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At least 307 records · Page 17Linked to original sources
PubMed1990

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↗
PubMed1999

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus.

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus. Four chimpanzees were immunized with 1 of 2 licensed recombinant hepatitis B vaccines. Shortly after the chimpanzees developed antibodies to hepatitis B surface antigen (anti-HBs), they were challenged intravenously with mutant HBV strain AS. Two unvaccinated chimpanzees served as positive controls. The 4 vaccinated chimpanzees did not develop evidence of HBV infection or hepatitis during 2 years following virus challenge. In contrast, the 2 unvaccinated chimpanzees developed HBV infection and hepatitis. Serum anti-HBs in the vaccinated chimpanzees reacted not only with wild-type surface antigen, but also with mutant surface antigen by competition enzyme-linked immunosorbent assay (ELISA). Thus, immunization of chimpanzees with licensed recombinant hepatitis B vaccines stimulates anti-HBs that is broadly reactive and affords protection against infection with a surface gene mutant of HBV, suggesting that properly immunized individuals are not at significant risk of infection with this prototype variant strain of HBV.

Animals↗
PubMed1993

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↗
PubMed1999

Sphingosine 1-phosphate: a prototype of a new class of second messengers.

Sphingosine 1-phosphate (SPP) is an important sphingolipid-derived second messenger in mammalian cells that acts to promote proliferation and to inhibit apoptosis. Various growth factors increase the intracellular concentration of SPP by activating sphingosine kinase, the molecular cloning of which has revealed that it defines a new type of lipid kinase. Cell fate is influenced by the balance between the intracellular concentration of SPP and that of ceramide, a pro-apoptotic sphingolipid metabolite. The observation that a similar "rheostat" is a determinant of cell survival in yeast cells exposed to heat shock indicates that it is an evolutionarily conserved mechanism of stress regulation. SPP also acts extracellularly to inhibit cell motility and to influence cell morphology, effects that appear to be mediated by the G protein-coupled receptor EDG1. These observations indicate that SPP is the prototype of a new class of lipid mediators that exert both intracellular and extracellular actions.

Animals↗
PubMed1988

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↗
PubMed1995

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↗
PubMed2001

Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively.

Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is mediated by Th1 cells. The major Th1 inducer, IL-12, enhances EAE, while its blockade suppresses it. IL-4 suppresses EAE. Here, we determined IFN-gamma and IL-4 production by myelin basic protein-stimulated lymphocytes from prototypically EAE-susceptible SJL/J and EAE-resistant BALB/c mice, 9 days after immunization with spinal cord homogenate. While lymphocytes from SJL/J mice produce IFN-gamma and no IL-4, lymphocytes from BALB/c mice produce IL-4 and no IFN-gamma. Since early endogenous production of IL-12/IFN-gamma or IL-4 is linked to Th1 or Th2 responses, respectively, we determined whether neutralization of IL-12 or IL-4 at immunization modifies susceptibility or resistance to EAE. SJL/J mice given neutralizing anti-IL-12 mAb are protected from EAE. BALB/c mice given neutralizing anti-IL-4 mAb develop EAE, while those treated with control antibody remain resistant. These studies confirm the pivotal role of IL-12 in EAE development and show that endogenous IL-4 is important for determining the genetic resistance to EAE.

Animals↗
PubMed1996

A model of the immune network with B-T cell co-operation. I--Prototypical structures and dynamics.

Hitherto, "second generation" network models of the immune system have all been restricted to B-lymphocytes and the Ig molecules they produce. These models have not so far been able to provide a convincing mechanism for the distinction between a "Central Immune System" (CIS) composed of a connected network of lymphocyte clones which couple with "self" antigens in a tolerant mode, and a "Peripheral Immune System" (PIS) composed of clones with little or no supra-clonal organization and which produce classical immune responses when interacting with "non-self" antigens. Here, we present a new network model which explicitly incorporates B-T cell co-operation. In this model, B-cell activation is dependent on T-cell help, and activated T-cells are down-regulated by engagement of their TCRs by soluble Ig. We discuss the underlying biology on which we base the system of ordinary differential equations which defines the present network model. We then illustrate some basic features of the model by examining several prototypical situations with a small number of clones. Depending on the idiotypic connectivity structure, the model exhibits two distinct modes of coupling with antigens: an "immune response" mode in which T- and B-cell clones grow exponentially; and a "tolerant" mode in which T-cell clones are controlled by inclusion of all TCRs in the repertoire of an idiotypic B-cell network. Finally, we discuss the simplifying assumptions of the present model and argue that its range of validity is indeed the region of the state-space of the system where the discrimination between the CIS and the PIS take place.

B-Lymphocytes↗
PubMed1999

A prototype model structure for mixed microbial populations in homogeneous food products.

An important factor which has not been included in many models in the field of predictive microbiology is the influence of a background of microflora in a food product. It is however generally known that the growth of a microorganism as a pure culture can be substantially different from its growth in a mixed culture, due to microbial interactions. Because of the importance of these interactions and the lack of suitable modeling techniques in the field of predictive microbiology to describe them, the potential of models in other research fields-namely ecology-to deal with interactions is explored in previous work of the authors. However, a model structure for microbial growth in food products cannot simply be copied from those elaborated in ecology. The structure of a predictive growth model is indeed typical, primarily due to the explicit modeling of a lag phase. The current paper proposes a prototype model structure for growth of mixed microbial populations in homogeneous food products. The model is able to describe a lag phase and reduces to a classical predictive growth model in the special case of single-species growth.

Bacteria↗
PubMed2002

Efficacy of gene therapy for a prototypical lysosomal storage disease (GSD-II) is critically dependent on vector dose, transgene promoter, and the tissues targeted for vector transduction.

Lysosomal storage diseases are an intriguing target for gene therapy approaches, as transduction of a "depot" organ with a transgene encoding a lysosomal enzyme can be followed by secretion, systemic distribution, downstream uptake, and lysosomal targeting of the enzyme into non-transduced tissues. These benefits are of utmost importance when considering gene therapy approaches for glycogen storage disease type-II (GSD-II). GSD-II is a prototypical lysosomal storage disorder caused by lack of intralysosomal acid alpha-glucosidase (GAA) activity. Lack of GAA can result in a proximal limb myopathy and respiratory and cardiac failure, each due to abnormal glycogen accumulation in the skeletal muscles or cardiac tissues, respectively. After converting the liver into a "depot" organ, we found that intravenous injection of the [E1-,polymerase-]AdGAA vector allowed for hepatic secretion of GAA over an at least 20-fold dosage range. We noted that very low plasma GAA levels (derived from hepatic secretion of GAA) can allow for GAA uptake by muscle tissues (skeletal or cardiac), but significantly higher plasma GAA levels are required before glycogen "cross-correction" can occur in these same tissues. We also demonstrated that liver-specific enhancer/promoters prolonged GAA transgene expression from persistent [E1-,polymerase-] adenovirus based vector genomes for at least 180 days, and significantly diminished the amounts of neutralizing anti-GAA antibodies elicited in this animal model. Finally, we demonstrated that skeletal muscles can also serve as a "depot" organ for GAA secretion, allowing for secretion of GAA and its uptake by noninfected distal tissues, although glycogen reductions in non-injected muscles were not achieved by the latter approach.

Adenoviridae↗
PubMed1993

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↗
PubMed1998

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1987

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↗
PubMed1993

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↗
PubMed1988

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↗
PubMed1993

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↗