Microcomputerized testing of drug effects on divided attention.
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Attention↗
Biomedical subjects
J L Taylor
Publications and source records attributed to J L Taylor.
Identification of epitestosterone in the plasma and testis of the lizard Tiliqua (Trachydosaurus) rugosa.
Blood and testicular extracts of the scincid lizard Tiliqua (Trachydosaurus) rugosa were analyzed using thin-layer, column, and high-performance liquid chromatography. The major androgens isolated were epitestosterone, testosterone, and androstenedione. Epitestosterone was characterized by chromatography in several systems, and by derivative formation. Epitestosterone was further identified in testicular extracts by gas chromatographymass spectrometry. Immunoreactive material was detected in tissue extracts using an antiserum specific to epitestosterone. The maximum concentration of epitestosterone in blood, measured by radioimmunoassay, was four times that of testosterone (approximately 900 and 200 nmol/l, respectively). Epitestosterone could not be detected in the blood of intact females and the concentration of this steroid was low in castrate males. The maximum testicular concentrations (pmol/testis) were 390 (nonincubated) and 2050 (incubated) for epitestosterone, and 2025 (nonincubated) and 1040 (incubated) for testosterone. Both plasma and testicular concentrations showed considerable seasonal variation. The identification of endogenous epitestosterone confirms the results of earlier investigations using radioactive substrates. The occurrence of this steroid as a major product of the testis in T. rugosa is discussed in relation to androgens in reptiles and other vertebrates.
17-alpha-Hydroxyprogesterone↗
Neuropharmacologic and neuropathologic effect of fenvalerate in mice and rats.
B6C3F1 mice and Sprague-Dawley rats displayed the characteristic signs of pyrethroid intoxication following single oral doses ranging from 56 to 320 and 133 to 1000 mg/kg fenvalerate, respectively. The LD50s for mice and rats were 180 and 776 mg/kg, respectively, with corn oil as the vehicle. Signs of neurologic deficit such as splayed gait, tremors, ataxia, and hind limb incoordination were observed at doses of greater than or equal to 100 mg/kg (mice) and greater than or equal to 133 mg/kg (rats) within 1-8 hr after dosing. These signs had disappeared in most animals within 72 hr. Slight peripheral nerve fiber damage was detected in surviving mice and rats sacrificed 10 days after dosing. The incidence and severity were dose related at doses greater than or equal to 56 and greater than or equal to 180 mg/kg; however, even at lethal doses, evidence was lacking for the presence of nerve lesions in several animals. Thus two distinct neurologic effects were observed: a reversible ataxia/incoordination and a neuropathologic effect manifested as sparse axonal damage in peripheral nerve.
Animals↗
Vitamin D prophylaxis in the elderly: a simple effective method suitable for large populations.
A comparison of two regimens of vitamin D prophylaxis in elderly institutionalized subjects has been made. Sixty-six subjects received 2.5mg vitamin D2 by mouth in December 1982; a further group of 62 received the same dose in December 1982 and again in June 1983. Blood samples have been analysed for 25-hydroxyvitamin D2 [25(OH)D2] in 10 subjects from each group over a 12-month period. The serum 25(OH)D2 was maintained at normal concentrations for most of the year in the once-a-year dosage group but at the end of 12 months only 60% were fully protected. The twice-per-year regimen offered complete protection maintaining the serum 25(OH)D2 above the threshold associated with osteomalacia. It is concluded that a twice-yearly regimen of vitamin D supplementation is a practical method for prophylaxis in institutionalized elderly people.
25-Hydroxyvitamin D 2↗
Interferon production and sensitivity of rabbit corneal epithelial and stromal cells.
The induction of interferon and the ability of interferon to induce the antiviral state were studied using rabbit corneal epithelial and stromal cells which were cultured for fewer than five passages. Interferon titers in the range of 7000 units/ml were induced in epithelial cell cultures and 76,000 units/ml in stromal cell cultures treated with UV-inactivated bluetongue virus. The interferon induced was stable to pH 2.0 treatment and heating to 56 degrees C for 16 hr. Infection of epithelial and stromal cell cultures with various strains of herpes simplex virus type 1 showed that all strains tested replicated to equivalent titers in the respective cell types, and that no detectable interferon was induced in stromal cells and only trace amounts in epithelial cells. Exogenously supplied rabbit interferon induced the antiviral state in cultures of both cell types restricting the replication of not only encephalomyocarditis virus but also herpes simplex virus. Sixty to ninety units of rabbit interferon reduced HSV-1 virus replication by 50%. Human interferons had less than 27% of the antiviral activity in rabbit cells than they had in a human cell line. The data indicate that exogenously supplied interferon may act to reduce the severity of herpetic keratitis by directly inducing the antiviral state in corneal epithelial and stromal cells. However, interferon endogenously produced by rabbit corneal cells in response to HSV-1 infection probably plays a minor role in the pathogenesis of ocular HSV-1 infections.
Animals↗
The determination of effective antiviral doses using a computer program for sigmoid dose-response curves.
A computer program was designed to construct best fit sigmoid dose-response curves for determination of the dose required to reduce the yield of virus by 50%, effective antiviral dose (ED50). A single antiviral agent, 9-beta-D-arabinofuranosyladenine, was examined for effectiveness against four strains of herpes simplex virus type 1. The resulting ED50 values were compared with those obtained by probit analysis. The statistical parameters obtained from sigmoid curve fit program were utilized to evaluate statistical differences between ED50 values for resistant and sensitive virus strains and to evaluate the goodness-of-fit of the regression line to the data. In addition, using this analytical method, it was shown that a change in one experimental variable, i.e., multiplicity of infection, in the yield reduction assay significantly affected the apparent ED50 value. The computer program was easily utilized for analysis of data obtained from both plaque reduction and yield reduction assays and generated the parameters necessary for statistical comparison of relative antiviral activity of any antiviral agent.
Animals↗
Markedly enhanced production of gamma interferon in murine T lymphocytes treated with lentil lectin and the diterpene ester, mezerein.
Gamma interferon (IFN-gamma) was induced in murine splenocytes first stimulated to grow by concanavalin A (Con A) and subsequently treated for 3 h with the diterpene ester, mezerein (MZN) and then with lectin from Lens culinaris for 24 h. Yields as high as 60,000 u/ml were obtained in cells from either male or female, random-bred, white Swiss mice or inbred C67B1/6 mice. Antibody to Thy 1.2 surface antigen completely obliterated the mouse gamma interferon (MuIFN-gamma) response, whereas anti-Lyt 1.2 and anti-Lyt 2.2 each destroyed a portion of the lymphocyte population responsible for MuIFN-gamma production. Kinetic analysis of production and release showed that IFN was detectable in culture fluids within 4 h after treatment with very little IFN remaining cell-associated (less than 10%). A simple, rapid, and economical two-step purification procedure involving ammonium sulfate fractionation and yeast RNA affinity chromatography resulted in as much as 770-fold purification to achieve specific activities greater than 10(7) u/mg protein. The purified MuIFN-gamma was shown to be predominantly acid-labile, inactivated by sodium dodecyl sulfate (SDS), and neutralized by antiserum to MuIFN-gamma. Approximately 10% of the MuIFN-gamma was acid-stable and SDS-resistant, but was still neutralized by anti-MuIFN-gamma serum. Two molecular weight peaks of about 40 and 20 kD were demonstrated by SDS-polyacrylamide gel electrophoresis. Isoelectric focusing in polyacrylamide slab gels gave a relatively heterogeneous band of activity between pH 5.5 and 6.5. The mechanism by which the combination treatment described enhances MuIFN-gamma production so markedly remains unknown, but the degree of enhancement is greater than additive.
Animals↗
The effects of retinoids on the replication of herpes simplex virus type 1.
Topical treatment of primary herpetic keratitis with 0.25% retinoic acid was effective in significantly diminishing the severity of epithelial lesions in rabbits. Antiviral activity against herpes simplex virus type 1 was also demonstrated in cell culture. Retinoic acid treatment of virus particles for 24 hours had no effect on the infectivity of the virus. At effective antiviral concentrations in cell culture, retinoic acid had toxic action on two different cell lines as detected by an increase in cellular generation time or inhibition of DNA synthesis. Topical instillation of retinoic acid into the eyes of rabbits at the effective antiviral dose (0.25%) had no inhibitory effect on corneal wound closure but did reduce the rate of incorporation of thymidine into DNA by 27%. These studies suggest that although retinoic acid may inhibit the replication of herpes simplex virus type 1, it is difficult to distinguish antiviral effects from anticellular effects.
Animals↗
Dual task performance measures in geriatric studies.
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Aged↗
Leucine catabolism during the differentiation of 3T3-L1 cells. Expression of a mitochondrial enzyme system.
Leucine can be utilized efficiently as a precursor for lipid biosynthesis by adipose tissue, especially in the presence of glucose or glucose and insulin. During the differentiation of 3T3-L1 fibroblasts to adipocytes, the rate of lipid biosynthesis from L-[U-14C]leucine increases at least 30-fold and lipogenesis, with [U-14C] acetate as the precursor, increases by 10- to 15-fold. The specific activities of two mitochondrial dehydrogenases in the leucine oxidative pathway, the branched chain alpha-ketoacid dehydrogenase and isovaleryl-CoA dehydrogenase, as well as of leucine:alpha-ketoglutarate transaminase, increase at least 20-fold during the adipose conversion. Isovaleryl-CoA dehydrogenase was assayed in crude extracts using a specific fluorimetric method employing electron transfer flavoprotein as the electron acceptor for the flavoprotein dehydrogenase. The specific activity of 3-hydroxy-3-methylglutaryl-CoA lyase, the mitochondrial enzyme catalyzing the terminal reaction in the leucine degradation pathway, increases 4-fold during differentiation. The increases in the specific activities of the mitochondrial enzymes occur without a change in the specific activity of cytochrome oxidase, indicating that the increases do not simply reflect proliferation of mitochondria. The biosynthesis of at least 20 soluble mitochondrial polypeptides is enhanced during the adipose conversion of the fibroblasts as determined by polyacrylamide gel electrophoresis following incubation of the cells with [35S] methionine. The results provide a conservative estimate of the extent of changes in mitochondrial soluble proteins during the adipose conversion. They also establish that differentiated 3T3-L1 adipocytes metabolize leucine like mature adipose tissue and illustrate the roles of the branched chain alpha-ketoacid dehydrogenase and isovaleryl-CoA dehydrogenase in lipogenesis.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Affinity chromatography of acetylcholinesterase from Electrophorus electricus electroplax. Investigations on 9-aminoalkylacridine affinity ligands.
The neural enzyme 11-S acetylcholinesterase (E.C. 3.1.1.7) was purified by affinity chromatography from a trypsin digest of Electrophorus electricus electric organ. Unquaternized affinity ligands were reported which were comparable in efficacy to the routinely employed "quaternized acridine MAC ligand". A study was made of the quaternization reactions of various 9-aminoalkylacridines and 9-aminoacridine along with their relative binding affinities to acetylcholinesterase. Ease of synthesis in conjunction with the column performance of these unquaternized 9-aminoalkylacridine compounds made them the preferred affinity ligand in acetylcholinesterase chromatography. A new carbodiimide synthetic route for these unquaternized ligands was described.
Acetylcholinesterase↗
Induction in rainbow trout of an acute phase (C-reactive) protein by chemicals of environmental concern.
1. Rainbow trout, Salmo gairdneri, produce elevated amounts of a serum acute phase (C-reactive) protein (CRP) when administered a variety of chemicals of environmental importance. 2. Compounds administered in doses which induce the cytochrome(s) P450 catalytic enzymes in trout hepatic microsomes also induce serum CRP. 3. However, an interferon-inducing virus does not induce CRP. Interferon induction by the virus is not significantly inhibited by chemicals which induce trout cytochrome(s) P450. 4. Simultaneous administration of chemicals and virus or virus alone results in depression of P450 protein production and only minor induction of CRP. 5. Thus, as with mammals, a reciprocating relationship appears to exist between the hemeprotein monooxygenase and immune systems of this freshwater teleost, and C-reactive protein appears to fit the reciprocating scheme closer to the cytochromes P450 response.
Animals↗
Listeria monocytogenes prosthetic valve endocarditis.
Listeria monocytogenes is a rare cause of prosthetic valve endocarditis and in all of the four reported cases has occurred as a late complication. Bacteriologic cure of the infection has been obtained in all reported patients, using a standard regimen of either penicillin or penicillin and an aminoglycoside. The two deaths were associated with Starr-Edwards prostheses in the aortic position and have been attributed to embolic phenomena occurring after bacteriologic sterilization of the infected valve.
Aged↗
Reconstitution of plant nitrate reductase by Escherichia coli extracts and the molecular cloning of the chlA gene of Escherichia coli K12.
Extracts from Escherichia coli, wild type and chlB, chlC, chlD, chlE, and chlG, but not chlA mutants, were able to reconstitute the nitrate reductase activity in Nicotiana tabacum cnx68 and Hyoscyamus muticus MA-2 mutant extracts. Because cnx68 and MA-2 lack the molybdenum cofactor required for nitrate reductase activity, these results indicate that the functional chlA gene is essential to produce the molybdenum cofactor in E. coli. A clone containing a gene capable of complementing the chlA mutation SA493 was obtained on a large cosmid pJT1. A 1.9 kb BclI fragment subcloned from pJT1 in the vector plasmid pBR322 was shown to complement the chlA SA493 mutant when inserted in either of the two possible orientations. This suggested that the chlA gene was contained intact, including its own promoter, on the 1.9 kb BclI fragment.
Cloning, Molecular↗
The medico-legal implications of ultrasound.
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Diagnostic Errors↗
Antibiotics, sore throats and acute nephritis.
A study was carried out of 274 children in Scotland aged 0 to 13 years recorded as having had acute nephritis over a four-year period (1976-79). The medical records for 223 of the patients were examined and 79 cases of poststreptococcal nephritis were identified, giving an estimated incidence of 2.1 episodes per 100,000 children per year. Using a number of assumptions, the authors sought the answers to two important questions: What is the risk that glomerulonephritis will develop after sore throat/inflamed throat illness? Is this risk influenced by the prescribing of an antibiotic for the original illness?The risks of developing nephritis after an antibiotic-treated sore throat and after a non-antibiotic treated sore throat were assessed as being equivalent (1:13,000 and 1:17,000 respectively). Furthermore, it appears that, during his lifetime, a general practitioner has a chance of only one in six of seeing a child with post-streptococcal nephritis after a sore throat.
Acute Disease↗
Raised intraocular pressure-time for a think on referral procedure?
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Aged↗
Chemotherapy of herpetic keratitis induced by acyclovir-resistant strains of herpes simplex virus type 1.
The severity of herpetic keratitis induced by 9-(2-hydroxyethoxymethyl) guanine-resistant strains of herpes simplex virus was significantly reduced by cotherapy with 9-beta-D-arabinofuranosyladenine (ara-A) and 2-deoxycoformycin. Therapy with 5-trifluoromethyl-2'-deoxyuridine (F3TdR) significantly reduced the severity of keratitis induced by an acyclovir-resistant strain with a defective DNA polymerase. Therapy with 3 percent acyclovir ointment slightly reduced the number of herpetic lesions produced by either deoxypyrimidine kinase or DNA polymerase defective viruses, despite these viruses being 100 to 1000 times more resistant to acyclovir than the wildtype strain. Therapy with 3 percent ara-A ointment alone significantly reduced the severity of lesions produced by the wildtype herpes strain. Therapy with ara-A alone did not reduce the severity of disease induced by any of the acyclovir-resistant mutants. The sensitivity of the wildtype and mutant viruses to nucleoside analogs was confirmed by yield-reduction assays conducted with Vero cells. These studies indicate that cotherapy with ara-A and an adenosine deaminase inhibitor was a reasonable alternative therapy for keratitis due to mutants resistant to therapy with nucleoside analogs which require the virus-specified deoxypyrimidine kinase or DNA polymerase, while ara-A alone was not an effective alternative.
Acyclovir↗