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991.
Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia 总被引:4,自引:0,他引:4
Georgitsi M Raitila A Karhu A van der Luijt RB Aalfs CM Sane T Vierimaa O Mäkinen MJ Tuppurainen K Paschke R Gimm O Koch CA Gündogdu S Lucassen A Tischkowitz M Izatt L Aylwin S Bano G Hodgson S De Menis E Launonen V Vahteristo P Aaltonen LA 《The Journal of clinical endocrinology and metabolism》2007,92(8):3321-3325
CONTEXT: Germline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two acromegalic patients. OBJECTIVE: Our objective was to evaluate the role of CDKN1B/p27(Kip1) in human tumor predisposition in patients clinically suspected of MEN1 but testing negative for MEN1 germline mutation as well as in familial and sporadic acromegaly/pituitary adenoma patients. DESIGN: Genomic DNA was analyzed for germline mutations in the CDKN1B/p27(Kip1) gene by PCR amplification and direct sequencing. SETTING: The study was conducted at nonprofit academic research and medical centers. PATIENTS: Thirty-six Dutch and one German suspected MEN1 patient, who previously tested negative for germline MEN1 gene mutations, were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary adenoma patients from Europe and the United States were included in the study. MAIN OUTCOME MEASURES: We analyzed germline CDKN1B/p27(Kip1) mutations in individuals with pituitary adenoma and MEN1-like features. RESULTS: A heterozygous 19-bp duplication (c.59_77dup19) leading to a truncated protein product was identified in one Dutch patient with suspected MEN1 phenotype, pituitary adenoma, carcinoid tumor, and hyperparathyroidism (one of 36, 2.8%). No mutations were detected in either familial or sporadic acromegaly/pituitary adenoma patients. CONCLUSIONS: Our results support the previous finding that germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition. However, such mutations appear uncommon in suspected MEN1 cases and rare or nonexistent in familial or sporadic acromegaly/pituitary adenoma patients. 相似文献
992.
Wedenoja S Ormälä T Berg UB Halling SF Jalanko H Karikoski R Kere J Holmberg C Höglund P 《Kidney international》2008,74(8):1085-1093
Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in childhood, the long-term renal outcome remains unclear. Here we describe two cases of congenital chloride diarrhea-associated end-stage renal disease with transplantation. Further, we show that there is a high incidence of mild chronic kidney disease in 35 other patients with congenital chloride diarrhea. The main feature of the renal injury was nephrocalcinosis, without hypercalciuria or nephrolithiasis with small sized kidneys and commensurately reduced glomerular filtration rates. This suggests that diarrhea-related sodium chloride and volume depletion, the first signs of non-optimal salt substitution, promote urine supersaturation and crystal precipitation. The poor compliance with salt substitution along with long-lasting hypochloremic and hypokalemic metabolic alkalosis is likely to induce progressive calcification and renal failure. Both our patients developed nephrocalcinosis in the transplanted kidneys suggesting that this complication is a consequence of intestinal SLC26A3 deficiency. Interestingly, the transporter is expressed in the distal nephron but the recurrence of nephrocalcinosis in the transplanted kidney suggests that it does not play a significant renal role in this syndrome. 相似文献
993.
Koskivuo I Talve L Vihinen P Mäki M Vahlberg T Suominen E 《Annals of surgical oncology》2007,14(12):3566-3574
Abstarct
Background Sentinel lymph node biopsy (SLNB) is the most precise method for staging invasive cutaneous melanoma, but its therapeutic
effect has been difficult to assess, and SLNB is not routinely used in all melanoma treatment centers.
Methods This case-control study of 305 prospective SLNB patients compared them with 616 retrospective patients who had not undergone
invasive nodal staging at diagnosis. Thin melanomas were included in both study groups.
Results A total of 50 SLNB patients were sentinel positive (16.4%) and 255 were sentinel negative (83.6%). A total of 49 of the 50
sentinel-positive patients underwent completion lymph node dissection, and 9 of them (18%) had additional metastases in the
nonsentinel nodes. The false-negative rate was 1.6% (five same-basin nodal recurrences during follow-up). There was a significant
difference in melanoma-related overall survival (OS) between sentinel-positive and sentinel-negative patients (P < .001). The tumor burden of the sentinel nodes was a significant prognostic factor for melanoma-related OS (P < .001). There was no significant difference in melanoma-related OS or disease-free survival between the study groups, but
the nodal disease-free survival was significantly longer among the SLNB patients (P = .004).
Conclusions SLNB is recommended for routine use in the treatment of cutaneous melanoma because the sentinel node status carries unique
prognostic information on the survival of melanoma patient. Improved regional disease control is an obvious therapeutic advantage
of SLNB and immediate completion lymph node dissection. 相似文献
994.
Bergamaschi R Quaglini S Trojano M Amato MP Tavazzi E Paolicelli D Zipoli V Romani A Fuiani A Portaccio E Berzuini C Montomoli C Bastianello S Cosi V 《Journal of neurology, neurosurgery, and psychiatry》2007,78(7):757-759
Aim
To propose a simple tool for early prediction of unfavourable long term evolution of multiple sclerosis (MS).Methods
A Bayesian model allowed us to calculate, within the first year of disease and for each patient, the Bayesian Risk Estimate for MS (BREMS) score that represents the risk of reaching secondary progression (SP).Results
The median BREMS scores were higher in 158 patients who reached SP within 10 years compared with 1087 progression free patients (0.69 vs 0.30; p<0.0001). The BREMS value was related to SP risk in the whole cohort (p<0.0001) and in the subgroup of 535 patients who had never been treated with immune therapies, thus reasonably representing the natural history of the disease (p<0.000001).Conclusions
The BREMS score may be useful both to identify patients who are candidates for early or for more aggressive therapies and to improve the design and analysis of clinical therapeutic trials and of observational studies.The widespread and early use of disease modifying drugs in multiple sclerosis (MS), such as β‐interferons and glatiramer acetate, is becoming more and more popular,1 even though patients with a favourable disease evolution could avoid these lifelong medications.2 It is therefore crucial to have reliable clinical predictors of the evolution of the disease to distinguish between patients requiring early/aggressive therapies from those who do not, and to improve the design and analysis of clinical therapeutic trials and of observational studies.Several studies have identified clinical factors related to poor MS outcome.3,4,5,6,7,8,9 However, these studies analysed the relationships between manifestations at onset and time of occurrence of specified end points, without considering information collected up to the end points. To make more accurate use of follow‐up information and to better assess the prognostic value of the early events, we performed a preliminary study by building a Bayesian model of the natural history of the disease.10 The model allowed us to calculate an individual risk score for each patient.In the present study we tested the trustworthiness of the Bayesian risk score on the basis of a new and larger sample of patients. 相似文献995.
Quantifying the clinical impact of multiple sclerosis (MS) is a critical issue for judging experimental therapies tested in clinical trials, and, in everyday practice, for optimizing individual patient care. Proposed clinical outcome measures for MS belong to four main categories. In the first, information is based on the objective neurological examination. Examples in this category include the Expanded Disability Status Scale and related instruments, the Scripps Neurological Rating Scale and the MS Impairment Scale. The second category is represented by quantitative tests of neurological function: the most important example is represented by the Multiple Sclerosis Functional Composite. In the third category, information is provided by the patient or a family member. Measures of disability and handicap (as the Incapacity Status Scale, and the Environmental Status Scale), and generic or disease-specific quality of life instruments are included in this class. Finally, the last category consists of measures which present hybrid characteristics, such as the Ambulation Index and the Cambridge Multiple Sclerosis Basic Score. To date, no single measure has emerged as the ideal outcome measure: the main advantages and disadvantages of currently available measurement tools are discussed. 相似文献
996.
Antwerpen MH Zimmermann P Bewley K Frangoulidis D Meyer H 《Molecular and cellular probes》2008,22(5-6):313-315
Specific identification of Bacillus anthracis and differentiation from closely related Bacillus cereus and Bacillus thuringiensis strains is still a major diagnostic problem. Commercially available diagnostic kits targeting plasmid-markers cannot differentiate between B. anthracis, non-anthracis Bacillus species harbouring anthrax-specific virulence plasmids, and plasmidless B. anthracis strains. A TaqMan PCR assay was designed targeting sequences of gene locus BA_5345 of the B. anthracis strain Ames. Specificity was determined by using a panel of 328 Bacillus strains; sensitivity was determined by probit analysis. All B. anthracis isolates (n=92) were specifically detected by using the genomic TaqMan PCR assay whereas 236 strains belonging to 19 Bacillus species other than B. anthracis were PCR negative. The detection limit was determined to be 12.7 copies per reaction (95% confidence interval 10.2-17.5 copies). Here we present an extensively evaluated and - to our current knowledge - specific TaqMan PCR assay for the detection of B. anthracis based on a chromosomal marker. 相似文献
997.
Carbone A Botti G Gloghini A Simone G Truini M Curcio MP Gasparini P Mangia A Perin T Salvi S Testi A Verderio P 《The Journal of molecular diagnostics : JMD》2008,10(6):527-536
An automated enzyme metallographic silver in situ hybridization method (SISH) has been reported to successfully determine human epidermal growth factor receptor 2 (HER2) gene amplification. We evaluated the staining and interpretative reproducibility of the HER2 SISH assay at five laboratories and compared SISH results with other in situ hybridization (ISH) methods. The HER2 gene status of 89 breast carcinomas was analyzed in parallel using manual dual-color fluorescence ISH, manual chromogenic ISH, and bright-field automated SISH. A total of 1098 SISH-stained slides were evaluated. For comparison, all specimens were stained by 4B5 immunohistochemistry for HER2 protein expression. Interpretation was performed by pathologists at five different laboratories using the algorithms provided by the manufacturers and the guidelines of American Society of Clinical Oncology/College of American Pathologists. Staining and interpretative reproducibility were measured through the computation of weighted kappa statistics. Following the optimization of SISH staining, 1077/1098 (98%) of slides were evaluable. Excellent reproducibility and efficacy of HER2 SISH staining, and interobserver interpretation (Kw = 0.91), were observed among five sites. For the 89 invasive breast cancer cases, the overall rate of concordance between consensus 4B5 and consensus SISH, fluorescence ISH, and chromogenic ISH was 96.6% (86/89), 97.8% (87/89), and 96.6% (86/89), respectively. Overall concordance between positive and negative SISH and fluorescence ISH results, as well as between individual and consensus positive and negative SISH results, was excellent (P < 0.001). 相似文献
998.
Hermann Neugebauer Pia Hartmann Sebastian Krenn Thomas Glück Jürgen Schölmerich Rainer Straub Reiner Wiest 《Liver international》2008,28(8):1149-1157
Aim: Bacterial translocation (BT) to mesenteric lymph nodes (MLN) in cirrhosis has been linked to impaired host defence. Phagocytosis by polymorphonuclear leucocytes (PMNLs) is the primary event in the killing of bacteria but has not been investigated in relation to the presence of BT. Methods: Mesenteric lymph nodes were harvested sterile and assessed for BT by culture techniques. Study groups included ascitic cirrhotic rats (LC), healthy controls (Con) as well as portal‐vein‐ligated (PVL) rats 2 days (acute PVL with and without norfloxacin) or 3 weeks after surgery (chronic PVL). PMNLs were isolated from systemic blood and the capacity to phagocytose opsonized Escherichia coli was evaluated by FACS analysis. Results: No BT was observed in Con and chronic PVL animals but 11/20 LC (55%) and six out of six acute PVL (100%) presented with BT. In the presence of BT, PMNL from PVL as well as LC rats showed significantly increased phagocytic activity as compared with controls. In contrast, PMNL from animals without BT, whether PVL or LC, exhibited phagocytic activity similar to those from control rats. The number of PMNLs involved in the phagocytic process was significantly increased only in portal‐hypertensive rats with but not without BT as compared with controls. Norfloxacin did prevent BT in acute PVL animals, thereby correcting the increase in phagocytic capacity in PMNL. Conclusions: Cirrhosis per se is not associated with alterations of the phagocytic capacity of PMNL. The occurrence of BT, however, increases the phagocytic capacity of PMNL, being observed likewise in prehepatic portal hypertension, indicating an in vivo‘priming’ of PMNL by BT independent of cirrhosis. 相似文献
999.
1000.
Pia H. Jensen Ole S. Jacobsen Trine Henriksen Bjarne W. Strobel Hans Christian B. Hansen 《Bulletin of environmental contamination and toxicology》2009,82(6):668-672
The potato glycoalkaloids α-chaconine and α-solanine are produced in high amounts in potato plants from where release to soil
takes place. Degradation of the compounds in groundwater was investigated, as their fate in the terrestrial environment is
unknown. Abiotic and microbial degradation were followed in groundwater sampled from below a potato field and spiked with
the glycoalkaloids (115 nmol/l). Degradation was primarily microbial and the glycoalkaloids were degraded within 21–42 days.
The metabolites β1-solanine, γ-solanine, and solanidine were formed from α-solanine, while β-chaconine, γ-chaconine and solanidine were detected
from α-chaconine. Thus, indigenous groundwater microorganisms are capable of degrading the glycoalkaloids. 相似文献