Genetic effects of chlorinated anilines and azobenzenes onSalmonella typhimurium

The mutagenicity of 19 herbicide-derived chlorinated azobenzenes and structurally related chlorinated anilines and nitrobenzenes was assayed towards several strains ofS. typhimurium, using the plate incorporation method and the fluctuation test, in the presence or in the absence of liver post-mitochondrial fractions, in aerobic and anaerobic conditions.Positive results were obtained with 4,4-dichloroazobenzene, 4,4-dichloroazoxybenzene, 3,4-dichloronitrobenzene and, to a much lesser extent, with 3,4,3,4-tetrachloroazobenzene. No mutagenic effect was observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin in any condition.     

Visual cortex activation recorded by dynamic emission computed tomography of inhaled xenon 133

Regional cerebral blood flow (CBF) was studied tomographically with ¹³³Xe administered by inhalation over a 1-min period at a concentration of 10 mCi/l. A fast rotating (dynamic) single-photon emission computed tomograph with four detector heads was used, an instrument that has been found to be well suited for detecting focal ischemia. In the present study its ability to detect focal hyperemia was investigated in 13 normal subjects studied during rest and during visual stimulation. A flickering light seen with eyes open and closed, increased blood flow in the visual cortex by 35% and 22% respectively. Looking at different pictures displayed on a screen raised regional CBF by 26%. The most complex task, reading and copying a text, increased blood flow by 45%. Averaging the different tasks resulted in a mean regional CBF increase in the visual cortex of 35%. The result is comparable with that obtained by positron emission tomography. Both forms of isotope tomography offer unique possibilities for the study of brain function in health and disease, possibilities not matched by X-ray tomography. The low cost and ready availability of appropriate single-photon radionucleides (¹³³Xe and ¹²⁷Xe) are mentioned.Supported by the Danish Medical Research Council, the Danish Sclerose Association, and the Johann and Hanne Weimann Foundation.     

Book reviews

Recent Advances in Avian Immunology Research. B. S. BHOGAL & G. KOCH (Eds), Progress in Clinical and Biological Research Volume 307, New York, Alan R. Liss, Inc., 1989. 238 pp. US$59–50. ISBN 0–8451–5157–6.

Mechanisms of Disease. A Textbook of Comparative General Pathology. D. O. SLAUSON & B. J. COOPER, Baltimore, Williams & Wilkins 2nd Ed., 1990. 541 pp., £43.50. ISBN 0–683–07743–0.

Poultry Diseases. F. T. W. JORDAN (Ed), London, Bailliere Tindall, 3rd Edition, 1990. 464 pp., £19.90. ISBN 0–7020–1339–0.     

Incidence of the morphological aspect on the rate of implantation of embryos obtained by fertilization in vitro]

1350 embryos obtained by In Vitro Fertilization (IVF) have been examined with the reverse microscope before their transfer in utero. Some embryos are "morphologically normal" (34.7%); some others are atypical. It is difficult to determinate the implantation rate by embryo according to morphological aspect because, most of the time we transfer several embryos to only one patient and we do not know, in case of pregnancy, which one or which ones have developed. Nevertheless, we have tried to appreciate, for 500 embryos transfers after IVF, the incidence of morphological aspect according to the presence or absence of "morphologically normal" embryos. The implantation rate is significantly higher in the groups in which you find "morphological normal" embryos than in the group where they are missing. (19.7% and 19.2% vs 10.2%). It seems that the aspect of the embryo when it is transferred, has an incidence on its future development.     

Unusual traumatic rupture of the thoracic aorta with avulsion of the left subclavian artery]

Of the many cases of traumatic rupture of the aorta diagnosed each year at l"H?pital du Sacré-Coeur, Montreal, most patients are already in irreversible shock when seen. However, during the period Oct. 1, 1974 to Sept. 30, 1975, prompt surgical treatment saved six patients. One of these six patients had a complete trans-section of the aortic arch between the left carotid and left subclavian arteries with avulsion and slight retraction of the left subclavian artery. Repair of the aortic arch and left subclavian artery was accomplished without extracorporeal circulation. A sutureless temporary bypass shunt was created by (a) cannulating the ascending and descending aorta, the cannulas being secured with purse-string sutures and joined by a 3/8-inch (94-mm) polyvinyl chloride (PVC) tube connected to a "double T" adapter, and (b) joining two small PVC tubes from the adapter with two straight cannulas, a no. 14 being inserted into the innominate artery and a no. 12 being inserted into the left carotid artery. With this temporary bypass created, the ascending and descending aorta and aortic arch vessels were all clamped. Aortic continuity was re-established with a tubular Dacron graft (diameter, 19 mm) to which was anastomosed a side-arm of knitted Dacron (diameter, 10 mm) to repair the left subclavian artery. Throughout the temporary perfusion the brain, spinal cord and all abdominal viscera were well protected. No sign of ventricular distension was detected. This report is the first in which complete transsection of the aortic arch has been managed by a sutureless bypass shunt allowing perfusion of all aortic arch vessels without extracorporeal circulation.     

Purification and mass spectroscopic analysis of human CB2 cannabinoid receptor expressed in the baculovirus system

Abstract: The cannabinergic system is present in a variety of organs and tissues that perform a wide range of essential physiologic functions making it an inherently important therapeutic target for drug discovery. In order to augment our knowledge regarding the interactions between cannabinoid receptors (CBs) and their ligands, efficient and effective tools are essential for robust expression and purification of these membrane‐bound proteins. In this report, we describe a suitable method for purification of the human cannabinoid receptor 2 (CB2) to a qualitative and quantitative level sufficient for mass spectral analysis. We utilized a baculovirus expression system, incorporating several epitope tags to facilitate purification and to ameliorate the effect the tags have on CB2 expression and function. Expressed protein encoded by a carboxy (C)‐terminal His‐tagged CB2 construct displayed a B_max value of 9.3 pmol/mg with a K_D of 7.30 nm using [3_H]CP–55⁹⁴⁰, a standard cannabinoid radioligand, and was selected for subsequent purification experiments. Western blot analysis of purified membrane protein yielded several forms of CB2, the most abundant being a 41 kDa peptide. A second protein species was observed with an apparent molecular weight of 46 kDa representing a glycosylated form of CB2. In addition, a CB2 homodimer was also identified. The purified receptor was subjected to mass spectroscopic analysis to confirm its identity and purity. Mass spectra corresponding to the intracellular, extracellular and transmembrane domains were obtained. These experiments exemplify the importance of high‐level expression systems when developing membrane‐bound protein purification strategies. This work will aid in the identification of receptor–ligand binding sites, the characterization of molecular features involved in receptor activation, and the elucidation of the CB2 receptor tertiary structure.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.