Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.     

Thrombosis and thrombolysis in unstable angina

Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures.     

Partial abnormal pulmonary venous return. An underestimated and unknown association in Turner-Ullrich syndrome. Presentation of an original case]

The authors report the case of a 59-year-old woman with a complex cardiac lesion consisting of degenerative major mitral insufficiency masking partial abnormal pulmonary venous return. These cardiac abnormalities fell within a context of genetic disease since the patient had Turner's syndrome, confirmed at the age of 58 by a 45 x 0 karyotype. They detail the originality of the clinical manifestations of partial abnormal pulmonary venous return and review the literature concerning cardiac malformations in Turner's syndrome.     

Association of DLG5 R30Q variant with inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect.     

Leishmania braziliensis Vianna, 1911 in French Guiana

A new case of cutaneous Leishmaniasis to L. braziliensis Vianna, 1911, contracted in French Guyana is reported. The parasite, isolated in culture, is identified by enzymatic typing (13 zymoden). The identified zymodem is zymodem MON-43. It is the same of the WHO reference strain L. braziliensis s. st.     

Aspects angiographiques et chirurgicaux des ponts musculaires compressifs et des trajets intramyocardiques de l'artère interventriculaire antérieure (à propos de 12 cas)

Seule une minorité de ponts myocardiques donne une constriction systolique de la portion intramurale des vaisseaux. L'ischémie et la douleur sont rares, et correspondent à des ponts musculaires épais, entraînant une diminution de calibre de l'artère de plus de 75%: le diagnostic est difficile et repose sur la coronarographie dont il faut savoir multiplier les incidences. On peut s'aider d'artifices, tels que l'augmentation de la fréquence cardiaque pour mettre en évidence l'anomalie, surtout si le réseau coronarien apparaît normal et lorsqu'il existe une Symptomatologie clinique évocatrice. Dans le cas de pont situé sur une artère athéromateuse, le diagnostic est difficile à porter de façon certaine.Le diagnostic d'IVA intramyocardique « simple » est plus difficile à évoquer, l'étranglement systolique étant absent. Seul un aspect rigide de l'IVA, associé à une bouche artérielle distalc signant l'émergence artérielle du myocarde peut faire évoquer le diagnostic; la lésion coronarographique est superposable à la lésion per-opératoire dans le cas de pont musculaire isolé. Par contre, le diagnostic d'IVA intramyocardique est parfois difficile, certaines pouvant être invisibles en coronarographie si le pont est plus fibreux que musculaire.     

Identification of group B streptococcal Sip protein, which elicits cross-protective immunity

A protein of group B streptococci (GBS), named Sip for surface immunogenic protein, which is distinct from previously described surface proteins, was identified after immunological screening of a genomic library. Immunoblots using a Sip-specific monoclonal antibody indicated that a protein band with an approximate molecular mass of 53 kDa which did not vary in size was present in every GBS strain tested. Representatives of all nine GBS serotypes were included in the panel of strains. Cloning and sequencing of the sip gene revealed an open reading frame of 1,305 nucleotides coding for a polypeptide of 434 amino acid residues, with a calculated pI of 6. 84 and molecular mass of 45.5 kDa. Comparison of the nucleotide sequences from six different strains confirmed with 98% identity that the sip gene is highly conserved among GBS isolates. N-terminal amino acid sequencing also indicated the presence of a 25-amino-acid signal peptide which is cleaved in the mature protein. More importantly, immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI. The data presented in this study suggest that this highly conserved protein induces cross-protective immunity against GBS infections and emphasize its potential as a universal vaccine candidate.     

A new bioassay for glucagon

1 The relaxant action of glucagon has been studied in strips of rabbit renal arteries partially contracted by a low concentration (1 ng/ml) of noradrenaline.

2 The preparation was relaxed in a dose-dependent manner by concentrations of glucagon varying between 25 ng/ml and 420 ng/ml.

3 The relaxant effect of glucagon (0.1 μg/ml ED₆₀) on this preparation was not affected by propranolol (5.0 μg/ml), cimetidine (10 μg/ml), diphenhydramine (10 μg/ml), indomethacin (5.0 μg/ml), phentolamine (1.2 μg/ml), atropine (10 μg/ml) and 8-Leu-AT_II (1.0 μg/ml) but was slightly potentiated by Des-Arg⁹ Leu-OMe⁸-Bk (25 μg/ml) and indomethacin (50 μg/ml).

4 The dose-response curve to glucagon remained parallel in the presence of papaverine (2.5 μg/ml) but was shifted to the left by a factor of 2.5 to 2.8. Theophylline (250 μg/ml) also potentiated the vascular relaxation induced by glucagon.

5 Insulin (10 μg/ml) did not influence the relaxant effect of glucagon.

6 The removal of the N-terminal amino acid (His) of glucagon reduced by 89% the biological activity of this fragment on the vascular preparation. The removal of the C-terminal amino acids Met-27, Asn-28 and Thr-29 of glucagon resulted in a fragment which was inactive either as an agonist or as an antagonist when tested at concentrations as high as 925 ng/ml.

7 It is concluded that the relaxation of partially contracted strips of rabbit renal arteries by glucagon constitutes a simple, sensitive, relatively specific and reliable bioassay which may be useful for the determination of glucagon in biological materials and for structure-activity relationship studies with this hormone.