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At least 1,495 records · Page 83Linked to original sources
PubMed1991

Structure-activity relationship study of human interleukin-3: role of the C-terminal region for biological activity.

A structure-activity relationship study of human interleukin-3 (huIL-3) was performed by functional analysis of huIL-3 deletion and substitution variants combined with epitope mapping of huIL-3 specific neutralizing monoclonal antibodies (mAb). Analysis of the huIL-3 variants was accomplished by defining their capacity to compete with wild-type huIL-3 for binding to the huIL-3 receptor and to induce the proliferation of the huIL-3 dependent cell line M-O7. HuIL-3 variants with either 14 amino acids (aa) deleted from the N-terminus or eight aa from the C-terminus retained full biological activity in vitro. An huIL-3 variant, with 18 N-terminal aa deleted, exhibited a greater than 7-fold reduced receptor binding capacity and proliferative activity. No biological activity could be detected with a variant where 22 C-terminal aa have been deleted. Neutralizing mAb recognizing presumed discontinuous epitopes failed to interact with the latter deletion variant indicating a possible location of their epitopes within the C-terminal region. Computer-aided structure prediction and sequence homology analysis of this region indicated the presence of an amphiphilic alpha-helix with highly conserved residues like Lys110 and Leu111. Substitution of Lys110 with either Glu or Ala resulted in variants with a 10-fold reduced activity in the receptor binding assay and the proliferation assay. Further variants, where Leu111 was substituted by Pro or Met, were totally inactive in these assays. Analysis of the binding of the two neutralizing mAb to these substitution variants showed that they did not bind to either of the Leu111 variants suggesting that Leu111 is part of an active site. Based on our results, a possible model for the structure of the huIL-3 molecule can be constructed with two active sites in close proximity.

Amino Acid Sequence↗
PubMed1998

Cloning of the mouse gene for D-dopachrome tautomerase.

D-Dopachrome tautomerase converts 2-carboxy-2,3-dihydroindole-5, 6-quinone (D-dopachrome) into 5,6-dihydroxyindole. The amino acid sequence of this protein is 27% identical with that of macrophage migration inhibitory factor, which is known as a cytokine, pituitary hormone, and glucocorticoid-induced immunomodulator. In this study, we isolated and sequenced a 3490 bp-long genomic DNA of mouse D-dopachrome tautomerase that consists of three exons and two introns. By two procedures, 5' rapid amplification of cDNA ends and cap site labeling, we determined the transcription initiation site, which is located 46 bp upstream of the translation initiation site. The possible polyadenylation sequence (AATAAA) is located 180 bp downstream of the termination codon. Computer-assisted analysis of the nucleotide sequence revealed a number of regulatory motifs, including multiple sites for Sp1, C/EBP, NF-Y, and USF. Although the precise pathophysiological functions of D-dopachrome tautomerase remain to be elucidated, the present results will contribute not only to elucidation of the mechanism of gene expression, but also to understanding of the molecular function of this protein.

Amino Acid Sequence↗
PubMed2003

Classification of galactograms with ramification matrices: preliminary results.

RATIONALE AND OBJECTIVES: The poor specificity of galactography, the imaging modality generally indicated in cases of nipple discharge, has led to a large number of biopsies with negative results. A quantitative scheme for classifying galactographic findings might help reduce the number of such biopsies in the future. As a first step toward that goal, the authors have studied one quantitative method for describing the branching of ducts by using ramification matrices (R matrices), and the correlation of the values of the matrix elements with clinical findings. MATERIALS AND METHODS: The ductal trees were manually segmented for 25 galactographic views from 15 patients, and corresponding R matrices were calculated. Patients were divided into two groups: those with no reported galactographic findings (NF) and those with reported findings (RF) of ductal ectasia, cysts, or papilloma. In a leave-one-out fashion, the authors evaluated a classification scheme that was based on R-matrix coefficients and used a Bayesian decision rule. The effects of segmentation were tested by successively removing each of the terminal ducts and computing the corresponding matrices of the pruned trees. RESULTS: With use of a single R-matrix element, 92% and 62% of NF and RF cases were correctly classified, respectively (P = .007). With use of two elements, 83% and 77% of NF and RF cases were correctly classified, but this result was not statistically significant (P = .108). In a test of robustness, an analysis of pruned trees yielded an average root-mean-square fractional difference of 9.7% between the elements of the original and the R matrix averaged over all pruned trees. CONCLUSION: The preliminary analysis indicates that it may be possible to identify cases with reported galactographic findings by using R matrices.

Adult↗
PubMed1998

Kinetic parameters for the vesicular acetylcholine transporter: two protons are exchanged for one acetylcholine.

The vesicular acetylcholine transporter (VAChT) mediates ACh storage in synaptic vesicles by exchanging cytoplasmic ACh with vesicular protons. This study sought to determine the stoichiometry of exchange by analysis of ligand binding and transport kinetics. The effects of different pH values inside and outside, external ACh concentrations, and electrical potential gradients on ACh transport by vesicles isolated from the electric organ of Torpedo were determined using a pH-jump protocol. The equilibrium binding of a high-affinity analogue of ACh is inhibited by protonation with a pKa of 7.4 +/- 0.3. A two-proton model fits the transport data much better than a one-proton model does, and uptake increases at more positive internal electrical potential, as expected for the two-proton model. Thus, the results support the two-proton model. The transport cycle begins with binding of external ACh to outwardly oriented site 2 (KACho = 20 mM) and protonation of inwardly oriented site 1 (pKa1 = 4.73 +/- 0.05). Loaded VAChT reorients quickly (73 000 min-1) and releases ACh to the inside (KAChi = 44 000 mM) and the proton to the outside. Unloaded, internally oriented site 2 binds a proton (pKa2 = 7.0), after which VAChT reorients (150 +/- 20 min-1) in the rate-limiting step and releases the proton to the outside to complete the cycle. Rate constants for the reverse direction also were estimated. Two protons provide a thermodynamic driving force beyond that utilized in vivo, which suggests that vesicular filling is regulated. Other phenomena related to VAChT, namely the time required to fill synaptic vesicles, the fractional orientation of the ACh binding site toward cytoplasm, orientational lifetimes, and the rate of nonquantal release of ACh from cholinergic nerve terminals, were computer-simulated, and the results are compared with physiological observations.

Acetylcholine↗
PubMed1988

[Computerized automatic analysis of the cardiotocogram (results of an international multicenter study].

By means of an international multicentre study (SU, Socialist Republic of Poland, Socialist Republic of Czechoslovakia, GDR) 403 patients with computerized CTG-analysis and 393 patients with visual CTG-analysis in labour were investigated in relation to course of labour and neonatal outcome. The following results were fixed: The computerized CTG-analysis by help of the equipment "robotron-NATALI" is equal the statement of high qualified perinatologists. The computerized CTG-analysis led significantly more frequently in various stages of labour to the diagnosis "prepathological" CTG-pattern (warn signs) in relation to visual CTG-analysis with a significantly higher rate of fetal pH-measurements. That means, that the sensitivity of this method is greater. The safety in frame of electronic supervision of labour is improved. The number of "acut-tocolysis" in various stages of labour for both collectives wasn't significantly too. The rate of caesarean section and the rate of operative vaginally deliveries (forceps, vacuum-extraction) showed in both collectives no significantly differences. The neonatal morbidity (APGAR score, pHUA) matured analogous results in the collective with and without computerized CTG-analysis. A decline of "acidotic" morbidity in the collective with computerized CTG-analysis wasn't mentioned. One stillbirth was found in the collective with visual CTG-analysis. In spite of that computerized CTG-analysis showed no better results in perinatological centres in relation to visual CTG-analysis this method is the basis for very important perinatological aims how computer controlled infusion in connection with termination of labour as well as computer steered tocolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Apgar Score↗
PubMed2005

Identification of the putative staphylococcal AgrB catalytic residues involving the proteolytic cleavage of AgrD to generate autoinducing peptide.

The P2 operon of the staphylococcal accessory gene regulator (agr) encodes four genes (agrA, -B, -C, and -D) whose products compose a quorum sensing system: AgrA and AgrC resemble a two-component signal transduction system of which AgrC is a sensor kinase and AgrA is a response regulator; AgrD, a polypeptide that is integrated into the cytoplasmic membrane via an amphipathic alpha-helical motif in its N-terminal region, is the propeptide for an autoinducing peptide that is the ligand for AgrC; and AgrB is a novel membrane protein that involves in the processing of AgrD propeptide and possibly the secretion of the mature autoinducing peptide. In this study, we demonstrated that AgrB had endopeptidase activity, and identified 2 amino acid residues in AgrB (cysteine 84 and histidine 77) that might form a putative cysteine endopeptidase catalytic center in the proteolytic cleavage of AgrD at its C-terminal processing site. Computer analysis revealed that the cysteine and histidine residues were conserved among the potential AgrB homologous proteins, suggesting that the Agr quorum sensing system homologues might also exist in other Gram-positive bacteria.

Amino Acid Sequence↗
PubMed2003

Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition.

The finite-difference time-domain (FDTD) method provides a flexible approach to studying the scattering that arises from arbitrarily inhomogeneous structures. We implemented a three-dimensional FDTD program code to model light scattering from biological cells. The perfectly matched layer (PML) boundary condition has been used to terminate the FDTD computational grid. We investigated differences in angle-dependent scattering properties of normal and dysplastic cervical cells. Specifically, the scattering patterns and phase functions have been computed for normal and dysplastic cervical cells at three different epithelial depths, namely, basal/parabasal, intermediate, and superficial. Construction of cervical cells within the FDTD computational grid is based on morphological and chromatin texture features obtained from quantitative histopathology. The results show that angle-dependent scattering characteristics are different not only for normal and dysplastic cells but also for cells at different epithelial depths. The calculated scattering cross-sections are significantly greater for dysplastic cells. The scattering cross-sections of cells at different depths indicate that scattering decreases in going from the superficial layer to the intermediate layer, but then increases in the basal/parabasal layer. This trend for epithelial cell scattering has also been observed in confocal images of ex vivo cervical tissue.

Algorithms↗
PubMed2003

A novel in vitro model for screening and evaluation of anti-asthenopia drugs.

Patients suffering asthenopia are steadily increasing with an expanding use of visual display terminals such as computers. An attempt was made to develop an in vitro model for asthenopia. Ciliary muscle removed from eyeballs of a rabbit was stimulated with acethylcholine, resulting in contraction of the muscle. Repeated stimulations caused decreased contraction, which may be related to fatiguing of ciliary muscle and hence asthenopia. Treatment of the repeatedly stimulated muscle with cyanocobalamin restored contraction dose-dependently. Thus, the model developed in this study can be used to screen drug candidates for treating asthenopia.

Acetylcholine↗
PubMed2004

Plane-wave expansion method for calculating band structure of photonic crystal slabs with perfectly matched layers.

We present a new algorithm for calculation of the band structure of photonic crystal slabs. This algorithm combines the plane-wave expansion method with perfectly matched layers for the termination of the computational region in the direction out of the plane. In addition, the effective-medium tensor is applied to improve convergence. A general complex eigenvalue problem is then obtained. Two criteria are presented to distinguish the guided modes from the PML modes. As such, this scheme can accurately determine the band structure both above and below the light cone. The convergence of the algorithm presented has been studied. The results obtained by using this algorithm have been compared with those obtained by the finite-difference time-domain method and found to agree very well.

Journal Article↗
PubMed1999

[An autopsied case of subacute progressive dementia with flactuated disturbance of consciousness, myoclonus and periodic synchronous discharges on EEGs].

We present an autopsied case which developed progressive dementia at the age of 45. EEGs showed periodic synchronous discharges (PSD) when he showed fluctuated cloudy consciousness with myoclonus. Cerebrospinal fluid examination showed mild to moderate increase in protein and monocytes for duration of illness, but antivirotics and antibiotics were not effective. He was not apallic even at the terminal stage when computed tomography (CT) revealed marked cerebral atrophy, and died of pneumonia 27 months after onset. He was clinically diagnosed as having Creutzfeldt-Jakob disease (CJD) because of subacute progressive dementia, myoclonus and PSD. Neuropathological examination revealed marked brain atrophy with severe neuronal loss and gliosis in the cerebral cortex and subcortical nuclei, although no spongiform degeneration was found. Senile plaques, neurofibrillaly tangles, argyrophilic glial inclusions and glial nodules were not detected. Prion protein immunoreactivity was negative. Therefore, this case can not be neuropathologically diagnosed as having CJD, Alzheimer's disease, non-Alzheimer-type degenerative dementias or any encephalitis. This case might have suffered from an unknown new disease.

Brain↗
PubMed1986

Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

The comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in rats at a dose of 6 mg/kg i.v. Doxorubicin was entrapped in cardiolipin liposomes by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. The peak plasma concentration with free doxorubicin at 5 min was 1.7 micrograms/ml which was reduced to 0.3 micrograms/ml by 1 h. With cardiolipin liposomes, the peak plasma concentration of doxorubicin achieved at 5 min was 20.9 micrograms/ml. The plasma levels of doxorubicin decreased gradually and by 1 h the drug concentration in plasma was 10 micrograms/ml. The plasma levels of free doxorubicin and doxorubicin entrapped in liposomes were fitted to a 3-compartment computer model. The terminal half-life with free doxorubicin in plasma was 17.3 h whereas it was 69.3 h with drug entrapped in liposomes. The area under the plasma concentration curve with liposomal doxorubicin was 81.4 micrograms X h X ml-1 compared to 1.95 micrograms X h X ml-1 observed with free doxorubicin. The steady state volume of distribution with free doxorubicin was about 23-fold higher than liposomal doxorubicin. The terminal half-life with free doxorubicin in cardiac tissue was 17.9 h compared to 12.6 h with drug encapsulated in liposomes. The terminal half-lives in liver and spleen following administration of liposomal doxorubicin were 15- and 2.3-fold higher, respectively, compared to free drug; furthermore, the concentration X time values of liposomal doxorubicin in liver were 26-fold higher and in spleen 6-fold higher than the free drug. Free doxorubicin and doxorubicin entrapped in liposomes demonstrated 17 and 20% excretion in bile of the injected dose, respectively, in rats. The present studies demonstrate that liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics in plasma and tissues compared to free drug.

Animals↗
PubMed1993

Ultrasound detection of fetal structural abnormalities in Auckland 1988-9.

AIMS: To conduct an audit of ultrasound screening for fetal abnormalities in central Auckland 1988-89. METHOD: All babies born at National Women's Hospital in the time period were examined and fetal abnormalities coded on to a computer database. All terminations of pregnancy for fetal abnormality in the area were similarly audited. RESULTS: There were 12,909 births. 218 babies had a congenital abnormality of whom 88% were scanned antenatally. 48% of abnormalities were detected (27% before 24 weeks). In fetuses that were scanned the detection rate was 52% (44% before 24 weeks). The range of detection of specific abnormalities included neural tube defects 95% and congenital heart defects 16%. CONCLUSIONS: 1. Major abnormalities of the central nervous system, renal tract and abdominal wall have a high detection rate. 2. Cardiovascular, facial and gastrointestinal abnormalities are either not detectable or difficult to detect. 3. Detection rates could be improved by routine scanning, better ultrasound equipment and training, and by the introduction of maternal biochemical screening tests. 4. The detection rate is similar to other overseas surveys.

Abortion, Therapeutic↗
PubMed1997

Summary of measured radiofrequency electric and magnetic fields (10 kHz to 30 GHz) in the general and work environment.

We have plotted data from a number of studies on the range of radiofrequency (RF) field levels associated with a variety of environmental and occupational sources. Field intensity is shown in units of volts/meter (V/m) for electric field strength and amps/meter (A/m) for magnetic field strength. Duty factors, modulation frequencies, and modulation indices are also reported for some sources. This paper is organized into seven sections, each cataloging sources into appropriate RF frequency bands from very-low frequency (VLF) to super-high frequency (SHF), and covers frequencies from 10 kHz to 30 GHz. Sources included in this summary are the following: Coast Guard navigational transmitters, a Navy VLF transmitter, computer visual display terminals (VDTs), induction stoves or range tops, industrial induction and dielectric heaters, radio and television broadcast transmitters, amateur and citizens band (CB) transmitters, medical diathermy and electrosurgical units, mobile and handheld transmitters, cordless and cellular telephones, microwave ovens, microwave terrestrial relay and satellite uplinks, and police, air traffic, and aircraft onboard radars. For the sources included in this summary, the strongest fields are found near industrial induction and dielectric heaters, and close to the radiating elements or transmitter leads of high power antenna systems. Handheld transmitters can produce near fields of about 500 V/m at the antenna. Fields in the general urban environment are principally associated with radio and TV broadcast services and measure about 0.1 V/m root-mean-square (rms). Peak fields from air traffic radars sampled in one urban environment were about 10 V/m, 300 times greater than the rms value of 0.03 V/m when the duty factor associated with antenna rotation and pulsing are factored in.

Electromagnetic Fields↗
PubMed2005

Relation of coronary atherosclerosis determined by electron beam computed tomography and plasma levels of n-terminal pro-brain natriuretic peptide in a multiethnic population-based sample (the Dallas Heart Study).

Elevated plasma levels of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are seen in the setting of cardiac ischemia and are associated with adverse outcomes in patients with coronary artery disease. The mechanisms leading to natriuretic peptide elevation in patients with coronary artery disease, including the contribution of coronary atherosclerosis itself, have not been fully elucidated. Measurement of NT-pro-BNP, electron beam computed tomography, and cardiac magnetic resonance imaging were performed in 2,445 subjects from the Dallas Heart Study who were free of heart failure and renal insufficiency. Electron beam computed tomography-determined coronary artery calcium scores were categorized as none (<10), mild (> or =10 to <100), moderate (> or =100 to <400), and severe (> or =400). NT-pro-BNP levels increased significantly across increasing coronary artery calcium score categories (p <0.0001 for trend). In multivariate models adjusted for age, gender, race, body mass index, hypertension, history of myocardial infarction, angina, angiotensin-converting enzyme inhibitor use, beta-blocker use, left ventricular (LV) ejection fraction, and LV mass, higher coronary artery calcium scores remained independently associated with higher log NT-pro-BNP levels (p = 0.03). This association persisted in similar models excluding patients with low LV ejection fractions, LV hypertrophy, angina pectoris, and a history of myocardial infarction. In conclusion, these findings support the hypothesis that coronary atherosclerosis may directly influence the activation of the cardiac neurohormonal system.

Adolescent↗
PubMedDate not supplied

Computer-aided system for diabetes care in Berlin, G.D.R.

In the Centre of Diabetes and Metabolic Disorders of Berlin, G.D.R., a computer-aided care system has been used since 1974, aiming at relieving physicians and medical staff from routine tasks and rendering possible epidemiological research on an unselected diabetes population of a defined area. The basis of the system is the data bank on diabetics (DB), where at present data from approximately 55,000 patients are stored. DB is used as a diabetes register of Berlin. On the basis of standardised criteria of diagnosis and therapy of diabetes mellitus in our dispensary care system, DB facilitates representative epidemiological analyses of the diabetic population, e.g. prevalence, incidence, duration of diabetes, and modes of treatment. The availability of general data on the population or the selection of specified groups of patients serves the management of the care system. Also, it supports the computer-aided recall of type II diabetics, treated either with diet alone or with diet and oral drugs. In this way, the standardised evaluation of treatment strategies in large populations of diabetics is possible on the basis of uniform metabolic criteria (blood glucose plus urinary glucose). The system consists of a main computer in the data processing unit and of personal computers in the diabetes centre which can be used either individually or as terminals to the main computer. During 14 years of experience, the computer-aided out-patient care of type II diabetics has proved efficient in a big-city area with a large population.

Ambulatory Care↗
PubMed1997

Characterization of microbial diversity by determining terminal restriction fragment length polymorphisms of genes encoding 16S rRNA.

A quantitative molecular technique was developed for rapid analysis of microbial community diversity in various environments. The technique employed PCR in which one of the two primers used was fluorescently labeled at the 5' end and was used to amplify a selected region of bacterial genes encoding 16S rRNA from total community DNA. The PCR product was digested with restriction enzymes, and the fluorescently labeled terminal restriction fragment was precisely measured by using an automated DNA sequencer. Computer-simulated analysis of terminal restriction fragment length polymorphisms (T-RFLP) for 1,002 eubacterial sequences showed that with proper selection of PCR primers and restriction enzymes, 686 sequences could be PCR amplified and classified into 233 unique terminal restriction fragment lengths or "ribotypes." Using T-RFLP, we were able to distinguish all bacterial strains in a model bacterial community, and the pattern was consistent with the predicted outcome. Analysis of complex bacterial communities with T-RFLP revealed high species diversity in activated sludge, bioreactor sludge, aquifer sand, and termite guts; as many as 72 unique ribotypes were found in these communities, with 36 ribotypes observed in the termite guts. The community T-RFLP patterns were numerically analyzed and hierarchically clustered. The pattern derived from termite guts was found to be distinctly different from the patterns derived from the other three communities. Overall, our results demonstrated that T-RFLP is a powerful tool for assessing the diversity of complex bacterial communities and for rapidly comparing the community structure and diversity of different ecosystems.

DNA, Bacterial↗
PubMed1995

Computer graphics as a tool in cytogenetic research and education.

Scanning microscope photometry has been extensively used for image analysis of nuclei and chromosomes and for automated karyotyping. Color graphics terminals, software development and appropriate data manipulation have expanded the scope of scanning microphotometry so that it is now particularly useful for the quantitative analysis of cell components. We have developed application software for displaying nuclear and chromosome densities on a computer terminal of in the form of pixeled images and pseudo-three-dimensional graphic diagrams, as well as for image transformation, object illumination and rotation to enhance chromatin features. The system allowed the microphotometrical scanning of human G-, R-, C-, T-banded chromosomes and sister chromatid exchanges, the measurement of nuclear heterochromatic segments, the detection of minute chromosome structures and the distribution of high staining densities in chromosomes which are difficult to observe with simple light microscopy. The new quantitative visual information given by our interactive graphic method contributes to a better understanding of the nuclear and chromosome structure for the students engaged in cytogenetic research and teaching. The analytical perspective of computer graphics in cytogenetic research and education is briefly discussed.

Animals↗
PubMedDate not supplied

Computer-assisted image analysis of the distributions of peptidergic terminals in the central nucleus of the amygdala: a preliminary study.

When viewed under dark-field illumination, peptidergic terminals in sections stained by the Sternberger PAP immunocytochemical method are seen as individual points of light. Under high magnification, the degree of brightness of various areas of immunoreactive terminals is seen to be a function of the density of terminals in these areas. By analyzying the relative brightness of the immunostained central nucleus of the amygdala (CNA) with an EyeCom II PDP-11/34 image analysis system, we have obtained a relative evaluation of the density distribution of neurotensin (NT)-, substance P (SP), VIP-, angiotensin II (AII), m-enkephalin (m-ENK) and somatostatin (SS)-immunoreactive terminals in terms of normal morphology and following a brain lesion. The EyeCom II system divides the presented image into 307200 picture elements (pixels) and assigns one of 256 grey values to the average brightness with each pixel. We have aggregated the grey level frequencies into 5 levels where level 1 corresponds to the highest terminal density and level 5 to the lowest density. At level 1, only NT- and VIP-immunoreactive terminals occupy a significant percentage of the cross-sectional area of the CNA (20%). About 15% of the area of the CNA has VIP terminals with level 5 density. The distributions of the top 20% of the terminal density range of NT, SP, AII and VIP support a classical medial/lateral division of the nucleus. The distribution of the same range of SS- and ENK terminals suggests a dorsoventral division of the CNA. A preliminary study indicates that comparison of grey level frequency histograms generated by image analysis from homologous lesioned and unlesioned sections of the CNA can yield useful information regarding post-lesion changes in the distribution of immunoreactive terminals.

Amygdala↗