Work in progress. Intraoperative neurosurgical ultrasound: localization of brain tumors in infants and children

Intraoperative real-time ultrasonic sector scanning was performed through the unincised dura mater or the intact brain surface of eight patients (aged six months to 13 years), each of whom had a previously documented mass lesion (four supratentorial, three infratentorial, one intraventricular). In each case, there was a clear definition of the location, configuration, and tissue consistency of the mass. With the exception of a choroid plexus papilloma, all lesions demonstrated both solid and fluid components. The location of a subcortical parietal lobe mass (ependymoma) was apparent only by prior sonography. All neoplastic tissue of one cerebellar astrocytoma that was identified at gross examination was removed, but additional intraoperative scanning following removal of the neoplasm suggested the presence of residual abnormal tissue. This was confirmed during further exploration, and additional gross tumor tissue was excised.     

Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition

The protein tyrosine phosphatase PTP-PEST displays remarkable substrate specificity, in vitro and in vivo for p130cas a signalling intermediate implicated in mitogenic signalling, cell-adhesion induced signalling, and in transformation by a variety of oncogenes. We have identified a high affinity interaction between the SH3 domain of p130cas and a proline-rich sequence (P335PPKPPR) within the C-terminal segment of PTP-PEST. Mutation of proline 337 within this sequence to alanine significantly impairs the ability of PTP-PEST to recognise tyrosine phosphorylated p130cas as a substrate, without qualitatively affecting the selectivity of the interaction. Thus the highly specific nature of the interaction between PTP-PEST and p130cas appears to result from a combination of two distinct substrate recognition mechanisms; the catalytic domain of PTP-PEST contributes specificity to the interaction with p130cas, whereas the SH3 domain-mediated association of p130cas and PTP-PEST dramatically increases the efficiency of the interaction. Furthermore, our results indicate that one important function of the p130cas SH3 domain is to associate with PTP-PEST and thereby facilitate the dephosphorylation of p130cas, resulting in the termination of tyrosine phosphorylation-dependent signalling events downstream of p130cas.     

Limiting amino acids in meat and bone and poultry by-product meals

In situ, digestion, and growth studies were conducted to evaluate four meat and bone meals and six poultry by-product meals as sources of escape protein and to predict the first-limiting amino acid for growing calves. Escape protein values, determined by 12-h in situ incubation, ranged from 41.7 to 51.0% of CP for meat and bone meals; poultry by-product meals ranged from 32.0 to 39.8%. True protein digestion in the gastrointestinal tract of lambs differed among protein sources (P < .05), ranging from 79 to 95%. In each of three growth trials, 60 steers (258 +/- 24, 241 +/- 23, and 230 +/- 16 kg for Trials 1, 2, and 3, respectively) were supplemented with 4 of the 10 protein sources along with a urea supplement. Protein sources were fed at 30, 40, 50, and 60% of the supplemental CP, with urea supplying the remainder. Protein efficiency differed among treatments ( P < .10), ranging from .61 to 1.55. Amino acid composition was determined for each protein source, and the individual metabolizable amino acids were regressed on the protein efficiency values. Escape protein values were correlated (R2 = .75) with protein efficiency but had a negative slope. Metabolizable methionine was the only amino acid moderately correlated (R2 = .40, slope = 1.9) to protein efficiency, whereas other amino acids either correlated poorly or had negative slopes. These data indicate that the protein value of meat and bone meal and poultry by-product meal is limited by the amount of metabolizable methionine they contain.     

Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat

BACKGROUND & AIMS: Inflammatory stimuli and lipid peroxidation up-regulate cyclooxygenase (COX)-2. This study evaluated the relationship between inflammatory mediators, COX expression, and pathological changes in experimental alcoholic liver disease. METHODS: Rats (5 per group) were fed ethanol and a diet containing saturated fat, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In the first set of experiments, whole livers were analyzed. In the second set of experiments, Kupffer cells, endothelial cells, and hepatocytes were isolated from rats in each group. Pathological analyses and measurements of lipid peroxidation, tumor necrosis factor (TNF)-alpha, COX-1 and COX-2 messenger RNA (mRNA), endotoxin, and liver and plasma thromboxane were performed. RESULTS: Increased expression of COX-2 mRNA was detected in the livers of rats showing necroinflammatory changes. The Kupffer cell was the cell primarily responsible for the increase in COX-2 mRNA level. Increased expression of COX-2 was associated with increased levels of endotoxin, TNF-alpha mRNA, lipid peroxidation, and synthesis of thromboxane. COX-1 mRNA was decreased in Kupffer cells in rats with the most severe liver injury. CONCLUSIONS: Up-regulation of COX-2 in alcoholic liver injury occurred in the presence of proinflammatory stimuli and resulted in increased synthesis of inflammatory and vasoactive eicosanoids. Down-regulation of COX-1 may result in decreased synthesis of cytoprotective eicosanoids and additionally exacerbate liver injury.     

Sensitivity of computed tomography in detecting local recurrence of prostatic carcinoma following radical prostatectomy

The aim of this study was to evaluate CT imaging in the post-operative follow-up and in the detection of recurrence after radical prostatectomy in cases of prostatic carcinoma. In over 500 patients undergoing radical prostatectomy for prostatic carcinoma, 22 cases with local recurrence were found. CT examinations of the pelvis were retrospectively evaluated in these patients. Local recurrence was detected by PSA uptake and confirmed by transrectal ultrasound (TRUS) in combination with guided biopsy. In 22 cases of confirmed local recurrence, positive results on CT were found in eight patients (36%) and negative results in nine patients (41%). In the remaining five cases (23%), no distinction could be made between scar and local recurrence. All cases definitively classified as recurrent tumour disease showed a soft tissue mass of 2 cm or more. CT sensitivity in local recurrence of prostatic carcinoma after surgery is low. Even in a very careful follow-up, the understaging would be up to 41%. In comparison, PSA, TRUS and needle biopsy are the methods of choice and are superior to CT imaging. Based on these results, there would be no reason for including pelvic CT examinations in the follow-up of prostatic carcinoma after radical prostatectomy.     

Ontogeny of Ia messenger RNA in the mouse small intestinal epithelium is modulated by age of weaning and diet

BACKGROUND: Exogenous antigenic peptides are presented to T cells by class II major histocompatibility complex (Ia) molecules on the surface of antigen-presenting cells. Class II-associated invariant chain (Ii) is also required for effective antigen presentation. Because messenger RNAs (mRNAs) for Ii chain and for class II I-A beta chain appear in the mouse intestinal epithelium after weaning, experiments were conducted to test the effect of age of weaning and diet on the appearance of Ia and Ii mRNA. METHODS: Four litters were split at day 17; one half was weaned and the other remained with the mother until day 24. On day 23, 25, 27, and 29, enterocytes were isolated from full-length small intestine by vascular perfusion with 30 mmol/L ethylenediaminetetraacetic acid, and the RNA was extracted. RESULTS: Appearance of Ii and I-A beta was significantly delayed by late weaning, as judged by RNA hybridization blots (Ii chain) and complementary DNA amplification (I-A beta chain). In mice on elemental diets, the appearance of Ii and I-A beta chain was delayed compared with littermates reared on standard chow. Ii mRNA failed to appear in mice maintained on the elemental diet by day 40, despite normal growth. CONCLUSIONS: Appearance of mRNA for both Ia and Ii depends on the introduction of a complex diet and not the "stress" of weaning or elimination of breast milk. Introduction of foreign dietary antigens or development of an altered intestinal flora may contribute to this process.     

Lymphocytes' cytotoxicity towards cells of human lymphoblastoid lines in patients with rheumatoid arthritis and systemic lupus erythematosus

A research study and discussion of antiinterferon immunoglobulin in the treatment of rheumatoid arthritis and systemic lupus erythematosus, and its possible value in the treatment of allergic diseases, autoimmune diseases and other diseases where it is presumed there may be an autoimmune genesis.