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Biomedical subjects

G Turner

Publications and source records attributed to G Turner.

At least 73 records · Page 4Linked to original sources

Cytokine expression in the brain in human cerebral malaria.

Evidence from clinical studies and murine models supports a role for cytokines in the pathogenesis of human cerebral malaria (CM). In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate expression of mRNA for transforming growth factor (TGF)-beta, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in human postmortem tissue. Immunohistochemistry was used to examine the distribution of cytokine protein. TGF-beta was expressed in normal brain, in CM, and in meningitis and encephalitis. IL-1beta was absent from normal brain but was detected in CM and other cerebral infections. TNF-alpha mRNA was expressed only in CM, although TNF-alpha protein was also seen in meningitis. Cytokine mRNA expression in the brain did not correlate with the density of parasitized erythrocytes detected using RT-PCR for major surface protein-2. This report of RT-PCR on postmortem human tissues infected with CM demonstrates induction of the proinflammatory cytokines TNF-alpha and IL-1beta in the brain.

Antigens, Protozoan↗

A method in search of a theory: peer education and health promotion.

Peer education has grown in popularity and practice in recent years in the field of health promotion. However, advocates of peer education rarely make reference to theories in their rationale for particular projects. In this paper the authors review a selection of commonly cited theories, and examine to what extent they have value and relevance to peer education in health promotion. Beginning from an identification of 10 claims made for peer education, each theory is examined in terms of the scope of the theory and evidence to support it in practice. The authors conclude that, whilst most theories have something to offer towards an explanation of why peer education might be effective, most theories are limited in scope and there is little empirical evidence in health promotion practice to support them. Peer education would seem to be a method in search of a theory rather than the application of theory to practice.

Adolescent↗

A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 microg/mL fentanyl for seventy-two hours of postoperative analgesia after major abdominal surgery.

UNLABELLED: Our aim in this prospective, randomized, double-blinded study was to compare the analgesic effectiveness and side effects of epidural infusions with ropivacaine 2 mg/mL alone (Group R; n = 60) and in combination with fentanyl 1 microg/mL (R1F; n = 59), 2 microg/mL (R2F; n = 62), and 4 microg/mL (R4F; n = 63) for up to 72 h after major abdominal surgery. Effective epidural neural blockade was established before surgery; postoperatively, the infusion rate was titrated to a maximum of 14 mL/h for analgesia. No additional analgesics other than acetaminophen were permitted during the infusion. The median of individual visual analog scale score with coughing were <20 mm for all groups (0 = no pain, 100 = worst pain) and was significantly lower (P < 0.01) for Group R4F at rest and with coughing (compared with Group R). Infusions were discontinued due to inability to control pain in significantly fewer patients in Group R4F (16%) than the other groups (34% to 39%; P < 0.01). For all groups, >90% of patients had no detectable motor block after 24 h. Hypotension, nausea, and pruritus were more common with the larger dose of fentanyl. We conclude that, after major abdominal surgery, an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL provided significantly more effective pain relief over a 3-day period than ropivacaine alone or ropivacaine with lower concentrations of fentanyl. IMPLICATIONS: Postoperative epidural analgesic infusions are widely used, but there is little information regarding optimal strengths of opioid with local anesthetic. In this blinded, prospective study, we compared four different epidural infusion solutions for efficacy and side effects over a clinically useful postoperative period and conclude that an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL was most effective.

Abdomen↗

Limonene synthase, the enzyme responsible for monoterpene biosynthesis in peppermint, is localized to leucoplasts of oil gland secretory cells

Circumstantial evidence based on ultrastructural correlation, specific labeling, and subcellular fractionation studies indicates that at least the early steps of monoterpene biosynthesis occur in plastids. (4S)-Limonene synthase, which is responsible for the first dedicated step of monoterpene biosynthesis in mint species, appears to be translated as a preprotein bearing a long plastidial transit peptide. Immunogold labeling using polyclonal antibodies raised to the native enzyme demonstrated the specific localization of limonene synthase to the leucoplasts of peppermint (Mentha x piperita) oil gland secretory cells during the period of essential oil production. Labeling was shown to be absent from all other plastid types examined, including the basal and stalk cell plastids of the secretory phase glandular trichomes. Furthermore, in vitro translation of the preprotein and import experiments with isolated pea chloroplasts were consistent in demonstrating import of the nascent protein to the plastid stroma and proteolytic processing to the mature enzyme at this site. These experiments confirm that the leucoplastidome of the oil gland secretory cells is the exclusive location of limonene synthase, and almost certainly the preceding steps of monoterpene biosynthesis, in peppermint leaves. However, succeeding steps of monoterpene metabolism in mint appear to occur outside the leucoplasts of oil gland cells.

Journal Article↗

Sulfate transport in Penicillium chrysogenum: cloning and characterization of the sutA and sutB genes.

In industrial fermentations, Penicillium chrysogenum uses sulfate as the source of sulfur for the biosynthesis of penicillin. By a PCR-based approach, two genes, sutA and sutB, whose encoded products belong to the SulP superfamily of sulfate permeases were isolated. Transformation of a sulfate uptake-negative sB3 mutant of Aspergillus nidulans with the sutB gene completely restored sulfate uptake activity. The sutA gene did not complement the A. nidulans sB3 mutation, even when expressed under control of the sutB promoter. Expression of both sutA and sutB in P. chrysogenum is induced by growth under sulfur starvation conditions. However, sutA is expressed to a much lower level than is sutB. Disruption of sutB resulted in a loss of sulfate uptake ability. Overall, the results show that SutB is the major sulfate permease involved in sulfate uptake by P. chrysogenum.

Amino Acid Sequence↗

The process of stroke rehabilitation: what happens and why.

OBJECTIVE: To assess the process of hospital-based stroke rehabilitation. DESIGN: A criterion-based process audit, combined with surveys of patient and staff opinions and basic outcome measures. SETTING: All wards and units treating stroke patients in a health care district, including an acute and a community National Health Service (NHS) trust. SUBJECTS: Process audit: documented notes of 115 stroke patients admitted over a four-month period. Patient satisfaction survey: 93 surviving stroke patients. Staff opinion survey: Hospital doctors, therapists and nurses treating stroke patients throughout the district. RESULTS: A disappointingly poor level of service. The main shortcomings were poor assessment of impairment (pass rate, 46%), inadequate communication between staff and with patients and carers (pass rate, 43%), and an absence of rehabilitation beyond the basic of activities of daily living and indoor mobility (pass rate for assessment of disability and emotional need, 50%). Thirty-three per cent of patients were dissatisfied with the hospital-based service they received, particularly lack of therapy, information and recovery. The main reasons for these shortcomings were low priority given to stroke patients, lack of time, shortage of staff, and lack of knowledge and awareness of stroke amongst the staff. Rehabilitation units and elderly care tended to perform better than general medical units in areas of assessment of impairment, self-care skills and mobility, and wheelchair provision. CONCLUSIONS: Evidence from previous publications suggests that this service was no worse than in other districts, but this audit methodology, by comprehensively examining many aspects of a service together, is better able to reveal inadequacies.

Activities of Daily Living↗

Genetic mapping and haplotype analysis of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscular dystrophy characterized by late onset ptosis, proximal muscle weakness and swallowing difficulties. This disease has been recently linked to chromosome 14q11.2-q13 in French-Canadian pedigrees. We studied three unrelated American families with OPMD of Hispanic descent and our results indicate that in this ethnic group, this disease also maps to chromosome 14q11.2-q13 (marker MYH7.24; Zmax = 3.98; theta max = 0). These results represent an independent demonstration of disease linkage in a second distinct ethnic group. Furthermore, our analysis demonstrates a unique haplotype that is shared by affected individuals from all three families suggesting a founder effect for OPMD in this population. Meiotic recombinants and radiation hybrid mapping permit the narrowing of the critical region to 1 Mb which will facilitate positional cloning of the OPMD disease gene.

Chromosome Mapping↗

Serotonin transporter (5-HTT) gene and bipolar affective disorder.

Interactions with antidepressants, as well as other biochemical evidence, implicate the serotonin transporter 5-HTT in the etiology of affective disorders. However, genetic studies have produced conflicting results concerning an association of 5-HTT with bipolar disorder. We examined a variable number tandem repeat in the regulatory region of this gene to investigate the possible contribution of 5-HTT to bipolar disorder susceptibility in a 22-pedigree series. By affected-sib-pair analysis and the transmission/disequilibrium test, we found no significant linkage or association of 5-HTT to bipolar disorder. During the course of this study, we adapted a PCR technique designed to amplify long templates to replicating long GC stretches with complex structure. We also refined the location of 5-HTT by radiation hybrid mapping, placing the locus between D17S1294 and SHGC11022 on 17q11.2.

Alleles↗

Identification and immunohistochemical localization of protein precursors to human axillary odors in apocrine glands and secretions.

OBJECTIVES: To determine the cellular localization in male and female axillary tissue for apocrine secretion odor-binding proteins 1 (ASOB1) and 2 (ASOB2) and the electrophoretic pattern of female apocrine proteins and to begin characterization of the ASOB1 protein. DESIGN: Immunohistochemical techniques were used with biopsy samples from axillary tissue of male and female subjects. Immunological techniques and microsequencing were used to characterize several of the proteins in male and female apocrine secretions. SETTING: A university medical center. PARTICIPANTS: Healthy male and female volunteers who donated apocrine secretions and/or axillary tissue. RESULTS: Specific immunoreactivity was localized only to the apocrine glands in both sexes. Furthermore, only preabsorption with a mixed apocrine secretion sample eliminated all immunoreactivity. The electrophoretic pattern of proteins in female apocrine secretions is similar to that in male secretions. Western blotting of the separated proteins from female samples using serum samples containing antibodies to ASOB1 and ASOB2 yielded identical results to those found with separated proteins from male samples. Partial sequence data obtained from the N-terminus of ASOB1 suggested that it shares homology with the alpha-chain of apolipoprotein J (Apo J). Apocrine secretion odor-binding protein 1 is not immunologically similar to ApoJ, but 2 other apocrine secretion proteins are. CONCLUSIONS: Male and female subjects appear to have the same glycoprotein carriers for (E)-3-methyl-2-hexenoic acid localized to the apocrine glands. The N-terminal sequence for ASOB1 may be homologous to Apo J, but it is not immunologically similar to it. However, 2 other proteins in the apocrine secretion appear to be the monomer and dimer forms of Apo J.

Adult↗

The optimization of penicillin biosynthesis in fungi.

Penicillin production by Penicillium chrysogenum is not only commercially important but arguably the most intensively investigated secondary-metabolic pathway in fungi. Isolation of the structural genes encoding the three main penicillin-biosynthetic enzymes has stimulated the use of molecular approaches to optimize yield and permitted genetic analysis of current production strains, which are themselves the products of 50 years of strain and process improvement. Parallel studies on the penicillin-producing genetic model organism Aspergillus nidulans are now addressing questions about the genetic regulation of primary and secondary metabolism, the compartmentalization of biosynthesis and the excretion of the end products.

Aspergillus nidulans↗

Phasic and tonic reflexes evoked in human antagonistic wrist muscles by tendon vibration.

The electromyographic reflex responses of the voluntarily contracting wrist flexor and extensor muscles to periods of vibration-evoked enhanced, Ia-dominated afferent discharge from flexor carpi radialis (FCR) were studied in normal human subjects. Three main response phases were characterised, namely, (i) phasic 'on' responses elicited at the commencement of stimulation, (ii) tonic response levels occurring during prolonged stimulation and (iii) phasic 'off' responses elicited at the termination of stimulation. The phasic 'on' reflex responses of FCR and extensor carpi radialis (ECR) comprised, respectively, a peak of autogenetic excitation of group mean latency 18.8 ms and a trough of reciprocal inhibition of group mean latency 38.0 ms. Prolonged (2 s) trains of FCR (agonist) vibration evoked a phase of tonic reflex excitation in FCR whose mean level was significantly increased, by 20%, above pre-stimulus activity and which did not change over the 0.5-2.0 s vibration period. Progressive reduction of the duration (from 2000 ms to 100 ms) of vibration trains demonstrated that phasic disfacilitatory 'off' troughs regularly occurred, with a consistent latency (mean 24.2 ms), on withdrawal of each period of enhanced Ia-input. This indicates that the responsible excitatory reflex mechanism was operational for the entire duration of each of the vibration periods tested. The extra latency (on average 5.4 ms) of phasic 'off' relative to 'on' responses may be attributed to factors (e.g. 5-10 ms duration of unitary muscle action potentials and afterdischarge in reflex pathways) which inevitably delay the appearance of overt disfacilitatory reductions in EMG rather than the involvement of different reflex pathways. Thus, short-latency, possibly monosynaptic, reflex excitation contributed throughout the entire tonic excitatory response. Sustained FCR (antagonist) vibration produced a significant tonic reciprocal inhibitory reflex depression, by 7% pre-stimulus EMG, of ECR activity which remained steady during the 0.5-2.0 s vibration period. The absence of well-defined phasic disinhibitory 'off' responses in ECR suggests that the contribution of oligosynaptic reflex inhibitory mechanisms to the tonic suppression of activity occurring during continuing vibration is relatively small.

Adult↗

Group specific antibodies against the putative AMP-binding domain signature SGTTGXPKG in peptide synthetases and related enzymes.

The superfamily of adenylate forming enzymes including peptide synthetases, acyl-CoA synthetases and insect luciferases is readily identified by the signature sequence SGTTGXPKG. This sequence including an invariant lysyl residue is located in a disordered loop region and was predicted to be of significant antigenicity. Antibodies were generated employing YTSGTTGRPKGC attached to bovine serum albumin and have been successfully used to identify respective enzymes and adenylate forming domains in multienzyme systems. These include the delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetases of Aspergillus nidulans and Acremonium chrysogenum, gramicidin S synthetase 1 and tyrocidine synthetase 1 from Bacillus brevis, acetyl-CoA synthetase from Alcaligenes eutrophus and a putative peptide synthetase from Metarhizium anisopliae. Weaker or no reactions are observed when the amino acid in position X in the protein is non-basic or hydrophobic, which is respectively the case for gramicidin S synthetase 1 and luciferase.

Adenosine Monophosphate↗

Examination of factors associated with instability of the FMR1 CGG repeat.

We examined premutation-female transmissions and premutation-male transmissions of the FMR1 CGG repeat to carrier offspring, to identify factors associated with instability of the repeat. First we investigated associations between parental and offspring repeat size. Premutation-female repeat size was positively correlated with the risk of having full-mutation offspring, confirming previous reports. Similarly, premutation-male repeat size was positively correlated with the daughter's repeat size. However, increasing paternal repeat size was associated also with both increased risk of contraction and decreased magnitude of the repeat-size change passed to the daughter. We hypothesized that the difference between the female and male transmissions was due simply to selection against full-mutation sperm. To test this hypothesis, we simulated selection against full-mutation eggs, by only examining premutation-female transmissions to their premutation offspring. Among this subset of premutation-female transmissions, associations between maternal and offspring repeat size were similar to those observed in premutation-male transmissions. This suggests that the difference between female and male transmissions may be due to selection against full-mutation sperm. Increasing maternal age was associated with increasing risk of expansion to the full mutation, possibly because of selection for smaller alleles within the offspring's soma over time; a similar effect of increasing paternal age may be due to the same selection process. Last, we have evidence that the reported association between offspring sex and risk of expansion may be due to ascertainment bias. Thus, female and male offspring are equally likely to inherit the full mutation.

Adult↗

The mutational specificity of 1-nitroso-6-nitropyrene in the lacI gene of Escherichia coli strains deficient in nucleotide excision repair.

We have examined the mutational specificity of 1-nitroso-6-nitropyrene (1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene, in the lacI gene of Escherichia coli strains which are deficient in nucleotide excision repair (strain NR6113, delta uvrB; strain CM6114, delta uvrB, plasmid pKM101). Separate collections of lacI- mutations and dominant lacI-d mutations, which contain DNA sequence alterations in the region of the lacI gene that encodes the DNA binding domain of the lacI repressor, were made following 1,6-NONP treatment. The DNA sequence of 418 mutations was determined, of which 228 were lacI- mutations and 190 were lacI-d mutations. Ninety three percent of the induced point mutations occurred at G:C residues.0 -(G:C) frameshifts were the dominant mutational class in the lacI- collections of both NR6113 and CM6114, and in the lacI-d collection of NR6113. The frameshift mutations occurred preferentially in runs of guanine residues and their frequency increased markedly with the length of the reiterated sequence. In strain CM6114, which contained the plasmid pKM101, there was a marked stimulation in the frequency of G:C-->T:A transversions that was particularly apparent in the lacI-d collection. We discuss models which might account for the apparent differences in mutational specificity resulting from the presence of the UmuD/C and MucA/B proteins. The results suggest that major classes of mutation are recovered in both the lacI- and lacI-d collections. However, the proportions of the major classes of mutations within the two collections can differ significantly. Depending on the genetic background of the host strain, the relative ratios of base substitutions to frameshift mutations in the lacI-d target can differ by almost an order of magnitude as compared with the lacI- target. This is primarily a function of the relative mutational target size of the different classes of mutation.

Bacterial Proteins↗

Parents' experiences of ambulatory care.

In view of the recent rapid developments in paediatric daycare provision and ambulatory care a qualitative study was undertaken to ascertain parents' experiences of this service. A high proportion of the research literature addresses issues in surgical day care only. This study was undertaken to redress the balance. Eleven parents who accessed local ambulatory care services were selected then interviewed at home following discharge. The interviews were analysed using a framework based on grounded theory in order to generate explanations from a parent's perspective. It transpired that parents' experiences of their children's illness extended the bounds of the hospitalised period and professional support was important throughout. Parents who felt cared for in the social sense and received adequate information, appeared to report the more positive experiences and coped better.

Adult↗

Community's role in the promotion of recovery from addiction and prevention of relapse among women: an exploratory study.

OBJECTIVE: This exploratory study examined the community's role in the promotion of recovery from addiction and the prevention of relapse among women, and the differences in women's addiction and recovery by ethnicity. Community was defined as six institutions: home, church, workplace, school, law enforcement and medical care system. METHODS: The study sample consisted of 39 Anglo and 24 ethnic minority women (21 African American; 3 Hispanic) between the ages of 21 and 70, living along the Gulf Coast of Texas, who had been in continuous recovery from addiction to alcohol or other drugs for at least six months. The study was cross-sectional, and data were collected through the use of structured interviews utilizing the Women in Recovery Questionnaire, an instrument developed by the investigative team. RESULTS: This study found that community institutions (church, school, home, workplace and law enforcement and medical systems) were seldom involved in promoting recovery or preventing relapse in women, with the exception of the home, which supported recovery. Anglo and ethnic minority women differed by primary drug usage, number of times in treatment, religion, perception of sexism, and likelihood of citations for traffic violations. CONCLUSION: Large, randomized studies are needed to investigate the community's role in women's recovery from alcohol and other drugs.

Adult↗