Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Epilepsy, retarded growth and onchocerciasis, in two areas of different endemicity of onchocerciasis in Burundi

A high prevalence of epilepsy (up to 1.3%) was observed in an area hyperendemic for onchocerciasis in the province of Bururi, Burundi. Following this observation, epileptics and controls were examined in 2 communes (administrative units) with different endemicity for onchocerciasis. Altogether, onchocerciasis was more frequent in epileptics (81.8%) than in controls from the same households (68.3%; P < 0.05). This difference was more marked in the hyperendemic area. Other possible causes of epilepsy, including cysticercosis, were infrequent (18 possible cases among 110 epileptics). During this survey, 9 epileptics with growth retardation were seen. They showed most characteristics of Nakalanga syndrome, which was described from Uganda. All 9 such cases were suffering from onchocerciasis. These findings give more evidence of a possible association between onchocerciasis and epilepsy, and between onchocerciasis and Nakalanga syndrome.     

Thoracic epidural anesthesia as the last option for treating angina in a patient before coronary artery bypass surgery

Robertsonian translocations, although relatively common as a constitutional genetic aberration, are rarely encountered in leukaemia. We report a case of acute myeloid leukaemia which showed an acquired Robertsonian translocation in the form of der(14;21) by cytogenetic analysis of leukaemic cells. This was confirmed by the PHA-stimulated culture of peripheral blood lymphocytes. A review of the literature identifies only eight reported cases of acquired Robertsonian translocations in leukaemia. In the majority of cases the Robertsonian translocation occurs as a secondary change in a complex abnormal clone, whereas in two out of nine patients reported, including ours, it is found as a sole karyotypic abnormality.     

Partial congenital defect of the left pericardium: angiographic diagnosis and treatment by thoracoscopic pericardiectomy: case report

Twenty-six patients with an intracardiac myxoma underwent surgical resection at our institution from 1977 through 1992. Left atrial myxoma was diagnosed in 22 patients, left ventricular in 1, right atrial in 2, and right ventricular in 1. Six patients were asymptomatic; preoperative symptoms included dyspnea, arrhythmias, embolic episodes, and syncope. The diagnosis was established with transthoracic echocardiography in all cases but one. Surgery was performed in all cases with the aid of cardiopulmonary bypass with moderate hypothermia and cold crystalloid cardioplegia. One patient with a left ventricular myxoma died in a comatose state during the immediate postoperative period. Long-term clinical and echocardiographic evaluation was performed in 19 patients; results were excellent (all the patients were in New York Heart Association functional class I or II), and no recurrences were documented. The clinical characteristics, diagnostic methods, and surgical approach are presented and discussed.     

High affinity presentation of an autoantigenic peptide in type I diabetes by an HLA class II protein encoded in a haplotype protecting from disease

Tissue composition and the distribution of body mass are described for four genera of East African Bovidae (Madoqua, Gazella, Damaliscus, Hippotragus) with supporting data from four others (Neotragus, Oryx, Tragelaphus, Connochaetes). These species are high in muscle mass, an adaptation convergent with other high-speed terrestrial cursors, bounders, and saltators. The segments below the elbow/cubitus and knee/stifle/genu joints in small bovids are both lighter in percent of total body mass (8.6% TBM) and less heavily muscled (10-15% of total limb musculature) than those segments in macaques (13.6% TBM, 20-25% of the limb musculature). Bovid species differ from one another in the regional distribution of muscle mass. Madoqua kirkii (4-5 kg) concentrates muscle in the lumbar extensors and hindlimbs; large species such as Damaliscus doreas (50-60 kg) and Hippotragus niger (160-220 kg) distribute it more evenly between the lumbar and cervical regions and between the hindlimbs and forelimbs. Gazella dorcas (10-20 kg) is quantitatively intermediate in those characteristics. The redistribution of muscle mass with increasing size correlates with the loss of axial bending of the vertebral column: in small, hindlimb dominant, 'dorsomobile' species such as Madoqua sagittal mobility increases stride length through 'extended' suspension; in large 'dorsostable' species such as Damaliscus and Hippotragus the vertebral column resists bending, consequently abbreviating or omitting this non-contact phase of the gait cycle. Locomotor adaptation as it is reflected in size, shape, and musculoskeletal structure is the key to habitat choice, dietary specialization, social structure, and male agonistic behavior and, therefore, central to the fabric of behavioral ecology.     

Novel NMDA antagonists: replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with heteroisoquinolinium cations

Replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with thiazolium (4a and 4b) and N-methylimidazolium (4c and 4d) resulted in equipotent compounds in the [3H]TCP binding assay. The corresponding N-methyl-1,2,4-triazolium analogs were less potent in this assay. The thiazolium derivative 4b, with a Ki = 2.9 nM, is being evaluated as a possible neuroprotective N-methyl-D-aspartic acid (NMDA) antagonist.     

Chemokine receptors: structure, function and role in microbial pathogenesis

The chemokine superfamily is composed of at least 20 different leukocyte chemoattractants that act by binding to a family of G protein-coupled receptors. Leukocyte subtypes respond preferentially to unique but overlapping subsets of chemokines as determined by the receptor distribution, yet the receptors appear to signal through a common Gi-type G protein. Since chemokines appear to play major roles in inflammatory pathology, their receptors may be good targets for developing leukocyte selective anti-inflammatory drugs. Two chemokine receptors, CC CKRS and ONCC, function pathologically as cell entry factors respectively for human immunodeficiency virus 1, the cause of AIDS, and Plasmodium vivax, the major cause of malaria.     

Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100

Exposure to cocaine during fetal development has been demonstrated to produce a variety of brain and behavioral changes. Cocaine is a potent releaser of a variety of neurotransmitters, such as serotonin, which act as developmental signals. Since serotonin plays an important role in astroglial maturation, migration, and growth factor production (e.g. S-100 beta), we proposed that these properties of astroglial cells will be altered in a brain prenatally exposed to cocaine. To observe cocaine's effects on astroglial development, we performed immunocytochemical analyses of a variety of developmental protein makers including BrdU, Gap-43, vimentin, and S100 beta. Our results demonstrate that prenatal cocaine administration produces decreased cell proliferation as measured by BrdU staining, retarded neurite outgrowth as ascertained by increased Gap-43 immunoreactivity, increased density of vimentin-positive radial glial cells, and diminished tissue S100 beta immunoreactivity. Overall, these results suggest that cocaine delays astroglial development. This delay would have profound effects on neuronal development and outgrowth and, thus, development of the entire brain.