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Multicenter clinical experience with the development of a novel short coronary stent and its prototype device.

Our initial experience with the Micro Stent PL and its prototype intracoronary stent is described. A total of 206 stents were implanted in 84 patients for threatened closure or restenosis following balloon angioplasty. The stenting procedure was successful and uncomplicated in 83 of 84 patients. Potential advantages of this particular stent relate to its short length, low surface area, expandability over a range of diameters, radiopacity, low profile, and ease of delivery.

Angioplasty, Balloon, Coronary

Responses given by A and B quasi-therapists to differing sexual roles in an intropunitive-neurotic prototype: an analogue study.

Twenty-four male undergraduate students were selected on the basis of their A--B status. Six Ss of each type were assigned randomly to one of two videotaped stimulus conditions, an adequate or an inadequate sexual role variant of an intropunitive neurotic prototype. Two dependent measures, response time and number of confrontations, were used and conceptualized in terms of an approach-avoidance continuum. Differential responding on the basis of the Ss' A--B status was not supported in this study.

Adolescent

Human rheumatoid factor cross-idiotypes. III. Bla monoclonal rheumatoid factor, prototype of the BLA cross-idiotype group, has distinct kappa chains related to the V kappa III subgroup and VH4 heavy chains.

The BLA cross-idiotype (XId) is present on a unique subset of rheumatoid factors (RF) that cross-react with DNA-histone. In this study, prototype Bla monoclonal RF was shown from serologic investigations and N-terminal amino acid sequence analysis to have distinct kappa chains related to the V kappa III subgroup and VH4 heavy chains. The amino terminus of the heavy chain was cyclized, rendering the protein resistant to Edman degradation and providing a possible investigator bias to the published Ig sequence data to date. This appears to be the first definitive report of a serum IgM that expresses the VH4 gene. RF with DNA cross-reactivity have been reported to be produced by human and mouse cloned cells that have the VH4 or homologous mouse Vh36-60 gene.

Amino Acid Sequence

Stability studies of the components of a prototype penicillinase (beta-lactamase)-linked ELISA kit.

Penicillinase (beta-lactamase) enzyme-linked immunosorbent assay (ELISA) for various reproductive hormones developed in the laboratory were found to have wide applicability in the fertility check clinic of the Institute. A need was thought to transform these assays into ready-to-use kit forms. Therefore, prototype ELISA kits for these hormones were developed and stability of the individual component was ascertained at various temperatures (room temperature, 37 degrees C and 2-8 degrees C). Stability studies were conducted on previously validated assay for pregnanediol-3 alpha-glucuronide (PdG). The studies showed that immunosorbents (antibody coated plates) are stable at room temperature for a period of 2 weeks, at 37 degrees C for 1 week and at 2-8 degrees C for a period of 9 months when preserved after treatment with glycerol solution. The lyophilised conjugate, standard and immunoassay buffer, colour reagent, and its substrate were stable at 37 degrees C up to 1 week and at room temperature up to 2 weeks and at 2-8 degrees C for a period of 6 months, during which the stability was studied.

Enzyme Stability

Circulating interferon in the guinea pig infected with the XJ, prototype Junin virus strain.

The interferon (IFN) induction capacity of the XJ prototype strain of Junín virus (JV) was investigated in the guinea pig model. Circulating alpha IFN was detected in 50% of the animals from days 2 to 9 postinfection (pi) and in 100% at day 11 pi, when all animals were in the premortem stage. Individual levels ranged from 20 to 1,280 guinea pig IFN units (GPIFNU)/ml. A correlation between XJ strain virulence and IFN titers was recorded. A possible role of IFN as a pathogenic factor in the outcome of the disease is discussed.

Animals

Enterovirus 71 isolated from China is serologically similar to the prototype E71 BrCr strain but differs in the 5'-noncoding region.

Enterovirus 71 H (E71 H), an isolate from an adult patient with hand-food-mouth disease (HFMD) in China, was serologically similar to the prototype strain E71 BrCr, which was isolated from a patient with aseptic meningitis. The study further analyzed the similarity of E71 H to E71 BrCr at the 5'-noncoding region (NCR), a location in genomic RNA that recently was found to be related to neurovirulence in poliovirus and Venezuelan equine encephalitis virus. Using a reverse transcription-polymerase chain reaction (RT-PCR) technique and a unique primer pair I, a 397 bp product was detected from E71 BrCr, Cox A9 (Griggs), Cox A16 (NIH), Cox B1 (HA antigen 201-468), Cox B5 (wild type), and ECHO 11 (Gregory), but not from E71 H, Cox A24 (Joseph), and ECHO 5 (Noyce). However, all of the viruses generated a 154 bp product using a universal enterovirus primer pair II. Further comparative analysis using primer-directed sequencing of both the E71 H and E71 BrCr 154 bp products revealed that they differed by 12 bases. The variations between the two viruses were clustered in two loci, one in the region of nucleotides 43-61 with eight variations, and the other in the region of nucleotides 120-133 with three variations. The differences within the 5'-NCR between the E71 H (HFMD) and the E71 BrCr (aseptic meningitis) viruses might provide a clue to explain why E71 was associated with two different clinical patterns: polio-like disease in the United States. Australia, and Eastern Europe, HFMD in China, Japan, and Singapore.

Adult

Analysis of G418-selected Rat2 cells containing prototype, variant, mutant, and chimeric JC virus and SV40 genomes.

The human polyomavirus JC virus (JCV) is highly tumorigenic in rodents, but transforms cells in culture inefficiently. To explore the basis for JCV's restricted transforming behavior, nonpermissive Rat2 cells were contransfected with pSV2-neo (encodes G418 resistance) and viral DNAs including prototype, variant, and mutant JCV genomes and two JCV-SV40 chimeras. By selecting cells displaying G418 resistance, lines were established that contain viral DNA and exhibit a wide range of transformed phenotypes. The G418-resistant lines were tested for their ability to grow under anchorage-independent conditions, to overgrow a monolayer of untransformed cells, and to form dense colonies on plastic. Expression of the viral T and t proteins and interaction of T protein with the cellular anti-oncoprotein p53 were measured. Also determined was the number of intact viral early coding regions integrated within the cellular DNA. The results of these studies suggested that most of the G418-resistant lines failed to express JCV T protein above a minimum threshold level required for their conversion to a fully transformed phenotype. In anchorage-independent growth assays, higher levels of a 17-kDa T-related peptide in JCV transformants appeared to compensate for decreased T antigen levels. Comparison of the T to p53 ratios in the cell lysates suggested that the quaternary structure of the JCV protein differed from that of its SV40 counterpart in the T-p53 complex. The presence of multiple vs single integrated copies of the viral genome in the cells did not correlate with elevated T antigen expression or an enhanced transformation status.

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