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1.
Zhonghua Fu Chan Ke Za Zhi ; 58(7): 489-494, 2023 Jul 25.
Artigo em Zh | MEDLINE | ID: mdl-37474321

RESUMO

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ2 test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27+4 weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.


Assuntos
Aborto Induzido , Placenta Acreta , Recém-Nascido , Gravidez , Feminino , Humanos , Lactente , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/cirurgia , Segundo Trimestre da Gravidez , Gestantes , Cesárea , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Placenta , Histerectomia
2.
Herz ; 44(8): 712-716, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30151710

RESUMO

Geminin, a key regulator of DNA replication licensing in the cell cycle, plays an essential role in determining the fate of cells via suppression of cell proliferation and cellular differentiation. Neuropeptide Y (NPY) intensifies the proliferation of vascular smooth muscle cells (VSMCs) directly by binding with Y1 receptors. In vitro experiments have shown that stimulation of NPY on VSMCs via regulation of geminin is a double-edged sword. Given that the proliferation and the phenotypic transformation of VSMCs increase the risk for progression of atherosclerosis, we focus on the role of geminin interference in determining the fate of VSMCs. Furthermore, we discuss the therapeutic potential of peripheral neurotransmitter interference, thus pointing toward future research directions in the treatment of atherosclerosis.


Assuntos
Geminina , Músculo Liso Vascular , Neuropeptídeo Y , Proliferação de Células , Geminina/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso , Neuropeptídeo Y/fisiologia
3.
Zhonghua Fu Chan Ke Za Zhi ; 54(4): 226-231, 2019 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-31006187

RESUMO

Objective: To explore the mutation characteristics of DMD gene in patients with Duchenne or Becker muscular dystrophy and female carriers, to provide effective prenatal diagnosis. Methods: Samples were collected from 94 male patients clinically diagnosed with Duchenne or Becker muscular dystrophy and 121 corresponding female relatives from Qingdao Women and Children's Hospital from June 2011 to October 2018. Multiplex ligation-dependent probe amplification (MLPA) was used to detect their DMD gene, and 23 high risk pregnants were performed prenatal diagnosis. Any candidate of DMD gene single-exon deletion was validated by further PCR amplification. The sample with whole DMD gene deletion was confirmed by chromosomal microarray analysis (CMA) to detect copy number variations and break site. Results: Among 94 clinical Duchenne or Becker muscular dystrophy patients, 66(70.2%, 66/94) were detected gene mutation; 56 cases were exon deletion mutation and 10 cases were duplication mutation. In 121 female relatives, 48 cases (39.7%, 48/121) were diagnosed as carriers. The mutation carrying rate, was 64.5% (40/62) identified in 62 mothers of Duchenne or Becker muscular dystrophy patients. Five Duchenne or Becker muscular dystrophy fetuses and 5 carrier fetuses were prenatally diagnosed in 23 high risk pregnants. Two children with the entire DMD gene deletion were identified more deletions at Xp21, with deletions of 6.66 Mb and 10.64 Mb respectively. Conclusions: MLPA may be an important method to detect DMD gene mutation of deletion and duplication. Therefore, the diagnosis of probands, female carriers and making an effective prenatal diagnosis are essential to reduce the birth of children with Duchenne or Becker muscular dystrophy.


Assuntos
Distrofina/genética , Deleção de Genes , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Diagnóstico Pré-Natal/métodos , Criança , Variações do Número de Cópias de DNA , Éxons , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Gravidez
4.
J Clin Pharm Ther ; 42(2): 135-146, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28177134

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when co-administered with a known CYP450 inducer, which may lead to treatment failure. The influence of some CYP450 inducers on the pharmacokinetics of voriconazole has been described in previous studies, but a systematic review was lacking. In this study, we carried out a systematic review to assess the influence of CYP450 inducers on the pharmacokinetic (PK) parameters of voriconazole. METHODS: Pubmed, Embase, Cochrane Library, Clinicaltrials.gov and three Chinese databases (CNKI, CBM and WanFang) were searched through January 2016. Interventional and observational studies comparing the PK parameters of voriconazole used alone or with CYP450 inducers in healthy volunteers and patients were included. The outcomes included were the area under the plasma concentration-time curve (AUC), peak plasma concentrations (Cmax ) and trough plasma concentrations (Cmin ). The quality of the included studies was assessed using Cochrane's risk of bias tool, Newcastle-Ottawa Scale (NOS) and a modified risk of bias tool for pharmacokinetic before-and-after studies. RESULTS AND DISCUSSION: Sixteen studies were included in this review: three randomized controlled trials (RCTs), five single-arm before-after studies (SBAs), six cohort studies and two case reports. All studies except case reports had moderate to high quality. Of the 11 inducers reviewed, efavirenz, ritonavir (chronic use), phenytoin, rifampin and rifabutin significantly decreased mean AUC and Cmax of voriconazole; St John's wort significantly decreased only mean AUC; rifampin, rifabutin, phenobarbital and carbamazepine significantly decreased mean Cmin . Etravirine and Ginkgo biloba did not reveal any such influence. The influence of glucocorticoids may depend on its type and dose. WHAT IS NEW AND CONCLUSIONS: To conclude, the combination use of high-dose efavirenz, high-dose ritonavir, St John's wort, rifampin, phenobarbital, or carbamazepine with voriconazole is contraindicated as instructed in the drug label. Low-dose efavirenz, low-dose ritonavir, rifabutin and phenytoin may be used together with voriconazole provided TDM and dose adjustment of voriconazole. Moreover, this study shows there is low risk of drug-drug interactions when voriconazole is co-administered with etravirine or G. biloba; however, whether the use of glucocorticoids has a clinically significant effect on voriconazole still requires more evidence. This study also highlights the lack of clinical studies and future high-quality studies assessing the influence of CYP450 inducers on voriconazole. PK parameters and dosing optimization should be designed to provide a more definitive answer regarding the necessity of TDM and the recommendations for dose adjustment of voriconazole.


Assuntos
Antifúngicos/farmacocinética , Indutores das Enzimas do Citocromo P-450/farmacologia , Voriconazol/farmacocinética , Citocromo P-450 CYP2C19/fisiologia , Citocromo P-450 CYP2C9/fisiologia , Interações Medicamentosas , Humanos
5.
Genet Mol Res ; 14(3): 10543-52, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26400286

RESUMO

In this study, the functions and mechanisms of γ δ T cells were analyzed in patients infected with Helicobacter pylori. Peripheral blood was collected from gastritis patients in the Gastroenterology Department of Ningbo No. 2 Hospital. Preliminary analyses revealed 24 H. pylori-positive and 17 H. pylori-negative patients. The wild-type and γ δ T knockout mice were infected with cultured H. pylori cells (obtained from the H. pylori-positive patients). H. pylori in mice was quantified by polymerase chain reaction; gastritis was confirmed by hematoxylin and eosin staining. The TCR-δ(-/-) mice were treated with vein adoptive immunotherapy 24 h prior to H. pylori inoculation; the same method was used to detect the extent of gastritis and bacterial colonization. The γ δ T knockout mice showed high levels of H. pylori infection than the wild-type mice; in addition, the knockout mice showed severe disease pathology. γ δ T knockout mice also displayed increased matrix metalloproteinase-9 (MMP-9) and decreased MMP-7 expression in the gastric mucosa. γ δ T cells play a protective role in patients infected with H. pylori. γ δ T cell [responsible for the production of interleukin-17 (IL-17) and IL-22] expression was increased in H. pylori-positive patients, indicating statistical significance. However, there was no significant difference in interferon-gamma + γ δ T expression between the positive and negative patients. This study demonstrated the probable involvement of γ δ T cells in the immune response of an organism, via the secretion of IL-17 and IL-22.


Assuntos
Gastrite/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/patogenicidade , Tolerância Imunológica , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Animais , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/genética , Gastrite/microbiologia , Gastrite/terapia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/terapia , Helicobacter pylori/imunologia , Humanos , Imunoterapia Adotiva , Interferon gama/genética , Interferon gama/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Interleucinas/genética , Interleucinas/imunologia , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/imunologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Antígenos de Linfócitos T gama-delta/deficiência , Receptores de Antígenos de Linfócitos T gama-delta/genética , Índice de Gravidade de Doença , Linfócitos T/microbiologia , Linfócitos T/patologia , Linfócitos T/transplante , Interleucina 22
6.
Eur J Clin Microbiol Infect Dis ; 33(4): 659-64, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24186726

RESUMO

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case-control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25-90), and 40 (67%) were male. Most patients had osteomyelitis (82%), predominantly from a contiguous source (87%). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50%) vs. 4 (20%); p = 0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55%) vs. 5 (25%); p = 0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p = 0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2-36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75%) vs. 27 (68%); p = 0.8] and 6 months [14 (70%) vs. 23 (58%); p = 0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5%) vs. 7 (18%); p = 0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.


Assuntos
Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Daptomicina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas Infecciosas/microbiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento
7.
Artigo em Zh | MEDLINE | ID: mdl-37805758

RESUMO

Although the treatment of patients with burns combined with inhalation injury has achieved great success, from the perspective of epidemiology, inhalation injury is still the most common cause of death in mass burns. Such patients often suffered burns of large total body surface area, which is difficult to treat, with airway management as one of the core links. Physical airway clearance technique (ACT) acts on a patient's respiratory system by physical means, to discharge secretions and foreign bodies in the airway, achieve airway clearance, and improve gas exchange. In addition, the technique can prevent or alleviate many complications, thereby improving the clinical outcome of patients with inhalation injury. This article reviews the application of physical ACT in the field of inhalation injury, and to provide decision-making basis for clinical medical staff to choose physical ACT corresponding to the patient's condition.


Assuntos
Queimaduras por Inalação , Queimaduras , Humanos , Estudos Retrospectivos , Queimaduras/terapia , Queimaduras/complicações , Manuseio das Vias Aéreas , Queimaduras por Inalação/terapia , Queimaduras por Inalação/complicações
8.
Artigo em Zh | MEDLINE | ID: mdl-37150993

RESUMO

Objective: To summarize clinical features and our experience of the diagnosis and treatment of laryngocele. Methods: Clinical data of 11 laryngocele patients in department of Otorhinolaryngology Head and Neck Surgery of the Second Affiliated Hospital of Shanxi Medical University from January 2012 to December 2021 were retrospectively reviewed, including 9 men and 2 women, aged from 12 to 75 years, with median age of 56 years. Electronic laryngoscope was performed in 10 of all patients, laryngeal CT in 10 and cervical color ultrasound in 5 before operation.All the operations were performed under general anesthesia, and the external cervical approach was used for external and combined laryngocele. The internal laryngocele was resected by low temperature plasma through transoral endoscopy. Patients were followed up regularly after operation to evaluate the effect. Clinical feature, types of lesions, imaging findings, surgical approaches and follow-up results were analyzed through descriptive statistical method. Results: Eleven laryngocele patients were divided into mixed type (n=6), internal type (n=4) and external type (n=1).Nine patients presented with hoarseness or dysphonia, 7 with cervical mass and 1 with airway obstruction. Surgical resections were done through external cervical approach (n=7)or transoral endoscopic approach (n=4). All the operations were successful and no complication occurred. All cases were followed up from 17 to 110 months. No recurrence was encountered. Conclusions: Laryngocele is a rare lesion with atypical clinical presentation. Preoperative imaging including CT scan and electronic laryngoscope is essential to evaluate the location, and extent of the lesion, and to make the surgical plan.Complete surgical excision is required. Surgical resection is the only effective method for the treatment of laryngocele.


Assuntos
Laringocele , Laringe , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Criança , Adolescente , Adulto Jovem , Adulto , Idoso , Laringocele/cirurgia , Laringocele/complicações , Laringocele/patologia , Estudos Retrospectivos , Laringe/cirurgia , Laringe/patologia , Laringoscopia/métodos , Rouquidão
9.
J Periodontal Res ; 46(1): 126-33, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21108645

RESUMO

BACKGROUND AND OBJECTIVE: The enhancing effects of chitosan on activation of platelets and differentiation of osteoprogenitor cells have been demonstrated in vitro. The purpose of this study was to evaluate the in vivo osteoinductive effect of chitosan-collagen composites around pure titanium implant surfaces. MATERIAL AND METHODS: Chitosan-collagen composites containing chitosan of different molecular weights (450 and 750 kDa) were wrapped onto titanium implants and embedded into the subcutaneous area on the back of 15 Sprague-Dawley rats. The control consisted of implants wrapped with plain collagen type I membranes. Implants and surrounding tissues were retrieved 6 wks after surgery and identified by Alizarin red and Alcian blue whole mount staining. The newly formed structures in the test groups were further analyzed by Toluidine blue and Masson-Goldner trichrome staining, and immunohistochemical staining with osteopontin and alkaline phosphotase. The bone formation parameters of the new bone in the two test groups were measured and compared. RESULTS: New bone formed ectopically in both chitosan-collagen groups, whereas no bone induction occurred in the negative control group. These newly formed bone-like structures were further confirmed by immunohistochemical staining. Comparison of bone parameters of the newly induced bone revealed no statistically significant differences between the 450 and 750 kDa chitosan-collagen groups. CONCLUSION: Our results demonstrated that chitosan-collagen composites might induce in vivo new bone formation around pure titanium implant surfaces. Different molecular weights of chitosan did not show significantly different effects on the osteoinductive potential of the test materials.


Assuntos
Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Osseointegração/efeitos dos fármacos , Fosfatase Alcalina/biossíntese , Animais , Quitosana/química , Colágeno Tipo I/farmacologia , Implantes Dentários , Combinação de Medicamentos , Implantes Experimentais , Masculino , Peso Molecular , Osteopontina/biossíntese , Ratos , Ratos Sprague-Dawley , Tela Subcutânea , Titânio
10.
J Appl Microbiol ; 109(4): 1422-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20553339

RESUMO

AIMS: Isolation and characterization of the clinically relevant amphizoic amoebas in vegetated farmlands, which may present a risk to farmers' health. METHODS AND RESULTS: Acanthamoeba species was isolated and characterized via morphological and molecular means in the rice field where the patient was exposed to rice paddy water which most probably was the point of infection. An Acanthamoeba sp. abundant in the rice field was identified. Genotyping showed the strain to be genotype T4, which was identical to the amoebic parasite found in patient's cerebrospinal fluid. During the course of the study, three nonpathogenic free-living amoeba species were also isolated and characterized for the first time in Taiwan. CONCLUSIONS: This study successfully located a possible source of granulomatous amoebic encephalitis in a patient and provided the first evidence that Acanthamoeba genotype T4 may be a potential pathogen in Taiwan. SIGNIFICANCE AND IMPACT OF THE STUDY: The integration of field survey, clinical data and morphological and genetic examination represents a sound strategy for investigation of the possible role of free-living amoebae in causing human diseases. Future work should include investigating the potential contributory role of other nonpathogenic free-living protozoa in disease of livestock or even human.


Assuntos
Acanthamoeba/isolamento & purificação , Amebíase/parasitologia , Infecções Parasitárias do Sistema Nervoso Central/parasitologia , Encefalite/parasitologia , Oryza , Acanthamoeba/classificação , Acanthamoeba/citologia , Genótipo , Humanos , Taiwan , Água/parasitologia
11.
Transplant Proc ; 40(8): 2696-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929838

RESUMO

BACKGROUND: Acute renal insufficiency and dysfunction are common complications after clinical liver transplantation. This study examined whether augmentor of liver regeneration (ALR) played a significant role to ameliorate renal tubular epithelial cell injury after liver transplantation. METHODS: Orthotopic liver transplantation was performed from Sprague-Dawley (SD) to SD rats. Twelve recipients were randomly divided into two groups: ALR group (with recombinated human ALR 100 microg/kg . d intramuscular injection postoperation) versus normal saline-treated group (with the same volume of normal saline injected intramuscularly postoperation). Rats were sacrificed at day 3 posttransplantation. Renal morphological changes in recipients were assessed with light microscopy. The expressions of tumor necrosis factor-alpha (TNF-alpha), proliferating cell nuclear antigen (PCNA) and caspase-3 protein and mRNA in the kidney were evaluated by real-time polymerase chain reaction and immunohistochemical staining. RESULTS: Morphological changes in renal tubular epithelial cells were not significant in either group at day 3 posttransplantation. The intragraft expression of TNF-alpha and caspase-3 was strikingly promoted in the normal saline-treated group and PCNA attenuated compared to the ALR group. CONCLUSION: These data suggested that ALR may play a role to reduce renal damage in liver transplant recipients.


Assuntos
Células Epiteliais/patologia , Túbulos Renais/patologia , Regeneração Hepática , Transplante de Fígado/patologia , Transplante de Fígado/fisiologia , Animais , Animais Recém-Nascidos , Biomarcadores , Imuno-Histoquímica , Túbulos Renais/lesões , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética
12.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 30(14): 1110-1114, 2016 Jul 20.
Artigo em Zh | MEDLINE | ID: mdl-29798432

RESUMO

Objective:To investigate the change of word recognition score(WRS) during the treatment of patients with idiopathic sudden sensorineural hearing loss(ISSNHL) and explore the role of WRS in outcomes assessment of ISSNHL.Method:Thirty-seven patients diagnosed with ISSNHL,whose pure-tone average(PTA) has no change but WRS has improved after treatment,were analyzed retrospectively.The WRS and the test intensity for WRS of pre-treatment and those of post-treatment were compared statistically.Result:There is statistical significance between WRS of post-treatment and that of pre-treatment(P<0.01).The increase of WRS score is consistent with improvement of symptom in these patients.Conclusion:More attention needs to be paid to WRS during treatment of ISSNHL patients,especially those whose PTA has no improvement but patients feel better about their hearing,and WRS could be an important factor in terms of outcome assessment during treatment of ISSNHL patients for the further treatment.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Percepção da Fala , Audiometria de Tons Puros , Testes Auditivos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
13.
Eur Rev Med Pharmacol Sci ; 20(11): 2235-48, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27338047

RESUMO

OBJECTIVE: G protein-coupled receptor, family C, group 6, member A, (GPRC6A) is a prostate cancer (PCa) susceptibility gene and has been shown to regulate PCa progression. However, its role in PCa metastasis is largely unknown. The aim of this study was to confirm the association between GPRC6A and aggressive PCa in a case-control analysis, and to explore the function of GPRC6A in PCa metastasis in vitro. PATIENTS AND METHODS: The association of 14 single nucleotide polymorphisms (SNPs) of GPRC6A and linked to GPRC6A were evaluated with PCa risk and aggressive PCa in 916 subjects. Metastasis behavior was determined in GPRC6A knockdown PC3 cells, and the expressions of matrix metalloproteinase (MMP)2 and MMP9 were detected. Bone transcription factor runt-related transcription factor 2 (RUNX2) and epithelial-mesenchymal transition (EMT) marker genes were examined in the GPRC6A overexpression PC3 cells. RESULTS: Among the 14 SNPs tested in PCa patients and controls, 4 were associated with aggressive PCa (p = 0.032-0.037, odds ratio = 1.38-1.41). Both the migration and invasion abilities were reduced in PC3 cells that were transiently transfected with GPRC6A short interfering RNA (siRNA). The GPRC6A knockdown cells showed reduced activity levels of MMP2 and MMP9. Furthermore, RUNX2, EMT and ERK signaling were shown to be up-regulated in GPRC6A overexpression cells. CONCLUSIONS: These findings suggest that GPRC6A is associated with aggressive PCa. GPRC6A knockdown inhibits the PCa cells migration and invasion, and GPRC6A overexpression promotes the EMT. It is suggested that GPRC6A may serve as a potential therapeutic target for metastatic PCa.


Assuntos
Linhagem Celular Tumoral , Neoplasias da Próstata/genética , Receptores Acoplados a Proteínas G/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal , Humanos , Masculino , Metástase Neoplásica , RNA Interferente Pequeno
14.
Leukemia ; 16(6): 1045-52, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12040436

RESUMO

It has been suggested that the expansion of the leukemic cells in chronic lymphocytic leukemia (CLL) is due to dysregulation of pathways of programmed cell death (apoptosis) rather than cell proliferation, although differences may exist in early vs late and treated vs untreated patients. In the present study, we analyzed the expression of 11 proteins in CLL cells that are implicated in the control of apoptosis, proliferation, and differentiation, and correlated this expression profile with survival. Using a quantitative solid-phase radioimmunoassay (RIA), we measured the cellular protein levels of Bcl-2, cyclin D1, PCNA, ATM, Fas, Bax, retinoic acid receptor alpha (RARalpha), retinoic acid receptor beta (RXRbeta), Flt1, VEGF, and cellular beta2-microglobulin in 230 samples of CLL. Univariate analysis using the Cox proportional hazard model showed a correlation with survival of only the following proteins: Bcl-2 (P < 0.001), cyclin D1 (P = 0.027), Fas (P = 0.055), PCNA (P < 0.001), and ATM (P = 0.028). In a multivariate analysis using classification and regression tree analysis (CART), five groups of patients (nodes) could be generated with significant differences of survival expectation (P < 0.0001) based on levels of expression of the above proteins. Based on CART analysis, Bcl-2 levels emerge as the most important protein in predicting survival between all 11 proteins studied. Patients with marked elevation in Bcl-2 levels had the worst outcome while patients with intermediate levels, but with high levels of PCNA and cyclin D1 or abnormal ATM expression had intermediate survival. These data indicate that intracellular levels of proteins such as Bcl-2, ATM, cyclin D1, and PCNA can be used as markers to predict clinical behavior and survival in patients with CLL. The pathways in which these proteins are involved may also represent possible targets for future therapeutic trials in CLL.


Assuntos
Biomarcadores Tumorais/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/mortalidade , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Western Blotting , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Análise de Sobrevida
15.
Cell Res ; 8(4): 285-93, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9934536

RESUMO

A simple method to create a chromosome-specific DNA library of rice, including microdissection, amplification, characterization and cloning, is described. Rice chromosome 4 from a metaphase cell has been isolated and amplified by the Linker Adapter PCR (LA-PCR). The PCR products were labeled as probes with DIG-11-dUTP using the random priming method. Southern blot analysis with rice genomic DNA and specific RFLP markers demonstrated that the PCR products were derived from rice chromosome 4. A large library comprising over 100,000 recombinant plasmid microclones from rice chromosome 4 was constructed. Colony hybridization showed that 58% of the clones contained single or low-copy sequences and 42% contained repetitive sequences. The size of inserts generated by PCR ranged from 140bp to 500bp. This method will facilitate cloning of the specific chromosome DNA markers and important genes of rice.


Assuntos
Cromossomos , Biblioteca Gênica , Oryza/genética , Mapeamento Cromossômico , DNA de Plantas/química , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Reação em Cadeia da Polimerase , Sitios de Sequências Rotuladas
16.
Pathol Oncol Res ; 7(3): 171-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11692142

RESUMO

The purpose of this study was to investigate the frequency of expression of the erbB/HER family of growth factor receptors, their ligand heregulin, and the two different signaling pathways p38 and mitogen-activated protein kinase (MAPK), as well as the status of HER-2 phosphorylation in tumor specimens from patients with primary breast cancer. The level of expression of these proteins was measured by quantitative immunohistochemistry combined with microscope-based image analysis in paraffin-embedded breast cancer tissue from 35 patients. The frequency of expression was: EGFR (51%), HER-2 (54%), P-HER-2 (48%), HER-3 (48%), HER-4 (57%), heregulin (48%), p38 (17%), MAPK (48%). There was evidence of associations among the coexpression of heregulin, EGFR, HER-2, and HER-3. Also, there was evidence of a positive association between P-MAPK and HER-4. HER-3 was expressed at high levels in patients younger than 50 years of age. There was a trend for expression of higher levels of HER-4 in tumors larger than 2 cm. The expression of EGFR, HER-2, heregulin, p38 and MAPK was independent of age, tumor size, number of lymph nodes involved or hormone receptor status. The HER family of growth factor receptors appear to be regulated independently in invasive breast cancer. Assessing the expression of multiple tumor markers by quantitative immuno-histochemistry is feasible. Further research is needed to determine the prognostic and predictive roles of the various associations between HER receptors, their ligands and signal transduction molecules in patients with early-stage breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Receptores ErbB/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neuregulina-1/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Estadiamento de Neoplasias , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno
17.
Am J Manag Care ; 7(4): 363-73, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11310191

RESUMO

OBJECTIVE: To examine physician and leader perceptions of the relationship between physician compensation and the productivity of physicians practicing in medical groups. STUDY DESIGN: Key informant interviews identified subjects' perceptions of factors influencing physician productivity and the behavioral effects of individual financial incentives. Interview transcripts were analyzed by a team of physicians, economists, and other researchers. STUDY POPULATION: Physicians, medical leaders, and group practice administrators (n = 114) representing 46 medical group practices in California, Oregon, Washington, and Wisconsin were interviewed. RESULTS: Five major themes emerged: (1) Most physicians reported that financial incentives did not substantially affect their own behavior, except for productivity. However, they suggested that specific compensation models do lead to certain seemingly undesirable physician behaviors. (2) By contrast, medical group leaders reported that financial incentives do affect a variety of physician behaviors. (3) Four productivity drivers emerged: financial incentives, demand-side factors, systems and infrastructure, and other individual or group attributes. (4) Physician compensation systems are evolving toward a blend of production-based and production-neutral incentives, plus new metrics aligned with the demands of managed care. (5) Culture, size, and specialty mix are significant determinants of group physician compensation systems. CONCLUSIONS: Compensation method is perceived to be a significant influence on physician productivity, particularly among group practice leaders. The changing context of medical practice represents another powerful "macro" lever on physician behavior.


Assuntos
Atitude do Pessoal de Saúde , Eficiência/classificação , Prática de Grupo/organização & administração , Médicos/economia , Reembolso de Incentivo , Salários e Benefícios , Prática de Grupo/economia , Humanos , Entrevistas como Assunto , Estados do Pacífico , Médicos/psicologia , Wisconsin
18.
J Ambul Care Manage ; 22(3): 47-57, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11184880

RESUMO

Medical groups are challenged to adopt a systematic, evidence-based approach to selecting a physician compensation method that supports the group's overall financial and organizational strategies, including managed care contracting strategies; is consistent with the philosophies, beliefs, and attitudes of the group's membership as they pertain to individual productivity; and can be supported by the organization's information technology, decision support, and management infrastructures. This article explains how research in physician profiling, benchmarking, general compensation theory, and physician productivity provides evidence that can serve as the foundation for a pragmatic approach to evaluating physician compensation method alternatives. It also presents a unique production-based compensation model for illustrative purposes.


Assuntos
Eficiência Organizacional/economia , Prática de Grupo/economia , Planos de Incentivos Médicos/economia , Salários e Benefícios , Benchmarking , Pesquisa sobre Serviços de Saúde , Programas de Assistência Gerenciada , Médicos/classificação , Estados Unidos
19.
Fa Yi Xue Za Zhi ; 15(3): 129-30, 189, 1999 Aug.
Artigo em Zh | MEDLINE | ID: mdl-12536440

RESUMO

The cortex and brainstem changes in death from head injury were observed. There were hemorrhage, edema and neuron necrosis in brain injury group, and also in disputed group of brainstem injury.


Assuntos
Lesões Encefálicas/patologia , Tronco Encefálico/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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