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Detection and quantitation of human respiratory syncytial virus (RSV) using minigenome cDNA and a Sindbis virus replicon: a prototype assay for negative-strand RNA viruses.

We describe here a novel approach for detecting and quantitating human respiratory syncytial virus (RSV) based on expression of a reporter gene from an RSV minigenome. BHK cells were cytoplasmically transformed with a noncytopathic Sindbis virus replicon expressing T7 RNA polymerase. These cells were then cotransfected with T7 expression plasmids that contain the cDNA of an RSV minigenome and the genes for RSV nucleocapsid proteins N, P, and L. The minigenome contains a reporter gene such as lacZ or CAT flanked by cis-acting RSV transcription signals. Subsequent infection of these cells with RSV resulted in a high level of reporter gene expression which could be inhibited by ribavirin. Mock-infected cells exhibited background levels of expression. This assay can be used to quantitate RSV and titer neutralizing antibody and may be a valuable tool for screening compounds for anti-RSV activity. It serves as a prototype for other negative-strand RNA viruses.

Animals↗

A prototype device for linear accelerator-based extracranial radiosurgery.

A prototype frame for accurate stereotactic localization and linear accelerator (LINAC)-based treatment of extracranial targets was developed. The ECRSF is designed to employ either spinal or skeletal osseous fixation to immobilize the area of interest and then encircle the targeted region with a traditional orthogonal, three-axis system. A series of experiments (n = 5) with semi-radiolucent calibration targets (n = 15) and computed tomography (CT) scanning using the EC showed that a mean localization error of 0.98 +/- 0.22 mm was obtainable in the last two and most accurate series of experiments with these targets (n = 8). Using the LINAC to irradiate these same targets demonstrated an overall radiation treatment accuracy ranging from 1.4 to 2.0 mm. This discrepancy between localization error and overall radiation treatment error can be explained by a lack of isocentricity of the LINAC treatment which is typically less than 1 mm and can be as low as 0.5 mm. These data demonstrate that extracranial stereotactic radiosurgery is now technically feasible and that the accuracy of such treatment would be acceptable for clinical treatment.

Equipment Design↗

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients.

Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.

Absorption↗

Serologically atypical adenovirus strains of subgenus D are different in their genome from the respective prototypes.

Seven adenovirus strains of subgenus D, related to adenovirus types 8, 10, 13, 19, 23, 24 and 26, but atypical in their serological reactions or in hemagglutinin properties, were characterized by neutralization and hemagglutination-inhibition. DNA restriction analysis with five endonucleases showed that each of the strains was strikingly different from the respective prototype.

Adenoviruses, Human↗

A neural model for nonassociative learning in a prototypical sensory-motor scheme: the landing reaction in flies.

Nonassociative learning is an important property of neural organization in both vertebrate and invertebrate species. In this paper we propose a neural model for nonassociative learning in a well studied prototypical sensory-motor scheme: the landing reaction of flies. The general structure of the model consists of sensory processing stages, a sensory-motor gate network, and motor control circuits. The paper concentrates on the sensory-motor gate network which has an agonist-antagonist structure. Sensory inputs to this circuit are transduced by chemical messenger systems whose dynamics include depletion and replenishment terms. The resulting circuit is a gated dipole anatomy and we show that it gives a good account of nonassociative learning in the landing reaction of the fly.

Animals↗

Pharmacokinetics and metabolism of the mixed-function hypoxic cell sensitizer prototype RSU 1069 in mice.

RSU 1069 is a leading compound in the class of mixed-function hypoxic cell sensitizers. Possessing an alkylating aziridine function as well as a nitro group, it represents an important prototype molecule for new sensitizer development. Using a novel HPLC assay for RSU 1069 and its metabolites with a cyanopropyl column, we studied the detailed pharmacokinetics and metabolism of this drug in mice. An i.v. dose of 100 mg kg-1 produced peak plasma concentrations of about 100 micrograms ml-1. Absorption was rapid after i.p. injection but peak plasma concentrations were some three- to fourfold lower, giving an i.p. bioavailability of 55%. The elimination t1/2 was route-dependent; e.g. after 50 mg kg-1 the t1/2 was 37.2 and 22.4 min for the i.v. and i.p. routes respectively (P less than 0.001). There was also an indication of dose-dependent kinetics, with a 37% increase in elimination t1/2 when the i.p. dose was doubled from 50 to 100 mg kg-1. Oral bioavailability was low. The volume of distribution was 0.65-1.31 ml g-1 at 50 mg kg-1, but tissue penetration was limited. Brain/plasma ratios ranged from 9.3% to 66.8%, while the mean steady-state tumour/plasma ratio was 28.4%, a value considerably less than the 80%-100% ratios occurring with the neutral 2-nitroimidazole misonidazole. About 18% and 8% of a dose were excreted as the parent drug and the ring-opened hydrolysis product (RSU 1137) in the 8 h urine, indicating the likelihood of extensive metabolism via aziridine-ring removal and nitroreduction. RSU 1137 was also detected in mouse plasma and tissues and, in contrast to the aziridine ring-intact parent compound, gave tumour/plasma ratios of 100%. These studies should provide a pharmacokinetic basis for the evaluation and development of improved mixed-function sensitizers.

Animals↗

A possible prototype of multifocal recurrence after liver resection of hepatocellular carcinoma: report of a case.

The clinical course of a 68-year-old male with HCC is herein reported. In addition to two tumor nodules detected preoperatively, the resected surgical specimen disclosed macroscopically invisible tumor-cell clusters as well as intrahepatic metastatic foci. These clusters had no clear border and were more basophilic with small-sized cells, high cellularity, and a higher nuclear/cytoplasm ratio, which was suggestive of early HCC with a form of de novo occurrence. The postoperative course, characterized by an early recurrence of small nodules in the remnant liver suggested the presence of a similar invisible tumor mixture at the time of operation. This case can thus be regarded as a prototype of the multifocal recurrence type.

Aged↗

The expression of Mlsc determinants on Mlsa, Mlsb, and Mlsx prototypic strains.

In the mouse system, specific determinants other than major histocompatibility complex (MHC) gene products are capable of inducing strong primary proliferative responses in naive T cells. These determinants are encoded by at least two gene loci designated as minor lymphocyte stimulatory (Mls) loci. In order to elucidate the biological role of the Mls system, an effort has been initiated to clarify the fundamental immunogenetic characteristics of the Mls system. In this report, we describe the unexpected finding that Mlsc determinants are expressed on splenocytes of strains including those which have been used as prototypic examples of three other Mls types: Mlsa (DBA/2, DBA/1), Mlsb (BALB/c), and Mlsx (PL/J). The expression of Mlsc by these strains was demonstrated both by the response patterns of unprimed T cells from MHC-identical inbred or F1 hybrid strains and by the responses of a panel of Mls-specific T-cell clones. The experimental results reported here also suggest that the expression of Mls determinants may be influenced by multiple other genes, including MHC-linked genes.

Animals↗

A longitudinal therapeutic comparison between two prototypic neuroleptics (haloperidol and chlorpromazine) in matched groups of schizophrenics. Nontherapeutic interactions with trihexyphenidyl. Theoretical implications for potency differences.

The treatment process with two prototypic neuroleptics--haloperidol and chlorpromazine--and the nontherapeutic effects of trihexyphenidyl on this process were studied in carefully matched groups of ten schizophrenics each, using a "double-blind", repeated-measure, longitudinal research design. Measurements of various aspects of psychopathology, social participation and clinical indices of arousal were made periodically and objective test of cognition and attention were given. The two treatment groups were highly comparable in epidemiological and clinical terms and differed significantly during the baseline period in only one of the 39 parameters. Longitudinal nonparametric analyses showed that significant therepeutic changes tended to occur more quickly and involved a wider spectrum of schizophrenic phenomena with haloperidol than with chlorpromazine. Parametric analyses also indicated that at the completion of the study, haloperidol-treated patients had significant improvement in many more dimensions than the chlorpromazine-treated patients and that the changes with haloperidol were generally of greater magnitude. At the same time, chlorpromazine treatment seemed to be more susceptible to the antagonistic effects of trihexyphenidyl. No differential patterns of responses were noted for the two neuroleptics to provide any clinical validity to the distinction often made between "sedative" and "activating" neuroleptics. These data were in agreement with those from a previous comparative study which had a very different research design and a somewhat different type of schizophrenic population. The clinical and potency differences between the two neuroleptics were again explained on the basis of the fact that chlorpromazine has much stronger built-in anticholinergic properties, which may be acting in opposition to the antipsychotic activity. It was suggested that the degree of inherent anticholinergic activity may be an important determinant of potency differences among presently known neuroleptics. The possible role of cholinergic mechanisms in schizophrenia was discussed.

Adult↗

Animal evaluation of the prototype omnicath atherectomy catheter.

A prototype directional atherectomy catheter (Omnicath) was evaluated in four Yucatan microswines. Atherectomy was performed on iliac or aortic target lesions. After control angiography, the animals were sacrificed and the target arteries were examined histologically. Atherectomy resulted in arterial ruptures in three cases, and the track of the blade was measured to be of an average depth of 0.38 mm. Maneuverability was satisfactory but aspiration was not efficient. Precise localization of the atherectomy window was difficult. We conclude that modification of the catheter seems mandatory before use in humans.

Animals↗

Testing of prototype antiepileptics in hippocampal slices.

The effects of six prototype anticonvulsant drugs, phenytoin, carbamazepine, midazolam, phenobarbital, ethosuximide and sodium valproate, were evaluated in two different experimental models of epileptiform activity using the in vitro slice preparation from the rat hippocampus. The relative potencies of the agents were determined: a) in the complete absence of synaptic transmission by recording spontaneous burst firing from the CA 1 pyramidal cell layer in a low calcium high magnesium solution and b) during blocked synaptic inhibition by observing the activity of each drug upon orthodromically evoked population spikes in penicillin containing medium. The rank order of potencies was a) in low Ca2+: carbamazepine, phenytoin, midazolam, phenobarbital, valproate, ethosuximide; b) in penicillin containing medium: midazolam, phenobarbital, carbamazepine, phenytoin, valproate, ethosuximide. These observations illustrate that the use of multiple paradigms is warranted when examining the mechanisms of action of new anticonvulsants.

Animals↗

A generalized laboratory software package--a prototype approach.

A prototyped model of a generalized table-driven software package for laboratory testing and results registration is presented. The need to computerize dozens of laboratories performing hundreds of tests, called for a radical approach which would enable the quick addition of new laboratories to the system, as well as ease of maintenance. The generalized laboratory software package (GLAB) relies on a set of data tables, maintained by users, and a menu controlled environment interfacing GLAB with the rest of the hospital's systems.

Clinical Laboratory Information Systems↗

A subtype of the prototypic karyotype in acute myeloid leukemia t (8; 21) (q22; q22), del 9 (q13; q23).

Two patients with acute myeloid leukemia are described in whom G- and C-banding analysis of bone marrow cells revealed, besides the translocation t(8;21), an additional structural anomaly characterized by the deletion of bands q13 to q23 of one chromosome no. 9. Findings in the literature support the proposal that this constellation represents a hitherto unreported subtype of the prototypic karyotype in AML.

Adult↗

Evaluation of a portable prototype to analyze heart rate variability.

Power spectrum analysis of heart rate fluctuations provide a quantitative noninvasive means of assessing the functioning of the cardiovascular control system. Until now the equipment used to study heart rate variability (HRV) have been complicated systems utilized mostly in research centers. Simpler systems are needed for routine clinical application. We have evaluated, through clinical practice, the usefulness of prototype equipment which allows acquisition and analysis of ECG signals by a portable electrocardiograph and a personal computer in which sophisticated software is installed. We performed one hundred forty-five recordings in twenty-two patients admitted to ICU. With this technique two different predictive patterns were detected: one concerning survivors, the other concerning nonsurvivors. Reliability, portability, simplicity and quality results are the main advantages of the system. The disadvantage is that it is difficult to perform HRV analysis in patients with ECG arrhythmia. This is because the program does not allow the choice of an arrhythmia-free section of the tachogram to analyze.

Adolescent↗

A new subgroup 2 bovine adenovirus proposed as the prototype strain 10.

A slowly growing subgroup 2 bovine adenovirus (BAV) strain designated Ruakura 78-5371 was isolated from a yearling heifer with systemic adenovirus infection. Cross neutralization tests and restriction endonuclease analysis of the viral DNA showed the virus to be distinct from the other 9 recognised types of BAV. It is proposed that this strain should be regarded as the prototype strain of the new type BAV-10.

Adenoviridae↗

DNA restriction analysis of adenovirus prototypes 1 to 41.

DNA restriction patterns of all known human adenovirus prototypes (1 to 41), ordered according to subgenera A to F, are presented for restriction endonucleases BamHI, BglII, BstEII, HindIII, and SmaI. This catalogue is a prerequisite for typing of adenoviruses by DNA restriction analysis in diagnostic laboratories and for strain identification in reference laboratories. To determine the genetic relationship of human adenoviruses within a subgenus and between subgenera, a pairwise analysis of comigrating fragments was performed. Adenoviruses of subgenus C were closely related. Adenoviruses of subgenus B showed two related clusters of four types each, whereas the numerous serotypes of subgenus D did not show any corresponding clustering. Little comigration was observed between DNA restriction fragments from members of subgenus A or F respectively.

Adenoviruses, Human↗

ABAC identibiogramme: prototype of an automated system for identification of enterobacteria.

The ABAC Identibiogramme, an automated, computerized system for the identification and antimicrobial susceptibility testing of the Enterobacteriaceae has been developed recently. The biological basis of the system resides in lyophilized, highly discriminating media enclosed in wells of an automatically inoculated disposable cartridge. The introduction of a suitable specimen rehydrates and inoculates the media in the wells. After incubation for 16 to 18 h at 37 degrees C and the addition of only one reagent (Kovacs reagent), the media changes and the results obtained are interpreted by an automated optical system and a computer. The antibiogram is also used by the computer to confirm the biochemical identification of the organism. The identification accuracy of a prototype of the ABAC Identibiogramme system was compared with that of API 20 E and conventional methods using a total of 1,290 clinical isolates. The ABAC Identibiogramme correctly identified 96.8% of the organisms tested, misidentified 2.4% and failed to identify 0.8%. The results demonstrate the high reliability and good identification performance of the ABAC Identibiogramme in comparison to API 20 E and conventional methods.

Enterobacteriaceae↗

Development of prototype equipment for innovative employment of blind and partially sighted persons.

Sensory Aids Foundation of Palo Alto, California, has funded development of a number of microprocessor-based or computer-related sensory aids to enable blind and partially sighted persons to enter innovative areas of employment previously inaccessible to them. Three of these devices are discussed in this paper: the prototype TSPS (Traffic Service Position System) console for blind telephone operators; an Optacon Tracking Guide for CRT displays; and a Digital Indexing System for cassette audio recorders. In addition, three other microprocessor-based products recently acquired by Sensory Aids Foundation for placement with blind or partially sighted clients are briefly described: the Speech Annunciator for digital laboratory instruments; the Large Print Video Terminal; and the TIM-II (Talking Information Management System). A new grant received from the Department of Health, Education and Welfare, the Projects With Industry Section, has allowed expansion of services to develop computer-related jobs for blind, deaf, and orthopedically disabled persons.

Blindness↗