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Results for “consensus molecular subtypes”

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PubMed2006

Molecular analysis of HIV strains from a cluster of worker infections in the adult film industry, Los Angeles 2004.

OBJECTIVES: In April 2004, 13 susceptible women were exposed to a single acutely HIV-1-infected man while employed to perform various sex acts for the production of adult films; three women were subsequently found to have acquired HIV infection (23% attack rate). As part of the investigation of this infection cluster, we evaluated whether viral strains collected from infected individuals were significantly related. METHODS: We determined nucleotide sequences from the C2V3C3 and gp41 region of env and the p17 region of gag in viruses from the three infected individuals from whom specimens were available. We then compared these sequences phylogenetically to comparable sequences from available reference strains. Genotypic and phenotypic antiretroviral drug resistance was determined for plasma virus from the male index case and one female contact at a separate commercial laboratory. RESULTS: The env and gag sequences of the HIV strains from the male index case and two of the infected women were 100% similar. Genotyping of the male index case's virus identified 12 mutations, which represented known naturally occurring polymorphisms in the subtype B consensus sequence that are not associated with antiretroviral drug resistance. Genotyping of the virus from the female contact identified 10 mutations, all of which were shared by the virus from the male index case. Phenotyping demonstrated that both viruses were susceptible to all antiretroviral drugs tested. CONCLUSION: Molecular and virological data strongly support the epidemiological conclusion that these women were infected with an identical strain of HIV through occupational exposure to an individual with an acute HIV infection.

Cluster Analysis↗
PubMed1993

Isolation and characterization of two new functional subtypes of HLA-B35.

Human minor histocompatibility antigen-specific, HLA-B*3501-restricted cytotoxic T-cell clones were assayed on a panel of 25 different target cells previously typed by serology as HLA-B35. Cells from 6 donors were not killed and cells from 2 of these were further studied by molecular cloning to characterize their HLA class I alleles. Two new HLA-B35 subtypes were identified. The sequence of one of them differs from B*3501 by one nucleotide change at codon 156, replacing a Leu for an Arg. The sequence of the other new subtype also shows a single nucleotide change compared to B*3501, with Gly-->Val substitution at residue 16. With these new variants, the allelic complexity of HLA-B35 extends now to eight subtypes.

Alleles↗
PubMed1992

Cloning of the genes for excitatory amino acid receptors.

Glutamate is the major excitatory neurotransmitter in the mammalian brain, with receptors on every neuron in the central nervous system; it has major roles in fast synaptic transmission and in the establishment of certain forms of memory. More than 20 years ago Olney and his colleagues described the 'Excitotoxic Hypothesis' which postulates that, in addition to its normal function in the healthy brain, glutamate can kill neurons by prolonged, receptor-mediated depolarization resulting in irreversible disturbances in ion homeostasis. Therefore, glutamate is a two-edged sword; in certain undefined, adverse conditions it undergoes a transition from neurotransmitter to neurotoxin. Its toxicity has been implicated in the death of neurons in ischemia, epilepsy, and the neurodegenerative disorders such as Alzheimer's, Huntington's, and Parkinson's disease. Recent advances in the molecular cloning of the genes for the glutamate family of receptors has revealed a plethora of receptor subtypes and an unexpected level of complexity in the mechanisms of receptor expression and function.

Amino Acid Sequence↗
PubMed2003

[A molecular epidemiological study on the human immunodeficiency virus infection in Jiangsu province].

OBJECTIVE: To identify subtypes of human immunodeficiency virus 1 (HIV-1) strains and their distribution, infection sources, and the trends of HIV infection in Jiangsu province. METHODS: Anticongulated bloods from 46 infected persons were collected to separate previrus DNA. HIV-1 env genes were then amplified by nested-PCR and sequenced for their C2-V3 region so as to identify subtypes. The analysis of consensus sequence, genetic distance and phylogenetic tree were conducted with GCG software. RESULTS: By the end of 2001, there had been six subtypes of HIV-1 strains identified in Jiangsu province: A, B, B', C, D and E. The predominant subtypes were C (accounting for 40.48%) and B' (accounting for 38.10%). Subtype C accounted for 86.67% among injecting DUs while subtype B' accounted for 91.67% among commercial blood donors and receivers. CONCLUSION: Subtype B'among commercial blood donors was brought to Jiangsu from neighboring provinces. The outbreak of HIV-1 infection among local DUs was caused by subtype C from Xinjiang province. Findings from HIV/AIDS molecular epidemiologic study suggest that it is challenging for Jiangsu to treat patients, apply vaccine, prevent and control AIDS in the future.

China↗
PubMed2000

Phylogenetic sequence analysis, recombinant expression, and tissue distribution of a channel catfish estrogen receptor beta.

An estrogen receptor beta (ERbeta) cDNA fragment was amplified by RT-PCR of total RNA extracted from liver and ovary of immature channel catfish. This cDNA fragment was used to screen an ovarian cDNA library made from an immature female fish. A clone was obtained that contained an open reading frame encoding a 575-amino-acid protein with a deduced molecular weight of 63.9 kDa. Maximum parsimony and Neighbor Joining analyses were used to generate a phylogenetic classification of channel catfish ERbeta on the basis of 25 full-length teleost and tetrapod ER sequences. The consensus tree obtained indicated the existence of two major vertebrate ER subtypes, alpha and beta. Within each subtype, and in accordance with established phylogenetic relationships, teleost and tetrapod ER were monophyletic confirming the results of a previous analysis (Z. Xia et al., 1999, Gen. Comp. Endocrinol. 113, 360-368). Extracts of COS-7 cells transfected with channel catfish ERbeta cDNA bound estrogen with high affinity (K(d) = 0.21 nM) and specificity. The affinity of channel catfish ERbeta for estrogen was higher than previously reported for channel catfish ERalpha. As determined by qualitative RT-PCR, the tissue distributions of ERalpha and ERbeta were similar but not identical. Both ER subtypes were present in ovary and testis. ERalpha was found in all other tissues examined from juvenile and mature fish of both sexes. ERbeta was also found in most tissues except, in most cases, whole blood and head kidney. Interestingly, the pattern of expression of ER subtypes in head kidney always corresponded to the pattern in whole blood. In conclusion, we isolated a channel catfish ERbeta with ligand-binding affinity and tissue expression patterns different from ERalpha. Also, we confirmed the validity of our previously proposed general classification scheme for vertebrate ER into alpha and beta subtypes and within each subtype, into teleost and tetrapod clades.

Amino Acid Sequence↗
PubMed2004

Pathogenetic role of BCL6 translocation in B-cell non-Hodgkin's lymphoma.

Chromosomal translocation affecting the 3q27 band, where the BCL6 gene is localized, is one of the most common genetic abnormalities in non-Hodgkin's lymphoma of B-cell type (B-NHL). The translocation occurs within the major translocation cluster (MTC) of BCL6, and as the result of translocation either one of the three immunoglobulin (Ig) genes or a heterogeneous non-Ig gene is juxtaposed to the coding regions of BCL6. On the other hand, somatic hypermutation involves the BCL6 gene of not only B-NHL but also B-cells from normal individuals. The mutations are clustered within a region of the MTC, suggesting that a common molecular mechanism is operating for the two genetic lesions of BCL6. The Bcl-6 protein is a transcriptional repressor that is an important regulator of lymphoid development and function. The protein is preferentially expressed in germinal center (GC) B-cells of normal lymphoid tissues as well as in a variety of B-NHL subtypes derived from GC B-cells irrespective of whether the BCL6 is rearranged. Although there is no consensus on the effect of BCL6 translocation on the clinical outcome of B-NHL, many studies coincide in showing that a high-level of BCL6 expression at either or both the mRNA and protein levels is a favorable prognostic marker of diffuse large B-cell lymphoma. In vitro evidence suggests that non-Ig/BCL6 translocation transiently enhances the level of Bcl-6 expression, which may perturb a molecular network that controls the differentiation of GC B-cells to Ig-secreting plasma cells, thereby predisposing the B-cells to neoplastic transformation.

Base Sequence↗
PubMed2006

Genomic diversity in the regulatory nef gene sequences in Indian isolates of HIV type 1: emergence of a distinct subclade and predicted implications.

The regulatory functional nef gene is known to mediate a cascade of events during pathogenesis in HIV infection. Variability in the nef gene sequences of HIV-1 A and B subtypes has been well documented. Reasonable data are also available on the pattern of genomic changes in the nef gene of African strains of HIV-1 subtype C, but very little is known about heterogeneity in the nef gene of Indian strains of HIV-1 subtype C, which accounts for 90% of the estimated 5.2 million cases of HIV infection in India. This is a huge number and, therefore, it is important to reveal the extent of sequence variability in the nef gene of HIV-1 subtypes circulating in different parts of India. We carried out full-length nef gene (approximately 620 bp) sequencing on a large number of clinical isolates of HIV-1 circulating in different geographic regions of India. Comparative and phylogenetic analysis revealed 88% (38/43) of cases was HIV-1 subtype C; four cases were diagnosed as subtype A and only one as subtype B. Although most of the crucial functional motifs of the nef gene were conserved, we did observe a few important variations in juxtapositions to functional domains. Interestingly, analyzed nef sequences showed an evolving pattern of segregation away from those reported from other parts of the world, to form a distinct Indian subclade. Deduced amino acid (aa) sequences used to predict HLA binding epitopes for consensus nef gene sequences of Indian strains of HIV-1 revealed two HLA subtype binding domains, GAFDLSFFL (at aa 83) and LTFGWCFKL (at aa 136), in high frequency. The findings from the present study may encourage use of nef gene in molecular diagnostics/genotyping, keeping track of the evolutionary trend and pinpointing the emergence of recombinant strains, and in the future, designing a multiepitope HIV vaccine suitable for the Indian population.

Adolescent↗
PubMed2026

Sodium Overload-Related Molecular Subtypes and a Four-Gene Prognostic Signature Predict Survival, Immune Landscape, and Therapeutic Response in Acute Myeloid Leukemia.

Sodium overload has recently emerged as a critical metabolic stressor involved in cancer progression; however, its molecular characteristics and clinical relevance in acute myeloid leukemia (AML) remain unexplored. RNA-seq data sets, clinical annotations, and mutational profiles of AML patients were annotations from The Cancer Genome Atlas and integrated with Genotype-Tissue Expression normal samples. Sodium overload-related genes (SORGs) were obtained from GeneCards. Differentially expressed SORGs (DESORGs) screened by applying the limma statistical model, followed by univariate Cox proportional hazards regression, consensus clustering, functional enrichment, immune infiltration analysis, and pathway evaluation. A prognostic signature was developed through least absolute shrinkage and selection operator regression followed by multivariate Cox modeling. The model's performance was further verified in two external GEO data sets (GSE71014 and GSE37642). Nomogram construction, subgroup analysis, tumor mutational burden (TMB) assessment, drug sensitivity prediction, transcription factor (TF) analysis, and competing endogenous RNA (ceRNA) network analyses were also performed. A total of 57 DESORGs were identified, and 2 sodium overload-related molecular subtypes exhibited distinct survival, immune infiltration, and inflammatory pathway activation. A robust four-gene signature (DOCK1, GABRE, HTR7, ACSM1) stratified patients into high- and low-risk categories with significantly different survival across training and validation cohorts. High-risk patients displayed increased immune infiltration, higher TMB, reduced sensitivity to multiple chemotherapeutic drugs, and inferior predicted response to PD-L1 blockade. TF and ceRNA networks revealed multilayered transcriptional and post-transcriptional regulation of the signature genes. This study identifies sodium overload-related molecular heterogeneity in AML and establishes a validated four-gene prognostic signature that integrates genomic, immunologic, and therapeutic features, offering potential utility for personalized risk assessment and treatment optimization.

Humans↗
PubMed1996

Cloning and quantification of galanin-1 receptor expression by mucosal cells lining the human gastrointestinal tract.

Recent studies suggest that galanin receptors may be expressed by mucosal epithelial cells lining the GI tract and play a role in regulating ion transport. However, no information exists as to which receptor subtype is expressed by these mucosal cells, or the relative distribution of such receptors within the GI tract. In this study we cloned the human galanin-1 receptor (huGal 1-R) from small intestinal RNA, and demonstrate its expression in endoscopically obtained mucosal pinch biopsies by RT-PCR from the esophagus to the rectum. Semi-quantitative PCR (SQ-PCR) was performed and revealed the largest amount of huGal 1-R message in the duodenum and the least amount in the gastric fundus. This study for the first time directly demonstrates the presence and quantity of huGal 1-R message in human G1 tract mucosal epithelial cells, and suggests that this subtype is of primary importance in regulating galanin-induced changes in intestinal absorption.

Base Sequence↗
PubMed1994

Molecular epidemiology of HTLV type I in Japan: evidence for two distinct ancestral lineages with a particular geographical distribution.

Japan is one of the highest endemic areas of the world for human T cell leukemia-lymphoma virus type I (HTLV-I). To gain new insight as to the origin of this virus in Japan and especially in the southern islands of the archipelago, we investigated the long terminal repeat (LTR) of 67 newly isolated HTLV-I proviral DNAs from peripheral blood mononuclear cells of HTLV-I-infected individuals for their restriction fragment length polymorphism (RFLP). The specimens were from Japanese living in different geographical areas (Hokkaido, Honshu, Kyushu, or the Ryukyu Islands) of Japan (59 cases) or Americans of Japanese ancestry living in Hawaii (8 cases). The analysis of the results, together with data for the 19 previously published LTR sequences, demonstrated the existence of 2 subtypes of HTLV-I in Japan. The first, which we propose to name Japanese subtype (previously named subtype III), is more frequent (67 of 86: 78%) than the second, the cosmopolitan subtype (previously named subtype II) (19 of 86: 22%). In parallel, a fragment of 413 base pairs of the U3/R region (nucleotide 22 to 434) was cloned and sequenced from 10 of the new Japanese samples. The alignment of these sequences and their comparison and phylogenetic analysis with previously published LTR HTLV-I sequences, demonstrated clearly the existence of the two distinct molecular subtypes of HTLV-I in Japan, diverging in this LTR region by about 1.6%. Furthermore, the study of the geographical distribution of the 2 subtypes among the 80 samples from patients whose place of residence in Japan was known showed an uneven distribution. While the Japanese subtype was present in all parts of Japan, the cosmopolitan subtype seemed to cluster in the southern islands of the archipelago (i.e., Kyushu and the Ryukyu Islands) as well as in immigrants from those areas who had lived in Hawaii for decades. These new molecular data raise questions and suggest hypotheses, discussed here, concerning the origin and means of dissemination of these human retrovirus subtypes in Japan.

Adult↗
PubMed2005

Chicken RFamide-related peptide (GnIH) and two distinct receptor subtypes: identification, molecular characterization, and evolutionary considerations.

RFamide-related peptides (RFRPs) regulate the release of various pituitary hormones in vertebrates. It is completely unknown how the functions of RFRPs vary among animal classes and whether vertebrate RFRPs are orthologous to each other and belong to the same peptide family. This report concerns identification of avian RFRP (gonadotropin-inhibitory hormone, GnIH) from the chicken. Chromosome-wide synteny conservation demonstrated the orthologous relationships among vertebrate RFRPs. The consensus motif for RFRP was modified to Pro-Xaa-Arg-Phe-NH2. We also describe the first identification of two distinct types of receptors for non-mammalian RFRP (RFRPR and NPFFR) from the chicken. Amino acid comparison revealed substantial differences in both termini of receptors among classes of vertebrates. The 5'-flanking regions of chicken RFRPR and NPFFR suggested their expressions in the pituitary gland, and this was confirmed by the RT-PCR analysis. Localizations of both chicken RFRP and its receptors were distinct from those of mammals. These results indicated that avian RFRP, unlike the mammalian one, directly acts on the pituitary gland via receptors to regulate gonadotropin release. It was also suggested that functional differences, especially between avian and mammalian RFRPs, are substantially due to divergences in the structures and expression sites of their receptors.

Amino Acid Sequence↗
PubMed2005

Therapy-related myeloid leukaemia: a model for leukemogenesis in humans.

Therapy-related myeloid leukemia (t-AML) is a distinctive clinical syndrome occurring after exposure to chemotherapy (CT) or radiotherapy (RT). We studied 306 consecutive patients referred to the University of Chicago with cytogenetic analyses. Since 1972, 141 males and 165 females with a median age of 51 years (range: 3-83 years) at primary diagnosis and 58 years (range: 6-86 years) at secondary diagnosis were analyzed. Patients had received various cytotoxic agents including alkylating agents (240 patients, 78%) and topoisomerase II inhibitors (115 patients, 39%). One hundred and twenty-one (40%) had received CT alone, 43 (14%) had received RT alone, and 139 (45%) had received both modalities. At diagnosis of t-AML, 282 (92%) had clonal abnormalities involving chromosome 5 (n=63), chromosome 7 (n=85), both chromosomes 5 and 7 (n=66), recurring balanced rearrangements (n=31), or other clonal abnormalities (n=39); 24 had a normal karyotype. Abnormalities of chromosomes 5 and/or 7 accounted for 76% of all cases with an abnormal karyotype. Seventeen patients had developed t-AML after autologous stem cell transplantation, but no unique pattern of cytogenetic abnormalities was observed. Patients presenting with acute leukemia were more likely to have a balanced rearrangement than those presenting with myelodysplasia (28% versus 4%, p<0.0001). Shorter latency was observed for patients with balanced rearrangements (median: 28 months versus 67 months; p<0.0001). Median survival after diagnosis of t-AML was 8 months; survival at 5 years was less than 10%. To gain insights into the molecular basis of this disease, we performed gene expression profiling of CD34+ hematopoietic progenitor cells from t-AML patients. We found distinct subtypes of t-AML that have characteristic gene expression patterns. Common to each of the subgroups are gene expression patterns typical of arrested differentiation in early progenitor cells. Leukemias with a -5/del(5q) have a higher expression of genes involved in cell cycle control (CCNA2, CCNE2, CDC2), checkpoints (BUB1), or growth (MYC), and loss of expression of the gene encoding interferon consensus sequence-binding protein (ICSBP). A second subgroup of t-AML is characterized by down-regulation of transcription factors involved in early hematopoiesis (TAL1, GATA1, and EKLF) and overexpression of proteins involved in signaling pathways in myeloid cells (FLT3) and cell survival (BCL2). Establishing the molecular pathways involved in t-AML may facilitate the identification of selectively expressed genes that can be exploited for the development of targeted therapies.

Acute Disease↗
PubMed2000

[Molecular epidemiology analysis of HIV-1 subtype E strains found in Shenzhen, China].

OBJECTIVE: To investigate the prevalent status of HIV-1 subtype E epidemic among different populations in Shenzhen, China. METHODS: HIV-1 proviral DNA from peripheral blood mononuclear cells (PBMCs) of 3 HIV-infected individuals found in Shenzhen was amplified by nested-PCR. The C2-V3 and its flanking region (350-450 nucleotides) of HIV- 1 env gene were sequenced directly from the PCR products and analysed. RESULTS: These 3 cases were confirmed to be infected with HIV-1 subtype E strain (sz-E). The innergroups distance of sz-E was 2.6%. In comparison with the consensus sequence of international A-E subgroups and some of subtype B epidemic in China, the genetic distances among sz-E and each of A-D subgroups and some of subtype B were more than 24 %. Furthermore, the phylogenetic tree analysis showed that sz-E clustered closely to Econ. CONCLUSIONS: These findings suggested that the epidemic time for HIV-1 subtype E, which was mainly prevalent among IDUs population and some professional blood donors, had been about 2-3 years in Shenzhen.

China↗
PubMed1995

Relationship between the V3 loop and the phenotypes of human immunodeficiency virus type 1 (HIV-1) isolates from children perinatally infected with HIV-1.

The third variable region (V3) of the envelope protein of human immunodeficiency virus type 1 (HIV-1) contains group- and type-specific epitopes for neutralizing antibodies and contains determinants involved in viral tropism and syncytium-inducing (SI) activity. We studied the in vivo relationship between V3 sequences and viral phenotypes in 24 perinatally HIV-1-infected children. To avoid in vitro selection of intrapatient minor variants, genetic studies were performed directly on uncultured peripheral blood mononuclear cells (PBMC), and the tropisms of HIV-1 isolates were evaluated by culturing patients' PBMC directly with monocyte-derived macrophages, lymphocytes, and MT-2 cells. According to their phenotypes, we could define five types of primary isolates: (i) non-syncytium-inducing (NSI) macrophagetropic, (ii) NSI macrophage-lymphotropic, (iii) NSI lymphotropic, (iv) SI lympho-T-cell line-tropic, and (v) SI pleiotropic. The SI viral phenotype was correlated with a more advanced status of disease. Genetic analysis of intrapatient molecular variants revealed that no relationship between the degree of intrapatient V3 variability and the pattern of viral tropism existed; moreover, within a single patient, the values for V3 variability between CD4+ lymphocytes and CD14+ monocytes were similar, thus suggesting that in vivo variability of the monocytotropic variants is more extensive than previously appreciated. A comparison between the intrapatient major variants and the phenotype of primary isolates disclosed that a negatively charged amino acid at residue site 25 was associated with an NSI macrophage- and macrophage-lymphotropic viral phenotype. Finally, by comparing the V3 sequences derived from our study population with those of several prototypes, we observed that the majority of isolates circulating in Italy are related to the North American subtype B macrophagetropic isolates.

Amino Acid Sequence↗