Amplified enzyme-linked-immunofilter assays enable detection of 50-10(5) bacterial cells within 1 hour

1. The hydrolysis of organophosphate pesticides (OP) and nerve gases by serum paraoxonase (PON1) is an important factor determining their toxicity to mammals including man. The PON1 gene contains 2 polymorphic sites at amino acid positions 55 (L-->M) and 192 (G-->A, classically defined as the A and B genotypes) which result in several alloenzymes of PON1 in human serum. 2. The 192 polymorphism has previously been shown to affect PON1 activity. We have investigated the effect of both polymorphisms on the hydrolysis of paraoxon by serum from 279 healthy human subjects. 3. The 55 polymorphism significantly influenced PON1 activity. MM homozygotes had over 50% less activity towards paraoxon compared to the LL and LM genotypes regardless of the 192 genotype (P < 0.001). 4. Multiple regression analysis indicated that the 192 polymorphism, 55 polymorphism and serum PON1 concentration were responsible for 46, 16 and 13% of the variation in PON1 activity, respectively (all P < 0.001). None of the other parameters investigated significantly affected PON1 activity. 5. Therefore both PON1 polymorphisms affect the hydrolysis of paraoxon. AA/MM and AB/MM individuals may be potentially more susceptible to OP intoxication. 6. Genotyping individuals for both PON1 polymorphisms may provide a method for identifying those individuals at most risk of OP poisoning. The effect of PON1 polymorphisms on activity may also explain why some Gulf War Veterans have developed Gulf War Syndrome and some have not.     

Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients

PURPOSE: An attempt was made to define the role of radiotherapy before operation for AGC. METHODS AND MATERIALS: From January 1978 to May 1989, a prospective randomized trial on preoperative radiotherapy (R+S) vs. surgery alone (S) for AGC was carried out in 370 patients. Patients were randomized into a combined group (R+S, 171 patients) or a surgery alone group (S, 199 patients) by the envelope method. 8-MV photon or telecobalt was used for the preoperative radiation therapy, using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia, lower segment of the esophagus, fundus, lesser curvature, and hepatogastric ligament. Surgery was performed after 2 to 4 weeks rest. RESULTS: The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10% and 19.75%, 20.26% and 13.30%, respectively. The survival curves of these two groups diverged right from the beginning after the operation over the ninth year. Statistics by Kaplan-Meier log rank test proves that the difference is significant (chi2 = 6.74, p = 0.0094). The immediate results were: resection rate 89.5% and 79.4% (p < 0.01); pathologic stage after resection T2 12.9% and 4.5% (p < 0.01), T4 40.3% and 51.3% (p < 0.05), lymph node metastasis rates 64.3% and 84.9% (p < 0.001); operative mortality rates 0.6% and 2.5%; intrathoracic leak rates 1.8% and 4.0%, respectively. The causes of failure were: local uncontrol and recurrence 38.6% vs. 51.7% (p < 0.025), regional lymph node metastasis 38.6% vs. 54.6% (p < 0.005), distant metastasis 24.3% vs. 24.7%. CONCLUSION: Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia.     

The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways

Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions.     

Stressful life events and personality styles: relation to impairment and treatment outcome in patients with social phobia

Forty-five patients with social phobia and 15 individuals with no mental disorder were compared on number and type of life events experienced. Social phobia patients were further examined to evaluate the effect of negative life events and of the interaction between personality style and life events on severity of impairment and reactions to cognitive-behavioral group therapy. Patients with social phobia reported more negative life events than participants with no mental disorder. Among patients with social phobia, more frequent negative life events were associated with higher scores on measures of depression and general anxiety. Patients high on autonomy who reported more negative autonomous (i.e., achievement-oriented) life events also scored higher on measures of social anxiety and general anxiety. There were no significant interactions between sociotropy and the frequency of reported socially oriented negative life events. However, patients high on sociotropy scored higher on measures of social anxiety, depression, and general anxiety. Patients who had experienced more negative life events improved more after treatment on measures of social anxiety than did those who had experienced fewer negative life events. Implications of these findings and recommendations for future research are discussed.     

Phosphorylation of tobacco eukaryotic translation initiation factor 4A upon pollen tube germination

Eukaryotic translation initiation factor eIF-4A is a member of the DEAD box family of RNA helicases and RNA-dependent ATPases. In tobacco, eIF-4A is encoded by a gene family with one isoform, eIF-4A8, being exclusively expressed in pollen. This pollen-specific isoform is a candidate for mediating translational control in the developing gametophyte. Here we show that eIF-4A is barely phosphorylated in mature pollen, but during pollen tube germination, two isoforms of eIF-4A become phosphorylated. Phosphoamino acid analysis indicated phosphorylation of threonine. In order to determine whether pollen-specific eIF-4A8 is among the phosphorylated isoforms, we raised transgenic tobacco plants overexpressing eIF-4A8 containing a histidine tag. Hereby, we could show that indeed eIF-4A8 is modified through phosphorylation. The biological relevance of the phosphorylation of eIF-4A is discussed.     

Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation

A novel property of hippocampal LTP, 'variable persistence', has recently been described that is, we argue, relevant to the role of LTP in information storage. Specifically, new results indicate that a particular pattern of synaptic activation can give rise, either to a relatively short-lasting LTP, or to a longer-lasting LTP as a function of the history of activation of the neuron. This has led to the idea that the induction of LTP is associated with the setting of a'synaptic tag' at activated synapses, whose role is to sequester plasticity-related proteins that then serve to stabilize temporary synaptic changes and so extend their persistence. In this article, we outline the synaptic tag hypothesis, compare predictions it makes with those of other theories about the persistence of LTP, and speculate about the cellular identity of the tag. In addition, we outline the requirement for aminergic activation to induce late LTP and consider the functional implications of the synaptic tag hypothesis with respect to long-term memory.     

1,N2-propanodeoxyguanosine adducts: potential new biomarkers of smoking-induced DNA damage in human oral tissue

Diarrhea is a non-specific symptom which may be associated with Addison's disease and several causes had been demonstrated in the aetiology. We describe a patient with Addison's disease who was suffering from chronic diarrhea for three months. She was diagnosed as having collagenous colitis and successfully treated with Sulphasalazine, 2 g/day. Collagenous colitis is an uncommon cause of chronic diarrhea and the association of collagenous colitis with Addison's disease has not previously been described. We think that collagenous colitis may play a role in the aetiology of diarrhea in patients with Addison's disease and therefore we suggest a full colonoscopic examination in other patients with Addison's disease and diarrhea to determine the incidence of collagenous colitis in the aetiology of diarrhea.