Does enamelin have pleiotropic effects on organs other than the teeth? Lessons from a phenotyping screen of two enamelin‐mutant mouse lines

We analyzed two mutant mouse lines, ATE1 and ATE2, that carry point mutations in the enamelin gene which result in premature stop codons in exon 8 and exon 7, respectively. Both mutant lines show amelogenesis imperfecta. To establish the effect of mutations within the enamelin gene on different organs, we performed a systematic, standardized phenotypic analysis of both mutant lines in the German Mouse Clinic. In addition to the initially characterized tooth phenotype that is present in both mutant lines, we detected effects of enamelin mutations on bone and energy metabolism, as well as on clinical chemical and hematological parameters. These data raise the hypothesis that enamelin defects have pleiotropic effects on organs other than the teeth.     

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

The analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non-allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease.     

A new method for selective measurement of joint movement in hand tremor in Parkinson's disease patients

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system with tremor being one of its four main clinical features. Currently used methods can directly evaluate tremor amplitude and frequency but not joint movement in the affected limb. Measurement of joint movement facilitates the location of muscle groups that participate in PD tremor and this is important for treatment with local botulinum toxin injections. We developed and tested a method that measured tremor amplitude and frequency in a specific joint of the hand in PD patients. The tremor analysis method was based on force transducers adapted to record rest tremor of the wrist and metacarpophalangeal joints in two degrees of freedom for each joint. Direct measurements of joint movement in the hand can evaluate tremor amplitude and frequency and also locate the muscle groups that are most active in tremor movement, thus enabling their local treatment.     

The effect of rat anterior cingulate inactivation on cognitive flexibility

The present experiment investigated the effects of muscimol injections into the rat dorsal anterior cingulate on the acquisition and reversal learning of a 4-choice odor discrimination. Long-Evans rats were trained to dig in cups that contained distinct odors. In the odor discrimination, one odor cup contained a cereal reinforcement in acquisition whereas a different odor cup contained a cereal reinforcement in reversal learning. The other 2 odor cups were never associated with reinforcement. Bilateral infusions of the gamma aminobutyric acid-A agonist muscimol did not impair acquisition of the odor discrimination but impaired reversal learning in a dose-dependent manner. During reversal learning, dorsal anterior cingulate inactivation did not lead to perseveration but selectively increased errors to the odor cups that were never reinforced. These findings suggest that the dorsal anterior cingulate supports learning when conditions require a shift in choice patterns and may enhance cognitive flexibility by decreasing interference of irrelevant stimuli.     

3D heart model for computer simulations in cardiac surgery

For a satisfactory computer simulation, a model, which imitates a natural situation, is needed. The Human heart is an irregular 3D object and thus difficult to reproduce. Basic data was taken from Visible Human Dataset (VHD), National Library of Medicine. The heart area was cut out of the original cross-sections and different tissues segmented. All the slices also had to be aligned to assure precise overlapping of the structures. A 3D computer heart model with the resolution of 1mm was designed. The heart model was dedicated to simulations of heat transfer during heart surgery however, it is applicable also to other medical simulations.     

A comparison of the sensitivity of diagnostic criteria for polymyalgia rheumatica

OBJECTIVE: To compare the performance of the several different diagnostic criteria sets currently in use for polymyalgia rheumatica (PMR). METHODS: 213 patients attending eight rheumatological centres in eight different European countries were studied. All had recently been referred and were considered by the senior investigator at each centre, selected because of their experience in treatment of PMR, to have this condition. By use of a standard international proforma, the requisite diagnostic points in each criteria set were sought. Sensitivity for each criterion from each set was then calculated, as well as the sensitivity of each criteria set as a whole. RESULTS: Of four criteria sets compared, the Bird (1979) criteria performed best with a sensitivity of 99.5%, and the Hunder (1982) criteria second best, with sensitivity of 93.3%. These both performed significantly better than the two other criteria sets, though each of these was admittedly developed for rather specialised reasons. CONCLUSIONS: Although this study compares homogeneity, we suggest the Bird 1979 or Hunder 1982 criteria should be used whenever possible. Studies that have used alternative criteria may have less sensitivity in diagnosis.