Analysis of CDKN1A polymorphisms: markers of cancer susceptibility?

The CDKN1A (TP21) gene encodes a 21-kD protein that is a critical downstream mediator of wild-type TP53 and an important regulator of the cell cycle. Failure in the function of this gene would be expected to result in abnormal cell proliferation and transformation. Tumor-associated mutations of the coding region of the TP21 are rare. On the other hand, some TP21 polymorphisms have been identified and characterized by single base substitutions. In the present study, we investigated the potential role of TP21 gene polymorphisms in skin, head, and neck tumorigenesis. A total of 261 samples were examined by polymerase chain reaction single-strand conformational analysis, and one mutation at codon 31 and four polymorphisms in exons 2 (codon 55) and 3 [nucleotide (nt)590] and in promoter region (nt2298) were identified. In conclusion, this investigation confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers. Also, our results show significant differences in nt2298 allele frequencies between normal individuals and skin malignant tumors (P < 0.05). The results suggest that this polymorphism affects TP21 transactivator binding and may be important during the pathogenesis of skin cancer.     

Erratum: Neurofibromatosis type 1 (NF1): Identification of eight unreported mutations in NF1 gene in Italian patients

In the original version of this article, the title was incorrect. Please find the correct title given here. The publisher deeply regrets this error. The original article to which this Erratum refers was published in Human Mutation 22:179–180 Human Mutation(2003) 22(2) 179–180     

Kinematic and dynamic analysis of running under conditions of variable gravity

A new training system was designed and realised by the engineer G. Scuderi: a centrifugal track for runners. The principal advantage of this track is to increase the forces on athlete during the run with an effect very similar to that of an "artificial gravity", so the athlete can develop more muscle power. A multibody numerical model of a runner was developed to analyse the behaviour of the athlete on the centrifugal track. The multibody model was calibrated by experimental analysis; in fact, the joint angles were measured by a digital image processing system and introduced as input in the numerical simulation. The numerical results obtained are the values of many kinematic and dynamic variables, in particular the ground reaction force and the moments in the hip, knee, and ankle joints. A comparison between the normal running and that on the centrifugal track was carried out, demonstrating the validity of training on the latter. The results of the numerical simulation confirm that the power developed during running on the track, and the corresponding work performed by the joints, is considerably greater than that found during normal running.     

Effect of the Addition of Vancomycin on the Performance of an Automated Nonradioactive System for Detection of Mycobacteria

 A recently developed automated, nonradioactive system for the detection of mycobacteria (MB/BacT; Organon Teknika, Belgium) has provided good results, but the contamination rate was found to be higher than that obtained with the radiometric Bactec 460 system (Becton Dickinson, USA). In the present study, the effects of adding vancomycin (1 μg/ml) to the antibiotic mixture of the nonradioactive system were evaluated, and the performance of the system with versus without vancomycin was compared. Three hundred sputum samples were tested, using the radiometric system as the reference method. Mycobacteria were isolated from 47 (15.7%) samples. The nonradioactive system with and without vancomycin detected 42 and 43 strains, respectively; the time to detection was 1 day shorter with the medium without vancomycin (15.7 days vs. 14.3 days). The radiometric system detected 42 strains of mycobacteria in a mean detection time of 13.6 days. Contamination rates with the nonradioactive system were 6.7% in the medium without vancomycin and 2.7% in the medium with vancomycin. The latter figure was approximately the same as the contamination rate found with the radiometric system (2.3%). Our data suggest that the addition of vancomycin considerably reduces the number of contaminants in the MB/BacT medium without affecting the performance of the system.     

Changes in bone turnover during tibolone treatment

OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period.