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V and C gene contribution in creating anti-alpha-1,3 dextran antibodies in mice. II. Characteristics of Ig-lb to e prototype responses.

The light (L) and heavy (H) chain and the idiotypic (Id) composition of the antibody (Ab) plaque-forming cells (PFC) and serum Ab specific for alpha-1,3 dextran have been characterized in murine strains exhibiting the CH-Ig-lb to e allotypes and in their F1 hybrids with Ig-la1, BALB/c prototypes. The Ab response of the Ig-lb to e mice to the alpha-1,3 dextran was low in the kappa (kappa) L chain class with only a minor, sporadic Ab in the lambda (lambda) L chain class discernible after prolonged immunization. Two of a total of sixty-eight C57Bl/6 Ig-lb mice, in a total of 318 Ig-lb to e mice tested, exhibited, in late responses, a significantly elevated Ab in the lambda L class at both serum and PFC levels, equalling at the PFC level the total non-specific lambda PFC values. An Id analysis showed this lambda Ab and the kappa Ab to lack the Id relatedness to the three BALB/c alpha-1,3 dextran-binding myeloma proteins (MP) Ab prototypes, J-558, 104 E, and UPC-102, exhibited by the lambda Id+ Ab of the Ig-la1 BALB/c prototypes and their F1 hybrids with the Ig-lb to e prototypes. Furthermore, affinity differences could be detected by alpha-1,3 nigerodextrans, PFC inhibition analysis, between the late C57Bl/6 anti-alpha-1,3 dextran lambda Id--Ab PFC and the lambda Id+ Ab PFC of the BALB/c and their F1 progeny.

Animals

Predominance of the prototypic T15 anti-phosphorylcholine junctional sequence in neonatal pre-B cells.

The primary antibody response to phosphorylcholine (PC) is dominated by T15 antibodies. There are three families of anti-PC antibodies which can be made in mice: T15, 511, and 603. All use the same H chain V, D, and J segments, but each anti-PC family has a different L chain, as well as a family-specific Vh-D junctional sequence. Here we test the hypothesis that T15 antibodies are dominant because the prototypic T15 V-D junction is generated in pre-B cells more often than the alternative non-T15 V-D junctional sequences. Rearranged IgH genes from DNA derived from fetal or newborn liver pre-B cells and from adult bone marrow pre-B cells of BALB/c mice were amplified by polymerase chain reaction, cloned, and sequenced. DNA from adult splenic B cells was also amplified, for comparison. All V1-DFL16.1 and DFL16.1-Jh1 junctional sequences were analyzed. Fifty-three percent (9/17) of all neonatal pre-B cell V-D junctions with V1 and DFL16.1 had the prototypic T15 junctional sequence, which has no N regions. In contrast, no prototypic T15 V-D junctions were observed in adult pre-B cells, and each junctional sequence was unique. Adult splenic B cells contained an intermediate number of T15-type V-D junctional sequences (7/21). The prototypic D-J junctional sequence used in many anti-PC antibodies was also observed in a high percentage of sequences. The high frequency of T15 junctions in the neonatal pre-B cells can be explained by two observations: 1) N regions are absent in neonatal but not adult junctions and 2) in the absence of N regions, joining of V, D, and J segments may be targeted to short regions of sequence homology near the ends of the genes. This mechanism would preferentially give rise to the T15 V-D and D-J junctions. Preservation of the T15 V-D junction in adult splenic B cells is most likely due to antigenic stimulation of long lived precursors, because a high frequency of T15-type D-J junctions are coexpressed with T15 V-D junctions in splenic sequences. These results predict that T15 anti-PC precursors would be made at a very high frequency in the neonate, and at a much lower frequency in the adult. This may explain why the neonatal period is critical in establishing T15 dominance.

Amino Acid Sequence

Prototypic sequences for human repetitive DNA.

We report a collection of 53 prototypic sequences representing known families of repetitive elements from the human genome. The prototypic sequences are either consensus sequences or selected examples of repetitive sequences. The collection includes: prototypes for high and medium reiteration frequency interspersed repeats, long terminal repeats of endogenous retroviruses, alphoid repeats, telomere-associated repeats, and some miscellaneous repeats. The collection is annotated and available electronically.

Animals

The relationship between depression and anxiety: construction of a prototypical anxiety and depression scale.

The question of the relationship between anxiety and depression remains to be solved. The fact that clinical pictures show substantial overlap makes it difficult, using conventional instruments, to distinguish between the co-occurrence of anxiety and depression and overlap in definitions and measurement of the two syndromes. This calls for the construction of scales which exclude symptoms common to both syndromes and incorporate symptoms specific only to anxiety or only to depression; i.e. scales with maximum discriminant validity. This article describes the construction of two such scales based on PSE symptoms; a prototypical anxiety scale and a prototypical depression scale. In a sample of 134 non-psychotic psychiatric out-patients these scales show good reliability and validity, both as a measure of severity and as a screening device. Compared to the Hamilton anxiety and depression scales (HARS and HRSD), the correlation between the prototypical anxiety and depression scales is low.

Adult

Emotion knowledge: further exploration of a prototype approach.

Recent work on natural categories suggests a framework for conceptualizing people's knowledge about emotions. Categories of natural objects or events, including emotions, are formed as a result of repeated experiences and become organized around prototypes (Rosch, 1978); the interrelated set of emotion categories becomes organized within an abstract-to-concrete hierarchy. At the basic level of the emotion hierarchy one finds the handful of concepts (love, joy, anger, sadness, fear, and perhaps, surprise) most useful for making everyday distinctions among emotions, and these overlap substantially with the examples mentioned most readily when people are asked to name emotions (Fehr & Russell, 1984), with the emotions children learn to name first (Bretherton & Beeghly, 1982), and with what theorists have called basic or primary emotions. This article reports two studies, one exploring the hierarchical organization of emotion concepts and one specifying the prototypes, or scripts, of five basic emotions, and it shows how the prototype approach might be used in the future to investigate the processing of information about emotional events, cross-cultural differences in emotion concepts, and the development of emotion knowledge.

Adult

Self-serving prototypes of social categories.

Why and when do people disagree on their conceptions or prototypes of social categories? In 6 studies, it was revealed that such differences tend to be self-serving. Ss tended to endorse self-descriptive attributes as central to their prototypes of desirable social concepts and emphasize features that were not self-descriptive in their conceptions of undesirable categories. Such disagreements were constrained to attributes potentially central to the domain in question and did not occur for clearly peripheral features. Self-serving differences in prototype structure were exhibited in social information processing tasks and led to disagreements in judgments of others. Potential mechanisms underlying the development of these egocentric cognitive structures and their implications for self-serving judgments of ability are discussed.

Adult

Prototype formation from imaged, kinesthetically, and visually presented geometric figures.

The issue of prototype formation from simple geometric figures presented in various modes was studied in four conditions. Base figures and their exemplars were scaled in terms of their physical similarity, which was considered to reflect cognitive similarity. Geometric exemplars were visually presented, imaged by the subject, and kinesthetically presented. Following initial presentation, a recognition task was given in which some old items, some new items, and the prototype (also a new item) were presented in the same modality as originally perceived. The results indicate that prototype formation spans a wide class of human experiences and that internal representations of geometric figures derived from experiences with one modality tend to be second-order isomorphic with similar experiences derived from another modality.

Discrimination Learning

Comparative anticonvulsant activity and neurotoxicity of felbamate and four prototype antiepileptic drugs in mice and rats.

Felbamate (2-phenyl-1,3-propanediol dicarbamate), phenytoin, phenobarbital, ethosuximide, and valproate were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that felbamate exhibits a wider range of experimental anticonvulsant activity than either phenytoin or ethosuximide and a somewhat more restricted range than either phenobarbital or valproate. Felbamate is effective in nontoxic intraperitoneal doses in mice by the maximal electroshock seizure (MES), pentylenetetrazol (s.c. PTZ), and picrotoxin (s.c. Pic) tests but ineffective against bicuculline- and strychnine-induced seizures; it is effective after nontoxic oral doses in both mice and rats by the MES and s.c. PTZ tests. When compared on the basis of protective indices (PI = TD50/ED50) calculated from the intraperitoneal data in mice, the PIs for felbamate were from 1.05 to 2.37 times higher than those of the prototype antiepileptics. Overall, except for the s.c. PTZ test in mice and rats after oral administration, the PIs were equal to or higher than those of the prototype agents. The PIs for the s.c. PTZ test in mice and rats after oral administration were within the range of the prototype agents. These data indicate that felbamate is a relatively nontoxic agent with a unique profile of anticonvulsant action.

Animals

Prospective studies evaluating the standard endotracheal tube and a prototype endotracheal tube.

Two prospective studies were designed to evaluate laryngeal injury sustained with the standard endotracheal tube (ETT) and the relative safety of a new prototype ETT. The first study followed patients after prolonged intubation with the standard ETT. Potential patient host factors were recorded and correlated with subjective complaints and objective findings on fiberoptic laryngoscopy. Nearly all patients sustained laryngeal injury after prolonged intubation, although over two thirds experienced resolution. Nasogastric feeding tubes and larger-diameter ETTs were associated with true vocal cord (TVC) granuloma formation. Duration of intubation was associated with delayed TVC immobility. The mechanisms of TVC granulomas and immobility are probably different, as suggested by the different host factor associations and onset times. The second study compared the standard ETT with the prototype ETT in short-term intubations. The prototype ETT was associated with no complications in this setting and is considered relatively safe for further testing in the patient with prolonged intubation.

Adult

Rapid prototyping of interactive software for automated instrumentation in rehabilitative therapy.

Rapid prototyping is a quick, efficient way to evaluate new electrical instruments. A hardware interface between a computer and an instrument can be simulated in software. The authors demonstrate the technique of rapid prototyping by developing interfaces for two therapeutic strength-testing devices and an electromagnetic tracker/digitizer. The LabVIEW rapid prototyping software tool was used to create "virtual instruments," which combine to form interfaces. The functions and connections of each virtual instrument are described.

Equipment Design

Serological comparison of the Escherichia coli prototype strains for the F(Y) and Att 25 adhesions implicated in neonatal diarrhoea in calves.

Slide agglutination tests using single absorbed and double absorbed antisera indicated that the Att 25 prototype Escherichia coli strain 25 KH9 produces the F(Y) adhesion; that this E coli also produces at least one other surface antigen not found on the F(Y) prototype E coli strain 11a; and that F(Y)+ E coli strain 28a produces at least one other surface antigen not produced by the prototype strains for the F(Y) and Att 25 antigens. These antigens were found on E coli isolated from outbreaks of calf diarrhoea in the United Kingdom.

Adhesins, Escherichia coli

Restriction site mapping of adenovirus prototypes of subgenus D.

Restriction site maps with the endonucleases HindIII, BglII, and Bam HI were elaborated for the majority of 23 adenovirus prototypes of subgenus D (AV8 to AV39). On the basis of four or five types which have been mapped by biochemical methods, the physical maps for other types were constructed by adapting restriction fragments of defined molecular weight, as the homology among types of the same subgenus is considerable. Prototypes of subgenus D shared several common restriction sites; different sites, however, were distributed at random over the genome. The gene loci for hexon and fiber did not show either higher or lower variability.

Adenoviridae

Rapid prototyping of database systems in human genetics data collection.

This work examines some of the problems encountered in developing small and large database application systems involving human genetics data collection efforts that include data on individuals as well as family pedigree data. Rapid prototyping of a database application requires software tools to produce the application with little or no programming. Features of MEGADATS-4 that provide for rapid prototyping and for producing stand-alone applications are examined.

Data Collection

Clinical impact of picture archiving and communication systems: evaluation of a prototype system.

Opinion surveys were gathered before and 6 months after installation of a prototype picture archiving and communication system (PACS) (PACS/1, Siemens Medical Systems, Iselin, NJ). Median turnaround times and the percent of delayed or missing reports were calculated for 1,026 baseline and 8,438 follow-up studies at 6 months. Neuroradiological (neuro) computed tomography (CT) used PACS, while neuro magnetic resonance (MR), body CT, and body MR served as controls. The opinion surveys showed improved service in all categories, including those not directly affected by PACS. PACS images favorably impressed 86% of respondents, but most considered the system too slow, unreliable, and the storage capacity too low. A majority of 81% recommended against purchase of PACS now. There was an overall increase in the median report turnaround time for both neuro CT and the controls. Neuro CT showed a 41% decrease in delayed or missing reports, but controls also showed similar decreases. The effects of this prototype PACS on turnaround time or on report delivery could not be distinguished from section-wide changes in CT and MR services. Future improvements in PACS should vigorously address increased speed, reliability, and storage capacity.

Attitude of Health Personnel

Aesthetic preference and syntactic prototypicality in music: 'tis the gift to be simple.

In the dominant aesthetic theory, composers are said to use unpredictable events to tease the listener, and make music optimally challenging and therefore aesthetically pleasing. We tested this claim that events optimally discrepant from a schema will be most pleasing. Experts and novices evaluated harmonic progressions at seven levels of syntactic prototypicality. Four results emerged: (1) even novices were extremely sensitive to syntactic atypicality; (2) all subjects found atypical progressions more interesting and complex; (3) novices and undergraduate music students preferred harmonic prototypes, contrary to most aesthetic theories; (4) only music graduate students preferred atypical progressions. We discuss the striking sensitivity of novices to harmonic syntax. We describe differences between an aesthetic theory based on information and uncertainty, and one based on schemas and schema divergence. We also consider the tonal conservatism of most subjects. This conservatism constrains aesthetic theories, and may have implications for music's stylistic evolution.

Adult

The complete nucleotide sequence of the JS strain of human parainfluenza virus type 3: comparison with the Wash/47885/57 prototype strain.

The nucleotide sequence of the JS strain of human parainfluenza virus type 3 (PIV3) was determined from a series of 14 overlapping cDNA clones and was compared to that of the previously sequenced prototype PIV3 strain, Wash/47885/57 (Galinski, 1991). Overall, there were 630 (4%) nucleotide differences between the two viruses. 15462 nucleotides comprised the JS genome in contrast to 15463 which constituted the genome of the prototype virus. This was accounted for by a single nucleotide deletion in the 5' non-coding region of the JS phosphoprotein gene. Four nucleotide substitutions were found in the leader region at the 3' end of the viral genome at positions 24, 28, 42 and 45, whereas no differences were found in the 44 base trailer region. All of the transcription start and stop signals and intergenic sequences were conserved between the two viruses with the exception of the transcription stop signal of the matrix (M) gene where there was a nucleotide transposition between bases 7 and 8. A comparison of all of the nucleotide differences in the 3' and 5' non-coding regions of each gene showed a variability of 9.8% and 10.5%, respectively. The 3' non-coding regions of the nucleocapsid (NP) and M genes were completely conserved in contrast to the polymerase (L) gene in which 25% of the nucleotides were different. Differences were observed in the 5' non-coding regions of each gene and ranged from 5.9% for the hemagglutinin neuraminidase (HN) gene to 14.6% for the M gene. An analysis of the amino acid differences in each open reading frame revealed that of all the genes, the coding region of the M gene was the most highly conserved (1.1% amino acid variability), while the phosphoprotein (P) gene was the most variable (5.8% amino acid variability). As these two viruses are wild type strains, these differences in nucleotide and amino acid sequence are compatible with efficient replication in vivo.

Base Sequence

Diagnostic function of the microhuman prototype of the expert system--MUNIN.

This paper describes the diagnostic function of a prototype expert system for electromyography (EMG). The prototype was restricted to a limited "Microhuman" anatomy with only 6 muscles and 8 nerves, and a corresponding limitation on the number of local nerve lesions. It attempted to give a detailed description of the most important groups of generalized nerve and muscle disorders, and the commonly used parameters from needle EMG and nerve conduction studies were included. The system can be used both for "diagnostic" and for "causal" reasoning. In diagnostic reasoning, the system's probabilistic inference engine is used to reason from test results through 14 different aspects of neuromuscular pathophysiology to disorders. In causal reasoning, the system reasons in the opposite direction from disorders through pathophysiology to expected test results. The diagnostic function of the system was illustrated by 3 cases: a normal subject, a patient with a bilateral carpal tunnel syndrome and a patient with both a diabetic polyneuropathy and a bilateral carpal tunnel syndrome.

Carpal Tunnel Syndrome

Evidence of two major genotypes of hepatitis C virus in France and close relatedness of the predominant one with the prototype virus.

Hepatitis C virus (HCV) cDNA sequence in the nonstructural region NS3 was amplified from the serum of 66% French non-A, non-B hepatitis patients by the nested polymerase chain reaction. A 407 base-pair sequence was determined from four such cases, which revealed the presence of two different virus genotypes F1 (three cases) and F2 (one case) with 19-20% sequence divergence. F1 showed close homology (97.5%) to the prototype US isolate, but only limited (79%) homology to the reported Japanese isolates. In contrast, F2 had 91.6% homology to the Japanese isolate, but only 81% homology to the prototype US virus. Hybridization of the amplified products from 50 French samples with labeled F1 and F2 fragments suggested the F1-related strain(s) as the major hepatitis C virus genotype. Further studies involving a greater variety of samples will confirm whether the F1-related strain is the predominant hepatitis C virus strain circulating in France. Such data will have important implications for the PCR detection of HCV infection and production of HCV vaccines.

Antisense Elements (Genetics)