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Biomedical subjects

K Larson

Publications and source records attributed to K Larson.

35 records · Page 2Linked to original sources
PubMed1985

In vitro models of mutagenesis.

The bypass of lesions in DNA with insertion of nucleotides opposite damaged bases has been studied as a model for mutagenesis in an in vitro system. Lesions introduced by dimethyl sulfate at adenines and by ultraviolet light at pyrimidine dimers act as termination sites on both double- and single-stranded DNA templates. Base selection opposite noninformational lesions is, in part, a property of the polymerases: different polymerases have different selectivities although all polymerases tested seem to prefer purines. The ability to insert "incorrect" bases is determined in part by the sequence 5' to the lesion on the template strand. The hypothesis that damaged purines tend to result in transversions can be applied to published data on activation of the c-ras oncogene.

Base Sequence↗
PubMed1983

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↗
PubMed1982

Minerals in the hair and nutrient intake of autistic children.

The concentrations of calcium, magnesium, zinc, copper, lead, and cadmium were determined in scalp hair samples from a group of 12 autistic children and a group of 12 nonautistic control children. The only statistically significant difference between median concentrations of minerals in the hair from the two groups was a 62% decrease in the concentration of cadmium in the hair of autistic children. This decrease was probably not physiologically significant. The nutrient intake of autistic children as a group was found to be adequate and typical of well-fed American children. It was concluded that the children in neither the autistic nor the nonautistic control group showed evidence of toxicity or deficiency of the minerals or nutrients studied, but because of food idiosyncracies nutrient intake should be monitored.

Animals↗
PubMed1982

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↗
PubMed1978

Characterization of glutathione reductase from porcine erythrocytes.

Glutathione reductase (NAD(P)H: oxidized-glutathione oxidoreductase, EC 1.6.4.2) was purified to homogeneity from porcine erythrocytes by use of affinity chromatography on 2',5'-ADP-Sepharose 4-B. Analytical ultracentrifugation experiments were analysed to give the following physical parameters for the enzyme: s20,w = 5.7 S, D20,w = 50 microgram2/s, and Mw = 103 000 (protein concentration, 0.5 mg/ml). The frictional ratio was 1.37 and the Stokes radius was 4.3 nm. The enzyme molecule is a dimer composed of subunits of equal size each containing a FAD molecule. The amino acid compositions and circular dichroism spectra of the porcine and human enzymes indicated extensive structural similarities. The isoelectric point was at pH 6.85 (at 4 degrees C). The absorption spectrum of the oxidized enzyme had maxima at 377 and 462 nm. In vivo the enzyme appears to be partially reduced. At a physiological concentration of reduced glutathione the apparent Michaelis constants for glutathione disulfide and NADPH were higher than in the absence of reduced glutathione. At 0.15 M ionic strength the catalytic activity obtained with NADPH as reductant was optimal at pH 7 and more than 200 times higher than that obtained with NADH. S-sulfoglutathione and some mixed disulfides of glutathione were poor substrates with the exception of the mixed disulfide of coenzyme A and reduced glutathione. The purified enzyme displayed low transhydrogenase activity with oxidized pyridine nucleotide analogs and diaphorase activity with 2,6-dichlorophenolindophenol as acceptor substrates; both NADPH and NADH served as donors.

Amino Acids↗
PubMed1978

Topical effects of 16,16 dimethyl prostaglandin E2 on gastric acid secretion and mucosal permeability to hydrogen ions in dogs.

The effects of luminal instillation of 16,16 dimethyl PGE2 (dmPGE2) on gastric acid secretion and back diffusion of H+ were studied in anaesthetised dogs which were prepared with a segment of the greater curvature of the stomach mounted in a double lumen chamber. This model permitted simultaneous evaluation of two segments of mucosa, one control and the other test, supplied by the same vascular pedicle. Imfusion of histamine (1.0 microgram/kg/min, intravenously) stimulated brisk acid secretion in both chambers. Topical application of 25 microgram dmPGE2 in 20 ml 0.3 M HC1 to the test chamber for 30 minutes prevented acid secretion from the test mucosa during a second histamine infusion. Since the control chamber showed no evidence of inhibition this indicates that dmPGE2 acted directly on the secretory cells, rather than after absorption from the bloodstream. This observation, however, does not exclude a possible local effect on mucosal blood flow. Direct exposure of the gastric mucosa to dmPGE2 increased the rate of back diffusion of H+ because of disruption of the permeability barrier, indicated by increased H+ back diffusion, Na+ efflux, and a reduction in potential difference. However, H+ loss was small compared to the reduction in acid output.

Animals↗
PubMed1978

Oxygen consumption during cimetidine and prostaglandin E2 inhibition of acid secretion.

Oxygen consumption was determined during cimetidine and 16,16-dimethyl prostaglandin E2 inhibition of acid secretion in exteriorized segments of the greater curvature of dog stomach. Steady-state acid secretion during histamine infusion correlated well with O2 consumption (r = 0.85, P less than 0.01). Cimetidine and 16,16-dimethyl prostaglandin E2 inhibition of acid secretion produced a reduction of oxygen consumption to resting levels. In contrast, oxygen consumption did not decrease appreciably during thiocyanate inhibition of acid secretion. These observations suggest that the inhibitory action of cimetidine and 16,16-dimethyl prostaglandin E2 precedes, whereas that of thiocyanate is at a point beyond the transfer of energy to the process of acid production.

Animals↗
PubMedDate not supplied

Methylation-induced blocks to in vitro DNA replication.

Single-stranded primed M13mp2 templates and double-stranded templates were treated with either dimethyl sulfate (DMS) or N-methyl-N'-nitro-N-nitrosoguanidine and used for DNA synthesis in vitro. Methylation inhibits the ability of the molecules to serve as templates. When either E. coli DNA polymerase I or AMV reverse transcriptase were used as polymerases, DNA synthesis terminated one nucleotide 3' to the site of adenine residues in the template. Heating of the templates resulted in the appearance of additional termination bands one nucleotide before the site of G's in the template. We assume that methylated A's but not methylated G's are blocks to in vitro DNA synthesis and that heating converts a portion of the sites of methylated G to AP sites which are blocks to synthesis.

Adenine↗
PubMedDate not supplied

A model program for providing health services for migrant farmworker mothers and children.

A bilingual, multidisciplinary team of health professionals collaborated with a migrant health center in North Carolina to develop a model program to deliver primary health care services to migrant farmworker women and children. The program included case finding and outreach, coordination of maternal and child health services locally as well as interstate, and innovative health education programming. Data were collected on the health status of 359 pregnant migrant farmworker women and 560 children, ages birth to 5 years, the majority of Mexican descent, who received primary care services at the center. The mean age of the women was 23.1 years and their mean gravidity was 2.9. Dietary assessments showed that the protein intakes of most met or exceeded the U.S. Recommended Dietary Allowances, but their consumption of foods in the milk-dairy group and the fruit-vegetable group was below recommended standards. Low hematocrit was a common problem among the women (43 percent) and, to a lesser extent, among the children (26 percent). Among the infants and children, 18 percent were obese. Black American women had the highest proportion of low birth weight infants. The project emphasized coordinated services for migrant farmworker mothers and children, such as transportation services, language translation, followup, and advocacy. An outreach strategy involved case finding, home visits, and services by lay health advisors. By the third year of the project, there were increases in the average number of prenatal visits, the proportion of women entering prenatal care in their first trimester, and in the use of well-child services. The project demonstrated effective methods for delivering culturally appropriate health care services to migrant farmworkermothers and children using bilingual public health professionals.

Adult↗