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PubMed1975

Use of computer program for diagnosing jaundice in district hospitals and specialized liver unit.

A computer-assisted model for diagnosing jaundice has been adapted for use on the University of London C.D.C. 7600 computer via an on-line terminal at King's College Hospital to provide a rapid turn-round time. The model was used prospectively in the diagnosis of 219 patients--135 seen in a specialized liver unit and 84 seen in one of four district hospitals in south-east London--with an overall accuracy in distinguishing among 11 different causes of jaundice of 69% and 62% respectively. These figures rose to 77% and 88% respectively when only those patients in whom the final diagnosis reached a "certain" probability were considered. When used to distinguish between a medical and a surgical cause of jaundice the accuracy was 86% in the liver unit and 77% in the district hospitals, rising to 95% in both series for those with a diagnosis of certain probability. The proposed improvements to the model--namely, the use of two deparate data bases and more diagnoses within the matrix--should be improve the accuracy even further. In practice the rapid feedback to the clinicians looking after patients provided help in managing difficult cases.

Bile Duct Neoplasms↗
PubMed2003

Proliferation-linked expression of the novel murine gene m4mbt encoding a nuclear zinc finger protein with four mbt domains.

Here we describe the cloning and characterization of a novel murine gene named m4mbt that encodes a homolog of the lethal (3) malignant brain tumor (l(3)mbt) and Scm proteins. It is localized on mouse chromosome 15E2 and is organized into 17 exons. As demonstrated by Northern blot analysis, m4mbt mRNA is expressed in virtually all tested tissues and cell lines with the exception of stomach and muscle. The m4mbt transcript was most abundant in the testes. m4mbt expression was shown to initiate early during mouse embryonal development (before day 7) and continue until adulthood. The expression of m4mbt mRNA also appears to correlate with cellular proliferation, since we observed down-regulation of m4mbt expression during terminal monocytic differentiation and in contact-inhibited fibroblasts. Computer analysis of the amino acid (aa) sequence revealed that the M4mbt protein comprises an amino-terminally located atypical C2C2 zinc finger and four centrally located mbt repeats. Mbt repeats are also found in proteins of the Polycomb group (PcG) that associate with heterochromatin and function as long-term repressors of transcription. Using Western blot analysis and confocal fluorescent microscopy, we demonstrated that the M4mbt protein is localized in the nucleus. Since M4mbt has structural domains similar to chromatin-associated proteins, its expression is associated with proliferation, and it has a nuclear localization, it may have a regulatory role related to proliferation and/or differentiation.

Amino Acid Sequence↗
PubMed1999

No free lunch: institutional preparations for computer-based patient records.

The Veterans Administration (VA) is aggressively pursuing computer-based medical records by deploying the Computerized Patient Record System (CPRS) across its 150 medical centers and 400 outpatient clinics. CPRS's client-server, patient-centered approach to clinical computing is a departure from VA's traditional terminal-compatible, department-centered approach. Although the CPRS software is freely distributed, institutional readiness for computer-based patient records has proven expensive. Preparations include organizational changes, human resource development, hardware deployment, physical plant upgrades, and software testing. This paper details CPRS preparations and their costs at one VA Medical Center. Lessons learned during the process are summarized.

Computer Systems↗
PubMed1989

Nerve terminal morphology in C57BL/6NNia mice at different ages.

The mammalian neuromuscular junction (NMJ) appears to undergo a dynamic remodeling process with advancing age. Previous studies suggest that the NMJ becomes progressively larger with age, to a greater degree in fast-twitch muscles than slow-twitch muscles. To better understand this process, quantitative morphometry was conducted on soleus and extensor digitorum longus (EDL) nerve terminals from C57BL/6NNia mice aged 4, 8, 10, 12, 18, 22, 24, and 32 months. Computer-aided morphometry of camera lucida drawings of aging nerve terminals indicated significant differences in the size and complexity of NMJs in both muscles between different age groups; however, there were no significant net trends with age. The magnitude and direction of the morphometric changes depended on the particular ages compared, and occurred to a greater degree in the EDL. This study is the first comprehensive morphometric study of C57BL/6NNia nerve terminals at so many ages. The results are similar to those obtained for the Fischer 344 rat, and support the hypothesis that nerve terminal remodeling is a dynamic process, not a progressive elaboration.

Aging↗
PubMed1988

Postnatal development of dendrites of relay neurons in the lateral geniculate nucleus of the marmoset (Callithrix jacchus): a quantitative Golgi study.

Dendrites of multipolar relay neurons in the lateral geniculate nucleus of the marmoset (Callithrix jacchus), at various ages from birth to adulthood, were studied in rapid Golgi preparations. The dendrites were analyzed by means of three-dimensional computer reconstructions and decomposed into intermediate and terminal segments, both of which were further classified according to their centrifugal order. Measurements were made of the number of segments per dendrite, the total length of dendrites, and the mean length of intermediate and terminal segments. In adult marmosets, there are four stem dendrites on average per neuron, and each dendrite divides into a mean of 14 segments. Between birth and 6 weeks of age, the mean dendritic length doubles, mainly because of changes in terminal segments. There is a significant decrease in dendritic length into adulthood. The total number of stem dendrites does not change after birth, but during the first postnatal week dendrites lose distal segments, after which there is a significant increase in the number of segments of orders 3 to 7. The mean length of intermediate segments does not change with age, nor with order, whereas the length of terminal segments increases from 50 to 120 microns from birth to 6 weeks of age, and then decreases to the adult value of 80 microns. In conclusion, during the period of most rapid visual development, important morphological changes occur in geniculate relay-cell dendrites, involving essentially terminal segments. These observations correlate well with changes of geniculate volume and neuronal density.

Animals↗
PubMed1992

Purification and characterization of an astrocyte GABA-carrier inducing protein (GABA-CIP) released from cerebellar granule cells in culture.

A glycoprotein that induces gamma-aminobutyric acid (GABA) carriers in cultured cerebellar astrocytes was isolated and purified from conditioned media from cultured cerebellar granule cells by anion exchange chromatography, affinity chromatography, and gel filtration. Following gel filtration three fractions corresponding to M(r) 30,000, 60,000, and 240,000 exhibited GABA carrier inducing activity. SDS-PAGE of the M(r) 30,000 fraction revealed under non-reducing conditions three bands corresponding to M(r) 30,000, 60,000, and 120,000. Under reducing conditions only the band corresponding to an M(r) of 30,000 was visible. An identical N-terminal amino acid sequence and amino acid composition was found in the M(r) 30,000 and the M(r) 60,000 fraction from the gel filtration. These results suggest that the protein polymerizes into di- and tetramers. Computer base analysis of the N-terminal amino acid sequence revealed no obvious homology with previously reported N-terminal amino acid sequences. Application of the glycoprotein to cerebellar astrocytes led time and dose dependently to an increased GABA uptake. The effect became maximal after 24 h exposure of the cells. Kinetic analysis of the GABA uptake showed that exposure of the astrocytes to the glycoprotein led to an increase in Vmax for GABA uptake without affecting Km, suggesting an increase in the number of GABA carrier molecules. Addition of actinomycin D together with the glycoprotein abolished this effect suggesting that the glycoprotein acts by stimulating de novo synthesis of GABA carriers. Hence, the newly purified protein secreted from neurons is named GABA-carrier inducing protein (GABA-CIP).

Amino Acid Sequence↗
PubMed2005

Advantages of terminating Zippy Estimation by Sequential Testing (ZEST) with dynamic criteria for white-on-white perimetry.

PURPOSE: A number of automated perimeters use the Zippy Estimation by Sequential Testing (ZEST) algorithm, which is an adaptive Bayesian method, for determining sensitivity measures. There are two popular rules for deciding when to terminate Bayesian procedures: (1) after a fixed number of presentations; or (2) when the probability density function (pdf) over all thresholds modified by the procedure becomes sufficiently narrow (a dynamic termination criterion). It has recently been argued that fixed termination criteria perform equally as well as dynamic criteria when applied in a fashion typical of laboratory-based visual psychophysics. Perimetry, however, has specific requirements; the tests must be very short, there is a wide range of possible sensitivities, and erroneous responses from the patient must be tolerated. This study used computer simulation to compare fixed and dynamic termination criteria for the ZEST algorithm using conditions typical of white-on-white perimetry. METHODS: Eight ZEST procedures were compared using the following termination criteria: fixed termination after 4, 5, 6, 7, and 8 presentations; dynamic termination when the standard deviation of the pdf was 1 dB, 1.5 dB, and 2 dB. Four patient error models were used: ideal, typical false-positive, typical false-negative, and unreliable patients. We also ran a version of ZEST that set the likelihood function exactly equal to the patient's frequency of seeing curve. RESULTS: The mean absolute error and standard deviation of error in threshold measurement was higher for the fixed termination criteria than for dynamic termination criteria of the same average number of presentations. CONCLUSIONS: The results of our simulations indicate that dynamic procedures have some distinct benefits over fixed termination procedures when a minimum of presentations are required and response errors are made as in a white-on-white perimetric setting. Dynamic termination criteria are at least partially successful in expending more presentations when required to enhance test precision.

Algorithms↗
PubMed1996

Activity-dependent modulation of the presynaptic potassium current in the frog neuromuscular junction.

1. Changes in the electrical properties of frog motor nerve endings caused by the invasion of an action potential were studied by the perineural recording technique. Two equal supramaximal stimuli separated by a variable time interval were applied to the nerve trunk. The latency and amplitude of the deflections associated with the nodal Na+ current and presynaptic K+ current elicited by the second pulse were compared with control currents. 2. The deflection associated with the presynaptic K+ current elicited in response to the second stimulus was absent at the shortest interstimulus interval and showed a progressive increase in its amplitude as the interstimulus interval was lengthened, reaching values greater than control in most terminals. During the same period the nodal Na+ current did not change. 3. The experimental results were compared with a computer model of the distal axonal segment and its terminal. Response of the model to twin-pulse stimulation was in marked disagreement with the experimental results unless an inactivating K+ channel, with properties derived ad hoc, was incorporated into the simulation. 4. These results suggest that in the first 6-7 ms after a nerve impulse has invaded a frog motor nerve ending, maximal K+ conductance remains below the value at rest due to the fast inactivation of a K+ conductance. Following this, there is a period in which K+ conductance is greater than control values although the basis for this is unknown.

4-Aminopyridine↗
PubMed1998

The translational signal database, TransTerm, is now a relational database.

TransTerm-97 contains more than 97 500 non-redundant coding-sequence initiation and termination contexts compiled from GenBank, release 101 (15-June-1997). In addition, several coding sequence parameters are available: coding sequence length, Nc, GC3, and, when it is computable, codon adaptation index (CAI). Codon usage tables and summaries of start and stop codon contexts are also included. The information covers more than 325 species and organelles, including seven complete bacterial genomes and one complete eukaryotic genome. To promote research in translational control of protein synthesis, TransTerm has been converted into a relational database to ease the process of making queries. The relational database manager, Postgresql, gives access to the database using SQL (Structured Query Language). A World Wide Web interface using forms is being completed to allow the casual user access to the database. Extensions are planned to include the full 5'-UTR, full coding sequence and 3'-UTR. TransTerm-97 is available on the World Wide Web at:http://biochem. otago.ac.nz:800/Transterm/homepage.html

Animals↗
PubMed1993

Nucleotide sequence of an abundant rice seed globulin: homology with the high molecular weight glutelins of wheat, rye and triticale.

A cDNA clone corresponding to a 19 kD salt-soluble globulin of rice (Oryza sativa L.) was isolated by screening a lambda gt11 expression library of endosperm mRNA with antibodies raised against the purified rice seed alpha-globulin. The cDNA contained a single large open reading frame encoding a putative globulin precursor of molecular weight of 21 kD. The polypeptide consists of 182 amino acids and is devoid of lysine residues. Computer analysis of the NH2-terminal sequence of the globulin precursor protein indicated the presence of an 18 amino acid signal peptide. Segments of the amino acid sequence of the rice globulin were homologous with sequences in high molecular weight glutelins of wheat. Antibodies specific for rice seed globulin also cross-reacted with seed proteins from wheat, rye and triticale.

Amino Acid Sequence↗
PubMed1995

Interactions of glutamate and dopamine in a computational model of the striatum.

A network model of simplified striatal principal neurons with mutual inhibition was used to investigate possible interactions between cortical glutamatergic and nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic inputs were represented by an excitatory synaptic conductance and a slow membrane potassium conductance, respectively. Neuronal activity in the model was characterized by episodes of increased action potential firing rates of variable duration and frequency. Autocorrelation histograms constructed from the action potential activity of striatal model neurons showed that reducing peak excitatory conductance had the effect of increasing interspike intervals. On the other hand, the maximum value of the dopamine-sensitive potassium conductance was inversely related to the duration of firing episodes and the maximal firing rates. A smaller potassium conductance restored normal firing rates in the most active neurons at the expense of a larger proportion of neurons showing reduced activity. Thus, a homogeneous network with mutual inhibition can produce equally complex dynamics as have been proposed to occur in a striatal network with two neuron populations that are oppositely regulated by dopamine. Even without mutual inhibition it appears that increased dopamine concentrations could partially compensate for the effects of reduced glutamatergic input in individual neurons.

Action Potentials↗
PubMed1994

Mechanisms for oscillation and frequency control in reciprocally inhibitory model neural networks.

We describe four different mechanisms that lead to oscillations in a network of two reciprocally inhibitory cells. In two cases (intrinsic release and intrinsic escape) the frequency of the network oscillation is insensitive to the threshold voltage of the synaptic potentials. In the other two cases (synaptic release and synaptic escape) the network frequency is strongly determined by the threshold voltage of the synaptic connections. The distinction between the different mechanisms blurs as the function describing synaptic activation becomes less steep and as the model neurons are removed from the relaxation regime. These mechanisms provide insight into the parameters that control network frequency in motor systems that depend on reciprocal inhibition.

Animals↗
PubMed2001

Complete nucleotide sequence of RNA-2 of Olive latent ringspot virus.

The complete nucleotide sequence of Olive latent ringspot virus (OLRSV) RNA-2 was determined. This RNA is 3969 nucleotides in length and contains a single open reading frame of 3448 nt, that encodes a polypeptide of 1146 amino acids, with a calculated Mr of 126,044. OLRSV RNA-2 has a structural organization typical of nepoviruses, with the coat protein (CP) cistron located in the C-terminal and the putative movement protein (MP) in the N-terminal regions of the polyprotein. Computer-assisted comparison of coat proteins of OLRSV and other nepoviruses disclosed relationships that tally with subgrouping based on physicochemical properties.

Amino Acid Sequence↗
PubMed1984

Primary structure of a high Mr form of rat atrial natriuretic factor.

During the purification of rat atrial natriuretic factor (ANF), low, intermediate and high Mr forms were observed. In this report we describe the purification and amino acid sequence of a 73 residue peptide containing at its C-terminus the previously sequenced 33 amino acid ANF peptide. The cleavage necessary to produce the 33 amino acid ANF from the 73 amino acid precursor occurs at a Leu-Leu bond. We also report the amino acid composition of an even longer form of ANF containing about 103 residues, in which the extension is amino terminal to the 73 peptide. A computer data bank search showed that the determined sequence is a novel one and is not homologous to any known proteins or segment thereof. The natriuretic activity of the 73 amino acid form when compared to that of a synthetic ANF peptide, comprising the sequence of the last 26 amino acids of ANF, was found to be slightly lower.

Amino Acid Sequence↗
PubMed1988

ProOmpA is stabilized for membrane translocation by either purified E. coli trigger factor or canine signal recognition particle.

We have isolated large amounts of E. coli outer-membrane protein A precursor (proOmpA). Purified proOmpA is active in membrane assembly, and this assembly is saturable with respect to the precursor protein. A proOmpA-Sepharose matrix allows affinity isolation of trigger factor, a soluble, 63,000 dalton monomeric protein that stabilizes proOmpA in assembly competent form. Comparison of trigger factor's amino-terminal sequence with those in a computer data bank and with those encoded by sec genes, as well as groEL and heat shock gene dnaK, suggests that trigger factor is encoded by a previously undescribed gene. Trigger factor and proOmpA form a 1:1 complex that can be isolated by gel filtration. Purified canine signal recognition particle (SRP) can also stabilize proOmpA for membrane insertion. This postribosomal activity of SRP suggests a unifying theme in protein translocation mechanisms.

Amino Acid Isomerases↗
PubMed1988

Calcium binding to tubulin.

Using flow dialysis, we found two classes of calcium-binding sites on tubulin: high-affinity binding sites (1.56 +/- 0.38 per tubulin dimer) with a dissociation constant of (4.86 +/- 0.12).10(-6) M and low-affinity binding sites (5.82 +/- 0.50 per tubulin dimer) with a dissociation constant of (6.4 +/- 0.4).10(-5) M. In the presence of 6.10(-5) M MgSO4, we found 0.64 +/- 0.18 calcium-binding sites per tubulin dimer with a dissociation constant of (4.7 +/- 0.5).10(-6) M and 1.2 +/- 0.2 sites per dimer with a dissociation constant of (3.5 +/- 0.4).10(-5) M. Under controlled conditions, trypsin and chymotrypsin selectively cleaved alpha- and beta-subunits, respectively, forming major fragments of 35 kDa and 20 kDa from the alpha-subunit, and major fragments of 31 kDa and 22 kDa from the beta-subunit. The high-affinity calcium-binding sites were detected in the carboxyl-terminal region of each tubulin subunit. Computer analysis of the subunit amino-acid sequences suggested possible locations of the putative calcium-binding sites.

Amino Acid Sequence↗
PubMed1996

Psychophysiological responses to changes in workload during simulated air traffic control.

In this investigation, eight Air Force air traffic controllers (ATCs) performed three scenarios on TRACON (Terminal Radar Approach Control), a computer-based air traffic control (ATC) simulation. Two scenarios were used each with three levels of difficulty. One scenario varied traffic volume by manipulating the number of aircraft to be handled and the second scenario varied traffic complexity by manipulating arriving to departing flight ratios, pilot skill and mixture of aircraft types. A third scenario, overload, required subjects to handle a larger number of aircraft in a limited amount of time. The effects of the manipulations on controller workload were assessed using performance, subjective (TLX), and physiological (EEG, eye blink, heart rate, respiration, saccade) measures. Significant main effects of difficulty level were found for TRACON performance, TLX, eye blink, respiration and EEG measures. Only the EEG was associated with main effects for the type of traffic. The results provide support for the differential sensitivity of a variety of workload measures in complex tasks, underscore the importance of traffic complexity in ATC workload, and support the utility of TRACON as a tool for studies of ATC workload.

Adult↗