A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia

The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.     

Potentiation of tumour necrosis factor-mediated cell killing by VP16 on human ovarian cancer cell lines. In vitro results and clinical implications

Synergism between recombinant human tumour necrosis factor (rHuTNF) and DNA topoisomerase II inhibitor VP16 during the killing of cells has been studied in six human ovarian cancer cell lines (A2774, A2780, SW626, IGROV-1, SKOV3, Pa1) and a cervical carcinoma cell line (Me180). Studies were performed using an assay of colony formation inhibition (drug treatment for 1 h) and a growth inhibition assay (continuous exposure for 20 h). Concomitant treatment of cells with VP16+rHuTNF enhanced cell killing in all the cell lines tested--an effect observed in both short- and long-term cytotoxicity assays. This study suggests that the activity of VP16 in ovarian cancer cell lines might be enhanced by rHuTNF in in vitro models.     

Influence of age and health on immune functions and trace elements

Apparently healthy elderly donors were screened according to a simple protocol that included clinical examination and the determination of hematological and biochemical values. This screening was performed to detect subclinical alterations which might interfere with immune responses and trace element status. The elderly were divided into two groups. The first group consisted of 22 (age 76 +/- 1 years) positively selected elderly (PSE), i.e. healthy subjects with no hematological and laboratory alterations, the second one comprised 13 (age 75 +/- 1 years) negatively selected elderly (NSE). Data were then compared with those obtained from 40 (age 35 +/- 2 years) healthy young controls. In both groups of elderly donors, plasma zinc levels were normal, while plasma copper concentrations were increased. Intracellular values of zinc and copper in mono- and polymorphonuclear cells from both groups of elderly were within reference limits. After in vitro activation, granulocyte chemiluminescence activity was impaired only in NSE. A decrement in the number of circulating CD3 lymphocytes and an increase in CD8d, CD57 cells were found in PSE, while NSE showed an increased number of CD3,DR cells and CD8d, CD57, CD8b,CD57 and CD16,CD56 positive cells. Our results indicate that only plasma copper levels were affected by age, whereas subclinical alterations in hematological or biochemical values appear to impair immune responses in the elderly.     

The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program

The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.     

Postoperative enteral feeding does not prevent intestinal bacterial translocation, but reduces the rate of pulmonary infections in pigs undergoing total orthotopic small bowel transplantation

OBJECTIVE: To assess the effects of a non-elemental liquid diet on nutritional state, composition of bowel flora, intestinal translocation, and pulmonary infections after small bowel transplantation in pigs. DESIGN: Prospective randomised experiment. SETTING: Teaching hospital, Italy. MATERIAL: 32 female Large White pigs. INTERVENTIONS: Group 1 (n = 6) underwent small bowel transplantation, were treated with immunosuppression, and fed on commercial chow. Group 2 (n = 6) were treated similarly except that they were fed with an enteral feed through a tube gastrostomy starting on day 4 postoperatively. Group 3 (n = 6) were treated similarly to group 1 except that they had no immunosuppression, and Group 4 (n = 6) underwent orthotopic small bowel autotransplantation; 8 further pigs underwent a sham operation only to act as controls. MAIN OUTCOME MEASURES: Signs of rejection, graft-versus-host-disease, luminal bacterial overgrowth, bacterial translocation, pneumonia, and the pigs' nutritional state. RESULTS: All animals in group 3 showed signs of acute rejection. There was appreciable overgrowth of aerobic and anaerobic bacteria in all three groups after allotransplantation compared with controls. The counts of anaerobic bacteria were significantly lower in group 2 (enterally fed animals) compared with those given free access to commercial chow [mean (SD) 2.81 (1.39) log CFU/cm2 compared with 4.80 (1.65), p = 0.047]. Bacterial translocation developed to a similar degree after autografts and allografts and pneumonia developed in fewer animals after enteral feeding (1/6) than after conventional feeding (5/6) but the difference was not significant (p = 0.08, odds ratio 25.0, 95% confidence interval of odds ratio 1.20 to 521.13). Enterally fed animals also lost less weight than conventionally fed animals [2.32 (1.23) kg compared with 4.53 (1.74), p = 0.016]. CONCLUSIONS: Enteral feeding for up to a month slightly reduced the rate of pneumonia and resulted in a better nutritional state in pigs after small bowel transplantation. It had no effect on luminal bacterial overgrowth or translocation.     

Causal modeling to estimate sensitivity and specificity of a test when prevalence changes

The suppressive effect of the halogenated inhalation anesthesia on cortical somatosensory evoked potentials (cSSEPs) has been well documented. Less studied and appreciated is the effect of nitrous oxide often with a narcotic as an alternative to a potent agent for spinal cord monitoring. This study sought to define more clearly the influence of nitrous oxide on cSSEPs elicited to posterior tibial nerve stimulation. A secondary purpose was to demonstrate the advantage of a total intravenous propofol anesthesia in facilitating uncompromised large-amplitude cSSEPs. Fifty adult patients undergoing anterior cervical discectomy served as the study sample. Brainstem and cortical posterior tibial nerve SSEPs were recorded under two independent anesthesia conditions, namely, nitrous oxide and propofol. Results demonstrated a significant amplitude reduction and latency prolongation with the nitrous oxide versus propofol protocol. cSSEP amplitude with propofol was, on the average, approximately two times larger than that with nitrous oxide. Based on these findings, the use of nitrous-oxide anesthesia is not recommended when limited to monitoring cSSEPs that are already amplitude compromised secondary to existing spinal cord disease.     

StAR protein is expressed in both medulla and cortex of the bovine and rat adrenal gland

We have employed polyclonal antibodies to a peptide sequence of bovine steroidogenic acute regulatory (StAR) protein and human placental 3beta-hydroxysteroid dehydrogenase (3beta-HSD) to determine the localisation and distribution of these proteins in rat and bovine adrenal glands. Immunohistochemical staining demonstrated the presence of StAR protein in the zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis (ZR) and in the medulla of both species. For 3beta-HSD, immunostaining was observed in the ZG, ZF and ZR of the rat adrenal and was absent in the medulla. Immunoblotting experiments showed intense bands for StAR protein (30 kDa, 37 kDa) in the mitochondria of bovine ZG, ZF and medulla and a less intense band (30 kDa) in the microsomes. In rat ZG and ZF/R mitochondria only the 30 kDa protein was present. For 3beta-HSD, an intense band (42 kDa) was found in microsomes and mitochondria of rat and bovine ZG and ZFR. A very faint signal for 3beta-HSD was seen in adrenal medulla. In conclusion, StAR (or a closely related) protein is present throughout the adrenal gland in rat and bovine species in contrast to 3beta-HSD which is confined to the steroidogenic zones. The possible function of StAR protein in the adrenal medulla merits investigation.