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Biomedical subjects

S Sullivan

Publications and source records attributed to S Sullivan.

At least 19 recordsLinked to original sources
PubMed1992

Trace quantitation of 4-hydroxy-2-nonenal in biological samples as its oxime-bis-tert.-butyldimethylsilyl derivative using 3-hydroxynonanal as an internal standard.

A gas chromatographic-mass spectrometric method for the determination of the lipid aldehyde 4-hydroxy-2-nonenal (4HNE) in trace quantities is described. The method utilizes the reaction of aldehydes with hydroxylamine leading to the formation of the oxime derivative. The aldehydes are recovered by octadecylsilyl solid-phase extraction and converted to the bis-tert.-butyldimethylsilyl derivatives for analysis using electron ionization. A novel 4HNE analogue, 3-hydroxynonanal, has been synthesized and is used as an internal standard. A limit of detection of approximately 1 pmol of 4 HNE in preparations of approximately 2.10(6) cells or 0.5 ml of whole blood, plasma or serum was observed. Standard addition analysis indicates that the method is accurate at these levels. Replicate analysis of the National Institutes of Standards and Technology Standard Reference Material SRM 909 indicates an average in-run precision of 8.1% and a between-run precision of 13.5% at an average concentration of 82.1 pmol/ml of reconstituted material.

Aldehydes↗
PubMed1992

Ribozymes as anti-HIV-1 therapeutic agents: principles, applications, and problems.

An emerging strategy in the treatment of viral infections is the use of antisense DNA or RNA to pair with, and block expression of viral transcripts. RNA, in addition to being an informational molecule, can also possess enzymatic activity. Thus, by combining anti-sense and enzymatic functions into a single transcript, it is now possible to design catalytic RNAs, or ribozymes, which can specifically pair with virtually any viral RNA, and cleave the phosphodiester backbone at a specified location, thereby functionally inactivating the viral RNA. In carrying out this cleavage, the ribozyme is not itself altered, and is thus capable of recycling and cleaving other molecules, making it a true enzyme. There are several different catalytic motifs which possess enzymatic activity, and each one of these can be incorporated into an enzymatic antisense with site-specific cleavage capabilities. By focusing on one type of catalytic motif, the hammerhead, we describe the principles behind the development of ribozymes as transacting, site-specific ribonucleases, several applications of ribozymes in functional destruction of target RNAs, as well as several of the problems confronting their use. We also describe a liposome delivery system which facilitates intracellular inclusion of ribozymes, and may provide a means for therapeutic delivery of ribozymes to HIV-1 infected cells.

Animals↗
PubMed1991

A manual sequencing method for identification of phosphorylated amino acids in phosphopeptides.

We describe a simple and inexpensive method for determining the location of phosphoamino acids in an isolated phosphopeptide. Phosphopeptides are immobilized on arylamine membrane discs using water-soluble carbodiimide, and the immobilized peptides are subjected to manual Edman degradation. The use of a membrane disc resulted in excellent recovery (65 to 80%) of radiolabeled phosphate following Edman degradation. Furthermore, interference from carryover and peptide washout is reduced to a minimum. The methodology should therefore be able to generate reliable results when used to analyze phosphopeptides that contain multiple phosphorylation sites. In addition to its advantage in sensitivity, the manual sequencing method is easy to perform and does not entail any sophisticated instrumentation.

Amino Acid Sequence↗
PubMed1991

Exploring the use of antisense, enzymatic RNA molecules (ribozymes) as therapeutic agents.

Antisense catalytic RNAs that specifically base-pair with and cleave target RNA sequences have potential for use as therapeutic agents against viral as well as endogenous gene expression. With the ultimate goal of developing anti-human immunodeficiency virus type 1 (HIV-1) ribozymes for therapeutic use, we have been exploring ways to improve upon the functional activity of ribozymes in living cells. This is being done by the systematic exploration of parameters that affect antisense, and hence ribozyme, function. These include target accessibility, stability of the catalyst, methods for delivery, and intracellular localization of the ribozyme. In addition, we have been examining the kinetic consequences of having extra, nontargeted sequences appended to the ribozyme flanking sequences. Perhaps the single most important consideration for ribozyme effectiveness in an intracellular environment is the accessibility of the target RNA for cleavage. By exploiting the mechanisms by which naturally occurring antisense RNAs interact with their target sequences, we hope to be able to address this problem of targeting and fully capitalize upon the potential of ribozymes as therapeutic agents.

Antiviral Agents↗
PubMed1990

Cytometric and histopathologic features of tumors detected in a randomized mammography screening program: correlation and relative prognostic influence.

Cytometric determination of S-phase fraction and ploidy type was performed on 430 tumors detected within a randomized trial of mammographic screening. The results were compared to several histopathologic features. A high S-phase fraction was estimated in tumors with a high grade of malignancy and other histopathologic findings related to rapid tumor progression, including lack of tubule formation, a high mitotic index, marked nuclear pleomorphism, multifocal cancer growth, tumor emboli in lymphatic and blood vessels, tumor necrosis, and inflammatory reaction. DNA aneuploidy was correlated with a high malignancy grade, frequent mitoses, a high degree of nuclear pleomorphism, vascular invasion, necrosis, and the presence of noninvasive ductal carcinoma. Both cytometric variables were inversely related to the degree of elastosis. Positive nodes, large tumor size, DNA aneuploidy, a high S-phase fraction, high grade of malignancy, lack of tubule formation, as well as high mitotic index and pleomorphism, presence of multifocal cancer, and vascular invasion, predicted a significantly shorter distant recurrence-free interval after a median follow-up time of 46.6 months. Elastosis and the presence of estrogen and progesterone receptors indicated favorable prognosis. In the multivariate analysis, only lymph node status, tumor size, S-phase fraction, and multifocal growth pattern had independent prognostic value.

Adult↗
PubMed1990

Conditioned flavor preferences in young children.

In this experiment 11 children participated in a series of 8 pairs of conditioning trials in order to investigate the hypothesis that children could form conditioned flavor preferences based on caloric density. Unfamiliar drink flavors were used in these trials, and the drinks were either high in caloric density (155 kcal/150 ml) or low (less than 5 kcal/150 ml). Caloric density was altered by the addition of low glucose maltodextrin. Each child always had the same caloric density/flavor pairing throughout the conditioning trials. Each trial pair included one high and one low density preload, followed by ad lib consumption. These conditioning trials substituted for the children's regularly scheduled morning snack four days per week, one trial per day. Conditioning trials were given as a series of two-part snacks, consisting of fixed volumes of initially unfamiliar drinks, followed by the opportunity to eat a variety of foods ad lib. Two measures, obtained before and after conditioning, provided evidence for the formation of conditioned flavor preferences: 1) preference assessments, and 2) two-flavor choice tests. In addition, the ad lib consumption data indicated that the children were responsive to the caloric density manipulation, by consistently eating more following the low than the high density drink. The potential contribution of such acquired flavor preferences to the reduction of neophobia is discussed.

Child Development↗
PubMed1990

Analysis of dose response of trinitrochlorobenzene contact hypersensitivity induction in mice: pretreatment with cyclophosphamide reveals an optimal sensitizing dose.

A detailed dose-response curve has been established for induction of contact hypersensitivity (CH) in mice with trinitrochlorobenzene (TNCB). It was determined that in BALB/c, CBA/J, and C57BL/6 mice, the dose required to sensitize via epicutaneous application was between 1 and 10 micrograms TNCB. When doses of hapten of 200 micrograms or greater were painted on abdominal skin, CH responses were induced which were only marginally greater than responses induced by sensitizing doses of hapten in the 10-50-micrograms range, implying that no further dose-response relationship exists beyond 50 micrograms of hapten. However, in companion experiments, in which panels of mice were pretreated with cyclophosphamide, it was determined that sensitizing doses of hapten in excess of 50 micrograms induced both CH and concomitant induction of down-regulation of CH. Thus, at 200 micrograms or higher doses of TNCB, CH responses of cyclophosphamide pretreated mice were invariably more intense than in their untreated, hapten-painted cohorts. In the animals pretreated with cyclophosphamide, it was possible to see that a dose-response relationship continued to exist between the amount of epicutaneously applied hapten over a 200 micrograms to 14 mg range and the intensity of the CH induced. We conclude that the optimal dose for immunizing mice epicutaneously with TNCB is between 10 and 50 micrograms. This is considered optimal since animals sensitized in this manner display no evidence of concomitant down-regulation of their CH responses.

Animals↗
PubMed1989

Cytometric characterization and clinical course of breast cancer diagnosed in a population-based screening program.

A randomized controlled trial evaluating mammographic screening was started in two Swedish counties in 1977. In one of these, Ostergötland county, the authors performed static cytofluorometry on 161 cancers detected at the second and third screening rounds, 50 interval cancers, and 219 cancers appearing in the nonscreened control group during the same time period. The median follow-up time was 42 months. No difference in mean S-phase was found between screening and control group cancers, but interval cancers, appearing between two screenings, had increased mean S-phase levels (P = 0.01) compared to both of the other groups. A high S-phase fraction was associated with distant recurrence in both node-negative and node-positive tumors. Aneuploid tumors were more often found in the control group (67%) and among interval cancers (72%) than among screening detected cancers (55%, P = 0.02). In Cox's multivariate analysis, including all patients, the lymph node status, tumor size, estrogen receptor content, and S-phase all contributed independent prognostic information about the clinical course. DNA ploidy predicted the outcome in simple but not in multivariate Cox's analysis. When analyzing screening-detected cancers separately, only the S-phase significantly predicted distant recurrence in multivariate analysis. In tumors with local recurrence, a high S-phase implicated an increased, although not statistically significant, risk for distant recurrence. Survival with metastatic disease was significantly influenced by the S-phase level (P = 0.002). The authors conclude that S-phase fraction provides valuable kinetic information related to the clinical outcome for all stages of the disease and serves as a prognostic factor in screened populations, which have tumors predominantly in early stages.

Adult↗
PubMed1989

Familial gigantiform cementoma: classification and presentation of a large pedigree.

Very few cases of gigantiform cementoma have been reported, and those associated with a positive family history are especially rare. Confusion exists about the relationship of gigantiform cementoma to florid osseous dysplasia, cementifying fibroma, and diffuse chronic sclerosing osteomyelitis. It has been unclear whether gigantiform cementoma should be accorded the status of a separate entity. In this article, we report our findings on a family that, over five generations, has exhibited clinical, radiographic, and/or histologic findings consistent with the designation familial gigantiform cementoma. This pedigree consists of 55 members. Significant heterogeneity in expression of this trait was noted. The pattern of occurrence of the trait is consistent with an autosomal dominant mode of inheritance with variable expressivity of the phenotype. We suggest that familial gigantiform cementoma should be recognized as a separate entity.

Cementoma↗
PubMed1989

Children's food intake following drinks sweetened with sucrose or aspartame: time course effects.

In two experiments, 2-5-year-old children's responsiveness to caloric density cues was examined. In a preloading protocol, consumption of fixed volumes of drinks (205 ml in Experiment 1; 150 ml in Experiment 2), sweetened with sucrose, aspartame, aspartame plus low glucose maltodextrin, or a water control, was followed by ad lib consumption from among a variety of foods. Caloric drinks had about 90 kcal in Experiment 1, 65 kcal in Experiment 2. The delay interval between the preload and the ad lib consumption was 0, 30 or 60 minutes. In Experiment 1, 24 4- and 5-year-old children participated in only one delay interval, while in Experiment 2, all 20 2- and 3-year-old children were seen in all conditions. Results revealed evidence of caloric compensation, but no evidence of preload x time delay interaction. In both experiments, aspartame also produced a significant suppression of intake relative to water, primarily due to the pattern at 30 min following the preload. Across conditions, the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks, providing evidence for postingestive effects. In Experiment 1, suppression of intake was related to the children's preferences for the foods, not to macronutrient content; consumption of nonpreferred foods was most suppressed. Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake, and this common feeding practice may also reduce dietary variety.

Aspartame↗
PubMed1989

Conditioned meal initiation in young children.

In two experiments the conditioning of meal initiation was investigated. Preschool children ate snacks repeatedly in the presence of visual and auditory cues (CS+). On other days, other visual and auditory cues (CS-) were presented in the absence of food. In the second experiment, location also served as a CS. To test for conditioned meal initiation, children were first fed a snack to ensure that they were sated. Immediately following this, on different days, food was presented in the presence of the CS+ or the CS- cues. Data on latency to eating and total consumption revealed evidence for conditioning, at least for children who could correctly identify which cues had and had not been paired with the presentation of food.

Child Behavior↗
PubMed1988

Gastrointestinal gas.

Complaints related to gastrointestinal gas are commonly encountered in clinical practice. Various therapies have been proposed, yet none has appeared to be extremely effective. A review of the literature revealed little hard evidence to support the use of simethicone, pancreatic enzymes, anticholinergic agents or antibiotics. Evidence supporting the use of prokinetic agents has been the strongest, and there may be a pathophysiologic basis for the use of these agents if the complaints are related to abnormal intestinal motility. The use of activated charcoal for adsorbing intestinal gas has been effective in healthy subjects but has not been properly investigated in patients with gas complaints. Dietary modification may be beneficial in certain cases. Additional controlled trials are necessary to clarify the issues in the treatment of this common problem.

Diet↗
PubMed1988

The effect of four narcotics on cholecystokinin octapeptide stimulated gallbladder contraction.

In an attempt to find the ideal analgesic to treat biliary tract pain we compared the effects of saline and equianalgesic doses of morphine, pentazocine, pethidine, and butorphanol on CCK-OP stimulated gallbladder emptying in healthy volunteers. Morphine produced a profound delay in gallbladder emptying while the other narcotics produced a significant delay in comparison to saline, but less than morphine. None of the drugs affected common bile duct diameter, bilirubin, liver enzymes or amylase. We recommend avoiding the use of morphine in the treatment of biliary and pancreatic pain, but although pethidine, pentazocine and butorphanol may be potentially detrimental we could find no definite superiority of one versus the others.

Adolescent↗
PubMed1988

Tools to measure sensory appeal of menus planned for children.

The Menu Variety Checklist and Score Sheet is a tool to facilitate evaluation of sensory appeal. Comparisons made across evaluators and across menus show it to be more reliable and more readily diagnostic than subjective summary ratings. Although further research and development are needed to make it more precise and test its criterion validity, the checklist has sufficient advantages to make it a useful starting place or backup tool in research and clinical applications.

Child↗
PubMed1987

Polymorphic DNA haplotypes at the human phenylalanine hydroxylase locus and their relationship with phenylketonuria.

Eight polymorphic restriction enzyme sites at the phenylalanine hydroxylase (PAH) locus were analyzed from the parental chromosomes in 33 Danish nuclear families with at least one phenylketonuric (PKU) child. Determination of haplotypes of 66 normal chromosomes and 66 chromosomes bearing mutant allele(s) demonstrated that there are at least two haplotypes which occur predominantly on PKU chromosomes and rarely otherwise. Overall, the relative frequencies of the various haplotypes are significantly different on PKU- and normal-allele bearing chromosomes, even though there is no predominantly occurring unique haplotype which can characterize the PKU chromosomes. In addition, no significant association (linkage disequilibrium) between any single polymorphic site and the mutant allele(s) was observed. The results suggest that either the phenylketonuric mutation was very ancient so that the polymorphic sites and the mutation have reached linkage equilibrium or the mutant allele(s) are the results of multiple mutations in the phenylalanine hydroxylase gene in man. Furthermore, a crude relationship between standardized linkage disequilibria and physical map distances of the polymorphic sites indicates that there is no apparent recombination hot-spot in the human phenylalanine hydroxylase gene, since the recombination rate within the locus appears to be uniform and likely to be occurring at a rate similar to that within the HLA gene cluster. The limitations of this later analysis are discussed in view of the sampling errors of disequilibrium measure used, and the potential utility of the PAH haplotypes for prenatal diagnosis and detection of PKU carriers is established.

Alleles↗