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1.
Sci Rep ; 14(1): 16177, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003304

ABSTRACT

This study proposes an innovative geometry of a microstrip sensor for high-resolution microwave imaging (MWI). The main intended application of the sensor is early detection of breast, lung, and brain cancer. The proposed design consists of a microstrip patch antenna fed by a coplanar waveguide with a metamaterial (MTM) layer-based lens implemented on the back side, and an artificial magnetic conductor (AMC) realized on as a separate layer. The analysis of the AMC's permeability and permittivity demonstrate that the structure exhibits negative epsilon (ENG) qualities near the antenna resonance point. In addition, reflectivity, transmittance, and absorption are also studied. The sensor prototype has been manufactures using the FR4 laminate. Excellent electrical and field characteristics of the structure are confirmed through experimental validation. At the resonance frequency of 4.56 GHz, the realized gain reaches 8.5 dBi, with 3.8 dBi gain enhancement contributed by the AMC. The suitability of the presented sensor for detecting brain tumors, lung cancer, and breast cancer has been corroborated through extensive simulation-based experiments performed using the MWI system model, which employs four copies of the proposed sensor, as well as the breast, lung, and brain phantoms. As demonstrated, the directional radiation pattern and enhanced gain of the sensor enable precise tumor size discrimination. The proposed sensor offers competitive performance in comparison the state-of-the-art sensors described in the recent literature, especially with respect to as gain, pattern directivity, and impedance matching, all being critical for MWI.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Lung Neoplasms , Microwave Imaging , Humans , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Brain Neoplasms/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/diagnosis , Female , Equipment Design , Phantoms, Imaging , Microwaves
2.
Biosensors (Basel) ; 12(10)2022 Oct 05.
Article in English | MEDLINE | ID: mdl-36290965

ABSTRACT

Microstrip patch antennas have been used in many applications since their appearance. Despite their great promise, their narrow bandwidth and the loss at high-frequency bands have limited their usage in medical applications. This work proposes a developed low-cost microstrip patch antenna suitable for microwave imaging (MWI) applications within the wideband frequency range. The proposed antenna is loaded with an artificial magnetic conductor (AMC) to improve the antenna performance. The simulated results obtained using computer simulation technology (CST) indicate that the presence of the AMC has improved the frequency selectivity of the antenna at 8.6 GHz with a peak realized gain of 9.90443 dBi and 10.61 dBi for simulated and measured results, respectively. The proposed microstrip antenna has been fabricated to validate the simulated results, and its performance is tested experimentally. Additionally, the fidelity factor of face-to-face (FtF) and side-by-side (SbS) scenarios have been presented. The breast phantom models with a tumor and the antenna operating as a transceiver have been numerically simulated for the application of cancer tumor cell detection. The work will have a significant impact on the design of electromagnetic biosensors.


Subject(s)
Breast Neoplasms , Human Body , Humans , Female , Computer Simulation , Equipment Design , Breast , Breast Neoplasms/diagnosis
3.
Braz J Biol ; 84: e249124, 2022.
Article in English | MEDLINE | ID: mdl-35946727

ABSTRACT

Current cross-sectional study was carried out between September 2019 to January 2020 at the Department of Pathology, Mardan Medical Complex (MMC), Mardan, and District Headquarter Hospital North Waziristan, Khyber Pakhtunkhwa (KP), Pakistan. The objectives of the current study were to determine the prevalence of leishmaniasis and its associated risk factors in selected districts of KP province, Pakistan. Altogether, three hundred and seventy-four (n=374) leishmaniosis patients were included in the current study. Skin specimen from the ulcer border were collected. The slides were stained by Giemsa stain and examined for the presence of amastigote. The prevalence of leishmania infected patients in different region of KP were as follows: North Waziristan region 53.7 (n=201) District Mardan 34.7% (n=130); District Nowshera 6.7% (n=25), District Swabi 1.1% (n=4) and other Districts i.e. Dir, Malakand, Buner and Bajawarr were 3.7% (n=14). The frequency of leishmaniasis were more in male and majority of the infected patients were in the age group of <10 years. Among n=374 patients 95.7% (n= 358) had cutaneous leishmaniasis while 3% (n= 11) had mucocutaneous type of infection and 1.3% (n= 5) patients had both cutaneous and mucocutaneous infection. Upon treatment by Sodium stibogluconate (SSG) 97% (n=362) showed clinical signs of complete or partial recovery of their skin lesions. Conclusively, highest incidence of leishmania infection occurred during short study period and majority of the cases showed positive response to treatment.


Subject(s)
Leishmaniasis, Cutaneous , Child , Cross-Sectional Studies , Female , Humans , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/etiology , Male , Pakistan/epidemiology , Prevalence , Risk Factors
4.
BMJ Glob Health ; 7(Suppl 4)2022 06.
Article in English | MEDLINE | ID: mdl-35764354

ABSTRACT

The WHO Eastern Mediterranean Region (EMR) is characterised by a large range in routine immunisation coverage. We reviewed progress in access, deployment efforts, and use of COVID-19 vaccines in the EMR to identify bottlenecks and propose recommendations. We compiled and analysed data reported to WHO regarding the number of vaccines provided emergency use authorisation (EUA) in each country, the number of vaccine doses allocated and delivered by COVAX, the number of vaccine doses received bilaterally, the date of initiation of vaccination, vaccine usage rate and overall vaccination coverage. In June-July and October-November 2021, we conducted two rounds of a regional survey to assess vaccine acceptance and calculated the weighted proportion of individuals who would get vaccinated once a vaccine is available and recommended. We stratified the analysis according to four groups based on their participation status in COVAX, from the highest to lowest income, that is, (1) fully self-financing high-income countries (group 1), (2) fully self-financing upper middle-income countries (group 2), (3) Advance Market Commitment (AMC) countries not eligible to receive Gavi support (group 3) and (4) AMC countries eligible for Gavi support (group 4). As of 31 December 2021, the median number of vaccines provided with EUA was 6 for group 1, 11 for group 2, 8 for group 3 and 9 for group 4. On the same date, COVAX had delivered 179 793 310 doses to EMR countries. Vaccination started on 10 December 2020 in group 1, on 13 December 2020 in group 2, on 30 December 2020 in group 3 and on 20 January 2021 in group 4. The regional acceptance survey (first round) pointed to higher vaccine acceptance in group 1 (96%), than in others, including group 2 (73.9%), group 3 (78.8%) and group 4 (79.3%), with identical patterns in the second round (98%, 78%, 84% and 76%), respectively. Usage of vaccine allocated by COVAX to participating countries was 89% in group 1, 75% in group 2, 78% in group 3 and 42% in group 4. The full dose and partial dose coverage decreased with the income groups of countries, from 70% and 6% in group 1, to 43% and 8% in group 2, to 33% and 11% in group 3, and 20% and 8% in group 4. All 22 EMR countries introduced COVID-19 vaccines by 21 April 2021, but with major inequities in coverage. Additional efforts are needed to address the determinants of unequal vaccine coverage at all stages of the result chain to improve vaccine equity.


Subject(s)
COVID-19 , Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunization Programs , World Health Organization
5.
J Endocrinol Invest ; 44(1): 83-93, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32358738

ABSTRACT

OBJECTIVES: The prevalence of CAH in Egypt is reported to be ten times more than that of the worldwide prevalence. The study aimed at genetic screening of children diagnosed with 21-alpha hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH). In addition, the study offers a rapid and easy guide for clinical reporting of common mutations for endocrinologists. METHODS: A cohort of 174 unrelated Egyptian children with 21OHD-CAH were screened for 11 common CYP21A2 gene mutations using a strip hybridization assay, and then, bioinformatics analysis was done to report the pathogenicity of the common mutations for clinical classification. RESULTS: The most common mutations were I2 splice and p.Q318X. Deletions/conversions comprised 45.9% of the cohort, whereas 7.4% of the cases were negative for all mutations. The least positively detected point mutations were p.P453S, cluster E6, p.R483P, and p.L307FS, which were detected in fewer than 5% of cases. CONCLUSION: Strip hybridization assay is a rapid screening tool for the diagnosis of CAH. The authors hypothesized an easy and rapid scheme for clinical interpretation of the strip results to gain the highest value of the strip in diagnosis.


Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Biomarkers/analysis , Genetic Testing/methods , Mutation , Phenotype , Steroid 21-Hydroxylase/genetics , Adrenal Hyperplasia, Congenital/epidemiology , Adrenal Hyperplasia, Congenital/pathology , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Egypt/epidemiology , Female , Follow-Up Studies , Genotype , Humans , Infant , Infant, Newborn , Male , Prognosis
6.
BJOG ; 127(4): 490-499, 2020 03.
Article in English | MEDLINE | ID: mdl-31778255

ABSTRACT

OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs. DESIGN: Prospective observational cohort study. SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia. POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT. METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records. MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile. RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile. CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy. TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.


Subject(s)
Birth Weight , Fetal Macrosomia/blood , Hyperlipidemias/blood , Adult , Asian People , Body Mass Index , Case-Control Studies , Female , Fetal Macrosomia/epidemiology , Humans , Hyperlipidemias/complications , Infant, Newborn , Malaysia/epidemiology , Male , Obesity/epidemiology , Pregnancy , Prospective Studies , Surveys and Questionnaires , Triglycerides/blood
7.
G Chir ; 39(2): 92-96, 2018.
Article in English | MEDLINE | ID: mdl-29694308

ABSTRACT

AIM: In the last years with the increase of bariatric surgery, first of all as a result of new indications, a rise in the incidence of nutrient-related complications has been observed. Currently little is known about the impact of post-bariatric malnutrition and neurological complications. Wernicke's encephalopathy is a severe neurological syndrome which occurs as a result of thiamine deficiency. Wernicke-Korsakoff syndrome must be considered a serious neurological complication of bariatric surgery with significant morbidity and mortality, with rapidly progressing neurological symptoms, and must be treated immediately. CASE REPORT: We report the case of a 35 years-old male patient, affected by morbid obesity, anxious-depressive syndrome and alcohol use disorder, who after adjustable gastric banding implanted in another hospital developed a severe malnutrition and neurological syndrome. The patient showed poor adherence to the follow-up and to the dietary indications and after all, we needed to place a PEG for enteral nutrition in order to resolve the malnutrition condition and the neurological syndrome. Our experience emphasizes that preoperative selection and assessment of a patient's nutritional status according to guidelines, is required to identify potential problems, and that bariatric surgeons or physicians caring for patient who have undergone bariatric surgery should be familiar with the constellation of nutritional and neurological disorder that may occur after surgery. CONCLUSION: We want to remark the importance of preoperative selection of the patients, the follow-up and the cooperation between patient and physician in order to obtain the best result and avoid severe complications.


Subject(s)
Gastroplasty/adverse effects , Malabsorption Syndromes/etiology , Postoperative Complications/etiology , Wernicke Encephalopathy/etiology , Adult , Alcoholic Korsakoff Syndrome/diagnosis , Deglutition Disorders/etiology , Diagnosis, Differential , Enteral Nutrition , Gastrointestinal Motility , Humans , Malabsorption Syndromes/metabolism , Malabsorption Syndromes/therapy , Male , Patient Compliance , Postoperative Complications/metabolism , Postoperative Complications/therapy , Postoperative Nausea and Vomiting/complications , Thiamine/pharmacokinetics , Vitamin B 12 Deficiency/etiology , Vitamin B 12 Deficiency/psychology , Vitamin B 12 Deficiency/therapy , Wernicke Encephalopathy/diagnosis
8.
J Infect Public Health ; 11(1): 9-17, 2018.
Article in English | MEDLINE | ID: mdl-28864360

ABSTRACT

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with mechanisms that may be driven by innate immune responses. Despite the effort of scientific studies related to this virus, Middle East Respiratory Syndrome (MERS) is still a public health concern. MERS-CoV infection has a high mortality rate, and to date, no therapeutic or vaccine has been discovered, that is effective in treating or preventing the disease. In this review, we summarize our understanding of the molecular and biological events of compounds acting as MERS-CoV inhibitors, the outcomes of existing therapeutic options and the various drugs undergoing clinical trials. Currently, several therapeutic options have been employed, such as convalescent plasma (CP), intravenous immunoglobulin (IVIG), monoclonal antibodies and repurposing of existing clinically approved drugs. However, these therapeutic options have drawbacks, thus the need for an alternative approach. The requirement for effective therapeutic treatment has brought the necessity for additional MERS treatments. We suggest that antimicrobial peptides (AMPs) may be used as alternative therapeutic agents against MERS-CoV infection. In addition, we propose the feasibility of developing effective agents by repurposing the existing and clinically approved anti-coronavirus and anti-viral peptide drugs.


Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/therapy , Clinical Trials as Topic , Drug Repositioning , Humans
9.
Article in English | WPRIM (Western Pacific) | ID: wpr-822796

ABSTRACT

@#Objective: The study was designed to determine the risk perception of the public population in Kota Kinabalu towards childhood immunisation. Methodology: This was a cross-sectional study where self-administered questionnaires were distributed to the public in Kota Kinabalu. The respondents who consented were 18 years old and older. The illiterate persons and the foreigners were excluded. The calculated sample size was 400. Only 313 samples collected were suitable for analysis using SPSS21.0. Results: Fever, pain swelling and allergic reaction were correctly identified as risks of immunisation. Autism, mental retardation and even death could also result from vaccination. Of the total respondents, 76.7% agreed with the practice of childhood vaccination, 70.0% thought that childhood vaccinations were safe and effective and 58.1% felt that its benefit outweighed the risk. Other than that, 32.0% refused childhood vaccination from fear of its risks, and this fear was the main reason for the refusal of childhood vaccination. Age, marital status, race and income were the factors which influenced parental willingness to vaccinate their children (p<0.05). Conclusions: Most participants understood the risks of childhood vaccination, but few agreed to the practice of childhood immunisation for herd immunity. Public health campaigns are needed, to increase the understanding and acceptance of childhood vaccination especially in the rural community.

10.
G Chir ; 38(5): 256-259, 2017.
Article in English | MEDLINE | ID: mdl-29280707

ABSTRACT

AIM: Enterocutaneous (EC) fistula is an abnormal communication between the gastrointestinal tract and the skin. The majority of EC fistulas result from surgery. Only 15-25% of EC fistulas are spontaneous and they often result from underlying diseases such as Crohn's disease, radiation and chemotherapy. CASE REPORT: A 62-year old woman who, in 2012, underwent Pylorus-preserving cephalic pancreaticoduodenectomy (PPPD sec. Traverso-Longmire), due to an advanced pancreatic ductal adenocarcinoma (pT3N1M1). After surgery, the patient underwent chemotherapy with folfirinox regimen. In December 2016, as a result of the appearance of metastatic liver lesions and perianastomotic recurrence, the patient underwent second line treatment with Gemcitabine and pab-paclitaxel. After five months from the beginning of this new second line therapy she presented an EC fistula. The fistula of the patient was successfully treated with total parenteral nutrition and with percutaneous injection of cyanoacrylic sealant. RESULTS: The result suggests the advisability of percutaneous injection of sealant devices, such as cyanoacrylate glue; in order to successfully control stable Enterocutaneous fistulas with acceptable morbidity and mortality especially in particular situations, such as, with low output EC fistulas without signs of complications or on patients considered not suitable for surgery, a conservative approach could ensure the control of the fistula. CONCLUSION: This approach is easy and safe, viable and useful for future trials on the efficacy in conservative treatment of EC fistula.


Subject(s)
Conservative Treatment , Cyanoacrylates/therapeutic use , Intestinal Fistula/therapy , Postoperative Complications/therapy , Tissue Adhesives/therapeutic use , Female , Humans , Middle Aged , Pancreaticoduodenectomy , Remission Induction
11.
Afr J AIDS Res ; 16(4): 329-334, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29132277

ABSTRACT

Since 1999, the HIV and AIDS epidemic in Swaziland has been declared a national disaster, and today HIV and AIDS still pose a great threat to the survival and development of Swaziland and its people. The impact of the pandemic necessitated a multi-faceted response from the government. This paper critically evaluates the Swaziland legal response to HIV and AIDS. The objective is to assess whether and to what extent Swazi law addresses human rights issues related to HIV and AIDS. Through the application of a human rights based theory, the paper analyses the domestication of Swaziland's treaty commitments, and the constitutional and the statutory frameworks. The paper advances the importance of "law" as a tool that can create an enabling environment for a national response to HIV and AIDS. It analyses how the government has successfully crafted the normative framework so as to make it responsive to the fight against HIV and AIDS, and the shortcomings of the Swaziland legal system in this fight. The paper argues that even though a credible legal and policy environment is in place, some laws still need to be supplemented, reviewed and amended so that the legal system adequately addresses the human rights issues related to HIV and AIDS. The paper suggests improvements to the legal system which mainly relate to aligning the legal framework with the Constitution of Swaziland and international conventions to which Swaziland is party.


Subject(s)
Acquired Immunodeficiency Syndrome/epidemiology , HIV Infections/epidemiology , Human Rights/legislation & jurisprudence , Legislation as Topic , Epidemics/legislation & jurisprudence , Eswatini/epidemiology , Female , Humans , International Law , Male
12.
J Fish Dis ; 40(10): 1267-1277, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28252175

ABSTRACT

The approaches of transcriptomic and proteomic have been widely used to study host-pathogen interactions in fish diseases, and this is comparable to the recently emerging application of metabolomic in elucidating disease-resistant mechanisms in fish that gives new insight into potential therapeutic strategies to improve fish health. Metabolomic is defined as the large-scale study of all metabolites within an organism and represents the frontline in the 'omics' approaches, providing direct information on the metabolic responses and perturbations in metabolic pathways. In this review, the current research in infectious fish diseases using metabolomic approach will be summarized. The metabolomic approach in economically important fish infected with viruses, bacteria and nematodes will also be discussed. The potential of the metabolomic approach for management of these infectious diseases as well as the challenges and the limitations of metabolomic in fish disease studies will be explored. Current review highlights the impacts of metabolomic studies in infectious fish diseases, which proposed the potential of new therapeutic strategies to enhance disease resistance in fish.


Subject(s)
Bacterial Infections/veterinary , Fish Diseases/metabolism , Fish Diseases/prevention & control , Metabolomics/methods , Nematode Infections/veterinary , Virus Diseases/veterinary , Animals , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Bacterial Physiological Phenomena , Fish Diseases/microbiology , Fish Diseases/parasitology , Fishes , Host-Parasite Interactions , Host-Pathogen Interactions , Metabolomics/instrumentation , Nematoda/physiology , Nematode Infections/metabolism , Nematode Infections/parasitology , Nematode Infections/prevention & control , Virus Diseases/metabolism , Virus Diseases/prevention & control , Virus Diseases/virology , Virus Physiological Phenomena
13.
Afr. j. AIDS res. (Online) ; 16(4): 329-334, 2017.
Article in English | AIM (Africa) | ID: biblio-1256639

ABSTRACT

Since 1999, the HIV and AIDS epidemic in Swaziland has been declared a national disaster, and today HIV and AIDS still pose a great threat to the survival and development of Swaziland and its people. The impact of the pandemic necessitated a multi-faceted response from the government. This paper critically evaluates the Swaziland legal response to HIV and AIDS. The objective is to assess whether and to what extent Swazi law addresses human rights issues related to HIV and AIDS. Through the application of a human rights based theory, the paper analyses the domestication of Swaziland's treaty commitments, and the constitutional and the statutory frameworks. The paper advances the importance of "law" as a tool that can create an enabling environment for a national response to HIV and AIDS. It analyses how the government has successfully crafted the normative framework so as to make it responsive to the fight against HIV and AIDS, and the shortcomings of the Swaziland legal system in this fight. The paper argues that even though a credible legal and policy environment is in place, some laws still need to be supplemented, reviewed and amended so that the legal system adequately addresses the human rights issues related to HIV and AIDS. The paper suggests improvements to the legal system which mainly relate to aligning the legal framework with the Constitution of Swaziland and international conventions to which Swaziland is party


Subject(s)
Confidentiality , Eswatini , Human Rights , Jurisprudence
15.
Indian Dermatol Online J ; 4(2): 90-2, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23741662

ABSTRACT

AIMS: To determine if there is a significant association between premature hair graying and cigarette smoking. MATERIALS AND METHODS: A cross-sectional observational study was conducted in a nonclinical setting on 207 participants on August 24 until 25, 2010. Participants were classified into two groups [premature hair graying (PHG) and normal hair graying]. PHG was defined as the first appearance of gray hair before the age of 30. Data were collected using an interview questionnaire and measurements of body mass index, waist circumference, fasting blood glucose and blood pressure. Collected data were statistically analyzed using SPSS 16, Chicago, IL. RESULTS: Of the 207 subjects, 104 (50.2%) had first appearance of gray hair before the age of 30 (PHG group) while the other 103 (49.8%) were considered normal hair graying group. The prevalence of smokers in the "PHG" group was higher (40.2% vs. 24.7%, P = 0.031). Smokers had earlier onset of hair graying (smokers: 31 (7.4) vs. nonsmokers: 34 (8.6), P = 0.034). Using multiple logistic regression with conditional likelihood, smokers were two and half times (95% CI: 1.5-4.6) more prone to develop PHG. CONCLUSION: This study suggests that there is a significant relation (with adjusted odds ratio of two and half) between onset of gray hair before the age of 30 and cigarette smoking.

16.
Oncogene ; 32(29): 3443-51, 2013 Jul 18.
Article in English | MEDLINE | ID: mdl-22869152

ABSTRACT

Amplification and overexpression of the receptor tyrosine kinase ErbB2 occur in up to 30% of human breast cancers, and high ErbB2 levels are correlated with poor prognosis for breast cancer patients. In contrast to the epithelial growth factor receptor (ErbB1), ErbB2 is not downregulated by ligand-induced mechanisms. Here we show that flotillins are involved in the stabilization of ErbB2 at the plasma membrane. In SKBR3 breast cancer cells and breast cancer tissue, a positive correlation between flotillin and ErbB2 expression levels could be demonstrated. Moreover, the tissue microarray analyses of biopsies from 194 patients diagnosed with carcinomas of the breast showed that flotillin-2 emerged as a potential predictor of prognosis in breast cancer. Depletion of flotillin-1 and flotillin-2 leads to internalization and degradation of ErbB2. Furthermore, flotillin-1 and -2 were found to be in a molecular complex with ErbB2 and Hsp90. The depletion of one of these proteins results in disruption of this complex, followed by destabilization of ErbB2 at the membrane, and its internalization and degradation. As a consequence, ErbB2-triggered downstream signalling is inhibited. Our data demonstrate a novel mechanism for interfering with ErbB2 signalling, which potentially can have clinical impact.


Subject(s)
Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/physiology , Membrane Proteins/metabolism , Receptor, ErbB-2/metabolism , Signal Transduction/physiology , Blotting, Western , Breast Neoplasms/genetics , Cell Line, Tumor , Female , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Humans , Immunohistochemistry , Immunoprecipitation , Membrane Proteins/genetics , Microscopy, Confocal , Receptor, ErbB-2/genetics , Tissue Array Analysis , Transfection
17.
J Postgrad Med ; 58(4): 235-41, 2012.
Article in English | MEDLINE | ID: mdl-23298916

ABSTRACT

BACKGROUND: Drugs with complex pharmacology are used in the management of drug use disorder (DUD) and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral. AIMS: Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia. SETTINGS AND DESIGN: The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals. MATERIALS AND METHODS: For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT) Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6*10, CYP2B6*2, CYP2B6*17, CYP2B6*11, CYP2B6*8, CYP2B6*14, CYP2B6*9, CYP2B6*4, CYP2B6*6, CYP2B6*27, and CYP2B6*20 were determined using multiplex nested allele-specific PCR. STATISTICAL ANALYSIS: Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test. RESULTS: CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6*6 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another 'reduced activity', CYP2B6*2 allele, was found at much lower percentages in the groups. CONCLUSIONS: The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Asian People/genetics , Gene Frequency , Haplotypes , Heroin Dependence/drug therapy , Methadone/therapeutic use , Oxidoreductases, N-Demethylating/genetics , Polymorphism, Genetic , Adult , Algorithms , Aryl Hydrocarbon Hydroxylases/metabolism , China , Cytochrome P-450 CYP2B6 , Female , Humans , India , Malaysia/ethnology , Male , Opiate Substitution Treatment , Oxidoreductases, N-Demethylating/metabolism , Polymerase Chain Reaction
18.
Folia Microbiol (Praha) ; 55(3): 211-4, 2010 May.
Article in English | MEDLINE | ID: mdl-20526831

ABSTRACT

Staphylococcus aureus ssp anaerobius strain S10 was isolated from an outbreak of sheep abscess disease. Sequence of the catalase gene of this strain showed 99% identity to the catalase gene (katB) sequence of the reference strain (S. aureus ssp. anaerobius strain MVF213) with mismatching of three base pairs. An important substitution located 1036 nucleotides upstream of the initiation codon from "C" in katB to "T" in the catalase gene of strain S10 originated a stop codon. The deduced protein (345 amino acids) is 105 amino acids shorter than that of katB. Partial sequence of the catalase gene of other 8 local isolates in addition to another reference strain (DSM 20714/ATCC 35844) revealed the same mutations in all local (African) strains, whereas the sequence of the reference (European) strain was typical to that of katB. Sequence of the catalase gene of S. aureus ssp. anaerobius strain S10 was deposited in GenBank under accession no. EU281993.


Subject(s)
Bacterial Proteins/genetics , Catalase/genetics , Polymorphism, Genetic , Staphylococcus aureus/classification , Staphylococcus aureus/enzymology , Abscess/epidemiology , Abscess/microbiology , Abscess/veterinary , Amino Acid Substitution/genetics , Animals , Codon, Nonsense , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Disease Outbreaks , Molecular Sequence Data , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid , Sheep , Sheep Diseases/epidemiology , Sheep Diseases/microbiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/veterinary , Staphylococcus aureus/isolation & purification
19.
Sudan j. med. sci ; 5(2): 137-144, 2010. tab
Article in English | AIM (Africa) | ID: biblio-1272368

ABSTRACT

Background: Teaching is associated with a number of stressful circumstances that promote unhealthy lifestyles capable of fuelling risk factors for metabolic and cardiovascular disorders. This study investigated the prevalence of selected non-invasive risk factors of Type 2 Diabetes (T2D) among higher education teachers. Methods: Higher education teachers numbering 876 from three tertiary institutions in Kano; North- Western Nigeria were assessed on selected non-invasive risk factors of T2D including Body Mass Index (BMI); Waist Circumference (WC); Waist-Hip-ratio (WHR); Percent Body Fat (PBF) and family history of diabetes. Lifestyle including smoking; alcoholism and physical inactivity were also assessed. Results: Female-male ratio of participants was 1:5 while the age range was 24-58 years. Female teachers had higher prevalence of poor adiposity markers represented by overweight (33.8); obesity (12.7); high PBF (21.7) and WC in the high risk domain (53.5). They also had higher prevalence of hypertension (22.5) while men had higher prevalence of WHR (31.2) in the high risk domain. Positive family history of diabetes was 6.5(males); 7.5(females); physical activity at walking level 46.0(males); sedentary activity 85.9(females); current smoking habit 42.8(males); 4.3(females) and current alcohol consumption was 11.9for males and 0for female teachers. Conclusion: There may be considerable chances of developing T2D among the higher education teachers based on prevalence of the selected risk factors and the risk may be higher among the female teachers. Measures to change the modifiable risk factors for the better in this population are urgently needed


Subject(s)
/prevention & control , Education, Graduate , Faculty , Nigeria , Prevalence , Risk Factors
20.
Am J Respir Cell Mol Biol ; 20(2): 352-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9922228

ABSTRACT

Accumulation of intracellular cyclic adenosine monophosphate (cAMP) has been shown to inhibit the growth of cultured airway smooth-muscle cells, but the precise mechanism underlying the antimitogenic action of cAMP in these cells is unknown. We examined the effects of forskolin, an activator of adenylate cyclase, on DNA synthesis, cyclin D1 expression, and cAMP response element-binding protein (CREB) phosphorylation and DNA binding in bovine tracheal myocytes. DNA synthesis was assessed by measurement of [3H]thymidine incorporation. Cyclin D1 protein abundance and CREB phosphorylation were assessed by immunoblotting. Cyclin D1 promoter transcriptional activation was determined by measurement of luciferase activity in cells transiently cotransfected with complementary DNAs encoding the full-length cyclin D1 promoter subcloned into a luciferase reporter and beta-galactosidase (to normalize for transfection efficiency). The binding of nuclear proteins to the cyclin D1 promoter cAMP response element (CRE) was determined by electrophoretic mobility shift assay. We found that forskolin attenuated platelet-derived growth factor-induced DNA synthesis in a concentration-dependent manner. In addition, forskolin pretreatment decreased both cyclin D1 promoter activity and protein levels. Forskolin treatment induced the phosphorylation of CREB and increased the binding of nuclear protein to the cyclin D1 promoter CRE. Finally, addition of an antibody against CREB1 induced supershift of at least one protein-DNA complex. Together, these data suggest that cAMP suppresses cyclin D1 gene expression via phosphorylation and transactivation of CREB. Further studies are needed to determine whether this is the primary mechanism of cAMP-induced growth inhibition, or whether additional pathways are also involved.


Subject(s)
Colforsin/pharmacology , Cyclin D1/metabolism , Muscle, Smooth/drug effects , Trachea/drug effects , Animals , Cattle , Cyclic AMP/pharmacology , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclin D1/genetics , DNA Replication/drug effects , Muscle, Smooth/cytology , Muscle, Smooth/metabolism , Nuclear Proteins/metabolism , Phosphorylation , Platelet-Derived Growth Factor/pharmacology , Promoter Regions, Genetic , Protein Binding , Trachea/cytology , Trachea/metabolism , Transcriptional Activation/drug effects
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