Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation

Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.     

Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation

Anticoagulants are widely used in the prevention of thromboembolic disease (particularly during the postoperative period) and in the curative treatment of deep vein thromboses. Two classes of anticoagulants are currently available: heparins (standard heparin, low molecular weight heparin) and coumarin anticoagulants. The choice of anticoagulant must take into account the clinical context (preventive or curative treatment), as well as the pharmacological and pharmacokinetic properties of the anticoagulant. This treatment requires laboratory monitoring adopted to the anticoagulant selected.     

Complexes of focal adhesion kinase (FAK) and Crk-associated substrate (p130(Cas)) are elevated in cytoskeleton-associated fractions following adhesion and Src transformation. Requirements for Src kinase activity and FAK proline-rich motifs

The focal adhesion kinase (FAK) and Crk-associated substrate, p130(Cas) (Cas), have been implicated in diverse signaling pathways including those mediated by integrins, G-protein-coupled receptors, tyrosine kinase receptors, and the v-src and v-crk oncogenes. The recent identification of a direct interaction between FAK and Cas prompted the examination of potential regulation of FAK.Cas complexes by factors that result in concomitant increase in their phosphotyrosine content, namely cell adhesion and transformation by Src. Both conditions resulted in elevated FAK.Cas complex levels in nonionic detergent-insoluble fractions, indicating increased association with the cytoskeleton. For activated Src, this effect requires an active Src catalytic domain but not its Src homology 2 (SH2) or Src homology 3 (SH3) domains. FAK kinase domain tyrosines 576 and 577 are also required, suggesting that direct phosphorylation of these sites by Src may influence the solubility and/or stability of the complex. FAK-Cas association was only observed in the context of Cas binding to at least one of two distinct proline-rich sites on FAK. These findings firmly establish a direct interaction between FAK and Cas and demonstrate that Src can influence the subcellular localization of the complex by a tyrosine phosphorylation-dependent mechanism.     

Adrenal masses in patients with familial adenomatous polyposis

PURPOSE: The aims of this study were 1) to report the characteristics and the clinical outcome of familial adenomatous polyposis (FAP) patients with adrenal masses in the FAP registry at the Cleveland Clinic Foundation and 2) to estimate the prevalence of adrenal masses detected by computed tomography in FAP patients compared with that expected in a normal population. METHODS: A retrospective review was undertaken of the FAP registry database at our institution. Only 738 patients treated at the Cleveland Clinic Foundation were included in the study. A meta-analysis was conducted to determine the relative risk of adrenal incidentaloma in this series of FAP patients and in a general population as reported in the four largest pertinent studies published in the past 15 years. RESULTS: Fifteen patients (11 females) were identified. Two patients had symptoms related to cortisol hypersecretion (arterial hypertension) and underwent surgery. The final pathology was adrenocortical carcinoma and bilateral nodular hyperplasia. Adrenal masses were found incidentally (incidentalomas) in 13 patients: 12 were detected by computed tomography and one during laparotomy for total abdominal colectomy. Only one patient underwent left adrenalectomy for a 5-cm mass. Pathologic report revealed adrenocortical adenoma. Among the 738 patients considered in this study, only 162 underwent abdominal computed tomographic scan, mainly for assessing intra-abdominal desmoid. The prevalence of incidentaloma in our series compared with that reported in the literature is significantly different (7.4 vs. 0.6-3.4 percent; P < 0.001 (chi-squared test)). DISCUSSION: Although the presence of other extracolonic manifestations represents a selection bias for computed tomographic study in our series, the incidence of incidentalomas in FAP patients seems to be higher than in a general population. However, incidental detection of an adrenal mass in FAP patients has probably a limited clinical relevance, and the management should be the same as that for the normal population.     

Juvenile pilocytic astrocytoma masquerading as amblyopia

PURPOSE: A healthy 13-year-old girl, previously diagnosed with amblyopia in her right eye, was seen in consultation after her vision continued to decrease. METHODS: A complete ophthalmologic examination including visual field testing and optic nerve photography was performed in the neuro-ophthalmologic clinic. Magnetic resonance imaging study was also obtained. RESULTS: Visual sensory deficits and pale optic nerves were noted on clinical examination. Visual field testing showed a chiasmatic junctional defect. Magnetic resonance imaging verified a large chiasmatic mass, histologically proven to be a juvenile pilocytic astrocytoma. CONCLUSION: Early recognition of signs and symptoms of chiasmatic lesions is essential for preventing visual loss.     

Role of lipopolysaccharide in colonization of the mouse intestine by Salmonella typhimurium studied by in situ hybridization

An avirulent, streptomycin-resistant Salmonella typhimurium strain, SL5319, and its lipopolysaccharide (LPS)-deficient mutant strain, SL5325, differ in their ability to colonize the large intestines of streptomycin-treated mice. When fed to mice independently, the strains colonize equally well, but when fed together, the LPS-deficient mutant is outcompeted by the wild-type strain during establishment in the gut (J.J. Nevola, B.A.D. Stocker, D.C. Laux, and P.S. Cohen, Infect. Immun. 50:152-159, 1985). In the present study, the spatial distribution in the intestinal mucosal layer of the two strains was visualized by specific hybridization to bacterial rRNA in histological sections of mouse colon and cecum. The first day after infection, 9.8% of the smooth SL5319 cells observed in mucus were found to be associated with the mouse epithelial cells, but three days after infection, the corresponding fraction of adhering bacteria was reduced to 2.1%. The LPS-deficient S. typhimurium strain was confined to the part of the mucosal layer closest to the colonic lumen and was not observed to adhere to the epithelium either at day 1 or 3 after infection. Quantitative determinations of the distance from the S. typhimurium cells to the epithelial wall confirmed that the average distance for the rough S. typhimurium SL5325 was much larger than for its smooth counterpart, S. typhimurium SL5319. Quantification of the hybridization signal from bacteria isolated from the cecal mucus revealed that the two strains had the same ribosome concentration, indicating that they have the same potential for growth in the intestinal environment. On the basis of these observations, we suggest that the better colonization ability of the strain carrying wild-type LPS is due to the better abilities to penetrate the intestinal mucosal layer and to subsequently bind to the epithelial cells in vivo.     

Sexual dimorphism in the physiques of World Championship divers

The aim of this study was to evaluate sexual dimorphism in male (n = 43) and female (n = 39) springboard and platform divers at the 1991 World Diving Championships in Perth, Western Australia. In addition to recording the age, height and body mass of each diver, measurements were taken of 8 skinfolds, 13 girths, 8 breadths and depths, and 11 lengths. The derived variables were somatotype, sum of 6 skinfolds (SUM6) and height-adjusted proportional z-scores. The mean (+/- s) values for the males were: age, 22.2 +/- 4.6 years; height, 171 +/- 9 cm; body mass, 66.7 +/- 10.2 kg; somatotype, 2.0-5.3-2.4 +/- 0.5-1.0-0.8; SUM6, 45.9 +/- 11.4 mm. For the females, these values were: age, 20.9 +/- 3.8 years; height, 161 +/- 6 cm; body mass, 53.7 +/- 5.5 kg; somatotype, 2.8-3.8-2.8 +/- 0.7-1.0-0.9; SUM6, 65.6 +/- 17.0 mm. The males were taller, heavier, more mesomorphic, less endomorphic and had a smaller SUM6 than the females (P < 0.01). A series of discriminant function analyses were applied to groups of variables. Wilks' lambda and the overall F-ratio were highly significant (P < 0.001), with correct classification of sex reaching 84-99%. The best combinations of variables were as follows: (1) absolute size, 3 girths + SUM6, or body mass + SUM6 + height (Wilks' lambda = 0.17-0.35); (2) relative size, 2 girths + SUM6 + body mass. Combinations of breadths and lengths, skinfolds, or somatotype components, were less successful, with 84-87% classified correctly (Wilks' lambda = 0.40-0.48). We conclude that, in addition to the expected absolute size differences, sexual dimorphism between male and female divers can be explained by differences in relative size, skinfolds and somatotype, and that these differences may have implications for coaching and selection in diving.     

Differences in the treatment of coronary heart disease between countries as revealed in the Scandinavian Simvastatin Survival Study (4S)

AIM: To assess differences in treatment of ischaemic heart disease in the Scandinavian countries. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study (4S) lasted 5.4 years and showed that death rates in 4444 patients with coronary heart disease were 30% lower in those treated with simvastatin to lower serum cholesterol than in those given placebo. Apart from this main result, the 4S provided detailed information on rates of death and other manifestations of coronary heart disease, as well as on use of non-lipid forms of therapy. There were substantial differences in 4S placebo group rates of mortality, coronary deaths and major coronary events between countries. Surgical and medical therapy varied importantly between countries. CONCLUSIONS: Major inter-country differences in rates of death and myocardial infarction in patients with coronary heart disease were likely to be due to a composite of differences in baseline characteristics including smoking. They occurred in a setting of very uneven exploitation of the potential for improving survival of patients with ischaemic heart disease.     

Grain feeding and the dissemination of acid-resistant Escherichia coli from cattle

The gastric stomach of humans is a barrier to food-borne pathogens, but Escherichia coli can survive at pH 2.0 if it is grown under mildly acidic conditions. Cattle are a natural reservoir for pathogenic E. coli, and cattle fed mostly grain had lower colonic pH and more acid-resistant E. coli than cattle fed only hay. On the basis of numbers and survival after acid shock, cattle that were fed grain had 10(6)-fold more acid-resistant E. coli than cattle fed hay, but a brief period of hay feeding decreased the acid-resistant count substantially.