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Biomedical subjects

D Valentino

Publications and source records attributed to D Valentino.

At least 19 recordsLinked to original sources
PubMed1992

Stereolithographic models for surgical planning: preliminary report.

Recent application of computer graphics, using standardized cephalometric analyses, have allowed the surgeon to visualize the predicted surgical outcome on the computer video monitor. Stereolithographic models constructed from digital image data (computed tomography and magnetic resonance) will allow the surgeon to view the external and internal anatomy prior to surgery. This article describes the development of such technology and reports its use in one case.

Adult↗
PubMed1991

Relating structure to function in vivo with tomographic imaging.

For the normal physiological responses of the brain or the pathophysiological changes that accompany disease states to be evaluated, it is necessary to compare data sets between different imaging modalities for individual subjects. Similarly, it is important to compare data between individuals both within and across imaging modalities for individual subjects. In a collaborative project with a number of university groups we have developed a system that allows for the within-subject alignment and registration of three-dimensional data sets obtained from different modalities for the same individual. This analysis takes into account the error induced by image acquisition, registration and alignment with regard to scaling, translation and rotation. A more difficult problem is the between-subject warping of individual brain anatomy to match that of another individual or of an idealized model. If the principles of morphometrics and homologous landmarks are applied, three-dimensional brain warping can provide this type of between-subject comparison. The results of accomplishing these two tasks is a system that allows data obtained in a given individual to be compared across structure and function, as obtained from magnetic resonance imaging (MRI) and from positron emission tomography (PET), respectively. It also allows comparison of the resultant information with averaged between-subject data from populations of normal individuals or patients with specific neurological disorders. This system provides the means by which to compare quantitative data between individuals in an objective and automated fashion.

Algorithms↗
PubMed1991

Region of interest issues: the relationship between structure and function in the brain.

The comparison of data sets from individual subjects between imaging modalities is necessary in order to evaluate the normal physiologic responses of the brain or the pathophysiological changes that accompany disease states. Similarly, it is critical to compare data between individuals both within and across imaging modalities. In a collaborative project with a number of university groups, we have developed a system that allows for the within-subject alignment and registration of three-dimensional data sets obtained from different modalities for the same individuals. These data make use of proposed criteria for the optimal solution to positron emission tomography image acquisition and analysis originally established through a series of international workshops. The analysis takes into account errors induced by image acquisition, registration, and alignment with regard to scaling, translation, and rotation. Using the principles of morphometrics and homologous landmarks, the between-subject warping of individual brain anatomy to match that of other individuals, groups or an idealized model can be obtained. Resultant information can provide averaged between-subject data for populations of normal individuals or patients with specific neurologic disorders. Such a system, provides the means by which to compare objectively quantitative data between individuals in a highly automated fashion.

Brain↗
PubMed1989

Comparison of 2048-line digital display formats and conventional radiographs: an ROC study.

Observer performance tests were conducted to compare the effects on diagnostic accuracy of digital hard copy and video display formats versus conventional radiographic film. Digital images were obtained by digitizing conventional chest radiographs to a 2048 x 2048 matrix with a laser film scanner. Three digital display formats were used: laser-printed digital film, a 2048-line video monitor without user interaction, and a 2048-line video monitor with user interaction. Thirty-one posteroanterior chest radiographs, determined by consensus of four thoracic radiologists to contain septal lines (n = 11), parenchymal nodules (n = 7), nodules and septal lines (n = 7), or neither abnormality (n = 6), were used for the study. Images were interpreted by four radiologists in four separate viewing sessions. Diagnostic accuracy was determined by receiver-operating characteristic analysis for each observer with each viewing technique. No statistical differences in diagnostic accuracy, determined by the area under the receiver-operating-characteristic curve, were found between the analog film, the digital film, and the two video digital display formats. This preliminary study suggests that 2048-line digital displays may be an acceptable alternative to the traditional lightbox viewing method for the perception of these two abnormalities commonly seen on chest radiographs.

Computer Systems↗
PubMed1987

"Streptomyces avermitilis" mutants defective in methylation of avermectins.

"Streptomyces avermitilis" mutants defective in the methylation of the avermectins have been isolated and characterized. Four mutant strains, CR-1, CR-2, CR-3, and CR-4, were unable to methylate the oxygen at C5 of the macrolide moiety and produced essentially only the avermectin B components. These four strains lack avermectin B2 O-methyltransferase (B2OMT) activity. Two mutant strains were unable to methylate the oleandrose moiety at the oxygens at C3' and C3'' and produced essentially only demethylavermectin components. One of these mutants, strain CR-5 (derived from wild-type "S. avermitilis"), produced demethylavermectin A and B components and possessed normal B2OMT levels. The other mutant, strain CR-6 (derived from strain CR-1, which lacks B2OMT activity), produced only demethylavermectin B components. Reaction of 3"-O-demethylavermectin B2a and S-adenosylmethionine with either cell extracts or purified B2OMT resulted in the methylation of the oxygen at C5 of the macrolide moiety and yielded only 3''-O-demethylavermectin A2a as the product. These experiments indicate that different enzymes are required for methylation of the macrolide (the oxygen at C5) and the oleandrose (oxygen at C3) and that methylation of the oleandrose occurs before attachment to the macrolide ring.

Adenosine↗
PubMed1986

Chronic desipramine attenuates morphine analgesia.

Two experiments were conducted to explore the effects of chronic antidepressant treatment on endogenous opioid systems. In the first study, mice received desipramine for 21 days, a regimen which down-regulates beta-adrenergic receptors [13]. Subsequently, hotplate jump latencies were measured after acute saline, morphine or naloxone, to test for dynamic changes in endogenous opioid systems. Chronic desipramine treatment resulted in a significant attenuation of morphine analgesia, but had no effect on latencies of saline and naloxone treated mice. In the second experiment, naltrexone or propranolol were given with desipramine for 21 days, in an attempt to block the development of subsensitivity to morphine. Naltrexone had no effect on desipramine attenuation of morphine analgesia. Propranolol given with desipramine slightly lowered jump latencies of acute saline controls, resulting in a significant analgetic effect of morphine. These data suggest that attenuation of morphine analgesia by chronic desipramine treatment may be mediated by actions on noradrenergic systems, rather than direct effects on opioid receptors.

Analgesics, Opioid↗
PubMed1986

Avermectin B2 O-methyltransferase activity in "Streptomyces avermitilis" mutants that produce increased amounts of the avermectins.

The level of activity of avermectin B O-methyltransferase, the enzyme which catalyzes the conversion of avermectin B components to avermectin A components, was analyzed in a series of "Streptomyces avermitilis" mutants selected for increased production of the avermectins. In all of the mutants, increased avermectin production was accompanied by increased avermectin B O-methyltransferase activity. Both the average specific activity and the maximum observed specific activity of avermectin B O-methyltransferase increased in direct proportion to avermectin production. The level of avermectin B O-methyltransferase alone did not determine the extent of conversion of avermectin B components to avermectin A components, since a constant ratio of B components to A components was maintained throughout the fermentation even though avermectin B O-methyltransferase specific activity varied three- to fivefold. These results indicate that avermectin B O-methyltransferase is not rate limiting. The correlation between avermectin B O-methyltransferase specific activity and avermectin production is compatible with the hypothesis that genes coding for successive steps in the same secondary metabolite biosynthetic pathway are coordinately regulated.

Bacterial Proteins↗
PubMed1986

Biosynthesis of the avermectins by Streptomyces avermitilis. Incorporation of labeled precursors.

The biosynthesis of the avermectins, a group of 16 membered macrolides with potent anthelmintic and insecticidal activity produced by Streptomyces avermitilis, was studied by supplying cultures with 14C and 13C precursors. [1-14C] and [2-14C]acetate and propionate were poor precursors of the avermectins and were instead rapidly oxidized to 14CO2. The S-methyl of methionine in contrast was incorporated extensively and equally into the three methoxyl groups of the avermectins. The carbon backbone of methionine was not a precursor of the avermectins. Feeding of [1-13C]glucose yielded avermectins labeled specifically in the C1' and C1" of the oleandrose moiety and in the aglycone moiety in carbons known to be derived from the methyl of acetate. Feeding [U-13C]glucose showed that the entire avermectin molecule is derived from glucose carbons.

Acetates↗
PubMed1985

Demethylavermectins. Biosynthesis, isolation and characterization.

Streptomyces avermitilis normally produces eight avermectins. Avermectin A components contain three methoxyl groups; two on the oleandrose disaccharide and one on the aglycone moiety at C5. Avermectin B components contain methoxyl groups only on the oleandrose disaccharide. Sinefungin inhibits methylation at all three sites. Addition of sinefungin to S. avermitilis Agly-1, a mutant which produces virtually only avermectin aglycone A components, alters the fermentation and causes an accumulation of avermectin aglycone B components. Addition of sinefungin to S. avermitilis 08, a high producing strain, results in accumulation of 8 new avermectins which lack methoxyl groups on the oleandrose moieties as well as the aglycone. These new avermectins were isolated and shown to possess anthelmintic and insecticidal activity.

Adenosine↗
PubMed1982

Escapability and generalization: effect on 'behavioral despair'.

Two experiments were conducted to investigate (1) whether 'behavioral despair' was related to inescapability of the warm swim and (2) whether 'behavioral despair' would generalize to a shock escape task. Results indicated that rats exhibited 'behavioral despair' independent of the escapability of the warm swim and that the phenomenon did not generalize to a shock escape task. Implications for the validity of the behavioral despair model was discussed.

Animals↗
PubMed1982

Mechanism of action of MK-401 against Fasciola hepatica: inhibition of phosphoglycerate kinase.

The effect of MK-401 (4-amino-6-trichloroethenyl 1,3-benzenedisulfonamide) on Fasciola hepatica phosphoglycerate kinase (EC 2.7.2.3) was investigated. MK-401 was a competitive inhibitor of both 3-phosphoglycerate and ATP and had a Ki of 0.29 mM. ATP, 1,3-diphosphoglycerate and MK-401 protected the Fasciola enzyme from inhibition by N-ethylmaleimide. Analogues of MK-401 with different substituents at the 6 position (R = Cl, CF3, C2 F3, C3 F7) were competitive inhibitors of both 3-phosphoglycerate and ATP and a good correlation between the Ki and in vivo activity of these analogues was observed.

Adenosine Triphosphate↗
PubMed1982

Purification, characterization and inhibition by MK-401 of Fasciola hepatica phosphoglyceromutase.

Phosphoglyceromutase (EC 2.7.5.3) of Fasciola hepatica was purified 1390-fold to homogeneity. The enzyme had a molecular weight of 120 000 and was a tetramer composed of identical 30 000 molecular weight subunits. The enzyme was 2,3-dephosphoglyceric acid dependent, possessed reactive sulfhydryl groups and was inhibited irreversibly by iodoacetamide, and N-ethylmaleimide and reversibly by p-chloromercuribenzoate and 5,5'-dithiobis(2-nitrobenzoic acid). Initial velocity studies suggest that reaction occurred via a sequential mechanism and that MK-401 was a competitive inhibitor versus both 3-phosphoglyceric acid and 2,3-diphosphoglyceric acid.

2,3-Diphosphoglycerate↗
PubMed1982

Dose-dependent pharmacokinetics and efficacy of MK-401 against old, and young-mature infections of Fasciola hepatica in the rat.

The dose-dependent pharmacokinetics and the efficacy of MK-401 (4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide) against old and young-mature infections of Fasciola hepatica were studied in experimentally infected rats. Fractionation of the host's blood after administration of 14C-MK-401 (0.77-15.8 mg/kg) showed that MK-401 was bound predominately to erythrocytes at doses below 4 mg/kg and at higher doses was distributed equally between the red cells and the plasma. Maximum amounts of MK-401 in the blood occurred 2 to 4 hr postadministration and were a hyperbolic function of dose, increasing almost linearly with dose up to 6 mg/kg and then beginning to saturate. Drug uptake by F. hepatica occurred at all doses and increased in direct proportion to the blood level. A single oral dose of MK-401 at 5 mg/kg was found to be highly effective (89%) against older infections (39-44 wk) but was virtually ineffective (1.5%) against younger flukes (9-16 wk). After administration of 14C-MK-401 at 5 mg/kg, drug concentrations in the blood and flukes of rats harboring older infections were significantly higher than those in the blood and flukes of rats with younger infections. Virtually identical differences in the blood level of MK-401 were observed in young and in old, noninfected rats after administration of 14C-MK-401 at 5 mg/kg. The increased efficacy of MK-401 against older infections of F. hepatica in the rat may be related to the age of the host rather than the parasite.

Age Factors↗
PubMed1981

Purification and characterization of phosphoglycerate kinase from Fasciola hepatica.

Phosphoglycerate kinase (EC 2.7.2.3) of Fasciola hepatica was purified 375-fold to homogeneity. The enzyme was monomeric, and had a molecular weight of 47 900 and a sedimentation coefficient of 3.0-3.5 S. The enzyme was composed of 397 amino acids and was relatively rich in sulfur amino acids containing 13 methionine and 2 cysteine residues per mole. The enzyme possessed a highly reactive essential sulfhydryl group and was inhibited irreversibly by iodoacetamide and N-ethylmaleimide and reversibly by p-chloromercuribenzoate and 5,5'-dithio-bis(2-nitrobenzoic acid). Initial velocity studies suggested that reaction occurred via a sequential mechanism. The Km values for 3-phosphoglycerate and ATP were 1.26 and 0.90 mM, respectively. ADP was a noncompetitive inhibitor with respect to both ATP and 3-phosphoglycerate.

Amino Acids↗