Organization, expression and polymorphism of the human persyn gene

Persyn is a recently identified member of the synuclein family with a distinct pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression were also found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumour progression. Here we have used an antibody specific to human persyn to demonstrate that the level of this protein is increased in ageing cerebral cortex and in breast tumours. We cloned, characterized and sequenced the human persyn genomic locus and localized it to the long arm of chromosome 10 in the q23.2-q23.3 region. Sequence information was used to search for specific mutations in the protein coding regions of persyn mRNA and the persyn gene in breast tumours and tumour cell lines. No tumour-specific mutations were found, but two linked polymorphisms in the coding region were detected, both in mRNA and exons III and IV of the gene. These results suggest that development of breast tumours correlates with overexpression of the wild-type persyn protein. Detailed characterization of the human persyn locus is important for further studies of the involvement of persyn in neurodegeneration and malignancy.      

Simulated pulmonary nodules: detection with dual-energy digital versus conventional radiography

Performance of a prototype dual-energy digital chest radiography unit in detecting calcified and noncalcified simulated pulmonary nodules was compared with that of a highly optimized, conventional system. Nodules ranging in size (0.5, 1.0, and 1.6 cm), in number (five to 11), and in calcium content (0-25 mg) were superimposed over the lungs of a frozen, unembalmed, human chest phantom. For each technique, six observers examined 50 posteroanterior projections with different randomized nodule locations. Detection consisted of locating and assigning a level of confidence to each perceived nodular opacity. The resulting plots of the true-positive fraction versus the mean number of false-positive calls per projection indicate that for both calcified and noncalcified nodules, the digital unit performed significantly better (P less than .01).     

The effect of cartilage and bone density of mushroom-shaped,photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species

Background  

Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation.     

Hyperpigmentation mimicking Laugier syndrome, levodopa therapy and Addison''s disease

The Laugier-Hunziker syndrome is an acquired, idiopathic, benign mucocutaneous hypermelanosis that usually occurs on the lips and oral mucosa, although it may appear at other sites. Nails are frequently involved, mainly forming longitudinal hyperpigmented bands. We report the case of a patient that presented a typical picture of this entity, nearly 1 year after the beginning of treatment with levodopa. Two years after the first lesions occurred, she developed Addison's disease. The patient suffered from a diffuse discrete hyperpigmentation (it was more remarkable on exposed areas) and an intensification of the melanotic macules that were previously noticeable before in oral and genital mucosa, fingers, toes and nails. Hormonal replacement treatment enabled the control of laboratory and general manifestations and to decrease the degree of mucocutaneous hyperpigmentation considerably, despite initial hyperpigmented lesions persisting in described areas.     

Acute spinal cord injury: MR imaging at 1.5 T

Thirty-seven magnetic resonance (MR) imaging studies were performed with a 1.5-T magnet and surface coils in 27 patients with suspected spinal cord injuries. Imaging was performed 1 day to 6 weeks after injury. Cord abnormalities were seen with MR in 19 patients, while skeletal and/or ligamentous injuries were seen in 21 (78%). Three types of MR signal patterns were seen in association with cord injuries. Acute intraspinal hemorrhage was seen in five patients with cord injuries and demonstrated decreased signal intensity on T2-weighted images obtained within 24 hours of injury. Cord edema and contusion had high signal intensity on T2-weighted images and were observed in 12 cases with cord injury. Neurologic recovery, determined in 16 patients, was insignificant in patients with intraspinal hemorrhage; however, patients with cord edema or contusion recovered significant neurologic function. MR at 1.5 T is extremely useful in the diagnosis of acute cord injury and also demonstrates potential in predicting neurologic recovery.     

Invasive pulmonary aspergillosis caused by Aspergillus versicolor in a patient on mechanical ventilation

Aspergillus spp. often colonise the respiratory tract of critically ill patients in intensive care units and subsequently cause invasive disease. The risk of developing invasive disease is more in immunocompromised patients. Here we report a case of fatal invasive pulmonary aspergillosis caused by Aspergillus versicolor in a post-operative patient on mechanical ventilation, who did not respond to intravenous itraconazole. We then discuss the challenges involved in the accurate diagnosis of this condition and appropriate management.     

Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia

Folylpolyglutamate synthetase (FPGS) is responsible for the metabolism of natural folates and a broad range of folate antagonists to polyglutamate derivatives. Recent studies indicated increased accumulation of methotrexate (MTX) polyglutamates (MTX-PG) in blast cells as a predictor of favorable treatment outcome in childhood acute lymphoblastic leukemia (ALL). We determined the expression of FPGS activity in blasts from children with ALL at diagnosis and after treatment with MTX as a single agent, before conventional remission induction therapy. The levels of enzyme activity in ALL blasts at diagnosis (median of 689 pmol/h/mg protein) were significantly higher (P = .003) than those found in acute nonlymphoblastic leukemia (ANLL) blasts (median of 181 pmol/h/mg protein). Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, FPGS activity increased in ALL blasts after in vivo exposure to MTX. The median increase in FPGS activity was significantly higher (P = .003) in B-lineage ALL (188%) than in T-lineage ALL (37%). Likewise, the percentage of intracellular long chain MTX-PG (Glu3-6) was significantly higher (P = .02) in B- lineage ALL (92%) than in T-lineage ALL (65%), consistent with higher FPGS activity in B-lineage blasts. This finding could explain, at least in part, the superior outcome in children with B-lineage ALL treated with antimetabolite therapy.