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At least 289 records · Page 16Linked to original sources
PubMed1989

Localization of cutaneous lesions in digital images.

Digital imaging could potentially provide a rapid, objective, and quantitative means of detecting changes in important skin conditions, especially the dysplasic nevus syndrome. Image analysis techniques can be applied to digital images to automate the search for changes in moles or other features. Consistent determination of lesion boundaries, perimeter, and area in digital images is a vital first step in this process. In this paper, we show how bilaterally symmetric Laplacian-of-a-Gaussian filters can be used to recover the borders of selected lesions while remaining robust with respect to factors such as the camera point spread function and additive noise. Tests on real and synthetic images demonstrate that lesion borders, area, and perimeter can be obtained with a high degree of reliability. Boundaries are routinely found to within +/- 0.2 pixels, and area and perimeter measurements vary by less than 10% when imaging spot targets and actual cutaneous lesions under a realistic range of experimental conditions.

Dysplastic Nevus Syndrome↗
PubMed1983

Teleonomical optimization of a fractal model of the pulmonary arterial bed.

Modeling the pulmonary arterial tree (PAT) is considered here as an optimal synthesis problem. Firstly, a class of candidate models is specified: the three-dimensional symmetric dichotomous fractal trees of elastic tubes described by Womersley's equations. Secondly, the parameters are shown to be constrained by interactions of PAT with the rest of the body; these constraints are used to limit the volume of the parametric space to which attention will be directed in the synthesis step. Thirdly, a teleonomical hypothesis is proposed: a naturally selected PAT must have a minimal input impedance under conditions keeping total arterial volume and distensibility as small as possible. This hypothesis is translated in mathematical terms and the resulting cost-function minimized in the limited parametric volume. The optimal model has parameter values and an impedance spectrum corresponding satisfactorily with real data. Moreover this model gives a clear picture of the internal hemodynamic behavior of PAT as an impedance matching device.

Blood Flow Velocity↗
PubMed1988

In vivo stimulation and restoration of the immune response by the noninflammatory fragment 163-171 of human interleukin 1 beta.

The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, showed in vivo immunomodulatory capacities qualitatively and quantitatively comparable to those of the mature human IL-1 beta protein. In fact, both IL-1 beta and the 163-171 fragment stimulated the immune response of normal mice and restored immune reactivities of immunocompromised animals. In addition, the synthetic IL-1 peptide was as efficient as the entire protein in inducing tumor rejection and radioprotection. On the other hand, the 163-171 fragment did not cause any of several inflammation-associated metabolic changes inducible by the whole IL-1 beta molecule in vivo: hypoferremia, hypoglycemia, hyperinsulinemia, increase in circulating corticosterone, SAA and fibrinogen, decrease in hepatic drug-metabolizing enzymes. Furthermore, at variance with IL-1 beta, the 163-171 peptide did not show the toxic effects causing shock and death in adrenalectomized mice. Thus, these results confirm our previous in vitro observations that functional domains are identifiable within the multipotent cytokine IL-1 beta, and demonstrate the biological relevance of this finding in a variety of in vivo systems. The identification of a selectively active fragment of a cytokine may thus represent a significant step towards a better directed and more rational immunotherapeutic approach.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1987

Patterns of outpatient consultation: a survey of outpatients attending a metropolitan psychiatric hospital.

A survey of all outpatients (n = 1135) attending a regional psychiatric hospital during a 3-month period. Psychoses constituted 72% and non-psychotic disorders 25%. Psychoses had a greater proportion of long-term attenders while non-psychotic disorders, though frequent (43%) among recent attenders, showed a high attrition rate. Demographic characteristics, patterns of attendance, selected clinical features, level of functioning and difficulties of management of the different diagnostic groups are presented and discussed. Reasons are adduced to explain why patients who were deemed suitable for transfer to other care had not been discharged from hospital. Steps taken to reduce the patient load and increase the efficiency of the services are described.

Adolescent↗
PubMed1996

UV photoaffinity labeling of Tn3 transposase--DNA complexes: identification of DNA binding domains.

The prokaryotic transposon Tn3 requires the transposase protein, as well as the cis-acting terminal inverted repeats (IRs), for transposition. The first step in the transposition process requires transposase binding to the IRs, as well as target site selection for element insertion. The primary aim of this study is to define the relationship between the structure of Tn3 transposase and its DNA binding functions. We have defined, by UV cross-linking, two broad regions of transposase that interact with DNA: a 70-kDa N-terminal domain and a 30-kDa C-terminal domain. The 70-kDa N-terminal domain encompasses the IR sequence specific binding domain, as well as a nonspecific DNA binding domain that has been previously described. We have also defined, by UV cross-linking, a region in the nonspecific DNA binding domain centered at amino acids 376 and 381 that is in contact with DNA. We have used site-directed mutagenesis of amino acids 376 and 381 to help delineate the function of this region of the transposase protein. Mutations in this region reduce transposition frequency to 30-40% of the wild type. These mutations reduce nonspecific DNA binding three- to four-fold but do not appear to affect specific binding to the IR. Transposition immunity is unaffected by mutations in the nonspecific DNA binding domain. This suggests that this region may be involved in target site selection.

Affinity Labels↗
PubMed1983

Age, sex, and body composition as predictors of children's performance on basic motor abilities and health-related fitness items.

The purpose of this study was to determine the contribution of age, sex, and body composition to children's motor performances on selected basic motor tasks, balance, speed, agility, power, coordination, and reaction time, and health-related fitness items, flexibility, muscle strength and endurance, and cardiovascular functions. 80 subjects were students in Grades 1, 2, 3. Data were submitted to a step-wise multiple linear regression for each criterion variable. Predictor variables were age, sex, and body composition. Age was a significant factor in predicting performance on all variables except muscle strength, endurance, and flexibility. Sex significantly predicted performance for only flexibility and cardiovascular function and body composition for the power and cardiovascular function variables. Beyond the biological potential of each individual are factors that influence his motor development. These factors need early identification to make possible opportunities for each person to reach the full perimeters of motor potential.

Age Factors↗
PubMed1993

Risk assessment of drug use in pregnancy: prevention of birth defects.

Some developmental disorders are preventable by primary prevention, i.e. by avoiding exposure to microorganisms or chemicals that cause developmental disorders. This is not only important for physicians prescribing drugs, midwives monitoring pregnancies, but especially for parents taking the responsibility of having a baby; moreover, this fact is of importance for teratogen information services and public health authorities, both having preventive roles to play. Knowledge of the different pre- and postnatal developmental stages and the reproductive cycle is essential to understand this statement. The basic principle in reproductive toxicology and teratology is that the response of an organism to a teratogen depends upon the nature and the dosage of the substance, the stage of development of the embryo/fetus and its genetic make up. Chemical agents of different nature can induce developmental disorders either via the mother and perhaps via the father. The common consent that the vulnerable stage of development is only the first trimester of pregnancy is not correct. From oogenesis and spermatogenesis to at least the first years of life the developing organism is susceptible to harmful effects of chemical agents, including drugs. Developmental disorders include not only malformations visible at birth, but also spontaneous abortions, fetal death and functional deficits including behavioural defects. Studies both in the human and in laboratory animals make it possible to select substances to avoid exposure to developmental toxicants which are already on the market or still under development. This implicates a multi-step procedure leading from risk-evaluation, risk-assessment, and risk-communication to risk-perception and the according action (risk-management).

Abnormalities, Drug-Induced↗
PubMed1991

Microglial cell-mediated anti-Candida activity: temperature, ions, protein kinase C as crucial elements.

An in vitro established microglial cell line, BV-2, constitutively exhibits high levels of anti-Candida activity. To elucidate the cascade of events leading to the accomplishment of such activity, we studied its dependence on temperature and ion availability. The role of protein kinases has also been studied by the specific inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and N-(2-guanidinoethyl)-5-isoquinoline sulfonamide hydrochloride (HA 1004). We found that (a) the BV-2 cell/Candida conjugate formation is a discrete step, temperature-, ion- and protein kinase-independent; (b) the phagocytic event, which is protein kinase-independent, is significantly impaired by temperature decrease and ion deprivation; (c) the fulfillment of anti-Candida effects is strictly dependent upon temperature, ion availability and functional protein kinase. Functional protein kinase C, but not other kinases, is required for the accomplishment of anti-Candida activity, which, in fact, is selectively abrogated by H7 but not HA. Furthermore, protein kinase C activators, such as 12-O-tetradecanoylphorbol 13-acetate (TPA) or 1-oleoyl-2-acetyl glycerol (OAG), consistently potentiate BV-2 cell-mediated anti-Candida activity, the phenomena being dose-dependent. These results indicate that the multistep events leading a microglial cell to express anti-Candida activity can be dissected and differentiated for biochemical and biological demands, the latest along the cascade being the most demanding steps.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Gallbladder stones--dissolve, blast, or extract? Laparoscopic cholecystectomy versus 'the rest'.

This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their 'functioning' gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tomography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision-making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their 'functioning' gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected 'early' by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment.

Administration, Oral↗
PubMed1989

A two-step timed sequential treatment for acute myelocytic leukemia.

Since 1980, adults with acute myelocytic leukemia (AML) have been treated on two clinical studies using intensive timed sequential therapy. All patients ages 16 to 80, including those with secondary AML (SAML) and those with AML preceded by a hematologic disorder (AHD), were treated, regardless of medical complications at the time of diagnosis. The first study combined high doses of cytarabine (ara-C, AC) and daunorubicin (DRN, D) in sequence (Ac2-D-Ac) and resulted in a complete remission rate of 55%. A group of these patients selected by functional status was able to receive a second course of therapy in remission, which resulted in a disease-free survival (DFS) of greater than 40% at 7 years. Because of toxicity in that study, 114 patients were entered on a second trial initiated 4 years ago, using a less aggressive first course, with amsacrine, to achieve a stable remission (Ac2-D-Amsa). This first treatment was followed by a more intensive second course (Ac6-D-Ac). With this two-step approach, a higher complete remission (CR) rate (76% for de novo AML and 54% for SAML-AHD) was achieved, and more patients were able to receive the second course of therapy. At the current median follow-up of 26 months, the median duration of DFS and overall survival are 11 and 14 months for patients with de novo AML. Age less than or equal to 55 is the most significant prognostic factor for both prolonged DFS and overall survival, with median durations of 17 and 18 months, respectively, for these younger patients. Patients with SAML-AHD remain relatively refractory to treatment despite aggressive chemotherapy, with median durations of DFS and overall survival of 9 months and 5 months, respectively.

Adolescent↗
PubMed1993

MUST, a computer package of Management Utilities for Sequences and Trees.

The MUST package is a phylogenetically oriented set of programs for data management and display, allowing one to handle both raw data (sequences) and results (trees, number of steps, bootstrap proportions). It is complementary to the main available software for phylogenetic analysis (PHYLIP, PAUP, HENNING86, CLUSTAL) with which it is fully compatible. The first part of MUST consists of the acquisition of new sequences, their storage, modification, and checking of sequence integrity in files of aligned sequences. In order to improve alignment, an editor function for aligned sequences offers numerous options, such as selection of subsets of sequences, display of consensus sequences, and search for similarities over small sequence fragments. For phylogenetic reconstruction, the choice of species and portions of sequences to be analyzed is easy and very rapid, permitting fast testing of numerous combinations of sequences and taxa. The resulting files can be formatted for most programs of tree construction. An interactive tree-display program recovers the output of all these programs. Finally, various modules allow an in-depth analysis of results, such as comparison of distance matrices, variation of bootstrap proportions with respect to various parameters or comparison of the number of steps per position. All presently available complete sequences of 28S rRNA are furnished aligned in the package. MUST therefore allows the management of all the operations required for phylogenetic reconstructions.

Amino Acid Sequence↗
PubMed1989

Synthesis and adsorption of a poly(N-acetylethyleneimine)-polyethyleneoxide-poly (N-acetylethyleneimine) triblock-copolymer at a silica/solution interface. Influence of its preadsorption on platelet adhesion and fibrinogen adsorption.

The synthesis of a triblock copolymer poly-(N-acetylethyleneimine)-polyethylenoxide-poly(N-acet ylethyleneimine) includes two successive steps: the first is the functionalization of a poly(ethyleneglycol) precursor by creating sulfonic esters at its chain ends, the second uses these esters to initiate the cationic polymerization of 2-methyl-2-oxazoline. Homopolymers appear in the raw product; hence successive selective extractions of the copolymer with benzene and dioxane are necessary. The final yield in pure copolymer was 11%. The copolymer was characterized by UV and 1H-NMR spectrometry and light scattering. Adsorption isotherms were determined on silica, for varying pH and salt concentration. Optimum conditions for coating silica with the polymer were determined. The efficiency of this precoating to reduce the adsorption of fibrinogen was very high (99.2% reduction with respect to bare silica). Steric exclusion chromatography of a variety of proteins gave a satisfactory calibration curve. Platelet accumulation on copolymer precoated glass was reduced to 10-20% of its value on bare glass, a result superior to that obtained by albumin passivation of the same glass surface.

Adsorption↗
PubMed1994

A model of selective processing of auditory-nerve inputs by stellate cells of the antero-ventral cochlear nucleus.

Stellate cells in the cat antero-ventral cochlear nucleus (AVCN) maintain a robust rate-place representation of vowel spectra over a wide range of stimulus levels. This rate-place representation resembles that of low threshold, high spontaneous rate (SR) auditory nerve fibers (ANFs) at low stimulus levels, and that of high threshold, low-medium SR ANFs at high stimulus levels. One hypothesis accounting for this phenomenon is that AVCN stellate cells selectively process inputs from different SR population of ANFs in a level-dependent fashion. In this paper, we investigate a neural mechanism that can support selective processing of ANF inputs by stellate cells. We study a physiologically detailed compartmental model of stellate cells. The model reproduces PST histograms and rate-versus-level functions measured in real cells. These results indicate that simple and plausible distribution patterns of excitatory and inhibitory inputs within the stellate cell dendritic tree can support level dependent selective processing. Factors affecting selective processing are identified. This study thus represents a first step towards the development of a computational model of the AVCN stellate cell receptive field.

Animals↗
PubMed1990

Targeted gene replacement at the endogenous APRT locus in CHO cells.

We demonstrate the feasibility of targeted gene replacement at an endogenous, chromosomal gene locus in cultured mammalian cells, employing a two-step strategy similar to an approach routinely used for genetic manipulation in yeast. Utilizing an APRT+ recombinant generated by targeted integration of plasmid sequences (including a functional copy of the gpt gene) at the CHO APRT locus, we have been able to select gpt- "pop-out" recombinants that have arisen by intrachromosomal recombination between APRT direct repeats at the targeted integration site. Reciprocal exchanges leading to "pop-out" of integrated plasmid/gpt gene sequences occur at a rate of approximately 6.3 x 10(-6) per cell generation. Depending on the site of crossover, such "pop-out" events result in either replacement or restoration of the original APRT target gene sequence.

Adenine↗
PubMed1996

Monoclonal antibodies against human immunodeficiency virus type 1 integrase: epitope mapping and differential effects on integrase activities in vitro.

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalyzes the integration of viral DNA into the host chromosome, an essential step in retroviral replication. As a tool to study the structure and function of this enzyme, monoclonal antibodies (MAbs) against HIV-1 IN were produced. Epitope mapping demonstrated that the 17 MAbs obtained could be divided into seven different groups, and the selection of MAbs representing these groups were tested for their effect on in vitro activities of IN. Four groups of MAbs recognized epitopes within the region of amino acids (aa) 1 to 16, 17 to 38, or 42 to 55 in and around the conserved HHCC motif near the N terminus of IN. MAbs binding to these epitopes inhibited end processing and DNA joining and either stimulated or had little effect on disintegration and reintegration activities of IN. Two MAbs binding to epitopes within the region of aa 56 to 102 in the central core or aa 186 to 250 in the C-terminal half of the protein showed only minor effects on the in vitro activities of IN. Three Mabs which recognized on epitope within the region of aa262 to 271 of HIV-1 IN cross-reacted with HIV-2 IN. MAbs binding to this epitope clearly inhibited end processing and DNA joining and stimulated or had little effect on disintegration. In contrast to the N-terminal-specific MAbs, these C-terminal-specific MAbs abolished reintegration activity of IN.

Animals↗
PubMed1992

Regularized linear method for reconstruction of three-dimensional microscopic objects from optical sections.

The inverse problem involving the determination of a three-dimensional biological structure from images obtained by means of optical-sectioning microscopy is ill posed. Although the linear least-squares solution can be obtained rapidly by inverse filtering, we show here that it is unstable because of the inversion of small eigenvalues of the microscope's point-spread-function operator. We have regularized the problem by application of the linear-precision-gauge formalism of Joyce and Root [J. Opt. Soc. Am. A 1, 149 (1984)]. In our method the solution is regularized by being constrained to lie in a subspace spanned by the eigenvectors corresponding to a selected number of large eigenvalues. The trade-off between the variance and the regularization error determines the number of eigenvalues inverted in the estimation. The resulting linear method is a one-step algorithm that yields, in a few seconds, solutions that are optimal in the mean-square sense when the correct number of eigenvalues are inverted. Results from sensitivity studies show that the proposed method is robust to noise and to underestimation of the width of the point-spread function. The method proposed here is particularly useful for applications in which processing speed is critical, such as studies of living specimens and time-lapse analyses. For these applications existing iterative methods are impractical without expensive and/or specially designed hardware.

Computer Simulation↗
PubMed1986

Construction and properties of a cell line constitutively expressing the herpes simplex virus glycoprotein B dependent on functional alpha 4 protein synthesis.

We report the construction of a cell line constitutively expressing the glycoprotein B (gB) of herpes simplex virus (HSV) 1. The cell line was constructed in two steps. In the first, a baby hamster kidney cell line was transfected with the DNA of a plasmid containing the neomycin phosphotransferase gene that confers resistance to the antibiotic G418 and the gene specifying a temperature-sensitive (ts-) alpha 4 protein of HSV-1, the major viral regulatory protein. A clonal cell line, alpha 4/c113, selected for resistance to the antibiotic G418, expressed high levels of alpha 4 protein constitutively. Superinfection of these cells with HSV-2 resulted in twofold induction of the resident HSV-1 alpha 4 gene. In the second step, alpha 4/c113 cells were transfected with the DNA of a plasmid carrying the gB gene and the mouse methotrexate resistance dihydrofolate reductase gene. A clonal cell line, alpha 4/c113/gB, selected for methotrexate resistance expressed gB constitutively. Expression of both gB and alpha 4 continued unabated for at least 32 serial passages. Cells passaged serially in medium containing both methotrexate and G418 after passage 10 contained a higher copy number of the alpha 4 gene and produced larger amounts of both gB and alpha 4 proteins than did cells maintained in medium containing methotrexate alone. Expression of gB was dependent on the presence of functional alpha 4 protein inasmuch as expression of gB ceased on shift up to nonpermissive temperatures, when shifted to permissive temperatures, the cell line reinitiated expression of gB after a delay commensurate with the length of incubation at the nonpermissive temperature, and the cell-resident HSV-1 gB gene was expressed at the nonpermissive temperature in cells infected with a recombinant expressing a ts+ alpha 4 protein and an HSV-2 gB. The properties of the alpha 4/c113 cell line suggest that it may express other viral genes induced by alpha 4 protein constitutively, provided that the product is not toxic to the cells.

Animals↗
PubMed1993

Routine tests of renal function, alcoholism, and nutrition improve the prognostic accuracy of Child-Pugh score in nonbleeding advanced cirrhotics.

In an attempt to improve the prognostic capacity of Child-Pugh score in nonbleeding cirrhotics, 110 consecutive in-patients without gastrointestinal hemorrhage at admission were studied and followed up for 24 months or until death. Fifty-five of the 110 patients (50%) died during this period. Mean survival time was 18.8 +/- 1.4 months (mean +/- SEM). In addition to Child-Pugh score, eight variables, including anthropometric nutritional parameters, routine renal function tests, and alcoholism markers, were recorded at admission. The ability of these variables to improve the prognostic capacity of the Child-Pugh score was assessed with the proportional hazard Cox's regression procedure, using a stepwise method for covariate selection, after including the Child-Pugh score at the first step. Thus, in addition to Child-Pugh score (beta = 0.302), three variables were included in the final model: serum urea (beta = 0.113), MCV (beta = 0.027), and mid-arm muscle circumference (beta = -0.025). According to the contribution of each of these factors to the model, a prognostic index was obtained to estimate survival in the individual patient. An assessment of the predictive power of the model was made by means of a split-sample technique. The prognostic index described in this study may contribute to improve the selection of nonbleeding patients with advanced cirrhosis to receive specific therapies such as transplantation. However, its true clinical relevance will be established only by prospectively comparing its prognostic value with that of the Child-Pugh score in a new sample of patients.

Alcohol Drinking↗