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PubMed1991

The occurrence and functions of ultradian rhythms.

Ultradian oscillations with periods between 5 min and 4 h have been described in cell-free extracts, single-celled eukaryotes, cultured cells and embryos. Whereas some of these potentially oscillatory systems (e.g. glycolysis) may only exhibit this type of behaviour rarely if at all in vivo, other ultradian oscillators in lower eukaryotes are rhythms and probably have timekeeping functions. Rhythms with ultradian periods of 10 min to 20 h in oxygen consumption and carbon dioxide production have also been studied in endotherm animals: these rhythms may be modified by variations of environmental parameters and by circadian and infradian synchronizers. Interspecies and interstrain differences strongly suggest that these rhythms are endogenous and have a genetic origin. We suggest that the temporal organization of biochemical and physiological processes facilitates optimization of thermodynamic maintenance of the organism within the random fluctuations of its physicochemical environment and contributes to genetic selection.

Animals↗
PubMed1995

Policy goals for health and safety.

Health management and safety regulation are separate disciplines but share the aim to extend expectancy of life in good health. The need to improve cost-effectiveness calls for their co-ordinated management according to a unified rationale. Three guiding principles of accountability, demonstrable net benefit and a uniform measure of performance, have been laid out in Canada by the Joint Committee on Health and Safety. They call for open accounting in terms of (health-related quality-adjusted) life expectancy. The principles are utilitarian in format but, it is argued, inequity is naturally diminished in the process of optimizing cost-effectiveness through maximum marginal returns. Comments are made on practical implementation. The need for public consent in practice calls for two additional principles reflecting fair procedure and sovereignty of the citizens. It is concluded that public health and safety measures should be surveyed, documented for cost-effectiveness and prioritized for improvement.

Canada↗
PubMed1994

Magnetocardiographic localization of the origin of ventricular ectopic beats.

Magnetocardiographic mapping opens new perspectives for three-dimensional localization of cardiac electrical activation. Using a 37-channel SQUID magnetometer equipment with high shielding, the origin of abnormal ventricular activation was investigated in 18 patients with Wolff-Parkinson-White syndrome prior to catheter ablation and in 5 of 31 patients with coronary artery disease having a sufficient number of monomorphic ventricular extrasystoles to enable evaluation. In all WPW-patients, the site of the earliest delta-wave activation was projected onto the AV-valve plane in accordance with the MR images. The result of magnetocardiographic localization was then compared to the site of successful catheter ablation determined by digital imaging processing. After optimization of the algorithms, both sites were in the various planes at the following distance from each other: X-plane: 0.8 +/- 0.9 cm, Y-plane: 1.1 +/- 1.0 cm and Z-plane: 1.5 +/- 1.0 cm. In three-dimensional projection, the mean difference in space between both positions was calculated to be 2.1 +/- 1.7 cm. After this validation ventricular premature beats were localized in another group of patients. In 4 of 5 patients their origin was found at the border of infarct areas. In each case, the progression of the ventricular activation could be pursued. The detected structure of the magnetic field distribution of the VBP's exhibited a stable bipolar pattern, which is comparable to that of ventricular tachycardia, and its algorithms may be used to localize the origin of ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Implementing an interdisciplinary healthcare quality project.

Bringing together healthcare professionals from several disciplines for a quality project can provide many benefits. This article describes the collaborative process between nursing and dental services at a Department of Veterans Affairs Medical Center as they assessed and evaluated the practice of oral hygiene among 120 long-term care patients. Enhancement of interdisciplinary collaboration occurred through appropriate disciplinary representation and leadership, clarification of disciplinary vocabularies, firsthand empirical assessment, and timely feedback. With each discipline combining resources, fostering open communication, and evaluating the project, the collaborative process was optimized. Benefits of this interdisciplinary quality project included (a) more comprehensive and holistic evaluation of patients' oral hygiene practices, (b) quality assessment in a timely fashion, (c) establishment of rapport between individuals who otherwise might not have an opportunity to interact, (d) improved communication and understanding between disciplines, and (e) development of better patient care indicators.

Communication↗
PubMed1994

Contributions of psychology to diabetes management.

Three contributions of psychology to diabetes management are considered in some detail: (a) measurement of psychological outcomes and processes, (b) optimizing blood glucose monitoring and (c) stress management. Two further applications are introduced: (d) weight management and (e) psychological treatments for sexual dysfunction. Six further applications of psychology to diabetes care are mentioned. The psychosocial, physical health and economic gains expected to result from the contributions considered are specified.

Adaptation, Psychological↗
PubMed2001

Rate and timing cues associated with the cochlear amplifier: level discrimination based on monaural cross-frequency coincidence detection.

The perceptual significance of the cochlear amplifier was evaluated by predicting level-discrimination performance based on stochastic auditory-nerve (AN) activity. Performance was calculated for three models of processing: the optimal all-information processor (based on discharge times), the optimal rate-place processor (based on discharge counts), and a monaural coincidence-based processor that uses a non-optimal combination of rate and temporal information. An analytical AN model included compressive magnitude and level-dependent-phase responses associated with the cochlear amplifier, and high-, medium-, and low-spontaneous-rate (SR) fibers with characteristic frequencies (CFs) spanning the AN population. The relative contributions of nonlinear magnitude and nonlinear phase responses to level encoding were compared by using four versions of the model, which included and excluded the nonlinear gain and phase responses in all possible combinations. Nonlinear basilar-membrane (BM) phase responses are robustly encoded in near-CF AN fibers at low frequencies. Strongly compressive BM responses at high frequencies near CF interact with the high thresholds of low-SR AN fibers to produce large dynamic ranges. Coincidence performance based on a narrow range of AN CFs was robust across a wide dynamic range at both low and high frequencies, and matched human performance levels. Coincidence performance based on all CFs demonstrated the "near-miss" to Weber's law at low frequencies and the high-frequency "mid-level bump." Monaural coincidence detection is a physiologically realistic mechanism that is extremely general in that it can utilize AN information (average-rate, synchrony, and nonlinear-phase cues) from all SR groups.

Audiometry, Pure-Tone↗
PubMed1978

Verification of the optimal probabilistic basis of aural processing in pitch of complex tones.

Periodicity pitch for complex tones has been quantitatively accounted for by a two-stage process of Fourier-frequency analysis subject to random errors and significant nonlinearities, followed by an harmonic pattern recognizer that makes an optimum probabilistic estimate of the fundamental period of musical and speech sounds. The theory predicts that periodicity pitch is a multimodal probabilistic function of a given stimulus. A clear and empirically supported distinction is made between limitations on the pitch mechanism caused by the stochastic nature of aural frequency representation and by the deterministic resolution bandwidths of aural frequency analysis. This model was developed earlier [J. L. Goldstein, J. Acoust. Soc. Am 54, 1496-1516 (1973)] to account for probabilistic data on pitch errors [A. J. M. Houtsma and J. L. Goldstein, J. Acoust. Soc. Am. 51, 520 (1972)] measured with periodic stimuli comprising two successive harmonics. This paper presents new predictions by the theory that were calculated, with computer simulation where needed, for known probabilistic pitch data from stimuli comprising three to six successive harmonics. Predicted pitch errors increase with increasing errors in estimating the frequencies of stimulus harmonics and decrease as more harmonics are added to the stimulus. Optimum processor theory fully accounts for the multicomponent pitch data on the basis of similar errors in estimating component stimulus frequencies as reported earlier, thus providing further evidence for the optimum probabilistic basis of aural signal processing in pitch of complex tones.

Auditory Cortex↗
PubMed2006

Quantification of the effects of salt stress and physiological state on thermotolerance of Bacillus cereus ATCC 10987 and ATCC 14579.

The food-borne pathogen Bacillus cereus can acquire enhanced thermal resistance through multiple mechanisms. Two Bacillus cereus strains, ATCC 10987 and ATCC 14579, were used to quantify the effects of salt stress and physiological state on thermotolerance. Cultures were exposed to increasing concentrations of sodium chloride for 30 min, after which their thermotolerance was assessed at 50 degrees C. Linear and nonlinear microbial survival models, which cover a wide range of known inactivation curvatures for vegetative cells, were fitted to the inactivation data and evaluated. Based on statistical indices and model characteristics, biphasic models with a shoulder were selected and used for quantification. Each model parameter reflected a survival characteristic, and both models were flexible, allowing a reduction of parameters when certain phenomena were not present. Both strains showed enhanced thermotolerance after preexposure to (non)lethal salt stress conditions in the exponential phase. The maximum adaptive stress response due to salt preexposure demonstrated for exponential-phase cells was comparable to the effect of physiological state on thermotolerance in both strains. However, the adaptive salt stress response was less pronounced for transition- and stationary-phase cells. The distinct tailing of strain ATCC 10987 was attributed to the presence of a subpopulation of spores. The existence of a stable heat-resistant subpopulation of vegetative cells could not be demonstrated for either of the strains. Quantification of the adaptive stress response might be instrumental in understanding adaptation mechanisms and will allow the food industry to develop more accurate and reliable stress-integrated predictive modeling to optimize minimal processing conditions.

Bacillus cereus↗
PubMed1994

Localized expression of mRNA for phagocyte-specific chemotactic cytokines in human periodontal infections.

In bacterial infections, mononuclear and polymorphonuclear phagocytes are key components of host defenses. Recent investigations have indicated that chemokines are able to recruit and activate phagocytes. In particular, interleukin-8 (IL-8) attracts polymorphonuclear leukocytes (PMNs), while monocyte chemoattractant protein-1 (MCP-1) is selective for cells of the monocyte/macrophage lineage. In this investigation, we analyzed the in situ expression of IL-8 and MCP-1 mRNAs in human periodontal infections. Specific mRNA was detected by in situ hybridization using 35S-labeled riboprobes in frozen tissue sections. Phagocytes (PMNs and macrophages) were specifically detected as elastase-positive or CD68+ cells by a three-stage immunoperoxidase technique. Results indicated that expression of phagocyte-specific cytokines was confined to selected tissue locations and, in general, paralleled phagocyte infiltration. In particular, IL-8 expression was maximal in the junctional epithelium adjacent to the infecting microorganisms; PMN infiltration was more prominent in the same area. MCP-1 was expressed in the chronic inflammatory infiltrate and along the basal layer of the oral epithelium. Cells of the monocyte/macrophage lineage were demonstrated to be present in the same areas. The observed expression pattern may be the most economic way to establish a cell-type-selective chemotactic gradient within the tissue that is able to effectively direct polymorphonuclear phagocyte migration toward the infecting microorganisms and modulate mononuclear phagocyte infiltration in the surrounding tissues. This process may optimize host defenses and contribute to containing leukocyte infiltration to the infected and inflamed area, thus limiting tissue damage.

Antigens, CD↗
PubMed1999

Construction and characterization of Moraxella catarrhalis mutants defective in expression of transferrin receptors.

We have previously reported the construction of an isogenic mutant defective in expression of OmpB1, the TbpB homologue, in Moraxella catarrhalis 7169. In this report, we have extended these studies by constructing and characterizing two new isogenic mutants in this clinical isolate. One mutant is defective in expression of TbpA, and the other mutant is defective in expression of both TbpA and TbpB. These isogenic mutants were confirmed by using PCR analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and sequencing. In vitro growth studies, comparing all three mutants, demonstrated that the tbpA mutant and the tbpAB mutant were severely limited in their ability to grow with human holotransferrin as the sole source of iron. In contrast, the ompB1 (tbpB) mutant was capable of utilizing iron from human transferrin, although not to the extent of the parental strain. While affinity chromatography with human holotransferrin showed that each Tbp was capable of binding independently to transferrin, solid-phase transferrin binding studies using whole cells demonstrated that the tbpA mutant exhibited binding characteristics similar to those seen with the wild-type bacteria. However, the ompB1 (tbpB) mutant exhibited a diminished capacity for binding transferrin, and no binding was detected with the double mutant. These data suggest that the M. catarrhalis TbpA is necessary for the acquisition of iron from transferrin. In contrast, TbpB is not essential but may serve as a facilitory protein that functions to optimize this process. Together these mutants are essential to provide a more thorough understanding of iron acquisition mechanisms utilized by M. catarrhalis.

Bacterial Outer Membrane Proteins↗
PubMed2001

Efficacy of two alternate vaccines based on Plasmodium falciparum merozoite surface protein 1 in an Aotus challenge trial.

In an attempt to produce a more defined, clinical-grade version of a vaccine based on Plasmodium falciparum merozoite surface protein 1 (MSP1), we evaluated the efficacy of two recombinant forms of MSP1 in an Aotus nancymai challenge model system. One recombinant vaccine, bvMSP1(42), based on the 42-kDa C-terminal portion of MSP1, was expressed as a secreted protein in baculovirus-infected insect cells. A highly pure baculovirus product could be reproducibly expressed and purified at yields in excess of 8 mg of pure protein per liter of culture. This protein, when tested for efficacy in the Aotus challenge model, gave significant protection, with only one of seven monkeys requiring treatment for uncontrolled parasitemia after challenge with P. falciparum. The second recombinant protein, P30P2MSP1(19), has been used in previous studies and is based on the smaller, C-terminal 19-kDa portion of MSP1 expressed in Saccharomyces cerevisiae. Substantial changes were made in its production process to optimize expression. The optimum form of this vaccine antigen (as judged by in vitro and in vivo indicators) was then evaluated, along with bvMSP1(42), for efficacy in the A. nancymai system. The new formulation of P30P3MSP1(19) performed significantly worse than bvMSP1(42) and appeared to be less efficacious than we have found in the past, with four of seven monkeys in the vaccinated group requiring treatment for uncontrolled parasitemia. With both antigens, protection was seen only when high antibody levels were obtained by formulation of the vaccines in Freund's adjuvant. Vaccine formulation in an alternate adjuvant, MF59, resulted in significantly lower antibody titers and no protection.

Animals↗
PubMed1998

Reverse gyrase from the hyperthermophilic bacterium Thermotoga maritima: properties and gene structure.

The hyperthermophilic bacterium Thermotoga maritima MSB8 possesses a reverse gyrase whose enzymatic properties are very similar to those of archaeal reverse gyrases. It catalyzes the positive supercoiling of the DNA in an Mg2+- and ATP-dependent process. Its optimal temperature of activity is around 90 degrees C, and it is highly thermostable. We have cloned and DNA sequenced the corresponding gene (T. maritima topR). This is the first report describing the analysis of a gene encoding a reverse gyrase in bacteria. The T. maritima topR gene codes for a protein of 1,104 amino acids with a deduced molecular weight of 128,259, a value in agreement with that estimated from the denaturing gel electrophoresis of the purified enzyme. Like its archaeal homologs, the T. maritima reverse gyrase exhibits helicase and topoisomerase domains, and its sequence matches very well the consensus sequence for six reverse gyrases now available. Phylogenetic analysis shows that all reverse gyrases, including the T. maritima enzyme, form a very homogeneous group, distinct from the type I 5' topoisomerases of the TopA subfamily, for which we have previously isolated a representative gene in T. maritima (topA). The coexistence of these two distinct genes, coding for a reverse gyrase and an omega-like topoisomerase, respectively, together with the recent description of a gyrase in T. maritima (O. Guipaud, E. Marguet, K. M. Noll, C. Bouthier de la Tour, and P. Forterre, Proc. Natl. Acad. Sci. USA 94:10606-10611, 1977) addresses the question of the control of the supercoiling in this organism.

Amino Acid Sequence↗
PubMed2002

Adaptation of sucrose metabolism in the Escherichia coli wild-type strain EC3132.

Although Escherichia coli strain EC3132 possesses a chromosomally encoded sucrose metabolic pathway, its growth on low sucrose concentrations (5 mM) is unusually slow, with a doubling time of 20 h. In this report we describe the subcloning and further characterization of the corresponding csc genes and adjacent genes. The csc regulon comprises three genes for a sucrose permease, a fructokinase, and a sucrose hydrolase (genes cscB, cscK, and cscA, respectively). The genes are arranged in two operons and are negatively controlled at the transcriptional level by the repressor CscR. Furthermore, csc gene expression was found to be cyclic AMP-CrpA dependent. A comparison of the genomic sequences of the E. coli strains EC3132, K-12, and O157:H7 in addition to Salmonella enterica serovar Typhimurium LT2 revealed that the csc genes are located in a hot spot region for chromosomal rearrangements in enteric bacteria. The comparison further indicated that the csc genes might have been transferred relatively recently to the E. coli wild-type EC3132 at around the time when the different strains of the enteric bacteria diverged. We found evidence that a mobile genetic element, which used the gene argW for site-specific integration into the chromosome, was probably involved in this horizontal gene transfer and that the csc genes are still in the process of optimal adaptation to the new host. Selection for such adaptational mutants growing faster on low sucrose concentrations gave three different classes of mutants. One class comprised cscR(Con) mutations that expressed all csc genes constitutively. The second class constituted a cscKo operator mutation, which became inducible for csc gene expression at low sucrose concentrations. The third class was found to be a mutation in the sucrose permease that caused an increase in transport activity.

Adaptation, Physiological↗
PubMed1998

PCR method for detection of adenovirus in urine of healthy and human immunodeficiency virus-infected individuals.

Adenoviruses (AdV) cause diseases that range from localized, self-limited illnesses to fatal infections in immunocompromised patients. Culture is assumed to be sensitive but requires viable virus and up to 3 weeks for detection, and it can be inhibited by bacterial contamination. A new PCR method amplifying a region of the hexon gene was developed in order to detect AdV in urine more rapidly and with greater sensitivity than obtainable by culture technology. All 18 serotypes tested were detected. Quantitatively, with optimized urine processing, AdV PCR detected 0.2 PFU/ml (serotype 11) and 10 DNA copies/ml (serotype 2). Serially collected urine samples from human immunodeficiency virus (HIV)-infected patients with concurrent cytomegalovirus retinitis were divided into three groups: AdV culture-positive samples, AdV culture-negative or bacterially contaminated samples from patients with a history of AdV culture-positive urines, and AdV culture-negative samples from patients without a history of AdV culture positivity. Urine samples from healthy adults were also tested by culture and PCR to screen for asymptomatic shedding. Amplification was assessed with and without prior DNA purification. AdV was detected by PCR in 90% of culture-positive urines (100% of unclotted samples, e.g., those culture positive after storage for PCR testing), 71% of culture-negative or bacterially contaminated urines from AdV-infected patients, and 28% from AdV culture-negative patients. Healthy volunteers were culture negative for AdV, and 96% were PCR negative. The new AdV PCR method is rapid and sensitive and can detect viral DNA in samples for which culturing is problematic. The role of AdV replication during HIV infection merits further investigation with sensitive tools such as PCR.

AIDS-Related Opportunistic Infections↗
PubMed2002

Optimal DNA isolation method for detection of bacteria in clinical specimens by broad-range PCR.

Broad-range amplification of bacterial DNA from clinical specimens has proved useful for the diagnosis of various bacterial infections, especially during antimicrobial treatment of the patient. Optimal sample processing protocols for diagnostic broad-range bacterial PCR should release DNA from an array of target organisms with equal efficiencies and wash out inhibitory factors from various sample types without introducing bacterial DNA contamination to the amplification reaction. In the present study, two physical cell wall disintegration methods, bead beating and sonication, for enhanced detection of organisms with difficult-to-lyse cell walls were studied. The analytical sensitivities of several commercially available DNA purification kits, which were used with and without additional cell disintegration steps, were compared by using dilution series of model bacteria. Selected purification methods were used to process routine clinical specimens in parallel with the standard phenol-ether DNA extraction, and the results obtained by bacterial PCR and sequencing with the two template preparations were compared. The method with the DNA isolation kit with the lowest detection limits from the bacterial suspensions (Masterpure) did not prove to be superior to the standard method when the two methods were applied to 69 clinical specimens. For another set of 68 clinical specimens, DNA purified with a glass fiber filter column (High Pure) with an additional sonication step yielded results well in accord with those obtained by the standard method. Furthermore, bacterial DNA was detected in four samples that remained PCR negative by the standard method, and three of these contained DNA from gram-positive pathogens. Three samples were positive by the standard method only, indicating the limitations of applying any single method to all samples.

Bacteria↗
PubMed2003

Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn's disease.

Mycobacterium avium subsp. paratuberculosis is a robust and phenotypically versatile pathogen which causes chronic inflammation of the intestine in many species, including primates. M. avium subsp. paratuberculosis infection is widespread in domestic livestock and is present in retail pasteurized cows' milk in the United Kingdom and, potentially, elsewhere. Water supplies are also at risk. The involvement of M. avium subsp. paratuberculosis in Crohn's disease (CD) in humans has been uncertain because of the substantial difficulties in detecting this pathogen. In its Ziehl-Neelsen staining-negative form, M. avium subsp. paratuberculosis is highly resistant to chemical and enzymatic lysis. The present study describes the development of optimized sample processing and DNA extraction procedures with fresh human intestinal mucosal biopsy specimens which ensure access to M. avium subsp. paratuberculosis DNA and maximize detection of these low-abundance pathogens. Also described are two nested PCR methodologies targeted at IS900, designated IS900[L/AV] and IS900[TJ1-4], which are uniquely specific for IS900. Detection of M. avium subsp. paratuberculosis in mucosal biopsy specimens was also evaluated by using mycobacterial growth indicator tube (MGIT) cultures (Becton Dickinson). IS900[L/AV] PCR detected M. avium subsp. paratuberculosis in 34 of 37 (92%) patients with CD and in 9 of 34 (26%) controls without CD (noninflammatory bowel disease [nIBD] controls) (P = 0.0002; odds ratio = 3.47). M. avium subsp. paratuberculosis was detected by IS900[L/AV] PCR in MGIT cultures after 14 to 88 weeks of incubation in 14 of 33 (42%) CD patients and 3 of 33 (9%) nIBD controls (P = 0.0019; odds ratio = 4.66). Nine of 15 (60%) MGIT cultures of specimens from CD patients incubated for more than 38 weeks were positive for M. avium subsp. paratuberculosis. In each case the identity of IS900 from M. avium subsp. paratuberculosis was verified by amplicon sequencing. The rate of detection of M. avium subsp. paratuberculosis in individuals with CD is highly significant and implicates this chronic enteric pathogen in disease causation.

Adolescent↗
PubMed2002

Value of a cognitive simulation in medicine: towards optimizing decision making performance of healthcare personnel.

Medical errors can be reduced or avoided by training in both factual knowledge and in optimal information processing. The latter is of special importance when task settings are complex, when information about a patient's condition is ambiguous and uncertain, and when rapid changes can occur. Simulations can contribute to effective training in these areas of functioning without putting patients at risk. The strategic management simulation (SMS) has been used worldwide with many high level professionals. Its application to assessing and training medical decision makers is discussed.

Cognition↗