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Selection of a subgroup A avian leukosis virus [ALV(A)] envelope resistant to soluble ALV(A) surface glycoprotein.

The host developing resistance to retroviral infection is believed to be a major force in the evolution of multiple receptor usage by retroviruses. The avian leukosis-sarcoma virus (ALV) group of retroviruses provides a powerful system for studying the envelope-receptor interactions involved in retrovirus entry; different members of this group of closely related viruses use distinct cellular receptors. Analysis of the ALV envelope subgroups suggests that the different ALVs evolved from a common ancestor by mutations in the env gene. Cells and animals that express subgroup A ALV envelope glycoproteins are highly resistant to ALV(A) infection due to receptor interference. In this study, we tested whether expression of a soluble form of subgroup A surface glycoprotein (SU) would result in receptor interference and whether this interference would select for resistant viruses with altered receptor usage. Chicken cells expressing the secreted ALV(A) SU immunoadhesin SU(A)-rIgG, which contains the subgroup A SU domain fused to the constant region of a rabbit immunoglobulin (IgG) heavy chain, showed significant receptor interference. A variant virus resistant to SU(A)-rIgG receptor interference was obtained. This virus had a six-amino-acid deletion in the subgroup A hr1 that altered receptor usage. This approach may identify regions of SU that play a critical role in receptor specificity.

Alpharetrovirus↗

Three antigenic variant groups in human respiratory syncytial virus subgroup B isolated in Japan.

Nineteen hybridomas producing monoclonal antibodies (MAbs) against the structural proteins of strain 58-17, a subgroup B field strain of respiratory syncytial virus (RSV) isolated in Japan, were obtained by fusion of X63 myeloma cells with spleen cells from BALB/c mice immunized with the virus-infected HEp-2 cells. Seven clones were found to produce antibodies against the fusion protein (F), five against the large glycoprotein (G), five against the nucleoprotein (NP) and two against the 22k protein by radioimmunoprecipitation assay. By competitive binding assay with the MAbs, at least seven, two, three and one epitopes were defined on the F, G, NP and 22k protein components of subgroup B strain, respectively. Of these epitopes, three, two and one epitopes on the F, G and NP components were different from subgroup A strain, respectively. Fifty-three other field strains of subgroup B isolated in Sapporo, Japan, during nine epidemic years from 1980 to 1989, were examined for reactivity with the MAbs by ELISA. Different reactivity to one anti-NP antibody suggested that the 53 strains can be divided into three groups (B-a: 26 strains, B-b: 26 strains, and one other strain). The dominant strain prevailing during the 1984 to 1988 epidemic years had changed from B-a to B-b. All of the 53 subgroup B strains reacted similarly with the other 18 MAbs.

Animals↗

The heat shock genes in the Drosophila montium subgroup: chromosomal localization and evolutionary implications.

The hsp70, hsp83, hsromega, and the small heat shock protein genes were mapped on the polytene chromosomes of six species, representative of the geographical distribution of the Drosophila montium subgroup of the melanogaster species group. In addition, based on hybridization conditions, the putative locus of the hsp68 gene is given. In contrast to the situation in the melanogaster subgroup species, the hsp70 locus is single in the montium species. The hsp83, hsromega and the small hsp loci are also single in the montium genomes studied here, a common feature of all Drosophila species. Among the hsp genes studied, the small hsp genes and the hsromega-homologous sequences exhibit a higher degree of divergence between the melanogaster and the montium subgroups. Our results support the idea that the montium subgroup species has a genome organization closer to that of the common ancestor compared with the melanogaster subgroup species.

Animals↗

Social phobia in Swedish university students: prevalence, subgroups and avoidant behavior.

BACKGROUND: Public speaking is a common situation that university students have to endure. This situation is feared or avoided by most individuals with social phobia, which has been associated with low levels of educational attainment. However, epidemiological data on social phobia in university students are scarce. The present study examined the prevalence of social phobia and its subgroups in a university student population. Demographic characteristics and avoidant behavior in educational settings were also examined. METHODS: The Social Phobia Screening Questionnaire (SPSQ)--a validated and DSM-IV compatible instrument, was distributed as a postal survey to 753 randomly selected university students in Sweden. Interpretable questionnaires were obtained from 523 students (69.5%). To investigate subgroups, students who met the SPSQ diagnostic criteria of social phobia were analyzed by hierarchical cluster analysis. RESULTS: The point prevalence of social phobia among the Swedish university students was 16.1%, comparable with 15.6% previously reported for the general population. Two clusters were distinguished consisting of students scoring either low (discrete subgroup) or high (generalized subgroup) on all cluster variables. The discrete subgroup was more common representing 83% of the cases. Social phobia was associated with use of dysfunctional avoidant strategies in educational situations and in anticipation of public speaking. The disorder was less common among students following a pedagogic university program. CONCLUSIONS: Social phobia was highly prevalent among Swedish university students, most cases pertaining to a mild or discrete form of the disorder. The commonness and severity of social phobia in students did not deviate significantly from the general population suggesting that socially anxious individuals do apply for higher education. However, since avoidance and low educational attainment are commonly reported features, future studies should investigate whether sufferers of social phobia underachieve or abolish their studies prematurely.

Adolescent↗

Phylogeny and the evolution of the Amylase multigenes in the Drosophila montium species subgroup.

To investigate the phylogenetic relationships and molecular evolution of alpha-amylase (Amy) genes in the Drosophila montium species subgroup, we constructed the phylogenetic tree of the Amy genes from 40 species from the montium subgroup. On our tree the sequences of the auraria, kikkawai, and jambulina complexes formed distinct tight clusters. However, there were a few inconsistencies between the clustering pattern of the sequences and taxonomic classification in the kikkawai and jambulina complexes. Sequences of species from other complexes (bocqueti, bakoue, nikananu, and serrata) often did not cluster with their respective taxonomic groups. This suggests that relationships among the Amy genes may be different from those among species due to their particular evolution. Alternatively, the current taxonomy of the investigated species is unreliable. Two types of divergent paralogous Amy genes, the so-called Amy1- and Amy3-type genes, previously identified in the D. kikkawai complex, were common in the montium subgroup, suggesting that the duplication event from which these genes originate is as ancient as the subgroup or it could even predate its differentiation. Thc Amy1-type genes were closer to the Amy genes of D. melanogaster and D. pseudoobscura than to the Amy3-type genes. In the Amy1-type genes, the loss of the ancestral intron occurred independently in the auraria complex and in several Afrotropical species. The GC content at synonymous third codon positions (GC3s) of the Amy1-type genes was higher than that of the Amy3-type genes. Furthermore, the Amy1-type genes had more biased codon usage than the Amy3-type genes. The correlations between GC3s and GC content in the introns (GCi) differed between these two Amy-type genes. These findings suggest that the evolutionary forces that have affected silent sites of the two Amy-type genes in the montium species subgroup may differ.

Amylases↗

Analysis of T-cell receptor BV gene sequences in cattle reveals extensive duplication within the BV9 and BV20 subgroups.

We investigated the repertoire of functional T-cell receptor beta-chain variable genes (TRBV genes) in cattle by analysing the nucleotide sequences and predicted amino acid sequences of a set of cDNA clones isolated from lymph node T cells. Thirty-nine distinct TRBV sequences were identified, bringing the total number of recognised bovine TRBV gene segments to more than 40. Sixteen TRBV subgroups were defined based on their sequence homology to each other and to human TRBV genes. All of the main phylogenetic lineages of BV gene subgroups described in humans and mice were represented. Eight of the subgroups were found to contain more than one member. The most striking feature of the results was the large number of sequences (more than half of the sequenced clones) in the BV9 and BV20 subgroups, which were found to contain 12 and 8 distinct sequences, respectively. In contrast, the corresponding human TRBV subfamilies contain a single member. The results indicate that, as in humans, there has been extensive gene duplication within the TRBV locus during evolution. However, duplication of different BV subgroups in cattle has resulted in a TRBV gene repertoire distinct from that found in other species.

Amino Acid Sequence↗

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987.

BACKGROUND: The relative effectiveness of plaque radiotherapy and enucleation in patients with choroidal or ciliochoroidal melanoma remains controversial. Most published comparative survival studies have evaluated clearly biased groups, short-term follow-up, or both. METHODS: The authors performed a retrospective, non-randomized, comparative survival study on 734 patients with a choroidal or ciliochoroidal melanoma treated by enucleation (n=237) or plaque radiotherapy (n=497) between July 1980 and June 1985, and on a residual group of 448 patients, 103 treated by enucleation and 345 treated by plaque radiotherapy, identified by variable-by-variable range matching. Melanoma-specific mortality and all-cause mortality were evaluated by the life-table method. RESULTS: The melanoma-specific mortality rate was substantially worse in the original enucleation subgroup throughout available post-treatment follow-up; however, differences in baseline prognostic factors between the subgroups are likely to explain much of the survival differential. After eliminating patients with nonoverlapping values of individual clinical variables to adjust for recognized intergroup differences at baseline, there was no significant difference in the mortality curves of the residual subgroups. The cumulative 15-year survival based on deaths from metastatic melanoma in the enucleation subgroup was 57.1% (standard error=6.4%), while that in the plaque radiotherapy subgroup was 61.8% (standard error=3.3%). CONCLUSION: On the basis of these results, we conclude that a large difference in survival between equivalent groups of patients with primary choroidal or ciliary body melanoma treated by enucleation or by plaque radiotherapy appears unlikely.

Adult↗

The SH-H subgroup of cardiac M2 receptors (M2 alpha) inhibits adenylate cyclase activity.

Muscarinic receptors in the guinea-pig heart seem to consist entirely of M2 receptors, but are coupled with several responses including inhibition of adenylate cyclase activity. On the other hand three affinity states (SH, H and L) can be distinguished in cardiac membranes with muscarinic agonists such as carbachol. We showed previously that the three agonist binding states were the sum of two equilibria (SH-H and H-L subgroup), both regulated by GTP-binding protein(s). In this study we determined which subgroup was responsible for the inhibitory effect of muscarinic M2 receptors on adenylate cyclase activity. The ED50 values for this response of four muscarinic agonists, acetylcholine, carbachol, pilocarpine and oxotremorine corresponded with the binding KD values of H (acetylcholine and carbachol) and LO/P (pilocarpine and oxotremorine) sites. After alkylation of spare receptors, the ED50 value of carbachol was changed from 4.3 to 5.6 microM, which corresponded with the KD value of the H site. Furthermore, the four agonists were almost fully active when membrane preparations were pretreated with propylbenzilylcholine mustard (PrBCM) in the presence of carbachol to destroy the H-L subgroup, whereas after pretreatment with PrBCM and atropine, which alkylated both types of subgroups evenly, the decrease in the number of receptors was proportional to the decrease in the inhibitory effect on adenylate cyclase activity. These results suggest that only the SH-H subgroup (M2 alpha) is responsible for the inhibitory action of muscarinic receptors on adenylate cyclase activity in the heart.

Adenylyl Cyclase Inhibitors↗

Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy.

BACKGROUND: The subdivision of undiagnosed patients with dyspepsia into symptomatic subgroups (ulcerlike, dysmotilitylike, refluxlike, and nonspecific) may give a clue to the underlying cause; however, the value of this approach in practice is unclear. This study aimed to determine the discriminant value of dyspeptic symptoms and combinations of these symptoms. METHODS: A consecutive sample of 820 outpatients (median age, 62 years; 47% male) completed, before endoscopy, a validated questionnaire that measured 46 gastrointestinal symptoms. RESULTS: Of patients with functional dyspepsia (n = 162), 17% had ulcerlike, 9% dysmotilitylike, and 16% refluxlike dyspepsia alone; 31% fell into two or more symptom subgroups; and 27% had nonspecific symptoms. A similar distribution of the dyspepsia subgroups was observed in patients without functional dyspepsia. Younger age, female gender, frequent upper abdominal pain, no (or sometimes) pain relief with antacid use, and infrequent vomiting were predictive of functional dyspepsia vs. all other diagnoses (at a specificity of 80%, the sensitivity was 60%). The dyspepsia subgroups were poor discriminators in a separate model for functional dyspepsia vs. all other diagnoses (at a specificity of 80%, the sensitivity was only 43%). CONCLUSIONS: The dyspepsia subgroups, as currently defined, appear to have little clinical utility and may be an inappropriate way of classifying dyspepsia.

Adolescent↗

Induction of tobacco chlorosis by certain cucumber mosaic virus satellite RNAs is specific to subgroup II helper strains.

Two satellite (sat) RNAs of cucumber mosaic virus (CMV), B2- and WL3-sat RNAs, which induce systemic chlorosis on tobacco, were inoculated onto tobacco with a number of CMV strains. Systemic chlorosis was observed only when these satellite RNAs were associated with subgroup II CMV strains. Infection of tobacco with various pseudorecombinants of subgroup I and II CMV strains, together with WL3- or B2-sat RNA, suggests that chlorosis is associated with RNA 2 of subgroup II CMV strains. Chlorosis was not induced when B2- or WL3-sat RNAs were inoculated onto tobacco with tomato aspermy virus. In contrast, the induction of chlorosis on tomato by B1-sat RNA did not show any clear dependence on the subgroup of its CMV helper strain although chlorosis did tend to be more severe in association with subgroup II CMV strains.

Helper Viruses↗

The use and abuse of subgroup analysis in epidemiological research.

Most epidemiology involves the analysis of subgroups. In observational studies, identification of associations within particular subgroups is the usual method of investigation, while in experimental studies the purpose is to compare the rate of occurrence of the outcome of interest in treated and control groups. Problems can arise through failure to specify the subgroups of interest a priori and through examining large numbers of subgroups after the fact, i.e., through multiple testing. Rules for interpretation of findings in subgroups are suggested, and the value of the systematic application of criteria for judgement of the causal significance of any associations that may be observed is noted.

Classification↗

Empirical Bayes estimates of subgroup effects in clinical trials.

At the completion of a clinical trial it is often desirable to compare the treatments within subgroups of patients. The results of the subgroup analysis are usually reported for the subgroups within which sizable treatment differences are found. This practice can lead to an overestimate of the difference between treatments within the subgroups reported. One way of adjusting for this bias is to use empirical Bayes methods which shrink the extreme estimates toward the overall measure of treatment difference. Both point and interval estimates can be obtained. The computations are illustrated with an example using subgroup data from the Lipid Research Clinics Coronary Primary Prevention Trial.

Bayes Theorem↗

Vaccination with a heterologous respiratory syncytial virus chimeric FG glycoprotein demonstrates significant subgroup cross-reactivity.

A subunit vaccine candidate, termed FG, is a chimeric glycoprotein composed of the extracellular domains of the fusion (F) glycoprotein and the attachment (G) glycoproteins of a subgroup A respiratory syncytial virus (RSV). Two subgroups, A and B, of RSV differ primarily within the G glycoprotein. Therefore, it has been suggested that a subunit vaccine composed of the G glycoprotein would need to contain the G glycoproteins from both RSV subgroups. We have engineered a second chimeric glycoprotein, FGB, which is composed of the F glycoprotein from RSV subgroup A and the G glycoprotein from RSV subgroup B and is expressed in baculovirus. A comparison of protection between the two subunit vaccines (FG and FGB) was performed in cotton rats after homologous and heterologous virus challenge. FG and FGB appeared to afford the same degree of protection against either homologous or heterologous challenge. Serum neutralization titres against homologous or heterologous virus were nearly equivalent following FG or FGB vaccination. Radioimmunoprecipitation using sera from rats immunized with FG or FGB revealed cross-reactivity between the two G glycoproteins. Adsorption of anti-F antibody from serum of rats immunized with FG significantly reduced the RSV neutralizing activity of the serum suggesting that enhanced neutralization previously observed with FG antisera compared with F antisera alone may not be entirely attributed to antibodies against the G glycoprotein but may be attributed to a function associated with the G glycoprotein portion of FG which enhances the immunogenicity of the F portion of FG.

Adsorption↗

Studies on the antigenic relationship between bovine subgroup 2 and conventional mammalian adenoviruses using immunofluorescence.

In double immunodiffusion tests between a bovine subgroup 2 adenovirus (serotype 8) and other mammalian adenoviruses, no group-specific crossing was demonstrated. However, in cross-fluorescent antibody tests (FAT) between bovine subgroup 2 viruses (serotypes 5, 7 and 8) and conventional (non-subgroup 2) adenoviruses from several species (bovine adenovirus serotypes 1 and 2, ovine serotypes 1, 4 and 5, porcine serotype 1, and human serotypes 2 and 5) sharing of antigens was demonstrated. The FAT titres observed when rabbit antisera to conventional adenoviruses were used to stain bovine subgroup 2 viruses were, however, much lower than titres with other non-subgroup 2 viruses. The converse was also true. The crossing was also predominantly one-sided. The low level cross was confirmed using antisera to selected viruses prepared in chickens to exclude interference by possible natural adenovirus infections in the rabbits used to prepare the antisera in the initial experiments.

Adenoviridae↗

Electropherotypes, subgroups and serotypes of human rotavirus strains causing gastroenteritis in infants and young children in Palermo, Italy, from 1985 to 1989.

During 1985-89, an epidemiological survey was conducted in Palermo, Sicily (Southern Italy) on group A human rotavirus (HRV) strains which cause gastroenteritis in infants and young children. Two hundred and thirty eight HRV strains were characterized for subgroup and serotype using monoclonal-antibody-based ELISA systems, and for electropherotype using polyacrylamide gel electrophoresis. Subgroup II strains were largely predominant, constituting 218/238 of the positive stool samples (91.6%). Among the serotypes, 192/238 strains (80.7%) were serotype 1 and 16 strains (6.7%) were serotype 4; serotype 2 circulated intermittently and serotype 3 was nearly absent (only one subgroup I strain was detected). Two electropherotypes, bbba and cbba, accounted for the largest proportion of the 345 HRV strains examined, 74 (21.4%) and 222 (64.3%) strains, respectively. Unexpected combinations of subgroup, serotype and electropherotype were detected in 5 subgroup I strains, of which 4 possessed a "long" RNA pattern (1 serotype 3 and 3 serotype 4 strains) and one a "short" RNA pattern (a serotype 4 strain). In addition, 4 group C HRV strains (atypical HRV or pararotaviruses) were detected on the basis of electropherotype. These findings emphasize the need for continuous surveillance of HRV infections in different geographic areas of the world in order to detect the appearance of new strains early and to adopt adequate strategies for vaccine preparation and administration.

Antibodies, Monoclonal↗

High and low rearing subgroups of rats selected in the open field differ in the activity of K+-stimulated p-nitrophenylphosphatase in the hippocampus.

Na(+)/K(+)-adenosinetriphosphatase (Na(+)/K(+)-ATPase) is of paramount importance for the proper functioning of the organism. The enzyme is involved in several aspects of brain function, such as the repolarization of the neuronal membranes and neurotransmitters uptake/release. Therefore, individual differences in the activity of brain Na(+)/K(+)-ATPase may result in differences in the functioning of the brain, which, in consequence, could lead to behavioral divergences. Individual differences in rearing, an exploratory behavior, have been shown to be genetically determined. In rats, the inhibition of the activity of Na(+)/K(+)-ATPase was reported to induce changes in the exploratory behavior. The aim of this work was to verify if subgroups of rats selected according to the number of rearings (high and low rearing subgroups) in the open field test differ in the activity of Na(+)/K(+)-ATPase in brain regions. Adult, male outbred Wistar rats were selected in the open field test according to the number of rearings in subgroups of high (HR) and low (LR) rearing responders. After a rest of about 20 days after the open field session, HR and LR rats were sacrificed. In the first experiment, frontal cortex, striatum, brainstem, hippocampus and the amygdala (including the overlying limbic cortex) were dissected. The reaction of dephosphorylation of Na(+)/K(+)-ATPase (K(+) stimulated p-nitrophenylphosphatase) was assayed in homogenates rich in synaptosomes. The results obtained showed a statistically significant higher activity of K(+)p-nitrophenylphosphatase only in the hippocampus of HR subgroup of rats. This result was replicated in two other subsequent experiments with different HR and LR subgroups of rats selected at different times of the year. Our data suggest that the difference in the activity of Na(+)/K(+)-ATPase in the hippocampus is innate and is involved in the expression of the rearing behavior.

4-Nitrophenylphosphatase↗

Effects of family functioning and self-image on adolescent smoking initiation among Asian-American subgroups.

PURPOSE: This study examined differences in smoking prevalence and differences in associations between family functioning, self-image and adolescent smoking behavior among four Asian-American subgroups. METHODS: Statistical analyses were conducted on responses about their smoking behaviors from 1139 students who self-identified as Chinese-Americans, Filipino-Americans, Korean-Americans, and Vietnamese-Americans. RESULTS: Significant differences in the prevalence of ever-tried smoking and 30-day smoking were found across subgroups, but there were no overall gender differences. Korean-American adolescents reported the highest lifetime smoking and 30-day smoking rates, followed by Vietnamese- and Filipino-Americans. Chinese-Americans reported the lowest smoking rates. There were also differences in the associations between smoking and family functioning and self-image across the four subgroups. High family functioning was inversely associated with smoking for Chinese- and Korean-American adolescents, but not for Filipino- and Vietnamese-Americans. On the other hand, high self-image was associated with decreased risk of smoking for Filipino- and Vietnamese-Americans, but not for the other two subgroups. CONCLUSION: Findings of this study demonstrate that family functioning and self-image varied across Asian-American subgroups. This suggests the need to understand etiological differences between the groups as well as potential implications for prevention cessation programs.

Adolescent↗

Structural determinants of rotavirus subgroup specificity mapped by cryo-electron microscopy.

The rotavirus double-layered particle (DLP) is a molecular machine that transcribes 11 genomic segments of double-stranded RNA into full-length mRNA segments during viral replication. DLPs from the human Wa strain of virus, belonging to subgroup II (SG II), possess a significantly reduced level of transcriptase activity compared to bovine UK DLPs that belong to subgroup I (SG I). Cryo-electron microscopy and icosahedral image analysis was used to define the structural basis for this difference in transcriptase activity and to derive three-dimensional density maps of bovine UK and human Wa DLPs at 26 angstroms and 28 angstroms resolution, respectively. The two rotavirus strains had the same diameter, T = 13 l icosahedral lattice symmetry and size of the VP6 trimers on the surface of the DLPs. However, the Wa particles displayed a remarkable absence of VP6 trimers surrounding each 5-fold vertex position. To further explore these structural differences, three-dimensional reconstructions were generated of DLPs decorated with Fab fragments derived from subgroup-specific monoclonal antibodies. The X-ray structures of VP6 and a generic Fab fragment were then docked into the cryo-electron microscopy density maps, which allowed us to propose at "pseudo-atomic" resolution the locations of the amino acid residues defining the subgroup-specific epitopes. Our results demonstrate a correlation between the structure of the VP6 layer and the transcriptase activity of the particles, and suggest that the stability of VP6 trimers, specifically those at the icosahedral 5-fold axes, may be critical for mRNA synthesis. Thus, subgroup specificity of rotavirus may reflect differences in the architecture of the double-layered particle, with resultant consequences for viral mRNA synthesis.

Animals↗