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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 55 records · Page 3Linked to original sources

Bisulfite-induced cytosine deamination rates in E. coli SSB:DNA complexes.

E. coli single-stranded binding protein (SSB) has been examined for its ability to modulate bisulfite-induced cytosine deamination rates in single-stranded DNA (ssDNA). We used a lacZ alpha-complementation reversion assay to detect C-->U rates at a single codon in M13mp2 DNA, whether in free ssDNA or in an SSB:ssDNA complex. When incubated at 37 degrees C, the average bisulfite-induced reversion rate constant was four-fold less in SSB:ssDNA complexes than in ssDNA, at a single codon. Across a 250 base pair target and over 23 scorable C-->U sites, the forward rate constant was 4.9-fold less in SSB:ssDNA complexes than in ssDNA alone. After treatment with N-uracil glycosylase, ssDNA incubated with bisulfite had reversion frequencies at the background rate of ssDNA incubated without bisulfite, indicating that virtually all mutations scored were due to C-->U events. The decrease in cytosine deamination rates occurred both in a single codon and over a 250 bp target, indicating that interactions between SSB and ssDNA reduce bisulfite-catalyzed mutations. The structural role of SSB is well recognized in multiple cellular processes; SSB can also function to minimize bisulfite-induced ssDNA mutations.

Cytosine↗

Multifidus EMG and tension-relaxation recovery after prolonged static lumbar flexion.

STUDY DESIGN: The electromyogram (EMG) from the in vivo feline L1 to the L7 multifidus was recorded during the application of a 20-minute static lumbar flexion and after 7 hours of rest. OBJECTIVE: To determine the recovery of tension-relaxation and laxity in the lumbar viscoelastic structures as well as the recovery of reflexive EMG activity in the multifidus after prolonged static flexion. SUMMARY OF BACKGROUND: It has been established that prolonged static flexion of the spine induces creep or tension-relaxation in its viscoelastic structures as well as a sharp decrease in the reflexive activity of the dorsal musculature and initiation of spasms. Epidemiologic studies have pointed out that such static flexion is associated with unusually high rates of low back disorders. The rate and pattern of recovery of reflexive muscular activity with rest after static flexion is still unknown. METHODS: The lumbar spines of seven in vivo feline preparations were subjected to 20 minutes of passive anterior flexion followed by 7 hours of rest while monitoring flexion tension, EMG from the L1-L7 multifidus muscles, and the strain of the L4/L5 supraspinal ligament. A model describing the pattern of recovery of muscular activity and viscoelastic tension was developed. RESULTS: Twenty minutes of lumbar flexion was associated with an initial sharp decrease of multifidus EMG activity followed by spasms. During rest, EMG activity demonstrated an initial hyperexcitability on flexion, followed by an exponential recovery of muscle activity. Full recovery of residual strain in the L4/L5 supraspinous ligament and multifidus activity was not obtained after 7 hours of rest. CONCLUSIONS: Static flexion of the lumbar spine is an extremely imposing function on its viscoelastic tissues, resulting in spasms and requiring long periods of rest before normal functions are re-established.

Animals↗

Determinants of chemotactic signal amplification in Escherichia coli.

A well-characterized protein phosphorelay mediates Escherichia coli chemotaxis towards the amino acid attractant aspartate. The protein CheY shuttles between flagellar motors and methyl-accepting chemoreceptor (MCP) complexes containing the linker CheW and the kinase CheA. CheA-CheY phosphotransfer generates phospho-CheY, CheY-P. Aspartate triggers smooth swim responses by inactivation of the CheA bound to the target MCP, Tar; but this mechanism alone cannot explain the observed response sensitivity. Here, we used behavioral analysis of mutants deleted for CheZ, a catalyst of CheY-P dephosphorylation, or the methyltransferase CheR and/or the methylesterase CheB to examine the roles of accelerated CheY-P dephosphorylation and MCP methylation in enhancement of the chemotactic response. The extreme motile bias of the mutants was adjusted towards wild-type values, while preserving much of the aspartate response sensitivity by expressing fragments of the MCP, Tsr, that either activate or inhibit CheA. We then measured responses to small jumps of aspartate, generated by flash photolysis of photo-labile precursors. The stimulus-response relation for Delta cheZ mutants overlapped that for the host strains. Delta cheZ excitation response times increased with stimulus size consistent with formation of an occluded CheA state. Thus, neither CheZ-dependent or independent increases in CheY-P dephosphorylation contribute to the excitation response. In Delta cheB Delta cheR or Delta cheR mutants, the dose for a half-maximal response, [Asp](50), was ca 10 microM; but was elevated to 100 microM in Delta cheB mutants. In addition, the stimulus-response relation for these mutants was linear, consistent with stoichiometric inactivation, in contrast to the non-linear relation for wild-type E. coli. These data suggest that response sensitivity is controlled by differential binding of CheR and/or CheB to distinct MCP signaling conformations.

Bacterial Proteins↗

Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18.

Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L-glutamate/D,L-aspartate cell-membrane transport protein. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter. It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment. In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism. Here we describe the identification and characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues. It localizes to the cell membrane and cytoplasm, and specifically interacts with carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1.

ATP-Binding Cassette Transporters↗

Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins.

Glutamate is the main excitatory neurotransmitter in the mammalian central nervous system and is removed from the synaptic cleft by sodium-dependent glutamate transporters. To date, five distinct glutamate transporters have been cloned from animal and human tissue: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5 (refs 1-5). GLAST and GLT-1 are localized primarily in astrocytes, whereas EAAC1 (refs 8, 9), EAAT4 (refs 9-11) and EAAT5 (ref 5) are neuronal. Studies of EAAT4 and EAAC1 indicate an extrasynaptic localization on perisynaptic membranes that are near release sites. This localization facilitates rapid glutamate binding, and may have a role in shaping the amplitude of postsynaptic responses in densely packed cerebellar terminals. We have used a yeast two-hybrid screen to identify interacting proteins that may be involved in regulating EAAT4--the glutamate transporter expressed predominately in the cerebellum--or in targeting and/or anchoring or clustering the transporter to the target site. Here we report the identification and characterization of two proteins, GTRAP41 and GTRAP48 (for glutamate transporter EAAT4 associated protein) that specifically interact with the intracellular carboxy-terminal domain of EAAT4 and modulate its glutamate transport activity.

Amino Acid Sequence↗

Potassium channel antibodies in two patients with reversible limbic encephalitis.

Limbic encephalitis (LE) is often associated with lung, thymic, or testicular tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it generally has a poor prognosis. Here we describe two patients with symptoms of LE, negative for typical paraneoplastic antibodies, in whom antibodies to voltage-gated potassium channels (VGKC) were detected retrospectively in serial serum samples. Patient 1 had a thymoma recurrence, but in patient 2 no tumour has been detected in the years following presentation. Plasma exchange was effective in reducing VGKC antibody levels, with substantial improvement in mental symptoms in patient 1. In patient 2, the VGKC antibodies fell spontaneously over two years, with almost complete recovery of mental function. Although neither patient had obvious neuromyotonia at presentation, both showed excessive secretions. We suggest that patients with limbic symptoms and excessive secretions should be tested for VGKC antibodies, and, if they are present, prompt and effective immunosuppressive treatment should be considered.

Aged↗

Non-tuberculous iliopsoas abscess due to perforated diverticulitis presenting with intestinal obstruction and a groin mass.

Psoas abscess is an uncommon condition and, contrary to traditional teaching, tends to be of non-tuberculous aetiology in developed countries. Diagnosis can be delayed since presenting features are non-specific and in many instances misleading, necessitating a high degree of clinical suspicion and early resort to cross-sectional imaging using CT or MRI. We present a case of iliopsoas abscess secondary to perforated diverticulitis to illustrate the difficulty encountered in early diagnosis and to show that successful management of secondary psoas abscess necessitates surgical resection of the underlying condition in most cases.

Aged↗

Violent behaviors in early adolescent minority youth: results from a "middle school youth risk behavior survey".

OBJECTIVES: To describe the prevalence and characteristics of violence and violence-related behaviors among six populations of U.S. minority adolescents in grades 6-8. METHODS: Six thousand four hundred non-White adolescents were recruited from six sites that were part of a collaborative project. Surveys were administered either during the school day or at community facilities. All students at each site were asked 10 questions about recent violence-related behaviors (including use of threats, fighting, weapon carrying, and weapon use). Prevalence of each violence-related behavior was reported within and across sites, and stratified by race/ethnicity, gender, age, and other characteristics expected to influence the behaviors. RESULTS: Sixty-six percent (66%) of the middle school students sampled reported being involved in some type of recent fighting and/or weapon-related behaviors. Sixty-one percent (61%) indicated some form of fighting behavior in the past 3 months (threatening to beat someone up, physical fighting, and/or being hurt in a fight). Thirty percent (30%) of participating youth reported one or more weapon-related behaviors (threatening to use a weapon, carrying a weapon, using a weapon, and/or being cut, stabbed or shot at). Reported gun carrying among males varied depending upon site, but was as high as 20%. Grade in school was positively associated with reported violent behaviors. Adolescents who reported living full-time with a parent or parent figure, and those who reported religious observance or beliefs, were less likely to report violence involvement. All violence-related behaviors were more common among male than female adolescents. CONCLUSIONS: Violence prevention efforts should begin in elementary school and continue throughout adolescence. Programs should be prepared to provide services or referrals to victims of violence, implement programs tailored toward females as well as males, and build partnerships with churches and other community organizations in which youth are involved.

Adolescent↗

Minority health risk behaviors: an introduction to research on sexually transmitted diseases, violence, pregnancy prevention and substance use.

AIMS: The goal of this article is to introduce the Research on Sexually Transmitted Diseases, Violence, and Pregnancy Prevention Project (RSVPP), which represents one response of the National Institutes of Health to reduce health disparities in racial and ethnic populations. METHODS: As part of this effort, seven independent projects were funded to design, implement, and evaluate community-based intervention strategies aimed at reducing risk behaviors among minority youth. The interventions and research designs varied across the sites; however, all sites included a common set of questions in their questionnaires. This study focuses on the lessons learned about community-based research across all sites. RESULTS: Sites learned many lessons regarding community-based research, including: the value of building trust, the dynamic nature of communities, the intensive time and resources necessary for success, dissimilarities between researcher and community goals, the value of clear communication, the importance of recognizing the contribution of community members and expressing gratitude for their efforts; the difficulty of disseminating findings regarding sensitive topics, and the need for continuation of interventions. CONCLUSION: Community involvement posed challenges, but enhanced the quality of the implementation and the evaluation of the interventions. This special issue includes findings from the RSVPP sites.

Adolescent↗

Beliefs about the causes of weight change in the Australian population.

OBJECTIVE: To describe self-reported weight change and beliefs about the causes of weight change and to examine whether these vary by sex and weight status. DESIGN: This cross-sectional population study examined data from the 1995 Australian National Health and Nutrition Surveys. SUBJECTS: A total of 10 624 randomly-selected adults provided data. MEASURES: Objectively measured height and weight, perceptions of current weight status, self-reported weight change over the past year, and reasons for weight change. RESULTS: Thirty-five percent of participants reported a weight gain in the last 12 months, with females, and those already overweight more likely to report a recent increase in weight. Approximately one in five participants reported a recent weight loss. Those who had recently gained weight were more likely to perceive themselves as overweight regardless of actual weight status. Commonly reported reasons for weight gain included a change in physical activity level (52% males and 35% females) and a change in the amount of food/drink consumed (30% males, 27% females). Similar reasons were given for weight loss. CONCLUSIONS: : Findings of widespread reported weight gain, particularly among those already overweight, suggest Australia's obesity epidemic may be worsening. Strategies are urgently required to better inform individuals about the factors impacting on their weight in order to prevent further weight gain.

Adolescent↗

Towards non-invasive screening of skin lesions by near-infrared spectroscopy.

A noninvasive tool for skin tumor diagnosis would be a useful clinical adjunct. The purpose of this study was to determine whether near-infrared spectroscopy can be used to noninvasively characterize skin lesions. In vivo visible- and near-infrared spectra (400--2500 nm) of skin neoplasms (actinic keratoses, basal cell carcinomas, banal common acquired melanocytic nevi, dysplastic melanocytic nevi, actinic lentigines, and seborrheic keratoses) were collected by placing a fiberoptic probe on the skin. Paired t tests, repeated measures analysis of variance and linear discriminant analysis were used to determine whether significant spectral differences existed and whether spectra could be classified according to lesion type. Paired t tests showed significant differences (p < 0.05) between normal skin and skin lesions in several areas of the near-infrared spectrum. In addition, significant differences were found between the lesion groups by analysis of variance. Linear discriminant analysis classified spectra from benign lesions compared with premalignant or malignant lesions with high accuracy. Near-infrared spectroscopy is a promising noninvasive technique for the screening of skin lesions.

Analysis of Variance↗

Pre- and postnatal diagnosis of patients with CLN1 and CLN2 by assay of palmitoyl-protein thioesterase and tripeptidyl-peptidase I activities.

Palmitoyl-protein thioesterase (PPT) and tripeptidyl-peptidase I (TPP-I) activities were measured in leucocytes and fibroblasts. Fourteen patients were confirmed as having late infantile neuronal ceroid lipofuscinosis due to a deficiency of TPP-I activity. This included one patient with a milder and more protracted form of the disease. In addition this enzyme deficiency was found in a clinically normal younger sibling of a patient. Of particular importance was the finding of normal TPP-I activity in two patients who had been diagnosed as having classical late infantile neuronal ceroid lipofuscinosis. A deficiency of PPT was confirmed retrospectively in stored fibroblasts from two patients who had already died having been diagnosed with infantile neuronal ceroid lipofuscinosis. Palmitoyl-protein thioesterase or TPP-I activities were measured in chorionic villi and cultured chorionic villi cells in three pregnancies. The enzyme results were confirmed by mutational analysis if the mutations were known, or, in the case of the pregnancy at risk for infantile neuronal ceroid lipofuscinosis by electron microscopy of the chorionic villi. Our results show that assay of PPT and TPP-I is reliable in the diagnosis of patients with mutations in the CLN1 and CLN2 genes. It is imperative to assay these enzymes in all patients to confirm the diagnosis and ensure accurate genetic counselling of other family members. Once an enzyme deficiency has been confirmed reliable prenatal diagnosis is available even if both mutations have not been detected.

Adult↗

Research Priorities Project, year 2000: establishing a direction for infection control and hospital epidemiology.

BACKGROUND: The field called "infection control" has expanded beyond hospitals to include many health care locations, some aspects of personnel health, elements of noninfectious complications, and occasionally the epidemiology of other problems that occur in care facilities. A research agenda that addresses these newer segments and provides a framework for answering fundamental questions is essential for the field and for the work of The Research Foundation for Prevention of Complications Associated with Health Care (formerly APIC Research Foundation). METHODS: We used a multiple-round iterative consensus process (Delphi technique) with 50 experts and a validation round among participants at the 4th Decennial Conference. RESULTS: The expert panel reduced 102 separate items to 21 high-ranked research priorities. The highest-ranked subject areas involved research to improve compliance with excellent practices, to study antibiotic usage and resistance, to measure the financial impact of complications and value of interventions, to perform surveillance of infectious and noninfectious complications across the spectrum of care delivery, and to study effectiveness of interventions to prevent complications at specific sites. There were differences in education and discipline between the expert panel and the 4th Decennial participants and with respect to ranking some of the individual priorities. Among respondents from outside the United States and Canada, occupational health issues were ranked more highly. CONCLUSIONS: The research priorities provide a blueprint for future progress and will require a collaborative, multicenter, multinational approach.

Adult↗

A new hydrogen peroxide--based medical-device detergent with germicidal properties: comparison with enzymatic cleaners.

BACKGROUND: The objective of this study was to evaluate the efficacy of the cleaning and bacterial killing ability of a new non-enzyme-based formulation (killing detergent solution [KDS]) compared with commercially available enzymatic detergents that included Metrizyme (Metrex Research Division of Sybron Canada Ltd. Morrisburg, Ontario) and Gzyme (Germiphene Corp, Brantford, Ontario). KDS is a hydrogen peroxide-based detergent formulation that combines cleaning efficacy with the ability to kill microorganisms. The KDS formulation helps ensure the protection of the health care worker from infectious risk during the soaking and cleaning stages of medical device reprocessing and reduces the bioburden on devices before sterilization/disinfection. METHODS: Test organisms that included Enterococcus faecalis, Salmonella choleraesuis, Staphylococcus aureus, and Pseudomonas aeruginosa were suspended in artificial test soil (ATS-B; patent submitted), inoculated at 10(6) colonyforming units per carrier and dried overnight before detergent exposure. The ATS-B mimics the blood, protein, carbohydrate, and endotoxin levels of patient-used medical devices. Plastic lumen carriers and a flexible colonoscope were used for surface and simulated-use testing, respectively. RESULTS: The results for the microbial challenge dried onto polyvinyl chloride (PVC) carriers demonstrated that the ability of KDS to remove protein, blood, carbohydrate, and endotoxin from surface test carriers was as effective as the enzyme detergents that were evaluated. Furthermore, KDS was able to effect approximately a 5-Log(10) reduction in microbial loads with a 3-minute exposure at room temperature, whereas none of the other detergents were as effective. In simulated-use testing of a soiled colonoscope, KDS was significantly better at ensuring microbial killing compared with Gzyme and Metrizyme and was equivalent to the enzymatic detergents in cleaning ability. CONCLUSIONS: In summary the KDS has excellent microbial-killing ability in 3-minute exposures at room temperature and cleans as well as the existing enzymatic detergent formulations that were tested.

Detergents↗

Habitual diet in four populations of African origin: a descriptive paper on nutrient intakes in rural and urban Cameroon, Jamaica and Caribbean migrants in Britain.

BACKGROUND: The prevalence of chronic diseases is increasing in West Africa, the Caribbean and its migrants to Britain. This trend may be due to the transition in the habitual diet, with increasing (saturated) fat and decreasing fruit and vegetable intakes, both within and between countries. OBJECTIVE: We have tested this hypothesis by comparing habitual diet in four African-origin populations with a similar genetic background at different stages in this transition. DESIGN: The study populations included subjects from rural Cameroon urban Cameroon Jamaica and African-Caribbeans in Manchester, UK all aged 25-74 years. Habitual diet was assessed by a food-frequency questionnaire, specifically developed for each country separately. RESULTS: Total energy intake was greatest in rural Cameroon and lowest in Manchester for all age/sex groups. A tendency towards the same pattern was seen for carbohydrates, protein and total fat intake. Saturated and polyunsaturated fat intake and alcohol intake were highest in rural Cameroon, and lowest in Jamaica, with the intakes in the UK lower than those in urban Cameroon. The percentage of energy from total fat was higher in rural and urban Cameroon than in Jamaica and the UK for all age/sex groups. The opposite was seen for percentage of energy from carbohydrate intake, the intake being highest in Jamaica and lowest in rural Cameroon. The percentage of energy from protein increased gradually from rural Cameroon to the UK. CONCLUSIONS: These results do not support our hypothesis that carbohydrate intake increased, while (saturated) fat intake decreased, from rural Cameroon to the UK.

Adult↗

Reproducibility and validity of a quantitative food-frequency questionnaire among Jamaicans of African origin.

BACKGROUND: An interviewer-administered quantitative food-frequency questionnaire (FFQ) was developed to determine the energy and nutrient intakes of adult Jamaicans of African origin as part of a study of the epidemiology of diabetes and hypertension. METHODS: Reproducibility of the questionnaire was investigated in 123 participants aged 25-74 years. The relative validity of the FFQ was assessed against twelve 24-hour recalls administered over 12 months in 73 of the participants. In addition, energy intakes (EI) were compared with estimated basal metabolic rates (BMR). RESULTS: Reproducibility correlation coefficients (Pearson and intraclass) varied between 0.42 for retinol and 0.71 for carbohydrate, with most values falling between 0.50 and 0.60. When compared with repeated 24-hour recalls, the FFQ estimated slightly higher energy (mean 6%) and macronutrient intakes (mean 2-14%), and was within 5% when expressed as a percentage of energy intake. Micronutrients were higher by 1.19 (calcium) to 1.61 times (vitamin C). Unadjusted correlations between the FFQ and the reference method ranged from 0.20 for beta-carotene to 0.86 for alcohol. Cross-classification of nutrients into quartiles showed that 46-48% of participants in the lowest and highest quartiles were jointly classified by both methods. Misclassifications were low for most nutrients with one or two persons misclassified at the extreme quartiles. EI/BMR ratios suggested light to moderate activity levels appropriate for an urban population in a developing country. CONCLUSIONS: The FFQ showed reasonable reproducibility and validity and is suitable for estimating the habitual intakes of energy and macronutrients, but was poor for some micronutrients (retinol and beta-carotene).

Adult↗