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PubMed1990

Immunocytochemical detection of kappa and lambda light chain V region subgroups in human B-cell malignancies.

We have used a sensitive immunoperoxidase method and highly specific anti-light chain antisera to determine the light chain variable region (VL) subgroup nature of cytoplasmic (c) and cell surface (s) Ig expressed by human monoclonal plasma cells and B lymphocytes. The immunocytochemical characterization of cIg and sIg used antisera specific for the established kappa light chain V kappa subgroups (V kappa I, V kappa II, V kappa III, and V kappa IV) and the lambda light chain V lambda subgroups (V lambda I, V lambda II/V, V lambda IV, and V lambda VI). Studies were performed using cytospin preparations of bone marrow-, peripheral blood-, and lymph node-derived cells from patients with multiple myeloma, amyloidosis AL, and Waldenström's macroglobulinemia and with low-, mid-, and high-grade B-cell malignancies. The V kappa or V lambda subgroup of the cIg or sIg also could be identified after deparaffinization and enzyme treatment of formalin-fixed, paraffin-embedded specimens. For those patients who had monoclonal serum or urinary Igs, there was complete concordance between the VL subgroup of the secreted Ig and that of the cIg or sIg. The percentage distribution of V kappa or V lambda subgroups on the sIg of cells from patients with chronic lymphocytic leukemia (CLL) and other cytomorphologic types of B-cell malignancies differed from that found for kappa- or lambda-type Bence Jones proteins obtained from patients with multiple myeloma, amyloidosis AL, and Waldenström's macroglobulinemia. In contrast to the plasma cell and lymphocytoid plasma cell diseases, a relative predominance of certain VL subgroups, ie, V kappa IV, V lambda III, and V lambda IV, and the absence of the amyloid-associated V lambda VI subgroup were found in CLL and related diseases. The immunocytochemical techniques used make possible a rapid means to demonstrate B-cell monoclonality and provide further evidence for the selective expression of certain VL genes in human B-cell neoplasia.

Amyloidosis↗
PubMed1989

Clinical and epidemiological features of acute gastroenteritis associated with human rotavirus subgroups 1 and 2 in northern India.

Rotavirus was detected in 111 (15.9%) of 694 children who presented to our hospital with acute diarrhoea over a period of 45 months (1982-1985). Subgrouping for rotavirus was done on 87 children by ELISA using specific monoclonal antibodies to find out any differences in the epidemiology and clinical profile of the two subgroups. Twenty six (29.9%) were found to belong to subgroup 1 and 61 (70.1%) to subgroup 2. Diarrhoea, vomiting and fever were present in both the subgroups in the same frequency. However, the severity of diarrhoea was more in children having subgroup 2 infection. Rotavirus infection showed two peaks, one during the early months of summer and the other during the early months of winter of each year. During most of the study period, infection was predominantly with subgroup 2, except for a few months in 1983 and 1985 when a majority of children had infection with subgroup 1.

Child, Preschool↗
PubMed1987

Serologically defined V region subgroups of human lambda light chains.

The availability of numerous antisera prepared against lambda-type Bence Jones proteins and lambda chains of known amino acid sequence has led to the differentiation and classification of human lambda light chains into one of five V lambda subgroups. The five serologically defined subgroups, V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI, correspond to the chemical classification that is based on sequence homologies in the first framework region (FR1). Proteins designated by sequence as lambda V react with specific anti-lambda II antisera and are thus included in the V lambda II subgroup classification. The isotypic nature of the five V lambda subgroups was evidenced through analyses of lambda-type light chains that were isolated from the IgG of normal individuals. Based on analyses of 116 Bence Jones proteins, the frequency of distribution of the lambda I, lambda II/V, lambda III, lambda IV, and lambda VI proteins in the normal lambda chain population is estimated to be 27%, 37%, 23%, 3%, and 10%, respectively. This distribution of V lambda subgroups was comparable to that found among 82 monoclonal Ig lambda proteins. Considerable V lambda intragroup antigenic heterogeneity was also apparent. At least two sub-subgroups were identified among each of the five major V lambda subgroups, implying the existence of multiple genes in the human V lambda genome. The V lambda classification of 54 Ig lambda proteins obtained from patients with primary or multiple myeloma-associated amyloidosis substantiated the preferential association of lambda VI light chains with amyloidosis AL and the predominance of the normally rare V lambda VI subgroup in this disease.

Amyloidosis↗
PubMedDate not supplied

Heavy and light chain variable region subgroups: antigenic analysis among human monoclonal immunoglobulins.

An antigenic analysis of human heavy and light chain variable region subgroups has been possible by means of heterologous specific antisera using a hemagglutination-inhibition procedure. The specificity of antisera had been shown to be directed against antigenic determinants of VkappaI, VkappaII, VkappaIII, VlambdaI, VlambdaII, VlambdaIII and VHIII by means of chemically subgrouped proteins. A series of IgG, IgA, IgM and IgD were examined for the presence of a VHIII variable region subgroup antigenic determinant. The data showed that 50% IgG, 62% IgA, 55% IgM, 45% IgD were positive for VHIII antigenic determinant. NH2 terminus blocked monoclonal immunoglobulin belonging to the VHIII subgroup were found, increasing incidence of this subgroup among IgG. A preferential association of VHIII antigenic determinant with IgG1, IgG3 subclasses was observed among IgG myeloma proteins while the preferential association was only observed with IgG1 subclass when anti-Rh antibodies were considered. Among 53 IgG of kappa type 20 (37%) kappaI, 30 (56%) kappaII, 3 (5%) kappaIII subgroups were found and among 42 IgG of lambda type 13 (31%) lambdaI, 13 (31%) lambdaII and 16 (38%) lambdaIII were observed. Although numbers are limited in each group for conclusions a study of VHIII and non VHIII antigenic subgroup determinant with respect to the light chain subgroups is given. The non-allelic behaviour of this VHIII antigenic determinant was observed. Preliminary data on the presence of these human antigenic determinants among different animals species were given.

Animals↗
PubMed1984

[Comparative studies on the rotavirus syndrome following infection with human rotavirus of the subgroup 1 or 2].

Human rotavirus infection which heals spontaneously causes gastroenteritis in newborns and infants. 150 pediatric patients infected with rotavirus as diagnosed by ELISA suffered from diarrhoea for an average of 3 days, from vomiting for 1 day, and/or fever for 1-2 days. Nowadays this disease is known as "human rotavirus syndrome". Human rotaviruses can be divided into at least 4 serotype antigens and some 3 further subgroup antigens. The serotype antigens are only detectable biologically (e.g. by neutralization test), whereas the subgroup antigens can be demonstrated as specific proteins by a solid-phase test (ELISA). This study investigated whether an infection with human rotavirus of subgroup 1 (21%) or 2 (77%), which occur most frequently causes different degrees of severity of the rotavirus syndrome. The clinical comparison of 27 (subgroup 1) and 98 (subgroup 2) infected patients shows that the disease is not significantly different. This means that the detection of subgroup antigens 1 and 2 does not result in a different prognosis for the disease. The diagnosis of subgroup antigens after human rotavirus infection is therefore clinically important only for the detection of nosocomial infections, especially due to the rarely occurring subgroups 1 and 3.

Antigens, Viral↗
PubMed2000

Assessing the potential for bias in meta-analysis due to selective reporting of subgroup analyses within studies.

Subgroup analysis is frequently used to investigate heterogeneity in meta-analysis. Subgroup data are not always available, and researchers should record what data were available for each trial. If data were not available, and it is known that the subgroup data were collected, the potential for selective reporting should be considered. Bias due to selective publishing of reports is widely recognized in meta-analysis. In contrast, selective reporting within studies is little discussed but potentially important. We explored this problem by evaluating the effect of potential bias in subgroup analysis due to within-study selective reporting with an existing meta-analysis. The review addressed malaria chemoprophylaxis in pregnancy. The conclusion in the original review, that benefit is limited to primigravidae, was based on subgroup analysis using the three trials out of five which reported on subgroups. We developed a method of sensitivity analysis that imputes data for the missing subgroups to assess the robustness of the results and the conclusions drawn. In this particular example, our analysis indicates that the estimate of effect reported in the review is most likely to overestimate the true effect and the conclusion that benefit is limited to primigravidae may be false.

Bias↗
PubMed1988

The relative frequency of subgroup I and II rotaviruses in black infants in South Africa.

Between March 1983 and December 1986, a total of 1571 stool specimens were collected from black South African infants and young children with acute gastroenteritis, and tested for the presence of rotavirus. Monoclonal antibodies against the major inner capsid protein were used in an enzyme linked immunosorbent assay to determine the subgroup specificity of the rotavirus isolates. Subgroup II rotaviruses occurred more frequently than subgroup I isolates (74.4% vs 12.3%), while 13.3% could not be typed and may indicate the presence of a third subgroup. Two of the subgroup I isolates had a long RNA profile (ie, faster moving gene segment 11) typical of the subgroup II human rotaviruses, and a single subgroup II strain had a short RNA profile possibly indicating an in vivo rotavirus reassortant.

Antibodies, Monoclonal↗
PubMed1994

Antigenic diversity of respiratory syncytial virus subgroup B strains circulating during a community outbreak of infection.

The epidemiological characteristics and relationship between respiratory syncytial virus (RSV) subgroup and virulence during an outbreak of RSV infection occurring in Southeast Texas in the winter season 1991/92 are described. Fifty-two infants and children were diagnosed with RSV infection by rapid viral antigen detection and/or viral isolation. Subgrouping of the isolates was carried out using 11-monoclonal anti-bodies. Ten isolates were found to be subgroup B, and 8 isolates were subgroup A. The subgroup B strains showed 3 different patterns of reaction with monoclonal antibodies; one of these subgroups was examined further by restriction analysis of parts of its nucleocapsid and attachment protein genes. The peak of RSV outbreak was in December 1991. Both subtypes A and B circulated simultaneously in the same territory, and caused lower respiratory tract infections in similar proportions. The more frequent occurrence of the B subgroup and the diversity of its simultaneously circulated RSV strains have made this outbreak unusual.

Antigens, Viral↗
PubMed1994

Human rotavirus subgroups and serotypes in children with acute gastroenteritis in Saudi Arabia from 1988 to 1992.

Rotavirus infection was detected in 524 (42.2%) of the 1,242 stool specimens collected from infants and young children with acute gastroenteritis admitted to a major pediatric hospital in Jeddah, Saudi Arabia, between March 1988 and December 1992. Enzyme-linked immunosorbent assay (ELISA) and monoclonal antibodies specific for subgroup I and II were used to examine 80 rotavirus positive specimens. Subgroup I was detected in 21 (26.3%) and subgroup II in 49 (61.3%) specimens. Six specimens reacted with both subgroup I and II monoclonal antibodies and four specimens were untypeable. Serotyping of 355 rotavirus positive specimens using monoclonal antibodies specific for the human rotavirus serotypes 1 to 4 revealed a distribution profile of serotype 1, 53.5%; serotype 2, 6.8%; serotype 3, 5.9%; and serotype 4, 22.8%, along with mixed and untypeable specimens (11%). When the correlation between subgroup and serotype specificities was examined in 62 specimens, all subgroup I specimens were found to be serotype 2 or untypeable and all subgroup II specimens belonged predominantly to serotypes 1 (54.7%) and 4 (9.4%). Serotype 1, followed by, to a lesser extent, serotype 4, exhibited a temporal predominance in the 5-year investigation. A significant clustering of the various serotypes during the cooler months was evident almost throughout the study, particularly in 1989 and 1990.

Acute Disease↗
PubMed2006

Distinct patterns of evolution between respiratory syncytial virus subgroups A and B from New Zealand isolates collected over thirty-seven years.

Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract infections in infants and children worldwide. In New Zealand, infants with RSV disease are hospitalized at a higher rate than other industrialized countries, without a proportionate increase in known risk factors. The molecular epidemiology of RSV in New Zealand has never been described. Therefore, we analyzed viral attachment glycoprotein (G) gene sequences from 106 RSV subgroup A isolates collected in New Zealand between 1967 and 2003, and 38 subgroup B viruses collected between 1984 and 2004. Subgroup A and B sequences were aligned separately, and compared to sequences of viruses isolated from other countries during a similar period. Genotyping and clustering analyses showed RSV in New Zealand is similar and temporally related to viruses found in other countries. By quantifying temporal clustering, we found subgroup B viruses clustered more strongly than subgroup A viruses. RSV B sequences displayed more variability in stop codon usage and predicted protein length, and had a higher degree of predicted O-glycosylation site changes than RSV A. The mutation rate calculated for the RSV B G gene was significantly higher than for RSV A. Together, these data reveal that RSV subgroups exhibit different patterns of evolution, with subgroup B viruses evolving faster than A.

Biological Evolution↗
PubMed2001

Cloning and molecular characterization of two splice variants of a new putative member of the Siglec-3-like subgroup of Siglecs.

The sialic acid binding immunoglobulin-like lectin (Siglec) family is a recently described member of the immunoglobulin superfamily. Within this Siglec family there exists a subgroup of molecules which bear a very high degree of homology with the molecule Siglec-3 (CD33), and has thus been designated the Siglec-3-like subgroup of Siglecs. The members of this subgroup have been localized to chromosome 19q13.4, through both in situ hybridization and precise genomic mapping at the nucleotide level. Through the positional cloning approach we have identified and characterized a Siglec-like gene (SLG), a putative novel member of the Siglec-3-like subgroup of Siglecs. We have characterized the complete genomic structure of SLG, as well as two alternative splice variants, and determined its chromosomal localization. The short isoform, SLG-S, consists of seven exons, with six intervening introns, while the longer isoform, SLG-L, consists of eight exons and seven intervening introns. The SLG gene is localized 32.9 kb downstream of Siglec-8 on chromosome 19q13.4. The putative SLG-S and SLG-L proteins, of 477 and 595 amino acid residues, respectively, show extensive homology to many members of the Siglec-3-like subgroup. This high degree of homology is conserved in the extracellular Ig-like domains, as well as in the cytoplasmic tyrosine-based motifs. Interestingly, the SLG-L protein contains two N-terminal V-set Ig-like domains, as opposed to SLG-S and other Siglec-3-like subgroup members which contain only one such domain. Through RT-PCR we have examined the expression profile of both SLG splice variants in a panel of human tissues and have found that SLG-S is highly expressed in spleen, small intestine and adrenal gland, while SLG-L exhibits high levels of expression in spleen, small intestine, and bone marrow. This gene is quite likely the latest novel member of the CD33-like subgroup of Siglecs, and given its high degree of homology, it may also serve a regulatory role in the proliferation and survival of a particular hematopoietic stem cell lineage, as has been found for CD33 and Siglec7.

Alternative Splicing↗
PubMed1997

Comparison of the rotavirus gene 6 from different species by sequence analysis and localization of subgroup-specific epitopes using site-directed mutagenesis.

The nucleotide sequence of gene 6 encoding the rotavirus major capsid protein VP6 of EDIM strain (EW) was determined and compared to that of 20 previously reported strains with known subgroup specificities. Multiple alignments of amino acid sequences exhibited a high level of sequence conservation (87 to 99.2%). Site-specific mutagenesis experiments were undertaken to localize regions involved in subgroup specificity. Amino acid positions 305, 315, and a region 296-299 (or 301 for equine strain H-2) were identified as contributing to subgroup epitopes. A single amino acid mutation at position 305 or 315 was sufficient to change the subgroup specificity of EW VP6 protein from non I/II to subgroup I- or subgroup II-like, respectively. Mutation at these sites may be another important mechanism for subgroup variation, along with gene reassortment.

Amino Acid Sequence↗
PubMed1984

Sarcoma growth in 15I5 x 7(2) chickens infected with avian sarcoma viruses of subgroup B or G.

A comparative study was made of sarcoma growth in 15I5 x 7(2) chickens infected in the wing web at 4 weeks of age with strains of subgroup B or G avian sarcoma viruses. Infection with sarcoma viruses of either subgroup B or G resulted in the formation of progressive wing web sarcomas at the site of inoculation. The survival times of the subgroup G virus-infected chickens were generally at least twice as great as the survival times of the subgroup B virus-infected chickens, which averaged 6-9 weeks postinoculation. At 5 weeks postinfection, a significantly higher titer of virus neutralizing antibody was detected in the subgroup G virus-infected chickens. Necropsy indicated that a high percentage of subgroup B virus-infected chickens exhibited fibrosarcomas at sites distal to the primary wing web sarcomas, whereas only a small percentage of subgroup G virus-infected chickens exhibited distal sarcomas. The results further indicated that the viral env gene is a determinant of the pattern of distal sarcoma formation.

Animals↗
PubMed1988

Role of RAV-0 genes in the permissive replication of subgroup E avian leukosis viruses on line 15Bev1 CEF.

Rous associated virus type-0 (RAV-0) is a replication-competent endogenous virus of chickens which grows more efficiently on chick embryo fibroblasts (CEFs) from line 15B chickens than on CEFs from line K28. Differences in viral growth on these two sources of cells have been attributed to an early event in the retrovirus life-cycle, at or before viral DNA synthesis. Five in vitro constructed avian leukosis viruses (ALVs) as well as RAV-0 (a subgroup E ALV), RAV-1 (subgroup A), and RAV-2 (subgroup B) have been assessed for their relative growth on 15Bev1 and K28 CEFs. More efficient replication on 15Bev1 CEFs than on K28 CEFs was determined by subgroup E-encoding sequences in env. Subgroup A and B envelope sequences as well as viral LTR, gag, and pol sequences did not obviously bias relative rates of viral replication on the two cell types. We suggest that the unusually permissive replication of subgroup E viruses on 15B CEFs is a receptor-mediated phenomenon and that the line 15B receptor for subgroup E ALVs is more efficient than that of line K28.

Animals↗
PubMed2005

Serum glucose and triglyceride determine high-risk subgroups in non-diabetic postinfarction patients.

A strategy was developed to identify subgroups at high risk for recurrent coronary events in non-diabetic postinfarction patients as a function of metabolic, inflammatory, and thrombogenic blood markers. A graphical screening technique for presumptively identifying high-risk subgroups from outcome prevalence maps was devised that was equally sensitive for all values of risk factors in contrast to traditional approaches where risk is presumed for the highest or the lowest values. Traditional statistical analysis confirms high risk in identified subgroups. Serum glucose and triglyceride served as bivariate search domain. Results demonstrated three high-risk subgroups. One was characterized as pre-diabetic; another as metabolic syndrome-enriched; and the third, with unexpectedly high risk, as normoglycemic and modestly hypertriglyceridemic. Within-subgroup risk as determined by Cox proportional hazards model gave for odds ratios and 95 percentile confidence intervals: glucose, 2.49 (1.17-5.33) in pre-diabetic; PAI-1, 3.95 (1.81-8.61) in metabolic syndrome-enriched; and BMI, 2.79 (1.17-6.63) and fibrinogen, 2.79 (1.29-6.04) in normoglycemic, modestly hypertriglyceridemic patients. We conclude that the graphical approach holds promise in screening for high-risk patient subgroups. Finding different within-subgroup predictors of risk underscores the notion of context-dependent risk, an observation that may be relevant for determining optimal use of emerging risk factors.

Biomarkers↗
PubMed2001

Long-term, non-specific spinal pain: reliable and valid subgroups of patients.

The aim of this study was to identify reliable and valid subgroups of spinal pain patients, using data from the Swedish version of the Multidimensional Pain Inventory (MPI-S). A second aim was to test the generalisability of the three patient profiles described in earlier studies on the MPI ("adaptive coper", "dysfunctional" and "interpersonally distressed" patients). The study base consisted of two samples of individuals suffering from long-term, non-specific spinal pain and the results were validated across these samples. Cluster analysis was used to detect distinct groups of patients and the validity of these subgroups was evaluated on variables not used to generate the cluster solution. One subgroup was characterised by lower pain severity, lower interference with everyday activities, lower affective distress and higher life control than the other two subgroups. This patient profile was similar to the MPI adaptive coper patients. A second subgroup resembled the dysfunctional patient profile, thus displaying a worse adjustment to chronic pain than the AC patients. The third patient group reported significantly lower levels of social support from "significant others" than the other subgroups. This patient profile was similar to that of the interpersonally distressed patient group. Taken together, the results support the reliability, validity and generalisability of three subgroups of chronic pain patients derived from the MPI-S.

Adaptation, Psychological↗
PubMed2003

Genetic diversity between human metapneumovirus subgroups.

Complete consensus nucleotide sequences were determined for human metapneumovirus (HMPV) isolates CAN97-83 and CAN98-75, representing the two proposed genotypes or genetic subgroups of HMPV. The overall level of genome nucleotide sequence identity and aggregate proteome amino acid sequence identity between the two HMPV subgroups were 80 and 90%, respectively, similar to the respective values of 81 and 88% between the two antigenic subgroups of human respiratory syncytial virus (HRSV). The diversity between HMPV subgroups was greatest for the SH and G proteins (59 and 37% identity, respectively), which were even more divergent than their HRSV counterparts (72 and 55% cross-subgroup identity, respectively). It is reasonable to anticipate that the two genetic subgroups of HMPV represent antigenic subgroups approximately comparable to those of HRSV.

Amino Acid Sequence↗
PubMed2002

Rotavirus subgroup characterisation by restriction endonuclease digestion of a cDNA fragment of the VP6 gene.

Human rotavirus strains characterised with subgroup-specific monoclonal antibodies were amplified using a VP6-specific RT-PCR and amplicons of 379 bp size (nt 747-1126) were analysed by restriction fragment length polymorphism (RFLP) using the restriction endonuclease AciI. The restriction patterns were compared to the subgroups determined serologically and to VP6 genogroups determined through sequence analysis. RFLP discriminated successfully between VP6 genogroups I and II. None of the strains characterised serologically as either subgroup nonI,nonII or subgroup I+II were distinguishable from subgroup II on the basis of their restriction pattern or sequence analysis. The results obtained by RFLP correlated well with the VP6 genogrouping results, providing a more reliable method for subgrouping of rotaviruses than ELISAs using subgroup-specific antibodies.

Antigens, Viral↗