Advance directives in psychiatry. Resolving issues of autonomy and competence.
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Advance Directive Adherence↗
Biomedical subjects
R Sklar
Publications and source records attributed to R Sklar.
Methylmalonyl-CoA mutase induction by cerebral ischemia and neurotoxicity of the mitochondrial toxin methylmalonic acid.
Differential screening of gerbil brain hippocampal cDNA libraries was used to search for genes expressed in ischemic, but not normal, brain. The methylmalonyl-CoA mutase (MCM) cDNA was highly expressed after ischemia and showed a 95% similarity to mouse and 91% similarity to the human MCM cDNAs. Transient global ischemia induced a fourfold increase in MCM mRNA on Northern blots from both hippocampus and whole forebrain. MCM protein exhibited a similar induction on Western blots of gerbil cerebral cortex 8 and 24 hr after ischemia. Treatment of primary brain astrocytes with either the branched-chain amino acid (BCAA) isoleucine or the BCAA metabolite, propionate, induced MCM mRNA fourfold. Increased concentrations of BCAAs and odd-chain fatty acids, both of which are metabolized to propionate, may contribute to inducing the MCM gene during ischemia. Methylmalonic acid, which is formed from the MCM substrate methylmalonyl-CoA and which inhibits succinate dehydrogenase (SDH), produced dose-related cell death when injected into the basal ganglia of adult rat brain. This neurotoxicity is similar to that of structurally related mitochondrial SDH inhibitors, malonate and 3-nitropropionic acid. Methylmalonic acid may contribute to neuronal injury in human conditions in which it accumulates, including MCM mutations and B12 deficiency. This study shows that methylmalonyl-CoA mutase is induced by several stresses, including ischemia, and would serve to decrease the accumulation of an endogenous cellular mitochondrial inhibitor and neurotoxin, methylmalonic acid.
Animals↗
Endoscopic median nerve decompression: early experience.
Open median nerve decompression is the gold standard for carpal tunnel syndrome; endoscopic median nerve decompression is an alternative. We compared our first 20 consecutive endoscopic releases with our last 20 open releases. The endoscopic procedure employed the two-portal Chow technique; the open procedure employed the Taleisnik technique. Postoperative patient assessment was performed by an independent occupational therapist blinded to the technique. There was no difference between the groups with respect to both subjective and objective outcomes. The time of return to work and to all activities averaged 3 and 6 weeks, respectively, for both groups. The choice between techniques should be based on informed consent by the patient in light of available data.
Carpal Tunnel Syndrome↗
The psychiatric technician: trespasser or welcomed ally?
1. The increasing shortage of nurses, higher patient acuity levels, and greater demands placed on nursing to meet standards of care have contributed to the use of psychiatric technicians to alleviate the burden on nursing and ensure the delivery of quality patient care. 2. Psychiatric technicians provide care for a select group of patients under the supervision of the primary nurse. The patients assigned to psychiatric technicians require minimal direct nursing intervention. 3. Psychiatric technicians reported increased self-confidence and self-esteem; the nurses were able to perform more professional nursing activities, increasing their job satisfaction and promoting staff retention; and the patients received high-quality care.
Hospitals, Urban↗
An endonuclease from Chlamydomonas reinhardtii that cleaves the sequence TATA.
An endodeoxyribonuclease, designated CreI, was purified 16,000-fold from zygotes of the eukaryote Chlamydomonas reinhardtii. CreI preferentially attacks the sequence TATA producing double strand breaks with 3'-phosphomonoester and 5'-hydroxyl termini. The endonuclease has an Mr = 27,000 and requires Ca2+ at pH 7.5 for optimal activity.
Base Sequence↗
Nutritional vitamin B12 deficiency in a breast-fed infant of a vegan-diet mother.
A 7-month-old male presented with lethargy and failure to thrive. The child was exclusively breast-fed from birth by a mother who was a strict vegetarian. Laboratory data revealed macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The patient responded well to supplementation with B12 alone and was developmentally normal by 11 months of age. This study emphasizes the need for assuring maternal dietary adequacy during pregnancy and after birth.
Adult↗
Cellular aspects of DNA repair.
DNA repair reactions are under cellular control. In bacteria, the reactions removing 0(6)-methylguanine and 3-methyladenine are inducible. It is not clear whether similar inducibility occurs in human lymphoblastoid cells. Nonetheless, the ability to manufacture the 0(6)-methylguanine acceptor protein does seem to be controlled by some chromosomal mechanism which is superimposed on the structural gene. This control system may affect reactions other than the removal of 0(6)-methylguanine. Insofar as this is so, transformed human lymphoblastoid cells have a system reminiscent of that found in bacteria.
Animals↗
Regulation of the capacity for O6-methylguanine removal from DNA in human lymphoblastoid cells studied by cell hybridization.
Hybrids were made between a ouabain-resistant, thioguanine-resistant human lymphoma line able to remove O6-methylguanine from its DNA (Mex+) and human lymphoblastoid lines deficient in this capability (Mex-). The formation of hybrids was confirmed by chromosomal analysis. Hybrid cells had an O6-methylguanine removal capacity per mole of guanine about one third to one half that of the Mex+ parents, i.e., about the same per cell. Cell hybrids removed the same amount of the alkylation adduct 3-methyladenine as did their parents per mole of guanine, i.e., about twice as much per cell. Although the cell hybrids had intermediate resistance to the cytotoxic action of N-methyl-N'-nitro-N-nitrosoguanidine used to induce O6-methylguanine and 3-methyladenine, there is evidence that the ability to remove O6-methylguanine and resistance to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine are dissociable characteristics.
Adenosine↗
Removal of O6-methylguanine from DNA of normal and xeroderma pigmentosum-derived lymphoblastoid lines.
The ability to excise (repair) UV-induced pyrimidine dimers in Escherichia coli is not related to its ability to remove N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced O6-methylguanine (O6-MeG) from DNA. It was therefore surprising that certain xeroderma pigmentosum cell lines, deficient in dimer excision, were also unable to remove O6-MeG. We find that removal of O6-MeG occurs rapidly with a half life of less than 1 h. Two cell types can be distinguished: mex+, which remove O6-MeG residues produced by incubation with 0.5 microgram ml-1 MNNG, and mex- cells, which are unable to remove the adduct. Xeroderma pigmentosum-derived lymphoblastoid lines of complementation groups A, C or D may be either mex+ or mex-. The biochemical mechanism for the removal of O6-MeG in human cells is distinct from the excision of adducts produced by compounds such as N-acetoxy-N-2-acetylaminofluorene (AAAF) or by UV irradiation but it is not clear whether the distinction between mex+ and mex- lines is genetic or epigenetic.
Alleles↗
Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line.
The Raji human lymphoma line is able to remove O6-methylguanine (O6MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The reaction has a rapid phase in which approximately 40% of the O6MeG is removed in the first 10 min. The capacity of cells for rapid O6MeG removal is limited and is saturated at concentrations of MNNG which do not saturate the systems removing 3-methyladenine. Pretreatment of cells with MNNG inhibits their ability to remove O6MeG produced by a subsequent dose given after 2 h. Treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) is effective in diminishing cellular capacity for O6MeG removal, and cells unable to remove O6MeG and sensitive to the cytotoxic effects of MNNG are also more sensitive to ENNG than their removal competent counterparts. Regeneration of the ability to remove O6MeG requires incubation of cells for periods greater than 24 h. The O6MeG removal system is similar to that found in adapted Escherichia coli although the capacity of the Raji lymphoma line much lower than that of the induced bacteria per unit of DNA.
Burkitt Lymphoma↗
Role of the uvrE gene product and of inducible O6-methylguanine removal in the induction of mutations by N-methyl-N'-nitro-N-nitrosoguanidine in Escherichia coli.
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Chloramphenicol↗
Role of cellular systems in modifying the response to chemical mutagens.
Neocarzinostatin (NCS) produces apurinic/apyrimidinic (AP) sites in DNA which are repaired by the AP excision repair system. Survival after NCS treatment is not determined exclusively by this repair system, presumably because of the production of other, lethal, lesions. MNNG also produces multiple lesions which may be handled by cells in different ways. In E. coli, MNNG treatment results in rapid induction of a system which removes O6-methylguanine. Inhibition of this induction with chloramphenicol results in a large increase in mutation frequency. Induction of an enzyme which removes O6-methylguanine probably accounts for the enrichment of mutations near DNA growing points. MNNG also induces multiple closely linked mutations. The production of multiple mutations but not of single-site mutations is blocked in rec A and uvr E strains. The exact nucleotide site at which DNA synthesis is blocked in vitro by reaction with mutagens can be observed in a phi X174 system in which the nucleotide sequence is known. DNA polymerase I catalyzed synthesis is blocked one nucleotide before the reacted base on the template strand. In contrast, with some damaged templates, AMV reverse transcriptase can insert a base at the level of the reacted nucleotide on the template.
Antibiotics, Antineoplastic↗
Selectivity of the excision of alkylation products in a xeroderma pigmentosum-derived lymphoblastoid line.
Lymphoblastoid cell derived from a complementation group C xeroderma patient were unable to remove 06-methyl guanine residues formed in DNA by treatment of cells with low concentration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The xeroderma cells were competent in their ability to excise 3-methyl adenine adducts. MNNG treatment induced excision repair in the xeroderma line and in addition the treatment resulted in the presence of numerous single-strand breaks in the DNA. The single gene, UV-excision-defective mutants of Escherichia coli, uvrA and uvrB, are able to excise MNNG-induced 06-methyl guanine adducts indicating that excision of this compound is not due to operation of UV endonuclease system.
Cell Line↗
Enchancement of nitrosoguanidine mutagenesis by chloramphenicol in Escherichia coli K-12.
N-methyl-N'-nitro-N-nitrosoguanidine-induced mutagenesis in E. coli K-12 can be enchanced up to 50-fold by the addition of chloramphenicol with minimal effect on survival. Chloramphenicol does not produce the expected proportionate increase in closely linked double mutations.
Chloramphenicol↗