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Biomedical subjects

J E Bailey

Publications and source records attributed to J E Bailey.

At least 109 records · Page 6Linked to original sources
PubMed1996

MCA has more to say.

The recent development of two mathematical frameworks for the analysis and design of metabolic systems is reviewed here. Both frameworks employ a (log)linear kinetic metabolic model that is constructed making direct, explicit use of the individual enzyme kinetic parameters which are a foundation of Metabolic Control Analysis (MCA) information. The first framework allows the description of the dynamic responses of metabolic systems subject to fluctuations in their parameters. The second framework considers the problem of optimizing the regulatory structure of metabolic networks. Both frameworks are powerful in enabling greater insights into metabolism based on MCA quantities.

Animals↗
PubMed1996

Hyperkalemic periodic paralysis episode during halothane anesthesia in a horse.

A 7-month-old Quarter Horse filly was admitted for surgical repair of a right olecranon fracture. Anesthesia was achieved with xylazine hydrochloride, guaifenesin, ketamine hydrochloride, and halothane. Two and a half hours after induction of anesthesia, myotonia, muscle fasciculations, and sweating, concurrent with high serum potassium concentration and associated electrocardiographic changes consistent with hyperkalemic periodic paralysis, were observed. Treatment included intermittent positive-pressure ventilation, changing intravenous administration of fluids from lactated Ringer's solution to 0.9% NaCl solution, and administration of calcium gluconate, glycopyrrolate, dopamine, and sodium bicarbonate. Clinical signs resolved with the return of serum potassium concentrations to the reference range. The horse was confirmed to be heterozygous for hyperkalemic periodic paralysis by DNA testing.

Anesthesia, General↗
PubMed1996

Engineered biosynthesis of novel polyketides: regiospecific methylation of an unnatural substrate by the tcmO O-methyltransferase.

TcmO is an O-methyltransferase that methylates the C-8 hydroxyl to Tcm B3, a four-ring aromatic intermediate in the tetracenomycin biosynthetic pathway of Streptomyces glaucescens. The gene encoding this enzyme was expressed in Streptomyces coelicolor CH999 together with the actinorhodin polyketide synthase (PKS) gene cluster, which is responsible for the biosynthesis of 3,8-dihydroxy-methylanthraquinone carboxylic acid (DMAC) and its decarboxylated analog, aloesaponarin. The resulting recombinant strain produced approximately equal quantities of aloesaponarin and a new product but no DMAC. Spectroscopic analysis revealed that the novel polyketide was the 3-O-methylated analog of DMAC. An in vitro radioisotopic assay was developed for tcmO. The enzyme requires S-adenosylmethionine as a co-substrate. It has a Km of 3 microM and a kcat of 2.7 min-1 for DMAC. A series of monocyclic, bicyclic, and tricyclic aromatic compounds were also tested as candidate substrates in vitro. Remarkably, none was modified by tcmO within detectable limits of the assay. Together, these results highlight the interesting molecular recognition features of this enzyme. On one hand, there appears to be some flexibility in the number and structures of unreactive rings, since both Tcm and B3 and DMAC are good substrates. However, 6-methylsalicylic acid, a monocyclic analog of the reactive ring, is not recognized by the enzyme. Likewise, neither aloesaponarin (which only differs from DMAC in the reactive ring) nor carminic acid (which only differs in the distal nonreactive ring) is modified. Thus, the binding energy for the tcmO-catalyzed methyl transfer appears to involve significant contributions from both the aromaticity and the functionality of polycyclic substrates.

Anthraquinones↗
PubMed1996

Asklepios: ancient hero of medical caring.

Western culture's demands of integrity, sacrifice, and compassion from its physician healers have roots in the mythic traditions of ancient Greece. By understanding these traditions, modern physicians can better understand their patients' expectations and the high expectations physicians often have for themselves. The mythic figure Asklepios was the focus of Greek and Roman medical tradition from approximately 1500 BC to 500 AD. As a physician-hero, Asklepios exemplified the ideal physician and the pitfalls he or she may face. With the progressive deification of Asklepios and the spread of his worship first in Greece and then in the Roman empire, Asklepios became generally recognized as the god of healing and served as an object of supplication, particularly for the poor and disregarded. Asklepian traditions for medical service provide historical insight into the role of modern physicians and their obligations to care for the underserved.

Humans↗
PubMed1996

Effectiveness of an Indonesian model for rapid training of Guatemalan health workers in diarrhea case management.

The aim of this study was to assess the effectiveness of a newly developed method for rapid tiered training of health workers in improving community health worker knowledge and case management skills. The interactive "Kader" method, developed in West Java, Indonesia, was compared with traditional didactic training in a prospective trial with rural health workers ("Tecnicos") and village health promoters ("Promotores") for the Public Health Department in the state of Alta Verapaz, Guatemala. Twenty-five tecnicos received one day of training concerning diarrhea and dehydration. One group was trained using the interactive Kader method of Indonesia; the other with didactic methods. A sample of these tecnicos then trained 49 randomized promotores utilizing the same training method with which they were trained. The tecnicos and promotores in each group completed a case-based pre-test and post-test before and after their training sessions. Both tecnicos and promotores trained using the Kader tiered training approach demonstrated significantly greater improvement in their ability to correctly diagnose and recommend treatment for diarrhea of varying type and severity. Non-significant differences favoring the experimental groups were found in the tecnicos' and promotores' general knowledge regarding diarrhea prevention practices, signs of dehydration and preparation of oral rehydration solution. This pilot study suggests that the Kader method for rapid tiered training of health workers has applicability to the populations of other developing nations and can be recommended for large scale implementation and evaluation in the training of public health workers, village health promoters and families in Guatemala.

Adult↗
PubMed1996

Barriers to cancer screening.

Many barriers to cancer screening have been summarized and discussed. Barriers have been documented in all patient populations, but some groups such as ethnic minorities and the elderly face unique barriers. The barriers to cancer screening, are multifactorial, but much of the responsibility for change must lie with health care providers and the health care delivery industry. This is not to free the patient of all responsibility, but some significant barriers are beyond their direct control. Take, for example, socioeconomic status, disease knowledge, and culturally related perceptions and myths about cancer detection and treatment. The health care industry must do a better job identifying and overcoming these barriers. The significant effects of provider counseling and advice must not be underestimated. Patients must first be advised, and then further actions must be taken if they reject the screening advice. Did they refuse adherence to recommendations because they do not view themselves as susceptible, because of overwhelming personal barriers, or because of a fatalistic attitude toward cancer detection and treatment? If that is the case, physicians and health care institutions must attempt to change perceptions, educate, and personalize the message so that patients accept their disease susceptibility [table: see text]. Multiple patient and provider risk factors have been identified that can be used to target patients particularly at high risk for inadequate cancer screening and providers at high risk for performing inadequate screening. Research has clearly demonstrated the effectiveness of interventions to improve tracking of patient and physician compliance with screening recommendations. Further research is needed to show the impact of managed-care penetration and payer status on screening efforts, and incentive schemes need to be tested that reward institutions and third-party payers who develop uniform standards and procedures for cancer screening. The greatest responsibility lies with medical and health care institutions and those who determine the priorities of these institutions. Patient and physician barriers to mass cancer screening can be addressed by institutional support. If the quality of care delivered by providers, group practices, managed-care organizations, and HMOs is assessed with priority given to the regularity and consistency with which basic screening procedures are performed, cancer screening will undoubtedly receive greater attention in the clinic. Medical institutions must collaborate to develop standards for cancer screening with attention to the cost-effectiveness of various screening techniques to determine how limited resources can best be spent in cancer control. Such efforts should keep in mind "that a very small change implemented over a broad population may have a greater effect in absolute numbers than a large level of change applied in a small segment of the population."

Cultural Characteristics↗
PubMed1996

Engineered biosynthesis of novel polyketides: properties of the whiE aromatase/cyclase.

The ORFVI from the cluster of genes, which is responsible for the biosynthesis of the Streptomyces coelicolor spore pigment, the whiE cluster, has been described as a bifunctional aromatase/cyclase. In order to evaluate its potential use for generating novel polyketides, combinations of this gene with those encoding minimal polyketide synthase enzymes with or without a ketoreductase from S. coelicolor A3(2) were constructed and analyzed in vivo. Analysis of the polyketide products generated from these constructs indicates that the whiE-ORFVI enzyme has properties similar to those of TcmN, although the whiE aromatase/cyclase normally acts on a polyketide intermediate that is four carbons longer than the TcmN substrate. The whiE aromatase/cyclase can influence the regiospecificity of the first cyclization of unreduced, but not reduced, backbones and is also responsible for the second ring aromatization. An unusual new polyketide, EM18, was identified which is not seen in equivalent strains expressing the tcmN aromatase/cyclase or the act aromatase genes. The structure of EM18 suggests that the WhiE-ORFVI product might have some unique properties within this family of polyketide synthase subunits, and may therefore be useful in the design of combinatorial biosynthetic strategies.

Anti-Bacterial Agents↗
PubMed1996

Physiology and metabolic fluxes of wild-type and riboflavin-producing Bacillus subtilis.

Continuous cultivation in a glucose-limited chemostat was used to determine the growth parameters of wild-type Bacillus subtilis and of a recombinant, riboflavin-producing strain. Maintenance coefficients of 0.45 and 0.66 mmol of glucose g-1 h-1 were determined for the wild-type and recombinant strains, respectively. However, the maximum molar growth yield of 82 to 85 g (cell dry weight)/mol of glucose was found to be almost identical in both strains. A nonlinear relationship between the specific riboflavin production rate and the dilution rate was observed, revealing a coupling of product formation and growth under strict substrate-limited conditions. Most prominently, riboflavin formation completely ceased at specific growth rates below 0.15 h-1. For molecular characterization of B. subtilis, the total amino acid composition of the wild type was experimentally determined and the complete building block requirements for biomass formation were derived. In particular, the murein sacculus was found to constitute approximately 9% of B. subtilis biomass, three- to fivefold more than in Escherichia coli. Estimation of intracellular metabolic fluxes by a refined mass balance approach revealed a substantial, growth rate-dependent flux through the oxidative branch of the pentose phosphate pathway. Furthermore, this flux is indicated to be increased in the strain engineered for riboflavin formation. Glucose catabolism at low growth rates with reduced biomass yields was supported mainly by the tricarboxylic acid cycle.

Amino Acids↗
PubMed1996

Angiotensin II in the evolution of experimental heart failure.

Although angiotensin II (Ang II) has been implicated in the pathophysiology of congestive heart failure, its temporal and regional changes during the development and progression of the disease are poorly defined. Our objective was to assess circulating, renal, cardiac, and vascular Ang II in a canine model of rapid ventricular pacing-induced heart failure that evolves from early left ventricular dysfunction to overt congestive heart failure. Ang II was measured by radioimmunoassay with low cross-reactivity to other angiotensins. Control, early left ventricular dysfunction, and overt congestive heart failure dogs were studied. Early left ventricular dysfunction was characterized by impaired cardiac function, cardiac enlargement, preserved renal perfusion pressure, maintained urinary sodium excretion, and normal plasma renin activity. Overt congestive heart failure was characterized by further impaired cardiac function and cardiac enlargement, reduced renal perfusion pressure, urinary sodium retention, and increased plasma renin activity and plasma Ang II. In early left ventricular dysfunction dogs, renal cortical, renal medullary, ventricular, and aortic Ang II were unchanged, and atrial Ang II was decreased. In overt congestive heart failure dogs, Ang II was increased in the kidney and heart compared with normal dogs and in all tissues compared with early left ventricular dysfunction dogs. The greatest increase in tissue Ang II occurred in the renal medulla. We conclude that early increases in local renal, myocardial, and vascular Ang II do not occur in this model of early left ventricular dysfunction and may even be suppressed. In contrast, increased myocardial and particularly renal Ang II in association with increased circulating Ang II are hallmarks of overt experimental congestive heart failure. These studies provide new insights into the temporal and regional alterations in Ang II during the progression of experimental congestive heart failure.

Angiotensin II↗
PubMed1996

Comparison of sedative and cardiorespiratory effects of medetomidine and medetomidine-butorphanol combination in dogs.

OBJECTIVE: Sedative, cardiorespiratory, and analgesic effects of intramuscular administration of medetomidine (40 micrograms/kg of body weight)-glycopyrrolate (0.01 mg/kg) and medetomidine (10 micrograms/kg)-butorphanol (0.2 mg/kg)-glycopyrrolate (0.01 mg/kg) combinations were compared. Additional evaluations were done on reversal of medetomidine, using atipamezole (200 micrograms/kg. IV), after 90 minutes of medetomidine-induced sedation. DESIGN: Crossover study, with each dog receiving each drug combination at 1-week intervals. ANIMALS: Six 2-year-old English hound-type dogs. PROCEDURE: Arterial blood pressure, ECG, respiratory rate, tidal volume, minute volume, arterial blood gas tensions, and serum biochemical variables were measured before, during, and after sedation. Analgesia was evaluated by needle prick on the skin and tail clamp. RESULTS: Heart rate decreased significantly from 100 beats/min to < 40 beats/min within 3 minutes of injection of medetomidine and medetomidine and butorphanol (MB). Mean arterial blood pressure in both groups were maintained above 100 mm of Hg throughout the recording period. There was no significant difference between medetomidine and MB in respiratory rate, tidal volume, and minute ventilation. Hypoxemia (PaO2 < 60 mm of Hg) was observed at 10 and 20 minutes in 2 dogs given MB. Atipamezole administration in the dogs given medetomidine significantly increased PaO2, and returned the values to baseline. Needle prick analgesia duration was longer in the medetomidine (80 +/- 7.7 minutes) than MB (56.0 +/- 19.2 minutes) group. Tail pinch analgesia was variable in both groups. Duration of lateral recumbency was longer after medetomidine (90 +/- 0 minutes) than MB (73.5 +/- 19.0 minutes). CONCLUSION: Medetomidine and MB were effective combination for mildly invasive procedures. CLINICAL RELEVANCE: MB induced a shorter period of analgesia and recumbency than did medetomidine.

Analgesics, Opioid↗
PubMed1996

Prevention in managed care: obstacles and opportunities.

Managed care will present many new challenges to health care providers in their efforts to improve the quality of the preventive care their patients receive. Managed care will present both formidable obstacles to prevention and previously unknown opportunities to enhance population-based preventive services. Whether these opportunities are realized depends on the degree and quality of the involvement of health care providers in managed care institutions. Provider and public health input is particularly needed to promote the development of uniform preventive care standards, the development of information systems for continuous monitoring of preventive service delivery, and to enhance clinic-based preventive efforts, and the development of reimbursement mechanisms that provide incentives for prevention. Independent research and oversight is needed to show the impact of various types of managed care on preventive service delivery and quality of care. The effects of managed care on the preventive care that patients receive will ultimately be determined by the quality, priorities, and determination of the management.

Forecasting↗
PubMed1995

The effects of clonidine on cardiovascular responses to standing in healthy volunteers.

This study assessed the effects of clonidine on blood pressure (BP) and heart rate responses to active standing, recorded continuously using a Finapres monitor. Ten subjects were given a placebo infusion over 1 h, followed by clonidine hydrochloride 1.5 micrograms/kg over 2 h. During placebo and at 1, 3 and 19 h following the clonidine infusion, heart rate and blood pressure were recorded during the second half of supine rest for 10 min, active standing and quiet standing for 7 min. Clonidine did not alter the size of immediate drop in BP on standing, although the nadir was lower. BP recovery was impaired, with a loss of the usual BP overshoot in most subjects and with delays in reaching supine levels of diastolic BP (6.1 versus 9.6 s; p < 0.01) and systolic BP (8.1 versus 12.3 s; p < 0.05). The compensatory initial heart rate rise was significantly increased from 47 to 53 beats/min (p < 0.05), although the peak rate reached was reduced from 114 to 104 beats/min (p < 0.05). These results demonstrate that impairment of central sympathetic vasomotor drive leads to a delay in BP recovery and loss of initial BP overshoot immediately after standing, together with impaired maintenance of early steady-state BP.

Adult↗
PubMed1995

A comparison of the effects of phenelzine treatment with moclobemide treatment on cardiovascular reflexes.

The effects of treatment with phenelzine (n = 15) and moclobemide (n = 20) on heart rate variability and cardiovascular responses to standing were examined using non-invasive beat-to-beat blood pressure (BP) monitoring in an open cross-sectional study. Phenelzine markedly impaired the BP response compared with moclobemide, with 83% vs 15% of patients lacking the normal initial BP overshoot (p < 0.01). BP recovery to supine levels was delayed (median time for diastolic BP 14.5 s after phenelzine vs 4.9 s after moclobemide; p < 0.002). Standing BP at 1 min and its change from supine levels were also significantly lower in the phenelzine group (delta diastolic BP 4 mmHg vs 15 mmHg; p < 0.001). Heart rate responses and variability were preserved and did not differ between treatments. These findings are consistent with impairment of sympathetic function but preservation of parasympathetic responses after phenelzine treatment.

Adolescent↗
PubMed1995

The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH) and a stable analogue, dimethyl proline-TRH, in healthy volunteers.

1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue, dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were assessed in healthy volunteers in two randomised, double-blind, placebo controlled crossover studies. 2. Both doses of TRH produced significant but transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg, 1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8 mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic: 8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea, acid taste, urethral sensations) and duration of subjective effects.

Adult↗
PubMed1994

Intracellular expression of Vitreoscilla hemoglobin alters Escherichia coli energy metabolism under oxygen-limited conditions.

An earlier stoichiometric analysis of oxygen-limited metabolism of Escherichia coli expressing cloned Vitreoscilla hemoglobin (VHb) suggested improved efficiency of ATP production relative to wild-type controls [Khosla, C., Curtis, J. E., DeModena, J., Rinas, J. & Bailey, J. E. (1990) BioTechnol. 8, 849-853]. This hypothesis has been further examined by determining several energetic parameters of different VHb-expressing E. coli (VHb+) strains relative to controls not expressing VHb (VHb-). The H+/O ratio, the transmembrane delta pH, and the ATP content of VHb+ constructs are 1.5, 1.6 and 2 times, respectively, corresponding values in VHb- controls. VHb was expressed using a low-copy-number vector in E. coli mutant strains lacking cytochrome o, cytochrome d, or both terminal oxidases; significant growth enhancement due to VHb expression was observed only in the strain having functional cytochrome o and lacking cytochrome d. All of these data obtained using different E. coli strains are consistent with a model of VHb action that hypothesizes enhancement by VHb of activity of the lower oxygen-affinity, higher proton-pumping-efficiency cytochrome o terminal oxidase under oxygen-limited growth conditions.

Aerobiosis↗
PubMed1994

Sponge-like electrophoresis media: mechanically strong materials compatible with organic solvents, polymer solutions and two-dimensional electrophoresis.

A new range of sponge-like media, called "electrophoresis sponges", is presented. They differ from electrophoresis gels primarily in that they are mechanically stronger, providing a permanent structure of directly measurable pore size dimensions. The new media are similar to capillary electrophoresis in terms of pore size range, they are mechanically strong with directly definable walls, and are compatible with polymer solutions. The sponges differ from capillary electrophoresis in that they provide large numbers of channels, with a corresponding high load capacity for simultaneous runs in multiple channels and they are compatible directly with multi-dimensional separations, such as high resolution two-dimensional electrophoresis. Furthermore, they can be molded (or cut) to any shape and retain that shape, they can be handled more easily than gels, they can be reused if necessary, they can be distributed in the same format between labs easily, and they can be stored indefinitely. Chemically, they can be hydrophilic or hydrophobic, with capability ranging from inert to reactive surfaces. Pore sizes can range from the sub-nanometer to 100 micron scale. Results with various hydrophobic sponges are reported for the carrier ampholyte-based isoelectric focusing of proteins. Broad and narrow pH gradients are established in the sponges that are more linear than those achieved with polyacrylamide gels. One- and two-dimensional electrophoresis of proteins has been achieved, for example with high resolution of the charge isomers of the haptoglobin beta chain, using sponge-based isoelectric focusing. Isoelectric focusing is about threefold faster in the tested sponges than in equivalent polyacrylamide gels. This improved speed is probably related to the larger sponge pores.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophoresis, Gel, Two-Dimensional↗
PubMed1994

A pharmacodynamic study of the alpha 2-adrenergic receptor antagonist ethoxyidazoxan in healthy volunteers.

Ethoxyidazoxan, a potent and highly selective alpha 2-adrenergic receptor antagonist, was administered intravenously to six healthy male volunteers in a double-blind, placebo-controlled, dose-rising design. Doses of 6 micrograms/kg and 8 micrograms/kg infused intravenously over 30 minutes produced significant elevations of plasma norepinephrine and body temperature and inhibited norepinephrine-induced platelet aggregation. Central activity was shown by reversal of the slowing of saccadic eye movements and an increase in saccade peak velocity at the higher dose. Modest increases in blood pressure were produced without change in heart rate. Ethoxyidazoxan was well tolerated, with slight changes in subjective alertness and sedation.

Adrenergic alpha-Antagonists↗