Abstract Transmembrane proteins, including multipass transmembrane proteins like GPCRs and ion channels, are important targets for therapeutic monoclonal antibody (mab) discovery. Therapeutic antibodies to this class of proteins are generally targeted to extracellular domains displayed on the surfaces of living cells. Challenges associated with developing antibodies to this class of targets are small numbers of extracellular amino acids, membrane-dependent protein conformation, difficulty in expression at high levels, high amino acid sequence homology of human and mouse proteins, and post-translational modifications. DNA immunization strategies with full-length constructs and high throughput flow cytometry screening of mab binding to transfected and control cells was used to generate and identify large numbers of mabs to CXCR4 and ADORA2A (GPCRs) and CD20. Panels of mabs were generated for all 3 targets with low numbers of hybridoma fusions. For each target the mab gene sequences were shown to be unique and contain levels of somatic hypermutation comparable to existing benchmark therapeutic antibodies. Functional assays including apoptosis and receptor modulation (calcium flux and cAMP modulation) further demonstrated that the technical approach generated diverse panels of antibodies that exhibit functional activity as good or better than existing benchmark therapeutic antibodies.

To the Editor: In the March issue of Gastrointestinal Endoscopy, Efthymiou et al1Efthymiou A. Markoglou C. Michalopoulou F. et al.Intracerebral hemorrhage after therapeutic upper-GI endoscopy: report of a case.Gastrointest Endosc. 2006; 63: 522-525Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar report a case of intracerebral hemorrhage after upper-GI endoscopy. We had a case that resembles this report. A 54-year-old woman was admitted to the hospital for evaluation of a recent history of epigastric pain, recurrent vomiting, and weight loss. Her medical history was unremarkable. A barium swallow revealed gastric dilatation and delayed gastric emptying. With the presumptive diagnosis of gastric outlet obstruction, the patient was scheduled for an EGD. Several hours before endoscopy, the patient passed black tarry stools. Endoscopy was performed after intravenous sedation with 2.5 mg midazolam. The esophagus seemed normal. The stomach was full of fresh blood and clots, and there was poor visibility. In the duodenal bulb, oozing of blood was identified from the posterior wall, and 4 mL adrenaline 1:10,000 was injected. Bleeding was uncontrollable. Because the patient became agitative, 1.5 mg midazolam was added, and, after several minutes, the procedure ended. At this point, the patient suddenly stopped breathing, and asystole developed. After cardiopulmonary resuscitation, cardiac rhythm resumed, but the patient remained unconscious. On CT, a massive subarachnoid hemorrhage was seen, with herniation through the foramen ovale. The patient died 6 days later.

Background The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. Aim To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. Methods Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. Results Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 ± 8.40 vs 9.36 ± 9.46,n= 229,P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used ‘never-smoked’ CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 ± 7.60 vs 8.04 ± 8.72,P< 0.05). Conclusion There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.Eur J Gastroenterol Hepatol12:975-979