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PubMed2003

Recognizing the fold of a protein structure.

This paper reports a graph-theoretic program, GRATH, that rapidly, and accurately, matches a novel structure against a library of domain structures to find the most similar ones. GRATH generates distributions of scores by comparing the novel domain against the different types of folds that have been classified previously in the CATH database of structural domains. GRATH uses a measure of similarity that details the geometric information, number of secondary structures and number of residues within secondary structures, that any two protein structures share. Although GRATH builds on well established approaches for secondary structure comparison, a novel scoring scheme has been introduced to allow ranking of any matches identified by the algorithm. More importantly, we have benchmarked the algorithm using a large dataset of 1702 non-redundant structures from the CATH database which have already been classified into fold groups, with manual validation. This has facilitated introduction of further constraints, optimization of parameters and identification of reliable thresholds for fold identification. Following these benchmarking trials, the correct fold can be identified with the top score with a frequency of 90%. It is identified within the ten most likely assignments with a frequency of 98%. GRATH has been implemented to use via a server (http://www.biochem.ucl.ac.uk/cgi-bin/cath/Grath.pl). GRATH's speed and accuracy means that it can be used as a reliable front-end filter for the more accurate, but computationally expensive, residue based structure comparison algorithm SSAP, currently used to classify domain structures in the CATH database. With an increasing number of structures being solved by the structural genomics initiatives, the GRATH server also provides an essential resource for determining whether newly determined structures are related to any known structures from which functional properties may be inferred.

Algorithms↗
PubMed1998

Morphometric multivariate analysis of field samples of adult Anopheles arabiensis and An. gambiae s.s. (Diptera: Culicidae).

The Afrotropical complex of sibling species Anopheles gambiae Giles includes the most efficient vectors of human malaria south of the Sahara. Anopheles arabiensis Patton and An. gambiae s.s. Giles are the members of the complex more adapted to the human environment. They are sympatric and synchronic over most of their distribution range; however, they show a different involvement in malaria transmission, with An. gambiae being more anthropophilic and endophilic than An. arabiensis. Discriminating between them is essential for a correct assessment of epidemiological parameters. The identification is currently achieved through recognition of species-specific chromosomal inversions or by molecular biology techniques. Both methods require considerable technical resources, not always available in the field. We carried out a morphometric analysis of field and laboratory samples of An. arabiensis and An. gambiae s.s. from sites in Madagascar, Burkina Faso, Mali, and Liberia to evaluate the degree of morphological differentiation. We examined 17 morphometric characters in samples representing each of the geographic sites. All of the measures were significantly larger for An. arabiensis (regardless of the collection site), demonstrating an intrinsic greater body size of this species. To assess the reliability associated with the multivariate statistic, we applied the discriminant function analysis, which provided a method for predicting to which group a new case will most likely be assigned. In a blind experiment, the morphometric method correctly identified approximately 85% of field-collected An. arabiensis and An. gambiae s.s., which provided a relatively simple method to approximate the relative frequencies of the 2 species in areas in which their concurrent presence was already known. The influence of laboratory conditions on the morphometrics of the 2 species was also analyzed.

Animals↗
PubMed2003

A computational study of the urinary excretion rates for 339Pu using new ICRP internal dosimetry models.

A computational study of the urinary excretion rates for 239Pu has been carried out using a methodology which involved the solution of a complete compartmental model describing the biokinetic behaviour of inhaled plutonium aerosols in the human body. The methodology, after proper validation, was applied to investigate the dependence of urinary excretion rates for 239Pu on the transfer rates given in the complete compartmental model. For this purpose, the default values of the transfer/absorption rates were modified by factors of 2 and 4 and urinary excretion rates were computed on 1, 10, 100, 1000 and 10,000 d post-intake. The percentage variations in the urinary excretion rates as a result of the modified transfer rates were computed for exposures to Type M and S aerosols of 239Pu. These results facilitated the identification of parameters significantly affecting the short-term and long-term urinary excretion rates. In addition, time variations of the predicted ratios of 239Pu activity in daily urine to that in blood (excretion ratios) were studied for the three biokinetic models of plutonium: the ICRP 67 model, the modified ICRP 67 model with the compartment STI to urinary bladder removed and Luciani and Polig's model. All the computational results are presented and discussed in this paper.

Air Pollution, Radioactive↗
PubMed2002

Seven days vs. 10 days ceftriaxone therapy in bacterial meningitis.

Ceftriaxone is recommended in children with acute bacterial meningitis (ABM) for 10 days. However, the drug is expensive, and shorter duration of therapy, if equally effective, would cut costs of therapy and hospitalization. The aim of this study was to compare the outcome of 7 days vs. 10 days' ceftriaxone therapy in children with ABM. Seventy-three children aged 3 months to 12 years with ABM, consecutively admitted to hospital were enrolled. Ceftriaxone was given for 7 days to all. Randomization to group I (7 days) and group II (10 days) therapy was done on the seventh day. At the end of 7 days' therapy in group I and 10 days in group II, children were evaluated using a clinical scoring system. Children with a score of more than 10 were labelled as 'treatment failures' and were continued on ceftriaxone. If a score was less than 10, the antibiotic was stopped. Complications were appropriately evaluated and managed. All children were followed-up 1 month after discharge: neurodevelopmental assessment, Denver Development Screening Tests, IQ and hearing assessment were done. After excluding four patients, there were 35 children in group I and 34 in group II. The two groups were comparable with respect to age, sex, nutritional status, presenting clinical features, and CSF parameters. Organism identification was possible in 38 per cent of children: (Streptococcus pneumoniae, 21 per cent; Haemophilus influenzae, 13 per cent; meningococcus, 4 per cent). Treatment failure rate was comparable in both groups (9 in group I and 8 in group II) as was the sequelae at discharge and at 1 month (9 in group I, 15 in group II,p > 0.1). Status epilepticus and focal deficits at presentation were significantly associated with treatment failures and sequelae in both the groups (p < 0.05). Length of hospital stay was shorter in group I (10.8 +/- 6.0 days) as compared with group II (14.4 +/- 7.2 days,p < 0.05) and frequency of nosocomial infection was significantly more in group II (p < 0.05). It was concluded that clinical outcome of patients treated with 7 days' ceftriaxone therapy is similar to that of 10 days' therapy, and is associated with lesser nosocomial infection and earlier hospital discharge. Seven days ceftriaxone therapy may be recommended for uncomplicated ABM in children in developing countries.

Ceftriaxone↗
PubMed2002

Endoscopic treatment of lower gastrointestinal bleeding.

Urgent colonoscopy has emerged as the initial diagnostic and main therapeutic tool in the evaluation and treatment of colonic lower gastrointestinal bleeding. Endoscopic therapy can effectively treat most cases of colonic bleeding with a demonstrable improvement in clinical outcome parameters. The identification of high-risk stigmata of hemorrhage enables selective targeting of endoscopic therapy to lesions at high risk of rebleeding. Advances in technologies such as novel mechanical methods of hemostasis (eg, metallic clips), injection techniques (eg, cyanoacrylate injection), and the widening application of established endoscopic hemostatic techniques (eg, rubber-band ligation) to colonic lesions offers the possibility of further improvements in the efficacy of endoscopic hemostasis. Clinical trials are needed to compare these novel endoscopic techniques with more conventional approaches to establish the best form of endoscopic therapy for different bleeding lesions and finally to establish more definitively the optimal timing of colonoscopy.

Journal Article↗
PubMedDate not supplied

Compartment syndrome.

Compartment syndrome is a possible complication for every patient with a fracture, sprain, or orthopaedic surgery. Complete evaluation of the patient is necessary on a continual basis to determine any deviation from the normal range of the neurovascular parameters. Early identification of the symptoms will prompt immediate treatment and prevent the loss of a limb.

Acute Disease↗
PubMed1998

Methodologic issues in low back pain research in primary care.

STUDY DESIGN: Narrative review and discussion of the selected literature. OBJECTIVES: To discuss some important methodologic challenges in low back pain research in primary care. SUMMARY OF BACKGROUND DATA: Many methodologic problems must be confronted when conducting low back pain research. Some of these problems are back pain specific or specific to the primary care setting. METHODS: Methodologic problems related to four research issues will be discussed: study designs, definition of low back pain, determinants of low back pain, and outcome assessment. RESULTS: Two fundamentally different study designs are frequently used in low back pain research, namely observational studies and experimental studies. The definition of low back pain is typically restricted to a highly variables self-reported symptom, the sensation of pain in the back. There clearly is a need for an evidence-based classification system for low back pain. Because a tenable theoretical framework is lacking, it is difficult to know which determinants of low back pain should be quantified. Low back pain studies focus usually on health-related quality-of-life outcome parameters. The identification of the minimum clinically relevant changes for the most important outcome instruments needs further consideration. CONCLUSIONS: In years to come, low back pain researchers are challenged to overcome some of these (and other) problems to enhance the quality of low back pain research in primary care.

Clinical Trials as Topic↗
PubMed2006

The importance of PET in the diagnosis and response evaluation of esophageal cancer.

The major aims of imaging in esophageal cancer are to distinguish between locoregional and systemic disease (M-stage), to determine local tumor extension (T- and N-stage), to assess response to chemo- or chemoradiotherapy and to identify recurrence of cancer. The sensitivity of computed tomography (CT) for detection of distant metastases ranges between < 50% and > 90%. In esophageal cancer, F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to detect metastatic disease in approximately 20% of patients who are considered as having only locoregional disease on CT. In locoregional pretherapeutic tumor staging, FDG-PET specificity of 80% is sufficient, but FDG-PET sensitivity of 50% is rather low. However, the initial staging of regional lymph nodes is less important because at the moment there is no pretherapeutic therapy stratification based on lymph node category. The accuracy for correct identification of recurrence in esophageal cancer is higher for FDG-PET than for CT scan. Unfortunately until today no reliable essays for prediction of response or prognosis exist for esophageal cancer in clinical practice for patients with neoadjuvant treatment. Thus the identification of parameters predicting response and/or prognosis is crucial for the future. Post-therapeutic assessment of tumor response by FDG-PET has been shown to correlate with histopathologic tumor regression and patient survival. Furthermore, quantitative measurements of tumor FDG-uptake may allow an early metabolic response evaluation after only 2 weeks of therapy. An association of metabolic response with histopathologic tumor regression and patient outcome 2 weeks after initiation of preoperative chemotherapy may be shown for esophageal cancer.

Esophageal Neoplasms↗
PubMed2000

New approaches to assess selenium status and requirement.

Selenium is one of the essential nutrients that may have beneficial effects on health at dietary intakes higher than the established Recommended Dietary Allowances in the United States. Dietary recommendations for this element have been the subject of much controversy, illustrating the difficulties involved in the definition of requirements based on the interpretation of biochemical markers. This review will show how concepts may differ and even change as a consequence of the evolution of the knowledge concerning classical parameters (e.g., identification of isoforms of the classical selenium-dependent enzyme glutathione peroxidase) or following the discovery of new biologic markers for selenium such as iodothyronine desiodinase, thioredoxin reductase, or the selenoproteins P and W.

Biomarkers↗
PubMed2002

Identification of cross-sectional parameters of lateral meniscal allografts that predict tibial contact pressure in human cadaveric knees.

To guide the development of improved procedures for selecting meniscal allografts, the objective of this study was to identify which cross-sectional parameters of a lateral meniscal allograft predict the contact pressure of the articular surface of the tibia. To meet the objective, the contact pressure of the articular surface of the tibia was measured with a lateral meniscal autograft and a lateral meniscal allograft using pressure sensitive film in 15 fresh-frozen human cadaveric knees. Allografts were matched only in transverse dimensions to the autograft but not in cross-sectional dimensions. Knees were loaded to 1200 N in compression at flexion angles of 0, 15, 30 and 45 degrees using a load application system that allowed unconstrained motion in the remaining degrees of freedom. Five cross-sectional parameters for both of the grafts in each of the anterior, middle, and posterior regions were derived from measurements obtained using a laser-based non-contacting three-dimensional coordinate digitizing system (3-DCDS) (Haut et al., J. Orthop Res, 2000). Five contact variables (i.e. the maximum pressure, mean pressure, contact area, and anterior-posterior and medial-lateral locations of the centroid of contact area) were determined from the pressure sensitive film. When each allograft was paired with the corresponding autograft, the root mean squared percent differences for the cross-sectional parameters ranged from a minimum of 28% for the width of the posterior region to 572% for the height of the posterior region. The root mean squared percent differences between the contact variables for paired grafts were 29% for the maximum pressure, 19% for the mean pressure, and 24% for the contact area. Differences in the cross-sectional parameters between the grafts were related to differences in the contact variables using regression analysis. Difference in the width was most often a predictor variable in the regression models with R2 values > or = 0.45. Differences in all of the four remaining cross-sectional parameters were also important predictor variables. Because failure to match cross-sectional parameters causes substantial difference in contact variables between an allograft and autograft and because cross-sectional parameters predict the contact pressure on the tibial plateau, protocols used to prospectively select allografts should concentrate on matching cross-sectional parameters and particularly the width to those of the original meniscus.

Adult↗
PubMed2002

groESL sequence determination, phylogenetic analysis, and species differentiation for viridans group streptococci.

The full-length sequences of the groESL genes (also known as cpn10/60) of Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordonii, and Streptococcus sanguis and the near full-length sequence of the groESL genes of Streptococcus intermedius, Streptococcus bovis, Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, and Streptococcus salivarius were determined. The lengths of the groES genes from the 10 species listed above ranged from 282 to 288 bp, and the full-length sequences of groEL determined for 4 species (S. anginosus, S. constellatus, S. gordonii, and S. sanguis) revealed that each was 1,623 bp. The intergenic region (spacer) between the groES and groEL genes varies in size (15 to 111 bp) and sequence between species. The variation of the groES sequences among the species tested was greater (62.1 to 95.1% nucleotide sequence identities) than that of the groEL sequences (77.2 to 95.2% nucleotide sequence identities). Phylogenetic analysis of the groES and groEL genes yielded evolutionary trees similar to the tree constructed by use of the 16S rRNA gene. The intraspecies variation of the spacer was minimal for clinical isolates of some species. The groESL sequence data provide an additional parameter for identification of viridans group streptococcal species.

Bacterial Proteins↗
PubMed2004

Spurious rise in the automated platelet count because of bacteria.

The era of automation in haematology, although improving the accuracy and precision of results, has also introduced the laboratory haematologist to a vast array of spurious parameters. The identification of these results is important so that inappropriate management decisions are avoided. The case presented here illustrates a spuriously raised automated platelet count resulting from bacterial overgrowth in the blood sample.

Adult↗
PubMed1989

Alternative method for minimal model analysis of intravenous glucose tolerance data.

The minimal models of glucose-insulin kinetics were used to analyze sets of data obtained from human subjects and dogs during frequently sampled intravenous glucose tolerance tests (FSIGTs). Analysis of some data sets from both species resulted in poor identification of parameters. To improve the parameter resolution, the information base on which the parameters are estimated was enlarged. This was accomplished by incorporating into the analysis 1) glucose data obtained between 0 and 8 min of the FSIGT and some of the insulin data obtained prior to the insulin peak and 2) a second set of FSIGT data for each individual obtained during a physiological perturbation. As a result, data analysis was considerably enhanced, with parameter fractional standard deviation being routinely reduced to less than 0.5. Analysis of stimulated data with noise levels for glucose and insulin set between 0.05 and 0.15 confirmed the improvement in parameter estimates. This modified approach to analysis of FSIGTs therefore consistently leads to well-defined kinetic descriptions of experimental data in various situations and supports the usefulness of the minimal model in examining the complex interplay between the parameters that influence overall glucose tolerance.

Adult↗
PubMed1993

Clonal analysis of human T-cell responses to fractionated house dust mite antigens (Dermatophagoides pteronyssinus).

In the present study, we investigated the cellular basis of house dust mite-driven immune responsiveness in an atopic individual with perennial rhinitis. We established 40 human T-cell clones (CD3+, 4+, 8-) reactive to Dermatophagoides pteronyssinus (Dp) antigen under the restriction of HLA-DR. By using the crude Dp antigen and its 14 molecular weight (MW) fractions, we analyzed the distribution of T-cell-recognizing sites in the whole Dp extract. We tested T-cell-mediated immunity through two parameters; the identification of Dp fractions inducing T-cell proliferation, and the ability of T-cell clones to secrete IL-2, IL-4, and IFN-gamma. According to a prominent peak among fraction-driven T-cell proliferation, we observed that T-cell clones that recognized 45,000- to 95,000-MW fractions were common, while clones reactive to 15,000- to 25,000-MW fractions were less frequent. Several clones were also reactive to antigens of Dermatophagoides farinae or other insects. Based on the responses of cloned T cells, we observed at least 9 distinct T epitopes in crude Dp antigen. These T-cell clones had a heterogenous secretory pattern of cytokines. T-cell clones showed no association between their ability to produce regulatory cytokine and their recognition of particular Dp fractions.

Adult↗
PubMed2005

SMN1 dosage analysis in spinal muscular atrophy from India.

BACKGROUND: Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. As there is no cure or effective treatment, genetic counseling becomes very important in disease management. SMN1 dosage analysis results can be utilized for identifying carriers before offering prenatal diagnosis in the context of genetic counseling. METHODS: In the present study we analyzed the carrier status of parents and sibs of proven SMA patients. In addition, SMN1 copy number was determined in suspected SMA patients and parents of children with a clinical diagnosis of SMA. RESULTS: Twenty nine DNA samples were analyzed by quantitative PCR to determine the number of SMN1 gene copies present, and 17 of these were found to have one SMN1 gene copy. The parents of confirmed SMA patients were found to be obligate carriers of the disease. Dosage analysis was useful in ruling out clinical suspicion of SMA in four patients. In a family with history of a deceased floppy infant and two abortions, both parents were found to be carriers of SMA and prenatal diagnosis could be offered in future pregnancies. CONCLUSION: SMN1 copy number analysis is an important parameter for identification of couples at risk for having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA. The dosage analysis is also useful for the counseling of clinically suspected SMA with a negative diagnostic SMA test.

Child↗
PubMed2006

From descriptive to predictive distribution models: a working example with Iberian amphibians and reptiles.

BACKGROUND: Aim of the study was to identify the conditions under which spatial-environmental models can be used for the improved understanding of species distributions, under the explicit criterion of model predictive performance. I constructed distribution models for 17 amphibian and 21 reptile species in Portugal from atlas data and 13 selected ecological variables with stepwise logistic regression and a geographic information system. Models constructed for Portugal were extrapolated over Spain and tested against range maps and atlas data. RESULTS: Descriptive model precision ranged from 'fair' to 'very good' for 12 species showing a range border inside Portugal ('edge species', kappa (k) 0.35-0.89, average 0.57) and was at best 'moderate' for 26 species with a countrywide Portuguese distribution ('non-edge species', k = 0.03-0.54, average 0.29). The accuracy of the prediction for Spain was significantly related to the precision of the descriptive model for the group of edge species and not for the countrywide species. In the latter group data were consistently better captured with the single variable search-effort than by the panel of environmental data. CONCLUSION: Atlas data in presence-absence format are often inadequate to model the distribution of species if the considered area does not include part of the range border. Conversely, distribution models for edge-species, especially those displaying high precision, may help in the correct identification of parameters underlying the species range and assist with the informed choice of conservation measures.

Journal Article↗
PubMed2001

Differential toxicity expression of gentamicine in five-sixths nephrectomized rats assigned to three progressive stages of renal dysfunction--establishment of a new screening approach.

Progressive renal dysfunction in 5/6 nephrectomized (NX) rats can be physiologically divided into three stages, coinciding with morphological stages, after definition of physiological parameters for identification of stage. Now, for the establishment of a toxicity screening approach using 5/6 NX rats, our concept, "Differential toxicity synchronized with renal dysfunction process could be identified using 5/6 NX rats" was examined by dosing gentamicin. Firstly, electrophoretic fractional changes of urinary proteins during gentamicin treatment were clarified with determination of amino acid sequences and the three differential features were proven, revealing the unpredictable depression of urinary albumin with progression of the stages in NX rats. Secondly, marked elevation of urinary lactate dehydrogenase (LDH) and glucose (GLU) was evident, indicating the intensified hypoxic conditions and glycolysis in tubular cells synchronized with increased tubular damage. Thirdly, these transit metabolic changes were proven as intensive cause for the advancement of renal dysfunction by the reduction of FRelectrolytes and water at the end of each dosing period. These results indicate that toxicity studies of newly developed drugs using 5/6 NX rats have potentiality prior to clinical dosing to the patients.

Albumins↗