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PubMed1991

Influence of dietary protein on renal function in dogs.

Two previously published studies in dogs with reduced renal function are reviewed. In the first study, renal function and biochemical responses to dietary changes were studied in four dogs with stable chronic renal failure. The objective was to determine if dogs with moderate stable failure adjust to diets with varied protein and electrolyte content. These dogs were found to have the capacity to adapt to a wide range of dietary protein and electrolyte intake. The only exception was found in dogs fed a reduced-protein diet, which failed to appropriately adjust renal tubular excretion of sodium and phosphate. The only advantage of reduced dietary protein in this study was a reduction in blood urea nitrogen (BUN). Disadvantages of reduced-protein diets were reduced glomerular filtration rate (GFR) and renal plasma flow. In the second study, the hypothesis that large amounts of dietary protein sustain renal hyperfunction and produce progressive glomerulosclerosis in dogs as previously reported in rats was tested. Results failed to find a pattern of deterioration of renal function over 4 y. Light microscopic changes and electron microscopy also failed to find glomerular injury similar to that reported in rodents. These results do not support the hypothesis that feeding a high protein diet had a significant adverse effect on renal function or morphology.

Amino Acids↗
PubMed1997

A universal procedure for primer labelling of amplicons.

Detection and visualisation of nucleic acids is integral to genome analyses. Exponential amplification procedures have provided the means for the manipulation of nucleic acid sequences, which were otherwise inaccessible. We describe the development and application of a universal method for the labelling of any PCR product using a single end-labelled primer. Amplification was performed in a single reaction with the resulting amplicon labelled to a high specific activity. The method was adapted to a wide range of PCRs and significantly reduced the expense of such analyses.

DNA Primers↗
PubMed1988

Coordinated amino acid changes in homologous protein families.

In the tobamovirus coat protein family, amino acid residues at some spatially close positions are found to be substituted in a coordinated manner [Altschuh et al. (1987) J. Mol. Biol., 193, 693]. Therefore, these positions show an identical pattern of amino acid substitutions when amino acid sequences of these homologous proteins are aligned. Based on this principle, coordinated substitutions have been searched for in three additional protein families: serine proteases, cysteine proteases and the haemoglobins. Coordinated changes have been found in all three protein families mostly within structurally constrained regions. This method works with a varying degree of success depending on the function of the proteins, the range of sequence similarities and the number of sequences considered. By relaxing the criteria for residue selection, the method was adapted to cover a broader range of protein families and to study regions of the proteins having weaker structural constraints. The information derived by these methods provides a general guide for engineering of a large variety of proteins to analyse structure-function relationships.

Amino Acid Sequence↗
PubMedDate not supplied

Applying an evaluation framework for health information system design, development, and implementation.

BACKGROUND: Dramatic advances in health information technologies necessitate a comprehensive evaluation framework covering all phases of development, from conception to routine operational use. OBJECTIVES: The purpose of this article was to illustrate the application of an informatics evaluation framework that provides a heuristic for matching the stage of system design and the level of evaluation. METHODS: An evaluation framework is illustrated in the context of five studies in different stages of system design. RESULTS: The studies discussed in this article represent the various stages of the framework. In addition, they are examples of how evaluation research studies not only contribute to the assessment of system design but also constitute distinct contributions to knowledge. DISCUSSION: The ability to engineer advanced information systems has exceeded the understanding of how to deploy them effectively in complex settings and to adapt them to a range of user populations. A systematic, continuous evaluation increases the likelihood that the conditions for success will be understood, including how to tailor a system, how to maintain the target population's use of the system, and how to innovate continually to enhance the functionality of the system and the users' experience. Without sound evaluation methodologies throughout the stages of system development, information systems have limited potential to influence healthcare processes positively.

Humans↗
PubMed1996

Influence of pharmacokinetic model on vancomycin peak concentration targets.

The aim of this study was to adapt the vancomycin therapeutic range to the kinetic models usually employed in clinical settings (one- and two-compartment models). Estimates of vancomycin pharmacokinetic parameters were obtained for both models in 22 hematologically malignant patients on vancomycin treatment using two serum concentrations and a bayesian algorithm. From these individually estimated pharmacokinetic parameters, an estimation of the maximum (Cssmax), 2 h postinfusion (Css2), and minimum (Cssmin) steady-state vancomycin serum concentrations for the one- and two-compartment models was made for a fixed 30 mg/kg/day dose. The linear regression equations between the predicted Css2 and Cssmin for the one- and two-compartment models do not differ significantly from the identity line, whereas the corresponding equation for Cssmax points to a 61% underestimation of Cssmax when the one-compartment model is used. From this latter regression equation, it is possible to define 20 mg/L (range of 18-21 mg/L) as a target Cssmax vancomycin serum concentration when a one-compartment model is used to monitor vancomycin therapy. Another practical approach would be to define the target concentration by a desired range at 2 h, which corresponds to a Cssmax value of 30-40 mg/L.

Anti-Bacterial Agents↗
PubMed2006

Unification of the revised trauma score.

BACKGROUND: The Revised Trauma Score (RTS) calculated with Major Outcome Trauma Study weights (MTOS-RTS) is currently the standard physiologic severity score in trauma research and quality control. It is often confused with the Triage-RTS (T-RTS), a version that is easier to calculate but only intended for clinical triage. OBJECTIVES: To compare the accuracy of the MTOS-RTS to the RTS calculated with weights derived from the study population (POP-RTS) and the T-RTS, for predicting mortality in a trauma population. METHODS: The study population consists of 22,388 patients, drawn from the trauma registries of three Level I trauma centers. The predictive accuracy of the MTOS-RTS, POP-RTS, and the T-RTS were compared using measures of discrimination and model fit from logistic regression models. RESULTS: The MTOS-RTS, the POP-RTS, and the T-RTS had the same discrimination (Area under the Receiver Operating Curve [AUC] = 0.841). The POP-RTS and the T-RTS had a slightly better model fit than the MTOS-RTS (AIC = 8010, 8010, and 8067, respectively). The T-RTS had equal discrimination and equal or better model fit than the MTOS-RTS in the whole sample, in each of the three trauma centers and in the population of patients with severe head trauma. The T-RTS was also equivalent to the POP-RTS in all of these population sub-groups. CONCLUSIONS: The T-RTS could replace the MTOS-RTS as the standard physiologic severity score for trauma outcome prediction. The advantages of using the T-RTS over the MTOS-RTS are ease of calculation, the need for only one measure for triage and mortality prediction purposes and universal adaptation to a broad range of trauma populations.

Aged↗
PubMed1999

Flow cytometry and other techniques show that Staphylococcus aureus undergoes significant physiological changes in the early stages of surface-attached culture.

The techniques of flow cytometry, scanning and transmission electron microscopy, and confocal scanning laser microscopy were used to study the physiology of Staphylococcus aureus in the early stages of surface-attached culture, and to make direct comparisons with planktonic bacteria grown under the same conditions. Attached bacteria growing in nutrient-rich batch culture were found to go through the same growth phases as equivalent planktonic cultures, but with an exponential growth rate of about half that of the planktonic bacteria. Viability of attached bacteria was very high (around 100%) throughout the first 24 h of growth. The size and protein content of attached bacteria varied with growth phase, and both measurements were always smaller than in planktonic bacteria at equivalent growth phases. Respiratory activity per bacterium, as measured by flow cytofluorimetry, and corrected for cell volume, peaked very early in attached cultures (before the first cell division) and declined from then on, whereas in planktonic bacteria it peaked in late exponential phase. Attached and planktonic bacteria showed thicker cell walls in stationary phase than in exponential phase. Membrane potentials of planktonic and attached bacteria were similar in stationary phase, but were much lower in exponential-phase attached cells than in the equivalent planktonic cells. It is apparent that a range of significant physiological adaptations occur during the early phases of attached growth.

Bacterial Adhesion↗
PubMed1997

Heat generation and dissipation in plants: can the alternative oxidative phosphorylation pathway serve a thermoregulatory role in plant tissues other than specialized organs?

A number of hypothetical physiological roles have been proposed for the cyanide-insensitive alternative pathway in plants (Palmer, 1976; Laties, 1982; Meeuse, 1984; Purvis and Shewfelt, 1994; Wagner and Krab, 1995). The calorimetric observations of Raskin and co-workers (Ordentlich et al., 1991; Nevo et al., 1992; Moynihan et al., 1995) are significant contributions showing an interesting metabolic, chilling-induced response of the alternative pathway activity and differences in the low-temperature response among species adapted to different climates. Since different oxidative pathways do not have large differences in enthalpy, and observed heat rate increases are insufficient to cause significant temperature increases of physiological importance in nonthermogenic plants, other explanations must be developed for the relationship between the partitioning of electron flow and physiological conditions such as low temperature. The induction and engagement of the alternative respiratory pathway is involved in metabolic stasis, maintaining proper balance between carbon flow, ATP-ADP ratio, and electron flow during fluctuating or extreme temperature conditions. The alternative oxidase is engaged when ATP requirements are adequately met, as discussed by Palmer (1976), Meeuse (1983), Lambers (1985), and Wagner and Krab (1995). The expression and kinetic activity of the alternative oxidase are regulated by concentrations of key metabolites (Day and Wiskich, 1995; Siedow and Umbach, 1995; Wagner and Krab, 1995; Day et al., 1996). Dynamic partitioning of electron flow between Cyt oxidase and the alternative oxidase depends on the kinetic behavior of the two oxidases and the substrate dehydrogenases (Day and Wiskich, 1995; Siedow and Umbach, 1995; Wagner and Krab, 1995; Day et al., 1996). Furthermore, Moynihan et al. (1995) found that Episces cupreata Hook, adapted to the tropics, has very little alternative oxidase activity compared with wheat (Nevo et al., 1992), adapted to a large range of temperature climates. This results is consistent with the general relation between the apparent alternative oxidase activity and the climate of origin of the species.

Hot Temperature↗
PubMed2000

Kinetics of photoacclimation in response to a shift to high light of the red alga Rhodella violacea adapted to low irradiance.

The unicellular rhodophyte Rhodella violacea can adapt to a wide range of irradiances. To create a light stress, cells acclimated to low light were transferred to higher irradiance and the kinetics of various changes produced by the light shift were analyzed. The proton gradient generated by excess light led to a non-photochemical quenching of the chlorophyll fluorescence and some photoinhibition of photosystem II centers was also produced by the light stress. After the shift to higher irradiance, the mRNA levels of three chloroplast genes that encode phycoerythrin and phycocyanin apoproteins and heme oxygenase (the first enzyme specific to the bilin synthesis) were negatively regulated. A change in the amount of thylakoids and in the total pigment content of the cells occurred during light acclimation after a light stress. The change in the size of the phycobilisome was limited to dissapearance of the terminal phycoerythrin hexamers in some of the rods. The ability of R. violacea to photoacclimate depends both on large changes in thylakoid number and pigment content and on smaller changes in the antenna size of photosystem II.

Acclimatization↗
PubMed1976

Adaptation of Nitrogen Fixation by Intact Soybean Nodules to Altered Rhizosphere pO(2).

The N(2)-fixing legume nodule requires O(2) for ATP production; however, the O(2) sensitivity of nitrogenase dictates a requirement for a low pO(2) inside the nodule. The effects of long term exposures to various pO(2)s on N(2)[C(2)H(2)] fixation were evaluated with intact soybean (Glycine max [L.] Merr., var. Wye) plants. Continuous exposure of their rhizosphere to a pO(2) of 0.06 atmospheres initially reduced nitrogenase activity by 37 to 45% with restoration of original activity in 4 to 24 hours and with no further change in tests up to 95 hours; continuous exposure to 0.02 atmosphere of O(2) initially reduced nitrogenase activity 72%, with only partial recovery by 95 hours. Similar exposures to a pO(2) of 0.32 atmospheres had little effect on N(2)[C(2)H(2)] fixation; a pO(2) of 0.89 atmospheres initially reduced nitrogenase activity by 98% with restoration to only 14 to 24% of that of the ambient O(2) controls by 95 hours. Re-exposure to ambient pO(2) of plants adapted to nonambient pO(2)s reduced N(2)[C(2)H(2)] fixation to similar magnitudes as the reductions which occurred upon initial exposure to variant pO(2) conditions, and a time period was required to readapt to ambient O(2). It is concluded that the N(2)[C(2)H(2)]-fixing system of intact soybean plants is able to adapt to a wide range of external pO(2)s as probably occur in soil. We postulate that this occurs through an undefined mechanism which enables the nodule to maintain an internal pO(2) optimal for nitrogenase activity.

Journal Article↗
PubMed2005

A large-scale screen for artificial selection in maize identifies candidate agronomic loci for domestication and crop improvement.

Maize (Zea mays subsp mays) was domesticated from teosinte (Z. mays subsp parviglumis) through a single domestication event in southern Mexico between 6000 and 9000 years ago. This domestication event resulted in the original maize landrace varieties, which were spread throughout the Americas by Native Americans and adapted to a wide range of environmental conditions. Starting with landraces, 20th century plant breeders selected inbred lines of maize for use in hybrid maize production. Both domestication and crop improvement involved selection of specific alleles at genes controlling key morphological and agronomic traits, resulting in reduced genetic diversity relative to unselected genes. Here, we sequenced 1095 maize genes from a sample of 14 inbred lines and chose 35 genes with zero sequence diversity as potential targets of selection. These 35 genes were then sequenced in a sample of diverse maize landraces and teosintes and tested for selection. Using two statistical tests, we identified eight candidate genes. Extended gene sequencing of these eight candidate loci confirmed that six were selected throughout the gene, and the remaining two exhibited evidence of selection in the 3' portion of each gene. The selected genes have functions consistent with agronomic selection for nutritional quality, maturity, and productivity. Our large-scale screen for artificial selection allows identification of genes of potential agronomic importance even when gene function and the phenotype of interest are unknown.

Agriculture↗
PubMed2005

An adaptive detector of genioglossus EMG reflex using Berkner transform for time latency measurement in OSA pathophysiological studies.

To investigate obstructive sleep apnea syndrome mechanisms, we developed a device to measure the surface electromyogram (EMG) time latency reflex of the genioglossus muscle stimulated by time and amplitude calibrated negative pharyngeal pressure drops. The reflex signals were found to be disturbed by transient signals that generate false alarms. Thus, to reduce false alarm occurrences we designed an adaptive multiscale method. Continuous wavelet transform (CWT) is widely used in biomedical signal event detection processes. The Berkner transform is an approximation of a CWT that is based on a hierarchical scheme similar to discrete wavelet transform. We used the Berkner transform to build a multiscale detector because it offers the possibility of maxima coefficients linkage that leads to good accuracy in reflex onset localization. As a contribution to this novel approach we used a reconstruction formula to develop an adaptive method for scale range determination in our surface EMG reflex detector. Finally, we characterized our detector in terms of accuracy and robustness, first on synthesized signals and second, on signals acquired on apneic patients and healthy subjects. Preliminary results showed a significant difference (p < 0.01) between the two populations regarding the genioglossus muscle mean latency time. These physiological findings may partly explain why the upper airway protective reflex occurring when a negative pressure is applied to the upper airway is ineffective in OSA patients, leading to pharyngeal collapse.

Algorithms↗
PubMed2003

Developing wearable bio-feedback systems: a general-purpose platform.

Microprocessors, even those in PocketPCs, have adequate power for many real-time biofeedback applications for disabled people. This power allows design of portable or wearable devices that are smaller and lighter, and that have longer battery life compared to notebook-based systems. In this paper, we discuss a general-purpose hardware/software solution based on industrial or consumer devices and a C++ framework. Its flexibility and modularity make it adaptable to a wide range of situations. Moreover, its design minimizes system requirements and programming effort, thus allowing efficient systems to be built quickly and easily. Our design has been used to build two brain computer interface systems that were easily ported from the Win32 platform.

Biofeedback, Psychology↗
PubMed2004

Immune escape and exploitation strategies of cytomegaloviruses: impact on and imitation of the major histocompatibility system.

Cytomegalovirus (CMV) has yielded many insights into immune escape mechanisms. Both human and mouse CMV encode a diverse array of gene products, many of which appear to modulate the immune response in the host. Some deflect the host response to infection and contribute to lifelong viral persistence while others exploit immune cells that respond to infection. Here, the viral functions that modulate and mimic host major histocompatibility complex (MHC) function will be reviewed. Viral gene products related to both classical and non-classical components of the MHC system assure the virus will persist in immunocompetent individuals. Examples of host countermeasures that neutralize viral immunomodulatory functions have emerged in the characterization of viral functions that contribute to this stand-off in CMVs that infect humans, other primates and rodents. CMV-induced disease occurs when the immune system is not yet developed, such as in the developing fetus, or when it is compromised, such as in allograft transplant recipients, suggesting that the balance between virus escape and host control is central to pathogenesis. Although evidence supports the dominant role of immune escape in CMV pathogenesis and persistence, MHC-related immunomodulatory functions have been ascribed only subtle impact on pathogenesis and the immune response during natural infection. Viral gene products that interface with the MHC system may impact natural killer cell function, antigen presentation, and T lymphocyte immune surveillance. Many also interact with other cells, particularly those in the myeloid lineage, with consequences that have not been explored. Overall, the virus-encoded modulatory functions that have been acquired by CMV likely ensure survival and adaptation to the wide range of mammalian host species in which they are found.

Adjuvants, Immunologic↗
PubMed2006

Changes in vascular flow after transdermal oestradiol therapy for prostate cancer: a mechanism for cardiovascular toxicity and benefit?

OBJECTIVE: To report the influence of transdermal oestradiol therapy on the vascular dynamics of men with advanced prostate cancer. PATIENTS AND METHODS: Twenty patients with newly diagnosed locally advanced or metastatic prostate cancer (10 each) were treated using transdermal oestradiol patches. The vascular flow was assessed 6-monthly before and during a year of therapy using arterial and venous Doppler and duplex ultrasonography, arterial and venous photoplethysmography and opto-electronic plethysmography. RESULTS: Arterial flow, as measured by the mean and peak systolic velocities and photoplethysmography, significantly increased over time. Arterial compliance initially decreased but had normalized after 12 months. The venous variables were unaffected. As a result, the total limb blood flow and the capillary filtration rate were significantly increased. CONCLUSION: Transdermal oestradiol therapy causes an increase in arterial but not venous flow, and an initial decrease in arterial compliance, which adapts to the physiological range with time. It is possible that these changes may account for the increase in cardiovascular toxicity seen in the early phase of oestrogen therapy, and the cardioprotective effect that accrues thereafter.

Administration, Cutaneous↗
PubMed2006

Function, ontogeny and canalization of shape variance in the primate scapula.

Primates have shoulders adapted to a wide range of locomotor functions from terrestrial pronograde quadrupedalism to highly arboreal suspensory behaviours. The shape of the scapula tightly follows these functional differences. Previous analyses of primate postcrania, including the scapula, indicate that quadrupedal monkeys are less variable than non-quadrupeds. It was previously suggested that this difference was due to a relationship between the strength of stabilizing selection and the functional demands of the upper limb. Here it is shown that intraspecific scapular shape variance is highly correlated with the degree of committed quadrupedalism. Primates that engage in frequent suspensory behaviours (e.g. apes and ateline monkeys) average twice the amount of shape variance as quadrupeds (e.g. Old World monkeys and Saimiri). Because this difference in intraspecific shape variance is apparent in infants and does not increase or decrease appreciably over ontogeny, it is not likely that differences in postnatal growth, neuromuscular control or environmental factors such as habitat structure/composition are the primary contributors to differences in adult shape variance. Instead variance in embryonic factors that affect the shape/size of the scapula or epigenetic factors associated with muscle attachments are more likely candidates. In particular, the heterogeneous functional demands of the non-quadrupedal shoulder probably reduce the stringency of stabilizing selection, resulting in the persistence into adulthood of increased amounts of embryonically generated scapular shape variance.

Animals↗
PubMed1992

Behavioral treatment of adipsia in a child with hypothalamic injury.

Damage to the hypothalamic region is known to affect a wide range of homeostatic and adaptive functions, including water and food regulation, temperature control, hormone secretion and behavior. Deficient thirst is a serious consequence of hypothalamic injury, since water losses are not replaced by drinking. The effectiveness of behavioral procedures in increasing drinking is described for a child with diminished thirst secondary to hypothalamic injury.

Behavior Therapy↗
PubMedDate not supplied

Scanning electron microscopic examination of third metacarpal/third metatarsal bone failure surfaces in thoroughbred racehorses with condylar fracture.

OBJECTIVE: To examine the fracture failure surfaces from Thoroughbred horses that had sustained a catastrophic condylar fracture. SAMPLE POPULATION: Bone specimens from the failure surface were obtained from 12 Thoroughbred racehorses with catastrophic injury and 2 non-racing horses with accidental long bone fracture. METHODS: Bone specimens from the failure surface of each fracture were incubated with gold microspheres to label microcracks before examination at x50 to x60,000 using scanning electron microscopy. Microcracking at the failure surface was assessed using a visual analog scale. RESULTS: Branching arrays or clusters of microcracks were seen over a range of magnifications in adapted subchondral bone in the distal end of the MC3/MT3 bone from racing Thoroughbreds with a catastrophic displaced condylar fracture. In the palmar/plantar region, microcracking was associated with the formation of an array of macroscopic cracks in the condylar groove. A different pattern of microcracking was seen in specimens of bone from distal metaphyseal and diaphyseal MC3/MT3 failure surfaces from Thoroughbred racehorses with catastrophic fracture and non-racing horses with an accidental diaphyseal long bone fracture. Few microcracks were seen and typically did not form branching arrays. CONCLUSION: These data suggest that propagation of condylar fracture in Thoroughbred racehorses is initiated by the formation of nanoscale microcracks in adapted subchondral bone that form during exercise-induced bone adaptation. CLINICAL RELEVANCE: Accumulation and coalescence of branching microcracks into arrays or clusters appears to eventually lead to the development of macroscopic subchondral cracks in the condylar groove and initiation of a condylar fracture.

Animals↗