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PubMed2006

T cell gene expression profiling identifies distinct subgroups of Japanese multiple sclerosis patients.

To clarify the molecular background underlying the heterogeneity of multiple sclerosis (MS), we characterized the gene expression profile of peripheral blood CD3+ T cells isolated from MS and healthy control (CN) subjects by using a cDNA microarray. Among 1258 cDNAs on the array, 286 genes were expressed differentially between 72 untreated Japanese MS patients and 22 age- and sex-matched CN subjects. When this set was used as a discriminator for hierarchical clustering analysis, it identified four distinct subgroups of MS patients and five gene clusters differentially expressed among the subgroups. One of these gene clusters was overexpressed in MS versus CN, and particularly enhanced in the clinically most active subgroup of MS. After 46 of the MS patients were treated with interferon-beta (IFNbeta-1b) for two years, IFNbeta responders were clustered in two of the four MS subgroups. Furthermore, the IFNbeta responders differed from nonresponders in the kinetics of IFN-responsive genes at 3 and 6 months after starting IFNbeta treatment. These results suggest that T-cell gene expression profiling is valuable to identify distinct subgroups of MS associated with differential disease activity and therapeutic response to IFNbeta.

Adjuvants, Immunologic↗
PubMed2005

Generation and recognition of abstract rules in different frontal lobe subgroups.

The Left Lateral cortex is known to have a role in inductive reasoning tasks. A more specific hypothesis on its role is that it is crucial in the generation of new abstract rules, rather than in the selection and implementation of a specific rule among a set of previously learned ones. Two new tests - the Generation of Hypotheses test and the Recognition of the Rule test - were administered to 46 patients with focal damage to the frontal cortex. Patients were divided in three frontal subgroups: Left Lateral, Right Lateral and Medial. On the basis of the new hypothesis, it was predicted that (i) the Left Lateral subgroup would fail in the Generation of Hypotheses test but would show spared performance on the Recognition of the Rule test and that (ii) the other frontal subgroups would perform normally on both tests. The findings on the Left Lateral and Right Lateral frontal subgroup were consistent with the predictions. This suggests that the Left Lateral frontal cortex is critical specifically for the generation of hypotheses in inductive reasoning. The Medial frontal subgroup, in contrast with our expectations, was impaired on Generation test; two hypotheses have been raised to explain this finding.

Adult↗
PubMed2005

Phylogeny and molecular evolution of the Drosophila hydei subgroup (Drosophila repleta group) inferred from the Xanthine dehydrogenase gene.

The hydei subgroup (Drosophila repleta group) consists of seven species divided into two complexes: bifurca and hydei, whose phylogenetic relationships are not well understood. To evaluate the molecular phylogeny of this subgroup, we analyzed 2085 bp of coding sequence of the Xanthine dehydrogenase gene in six available species of the hydei subgroup, with Drosophila buzzatii and Drosophila mulleri as an outgroup. For phylogenetic reconstruction we adopted a maximum-likelihood framework, based on the adjustment of descriptive models of nucleotide substitution to real data. We employed distance-based and weighted parsimony methods to construct candidate phylogenies. In all cases, we obtained only one completely resolved tree with strong statistical support for each node, that shows a phylogeny that is partially discordant with the proposed systematics of the subgroup. This tree suggests that the two species complexes are paraphyletic, as opposed to classic phylogenies using morphologic and cytologic traits. This discordance is discussed in relation to its implication for the evolutionary history of the hydei subgroup.

Animals↗
PubMed2000

Subgroup analysis and other (mis)uses of baseline data in clinical trials.

BACKGROUND: Baseline data collected on each patient at randomisation in controlled clinical trials can be used to describe the population of patients, to assess comparability of treatment groups, to achieve balanced randomisation, to adjust treatment comparisons for prognostic factors, and to undertake subgroup analyses. We assessed the extent and quality of such practices in major clinical trial reports. METHODS: A sample of 50 consecutive clinical-trial reports was obtained from four major medical journals during July to September, 1997. We tabulated the detailed information on uses of baseline data by use of a standard form. FINDINGS: Most trials presented baseline comparability in a table. These tables were often unduly large, and about half the trials inappropriately used significance tests for baseline comparison. Methods of randomisation, including possible stratification, were often poorly described. There was little consistency over whether to use covariate adjustment and the criteria for selecting baseline factors for which to adjust were often unclear. Most trials emphasised the simple unadjusted results and covariate adjustment usually made negligible difference. Two-thirds of the reports presented subgroup findings, but mostly without appropriate statistical tests for interaction. Many reports put too much emphasis on subgroup analyses that commonly lacked statistical power. INTERPRETATION: Clinical trials need a predefined statistical analysis plan for uses of baseline data, especially covariate-adjusted analyses and subgroup analyses. Investigators and journals need to adopt improved standards of statistical reporting, and exercise caution when drawing conclusions from subgroup findings.

Bias↗
PubMed1998

Diagnostic subgrouping of depressed patients by principal component analysis and visualized pattern recognition.

A data-analytical method is described for identifying behavioral and biological variables in psychiatric patients with predictive value in defining clinical subgroups. The procedure, based on principal component analysis (PCA) and graphical analysis, was applied in a group of 28 depressed patients. The 28 depressed patients of unipolar type were observed for up to 15 years for re-evaluation of the diagnoses at the start of the study. Platelet monoamine oxidase activity, post-dexamethasone serum cortisol and serum melatonin predicted two main clinical subgroups as well as a smaller subgroup of bipolar patients. The selection procedure revealed which of several variables were predictive of subgroups that were not possible to identify by univariate methods. The three biological variables may thus be useful in further assessment of clinical subgroups of unipolar depressed patients studied by other research groups.

Adult↗
PubMed1985

Legionella pneumophila serogroup 1 subgrouping by monoclonal antibodies--an epidemiological tool.

A panel of 10 monoclonal antibodies was used to subgroup 326 strains of Legionella pneumophila serogroup 1. All but two strains could be classified into three major subgroups named after their representative strains Pontiac 1, Olda and Bellingham 1. Of the 50 isolates from patients, 44 representing 32 separate incidents were of the Pontiac subgroup. This subgroup was also found in 16 of 18 buildings epidemiologically associated with Legionnaires' Disease. In contrast, strains of the Olda subgroup predominated in buildings where no infections had occurred. In 9 of the 11 incidents where isolates were available from at least one patient as well as from the suspected environmental source, the monoclonal antibody reaction patterns of strains from patients were identical to those of one or more of their environmental counterparts.

Antibodies, Monoclonal↗
PubMed2001

The benefits of chemotherapy in patient subgroups with unresectable non-small-cell lung cancer.

BACKGROUND: Cisplatin-based chemotherapy improves survival in advanced non-small-cell lung cancer. Using data from phase III trials of mitomycin, ifosfamide and cisplatin, this paper investigates whether the beneficial effect of chemotherapy on survival and quality of life seen overall is limited to certain patient subgroups. PATIENTS AND METHODS: The survival benefit of chemotherapy was compared with standard treatment using hazard ratios for subgroups specified by stage, sex, age, histology and performance status (PS). The effect on quality of life was investigated for three subgroups defined by performance status. RESULTS: The overall unstratified hazard ratio for all 797 eligible patients shows a 16% reduction in the risk of death with chemotherapy (P = 0.02). This benefit was seen for both locally advanced and extensive stage disease (significantly in extensive disease). Subgroups defined by sex, age and histology consistently benefitted from chemotherapy. The hazard ratios for the three levels of performance status suggest that PS2 patients gain no survival benefit from chemotherapy. In contrast, these patients experienced the greatest improvement in quality of life during the first six weeks of chemotherapy. CONCLUSIONS: Subgroup analysis suggests that the prolongation of life from cisplatin-based chemotherapy is confined to PS0/1 patients. Palliation is greater in PS2 patients.

Aged↗
PubMed2025

Alternative spliceosomal protein Eftud2 mediated Kif3a exon skipping promotes SHH-subgroup medulloblastoma progression.

Alternative splicing plays a pivotal role in various facets of organogenesis, immune response, and tumorigenesis. Medulloblastoma represents a prevalent childhood brain tumor, with approximately one-third classified as the Sonic Hedgehog (SHH) subgroup. Nevertheless, the contribution of alternative splicing to medulloblastoma oncogenesis remains elusive. This investigation delineated an upregulation of the spliceosomal protein Eftud2 in the SHH-subgroup medulloblastoma mouse model and human medulloblastoma patients. Targeted ablation of Eftud2 in granule precursor cells (GNPs) within the cerebellum prolonged the survival of SHH-subgroup medulloblastoma mice, indicating a putative association between Eftud2 expression and medulloblastoma prognosis. Functional assays unveiled that EFTUD2 depletion in human medulloblastoma cells significantly curtailed cellular proliferation by impeding the activation of the SHH signaling pathway. Through multi-omics sequencing analysis, it was discerned that Eftud2 influences exons 10-11 skipping of Kif3a, a kinesin motor critical for primary cilia formation. Notably, exons 10-11 skipping in Kif3a augmented human medulloblastoma cell proliferation by potentiating the transcriptional activity of Gli2. These findings underscore a robust correlation between Eftud2 and SHH-subgroup medulloblastoma, emphasizing its regulatory role in modulating downstream transcription factors through the alternative splicing of pivotal genes within the SHH signaling pathway, thereby propelling the aggressive proliferation of SHH-subgroup medulloblastoma.

Medulloblastoma↗
PubMed1998

Comparison of health-related quality of life in three subgroups of spinal cord injury patients.

Health-related quality of life (HRQL) was evaluated in three subgroups of spinal cord injury (SCI) patients: (1) persons who had sustained a pediatric SCI (mean time from injury 20 years, age at injury 11.3 years, n = 36), (2) newly injured patients at the beginning of acute rehabilitation (mean age 35.3 years, n = 31), and (3) patients with a chronic SCI (mean time from injury 4.8 years, mean age at injury 35.2 years, n = 34). All the patients were clinically examined and structurally interviewed with a list of questions dealing with details of anamnestic information about injury, its treatment, possible complications and persons past and present psycho-social condition. HRQL was assessed by a generic fifteen-dimensional self-administered instrument (15D). The relative importance of the 15D dimensions and an overall judgement of health status were measured by a 0-100 visual analogue scale. Average importance weights of the dimensions of moving and working differed significantly in the three subgroups. Patients with pediatric SCI assigned the lowest importance for moving. The newly injured patients highly valued working capability. The HRQL scores of the patients who had sustained their injury in childhood were significantly higher than those of the newly injured patients or chronic patients. The tetraplegic patients estimated their HRQL significantly lower than patients with incomplete paraplegia. Of the three subgroups studied, those with pediatric SCI were well adjusted on the basis of anamnestic information and scored high on HRQL when compared with the other two subgroups. Patients injured in adulthood rated their overall HRQL lower and were often unable to return to work. Patients injured in childhood expressed better performance in physical functions than patients who had sustained their injury in adulthood. The subgroups did not differ in psychological functions.

Adult↗
PubMed2003

Subgrouping in obesity based on Rorschach personality characteristics.

Conceptual (a priori) subgroups in obesity based on personality findings from the Rorschach Comprehensive System were suggested for 100 obese patients. The subgroups were further compared in terms of general anamnestic and behavioral data. The largest subgroup was Rorschach characterized by difficulties with emotions and a tendency towards depression. Demographic and behavioral data for this subgroup revealed intermediate or higher education, regular meals, eating disorders like binge eating, periodic variations in eating during the year and experiencing body size as having a psychological meaning. The other subgroup was characterized by coping liabilities and was further associated with a lower socio-economic level and irregular or chaotic meal patterns. For the group with emotional difficulties, the results suggest a more complex psychological pattern, where eating and emotions could be closely related. The group with coping liabilities could have difficulties other than emotional ones concerning food and eating, such as finding a structure for eating and making changes in lifestyle and habits.

Adaptation, Psychological↗
PubMed2003

Multidimensional subgroups in migraine: differential treatment outcome to a pain medicine program.

OBJECTIVE: The present study compared two different approaches for deriving patient profiles on their ability to predict treatment outcome to a pain medicine program for migraine headache. DESIGN/METHODS: Using visual analog scale measures of pain intensity and functional limitations and the Beck Depression Inventory (BDI), as a measure of depression, 235 migraine patients were classified into statistical clusters. The same patients were also classified using the Multidimensional Pain Inventory (MPI) algorithm into three subgroups: Adaptive copers (AC), characterized by lower reported levels of pain intensity, life interference, and distress, as well as higher levels of perceived life control; interpersonally distressed (ID), characterized by more intermediate levels of pain, distress, and interference, with a predominant perception of inadequate support and punishing responses from significant others; and dysfunctional (Dys), characterized by high levels of pain severity, life interference, and distress and low levels of perceived life control and activity. RESULTS: The results of the K-cluster analysis yielded a three-cluster solution: The low impact cluster, was characterized by low pain, low functional limitations and low depression and showed significant reductions in pre-to-posttreatment pain; the moderate impact cluster displayed higher levels of pain and functional limitations and low depression and showed only slight pre-to-posttreatment pain reduction; and the high impact cluster displayed the highest levels of pain, functional limitations, and depression and showed significant increases in pre-to-posttreatment pain. Unlike the K-clustered groups, MPI subgroups failed to differentially predict treatment outcome. When the K-clustered groups were crosstabulated with the MPI subgroups, the predictive validity of the MPI subgroups was enhanced. CONCLUSION: This study questions the validity of the MPI subgroup classification algorithm. The results indicate that the K-clustering approach is more useful than the MPI in deriving meaningful patient clusters that differentially predict treatment outcome in a migraine population.

Adolescent↗
PubMed2000

Specific subgroup B adenovirus diagnosis by PCR of the fibre gene.

OBJECTIVE: A highly sensitive and specific PCR assay targeting regions of the fibre gene was developed for the identification of subgroup B adenovirus strains. This is critical, since these adenovirus strains are frequently associated with severe respiratory infections in infants and new-borns. METHODS: Clinical samples from nasopharyngeal aspirates were analysed by PCR using several sets of primers corresponding to sequences of the gene coding for the fibre protein. RESULTS: The assay allowed the detection and identification of all the genotypes of adenovirus subgroup B, based on the size of the amplified product when analysed on polyacrilamide gel electrophoresis. Specifically, one set of primers was able to amplify DNA of subgroup B but not subgroup C and E viruses. CONCLUSION: The detection of adenovirus and the genotyping can be done on a routine basis by a PCR assay using the fibre gene as a target. The assay allows the identification of ADV subgroup B, including genotype 7h, which is the single most important viral pathogen associated with respiratory diseases in infants and young children in the southern part of South America.

Adenovirus Infections, Human↗
PubMed1987

The G glycoprotein of human respiratory syncytial viruses of subgroups A and B: extensive sequence divergence between antigenically related proteins.

Two major antigenic subgroups (designated A and B) have been described for human respiratory syncytial virus (RSV). Previously, on the basis of reactivity patterns with monoclonal antibodies, the greatest intersubgroup variation was shown to occur in the G protein, the putative attachment glycoprotein. To delineate the molecular basis for this variation, we have determined the nucleotide and deduced amino acid sequences of the G mRNAs and proteins representing a subgroup A (Long strain) and a subgroup B (18537 strain) virus. These sequences were compared to the available G mRNA sequence for another subgroup A (A2 strain) virus. The Long G protein shared 94% amino acid identity with the A2 G protein. In contrast, the 18537 G protein shared only 53% amino acid identity with the A2 sequence; interestingly, most of the sequence divergence occurred in the proposed extracellular domain of the G protein. This extensive divergence for the G protein was significantly greater than that observed for other RSV proteins. Despite this considerable divarication, the proposed extracellular domains of the G proteins contained a single region of highly conserved sequence and secondary structure that may represent a conserved structural or function domain, perhaps involved in attachment to cellular receptors. Furthermore, this conserved region may comprise part of an epitope that is shared between the two subgroup G proteins and may significantly contribute to the fact that, despite extensive overall amino acid sequence divergence, the RSV G proteins maintain significant antigenic relatedness.

Amino Acid Sequence↗
PubMed1992

Feline leukemia virus subgroup C phenotype evolves through distinct alterations near the N terminus of the envelope surface glycoprotein.

Feline leukemia viruses (FeLVs) belonging to the C subgroup induce aplastic anemia in domestic cats and have the ability, unique among FeLV strains, to proliferate in guinea pig fibroblasts in tissue culture. Previous studies have shown that the pathogenic and host range specificity of a prototype molecular clone of FeLV-C [FeLV-Sarma-C (FSC)] colocalize to a region encoding the 3' 73 amino acids of the pol gene product and the N-terminal 241 amino acids of the envelope surface glycoprotein named SU. Here, we amplified, via PCR, cloned, and sequenced the SU coding sequence from three additional anemia-inducing subgroup C FeLV isolates. Chimeric viruses were constructed by replacement of fragments of FeLV-C envelope genes into the FeLV-A prototype virus 61E. Using a modified vesicular stomatitis virus-FeLV pseudotype assay, we demonstrated that the subgroup C receptor specificity for each virus was determined by changes within the N-terminal 87-92 amino acids of SU, in which most changes occurred within the 15- to 20-amino-acid first variable region (V1). Determinants for growth in guinea pig cells colocalized to this region. Despite the consistent localization of biological determinants, the only consistent features that distinguished the deduced FeLV-A and FeLV-C proteins was one lysine-to-arginine change and a structural prediction of an alpha-helix in FeLV-A proteins versus random coil in FeLV-C proteins within V1. However, arginine in equilibrium with lysine substitutions were not sufficient to convert the subgroup A virus to the subgroup C phenotype or vice versa. Thus, certain distinct structural changes within the N-terminal region of FeLV SU can result in convergent viral phenotypes.

Anemia↗
PubMed2005

The Study on COgnition and Prognosis in the Elderly (SCOPE) - major CV events and stroke in subgroups of patients.

The Study on COgnition and Prognosis in the Elderly (SCOPE) assessed the effect of candesartan on cardiovascular outcomes in elderly patients with mild to moderate hypertension. Patients were randomized to candesartan 8-16 mg daily (n = 2477) or placebo (n =2460). Due to extensive add-on therapy, blood pressure reduction was only about 3/2 mmHg greater in the candesartan group than in the control group. Nevertheless, non-fatal stroke was reduced by 28% (p = 0.04) in the candesartan group compared to the control group, and there was a non-significant 11% reduction in major cardiovascular events (p = 0.19). This report provides results in pre-specified subgroups of patients (age, gender, diabetes, history of stroke, smoking and cardiovascular risk at randomization). Reductions in major cardiovascular events and stroke with candesartan-based therapy were indicated in all subgroups. A significant interaction between treatment and subgroups was found for one pair of subgroups only; the reduction in major cardiovascular events with candesartan was greater in patients with a previous stroke (64% reduction, p = 0.004) than in those without (5% reduction, p > 0.20). In conclusion, this analysis indicated consistent favourable effects of candesartan-based therapy on major cardiovascular events and stroke across the different subgroups of patients. However, the benefit was particularly pronounced in patients who entered the study with a previous stroke.

Aged↗
PubMed2005

Neuropsychological subgroups of cognitively-impaired-not-demented (CIND) individuals: delineation, reliability, and predictive validity.

The objectives of the present investigation were to determine whether subgroups of Cognitively-Impaired-Not-Demented (CIND) individuals with distinct neuropsychological profiles exist in two independent samples, and whether subgroup membership is related to diagnostic outcome over periods of 2 to 5 years. A series of cluster analyses was performed on ipsative factor z-scores derived from principal component analyses. Five subgroups were identified in the Base Sample (n = 461): Verbal Dysfunction, Verbal/Visuospatial Dysfunction, Memory/Verbal Dysfunction, Memory Dysfunction, and Visuospatial Dysfunction. This five-cluster solution was replicated in an independent sample of CIND individuals (n = 166). The highest rates of conversion to dementia were observed in the Memory Dysfunction and Memory/Verbal Dysfunction subgroups. The Verbal Dysfunction subgroup was most likely to show improvement in cognitive status. The cognitive heterogeneity of the CIND condition must be taken into account in future research focusing on the early identification of dementia.

Aged↗
PubMed1964

H CHAIN SUBGROUPS OF MYELOMA PROTEINS AND NORMAL 7S GAMMA-GLOBULIN.

Through the use of a variety of antisera to isolated myeloma proteins, four subgroups of 7S gamma-globulin type proteins were readily distinguished. The first, the Vi subgroup, consisted of ten of 64 myeloma proteins studied. The second, the We group, contained the majority of myeloma proteins. The third, the Ge subgroup, included three of 50 myeloma proteins. The fourth remains ill-defined and appears heterogeneous. Counterparts for both the Vi and the Ge subgroup, were found in the Fr II gamma-globulin and in the normal gamma-globulin of all of a large number of individual sera studied. The unique antigenic character of both groups was localized to the H chains, although different determinants were involved for different antisera. An essential role of intact disulfide bonds was apparent with certain rabbit antisera. In addition to the special antigenic characteristics, the Ge subgroup showed in each instance a fast mobility for the F fragments produced by papain which was not found for other myeloma proteins.

Antigen-Antibody Reactions↗
PubMed1967

Studies of the Vi (gamma-2c) subgroup of gamma-globulin. A relationship between concentration and genetic type among normal individuals.

Further delineation of the antigens characteristic of the Vi or gamma(2c) subgroup of gamma-globulin was carried out utilizing a number of rabbit and primate antisera. Two genetic antigens characteristic of this subgroup, Gm(b) and Gm(g), were also detected by precipitation techniques with certain of the antisera. These were clearly differentiated from antigens common to all proteins of this subgroup. The concentration, of Vi protein in normal and pathological sera from several population groups was measured quantitatively utilizing a variety of immunological procedures. All sera studied showed measurable levels. The mean value for Caucasian sera was 1.06 mg/ml, representing approximately 8% of gammaG-globulin. This agreed closely with a figure of 8.4% for the incidence of myeloma proteins of the Vi subgroup among all gammaG-myeloma proteins in Caucasians. A relationship was found between the Vi subgroup concentration and the specific genetic type of a given individual. Measurements of the Gm(b) genetic determinants, which are found solely in Vi-type proteins, brought forward this relationship. Gm(b+) individuals showed higher concentrations of Vi-type gamma-globulin than those who were Gm(b-), and this difference was statistically significant for both the homozygous and heterozygous states. It appeared that the structural genes for Gm(b+) polypeptide chains showed a greater synthetic capacity than those for Gm(b-) types. The possible significance of such effects in governing the relative composition of the antibody population in a given individual is discussed.

Black or African American↗