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Biomedical subjects

J P Hill

Publications and source records attributed to J P Hill.

At least 19 recordsLinked to original sources
PubMed2006

Lower consumption of cow milk protein A1 beta-casein at 2 years of age, rather than consumption among 11- to 14-year-old adolescents, may explain the lower incidence of type 1 diabetes in Iceland than in Scandinavia.

AIM: To compare the consumption of the cow milk proteins A1 and B beta-casein among children and adolescents in Iceland and Scandinavia (Norway, Denmark, Sweden and Finland) as this might explain the lower incidence of type 1 diabetes (per 100,000/year, 0-14 years) in Iceland. METHODS: The consumption of A1 beta-casein in each country among 2- and 11- to 14-year-old children was calculated from results on food intake and on cow milk protein concentration. The consumption values were then compared and evaluated against the incidence of type 1 diabetes. RESULTS: There was a significant difference between the consumption of A1 (p = 0.034) as well as the sum of A1 and B (p = 0.021) beta-casein in Iceland and Scandinavia for 2-year-old children. In the same age group, consumption of A1 beta-casein correlated with the incidence of type 1 diabetes in the countries (r = 0.9; p = 0.037). No significant difference in consumption of A1 or the sum of A1 and B beta-casein was found for 11- to 14-year-old adolescents. CONCLUSION: This study supports that lower consumption of A1 beta-casein might be related to the lower incidence of type 1 diabetes in Iceland than in Scandinavia. Additionally it indicates that consumption in young childhood might be of more importance for the development of the disease incidence than consumption in adolescence.

Adolescent↗
PubMed2005

Orbital ordering transition in Ca2RuO4 observed with resonant X-ray diffraction.

Resonant x-ray diffraction performed at the L(II) and L(III) absorption edges of Ru has been used to investigate the magnetic and orbital ordering in Ca2RuO4 single crystals. A large resonant enhancement due to electric dipole 2p-->4d transitions is observed at the wave-vector characteristic of antiferromagnetic ordering. Besides the previously known antiferromagnetic phase transition at T(N)=110 K, an additional phase transition, between two paramagnetic phases, is observed around 260 K. Based on the polarization and azimuthal angle dependence of the diffraction signal, this transition can be attributed to orbital ordering of the Ru t(2g) electrons. The propagation vector of the orbital order is inconsistent with some theoretical predictions for the orbital state of Ca2RuO4.

Journal Article↗
PubMed2005

d-d excitations in manganites probed by resonant inelastic x-ray scattering.

We report a study of electronic excitations in manganites exhibiting a range of ground states, using resonant inelastic x-ray scattering (RIXS) at the Mn K edge. Excitations with temperature dependent changes correlated with the magnetism were observed as high as 10 eV. By calculating Wannier functions, and finite-q response functions, we associate this dependence with intersite d-d excitations. The calculated dynamical structure factor is found to be similar to the RIXS spectra.

Journal Article↗
PubMed2004

Soft x-ray resonant diffraction study of magnetic and orbital correlations in a manganite near half doping.

We have utilized resonant x-ray diffraction at the Mn L(II,III) edges in order to directly compare magnetic and orbital correlations in Pr0.6Ca0.4MnO3. Comparing the widths of the magnetic and orbital diffraction peaks, we find that the magnetic correlation length exceeds that of the orbital order by nearly a factor of 2. Furthermore, we observe a large (approximately 3 eV) spectral weight shift between the magnetic and orbital resonant line shapes, which cannot be explained within the classic Goodenough picture of a charge-ordered ground state. To explain the shift, we calculate the orbital and magnetic resonant diffraction line shapes based on a relaxed charge-ordered model.

Journal Article↗
PubMed2004

Resonant inelastic X-ray scattering of the holon-antiholon continuum in SrCuO2.

We report a resonant inelastic x-ray scattering study of charge excitations in the quasi-one-dimensional Mott insulator SrCuO2. We observe a continuum of low-energy excitations, the onset of which exhibits a small dispersion of approximately 0.4 eV. Within this continuum, a highly dispersive feature with a large sinusoidal dispersion (approximately 1.1 eV) is observed. We have also measured the optical conductivity, and studied the dynamic response of the extended Hubbard model with realistic parameters, using a dynamical density-matrix renormalization group method. In contrast to earlier work, we do not find a long-lived exciton, but rather these results suggest that the excitation spectrum comprises a holon-antiholon continuum together with a broad resonance.

Journal Article↗
PubMed2004

Effect of genetic variation on the tryptic hydrolysis of bovine beta-lactoglobulin A, B, and C.

The structure, stability, and hydrolysis characteristics of beta-lactoglobulin (LG) A are different from those of either beta-LG B or beta-LG C. Purified samples of these proteins were hydrolyzed with trypsin and the rates of loss of native monomeric beta-LG structure were measured using sodium dodecyl sulfate PAGE. At the same time, the appearance of many individual peptides were identified and followed in time by HPLC, measuring their concentration as a function of solution pH, temperature, protein concentration, and added urea or palmitate. The identity of the peptides was confirmed by liquid chromatography-mass spectrometry. This semiquantitative exploration showed that the rate of hydrolysis was in the order beta-LG A > beta-LG B > beta-LG C under most circumstances, and that 12 of the 18 trypsin-susceptible bonds were cleaved at very similar rates that were governed by the variant type. Consequently, the rate of hydrolysis of the intact protein was related to the overall structural stability of the individual proteins and the accessibility of certain peptide bonds to the enzyme. The hydrolysis of mixtures of 2 or more variants or of denatured beta-LG gave more heterogeneous peptide mixtures.

Animals↗
PubMed2003

A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice.

Dietary antigens are candidate environmental factors in the pathogenesis of type 1 diabetes. In the non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, cereal-based diets promote disease development, whereas the diets based on hydrolysed proteins or non-diabetogenic proteins are protective. The hypothesis that diabetogenic diets modulate the cytokine balance in the gut was tested. NOD mice were fed with NTP-2000 (mainly a wheat-based milk-free diet) or Prosobee (a semi-purified hypoallergenic diet based on soy protein isolate) or Prosobee plus casein (milk protein fraction). The mRNA levels of IFN-gamma, IL-10, TNF-alpha, TGF-beta, and inducible NO synthase in the small intestine and the Peyer's patches were determined by semi-quantitative RT-PCR. Mice fed on the cereal-based NTP-2000 diet expressed higher levels of the Th1-type and pro-inflammatory markers IFN-gamma, TNF-alpha, and inducible NO synthase mRNA compared to the Prosobee-fed animals. The expression of the counterregulatory cytokines IL-10 and TGF-beta was unaffected. This resulted in a significant bias of the intestinal cytokine balance towards T helper cell type 1 after feeding NTP-2000. The cytokine mRNA levels in the gut-associated Peyer's patches were not affected. Thus, modulation of gut immunoreactivity by diet may contribute to disease development in NOD mice.

Animal Feed↗
PubMed2002

Resonant inelastic x-ray scattering study of charge excitations in La(2)CuO(4).

We report a resonant inelastic x-ray scattering study of the dispersion relations of charge-transfer excitations in insulating La(2)CuO(4).. These data reveal two peaks, both of which show two-dimensional characteristics. The lowest energy excitation has a gap energy of approximately 2.2 eV at the zone enter, and a dispersion of approximately 1 eV. The spectral weight of this mode becomes dramatically smaller around (pi, pi). The second peak shows a smaller dispersion ( approximately 0.5 eV) with a zone-center energy of approximately 3.9 eV. We argue that these are both highly dispersive exciton modes damped by the presence of the electron-hole continuum.

Journal Article↗
PubMed2002

A multi-centre, blinded international trial of the effect of A(1) and A(2) beta-casein variants on diabetes incidence in two rodent models of spontaneous Type I diabetes.

AIMS/HYPOTHESIS: The diabetes-inducing potential of cows' milk is still debated and there is no consensus on the diabetogenicity of individual milk proteins. A(1)-beta-casein has been associated with increased diabetes frequency in ecological studies and in NOD mice. Our aim was to ascertain whether A(1)-beta-casein was more diabetogenic than A(2) and to test the diabetogenicity of a milk-free diet in animals representing different forms of spontaneous Type I (insulin-dependent) diabetes mellitus. METHODS: Defined diets were coded and shipped to laboratories in New Zealand (NOD/NZ), Canada (BB) and the UK (NOD/Ba). Base diets were Pregestimil (PG) and ProSobee (PS). Purified fractions of whole casein (WC), A(1)or A(2)-beta-casein were added at 10%. A milk-free, wheat-predominant, NTP-2000 diet was the control. Animals were fed from weaning up to 150 or 250 days, and insulitis, diabetes frequency and expression of pancreatic cytokines were assessed. RESULTS: Diabetes incidence was highest in three locations in animals fed NTP-2000. PG and PS diets were protective except for NOD/Ba mice fed PG+WC where incidence was similar to NTP-2000. A(1) and A(2) diets were protective in both models, but A(1) beta-casein was slightly more diabetogenic in PS-fed BB rats. The New Zealand study was confounded by an infection. CONCLUSION/INTERPRETATION: A milk-free, wheat-predominant diet was highly diabetogenic in three widely separate locations in both animal models. A previous result that A(1) beta-casein was more diabetogenic than A(2) beta-casein in NOD mice was not confirmed; both beta-casein variants were protective in BB rats and NOD mice. Whole Casein promoted diabetes in NOD/Ba but protected BB showing that unique diabetes haplotypes react differently to dietary proteins. A(1)- was more diabetogenic than A(2)-beta-casein only in PS-fed BB rats. Neither the analysis of insulitis nor of pancreatic cytokine gene expression showed a difference between A(1) or A(2) beta-casein fed animals. Milk caseins are unlikely to be exclusive promoters of Type I diabetes, but could enhance the outcome of diabetes in some cases. Other diet components such as wheat could be more important promoters of Type I diabetes.

Animals↗
PubMed2002

Variation in consumption of cow milk proteins and lower incidence of Type 1 diabetes in Iceland vs the other 4 Nordic countries.

BACKGROUND: The incidence of Type 1 diabetes is lower in Iceland than in the other 4 Nordic Countries. Earlier studies have showed that the cow milk proteins A1 and B beta-casein, suggested to be diabetogenic, are in lower amount in Icelandic cow milk than in milk from the other 4 Nordic Countries, and the per capita consumption of these proteins correlates with the incidence of Type 1 diabetes. OBJECTIVE: To investigate whether lower consumption of the cow milk protein bovine serum albumin (BSA) (suggested to be diabetogenic) or higher consumption of immunoglobulin (Ig) or lactoferrin (LF) (suggested to be protective) is related to the lower incidence of Type 1 diabetes in Iceland. METHODS: The per capita consumption of milk proteins was calculated from an international database on consumption of milk and milk products and from the analysis of cow's milk samples. The samples were randomly collected from the largest consumption areas in Iceland and in the other 4 Nordic Countries. RESULTS: The per capita consumption of BSA was higher in Iceland (0.79 +/- 0.02 g/person per day) (mean +/- SEM) than in the other 4 Nordic Countries (0.43 +/- 0.05 g/person per day) (p = 0.025). The per capita consumption of Ig was also higher in Iceland than in the other 4 Nordic Countries (p = 0.025), while the consumption of LF was similar. Consumption of these 3 individual milk proteins did not correlate with the incidence of Type 1 diabetes in the 5 countries studied. CONCLUSION: Consumption of BSA, Ig or LF does not seem to explain the lower incidence of Type 1 diabetes in Iceland, compared with the other 4 Nordic Countries, while A1 and B beta-casein may contribute to varying diabetogenicity of cow's milk and explain the difference in incidence of Type 1 diabetes.

Animals↗
PubMed2001

Simultaneous analysis of surface marker expression and cell cycle progression in human peripheral blood mononuclear cells.

One method for examining cell cycle kinetics by flow cytometry uses continuous DNA labeling with bromodeoxyuridine (BrdU), a thymidine analogue. Upon incorporation into DNA, BrdU causes stoichiometric quenching of the DNA fluorochrome Hoechst 33258. After counterstaining with a secondary DNA fluorochrome (e.g., ethidium bromide), the analyst can distinguish cells in different phases of the cell cycle over a number of mitotic cycles with flow cytometry. In this report, we describe a modification of the flow cytometric BrdU-Hoechst assay that allows combined analysis of cell proliferation and immunophenotyping at the single cell level. To demonstrate an application of this method, human peripheral blood mononuclear cells were stimulated with tetanus toxoid or interleukin-2 for up to 6 days in the presence of BrdU, harvested, and immunostained for the cell surface markers CD3, CD4, CD8, CD14, CD19, and the cytokine receptor, CCR5. We used four-color flow cytometry analyses to simultaneously measure cell proliferation and surface marker expression, for the purpose of immunophenotyping and identifying specific cell subsets responding to antigen stimulation. Our successful application of this method suggests that it may be used to study immune responses at the molecular and cellular level and to identify mechanisms of immune system modulation.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2001

Barley yellow rust in North America.

Yellow rust of barley is an invasive disease that was found in the past 10 years in North America. The causal agent, Puccinia striiformis f. sp. hordei, was introduced into Colombia, South America, from Europe in 1975. It spread to all major barley-producing areas in South America by 1982. In 1988 it was found in Mexico and in 1991 in Texas. Since then it has been found in all major barley-producing areas of the American West. Originally described as race (R) 24, barley yellow rust in North America is now known to be a very heterogeneous population. Resistance has been identified, evaluated, and is being introduced into commercial malting and other barley cultivars. Cultural and chemical controls are effective and available. An integrated approach using general field resistance and other tactics is described for sustainable management of barley yellow rust.

Agriculture↗
PubMed2000

Effects of pasture allowance on the yield and composition of milk from cows of different beta-lactoglobulin phenotypes.

The objective of this study was to determine whether the differences in the composition of milk from cows of different beta-lactoglobulin beta-LG) phenotypes are affected by the amount of pasture available and, hence, pasture dry matter intake. Twenty-two Friesian cows of each of the AA and BB variants of the beta-LG phenotype were subjected to ad libitum grazing or restricted grazing in crossover experiments during spring (early lactation, approximately 60 d in milk) and summer (mid to late lactation, approximately 180 d in milk). Milk samples were collected from each cow at the end of each 8-d treatment period and analyzed for composition. Cows of the AA variant of the beta-LG phenotype had higher concentrations of whey protein and beta-LG, but lower concentrations of casein (CN), alpha-CN, kappa-CN (summer only), and BSA, than cows of the BB variant. Compared with cows with a restricted allowance, cows grazing ad libitum had higher milk yields and concentrations of protein, casein, whey protein, and all individual proteins except BSA and immunoglobulin. There were no interactions between effects of pasture allowance and phenotype on milk yield or composition. The data show that having adequate pasture for grazing cows is important not only to maximize milk yield, but also to optimize concentrations of protein and casein, and hence the manufacturing potential of milk. Further, the differences in composition of milk from cows of differing beta-LG phenotypes persisted during short-term restrictions in pasture allowance, and between spring and summer.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption.

Previously published Type I (insulin-dependent) diabetes mellitus incidence in 0 to 14-year-old children from 10 countries or areas was compared with the national annual cow milk protein consumption. Countries which were selected for study had appropriate milk protein polymorphism studies, herd breed composition information and low dairy imports from other countries. Total protein consumption did not correlate with diabetes incidence (r = +0.402), but consumption of the beta-casein A1 variant did (r = +0.726). Even more pronounced was the relation between beta-casein (A1+B) consumption and diabetes (r = +0.982). These latter two cow caseins yield a bioactive peptide beta-casomorphin-7 after in vitro digestion with intestinal enzymes whereas the common A2 variant or the corresponding human or goat caseins do not. beta-casomorphin-7 has opioid properties including immunosuppression, which could account for the specificity of the relation between the consumption of some but not all beta-casein variants and diabetes incidence.

Adolescent↗
PubMed1999

Nutritional influences on the composition of milk from cows of different protein phenotypes in New Zealand.

The objective of this study was to investigate the effects of contrasting nutritional regimens on milk composition from cows of different protein phenotypes. Twenty sets of seasonally calving identical twin cows that constituted five different protein phenotypes (four sets of twins per phenotype) were subjected to two nutritional treatments in crossover experiments during spring (early lactation) and summer (mid to late lactation). The phenotypes studied allowed a comparison of the AA, AB, and BB variants of both beta-lactoglobulin (beta-LG) and kappa-casein. Nutritional treatments were 1) ad libitum grazing (i.e., cows were allocated a pasture allowance of approximately 40 kg of dry matter/d per cow) plus 5 kg of a concentrate based on barley and 2) restricted grazing (pasture allowance of 20 kg of dry matter/d per cow). Milk samples were collected from each cow near the end of each 14-d treatment period and were analyzed for a detailed range of individual protein and fat constituents. Diet had significant effects on the concentrations of all milk components measured. Protein phenotype affected some protein components but not fat components. Interactions between the effects of beta-LG phenotype and diet were noted for the concentrations of some milk components. Diet and protein phenotype have important effects on the manufacturing potential of milk produced under the dairying systems of New Zealand, which rely heavily on grazing. The effects of nutrition on milk composition may depend on the beta-LG phenotype.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Micelle stability: kappa-casein structure and function.

The stability of the casein micelle is dependent on the presence of kappa-casein (CN) on the surface of the micelle where it functions as an interface between the hydrophobic caseins of the micelle interior and the aqueous environment. kappa-Casein is also involved in thiol-catalyzed disulfide interchange reactions with the whey proteins during heat treatments and, after rennet cleavage, in the facilitation of micelle coagulation. These functions of kappa-CN are regulated by the three-dimensional structure of the protein on the micelle surface. The usual means of determining structure are not available for kappa-CN because this protein is strongly self-associating and has never been crystallized. Instead, algorithms were used to predict selected secondary structures and circular dichroism spectroscopy on kappa-CN and the macropeptide released by chymosin. Three peptides were synthesized to cover the chymosin-sensitive site (His98-Lys111), the region in the macropeptide that could be helical (Pro130-Ile153), and the region between. Nuclear magnetic resonance spectroscopy showed that the peptide His98-Lys111 was probably a beta-strand with tight turns at each end. This hypothesis was confirmed by a study of the molecular dynamics showing that the C variant of kappa-CN interacted less strongly with chymosin; consequently, the slow renneting time of milk that contains this protein was explainable. Both circular dichroism and nuclear magnetic resonance indicated that the peptide Pro130-Ile153 was probably helical under normal physiological conditions. A preliminary study using nuclear magnetic resonance showed that the intervening peptide had no discernible secondary structure. Consequently, most of the beta-sheet structure of kappa-CN is likely in the para-kappa-CN region.

Amino Acid Sequence↗
PubMed1997

Greater cross education following training with muscle lengthening than shortening.

The hypothesis was tested that the magnitude of cross education is greater following training with muscle lengthening than shortening. Changes in contralateral concentric, eccentric, and isometric strength and vastus lateralis and biceps femoris surface electromyographic (EMG) activity were analyzed in groups of young men who exercised the ipsilateral quadriceps with either eccentric (N = 7) or concentric (N = 8) contractions for 36 sessions over 12 wk. Control subjects (N = 6) did not train. Concentric training increased concentric strength 30% and isometric strength 22%, and eccentric training increased eccentric strength 77% and isometric strength 39% (all P < 0.05). Eccentric training improved eccentric strength three times more than the concentric training improved concentric strength (P < 0.05), and eccentric compared with concentric training improved isometric strength about 2 times more (P < 0.05). The eccentric group improved significantly from pre- to mid-training in eccentric and isometric strength (P < 0.05). The control group showed no significant changes (P < 0.05). Surface EMG activity of the vastus lateralis increased 2.2 times (pre- to mid-training), 2.8 (mid- to post-training) and 2.6 more (pre- to post-training) (P < 0.05) in the eccentric than concentric group. No significant changes in EMG activity occurred in the control group (P > 0.05). It was concluded that the greater cross education following training with muscle lengthening is most likely being mediated by both afferent and efferent mechanisms that allow previously sedentary subjects to achieve a greater activation of the untrained limb musculature.

Electromyography↗