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Biomedical subjects

M C Sullivan

Publications and source records attributed to M C Sullivan.

33 records · Page 2Linked to original sources
PubMed1991

Crystallization and preliminary crystallographic analysis of a novel nuclease from Serratia marcescens.

Crystals have been obtained of the extracellular endonuclease from the bacterial pathogen Serratia marcescens. This magnesium-dependent enzyme is equally active against single and double-stranded DNA, as well as RNA, without any apparent base preference. The Serratia nuclease is not homologous with staphylococcal nuclease, the only other broad specificity endonuclease for which a structure exists, nor is it homologous with other nucleases that have been solved by X-ray diffraction. The structure of this enzyme should, therefore, provide new information about this class of enzyme. At present we have succeeded in obtaining large, high quality crystals using ammonium sulfate. They crystallize in the orthorhombic space group P2(1)2(1)2(1), with cell dimensions a = 106.7 A, b = 74.5 A, c = 68.9 A, and diffract to beyond 2 A. Low-resolution native data sets have been recorded and a search is under way for heavy-atom derivatives.

Endodeoxyribonucleases↗
PubMed1983

Descending serotonergic, peptidergic and cholinergic pathways from the raphe nuclei: a multiple transmitter complex.

The localization of serotonergic, various peptidergic and possibly cholinergic neurons in the medullary raphe nuclei that project to the lumbosacral spinal cord have been studied using a retrograde transport method combined with immunocytochemical and histochemical techniques. Spinally projecting neurons stained for serotonin-like, substance P-like, enkephalin-like and thyrotropin-releasing hormone-like immunoreactivity and for the histochemical marker acetylcholinesterase were all observed in each of the raphe nuclei of the medulla, as well as in the adjacent ventrolateral reticular formation. The similar distributions of the descending serotonergic and peptidergic neurons in the raphe nuclei as well as quantitative data on their relative numbers suggest that a large fraction of raphe-spinal neurons contain serotonin co-existing with one or more peptides in the same cell.

Acetylcholine↗
PubMed1980

Genetic and functional analysis of tryptophan transport in Malpighian tubules of Drosophila.

Dissected Malpighian tubules from wild type and the eye color mutant white of Drosophila were compared with respect to their abilities to transport tryptophan and kynurenine into tubule cells. It was determined that mutation at white greatly impairs the ability of Malpighian tubule cells to take up tryptophan. Functional studies on the extracellular spaces and ultrastructural observations indicated no differences in these respects between wild type and white tubules. It is consistent with several observations that much of the tryptophan associated with white exists in the intercellular spaces. Furthermore, the uptake of tryptophan by the w+ system of wild type tubules is inhibited by the analogue 5-methyl-tryptophan. However, the incorporation of radioactive tryptophan into protein in tubule cells from wild type and white occurs at the same rates and is not affected by 5-methyl-tryptophan. Therefore, it is apparent that Malpighian tubules have a transport system that enables entry of tryptophan into a cellular pool and that this cellular pool is initially independent of the tryptophan pool used for protein synthesis. The mutant white lacks this transport system. From these studies and others it appears that compartmentalization of cellular pools may be brought about via the utilization of specific membrane transport systems.

Animals↗
PubMed1979

Purine transport by malpighian tubules of pteridine-deficient eye color mutants of Drosophila melanogaster.

Uptakes of guanine into Malpighian tubules of wild-type Drosophila and the eye color mutants white (w), brown (bw), and pink-peach (pp) have been compared. Tubules for each of these mutants are unable to concentrate guanine intracellularly. The transport of xanthine and riboflavin is also deficient in w tubules. The transport of guanosine, adenine, hypoxanthine, and guanosine monophosphate is similar in wild-type and white Malpighian tubules. These data and other information about these mutants make it likely that these pteridine-deficient eye color mutants do not produce pigments because of the inability to transport a pteridine precursor. This view supports the hypothesis that mutants which lack both pteridine and ommochromes do so because precursors to both classes of pigments share a common transport system.

Animals↗
PubMed1975

Transport defects as the physiological basis for eye color mutants of Drosophila melanogaster.

Kynurenine-H3 transport and conversion to 3-hydroxykynurenine were studied in organ culture using the Malpighian tubules and developing eyes from wild type and the eye color mutants w, st, ltd, ca, and cn of Drosophila melanogaster. Malpighian tubules from wild type have the ability to concentrate kynurenine and convert it to 3-hydroxykynurenine. The tubules from w, st, ltd, and ca are deficient in the ability to transport kynurenine, as are the eyes of the mutants w, st, and ltd. This defect in kynurenine transport provides a physiological explanation for the phenotypic properties of the mutants. The relationship of these measurements to previous observations on these eye color mutants is discussed and the transport defect hypothesis is consistently supported. We have concluded that several of the eye color mutants in Drosophila are transport mutants.

Animals↗
PubMed1973

Developmental and genetic studies on kynurenine hydroxylase from Drosophila melanogaster.

The level of kynurenine hydroxylase was measured throughout the development of wild type and the eye color mutants v, cn, st, ltd, cd, kar, w, ca, bri and p(P) of Drosophila melanogaster. In all cases except cn a bimodal distribution of enzyme activity during development was observed. Activity is initially detectable in second instar. A maximum is reached in early third instar. Activity declines prior to puparium formation. Shortly after pupation, activity rises dramatically to reach a maximum about five times the peak larval level. Maximum activity persists for a short time, and then falls sharply prior to emergence. No activity is detectable in cn, cn(3), or cn(35K). In pupae which have zero, one, two or three doses of the cn(+) allele, activity is proportional to the number of the + alleles. This provides further evidence that the cn locus contains the structural gene for kynurenine hydroxylase. Kynurenine hydroxylase is a useful gene product for studying the events of imaginal disc differentiation.

Alleles↗
PubMedDate not supplied

Transmitters of the raphe-spinal complex: immunocytochemical studies.

The localization of serotonergic and various peptidergic neurons in the medullary raphe nuclei that project to the lumbosacral spinal cord have been studied using a retrograde transport method combined with immunocytochemistry. Spinally projecting neurons stained for serotonin-like, substance P-like, enkephalin-like and thyrotropin-releasing hormone-like immunoreactivity were all observed in the raphe nuclei of the medulla, as well as in the adjacent ventrolateral reticular formation. The distribution of the descending serotonergic and peptidergic neurons in the raphe nuclei as well as quantitative data on their relative numbers suggest that a large fraction of raphe-spinal neurons contain serotonin co-existing with one or more peptides in the same cell.

Animals↗
PubMedDate not supplied

Maternal interaction patterns and preschool competence in high-risk children.

BACKGROUND: The influence of specific maternal interaction patterns as compensatory mechanisms in promoting development of medically high-risk children has been understudied. OBJECTIVES: To investigate the association of three maternal interaction patterns, maternal responsivity, involvement, and control style, with preschool competency in a medically heterogeneous sample. METHOD: Children (N= 184) and their mothers participating in a prospective longitudinal study were assessed in a laboratory protocol and home visit. The methods of measurement were maternal self-report, global rating scales, interview, and nationally standardized instruments. RESULTS: Evidence of a maternal compensatory mechanism was exhibited in mothers' higher involvement with their children who were born at high medical risk (F(1,183) = 6.26, p = .01). Mothers of the most competent children demonstrated higher maternal responsivity, involvement, and more appropriate control than mothers of children who were not as competent. In hierarchical regression models, the three maternal interaction patterns were significant predictors after perinatal risk and maternal education were controlled explaining 29-37% of the variance in child competence scores. CONCLUSION: These findings imply that differential child outcomes are associated with specific maternal interaction patterns. It suggests that a combination of diverse information revealed in specific maternal interaction pattern is needed to predict cognitive, linguistic, and problem-solving competencies. Future research should consider individual differences in mother-child interaction patterns in order to isolate their significance for optimal child development.

Adult↗
PubMedDate not supplied

Comparison of the pharmacodynamic activity of cefotaxime plus metronidazole with cefoxitin and ampicillin plus sulbactam.

STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic activity of three drug regimens: cefotaxime plus metronidazole, cefoxitin, and ampicillin-sulbactam against two organisms frequently isolated in intraabdominal infection, Escherichia coli and Bacteroides fragilis. DESIGN: Open-label, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: Subjects received the following regimens: (1) a single 1-g intravenous dose of cefotaxime plus a single 500-mg oral dose of metronidazole; (2) two intravenous doses of cefoxitin, 2 g each dose given every 6 hours; and (3) two intravenous doses of ampicillin-sulbactam, 3 g each dose given every 6 hours. MEASUREMENTS AND MAIN RESULTS: Serum bactericidal titers and drug concentrations were measured over a 12-hour period. The cefotaxime-metronidazole regimen showed superior activity against E. coli compared with ampicillin-sulbactam and cefoxitin. The mean areas under the bactericidal activity curve (AUBC) for the three regimens were 550.2, 68.7, and 48.9, respectively (p = 0.0001). There was no significant difference in AUBC among the three regimens for B. fragilis. Serum concentrations of cefotaxime remained above the minimum inhibitory concentration (MIC) for E. coli significantly longer than did concentrations of ampicillin-sulbactam and cefoxitin (p = 0.0002 and p = 0.0023, respectively). Serum concentrations of metronidazole were still at 9 times the MIC for B. fragilis at the end of the 12-hour dosing interval; for ampicillin-sulbactam and cefoxitin concentrations remained above the MIC for one-half and less than one-fourth, respectively, of the dosing interval (p < 0.0001). The ratio of AUC:MIC was also favorable for metronidazole (212.2) compared with 63.4 for ampicillin-sulbactam and 9.2 for cefoxitin. CONCLUSIONS: The combination of cefotaxime-metronidazole, even at the relatively low doses used in this study, provides coverage against gram-negative and anaerobic pathogens that is at least as effective as that of cefoxitin and ampicillin-sulbactam. In addition, its cost is considerably less expensive than that of the other regimens.

Administration, Oral↗
PubMedDate not supplied

Comparison of the pharmacokinetic and pharmacodynamic activity of piperacillin and mezlocillin.

STUDY OBJECTIVE: To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ). DESIGN: Open-label, randomized, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PATIENTS: Nine healthy volunteers. INTERVENTIONS: Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg. MEASUREMENTS AND MAIN RESULTS: Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2- to 3-fold higher peak serum bactericidal activity at the end of infusion and 4- to 5-fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g. CONCLUSION: Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.

Adult↗