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Biomedical subjects

S Fuller

Publications and source records attributed to S Fuller.

At least 55 records · Page 3Linked to original sources
PubMed1993

Immunization with recombinant woodchuck hepatitis virus nucleocapsid antigen or hepatitis B virus nucleocapsid antigen protects woodchucks from woodchuck hepatitis virus infection.

Woodchucks were immunized with recombinant woodchuck hepatitis virus (WHV) nucleocapsid antigen (WHcAg) or hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) and challenged with 10(6) WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (< 1%). This confirms and extends previous reports of protection against homologous challenge after immunization with HBcAg/WHcAg which are both internal viral antigens. As the dominant B-cell epitope(s) on particulate WHcAg and HBcAg appear not to be conserved it also demonstrates that antibodies against HBcAg/WHcAg are not important for this protection. Woodchucks immunized with WHcAg/HBcAg reacted with a fast serum antibody response against viral envelope proteins upon challenge with WHV, indicative of functional intrastructural/intermolecular T-cell help as one potential mechanism of protection after immunization with an internal viral antigen.

Animals↗
PubMed1993

Creating the integrated information infrastructure for the 21st century at the University of Washington Warren G. Magnuson Health Sciences Center.

Successful integrated information systems implementation requires an effective marriage of technology and information resources in response to critical institutional needs. The University of Washington technical infrastructure, developed over the past five years, includes ubiquitous, high-speed network access throughout the Health Sciences Center and hospitals, agreement on network standards and protocols, uniform interface to common databases (character-based and GUI) and network availability of a variety of databases and information resources at no charge to the individual. As a result of this heavy institutional investment in technical infrastructure, our implementation process will focus on expanding the number of available resources as well as developing and refining tools and services to enhance the utility of electronic information resources. Above all we will study and develop strategies for dealing with the myriad of information policy issues which confront and confound us all today.

Academic Medical Centers↗
PubMed1993

From bench to bedside: research and testing of Internet resources and connections in community hospital libraries.

Access to information becomes more valuable with the continuing proliferation of medical knowledge and the increasing economic pressure being experienced by health care organizations. This is particularly so for community hospitals in rural or isolated areas, where the economic pressures are at least as great as in urban areas and where access to information is often inadequate. These conditions have implications for the quality of patient care and for economic viability. In response to this, the National Library of Medicine, the University of Washington, and seven community hospitals in five Pacific Northwest states have joined forces in a broad-scale technology diffusion project to facilitate the application of research work to clinical care. There are three components to the project: 1) a pilot connections component to extend Internet access to the community hospitals, 2) a research component to test the performance of a client/server model for network access to anatomical text and images, and 3) a clinical component to develop a registry of DNA diagnostic laboratories facilitating the provision of genetic information to clinicians. The pilot connections component is described and preliminary findings are reported.

Computer Communication Networks↗
PubMed1992

Blood spot screening and confirmatory tests for syphilis antibody.

We developed a blood spot test for syphilis antibody using enzyme-linked immunosorbent assay (ELISA) technology. Dried blood was eluted by buffered saline or, for a supplementary confirmatory test, by treponemal-antibody test diluent. Eluates were diluted in an absorption buffer (Calypte Biomedical, Berkeley, Calif.) and added to plate wells coated with cardiolipin antigen (ADI Diagnostics, Toronto, Ontario, Canada). The wells were washed and treated sequentially with an immunoglobulin G conjugate, buffer washes, and enzyme substrate. Substrate conversion was measured photometrically, and specimen reactivity was determined by reference to nonreactive controls. The optimum test protocol was established by tests of serum and plasma. The serum ELISA specificity with normal specimens was 98.9%. The sensitivity with sera from patients with undefined syphilis was 97.4%, that with sera from patients with documented primary and secondary disease was 100%, and that with sera from patients with early and late latent disease was 95.7%. The specificity of the spot test with donor blood was 94.2%, and its specificity with newborn blood was 94.9%. The sensitivity with 25 spots spiked with reactive sera was 96%. The seroprevalence rates for parturient women in one hospital were 6.01% according to spot tests of sera from 599 newborns and 6.81% according to Rapid Plasma Reagin tests of 499 maternal serum specimens. Seventy percent of infants born to 50 seropositive women were reactive by either the newborn spot or the Rapid Plasma Reagin serum test. The results show that blood spots may be used in seroprevalence or serodiagnostic studies, especially to identify women who are infected or to identify possible cases of congenital infection. The test provides for studies of children and adults when routine venipuncture and serum handling and storage are problematic.

Antibodies, Bacterial↗
PubMed1991

Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis.

We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6-3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues.

Adult↗
PubMed1990

The amyloid precursor protein of Alzheimer's disease is released by human platelets.

Western blots of normal human platelets, employing a monoclonal antibody raised against the full-length amyloid precursor protein of Alzheimer's disease (APP695), revealed major bands of 100-110 and 120-130 kDa in both cytosolic, membrane, and released fractions. These species were similar in size to forms seen in brain preparations and in plasma. There was no difference in Western blots of platelet preparations from Alzheimer patients compared with controls. Purified platelet amyloid precursor proteins were sequenced and shown to be amino terminally homogeneous. Immunohistochemistry localized the antigen to the platelet and megakaryocyte and demonstrated weak immunostaining of some lymphocytes. Immunoprecipitation of material released from platelets demonstrated that sedimentable full-length APP with the carboxyl-terminal epitope, and soluble APP lacking the carboxyl-terminal epitope, may exist in the circulation. Western blots and carboxyl-terminal and amino-terminal APP radioimmunoassay of material released by platelets in response to stimulation revealed that platelets release APP during degranulation. The function of platelet APP is yet to be determined, but the present studies suggest a role in regulation of the coagulation cascade or in platelet aggregation.

Alzheimer Disease↗
PubMed1990

Identification by anti-idiotype antibodies of an intracellular membrane protein that recognizes a mammalian endoplasmic reticulum retention signal.

Monoclonal antibodies were raised against antibodies to distinct carboxy-terminal KDEL sequences of two soluble, resident endoplasmic reticulum proteins. These anti-idiotype reagents recognize an intrinsic membrane protein with characteristics expected of a receptor responsible for the recognition and return of resident proteins to the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed1990

Comparative in vitro activities of several new fluoroquinolones and beta-lactam antimicrobial agents against community isolates of Streptococcus pneumoniae.

The in vitro susceptibilities of 551 community isolates of Streptococcus pneumoniae from the Canadian province of Ontario to several new fluoroquinolones and beta-lactam antimicrobial agents were determined by a broth microdilution technique. Eight (1.5%) of these isolates were moderately susceptible (MICs, greater than or equal to 0.12 and less than or equal to 1.0 microgram/ml) to penicillin; none was resistant. Temafloxacin, ciprofloxacin, and ofloxacin (MICs for 90% of strains tested, between 1 and 2 micrograms/ml) were the most active fluoroquinolones tested, and BMY-28100 (MIC for 90% of strains tested, 0.25 microgram/ml) was the most active of the new beta-lactams tested.

4-Quinolones↗
PubMed1990

Amino acid metabolism after intense exercise.

We studied postexercise amino acid metabolism, in the whole body and across the forearm. Seven volunteers were infused with L-[alpha-15N]lysine and L-[1-13C]-leucine twice [one time during 3 h after cycle exercise (75% VO2max), and one time in the resting state]. Whole body protein breakdown was estimated from dilution of L-[alpha-15N]lysine and L-[1-13C]ketoisocaproic acid (KIC) enrichments in plasma. Leucine oxidation was calculated from 13CO2 enrichments in expired air. Whole body protein breakdown was not increased above resting levels during the recovery period. Leucine oxidation was decreased after exercise (postexercise 13 +/- 2.3 vs. resting 19 +/- 3.2 mumol.kg-1.h-1; P less than 0.02), while nonoxidative leucine disposal was increased (115 +/- 6.1 vs. 103 +/- 5.6 micrograms.kg-1.min-1; P less than 0.02). After exercise, forearm net lysine balance was unchanged (87 +/- 25 vs. 93 +/- 28 nmol.100 ml-1.min-1), but there were decreases in forearm muscle protein degradation (219 +/- 51 vs. 356 +/- 85 nmol.100 ml-1.min-1; P less than 0.05) and synthesis (132 +/- 41 vs. 255 +/- 69 nmol.100 ml-1.min-1; P less than 0.01). In conclusion, after exercise 1) whole body protein degradation is not increased, 2) leucine disposal is directed away from oxidative and toward nonoxidative pathways, 3) forearm protein synthesis is decreased. Postexercise increases in whole body protein synthesis occur in tissues other than nonexercised muscle.

Adult↗
PubMed1988

The development of phenylalanine hydroxylase in rat liver; in vivo, and in vitro studies utilizing fetal hepatocyte cultures.

Phenylalanine hydroxylase (PAH) is first detected in the liver of 21-day-gestation rats. Activity increases after birth, and in 10-day-postnatal rats it is about equal to that observed in the adult. The developmental pattern for the enzyme is reflected in the level of its mRNA determined by hybridization to 32P-cDNA, which is specific for PAH. Studies with cultured adult hepatocytes reveal that the addition of dexamethasone and dibutyryl cAMP to the medium maximizes the yield of enzyme. Hepatocytes derived from 21-day-gestation rats will produce enzyme in cultures maintained in medium supplemented with dexamethasone and dibutyryl cAMP. However, less mature cells, taken from 19-day-gestation rats do not produce measurable levels of enzyme activity. The relative amounts of PAH mRNA in the respective cultures reflect the level of PAH activity. Interestingly, after 3 days of culture, 19-day-gestation hepatocytes can be shown to express PAH mRNA. Therefore, with respect to the expression of PAH, we conclude that 19-day-gestation liver cells will differentiate during culture.

Animals↗
PubMed1987

Immunologic competence of hemodialysis patients following withdrawal of vitamin C supplement.

Twelve stable nondiabetic patients on chronic hemodialysis were studied for their immunobiologic competence while receiving vitamin C supplement and 1-2 months following its withdrawal. These subjects, on prescribed diets, were checked for their food intake at the beginning of the study and at 1-month intervals thereafter. Immunological parameters tested were: (1) plasma vitamin C levels; (2) number of mononuclear cells isolated from blood and their vitamin C contents; (3) lymphocyte blastogenic response to mitogens; (4) leukocyte metabolic functions in presence of endotoxin by nitroblue tetrazolium reduction test, and (5) delayed hypersensitivity to skin-testing antigens, e.g. Candida and mumps antigens and purified protein derivative. Patients on vitamin C had significantly higher plasma ascorbic acid levels compared to normal healthy subjects. These decreased to low normal levels 1 month following withdrawal of the supplement and stayed comparable thereafter, up to 12 months of the study period. Ascorbic acid contents in the isolated mononuclear cells remained unchanged in patients on or off vitamin C. The number of blood mononuclear cells isolated and mitogenic responses to concanavalin A and phytohemagglutinin did not change following withdrawal of vitamin C supplement. All patients had positive delayed hypersensitivity to Candida, 60% to mumps and all were unresponsive to purified protein derivative. Leukocyte metabolic functions by nitroblue tetrazolium reduction test were higher in patients on vitamin C than when off, but this was not statistically significant. Vitamin C supplement is not necessary in hemodialysis patients when they are on an adequate diet.

Aged↗
PubMed1986

The effect of dexamethasone on transferrin secretion by cultured fetal rat hepatocytes.

Cultured fetal rat hepatocytes derived from 12, 15 and 19-day gestation rats are capable of secreting transferrin. When dexamethasone is added to the medium an increased secretion rate is observed. The changes in secretion rates in control as well as dexamethasone-treated cells during culture have been shown to correlate with the level of mRNA coding for transferrin. Immunocytochemical experiments show that initially all hepatocytes contain transferrin which is localized in the lumina of the perinuclear space, rough endoplasmic reticulum and in the saccules and vesicles of the Golgi apparatus. During culture, particularly in control cells, the intensity of labelling varies from cell to cell. In addition, adjacent cells are observed to label more intensely in different intracellular organelles.

Animals↗
PubMed1984

Vesicular stomatitis virus infects and matures only through the basolateral surface of the polarized epithelial cell line, MDCK.

We have used Madin-Darby canine kidney (MDCK) cells grown on nitrocellulose filters to study the polarity of virus infection and maturation. The cells form epithelia-like monolayers, which display high (greater than 1000 omega cm2) electrical resistance and a cuboidal morphology. Vesicular stomatitis virus (VSV) was found to infect the monolayer at least 100 times more efficiently when applied through the filter to the basolateral surface than when applied to the apical surface. The avian influenza, fowl plague virus (FPV), infected the monolayer through either the apical or basolateral surface. The polarity of virus budding was evaluated by harvesting virus from the two sides of the monolayer. More than 99% of released influenza hemagglutinin titre was found on the apical side of the filter, while more than 98% of budded VSV was found on the basal side. This polarity of budding was retained through 10 hr of viral infection, as was the polarity of surface expression of viral envelope proteins revealed by immunofluorescence. The strong preference of VSV for basolateral maturation is paralleled by an equally strong preference for infection through the basolateral membrane of this polar epithelial cell.

Animals↗
PubMed1984

Nucleotide sequence of the tms genes of the pTiA6NC octopine Ti plasmid: two gene products involved in plant tumorigenesis.

The nucleotide sequence of the tumor morphology locus, tms, from pTiA6NC has been determined. The sequence analysis indicates that each of two polyadenylylated transcripts encoded by this locus contains an open reading frame; the predicted transcript 1 gene product has a molecular size of 83,769 daltons, and the predicted transcript 2 gene product, of 49,588 daltons. The precise start and stop positions of the transcript 2 RNA have been mapped with S1 nuclease. Several insertion mutations have been constructed. One of these localizes the transcript 2 promoter within the 72 base pairs 5' to transcription initiation. Significant homology was observed between the protein encoded by transcript 1 and the adenine binding region of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens, suggesting that the transcript 1 protein binds adenine either as substrate or cofactor.

Amino Acid Sequence↗