent staining were also present. In addition, two smaller molecular weight non-structural proteins NS4B and NS2B were also observed. Generally, all the non-structural proteins found in the purified plasma membranes were of the same molecular weights as those found in infected whole cell lysate. Interestingly, both the structural proteins, i.e., envelope (E) and prM proteins in the plasma membrane sample were of higher molecular weights as compared to the counterparts in the infected whole cell lysate. The envelope protein of purified extracellular Kunjin virus was also lower in molecular weight compared to the same protein in the plasma membrane.


Assuntos
Antígenos Virais/isolamento & purificação , Flavivirus/imunologia , Virologia/métodos , Animais , Membrana Celular/imunologia , Membrana Celular/microbiologia , Eletroforese em Gel de Poliacrilamida , Estudos de Avaliação como Assunto , Imunofluorescência , Células Vero , Proteínas Virais/imunologia , Proteínas Virais/isolamento & purificação
19.
Int J Impot Res ; 16(1): 60-3, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14963472

RESUMO

The objective of this study was to explore the roles and perceptions of general practitioners (GPs) in the management of erectile dysfunction (ED). This qualitative study used focus group discussions and in-depth interviews. This study was conducted based on 28 GPs from an urban area in Malaysia who had managed patients with ED and prescribed anti-ED drugs. Main outcome measures included the roles of GPs in managing patients with ED (active or passive), perceptions regarding ED and the treatment, and factors influencing their decision to prescribe. Majority of the GPs assumed a passive role when managing patients with ED. This was partly due to their perception of the disease being nonserious. Some also perceived ED as mainly psychological in nature. The anti-ED drugs were often viewed as a lifestyle drug with potentially serious side effects. The fear of being perceived by patients as 'pushing' for the drug and being blamed if the patients were to develop serious side effects also hampered the management of this disease. GPs who participated in this study remained passive in identifying and treating patients with ED and this was attributed to their perception of the disease, drug treatment and patient's background.


Assuntos
Atitude do Pessoal de Saúde , Disfunção Erétil/tratamento farmacológico , Relações Médico-Paciente , Médicos de Família/psicologia , Atenção Primária à Saúde , Adulto , Feminino , Humanos , Estilo de Vida , Malásia , Masculino , Anamnese , Medicina , Pessoa de Meia-Idade , Padrões de Prática Médica , Classe Social , Valores Sociais , Especialização
20.
Ann Acad Med Singap ; 31(1): 30-6, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11885493

RESUMO

With an ageing population in Singapore, it is anticipated that postmenopausal osteoporosis and related fractures will be an increasingly important health issue in the coming decades. Oestrogen replacement therapy has a long history of use to treat postmenopausal problems including osteoporosis. The availability of other potent agents such as bisphosphonates, calcitonin and selective oestrogen receptor modulators has enriched the therapeutic options. This article reviews the evidence for the choice of appropriate agents, and strategies to prevent and treat postmenopausal osteoporosis.


Assuntos
Terapia de Reposição Hormonal/métodos , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/prevenção & controle , Distribuição por Idade , Idoso , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Prevenção Primária/métodos , Prognóstico , Fatores de Risco , Singapura/epidemiologia
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