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Biomedical subjects

K Baker

Publications and source records attributed to K Baker.

At least 37 records · Page 2Linked to original sources
PubMed1996

Unexplained hepatitis C virus antibody seroconversion in established blood donors.

BACKGROUND: Understanding of the epidemiology and natural history of hepatitis C virus (HCV) infection is incomplete without reference to the early phase of infection. The prevalence of HCV infection is well documented in numerous reports. The seroconversion pattern in previously antibody-negative blood donors provides a model for the study of the incidence and transmission of HCV infection. STUDY DESIGN AND METHODS: Records of HCV antibody tests at the West Midlands Blood Transfusion Centre were reviewed to determine the seroconversion rate in 1994 among previously anti-HCV-negative blood donors. Seroconverting donors were counseled to investigate the possible routes of infection. RESULTS: In 1994, blood donations (n = 256,935) were collected from 149,370 donors; 24 donors (0.016%; 1/6224) were positive in the screening enzyme-linked immunosorbent assay (ELISA) and the third-generation recombinant immunoblot assay (RIBA-3). Two donors previously negative for HCV antibody in ELISA were positive in both tests in 1994. Four donors positive in ELISA and indeterminate in RIBA-3 in 1993 reacted positively in both tests in 1994. One donor negative for HCV antibody on previous screening reacted positively in ELISA and was indeterminate in RIBA-3 in 1994 and has become positive in both tests in 1995. A further 43 donors negative for HCV antibody on previous screening reacted positively in ELISA and were indeterminate in RIBA-3 in 1994. CONCLUSION: Documented seroconversion can take place in the absence of exposure to recognizable risk factors for the infection. The index donation or the donation immediately preceding seroconversion may be positive for HCV RNA in the polymerase chain reaction.

Blood Donors↗
PubMed1995

Inhibition of cysteine proteinases by Carica papaya cystatin produced in Escherichia coli.

A papaya cystatin (Cst)-encoding cDNA clone was isolated from a papaya leaf cDNA library and the active protein produced in Escherichia coli. The amino-acid sequence reveals a protein of 11,262 Da with over 40% identity to other published plant Cst. Unique features of the papaya Cst include a single Cys residue, variation in the papain-binding region, and the first reported inhibition of papaya proteinase IV by a Cst.

Base Sequence↗
PubMed1995

Comparison of experimental and theoretical parameters of the Moolgavkar-Venzon-Knudson incidence function for the stages of initiation and promotion in rat hepatocarcinogenesis.

Mathematical descriptions of complex biological phenomena, such as cancer, require an experimental format that faithfully recapitulates the biological process. In addition, the biological process must dictate the parameters in the mathematical formula. Evidence from the epidemiology of several human cancers and from experimental carcinogenesis in several organ systems indicates that cancer is a multistage process. The initiation-promotion-progression format of experimental carcinogenesis mimics the development of cancer in humans and other animals. In rats, the altered hepatic focus model of hepatocarcinogenesis has been well characterized and, coupled with the method of quantitative stereology, permits accurate determination of the number and the volume fraction of such altered foci per liver. The placental isozyme of glutathione S-transferase (PGST) is reportedly the best single marker of preneoplasia in the rat liver. Recently, single hepatocytes expressing PGST have been proposed as putatively initiated cells. Quantitation of individual hepatic cells and altered hepatic foci expressing PGST in the livers of rats subjected to an initiation-promotion protocol permits determination of the congruence of the Moolgavkar-Venzon-Knudson (MVK) model with experimental data. The best fit of the MVK model for the preneoplastic stages of hepatocarcinogenesis assumes that all hepatocytes are susceptible and that single hepatocytes expressing PGST are the initiated cell population for the focal lesions that express PGST. Further refinement of the initiation-promotion-progression model to permit accurate quantitation of early malignant conversion should allow a more complete analysis of the congruence of the MVK model for human cancer risk determination. In addition, the MVK model may be extended to other model systems and to human cancers in which early preneoplasia can be quantitated. Furthermore, the use of a more biologically based risk-assessment protocol, such as the MVK model rather than the stochastic one-hit model presently used, would permit incorporation of the present knowledge on the pathogenesis of cancer. To apply experimental data to a mathematical model that reflects the biological processes underlying human cancer development will require integration of the cell kinetics and experimental data to a mathematical model that reflects the biological processes underlying human cancer development including the pharmacokinetic and pharmacodynamic properties of the treatment chemicals.

Animals↗
PubMed1995

Enzymatic synthesis and purification of uridine diphosphate [14C]galacturonic acid: a substrate for pectin biosynthesis.

Pectins are complex polysaccharides that contain 1,4-linked alpha-D-galactosyluronic acid residues found in the primary wall of all higher plant cells. The pectic polysaccharides play critical roles in cell wall structure and in plant growth and development. As a first step in studying pectin biosynthesis a method was developed to routinely generate and purify UDP-[U-14C]galacturonic acid (UDP-[14C]GalA), the nucleotide sugar substrate for homogalacturonan biosynthesis. UDP-[14C]GalA was enzymatically synthesized by 4-epimerization of commercially available UDP-[U-14C]glucuronic acid (UDP-[14C]GlcA) using a particulate preparation from radish roots. The resulting mixture of UDP-[14C]GalA and UDP-[14C]GlcA was separated by high-performance anion-exchange chromatography using a Dionex CarboPac PA1 anion-exchange column. The UDP-sugars were detected by their absorbance at 262 nm or by pulsed amperometric detection following postcolumn addition of NaOH. The yield of UDP-[14C]GalA obtained using this procedure was 16% of the starting UDP-[14C]GlcA. Establishment of a reliable method to synthesize and purify UDP-[14C]GalA will facilitate the identification and purification of the galacturonosyltransferase(s) involved in pectin biosynthesis.

Anions↗
PubMed1995

Effects of K+ on the binding of Ca2+ to the Ca(2+)-ATPase of sarcoplasmic reticulum.

Equilibrium and kinetic fluorescence methods have been used to characterize the interactions between K+ and the Ca(2+)-ATPase of skeletal-muscle sarcoplasmic reticulum. K+ shifts the E2-E1 equilibrium of the ATPase towards E1 and increases the rate of Ca2+ binding to the ATPase, as detected by changes in tryptophan fluorescence intensity, suggesting that K+ increases the rate of the E2-E1 transition. The data are consistent with binding of K+ at the inner Ca(2+)-binding site on the ATPase in competition with H+ and Mg2+, with a higher affinity in the E1 than in the E2 conformation. K+ has no effect on the affinity for Mg2+, as detected by changes in tryptophan fluorescence intensity; since it has been proposed that the changes in tryptophan fluorescence follow from binding to Mg2+ at the outer Ca(2+)-binding site, this suggests that K+ is unable to bind at the outer Ca(2+)-binding site. K+ increases the rate of dissociation of Ca2+ from the Ca(2+)-bound ATPase and reduces the effect of Mg2+ on the fluorescence intensity of the ATPase labelled with 4-(bromomethyl)-6,7-dimethoxycoumarin. It is suggested that these effects of K+ are the result of binding at a 'gating' site on the ATPase, in competition with binding of H+. Binding of K+ at the inner Ca(2+)-binding site and at the gating site account for the observed effects of K+ on the affinity of the ATPase for Ca2+.

Animals↗
PubMed1995

Serotonin and alcohol-related brain damage.

Preliminary results from the immunohistochemical examination of the brainstems of chronic alcoholics, suggest that alcohol may have a role in damage to the principal serotonergic (5HT) nuclei. This view is reinforced by evidence from previous animal experiments which demonstrated a reduction in 5HT neurons in the brains of alcohol-preferring rats and selective neurotoxicity to 5HT neurons following 5,6-dihydroxytryptamine-induced increased ethanol intake. It is speculated that, like other neurotoxins, alcohol or its metabolites cause degeneration of 5HT axons and axon terminals. It is possible that if axonal damage is sufficiently severe and chronic, the eventual consequence is cell death. This could be due to insufficient opportunity for repair and regrowth under repeated and sustained insults of high alcohol consumption.

5,6-Dihydroxytryptamine↗
PubMed1995

Nurse managers and their future in New South Wales.

The goal of International Perspectives is to share the views of nurse leaders, from countries other than the United States, on global healthcare issues. The focus is on identifying healthcare management problems and their implications, research priorities, policy development, and ethicalmoral dilemmas faced by nurse administrators. You are encouraged to send the names and addresses of international nurse leaders who might be interested in participating, as well as your ideas, for format and content of the department.

Forecasting↗
PubMed1994

Rupture of the mitochondrial outer membrane impairs porin assembly.

Outer membranes isolated from yeast mitochondria were capable mediating the in vitro insertion of porin. As with the outer membrane of intact mitochondria, the insertion was ATP-dependent, and the inserted porin was resistant to trypsin treatment after detergent solubilization. However, the extent of porin insertion into isolated outer membranes was much less per mg of outer membrane protein than with intact mitochondria. The greater efficiency of intact mitochondria was not due to contact site-mediated translocation as isolated contact sites were less able to insert porin than isolated outer membranes, and blockade of the contact site channel in intact mitochondria did not affect porin insertion. However, mitochondria that had been subjected to osmotic shock sufficient to rupture the outer membrane and deplete the contents of the intermembrane space (i.e. mitoplasts) lost most of their ability to insert porin. Since outer membranes are isolated from mitoplasts, the low insertion activity of mitoplasts explains the low efficiency of insertion into isolated outer membranes. These results also indicate that, unlike proteins that are imported to the inner membrane and matrix of the mitochondria, porin's assembly is severely reduced by breaching the outer membrane and depletion of the intermembrane space contents.

Adenosine Triphosphate↗
PubMed1994

Focal and non-focal hepatic expression of placental glutathione S-transferase in carcinogen-treated rats.

Carcinogenesis develops in stages that have been operationally defined as initiation, promotion and progression. Although morphological end points have been described for detection and quantitation of these stages, to date initiation has been assessed only in the context of clonal growth in response to certain promoting agents. Initiated cells are morphologically indistinguishable from surrounding cells and early changes at the cellular level during initiation have not been clarified. One commonly used end point for the detection of preneoplastic hepatic lesions i their aberrant expression of the placental isozyme of glutathione S-transferase (PGST). Because single hepatocytes expressing PGST have been detected in aged rats and in those administered hepatocarcinogens, it has been suggested that such cells constitute a population of putatively initiated hepatocytes. In order to further elucidate the characteristics of single PGST-positive hepatocytes, we analyzed the number of these cells 2 and 18 weeks after various doses (0-100 mg/kg) of diethylnitrosamine (DEN) and of dimethylbenz[a]anthracene (DMBA). When determined 14 days after carcinogen administration, the number of single hepatocytes expressing PGST was greater after DEN administration (ranging from 0.8 +/- 0.3 per cm2 transection of liver at 1 mg/kg to 33.0 +/- 4.7 at 100 mg/kg) than after DMBA administration (ranging from 0.25 +/- 0.14 at 10 mg/kg to 3.03 +/- 0.5 at 100 mg/kg); none were detected in control rats of the same age. Additional rats were maintained on a basal diet or a basal diet plus phenobarbital for a further 4 month period. Whereas individual PGST-positive hepatocytes were only sporadically detected in rats treated with DMBA and maintained on a basal diet for 18 weeks, those rats placed on phenobarbital for 16 weeks had an even higher number of such PGST-positive hepatocytes than at 2 weeks after DMBA administration. In contrast, the dose-response curve observed for DEN-treated rats 18 weeks after carcinogen administration was similar to that observed 2 weeks after carcinogen treatment for both phenobarbital- and non-phenobarbital-treated rats. In addition, the number of single PGST-positive hepatocytes detected at 2 weeks was directly parallel to the number of altered hepatic foci expressing PGST 18 weeks after DEN administration. The dose-dependent induction of PGST-positive single hepatocytes after treatment with two hepatocarcinogens, the dose-dependent growth of altered hepatic foci (AHF) expressing PGST with phenobarbital administration and the parallel dose-response curve of single hepatocytes expressing PGST and later of AHF expressing PGST argue strongly for a precursor role of single PGST-positive cells in the development of AHF expressing PGST.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Work practices, fatigue, and nuclear power plant safety performance.

This paper focuses on work practices that may contribute to fatigue-induced performance decrements in the commercial nuclear power industry. Specifically, the amount of overtime worked by operations, technical, and maintenance personnel and the 12-h operator shift schedule are studied. Although overtime for all three job categories was fairly high at a number of plants, the analyses detected a clear statistical relationship only between operations overtime and plant safety performance. The results for the 12-h operator shift schedule were ambiguous. Although the 12-h operator shift schedule was correlated with operator error, it was not significantly related to the other five safety indicators. This research suggests that at least one of the existing work practices--the amount of operator overtime worked at some plants--represents a safety concern in this industry; however, further research is required before any definitive conclusions can be drawn.

Fatigue↗
PubMed1993

Case-control study of leukaemia and non-Hodgkin's lymphoma among children aged 0-4 years living in west Berkshire and north Hampshire health districts.

OBJECTIVE: To investigate the relation between parental employment in the nuclear industry and childhood leukaemia and non-Hodgkin's lymphoma. DESIGN: Case-control study. SETTING-West Berkshire and Basingstoke and North Hampshire District Health Authorities. SUBJECTS: 54 children aged 0-4 years who had leukaemia or non-Hodgkin's lymphoma diagnosed during 1972-89, who were born in the study area and were resident there when cancer was diagnosed. Six controls were selected for each case: four from hospital delivery registers and two from livebirth registers maintained by the NHS central register. Controls were matched for sex, date of birth (within six months), and area of residence at birth and time of diagnosis. MAIN OUTCOME MEASURES: Parents' employment by the nuclear industry and exposure to ionising radiation at work. RESULTS: Five (9%) of the 54 cases and 14 (4%) of the 324 controls had fathers or mothers, or both, who had been employed by the nuclear industry (relative risk 2.2, 95% confidence interval 0.6 to 6.9). Nuclear industry employees who work in areas where exposure to radiation is possible are given film badges to monitor their exposure to external penetrating ionising radiation. Three fathers of cases and two fathers of controls (and no mothers of either) had been monitored in this way before their child was conceived (relative risk 9.0, 95% confidence interval 1.0 to 107.8). No father (of a case or control) had accumulated a recorded dose of more than 5 mSv before his child was conceived, and no father had been monitored at any time in the four years before his child was conceived. A dose-response relation was not evident among fathers who had been monitored. CONCLUSIONS: These results suggest that the children of fathers who had been monitored for exposure to external penetrating ionising radiation in the nuclear industry may be at increased risk of developing leukaemia before their fifth birthday. The finding is based on small numbers and could be due to chance. If the relationship is real the mechanisms are far from clear, except that the effect is unlikely to be due to external radiation; the possibility that it could be due to internal contamination by radioactive substances or some other exposure at work should be pursued. The above average rates of leukaemia in the study area cannot be accounted for by these findings.

Case-Control Studies↗