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2.
J Chin Med Assoc ; 86(10): 940-944, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796445

RESUMO

BACKGROUND: Nurses are a high-risk group for overweight and obesity due to high stress, low-labor medical work, irregular diet, and lack of exercise. There is scarce information on relationship between job characteristics and overweight and obesity among nurses. This study aimed to answer the question. Does the nature of the work including job position, seniority relate to overweight and obesity among nurses? Their incidence was also investigated. METHODS: We conducted a retrospective cohort study of nurses who underwent annual checkups during 2007 to 2016 in a medical center. Overweight was defined as a body mass index between 24 and 27 kg/m 2 . Obesity was defined as a body mass index higher than 27 kg/m 2 . We calculated the prevalence and incidence of overweight and obesity and estimated relative risks using logistic regression. RESULTS: Overall, 4253 participants were enrolled for the incidence of overweight and obesity. We found that junior staff, administrative directors, working in intensive care units, and old age had a high possibility of overweight. Junior staff, administrative directors, old age, and male sex tend to be obesity. Overweight and obesity occurred rapidly in the first 2 years of their career. CONCLUSION: Our findings suggest that policies should be set up to achieve the goal of workplace health promotion. Health plans focusing on these factors may help nurses avoid obesity and overweight. The director of the hospital should keep track of the health checkup database to confirm the benefits of its long-term implementation.


Assuntos
Obesidade , Sobrepeso , Humanos , Masculino , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Estudos de Coortes , Estudos Retrospectivos , Obesidade/epidemiologia , Índice de Massa Corporal , Hospitais
3.
Pediatr Neonatol ; 63(5): 520-526, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35811287

RESUMO

BACKGROUND: In children, fruit and vegetable allergies are often overlooked compared with well-known allergies such as those to eggs, milk, and shellfish. Therefore, this study aimed to analyze fruit and vegetable allergies in children, including prevalence, types of food allergens, clinical presentation, management, and associated comorbid atopic diseases. METHODS: In 2012, a nationwide, cross-sectional, random sampling questionnaire-based survey for common fruit and vegetable allergies was conducted in Taiwan. Information regarding these plant food allergies was collected. Physicians diagnosed food allergies according to the descriptions of convincing symptoms. Enrolled questionnaires were reviewed by expert pediatricians. RESULTS: A total of 9,982 valid questionnaires were analyzed. The overall prevalence of fruit and vegetable allergies was 5.6% (n = 560) and 3.0% (n = 304), respectively. The most common fruit allergen was mango, followed by kiwifruit, whereas taro and bamboo shoot were the most common vegetable allergens. Meanwhile, most allergic symptoms were of the mucocutaneous tissue, followed by the upper airway and gastrointestinal tract. Most only required avoidance of allergens and not medical treatment. Children with fruit or vegetable allergies had a higher percentage of comorbid atopic dermatitis, allergic rhinitis, and asthma than those without food allergies; additionally, the proportion of comorbid atopic diseases was similar between fruit and vegetable allergies and shellfish allergy. One child developed anaphylaxis due to a corn allergy. CONCLUSIONS: Fruits and vegetables are common food allergens in Taiwanese children who present with diverse and potentially severe symptoms. Children with plant food allergies had a percentage of comorbid atopic diseases similar to that of shellfish allergy, the most common allergen. These findings indicate the importance of considering fruit and vegetable allergies in children.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Frutos do Mar , Alérgenos , Criança , Estudos Transversais , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/terapia , Frutas , Humanos , Prevalência , Verduras
4.
Mol Clin Oncol ; 17(1): 122, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35761897

RESUMO

The present report described the case of a 71-year-old man who was admitted to the emergency department with a 7-day history of progressive left flank pain and tarry stool. Bedside point-of-care ultrasound of the left kidney showed lobulated ill-defined hypoechoic foci in the perirenal spaces with mild hydronephrosis. Subsequent contrast-enhanced abdominal computed tomography revealed lobulated low-density lesions in the bilateral perirenal space and paraaortic space. The patient was subsequently admitted to the internal medicine department of the hospital. Renal and duodenal biopsies were arranged, and pathology reports were consistent with the findings of plasmablastic lymphoma (PBL). This unusual presentation of flank pain and tarry stool caused by recurrent PBL highlighted that genitourinary or gastrointestinal manifestations could occur in cases of PBL recurrence. The patient received intensive chemotherapy regimens comprising a combination of etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride for aggressive non-Hodgkin's lymphoma to achieve a good response.

5.
Front Aging Neurosci ; 14: 771486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401144

RESUMO

Background: To explore the association between leptospirosis, the risk of dementia, and the potential protective role of antibiotic treatment. Methods: We conducted a retrospective cohort nationwide, population-based study, from Taiwan's National Health Insurance Research Database (NHIRD). We enrolled 1,428 subjects aged 50 years or above, in the index year of 2000, which included those retrieved from the NHIRD record. Dementia diagnosis and incidence over 16 years follow-up was retrieved from the NHIRD records. The Fine and Gray survival analysis was used to determine the risk of dementia, and the results were presented as a sub-distribution hazard ratio (SHR) with a 95% confidence interval. Results: In the study period, 43 of the 357 leptospirosis patients developed dementia, as compared to 103 of the control group (930.90 vs. 732.49 per 105 person-years). By the Fine and Gray survival analysis, the leptospirosis was associated with the risk of dementia, and the adjusted SHR was 1.357 (95% confidence interval [CI]: 1.213-1.519, P < 0.001), across 16-year of the follow-up period. To exclude the protopathic bias, the sensitivity analysis was conducted. This analysis revealed that the leptospirosis was associated with the increased risk of dementia, even after excluding the dementia diagnosis within the first year (adjusted SHR = 1.246, 95%CI: 1.114-1.395, P < 0.001) or within the first 5 years (adjusted SHR = 1.079, 95%CI: 1.023-1.152, P = 0.028), antibiotic treatment for leptospirosis was associated with the reduced risk of dementia (P = 0.001). Conclusion: Leptospirosis was associated with an increased risk for dementia, and antibiotic treatment was associated with a reduced risk. Further research will be necessary to explore the underlying mechanisms of this association.

6.
Int J Cardiol ; 351: 55-60, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34954280

RESUMO

BACKGROUND: There is a positive association between electrical cardioversion (ECV) and acute ischemic stroke (AIS). Although 4 weeks of anticoagulation therapy after ECV in atrial fibrillation (AF) patients is generally suggested by current guidelines to reduce the risk of AIS, limited studies have been conducted in Asian populations to determine the risk and timing of AIS after ECV for AF in recent years. Therefore, we aim to use the National Health Insurance Research Database (NHIRD) in Taiwan to determine the risk and timing of AIS after ECV for AF. METHODS: The data analyzed in this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan. The outcome in this study was the cumulative incidence of AIS in patients with AF during 7-day and 30-day follow-up periods after the patients underwent ECV. RESULTS: Our analysis included 39,697 patients with AF, of whom 5723 received ECV and 5723 were propensity score-matched controls. Compared to the controls, patients who received ECV exhibited a significantly increased incidence of 7-day AIS development (adjusted hazard ratio [HR] = 1.524, p = 0.003). In contrast, the incidence of 30-day AIS development showed no significant increase (adjusted HR = 1.301, p = 0.426). CONCLUSIONS: AF patients who underwent ECV had a higher incidence of 7-day AIS development but not 30-day AIS development. Considering the timing of AIS development after ECV in AF patients, the optimal duration of antithrombotic therapy after ECV deserves further investigation.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Cardioversão Elétrica/efeitos adversos , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/etiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do Tratamento
7.
Nutrients ; 13(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34835940

RESUMO

Mounting evidence demonstrates that a high-salt diet (HSD) not only affects hemodynamic changes but also disrupts immune homeostasis. The T helper 17 (Th17) and regulatory T cells (Tregs) are susceptible to hypersalinity. However, research on the influence of sodium on Th2-mediated food allergies remains scarce. We aimed to investigate the effect of dietary sodium on the immune response to food allergies. Mice maintained on an HSD (4% NaCl), low-salt diet (LSD; 0.4% NaCl), or control diet (CTRL; 1.0% NaCl) were orally sensitized with ovalbumin (OVA) and a cholera toxin (CT) adjuvant, and then subjected to an intragastric OVA challenge. OVA-specific immunoglobulin G (IgG), IgG1, IgG2a, and IgE antibodies were significantly higher in the HSD group than in the CTRL group (p < 0.001, p < 0.05, p < 0.01, and p < 0.05, respectively). Mice on HSD had significantly higher interleukin (IL)-4 levels than the CTRL group (p < 0.01). The IL-10 levels were significantly lower in the HSD group than in the CTRL group (p < 0.05). The serum levels of interferon-γ (IFN-γ), sodium, and chloride did not differ among the three groups. This study indicates that excessive salt intake promotes Th2 responses in a mouse model of food allergy.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal/imunologia , Dieta/efeitos adversos , Hipersensibilidade Alimentar/imunologia , Tolerância ao Sal/imunologia , Sódio na Dieta/imunologia , Animais , Dieta/métodos , Dieta Hipossódica/métodos , Modelos Animais de Doenças , Hipersensibilidade Alimentar/etiologia , Imunidade , Camundongos , Ovalbumina/imunologia , Sódio na Dieta/administração & dosagem , Linfócitos T Reguladores/imunologia , Células Th2/imunologia
8.
BMC Pharmacol Toxicol ; 21(1): 83, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256848

RESUMO

BACKGROUND: Tetramethylammonium hydroxide (TMAH) is a quaternary ammonium compound that is both a base corrosive and a cholinergic agonist, and it is widely used in the photoelectric and semiconductor industries. It causes corrosive skin injuries and systemic cholinergic toxicity with death primarily resulting from respiratory failure without efficacious early decontamination. METHODS: A retrospective observational study was performed of all cases of TMAH exposure reported to the Taiwan Poison Control Center between July 2010 and October 2017. Retrieved medical records were independently reviewed by two trained clinical toxicologists. RESULTS: Despite immediate (< 5 min) skin decontamination with copious amounts of tap water, one patient exposed to 25% TMAH involving ≥5% of total body surface area (TBSA) developed significant systemic toxicity. Patients exposed to 25% TMAH involving ≤1% TBSA developed first-degree chemical skin injuries but no systemic toxicity. Among patients exposed to lower concentrations (≤2.38%) of TMAH, the majority only experienced first-degree chemical skin injuries without systemic signs. Patients exposed to 0.5% TMAH involving nearly their entire TBSA developed no chemical skin injuries or systemic toxicity. All patients who had only first-degree chemical skin injuries did not develop systemic toxicity after exposure to either 2.38% or 25% TMAH. CONCLUSIONS: TMAH acts as an alkaline corrosive and cholinergic agonist. Systemic signs attributable to TMA+ can rapidly lead to respiratory failure and death after dermal exposure. We have demonstrated that an amphoteric solution may be efficacious for skin decontamination on-site immediately to prevent or ameliorate such toxicity. This practice especially carries a valuable potential in managing victims (patients) who have been exposed to those chemicals with immediate life-threatening toxicity (e.g. TMAH), suggesting that its early utilization deserves further study.


Assuntos
Descontaminação/métodos , Exposição Ocupacional/efeitos adversos , Soluções Oftálmicas/administração & dosagem , Compostos de Amônio Quaternário/toxicidade , Pele/efeitos dos fármacos , Adulto , Feminino , Estimulantes Ganglionares/metabolismo , Estimulantes Ganglionares/toxicidade , Humanos , Masculino , Compostos Orgânicos/administração & dosagem , Compostos de Amônio Quaternário/metabolismo , Estudos Retrospectivos , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Taiwan/epidemiologia , Adulto Jovem
9.
Lab Med ; 51(4): 408-415, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31875889

RESUMO

BACKGROUND: Individuals whose copies of the survival motor neuron 1 (SMN1) gene exist on the same chromosome are considered silent carriers for spinal muscular atrophy (SMA). Conventional screening for SMA only determines SMN1 copy number without any information regarding how those copies are arranged. A single nucleotide variant (SNV) rs143838139 is highly linked with the silent carrier genotype, so testing for this SNV can more accurately assess risk to a patient of having an affected child. METHODS: Using a custom-designed SNV-specific Taqman genotyping assay, we determined and validated a model for silent-carrier detection in the laboratory. RESULTS: An initial cohort of 21 pilot specimens demonstrated results that were 100% concordant with a reference laboratory method; this cohort was utilized to define the reportable range. An additional 177 specimens were utilized for a broader evaluation of clinical validity and reproducibility. Allelic-discrimination analysis demonstrated tight clustering of genotype groupings and excellent reproducibility, with a coefficient of variation for all genotypes ranging from 1% to 4%. CONCLUSION: The custom-developed Taqman SNV genotyping assay we tested provides a rapid, accurate, and cost-effective method for routine SMA silent-carrier screening and considerably improves detection rates of residual risk for SMA carriers.


Assuntos
Triagem de Portadores Genéticos/métodos , Técnicas de Genotipagem/métodos , Atrofia Muscular Espinal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Triagem de Portadores Genéticos/normas , Técnicas de Genotipagem/normas , Heterozigoto , Humanos , Atrofia Muscular Espinal/diagnóstico , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Sensibilidade e Especificidade
10.
Am J Emerg Med ; 36(6): 1127.e1-1127.e3, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29588148

RESUMO

Acute cardiopulmonary distress in pregnancy always carries exceptionally arduous challenge for physicians. Here we report a patient who sustained spontaneous chordae tendineae rupture complicated with severe mitral regurgitation and acute pulmonary edema during peripartum period. Probable causes of chordae tendineae rupture include mitral valve prolapse, infectious endocarditis, congenital heart disease, rheumatic heart disease, ischemic heart disease, connective tissue diseases, previous mitral valve surgery or pregnancy itself. The pathophysiology of spontaneous chordae tendineae rupture due to pregnancy remains unclear. However, certain physiological stress, including hormone changes related matrix remodeling, increased cardiac output during pregnancy or labor pain may precipitate to this condition. Literature reviews from previously reported cases showed that those who were diagnosed chordae tendineae rupture at very preterm period all had preterm delivery.


Assuntos
Cordas Tendinosas/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Período Periparto , Complicações Cardiovasculares na Gravidez/fisiopatologia , Edema Pulmonar/diagnóstico por imagem , Ruptura Espontânea/diagnóstico por imagem , Adulto , Antibacterianos/uso terapêutico , Cordas Tendinosas/patologia , Diuréticos/uso terapêutico , Ecocardiografia Doppler em Cores , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Insuficiência da Valva Mitral/fisiopatologia , Gravidez , Edema Pulmonar/fisiopatologia , Ruptura Espontânea/complicações , Ruptura Espontânea/patologia , Resultado do Tratamento
12.
Mol Cytogenet ; 7(1): 85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25484916

RESUMO

Reports of interstitial deletions involving proximal long arm of chromosome 2 are limited. Based on early chromosomal analysis studies, the phenotypic consequence of deletions at the ancestral chromosome fusion site at chromosome 2q13q14.1 remains unclear. A recurrent 1.71 Mb deletion at 2q13 has recently been proposed as a new genomic disorder, associated with an increased risk of intellectual disability and craniofacial dysmorphism. Herein, we report the case of a 12 year-old girl with unique clinical features including global developmental delay, mullerian agenesis, and hypothyroidism associated with a normal size and position of the thyroid gland, as well as negative thyroid antibodies. Microarray-based comparative genomic hybridization study revealed a de novo 10.79 Mb deletion at 2q13q14.2 (111,548,932-122,336,492), which involves more than 88 UCSC genes, 38 of which are OMIM genes, 7 of which are disease-causing and 3 of which (including GLI2, IL1B and PAX8) show a dominant inheritance pattern.. Interestingly, PAX8 (chr2:113,973,574-114,036,498), a member of the paired-box gene family, is essential for the formation of thyroxine-producing follicular cells. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8 suggests a possible haploinsufficiency effect. Additionally, PAX8 is also expressed in the tissue primordia that form both the mullerian duct derivatives and the upper urinary tracts. A recent study has associated a novel PAX8 mutation with a severe form of hypothyroidism and abnormalities in the urogenital tract. Taken together, the unique clinical manifestation seen in this patient could be attributed to the heterozygous deletion of PAX8 gene. A prospective investigation is merited to fully evaluate the pathogenic effect of the interstitial deletion of 2q13q14.2.

13.
PLoS One ; 8(4): e59135, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23565142

RESUMO

The transport and accumulation of anticancer nanodrugs in tumor tissues are affected by many factors including particle properties, vascular density and leakiness, and interstitial diffusivity. It is important to understand the effects of these factors on the detailed drug distribution in the entire tumor for an effective treatment. In this study, we developed a small-scale mathematical model to systematically study the spatiotemporal responses and accumulative exposures of macromolecular carriers in localized tumor tissues. We chose various dextrans as model carriers and studied the effects of vascular density, permeability, diffusivity, and half-life of dextrans on their spatiotemporal concentration responses and accumulative exposure distribution to tumor cells. The relevant biological parameters were obtained from experimental results previously reported by the Dreher group. The area under concentration-time response curve (AUC) quantified the extent of tissue exposure to a drug and therefore was considered more reliable in assessing the extent of the overall drug exposure than individual concentrations. The results showed that 1) a small macromolecule can penetrate deep into the tumor interstitium and produce a uniform but low spatial distribution of AUC; 2) large macromolecules produce high AUC in the perivascular region, but low AUC in the distal region away from vessels; 3) medium-sized macromolecules produce a relatively uniform and high AUC in the tumor interstitium between two vessels; 4) enhancement of permeability can elevate the level of AUC, but have little effect on its uniformity while enhancement of diffusivity is able to raise the level of AUC and improve its uniformity; 5) a longer half-life can produce a deeper penetration and a higher level of AUC distribution. The numerical results indicate that a long half-life carrier in plasma and a high interstitial diffusivity are the key factors to produce a high and relatively uniform spatial AUC distribution in the interstitium.


Assuntos
Modelos Teóricos , Nanopartículas , Neoplasias/metabolismo , Algoritmos , Área Sob a Curva , Transporte Biológico , Permeabilidade Capilar , Simulação por Computador , Dextranos/metabolismo , Dextranos/farmacocinética , Sistemas de Liberação de Medicamentos , Humanos , Substâncias Macromoleculares/metabolismo , Modelos Biológicos , Distribuição Tecidual , Microambiente Tumoral
14.
Am J Med Genet A ; 155A(4): 825-32, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21416589

RESUMO

We report on the clinical and array-based characterization of an interstitial 1p31.3 deletion in a 15-year-old male patient with obesity, behavioral problems including multiple psychiatric diagnoses, mild intellectual impairment, facial dysmorphism, and a strong family history of psychiatric illness. The deletion breakpoints were determined by molecular karyotyping, revealing a 3.2 Mb excision. Patients previously reported with hemizygous deletions including this cytogenetic band had intellectual impairment and some facial features that overlap with our patient's phenotype. However, their deletions were larger, encompassing several cytogenetic bands, making this case the smallest deletion to date that we are aware of sharing these phenotypic characteristics. There are 17 genes that map to the interval. Two genes within the interval, LEPR and PDE4B, are interesting candidates for these phenotypes because of their potential role in obesity and psychiatric illness, respectively. Identification of the smaller deletion underscores the importance of combining clinical investigation and array comparative genomic hybridization analysis for appropriate diagnosis, genetic counseling and potentially for prenatal diagnosis.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Transtornos Mentais/genética , Obesidade Abdominal/genética , Adolescente , Hibridização Genômica Comparativa , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Ordem dos Genes , Estudos de Associação Genética , Humanos , Masculino , Linhagem , Fenótipo , Receptores para Leptina/genética
15.
Am J Clin Pathol ; 128(5): 865-74, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17951211

RESUMO

The correlation of JAK2V617F with a proportion of chronic myeloproliferative disorders has generated numerous studies focused on the development of molecular-based assays for JAK2V617F detection. The current parallel study comparatively evaluated 3 JAK2V617F molecular detection methods. Genomic DNA from blood or bone marrow was assayed by 3 laboratories using allele-specific polymerase chain reaction (AS-PCR) or kit-based restriction fragment length polymorphism methods, which used polyacrylamide gel or capillary electrophoresis analysis. In addition, samples were sequenced in 2 of the laboratories. Results found 100% concordance among the 3 methods, with analytic sensitivities of 5% for both kit methods and 0.01% for AS-PCR. The kitbased assays detect JAK2V617F with equal sensitivity regardless of analysis method, and, despite greater sensitivity of AS-PCR, all 3 methods yielded 100% concordant results for this 36-sample set. Consistent with other reports, direct sequencing was insufficiently sensitive to serve as an initial diagnostic tool for JAK2V617F detection.


Assuntos
Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Janus Quinase 2/genética , Mutação , Polimorfismo de Fragmento de Restrição/genética , Kit de Reagentes para Diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Análise Mutacional de DNA/métodos , Eletroforese , Feminino , Humanos , Janus Quinase 2/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
16.
Diagn Mol Pathol ; 16(3): 184-6, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17721328

RESUMO

The annual incidence of venous thromboembolism is approximately 117 per 100,000 persons or about 1 per 1000 person-years, with the majority of the disease occurring in the older age groups. Factor V Leiden gene (most common) and the prothrombin G20210A gene mutation are inherited mild to moderate risk factors for hypercoagulability. The anticoagulant warfarin requires close monitoring of the patient's prothrombin time, normalized as the international normalization ratio. Patients with either Cytochrome P-450 CYP2C9*2, CYP2C9*3, or VKORC1*2 genotype (c.-1639G>A) require significantly reduced doses, and are at a higher risk of serious bleeding. Thirty-five samples in total, 15 with Factor V Leiden, 18 with prothrombin G2021A mutation, and 2 with both were analyzed for 2C9*2, 2C9*3, and VKORC1 (-1639) allele variants by using the Invader CYP2C9 and VKORC1 polymorphism analysis kit. Eight with CYP2C9*2 C/T, 2 with CYP2C9*3 A/C, 5 with VKORC1 (-1639) A/A, and 22 with VKORC1 (-1639) G/A genotypes or 29 out of 35 (83%) samples analyzed were found with CYP2C9*2 C/T, CYP2C9*3 A/C, VKORC1 (-1639) G/A, or/and VKORC1 (-1639) A/A genotypes. CYP2C9*2 C/T, CYP2C9*3 A/C, VKORC1 (-1639) G/A genotyping might be necessary for patients with Factor V Leiden and/or prothrombin G2021A mutation before warfarin anticoagulant therapy.


Assuntos
Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases/genética , Transtornos Herdados da Coagulação Sanguínea/tratamento farmacológico , Transtornos Herdados da Coagulação Sanguínea/genética , Oxigenases de Função Mista/genética , Polimorfismo Genético , Citocromo P-450 CYP2C9 , Fator V/genética , Humanos , Mutação , Protrombina/genética , Vitamina K Epóxido Redutases , Varfarina/administração & dosagem
17.
Diagn Mol Pathol ; 16(2): 121-3, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17525684

RESUMO

Supplies, such as bags of plastic reaction tubes, are sometimes left in the laminar flow hoods unintentionally while the ultraviolet (UV) lamp is illuminated overnight. In addition, UV irradiation is used for sterilization and amplicon inactivation to avoid contamination. The oligonucleotide ligation assay (OLA) is a unique approach to mutation detection of point mutations, small deletions, and small insertions. Recently, we encountered problems with this assay and peak heights were much lower or disappeared. After going through systemic trouble-shooting, we found that profound inhibition of the polymerase chain reaction (PCR) step of CF V3 multiplex PCR/OLA assay by the use of UV-irradiated plastic reaction tubes. When UV-irradiated tubes used throughout the assay, tubes exposed for 8 weeks at 0.7 m from the UV source gave a reduction of 60% and 67% in the assay products on the basis of sum of peak heights. Tubes exposed for 3 weeks at 0.1 m from the UV source totally eliminated assay product yielding no peaks. Further experiments showed that the inhibition happened mostly in the PCR step. Burgess and Hall had reported that inhibition of PCR of human glyceraldehydes-3-phosphate dehydrogenase transcripts after UV irradiating the tubes. This showed that the inhibition was not assay-specific. The reason that the inhibition of PCR was more profound could be due to a multiplex PCR assay and small reaction volume. The mechanism of PCR inhibition by UV irradiation is not clear. In conclusion, plastic reaction tubes intended for PCR/OLA assays should not be exposed to UV.


Assuntos
Artefatos , DNA/efeitos da radiação , Sondas de Oligonucleotídeos/efeitos da radiação , Plásticos/efeitos da radiação , Reação em Cadeia da Polimerase/efeitos da radiação , Raios Ultravioleta , Humanos , Reação em Cadeia da Polimerase/métodos
18.
Diagn Mol Pathol ; 16(1): 50-3, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17471158

RESUMO

UDP glucuronosyltransferase (UGT) 1A1 gene promoter polymorphism can affect the expression level of the UGT 1A1 enzyme. The polymorphism consists of an insertion of a TA nucleotide sequence into a (TA)6TAA sequence in the gene promoter resulting in (TA)7TAA (UGT1A1*28). This results in a reduced UGT 1A1 expression with 70% less glucuronidation capacity for bilirubin and other UGT1A1 substrates. Other polymorphisms include (TA)8TAA (UGT1A1*37) and (TA)5TAA (UGT1A1*36). The longer the TA repeats the lower the enzyme expression level. The anticancer agent irinotecan is metabolized to the active SN-38, which is further glucuronidated and detoxified by UGT 1A1. Decreased glucuronidation leads to SN-38 accumulation with severe neutropenia and diarrhea. We have developed a rapid polymerase chain reaction (PCR)-based detection of all length polymorphisms in the UGT 1A1 gene promoter. It uses PCR and DNA fragment analysis using an ABI Genetic Analyzer. Thirty-two blood samples were analyzed for UGT 1A1 promoter polymorphism. We found 2 (TA)(5)TAA/(TA)(5)TAA, 4 (TA)(5)TAA/(TA)(6)TAA, 2 (TA)(5)TAA/(TA)(7)TAA, 9 (TA)(6)TAA/(TA)(6)TAA, 11 (TA)(6)TAA/(TA)(7)TAA, 2 (TA)(7)TAA/(TA)(7)TAA, and 2 (TA)(7)TAA/(TA)(8)TAA in our sample group. To confirm the results, 6 samples with different repeats were also analyzed by DNA sequencing method. This is a rapid and reliable method for analysis of the promoter length polymorphisms of UGT 1A1 gene.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Camptotecina/análogos & derivados , Glucuronosiltransferase/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Pró-Fármacos/farmacocinética , Camptotecina/farmacocinética , DNA/análise , Humanos , Irinotecano , Regiões Promotoras Genéticas/genética
19.
Diagn Mol Pathol ; 16(1): 57-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17471160

RESUMO

Cystic fibrosis (CF) is one of the most common autosomal recessive diseases in the white population, with a prevalence estimate of 1 in 2500 to 3300 live births. CF is characterized by viscous mucus in the lungs with involvement of digestive and reproductive systems as well as sweat glands (excess salt loss). Treatment for CF patients is palliative. Over 1300 mutations have been identified in the CFTR gene. However, most of the mutations are at frequencies of <0.1% or represent private mutations. Although other methodologies are available for CF testing, the oligonucleotide ligation assay is a unique approach to mutation detection of point mutations, small deletions, and small insertions, and consists of 2 phases. Applied Biosystems 3130 Series Genetic Analyzers are the next-generation platform for low to medium throughput laboratories and deliver improved performance. One disadvantage of the Genetic Analyzers is that there is no template of instrument settings for POP-6 polymer using 36-cm array. The Abbott CF oligonucleotide ligation assay ASRs can be run only using POP-6 polymer. We are the first to have optimized the instrument settings for POP-6 polymer based on the template of Rapidseq36-POP6 for Abbott Diagnostics CF V3 ASRs. Several conditions were tried, and the conditions of sample injection voltage at 10,000 v and sample injection time at 5 seconds gave better results, which were with clearer peaks and lower background signals. Twenty cell line DNA samples from Coriell were analyzed, and the results were matched. In addition, Synthetic Controls from AcroMetrix were analyzed, and the results were same as expected. Also, about 1500 clinical samples were analyzed, and high-quality reportable results were obtained. In conclusion, our modified protocol is robust and reliable on this ABI 3130XL instrument.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Análise Mutacional de DNA/instrumentação , Pneumopatias/genética , Humanos , Mutação
20.
J Allergy Clin Immunol ; 113(2): 268-76, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14767441

RESUMO

BACKGROUND: T(H)2 cytokines play a central role in the pathogenesis of allergic asthma. We previously showed that the "antiasthma" Chinese herbal formula MSSM-002 exhibited therapeutic effects on established allergic airway responses in a murine model of allergic asthma. However, the mechanisms underlying these effects are largely unknown. OBJECTIVE: The objective of this study was to determine whether and how MSSM-002 modulates an established T(H)2 response and whether the actions of MSSM-002 on T(H)2 cell differs from corticosteroids. METHODS: T(H)2 polarized splenocytes (T(H)2-SPCs) from mice with antigen-induced airway hyperresponsiveness and T(H)2 cloned cells, D10 G4.1 (D10), were cultured in the presence or absence of antigen with or without MSSM-002 and dexamethasone, and the proliferative responses and cytokine profiles were determined. Apoptosis and T(H)2 transcription factor GATA-3 expression and binding to IL-4 gene promoter and V(A) enhancer in MSSM-002-treated D10 cells were also determined. RESULTS: MSSM-002 significantly decreased antigen-induced proliferation and IL-4 and IL-5 production but increased IFN-gamma production by T(H)2-SPCs, whereas dexamethasone suppressed IFN-gamma as well as IL-4 and IL-5. Anti-IL-12 antibody, although abrogating MSSM-002 induction of IFN-gamma, had no significant effect on MSSM-002 suppression of IL-4 and IL-5 secretion. MSSM-002 also suppressed T(H)2 cytokine secretion by D10 cells, and in contrast to dexamethasone, MSSM-002 did not induce apoptosis of D10 cells. MSSM-002 markedly suppressed GATA-3 mRNA and protein expression and the binding to IL-4 gene promoter and V(A) enhancer in D10 cells. CONCLUSION: MSSM-002, in contrast to the overall suppression of T cells by dexamethasone, exhibits immunomodulatory actions on T(H)2 cells caused, at least partially, by downregulation of GATA-3.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Hiper-Reatividade Brônquica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipersensibilidade Imediata/tratamento farmacológico , Células Th2/imunologia , Animais , Antiasmáticos/farmacologia , Antígenos/farmacologia , Asma/imunologia , Hiper-Reatividade Brônquica/imunologia , Células Cultivadas , Citocinas/metabolismo , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Fator de Transcrição GATA3 , Glucocorticoides/farmacologia , Humanos , Hipersensibilidade Imediata/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos AKR , Células Th2/efeitos dos fármacos , Transativadores/efeitos dos fármacos , Transativadores/metabolismo
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