Energy metabolism and selective neuronal vulnerability following global cerebral ischemia

A short period of global ischemia results in the death of selected subpopulations of neurons. Some advances have been made in understanding events which might contribute to the selectivity of this damage but the cellular changes which culminate in neuronal death remain poorly defined. This overview examines the metabolic state of tissue in the post-ischemic period and the relationship of changes to the development of damage in areas containing ischemia-susceptible neurons. During early recirculation there is substantial recovery of ATP, phosphocreatine and related metabolites in all brain regions. However, this recovery does not signal restitution of normal energy metabolism as reductions of the oxidative metabolism of glucose are seen in many areas and may persist for several days. Furthermore, decreases in pyruvate-supported respiration develop in mitochondria from at least one ischemia-susceptible region at times coincident with the earliest histological evidence of ischemia-induced degeneration. These mitochondrial changes could simply be an early marker of irreversible damage but the available evidence is equally consistent with these contributing to the degenerative process and offering a potential site for therapeutic intervention.Submitted as an Overview article for the volume of Neurochemical Research in honor of Alan N. Davison.     

Photoinhibition of holly (Ilex aquifolium) in the field during the winter

The distribution of holly ( Ilex aquifolium ) and its habitat preferences indicate a sensitivity to low temperature, particularly when exposed to high light. Experiments were conducted to determine whether photoinhibition of photosynthesis occurs in holly leaves in the field in United Kingdom during the winter. Photosynthetic efficiency was assessed in holly leaves that were exposed to or shaded from direct sunlight using measurements of photosynthetic oxygen evolution and chlorophyll fluorescence. Field measurements were conducted over 3 weeks during January and February. Correlation of the measurements of photosynthetic efficiency with weather conditions indicated that holly was suffering photoinhibition, particularly in leaves exposed to direct sunlight. Controlled environment studies demonstrated that exposure of leaves to low temperature and high light resulted in reductions in photosynthetic efficiency; however, leaves recovered rapidly when exposed to a higher temperature and reduced light level.     

Effect of polydimethylsiloxane oxygen carriers on the biological bleaching of hardwood kraft pulp by Trametes versicolor

Summary Improving the availability of oxygen by adding polydimethylsiloxanes (PDMS) oxygen carriers to Trametes versicolor cultures increased pulp brightening. The presence of the oxygen carriers in cultures of T. versicolor with hardwood kraft pulp increased the growth rate of the fungus, but not the ultimate biomass yield. The PDMS also stimulated brightening of hardwood kraft pulp by it T. versicolor immobilized in polyurethane foam. A threefold increase in the oxygen uptake rate in T. versicolor cultures with PDMS was observed. This increase can be explained by elevated oxygen transfer rate and attributed to the surfactant properties of PDMS. Offprint requests to: E. ZiomekIssued as NRCC 32760     

Implications of the human genome initiative for the primary care physician

... Despite the need for physicians to be knowledgeable about and open to advances in genetic technology, little is known about the level of preparedness of primary care physicians to offer new genetic tests. Evidence suggests that several barriers exist to physicians adopting genetic tests. These include lack of knowledge, inability to interpret probabilistic information, low tolerance for uncertainty, negative attitudes about their responsibility for genetic counseling and testing, lack of confidence in their clinical skills, and unfamiliarity with ethical issues raised by testing. This paper will explore some of these barriers in further depth, discuss the ethical impact of physician unpreparedness on both patient care and the diffusion of genetic tests, and describe a study that is currently underway to investigate some of these issues.     

Decreased Muscarinic Acetylcholine Receptor Number in the Central Nervous System of the Tottering (tg/tg) Mouse

The tottering mouse (tg/tg) is a single-locus mutant, phenotypically characterized by the development of epilepsy associated with distinct electroencephalographic abnormalities. Because of reported alterations in muscarinic receptor (mAChR) number in various seizure states, mAChR density was examined in discrete brain regions of tottering (tg/tg) and coisogenic wild-type (+/+) mice. Saturation binding experiments revealed a widespread decrease in membrane mAChR density in the CNS of adult tottering (tg/tg) mice as compared with age-matched control wild-type (+/+) mice. The decrease was most pronounced in the hippocampus, where tg/tg mice exhibited a 40-60% reduction in mAChR density with no change in the affinity of the receptor for antagonists or agonists. At postnatal day 10, before the reported onset of electroencephalographic abnormalities, 114 and 65% increases in mAChR density were observed in the tg/tg hippocampus and cortex, respectively. Following the development of seizure activity at postnatal day 22, mAChR density in the tg/tg hippocampus was reduced by 29%. No change in brain mAChR density was seen in adult heterozygotes (+/tg), which do not develop electroencephalographic or seizure abnormalities. These results indicate that the development of reduced mAChR number in the CNS of the tg/tg mouse is secondary to abnormal neuronal activity, providing further support for the hypothesis that membrane depolarization can cause a decrease in neuronal mAChR density.     

Plasmid-mediated drug resistance of shigellae in Kuwait

Of 153 clinical isolates of shigellae examined, 64.7% belonged toShigella flexneri, 18.9% toSh. sonnei, 11.8% toSh. boydii and 4.6% toSh. dysenteriae. Part of these isolates were resistant to sulfamethoxazole and streptomycin (88.2% each), ampicillin (66.70, tetracycline (63.40 and co-trimoxazole (43.10, with levels of resistance (MIC₅₀ and MIC₉₀) being invariably high. Resistance to three or more drugs (multidrug resistance) was seen in 77.8% of the isolates. All the 25 strains examined for transfer of resistance contained R-plasmids, both autotransferable and non-autotransferable (mobilized by transfer factor X). The frequency of transfer of different r-determinants varied from 2.7 · 10^–8 to 1.4 · 10.     

Versatile shuttle cloning vectors for the unicellular cyanobacterium Anacystis nidulans R2

Abstract 3 new shuttle cloning vectors for gene transfer into Escherichia coli and Anacystis nidulans have been constructed by utilizing the cyanobacterial origin of replication of the small plasmid pANS from A. nidulans . 2 of these new vectors, pXB7 (pDPL13 derivative) and pECAN8 (pUC8 derivative), convey ampicillin resistance, and transform A. nidulans with relatively high frequencies. Vector pXB7 has 10 unique cloning sites; pECAN8 contains 4 cloning sites within the lacZ gene permitting rapid detection of DNA inserts in the presence of Xgal. The third vector, pKBX, has a lower transformation frequency but adds kanamycin resistance as a selectable gene for shuttle vectors of cyanobacteria.     

Appearance of a State 1 – State 2 transition during chloroplast development in the wheat leaf: Energetic and structural considerations

The ability of developing chloroplasts to dynamically regulate the distribution of excitation energy between photosystem 1 and photosystem 2, and thus perform a State 1 – State 2 transition, was examined from analyses of chlorophyll fluorescence kinetics in 4- and 8-day-old Triticum aestivum L. cv. Maris Dove leaves grown under a diurnal light regime. Chloroplasts at all stages of development in the two leaf systems could undergo a State 1 – State 2 transition, except those found in the basal 0.5 cm of the 4-day-old leaf. The ability to physiologically modify the excitation energy distribution between the chlorophyll matrices of the two photosystems developed after the development of mature, fully photochemically competent photosystem 2 units and the appearance of excitation energy transfer between photosystem 2 and photosystem 1. Also, changes in the degree of energetic interaction between the two photosystems, in vivo rates of electron transport and the chlorophyll a/b ratio could not be correlated with the appearance of a State 1 – State 2 transition. Ultrastructural studies demonstrated a 32% increase in the degree of thylakoid appression in chloroplasts at the base of the 8-day-old leaf compared to the situation in the basal 0.5 cm of the 4-day-old leaf. This difference in thylakoid stacking can account for the differing abilities of these two tissues to perform a State 1 – State 2 transition when considered in the context of the distribution of the two photosystems within appressed and non-appressed regions of thylakoid membranes.     

Structural investigation of the capsular polysaccharide produced by a novel Klebsiella serotype (SK1). Location of O-acetyl substituents using NMR and MS techniques

The capsular polysaccharide of Klebsiella SK1 was investigated by methylation analysis, Smith degradation, and ¹H NMR spectroscopy. The oligosaccharides (P1 and P2) obtained by bacteriophage ΦSK1 degradation of the polymer were studied by methylation analysis, and 1D- and 2D-NMR spectroscopy. The resulting data showed that the patent repeating unit is a branched pentasaccharide having a structure identical to the revised structure recently proposed for Klebsiella serotype K8 capsular polysaccharide.

The 2D-NMR data showed that one third of the glucuronic acid residues in the SK1 polymer are acetylated at O-2, O-3, or O-4. FABMS studies confirmed the presence of monoacetylated glucuronic acid residues. Thus, the relationship between the Klebsiella K8 and SK1 polymers is akin to that found for Klebsiella polysaccharides K30 and K33, which have been typed as serologically distinct yet their structures differ only in the degree of acetylation.