Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II

Chromosome band 11q23 is frequently involved in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) de novo, as well as in myelodysplastic syndromes (MDS) and lymphoma. Five percent to 15% of patients treated with chemotherapy for a primary neoplasm develop therapy-related AML (t-AML) that may show rearrangements, usually translocations involving band 11q23 or, less often, 21q22. These leukemias develop after a relatively short latent period and often follow the use of drugs that inhibit the activity of DNA-topoisomerase II (topo II). We previously identified a gene, MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia), at 11q23 that is involved in the de novo leukemias. We have studied 17 patients with t-MDS/t-AML, 12 of whom had cytogenetically detectable 11q23 rearrangements. Ten of the 12 t-AML patients had received topo II inhibitors and 9 of these, all with balanced translocations of 11q23, had MLL rearrangements on Southern blot analysis. None of the patients who had not received topo II inhibitors showed an MLL rearrangement. Of the 5 patients lacking 11q23 rearrangements, some of whom had monoblastic features, none had an MLL rearrangement, although 4 had received topo II inhibitors. Our study indicates that the MLL gene rearrangements are similar both in AML that develops de novo and in t-AML. The association of exposure to topo II-reactive chemotherapy with 11q23 rearrangements involving the MLL gene in t-AML suggests that topo II may play a role in the aberrant recombination events that occur in this region both in AML de novo and in t-AML.     

Expression of the c-erbB-3 gene product in gastric cancer

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.     

Lymphography in patients with suspected malignancy or fever of unexplained origin

Forty-four patients underwent bipedal lymphography for evaluation of fever of unexplained origin, or because a malignant tumor (usually lymphoma) was suspected clinically. Extensive prior medical evaluation was inconclusive. The lymphograms were of no apparent value in detecting the etiology of the illness. Reactive follicular hyperplasia was frequently seen and sometimes simulated lymphoma on the lymphogram. The primary value of lymphography in such cases is as an aid in planning biopsy and surgery.     

Posttraumatic amnesia: its relation to functional outcome

OBJECTIVE: To investigate the relation between duration of posttraumatic amnesia (PTA) and functional outcome in a traumatically brain injured population. PATIENTS: Two hundred seventy-six patients with traumatic brain injury (TBI) who were admitted to a Level I university trauma center and required inpatient rehabilitation. MEASURES: Duration of PTA was assessed by serial administrations of the Galveston Orientation Amnesia Test (GOAT). Functional Independence Measure (FIM) total scores, FIM cognitive and motor subscores, and Disability Rating Scale (DRS) scores were obtained at admission and discharge from inpatient rehabilitation. RESULTS: Duration of PTA was a significant predictor of all admission and discharge DRS and FIM scores. Duration of PTA and age at the time of injury, in combination, contributed significantly to the prediction of the DRS score and FIM total, cognitive, and motor scores at discharge. CONCLUSION: Duration of PTA appears to be a useful variable in predicting specific functional outcome in the TBI population receiving inpatient rehabilitation services. The use of age as a factor in addition to duration of PTA enhances the prediction of functional outcome.     

Competition for neurotrophic factors: ocular dominance columns

Activity-dependent competition between afferents in the primary visual cortex of many mammals is a quintessential feature of neuronal development. From both experimental and theoretical perspectives, understanding the mechanisms underlying competition is a significant challenge. Recent experimental work suggests that geniculocortical afferents might compete for retrograde neurotrophic factors. We show that a mathematically well-characterized model of retrograde neurotrophic interactions, in which the afferent uptake of neurotrophic factors is activity-dependent and in which the average level of uptake determines the complexity of the axonal arbors of afferents, permits the anatomical segregation of geniculocortical afferents into ocular dominance columns. The model induces segregation provided that the levels of neurotrophic factors available either by activity-independent release from cortical cells or by exogenous cortical infusion are not too high; otherwise segregation breaks down. We show that the model exhibits changes in ocular dominance column periodicity in response to changes in interocular image correlations and that the model predicts that changes in intraocular image correlations should also affect columnar periodicity.