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Biomedical subjects

R W Carlson

Publications and source records attributed to R W Carlson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Computer-based screening of patients with HIV/AIDS for clinical-trial eligibility.

OBJECTIVE: To assess the potential effect of a computer-based system on accrual to clinical trials, we have developed methodology to identify retrospectively and prospectively patients who are eligible or potentially eligible for protocols. DESIGN: Retrospective chart abstraction with computer screening of data for potential protocol eligibility. SETTING: A county-operated clinic serving human immunodeficiency virus (HIV) positive patients with or without acquired immune deficiency syndrome (AIDS). PATIENTS: A randomly selected group of 60 patients who were HIV-infected, 30 of whom had an AIDS-defining diagnosis. DESIGN: Using a computer-based eligibility screening system, for each clinic visit and hospitalization, patients were categorized as eligible, potentially eligible, or ineligible for each of the 17 protocols active during the 7-month study period. Reasons for ineligibility were categorized. RESULTS: None of the patients was enrolled on a clinical trial during the 7-month period. Thirteen patients were identified as eligible for protocol; three patients were eligible for two different protocols; and one patient was eligible for the same protocol during two different time intervals. Fifty-four patients were identified as potentially eligible for a total of 165 accrual opportunities, but important information, such as the result of a required laboratory test, was missing, so that eligibility could not be determined unequivocally. Ineligibility for protocol was determined in 414 (35%) potential opportunities based only on conditions that were amenable to modification, such as the use of concurrent medications; 194 (17%) failed only laboratory tests or subjective determinations not routinely performed; and 346 (29%) failed only routine laboratory tests. CONCLUSIONS: There are substantial numbers of eligible and potentially eligible patients who are not enrolled or evaluated for enrollment in prospective clinical trials. Computer-based eligibility screening when coupled with a computer-based medical record offers the potential to identify patients eligible or potentially eligible for clinical trial, to assist in the selection of protocol eligibility criteria, and to make accrual estimates.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Rhizobial lipo-oligosaccharide nodulation factors: multidimensional chromatographic analysis of symbiotic signals involved in the development of legume root nodules.

Nod factors are a group of biologically active oligosaccharide signals that are secreted by symbiotically competent bacteria of the family Rhizobiaceae. Their biosynthesis is determined by rhizobial nodulation (nod) genes, and is specifically induced in response to flavonoids secreted from the roots of host leguminous plants. The biological activity of Nod factors on these host legumes dramatically mimics the early developmental symptoms of the Rhizobium-legume symbiosis including, amongst other effects, root hair deformations and nodule initiation. Structurally, all Nod factors are short oligomers of beta-1,4-linked N-acetylglucosamine residues [usually degree of polymerization (dp) 4 or 5] that are N-acylated on the distal glucosamine. This common 'core' structure may be modified by a number of species-specific substituents on the distal or reducing sugars. These modifications are governed by rhizobial host specificity nod genes. The biological activity of purified Nod factors mirrors this host specificity, indicating that the symbiotic host range of individual Rhizobium species is, at least partially, determined by the variety of Nod factors they are able to produce. Here we describe techniques that are universally applicable to the extraction, chromatographic separation and identification of Nod factors. We have applied these techniques to Nod factors from the broad-host-range species Rhizobium fredii USDA257 and Rhizobium spp. NGR234, and the more narrow-host-range Bradyrhizobium japonicum USDA110, and have identified a group of novel, relatively hydrophilic Nod factors from the NGR234 species that may have implications for Nod factor biosynthesis.

Antigens, Bacterial↗
PubMed1995

Structural requirements of synthetic and natural product lipo-chitin oligosaccharides for induction of nodule primordia on Glycine soja.

Rhizobia synthesize a class of lipo-chitin oligosaccharides that induce root hair deformation and induce the initiation of nodule structures on legume roots. These lipo-chitin oligosaccharides are tetra- and penta-lipo-oligosaccharides of N-acetylglucosamine with an acyl substitution on the nonreducing end and are commonly known as Nod factors. In this study, we demonstrate that synthetic analogs of natural product Nod factors have the same biological activities. To determine structure-activity relationships, a collection of synthetic and natural product lipo-chitin oligosaccharides was assayed on Glycine soja. All biologically active lipo-chitin oligosaccharides induced both root hair deformation and nodule initiations on G. soja. The most active lipo-chitin oligosaccharides deformed root hairs at 10(-15) M and induced nodules at 1 ng of lipo-chitin oligosaccharide per spot inoculation. Plant responses demonstrate an interdependence of backbone length and the presence of substitutions on the reducing end. Lipo-chitin oligosaccharides containing four N-acetylglucosamine residues were active only without a reducing end modification, whereas lipo-chitin oligosaccharides containing five N-acetylglucosamine residues were active only with reducing end modification. The plant thus recognizes lipo-chitin oligosaccharides without reducing end substitutions despite the importance of these modifications for host range.

Carbohydrate Sequence↗
PubMed1995

Suppression of the Fix- phenotype of Rhizobium meliloti exoB mutants by lpsZ is correlated to a modified expression of the K polysaccharide.

The rhizobial production of extracellular polysaccharide (EPS) is generally required for the symbiotic infection of host plants that form nodules with an apical meristem (indeterminate nodules). One exception is Rhizobium meliloti AK631, an exoB mutant of Rm41, which is deficient in EPS production yet infects and fixes nitrogen (i.e., is Fix+) on alfalfa, an indeterminate nodule-forming plant. A mutation of lpsZ in AK631 results in a Fix- strain with altered phage sensitivity, suggesting that a cell surface factor may substitute for EPS in the alfalfa-AK631 symbiosis. Biochemical analyses of the cell-associated polysaccharides of AK631 and Rm5830 (AK631 lpsZ) demonstrated that the lpsZ mutation affected the expression of a surface polysaccharide that is analogous to the group II K polysaccharides of Escherichia coli; the polysaccharide contains 3-deoxy-D-manno-2-octulosonic acid or a derivative thereof in each repeating unit. Rm5830 produced a polysaccharide with altered chromatographic and electrophoretic properties, indicating a difference in the molecular weight range. Similar results were obtained in a study of Rm1021, a wild-type isolate that lacks the lpsZ gene: the introduction of lpsZ into Rm1021 exoB (Rm6903) both suppresses the Fix- phenotype and results in a modified expression of the K polysaccharide. Chromatography and electrophoresis analysis showed that the polysaccharide extracted from Rm6903 lpsZ+ differed from that of Rm6903 in molecular weight range. Importantly, the effect of LpsZ is not structurally specific, as the introduction lpsZ+ into Rhizobium fredii USDA257 also resulted in a molecular weight range change in the structurally distinct K polysaccharide produced by that strain. This evidence suggests that LpsZ has a general effect on the size-specific expression of rhizobial K polysaccharides.

Chromatography, Gel↗
PubMed1995

Semantic visualization of oncology knowledge sources.

Visualization of knowledge sources can have a substantial impact on the use of such sources at the point of care. This is because barriers to use at the point of care include hours required to master the electronic interfaces to those sources, and minutes required to master the electronic interfaces to those sources, and minutes required to accomplish any one retrieval. For a system to be used regularly at the point of care, therefore, it must be intuitive and fast. This paper presents a three dimensional interface to oncology knowledge sources that aims to meet this challenge.

Databases, Factual↗
PubMed1995

Accessing oncology information at the point of care: experience using speech, pen, and 3-D interfaces with a knowledge server.

Oncologists' information needs arise at diverse times and settings. For example: "Is superior vena cava syndrome a medical emergency?" Our collaborative group is developing a system that supports an interface with combinations of spoken, gestural, and simulated three-dimensional manipulation to help an oncologist focus on the information need, not the system. The system requires a small amount of input from the oncologist, and then anticipates what information is pertinent to the patient at hand, based on the sources it has available. The system makes use of a "Knowledge Server" to find relevant information. The Knowledge Server uses selected data for the particular patient from a Computer-based Patient Record (CPR) to provide context for the information needs. The Knowledge Server leverages the Unified Medical Language System (UMLS) resources as well as relevant communications standards. A layered, interaction protocol is used to help manage the fulfillment of information needs. Each of the oncology knowledge sources is transformed into a uniform representation that utilizes both its formal schema (e.g., its table of contents) and its concepts and words indexed through the UMLS Metathesaurus. Our focus on the appropriate use of information from a CPR, and on anticipating oncologists' information needs, resulted from our study of several longitudinal patient scenarios. We believe that our use of scenario-based design techniques will help to ensure the system's success.

California↗
PubMed1994

Structure of lipid A component of Rhizobium leguminosarum bv. phaseoli lipopolysaccharide. Unique nonphosphorylated lipid A containing 2-amino-2-deoxygluconate, galacturonate, and glucosamine.

The structure of lipid A from the lipopolysaccharide of Rhizobium leguminosarum bv. phaseoli (wild type strain CE3) was investigated by alkylation analysis, nuclear magnetic resonance spectroscopy, and electrospray and fast atom bombardment mass spectrometry of the de-O-acylated lipid A. The lipid A carbohydrate backbone was shown to be a trisaccharide containing galacturonic acid, glucosamine, and the unique sugar 2-amino-2-deoxygluconic acid, previously unreported in lipopolysaccharides. Nuclear magnetic resonance spectroscopy and ethylation analyses revealed that the galacturonic acid is alpha-1,4-linked to the glucosamine, while the amino aldonic acid residue, which may exist as the 1,5-lactone, is attached as an aglycone to the glucosamine and, thus, occupies the reducing end of the molecule. The resulting backbone is hydrophilic and analogous to the commonly observed bisphosphorylated glucosamine disaccharide from enteric bacterial lipopolysaccharides in that both the nonreducing and reducing ends carry negatively charged substituents. The fatty acids of the R. leguminosarum lipid A are attached both as O- and N-acyl substituents to glucosamine and 2-aminogluconate. All fatty acids are hydroxylated consisting of 3-hydroxymyristate (3-OH-C14.0), 3-hydroxypentadecanoate (3-OH-C15.0), 3-hydroxypalmitate (3-OH-C16.0), 3-hydroxystearate (3-OH-C18.0), and 27-hydroxyoctacosanoate (27-OH-C28.0) in the approximate mole ratio 3:0.2:1:0.6:1. Unlike lipid As from enteric bacteria, the R. leguminosarum lipid A lacks 3-acyloxyacyl substituents; however, the long chain 27-hydroxy fatty acid carries ester-linked beta-hydroxybutyrate at the 27-hydroxy position. Fast atom bombardment mass spectrometry of the de-O-acylated lipid A demonstrated the presence of 2 molecular species that differ by 28 mass units due to fatty acid heterogeneity at the two amide linkages. One species carries amide-linked 3-OH-C14.0 and 3-OH-C16.0; the second species carries 3-OH-C14.0 and 3-OH-C18.0. Each molecular species also exists as the aldonolactone, yielding molecular ions at ((M+H)+)-18. The heterogeneity in the amide-linked fatty acids further distinguishes the Rhizobium lipid A from enteric lipid As.

Carbohydrate Conformation↗
PubMed1994

Concentrated potassium chloride infusions in critically ill patients with hypokalemia.

Although concentrated infusions of potassium chloride commonly are used to treat hypokalemia in intensive care unit patients, few studies have examined their effects on plasma potassium levels. Forty patients with hypokalemia were given infusions of 20 mmol of potassium chloride in 100 mL of normal saline over 1 hour; 26 patients received the infusions through the central vein and 14 patients through the peripheral vein. Plasma potassium ([K]p) was measured at 15-minute intervals during and after the infusion in 31 patients. delta K was defined as the difference between each potassium determination and baseline plasma potassium concentration. Continuous electrocardiographic recording was carried out during the infusion and during the 1-hour period immediately preceding the infusion. Mean baseline [K]p was 2.9 mmol/L and all subsequent plasma concentrations significantly increased from baseline. Mean peak [K]p was 3.5 mmol/L, [K]p (1 hour postinfusion) was 3.2 mmol/L, and mean postinfusion delta K was 0.48 mmol/L (range -0.1-1.7 mmol/L). Arrhythmias, changes in cardiac conduction intervals, and other complications did not occur. The frequency of premature ventricular beats decreased significantly during the infusion compared with that of the control period. The high concentration (200 mmol/L) and rate of delivery (20 mmol/hr) of the potassium chloride infusions were well tolerated, decreased the frequency of ventricular arrhythmias, and did not cause transient hyperkalemia.

Adult↗
PubMed1994

Biosynthesis of a structurally novel lipid A in Rhizobium leguminosarum: identification and characterization of six metabolic steps leading from UDP-GlcNAc to 3-deoxy-D-manno-2-octulosonic acid2-lipid IVA.

Lipopolysaccharides (LPSs) are prominent structural components of the outer membranes of gram-negative bacteria. In Rhizobium spp. LPS functions as a determinant of the nitrogen-fixing symbiosis with legumes. LPS is anchored to the outer surface of the outer membrane by the lipid A moiety, the principal lipid component of the outer bacterial surface. Several notable structural differences exist between the lipid A of Escherichia coli and that of Rhizobium leguminosarum, suggesting that diverse biosynthetic pathways may also exist. These differences include the lack of phosphate groups and the presence of a 4'-linked GalA residue in the latter. However, we now show that UDP-GlcNAc plays a key role in the biosynthesis of lipid A in R. leguminosarum, as it does in E. coli. 32P-labeled monosaccharide and disaccharide lipid A intermediates from E. coli were isolated and tested as substrates in cell extracts of R. leguminosarum biovars phaseoli and viciae. Six enzymes that catalyze the early steps of E. coli lipid A biosynthesis were also present in extracts of R. leguminosarum. Our results show that all the enzymes of the pathway leading to the formation of the intermediate 3-deoxy-D-manno-2-octulosonic acid (Kdo2)-lipid IVA are functional in both R. leguminosarum biovars. These enzymes include (i) UDP-GlcNAc 3-O-acyltransferase; (ii) UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase; (iii) UDP-3-O-(R-3-hydroxymyristoyl)-GlcN N-acyltransferase; (iv) disaccharide synthase; (v) 4'-kinase; and (vi) Kdo transferase. Our data suggest that the early steps in lipid A biosynthesis are conserved and that the divergence leading to rhizobial lipid A may occur at a later stage in the pathway, presumably after the attachment of the Kdo residues.

Acetates↗
PubMed1993

nolMNO genes of Bradyrhizobium japonicum are co-transcribed with nodYABCSUIJ, and nolO is involved in the synthesis of the lipo-oligosaccharide nodulation signals.

A host-inducible lacZ fusion was mapped down-stream of the nodYABCSUIJ operon in Bradyrhizobium japonicum strain USDA110. Sequencing of this region identified three novel genes, nolMNO. RNA dot blot analysis showed that nolO transcription is nodD1-dependent and that a polar mutation in nodS, located 5 kilobases upstream of nolO, blocks the transcription of nolO. Coupled with the host-inducible nature of nolO expression, these results indicate that nolMNO are part of a 9-kilobase operon, nodYABCSUIJnolMNO. The lipo-oligosaccharide nodulation signals produced by strains SL67 (nolO-) and SL65(nolNO-) were purified, and their chemical structures were determined. In addition to the wild-type signal molecules, both mutants produced modified compounds that are not produced by the parent strain USDA110. The most prevalent difference observed was the absence of the 2-O-methylfucosyl residue from the mutant structures. In addition, metabolites were found in which the N-acetylglucosamine residue at the reducing end was glycosidically linked to glycerol. These alterations in the profiles of nodulation signals produced by strains SL67 and SL65 were accompanied by reduced nodulation efficiency on all hosts tested.

Amino Acid Sequence↗
PubMed1993

The structures and biological activities of the lipo-oligosaccharide nodulation signals produced by type I and II strains of Bradyrhizobium japonicum.

Bradyrhizobium japonicum produces lipo-oligosaccharide signal molecules that induce deformation of root hairs and meristematic activity on soybeans. B. japonicum USDA135 (a Type I strain) produces modified chitin pentasaccharide molecules with either a terminal N-C16:0- or N-C18:1-glucosamine with and without an O-acetyl group at C-6 and with 2-O-methylfucose linked to C-6 of the reducing N-acetylglucosamine. An additional molecule has N-C16:1-glucosamine and no O-acetyl group. All of these molecules cause root hair deformation on Vicia sativa and Glycine soja. The C18:1-containing molecules were tested and found to induce meristem formation on G. soja. USDA61 (a Type II strain) produces eight additional molecules. Five have a carbamoyl group on the terminal N-acylglucosamine. Six have chitin tetrasaccharide backbones. Three have a terminal N-acyl-N-methylglucosaminosyl residue. In four molecules, the reducing-end N-acetylglucosamine is glycosidically linked to glycerol and has a branching fucosyl, rather than a 2-O-methylfucosyl, residue. One molecule has a terminal N-acylglucosamine that has both acetyl and carbamoyl groups (one each).

Antigens, Bacterial↗
PubMed1993

Impact of omeprazole on the plasma clearance of methotrexate.

Omeprazole inhibits the gastric hydrogen pump and is an effective treatment for peptic ulcers. Methotrexate is a chemotherapeutic agent that inhibits dihydrofolate reductase and is eliminated by a hydrogen-ion-dependent mechanism in the kidney. We present evidence that omeprazole inhibits methotrexate clearance and may result in potentially toxic methotrexate levels.

Adult↗