Association of red cell spherocytosis with deletion of the short arm of chromosome 8

Congenital spherocytic anemia is a common disorder, but in most cases the nature of the underlying membrane lesion is unknown and the genetic defect has not yet been unequivocally mapped to a chromosome. We studied two dysmorphic siblings with neurologic findings and hemolytic anemia. Clinical and laboratory findings in these two siblings were consistent with the diagnosis of congenital spherocytosis whereas both parents and two unaffected siblings were normal. The two affected children had an abnormal chromosomal complement as a result of a deletion of the short arm of chromosome 8 [(46,XX,del(8)(p11.1p21.1)]. These results suggest that a gene whose deletion results in a congenital spherocytic anemia phenotype resides on this region on the short arm of chromosome 8.     

Interaction of Grb2 via its Src homology 3 domains with synaptic proteins including synapsin I.

Grb2 is a 25-kDa adaptor protein composed of a Src homology 2 (SH2) domain and two flanking Src homology 3 (SH3) domains. One function of Grb2 is to couple tyrosine-phosphorylated proteins (through its SH2 domain) to downstream effectors (through its SH3 domains). Using an overlay assay, we have identified four major Grb2-binding proteins in synaptic fractions. These proteins interact with wild-type Grb2 but not with Grb2 containing point mutations in each of its two SH3 domains corresponding to the loss of function mutants in the Caenorhabditis elegans Grb2 homologue sem-5. Two of the proteins, mSos and dynamin, were previously shown to bind Grb2. The third protein of 145 kDa is brain specific and to our knowledge has not been previously described. The fourth protein is synapsin I. Dynamin is required for synaptic vesicle endocytosis and synapsin I is thought to mediate the interaction of synaptic vesicles with the presynaptic cytomatrix. These data suggest that Grb2, or other proteins containing SH3 domains, may play a role in the regulation of the exo/endocytotic cycle of synaptic vesicles and therefore of neurotransmitter release.     

Quantitative analysis of breast parenchymal density: correlation with women's age

RATIONALE AND OBJECTIVES: The authors evaluated the relationship between a woman's breast parenchymal density and her age by means of a quantitative method for measuring density from digitized mammograms. MATERIALS AND METHODS: The percentage of the breast considered to be dense was evaluated from mammograms of 50 women stratified by age. Quantitative analysis based on the computer segmentation of tissue in digitized mammograms was performed by three expert mammographers. The results of this analysis were compared with results from a review of the film mammograms by three expert mammographers. RESULTS: A slight decrease in the percentage of breast considered to be dense with increased age was observed. The average difference in the percentage of dense breast tissue between the youngest and the oldest age groups was 6.4% based on the digital review and 14.6% based on the film review. Within each age group, the total variability was on the order of 75%. CONCLUSION: The difference in mean magnitude between the youngest and oldest age groups was small and may not be clinically important. The variability within an age group was large, which suggests that age is not a reliable indicator of percentage of dense breast tissue.     

The treatment of localized non-Hodgkin's lymphoma in children: a report from the Children's Cancer Study Group

Investigators of the Children's Cancer Study Group entered 73 children with previously untreated localized non-Hodgkin's lymphoma on a prospective randomized trial of systemic treatment with either a four-drug program (cyclophosphamide, vincristine, methotrexate, prednisone [COMP]) or a 10-drug (LSA2-L2 modified) program of 18 months duration. All patients received central nervous system prophylaxis with intrathecal methotrexate and most received local or regional radiation treatment. The three-year relapse-free survival rate for all patients (N = 73) was 84%; for COMP (N = 42) was 85%, and for LSA2-L2 (N = 31) was 84%. Of the 12 patients who suffered adverse events eight relapsed and four died of toxicity. Histopathology was reviewed centrally. Of 32 patients with nonlymphoblastic disease treated with COMP only one relapsed. Of 26 patients treated with LSA2-L2, four relapsed. Patients with localized lymphoblastic disease were uncommon. None of three patients treated with LSA2-L2 relapsed compared with three of nine treated with COMP. COMP is an excellent treatment for patients with localized disease of nonlymphoblastic type, but the relative value of the two regimens for patients with localized lymphoblastic disease is uncertain.     

Volume and planar gated cardiac magnetic resonance imaging: a correlative study of normal anatomy with thallium-201 SPECT and cadaver sections

Magnetic resonance (MR) gated cardiac imaging was performed in ten subjects using a prototype 0.15-T resistive magnet imaging system. Volume and planar imaging techniques utilizing saturation recovery, proton Tl-weighted relaxation time pulse sequences produced images of the heart and great vessels with exquisite anatomic detail that showed excellent correlation with cadaver sections of the heart. The left ventricular myocardial segments also showed excellent correlation with the thallium-201 cardiac single photon emission computed tomography images. Volume acquisition allowed postprocessing selection of tomographic sections in various orientations to optimize visualization of a particular structure of interest. The excellent spatial and contrast resolution afforded by MR volume imaging, which does not involve the use of ionizing radiation and iodinated contrast material, should assure it a significant role in the diagnostic assessment of the cardiovascular system.     

How new technology is changing mammography and breast cancer management

Breast-imaging technology has improved in ways that allow one not only to detect breast cancer earlier, but also to distinguish benign from malignant lesions better. These capabilities are influencing the approach to breast cancer. We review current trends and issues for the non-radiologist.     

Primary Mediastinal Large Cell Lymphoma in Children: A Report from the Childrens Cancer Group

Malignant lymphomas arising in the mediastinum account for approximately 60% of all mediastinal tumors in children; two-thirds are non-Hodgkin's lymphomas and one-third represent Hodgkin's disease. In contrast to adults, in children mediastinal non-Hodgkin's lymphomas are usually synonymous with lymphoblastic lymphoma, and nonlymphoblastic lymphomas are rare. We describe nine children with primary mediastinal large cell lymphoma who were treated with the Children's Cancer Group protocol CCG-503, a randomized phase III protocol for disseminated nonlymphoblastic lymphoma. Histologic subclassification revealed three immunoblastic lymphomas, three multilobated large cell lymphomas, one with clear cell features, and two large noncleaved cell lymphomas. Sclerosis, of variable degrees, was seen in all tumors. Immunophenotyping revealed all tumors to be of B cell lineage. Thymic epithelial cells could be demonstrated, utilizing antibody to keratin, in two of nine patients, suggesting that some of the tumors are of thymic origin. None of the patients had central nervous system or bone marrow involvement. It appears that primary mediastinal nonlymphoblastic lymphomas in children, although much less common, are similar to those seen in adults. These tumors must be differentiated from lymphoblastic lymphoma and Hodgkin's disease, as the therapeutic approach may depend on histologic subtype. Primary mediastinal large cell lymphoma in children appears curable with aggressive treatment in the majority of patients.