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Biomedical subjects

R D Hill

Publications and source records attributed to R D Hill.

At least 19 recordsLinked to original sources
PubMed1999

The heme environment in barley hemoglobin.

To elucidate the environment and ligand structure of the heme in barley hemoglobin (Hb), resonance Raman and electron paramagnetic resonance spectroscopic studies have been carried out. The heme is shown to have bis-imidazole coordination, and neither of the histidines has imidazolate character. Barley Hb has a unique heme environment as judged from the Fe-CO and C-O stretching frequencies in the CO complex. Two Fe-CO stretching modes are observed with frequencies at 534 and 493 cm-1, with relative intensities that are pH sensitive. The 534 cm-1 conformer shows a deuterium shift, indicating that the iron-bound CO is hydrogen-bonded, presumably to the distal histidine. A C-O stretching mode at 1924 cm-1 is assigned as being associated with the 534 cm-1 conformer. Evidence is presented that the high Fe-CO and low C-O stretching frequencies (534 and 1924 cm-1, respectively) arise from a short hydrogen bond between the distal histidine and the CO. The 493 cm-1 conformer arises from an open conformation of the heme pocket and becomes the dominant population under acidic conditions when the distal histidine moves away from the CO. Strong hydrogen bonding between the bound ligand and the distal histidine in the CO complex of barley Hb implies that a similar structure may occur in the oxy derivative, imparting a high stability to the bound oxygen. This stabilization is confirmed by the dramatic decrease in the oxygen dissociation rate compared with sperm whale myoglobin.

Electron Spin Resonance Spectroscopy↗
PubMed1999

The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus.

AIMS: To assess mortality in patients with diabetes incident under the age of 30 years. METHODS: A cohort of 23 752 diabetic patients diagnosed under the age of 30 years from throughout the United Kingdom was identified during 1972-93 and followed up to February 1997. Following notification of deaths during this period, age- and sex-specific mortality rates, attributable risks and standardized mortality rates were calculated. RESULTS: The 23 752 patients contributed a total of 317 522 person-years of follow-up, an average of 13.4 years per subject. During follow-up 949 deaths occurred in patients between the ages of 1 and 84 years, 566 in males and 383 in females. All-cause mortality rates in the patients with diabetes exceeded those in the general population at all ages and within the cohort were higher for males than females at all ages except between 5 and 15 years. The relative risk of death (standardized mortality ratio, SMR), was higher for females than males at all ages, being 4.0 (95% CI 3.6-4.4) for females and 2.7 (2.5-2.9) for males overall, but reaching a peak of 5.7 (4.7-7.0) in females aged 20-29, and of 4.0 (3.1-5.0) in males aged 40-49. Attributable risks, or the excess deaths in persons with diabetes compared with the general population, increased with age in both sexes. CONCLUSIONS: This is the first study from the UK of young patients diagnosed with diabetes that is large enough to calculate detailed age-specific mortality rates. This study provides a baseline for further studies of mortality and change in mortality within the United Kingdom.

Adolescent↗
PubMed1999

The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus.

AIMS: To measure cause-specific mortality, by age, in patients with insulin-treated diabetes incident at a young age. METHODS: A cohort of 23 752 patients with insulin-treated diabetes diagnosed under the age of 30 years, from throughout the United Kingdom, was identified during 1972-93 and followed to February 1997. Death certificates have been obtained for deaths during the follow-up period and cause-specific mortality rates and standardized mortality ratios by age and sex are reported. RESULTS: During the follow-up period 949 deaths occurred and at all ages mortality rates were considerably higher than in the general population. Acute metabolic complications of diabetes were the greatest single cause of excess death under the age of 30 years. Cardiovascular disease was responsible for the greatest proportion of the deaths from the age of 30 years onwards. CONCLUSIONS: Deaths in patients with diabetes diagnosed under the age of 30 have been reported and comparisons drawn with mortality in the general population. To reduce these deaths attention must be paid both to the prevention of acute metabolic deaths and the early detection and treatment of cardiovascular disease and associated risk factors.

Adolescent↗
PubMed1998

Altering hemoglobin levels changes energy status in maize cells under hypoxia.

Nonsymbiotic hemoglobins are broadly present across the plant kingdom; however, the function of these proteins is unknown. Cultured maize cells have been transformed to constitutively express a barley hemoglobin gene in either the sense (HB+) or antisense (HB-) orientation. Hemoglobin protein in the transformed cell lines correspondingly was higher or lower than in wild-type cells under normal atmospheric conditions. Limiting oxygen availability, by placing the cells in a nitrogen atmosphere for 12 hr, had little effect on the energy status of cells constitutively expressing hemoglobin, but had a pronounced effect on both wild-type and HB- cells, where ATP levels declined by 27% and 61%, respectively. Total adenylates in these cells were approximately 35% lower than in HB+ cells. Energy charge was relatively unaffected by the treatment in HB+ and wild-type cells, but was reduced from 0.91 to 0.73 in HB- cells, suggesting that the latter were incapable of maintaining their energy status under the low oxygen regime. Treatment of the cells grown in an air atmosphere with antimycin A gave essentially the same results. It is suggested that nonsymbiotic hemoglobins act in plants to maintain the energy status of cells in low oxygen environments and that they accomplish this effect by promoting glycolytic flux through NADH oxidation, resulting in increased substrate-level phosphorylation. Hypoxic acclimation of plants is an example of this effect in nature. Nonsymbiotic hemoglobins are likely ancestors of an early form of hemoglobin that sequestered oxygen in low oxygen environments, providing a source of oxygen to oxidize NADH to provide ATP for cell growth and development.

Journal Article↗
PubMed1998

Evidence of an increasing prevalence of diagnosed diabetes mellitus in the Poole area from 1983 to 1996.

This study examined the prevalence of diagnosed diabetes mellitus in a defined population over 13 years by undertaking cross-sectional surveys on 3 occasions between 1983 and 1996. The study population consisted of all the people registered with 10 general (primary care) practices at the time of each survey; 90660 in 1983/4; 97122 in 1988/9; and 86287 in 1996. Ascertainment of cases was by a surveillance programme in general practice and the hospital diabetes department. The number of diabetic patients increased significantly over the study period: in 1983/4, there were 917 patients, crude prevalence 1.01% (95% CI 0.95-1.08%); in 1988/9, 1150 patients, crude prevalence 1.17% (1.12-1.25%); and in 1996, 1604 patients, crude prevalence 1.86% (1.77-1.95%). The prevalence adjusted to the age and sex distribution of the UK was 0.97% (95% CI 0.90-1.03%) in 1983/4, 1.05% (0.99-1.11%) in 1988/9 and 1.55% (1.48-1.63%) in 1996. The main increase in prevalence was due to Type 2 diabetes mellitus, crude prevalence 0.75% (95% CI 0.69-0.81%) in 1983/4, 0.92% (0.86-0.98%) in 1988/9 and 1.52% (1.44-1.60%) in 1996 rather than Type 1 diabetes mellitus, crude prevalence 0.25% (0.21-0.28%) in 1983/4, 0.25% (0.22-0.28%) in 1988/9 and 0.34% (0.30-0.38%) in 1996. During the study period, the crude prevalence of diagnosed diabetes was significantly greater in men than women; in 1983/4 men 1.1% (95% CI 1.00-1.20%) versus women 0.93% (0.84-1.02%); in 1988/9, men 1.31% (1.21-1.41%) versus women 1.07% (0.98-1.16%); and in 1996, men 2.13% (2.00-2.27%) versus women 1.60% (1.49-1.72%). This difference was statistically significant in the 1988/9 and 1996 surveys. In conclusion, over 13 years there was a significant increase of 83.6% in the prevalence of diagnosed diabetes mellitus in the Poole area, with the UK age and sex adjusted prevalence increasing by 60.7%.

Adolescent↗
PubMed1998

Preferences of old and young Navaho Indians for Western and indigenous health care providers: an exploratory study.

References for Western versus traditional health care providers were assessed in 27 older (M = 61.5 years) and 21 younger (M = 22.6 years) American Indians living on the Navaho reservation. Participants were read standardized vignettes depicting diagnosable physical and emotional illnesses, and they completed a series of forced-choice questions indicating their preference for traditional or Western health care providers for treating these conditions. Analysis of variance (ANOVA) was used to assess health care provider preference with age, interviewer, and illness type as independent variables. Medical doctors were preferred over all other health care providers for physical problems, and this was particularly true for the younger group. Although it was anticipated that the older participants would favor traditional healers and the younger participants would prefer Western options, there was no main effect for age. This lack of differentiation by age in provider preference was interpreted in terms of informal utilization patterns and the role of the family referral system inherent in this group of indigenous adults.

Adolescent↗
PubMed1997

Expression, purification, and properties of recombinant barley (Hordeum sp.) hemoglobin. Optical spectra and reactions with gaseous ligands.

A cDNA encoding barley hemoglobin (Hb) has been cloned into pUC 19 and expressed in Escherichia coli. The resulting fusion protein has five extra amino acids at the N terminus compared with the native protein, resulting in a protein of 168 amino acids (18.5 kDa). The recombinant Hb is expressed constitutively. Extracts made from the bacteria containing the recombinant fusion construct contain a protein with a subunit molecular mass of approximately 18.5 kDa comprising approximately 5% total soluble protein. Recombinant Hb was purified to homogeneity according to SDS-polyacrylamide gel electrophoresis by sequential polyethylene glycol precipitation and fast protein liquid chromatography. Its native molecular mass as assessed by fast protein liquid chromatography-size exclusion was 40 kDa suggesting that it is a dimer. Ligand binding experiments demonstrate that 1) barley Hb has a very slow oxygen dissociation rate constant (0.0272 s-1) relative to other Hbs, and 2) the heme of ferrous and ferric forms of the barley Hb is low spin six-coordinate. The subunit structure, optical spectrum, and oxygen dissociation rate of native barley hemoglobin are indistinguishable from those obtained for the recombinant protein. The implications of these kinetic data on the in vivo function of barley Hb are discussed.

Amino Acid Sequence↗
PubMed1997

Mortality rates in diabetic patients from a community-based population compared to local age/sex matched controls.

Using a population-based cohort from 10 general practices in East Dorset, the mortality rate of diabetic patients compared to non-diabetic controls was investigated during 8 years follow-up. From a total population of 90660, 917 diabetic patients were identified; 693 (75%) with non-insulin-dependent (Type 2) diabetes and 224 (25%) with insulin-dependent (Type 1) diabetes. A control group of 917 non-diabetic subjects were selected, matched by age and sex. After 8 years, significantly more diabetic patients (334 or 36.4%) had died than controls (219 or 24%), (odds ratio (OR) 1.99, 95% CI 1.60-2.47). Compared with the controls, the odds ratio of all causes of mortality for diabetic men was 1.89 (CI 1.4-2.54) and for diabetic women 2.16 (CI 1.57-2.96). Compared with controls, the odds ratio for mortality from circulatory disease was significantly increased for diabetic patients 2.0 (CI 1.5-2.6) but mortality for respiratory disease or neoplasms was not significantly different (OR 0.7, CI 0.4-1.2 and OR 0.7, CI 0.6-1.0, respectively). Control data were lower than would be expected from national database data. The diabetic population had a significantly higher mortality than controls, both from all causes and circulatory diseases. Our data incidentally show the importance of appropriate controls for estimating the impact of a chronic disease.

Adolescent↗
PubMed1996

Cloning and expression pattern of Hor v 9, the group 9 pollen isoallergen from barley.

In this study we report the cloning, sequence, and characterization of Hor v 9 allergen cDNAs from barley (Hordeum vulgare) pollen. Structural homologues of Kentucky bluegrass (Poa pratensis) group 9 pollen allergens were identified in a cDNA library of barley pollen expressed mRNAs. The Hor v 9 cDNA clone (hvp9742) contained an open reading frame encoding 313 amino acids which included a putative 27-residue signal peptide and one asparagine sequon for glycosylation. The mRNA corresponding to clone hvp9742 was produced abundantly in pollen during the late stages of anther development. The protein encoded by clone hvp974 was synthesized as a fusion protein in the E. coli expression vector pMAL. Immunoblots using antibodies to this recombinant allergen, rHor v 9, showed that Hor v 9 protein accumulated during pollen development and was produced maximally at pollen maturity. Using these antibodies, we also provide evidence that Hor v 9 protein localized to the extracellular matrix of mature pollen. Southern blots suggested that Hor v 9 allergens exist as multiple isoforms in barley. Sequence comparisons showed that the Hor v 9 cDNA clones were also homologous to group 5 allergens of Timothy grass (Phleum pratense) pollen and canary grass (Phalaris aquatica) pollen, and the group 9 allergen of ryegrass (Lolium perenne) pollen.

Allergens↗
PubMed1996

The influence of depressive symptomatology on episodic memory functioning among clinically nondepressed older adults.

The authors examined a community-based sample of 303 clinically nondepressed individuals aged 75 through 96 years on 4 recall tasks: free recall of rapidly presented random words, free recall of slowly presented random words, free recall of organizable words, and cued recall of organizable words. Using a classification taxonomy that identified mood- and motivation-related symptoms of depression, it was found that motivation-related symptoms had a negative effect on performance across all tasks, whereas mood-related symptoms had no effects. In addition, motivation-related symptoms negatively influenced the ability to benefit from more study time but had no effect on the ability to make use of item organization or category cues. An analysis of the specific motivation-related symptoms suggested that symptoms that may affect the ability to focus and sustain attention (e.g., concentration difficulties, lack of interest) were most strongly associated with performance deficits.

Affect↗
PubMed1996

Effects of serum vitamin B12 and folate status on episodic memory performance in very old age: a population-based study.

We examined the relationship between low levels of serum vitamin B12 (< 200 pmol/L) and folic acid (< 11 nmol/L), separately or combined, and episodic memory performance in very old age. Participants with low serum vitamin values were compared with a control group matched for age and educational level. Participants (N = 250) were selected from a group of nondemented, community-dwelling persons ages 75-96. Episodic memory was tested by means of free recall and recognition of slowly and rapidly presented words. Results indicated a deterioration in both free recall and recognition as a function of serum vitamin status. However, no linear effects of vitamin levels on memory were observed, indicating that vitamin B12 and folic acid status may effect memory only among individuals at the low end of the distribution. We speculate that the vitamin-related memory deficit may reflect encoding problems, possibly due to alterations in brain metabolism.

Age Factors↗
PubMed1996

Molecular characterization of Hor v 9. Conservation of a T-cell epitope among group IX pollen allergens and human VCAM and CD2.

We have cloned, sequenced and expressed a recombinant group IX pollen allergen from barley (Hordeum vulgare). Hor v 9 is a polypeptide of 313 amino acids. The Hor v 9 cDNA clone was engineered into the E. coli protein expression vector pMAL and expressed as a fusion of maltose binding protein and truncated Hor v 9. Polyclonal antibodies to the fusion protein were raised in mice. Cross-reactive proteins, RNA and DNA homologues were found in many agricultural species including wheat, rye, triticale, oats, maize, sunflower and flax. The presence of group IX-like proteins in a variety of agricultural crops may represent a previously uncharacterized aeroallergenic occupational hazard. Sequence comparisons of the barley allergen, Hor v 9, with Poa p 9 and other cloned group IX pollen allergens revealed putative structural domains common to all. These include a signal peptide, two conserved immunoglobulin-like motifs, a 150 amino acid highly conserved carboxyterminal domain and a carboxyterminal transmembrane helix. This structural arrangement is also found in cell adhesion molecules. The highly conserved T-cell epitope previously characterized and mapped in group IX allergens (and present in Hor v 9) was found in several human cell adhesion molecule sequences (VCAM, NCAM and CD2). This T-cell epitope corresponded to the most highly conserved amino acid residues common to all group IX homologues sequenced to date. CD2 and VCAM are known to play a role in allergic inflammation: VCAM is involved in the recruitment of lymphocytes to sites of inflammation, and cross-linking CD2 leads to T-cell activation. We anticipate that the similar structural arrangement of group IX allergens and human cell adhesion molecules, as well as the presence of a T-cell epitope common to group IX pollen allergens and cell adhesion molecules, will have important consequences in the natural history of the atopic immune response.

Allergens↗
PubMed1995

Post-transcriptional regulation of bifunctional alpha-amylase/subtilisin inhibitor expression in barley embryos by abscisic acid.

Changes in bifunctional alpha-amylase/subtilisin inhibitor (BASI) expression induced by abscisic acid (ABA) were studied using in vitro cultured barley (Hordeum vulgare cv. Bonanza) embryos. The steady-state levels of BASI mRNA and BASI protein were increased by exogenously applied ABA. Accumulation of BASI protein was preceded by an increase in message level. The results suggest that ABA does not affect BASI mRNA translation. Nuclear run-on assays demonstrated that ABA had no effect on transcriptional activity. BASI mRNA was not detectable in the embryos treated with a protein synthesis inhibitor, cycloheximide, which had no inhibitory effect on BASI transcription rate. We propose that ABA increases the stability of BASI mRNA through synthesis of a short-lived protein that protects the message.

Abscisic Acid↗
PubMed1995

The relationship between the mini-mental state examination and cognitive functioning in normal elderly adults: a componential analysis.

The relationship between the Mini-Mental State Examination (MMSE) and selected cognitive performance indices was examined in a sample of 251 non-demented adults over 75 years of age. MMSE items were divided into I 1 binomial content domains and an examination of these revealed that only seven had sufficient variability to predict cognitive performance. A factor analysis with these items yielded three factors, reflecting memory, spatial skill, and the ability to follow commands. After controlling for age and education, these factor scores were included as predictors of specific cognitive tasks including two measures of free recall, and two measures of visuospatial skill. The memory factor score was a strong predictor of the two free recall tasks and block design. The spatial factor score contributed to the prediction of the two visuospatial measures, as well as free recall of organizable words. The results suggest that, in normal ageing, the predictive value of the MMSE is due to subset of cognitively demanding items that are heavily influenced by both memory and visuospatial skills.

Aged↗
PubMed1995

Episodic memory and visuospatial ability in detecting and staging dementia in a community-based sample of very old adults.

BACKGROUND: This study examined the efficacy of a cognitive test battery in detecting and staging dementia in a community-based sample of very old adults. METHOD: The sample consisted of 398 nondemented and 108 demented adults taken from all the inhabitants in the Kungsholmen parish of Stockholm, Sweden (2,368 individuals), aged 75 years and older, who were part of a large-scale epidemiological study on aging and dementia. Participants received a cognitive test battery that consisted of specialized episodic memory tasks, as well as standardized psychometric measures of visuospatial ability and primary memory. RESULTS: A discriminant analysis revealed that highly supported episodic memory tasks (recognition, cued recall) were primarily responsible for correctly classifying normal old adults (94.5%) from those with the diagnosis of dementia (66.7%). Using the Mini-Mental State Exam (MMSE) as the criterion of dementia severity, a correct classification of 88.9% was achieved for mildly demented subjects and 77.8% for moderately demented subjects. Visuospatial tasks made the greatest contribution in distinguishing those at different levels of dementia severity. CONCLUSION: The results of this investigation indicate that cognitively supported measures assessing episodic memory may be particularly useful in the detection of dementia, whereas visuospatial measures are more effective in staging the disease. Consistent with biological models of the progression of dementia, this suggests that visuospatial abilities may deteriorate later and/or at a slower rate than episodic memory skills in the early stages of dementia. It is noteworthy that these conclusions are based on samples of very old adults taken from the general population.

Aged↗
PubMed1995

The role of demographic and life style variables in utilizing cognitive support for episodic remembering among very old adults.

This research investigated the influence of individual difference variables within demographic and life-style domains on episodic recall tasks in which the level of cognitive support increased incrementally. The community-based sample consisted of 253 healthy older adults taken from the Kungsholmen parish in Stockholm, Sweden. Utilizing hierarchical regression procedures, two questions were addressed with regard to the selected individual difference variables: (a) the degree to which they could predict episodic recall and (b) whether they differentially influenced the magnitude of performance gains from the provision of cognitive support in the form of study time, item organizability, and retrieval cues. The results showed that age was negatively related to performance, whereas education and participation in social activities exerted a positive influence on performance. Exercise was also positively related to performance, but only in the least supported tasks. With regard to utilization of cognitive support, education was positively related to performance benefits from more study time and item organizability, age was negatively related to the effect of item organizability, and social activity was positively associated with the ability to benefit from retrieval cues. These results highlight the role of individual difference measures in episodic memory functioning in late adulthood and indicate that these variables are important in predicting the extent to which older adults are able to utilize cognitive support to enhance episodic recall.

Adaptation, Psychological↗
PubMed1995

Video Respite: an innovative resource for family, professional caregivers, and persons with dementia.

The development of a new and promising resource for family, professional caregivers, and persons with dementia is detailed in this article. The concept, Video Respite, refers to the initial goal of creating videotapes specifically for persons with dementia to capture and maintain their attention, enabling caregivers to have respite time. Ten 20-53-minute videotapes are described along with their potential benefits and limitations. Early research findings reveal that most persons with Alzheimer's disease (AD) watch and participate with the tapes, caregivers use the time for respite, and staff of SCU's report the tapes to be calming for the residents.

Aged↗