Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer

Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.     

Gastrointestinal zygomycosis caused by Mucor indicus in a patient with acute traumatic brain injury.

We report a gastrointestinal infection caused by Mucor indicus in a patient with severe head injuries. Monotherapy with high-dose liposomal amphotericin B successfully eradicated the mucormycosis. Nevertheless, subsequently a hemicolectomy was necessary due to recurrent bleeding from a deep ulcer. Mucor indicus is an uncommon fungal pathogen, typically found in starters used for food fermentation. Reviewing other reports on Mucor indicus infections, primary gastrointestinal manifestations seem to be typical and indicate an oral route of infection.     

Electron microscopic studies of endocrine hyperplasia in duodenal adenomas in familial adenomatous polyposis

Summary Electron microscopical studies on endocrine cell hyperplasia of duodenal adenomas from five patients with familial adenomatous polyposis were performed. All the endocrine cell types normally found in the duodenal mucosa were identified. A constant feature was proliferation of duodenal-enterochromaffin cells but an increase in the number of all other endocrine cell types apart from pyloricgastrin cells and somatostatin cells, was also observed. Certain types of intestinal endocrine cells (the intestinal enterochromaffin cell and the glicentin cell) are rare cells in the normal duodenal mucosa. The finding of these cells may indicate increased biological aggressivity.     

Separate and variably shaped chromosome arm domains are disclosed by chromosome arm painting in human cell nuclei

Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding.     

Gestörte alpha2-Adrenozeptorfunktion bei Hämodialysepatienten mit renaler Anämie — eine mögliche Ursache der Blutdrucksteigerung unter rekombinantem humanem Erythropoietin?

Summary Nine patients on maintenance hemodialysis and transfusion-demanding renal anemia (group A) were treated with rHuEPO 120 IU/kg i.v. three times per week. Hemoglobin-content was raised from 7.2±0.9 to 10.4±0.8 g/dl. In all patients blood pressure rose, three patients developed arterial hypertension. Mean diastoloic blood pressure was 66±12 and 78±16 mmHg (p<0.001) before and after rHuEPO. Rise in blood pressure was accompanied by a significant fall in plasma-noradrenaline-levels (from 498±100 to 383±75 pg/ml;p<0.05) and alpha₂-adrenoceptor-density (from 574±76 to 384±49;p<0.05). Compared to nine patients on maintenance hemodialysis and hematocrit over 30% (group B), patients with severe renal anemia (group A before treatment) had higher densities of alpha₂-adrenoceptors (574±76 vs. 218±32;p<0.001) despite higher plasma-noradrenaline-levels (498±100 vs. 399±63; n.s.). We suppose a anemia-related disturbance of alpha₂-receptor-function with the result of abolished receptor down-regulation and impaired vascular reagibility to vasoconstricting stimuli. With the correction of anemia receptor-function improves, receptor down-regulation as well as vascular reagibility is re-established resulting in augmented vascular resistance and higher blood pressure.

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Abkürzungen rHuEPO rekombinantes humanes Erythropoietin - teMAP mittlerer arterieller Blutdruck - RR Blutdrucknach RIVA-ROCCI - RBF regionaler Blutfluß - RPR regionaler peripherer Widerstand     

Hepatitis B vaccination of high-risk individuals in the canton of Zurich

In an effort to vaccinate as many high-risk individuals as possible against hepatitis B, 10,484 persons received a total of 27,818 injections of H-B-Vax (Merck Sharp & Dohme) or HEVAC B (Sanofi/Pasteur) between January 1982 and January 1983. They represented 1.1 % of the total population of the canton of Zurich including approximately 70% of all medical and dental personnel, a great proportion of eligible high-risk patients and contacts of HBs Ag carriers, but not more than 10% of drug addicts and promiscuous homosexuals. Twelve to 17 % of the vaccine injections were accompanied by side effects which were benign in nature and transitory. Six vaccinated individuals developed hepatitis B, all within 60 days after the first vaccine dose. One hundred and seventy-seven cases of hepatitis B were recorded in 1982, 109 in the first half of the year and 68 in the second half. It was concluded that the vaccination campaign provided protection for medical and dental personnel. There was still no conclusive evidence of a vaccine-related drop in the incidence of hepatitis B in other high-risk groups vaccinated or — as a secondary effect — in other non-vaccinated populations.     

Effects of aging on exocrine immune responses to Mycoplasma pulmonis.

Formalinized Mycoplasma pulmonis was used to immunize 3 different age groups of Fischer 344 rats. A specific antibody to this antigen was detected in both saliva and lung lavage fluids and differences were noted in the elicitation of secretory antibody between the different ages of the animals. Few statistical differences were noted between the three age groups for salivary IgG responses to M. pulmonis, regardless of the dosage given, even though all responses were greater than their respective control groups. The principal differences among the three age groups were noted in the kinetics of the response, that is, the amount of time that was necessary to produce a peak response. The younger group of animals took less time to produce a peak response than the older two groups, even though the magnitude of the response was lower. Salivary IgA responses to M. pulmonis appeared predominantly as a primary response, particularly in the senescent animals. Secondary salivary IgA responses were not significantly greater than their respective primary responses, suggesting that secretory IgA did not display classic anamnestic responses that were observed with salivary IgG. As with IgG responses, the senescent animals took longer to produce a peak salivary IgA response when compared to the other age groups. Lung lavage IgG responses, normalized to total protein, were greatest in the youngest group of animals and appeared to diminish as the age of the animal increased. In contrast, lung lavage IgA responses to M. pulmonis were of a greater magnitude in the senescent animals. These studies suggest that senescent animals are capable of eliciting a humoral immune response in mucosal secretions to Mycoplasma pulmonis. However, differences noted with regard to disease severity and mortality to respiratory mycoplasmosis in senescent animals may result from intrinsic defects in the quality of the humoral response or as a consequence of deficient cellular responses to this pathogen.     

Malaria prophylaxis and self-therapy in airline crews

The risk of malaria infection in airline crews is estimated to be 0.5 per 1,000 persons per night in areas with high levels of malaria transmission. Routine chemoprophylaxis for years is not recommended because of possible side effects. Airline crews should therefore use appropriate measures to prevent mosquito bites. In addition, they may need to carry "standby" medication with them to be used for presumptive treatment of a febrile illness if medical attention is not readily available.     

Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat

This study examined the effect of a pharmacologically induced rightward shift in the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) on outcome from transient focal cerebral ischemia in the rat. Halothane anesthetized rats (n=20 per group) were given saline or a single 15-min infusion of 150 mg/kg RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylproprionic acid) intravenously before or 30 min after onset of 75 min of middle cerebral artery filament occlusion (MCAO). Seven days later, severity of hemiparesis and cerebral infarct size were examined. RSR13 alone did not significantly improve outcome. Conscious normothermic rats (n=12 per group) were also given RSR13 (150 mg/kg) or 0.9% NaCl intravenously and subjected to 75 min of MCAO with 7 days of recovery. Again, RSR13 alone did not significantly reduce infarct size or improve neurologic score. A dose-response curve for dizocilpine (MK-801) was then constructed in conscious normothermic rats subjected to 75 min of MCAO. Dizocilpine (0.5 mg/kg i.v.) caused a 90% reduction in mean infarct size while 0.25 mg/kg reduced infarct size by 48%. Other rats were then subjected to 75 min of MCAO after being given dizocilpine (0.25 mg/kg i.v.; n=18) or RSR13 (150 mg/kg i.v. )+dizocilpine (0.25 mg/kg i.v.; n=15). RSR13+dizocilpine resulted in smaller cortical infarct volume (8+/-14 mm3 vs. 34+/-37 mm3, p<0.02) and total cerebral infarct volume (46+/-28 mm3 vs. 81+/-60 mm3, p<0. 05) compared to dizocilpine alone, respectively. We conclude that a pre-ischemic peak increase in P50 of approximately 25 mmHg alone is insufficient to reduce focal ischemic injury, but may be advantageous when used in conjunction with other neuroprotective agents.     

Local anaesthetic injection with and without corticosteroids for subacromial impingement syndrome

Fifty patients with impingement syndrome refractory to long-term conservative treatment were randomized to three treatment groups. All patients received an injection of 10 ml 0.5% bupivacaine, in group 1 without corticosteroid, in group 2 with crystalline corticosteroid and in group 3 with lipoid corticosteroid. Treatment in group 1 had to be stopped because of inefficacy. In groups 2 and 3 favorable results were achieved in 19 out of 40 patients.

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Résumé  50 patients avec conflit sous-aeromial, qui ne montraient pas d’amélioration après un long traitement conservatif récevaient une injection dans la bourse subacromiale. Le premier groupe récevait une injection contenant un anaesthétique local pur, groupe 2 une mixture d’anaesthétique avec des corticostéroides cristalins et groupe 3 avec des corticostéroides lipoides. Le traitement du groupe 1 devait être arrété cause d’inificacité. 19 de 40 patients du groupe 2 et 3 montraient une amélioration après 6 mois.

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Accepted: 6 January 2000