Differential expression of 2′∶3′-cyclic nucleotide 3′-phosphodiesterase in cultured central,peripheral, and extraneural cells

The relative levels of the central nervous system myelin marker enzyme 2:3-cyclic nucleotide 3-phosphodiesterase (EC 3.1.4.37, CNPase) were determined in neuroblastoma, astrocyte, oligodendrocyte and Schwann cell cultures and in freshly isolated human lymphocytes and platelets. The highest specific activities were associated with the cells that elaborate myelin membrane in the central and peripheral nervous system, oligodendrocytes and Schwann cells, respectively. Antiserum to bovine CNPase recognized both CNP1 and CNP2 in CNS myelin and human oligodendroglioma. In addition, a 53,000 dalton protein was evident on autoradiographs of immunoblotted PNS myelin and human oligodendroglioma proteins. Cultured rat oligodendrocyte, C₆ and mouse NA neuroblastoma CNPase appear to share common determinants with the corresponding normal rat CNS enzyme.     

Early neurological complications of coronary artery bypass surgery.

A prospective study of 312 patients undergoing elective coronary artery bypass surgery was undertaken to determine the incidence, severity, and functional impact of postoperative neurological complications. Detailed evaluation of the patients showed that neurological complications after surgery were common, occurring in 191 of the 312 patients (61%). Although such a high proportion of the total developed detectable changes, serious neurological morbidity was rare. Neurological disorders resulted in death in only one patient (0.3%) and severe disability in only four (1.3%). Forty eight patients were mildly disabled during the early postoperative period, and the remaining 138 with neurological signs had no serious functional disability. The postoperative neurological disorders detected included one death from cerebral hypoxic damage. Prolonged depression of conscious level was observed in 10 patients (3%) and definite stroke in 15 (5%); 78 (25%) developed ophthalmological abnormalities and 123 (39%) primitive reflexes; postoperative psychosis was observed in four (1%); and 37 (12%) developed disorders of the peripheral nervous system. The incidence of serious neurological problems such as fatal cerebral damage, stroke, and brachial plexopathy is in accordance with experience elsewhere. Lesser abnormalities, whose detection required detailed neurological examination, were much commoner than expected from previous reports.     

Conserved plasmid/chromosome sequences in fast- and slow-growing rhizobia that nodulate the same plant

Apart from the ability to nodulate legumes, fast-and slow-growing rhizobia have few bacteriological traits in common. Given that there is only one pathway to nodulation, DNA sequences conserved in fast- and slow-growing organisms that nodulate the same host should be strongly enriched in infectivity genes. We tested this hypothesis with seven fast-growing and five slow-growing strains that produced responses varying from fully effective nodulation through various ineffective associations to non-nodulation on four different hosts (Lotus pedunculatus, Lupinus nanus, Macroptilium atropurpureum, and Vigna unguiculata). When restriction enzyme digested total DNA from 10 of the strains was separately hybridized with nick-translated plasmid DNA isolated from 4 fast-growing strains, variable but significant homologies were found with all 10 strains. Part of this homology was shown to be associated with the nifKDH genes for nitrogenase and part with putative nodulation genes carried on pC2, a cosmid clone containing a 37 kbp region of the large sym plasmid present in the fast-growing broad-host range Rhizobium sp. strain NGR234. Analysis of the extent of homology between the plasmids of 3 fastgrowing strains (NGR234, TAL 996 and UMKL 19) able to effectively nodulate Vigna unguiculata showed them to have homologous DNA fragments totalling 47 kbp. This core homology represents less than 12% of the total coding capacity of the sym plasmid present in each of these strains.Abbreviations Sym symbiotic sequences/plasmids - nod genes required for nodulation - nod putative nod genes - nif genes required for the synthesis of the enzyme nitrogenase     

Isolation and Genetic Analysis of Caulobacter Mutants Defective in Cell Shape and Membrane Lipid Synthesis

In this paper we report the isolation, characterization and genetic analysis of several C. crescentus mutants altered in membrane lipid synthesis. One of these, a fatty acid bradytroph, AE6002, was shown to be due to a mutation in the fatA gene. In addition to the presence of the fatA506 mutation, this strain was found to contain two other mutations, one of which caused the production of a water-soluble brown-orange pigment (pigA) and another which caused formation of helical cells (hclA). Expression of the latter two phenotypes required complex media and both were repressed by glucose. However, the lesions were mapped to loci that are separated by a substantial distance. The hclA and the fatA genes mapped close together, possibly implying that comutation had occurred in AE6002. Data are presented that allow the unambiguous identification of a second Fat gene (fatB) in C. crescentus. The map position of another mutation in membrane lipid biogenesis, the glycerol-3-PO₄ auxotroph gpsA505, was also determined. During this study the flaZ gene was fine-mapped and the positions of proC and rif changed from the previously reported location.     

The effect of chronic alcohol feeding on lipid peroxidation in microsomes: lack of relationship to hydroxyl radical generation

Chronic alcohol feeding causes microsomal induction including increased generation of hydroxyl radicals. Ethanol induced liver injury may be mediated by lipid peroxidation for which hydroxyl radicals have been proposed as major mediators. Ethanol promotes lipid peroxidation when given acutely but also may serve as a hydroxyl radical scavenger. Therefore, we studied the acute and chronic effects of alcohol on microsomal lipid peroxidation and hydroxyl radical generation. Chronic alcohol feeding in rats increased microsomal generation of hydroxyl radicals but lipid peroxidation of endogenous lipid was inversely related to hydroxyl radical generation. Ethanol (50mM) had a slight inhibitory effect on hydroxyl radical production in peroxidizing microsomes, no effect on endogenous lipid peroxidation and enhanced the lysis of RBCs added as targets of peroxidation. Enhanced microsomal generation of hydroxyl radicals following chronic alcohol feeding is not an important mediator of lipid peroxidation.     

Prevention of stress-induced gastric ulcers by dopamine agonists in the rat

Dopamine (DA) and DA agonists have been shown to exert a protective role against the formation of duodenal ulcers. The effect of stimulation of DA receptors on the development of stress-induced gastric ulcers is currently unknown. Accordingly, we evaluated the effect of several DA agonists on the development of gastric ulcers induced by 3 h of cold + restraint stress (CRS) in rats. Apomorphine, d-amphetamine, methylphenidate, and threo-dl-p-hydroxymethylphenidate (an hydroxylated analog of methylphenidate), significantly reduced both the incidence and severity of CRS-induced gastric ulcers. The gastric cytoprotection afforded by these agents was dose-related, and completely antagonized by pretreatment with the peripheally acting DA antagonist domperidone. Because domperidone blocks peripheral, but not central, DA receptors, and since the entry of threo-dl-p-hydroxymethylphenidate across the blood-brain barrier into the brain is restricted to a great extent, we conclude that stimulation of peripheral DA receptors is primarily involved in the gastric cytoprotection induced by dopamimetics.The pathogenesis of stress-induced gastric ulcers remains largely unknown, and significant efforts have been made over the last decade to functionally characterize some of the factors involved in the etiology of this disease. Considerable attention has been focused on gastric acid secretion, but its primary role in stress-induced gastric ulcer disease remains uncertain. In fact, agents which effectively inhibit or neutralize gastric acid secretion such as cimetidine or antacids do not necessarily exert protection against stress-induced gastric ulcers (1,2). Moreover, in our original studies with neurotensin, a brain and gastrointestinal peptide, we have found that central administration of this neuropeptide, which completely prevents the development of cold + restraint stress (CRS)-induced gastric ulcers, does not appreciably alter gastric acid secretion (2). These findings support the contention that gastric acid secretion may not be an important factor in the development of this type of gastric ulcer.There is, however, considerable evidence that the automatic nervous system plays an intermediary role in the development of these ulcers (3,4). In this regard, surgical or pharmacological blockade of the vagal (cholinergic) division of the autonomic nervous system prevents the appearance of stress-associated gastric ulcers (5,6). Direct stimulation of catecholamine receptors, or indirect activation via increased sympathetic outflow to the periphery (7,4,8–11) appears to produce a salutary effect of stress-induced gastric ulcers.Szabo and his associates (12, 13, 14) have extensively studied the anti ulcer effects of dopamine (DA) in duodenal ulcer formation. Whether DA also modifies the development of stress-induced gastric ulcers is currently unknown.We have therefore evaluated the effect of selected DA receptor agonists and antagonists on CRS-induced gastric ulcer formation in rats.     

Adrenalectomy of Rats Results in Hypomyelination of the Central Nervous System

The effect of adrenalectomy on CNS myelin accumulation was investigated to determine whether glucocorticoids play a role in regulating myelination. When 14-day-old rats were adrenalectomized and sacrificed 7-8 days later, the amount of bulk-isolated myelin in whole brain, as expressed per gram wet weight of brain or per milligram DNA-phosphate, was reduced to about 75% that of sham-operated controls. Both brain weight and DNA content were unchanged by adrenalectomy. Examination of individual brain regions also revealed decreased amounts of myelin in adrenalectomized animals. Brain glycerol 3-phosphate dehydrogenase specific activity was reduced in adrenalectomized animals to 40-60% that of controls, and serum corticosterone levels were less than 0.6% of control levels. The amount of cerebral myelin in animals adrenalectomized on day 21 and sacrificed 9 days later was not significantly reduced. This suggests a possible role of glucocorticoids during the early period of rapid myelination.