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Genetic characterization of APOB and D17S5 AFLP loci in a sample from the Basque Country (northern Spain).

VNTR polymorphism of AFLP loci D17S5 and APOB was analyzed in 100 unrelated individuals residing in the Basque Country by PCR amplification and polyacrylamide gel electrophoresis. Population parameters were estimated to validate these loci as routine markers in human identification. Thus, although both loci showed extensive polymorphism (with gene diversities of approximately 80% for both systems) and although concordance with Hardy-Weinberg equilibrium and linkage equilibrium was observed, comparisons with other populations displayed significant differences. Moreover, further analysis of neutral parameters limits this validation to D17S5 because APOB displays excesses of both the total number of alleles and the number of rare alleles; possible reasons for this discrepancy (presence of deleterious alleles, bottleneck effect, admixture, complexity of APOB polymorphism) are discussed.

Alleles↗

Breast cancer: pretreatment drug resistance parameters (GSH-system, ATase, P-glycoprotein) in tumor tissue and their correlation with clinical and prognostic characteristics.

BACKGROUND: The identification of new factors predicting relapse, outcome and response to systemic therapy in breast cancer is warranted. The measurement of biological markers such as drug resistance parameters (DRPs), which are part of the phenotype of malignant cells and contribute to resistance to anti-cancer drugs may be a possibility, which may ultimately lead to improvement of therapeutic results. PATIENTS AND METHODS: The level of glutathione (GSH), activities of glutathione-S-transferase (GST), glutathione-peroxidase (GPx), 06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) were measured in tumor and adjacent tumor free tissue samples from 89 consecutive, untreated females with breast cancer and correlated with clinical and prognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients, 22 patients had locally advanced (LABC) and 11 patients metastatic breast cancer. RESULTS: All DRPs showed significantly higher expression in tumor than in tumor free tissues. GPx was positively correlated with GST (r = 0.3, P = 0.0048) and with GSH (r = 0.5, P = 0.0001) in tumor as well as in normal tissue. GST activity was significantly higher in EBC than in LABC or metastatic breast cancer (P = 0.02). GSH level was significantly higher in grade 1 than in grade 2 or grade 3 tumors (P = 0.01). When clinical characteristics were related to the level of DRP, 'high' GSH was associated with age > 60 years (P = 0.01) in EBC, and with grade 1-2 tumors (P = 0.05) in LABC. No differences in OS were apparent between groups of 'high' and 'low' DRP-expression. However, the four-year estimated disease-free survival of EBC tended to be higher in patients with 'high' GST (P = 0.10) and of LABC in patients with 'high' GPx levels (P = 0.06). CONCLUSION: We conclude that 'high' levels of DRP in tumor tissue of breast cancer patients are part of the initial phenotype of the malignant cells. Due to its high prevalence (83% in EBC, 100% in primarily metastatic breast cancer), PGP did not add to prognostic information. High levels of GSH, GST and GPx were associated with favorable clinical characteristics and good prognosis, whereas low levels of GSH and GST activity were associated with more aggressive or more advanced disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Identification of twins from pure (single speaker) and hybrid (fused) syllables: an acoustic and perceptual case study.

This study describes a speaker-identification task carried out using two sets of single monosyllables and two sets of hybrid monosyllables prepared from monosyllabic words spoken by a set of monozygotic twins. The task was carried out by 6 listeners who were all very familiar with the twins and by the twins themselves. The identification scores for the pure syllables showed that both twins were identified with accuracy above chance; however, the percentage scores were less than perfect in both cases (71.4% and 72.9%). Analysis of the identification scores for the hybrid syllables showed that listeners had difficulty in attributing the hybrid syllables to a single twin. This was confirmed by the lack of significance in three binomial tests. The pure syllables were analysed acoustically to obtain a set of acoustic parameters for each twin. The results of the perceptual study are discussed with reference to the acoustic parameters. In addition, the implications of the study for issues in speaker identification are considered.

Adult↗

[Analysis of immunoglobulins and complement factors in synovial fluid and serum in rheumatoid arthritis, seronegative spondyloarthropathies and osteoarthritis: pathophysiology and retrospective analysis of clinical value].

UNLABELLED: Synovial fluid (SF) analysis was a mandatory investigation in rheumatological practice. In recent time, synovial fluid analysis lost importance predominantly due to unclear defined guidelines for the practical use. OBJECTIVE: To evaluate the clinical value of the determination of the complement components C'3c and C'4 and immunoglobulines IgG, IgA and IgM synovial fluid concentrations with regard to pathophysiology and currently used RA and SpA classification criteria. METHODS: Synovial fluid samples were obtained from 22 patients fulfilling ACR criteria for rheumatoid arthritis (RA), and 18 patients suffering from seronegative spondyloarthropathy (SpA) according to the ESSG criteria. Sixteen osteoarthritis (OA) SF samples were used as controls. IgG, IgA, IgM, C'3c and C'4 in SF and sera were determined by nephelometry. Comparison of the diseases, and linear as well as stepwise logistic regression analyses were performed in order to determine the interrelation of the determined parameters and a ranking of their diagnostic value for the identification of RA or SpA synovial fluids. RESULTS: SF-IgA, SF-IgG and SF-IgM concentrations were closely correlated with their corresponding serum levels (p < 0.01), while SF-C'3c and SF-C'4 depended on articular factors (p < 0.01). Determination of SF-C'3c (accuracy = 80.4%, improved chi 2 = 22.02, p < 0.001) and SF-C'4 (accuracy = 75.0%, improved chi 2 = 21.81, p < 0.001) both provided a good predictive value for the diagnosis of SpA when exceeding the cut off level of about 40 mg/dl (C'3c) or 15 mg/dl (C'4), respectively. Calculation of the C'-SF/S ratios did not provide an additional diagnostic benefit. SF-IgG, IgA and IgM as well as the calculated SF/S ratios were within the same range in RA and SpA fluids. CONCLUSIONS: SF concentration of complement components primarily depends on local articular factors. Significant differences of SF complement concentrations in established RA and SpA give reason for prospective analysis of these parameters in early undifferentiated oligoarthritis and evaluation in large studies, e.g. when re-evaluating the preliminary criteria for spondyloarthropathy.

Adult↗

The qualitative and quantitative determination of quinolones of first and second generation by capillary electrophoresis.

Capillary electrophoresis (CE) was applied to the study of 10 quinolones of first and second generation--nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, fleroxacin, and flumequine. Separation was performed on a fused silica capillary (75 microm-60 cm) using a phosphate buffer (pH 7.0, 125 mM). Detection was at 214 nm. Only norfloxacin and ciprofloxacin cannot be separated in this way. Because of the specificity of the method, the identification of the individual quinolones by their migration time was possible. The same system has been applied for the quantitative determination of quinolones in tablets and capsules. Excipients do not adversely affect the results. Some parameters (linearity, precision, accuracy) were validated. Especially the possibility of simultaneous quantification and identification of the active ingredient in the finished product is very attractive.

Electrophoresis, Capillary↗

[Transcranial Doppler study of sylvian vascular reactivity as affected by a calcium inhibitor. Preliminary results apropos of 28 cases].

The transcranial Doppler 2 MHz test, a new non-invasive investigatory method, allows direct instantaneous recording from middle cerebral artery in 96% of healthy subjects and, in contrast to classical means of measuring cerebral blood flow, the possibility of continuous monitoring of middle cerebral artery in bedridden patients or during operation. This transcranial pulsed Doppler (T.P.D.) test was used to study the effect of a calcium inhibitor, Nifedipine, on middle cerebral artery smooth muscle and its cerebrovascular effects in 28 subjects: 8 cases of hypertension, 9 of sylvian artery stenosis confirmed by arteriography (5 approximately equal to 30% and 4 greater than or equal to 50%) and 11 healthy volunteers. Recording of middle cerebral artery flow by T.P.D. was preceded by cervicocephalic continuous emission Doppler exploration (DMS, MIRA 4 MHz) and vascular echotomography (Duplex Sonedap 10 MHz). Recordings from the first segment of middle cerebral artery were obtained from a low frequency (2 MHz) and high power (maximum 350 mW) probe introduced facing squamous portion of temporal bone. Identification of this artery is dependent on its depth of access--average 5 cm--its response to homolateral carotid artery compression and the convergence of its flux towards the probe. After sublingual absorption of 2 to 3 capsules of Nifedipine, systolic and diastolic blood pressure and systolic and diastolic frequencies of middle cerebral activity were recorded regularly over 20 minutes with the patient at rest in dorsal decubitus. Variations in these parameters were considered significant when 10% or more. Criteria proposed for identification of middle cerebral artery stenosis were segmental acceleration of 3 kHz or more with or without associated turbulence (fig. 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Automatic classification and speaker identification of African elephant (Loxodonta africana) vocalizations.

A hidden Markov model (HMM) system is presented for automatically classifying African elephant vocalizations. The development of the system is motivated by successful models from human speech analysis and recognition. Classification features include frequency-shifted Mel-frequency cepstral coefficients (MFCCs) and log energy, spectrally motivated features which are commonly used in human speech processing. Experiments, including vocalization type classification and speaker identification, are performed on vocalizations collected from captive elephants in a naturalistic environment. The system classified vocalizations with accuracies of 94.3% and 82.5% for type classification and speaker identification classification experiments, respectively. Classification accuracy, statistical significance tests on the model parameters, and qualitative analysis support the effectiveness and robustness of this approach for vocalization analysis in nonhuman species.

Acoustics↗

The whale forgetting factor in recursive AR spectral analysis of heart rate variability signals.

Spectral parameters extracted from the heart rate variability signal are obtained on a beat-to-beat basis by means of autoregressive recursive identification. In this paper a whale forgetting window is introduced, instead of the classical exponential one, in order to reduce the noise influence on the estimated parameters. After proper simulation it was found that the whale forgetting window markedly reduces the noise in the identification, but maintains a good response to abrupt changes in the signal. The algorithm was thus applied to the analysis of the HRV data recorded during different transient situations in physiological and pathological conditions. The spectral parameters were obtained on a beat-to-beat basis and their trends were smoother and more accurate with respect to the traditional exponential window also in presence of noise or artifacts in the time series (sudden and short time changes, ectopic beats, etc.), without losing the signal variations of physiological interest.

Adult↗

Analyte identification in capillary electrophoretic separation techniques.

A review on applications of on-line hyphenation in capillary electrophoresis and capillary electrochromatography for the identification of migrating analytes is presented. There is an urgent need for unambiguous analyte identification by combining spectral information and observed migration times, because the parameters influencing the migration times and separation efficiencies in these separation techniques are not easily controlled, especially when real samples containing unknown interferences have to be analyzed. The spectrometric techniques covered here are ultraviolet and visible radiation (UV/Vis) absorption, fluorescence including fluorescence line-narrowing spectroscopy, Raman spectroscopy, nuclear magnetic resonance and mass spectrometry. Attention is essentially confined to literature reports in which the extra information provided by the detector is really used for identification purposes, especially in real-life samples, while the interfacing as such and analyte detectabilities in standard solutions are only briefly discussed. This article covers an extensive fraction of the literature published on this topic until the beginning of 1998.

Electrophoresis, Capillary↗

World Wide Web-based system for the calculation of substituent parameters and substituent similarity searches.

Easy to use, interactive, and platform-independent WWW-based tools are ideal for development of chemical applications. By using the newly emerging Web technologies such as Java applets and sophisticated scripting, it is possible to deliver powerful molecular processing capabilities directly to the desk of synthetic organic chemists. In Novartis Crop Protection in Basel, a Web-based molecular modelling system has been in use since 1995. In this article two new modules of this system are presented: a program for interactive calculation of important hydrophobic, electronic, and steric properties of organic substituents, and a module for substituent similarity searches enabling the identification of bioisosteric functional groups. Various possible applications of calculated substituent parameters are also discussed, including automatic design of molecules with the desired properties and creation of targeted virtual combinatorial libraries.

Chemistry, Organic↗

Automated methods for improved protein identification by peptide mass fingerprinting.

In order to maximize protein identification by peptide mass fingerprinting noise peaks must be removed from spectra and recalibration is often required. The preprocessing of the spectra before database searching is essential but is time-consuming. Nevertheless, the optimal database search parameters often vary over a batch of samples. For high-throughput protein identification, these factors should be set automatically, with no or little human intervention. In the present work automated batch filtering and recalibration using a statistical filter is described. The filter is combined with multiple data searches that are performed automatically. We show that, using several hundred protein digests, protein identification rates could be more than doubled, compared to standard database searching. Furthermore, automated large-scale in-gel digestion of proteins with endoproteinase LysC, and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis, followed by subsequent trypsin digestion and MALDI-TOF analysis were performed. Several proteins could be identified only after digestion with one of the enzymes, and some less significant protein identifications were confirmed after digestion with the other enzyme. The results indicate that identification of especially small and low-abundance proteins could be significantly improved after sequential digestions with two enzymes.

Animals↗

[Possibilities of ultrasonic estimation of gestational age in the second and third trimesters of pregnancy].

A total of 351 females with physiological pregnancies repeatedly (1928 examinations) underwent ultrasonic fetometry. The investigations revealed clear-cut correlations between the term of gestation and biometric parameters such as the mean diameter of the fetal head, abdomen, heart as well as the length of its foot, femur and humerus. The average mistake in the identification of pregnancy terms which was performed on the basis of simultaneous analysis of the parameters considered was 5.73 days in all terms of gestation.

Anthropometry↗

Cues and strategies for color constancy: perceptual scission, image junctions and transformational color matching.

The identification of objects, illuminants, and transparencies are probably the most important perceptual functions of color. This paper examines the effects of perceptual scission, image junctions, color adaptation, and color correlations on identification. Simulations of natural illuminants, materials, and filters were used in a forced-choice procedure to simultaneously measure thresholds for identifying filters and objects across illuminants, and discrimination thresholds within illuminants. In the vast majority of the cases, if observers could discriminate within illuminants they could identify across illuminants. Since results were similar for identical color distributions, whether transparency cues like X-junctions were present or not, the primary cues for color identification were systematic color shifts across illuminants. These color shifts can be well described by three-parameter affine transformations, and the parameters can be derived from differences and ratios of mean chromaticities. A strategy based on post-transformation color matching predicts generally accurate identification despite perceptible color shifts, and also provides plausible reasons for those few conditions where identification thresholds are significantly higher than discrimination thresholds.

Color Perception↗

Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases.

Adult chronic myelomonocytic leukemia (CMML), as defined by the French-American-British (FAB) group, is associated with a variable survival, ranging from a few weeks to several years. From 1971 to 1986, we made the diagnosis of CMML in 107 cases, according to FAB criteria (except for patients with 20% to 30% bone marrow [BM] blasts who were also included). Median survival was 30 months (range 1 to 81 months) and life expectancy did not seem to be influenced by treatment modalities other than supportive care. Eighteen patients (17%) progressed to acute nonlymphoblastic leukemia (ANLL). In a Cox regression model, main factors associated with short survival were: an excess of marrow blasts (P = 10(-6], anemia (P = .17 x 10(-5], high peripheral blood (PB) monocytosis (P = .26 x 10(-5], presence of PB blasts (P = .49 x 10(-4], and to a lesser extent hyperleukocytosis (P = .001), presence of PB immature granulocytes, thrombopenia, and splenomegaly. Survival (less than 1 year v greater than 1 year) could be predicted at diagnosis in a multivariate stepwise discriminant analysis using two parameters only (percentage of BM blasts and hemoglobin level), with 82% accuracy. Among patients surviving greater than 1 year, initial PB leukocyte count was higher in patients with intermediate survival (12 to 42 months) than in long survivors (greater than 42 months) and was the only discriminating factor between these two subgroups in multivariate analysis. Abnormal cytogenetic findings and increased lysozymuria were also poor prognostic factors, but could not be analyzed in the multivariate models, as they were determined in a minority of patients. Parameters associated with subsequent progression to ANLL included younger age at diagnosis, thrombopenia, increased BM blasts, and splenomegaly. Our study allows for the identification of subgroups with different prognoses in CMML, on the basis of a small number of hematologic parameters, particularly initial percentage of BM blasts, hemoglobin level, and leukocytosis. These subgroups probably require different therapeutic approaches.

Aged↗

A new HLA-DRB1 allele within the DRw52 supertypic specificity (DRw13-DwHAG): sequencing and direct identification by oligonucleotide typing.

Molecular analysis of HLA class II polymorphism represents a crucial parameter for HLA matching in transplantation immunology, for the study of HLA-disease association and for the understanding of major histocompatibility complex (MHC)-restricted antigen presentation. We report here the DNA sequence and the deduced amino acid sequence of the polymorphic first domain exon of the DRB1 and DRB3 alleles of the homozygous cell line HAG (DRw13-DwHAG-DQw7). The DRB1 sequence represents a new DRB allele, which clearly shows a close relationship to other DRB1 genes from the DRw52 group and is now officially named DRB1* 1303. The DRB1* 1303 allele is very similar to the two DRw13 alleles we have described earlier, with only five amino acid differences at positions 32, 37, 47, 57 and 71. Furthermore, its sequence in the third hypervariable region is unique among all known DRB1 and DRB3 alleles. The sequence of the DRB3 gene of HAG shows that it corresponds to the previously described DRB3* 0101 (DRw52a) allele. In addition we present analyses of a panel of healthy blood donors and leukemic patients by oligonucleotide typing showing that this new HLA-DR specificity can now be unequivocally identified in routine oligotyping with an allele-specific oligonucleotide probe.

Alleles↗

Clinical significance of alcohol intake parameters at initiation of drinking.

A considerable effort is now being focused upon the identification in young adulthood of predictive variables that can be used to detect individuals at risk for developing future alcohol problems. One goal is that such individuals may be targeted for early intervention efforts aimed at preventing the development of serious alcohol-related problems. Another goal is to extend the understanding of the etiology of alcoholism by identifying physiological and behavioral mechanisms underlying the addictive process. Reviewed below are efforts focused upon the importance and predictive value of the response to early exposures to ethanol, including alcohol intake variables at onset of drinking.

Adolescent↗