Cow's milk protein allergy.

CMPA is a common food allergy that presents with diverse manifestations affecting more than one body system. Early recognition of the condition and prompt initiation of dietary elimination of cow's milk protein is important. A future challenge with cow's milk protein can confirm a positive diagnosis.

Epigenetic consequences of AML1-ETO action at the human c-FMS locus.

Although many leukaemia-associated nuclear oncogenes are well characterized, little is known about the molecular details of how they alter gene expression. Here we examined transcription factor complexes and chromatin structure of the human c-FMS gene in normal and leukaemic cells. We demonstrate by in vivo footprinting and chromatin immunoprecipitation assays that this gene is bound by the transcription factor AML1 (RUNX1). In t(8;21) leukaemic cells expressing the aberrant fusion protein AML1-ETO, we demonstrate that this protein is part of a transcription factor complex binding to extended sequences of the c-FMS intronic regulatory region rather than the promoter. The AML1-ETO complex does not disrupt binding of other transcription factors, indicating that c-FMS is not irreversibly epigenetically silenced. However, AML1-ETO binding correlates with changes in the histone modification pattern and increased association of histone deacetylases. Our experiments provide for the first time a direct insight into the chromatin structure of an AML1-ETO-bound target gene.

Detection by fluorescence in situ hybridization of microdeletions at 1p36 in lymphomas, unidentified on cytogenetic analysis.

The chromosomal band 1p36 exhibits frequent loss of heterozygosity in a variety of human malignancies, suggesting the presence of an as yet unidentified tumor suppressor gene. The faint terminal subbands often make cytogenetic analysis of 1p36 particularly difficult. Small deletions at this locus may therefore escape detection on analysis by conventional cytogenetics, a hypothesis that we have explored using fluorescence in situ hybridization (FISH) in malignant lymphoma. The study cohort consisted of 20 cases of lymphoma of various subtypes without any 1p abnormality on G-banded karyotyping. FISH was performed using a human chromosome 1 paint and a bacterial artificial chromosome probe RP4-755G5 localizing to 1p36.33, the most telomeric subband of 1p36. Tumors demonstrating 1p36.33 deletions were additionally analyzed by FISH using a second probe from the proximal 1p36.1 subband, to further define the breakpoint. Eight cases of follicular lymphoma (FL), 5 diffuse large B-cell lymphomas (DLBCL), 2 Hodgkin disease, 2 B-cell small lymphocytic lymphomas, 2 T-cell lymphomas, and 1 marginal zone lymphoma were analyzed. FISH identified deletions at 1p36.33 in 5 of the 20 cases: 3 DLBCL and 2 FL. FISH is considerably more sensitive for identifying lymphoma genetic alterations than conventional cytogenetics. Deletion of the distal part of the 1p36 may be a much more common aberration than previously recognized in lymphoma.

Calciphylaxis, proteases, and purpura: an alternative hypothesis for the severe shock, rash, and hypocalcemia associated with meningococcal septicemia.

The hallmarks of severe meningococcal sepsis include the rapid onset of shock, purpuric rash, and metabolic derangement, in particular, hypocalcemia. The severe ecchymoses and purpura associated with meningococcal sepsis are usually attributed to acute thrombotic episodes, attributable to the associated procoagulation disorder. An alternative explanation for the rash is a sudden extravasation of calcium from the intravascular space into the tissues. We will argue that in meningococcal sepsis, cleavage of albumin into fragments by protease(s) occurs and these fragments, along with calcium, cross the endothelium into the interstitium. The fragmentation of albumin and its loss through the endothelium would also provide a more rational explanation for the rapidity of the shock and the hypocalcemia that is so characteristic of the disease.