SEPT9_v4 expression induces morphological change, increased motility and disturbed polarity

Several lines of evidence indicate that altered expression of SEPT9 is seen in human neoplasia. In particular there is evidence of altered expression of the SEPT9_v4 isoform. The functional consequences of this remain unclear. We have studied the expression of wild-type- and GTP-binding mutants (G144V and S148N) of the SEPT9_v4 isoform in the MCF7 cell line as a model for its deregulation in neoplasia. We find that SEPT9_v4 expression induces dramatic actin cytoskeletal reorganization with the formation of processes around the cell periphery. Expression of the SEPT9_v4 isoform and a G144V mutant cause delocalization of endogenous SEPT9 from filamentous structures but the S148N mutant does not have this effect. In addition SEPT9_v4 isoform expression enhances cell motility and is associated with perturbation of directional movement. Expression of SEPT9_v4 GTP binding mutants also has potent effects on morphology and motility and causes loss of normal polarity, as judged by Golgi reorientation assays. The phenotypes induced by expression of the SEPT9_v4 isoform and the GTP mutants provide an insight into possible mechanisms of SEPT9_v4 function and suggest that the GTPase functions have both ras- and rab-like features. We propose a model in which overexpression of the SEPT9_v4 isoform in neoplasia is associated with perturbation of SEPT9 complexes, leading to phenotypes associated with neoplasia.     

Late stage (III and IV) non-small cell cancer of the lung: results of surgical resection at Inova Fairfax Hospital

One hundred forty-two patients underwent surgery and related treatment for advanced stage (III, IV) non-small cell cancer of the lung. One hundred seventeen patients underwent up-front surgery, with a hospital mortality rate of 1.7% (2/117). Kaplan-Meier 5-year survival in this group was 31% (+/- 5). Twenty-five patients underwent neoadjuvant therapy followed by surgical resection, with respective rates of hospital mortality, complete pathologic response, and major pathologic response of 0%, 16%, and 64%. Kaplan-Meier 5-year survival in this latter group was 34% (+/- 11). Of the 16 patients undergoing neoadjuvant therapy who had complete pathologic response or significant downstaging from stage III disease, Kaplan-Meier 5-year survival was 61% (+/- 15).Three clinical observations of interest emerged regarding survival. First, in those patients with postresection FEV1 < 1.0 L, hospital mortality rate was 20%, and there were no 5-year survivors (P < 0.0001). Second, where neoadjuvant therapy was associated with complete pathologic response or significant downstaging of disease, there was a trend for improved survival in the downstaged group, but it did not reach statistical significance (P = 0.14). Third, adjuvant therapy was associated with improved 5-year survival (P = 0.03), particularly for combination chemotherapy and radiotherapy (P = 0.02).     

Altered cerebral glucose utilization following blood-brain barrier opening by hypertonicity or hypertension

The blood-brain barrier (B-BB) in conscious rats was opened to Evans blue dye by carotid infusion of a 1.8 m arabinose solution or by acute unilateral carotid hypertension, following which [¹⁴C]2-deoxy-d-glucose was injected intravenously. Rats were killed 45 min later, and autoradiographs were made from frozen brain sections. Focal areas of increased optical density, or “hot spots,” were noted in brain regions when the B-BB was opened but were absent when B-BB integrity was unaffected. These hot spots, which represented accumulations of brain radioactivity, were not prevented by diet-induced hypokalemia or by systemic pretreatment with high doses of phenoxybenzamine or propranolol. Their cause remains unclear, but their induction by both hypertensive and osmotic B-BB opening suggests that B-BB damage, regardless of cause, can markedly disturb cerebral metabolism.     

Ethnic differences in cerebral venous thrombosis

BACKGROUND: Cerebral venous thromboses (CVT) with distinct clinical presentations have been shown worldwide. However, there is little information regarding race-ethnic differences in this disease. METHODS: We prospectively studied 50 CVT patients from Brazil, comparing clinical and laboratory data among white (W) and African-Brazilian (AB) patients. RESULTS: Seventy percent of the patients were female, 26 W and 23 AB, mean age 34.7 years. Multiple sinus CVT, deep CVT and worse outcome were significantly more frequent in AB than in W patients. There was a trend towards a higher frequency of factor V Leiden and prothrombin mutation in W than in AB, and of protein C deficiency in AB. CONCLUSIONS: CVT was more severe in AB patients than in W patients. Race-ethnic differences may account for the heterogeneous distribution of inherited thrombophilia in this series.     

Improved naming after TMS treatments in a chronic, global aphasia patient--case report

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca's homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming.