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Biomedical subjects

L Rogers

Publications and source records attributed to L Rogers.

At least 37 records · Page 2Linked to original sources

Goniotriocin and (2,4-cis- and -trans)-xylomaticinones, bioactive annonaceous acetogenins from Goniothalamus giganteus.

Goniotricin (1) and a mixture of (2,4-cis and -trans)-xylomaticinones (2), new bioactive annonaceous acetogenins, were isolated from the bark of Goniothalamus giganteus (Annonaceae) by activity-directed fractionation using the brine shrimp lethality test. Compound 1 is the first nonadjacent ring-hydroxylated bis-tetrahydrofuran (THF) acetogenin to be reported. Compound 2 is the cis- and trans-ketolactone mixture of xylomaticin, a known compound whose absolute stereochemistry has not been previously determined. The absolute stereochemistry of 2 was determined by the advanced Mosher's ester method. Both 1 and 2 showed significant and selective cytotoxicities among the six tumor cell lines in our seven-day MTT human solid tumor panel. In the yellow fever mosquito larvae microtiter assay, 1 was quite active, with an ED50 value of 3. 5 microg/mL.

Animals↗

Health screening for people with intellectual disability: the New Zealand experience.

People with intellectual disability have considerable health needs and variable health care. The introduction of annual health screens for IHC residents in New Zealand resulted in some 73% of screened people requiring follow-up interventions. The introduction of the health screens raised a number of issues for management, staff, health professionals and clients who might subsequently be involved in an exercise of this type and magnitude. The importance of applying principles of management promoted by proponents of total quality management has been apparent throughout the whole exercise.

Community Health Services↗

Lysine 58 and histidine 66 at the C-terminal alpha-helix of monocyte chemoattractant protein-1 are essential for glycosaminoglycan binding.

Monocytes rolling on the endothelial cell layer interact with monocyte chemoattractant protein-1 (MCP-1) that is tethered to the proteoglycans on the luminal side of the endothelial cells and consequently initiate adhesion of monocytes in the early phase of immune response. The amino acid residues in MCP-1 involved in tethering to the proteoglycans have not been elucidated. MCP-1 showed binding to [3H]heparin with a KD of 1.5 microM. We substituted lysine or histidine residues at the C-terminal end of MCP-1 with alanine residues and tested these mutants for their ability to bind heparin, heparan sulfate, hyaluronic acid, and chondroitin sulfate-C. Substitution of Lys-58 or His-66 drastically reduced glycosaminoglycan binding. Substitution of Lys-56 or deletion of the five amino acid residues at the C terminus, including Lys-75, did not alter the heparin binding ability, suggesting that the other lysine residues at the C terminus are not involved in glycosaminoglycan binding. MCP-1 and its mutants did not bind hyaluronic acid as strongly as the other subunits of the GAGs. Substitution of Lys-58 or His-66 by alanine that prevented glycosaminoglycan binding did not affect Ca2+ influx, receptor binding, or chemotactic activity elicited by the chemokine on monocytic THP-1 cells. Therefore, we conclude that the Lys-58 and His-66 residues in the C-terminal alpha-helix of MCP-1 are essential for glycosaminoglycan binding and probably for the binding to the endothelial surface proteoglycans.

Amino Acid Sequence↗

Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication.

We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhibitory C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBPbeta, but pulmonary tuberculosis abolished inhibitory C/EBPbeta expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBPbeta transcriptional repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.

Base Sequence↗

Mono-tetrahydrofuran acetogenins from Goniothalamus giganteus.

Goniotetracin and a mixture of (2,4-cis and trans)-gonioneninone, new, bioactive, mono-tetrahydrofuran (THF) gamma-lactone and ketolactone acetogenins, were isolated from the bark of Goniothalamus giganteus (Annonaceae) by activity-directed fractionation using the brine shrimp lethality test (BST). The structures were elucidated based on spectroscopic and chemical methods. Their absolute stereochemistries were determined by the advanced Mosher ester method. Both showed selective and significant cytotoxicities, comparable to the potency of adriamycin, to the human pancreatic tumour cell line (PACA-2), while goniotetracin and goniothalamicin were comparable to the activity of rotenone against yellow fever mosquito larvae.

4-Butyrolactone↗

Cloning and expression of cDNA encoding a mitogen-activated protein kinase from a phytopathogenic filamentous fungus.

We have cloned a mitogen-activated protein kinase (MAPK) designated Fusarium solani f. sp. pisi mitogen-activated protein kinase (FsMAPK) from the phytopathogenic filamentous fungus F. solani f. sp. pisi T8 strain. A single open reading frame (ORF) of 1068 bp encoding a polypeptide of 355 amino acids (aa) with a predicted molecular mass of 41,194 Da was found in the cloned 1583-bp cDNA insert. FsMAPK is highly homologous to SPK1 of fission yeast, FUS3 of budding yeast, MsERK1 of alfalfa, Sur-1 of nematode, and hERK1 of human. That this gene is expressed in F. solani f. sp. pisi was shown by the finding that immunoblot of the fungal extracts with anti-FsMAPK antibodies (Ab) raised in a rabbit against the FsMAPK, expressed in Escherichia coli (E. coli), detected the corresponding protein. DNA blot analysis indicated that Fsmapk is present as a single copy in the fungal genome.

Amino Acid Sequence↗

The relationship between socioeconomic status and eating-disordered behaviors in a community sample of adolescent girls.

OBJECTIVE: Although previous research has demonstrated a relationship between socioeconomic status (SES) and weight, the research has not been consistent regarding the relationship between SES and eating disorders. This analysis was designed to examine this relationship in a large community sample of adolescent girls (Grades 7 to 12). METHOD: Items were selected from a comprehensive self-report health survey completed by 17,571 adolescent girls. The relationships between SES and dieting behaviors and attitudes were examined using chi-square tests and analysis of variance (ANOVA) to control for body mass index. RESULTS: Although there was a significant positive relationship between SES and some of the unhealthy dieting behaviors, there was no relationship between self-report of clinically significant eating-disordered behaviors (e.g., vomiting twice a week or more) and SES in this community sample. DISCUSSION: This study suggests that while there may be a significant relationship between SES and dieting or other behaviors associated with eating disorders, this relationship does not apply to diagnostically significant behaviors. SES may be associated with differences in dieting or eating behaviors; however, among those young women who meet psychiatric criteria for an eating disorder, SES does not appear to be a significant factor.

Adolescent↗

A suicide vector for allelic recombination involving the gene for glutamate 1-semialdehyde aminotransferase in the cyanobacterium Synechococcus PCC 7942.

Gabaculine (2,3-dihydro 3-amino benzoic acid) is a potent inhibitor of tetrapyrrole biosynthesis in organisms that use the C5 pathway for the synthesis of delta-aminolaevulinic acid. Glutamate semialdehyde aminotransferase (GSA-AT), the enzyme catalysing the formation of this key precursor of tetrapyrroles, is normally inhibited by concentrations of gabaculine in the order of 5 microM. However, in Synechococcus 6301 strain GR6, a cyanobacterium that is resistant to 100 microM gabaculine, this enzyme has undergone two changes in structure: a deletion of three amino acids from positions 5 to 7 and the substitution of isoleucine for methionine at position 248. To establish the effect in vivo of these specific changes in the gene for GSA-AT (hemL), a suicide vector (pHS7) containing an antibiotic cassette was constructed to achieve the replacement, by homologous recombination, of the wild-type hemL gene in the chromosome by a modified form of the gene. Recombinant strains of Synechococcus 7942 obtained using pHS7-hemLGR6 were indistinguishable from Synechococcus 6301 GR6 in terms of the resistance of growth and of chlorophyll accumulation to high concentrations of gabaculine, while a wild-type recombinant produced using pHS7-hemLWT had retained its sensitivity. Southern hybridisation using gene probes for hemL, ampr and cmr confirmed that chromosomal integration of the plasmids had occurred in both WT and GR6 recombinants. Growth and chlorophyll accumulation in equivalent strains with the hemL gene containing either the deletion or the transition characteristic of Synechococcus 6301 GR6 were inhibited by 10 microM gabaculine. Consequently, resistance in vivo to high concentrations of this compound is dependent on both the changes in gene/enzyme structure. This investigation has established the effectiveness of the suicide vector pHS7 for studying the effect in vivo of specific changes in the hemL gene. It has also demonstrated that replacement of the wild-type gene by that from Synechococcus 6301 GR6 is sufficient to confer resistance in vivo to high concentrations of gabaculine.

Alleles↗

(2,4-cis and trans)-gigantecinone and 4-deoxygigantecin, bioactive nonadjacent bis-tetrahydrofuran annonaceous acetogenins, from Goniothalamus giganteus.

Two new acetogenins, (2,4-cis and trans)-gigantecinone (1), isolated as a mixture, and 4-deoxygigantecin (2), a known acetogenin whose absolute stereochemistry has not been determined previously, were isolated using activity-directed fractionation, from the bark of Goniothalamus giganteus. A key step in solving their absolute stereochemistries was the preparation of 1,4-diol formaldehyde acetal derivatives (1b and 2a). Using the advanced Mosher ester method and circular dichroism, the absolute stereochemistries of 1 and 2 were revealed and were found to be the same as that of gigantecin (3), which supports a common biogenetic origin. Both 1 and 1b showed potent and selective cytotoxicities against the PC-3 human prostate adenocarcinoma cell line. Against yellow fever mosquito larvae, 1 and 2 were more potent than rotenone in pesticidal activity. Longimicin C and a mixture of (2,4-cis and trans)-isoannonacin were also isolated for the first time from this species.

Acetylation↗

Long-term response to crisnatol mesylate in patients with glioma.

A total of 26 patients (6 with anaplastic astrocytoma; 20 with glioblastoma) were treated with crisnatol mesylate. All patients had residual or progressive disease following surgery and standard radiotherapy; nine patients had prior chemotherapy. Crisnatol was administered as a 72-hour infusion every 21 days at a starting dose of 2250 mg/m2. Two patients who had not received prior chemotherapy achieved a complete response and remain in continuous complete remission over seven and six years, respectively, post-diagnosis. Two other patients remained stable on crisnatol for 10 months before disease progression. One patient with mixed oligodendroglioma/glioblastoma progressed after 12 months on crisnatol. He survives at 7 years post-diagnosis, with Karnofsky Performance Status of 60 following other therapies. One patient with anaplastic astrocytoma stopped treatment by request after 10 months and remains stable 64 months post diagnosis. Seventeen evaluable patients, including nine patients with prior chemotherapy, progressed after 2-9 courses of therapy. Median survival is 9.25 months, with a one year survival rate of 30% and 2 years survival rate of 17%. Neurotoxicity was acute and dose-limiting. Side effects were tolerable and limited to duration of infusion. Two complete, long-lasting responses to crisnatol mesylate in patients with progressive malignant glioma are encouraging results and warrant further investigation.

Adult↗

An evaluation of dipstick-dot immunoassay in the detection of antibodies to HIV-1 and 2 in Zimbabwe.

There is a need, in many developing countries, for simple and inexpensive HIV serology tests for use at the district level of health care. The Programme for Appropriate Technology in Health has developed a simple dipstick ELISA to detect antibodies to HIV-1 and 2, at a cost considerably lower than current ELISAs, which requires no specialized washing or reading equipment. In order to evaluate this dipstick under local conditions we used a panel of 546 sera selected from frozen stocks maintained by the Zimbabwe AIDS Prevention Project in Harare, Zimbabwe. Prior to storage, the sera had been tested by Abbott recombinant peptide HIV-1 and 2 ELISA and Enzygnost synthetic peptide HIV-1 and 2 ELISA. The panel included sera that were positive by both (including symptomatics and asymptomatics), negative by both, and sera showing discrepant test results. The panel was not representative of a "normal' batch of sera in Zimbabwe, and in particular included an abnormally high number of sera showing discrepant results. Thawed sera were retested using the Abbott recombinant peptide HIV-1 and 2 ELISA and concurrently with the synthetic peptide ICL-Dipstick ELISA. Both the sensitivity and specificity of the ICL Dipstick exceeded 99% when using sera that were positive or negative in all 3 plate ELISAs as the gold standard. When using sera that gave discrepant results between the two pre-storage ELISAs, most results with the ICL Dipstick concurred with findings from other test systems, including Western blot and p24 antigen detection. Considering the accuracy, low cost and case of operation of the ICL Dipstick ELISA, this test can be recommended for use for the rapid detection of antibodies to HIV at district level in developing countries.

Enzyme-Linked Immunosorbent Assay↗

Nucleotide regulation and characteristics of potassium channel opener binding to skeletal muscle membranes.

[3H]P1075 binding to membrane preparations of rabbit skeletal muscle were observed in the presence of nucleotide triphosphates or diphosphates but not AMP, cAMP, adenosine, tripolyphosphate, or pyrophosphate. Nonhydrolyzable or poorly hydrolyzable ATP analogs inhibited MgATP-supported binding. The EC50 value for MgATP-supported binding (0.4 mM) was decreased approximately 10-fold in the presence of an ATP-regenerating system, and significant metabolism by membrane nucleotidases was confirmed by high performance liquid chromatographic analysis. [3H]P1075 bound to skeletal muscle with a Kd value of 37 +/- 3 nM and a Bmax value of 280 +/- 14 fmol/mg of protein. [3H]P1075 binding to subcellular fractions was highest in membranes enriched in T tubules. Specific binding was reversible, trypsin-sensitive, maximal at pH 8, and stereoselective for the (3S,4R)-enantiomer of cromakalim. Potassium channel openers exhibited a rank order of potency of P1075 > pinacidil > levcromakalim = BMS-180448 > nicorandil > diazoxide = BRL 38226. Fluorescein analogs (ethyleosin, phloxine B, and rose bengal) were relatively potent inhibitors of binding (Ki = 200-300 nM). The potassium channel openers cromakalim and BMS-180448 were competitive inhibitors of [3H]P1075 binding. In contrast, rose bengal and the ATP-regulated potassium channel antagonist glyburide increased the rate of [3H]P1075 dissociation in a manner consistent with noncompetitive interaction.

Adenosine Triphosphate↗

Behavioral, structural and neurochemical asymmetries in the avian brain: a model system for studying visual development and processing.

The emphasis of this review is on the visual systems and lateralized visually guided behavior in several avian species. Lateral asymmetry is known to be present in the tectofugal visual projections to the forebrain of the pigeon and in the thalamofugal visual projections to the forebrain of the chicken. These structural asymmetries are discussed in the context of the behavioral and neurochemical asymmetries. While recognizing the need to investigate the organization of both of the visual pathways within one avian species; this review reasons inductively that the lateralized organization of the two visual pathways leads to binocular input to the right hemisphere via the thalamofugal visual system and to the left hemisphere via the tectofugal visual system. For each system, input to the other hemisphere is primarily monocular. This specialization of the hemispheres for visual processing has predictable effects on behavior. The role of asymmetrical light stimulation of the eyes of the embryo in determining the lateralizations in the visual pathways and some behaviors is discussed, as are other lateralizations generated or altered by imprinting and passive avoidance learning.

Animals↗

Evolving cooperation: the role of individual recognition.

To evaluate the role of individual recognition in the evolution of cooperation, we formulated and analyzed genetic algorithm model (EvCo) for playing the Iterated Prisoner's Dilemma (IPD) game. Strategies compete against each other during each generation, and successful strategies contribute more of their attributes to the next generation. Each strategy is encoded on a 'chromosome' that plays the IPD, responding to the sequences of most recent responses by the interacting individuals (chromosomes). The analysis reported in this paper considered different memory capabilities (one to five previous interactions), pairing continuities (pairs of individuals remain together for about one, two, five, or 1000 consecutive interactions), and types of individual recognition (recognition capability was maximal, nil, or allowed to evolve between these limits). Analysis of the results focused on the frequency of mutual cooperation in pairwise interactions (a good indicator of overall success in the IPD) and on the extent to which previous responses by the focal individual and its partner were associated with the partner's identity (individual recognition). Results indicated that a fixed, substantial amount of individual recognition could maintain high levels of mutual cooperation even at low pairing continuities, and a significant but limited capability for individual recognition evolved under selection. Recognition generally increased mutual cooperation more when the recent responses of individuals other than the current partner were ignored. Titrating recognition memory under selection using a fitness cost suggested that memory of the partner's previous responses was more valuable than memory of the focal's previous responses. The dynamics produced to date by EvCo are a step toward understanding the evolution of social networks, for which additional benefits associated with group interactions must be incorporated.

Algorithms↗

Using individual and group reflection in and on assessment as a tool for effective learning.

This paper outlines the background to the current United Kingdom educational scene for post-registration nurse education, highlighting the influence of the English National Board (ENB) framework and higher award. The study reported was undertaken with the help of two student cohorts who were registered consecutively on a 6 month ENB course at diploma level. Formal reflection using both individual written and group discussion was introduced focusing on the two summative course assessments. This kind of formal reflection was seen as a learning strategy to influence positively students' educational outcomes and professional practice via six key factors: (a) academic self-concept; (b) task awareness; (c) views of knowledge; (d) the influence of knowledge on behaviour; (e) writing as a learning activity; and (f) generating knowledge by reflecting in and on assessment with discussion. The findings, reported under the six factor-headings, fully support the use of reflection in this way for these purposes.

Curriculum↗