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PubMedDate not supplied

Episodic secretion of ACTH in rats.

While the circadian rhythm of pituitary adrenocorticotropin (ACTH) secretion has been well characterized, the ultradian rhythm has been less thoroughly investigated. To study the episodic nature of ACTH secretion, unrestrained, unanesthetized rats were bled continuously through indwelling jugular venous cannulae and blood sampled for up to 75 minutes at one-minute intervals beginning at 1100 hr (n=6) or 1730 hr (n=4). Sporadic low-amplitude micropulses were observed at both times of day. In addition, infrequent "superpulses" were observed in the evening. Analysis of pulse parameters revealed a significant (p less than 0.001) difference in pulse amplitude but no difference in pulse frequency of interpeak interval between morning and evening. As with other episodically secreted hormones, the threshold for pulse identification and the sampling interval were found to influence the observed pulse parameters.

Activity Cycles↗
PubMedDate not supplied

The effect of lymphatic tumor burden on sentinel lymph node biopsy results.

Increasing tumor burden in the axilla, as determined by the number of positive lymph nodes, adversely affects sentinel lymph node (SLN) identification and false-negative rates. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective, multi-institutional study. All enrolled patients underwent SLN biopsy, followed by complete level I/II axillary dissection. Participating surgeons represent a variety of practice settings, mostly community-based private practice. A total of 229 surgeons enrolled 2206 patients between August 1997 and November 2000. SLN biopsy was performed using blue dye injection alone, radioactive colloid alone, or a combination of the two agents. Two key parameters used to measure SLN biopsy success are the SLN identification rate and SLN false-negative rate. The overall SLN identification and false-negative rates were 92.5% and 8.0%, respectively. With increasing numbers of positive axillary nodes, there was a decreased sentinel node identification rate. There was no difference in the false-negative rate with increasing axillary tumor burden. Increased tumor burden in the axilla (as determined by the mean number of positive nodes) is associated with failure to identify a SLN in some cases, but is not an explanation for false-negative results. Standard axillary dissection should be performed when a SLN cannot be identified.

Axilla↗
PubMed2001

HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus.

A major problem in the management of SLE patients is to predict a flare or to distinguish between active and quiescent disease. Serological markers are widely used to assess disease activity, but many patients have close to or normal values for these parameters while exhibiting obvious disease-related signs and symptoms. This study aimed to determine which serological parameters, among ESR, ANA and anti-dsDNA antibody titres, CH50 and the HLA-DR expression on circulating T-lymphocyte subsets, best reflected the development of SLE flares. Sixty SLE patients were included, 34 with quiescent disease throughout the entire follow-up period and 26 who experienced an SLE flare defined as having active disease. According to univariate analysis, all parameters were significantly higher for patients with active disease, with the percentage of CD8+DR+ cells being the most significant parameter (P = 10-7). Multivariate logistic regression analysis identified three independent variables enabling the identification of a lupus flare: CH50, the CD8+DR+ and CD4+DR+ cell percentages among total lymphocytes. The CD8+DR+ cell percentage is the biological parameter most significantly associated with a flare (P < 0.001), even more powerful than CH50 (P < 0.01). HLA-DR expression on CD8+ lymphocytes clearly coincided with disease evolution in seven patients enrolled as having quiescent disease, but who experienced one flare during follow-up that subsequently resolved. The percentage of circulating CD8+DR+ lymphocytes appears to be a biological marker which accurately reflects disease activity. A larger prospective study is needed to demonstrate the real efficacy of this marker in predicting an exacerbation in SLE patients.

Adolescent↗
PubMed2005

Atomically detailed potentials to recognize native and approximate protein structures.

Atomically detailed potentials for recognition of protein folds are presented. The potentials consist of pair interactions between atoms. One or three distance steps are used to describe the range of interactions between a pair. Training is carried out with the mathematical programming approach on the decoy sets of Baker, Levitt, and some of our own design. Recognition is required not only for decoy-native structural pairs but also for pairs of decoy and homologous structures. Performance is tested on the targets of CASP5 using templates from the Protein Data Bank, on two test ab initio decoy sets from Skolnick's laboratory, and on decoy sets from Moult's laboratory. We conclude that the newly derived potentials have significant recognition capacity, comparable to the best models derived from other techniques. The new potentials require a significantly smaller number of parameters. The enhanced recognition capacity extends primarily to the identification of structures generated by ab initio simulation and less to the recognition of approximate shapes created by homology.

Computational Biology↗
PubMed1983

Bone metabolism in idiopathic juvenile osteoporosis: a case report.

A previously healthy 12-year-old boy developed pain on walking and x-rays showed osteoporosis. Over the next 2 years deterioration occurred, the condition became extremely severe, and he was confined to a wheelchair. After 5 years, marked kyphoscoliosis and pigeon chest deformity were present and little increase in height occurred. A wheelchair accident at the age of 17 resulted in several major long bone fractures. Iliac crest biopsies were taken at ages 15 and 17, and subjected to quantitative histology. A histochemical technique for osteoclast recognition by acid phosphatase activity showed resorption parameters to be normal. Double tetracycline labeling and histochemical identification of osteoblasts showed no abnormality of endosteal bone formation. Because of "coupling" of endosteal formation and resorption, these measurements might primarily reflect bone turnover. Failure of periosteal bone formation as shown by failure of radial growth of long bones and of epiphyseal growth was clearly evident. It is likely that osteoporosis developed in this patient due to a reduction in bone formation of unknown etiology rather than by increased bone resorption.

Adolescent↗
PubMed2005

[Neural correlates of working memory deficits in schizophrenic patients. Ways to establish neurocognitive endophenotypes of psychiatric disorders].

This article briefly reviews some methodological limitations of functional neuroimaging studies in psychiatric patients. We argue that the investigation of the neural substrates of cognitive deficits in psychiatric disorders requires a combination of functional neuroimaging studies in healthy subjects with corresponding behavioral experiments in patients. In order to exemplify this methodological approach we review recent findings regarding the functional neuroanatomy of distinct components of human working memory and provide evidence for selective dysfunctions of cortical networks that underlie specific working memory deficits in schizophrenia. This identification of subgroups of schizophrenic patients according to neurocognitive parameters may facilitate the establishment of behavioral and neurophysiological endophenotypes and the development of a neurobiological classification of psychiatric disorders.

Brain Mapping↗
PubMed2004

Identification of the head-neck complex in response to trunk horizontal vibration.

A method is proposed for identifying the head-neck complex (HNC) in the seated human body when it is exposed to the trunk horizontal (fore-and-aft) vibration. It is assumed that the HNC only has the anteroposterior (flexion/extension) motion in the sagittal plane. An electrohydraulic vibrator is used as a source of vibration. To generate the trunk horizontal vibration, the trunk of the seated subject is fixed to the seatback. The subjects are exposed to the random vibration at a magnitude of 1.60 ms(-2) rms (root-mean-square) for 50 s. The coherence and frequency response function are then obtained in the frequency range 0.5-3 Hz. The results show that the HNC behavior is quasilinear with a resonance frequency between 1 and 1.4 Hz. Accordingly, a two-dimensional single-inverted pendulum is considered as a model for the HNC. The frequency domain identification method is then used to estimate the unknown parameters, including the HNC viscoelastic and inertia parameters. The model is examined in a time domain using the random vibration. Good agreement is obtained between experimental and simulation results, indicating the reliability of the proposed method.

Acceleration↗
PubMed1988

EZ-FIT: a practical curve-fitting microcomputer program for the analysis of enzyme kinetic data on IBM-PC compatible computers.

EZ-FIT, an interactive microcomputer software package, has been developed for the analysis of enzyme kinetic and equilibrium binding data. EZ-FIT was designed as a user-friendly menu-driven package that has the facility for data entry, editing, and filing. Data input permits the conversion of cpm, dpm, or optical density to molar per minute per milligram protein. Data can be fit to any of 14 model equations including Michaelis-Menten, Hill, isoenzyme, inhibition, dual substrate, agonist, antagonist, and modified integrated Michaelis-Menten. The program uses the Nelder-Mead simplex and Marquardt nonlinear regression algorithms sequentially. A report of the results includes the parameter estimates with standard errors, a Student t test to determine the accuracy of the parameter values, a Runs statistic test of the residuals, identification of outlying data, an Akaike information criterion test for goodness-of-fit, and, when the experimental variance is included, a chi 2 statistic test for goodness-of-fit. Several different graphs can be displayed: an X-Y, a Scatchard, an Eadie-Hofstee, a Lineweaver-Burk, a semilogarithmic, and a residual plot. A data analysis report and graphs are designed to evaluate the goodness-of-fit of the data to a particular model.

Enzymes↗
PubMed1993

Cooking procedures and food mutagens: a literature review.

Commonly eaten meat products prepared from beef, pork, mutton and chicken show some level of mutagenic activity following normal frying. Food preparation methods have a significant influence on the formation of the mutagenic activity. The main food mutagens found in cooked meat products are heterocyclic amines. Several of them have been tested in long-term animal studies and shown to be carcinogenic in rodents. From a health point of view, it is desirable to reduce or prevent the formation of food mutagens. Therefore, a deeper understanding of the precursors and reaction conditions for mutagen formation during normal domestic cooking is very important. Modelling experiments are useful tools for studying the influence of different physical parameters and various precursors on the mutagenic activity. The identification of several thermic mutagens from the modelling experiments support the theory that creatine or creatinine, amino acids and sugars are precursors in the formation of thermic mutagens. Creatine is generally accepted to be a precursor of the mutagens and, interestingly, the conversion of creatine to creatinine has been shown to be blocked by an excess of sugars, which also caused the mutagenic activity to decrease. The mutagenic activity differed for different amino acids used in the model systems, and various thermic mutagens were produced from the amino acids. The incorporation of carbon atoms originating from glucose into food mutagen molecules has shown glucose to be a precursor. Sugar has also been shown to either enhance or inhibit the yield of mutagenic activity, depending on its molar ratio versus the other reactants, which suggests that the Maillard reaction may be used to control the formation of mutagens.

Animals↗
PubMed1999

Admission level of Gc-globulin predicts outcome after multiple trauma.

BACKGROUND: Actin is the dominating protein in mammalian cells. Release of excessive amounts of actin into the circulation may result in a condition resembling multiple organ failure. The purpose of this study was to determine if admission levels of Gc-globulin can predict survival after multiple trauma. Also, we wanted to compare the predictive ability of Gc-globulin with that of the TRISS-Like scoring system. METHODS: Fifty-seven patients with a median ISS 18 (16-75) were included. All patients had a blood sample taken median 42 min after the injury (19-110 min). Serum Gc-globulin was measured by rocket immunoelectrophoresis. RESULTS: On admission, all patients had significantly reduced levels of Gc-globulin compared with normal controls. Gc-globulin was significantly higher in the group of survivors (n = 41), compared with non-survivors (n = 16). Median 237 mg/l vs. 188 mg/l (P < 0.01). The predictive ability of Gc-globulin regarding death was similar to that of TRISS-Like with positive predictive values of 69%, a negative predictive value of 84%, a sensitivity of 56% and a specificity of 90%. CONCLUSIONS: The predictive value of Gc-globulin regarding survival was similar to that of an established scoring system. Gc-globulin, alone or in combination with other parameters, may serve as a routine tool for early identification of patients at risk after severe injury, increasing the possibility of early intervention.

Adolescent↗
PubMed2003

Numerical non-identifiability regions of the minimal model of glucose kinetics: superiority of Bayesian estimation.

The so-called minimal model (MM) of glucose kinetics is widely employed to estimate insulin sensitivity (S(I)) both in clinical and epidemiological studies. Usually, MM is numerically identified by resorting to Fisherian parameter estimation techniques, such as maximum likelihood (ML). However, unsatisfactory parameter estimates are sometimes obtained, e.g. S(I) estimates virtually zero or unrealistically high and affected by very large uncertainty, making the practical use of MM difficult. The first result of this paper concerns the mathematical demonstration that these estimation difficulties are inherent to MM structure which can expose S(I) estimation to the risk of numerical non-identifiability. The second result is based on simulation studies and shows that Bayesian parameter estimation techniques are less sensitive, in terms of both accuracy and precision, than the Fisherian ones with respect to these difficulties. In conclusion, Bayesian parameter estimation can successfully deal with difficulties of MM identification inherently due to its structure.

Bayes Theorem↗
PubMed2006

Microfluidic liquid chromatography system for proteomic applications and biomarker screening.

A microfluidic liquid chromatography (LC) system for proteomic investigations that integrates all the necessary components for stand-alone operation, i.e., pump, valve, separation column, and electrospray interface, is described in this paper. The overall size of the LC device is small enough to enable the integration of two fully functional separation systems on a 3 in. x 1 in. glass microchip. A multichannel architecture that uses electroosmotic pumping principles provides the necessary functionality for eluent propulsion and sample valving. The flow rates generated within these chips are fully consistent with the requirements of nano-LC platforms that are routinely used in proteomic applications. The microfluidic device was evaluated for the analysis of a protein digest obtained from the MCF7 breast cancer cell line. The cytosolic protein extract was processed according to a shotgun protocol, and after tryptic digestion and prefractionation using strong cation exchange chromatography (SCX), selected sample subfractions were analyzed with conventional and microfluidic LC platforms. Using similar experimental conditions, the performance of the microchip LC was comparable to that obtained with benchtop instrumentation, providing an overlap of 75% in proteins that were identified by more than two unique peptides. The microfluidic LC analysis of a protein-rich SCX fraction enabled the confident identification of 77 proteins by using conventional data filtering parameters, of 39 proteins with p < 0.001, and of 5 proteins that are known to be cancer-specific biomarkers, demonstrating thus the potential applicability of these chips for future high-throughput biomarker screening applications.

Biomarkers, Tumor↗
PubMed1998

The H2O2 stimulon in Saccharomyces cerevisiae.

The changes in gene expression underlying the yeast adaptive stress response to H2O2 were analyzed by comparative two-dimensional gel electrophoresis of total cell proteins. The synthesis of at least 115 proteins is stimulated by H2O2, whereas 52 other proteins are repressed by this treatment. We have identified 71 of the stimulated and 44 of the repressed targets. The kinetics and dose-response parameters of the H2O2 genomic response were also analyzed. Identification of these proteins and their mapping into specific cellular processes give a distinct picture of the way in which yeast cells adapt to oxidative stress. As expected, H2O2-responsive targets include an important number of heat shock proteins and proteins with reactive oxygen intermediate scavenging activities. Exposure to H2O2 also results in a slowdown of protein biosynthetic processes and a stimulation of protein degradation pathways. Finally, the most remarkable result inferred from this study is the resetting of carbohydrate metabolism minutes after the exposure to H2O2. Carbohydrate fluxes are redirected to the regeneration of NADPH at the expense of glycolysis. This study represents the first genome-wide characterization of a H2O2-inducible stimulon in a eukaryote.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2004

Biomechanical analysis of pedalling for rehabilitation purposes: experimental results on two pathological subjects and comparison with non-pathological findings.

In this paper the experimental results obtained by means of a prototype measuring device dedicated to the evaluation of the rehabilitation level of the lower limb are presented. The analysis of the experimental data collected on non-pathological subjects allows the identification of the characteristic meaning of the most significant parameters typical of healthy subjects. These data have been employed for a systematic comparison with the same parameters measured on two pathological subjects, in order to define quantitative indicators of the rehabilitation degree of the lower limbs and indicators of the "quality" of the movement.

Adult↗
PubMed2002

Current management of polycythemia vera.

Over a century has elapsed since the first description of polycythemia vera (PV), and current treatment recommendations are primarily based on the results of clinical trials that were performed in the late 1960s and early 1970s. Continued identification and appropriate utilization of PV-specific biologic parameters may allow substantial modification of early diagnostic criteria. New cytoreductive treatment agents are increasingly being used without any evidence of superiority over conventional therapy. The role of aspirin is being readdressed by an ongoing controlled study. Transformation of PV into either myelofibrosis with myeloid metaplasia or acute leukemia remains a major complication that may not be influenced by current therapy.

Acute Disease↗
PubMed2003

Looking beyond morphology: cancer gene expression profiling using DNA microarrays.

Although molecular testing has been increasingly used in clinical practice, the precise diagnosis and prognosis of most human cancers still heavily rely on descriptive histopathological data. Identification of robust molecular markers associated with distinctive morphological parameters will assist in diagnostic and prognostic assessment. On the other hand, the diversity of morphologically identical/similar cancers can be manifested at multiple levels, most importantly at the level of clinical outcome. In the past several years, DNA microarray technology has been widely used in the context of cancer research, resulting in a deluge of new information that can be used to identify molecular alterations common to all tumors as well as signatory profiles unique to a subcategory of cancers. These new findings will very likely transform the clinical management of cancer patients in the near term. This article reviews recent advances in cancer gene expression-profiling results derived from the application of DNA microarray technology, with an emphasis on studies performed on human prostate cancer specimens. We discuss broad issues relevant to cancer expression profiling and attempt to illustrate the rapid pace of novel discoveries using prostate cancer as examples wherever appropriate.

DNA, Neoplasm↗
PubMed1998

Serial isolates of Cryptococcus neoformans from patients with AIDS differ in virulence for mice.

Serial isolates of Cryptococcus neoformans from patients with chronic infection can exhibit minor karyotype changes as a result of chromosome length polymorphism (CLP). This study investigated whether serial C. neoformans isolates with CLP from 4 patients with AIDS exhibited biologic and phenotypic differences. CLP permits the identification of serial isolates in murine mixed infection. The parameters studied were virulence in mice, capsule size, colony morphology, melanization, protease production, MICs of antifungal drugs, and growth rates in vitro. Two parameters of virulence in mice were studied: persistence in tissue and survival time after lethal infection. Serial C. neoformans isolates were shown to differ in ability to persist in vivo, virulence in a murine infection model, in vitro growth rates at 37 degreesC, and capsule size. Melanin and protease production and MICs of antifungal drugs were comparable for serial isolates. These observations suggest microevolution of C. neoformans during human infection. This process may allow the fungal population to change, escape eradication by the immune system, and thus cause chronic infections.

AIDS-Related Opportunistic Infections↗
PubMed2004

Evolutionary optimization with data collocation for reverse engineering of biological networks.

MOTIVATION: Modern experimental biology is moving away from analyses of single elements to whole-organism measurements. Such measured time-course data contain a wealth of information about the structure and dynamic of the pathway or network. The dynamic modeling of the whole systems is formulated as a reverse problem that requires a well-suited mathematical model and a very efficient computational method to identify the model structure and parameters. Numerical integration for differential equations and finding global parameter values are still two major challenges in this field of the parameter estimation of nonlinear dynamic biological systems. RESULTS: We compare three techniques of parameter estimation for nonlinear dynamic biological systems. In the proposed scheme, the modified collocation method is applied to convert the differential equations to the system of algebraic equations. The observed time-course data are then substituted into the algebraic system equations to decouple system interactions in order to obtain the approximate model profiles. Hybrid differential evolution (HDE) with population size of five is able to find a global solution. The method is not only suited for parameter estimation but also can be applied for structure identification. The solution obtained by HDE is then used as the starting point for a local search method to yield the refined estimates.

Algorithms↗