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Biomedical subjects

M A Harris

Publications and source records attributed to M A Harris.

At least 37 records · Page 2Linked to original sources

Effects of conjugated linoleic acids and docosahexaenoic acid on rat liver and reproductive tissue fatty acids, prostaglandins and matrix metalloproteinase production.

Long chain n-6 and n-3 fatty acids play important roles in labor and delivery. These effects may be mediated by prostaglandin (PG) synthesis and by regulation of matrix metalloproteinases (MMPs), both of which play roles in uterine contraction, cervical ripening and rupture of fetal membranes. The effects of altering dietary n-6:n-3 long chain fatty acid ratios, and the addition of dietary conjugated linoleic acids (CLA) and docosahexaenoic acid (DHA) on fatty acid composition of reproductive tissues, PG synthesis in liver and reproductive tissue and serum MMP levels were examined in pregnant rats. Modified AIN-96G diets with n-6:n-3 ratios of 7:1 and 34:1 with and without added 1.1% (by weight) conjugated linoleic acid (CLA) and/or 0.3% (by weight) DHA were fed through day 20 of gestation. Reproductive tissues readily incorporated both DHA and CLA. CLA significantly (P<0.05) depressed PGF(2 alpha)synthesis in placenta, uterus and liver by 50% when the n-6:n-3 ratio was 7:1 and by 66% at 34:1 ratio. Significant differences (P<0.05) in PGE(2)synthesis in uterus and liver were seen only between groups fed the high ratio of n-6:n-3 without CLA, and the low ratio with CLA. Addition of CLA to DHA containing diets depressed PGF(2alpha) by one-third in uterus and liver (P<0.05). Serum MMP-9 and active MMP-2 were suppressed (P<0.05) by addition of either CLA or DHA.

Animals↗

Bone morphogenetic protein-2 (BMP-2) signaling to the Col2alpha1 gene in chondroblasts requires the homeobox gene Dlx-2.

To understand the role of Dlx genes in the process of chondrogenesis, we studied the expression of Dlx-2 and Dlx-5 mRNAs in a mouse clonal chondroblast cell line, TMC23. We also examined the involvement of Dlx2 in the bone morphogenetic protein-2 (BMP-2) signaling to the type II collagen gene, Col2alpha1, in this cell line. In this report, we show that the TMC23 cells express Dlx-2 and Dlx-5 mRNAs, and the levels can be upregulated by recombinant BMP-2 at an early stage of chondroblast differentiation. Addition of rBMP-2 dramatically increased type II collagen expression at both the mRNA and the protein level. Also, rBMP-2 increased transcription of Col2alpha1, as shown by stimulation of a chondrocyte-specific Col2alpha1 enhancer. The mechanism involves Dlx-2, as the stimulatory effect of rBMP-2 on the Col2alpha enhancer was blocked by an antisense oligonucleotide against Dlx-2 mRNA. The rBMP-2 signaling to the Col2alpha1 enhancer was also blocked by a dominant-negative Smad1 expression vector. These data demonstrate that Dlx-2 is a downstream target of the BMP-2 signaling pathway in chondroblasts. Therefore, we propose a model in which rBMP-2 stimulates Dlx-2 expression, which then serves as a necessary transcription factor for Col2alpha1 gene expression through a chondrocyte-specific enhancer fragment.

Bone Morphogenetic Protein 2↗

The role of n-3 fatty acids in gestation and parturition.

Preterm birth is the most common cause of low infant birth weight and infant morbidity and mortality. Evidence from human and animal studies indicates that essential fatty acids of both the n-3 and n-6 series, and their eicosanoid metabolites, play important and modifiable roles in gestational duration and parturition, and n-3 fatty acid intake during pregnancy may be inadequate. Prostaglandins (PG) of the 2-series are involved in parturition and connective tissue remodeling associated with cervical maturation and rupture of membranes. In the absence of infections, preterm birth is characterized by lower reproductive tissue PG production and decreased inducible cyclooxygenase expression. Women who deliver prematurely have increased pools of n-6 fatty acid and decreased n-3 fatty acids, despite the lower PG production. Several human pregnancy supplementation trials with n-3 fatty acids have shown a significant reduction in the incidence of premature deliver and increased birth weight associated with increased gestational duration. Supplementation with long chain n-3 fatty acids such as docosahexaenoic acid may be useful in prolonging the duration of gestation in some high-risk pregnancies. Evidence presented in this review is discussed in terms of the roles of dietary n-3 and n-6 fatty acids in gestation and parturition, mechanisms by which they may influence gestational duration and the human trials suggesting that increased dietary long-chain n-3 fatty acids decrease the incidence of premature delivery.

Animals↗

Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects.

OBJECTIVE: This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral-Family Systems Therapy (BFST). RESEARCH DESIGN AND METHODS: A total of 119 families of adolescents with type 1 diabetes were randomized to 3 months of treatment with either BFST, an education and support (ES) group, or current therapy (CT). Family relationships, adjustment to diabetes, treatment adherence, and diabetic control were assessed at baseline, after 3 months of treatment, and 6 and 12 months later. This report focuses on the latter two evaluations. RESULTS: Compared with CT and ES, BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict. Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups. There were no immediate or delayed effects on adolescents' adjustment to diabetes or diabetic control. CONCLUSIONS: BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence, but it had no effect on adjustment to diabetes or diabetic control. A variety of adaptations to BFST could enhance its impact on diabetes outcomes.

Adolescent↗

Integrating functional genomic information into the Saccharomyces genome database.

The Saccharomyces Genome Database (SGD) stores and organizes information about the nearly 6200 genes in the yeast genome. The information is organized around the 'locus page' and directs users to the detailed information they seek. SGD is endeavoring to integrate the existing information about yeast genes with the large volume of data generated by functional analyses that are beginning to appear in the literature and on web sites. New features will include searches of systematic analyses and Gene Summary Paragraphs that succinctly review the literature for each gene. In addition to current information, such as gene product and phenotype descriptions, the new locus page will also describe a gene product's cellular process, function and localization using a controlled vocabulary developed in collaboration with two other model organism databases. We describe these developments in SGD through the newly reorganized locus page. The SGD is accessible via the WWW at http://genome-www.stanford.edu/Saccharomyces/

Database Management Systems↗

A general practice-based recruitment strategy for colorectal cancer screening.

OBJECTIVE: To determine whether a screening recruitment strategy for first degree relatives of people with colorectal cancer is effective in enabling eligible relatives to request screening from their general practitioner (GP) and to assess acceptability to GPs and patients. METHODS: Thirty GPs, from 26 practices, and 303 of their patients aged over 50 who were first degree relatives of a person with colorectal cancer, participated in a randomised controlled trial of a GP-based recruitment strategy, in the Newcastle Area of New South Wales, Australia. RESULTS: The proportion of relatives requesting screening was statistically significantly higher in the intervention group than in the control group (18% compared to 4%, respectively; p = 0.01). CONCLUSIONS: Interest in the study by GPs was low, however for GPs who were involved, the recruitment strategy did prompt first degree relatives to discuss screening. The strategy may be even more effective when combined with other interventions such as a media campaign. The results may be generalizable to feasibility studies of general population screening for colorectal cancer in Australia. IMPLICATIONS: The results of this work are potentially informative to public health practice in Australia given the ensuing pilot programs of colorectal cancer screening.

Aged↗

Presence-absence sequential sampling plan for northern fowl mite, Ornithonyssus sylviarum (Acari: Macronyssidae), on caged-layer hens.

Caged-layer hens were scored as infested or uninfested by visual examination of the vent region, and the number of northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago), per hen was estimated. The proportion infested and average number of mites per hen were shown to have a highly significant, positive relationship (r = 0.936). Sampling among houses within a flock, and rows and sections within houses were analyzed to determine the reliability of sampling a representative portion of a flock. Low- and moderate-tolerance treatment thresholds, based on percentage of hens infested with mites, were developed from sampling 1 wk before and 1 wk after acaricide treatments determined necessary by the producer. These thresholds were used to compare a fixed (single) sampling plan, a curtailed procedure of the fixed sampling plan, and a sequential sampling plan based on a sequential probability ratio test, by sampling 174 hens (the maximum number needed for the single sampling plan). The sequential sampling plan required fewer hen examinations on average to reach a treatment decision than did the other plans, depending on the infestation tolerance limits. Using a low tolerance approach in which infestations below 15% are considered noneconomic (safe threshold) and infestations above 25% are considered economically important (action threshold), as few as 5 hens required examination to reach a treatment decision. Sequential sampling plan graphs are presented for 2 tolerance threshold scenarios (a 15% safe-threshold paired with a 25% action threshold and a 35% safe-threshold paired with a 45% action threshold). These sequential sampling plans using presence absence assessments should greatly facilitate monitoring and treatment decisions for this important pest.

Animals↗

Validation of a structured interview for the assessment of diabetes self-management.

OBJECTIVE: The authors developed and validated a semi-structured interview; the Diabetes Self-Management Profile (DSMP), to measure self-management of type 1 diabetes. The DSMP includes the following regimen components: exercise, management of hypoglycemia, diet, blood glucose testing, and insulin administration and dose adjustment. RESEARCH DESIGN AND METHODS: Families of youths with type 1 diabetes (n = 105) who were entering a controlled trial of intensive therapy (IT) versus usual care (UC) were administered the DSMP Analyses assessed the reliability and validity of the DSMP, including its associations with HbA1c and quality of life. RESULTS: The DSMP total score has adequate internal consistency (Cronbach's alpha 0.76), 3-month test-retest reliability (Pearson correlation, r = 0.67), inter-interviewer agreement (r = 0.94), and parent-adolescent agreement (r = 0.61). DSMP total scores (r = -0.28) and 3 subscales correlated significantly with HbA1c (diet [r = -0.27], blood glucose testing [r = -0.37], and insulin administration and dose adjustment [r = -0.25 ]). Adolescents' reports of self-management did not differ from parental reports. Higher DSMP scores were associated with more favorable quality of life for mothers and youths. CONCLUSIONS: The DSMP is a convenient measure that yields a reliable and valid assessment of diabetes self-management. Compared with extant similar measures, the DSMP is more strongly correlated with HbA1c.

Adolescent↗

Neonates with congenital heart disease: an overview.

The chest x-ray can be a valuable tool as part of the initial evaluation of a neonate with clinical signs of congenital heart disease. The radiographic appearance of pulmonary vascularity, as well as cardiac size and configuration, can provide information about the pathophysiologic effect of a cardiac lesion. Along with clinical evaluation of the infant, information gathered from the x-ray may be helpful in indicating which cardiac defect is involved. However, final identification of a defect would require further evaluation by echocardiogram or cardiac catheterization.

Female↗

Neonates with congenital cardiac defects with increased pulmonary blood flow.

Generally, cardiac lesions with increased pulmonary blood flow demonstrate cardiomegaly, increased pulmonary vascular markings, and pulmonary congestion on the chest x-ray. These findings occur as a result of the following: (1) A left-to-right shunt or mixing lesion in which excess volume of blood flow causes dilation of cardiac chambers, resulting in the appearance of cardiomegaly, and in which increased pulmonary artery blood flow causes increased pulmonary vascular markings; (2) Obstruction of blood flow that produces pulmonary venous hypertension and resultant pulmonary edema.

Blood Flow Velocity↗

Neonates with congenital cardiac defects with decreased pulmonary blood flow.

Lesions that cause decreased pulmonary blood flow are those that obstruct the RVOT. In general, the radiographic presentation includes the following: (1) Thin, poorly visualized pulmonary blood vessels with little extension beyond the perihilar region; (2) Dark, hyperlucent lung fields; and (3) Moderate to severe cardiomegaly, depending on the cardiac defect(s) present.

Blood Flow Velocity↗

Using the Saccharomyces Genome Database (SGD) for analysis of protein similarities and structure.

The Saccharomyces Genome Database (SGD) collects and organizes information about the molecular biology and genetics of the yeast Saccharomyces cerevisiae. The latest protein structure and comparison tools available at SGD are presented here. With the completion of the yeast sequence and the Caenorhabditis elegans sequence soon to follow, comparison of proteins from complete eukaryotic proteomes will be an extremely powerful way to learn more about a particular protein's structure, its function, and its relationships with other proteins. SGD can be accessed through the World Wide Web at http://genome-www.stanford.edu/Saccharomyces/

Computational Biology↗

Clinical versus polysomnographic profiles in children with obstructive sleep apnoea.

OBJECTIVE: To examine the clinical and polysomnographic (PSG) profiles of neurologically normal and abnormal children with obstructive sleep apnoea (OSA) and explore the relationship between these profiles. METHODOLOGY: We enrolled 56 children with persistent snoring and OSA for the study, 16 of whom were neurologically abnormal. All children were examined clinically and attended an overnight PSG study. Total clinical scores, PSG scores, and mild/moderate or severe ratings were derived for each child. RESULTS: Comparison of individual PSG parameters with neurological status demonstrated that the abnormal children had significantly increased obstructive apnoea indices, increased desaturation events and lower mean arousal indices compared to their neurologically normal OSA peers. For the neurologically abnormal children, there was a significant correlation between severity ratings of disease according to clinical and PSG profiles (r = 0.56, P = 0.03, sensitivity 82%) using the clinical summary as the gold standard, although the association was less marked in the neurologically normal children (r = -0.08, P = NS, sensitivity 69%). CONCLUSION: Neurologically abnormal children are likely to have more severe abnormalities in selected polysomnographic indices and overall scores. However, the clinical assessment is only likely to reflect this at the severe end of the spectrum. These relationships are not seen in the neurologically normal child, where little or no reliance can be placed upon predicting the severity of the polysomnographic findings from the clinical data. Decisions regarding the severity of disease and treatment should be based on the combined findings of the clinical and PSG data rather than overall clinical and polysomnographic scores or selected clinical and polysomnographic parameters.

Arousal↗

Six-month follow-up of children with obstructive sleep apnoea.

OBJECTIVES: This study examined prospectively changes in development, temperament and sleep related behaviour in children referred for obstructive sleep apnoea (OSA) and polysomnographic sleep study, some of whom had surgical intervention. METHODOLOGY: Using a prospective cohort study design, parents of 56 children referred for OSA completed sleep and temperament questionnaires and their child was assessed developmentally at the time of the polysomnographic sleep study. Forty (72%) of the children were neurologically normal. At 6 months, 42 children were reassessed using sleep and temperament questionnaires and a developmental assessment. After excluding the primary snorers, subjects were categorised as having had intervention (n = 24) or not (n = 15), and differences over the 6-month period in Griffiths scores, temperament and sleep related behaviour were examined. RESULTS: Regardless of intervention status, there was an improvement in night-time and day-time sleep behaviour for the total group, though the extent of improvement was more marked in the intervention group. For the neurologically normal children, improvement in the sleep behaviour was only significant for the intervention group (P < 0.05). Intervention did not result in any significant changes in Griffiths developmental score or temperament. CONCLUSION: Surgical intervention improves sleep behaviour in children though not temperament or development.

Adenoidectomy↗

Aetiological factors and development in subjects with obstructive sleep apnoea.

OBJECTIVE: To examine whether maternal pregnancy complications, adverse birth events, respiratory illnesses, or developmental difficulty were increased in neurologically normal children with obstructive sleep apnoea (OSA) and whether severity of OSA adversely affects the child's development and temperament. METHODOLOGY: Maternal report of perinatal events, respiratory illness and developmental difficulty in 37 children with OSA was contrasted with a comparison group (n = 67). Children with OSA were assessed developmentally (Griffiths Scales), had a parental rating of temperament (Australian Temperament Scale) and attended an overnight polysomnographic sleep study. RESULTS: Children with OSA had an increased prevalence of adverse maternal pregnancy and perinatal events, respiratory disease and developmental concerns. Limited associations were found between the severity of OSA and development or temperament difficulty. CONCLUSIONS: This study suggests a relationship between OSA, though not its severity, and pre/perinatal adversity and child development. Polysomnographic and detailed developmental assessment of community-based samples of children with OSA and control children are necessary to confirm these findings.

Australia↗

Risk factors for cardiovascular disease and diabetes in two groups of Hispanic Americans with differing dietary habits.

OBJECTIVE: The purpose of this study was to determine if Hispanic Seventh-Day Adventists (SDAs), who typically eat a diet lower in fat, saturated fat and protein, and higher in complex carbohydrates and dietary fiber than the usual omnivorous diet, exhibit lower risk factors for cardiovascular disease (CVD) and Type 2 diabetes compared to Hispanic Catholic omnivores. METHODS: Anthropometric characteristics, dietary intake, blood pressure, serum lipids, glucose and insulin, as well as plasma ascorbic acid and vitamin E concentrations, were measured in two groups of Hispanic study participants residing in Denver, Colorado: 74 SDA study participants (x age: 42+/-1.5 y) and 45 Catholic participants (x age: 44+/-2.2 y). RESULTS: The SDAs reported lower dietary intakes of total fat, saturated fat and cholesterol and higher relative intakes of carbohydrate and dietary fiber compared to their Catholic counterparts. The SDAs exhibited significantly lower body mass index (BMI = 27.2+/-0.6) and waist-to-hip ratios (WHR = 0.84+/-0.01) compared to the Catholics (BMI = 31.4+/-1.1; WHR = 0.88+/-0.01). The SDAs, compared to the Catholics, had lower fasting insulin (11.4+/-0.6 vs. 18.9+/-3.1 microu/ml) and glucose concentrations (88.6+/-1.1 vs. 104.1+/-5.4 mg/dl). The SDA Hispanics, compared to the Catholic Hispanics, exhibited significantly lower values for systolic blood pressure (SBP = 1102 vs. 118+/-3 mm Hg), serum total cholesterol (STC = 198+/-5 vs. 214+/-6 mg/dl) and serum triglycerides (TG = 152+/-12 vs. 232+/-27) and higher serum concentrations of high-density lipoprotein cholesterol (HDL-C = 44.7+/-1.3 vs. 39.1+/-1.4 mg/dl) and ascorbic acid (1.14+/-0.08 vs. 0.87+/-0.07 mg/dl). Low-density lipoprotein cholesterol (LDL-C) and vitamin E concentrations were not significantly different between groups, but the SDAs exhibited lower ratios of STC/HDL-C and LDL-C/HDL-C. CONCLUSION: Hispanic American SDAs, who eat a plant-based diet, exhibit a more favorable blood lipid profile, lower blood pressure and lower risk for Type 2 diabetes compared to Hispanic American Catholics, who do not eat a plant-based diet.

Adolescent↗