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Biomedical subjects

C Herring

Publications and source records attributed to C Herring.

At least 19 recordsLinked to original sources

14C activity and global carbon cycle changes over the past 50,000 years.

A series of 14C measurements in Ocean Drilling Program cores from the tropical Cariaco Basin, which have been correlated to the annual-layer counted chronology for the Greenland Ice Sheet Project 2 (GISP2) ice core, provides a high-resolution calibration of the radiocarbon time scale back to 50,000 years before the present. Independent radiometric dating of events correlated to GISP2 suggests that the calibration is accurate. Reconstructed 14C activities varied substantially during the last glacial period, including sharp peaks synchronous with the Laschamp and Mono Lake geomagnetic field intensity minimal and cosmogenic nuclide peaks in ice cores and marine sediments. Simulations with a geochemical box model suggest that much of the variability can be explained by geomagnetically modulated changes in 14C production rate together with plausible changes in deep-ocean ventilation and the global carbon cycle during glaciation.

Journal Article↗

Monitoring xenotransplant recipients for infection by PERV.

OBJECTIVES: Concerns have been raised over the possibility of transmission of porcine endogenous retrovirus (PERV) to porcine xenograft recipients. METHODS: To help assess this risk, diagnostic assays capable of detection of an active, latent or cleared PERV infection, and the presence of pig cell microchimerism have been developed by a number of groups. Retrospective studies of patients exposed to living pig tissues have been performed using these assays to look for evidence of cross species transmission. RESULTS: To date no evidence of PERV infection has been found in studies of humans exposed to pig tissues, despite evidence of long lived microchimerism. CONCLUSIONS: These data suggest that PERV infection has not occurred in a clinical setting. However, as infection has been seen in a small animal model further investigation of the risk from PERV is warranted.

Animals↗

Analysis of patients treated with living pig tissue for evidence of infection by porcine endogenous retroviruses.

The use of pigs as a source of cells and organs for transplantation has the potential to reduce the current chronic shortage of organs for the treatment of many end-stage diseases. The risk of transmission of infectious agents across the species barrier (zoonoses) has to be assessed. Many such agents can be eliminated from the pig herd. However, porcine endogenous retroviruses, which are carried within the pig genome, are not easily eliminated. They can infect primary and immortalized human cells in vitro, but to date no evidence for in vivo infection has been found in retrospective studies of humans exposed to viable porcine cells. Small-scale clinical trials using porcine cells for the treatment of Parkinson's and Huntington's disease are currently in progress. The prospective monitoring of these patients in conjunction with further research into the biology of this virus will help address safety issues.

Animals↗

The use of the Australian Basic Treatment Equivalent (BTE) workload measure for linear accelerators in Canada.

The Inter Society of Radiation Oncologists of North America (ISRON) workload standard for linear accelerators is the one most widely used; it regards the treatment of 250 or more patients per year as an acceptable limit. Nevertheless, there is concern that this standard does not represent the current workload of linear accelerators, given that the complexity of techniques and equipment has increased significantly since the ISRON model was developed in the late 1980s. Delaney et al. recently validated a workload indicator for Australian (AUS) centres, known as the basic treatment equivalent (BTE). They showed that this was a better predictor of workload and that there was less variation between centres using this model than there would have been by using fields/hour. This centre attempted to validate this model for use in a Canadian centre, by collecting treatment data on all linear accelerator-treated patients during February 1998. The linear accelerators at this centre delivered 2,295 fractions (6,928 fields) in 662 hours during February 1998. When 15 minutes was used as a denominator, the BTE model functioned as a better workload indicator than simple measures such as fields/hour. It also had better performance in reducing variability between machines. A BTE of 3,403 was calculated for these machines. The mean value for fields/hour, BTE/hour and BTE/fraction for this centre fell within the range of values quoted by AUS centres. The BTE/fraction value for this centre was relatively high compared with the AUS mean, indicating this centre's reliance on the use of a high number of complex techniques. We recommend that the model should be further refined for the Canadian context by developing BTE values with the use of local time and motion studies, including factors such as multileaf collimators and enhanced dynamic wedges.

Australia↗

Mapping full-length porcine endogenous retroviruses in a large white pig.

Xenotransplantation may bridge the widening gap between the shortage of donor organs and the increasing number of patients waiting for transplantation. However, a major safety issue is the potential cross-species transmission of porcine endogenous retroviruses (PERV). This problem could be resolved if it is possible to produce pigs that do not contain replication-competent copies of this virus. In order to determine the feasibility of this, we have determined the number of potentially replication-competent full-length PERV proviruses and obtained data on their integration sites within the porcine genome. We have screened genomic DNA libraries from a Large White pig for potentially intact proviruses. We identified six unique PERV B proviruses that were apparently intact in all three genes, while the majority of isolated proviruses were defective in one or more genes. No intact PERV A proviruses were found in this pig, despite the identification of multiple defective A proviruses. Genotyping of 30 unrelated pigs for these unique proviruses showed a heterogeneous distribution. Two proviruses were uncommon, present in 7 of 30 and 3 of 30 pigs, while three were each present in 24 of 30 pigs, and one was present in 30 of 30 animals examined. Our data indicate that few PERV proviruses in Large White pigs are capable of productive infection and suggest that many could be removed by selective breeding. Further studies are required to determine if all potentially functional proviruses could be removed by breeding or whether gene knockout techniques will be required to remove the residuum.

Amino Acid Sequence↗

Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2.

The human double-stranded RNA-dependent protein kinase (PKR) is an important component of the interferon response to virus infection. The activation of PKR is accompanied by autophosphorylation at multiple sites, including one in the N-terminal regulatory region (Thr-258) that is required for full kinase activity. Several protein kinases are activated by phosphorylation in the region between kinase subdomains VII and VIII, referred to as the activation loop. We show that Thr-446 and Thr-451 in the PKR activation loop are required in vivo and in vitro for high-level kinase activity. Mutation of either residue to Ala impaired translational control by PKR in yeast cells and COS1 cells and led to tumor formation in mice. These mutations also impaired autophosphorylation and eukaryotic initiation factor 2 subunit alpha (eIF2alpha) phosphorylation by PKR in vitro. Whereas the Ala-446 substitution substantially reduced PKR function, the mutant kinase containing Ala-451 was completely inactive. PKR specifically phosphorylated Thr-446 and Thr-451 in synthetic peptides in vitro, and mass spectrometry analysis of PKR phosphopeptides confirmed that Thr-446 is an autophosphorylation site in vivo. Substitution of Glu-490 in subdomain X of PKR partially restored kinase activity when combined with the Ala-451 mutation. This finding suggests that the interaction between subdomain X and the activation loop, described previously for MAP kinase, is a regulatory feature conserved in PKR. We found that the yeast eIF2alpha kinase GCN2 autophosphorylates at Thr-882 and Thr-887, located in the activation loop at exactly the same positions as Thr-446 and Thr-451 in PKR. Thr-887 was more critically required than was Thr-882 for GCN2 kinase activity, paralleling the relative importance of Thr-446 and Thr-451 in PKR. These results indicate striking similarities between GCN2 and PKR in the importance of autophosphorylation and the conserved Thr residues in the activation loop.

3T3 Cells↗

Rural-urban differences in black family structure: an analysis of the 1990 census.

This article examines the relationship between family structure and persisting disadvantage among U.S. blacks. The "article employs data from the 1990 Public Use Microdata Samples to compare the rural African American family to its urban counterpart. Results from the logistic regression analysis reveal that for rural Blacks, family structure is less important than community type and race relative to poverty status. These findings suggest a need for a refinement of the underclass debate."

Black or African American↗

Identification of a phosphoenolpyruvate:fructose phosphotransferase system (fructose-1-phosphate forming) in Listeria monocytogenes.

Listeria monocytogenes is a gram-positive bacterium whose carbohydrate metabolic pathways are poorly understood. We provide evidence for an inducible phosphoenolpyruvate (PEP):fructose phosphotransferase system (PTS) in this pathogen. The system consists of enzyme I, HPr, and a fructose-specific enzyme II complex which generates fructose-1-phosphate as the cytoplasmic product of the PTS-catalyzed vectorial phosphorylation reaction. Fructose-1-phosphate kinase then converts the product of the PTS reaction to fructose-1,6-bisphosphate. HPr was shown to be phosphorylated by [32P]PEP and enzyme I as well as by [32P]ATP and a fructose-1,6-bisphosphate-activated HPr kinase like those found in other gram-positive bacteria. Enzyme I, HPr, and the enzyme II complex of the Listeria PTS exhibit enzymatic cross-reactivity with PTS enzyme constituents from Bacillus subtilis and Staphylococcus aureus.

Bacterial Proteins↗

The relationship of cocaine to headache in polysubstance abusers.

In a questionnaire survey of inpatient polysubstance abusers it was found that cocaine relieved migraine-type headaches much more often in chronic headache sufferers than in those with only occasional headaches (p less than .05). However, cocaine could also bring on headaches after several hours, both in chronic headache sufferers and in those not subject to headaches. The facts that cocaine may relieve headache immediately, and also may precipitate headaches several hours after use, suggests that the well-known vasoconstrictive actions of cocaine may be responsible. Migraineurs seem more susceptible to some of these effects of cocaine than are people without chronic headaches.

Adult↗