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Biomedical subjects

K Straub

Publications and source records attributed to K Straub.

At least 19 recordsLinked to original sources
PubMed2001

Prosodic structure and wh-questions.

This study examines the influence of wh-gaps on the prosodic contour of spoken utterances. A previous study (Nagel, Shapiro, & Nawy, 1994) claimed that the phonological representation of a sentence containing a filler-gap dependency explicitly encodes the location of the syntactic gap. In support of this hypothesis, Nagel et al. presented evidence that the word immediately preceding a gap is lengthened and that there is a reliable increase in pitch excursion across the gap location. Our study challenges Nagel et al.'s claim. We argue that their materials confounded the presence/ absence of a gap with other factors that are known to affect intonational phrasing independently. We show that, when these factors are separated, the evidence that syntactic gaps are explicitly encoded in the phonological representation of a sentence disappears.

Adult↗
PubMed1999

How to do HIMSS.

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Congresses as Topic↗
PubMed1998

Financial systems: the next generation.

Changes in health care organizations and business styles are creating demand for new financial applications that span enterprises, deliver managed care muscle to providers, mesh with CPRs and solve Year 2000 concerns.

Cost Savings↗
PubMed1998

Lives and livelihoods on the line.

Linking telephone and computer technologies to deliver information can help a health care organization accomplish strategic business goals: better customer service and bottom line.

Computer Communication Networks↗
PubMed1998

Technology and the business office.

Providing access to information is the key to streamlining business office operations. Because they broaden access, document imaging, data marts, EDI and Web-enabled applications are winning a back-office following.

Ambulatory Care Information Systems↗
PubMed1997

Rationally designed inhibitors of inosine monophosphate dehydrogenase.

Functionalized 2-alkyl derivatives of inosinic acid have been synthesized to serve as reversible as well as irreversible inhibitors of the human type II enzyme inosine monophosphate dehydrogenase. These compounds were designed to react with Cys-331 of the enzyme to form covalent bonds so as to interfere with the normal enzyme mechanism which involves attack of Cys-331 at C-2 of the substrate. Mass spectrometric analysis of the reaction products after enzymatic degradation confirmed the appropriateness of the inhibitor design.

Chromatography, High Pressure Liquid↗
PubMed1997

Chaos theory.

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Cost-Benefit Analysis↗
PubMed1995

The glutamine hydrolysis function of human GMP synthetase. Identification of an essential active site cysteine.

GMP synthetase (EC 6.3.5.2) is an amidotransferase that catalyzes the amination of xanthosine 5'-monophosphate to form GMP in the presence of glutamine and ATP. Glutamine hydrolysis produces the necessary amino group while ATP hydrolysis drives the reaction. Ammonia can also serve as an amino group donor. GMP synthetase contains two functional domains, which are well coordinated. The "glutamine amide transfer" or glutaminase domain is responsible for glutamine hydrolysis. The synthetase domain is responsible for ATP hydrolysis and GMP formation. Inorganic pyrophosphate inhibits the synthetase and uncouples the two domain functions by allowing glutamine hydrolysis to take place in the absence of ATP hydrolysis or GMP formation. Acivicin, a glutamine analog, selectively abolishes the glutaminase activity. It inhibits the synthetase activity only when glutamine is the amino donor. When ammonia is used in place of glutamine, acivicin has no effect on the synthetase activity. Acivicin inhibits GMP synthetase irreversibly by covalent modification. Enzyme inactivation is greatly facilitated by the presence of substrates. Acivicin labels GMP synthetase at a single site, and a tryptic peptide containing the modified residue was isolated. Mass spectrometry and Edman sequence analysis show that Cys104 is the site of modification. This residue is conserved among GMP synthetases and is located within a predicted glutamine amide transfer domain. These data suggest that Cys104 is an essential residue involved in the hydrolysis of glutamine to produce an amino group and is not needed for the hydrolysis of ATP or amination of xanthosine 5'-monophosphate to produce GMP.

Adenosine Triphosphate↗
PubMed1995

High-level production from a baculovirus expression system and biochemical characterization of human GMP synthetase.

GMP synthetase, a key enzyme in the de novo synthesis of guanine nucleotides, is a potential target for immunosuppression and anticancer chemotherapy. In order to closely examine the catalytic mechanism and active-site topography of this enzyme, large amounts of pure protein are needed. Catalytically active human GMP synthetase was expressed in a baculovirus system. A high-level production system has been established from which the yield of pure protein is routinely more than 50 mg/10 liters of cell culture. The recombinant enzyme was purified to homogeneity and characterized. Like native GMP synthetase, the recombinant enzyme was resolved into two forms by ion-exchange chromatography. The two forms are both monomers and they differ in their isoelectric points. There is no evidence that these forms are in equilibrium or interconvertible. Protein sequence analysis reveals that both forms are blocked at the amino-terminus and they are essentially identical in sequence. Since they can be produced by a cDNA with a single open reading frame, we believe that they represent post-translational modification variants. The recombinant GMP synthetase is not distinguishable from the native enzyme in terms of chromatographic profiles, subunit composition, molecular weight, and kinetic properties. The inhibition constants and the modes of inhibition toward decoyinine, a selective inhibitor of GMP synthetase, are also the same as the native enzyme. The high-level production of active enzyme is invaluable to the determination of the three-dimensional structure and the discovery of potent and selective drug candidates.

Animals↗
PubMed1995

Effectiveness of oral antibiotic treatment in nursing home-acquired pneumonia.

OBJECTIVE: To determine factors associated with success or failure of oral antibiotic treatment for nursing home-acquired pneumonia (NHAP). DESIGN: Retrospective study of outcomes for all identifiable NHAP cases in 1991. SETTING: The Nursing Home Services Program of St. Paul Ramsey Medical Center and 31 metropolitan St. Paul, Minnesota, community nursing homes. PARTICIPANTS: Nursing home (NH) cohort: 124 patients (mean age 85.2 years) with a new respiratory symptom and new infiltrate on portable chest X-ray for whom oral antibiotics were prescribed. Hospital cohort: 74 NH patients (mean age 84.3 years) admitted to hospital with new X-ray infiltrate and pneumonia diagnosis. Supportive care status patients were excluded. Forty-three physician/nurse practitioner (MD/NP) teams were represented. MEASUREMENTS: Nursing home cohort: Outcomes of hospitalization within 14 days or 30-day mortality. A discriminant model was applied to predict outcome and discriminant rule performance was analyzed. Hospital cohort: 30-day mortality. RESULTS: Of 198 episodes of NH pneumonia, 63% were treated in the facility; 30.6% (38) failed NH treatment. Thirty-day mortality was 13%. There was no examination by the MD or NP for 59% of NH-treated episodes. The hospital cohort had a higher mean pulse (P < .05) but a similar frequency of feeding dependence. Hospital cohort mortality was 17.6%. The NH treatment failure group had significantly higher proportions of pulse > 90/min, temperature > 100.5 degrees F, respirations > 30/min, feeding dependence, and mechanically altered diets. A discriminant model using these factors was significant (P = .002). The NH treatment failure rate was 11% for no factors present, 23% for two or fewer factors, and 59.5% for three or more (likelihood ratio 3.1). Thirty-two percent of the hospital cohort had zero or one factor present and were alive at 30 days. CONCLUSION: The majority of NHAP episodes were treated successfully with oral antibiotics, but 31% failed treatment in the NH. Patients with a mechanically altered diet or requiring feeding assistance by staff had significantly higher failure rates. Feeding dependence and need for a mechanically altered diet as well as abnormal vital signs are associated with oral antibiotic treatment failure. These factors should be considered in treatment decisions for NHAP.

Administration, Oral↗
PubMed1994

Probing the active site of human IMP dehydrogenase using halogenated purine riboside 5'-monophosphates and covalent modification reagents.

Active-site amino acid residues of human type II inosine 5'-monophosphate dehydrogenase (IMPDH) were investigated using the covalent modification reagents 6-chloroinosine 5'-monophosphate (6-Cl-IMP) and iodoacetamide. IMPDH was incubated with these reagents in the presence and absence of IMP, NAD, and NADH, and the activity of the enzyme for IMP dehydrogenation or 2-Cl-IMP dehalogenation was followed. IMPDH activity was rapidly lost when the enzyme was incubated with the IMP analog, 6-Cl-IMP, or with iodoacetamide. The enzyme was protected against inactivation in the presence of the substrate IMP. It was not protected against inactivation by NAD alone. Saturating concentrations of IMP and NADH reduced the inactivation rate by about the same amount as with IMP alone. IMPDH samples labeled with 6-Cl-IMP and an unlabeled control were alkylated with iodoacetamide, digested with trypsin, and analyzed by HPLC-mass spectrometry (HPLC-MS). All eight cysteines of human type II IMPDH were found to exist as free sulfhydryls on the active, unlabeled form of the enzyme. At an enzyme/inactivator ratio of 1:4, only one cysteine residue, Cys-331, was found to be covalently modified by 6-Cl-IMP. From the results of the substrate protection experiments and HPLC-MS data, it is concluded that 6-Cl-IMP binds in the IMP binding site of IMPDH and reacts covalently with Cys-331 to form a purine riboside 5'-monophosphate-enzyme adduct.

Binding Sites↗