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Biomedical subjects

J E Hill

Publications and source records attributed to J E Hill.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗
PubMed2006

Charge and spin Hall conductivity in metallic graphene.

Graphene has an unusual low-energy band structure with four chiral bands and half-quantized and quantized Hall effects that have recently attracted theoretical and experimental attention. We study the Fermi energy and disorder dependence of its spin Hall conductivity sigma(xy)(SH). In the metallic regime we find that vertex corrections enhance the intrinsic spin Hall conductivity and that skew scattering can lead to sigma(xy)(SH) values that exceed the quantized ones expected when the chemical potential is inside the spin-orbit induced energy gap. We predict that large spin Hall conductivities will be observable in graphene even when the spin-orbit gap does not survive disorder.

Journal Article↗
PubMed2006

Downregulation of topoisomerase IIbeta in myeloid leukemia cell lines leads to activation of apoptosis following all-trans retinoic acid-induced differentiation/growth arrest.

Among the topoisomerase (topo) II isozymes (alpha and beta), topo IIbeta has been suggested to regulate differentiation. In this study, we examined the role of topo IIbeta in all-trans retinoic acid (ATRA)-induced differentiation of myeloid leukemia cell lines. Inhibition of topo IIbeta activity or downregulation of protein expression enhanced ATRA-induced differentiation/growth arrest and apoptosis. ATRA-induced apoptosis in topo IIbeta-deficient cells involved activation of the caspase cascade and was rescued by ectopic expression of topo IIbeta. Gene expression profiling led to the identification of peroxiredoxin 2 (PRDX2) as a candidate gene that was downregulated in topo IIbeta-deficient cells. Reduced expression of PRDX2 validated at the mRNA and protein level, in topo IIbeta-deficient cells correlated with increased accumulation of reactive oxygen species (ROS) following ATRA-induced differentiation. Overexpression of PRDX2 in topo IIbeta-deficient cells led to reduced accumulation of ROS and partially reversed ATRA-induced apoptosis. These results support a role for topo IIbeta in survival of ATRA-differentiated myeloid leukemia cells. Reduced expression of topo IIbeta induces apoptosis in part by impairing the anti-oxidant capacity of the cell owing to downregulation of PRDX2. Thus, suppression of topo IIbeta and/or PRDX2 levels in myeloid leukemia cells provides a novel approach for improving ATRA-based differentiation therapy.

Antineoplastic Agents↗
PubMed2005

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Journal Article↗
PubMed2005

An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray bursts.

'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result in internal shock waves that are believed to produce the gamma-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.

Journal Article↗
PubMed2005

Bright x-ray flares in gamma-ray burst afterglows.

Gamma-ray burst (GRB) afterglows have provided important clues to the nature of these massive explosive events, providing direct information on the nearby environment and indirect information on the central engine that powers the burst. We report the discovery of two bright x-ray flares in GRB afterglows, including a giant flare comparable in total energy to the burst itself, each peaking minutes after the burst. These strong, rapid x-ray flares imply that the central engines of the bursts have long periods of activity, with strong internal shocks continuing for hundreds of seconds after the gamma-ray emission has ended.

Journal Article↗
PubMed2005

Neuronal ceroid-lipofuscinosis in a Holstein steer.

A young, partially blind Holstein steer was affected by mild cerebral atrophy. Formalin-fixed cerebral gray matter was diffusely yellow brown. Microscopically, there were eosinophilic, autofluorescent granules primarily in the cytoplasm of cerebral neurons. There was also extensive retinal atrophy with complete loss of the rod and cone layers. Ultrastructural examination of affected cerebral neurons revealed a mixture of granular osmiophilic and lamellar patterns in the cytoplasmic storage bodies. This suggests the existence of neuronal ceroid-lipofuscinosis in the Holstein breed.

Animals↗
PubMed2001

Streptococcus suis serotypes characterized by analysis of chaperonin 60 gene sequences.

Streptococcus suis is an important pathogen of swine which occasionally infects humans as well. There are 35 serotypes known for this organism, and it would be desirable to develop rapid methods methods to identify and differentiate the strains of this species. To that effect, partial chaperonin 60 gene sequences were determined for the 35 serotype reference strains of S. suis. Analysis of a pairwise distance matrix showed that the distances ranged from 0 to 0.275 when values were calculated by the maximum-likelihood method. For five of the strains the distances from serotype 1 were greater than 0.1, and for two of these strains the distances were were more than 0.25, suggesting that they belong to a different species. Most of the nucleotide differences were silent; alignment of protein sequences showed that there were only 11 distinct sequences for the 35 strains under study. The chaperonin 60 gene phylogenetic tree was similar to the previously published tree based on 16S rRNA sequences, and it was also observed that strains with identical chaperonin 60 gene sequences tended to have identical 16S rRNA sequences. The chaperonin 60 gene sequences provided a higher level of discrimination between serotypes than the 16S RNA sequences provided and could form the basis for a diagnostic protocol.

Animals↗
PubMed2001

Streptozocin-induced pancreatic islet destruction in beef cows.

Streptozocin (STZ) induces diabetes mellitus in sheep and pigs. To test the effect of STZ in cattle, cows were given 75-150 mg STZ per kilogram of body weight. Cows receiving 150 mg/kg required euthanasia within 24 hours after infusion because of the severe systemic effects of STZ. Seven cows receiving doses of < or = 100 mg/kg had mild to marked decrease in islet immunoreactivity for insulin and in pancreatic islet density and mild to severe tubulointerstitial nephritis. Two cows receiving 75 and 85 mg/kg STZ regained their ability to produce insulin and return blood glucose to basal levels. One cow given 100 mg/kg STZ developed insulin insufficiency consistent with type I diabetes mellitus. These findings demonstrate the susceptibility of the bovine pancreas to STZ: however, severe systemic complications were encountered. Alternative dosages and methodologies should be considered in future attempts to induce diabetes in cattle using STZ.

Animals↗
PubMed2001

Arabidopsis thaliana type I and II chaperonins.

An examination of the Arabidopsis thaliana genome sequence led to the identification of 29 predicted genes with the potential to encode members of the chaperonin family of chaperones (CPN60 and CCT), their associated cochaperonins, and the cytoplasmic chaperonin cofactor prefoldin. These comprise the first complete set of plant chaperonin protein sequences and indicate that the CPN family is more diverse than previously described. In addition to surprising sequence diversity within CPN subclasses, the genomic data also suggest the existence of previously undescribed family members, including a 10-kDa chloroplast cochaperonin. Consideration of the sequence data described in this review prompts questions about the complexities of plant CPN systems and the evolutionary relationships and functions of the component proteins, most of which have not been studied experimentally.

Amino Acid Sequence↗
PubMed2001

Disagreement between height/weight classifications of underweight, normal weight, and obesity in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients are classified as underweight, normal weight, or obese by height/weight indices including body mass index (BMI) and the body weight/desired weight (W/DW) ratio. We compared these classifications of degree of obesity in 378 women and 555 men on PD. We used these cut-off values: for underweight, BMI < or = 18.5 and W/DW < or = 0.9; for obesity, BMI > or = 30.0 and W/DW > or = 1.2. The W/DW values were calculated assuming first a small frame, then a medium frame, and finally a large frame for all subjects. Regardless of sex or skeletal frame, BMI correlated highly with W/DW (r value between 0.98 and 0.99); however, the range of BMI values corresponding by linear regression to the normal range of W/DW (0.9-1.2) was narrower than the range of "normal" BMI (18.5-30.0). Consequently, regardless of sex or skeletal frame, smaller fractions of the patient population were classified as underweight or obese by BMI standards than by W/DW standards. The degree of agreement of the classifications of subjects as underweight, normal weight, or obese by BMI and W/DW was evaluated by Cohen's kappa ratio. The kappa ratio varied between 0.47 and 0.58, indicating a reasonable--but not high--degree of agreement beyond chance. The highest kappa ratios were obtained assuming a medium skeletal frame for both women and men. Substantial discrepancies are observed in the classification of PD patients as underweight, normal weight, or obese by BMI and W/DW. Further research is needed to identify the height/weight index that has the strongest association both with clinical outcomes and with other, more precise measurements of body fat content.

Body Constitution↗
PubMed2000

Cloning and functional expression of a gene encoding a vacuolar-type proton-translocating pyrophosphatase from Trypanosoma cruzi.

Acidocalcisomes are acidic Ca(2+)-storage organelles found in trypanosomatids that are similar to organelles known historically as volutin granules. Acidification of these organelles is driven in part by a vacuolar H(+)-pyrophosphatase (V-H(+)-PPase), an enzyme that is also present in plant vacuoles and in some bacteria. Here, we report the cloning and sequencing of a gene encoding the acidocalcisomal V-H(+)-PPase of Trypanosoma cruzi. The protein (T. cruzi pyrophosphatase, TcPPase) predicted from the nucleotide sequence of the gene has 816 amino acids and a molecular mass of 85 kDa. Several sequence motifs found in plant V-H(+)-PPases were present in TcPPase, explaining its sensitivity to N-ethylmaleimide and N,N'-dicyclohexylcarbodi-imide. Heterologous expression of the cDNA encoding TcPPase in the yeast Saccharomyces cerevisiae produced a functional enzyme. Phylogenetic analysis of the available V-H(+)-PPase sequences indicates that TcPPase is nearer to the vascular plant cluster and the branch containing Chara, a precursor to land plants, than to any of the other pyrophosphatase sequences included in the analysis. The apparent lack of such a V-H(+)-PPase in mammalian cells may provide a target for the development of new drugs.

Amino Acid Motifs↗
PubMed2000

Identification of Enterococcus species and phenotypically similar Lactococcus and Vagococcus species by reverse checkerboard hybridization to chaperonin 60 gene sequences.

Data from four recent studies (S. H. Goh et al., J. Clin. Microbiol. 36:2164-2166, 1998; S. H. Goh et al., J. Clin. Microbiol. 34:818-823, 1996; S. H. Goh et al., J. Clin. Microbiol. 35:3116-3121, 1997; A. Y. C. Kwok et al., Int. J. Syst. Bacteriol. 49:1181-1192, 1999) suggest that an approximately 600-bp region of the chaperonin 60 (Cpn60) gene, amplified by PCR with a single pair of degenerate primers, has utility as a potentially universal target for bacterial identification (ID). This Cpn60 gene ID method correctly identified isolates representative of numerous staphylococcal species and Streptococcus iniae, a human and animal pathogen. We report herein that this method enabled us to distinguish clearly between 17 Enterococcus species (Enterococcus asini, Enterococcus rattus, Enterococcus dispar, Enterococcus gallinarum, Enterococcus hirae, Enterococcus durans, Enterococcus cecorum, Enterococcus faecalis, Enterococcus mundtii, Enterococcus casseliflavus, Enterococcus faecium, Enterococcus malodoratus, Enterococcus raffinosus, Enterococcus avium, Enterococcus pseudoavium, Enterococcus new sp. strain Facklam, and Enterococcus saccharolyticus), and Vagococcus fluvialis, Lactococcus lactis, and Lactococcus garvieae. From 123 blind-tested samples, only two discrepancies were observed between the Facklam and Collins phenotyping method (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27:731-734, 1989) and the Cpn60 ID method. In each case, the discrepancies were resolved in favor of the Cpn60 ID method. The species distributions of the 123 blind-tested isolates were Enterococcus new sp. strain Facklam (ATCC 700913), 3; E. asini, 1; E. rattus, 4; E. dispar, 2; E. gallinarum, 20; E. hirae, 9; E. durans, 9; E. faecalis, 12; E. mundtii, 3; E. casseliflavus, 8; E. faecium, 25; E. malodoratus, 3; E. raffinosus, 8; E. avium, 4; E. pseudoavium, 1; an unknown Enterococcus clinical isolate, sp. strain R871; Vagococcus fluvialis, 4; Lactococcus garvieae, 3; Lactococcus lactis, 3; Leuconostoc sp., 1; and Pediococcus sp., 1. The Cpn60 gene ID method, coupled with reverse checkerboard hybridization, is an effective method for the identification of Enterococcus and related organisms.

Bacterial Typing Techniques↗
PubMed1999

Structure and regulation of the mouse ing1 gene. Three alternative transcripts encode two phd finger proteins that have opposite effects on p53 function.

The human ING1 gene encodes nuclear protein p33(ING1), previously shown to cooperate with p53 in cell growth control (Garkavtsev, I., Grigorian, I. A., Ossovskaya, V. S., Chernov, M. V., Chumakov, P. M., and Gudkov, A. V. (1998) Nature 391, 295-298). p33(ING1) belongs to a small family of proteins from human, mouse, and yeast of approximately the same size that show significant similarity to one another within the C-terminal PHD finger domain and also contain an additional N-terminal region with subtle but reliably detectable sequence conservation. Mouse ing1 is transcribed from three differently regulated promoters localized within a 4-kilobase pair region of genomic DNA. The resulting transcripts share a long common region encoded by a common exon and differ in their 5'-exon sequences. Two transcripts are translated into the same protein of 185 amino acids, the mouse equivalent of the human p33(ING1), while the third transcript encodes a longer protein that has 94 additional N-terminal amino acids. Overexpression of the longer protein interferes with the accumulation of p53 protein and activation of p53-responsive promoters after DNA damage. Between the two products of ing1, only the longer one forms a complex with p53 detectable by immunoprecipitation. These results indicate that a single gene, ing1, encodes both p53-suppressing and p53-activating proteins that are regulated by alternative promoters.

3T3 Cells↗
PubMed1998

PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori.

Genes that are characteristic of only certain strains of a bacterial species can be of great biologic interest. Here we describe a PCR-based subtractive hybridization method for efficiently detecting such DNAs and apply it to the gastric pathogen Helicobacter pylori. Eighteen DNAs specific to a monkey-colonizing strain (J166) were obtained by subtractive hybridization against an unrelated strain whose genome has been fully sequenced (26695). Seven J166-specific clones had no DNA sequence match to the 26695 genome, and 11 other clones were mixed, with adjacent patches that did and did not match any sequences in 26695. At the protein level, seven clones had homology to putative DNA restriction-modification enzymes, and two had homology to putative metabolic enzymes. Nine others had no database match with proteins of assigned function. PCR tests of 13 unrelated H. pylori strains by using primers specific for 12 subtracted clones and complementary Southern blot hybridizations indicated that these DNAs are highly polymorphic in the H. pylori population, with each strain yielding a different pattern of gene-specific PCR amplification. The search for polymorphic DNAs, as described here, should help identify previously unknown virulence genes in pathogens and provide new insights into microbial genetic diversity and evolution.

Animals↗
PubMed1998

Asymmetric infectivity of pseudorecombinants of cabbage leaf curl virus and squash leaf curl virus: implications for bipartite geminivirus evolution and movement.

The bipartite geminiviruses squash leaf curl virus (SqLCV) and cabbage leaf curl virus (CLCV) have distinct host ranges. SqLCV infects a broad range of plants within the Cucurbitaceae, including pumpkin and squash, and CLCV has a broad host range within Brassicaceae that includes cabbage and Arabidopsis thaliana. Despite this, the genomic A components of these viruses share a high degree of sequence identity, particularly in the gene encoding the replication protein AL1, and their common regions are 77% identical. However, there is unexpected sequence diversity in the common regions of the two CLCV genomic A and B components, these being only 80% identical. Based on these sequence similarities, we investigated the host range properties of pseudorecombinants of SqLCV and CLCV. We found that in a pseudorecombinant virus consisting of the A component of CLCV and the B component of SqLCV, both components replicated in tobacco protoplasts, and this pseudorecombinant was infectious and caused systemic disease in Nicotiana benthamiana, a common host to all bipartite geminiviruses. However, this pseudorecombinant did not move systemically in pumpkin or Arabidopsis, despite the demonstrated replication compatibility of the genome components. As a result of the greater sequence differences between the common regions, the pseudorecombinant of SqLCV A and CLCV B components neither replicated the CLCV B component nor systemically infected any of the hosts tested. These findings demonstrate that for different geminiviruses with distinct host ranges, the replication origins and AL1 proteins can be sufficiently similar to permit infectious pseudorecombinants, but replication alone is not sufficient to cause systemic disease, and host range may ultimately be limited at the level of movement. The results of this study further suggest that CLCV is an evolving virus that can provide insights into how new bipartite geminiviruses arise from mixed infections.

Base Sequence↗
PubMed1998

Stress-induced secretion of growth inhibitors: a novel tumor suppressor function of p53.

p53 tumor suppressor gene controls cell response to a variety of stresses inducing growth arrest or apoptosis in damaged cells. It largely determines the sensitivity of tumor and normal cells to radiation and chemotherapy, and, therefore, defines both the efficacy and limitations of anti-cancer treatment. To determine molecular mechanisms of p53-dependent stress response in normal tissues we identified and compared the spectra of radiation-responsive genes in cells of different origin and p53 status using a cDNA array hybridization technique. The majority of genes identified were p53-dependent and cell type specific. Several of the new p53 responders encode known secreted growth inhibitory factors. This suggests that p53, in addition to its intrinsic antiproliferation activity, can cause 'bystander effect' by inducing export of growth suppressive stimuli from damaged cells to neighboring cells. Consistently, a p53-dependent accumulation of factors, which causes growth inhibitory effects in a variety of cell lines, was found after gamma irradiation in the media from established and primary cell cultures and in the urine of irradiated mice. Moreover, p53-dependent factors released by normal human fibroblasts potentiated the cytotoxic effect of a chemotherapeutic drug on co-cultivated tumor cells. This suggests a previously unknown role for normal cells in chemo- and radiation therapy of cancer.

3T3 Cells↗