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Biomedical subjects

C A Baker

Publications and source records attributed to C A Baker.

At least 19 recordsLinked to original sources
PubMed2006

Improved experimental limit on the electric dipole moment of the neutron.

An experimental search for an electric dipole moment (EDM) of the neutron has been carried out at the Institut Laue-Langevin, Grenoble. Spurious signals from magnetic-field fluctuations were reduced to insignificance by the use of a cohabiting atomic-mercury magnetometer. Systematic uncertainties, including geometric-phase-induced false EDMs, have been carefully studied. The results may be interpreted as an upper limit on the neutron EDM of |d(n)|< 2.9 x 10(-26)e cm (90% C.L.).

Journal Article↗
PubMed2005

Transcriptional response of human microglial cells to interferon-gamma.

Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-gamma, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-gamma signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-gamma induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia-T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-gamma-a key to understanding cell-mediated immunity of the CNS.

Cells, Cultured↗
PubMed2000

Intrusive thoughts and auditory hallucinations: a comparative study of intrusions in psychosis.

Several theories of auditory hallucinations implicate the involvement of intrusive thoughts and other theories suggest that the interpretation of voices determines the distress associated with them. This study tested the hypotheses that patients who experience auditory hallucinations will experience more intrusive thoughts and be more distressed by them and interpret them as more uncontrollable and unacceptable than the control groups. It also examines whether the interpretation of hallucinations is associated with the distress caused by them and whether there are differences in the way that patients respond to and interpret their thoughts and voices. A questionnaire examining the frequency of intrusive thoughts and the reactions to them was administered to a group of patients with a diagnosis of schizophrenia who experienced auditory hallucinations, a psychiatric control group and a non-patient control group. In addition, the patients in the first group completed a similar questionnaire in relation to their voices. Analyses of covariance showed that patients who experienced auditory hallucinations had more intrusive thoughts than the control groups and that they found their intrusive thoughts more distressing, uncontrollable and unacceptable than the control groups. Correlational analyses revealed that patients' interpretations of their voices were associated with the measures of distress in relation to them. Repeated measures analyses of covariance found no differences between thoughts and voices on the dimensions assessed. The theoretical and clinical implications of these findings are discussed.

Adult↗
PubMed2000

Fibrinogen and fibrin protect fibroblast growth factor-2 from proteolytic degradation.

We have recently reported that fibrinogen and fibrin bind to fibroblast growth factor-2 (FGF-2) and potentiate its ability to stimulate proliferation of endothelial cells. In the present report, we have investigated the potential of fibrinogen and fibrin to protect FGF-2 from proteolytic degradation. FGF-2 was incubated with trypsin or chymotrypsin in the presence or absence of fibrinogen or fibrin and proteolysis of FGF-2 was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. In the absence of fibrinogen there was progressive tryptic degradation of FGF-2, but in the presence of fibrinogen, FGF-2 was completely protected from trypsin with no evidence of degradation. The degree of protection was maximum at a molar ratio of FGF-2 to fibrinogen 1:2. Fibrinogen afforded similar protection from degradation by chymotrypsin. Polymerized fibrin provided partial protection of FGF-2 from tryptic degradation, with intact FGF-2 present for up to 360 min. Fibrin provided nearly complete protection from chymotrypsin. These observations indicate that binding of FGF-2 to fibrinogen or fibrin provides protection from proteolytic degradation, and this may modulate its cell proliferative activity.

Biopolymers↗
PubMed1999

Improving the appropriateness of vancomycin use by sequential interventions.

BACKGROUND: Vancomycin usage is directly associated with the incidence of vancomycin-resistant enterococci. Optimal methods to reduce inappropriate use have not been delineated. We determined the appropriateness of vancomycin prescribing at our hospital on the basis of national guidelines and assessed the effect of sequential administrative and educational interventions. METHODS: In this prospective 3-phase study conducted in a Veterans Affairs Medical Center, we monitored vancomycin prescribing at baseline and in 2 follow-up periods. Administrative interventions included discussions with service chiefs and revising routine perioperative antibiotic prophylaxis orders. Educational interventions included in-services about vancomycin-resistant enterococci and appropriate vancomycin prescribing. In each monitoring period, 50 consecutive new vancomycin orders that could be evaluated were classified for appropriateness and categorized by indication. RESULTS: At baseline, 70% of vancomycin use was inappropriate. Surgical services accounted for 84% of orders. Interventions targeted services with high or frequently inappropriate vancomycin use. After administrative interventions, inappropriate vancomycin use dropped to 40% of orders (P =.003). Improvements were noted in targeted services. Educational interventions further decreased inappropriate vancomycin use, but the effect appeared transient. CONCLUSIONS: The simple, nonrestrictive administrative interventions used resulted in a statistically significant (30%) reduction in inappropriate vancomycin prescribing. However, educational interventions provided only transient benefit on institutional prescribing patterns.

Anti-Bacterial Agents↗
PubMed1999

Fluoroquinolone toxicity profiles: a review focusing on newer agents.

For 2 decades fluoroquinolones have been found to be generally well-tolerated and safe. Adverse events may be inherent to the class or influenced by structural modifications. The commonest adverse events are gastrointestinal tract (GI) and central nervous system (CNS) reactions; nephrotoxicity and tendinitis are infrequent, but agents differ greatly in phototoxic potential. Fluoroquinolones are safe in elderly, human immunodeficiency virus-infected, and neutropenic patients, but because of possible effects on articular cartilage, they are not currently recommended for children or pregnant women. Four new agents have recently been licensed. Levofloxacin causes few GI or CNS adverse events and is minimally phototoxic. Sparfloxacin infrequently causes GI or CNS effects but is associated with relatively high rates of phototoxicity and prolongation of the electrocardiographic QTc interval (Q-T interval, corrected for heart rate). Grepafloxacin causes relatively high rates of GI effects, taste perversion, and QTc interval prolongation, but it is minimally phototoxic. Trovafloxacin is associated with a moderate rate of GI effects and a relatively high incidence of dizziness but has low phototoxic potential.

Anti-Infective Agents↗
PubMed1999

Microglial activation varies in different models of Creutzfeldt-Jakob disease.

Progressive changes in host mRNA expression can illuminate crucial pathogenetic pathways in infectious disease. We examined general and specific approaches to mRNA expression in three rodent models of Creutzfeldt-Jakob disease (CJD). Each of these models displays distinctive neuropathology. Although mRNAs for the chemokine receptor CCR5, the lysosomal protease cathepsin S, and the pleiotropic cytokine transforming growth factor beta1 (TGF-beta1) were progressively upregulated in rodent CJD, the temporal patterns and peak magnitudes of each of these transcripts varied substantially among models. Cathepsin S and TGF-beta1 were elevated more than 15-fold in mice and rats infected with two different CJD strains, but not in CJD-infected hamsters. In rats, an early activation of microglial transcripts preceded obvious deposits of prion protein (PrP) amyloid. However, in each of the three CJD models, the upregulation of CCR5, cathepsin S, and TGF-beta1 was variable with respect to the onset of PrP pathology. These results show glial cell involvement varies as a consequence of the agent strain and species infected. Although neurons are generally assumed to be the primary sites for agent replication and abnormal PrP formation, microglia may be targeted by some agent strains. In such instances, microglia can both process PrP to become amyloid and can enhance neuronal destruction. Because microglia can participate in agent clearance, they may also act as chronic reservoirs of infectivity. Finally, the results here strongly suggest that TGF-beta1 can be an essential signal for amyloid deposition.

Animals↗
PubMed1998

Recombinant human cytomegalovirus protease with a C-terminal (His)6 extension: purification, autocatalytic release of the mature enzyme, and biochemical characterization.

Human cytomegalovirus protease (CMV PR) is a target for the development of antiviral therapeutics. To obtain large amounts of native protease, a 268-amino-acid polypeptide with a hexahistidinyl tag at the C terminus was expressed in Escherichia coli. The first 262 amino acids of the recombinant protein were identical to the amino acid sequence of native CMV PR, except for mutations introduced at the internal cleavage site to eliminate autoproteolysis at that site. The hexahistidinyl tag was placed downstream of amino acid 262 of the native CMV PR sequence. In this design, the Ala-Ser bond at amino acids 256-257 constitutes a site naturally cleaved by the protease during capsid maturation. The 268-amino-acid polypeptide with the (His)6 tag was expressed at high levels in E. coli as inclusion bodies. After solubilization of the inclusion bodies, the protease was purified to homogeneity by a single step using Ni2+ affinity chromatography. The protease was refolded to an active enzyme using dialysis which leads to effective autocleavage of the Ala-Ser bond at amino acids 256-257 to remove 12 amino acids including the (His)6 tag from the C terminus of the protein. This strategy yielded large amounts of highly purified CMV PR with the native N terminus and C terminus. Approximately 40 mg of purified CMV PR was obtained per liter of cell culture using this strategy. The enzymatic activity of CMV PR purified from inclusion bodies and refolded to an active enzyme was similar to the enzymatic activity of CMV PR expressed as a soluble protein in E. coli. In addition, the refolded CMV PR could be crystallized for X-ray diffraction.

Amino Acid Sequence↗
PubMed1998

Cognitive processes in auditory hallucinations: attributional biases and metacognition.

BACKGROUND: Cognitive models suggest that auditory hallucinations are experienced when mental events are misattributed to an external source; therefore, this study was designed to examine attributional biases in patients experiencing auditory hallucinations. The study also examined the role of metacognitive beliefs in the experience of auditory hallucinations, as some theories have implicated metacognition in the development and maintenance of auditory hallucinations. METHODS: Fifteen participants with a diagnosis of schizophrenia experiencing auditory hallucinations were compared with 15 non-hallucinating schizophrenics and 15 non-psychiatric control subjects on several measures, including an immediate source monitoring task and a questionnaire assessing metacognitive beliefs. RESULTS: Results indicated that patients experiencing hallucinations exhibited the predicted bias towards misattributing internal events to an external source, as measured by ratings of internality of responses in a word association task. All groups had lower perceived levels of internality and control for emotionally salient words, which provides further evidence for the importance of emotional content in hallucinations. Patients experiencing hallucinations were found to score higher than the other two groups on metacognitive beliefs about uncontrollability and danger and positive beliefs about worry. In addition, a logistic regression analysis showed that beliefs about uncontrollability and danger were predictive of whether subjects experienced auditory hallucinations or not. CONCLUSIONS: These results offer considerable support to cognitive bias models of auditory hallucinations, particularly those that implicate metacognition.

Adult↗
PubMed1998

The effectiveness of a nurse-managed minimal smoking-cessation intervention among hospitalized patients with cancer.

PURPOSE/OBJECTIVES: To determine the effectiveness of a nurse-managed minimal smoking-cessation intervention among hospitalized patients with cancer. DESIGN: Prospective, two-group, randomized clinical trial. SETTING: Urban, academic, tertiary-care setting. SAMPLE: 28 adult male and female smokers with a diagnosis of cancer who are hospitalized for a surgical procedure. METHODS: During hospitalization, subjects were assigned to a minimal smoking-cessation intervention group (n = 14) or a usual care group (n = 14). Verification of smoking status was performed at a clinic visit six weeks postintervention. Nonsmoking status was defined as self-report of zero cigarettes/day during the prior week and confirmed by saliva cotinine analysis. MAIN RESEARCH VARIABLES: One-time, Inpatient, nurse-managed, minimal smoking-cessation intervention, self-reported smoking status, and saliva cotinine level of < or = 14 ng/ml. FINDINGS: Upon hospital admission, 64% of the intervention group and 71% of the usual care group reported their intention to quit smoking. At six weeks postintervention, only 21% and 14% of the intervention and usual care group, respectively, were classified as abstinent from smoking. More than 90% of the intervention group members who resumed smoking did so within first week of discharge. IMPLICATIONS FOR NURSING PRACTICE: A more intensive intervention may be necessary to assist hospitalized surgical patients in achieving smoking cessation. Additional contact prior to discharge or within the first few days postdischarge may be necessary to reinforce strategies for remaining abstinent.

Adult↗
PubMed1997

Expression of a P-selectin ligand in zona pellucida of porcine oocytes and P-selectin on acrosomal membrane of porcine sperm cells. Potential implications for their involvement in sperm-egg interactions.

The selectin family of cell adhesion molecules mediates initial leukocyte adhesion to vascular endothelial cells at sites of inflammation. O-glycan structural similarities between oligosaccharides from human leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) and from zona pellucida glycoproteins of porcine oocytes indicate the possible existence of a P-selectin ligand in the zona pellucida. Here, using biochemical as well as morphological approaches, we demonstrate that a P-selectin ligand is expressed in the porcine zona pellucida. In addition, a search for a specific receptor for this ligand leads to the identification of P-selectin on the acrosomal membrane of porcine sperm cells. In vitro binding of porcine acrosome-reacted sperm cells to oocytes was found to be Ca2+ dependent and inhibitable with either P-selectin, P-selectin receptor-globulin, or leukocyte adhesion blocking antibodies against P-selectin and PSGL-1. Moreover, porcine sperm cells were found to be capable of binding to human promyeloid cell line HL-60. Taken together, our findings implicate a potential role for the oocyte P-selectin ligand and the sperm P-selectin in porcine sperm-egg interactions.

Acrosome↗
PubMed1996

A scintillation proximity assay for UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase.

A rapid and simple method for quantitating the reaction product of UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase (GalNAc-transferase) by scintillation proximity assay (SPA) was developed. The assay quantitates the radioactivity incorporated from 3H-labeled UDP-GalNAc into a biotin-labeled acceptor peptide, as measured after adsorption of the acceptor peptide to avidin-coated SPA beads. The acceptor peptide, PPASTSAPG (Elhammer et al. (1993) J. Biol. Chem. 268, 10029-10038) was conjugated to biotin using a di-beta-alanine spacer arm. The conjugated peptide reacted readily with the enzyme and it had an apparent Km comparable to that of the parent peptide. Using a reaction mixture consisting of 4 mg of SPA beads, 17 microM acceptor, 0.5 microM nucleotide sugar, and 7.5 U/ml enzyme, the time dependence of product formation obeyed Michaelis-Menten-type kinetics throughout the full course of the reaction-until exhaustion of the donor substrate-and the beginning portion of the reaction was sufficiently linear for calculating accurate initial rates. Analysis of the time dependency yielded an apparent Km of 0.38 +/- 0.12 microM for UDP-GalNAc. The assay is conveniently carried out in 96-well microtiter plates; it is ideally suited for assaying large numbers of samples and for screening large collections of chemicals for competitive inhibitors.

Amino Acid Sequence↗
PubMed1996

L-trans-2,3-pyrrolidine dicarboxylate: characterization of a novel excitotoxin.

This study investigated the in vitro and in vivo excitotoxic properties of a novel conformationally constrained analogue of L-glutamate, L-trans-2,3-pyrrolidine dicarboxylate (L-trans-2,3-PDC). When tested for excitotoxic activity in rat cortical cultures, L-trans-2,3-PDC mimicked the action of NMDA in both acute (30 min) and chronic (24 h) exposure paradigms. This neurotoxicity was attenuated by co-addition of MK-801 (10 microM). Microinjections of L-trans-2,3-PDC into the dorsal hippocampus of male rats also induced a selective pattern of pathology indicative of an NMDA receptor excitotoxin. In contrast to the equipotency observed in vitro, 100 nmol of L-trans-2,3-PDC were needed to produce cellular damage comparable to that induced by 25 nmol of NMDA. Consistent with an action at NMDA receptors, L-trans-2,3-PDC-induced damage could be significantly reduced by co-administration of MK-801 (3 mg/kg i.p.), but not by NBQX (25 nmol). In radioligand binding assays L-trans-2,3-PDC inhibited the binding of 3H-L-glutamate to NMDA receptors (IC50 1 microM), although it also exhibited some cross reactivity with KA and AMPA receptors. L-trans-2,3-PDC was also identified as a competitive inhibitor (Ki = 33 microM) of 3H-D-aspartate uptake into rat forebrain synaptosomes. In contrast to the action of a transported substrate, such as L-glutamate, L-trans-2,3-PDC did not exchange with 3H-D-aspartate that had been previously loaded into the synaptosomes.

Animals↗
PubMed1995

Conversion of a bovine UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase to a soluble, secreted enzyme, and expression in Sf9 cells.

A soluble, secreted UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase, was prepared by substituting the honeybee melittin leader sequence for the sequences coding for the cytoplasmic and membrane spanning domains of a cloned, bovine full-length cDNA (F. L. Homa et al., 1993, J. Biol. Chem. 268, 12609-12616). When this construct was expressed in insect cells using a recombinant baculovirus, a fully active soluble enzyme was recovered from the culture medium. In large-scale preparations, approximately 2-3 mg of enzyme protein was produced per liter of medium. A one-step purification of the soluble molecule on apomucin-Sepharose yielded an essentially homogeneous enzyme preparation. The purified soluble enzyme has a molecular mass of approximately 61 kDa and appears to contain both N- an O-linked oligosaccharides. NH2-terminal sequencing demonstrated that the melittin leader sequence is cleaved at the predicted site and amino acid analysis gave results in close agreement with the composition predicted by the nucleic acid sequence. The enzymatic properties of the soluble, recombinant molecule are similar to those of the enzymes isolated from bovine colostrum and porcine submaxillary gland: the specific activity is approximately 2160 U/mg protein and the Kms for UDP-GalNAc and the synthetic acceptor peptides PPASTSAPG and PPDAASAAPLR are approximately 1.7 microM, 6.5 mM, and 3.6 mM, respectively.

Amino Acid Sequence↗
PubMed1995

cDNA cloning, expression, and chromosomal localization of a human UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase.

Oligonucleotide primers derived from the cDNA encoding a full-length bovine UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase (GalNAc-transferase) [Homa, F. L., Hollander, T., Lehman, D. J., Thomsen, D. R., and Elhammer, A. P. (1993) J. Biol. Chem. 268, 12609-12616], were used for PCR to isolate sequences encoding a homologous enzyme from human salivary gland cDNA. Comparison of the human and bovine nucleotide sequences reveals 94.8% sequence identity in their coding regions and 87% identity in their 3-untranslated regions. The translation of the human GalNAc-transferase coding region predicts an amino acid sequence which is nearly identical (99.6%) to that of the bovine counterpart; there are five conservative and one non-conservative amino acid substitutions between the two enzymes. Expression of the bovine and human cDNAs in the insect cell line, Sf9, resulted in the synthesis of proteins which appeared identical on SDS-PAGE and which had similar enzymatic properties. Screening of a somatic cell human/rodent hybrid panel with a probe derived from the human GaLNAc-transferase cDNA sequence indicated that the human GalNAc-transferase gene is localized to chromosome 18.

Amino Acid Sequence↗
PubMed1994

Minoxidil sulfation in the hair follicle.

The in vivo model which may be the most accurate for the ability to predict hair growth in humans, and which was utilized in the preclinical development of minoxidil, is the adult stumptailed macaque. Previous reports have suggested that the enzyme activity which accounts for the activation of minoxidil, i.e., minoxidil sulfotransferase, is present in skin. We have demonstrated that scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity, and further with dissection of that scalp skin into epidermis, dermis and hair follicle, most of sulfotransferase activity was present in the follicle. Sulfotransferase activity in the hair follicle in freeze-dried scalp skin sections from 9 stumptailed macaques ranged from 47 to 84% of the total (mean 61 +/- 12%). Much less minoxidil sulfotransferase activity was measured in the epidermis (mean 18 +/- 11%, with a range of 2-37%) and the dermis (mean 21 +/- 8%, with a range of 4-35%) of these scalp sections. These results indicate that the scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity and this activity is largely localized in the hair follicle which may account for its ability to stimulate hair growth in this animal model.

Animals↗
PubMed1994

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans.

The cellular mechanisms responsible for conversion of islet amyloid polypeptide (IAPP) into insoluble amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM) are not clear. Overexpression of IAPP and the amino acid sequence of human IAPP (hIAPP) have both been implicated. To examine factors involved in amyloid formation, transgenic mice expressing the hIAPP or rat IAPP (rIAPP) gene were generated. These mice had elevated plasma IAPP concentrations, and they were normoglycemic and normoinsulinemic. No amyloid deposits were detected by light microscopy. To examine the ultrastructure of islets, pancreatic tissue was studied from hIAPP and rIAPP transgenic mice and from age-matched control mice by immunoelectron microscopy. IAPP was immunolocalized in beta-cell secretory granules of all mice, and the COOH- and NH2-terminal flanking peptides of hIAPP were localized in beta-cell granules of hIAPP mice. Accumulations of nonfibrillar perivascular IAPP-immunoreactive material were found between capillaries and beta-cells in hIAPP transgenic mice but not in rIAPP transgenic or control mice. Similar nonfibrillar masses were identified in islets of an NIDDM patient. Secondary lysosomes in beta-cells and macrophages of hIAPP transgenic mice showed dense labeling for IAPP. We suggest that hIAPP is degraded more slowly than rIAPP or mouse IAPP by beta-cell lysosomes. Accumulations of IAPP in islet perivascular spaces may represent the early stages of islet amyloid formation.

Aged↗