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241.
An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection 总被引:2,自引:0,他引:2
Watnick TJ; Piontek KB; Cordal TM; Weber H; Gandolph MA; Qian F; Lens XM; Neumann HP; Germino GG 《Human molecular genetics》1997,6(9):1473-1481
The gene for the most common and severe form of autosomal dominant
polycystic kidney disease, PKD1, encodes a 14 kb mRNA that is predicted to
result in an integral membrane protein of 4302 amino acids. The major
challenge faced by researchers attempting to complete mutation analysis of
the PKD1 gene has been the presence of several homologous loci also located
on chromosome 16. Because the sequence of PKD1 and its homologs is nearly
identical in the 5' region of the gene, most traditional approaches to
mutation analysis cannot distinguish sequence variants occurring uniquely
in PKD1. Therefore, only a small number of mutations have been identified
to date and these have all been found in the 3', unique portion of the
gene. In order to begin analysis of the duplicated region of PKD1, we have
devised a novel strategy that depends on long-range PCR and a single
gene-specific primer from the unique region of the gene to amplify a
PKD1-specific template that spans exons 23-34. This 10 kb template,
amplified from genomic DNA, can be employed for mutation analysis using a
wide variety of sequence- based approaches. We have used our long-range PCR
strategy to begin screening for sequence variants with heteroduplex
analysis, and several affected individuals were discovered to have clusters
of base pair substitutions in exons 23 and 25. In two patients, these
changes, identified in exon 23, would be predicted to result in multiple
amino acid substitutions in a short stretch of the protein. This clustering
of base pair substitutions is unusual and suggests that mutation may result
from unique structural features of the PKD1 gene.
相似文献
242.
Tumor diameter and volume assessed by magnetic resonance imaging in the prediction of outcome for invasive cervical cancer 总被引:7,自引:0,他引:7
Wagenaar HC Trimbos JB Postema S Anastasopoulou A van der Geest RJ Reiber JH Kenter GG Peters AA Pattynama PM 《Gynecologic oncology》2001,82(3):474-482
OBJECTIVE: The aim of this study was to evaluate the predictive value of pretherapeutic magnetic resonance imaging (MRI)-based measurements of tumor diameter and volume with regard to recurrent disease. METHODS: MRI on 0.5- or 1.5-T scanners was performed in 126 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T(2)-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a combined approach based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and lymph-node involvement) were associated and linked to patient outcome. RESULTS: MRI-based tumor diameter correlated strongly with histological tumor invasion depth and lymph-node status (P < 0.01 and P = 0.01) while tumor volume on MRI was significantly associated only with tumor invasion depth into adjacent tissues (P < 0.01). Univariate analysis demonstrated graphically that MRI-derived tumor diameter and volume and clinical FIGO stage are associated with progression-free survival. Correlation analysis showed a strong association between MRI-derived tumor diameter and volume on MRI (r = 68%, P < 0.01) and also demonstrated a correlation between tumor diameter on MRI and FIGO stage Ib (Ib1 versus Ib2) cervical tumors (r = 46.7%, P < 0.01). CONCLUSION: Tumor diameter and volume, determined by pretreatment MRI examinations, predict progression-free survival for patients with invasive cervical carcinoma. This study demonstrates the value of MRI as an adjunct to clinical evaluation of invasive cervical cancer, providing more complete assessment of morphological risk factors important in patient prognosis and treatment planning. 相似文献
243.
The long learning curve of gynaecological cancer surgery: an argument for centralisation 总被引:1,自引:0,他引:1
Trimbos JB Hellebrekers BW Kenter GG Peters LA Zwinderman KH 《BJOG : an international journal of obstetrics and gynaecology》2000,107(1):19-23
Objective To study the development of surgical performance of an unchanging surgical team over 13 years.
Design Prospective, observational study.
Setting A university hospital, The Netherlands.
Participants Three hundred and eight women who underwent surgical treatment for early cervical cancer.
Interventions Radical hysterectomy and pelvic lymphadenectomy between 1 January 1984 and 31 December 1996.
Results The surgical procedure and indication for treatment remained unchanged during the study period. This applied also to the surgical team. The women's age increased significantly during the study years, as was the case with the number of nodes removed. The depth of infiltration by the tumour increased steadily throughout the study, but this failed to reach statistical significance. The distribution of FIGO stages, percentage of positive lymph nodes, radicality of the surgical margins and post-operative morbidity remained the same. Overall, the five year survival rate was 83%; for women with negative nodes 91%, and for women with positive nodes 53%. Survival tended to improve during the course of the study, but this was not statistically significant. Blood loss during surgery decreased consistently during the whole study period, from a mean of 1515 mL at the beginning of the study to a mean of 1071 mL at the end ( P < 0.0001 ). The operating time also diminished significantly by 8 minutes per year ( P < 0.0001 ). In 1985 the average operating time was 270 minutes, compared with 187 minutes in 1996.
Conclusions These findings indicate that it takes a long time to acquire skill in the surgical treatment of early cervical cancer. Centralisation of relatively infrequent operations for cancer should be encouraged. 相似文献
Design Prospective, observational study.
Setting A university hospital, The Netherlands.
Participants Three hundred and eight women who underwent surgical treatment for early cervical cancer.
Interventions Radical hysterectomy and pelvic lymphadenectomy between 1 January 1984 and 31 December 1996.
Results The surgical procedure and indication for treatment remained unchanged during the study period. This applied also to the surgical team. The women's age increased significantly during the study years, as was the case with the number of nodes removed. The depth of infiltration by the tumour increased steadily throughout the study, but this failed to reach statistical significance. The distribution of FIGO stages, percentage of positive lymph nodes, radicality of the surgical margins and post-operative morbidity remained the same. Overall, the five year survival rate was 83%; for women with negative nodes 91%, and for women with positive nodes 53%. Survival tended to improve during the course of the study, but this was not statistically significant. Blood loss during surgery decreased consistently during the whole study period, from a mean of 1515 mL at the beginning of the study to a mean of 1071 mL at the end ( P < 0.0001 ). The operating time also diminished significantly by 8 minutes per year ( P < 0.0001 ). In 1985 the average operating time was 270 minutes, compared with 187 minutes in 1996.
Conclusions These findings indicate that it takes a long time to acquire skill in the surgical treatment of early cervical cancer. Centralisation of relatively infrequent operations for cancer should be encouraged. 相似文献
244.
Mari?tte I E van Poelgeest Manon van Seters Marc van Beurden Kitty M C Kwappenberg Claudia Heijmans-Antonissen Jan W Drijfhout Cornelis J M Melief Gemma G Kenter Theo J M Helmerhorst Rienk Offringa Sjoerd H van der Burg 《Clinical cancer research》2005,11(14):5273-5280
PURPOSE: Topical application of the immune response modifier imiquimod is an alternative approach for the treatment of human papillomavirus (HPV)-positive vulvar intraepithelial neoplasia (VIN) and aims at the immunologic eradication of HPV-infected cells. We have charted HPV16-specific immunity in 29 patients with high-grade VIN and examined its role in the clinical effect of imiquimod treatment. EXPERIMENTAL DESIGN: The magnitude and cytokine polarization of the HPV16 E2-, E6-, and E7-specific CD4+ T-cell response was charted in 20 of 29 patients by proliferation and cytokine bead array. The relation between HPV16-specific type 1 T-cell immunity and imiquimod treatment was examined in a group of 17 of 29 patients. RESULTS: HPV16-specific proliferative responses were found in 11 of the 20 patients. In eight of these patients, T-cell reactivity was associated with IFNgamma production. Fifteen of the women treated with imiquimod were HPV16+, of whom eight displayed HPV16 E2- and E6-specific T-cell immunity before treatment. Imiquimod neither enhanced nor induced such immunity in any of the subjects. Objective clinical responses (complete remission or >75% regression) were observed in 11 of the 15 patients. Of these 11 responders, eight patients displayed HPV16-specific type 1 CD4+ T-cell immunity, whereas three lacked reactivity. Notably, the four patients without an objective clinical response also lacked HPV16-specific type 1 T-cell immunity. CONCLUSIONS: HPV16-specific IFNgamma-associated CD4+ T-cell immunity, although not essential for imiquimod-induced regression of VIN lesions, may increase the likelihood of a strong clinical response (P = 0.03). 相似文献
245.
LT Rekers-Mombarg JM Wit GG Massa MB Ranke JM Buckler O Butenandt JL Chaussain H Frisch E Leiberman 《Archives of disease in childhood》1996,75(3):175-180
Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references. 相似文献
246.
近红外光谱技术在元胡止痛散定量分析中的初步应用研究 总被引:8,自引:0,他引:8
目的为元胡止痛散建立一种快速有效的定量分析方法,并为将近红外光谱分析技术应用于中药的定量分析提供指导。方法按处方配制25个模拟样本,随机挑选18个组成训练集,另外7个组成预示集,采集各样本的近红外光谱数据,用BP神经网络和PIS法对数据进行处理,并实际分析了三批样品。结果模拟样本中,对于元胡,采用BP网络和PLS法,平均相对预示误差分别为1.5%,2.5%,对于白芷,平均相对预示误差分另为2.9%,4.4%,对于实际样本,各组分标示量的百分含量都在95%~105%之间。结论近红外光谱结合BP神经网络或PLS应用于元胡止痛散的定量分析是可行和有效的。 相似文献
247.
A nerve-sparing radical hysterectomy: Guidelines and feasibility in Western patients 总被引:10,自引:0,他引:10
J. B. Trimbos C. P. Maas M. C. Deruiter† A. A. W. Peters & G. G. Kenter 《International journal of gynecological cancer》2001,11(3):180-186
Abstract. Trimbos JB, Maas CP, DeRuiter MC, Peters AAW, Kenter GG. A nerve-sparing radical hysterectomy: Guidelines and feasibility in Western patients.
Surgical damage to the pelvic autonomic nerves during radical hysterectomy is thought to be responsible for considerable morbidity, i.e., impaired bladder function, defecation problems, and sexual dysfunction. Previous anatomical studies and detailed study of surgical techniques in various Japanese oncology centers demonstrated that the anatomy of the pelvic autonomic nerve plexus permits a systematic surgical approach to preserve these nerves during radical hysterectomy without compromising radicality. We introduced elements of the Japanese nerve-preserving techniques and carried out a feasibility study in ten consecutive Dutch patients. The technique involved three steps: first, the identification and preservation of the hypogastric nerve in a loose tissue sheath underneath the ureter and lateral to the sacro-uterine ligaments; second, the inferior hypogastric plexus in the parametrium is lateralized and avoided during parametrial transsection; third, the most distal part of the inferior hypogastric plexus is preserved during the dissection of the posterior part of the vesico-uterine ligament. The clinical study showed that the procedure is feasible and safe, except possibly when used with very obese patients and patients with broad, bulky tumors. Surgical preservation of the pelvic autonomic nerves in radical hysterectomy deserves consideration in the quest to improve both cure and quality of life in cervical cancer patients. 相似文献
Surgical damage to the pelvic autonomic nerves during radical hysterectomy is thought to be responsible for considerable morbidity, i.e., impaired bladder function, defecation problems, and sexual dysfunction. Previous anatomical studies and detailed study of surgical techniques in various Japanese oncology centers demonstrated that the anatomy of the pelvic autonomic nerve plexus permits a systematic surgical approach to preserve these nerves during radical hysterectomy without compromising radicality. We introduced elements of the Japanese nerve-preserving techniques and carried out a feasibility study in ten consecutive Dutch patients. The technique involved three steps: first, the identification and preservation of the hypogastric nerve in a loose tissue sheath underneath the ureter and lateral to the sacro-uterine ligaments; second, the inferior hypogastric plexus in the parametrium is lateralized and avoided during parametrial transsection; third, the most distal part of the inferior hypogastric plexus is preserved during the dissection of the posterior part of the vesico-uterine ligament. The clinical study showed that the procedure is feasible and safe, except possibly when used with very obese patients and patients with broad, bulky tumors. Surgical preservation of the pelvic autonomic nerves in radical hysterectomy deserves consideration in the quest to improve both cure and quality of life in cervical cancer patients. 相似文献
248.
肝硬化门静脉高压症患者内脏血流动力学紊乱的研究 总被引:4,自引:0,他引:4
门静脉高压症是一种由多种病因引起门静脉系统血液动力学紊乱的临床综合征。本研究,应用多普勒超声检测,正常人和肝硬化门静脉高压症患者门静脉系统血流量,以了解肝硬化门静脉高压症中门静脉血流动力学的变化。临床资料1996年3月至1997年4月用多普勒超声(DUS)检测20例健康成人和34例门脉高压患者门静脉系统血流动力学参数。20例健康成人(男16例,女4例,平均年龄为49.95±15.49岁)为我院行健康体检者。34例门脉高压患者中,男31例,女3例,平均年龄为50.00±12.78岁,病因为肝炎后肝… 相似文献
249.
Hannah S. van Meurs Ewoud Schuit Hugo M. Horlings Jacobus van der Velden Willemien J. van Driel Ben Willem J. Mol Gemma G. Kenter Marrije R. Buist 《Gynecologic oncology》2014
Objective
Models to predict the probability of recurrence free survival exist for various types of malignancies, but a model for recurrence free survival in individuals with an adult granulosa cell tumor (GCT) of the ovary is lacking. We aimed to develop and internally validate such a prognostic model.Methods
We performed a multicenter retrospective cohort study of patients with a GCT. Demographic, clinical and pathological information were considered as potential predictors. Univariable and multivariable analyses were performed using a Cox proportional hazards model. Using backward stepwise selection we identified the combination of predictors that best predicted recurrence free survival. Discrimination (c-statistic) and calibration were used to assess model performance. The model was internally validated using bootstrapping techniques to correct for overfitting. To increase clinical applicability of the model we developed a nomogram to allow individual prediction of recurrence free survival.Results
We identified 127 patients with a GCT (median follow-up time was 131 months (IQR 70-215)). Recurrence of GCT occurred in 81 out of 127 patients (64%). The following four variables jointly best predicted recurrence free survival; clinical stage, Body Mass Index (BMI), tumor diameter and mitotic index. The model had a c-statistic of 0.73 (95% CI 0.66–0.80) and showed accurate calibration.Conclusions
Recurrence free survival in patients with an adult GCT of the ovary can be accurately predicted by a combination of BMI, clinical stage, tumor diameter and mitotic index. The introduced nomogram could facilitate in counseling patients and may help to guide patients and caregivers in joint decisions on post-treatment surveillance. 相似文献250.
Immunotherapeutic strategies for cervical squamous carcinoma 总被引:2,自引:0,他引:2
van Driel WJ Kenter GG Fleuren GJ Melief CJ Trimbos BJ 《Hematology / Oncology Clinics of North America》1999,13(1):259-273
Progress in developing preventive and therapeutic vaccines for HPV-associated diseases has been made in the last few years, but continued studies are needed to evaluate the clinical feasibility of different vaccination approaches and to determine a clinically effective and safe one. The perfect HPV vaccine will have both preventive and therapeutic capabilities, and because it is likely to be used world-wide, especially in developing countries, it must also have low production costs. 相似文献