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PubMed2005

Characteristics of HIV-1 env V3 loop sequences for subtype A1 variant spread in Eastern Europe.

OBJECTIVES: The aim of our investigation was to study the HIV-1 env V3 loop sequences of the subtype A variant of the virus actively circulating in the territory of Eastern Europe (A1-EE). DESIGN: It appears that the characteristics of HIV-1 V3 loop sequences of the thoroughly studied subtype B strains determine the viruses tropism and phenotype. We were interested to find out to what extent these trends are preserved with the subtype A isolates spread in Eastern Europe. METHODS: About 474 HIV-1 strains were isolated by cocultivation with phytohemagglutinin stimulated and interleukin-2 activated PBMC. Isolates were subtyped after distinct regions gag, pol and env were amplified by nested polymerase chain reaction. V3 sequences were studied in detail and compared with the isolates that appeared as SI or NSI in test-cultures MT-2. RESULTS: The subtype A HIV-1 strains spread in Eastern Europe appeared to have V3 loop sequences with a high level of conservatism. The consensus sequences of the SI and NSI isolates proved identical, and correspond to the phenotype markers of subtype B NSI strains. Nevertheless, the subtype A SI isolates induced active syncytium-formation processes in the MT-2 test culture. CONCLUSION: The data obtained evidenced to the following: the HIV-1 subtype A variant spread in Eastern Europe, is capable of using for interaction with receptor structures of sensitive cells the tools and mechanisms, which are significantly different from those described for subtype B.

Amino Acid Motifs↗
PubMed2001

Tamoxifen agonism and estrogen antagonism of c-fos gene promoter activity through non-consensus-responsive elements in MC3T3-E1 osteoblasts.

We find that the activity of a 0.4-kb human c-fos gene promoter (-404/+41), which lacks consensus estrogen-responsive elements (EREs), is regulated by estrogen receptor (ER) ligands in MC3T3-E1 osteoblastic cells through ERs in a manner distinct from ERE-mediated regulation. When ERalpha is coexpressed, both estrogens and antiestrogens upregulate promoter activity. When ERbeta is coexpressed, however, three tested antiestrogens affect c-fos promoter activity, with tamoxifen exerting the greatest effect, while estrogens have no such effect. The tamoxifen agonism through ERbeta is antagonized by 17beta-estradiol, while the 17beta-estradiol agonism through ERalpha is canceled by excess-level coexpression of ERbeta. Deletion analysis revealed that the sequence -206/-110 plays a crucial role in the ERbeta-mediated tamoxifen agonism. Interestingly, there is no ERbeta-mediated tamoxifen agonism when nonosteoblastic cells are tested. Taken together, these results suggest that the transcription of the c-fos gene is regulated by ER ligands possibly through non-ERE elements in ligand structure-, cell type-, and ER subtype-dependent manners.

Animals↗
PubMed2006

Hepatitis C virus complete genome sequences identified from China representing subtypes 6k and 6n and a novel, as yet unassigned subtype within genotype 6.

Here, the complete genome sequences for three hepatitis C virus (HCV) variants identified from China and belonging to genotype 6 are reported: km41, km42 and gz52557. Their entire genome lengths were 9430, 9441 and 9448 nt, respectively; the 5' untranslated regions (UTRs) contained 341, 342 and 339 nt, followed by single open reading frames of 9045, 9045 and 9057 nt, respectively; the 3' UTRs, up to the poly(U) tracts, were 41, 51 and 52 nt, respectively. Phylogenetic analyses showed that km41 is classified into subtype 6k and km42 into subtype 6n. Although gz52557 clustered distantly with subtype 6g, it appeared to belong to a distinct subtype. Analysis with 53 and 105 partial core and NS5B region sequences, respectively, representing 17 subtypes from 6a to 6q and three unassigned isolates of genotype 6 in co-analyses demonstrated that gz52557 was equidistant from all of these isolates, indicating that it belongs to a novel subtype. However, based on a recent consensus that three or more examples are required for a new HCV subtype designation, it is suggested that gz52557 remains unassigned to any subtype.

China↗
PubMed1993

Molecular diversity of the Lyssavirus genus.

The sequence of 5568 nucleotides of the 3' moiety of the Mokola virus genome (serotype 3 of lyssaviruses) encompassing the nucleoprotein (N), phosphoprotein, matrix protein, and glycoprotein genes is presented and compared to that of the vaccinal strains of serotype 1. It allowed us to determine consensus sequences derived from the transcriptional start/stop signals and the order of protein conservation (nucleoprotein > matrix protein > phosphoprotein) in lyssaviruses. The sequences of the N gene of a fox rabies virus isolate from France (serotype 1), Lagos bat virus (serotype 2), Duvenhage virus (serotype 4), two European bat lyssaviruses (EBL) subtype 1, and two EBL subtype 2 were also determined to study the genetic diversity throughout the whole Lyssavirus genus and reinvestigate the classification of this genus. Six clearly distinct genotypes can be distinguished according to their percentage of amino acid similarity. Genotypes 2 (Lagos bat virus) and 3 (Mokola virus) are the most phylogenetically distant from the vaccinal and classical rabies viruses of genotype 1. Genotypes 4 (Duvenhage virus) and 5 (EBL1) are closely related to each other. Genotype 6 is represented by EBL2. Compared to the N proteins of the four principal serotypes of the Vesiculovirus genus (vesicular stomatitis virus serotype New Jersey and serotype Indiana, Chandipura virus, and Piry virus), the N gene of lyssaviruses exhibits a lower genetic variability.

Amino Acid Sequence↗
PubMed1996

HLA-B27 subtypes in Japanese with seronegative spondyloarthropathies and healthy controls.

OBJECTIVE: To determine HLA-B27 subtype frequencies in Japanese patients with seronegative spondyloarthropathies (SpA) and healthy controls. METHODS: We determined HLA-B27 subtypes of 20 Japanese patients with ankylosing spondylitis and one with Reiter's syndrome, and 11 healthy Japanese individuals using a polymerase chain reaction sequence specific oligonucleotide hybridization method specifically designed for the discrimination of B*2701-09. RESULTS: 14 of 21 (67%) patients and 9 of 11 (82%) controls were typed as B*2704. The remainder were B*2705. CONCLUSION: HLA-B*2704 and B*2705 are present in the Japanese population, the former being the predominant subtype of HLA-B27. Both subtypes are associated with SpA.

Asian People↗
PubMed1994

Ocular manifestations of metabolic disorders.

Articles published during the past year on the ocular manifestations of metabolic diseases and related issues are reviewed. The focus is on clarifying the genetic or molecular basis of various metabolic disorders. Mutations of the P gene were reported in tyrosinase-positive oculocutaneous albinism and autosomal recessive ocular albinism, and were associated with a wide range of clinical phenotypes. This finding should aid in more accurate diagnosis and facilitate genetic counseling. There is no consensus but the horizontal supranuclear gaze palsy in Gaucher's disease may aid in subtyping. The report of a family with Morquio syndrome suggests that lenticular opacities should be considered as an additional finding in this syndrome. Patients with nephropathic cystinosis, which had been a fatal disease in childhood, are now surviving to adulthood. Serious ocular complications were described in adults.

Amino Acids↗
PubMed1994

Molecular subtypes of env sequences around V3 region of human immunodeficiency virus type 1 in Taiwan.

Samples of peripheral blood mononuclear cells (PBMC) were collected during 1990-91 from seropositive healthy, male HIV-1 carriers visiting Taipei Venereal Disease Control Center, and a male AIDS patient admitted to a general hospital. The V3 and its flanking nucleotide (nt) sequences in their DNA were amplified by polymerase chain reaction (PCR) and compared with those of known HIV-1 prototypes. The nt sequences obtained from 21 individuals (e.g., TW92) clustered as Group A, which were highly homologous (95.6-99.5%) to that of HXB2 virus while those from 6 individuals (TW90, TW91, TW97, TW99, TW102 and TW104) were classified as Group B showing low similarities (73.2-84.2%) to those of HXB2 and moderate similarities (80.7-90.0%) to those of SC and Bangkok (BK) viruses. By comparison of their deduced amino acid sequences with those of consensus sequences for subtypes A-F as defined by Myers et al. (1993), both Groups A and B viruses (except TW102) together with those of HXB2, SC and BK viruses could be identified as members or variants of subtype B, and the TW102 virus as a member of subtype E viruses. Individuals with the Group A viruses included 4 homosexual and 17 heterosexual Taiwanese males, 2 of the latter having a history of i.v. drug abuse. Among individuals with Group B viruses, those with TW97, TW99, TW104 and TW91, who was an AIDS patient, were heterosexual Taiwanese males, whereas both TW90 and TW102 viruses were from individuals who were overseas heterosexual Chinese from Thailand, the former with a history of i.v. drug abuse and the latter without.

Acquired Immunodeficiency Syndrome↗
PubMed1998

JC virus Type 1 has multiple subtypes: three new complete genomes.

The complete genomes of three new Type 1 strains of JC virus (JCV) from urine have been analysed. These were subtype 1A, subtype 1B and Type 4 as assigned from a short typing fragment in the VP1 gene. They differ from Mad1 (subtype 1A) by less than 1.0% of the DNA sequence. Based on its complete genome, the JCV Type 4 strain falls into a Type 1 subgroup. Type 4, with several Type 3-like sites in the short typing fragment, is a possible recombinant strain. The consensus of Type 1 DNA sequences is distinguished within the coding region from both Type 2 (strain GS/B) and five Type 3 (African and African American) strains at 64 sites. Most mutations are silent, but at 21 positions amino acid changes occur. Our findings define the subtypes of JCV Type 1 and support the validity of genotyping within the short VP1 fragment.

Base Sequence↗
PubMed2001

Predicted amino acid sequences for 100 JCV strains.

DNA sequence variation between JCV genotypes is confined largely to noncoding intergenic regions and introns. Nevertheless, evidence suggests that the amino acid sequence variations among the 8 genotypes of JCV can influence the potential for neurovirulence of the virus. In the current study, the amino acid sequences for 100 JCV genomes were translated and grouped into genotype families. Subtype consensus sequences were determined and the type-specific amino acid sequence variants were identified.

Amino Acid Sequence↗
PubMed1994

Characterization of human immunodeficiency virus type 1 isolates from children in Romania: identification of a new envelope subtype.

Human immunodeficiency virus type 1 (HIV-1) isolates recovered from infected children in Romania were characterized for their biologic, serologic, and molecular properties. The isolates were from subjects in different clinical states, and all showed cytopathic properties in peripheral blood mononuclear cells and varying kinetics of replication. The isolates grew to varying titers in macrophages and established T cell lines. Serologic evaluation with Romanian sera indicated stronger antibody response to the gp120 of Romanian isolates than to the envelope protein of HIV-1 isolates from other countries. Although there was cross-neutralization among the Romanian isolates, no substantial activity was noted against HIV-1 prototype strains from the United States, Africa, and Thailand. Genetic analysis of the envelope C2-V3 region strongly suggests that the Romanian isolates are a subtype distinct from those assigned to other HIV-1 strains analyzed to date. This finding raises questions about the origin of HIV-1 in Romania.

Amino Acid Sequence↗
PubMed1997

Nucleotide receptors in the nervous system. An abundant component using diverse transduction mechanisms.

Extracellular nucleotides achieve their role as cell-to-cell communicators by acting at cell surface transmembrane receptors-the P2 receptors. Before molecular cloning led to the isolation of any P2-receptor sequence, a small number of receptor types had been proposed on the basis of pharmacological evidence. The application of molecular biology to this field of receptor research has indicated that a great underestimation of the number of receptor subtypes and of their abundance had occurred. There are now known to be seven characterized P2Y (G protein linked) receptors and the same number again of P2X receptors of the transmitter-gated ion channel type. In this review, we discuss the properties of these cloned receptors, their distribution within the nervous system, and their methods of signal transduction.

Adenosine Triphosphate↗
PubMed2002

The WHO classification of tumors of the nervous system.

The new World Health Organization (WHO) classification of nervous system tumors, published in 2000, emerged from a 1999 international consensus conference of neuropathologists. New entities include chordoid glioma of the third ventricle, cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor, and perineurioma. Several histological variants were added, including tanycytic ependymoma, large cell medulloblastoma, and rhabdoid meningioma. The WHO grading scheme was updated and, for meningiomas, extensively revised. In recognition of the emerging role of molecular diagnostic approaches to tumor classification, genetic profiles have been emphasized, as in the distinct subtypes of glioblastoma and the already clinically useful 1p and 19q markers for oligodendroglioma and 22q/INI1 for atypical teratoid/rhabdoid tumors. In accord with the new WHO Blue Book series, the actual classification is accompanied by extensive descriptions and illustrations of clinicopathological characteristics of each tumor type, including molecular genetic features, predictive factors, and separate chapters on inherited tumor syndromes. The 2000 WHO classification of nervous system tumors aims at being used and implemented by the neuro-oncology and biomedical research communities worldwide.

Humans↗
PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗
PubMed2026

Chinese expert consensus on precision testing and molecular diagnosis of pancreatic cancer (2025).

This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4-9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.

Humans↗
PubMed2006

Cell mediated immunity to meet the avian influenza A (H5N1) challenge.

Avian influenza A subtype H5N1 virus with its recombination potential with the human influenza viruses presents a threat of producing a pandemic. The consensus is that the occurrence of such a pandemic is only a matter of time. This is of great concern, since no effective vaccine is available or can be made before the occurrence of the event. We present arguments for the use of cell mediated immunity for the prevention of the infection as well as for the treatment of infected patients. Transfer factor (TF), an immunomodulator of low molecular weight capable of transferring antigen-specific cell mediated immune information to T-lymphocytes, has been used successfully over the past quarter of a century for treating viral, parasitic, and fungal infections, as well as immunodeficiencies, neoplasias, allergies and autoimmune diseases. Moreover, several observations suggest that it can be utilised for prevention, transferring immunity prior to infection. Because it is derived from lymphocytes of immune donors, it has the potential to answer the challenge of unknown or ill-defined pathogens. Indeed, it is possible to obtain an antigen-specific TF preparation to a new pathogen before its identification. Thus, a specific TF to a new influenza virus can be made swiftly and used for prevention as well as for the treatment of infected patients.

Animals↗
PubMed1996

[Classification of malignant lymphomas--current status and clinical implications].

New techniques such as cytogenetics, molecular biology and immunology have provided new insights into the pathogenesis and development of malignant lymphomas. By this way they provided a new basis for a classification of lymphoid malignancies which is increasingly oriented on biology and pathogenesis. This process resulted in the 'Revised European-American Lymphoma' (R.E.A.L.) classification, which was recently proposed by an international group of pathologists. This classification comprises a preliminary end point of a continuing process which will require a reevaluation and adaptation to new knowledge in the future again. In order to facilitate the clinical use of this histopathologically and biologically oriented classification, a proposal for a clinical grouping was developed, which divides the R.E.A.L. lymphoma subtypes into the following categories: I. Indolent lymphomas (low risk group). II. Aggressive lymphomas (intermediate risk group). III. Very aggressive lymphomas (high risk group). IV. Morbus Hodgkin. This internationally developed consensus of a histopathologic classification and a clinical grouping is a substantial step forward towards an international cooperation in the management of malignant lymphomas. It is background for cooperative studies and justifies the hope that further advances will be achieved in the treatment of malignant lymphomas and that more effective strategies can be developed in the near future.

Cytogenetics↗