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PubMed2005

Plasma protein profiling for diagnosis of pancreatic cancer reveals the presence of host response proteins.

Plasma protein profiling using separations coupled to matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has great potential in translational research; it can be used for biomarker discovery and contribute to disease diagnosis and therapy. Previously reported biomarker searches have been done solely by MS protein profiling followed by bioinformatics analysis of the data. To add to current methods, we tested an alternative strategy for plasma protein profiling using pancreatic cancer as the model. First, offline solid-phase extraction is done with 96-well plates to fractionate and partially purify the proteins. Then, multiple profiling and identification experiments can be conducted on the same protein fractions because only 5% of the fractions are used for MALDI MS profiling. After MALDI MS analysis, the mass spectra are normalized and subjected to a peak detection algorithm. Over three sets of mass spectra acquired using different instrument variables, approximately 400 unique ion signals were detected. Classification schemes employing as many as eight individual peaks were developed using a training set with 123 members (82 cancer patients) and a blinded validation set with 125 members (57 cancer patients). The sensitivity of the study was 88%, but the specificity was significantly lower, 75%. The reason for the low specificity becomes apparent upon protein identification of the ion signals used for the classification. The identifications reveal only common serum proteins and components of the acute phase response, including serum amyloid A, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and inter-alpha-trypsin inhibitor.

Acute-Phase Proteins↗

PubMed1995

[Risk factors of wound infection following cardiac surgery and antimicrobial prophylaxis].

To make investigation about risk of wound infection following cardiac surgery, we analyzed cases of primary aorto-coronary bypass surgery and/or primary valvular surgery. Cases required respirator for longer than 2 days, and those with drainage tube for longer than 5 days were excluded from this study, because these cases had antimicrobial agent postoperatively as therapeutic use rather than prophylactic use. Those received preoperative antimicrobial agent for infectious endocarditis and so on were also excluded for the same reason. 523 cases were entered this study. These cases received cefazolin (CEZ) postoperatively as prophylaxis. Sternal wound and leg/groin wound were separately analyzed. Risk factors (age, sex, diabetes mellitus, unstable angina, use of intraaortic balloon, internal thoracic artery harvest, re-exploration, previous myocardial infarction, NYHA classification, emergent operation, operation time, extracorporeal circulation time, blood product use, preoperative blood hemoglobin concentration, preoperative serum albumin, preoperative creatinine clearance (Ccr), duration of drainage tube insertion, body surface area, daily dose of CEZ, duration of prophylaxis) were examined using univariate (Chi square test was used for contingency table analysis, unpaired t test was used to compare averages) and multiple regression analysis. For sternal wound infection, only Ccr showed significant (P = 0.027) correlation. For leg/groin wound infection, 2 factors (smaller daily dose of CEZ: P = 0.009, more severe NYHA class: P = 0.03) showed significant correlation. To investigate appropriate duration of CEZ prophylaxis, cases were divided into 2 groups, those had CEZ within 48 hours postoperatively (group S) and those had CEZ for longer than 48 hours (group L).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMedDate not supplied

Predictors of quality of life in patients with advanced heart failure awaiting transplantation.

BACKGROUND: Quality of life is an important outcome to measure in patients with end-stage heart disease who are awaiting heart transplantation. The purposes of this study were threefold: (1) to assess life satisfaction in multiple areas, (2) to examine correlations between life satisfaction and demographic, physiologic, and psychosocial variables, and (3) to identify predictors of quality of life in patients with advanced heart failure who were awaiting heart transplantation. METHODS: Data were collected from a convenience sample of 359 adult heart transplant candidates from a midwestern and a southern medical center. Eight instruments were used to gather data from patients. All tools had adequate psychometric support. Data were analyzed by using descriptive statistics, Pearson correlations, and stepwise multiple regression analysis. RESULTS: Results showed that patients were most satisfied with significant others (e.g., emotional support from others, children, and family's health) and least satisfied with their health and functioning (e.g., current health status, ability to travel, and energy for daily activities). Significant correlations were found between total life satisfaction and age, New York Heart Association Functional classification, total number of daily medications, functional disability, symptom distress, stress, coping, helpfulness of heart transplant team interventions, health perception, expectation of transplant success, and overall quality of life. CONCLUSIONS: Eleven of 19 variables were significant predictors of higher quality of life in patients with advanced heart failure awaiting heart transplantation and accounted for 49% of explained variance: less symptom distress, better health perception, greater helpfulness of heart transplant team interventions, less stress, better coping ability, less functional disability, less use of fatalistic coping, older age, greater effectiveness of optimistic coping, being unemployed, and the expectation of transplant success.

Activities of Daily Living↗

PubMed2006

Sequence representation and prediction of protein secondary structure for structural motifs in twilight zone proteins.

Characterizing and classifying regularities in protein structure is an important element in uncovering the mechanisms that regulate protein structure, function and evolution. Recent research concentrates on analysis of structural motifs that can be used to describe larger, fold-sized structures based on homologous primary sequences. At the same time, accuracy of secondary protein structure prediction based on multiple sequence alignment drops significantly when low homology (twilight zone) sequences are considered. To this end, this paper addresses a problem of providing an alternative sequences representation that would improve ability to distinguish secondary structures for the twilight zone sequences without using alignment. We consider a novel classification problem, in which, structural motifs, referred to as structural fragments (SFs) are defined as uniform strand, helix and coil fragments. Classification of SFs allows to design novel sequence representations, and to investigate which other factors and prediction algorithms may result in the improved discrimination. Comprehensive experimental results show that statistically significant improvement in classification accuracy can be achieved by: (1) improving sequence representations, and (2) removing possible noise on the terminal residues in the SFs. Combining these two approaches reduces the error rate on average by 15% when compared to classification using standard representation and noisy information on the terminal residues, bringing the classification accuracy to over 70%. Finally, we show that certain prediction algorithms, such as neural networks and boosted decision trees, are superior to other algorithms.

Algorithms↗

PubMed1988

[Biochemical analysis of the cerebrospinal fluid in multiple sclerosis: study of various formulas].

Multiple sclerosis (MS) is often characterized by a intrathecal synthesis of immunoglobulins (Ig) in cerebrospinal fluid (CSF), which may be evaluated in several ways: ratio methods (IgG index, Schuller's or Tourtelotte's formulae) or demonstration of an oligoclonal distribution, or both. In a retrospective study, 256 CSF analyses were evaluated. The 4 parameters studied were disturbed in about the same proportions in each of the 3 MS subgroups of Mac Alpine's classification. An oligoclonal distribution is more rarely present in pathologies other than MS. None of these tests is specific for the diagnosis of MS. Haptoglobin index variations do not distinguish between the different groups of patients. From a physiopathological point of view, however, they may perhaps reveal an acute local inflammatory reaction, different from the immune reaction giving rise to the Ig synthesis.

Adult↗

PubMed2007

Single nucleotide polymorphism array analysis of cancer.

PURPOSE OF REVIEW: Classifying tumors and identifying therapeutic targets requires a description of the genetic changes underlying cancer. Single nucleotide polymorphism (SNP) arrays provide a high-resolution platform for describing several types of genetic changes simultaneously. With the resolution of these arrays increasing exponentially, they are becoming increasingly powerful tools for describing the genetic events underlying cancer. RECENT FINDINGS: The ability to map loss of heterozygosity (LOH) and overall copy number variations using SNP arrays is known. Techniques have recently been developed to map LOH at high resolution in the absence of paired normal data. Copy number variations described by SNP array studies are now reaching resolutions enabling the identification of novel oncogenes and tumor suppressor genes. The ability to determine allele-specific copy number changes has only recently been described. Moreover, SNP arrays offer a high-throughput platform for large-scale association studies that are likely to lead to the identification of multiple germline variants that predispose to cancer. SUMMARY: SNP arrays are an ideal platform for identifying both somatic and germline genetic variants that lead to cancer. They provide a basis for DNA-based cancer classification and help to define the genes being modulated, improving understanding of cancer genesis and potential therapeutic targets.

Chromosome Aberrations↗

PubMed2006

Genomic scale sub-family assignment of protein domains.

Many classification schemes for proteins and domains are either hierarchical or semi-hierarchical yet most databases, especially those offering genome-wide analysis, only provide assignments to sequences at one level of their hierarchy. Given an established hierarchy, the problem of assigning new sequences to lower levels of that existing hierarchy is less hard (but no less important) than the initial top level assignment which requires the detection of the most distant relationships. A solution to this problem is described here in the form of a new procedure which can be thought of as a hybrid between pairwise and profile methods. The hybrid method is a general procedure that can be applied to any pre-defined hierarchy, at any level, including in principle multiple sub-levels. It has been tested on the SCOP classification via the SUPERFAMILY database and performs significantly better than either pairwise or profile methods alone. Perhaps the greatest advantage of the hybrid method over other possible approaches to the problem is that within the framework of an existing profile library, the assignments are fully automatic and come at almost no additional computational cost. Hence it has already been applied at the SCOP family level to all genomes in the SUPERFAMILY database, providing a wealth of new data to the biological and bioinformatics communities.

Computational Biology↗

PubMedDate not supplied

An oligonucleotide probe derived from kDNA minirepeats is specific for Leishmania (Viannia).

Sequence analysis of Leishmania (Viannia) kDNA minicircles and analysis of multiple sequence alignments of the conserved region (minirepeats) of five distinct minicircles from L. (V.) braziliensis species with corresponding sequences derived from other dermotropic leishmanias indicated the presence of a sub-genus specific sequence. An oligonucleotide bearing this sequence was designed and used as a molecular probe, being able to recognize solely the sub-genus Viannia species in hybridization experiments. A dendrogram reflecting the homologies among the minirepeat sequences was constructed. Sequence clustering was obtained corresponding to the traditional classification based on similarity of biochemical, biological and parasitological characteristics of these Leishmania species, distinguishing the Old World dermotropic leishmanias, the New World dermotropic leishmanias of the sub-genus Leishmania and of the sub-genus Viannia.

Animals↗

PubMed2007

Relevance of Ras gene mutations in the context of the molecular heterogeneity of multiple myeloma.

Ras gene mutations are a recurrent genetic lesion in multiple myeloma (MM). Here, we report a mutation analysis of N- and K-Ras genes in purified plasma cell populations from a panel of 81 newly diagnosed MM patients stratified according to the most frequent genetic and molecular features associated with the neoplasia. Ras gene mutations, mostly involving the N-Ras gene, were detected in 20% of the patients. Ras mutations did not correlate with the presence of chromosome 13q deletion, trisomy of chromosome 11, 1q amplification or hyperdiploidy. In addition, despite an appreciable association with tumours overexpressing Cyclin D1, Ras mutations did not correlate at significant levels with any of the proposed groups in the TC classification, based on the presence of the major IgH chromosomal translocations and expression of Cyclin D genes. Finally, transcription analyses revealed the presence of differentially expressed transcripts in human multiple myeloma cell lines carrying the Ras gene mutations but not in primary tumours. Overall, these data suggest that Ras gene mutations are not likely to represent a master lesion in MM but its relevance needs to be considered in the context of other genetic abnormalities.

Adult↗

PubMed1986

Injury prediction in female gymnasts.

In order to identify injury-proneness in female competitive gymnasts, 20 measures of flexibility, hypermobility, spinal posture and anthropometry were performed on 40 competitive gymnasts and injury scores were derived from the severity and extent of previous gymnastic injury and inherent hypermobility traits. Results were compared between contrasting groups of "low" and "high" injury gymnasts respectively (both N = 10). Nine variables demonstrated significant differences between the "low" and "high" injury risk status groups namely, weight (p less than 0.001), height (p less than 0.001), age (p less than 0.001), mesomorphy (p less than 0.01), Quetelet Index (p less than 0.01), shoulder flexion (p less than 0.05) and lumbar extension (p less than 0.05), standing lumbar curvature and total peripheral flexibility score (both p less than or equal to 0.05). Multiple regression analysis was applied to determine the relative contribution of these variables to the estimation of injury-proneness as evidenced by previous history of injury and hypermobility traits. Using 9 independent variables, multiple regression yielded a multiple correlation coefficient (R) = 0.840, accounting for over 70% of the observed variance (R2 = 0.706) in injury scores among the total group of gymnasts. However, a subset of five variables, (weight, mesomorphy, standing lumbar curvature, age and height) yielded a multiple correlation coefficient (R) = 0.834 accounting for almost 70% of the observed variance (R2 = 0.696). This was not significantly different from the larger subset. Using injury classification system of "low", "medium", and "high" risk categories, comparisons were made between predicted and observed injury scores in the respective risk categories. In "high" risk and "low" risk gymnasts, injury scores could be classified correctly with 70% and 79% accuracy respectively, so that relative risk status could be determined from simple physical tests which may be employed by practitioners in the field.

Adolescent↗

PubMedDate not supplied

Characterization of BOLD activation in multi-echo fMRI data using fuzzy cluster analysis and a comparison with quantitative modeling.

A combination of multiple gradient-echo imaging and exploratory data analysis (EDA), i.e. fuzzy cluster analysis (FCA), is proposed for separation and characterization of BOLD activation in single-shot spiral functional magnetic resonance imaging (fMRI) experiments at 3 T. Differentiation of functional activation using FCA is performed by clustering pixel signal changes (DeltaS) as a function of echo time (TE). Further vascular classification is supported by the localization of activation and the comparison with a single-exponential decay model. In some subjects, an additional indication for large vessels within a voxel was found as oscillation of the fMRI signal difference vs echo time (TE). Such large vessels may be separated from small vessel activation and, therefore, our proposed procedure might prove useful if a more specific functional localization is desired in fMRI. In addition to the signal change DeltaS, DeltaT(2)*/T(2)* is significantly different between activated regions. Averaged over all eight subjects DeltaT(2)* is 1.7 +/- 0.2 ms in ROIs with the highest signal change characterized as containing large vessels, whereas in ROIs corresponding to microvascular environment average DeltaT(2)* values are 0.8 +/- 0.1 ms.

Brain↗

PubMed1986

Data sources for accident modelling.

The value of modelling for the study of accidents and for devising and assessing methods of prevention depends on the reliability of data sources. Police statistics are commonly used for accidents which cause death or injury. Several studies, however, show their deficiencies particularly for injury accidents of pedestrians and pedal cyclists. Hospital records give better information on injuries and diagnostic classification by the ICD code can be usefully improved by inclusion of the "E" (circumstance) detail. Insurance data can provide another source which is likely to be best for accidents involving multiple vehicles and damage to the property of third parties. The special "no fault" compensation system in New Zealand gives an unusually full source of data suitable for statistical analysis of accidents.

Accidents, Traffic↗

PubMed2006

Cyclic alternating pattern (CAP) alterations in narcolepsy.

BACKGROUND AND PURPOSE: Narcolepsy is a sleep disorder with clinical symptoms attributed to a reduced activation of the arousal system. Cyclic alternating pattern (CAP) is the expression of rhythmic arousability during non-rapid eye movement (NREM) sleep. CAP parameters, arousals and conventional sleep measures were studied in narcoleptic patients with cataplexy. PATIENTS AND METHODS: Data were collected from all-night polysomnographic (PSG) recordings and the multiple sleep latency test (MSLT) on the intervening day of 25 drug-naive patients (10 males and 15 females; mean age: 34+/-16 years) after adaptation and exclusion of other sleep disorders. A group of 25 age- and gender-matched normal sleepers were selected as controls. Each PSG recording was subdivided into sleep cycles. Analysis of CAP included classification of A phases into subtypes A1, A2, and A3. RESULTS: There was an increase in sleep period time mainly due to an increased wake time after sleep onset. REM latency was sharply reduced. The percentage of NREM sleep was slightly reduced and the balance between light sleep (S1+S2) and deep sleep (S3+S4) showed a curtailment of the former, while deep sleep was slightly increased. Excluding sleep cycles with sleep onset REM periods (SOREMPs), the duration of ordered sleep cycles was not different between narcoleptics and controls. The two groups showed similar values of arousal index, while CAP time, CAP rate, number of CAP cycles and of phase A subtypes (in particular subtypes A1) were significantly reduced in narcoleptic patients. CONCLUSIONS: The reduced periods of CAP in narcoleptic NREM sleep could be the electroencephalographic (EEG) expression of a generally reduced arousability or an increased strength of sleep-promoting forces in the balance between sleep and arousal systems. This can explain some of the clinical correlates of the disorder, i.e. excessive sleepiness, short sleep latency and impaired attentive performances, even without any sign of arousal-induced sleep fragmentation.

Adolescent↗

PubMed1999

Cytogenetic analysis and RAS mutations in primary myelodysplastic syndromes.

Cytogenetic analysis was performed in 60 patients with primary myelodysplastic syndromes--diagnosed, treated, and followed in our department. In 41 cases, the presence of the NRAS mutation was also evaluated. The aim of this study was to evaluate the prognostic value of chromosomal abnormalities and NRAS mutation. The median age of the patients was 67 years (18-88 years), and the French-American-British classification was as follows: refractory anemia 26, refractory anemia with ring sideroblasts 4, refractory anemia with excess of blast cells 15, refractory anemia with excess of blast cells in transformation 3, and chronic myelomonocytic leukemia 12. Survival analysis was performed for the patients with a normal (n = 35), an abnormal (n = 25) karyotype and with a single (n = 15) or multiple (n = 10) cytogenetic abnormalities. Abnormal karyotypes were detected in 25 of the 60 patients (41.6%). Fifteen of these patients had a single and 10 had two or more lesions. The median survival of the patients with a normal (33.1 months) and with an abnormal (36.5 months) karyotype was not significantly different. Patients with multiple lesions had a reduced median survival compared with patients with single anomalies (19.2 versus 39.7 months, p = 0.5). Patients with an abnormal karyotype progressed to acute leukemia more frequently compared with patients without lesions (36 versus 28.6%, p = 0.5). NRAS mutation was detected in 2 of 10 CMMoL patients studied and in none of the 31 patients with other types of myelodysplastic syndrome. Marrow blasts more than 10% significantly affected survival.

Adolescent↗

PubMed1978

Computer use in diagnosis, prognosis, and therapy.

Computers are used to influence diagnostic and therapeutic decisions. The computer's information-handling capabilities allow it to serve as a reliable extension of the physician's memory and expander of the physician's information and synthesized knowledge resources. Computers have been used to facilitate decisions through organization of patient data, improved classification of patients, decision analysis in clinical settings, and simulation of expert clinical reasoning. Computer programs are more successful in narrow, constrained, single arenas of medicine with much underlying pathophysiologic understanding and where decisions are based largely on hard laboratory data. New models of synthetic reasoning that simulate expert clinical behavior show promise of supporting complicated decisions concerning problems of multiple diseases. All systems are confronted by problems of consensus and authority of the underlying information used.

Computers↗

PubMed2006

Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer.

PURPOSE: Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity. EXPERIMENTAL DESIGN: Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose. RESULTS: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), >25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (>25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI <25, and for MPO, those with high BMI (>25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI <25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women. CONCLUSIONS: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment.

Adult↗

PubMed2006

Molecular characterization and typing of chicken and turkey astroviruses circulating in the United States: implications for diagnostics.

Avian astroviruses were detected by reverse transcriptase and polymerase chain reaction in intestinal contents collected from commercial chickens and turkeys from throughout the United States from 2003 through 2005. Astroviruses were detected in birds from both healthy and poorly performing flocks with or without enteric disease. Phylogenetic analysis was performed with sequence data from the polymerase (ORF-1b) genes of 41 turkey-origin astroviruses and 23 chicken-origin astroviruses. All currently available avian astrovirus sequence data and selected mammalian astrovirus sequence data were included in the analysis. Four groups of avian astroviruses were observed by phylogenetic analysis: turkey astrovirus type 1 (TAstV-1)-like viruses, turkey astrovirus type 2 (TAstV-2)-like viruses, both detected in turkeys; avian nephritis virus (ANV)-like viruses, detected in both chickens and turkeys; and a novel group of chicken-origin astroviruses (CAstV). Among these four groups, amino acid identity was between 50.1% and 73.8%, and was a maximum of 49.4% for all avian isolates when compared with the mammalian astroviruses. There were multiple phylogenetic subgroups within the TAstV-2, ANV, and CAstV groups based on 9% nucleotide sequence divergence. Phylogenetic analysis revealed no clear assortment by geographic region or isolation date. Furthermore, no correlation was observed between the detection of a particular astrovirus and the presence of enteric disease or poor performance. Based on these data, a revision of the present taxonomic classification for avian astroviruses within the genus Avastrovirus is warranted.

Animals↗

PubMed1990

DNA analysis in the diagnosis of infection and in the speciation of nematode parasites.

DNA analysis is playing an increasingly important role in characterising and classifying nematode parasites. Though less emphasis has been placed on utilising DNA elements to study nematodes of veterinary importance, correct diagnosis is, nevertheless, critical to proper treatment and control. The genus Trichinella presents a particularly interesting problem since the level of classification within this genus remains unclear. Herein we discuss the application of DNA analysis to the diagnosis and speciation of the parasitic nematode Trichinella spiralis, where the study of cloned repetitive DNA elements and ribosomal RNA genes has led to significant advances in the understanding of the species-level systematics of this nematode. Despite advances in the recognition of multiple gene pools within the genus Trichinella, their taxonomic level is still uncertain because of insufficient knowledge regarding intraspecific variation within this genus. The utility of mitochondrial DNA and ribosomal DNA sequence analysis in studying the phylogeny and evolutionary history of parasites within this genus is also discussed.

Animals↗