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Biomedical subjects

J A Nelson

Publications and source records attributed to J A Nelson.

At least 145 records · Page 8Linked to original sources
PubMed1993

Correlates of physical activity at home in Mexican-American and Anglo-American preschool children.

Twenty-two potential correlates of children's physical activity were examined. Two hundred and one Mexican-American and 146 Anglo-American families with 4-year-old children were studied. Children's physical activity was directly observed in the evening at home on 4 visits for 1 hr each time. Anglo-American children and male children were found to be more active. Demographic variables explained 11% of the variance in children's physical activity. After adjusting for demographics, 3 children's variables and 6 social-family variables did not account for significantly more variance. Five environmental variables accounted for 11% additional variance. Variables observed concurrently with physical activity, such as time spent outdoors and prompts to be active, were highly associated with children's physical activity.

Child Behavior↗
PubMed1993

Animal model of portal hypertension with observations regarding the relationship between portal flow and pressure.

RATIONALE AND OBJECTIVES: The feasibility of producing acute portal hypertension in a porcine model was evaluated to test the relationship between portosystemic shunt flow and portal pressure. METHODS: Percutaneous transhepatic cannulation of the portal vein and cutdown of a systemic vein was accomplished in anesthetized pigs. The portal system was subsequently embolized with polyvinyl alcohol (Ivalon) particles. Portosystemic shunting was performed with the assistance of a centrifugal pump. RESULTS: Portal hypertension could be routinely produced, and portosystemic shunting was successfully studied in three of four animals. Linear changes in shunt flow led to exponential pressure changes. CONCLUSIONS: This animal model provides a representation of acute portal hypertension that provides useful data regarding the compliance of the portal system and illustrates the pressure/flow relationship.

Animals↗
PubMed1993

Pharmaceutical properties, biodistribution, and imaging characteristics of manganese-mesoporphyrin. A potential hepatobiliary contrast agent for magnetic resonance imaging.

OBJECTIVES: Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was investigated for its pharmaceutical properties and magnetic resonance imaging characteristics as a potential hepatobiliary contrast agent. METHODS: Solubility, partition coefficient, plasma binding, proton relaxation enhancement, biodistribution, biliary excretion, liver extraction ratio, and liver enhancement were measured in various in-vitro and in-vivo systems. RESULTS: Mn-mesoporphyrin was soluble and stable at moderate alkaline pH in phosphate buffer. The octanol/water coefficient was 25.98, and the compound was highly protein bound. R1 for water and plasma were 1.94 and 2.35 L/mmol sec, respectively. R1 in liver was calculated to be 15.72 L/mmol sec. Biodistribution studies in rats and mice confirmed hepatotrophic properties and biliary excretion was 65% over 24 hours. First pass liver uptake was 15%. Magnetic resonance imaging studies showed persistent liver enhancement at 0.05 mmol/kg. CONCLUSION: Mn-mesoporphyrin is a lipophilic compound that shows potential as a hepatobiliary magnetic resonance contrast agent.

Animals↗
PubMed1993

Antibody profiles to the group B streptococcal beta antigen in maternal and infant paired sera.

Antibody profiles to the purified beta antigen of the c protein of group B streptococci (GBS) were studied by ELISA and Western immunoblot (WB). The sera from 139 parturient women colonized with GBS, 35 non-colonized parturients and their newborn infants were studied by ELISA; WB was done on 76 maternal and 26 infant sera. Enzyme-labeled anti-IgA (alpha), -IgG (gamma), -IgM (mu), or -IgG (H&L) were used as secondary antibodies. A high prevalence of antibody to the beta antigen was observed by both ELISA and WB among parturient women and their newborns. IgG (H&L) ELISA titers > or = 200 were found in 84% and > or = 800 in 31% of the maternal sera. A significantly higher percentage of women colonized than those non-colonized with GBS had IgG (gamma) titers > or = 800. A significantly higher percentage of women colonized with c protein-positive than c-negative strains of GBS had IgG (H&L) titers > or = 3200. Twelve of 27 women with IgM antibody to the beta antigen also had IgG (gamma) titers > or = 800 and were, in addition, colonized with GBS. Multiple molecular forms of the antigen from 25 to 140 kDa were blotted by the maternal and infant sera. Concordance in the IgG but not in IgA or IgM antibody profiles of maternal and infant paired sera was observed in the overall blotting patterns and ELISA titers. The same titer as the mother was found in 55% of the infant sera and within one dilution in 97%. This suggests active transfer of IgG antibody to the beta antigen across the placenta from mother to baby.

Antibodies, Bacterial↗
PubMed1993

In vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents.

The in vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents was investigated. The antimicrobial agents evaluated included ceftizoxime, FK037, cefotaxime, dirithromycin, clarithromycin and its metabolite 14-hydroxy-clarithromycin, erythromycin, doxycycline, amoxicillin, ciprofloxacin, and ofloxacin. Isolates of B. burgdorferi tested included two reference strains (B31 and ATCC 53899), six isolates from the midwestern United States, and three from Europe. A broth macrodilution method was used to determine MICs and MBCs. B. burgdorferi was inhibited by < or = 0.5 micrograms of each of the agents except the quinolones per ml. The MBCs for 90% of strains tested of ceftizoxime, FK037, clarithromycin, 14-OH clarithromycin, and dirithromycin (< or = 1.0 microgram of each per ml) were superior to those of amoxicillin (2.0 micrograms/ml) and doxycycline (4.0 micrograms/ml). Further in vivo studies are warranted to determine whether these agents may be efficacious in the treatment of Lyme borreliosis.

Anti-Bacterial Agents↗
PubMed1993

Human cytomegalovirus IE86 protein interacts with promoter-bound TATA-binding protein via a specific region distinct from the autorepression domain.

The major immediate-early gene of human cytomegalovirus encodes several isoforms of an immediate-early protein which has distinct transcriptional regulatory properties. The IE86 isoform autorepresses the major immediate-early promoter by directly binding the cis repression signal element located between the TATA box and the mRNA cap site. In addition to this activity, IE86 stimulates other viral and cellular promoters. One mechanism by which eukaryotic regulatory proteins are thought to stimulate transcription is by contacting one or more general transcription factors. We show that the IE86 protein physically interacts with the DNA-binding subunit (TATA-binding protein) human transcription factor IID via the TATA-binding protein-contacting domain in the N terminus of IE86. In a mobility shift assay, IE86 was also observed to stabilize the binding of TATA-binding protein to promoter DNA. The domains within IE86 responsible for mediating transactivation and repression functioned independently. These experiments thus demonstrate the elegant ability of human cytomegalovirus to join different protein domains to produce distinct multifunctional proteins.

Base Sequence↗
PubMed1993

Site-specific inhibition of RNA polymerase II preinitiation complex assembly by human cytomegalovirus IE86 protein.

The human cytomegalovirus major immediate-early gene encodes several protein isoforms which autoregulate the major immediate-early promoter (MIEP). One of these isoforms, the IE86 protein (UL122, IE2), is a DNA-binding protein that represses the MIEP through its cognate recognition sequence (designated the cis repression signal [crs]) located between the TATA box and the initiation site of transcription. Purified recombinant IE86 protein was shown to repress MIEP transcription in vitro, in a cis-acting mediated pathway, with nuclear extracts from HeLa S3, U373-MG, and primary human foreskin fibroblast cells. Repression of the MIEP by IE86 was shown by two criteria to be dependent on the direct interaction of IE86 with the crs element. Core promoter constructs containing essentially the MIEP TATA box and crs element were also specifically repressed by IE86 but not by a mutant IE86 protein, indicating the general transcription machinery as the target for IE86 repression. Kinetic and template commitment experiments demonstrated that IE86 affects preinitiation complex formation but not the rate of reinitiation. Sarkosyl inhibition experiments further revealed that IE86 was unable to effect repression by either disassembling or preventing the elongation of a preexisting transcription complex. Further, the ability of IE86 to interact with the DNA-binding subunit of TFIID was shown not to be required for repression. These functional protein-DNA and protein-protein interaction experiments demonstrate that IE86 specifically interferes with the assembly of RNA polymerase II preinitiation complexes. The biological significance of these results and the precise mechanism by which IE86 represses transcription are discussed.

Cell Nucleus↗
PubMed1993

Direct interaction of the human cytomegalovirus IE86 protein with the cis repression signal does not preclude TBP from binding to the TATA box.

The human cytomegalovirus major immediate-early gene encodes several protein isoforms which autoregulate the major immediate-early promoter (MIEP). One of these isoforms, the IE86 protein, represses the MIEP through a DNA sequence located between the TATA box and the transcription initiation site, designated the cis repression signal (crs). Through mutational analysis, amino acid domains within IE86 responsible for binding the crs element were located at the C terminus. Mutation of the putative zinc finger domain, which precluded IE86 from binding DNA, converted the protein from a repressor of MIEP transcription into an activator. DNase I protection analysis demonstrated that the IE86 footprint overlapped the sequence protected by the TATA-binding protein (TBP). Investigation of whether IE86 was able to displace TBP from DNA revealed that both proteins could bind DNA simultaneously. However, higher concentrations of IE86 were required to obtain protection of the crs element in the presence of prebound TBP. Similarly, higher concentrations of TBP were required to obtain protection in the presence of prebound IE86. These observations indicate that steric hinderance impairs but does not prevent both proteins from binding DNA synchronously.

Base Sequence↗
PubMed1993

Seven-day recall and other physical activity self-reports in children and adolescents.

There is need to develop low cost, practical, and accurate measures of physical activity in children and adolescents, and self-report is a promising methodology for children that is applicable for large studies. The purpose of the present study was to assess the reliability and validity of several self-reports of physical activity. Subjects were 36 fifth-, 36 eighth-, and 30 eleventh-grade male and female students. The test-retest reliabilities were r = 0.77 for the 7-d recall interview, r = 0.81 for the Godin-Shephard self-administered survey, and r = 0.93 for a simple activity rating. For the former two measures, reliability improved with age but was significant at all ages, and for the last measure there were no age effects. Memory skills and obesity status were not related to the reliability of recall, but males were more reliable reporters than females. Validity of the 7-d recall was determined by comparing heart rate monitoring records with recalls of very hard activities on the same day. A correlation of 0.53 (P < 0.001) for the total group supported the validity of the reports. Validity improved with age, but validity coefficients were significant in all age groups. These data indicate that physical activity recalls of children as young as the fifth grade are of adequate reliability and validity to use in research on physical activity in children.

Adolescent↗
PubMed1993

Measurements of acoustic impedance at the input to the occluded ear canal.

Multi-frequency (multi-component) acoustic impedance measurements may evolve into a sensitive technique for the remote detection of aural pathologies. Such data are also relevant to models used in hearing aid design and could be an asset to the hearing aid prescription and fitting process. This report describes the development and use of a broad-band procedure which acquires impedance data in 20 Hz intervals and describes a comparison of data collected at two sites by different investigators. Mean data were in excellent agreement, and an explanation for a single case of extreme normal variability is presented.

Acoustic Impedance Tests↗
PubMed1993

Vascular volume expansion and thermally induced asthma.

To determine whether a relationship exists between intravenous infusion of isotonic fluid and reactivity to hyperpnoea, eight normal and eight asthmatic subjects underwent rapid intravascular administration of approximately 2 l of warm normal saline, by itself and before and after hyperventilation of cold air. In the asthmatic subjects, saline infusion mirrored the obstruction seen with hyperventilation; whereas, in normal subjects saline produced more bronchial narrowing than hyperventilation. When the two stimuli were given together, the timing of the infusion altered the asthmatic subjects' responses. Giving fluid early in the hyperventilation challenge blunted obstruction, whereas giving it later amplified the airway narrowing. Similar findings, but on a smaller scale, occurred in normal subjects. These data demonstrate that sudden elevations in intrathoracic vascular volume with warm saline produce airway obstruction that is quantitatively similar to that seen with hyperventilation in asthmatic individuals. They also demonstrate that these two stimuli interact together in such a manner that a common mechanism may exist to account for the decrease in airflow.

Adult↗
PubMed1992

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗
PubMed1992

Mechanisms of resistance to 6-thioguanine in a murine pancreatic tumor.

PANC02 is a unique experimental animal tumor that fails to respond significantly to any known clinically active antitumor agent. In this regard, the murine ductal adenocarcinoma resembles its human counterpart. To study the mechanism for its intrinsic resistance to 6-thioguanine (TG), we compared the metabolism of the drug in PANC02 and a reference, TG-sensitive adenocarcinoma, CA-755. In comparison with CA-755, PANC02 cells were approximately 6 times less sensitive to TG and CHO cells were 80 times less sensitive in tissue culture. Nevertheless, the incorporation of TG into the DNA of these three cell lines was approximately equal at the lowest concentrations capable of reducing cloning efficiency by 50%, i.e., 3.0-3.8 pmol (dthioGMP)/nmol (dGMP). In mice bearing bilateral implants of CA-755 and PANC02, only CA-755 responded to TG treatment. At various doses used on various schedules, the incorporation of TG into CA-755 DNA readily achieved that observed to be cytotoxic to the cells in vitro, whereas the incorporation into the DNA of PANC02 tumor cells did not. Although the biochemical basis for the poor incorporation of TG into the DNA of PANC02 in vivo is not known, this factor appears to explain the refractoriness of PANC02 as compared with CA-755 to this antitumor antimetabolite.

Adenocarcinoma↗
PubMed1992

Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02.

PANC02 is a ductal adenocarcinoma of the pancreas that is resistant to every known class of clinically active antitumor agent. To study the mechanism(s) underlying the intrinsic drug resistance of this tumor, a mammary adenocarcinoma (CA-755) that also grows in C57/BL mice and is known to be drug sensitive was used for comparison. PANC02 resistance and CA-755 sensitivity to several antitumor agents and to X-ray therapy was confirmed in mice, and PANC02 also demonstrated relative resistance in tissue culture. Relative to Chinese hamster ovary (CHO) and CA-755 cells, PANC02 did not appear to show a higher rate of mutation to drug resistance in culture as based on the 6-thioguanine resistance marker. Although P-glycoprotein characteristic of the multidrug resistance (MDR) phenomenon could be demonstrated at the mRNA level using a sensitive RNAse protection assay, the level of expression found was several orders of magnitude lower than that observed in phenotypic MDR cell lines. Furthermore, quinidine failed to increase the sensitivity of PANC02 cells to Adriamycin under conditions that clearly potentiated the toxicity of the drug to a CHO cell line exhibiting classic MDR traits. The heterogeneity in the distribution of drugs was inferred as being significantly greater in PANC02 versus CA-755 cells in vivo as based on measurements of within-animal, within-tumor variance in the distribution of the marker compounds inulin and antipyrine. Although it may not be the only mechanism involved, this greater intratumor heterogeneity in drug distribution could theoretically play a major role in the intrinsic drug resistance of PANC02 in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Plasmodium falciparum: cytoadherence of malaria-infected erythrocytes to human brain capillary and umbilical vein endothelial cells--a comparative study of adhesive ligands.

The cytoadherence of Plasmodium falciparum-infected erythrocytes (FCR-3 line) to human brain capillary endothelial cells (HBEC), C32 amelanotic melanoma cells, and human umbilical vein endothelial cells (HUVEC) was studied. The adhesion of infected red cells was HBEC > amelanotic melanoma > HUVEC. The presence or absence of the adhesive ligands ICAM-1 (CD54 or intercellular adhesion molecule 1), ICAM-2, and CD36 (= glycoprotein IV) was determined for each of these cells by indirect immunofluorescence using the monoclonal antibodies RR1/1, 6D5, and OKM 5/OKM 8, respectively. It appeared that a major ligand for the FCR-3 line of P. falciparum with amelanotic melanoma cells and HBECs was CD36. Binding to HUVECs was very low, presumably due to their lack of expression of CD36. HBECs, because of their ease of in vitro propagation, long-term maintenance of cytoadherent properties, and their high degree of adhesiveness, will be useful for in vitro studies of adherence.

Antigens, CD↗
PubMed1992

An isoform variant of the cytomegalovirus immediate-early auto repressor functions as a transcriptional activator.

The major immediate-early promoter (MIEP) of human cytomegalovirus directs the expression of several differentially spliced and polyadenylated mRNAs. These mRNAs encode nuclear phosphorproteins (IE55, IE72, and IE86), which consist of common and unique amino acid sequences. To date, very little is known of the functional role of the 55-kDa (IE55) protein. Here we present evidence that the IE55 protein is a positive activator of the MIEP. In human fibroblast cells IE55 protein activated the MIEP between 10- and 30-fold. Fusion of IE55 to the GAL4 DNA binding domain resulted in a chimeric protein capable of trans-activating a reporter with GAL4 recognition sequences. These results strongly suggest that IE55 is a bona fide transcriptional activator protein. In addition, the IE55 protein was found not to act synergistically with the IE72 activator protein. The IE55 protein shares the same amino acid sequence as IE86 except for a 154-amino-acid deletion at the C-terminal end of the protein. These proteins were functionally antagonistic; IE55 relieved repression by IE86 and, conversely, IE86 negated IE55 activation. Mutagenesis of the MIEP revealed that the target sequence for activation by IE55 is different from the IE86 autorepressive response element. These experiments suggest that the mechanism of action of the IE55 and IE86 isoforms is distinct. Moreover, from these results it is apparent that the interplay of these factors might be critical in determining the level of HCMV replication in the host.

Base Sequence↗