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Biomedical subjects

K Holt

Publications and source records attributed to K Holt.

At least 19 recordsLinked to original sources
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2005

A longitudinal study to explain strategies to change weight and muscles among normal weight and overweight children.

Previous research has indicated that both boys and girls strive for a slim body, with boys having an additional focus on a muscular body build. The current study was designed to evaluate the utility of a biopsychosocial model to explain body image and body change strategies among children. The study evaluated changes over time in body image and strategies to lose weight and increase muscles among 132 normal weight and 67 overweight boys (mean age = 9.23 years) and 158 normal weight and 55 overweight girls (mean age = 9.33 years). The predictive role of BMI, positive and negative affect, self-esteem and perceived sociocultural pressures to lose weight or increase muscle on body image and body change strategies over a 16 month period was evaluated. All participants completed the questionnaire on both occasions. The results demonstrated that both overweight boys and girls were more likely to be dissatisfied with their weight, place more importance on their weight, engage in more strategies to lose weight as well as perceive more pressure to lose weight. Overweight boys and girls were also more likely to report lower levels of self-esteem and positive affect, and higher levels of negative affect, and reported a reduction in their self-esteem over time. Regression analyses demonstrated that among overweight boys, low self-esteem and high levels of perceived pressure to lose weight predicted weight dissatisfaction; for overweight girls, weight dissatisfaction was also predicted by low levels of self-esteem. The implication of these findings in terms of factors contributing to the adoption of health risk behaviors among children is discussed.

Body Composition↗
PubMed2001

Oral steroids for bronchiectasis (stable and acute exacerbations).

BACKGROUND: Inflammation plays a significant role in the pathophysiology of bronchiectasis. Two small studies have shown small benefits from inhaled corticosteroids and oral corticosteroids may be of benefit in bronchiectasis OBJECTIVES: To determine the efficacy of oral corticosteroids in acute and stable bronchiectasis SEARCH STRATEGY: The Cochrane Airways Group clinical trials register, derived from MEDLINE, EMBASE and hand searching of major journals, was searched using the terms bronchiectasis AND corticosteroid* OR (beclomethasone, cortisone, deflazacort, hydrocortisone, methylprednisolone, prednisolone, dexamethasone and triamcinolone SELECTION CRITERIA: Only randomised controlled trials were considered DATA COLLECTION AND ANALYSIS: No trials met the inclusion criteria for the review MAIN RESULTS: No randomised controlled trials were identified REVIEWER'S CONCLUSIONS: There are no randomised trials upon which to make recommendations about the use of oral corticosteroids in acute or stable bronchiectasis.

Acute Disease↗
PubMed2001

Anticholinergic therapy for bronchiectasis.

BACKGROUND: Anticholinergic agents block bronchoconstriction mediated by the vagus nerve and may also dry up bronchial secretions. They are effective in obstructive airways disease and may be beneficial in bronchiectasis OBJECTIVES: To determine the effect of anticholinergic therapy in acute exacerbations and stable bronchiectasis. SEARCH STRATEGY: The Cochrane Airways Group clinical trials register was searched using the terms bronchiectasis AND anticholinergic OR ipratropium bromide OR tiotropium OR atropine. SELECTION CRITERIA: Only randomised controlled trials were considered. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the retrieved studies working independently. MAIN RESULTS: Twelve studies were identified, of which six were obtained for further scrutiny. One was translated from Italian. None met the inclusion criteria. REVIEWER'S CONCLUSIONS: No formal recommendations can be made about the use of anticholinergic therapy in acute or stable bronchiectasis based on the literature currently available.

Acute Disease↗
PubMed1999

From the Oklahoma State Department of Health. CDC recommendations for diagnosis and initial management of hepatitis C virus infection.

Hepatitis C is a growing public health concern in the United States. All physicians should be aware of who should be tested for HCV, based upon risk factors for infection, as well as how to manage persons found to have positive screening tests. The following recommendations focus primarily on the role of the primary care physician in the initial evaluation and management of persons who test positive for HCV and are excerpted from the Centers for Disease Control document "Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease," Oct. 16, 1998/47(RR19); 1-39.

Algorithms↗
PubMed1998

Brown-midrib maize (bm1)--a mutation affecting the cinnamyl alcohol dehydrogenase gene.

Brown-midrib (bm) mutants of maize have modified lignin of reddish-brown colour. Although four independent bm loci are known, only one of the mutant genes has been previously identified. We report here that maize bm1, one of the less characterised mutants, shows severely reduced CAD activity in lignified tissues, resulting in the production of a modified lignin. Both the total lignin content and the structure of the polymer are altered by the mutation. We further describe the isolation and characterisation of the maize CAD cDNA and mapping of the CAD gene. CAD maps very closely to the known location of bm1 and co-segregates with the bm1 locus in two independent recombinant inbred populations. These data strongly support the premise that maize bm1 directly affects expression of the CAD gene.

Alcohol Oxidoreductases↗
PubMed1998

Genetic manipulation of alcohol dehydrogenase levels in ripening tomato fruit affects the balance of some flavor aldehydes and alcohols

Tomato (Lycopersicon esculentum) plants were transformed with gene constructs containing a tomato alcohol dehydrogenase (ADH) cDNA (ADH 2) coupled in a sense orientation with either the constitutive cauliflower mosaic virus 35S promoter or the fruit-specific tomato polygalacturonase promoter. Ripening fruit from plants transformed with the constitutively expressed transgene(s) had a range of ADH activities; some plants had no detectable activity, whereas others had significantly higher ADH activity, up to twice that of controls. Transformed plants with fruit-specific expression of the transgene(s) also displayed a range of enhanced ADH activities in the ripening fruit, but no suppression was observed. Modified ADH levels in the ripening fruit influenced the balance between some of the aldehydes and the corresponding alcohols associated with flavor production. Hexanol and Z-3-hexenol levels were increased in fruit with increased ADH activity and reduced in fruit with low ADH activity. Concentrations of the respective aldehydes were generally unaltered. The phenotypes of modified fruit ADH activity and volatile abundance were transmitted to second-generation plants in accordance with the patterns of inheritance of the transgenes. In a preliminary taste trial, fruit with elevated ADH activity and higher levels of alcohols were identified as having a more intense "ripe fruit" flavor.

Journal Article↗
PubMed1995

Risk of child abuse or neglect in a cohort of low-income children.

The purposes of this research were to identify risk factors for reported child abuse or neglect and to examine the roles of stress and social support in the etiology of child maltreatment. Mothers of newborn infants with biomedical and sociodemographic risk factors were recruited from community and regional hospitals and local health departments in 42 counties of North and South Carolina selected for geographic distribution and for large numbers of such newborns. For every four such mothers, the next mother to deliver an otherwise normal newborn was sought. Mothers were interviewed shortly after giving birth, and state Central Registries of Child Abuse and Neglect were reviewed when each infant was 1 year of age. Eight hundred forty-two of 1,111 recruited mothers were successfully interviewed in their homes between March 1986 and June 1987. Seven hundred forty-nine North Carolina births who resided in the state more than 6 months were eligible for inclusion in the analysis. Logistic regression with backward elimination procedures was used in the analysis. Maternal education (p < .01), number of other dependent children in the home (p < .01), receipt of Medicaid (p < .01), maternal depression (p < .05), and whether the maternal subject lived with her own mother at age 14 years (p < .05) were the best predictors of a maltreatment report. Further examination revealed an interaction effect between stressful life events, as measured by life event scores, and social well-being (p < .01). For children born at risk for social and/or medical problems, extreme low income (participation in public income support programs), low maternal education, maternal depression, the presence of any other young children in the home, and a mother's separation at age 14 years from her own mother significantly predict child maltreatment reports in the first year of life. In addition, stressful life events, even if perceived positively, may increase or decrease the risk of maltreatment reports, depending upon the presence of social support.

Adolescent↗
PubMed1995

Tomato exo-(1-->4)-beta-D-galactanase. Isolation, changes during ripening in normal and mutant tomato fruit, and characterization of a related cDNA clone.

An exo-(1-->4)-beta-D-galactanase was isolated from ripe tomato fruit (Lycopersicon esculentum Mill. cv Ailsa Craig and cv Better Boy) using anion-exchange, gel filtration, and cation-exchange chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the most active fraction revealed a predominant protein band at 75 kD and several minor bands. A 30-amino acid N-terminal sequence from this 75-kD protein showed a high degree of homology with other recently identified beta-galactosidase/ galactanase proteins from persimmon and apple fruits (I.-K. Kang, S.-G. Suh, K.C. Gross, J.-K. Byun [1994] Plant Physiol 105: 975-979; G.S. Ross, T. Wegrzyn, E.A. MacRae, R.J. Redgwell [1994] Plant Physiol 106: 521-528) and with the predicted polypeptide sequence encoded by the ethylene-regulated SR12 gene in carnation (K.G. Raghothama, K.A. Lawton, P.B. Goldsbrough, W.R. Woodson [1991] Plant Mol Biol 17: 61-71). The enzyme focused to a single band of beta-galactosidase activity on an isoelectrofocusing gel at pH 9.8. The enzyme was specific for (1-->4)-beta-D-galactan substrates with a pH optimum of 4.5. The only reaction product detected was monomeric galactose, indicating that the enzyme was an exo (1-->4)-beta-D-galactanase. beta-Galactanase activity increased at the onset of ripening in normal fruit, but no similar increase was detected in the nonripening mutants nor and rin. A tomato homolog (pTombetagal1) was isolated using the SR12 cDNA clone from carnation as a probe. This clone showed 73% identify at the amino acid level with beta-galactosidase-related sequences from apple and asparagus and 66% identity with SR12. pTombetagal1 is a member of a gene family. Northern analysis demonstrated that pTombetagal1 expression was ripening related in normal fruits, with lower levels apparent in the nonsoftening mutants.

Amino Acid Sequence↗
PubMed1993

Phosphatidylinositol 3-kinase functions upstream of Ras and Raf in mediating insulin stimulation of c-fos transcription.

Insulin treatment of Chinese hamster ovary (CHO) cells expressing high levels of the insulin receptor (CHO-IR) was found to markedly activate (10-20-fold) transcription of the luciferase reporter gene (Luc) driven by the serum response element (SRE) of the c-fos promoter. SRE-Luc expression was also strongly activated by co-transfection with expression plasmids encoding for either v-Ras or v-Raf. In contrast, insulin-stimulated SRE-Luc activity was inhibited by expression of a negative-dominant Ras (RasAsn-17)- or a negative-dominant Raf (p301-1)-encoding plasmid. Furthermore, the negative-dominant Raf mutant blocked v-Ras activation whereas the negative-dominant Ras mutant had no significant effect on v-Raf activation. Together, these data demonstrate that insulin utilizes the Ras and Raf signaling pathways and that Ras functions upstream of Raf in terms of transcriptional activation of the serum response element. To assess the role of the phosphatidylinositol (PI) 3-kinase in this insulin signaling pathway, CHO-IR cells were co-transfected with the p85 regulatory subunit of the PI 3-kinase. Expression of the p85 subunit inhibited the insulin stimulation of SRE-Luc activity without affecting v-Ras or v-Raf activation. Thus, these data demonstrate that the PI 3-kinase is necessary for insulin signaling of transcriptional events and that, in a linear model of intracellular signaling, the PI 3-kinase functions upstream of both Ras and Raf.

Animals↗
PubMed1993

Coping with rheumatoid arthritis: is one problem the same as another?

This study examined how individuals with rheumatoid arthritis (RA) cope with illness-related problems in four different areas: daily activities, leisure activities, work, and social relationships. Eighty-five people with RA took part in the study. They participated in an in-depth interview that focused on the types of changes they had experienced in their lives as a result of their arthritis and how they had coped with these changes. Audiotapes of the interviews were transcribed and content analyzed to assess participants' coping behavior. In addition, standardized measures of psychological and physical functioning were administered shortly following the original interview and at a 4-month follow-up. Three major findings emerged. First, people relied less heavily on behavioral coping strategies when dealing with problems involving social relationships than when dealing with problems involving daily activities, leisure activities, or work. Second, there was little consistency in individuals' use of either cognitive or behavioral strategies across different problem areas. Finally, individuals who exhibited limited flexibility in their coping responses experienced poorer psychological functioning compared with more flexible copers. Implications of these findings for health education practice and future research on coping with RA are discussed.

Activities of Daily Living↗
PubMed1987

Depression, self-focused attention, and expectancies for positive and negative future life events for self and others.

In two studies, we examined depressed and nondepressed persons' judgments of the probability of future positive and negative life events occurring to themselves and to others. Study 1 demonstrated that depressed subjects were generally less optimistic than their nondepressed counterparts: Although nondepressed subjects rated positive events as more likely to happen to themselves than negative events, depressed subjects did not. In addition, relative to nondepressed subjects, depressed subjects rated positive events as less likely to occur to themselves and more likely to occur to others and negative events as more likely to occur to both self and others. Study 2 investigated the role that differential levels of self-focused attention might play in mediating these differences. On the basis of prior findings that depressed persons generally engage in higher levels of self-focus than nondepressed persons do and the notion that self-focus activates one's self-schema, we hypothesized that inducing depressed subjects to focus externally would attenuate their pessimistic tendencies. Data from Study 2 supported the hypothesis that high levels of self-focus partially mediate depressive pessimism: Whereas self-focused depressed subjects were more pessimistic than nondepressed subjects, externally focused depressed subjects were not. The role of attentional focus in maintaining these and other depressive pessimistic tendencies was discussed.

Adult↗
PubMed1986

Serum antibody levels to Taenia saginata in cattle grazed on Scottish pastures.

The serum antibody levels to Taenia saginata of three groups of cattle were assessed by an enzyme-linked immunosorbent assay (ELISA). The first group of cattle were from four farms which had a confirmed T saginata cysticercosis outbreak, all of which had cattle classed as infected by ELISA. The second group were from four farms where sewage sludge had been applied to pasture subsequently grazed by the cattle. One of these farms had cattle classed as infected by ELISA. The control cattle, which were all classed as uninfected by ELISA, came from five farms whose pasture had not been treated with sewage sludge. In a wider survey, involving sera from 47 additional farms, the majority could not be distinguished from the control farms in the earlier survey. However, samples from three of the farms had a similar number of positives to two of the known infected farms in the initial survey. Since the ELISA assay may indicate infected herds, farms such as these warrant further investigation.

Animal Feed↗
PubMed1985

Isotope bone scans in the assessment of children with hip pain or limp.

Bone scans from 43 children referred with hip pain of uncertain cause were reviewed. The bone scan was abnormal in 36 patients: normal in 7. In 12 the findings were diagnostic: osteomyelitis, osteoid osteoma, osteomyelitis with septic arthritis, Perthes' Disease and juvenile chronic arthritis. Twenty-four patients had abnormal scans including diffuse peri-articular increase and of these 18 had transient synovitis. Immobilisation and trauma accounted for the remainder. Isotope bone scans have been found to be a valuable investigation in children presenting with hip pain or limp, where the x-rays may appear normal or nondiagnostic.

Adolescent↗
PubMed1983

Natural urinary macromolecular inhibitors: attenuation of inhibitory activity by urate salts.

The interaction between naturally occurring urinary macromolecular inhibitors of calcium oxalate nucleation and crystal growth and the various urate salts was explored in vitro. The fraction of macromolecules chosen for the study was the one which was previously shown to have a potent inhibitor activity against calcium oxalate nucleation and one which gave a satisfactory yield. As little as 0.025 mg/ml of this fraction (Y-b) was found to inhibit calcium oxalate nucleation by nearly 50% and crystal growth by 31%. Prior incubation of the solution containing Y-b with increasing crystal surface areas (1.1 to 26.2 mm2/ml) of monosodium urate (NaU), monopotassium urate (KU), or uric acid (UA) attenuated the inhibitory action of the Y-b fraction for both nucleation and crystal growth of calcium oxalate. The most prominent effect was elicited by NaU at surface areas as small as 1.1 mm2/ml. Potassium urate and UA were without significant effects until surface areas of 13.1 and 2.6 mm2/ml, respectively, were achieved. These results support an important pathogenetic role for urates (particularly NaU) in the development of hyperuricosuric calcium urolithiasis.

Calcium Oxalate↗