Search PubMed⌕ Search

Biomedical subjects

M A Harris

Publications and source records attributed to M A Harris.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

Comparison of the complete protein sets of worm and yeast: orthology and divergence.

Comparative analysis of predicted protein sequences encoded by the genomes of Caenorhabditis elegans and Saccharomyces cerevisiae suggests that most of the core biological functions are carried out by orthologous proteins (proteins of different species that can be traced back to a common ancestor) that occur in comparable numbers. The specialized processes of signal transduction and regulatory control that are unique to the multicellular worm appear to use novel proteins, many of which re-use conserved domains. Major expansion of the number of some of these domains seen in the worm may have contributed to the advent of multicellularity. The proteins conserved in yeast and worm are likely to have orthologs throughout eukaryotes; in contrast, the proteins unique to the worm may well define metazoans.

Animals↗
PubMed1998

Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages.

Cumulative evidence indicates that osteoblasts and adipocytes share a common mesenchymal precursor and that bone morphogenetic proteins (BMPs) can induce both osteoblast and adipocyte differentiation of this precursor. In the present study, we investigated the roles of BMP receptors in differentiation along these separate lineages using a well-characterized clonal cell line, 2T3, derived from the mouse calvariae. BMP-2 induced 2T3 cells to differentiate into mature osteoblasts or adipocytes depending upon culture conditions. To test the specific roles of the type IA and IB BMP receptor components, truncated and constitutively active type IA and IB BMP receptor cDNAs were stably expressed in these cells. Overexpression of truncated type IB BMP receptor (trBMPR-IB) in 2T3 cells completely blocked BMP-2-induced osteoblast differentiation and mineralized bone matrix formation. Expression of trBMPR-IB also blocked mRNA expression of the osteoblast specific transcription factor, Osf2/ Cbfa1, and the osteoblast differentiation-related genes, alkaline phosphatase (ALP) and osteocalcin (OC). BMP-2-induced ALP activity could be rescued by transfection of wild-type (wt) BMPR-IB into 2T3 clones containing trBMPR-IB. Expression of a constitutively active BMPR-IB (caBMPR-IB) induced formation of mineralized bone matrix by 2T3 cells without addition of BMP-2. In contrast, overexpression of trBMPR-IA blocked adipocyte differentiation and expression of caBMPR-IA induced adipocyte formation in 2T3 cells. Expression of the adipocyte differentiation-related genes, adipsin and PPARgamma, correlated with the distinct phenotypic changes found after overexpression of the appropriate mutant receptors. These results demonstrate that type IB and IA BMP receptors transmit different signals to bone-derived mesenchymal progenitors and play critical roles in both the specification and differentiation of osteoblasts and adipocytes.

Adipocytes↗
PubMed1998

Mcm1 regulates donor preference controlled by the recombination enhancer in Saccharomyces mating-type switching.

Switching of Saccharomyces mating type by replacement of sequences at the MAT locus involves a choice between two donors, HML and HMR. MATalpha cells inhibit recombination along the entire left arm of chromosome III, including HML, whereas MATa cells activate this same region. MATa-dependent activation of HML depends on a small, cis-acting DNA sequence designated the recombination enhancer (RE), located 17 kb centromere-proximal to HML. A comparison of RE sequences interchangeable between Saccharomyces cerevisiae and Saccharomyces carlsbergensis defines a minimum RE of 244 bp. RE activity is repressed in MATalpha cells by binding of the Matalpha2-Mcm1 corepressor to a site within the RE. Mutation of the two Matalpha2 binding sites removes most, but not all, of this repression, and RE chromatin structure in MATalpha cells becomes indistinguishable from that seen in MATa. Surprisingly, a 2-bp mutation in the Mcm1 binding site completely abolishes RE activity in MATa cells; moreover, RE chromatin structure in the MATa mutant becomes very similar to that seen in MATalpha cells with a normal RE, displaying highly ordered nucleosomes despite the absence of Matalpha2. Further, a mutation that alters the ability of Mcm1 to act with Matalpha2 in repressing a-specific genes also alters donor preference in either mating type. Thus, Mcm1 is critically responsible for the activation as well as the Matalpha2-Mcm1-mediated repression of RE activity.

Base Sequence↗
PubMed1998

Expanding yeast knowledge online.

The completion of the Saccharomyces cerevisiae genome sequencing project and the continued development of improved technology for large-scale genome analysis have led to tremendous growth in the amount of new yeast genetics and molecular biology data. Efficient organization, presentation, and dissemination of this information are essential if researchers are to exploit this knowledge. In addition, the development of tools that provide efficient analysis of this information and link it with pertinent information from other systems is becoming increasingly important at a time when the complete genome sequences of other organisms are becoming available. The aim of this review is to familiarize biologists with the type of data resources currently available on the World Wide Web (WWW).

Amino Acid Sequence↗
PubMed1998

Cardiovascular disease risk factors are lower in African-American vegans compared to lacto-ovo-vegetarians.

OBJECTIVE: This study was undertaken to determine if African-American strict vegetarians (vegans) exhibit lower blood pressure (BP) and a more favorable serum lipid profile than their lacto-ovo vegetarian (LOV) counterparts, and if plasma ascorbic acid (AA) concentrations could explain any group differences in these cardiovascular disease (CVD) risk factors. METHODS: Habitual dietary intake, anthropometric characteristics, blood pressure, and blood lipids and ascorbic acid concentrations were determined in African-American study participants (male vegans, n = 14, age = 45.6 years; male LOV, n = 49, age = 49.8; female vegans, n = 31, age = 51.1, female LOV, n = 94, age = 52.1) recruited from Seventh-Day Adventist Churches in several cities in the northeastern United States. RESULTS: Body mass index (BMI) was significantly lower in the vegans (24.7 +/- 1.9 kg/m2) compared to LOV (26.4 +/- 0.45 kg/m2). There were no diet or gender differences in BP. Serum total cholesterol (3.75 +/- 0.12 vs. 4.51 +/- 0.10 mmol/L), LDL-cholesterol (2.06 +/- 0.13 vs. 2.65 +/- 0.09 mmol/l), and triglycerides (0.94 +/- 0.07 vs. 1.17 +/- 0.04 mmol/L) were significantly (p < 0.05) lower in vegans compared to LOV, but there were no dietary group differences in HDL-C. The ratio of total to HDL-cholesterol was significantly lower in vegans than in LOV (3.0 +/- 0.13 vs. 3.7 +/- 0.13). There were no dietary group differences in plasma AA concentrations. However, in the entire sample, plasma AA was inversely associated with BP (SBP: r = -0.46, p < 0.001, DBP: r = -0.32, p < 0.001), but unrelated to the serum lipid concentrations. CONCLUSION: African-American vegans exhibit a more favorable serum lipid profile than lacto-ovo-vegatarians and plasma AA is inversely related to BP in African-American vegetarians but does not explain any of the differences in CVD risk factors between vegans and lacto-ovo vegetarians.

Anthropometry↗
PubMed1998

Colorectal cancer screening: discussions with first degree relatives.

Screening by faecal occult blood test and colonoscopy is recommended for first degree relatives of people with colorectal cancer. While it is known that screening participation among relatives is low, relatives' beliefs and attitudes towards screening have not been explored at an in-depth level. In this study, four focus group discussions with first degree relatives of people with colorectal cancer were held. Discussions were audio-taped, transcribed verbatim and the data were independently coded and analysed by the authors. Three main themes were identified: risk, understanding, and screening. Perceived risk was determined by family history, age and gender. Of concern, there was limited understanding of the asymptomatic nature of screening with most relatives initially 'screened' after consulting a doctor with colorectal symptoms. These findings need to be considered in screening programs.

Attitude to Health↗
PubMed1998

Measuring tidal volume and functional residual capacity change in sleeping infants using a volume displacement plethysmograph.

The noninvasive measurement of infant lung function during unsedated sleep in infants has been a long-standing objective in paediatric respiratory medicine. This note reports on the design and performance of a head-out volume-displacement plethysmograph (VDP) that overcomes some of the limitations of traditional lung function apparatus. The VDP comprises a rigid acrylic box with an integral water-sealed spirometer and a novel neck seal. The bilayer neck seal is of variable compliance and is comfortable and simple to use. The spirometer permits volume resolution of 1.5 mL and a dynamic range in excess of 100 mL. The frequency response extends from 0-7 Hz. Spirometer inertance was measured as 0.0015 kPa.L(-1).s(-2), resistance 0.021 kPa.L(-1).s(-1) and box capacitance 0.18L.kPa(-1). Tidal volume, respiratory rate and changes in functional residual capacity can be recorded during unsedated rapid eye movement and nonrapid eye movement whilst monitoring with conventional polysomnographic methods. The head-out configuration allows additional instrumentation to be implemented with ease, avoids facial stimulation and allows unimpeded access to the upper airway. A polysomnograph illustrating the limitations of respiratory inductance plethysmography signals and typical changes in functional residual capacity are shown.

Functional Residual Capacity↗
PubMed1997

Clonal osteoblastic cell lines from p53 null mouse calvariae are immortalized and dependent on bone morphogenetic protein 2 for mature osteoblastic phenotype.

p53 protein regulates cell cycle progression and its absence will result in unlimited cell divisions required for immortalization of cells. Immortalized osteoblastic cell lines were established from p53 null mouse calvariae of normal phenotype. The clonal murine cell lines demonstrated osteoblastic phenotype as exemplified by alkaline phosphatase enzyme activity. They also express bone morphogenetic protein 2 (BMP2) mRNA. Addition of recombinant BMP2 to these cells dramatically increased the alkaline phosphatase activity in a dose dependent manner. In the absence of BMP2 these cells do not undergo osteoblastic differentiation. Treatment of these cells with recombinant bone morphogenetic protein 2 stimulated differentiated osteoblast formation, as determined by mineralized nodule formation. Thus, these immortalized cells in culture represent osteoblast progenitors that lack p53 protein and respond to osteogenic stimuli. These cell lines offer a model system to study the role of p53 in osteoblastic differentiation and programmed cell death. Also these cells will be useful in studying the effects of p53 on transcriptional regulation of osteoblast specific gene expression.

Alkaline Phosphatase↗
PubMed1997

Recombinant bone morphogenetic protein (BMP)-2 regulates costochondral growth plate chondrocytes and induces expression of BMP-2 and BMP-4 in a cell maturation-dependent manner.

This study examined the effect of recombinant human bone morphogenetic protein-2 on several parameters of growth, differentiation, and matrix synthesis and on the endogenous production of mRNA of bone morphogenetic proteins 2 and 4 by growth plate chondrocytes in culture. Chondrocytes from resting and growth zones were obtained from rat costochondral cartilage and cultured for 24 or 48 hours in medium containing 0.05-100 ng/ml recombinant human bone morphogenetic protein-2 and 10% fetal bovine serum. Incorporation of [3H]thymidine, cell number, alkaline phosphatase specific activity, incorporation of [3H]proline into collagenase-digestible protein and noncollagenase-digestible protein, and incorporation of [35S]sulfate were assayed as indicators of cell proliferation, differentiation, and extracellular matrix synthesis. mRNA levels for bone morphogenetic proteins 2 and 4 were determined by Northern blot analysis. Recombinant human bone morphogenetic protein-2 increased the incorporation of [3H]thymidine by quiescent resting-zone and growth-zone cells in a similar manner, whereas it had a differential effect on nonquiescent cultures. At 24 and 48 hours, 12.5-100 ng/ml recombinant human bone morphogenetic protein-2 caused a dose-dependent increase in cell number and DNA synthesis in resting-zone chondrocytes. No effect was seen in growth-zone cells. Recombinant human bone morphogenetic protein-2 stimulated alkaline phosphatase specific activity in resting-zone chondrocytes in a bimodal manner, causing significant increases between 0.2 and 0.8 ng/ml and again between 25 and 100 ng/ml. In contrast, alkaline phosphatase specific activity in growth-zone chondrocytes was significantly increased only between 12.5 and 100 ng/ml. Recombinant human bone morphogenetic protein-2 increased the production of both collagenase-digestible protein and noncollagenase-digestible protein by resting-zone and growth-zone cells, but incorporation of [35S]sulfate was unaffected. Administration of recombinant human bone morphogenetic protein-2 also increased incorporation of [3H]uridine in both resting-zone and growth-zone chondrocytes; these cells produced mRNA for bone morphogenetic proteins 2 and 4. Bone morphogenetic protein-2 mRNA levels in both resting-zone and growth-zone chondrocytes increased in the presence of recombinant human bone morphogenetic protein-2; however, bone morphogenetic protein-4 mRNA levels in growth-zone cells decreased under its influence, and those in resting-zone cells were upregulated only with a dose of 10 ng/ml. This indicates that recombinant human bone morphogenetic protein-2 regulates chondrocyte proliferation, differentiation, and matrix production, and the effects are dependent on the stage of cell maturation. Resting-zone chondrocytes were more sensitive, suggesting that they are targeted by bone morphogenetic protein-2 and that this growth factor may have autocrine effects on these cells.

Alkaline Phosphatase↗
PubMed1997

Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts.

Normal bone formation is a prolonged process that is carefully regulated and involves sequential expression of growth regulatory factors by osteoblasts as they proliferate and ultimately differentiate. Since this orderly sequence of gene expression by osteoblasts suggests a cascade effect, and BMP-2 is capable of initiating and maintaining this effect, we examined the effects of BMP-2 on expression of other BMPs and compared these effects with the expression pattern of bone cell differentiation marker genes in primary cultures of fetal rat calvarial (FRC) osteoblasts. To examine the gene expression profile during bone cell differentiation and bone formation, we also examined the effects of rBMP-2 on bone formation in vivo and in vitro. rBMP-2 stimulated bone formation on the periosteal surface of mice when 500 ng/day rBMP-2 was injected subctaneously. When rBMP-2 was added to primary cultures of FRC osteoblasts, it accelerated mineralized nodule formation in a time and concentration-dependent manner (10-40 ng/ml). rBMP-2 (40 ng/ml) enhanced BMP-3 and -4 mRNA expression during the mineralization phase of primary cultures of FRC osteoblasts. Enhancement of BMP-3 and -4 mRNA expression by rBMP-2 was associated with increased expression of bone cell differentiation marker genes, alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), osteopontin (OP), and bone sialoprotein (BSP). These results suggest that BMP-2 enhances expression of other BMP genes during bone cell differentiation. BMP-2 may act in a paracrine fashion in concert with other BMPs it induces to stimulate bone cell differentiation and bone formation during remodeling.

Amino Acid Sequence↗
PubMed1997

Acute renal failure in the first trimester resulting from uterine leiomyomas.

A primigravid woman with multiple uterine leiomyomas was seen at 8 weeks' gestation with acute renal failure and hypertension. After placement of bilateral nephrostomy tubes, renal function improved and blood pressure normalized. The pregnancy was complicated by maternal abdominal discomfort, intrauterine growth restriction, and perinatal death. A myomectomy performed post partum revealed a 24.4 pound pedunculated leiomyoma compressing the right kidney and liver. Large uterine leiomyomas may cause obstructive nephropathy and renal failure in pregnancy.

Acute Kidney Injury↗
PubMed1997

Maternal and perinatal long-chain fatty acids: possible roles in preterm birth.

OBJECTIVE: We conducted a case-control study to evaluate whether maternal and fetal omega-3 and omega-6 essential fatty acid status play possible roles in the pathogenesis of preterm birth. STUDY DESIGN: Essential fatty acid status in blood and trophoblast tissues was measured in (1) women and their newborns with spontaneous preterm birth and (2) control women and newborns at 34 weeks' gestation (maternal blood) and at term delivery. RESULTS: Thirty-seven preterm (mean gestational age 34 weeks) and 34 control mother-baby dyads (gestational age 40 weeks) were evaluated. The maternal percent of total arachidonic acid in red blood cells and plasma was increased in preterm cases versus controls at delivery (3.8- and 1.6-fold, respectively, p < 0.05). Maternal red blood cell eicosapentaenoic acid (1.98 +/- 0.15, p < 0.0001) and omega-3/omega-6 ratios (0.58 +/- 0.22, p < 0.009) were lower in preterm cases than in controls at delivery (4.64 +/- 0.32 and 1.27 +/- 0.12, respectively). Docosapentaenoic acid, a marker of omega-3 essential fatty acid deficiency, was higher in preterm maternal red blood cells (1.26 +/- 0.18, p < 0.0001) and amnion (1.27 +/- 0.19, p < 0.001) compared with term controls (0.12 +/- 0.07 and 0.58 +/- 0.13, respectively). CONCLUSION: Women delivered preterm demonstrated higher arachidonic acid and docosapentaneoic acid levels in maternal blood and trophoblast tissue than did women delivered at term. This suggests (1) altered essential fatty acid intake or metabolism in a portion of women delivered preterm and (2) increased maternal red blood cell arachidonic acid is associated with an increased risk of preterm birth.

Adult↗
PubMed1997

Postexercise energy expenditure and substrate oxidation in young women resulting from exercise bouts of different intensity.

OBJECTIVE: The effects of low and high intensity exercise, of similar energy output, on exercise and post-exercise energy expenditure and substrate oxidation were studied in eight active, eumenorrheic females (aged 22 to 31). METHODS: Continuous indirect calorimetry was performed during cycle ergometry exercise and for 3 hours following each of the following three protocols administered in random order: 1) low intensity exercise (LIE: 500 calories 50% VO2 max), 2) high intensity exercise (HIE: 500 calories 75% VO2 max), and 3) control condition (C) of quiet sitting for 1 hour, rather than exercise. Excess postexercise oxygen consumption (EPOC), energy expenditure and total fat and carbohydrate oxidation for the entire exercise/control plus 3-hour recovery period were determined by indirect calorimetry. RESULTS: Mean EPOC for the 3-hour post-exercise period for HIE (9.0 +/- 1.7 L, 41 kcals) was significantly greater than EPOC for low intensity exercise (4.8 +/- 1.6 L, 22 kcals). Oxygen consumption (VO2) following HIE, but not LIE remained elevated at the end of the 3-hour post-exercise period. Total carbohydrate oxidation (exercise plus postexercise period) was significantly higher for HIE (116 +/- 8.6 g) compared to LIE (85.0 +/- 5.2 g). Total fat oxidation was lower for HIE (27.7 +/- 3.3 g) compared to LIE (36.9 +/- 3.0 g), but this difference did not reach statistical significance (p = 0.07). At the end of the 3-hour recovery period, the rate of fat oxidation was higher following HIE compared to LIE. CONCLUSION: These data indicate that the recovery period should also be considered when determining the impact of different exercise intensities on total energy expenditure and fat and carbohydrate utilization in women.

Adult↗
PubMed1997

Background air concentrations of Cr(VI) in Hudson County, New Jersey: implications for setting health-based standards for Cr(VI) in soil.

An accurate measure of "background" airborne Cr(VI) concentrations will be necessary to derive site-specific health-based Cr(VI) soil concentrations at sites containing chromite ore processing residues (COPR) in Hudson County, NJ. To date, no such data have been collected in New Jersey. This paper describes an air sampling program designed to measure background concentrations of Cr(VI) in Hudson County and compare those concentrations with the air sampling results obtained previously at 30 COPR sites in Hudson County. Background airborne Cr(VI) concentrations ranged from 0.2 to 3.8 ng/m3 with an arithmetic mean of 1.2 ng/m3. Comparisons of the airborne Cr(VI) concentrations previously measured at 30 COPR sites indicated that more than two-thirds of the sites had mean airborne Cr(VI) concentrations that were not statistically significantly greater than background. Our findings suggest that, in general, vehicle disturbance is required for significant soil suspension to occur at these sites. Since airborne Cr(VI) concentrations at many of these sites are close to background, it is critical that background airborne Cr(VI) levels be considered when deriving health-based soil standards at the COPR sites.

Air Pollution↗
PubMed1997

Social validity of support group and behavior therapy interventions for families of adolescents with insulin-dependent diabetes mellitus.

Compared the social validity of behavior therapy vs. support group interventions for reduction of parent-adolescent conflict among families of adolescents with diabetes. Families were randomized to 10 sessions of an Education and Support group (ES) or 10 sessions of Behavioral Family Systems Therapy (BFST). We compared participants' social validity ratings of BFST and ES using the Treatment Evaluation Questionnaire (TEQ). Mean TEQ scores were significantly more positive for BFST than ES and, for 13 of 20 items, BFST was rated significantly more positively by parents and/or adolescents. Adolescents rated ES less positively than did parents. Fathers' responses reflected fewer differences between ES and BFST. Results extend previous research on BFST and confirm its superiority over ES for targeting family conflict.

Adaptation, Psychological↗
PubMed1997

A survey of screening compliance among first degree relatives of people with colon cancer in New South Wales.

OBJECTIVE: To survey screening practices, knowledge, and attitudes towards screening among first degree relatives of people with colon cancer. SETTING: A random sample of people with colon cancer listed on the New South Wales (NSW) Cancer Registry were mailed a questionnaire to be passed on to an appropriate first degree relative. METHODS: Two hundred and twenty five first degree relatives completed a self administered questionnaire. RESULTS: Although there were high levels of awareness about colorectal cancer, and attitudes towards colorectal cancer were generally positive, screening rates were low, and only three relatives had been screened in accordance with current Australian recommendations. Factors associated with previous participation in any type of screening test (usually once) included receiving a medical recommendation to screen, having more than one relative with colorectal cancer, being a sibling of the relative with colon cancer, the relative with cancer being female, and perceiving screening as messy, but not painful. CONCLUSIONS: Strategies to enhance screening awareness and participation among relatives need to be considered. This study provides some insight into factors to be considered in developing awareness programmes. Further research is required to explore these factors, and to identify ways to overcome barriers.

Adult↗