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PubMedDate not supplied

[Mechanism of action of cAMP-dependent protein kinase. II. Solvolysis by additional nucleophilic agents].

The reaction of the solvolysis of the phosphointermediate, formed in the course of the phosphotransferase reaction was studied using a number of non-specific nucleophilic agents. The methods of identification of the solvolysis products and determination of kinetic parameters were developed. The estimated dependence of the reaction of the reactivity of the nucleophilic agents versus their basicity allowed some conclusions about the transition state structure in the cases of enzyme's interaction with nucleophilic agents and protein substrate. The energy contribution of the specific interaction of the enzyme with histone H1 was evaluated.

Animals↗
PubMed1994

[Computerized digital thermometry in acrosyndromes. Personal experience].

A diminution of the cutaneous temperature of the fingers and the latter's delayed recovery are constant features in the symptomatological triad of Raynaud's disease (RD). Thermometry is a method which can provide an objective evaluation of this phenomenon. The authors aimed to verify the value of thermometry using a computerised digital thermometer to measure basal temperature, that during cooling to 10 C, and the response. A computerised system with an AVTR interface was utilized using different probes for the 10 fingers and measuring temperature minute by minute up to 25 degrees. A total of 51 subjects were examined: 19 were asymptomatic for acrolocalised pathologies and 32 were symptomatic. No close correlation was observed between clinical and instrumental data. In fact 31.5% of the asymptomatic subjects had a "non-normal" reaction to the test; on the other hand, in the group of female over-50-years-old with symptoms suggesting RD, 44.4% of cases revealed normal instrumental patterns. Therefore no discriminating parameters were identified which might have allowed the instrumental identification of subjects suffering from RD compared to healthy individuals: there was a good level of sensitivity but scarce specificity.

Adult↗
PubMed1995

Evaluation of the endocrine function of the heart in humans: proposal for an integrated approach for the assessment of production, secretion, distribution and degradation of atrial natriuretic factor and related peptides.

It has become established that heart has an endocrine function because it synthesizes and secretes a family of peptide hormones, called Atrial Natriuretic Peptide (ANP), with potent diuretic, natriuretic, vascular smooth muscle-relaxing activity and complex interactions with the hormonal and nervous systems. Because ANP has important volume-regulatory characteristics, it is postulated to play a central role in volume homoeostasis under normal conditions and in several pathophysiological states, such as congestive heart failure. ANP is able to counterbalance all the detrimental effects of activation of the neuro-hormonal system in patients with heart failure may lead to new therapeutical protocols that can prevent the progression from compensation to overt heart failure. An integrated approach for the assessment of the endocrine function of the heart is proposed, consisting of four different, but complementary, steps: 1) evaluation of gene expression of ANP in the myocardial cell; 2) determination of circulating and tissue levels of ANP; 3) in-vivo assessment of the main turnover parameters of the hormone; 4) studies on localization and identification of ANP receptors. These procedures have been employed in physiological, pharmacological and/or clinical studies. The development and the standardization of new methods for the assessment of endocrine function of the heart will not only increase our understanding of the physiological regulation of production, secretion, and function, and of the pathophysiological role of ANP and its related peptides, but also may pave the way for further progress concerning our knowledge of more general physiological and pathophysiological mechanisms of the cardiovascular system itself.

Amino Acid Sequence↗
PubMed1998

[Dispersion of ventricular recovery time following surgery for tetralogy of Fallot: correlation with negative prognostic factors].

Malignant ventricular arrhythmias have been reported in patients with repaired tetralogy of Fallot. The aim of this study was to examine ventricular repolarization time indexes, in terms of both absolute measures and dispersion across the myocardium, in young patients operated on for tetralogy of Fallot (32 patients; 19 males and 13 females, mean age 11.1 +/- 3.4 years); these electrocardiographic parameters have been shown to be effective in the identification of electrical myocardial instability and hence of risk for ventricular arrhythmias too. The electrocardiographic data of the study group were compared with those of 22 age-matched asymptomatic control subjects (14 males and 8 females, mean age 12 +/- 1.5 years). Furthermore it has also been investigated the possible influence on ventricular repolarization of known negative prognostic factors relative to the surgical approach, age at intervention, and presence of pulmonary obstruction and/or regurgitation. No patients in the study group revealed at the Holter recordings and/or at the exercise test severe ventricular arrhythmias. From the analysis of ventricular depolarization, expressed by QRS duration, emerged that it resulted significantly longer in total Fallot group (p < 0.0001), and in each subgroup (p < 0.05) compared to the control group. Particularly, patients operated through a right ventricular approach showed higher values of QRS interval (p < 0.05) than those operated through combined transatrial-transpulmonary approach. All patients operated on for tetralogy of Fallot showed, compared to control subjects, a non homogeneous prolongation of ventricular repolarization across the myocardium, as confirmed by the significant increase in the absolute indexes of ventricular repolarization, JTc (p < 0.001), QT (p < 0.0001) and QTc (p < 0.0001) with a concomitant prolongation of the indexes of dispersion of ventricular recovery time, QTc dispersion (p < 0.0001), JTc dispersion (p < 0.0001), "adjusted" QTc dispersion (p < 0.05) and T peak-T end interval (p < 0.0001). The non homogeneous ventricular repolarization across the myocardium, preceding the development of arrhythmic events, could be the effect of the right ventricular morphological and functional changes of tetralogy of Fallot predisposing to the development of ventricular reentry tachyarrhythmias.

Adolescent↗
PubMed1998

Alzheimer's disease. AMA Council on Scientific Affairs Reference Committee D.

OBJECTIVE: This report responds to Substitute Resolution 518, I-96, which asks that the AMA, in cooperation with appropriate medical specialty societies, study Alzheimer's disease (AD) and other dementias, with particular emphasis on their diagnosis and treatment, issues relating to patient and caregiver education, the financing of care of affected individuals, the identification of research needs, and consideration of issues pertaining to the quality of life of individuals with these conditions. METHODS: This report is based on a review of guidelines produced by the Agency for Health Care Policy and Research (AHCPR), the American Academy of Neurology (AAN), the Veterans Health Administration (VHA), and the American Psychiatric Association (APA), combined with review of the latest published literature on AD and related disorders and consultation with experts in the field. This analysis was used as a basis for policy formulation. RESULT: The guidelines reviewed were: (1) Recognition and Initial Assessment of Alzheimer's Disease and Related Disorders, published by the AHCPR; (2) Dementia Identification and Assessment, published by the VHA; (3) Practice Parameter: Diagnosis and Evaluation of Dementia. published by the AAN; and (4) Practice Guideline for the Treatment of Patients with Alzheimer's Disease and Other Dementias of Late Life, published by the APA. These documents are targeted for the following audiences: primary care physicians (VHA and AHCPR), neurologists (AAN), and psychiatrists (APA). Only the APA guide makes provision for continuity of care. The literature review revealed that ongoing research into AD focuses on three broad areas: etiology/risk factors, diagnosis and treatment. CONCLUSIONS: AD is a common and costly public health problem. With the increase in life expectancy in the United States, AD is expected to afflict approximately 14 million people within the next few decades. Irreversible dementia takes a heavy economic, social, physical, and psychological toll on patients and families. The financial costs to society are enormous. There is currently no cure for AD, only interventions that can temporarily ameliorate the profound cognitive losses and behavioral manifestations of the disorder. Community services for AD patients and families are fragmented and underutilized. As traditional gatekeepers for services, physicians can encourage more families to use supportive services. Several valuable guidelines exist related to the diagnosis and treatment of AD and related disorders.

Alzheimer Disease↗
PubMedDate not supplied

[Computerized digital thermometry in Raynaud's disease. Personal experience].

BACKGROUND: Computerized digital thermometry has been used for instrumental diagnosis of Raynaud's disease, that is characterized by diminution of the cutaneous temperature of the fingers and the late delayed recovery. Thermometry permits to measure basal temperature of the ten fingers, during cooling to 10 degrees C ("cold test") and the response, measuring temperature minute by minute up to 25 degrees. METHODS: In order to assess vasospastic ischemic disease a total of 66 subjects have been examined: 19 were asymptomatic for acrolocalised pathologies (control subjects) and 47 were symptomatic. RESULTS: No close correlation was observed between clinic and instrumental data. In fact 31.5% of the asymptomatic subjects had a "non-normal" reaction to the test; on the other hand, in the group of female over-50-years-old with symptoms suggesting Raynaud's disease, 38.5% of cases revealed "normal" instrumental patterns. Therefore no discriminating parameters were identified which might have allowed the instrumental identification of subjects suffering from Raynaud's disease compared to healthy individuals. CONCLUSIONS: In conclusion, computerised digital thermometry is a technique with a good level of sensitivity, while the specificity is scarce.

Adult↗
PubMed2006

Towards a synthesis of data-based and theory-based models of environmental systems.

A two-pronged approach to interpreting field data through the use of models is presented. This approach builds upon both data- and theory-based models and their associated methods of system identification. It seeks to overcome their respective limitations: that theory-based models are not unambiguously identifiable from the observations, while a well identified data-based model may not be capable of a satisfactory theoretical interpretation. The purpose of the approach is thereby to gain a deeper understanding of complex environmental systems. Recursive methods of time-series analysis are used to identify the data-based models and the modified recursive prediction error algorithm is employed for parameter estimation of the theory-based models. The results of these identification exercises for the two classes of models can be compared in terms of the macro-parameters of the studied system's time constant and steady-state gain. Two case studies are presented to illustrate the overall performance of the two-pronged approach. It is found that: (1) more is to be gained through the joint application of the two classes of models than the exclusive use of either; (2) to some extent, identifying the structure and estimating the parameters of one type of model can be improved by recourse to the corresponding results for the other; and (3) reconciliation of the results from identifying the two classes of model in the parameter space has significant advantages over the more familiar process of evaluating a model's performance in the terms of its (observed) state space features.

Aquaculture↗
PubMed2001

A new algorithm for linear and nonlinear ARMA model parameter estimation using affine geometry.

A linear and nonlinear autoregressive (AR) moving average (MA) (ARMA) identification algorithm is developed for modeling time series data. The new algorithm is based on the concepts of affine geometry in which the salient feature of the algorithm is to remove the linearly dependent ARMA vectors from the pool of candidate ARMA vectors. For noiseless time series data with a priori incorrect model-order selection, computer simulations show that accurate linear and nonlinear ARMA model parameters can be obtained with the new algorithm. Many algorithms, including the fast orthogonal search (FOS) algorithm, are not able to obtain correct parameter estimates in every case, even with noiseless time series data, because their model-order search criteria are suboptimal. For data contaminated with noise, computer simulations show that the new algorithm performs better than the FOS algorithm for MA processes, and similarly to the FOS algorithm for ARMA processes. However, the computational time to obtain the parameter estimates with the new algorithm is faster than with FOS. Application of the new algorithm to experimentally obtained renal blood flow and pressure data show that the new algorithm is reliable in obtaining physiologically understandable transfer function relations between blood pressure and flow signals.

Algorithms↗
PubMed2002

Modeling [18 F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection.

The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2;-methoxyphenyl)-1-[2;-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential were compared with indices generated by Logan-Patlak graphical analysis. The 5HT1A specificity for MPPF was evidenced. A Bmax of 2.9 pmol/mL and a Kd of 2.8 nmol/L were found in hippocampal regions, Kd and distribution volume in the free compartment were regionally stable, and the Logan binding potential was linearly correlated to Bmax. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols.

Adult↗
PubMedDate not supplied

Compact and accurate linear and nonlinear autoregressive moving average model parameter estimation using laguerre functions.

A linear and nonlinear autoregressive moving average (ARMA) identification algorithm is developed for modeling time series data. The algorithm uses Laguerre expansion of kernals (LEK) to estimate Volterra-Wiener kernals. However, instead of estimating linear and nonlinear system dynamics via moving average models, as is the case for the Volterra-Wiener analysis, we propose an ARMA model-based approach. The proposed algorithm is essentially the same as LEK, but this algorithm is extended to include past values of the output as well. Thus, all of the advantages associated with using the Laguerre function remain with our algorithm; but, by extending the algorithm to the linear and nonlinear ARMA model, a significant reduction in the number of Laguerre functions can be made, compared with the Volterra-Wiener approach. This translates into a more compact system representation and makes the physiological interpretation of higher order kernels easier. Furthermore, simulation results show better performance of the proposed approach in estimating the system dynamics than LEK in certain cases, and it remains effective in the presence of significant additive measurement noise.

Algorithms↗
PubMed2005

Improved parameter estimation for systems with an experimentally located Hopf bifurcation.

When performing system identification, we have two sources of information: experimental data and prior knowledge. Many cell-biological systems are oscillating, and sometimes we know an input where the system reaches a Hopf bifurcation. This is the case, for example, for glycolysis in yeast cells and for the Belousov-Zhabotinsky reaction, and for both of these systems there exist significant numbers of quenching data, ideal for system identification. We present a method that includes prior knowledge of the location of a Hopf bifurcation in estimation based on time-series. The main contribution is a reformulation of the prior knowledge into the standard formulation of a constrained optimisation problem. This formulation allows for any of the standard methods to be applied, including all the theories regarding the method's properties. The reformulation is carried out through an over-parametrisation of the original problem. The over-parametrisation allows for extra constraints to be formed, and the net effect is a reduction of the search space. A method that can solve the new formulation of the problem is presented, and the advantage of adding the prior knowledge is demonstrated on the Brusselator.

Algorithms↗
PubMed1992

Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function.

BACKGROUND: A number of parameters reflecting the effects of idiopathic dilated cardiomyopathy (IDC) on the structure and function of myosin from the human myocardium were analyzed. METHODS AND RESULTS: The content of the regulatory light chain, LC2, was reduced in myopathic heart myosin in contrast to the controls in which it was present in stoichiometric amounts relative to the essential light chain, LC1. In IDC hearts, the absence or significant reduction in amount of LC2 was related to the presence of an active protease, which was isolated and purified about 130-fold. The protease exhibited a significant degree of specificity: It cleaved LC2 almost totally (but not the heavy chains) in human control heart myosin but only partially cleaved LC2 in canine heart or in rabbit skeletal muscle myosins. The protease was present at a very low level or was inactive in control heart tissue. When the LC1/LC2 molar ratio was calculated, it was found to be 1:1.0 in control heart myosin and remained constant in various samples analyzed, whereas in myopathic myosin from different individuals, this ratio varied from 1:0.1 to 1:0.69. The rates of ATP binding to control and myopathic myosins were similar, whereas the Vm of actin-activated ATPase of myopathic myosin was about 25% less than that of the control. However, ATP binding and its hydrolysis by control S1, i.e., the myosin head, were faster by a factor of 2 than that of the myopathic S1. In addition, control myosin synthetic thick filament length as well as turbidity in solution, measured by light scattering, were twice as large as those of the myopathic heart myosin. These effects induced by myopathy in both filament assembly and turbidity were reversed upon reassociation of IDC myosin with LC2. CONCLUSIONS: The changes in myosin structure and function were linked to a protease-mediated cleavage of LC2 in myosin; a possible role for the protease in the degenerative effects of idiopathic dilated cardiomyopathy is thus defined.

Adenosine Triphosphate↗
PubMed1977

A direct radioimmunoassay for human renin substrate and identification of multiple substrate types in plasma.

Plasma renin substrate, a widely measured parameter of the renin reaction, is quantitated indirectly by the measurement of liberated angiotensin I upon exhaustive incubation of plasma with added renin. To overcome methodological problems of this assay system, we have developed a direct radioimmunoassay for this plasma protein using renin substrate purified from pooled plasma of normotensive subjects as the antigen. Comparison of substrate quantitated by the two assay systems (direct and indirect) indicates a 1:1 correlation with the exception of certain subjects with elevated substrate levels induced by estrogen therapy. To study the possibility of multiple substrate forms, we have made a comparison of substrate quantitated by both radioimmunoassays in conjunction with electrophoresis of plasma on polyacrylamide gel. One major form of substrate with a retardation factor (Rf) = 0.60 was found in normotensive and essential hypertensive subjects which gave a 1:1 correspondence on quantitation by the two methods. In contrast, six of 16 women on oral contraceptives demonstrated three forms of substrate (Rf = 0.16, 0.35, and 0.60) on electrophoresis. Substrate with Rf = 0.16 and 0.35 did not cross-react with the antiserum prepared against substrate from normotensive subjects, implying structural differences in these proteins.

Angiotensinogen↗
PubMed1987

Use of transmembrane potentials in the identification of tumour cells.

The electrical properties of the cancer cell are useful parameters associated with neoplastic pathophysiological events. Although transmembrane potentials may not serve as inherent tumour markers in many instances, electrophysiological properties are, indeed, very useful in the investigation of malignant cellular proliferation, the influence of malignant disease on normal cell physiology and chemical carcinogenic events and possibly as an in vivo measurement in the cancer patient.

Biomarkers, Tumor↗
PubMed1995

Cross-species identification of proteins separated by two-dimensional gel electrophoresis using matrix-assisted laser desorption ionisation/time-of-flight mass spectrometry and amino acid composition.

Amino acid analysis and matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry were used to identify nine of twelve proteins originally separated by two-dimensional electrophoresis and derived from an organism poorly defined at the molecular level (Spiroplasma melliferum). Two of three unidentified proteins appeared to be novel. The percentage amino acid composition and the molecular mass of peptide fragments generated by tryptic digestion were used to search the PIR/SWISS-PROT and MOWSE databases respectively. Lists of candidate proteins were independently generated and ranked from data obtained by both methods. A putative identification was allocated when a single candidate protein appeared in both lists of computer-generated rankings. Results were verified using N-terminal protein microsequencing. The combined use of amino acid composition and MALDI-TOF mass spectrometry allowed a high degree of confidence to be placed in such identifications because they were based upon homologous data sets of at least 20 parameters (16 amino acids and 4-10 tryptic digest fragments). A further two parameters, estimated M(r) and, to a lesser extent, pI, were also used to reinforce this measure of confidence. Ranking of candidate proteins by one method alone could lead to false identification. Both techniques can process large numbers of samples rapidly. In light of the increasing number of entries in both gene and protein databases, this approach is likely to become an essential first step for the characterisation of proteins, particularly across species boundaries.

Amino Acid Sequence↗
PubMed2006

Use of single-point genome signature tags as a universal tagging method for microbial genome surveys.

We developed single-point genome signature tags (SP-GSTs), a generally applicable, high-throughput sequencing-based method that targets specific genes to generate identifier tags from well-defined points in a genome. The technique yields identifier tags that can distinguish between closely related bacterial strains and allow for the identification of microbial community members. SP-GSTs are determined by three parameters: (i) the primer designed to recognize a conserved gene sequence, (ii) the anchoring enzyme recognition sequence, and (iii) the type IIS restriction enzyme which defines the tag length. We evaluated the SP-GST method in silico for bacterial identification using the genes rpoC, uvrB, and recA and the 16S rRNA gene. The best distinguishing tags were obtained with the restriction enzyme Csp6I upstream of the 16S rRNA gene, which discriminated all organisms in our data set to at least the genus level and most organisms to the species level. The method was successfully used to generate Csp6I-based tags upstream of the 16S rRNA gene and allowed us to discriminate between closely related strains of Bacillus cereus and Bacillus anthracis. This concept was further used successfully to identify the individual members of a defined microbial community.

Bacillus anthracis↗
PubMed2006

Use of strontium isotopes to identify buried water main leakage into groundwater in a highly urbanized coastal area.

Previous studies indicate that the local aquifer systems in the Mid-Levels, a highly urbanized coastal area in Hong Kong, have commonly been affected by leakage from water mains. The identification of leakage locations was done by conventional water quality parameters including major and trace elements. However, these parameters may lead to ambiguous results and fail to identify leakage locations especially where the leakage is from drinking water mains because the chemical composition of drinking water is similar to that of natural groundwater. In this study, natural groundwater, seepage in the developed spaces, leakage from water mains, and parent aquifer materials were measured for strontium isotope (87Sr/86Sr) compositions to explore the feasibility of using these ratios to better constrain the seepage sources. The results show that the 87Sr/86Sr ratios of natural groundwater and leakage from water mains are distinctly different and thus, they can provide additional information on the sources of seepage in developed spaces. A classification system based on the aqueous 87Sr/86Sr ratio is proposed for seepage source identification.

Cities↗
PubMed1999

35Cl and (37)Cl Magic-Angle Spinning NMR Spectroscopy in the Characterization of Inorganic Perchlorates.

35Cl quadrupole coupling constants (C(Q)), asymmetry parameters (eta(Q)), and isotropic chemical shifts (delta(iso)) have been determined for a series of inorganic perchlorates from (35)Cl magic-angle spinning (MAS) NMR spectra at 14.1 T. Illustrative (37)Cl MAS NMR spectra are obtained and analyzed for some of the samples. For perchlorate anions with quadrupolar couplings less than about 1 MHz, the (35)Cl/(37)Cl NMR parameters are most precisely determined from the full manifold of spinning sidebands observed for the satellite transitions while line-shape analysis of the central transition is employed for the somewhat larger quadrupolar couplings. The environments for the individual perchlorate anions are best characterized by the quadrupole coupling parameters (e.g., C(Q) ranges from 0.3 to 3.0 MHz), while the dispersion in the isotropic (35)Cl chemical shifts is small (1029 ppm < delta(iso) < 1049 ppm) for the perchlorates studied. Due to the variation in quadrupole coupling parameters, (35)Cl MAS NMR may conveniently be employed for identification of anhydrous and hydrated phases of perchlorates, in studies of phase transitions, hydration reactions, and the composition of mixed phases. The perchlorates studied include anhydrous KClO(4), RbClO(4), CsClO(4), (CH(3))(4)NClO(4), and the anhydrous and/or hydrated forms of LiClO(4), NaClO(4), Mg(ClO(4))(2), Ba(ClO(4))(2), and Cd(ClO(4))(2). The (35)Cl MAS NMR spectra of LiClO(4), Mg(ClO(4))(2), and Ba(ClO(4))(2), for which the crystal structures are unknown, reveal that each of these salts possesses a single perchlorate site in the asymmetric unit. The (35)Cl NMR data for Mg(ClO(4))(2) and Ba(ClO(4))(2) suggest that these two samples are isostructural. Relationships between the (35)Cl NMR parameters and crystal symmetries are discussed for the other perchlorates where crystal structure data have been reported.

Journal Article↗