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Morphometry, densitometry and pattern analysis of plastic-embedded histologic material from urothelial cell carcinoma of the bladder.

An image analysis method of grading histologic sections of bladder carcinoma was tested. The method was new in four respects. First, for fixation of the biopsies a coagulant fixative was used. Second, 2-microns plastic sections were used to ensure the reproducibility of nuclear imaging. Third, a new stereologic approach was used for calculation of the nuclear volume and DNA content. Fourth, for the classification rule the morphometric, densitometric and texture features were used in concert. The IBAS 2000 instrument was used for the measurements. Texture analysis of the chromatin patterns was performed using Markovian texture features. Using discriminant analysis, of 22 parameters, 2 morphometric, 2 densitometric and 3 texture features were selected for the classification rule. With them, 89% of the bladder carcinomas were correctly classified into the three grades. All grade III tumors were classified correctly. Among the features tested, the densitometry of the DNA had the highest F values. All of the grade III tumors and 45% of the grade II tumor group had DNA histograms indicating aneuploidy. This study showed that plastic-embedded material is well suited to morphometry and densitometry and can be used for quantitative grading of bladder carcinoma.

Carcinoma, Transitional Cell↗

Dispersion of single-walled carbon nanotubes of narrow diameter distribution.

The dispersibility and bundle defoliation of single-walled carbon nanotubes (SWNTs) of small diameter (<1 nm) have been evaluated on CoMoCAT samples with narrow distribution of diameters. As previously observed by photoluminescence and Raman spectroscopy, the CoMoCAT sample exhibits a uniquely narrow distribution of (n,m) structures that remains unchanged after different dispersion conditions. This narrow distribution allowed us to develop a method for quantifying the dispersability of the samples from their optical absorption spectra in terms of two ratios: the "resonance ratio" and the "normalized width." The former is defined as the quotient of the resonant band area and its nonresonant background. The latter is defined as the ratio of the width of the band at half-height to the peak height on a spectrum that has been normalized at 900 nm, making this an intensive property, rather than varying with the path length. In this study of the CoMoCAT sample, we have used the S22 transition corresponding to the (6,5) nanotube to do these calculations, which is the most abundant species. These two ratios provide a quantitative tool to compare different dispersion parameters (time of sonication, degree of centrifugation, etc.) on the same type of sample. From this comparison, an optimal procedure that maximizes the spectral features was selected; this procedure allowed us to contrast various surfactants at different pH values and concentrations. Several surfactants were as good or even better than the one we have used in previous studies, dodecylbenesulfonic acid sodium salt (NaDDBS). Despite differences in their dispersion abilities, none of the surfactants investigated generated new features in the absorption spectra nor changed the distribution of nanotube types, which confirms that the high selectivity of the CoMoCAT sample is in the original sample rather than caused by selective suspension of specific (n,m) nanotubes.

Nanotubes, Carbon↗

A rapid method for diagnosing regional metastases of papillary thyroid cancer with morphometry.

Morphometry of the lymphoid cells was performed with a computerized image analyzer. Database formation was performed automatically using our own new software. The initial database of calculated mean values, of constructed histograms, of regression, and of discriminant analysis was transformed into a set of morphometric features. Eight morphometric features were selected for characterizing two separate populations of the lymphoid cells: one from the lymph node tissue with a malignant tumor and the other without any tumor (control). The eight features ensured the least overlap between the two groups of lymphoid cells. The eight features formed the basis of the decision criteria for identifying a patient with a malignant pathology. A weighting coefficient was calculated for each feature. It was ascertained that the presence of the regional papillary thyroid cancer metastases causes significant changes in the relationship between small (diameter </= 7.5 mum) and large (>7.5 mum) lymphoid cells of the cervical lymph nodes. The morphometric changes were assessed by our diagnostic index. The expert diagnostic system was developed on the basis of a set of quantitative features and their boundary values. This system highlights the morphometric changes in the population of the cervical lymph nodes lymphoid cell with metastases versus control. Clinical trials have shown that the expert diagnostic system's conclusions coincided with the histological diagnosis in all the cases. The expert diagnostic system, image processing, database formation, assessment of lymphoid cells morphometric features formed the basis of the rapid method of diagnosing regional metastases of papillary thyroid cancer. The diagnosis was performed in automatic mode. Taking into account that about 30-50% of aspiration smears contain only blood cells (absence of specialized cells such as thyrocytes), the use of our method should greatly improve the cytologic diagnosis of regional metastases of papillary thyroid cancer.

Carcinoma, Papillary↗

Adaptive texture feature extraction with application to ultrasonic image analysis.

Computer texture analysis methods use texture features that are traditionally chosen from a large set of fixed features known in literature. These fixed features are often not specifically designed to the problem at hand, and as a result they may have low discriminative power, and/or may be correlated. Increasing the number of selected fixed features is statistically not a good solution in limited data environments such as medical imaging. For that reason, we developed an adaptive texture feature extraction method (ATFE) that extracts a small number of features that are tuned to the problem at hand. By using a feed-forward neutral network, we ensure that even nonlinear relations are captured from the data. Using extensive, repeated synthetic ultrasonic images, we compared the performance of ATFE with the optimal feature set. We show that the ATFE method is capable of robust operation on small data sets with a performance close to that of the optimal feature set. Another experiment confirms that our ATFE is capable of capturing nonlinear relations from the dataset. We conclude that our method can improve performance in practical, limited dataset situations where an optimal fixed feature set can be hard to find.

Artificial Intelligence↗

Peripheral vision and oculomotor control during visual search.

The present study concerns the dynamics of multiple fixation search. We tried to gain insight into: (1) how the peripheral and foveal stimulus affect fixation duration; and (2) how fixation duration affects the peripheral target selection for saccades. We replicated the non-corroborating results of Luria and Strauss (1975) ('Eye movements during search for coded and uncoded targets', Perception and Psychophysics 17, 303-308) (saccades were selective), and Zelinsky (1996) (Using eye movements to assess the selectivity of search movements. Vision research 36(14), 2177-2187) (saccades were not selective), by manipulating the critical features for peripheral selection and discrimination separately. We found search to be more selective and efficient when the selection task was easy or when fixations were long-lasting. Remarkably, subjects did not increase their fixation durations when the peripheral selection task was more difficult. Only the discrimination task affected the fixation duration. This implies that the time available for peripheral target selection is determined mainly by the discrimination task. The results of the present experiment suggest that, besides the difficulty of the peripheral selection task, fixation duration is an important factor determining the selection of potential targets for eye movements.

Adult↗

3D presentation of the nuclear cell features in quantitative cytometry.

The use of an image cytometer in analysis of smears and needle aspirates provides valuable information to a cytologist. It allows to combine the overall impression, formed by visually inspecting the cells, with measured and numerically expressed nuclear cell features. Both types of information can be used efficiently only if presented to the expert in an appropriate way. Cell images (as they are seen with a microscope) are easily analysed by the experts. However, measured nuclear features can not be presented as a list of numerical values. Instead, an user interface should be developed, providing graphical presentation of the nuclear features. It should show as much information as possible and provide a comprehensive link between nuclear features and cell images. The user interface described in this paper shows nuclear features in three dimensions. It is based on a perspective projection of the three dimensional feature space onto a two dimensional surface. It allows the user to dynamically change the perspective, i.e., to look at the virtual three dimensional structure from different viewpoints. Each nucleus is represented by a single object in the three dimensional space. When an object in the three dimensional feature space is selected, the image (or the visual appearance) of the corresponding cell is shown. When a nucleus image is selected, its position in the feature space is highlighted. This provides an interconnection between nuclear cell features and cell images allowing simultaneous analysis of both types of information.

Cell Nucleus↗

Sex dimorphism in development dynamics and in development progression of morphological features in human foetuses.

The study material comprised 3889 foetuses of both sexes, aged 20-42 weeks. t-Student test has been applied to evaluate the existence of potential sex-dependent differentiation of developmental trends as assessed by weekly measurements of selected somatic features and by the weight of internal organs. The regression coefficients of the analysed variables have been compared against the opposite sex. The rate of development of the analysed features in consecutive weeks has been found to be sex-related. Highest sex-related differences have been observed for the total body weight and for the weight of internal organs, with the exception of the adrenals, and the differences have been significant enough to justify the existence of contrasting, sex-dependent patterns of development of the analysed variables. The development of the analysed morphological features has been depicted by curvilinear regression. When described by various degree polynomials the development course of the analysed features displays sex-related differences. Only the change in the weight of the adrenals is similar for both sexes. The evaluation of the developmental advancement of the analysed features has revealed that they are usually at a more advanced development level in female foetuses.

Body Height↗

A multicenter comparison of related pharmacologic features of cephalexin and dicloxacillin given for two months to young children with cystic fibrosis.

Twenty-one cystic fibrosis patients under 3 years of age were enrolled in an open multicenter study to assess the feasibility of the study design and to compare selected pharmacologic features of cephalexin or dicloxacillin administered orally for 2 months. Patient tolerance and compliance were significantly less for dicloxacillin (p less than .01 and p less than .001, respectively). Superficial Candida infections were more common in the cephalexin group (p = 0.02), however increased stool frequency and nonspecific diaper rashes were more prevalent in patients receiving dicloxacillin (p less than .05). Staphylococcus aureus was isolated from respiratory secretions after 2 months from two dicloxacillin and no cephalexin patients. Areas under the curve and peak serum concentrations were higher for cephalexin (p less than .05 and p = .02), but antistaphylococcal activity in serum was higher for dicloxacillin (p less than .05) due to a lower mean MIC compared to cephalexin. Deep pharyngeal plus routine throat culture yielded more pathogens than either method alone. Express mail and central processing of respiratory specimens was efficient for most organisms, however there was some loss of Streptococcus pneumoniae and Haemophilus influenzae. Cephalexin was associated with better patient acceptance and compliance despite higher rates of superficial fungal infections as compared to dicloxacillin. Cephalexin, routine bacteriologic throat swabs processed locally or centrally, mail-in urine compliance assessment and a multicenter design are feasible components for a long-term prospective evaluation of antibiotic prophylaxis in patients with cystic fibrosis.

Administration, Oral↗

Evans' syndrome in IgA deficiency. Episodic autoimmune haemolytic anaemia and thrombocytopenia during a 10 years observation period.

A 26-year-old male with a 10-year history of complete selective IgA deficiency and recurrent autoimmune anaemia and thrombocytopenia (Evans syndrome) is presented. Both serum IgA and saliva secretory IgA were below the detection limit (less than 0.05 mg/l). No other features of autoimmunity were seen. The patient had a normal % of peripheral blood lymphocytes with surface IgM and IgG cells and normal in vitro lymphocyte transformation after stimulation with mitogens and antigens. The pleomorphic and randomly appearing immunologic features of selective IgA deficiency are emphasized by the present case.

Adolescent↗

Peripheral selection of antigen receptor junctional features in a major human gamma delta subset.

Recent studies demonstrating the existence of murine gamma delta T cell subsets with structurally identical T cell receptors (TcR) suggest that unlike alpha beta T cells, some gamma delta T cells are specialized in the recognition of a limited number of monomorphic antigens. However, this question still remains open in humans, since the TcR structural diversity of their peripheral gamma delta T cells was shown to be extensive. Here we have analyzed in detail the TcR chain genes expressed by human V gamma 9+V delta 2+ peripheral blood lymphocytes (PBL), a major peripheral gamma delta T cell subset in adults and present evidence for an antigen-driven peripheral selection of both TcR gamma and delta junctional motifs among these cells. First, it is shown that the proportion of V gamma 9+V delta 2+ cells expressing the V9JPC1 gamma chain is much higher among PBL than among thymus-derived clones, indicating that preferential use of this J gamma segment is not due to pairing or combinatorial constraints. Second, analysis of V9JPC1 gamma transcripts derived from V gamma 9+V delta 2+ PBL clones revealed a high prevalence of a unique V9JP gamma sequence with limited "N" nucleotide additions and VJ trimming, which could not be accounted for by enzymatic or antigen-independent structural limitations. Third, the TcR delta chain expressed by most V gamma 9+V delta 2+ PBL clones, though diverse in amino acid composition and length, carried a highly distinctive junctional motif, found at a much lower frequency among V2DJ delta sequences derived from V gamma 9-V delta 2+ PBL or V gamma 9+V delta 2+ thymocytes. Together, these results which demonstrate shared gamma and delta junctional features by cells using unique V gamma and V delta genes, suggest that in vivo selection of V gamma 9+V delta 2+ lymphocytes is mediated by a highly restricted number of nominal ligands.

Amino Acid Sequence↗

Spectral analysis of cervical cells using the discrete Fourier transform.

This paper contains results from a preliminary study of spectral analysis techniques applied to the classification of cervical cells from routinely prepared Papanicolaou cervical smears. Experiments were conducted using a subset of 110 normals and 110 dyskaryotic single cell images randomly selected from a larger cell image data base. An assessment was made of the contribution of different regions within a cell image to the frequency spectrum. Three image sets were used, the original image itself plus two derived from it. In the first derived set, only nuclear size and shape were used. In the second set nuclear morphology and texture were included. Nuclear masking was performed using an interactive segmentation procedure. The discrete Fourier transform was applied to each image in the three image sets and classification experiments were performed using 80 features derived from the frequency spectra. An optimum set of features was selected for each experiment by canonical analysis. Good classification results were obtained when features extracted solely from nuclear shape were used. The inclusion of information relating to nuclear texture improved the results. However, inclusion of the extra nuclear region degraded the classifier's ability to discriminate between cell groups.

Cervix Uteri↗

Ambient noise and the design of begging signals.

The apparent extravagance of begging displays is usually attributed to selection for features, such as loud calls, that make the signal costly and hence reliable. An alternative explanation, however, is that these design features are needed for effective signal transmission and reception. Here, we test the latter hypothesis by examining how the begging calls of tree swallow (Tachycineta bicolor) nestlings and the response to these calls by parents are affected by ambient noise. In a field study, we found that call length, amplitude and frequency range all increased with increasing noise levels at nests. In the laboratory, however, only call amplitude increased in response to the playback of noise to nestlings. In field playbacks to parents, similar levels of noise abolished parental preferences for higher call rates, but the preference was restored when call amplitude was increased to the level that nestlings had used in the laboratory study. Our results show that nestling birds, like other acoustic signallers, consistently increase call amplitude in response to ambient noise and this response appears to enhance discrimination by receivers. Thus, selection for signal efficacy may explain some of the seemingly extravagant features of begging displays.

Acoustics↗

A smart magnetic resonance contrast agent for selective copper sensing.

We describe the synthesis and properties of Copper-Gad-1 (CG1), a new type of smart magnetic resonance (MR) sensor for selective detection of copper. CG1 is composed of a gadolinium contrast agent core tethered to copper-selective recognition motif. Cu2+-induced modulation of inner-sphere water access to the Gd3+ center provides a sensing mechanism for reporting Cu2+ levels by reading out changes in longitudinal proton relaxivity values. CG1 features good selectivity for Cu2+ over abundant biological cations and a 41% increase in relaxivity upon Cu2+ binding and is capable of detecting micromolar changes in Cu2+ concentrations in aqueous media.

Contrast Media↗

The structure of an RNA/DNA hybrid: a substrate of the ribonuclease activity of HIV-1 reverse transcriptase.

The structure of a complementary hybrid duplex of RNA and DNA has been determined by X-ray crystallography. A ten residue DNA oligonucleotide of sequence 5'-G-G-C-G-C-C-C-G-A-A-3' was annealed to complementary RNA (5'-u-u-c-g-g-g-c-g-c-c-3') and crystallized, producing tetragonal crystals that diffract to 2.3 A resolution. The hybrid adopts a geometry that is neither strictly A nor B-form, rather the helix possesses qualities of both, reminiscent of spectroscopic descriptions of a hybrid conformation, or H-form. All of the ribonucleotides maintain the C3'-endo conformation seen in A-form, while both C3'-endo and C2'-endo conformations are found in the deoxyribonucleotides. The minor groove width (8.5 to 10.5 A) is intermediate between standard values for A (11 A) and B-form (7.4 A) DNA. The global parameters rise and base-pairs tilt (or inclination) are like that of A-DNA, however the slide and x displacement (Dx) are more like that of A-RNA, thus giving the hybrid a unique conformation. In addition, the 10-mer crystallizes in a manner that allows the formation of dimers that stack end-to-end, thereby providing a glimpse of how an extended (20 base-pair) helix of RNA-DNA hybrid might appear. This duplex sequence was selected for study because it is specifically recognized by the ribonuclease H function of HIV reverse transcriptase. A structure of a substrate of this enzyme is of potential value in understanding requirements for the selectivity of this important drug target. The minor groove of the hybrid duplex, lined with the 2-OH of the ribose rings, is the single distinguishing characteristic of the RNA/DNA hybrid, undoubtedly an important structural feature conferring selectivity.

Crystallography, X-Ray↗

Accuracy of screening for inhalational anthrax after a bioterrorist attack.

BACKGROUND: Bioterrorism using anthrax claimed five lives in the United States in 2001 and remains a potential public health threat. In the aftermath of a large-scale anthrax attack, mass screening to identify early inhalational anthrax may improve both the management of individual cases and the efficiency of health resource utilization. PURPOSE: To develop the evidence base for outpatient anthrax screening protocols by quantifying differences in clinical presentation between inhalational anthrax and common viral respiratory tract infections. DESIGN: Review, compilation, and data extraction from English-language case reports of inhalational anthrax and epidemiologic studies of influenza and other viral respiratory infections. DATA SOURCES: 13 reports of 28 cases of inhalational anthrax from 1920 to 2001 and 5 studies reporting on the clinical features of 2762 cases of influenza and 1932 cases of noninfluenza viral respiratory disease. DATA SYNTHESIS: Characterization of presenting clinical symptoms in anthrax and viral disease and calculation of likelihood ratios for the presence of selected clinical features. RESULTS: Fever and cough do not reliably discriminate between inhalational anthrax and viral respiratory tract infection. Features suggestive of anthrax include the presence of nonheadache neurologic symptoms (positive likelihood ratio cannot be calculated), dyspnea (positive likelihood ratio, 5.3 [95% CI, 3.7 to 7.4]), nausea or vomiting (positive likelihood ratio, 5.1 [CI, 3.0 to 8.5]), and finding of any abnormality on lung auscultation (positive likelihood ratio, 8.1 [CI, 5.3 to 12.5]). In contrast, rhinorrhea (positive likelihood ratio, 0.2 [CI, 0.1 to 0.4]) and sore throat (positive likelihood ratio, 0.2 [CI, 0.1 to 0.5]) are more suggestive of viral respiratory tract infection. CONCLUSION: Inhalational anthrax has characteristic clinical features that are distinct from those seen in common viral respiratory tract infections. Screening protocols based on these features may improve rapid identification of patients with presumptive inhalational anthrax in the setting of a large-scale anthrax attack.

Anthrax↗

Percutaneous mitral balloon valvotomy and the new demographics of mitral stenosis.

OBJECTIVE: This review discusses the latest developments in selected clinical features and catheter-based therapy of mitral stenosis. DATA SOURCES: English-language journal articles and reviews in the clinical and epidemiological literature as related to mitral valve stenosis from 1965 through March 1993, identified by bibliography review and expert consultation. STUDY SELECTION: Selected studies included clinical trials with adequate patient population description and short- and long-term (5 years) follow-up for topics related to mitral valve stenosis in the clinical literature. DATA EXTRACTION: Two reviewers participated in extracting the data with the aim of presenting a balanced and comprehensive review of the subject. DATA SYNTHESIS AND CONCLUSIONS: The main conclusions are (1) mitral stenosis should no longer be viewed as a largely "geriatric disease" in the United States due to a recent inflow many young immigrants from countries where rheumatic fever continues partially or wholly unabated; (2) clinical and anatomical features of mitral stenosis are age-dependent; when clinical presentation occurs at 30 vs 70 years of age, for example, the degree of valve obstruction may be similar but differences exist in the frequency of atrial fibrillation, the magnitude of reduction in cardiac output, the degree of valve deformity and calcification, and the frequency of coexistent coronary artery disease; and (3) mitral stenosis therapy has undergone a reorientation with the introduction of percutaneous mitral balloon valvotomy, which has proven to be safe, cost-effective, and to provide short- and long-term improvements in symptomatic and hemodynamic status in selected patients.

Catheterization↗

[Thrombolytic drugs in acute myocardial infarct].

Thrombolytic therapy has a primary role in modifying evolving acute myocardial infarction by restoration of patency of infarct-related artery. All thrombolytic agents convert plasminogen to plasmin; 3 of them (streptokinase, urokinase and anisoylated human plasminogen streptokinase activator complex-APSAC) are not specific for fibrin and 2 (rt-PA, scu-PA) are relatively clot-specific and have limited systemic fibrinolytic activity. To date, the largest experience has been with streptokinase, which is derived from streptococci and therefore has the potential to cause allergic reactions, more frequent with repeat doses of the drug. Streptokinase is not clot-selective; despite significant systemic fibrinolysis, which is an usual consequence, major bleeding complications are uncommon. Another problem with streptokinase is hypotension, which depends on infusion rate. APSAC differs from the parent streptokinase-plasminogen complex with kinetics well suited to a sustained thrombolytic effect. Although it was expected to have clot selectivity, this feature is missed at the dose needed in the treatment of acute myocardial infarction. rt-PA is a natural occurring serum protease which presents important clot specificity with limited systemic fibrinolytic activity. However, the risk of major bleeding is not less than that observed with thrombolytic agents without clot selectivity. Of considerable interest is the potential for urokinase and prourokinase to act synergistically with other thrombolytic agents, with hypothetic improvement in efficacy and safety of thrombolytic therapy. Despite some different features among various thrombolytic agents, they are equally safe and effective in salvaging myocardium and in assuring survival benefit after acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anistreplase↗