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At least 19 recordsLinked to original sources

Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I.

Mutations in NF1 cause neurofibromatosis type I (NF1), a disorder characterized, among other clinical manifestations, by generalized and focal bony lesions. Dystrophic scoliosis and tibial pseudoarthrosis are the most severe skeletal manifestations for which treatment is not satisfactory, emphasizing the dearth of knowledge related to the biology of NF1 in bone cells. Using reporter mice, we report here that the mouse Col2α1-Cre promoter (collagen, type II, alpha 1) is active not only in chondrocytes but also in adult bone marrow osteoprogenitors giving rise to osteoblasts. Based on this finding, we crossed the Col2α1-Cre transgenic and Nf1(flox/flox) mice to determine whether loss of Nf1 in axial and appendicular osteochondroprogenitors recapitulates the skeletal abnormalities of NF1 patients. By microtomographic and X-rays studies, we show that Nf1(Col2)(-/-) mice display progressive scoliosis and kyphosis, tibial bowing and abnormalities in skull and anterior chest wall formation. These defects were accompanied by a low bone mass phenotype, high bone cortical porosity, osteoidosis, increased osteoclastogenesis and decreased osteoblast number, as quantified by histomorphometry and 3D-microtomography. Loss of Nf1 in osteochondroprogenitors also caused severe short stature and intervertebral disc defects. Blockade of the RAS/ERK activation characteristic of Nf1(-/-) osteoprogenitors by lovastatin during embryonic development could attenuate the increased cortical porosity observed in mutant pups. These data and the skeletal similarities between this mouse model and NF1 patients thus suggest that activation of the RAS/ERK pathway by Nf1 loss-of-function in osteochondroprogenitors is responsible for the vertebral and tibia lesions in NF1 patients, and that this molecular signature may represent a good therapeutic target.

Animals↗

Contribution of computed tomography to the treatment of lymphomas.

The effectiveness of computed body tomography (CT) in the workup, treatment planning, and follow-up of 38 patients with Hodgkin's disease and 59 with non-Hodgkin's lymphoma was analyzed. CT scanning can frequently define lymphoma in the retroperitoneum, and occasionally in mesenteric lymph nodes, spleen, and liver. These data are useful for staging, for radiotherapy treatment planning, and in monitoring response to radiotherapy or chemotherapy. CT was found to be particularly useful in patients with large mediastinal masses. Analysis of patterns of intrathoracic spread allowed modification of treatment techniques in 60% of patients with spread along the chest wall, in order to reduce the volume of normal tissue irradiated, while obtaining adequate dose distributions within the tumor volume. It is anticipated that chest CT scanning in lymphoma patients will lead to improved tumor control and reduction of radiation complications.

Adult↗

Fatty tumors of the thorax demonstrated by CT.

The radiographic signs previously described for fatty tumors of the thorax although helpful are nonspecific. In the past, the diagnosis of benign fatty tumors of the chest in asymptomatic patients required surgical intervention. This report illustrates the gamut of fat-containing tumors of the thorax encountered over a recent 1 year period. CT proved to be helpful in the diagnosis and management on these cases. When the CT numbers of the fatty lesion was around -55 EMI units, intervention was felt to be unnecessary. However, when the CT number of the mass ranged from --10 to--20 EMI units, intervention was felt to be necessary since a malignancy could not be excluded on the basis of the CT findings alone.

Adult↗

Observations on the medical efficacy of computed tomography of the chest and abdomen.

In a retrospective study of 687 computed tomographic (CT) examinations of the chest and abdomen performed over a 1 year period, 16% of the examinations produced information not otherwise available which altered patient diagnosis, prognosis, or therapy. Sixteen thoracotomies and 18 laparotomies were avoided as a result of information available only from CT examinations. CT was of particular value in the evaluation of mediastinal masses, in the assessment of suspected or proven lung cancer, and in the evaluation of pleural and extrapleural masses. It was of notable clinical value in evaluating patients with intraabdominal abscesses, pancreatic disease, staging of malignancies for radiation therapy and surgery, and excluding the presence of suspected masses.

Abdomen↗