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Biomedical subjects

B J Baker

Publications and source records attributed to B J Baker.

At least 37 records · Page 2Linked to original sources

The punaglandins: 10-chloroprostanoids from the octocoral Telesto riisei.

Telesto riisei, an octocoral from Hawaii, produces nineteen highly functionalized prostanoids, the punaglandins, which are characterized by various oxygenation at C-5, -6, -7, and -12, and a 10-chloro-9-cyclopentenone moiety. The absolute stereochemistry of the 10-chloroprostanoids is epimeric to that of the Pacific marine prostanoids without halogen. The punaglandins have shown anti-inflammatory and antitumor activity. A synthetic 10-thiomethyl derivative enhances in vivo mineralization in human osteoblasts.

Animals↗

High-frequency germinal transposition of DsALS in Arabidopsis.

We have established an efficient transposontagging system in Arabidopsis thaliana using the Activator/Dissociation (Ac/Ds) elements from maize. This system consists of two components, a stable trans-activator, Acst, that supplies transposase, and a cis-responsive Ds element. Ds and Acst were constructed with different selectable and screenable markers to facilitate monitoring of Ds excisions and insertions as well as segregation of Ds and Acst. Fusions of the 35S, rbcS, or CHS promoters to Ac transposase were used to trans-activate DsALS, a Ds element carrying an herbicide-resistance gene. The ALS gene encoding acetolactase synthase, which confers resistance to chlorsulfuron, functioned as a versatile marker for selection of plants grown in tissue culture as well as in soil. Thirty-five Acst lines were crossed to two DsALS lines, and the resulting progeny were assayed for germinal transposition of DsALS. Trans-activation of DsALS by Acst resulted in germinal excision frequencies of up to 64% when using 35S promoter-Ac transposase fusions, up to 67% when using rbcS-transposase fusions, and up to 1% when using CHS-transposase fusions. Amongst progeny bearing terminal excisions, Southern analysis revealed that 45% from 35S-Acst crosses and 29% from rbcS-Acst crosses carried reintegrated DsALS elements. The Ac/Ds system we have developed should prove to be an effective tool for stable gene tagging in Arabidopsis.

Arabidopsis↗

Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus. Purification, characterization, bifunctionality, and evolutionary implication.

Deacetoxycephalosporin C hydroxylase from cell-free extracts of Streptomyces clavuligerus was stabilized partially and purified to near homogeneity by three anion-exchange chromatographies, ammonium sulfate fractionation, and two gel filtrations. The hydroxylase was a monomer with a Mr of 35,000-38,000. alpha-Ketoglutarate, ferrous iron, and molecular oxygen were required for the enzyme activity. The hydroxylase was optimally active between pH 7.0 and 7.4 in a 3-(N-morpholino)propanesulfonic acid buffer and at 29 degrees C. It was stimulated by a reducing agent, particularly dithiothreitol or reduced glutathione, and ATP. The requirement for ferrous ion was specific, and at least one sulfhydryl group was apparently essential for the enzymatic hydroxylation. The Km values of the hydroxylase for deacetoxycephalosporin C and alpha-ketoglutarate were 59 and 10 microM, respectively, and the Ka for ferrous ion was 20 microM. In addition to its known hydroxylation of deacetoxycephalosporin C to deacetylcephalosporin C, the hydroxylase catalyzed effectively an analogous hydroxylation of 3-exomethylenecephalosporin C to deacetoxycephalosporin C. Surprisingly, the hydroxylase also mediated slightly a novel ring-expansion of penicillin N to deacetoxycephalosporin C. The substrate specificity of the hydroxylase is overlapping with but distinguishable from that of deacetoxycephalosporin C synthase, the enzyme which normally mediates the ring-expansion reaction (Dotzlaf, J. E., and Yeh, W. K. (1989) J. Biol. Chem. 264, 10219-10227). Furthermore, the hydroxylase exhibited an extensive sequence similarity to the synthase. Thus, the two enzymes catalyzing the consecutive reactions for cephamycin C biosynthesis in S. clavuligerus represent apparent products from a divergent evolution.

Amino Acid Sequence↗

Exercise increases the circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in normal individuals.

Recently two peptides consisting of amino acids (aa) 1 to 30 and 31 to 67 of the N-terminus of the 126 aa prohormone of atrial natriuretic factor (proANF), as well as atrial natriuretic factor (ANF, aa 99 to 126; C-terminus), were found to have vasodilatory and natriuretic properties. These peptides, as well as ANF, circulate in humans as part of the N-terminus of the prohormone. To determine the effect of graded exercise on the circulating concentrations of the N-terminus and C-terminus of the ANF prohormone in normal persons, 12 healthy individuals (mean age 45 +/- 2 years) were evaluated before, for 2 hours after, and during bicycle exercise at a work loads of 25, 50, 75, 100, 125, 150, and 175 W. Both the N- and C-terminus of the ANF prohormone were released simultaneously with graded exercise in direct proportion to the intensity of the work load, measured objectively via maximal oxygen consumption (VO2max), respiratory quotient, and heart rate. Both the N-terminus and C-terminus of the ANF prohormone had strong positive correlations (p less than 0.001) with blood pressure, heart rate, VO2max, and respiratory quotient. Following exercise, the C-terminus returned to preexercise levels within 30 minutes, while the N-terminus remained significantly elevated at 30 and 60 minutes postexercise, reflecting the longer half-life of the N-terminus in the circulation.

Adult↗

A rapid method for standardization of the gated radionuclide left ventricular ejection fraction.

Radionuclide ventriculography has become the standard method for serially evaluating left ventricular ejection fraction (EF). The "gold standard" for evaluating EF is the contrast ventriculogram, which uses mathematical models to arrive at the volumes used to calculate EF. These models are subject to possible error. This paper reports the standardization of volume measurements of a digital angiographic camera system using a series of cardiac phantoms and the correlation of measurement of the EF of a series of patients whose EF was determined by digital angiography and radionuclide ventriculography.

Aged↗

Effects of dl-fenfluramine on dextrin and casein intakes influenced by textural preferences.

The effects of dl-fenfluramine (2.5 mg/kg) on selection between the textures of nutrient preparations were tested by presenting rats with a choice between pairs of three sizes of chow crumb with 45% dextrin, casein, maltodextrin, or calcium caseinate added or with no nutrient added. The usual effect of fenfluramine was to reduce the intake preference for a coarser over a finer crumb. This drug effect differed, however, with the preparation of protein or of carbohydrate added to each crumb size. There was no consistent effect of nutrient, and hence the reported effects of this dose of dl-fenfluramine cannot be attributed to nutrient-specific selection.

Animals↗

dl-fenfluramine challenge to nutrient-specific textural preference conditioned by concurrent presentation of two diets.

Effects of the ingestion of protein and carbohydrate conditioned a preference for one size of chow particle over another, which was triggered by need for a specific nutrient. This learned elicitation of nutrient-specific dietary selection was not changed by injection of dl-fenfluramine HCl (2.5 mg/kg). This indicates that previously observed effects of fenfluramine on differential intakes of dextrin- and casein-rich diets do not depend on nutrient-specific self-selection.

Animals↗

Preference conditioning by concurrent diets with delayed proportional reinforcement.

Mildly food-deprived rats were presented at the same time either high- and low-carbohydrate diets or protein-containing and nonnutritive diets differing in flavor in parallel with nutrient composition. After a few days of these concurrent 10-minute presentations, the rats preferred the flavor of the richer or nutritive diet. Such preference conditioning also occurred when there was a 10-minute delay between the presentation of two flavors in nonnutritive diet and intubation of a mixture of nutrients in proportion to the flavor intakes. Thus, rats are able to perceive the difference between the nutritional aftereffects of two distinctive diets presented concurrently and to learn to respond differentially to associated flavors even when there was a delay as long as that used in earlier studies with pyloric closure. Therefore, the reinforcement that has been suggested to arise from gastric chemoreception can be attributed instead to delayed postgastric effects.

Animals↗

Genuinely olfactory preferences conditioned by protein repletion.

Effects of protein on mild food deprivation in the rat conditioned a relative preference for an intense, insoluble and tasteless odorant. This learned preference for the protein-paired odorant over a non-nutritive-paired odorant was temporarily obliterated by insertion of tubes in the nares to bypass the olfactory mucosa. This demonstrates truly olfactory conditioning, contrary to assertions that gustatory conditioning had not been excluded.

Animals↗

Prohormone atrial natriuretic peptides 1-98 and 31-67 increase with exercise in congestive heart failure patients.

Recently two peptides consisting of amino acids (a.a.) 1-30 and 31-67 of the N-terminus of the 126 a.a. prohormone of atrial natriuretic factor (pro ANF), as well as atrial natriuretic factor (ANF, a.a. 99-126; C-terminus) were found to have vasodilatory and natriuretic properties. These peptides, as well as ANF, circulate in man as part of the N-terminus of the prohormone. To determine the effect of graded exercise on the circulating concentration of the N-terminus and C-terminus of the ANF prohormone in persons with abnormal salt and water metabolism, 12 individuals with stable congestive heart failure (CHF) were evaluated before and after bicycle exercise testing and the results were subdivided based on the maximal exercise they could achieve. In all of the CHF patients, the circulating concentration of the whole N-terminus (ie, a.a. 1-98), the midportion of the N-terminus (pro ANF 31-67), which circulates as a distinct 3900 molecular weight (m.w.) peptide after being proteolytically cleaved from the N-terminus, and the C-terminus (ANF) increased with exercise. The patients who were able to achieve 100 and 125 watts of workload had a greater maximal oxygen consumption and, in general, a greater percent increase in the circulating concentration of both the N-terminus and the C-terminus of the ANF prohormone than those who had less exercise capacity. Evaluation of the echocardiographic, radionucleotide, and the exercise parameters revealed that the circulating concentrations of these atrial peptides correlated best with left atrial dimension, but that left ventricular systolic and diastolic dimensions also correlated positively with their concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure.

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531 +/- 25, 371 +/- 18, and 22 +/- 1 fmol/ml (+/- SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10- to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increased proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.

Adult↗

Snakebite in captive Rocky Mountain elk (Cervus elaphus nelsoni).

Eight cases of snakebite occurred in seven of 11 captive Rocky Mountain elk (Cervus elaphus nelsoni) during June and July 1987. Severity of reactions to envenomation varied; affected elk presented with combinations of signs that included painful swelling restricted to the face and muzzle, submandibular edema, inspiratory dyspnea, epistaxis, frothy, blood-tinged nasal discharge, epiphora, anorexia and anxiousness or depression. We observed puncture wounds in only two cases. Treatment consisted of dexamethasone (about 0.1 mg/kg subcutaneously, single dose) and procaine penicillin G (about 25,000 IU/kg subcutaneously, once or twice daily, for 5 to 6 days), as well as revaccination using clostridium and tetanus toxoids. Swelling resolved and elk recovered in 3 to 5 days without complications. Using immunodiffusion, we detected serum antibodies to prairie rattlesnake (Crotalus viridis viridis) venom in six of seven affected elk, demonstrating seroconversion in three cases and anamnesis in one elk bitten twice. Venom was undetectable in any serum samples using similar techniques.

Animals↗

Tuberculosis in San Antonio: 1960-1984.

San Antonio, Tex, has a long history of having a high rate of tuberculosis, but from 1960 through 1984, the rate was reduced by 82.6%. In 1984 it had a lower case rate than all but one of the six major Texas cities. The rate reduction involved all ethnic groups. The City Chest Clinic treats most of the new active cases, either by providing all necessary services or by supplying medication in cooperation with local physicians. The use of chemotherapeutic drugs has greatly reduced the transmission of the disease. Preventive therapy may prevent infection or reduce the bacterial population in contacts of active cases. The city health department's nursing division provides follow-up of patients and contacts. To prevent premature discontinuation of medications, nurses observe selected patients as they take their medicines. High case rates among minority ethnic groups, although improved, still are observed. Furthermore, high rates of new active cases are still found in areas of the city with the lowest median family income, low median values of homes, and overcrowding.

Ethnicity↗

Effects of dl-fenfluramine and xylamidine on gastric emptying of maintenance diet in freely feeding rats.

Freely feeding rats received an anorexigenic dose of dl-fenfluramine HCl (5 mg/kg). Two hours following injection, their stomachs retained significantly greater dry weight contents than saline-injected controls. The same dose of fenfluramine decreased the rate of gastric emptying over a 2 h period to a similar extent in mildly food-deprived rats. The peripherally acting serotonin antagonist xylamidine counteracted the effect of fenfluramine in prolonging the satiating effect of an ad libitum meal of a given size. We propose therefore that the principal mechanism by which fenfluramine reduces food consumption in freely feeding rats is through a prolongation of the satiating effect of absorption as a result of slowing of gastric emptying, presumably via enhanced release of serotonin from nerve terminals in the wall of the gastrointestinal tract.

Amidines↗

Sustained therapeutic efficacy and safety of oral propafenone for treatment of chronic ventricular arrhythmias: a 2-year experience.

Thirty-two men with chronic ventricular arrhythmias responded to propafenone, a new potent antiarrhythmic agent, in short-term trials with 85% or greater reduction of total ventricular premature complexes (VPCs) per hour, 95% or greater reduction of ventricular couplets (VCs) per hour, and 100% abolition of ventricular tachycardia (VT) beats per 24 hours. These patients were continued on long-term propafenone therapy to assess sustained therapeutic efficacy and safety. Thirty patients completed 1 year and 26 patients completed 2 years of testing with this agent; one patient died of sudden death and another died of a noncardiac cause. Although there were significantly fewer patient responders at 1 and 2 years, the majority of patients (greater than 79%) continued to respond optimally to propafenone. Side effects were minor and included bitter taste, dizziness, congestive heart failure, fatigue, and significant prolongation of the PR and QRS intervals. Propafenone has sustained antiarrhythmic efficacy after 2 years without serious toxicity.

Aged↗