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Subtype B (subtype + b)
Selected AbstractsCellular and subcellular localization of the GABAB receptor 1a/b subunit in the rat periaqueductal gray matterTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 5 2007Paolo Barbaresi Abstract The inhibitory effects of ,-aminobutyric acid (GABA)ergic neurotransmission in the periaqueductal gray matter (PAG) are mediated, at least partly, by metabotropic GABAB receptor subtypes whose cellular and subcellular localization is still unknown. We performed immunohistochemical experiments with an antibody against GABAB receptor subtype 1a/b (GABABR1a/b) by using light and electron microscopy. On light microscopy, GABABR1a/b immunoreactivity (IR) was in all columns, defined by cytochrome oxidase histochemistry. Neuropil labeling was strongest in the lateral portion of dorsolateral PAG. Labeled neurons, albeit not numerous, were in ventrolateral, dorsal, and medial subdivisions and were sparser in dorsolateral PAG. Labeling was mostly on the soma of PAG neurons. Sometimes GABABR1a/b IR spread along proximal dendrites; in these cases bipolar neurons were the most common type. On electron microscopy, GABABR1a/b IR was mainly on dendrites (54.92% of labeled elements) and axon terminals (21.90%) making synapses with labeled and unlabeled postsynaptic elements. Presynaptic labeling was also on unmyelinated and myelinated axons (overall 8% of all labeled elements). Postsynaptically, GABABR1a/b IR was at extrasynaptic sites on dendritic shafts; spines were always unlabeled. On axon terminals, GABABR1a/b IR was on extrasynaptic membranes and sometimes on presynaptic membrane specializations. Of the labeled elements, 13.03% elements were distal astrocytic processes (dAsPs) surrounding both symmetric and asymmetric synapses whose pre- and postsynaptic elements were often labeled. Immunoreactive dAsPs were around the soma and dendrites of both labeled and unlabeled neurons. These findings provide insights into the intrinsic PAG organization and suggest that presynaptic, postsynaptic, and glial GABAB receptors may play crucial roles in controlling PAG neuronal activity. J. Comp. Neurol. 505:478,492, 2007. © 2007 Wiley-Liss, Inc. [source] HIV-1 genetic diversity in Western Brittany, FranceFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2002Sophie Vallet Abstract We describe human immunodeficiency virus type 1 (HIV-1) diversity in Western Brittany, France, and trace the dissemination of HIV-1 non-B subtype infection. The strategy for HIV-1 subtyping used involved subtype specific enzyme immunoassays, heteroduplex mobility assays and phylogenetic analysis of the sequences of env encoding the V3 loop region. Samples were obtained from 567 patients: 465 (82%) were of subtype B and 66 (11.6%) were not (20 were subtype A, 11 subtype C, four subtype D, seven subtype F, five subtype G and 19 others with circulating recombinant forms: 4CRF01_AE, 11CRF02_AG, 1H, 3CRF11_cpx). These findings are consistent with other studies of French populations. There is an epidemiological correlation between subtype B and homosexual or heterosexual contamination in France and between non-B subtype and heterosexual contamination in Africa. [source] Emergence and diversity of different HIV-1 subtypes in South Africa, 2000,2001JOURNAL OF MEDICAL VIROLOGY, Issue 11 2009G.B. Jacobs Abstract HIV-1 is a major health problem in South Africa with an average prevalence rate of 29.1% in pregnant women and between 4.9 and 6.1 million people infected. Using env gp120 V3 serotyping and genotyping techniques 410 patient samples were investigated. Most of the samples were obtained from different clinics in the greater Cape Town area of the Western Cape Province in South Africa. These included an academic hospital, state and private clinics, an informal settlement, sex worker cohorts, and the blood transfusion services. RNA was extracted from plasma samples followed by RT-PCR and sequencing of the env gp120 V3 region. Sequence fragments were assembled using Sequencher V4.7 and subsequently codon aligned. Distance calculation, tree construction methods, and bootstrap analysis were implemented using MEGA version 4.0. Viral load measurements indicated that HIV-1 RNA levels from 74 samples were below the assay detection limit. Three hundred thirty-six samples were used for env PCR and sequencing and 320 were assigned to subtypes. The majority of the sequences were subtyped as C (n,=,285, 89.0%). Other subtypes detected were subtype A (n,=,10, 3.1%); subtype B (n,=,22, 6.8%); one each of subtypes F1, G, U, and a CH recombinant. Whether this diversity will have major implications for HIV-1 evolution and vaccine development in this region remains undetermined. J. Med. Virol. 81:1852,1859, 2009. © 2009 Wiley-Liss, Inc. [source] Changes in circulation of B and non-B HIV strains: Spotlight on a reference centre for infectious diseases in Northern ItalyJOURNAL OF MEDICAL VIROLOGY, Issue 6 2008Fausto Baldanti Abstract Stored demographic data and HIV RT and protease sequences of 877 HIV patients attending for the first time the HIV/AIDS outpatient clinics of a reference Infectious Diseases centre in Northern Italy between 1999 and 2006 were stratified by 3-year spanning periods according to date of HIV infection. In the period 1980,1982, new infections were entirely caused by HIV-1 subtype B strains and were all diagnosed in injection drug users, 88.9% of whom were males. Injection drug users accounted for 12.8% of new infections in 2004,2006. The frequency of heterosexually-transmitted infections consistently increased until 2000 (from almost none to 51.5%) remaining stable afterwards. About half of heterosexual patients were females. HIV infections among homosexual men increased from 0% in 1980,1982 to 15,21% between 1998 and 2006. Overall, the frequency of non-B subtypes HIV strains increased from 0% in 1980,1982 to 20.3% in 2004,2006 with a greater impact in heterosexuals (from 0% in 1980,1982 to 30.5% in 2004,2006). In conclusion, a picture of the changing scenario of circulating HIV types and subtypes in a reference Infectious Diseases centre in Northern Italy over the past 26 years is provided. A progressive modification in risk factors for HIV infection and a significant increase in the frequency of non-B HIV strains were observed. J. Med. Virol. 80:947,952, 2008. © 2008 Wiley-Liss, Inc. [source] Structural effects of amino acid variations between B and CRF02-AG HIV-1 integrasesJOURNAL OF MEDICAL VIROLOGY, Issue 5 2008Isabelle Malet Abstract HIV-1 integrase is one of the three essential enzyme required for viral replication and has a great potential as a novel target for anti-HIV drugs. The sequence variability of the entire integrase (IN) was examined in HIV-1 subtype B and CRF02-AG antiretroviral naïve infected patients for the presence of naturally occurring polymorphisms IN gene sequences and protein structures from both subtypes were compared. The phylogenetic analysis showed a total concordance between the 3 pol gene sequences for patients identified as subtype B whereas 3% of patients identified as CRF02-AG showed a mixture of subtypes. The analysis of IN aa sequences showed that 13 positions (K/R14, V/I31, L/I101, T/V112, T/A124, T/A125, G/N134, I/V135, K/T136, V/I201, T/S206, L/I234, and S/G283) differed between subtypes B and CRF02-AG. As observed in the 3D model of the preintegration complex, these differences may impact the functional property of IN. The fact that most variations were grouped suggests that some of them are linked together through compensatory mechanisms. This comparison allowed us to identify several variations of amino acids in HIV-1 IN subtype CRF02-AG that could have a putative impact on anti-integrase sensitivity. In particular, the region formed by Thr125, Thr124, Val31 contains at least one residue, T125, which variation has been involved in eliciting resistance to the naphtyridine carboxamide L870,810 IN inhibitor. In conclusion, virological response to anti-integrase should be studied carefully, according to the subtype, in clinical trials. J. Med. Virol. 80:754,761, 2008. © 2008 Wiley-Liss, Inc. [source] Molecular and epidemiological characteristics of blood-borne virus infections among recent immigrants in SpainJOURNAL OF MEDICAL VIROLOGY, Issue 12 2006Carlos Toro Abstract The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country. J. Med. Virol. 78:1599,1608, 2006. © 2006 Wiley-Liss, Inc. [source] Neutralization kinetics of sensitive and resistant subtype B primary human immunodeficiency virus type 1 isolatesJOURNAL OF MEDICAL VIROLOGY, Issue 7 2006David Davis Abstract The aim of the study was to determine if sensitive and resistant human immunodeficiency virus type 1 (HIV-1) subtype B primary isolates have different neutralization kinetics. Neutralization assays were undertaken where either the time allowed for virus to react with antibodies or the subsequent period of this mixture's exposure to target cells were varied. The relative neutralization sensitivity/resistance is a reproducible property of the isolates. In a minority of combinations, the titre falls exponentially for as long as the free virions are exposed to antibody. In the remainder, neutralization kinetics shows deviations which may be attributed to events occurring after the virus,antibody mixture is added to the target cells: significant neutralization with minimal exposure of the free virions to antibody; a plot where reduction in virus titre is parallel to the duration of the incubation phase of the assay. Neutralization rate constants are similar for primary HIV-1 SF33, HIV-1 SF162, and HIV-1 89.6, reaching 5,×,105,1,×,106/M sec for the monoclonal antibody IgG1 b12. However, although increased antibody levels produced greater reductions in virus titre the rate of neutralization was not proportional to the antibody concentration. Neutralization of either the free virion or cell-associated virus does not correlate with the resistance/sensitivity of primary subtype B isolates. The target cells play an active role, so that in designing neutralization assays with primary isolates of HIV-1, events following the virus,antibody complex binding to the cell surface have to be taken into consideration. J. Med. Virol. 78:864,876, 2006. © 2006 Wiley-Liss, Inc. [source] Human immunodeficiency virus type 1 and hepatitis C virus Co-infection and viral subtypes at an HIV testing center in BrazilJOURNAL OF MEDICAL VIROLOGY, Issue 6 2006G.A.S. Pereira Abstract Human immunodeficiency virus (HIV) testing sites have been recognized recently as potential settings for hepatitis C virus (HCV) screening since both viruses share common routes of transmission. HIV and HCV prevalence, predictors, co-infection rates, and viral subtypes were studied in 592 attendants at an anonymous HIV Counseling and Testing Center in central Brazil. Anti-HIV-1 and -HCV antibodies were screened by ELISA, and Western blots were used to confirm HIV infection. Among HIV-seropositive samples, reverse transcriptase-polymerase chain reaction (RT-PCR) and nested-PCR were used to subtype HIV-1 by the Heteroduplex Mobility Analysis (HMA) and HCV by the line probe assay (INNO-LiPA). HIV and HCV seroprevalence was 3.2% (95% CI 2.0,4.9) and 2.5% (95% CI 1.5,4.0), respectively. Intravenous drug use was the risk factor most strongly associated with both HIV and HCV infections, even in a population with few intravenous drug users (n,=,6); incarceration was also associated with HCV. HIV/AIDS-positive sexual partner and homosexual/bisexual behaviors were associated independently with HIV-1. The prevalence of HCV infection among HIV-positive persons was 42% (95% CI 20,66), higher than in HIV-negative persons (1.2%; 95% CI 0.5,2.5). HIV-1 subtype B was identified in the env and gag regions of the genome. HCV subtype 3a predominated among co-infected persons and one HCV subtype 1a was detected. Overall, a similar prevalence of HIV and HCV infections and a higher prevalence of HCV among HIV-positive persons were observed. Integrated HIV and HCV screening at HIV testing sites may represent a unique opportunity to provide diagnosis and prevention strategies at a single visit. J. Med. Virol. 78:719,723, 2006. © 2006 Wiley-Liss, Inc. [source] Measurement of HIV RNA in patients infected by subtype C by assays optimized for subtype B results in an underestimation of the viral loadJOURNAL OF MEDICAL VIROLOGY, Issue 2 2004Bat-Sheva Gottesman Abstract Quantitation assays of HIV-1 RNA used currently were designed and optimized for subtype B viruses. However, infection with non-B HIV viruses has become more common worldwide. Unfortunately, little information is available regarding the suitability of these assays for measurement of viral load in specific non-B subtypes. The performance of two commercial HIV-1 RNA quantitation assays was evaluated in 82 HIV subtype C-infected patients and in 43 HIV-1 subtype B-infected patients. Blood samples were tested by the Amplicor HIV-1 Monitor Assay, Version 1.5, and by the nucleic acid sequence-based amplification HIV-1 assay (NucliSens). The results were compared by using a paired, two-tailed Student's t -test; the difference between the assays was found to be significant only for subtype C. Discordant results (>0.5 log difference) between the two assays were detected in 39% of subtype C samples, compared to 23.2% of subtype B samples. In all cases in which a discordant result was detected, the lower results were obtained by the NucliSens assay. Discordant results between CD4 and viral load (CD4,<,200 cells/ml with a viral load <5,000 copies/ml) were observed in eight of the subtype C-infected patients when a viral load was measured by NucliSens (9.7%), compared to three patients (3.6%) when measured by the Amplicor assay. In conclusion, in patients with HIV subtype C infection, measurement of HIV RNA by the NucliSens assay resulted in a significant underestimation of the viral load as compared to the Amplicor assay. As a consequence, such an underestimation may result in sub-optimal care of patients infected with HIV subtype C. J. Med. Virol. 73:167,171, 2004. © 2004 Wiley-Liss, Inc. [source] Introduction of HIV type 1 non-B subtypes into Eastern Andalusia through immigrationJOURNAL OF MEDICAL VIROLOGY, Issue 1 2003Marta Alvarez Abstract A study of the distribution of HIV-1 subtypes in the native and immigrant populations of Eastern Andalusia (Southern Spain) was conducted to determine any changes between 1983 and 2001 and to identify antiretroviral resistance mutations in non-B subtype strains among the immigrant population. The study included 111 native patients from Eastern Andalusia: 94 infected with HIV before 1996 and 17 infected since 1996. A parallel study was conducted on 26 HIV-positive immigrants from Africa. Subtyping was done with the heteroduplex mobility assay. Resistance mutations were determined by line probe assay. A total of 137 patients were studied: 9.2% had subtype A (n,=,12), 80.8% subtype B (n,=,105), and 1.5% subtype C (n,=,2). Among the Eastern Andalusia population infected before 1996, 10.9% had non-B subtypes, compared with 23.5% of those infected after that year. The greatest percentage of non-B subtypes (52.4%) was found among the immigrant population. Resistance mutation K70R was detected in one of the six immigrants with non-B subtype and M41L in another. There has been a slight increase in the diversity of HIV-1 subtypes in Eastern Andalusia over the past few years, possibly influenced by non-B subtypes introduced by immigrants from sub-Saharan Africa. J. Med. Virol. 70: 10,13, 2003. © 2003 Wiley-Liss, Inc. [source] Hereditary iron overload: Update on pathophysiology, diagnosis, and treatmentAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2006Massimo Franchini Abstract Hereditary hemochromatosis, a very common genetic defect in the Caucasian population, is characterized by progressive tissue iron overload which leads to irreversible organ damage if it is not treated timely. The elucidation of the molecular pathways of iron transport through cells and its control has led to the understanding of various genetic iron-loading conditions. Four types of inherited iron overload have been recognized: type 1, the most common form with an autosomal recessive inheritance, is associated with mutations in the HFE gene on chromosome 6; type 2 (juvenile hemochromatosis) is an autosomal recessive disorder with causative mutations identified in the HJV gene (subtype A) on chromosome 1 and the HAMP gene (subtype B) on chromosome 19; type 3 has also an autosomal recessive inheritance with mutations in the TfR2 gene on chromosome 3; type 4 is an autosomal dominant condition with heterozygous mutations in the ferroportin 1 gene on chromosome 2. In this review, the genetics, pathophysiology, diagnosis, clinical features, and management of these different types of hereditary hemochromatosis are briefly discussed. Am. J. Hematol. 81:202,209, 2006. © 2006 Wiley-Liss, Inc. [source] Intrinsic subtype-associated changes in the plasma proteome in breast cancerPROTEOMICS - CLINICAL APPLICATIONS, Issue 11 2009Harikrishna Nakshatri Abstract Breast cancers are classified into five intrinsic subtypes: Luminal subtype A, Luminal subtype B, HER2+, Basal, and Normal-like. In this study, we compared the plasma proteome of patients with Luminal A, Luminal B, HER2+, and Basal subtype with plasma from healthy individuals. Protein changes were considered significant if q -value (false discovery rate) was less than 5%. The highest number of changes in the plasma proteome was observed in patients with Luminal type B followed by Basal type breast cancers. The plasma proteome of Luminal A and HER2+ breast cancer patients did not differ significantly from healthy individuals. In Basal breast cancer, a significant number of plasma proteins were downregulated compared with healthy individuals. Acute phase-response proteins ,-glycoprotein orosomucoid 1 and serum amyloid protein P were specifically upregulated in the plasma of Luminal B breast cancer patients, suggesting prevalence of low-grade inflammation. Proteins involved in immune response and free radical scavenging were downregulated in the plasma of Luminal B patients, which is in agreement with defective immune system observed in cancer patients. These results reveal intrinsic subtype specific changes in the plasma proteome that may influence tumor progression as well as the systemic effects of cancer. [source] Structure of the unbound form of HIV-1 subtype A protease: comparison with unbound forms of proteases from other HIV subtypesACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2010Arthur H. Robbins The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7,Å resolution and refined as a homodimer in the hexagonal space group P61 to an Rcryst of 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations. [source] Structural effects of amino acid variations between B and CRF02-AG HIV-1 integrasesJOURNAL OF MEDICAL VIROLOGY, Issue 5 2008Isabelle Malet Abstract HIV-1 integrase is one of the three essential enzyme required for viral replication and has a great potential as a novel target for anti-HIV drugs. The sequence variability of the entire integrase (IN) was examined in HIV-1 subtype B and CRF02-AG antiretroviral naïve infected patients for the presence of naturally occurring polymorphisms IN gene sequences and protein structures from both subtypes were compared. The phylogenetic analysis showed a total concordance between the 3 pol gene sequences for patients identified as subtype B whereas 3% of patients identified as CRF02-AG showed a mixture of subtypes. The analysis of IN aa sequences showed that 13 positions (K/R14, V/I31, L/I101, T/V112, T/A124, T/A125, G/N134, I/V135, K/T136, V/I201, T/S206, L/I234, and S/G283) differed between subtypes B and CRF02-AG. As observed in the 3D model of the preintegration complex, these differences may impact the functional property of IN. The fact that most variations were grouped suggests that some of them are linked together through compensatory mechanisms. This comparison allowed us to identify several variations of amino acids in HIV-1 IN subtype CRF02-AG that could have a putative impact on anti-integrase sensitivity. In particular, the region formed by Thr125, Thr124, Val31 contains at least one residue, T125, which variation has been involved in eliciting resistance to the naphtyridine carboxamide L870,810 IN inhibitor. In conclusion, virological response to anti-integrase should be studied carefully, according to the subtype, in clinical trials. J. Med. Virol. 80:754,761, 2008. © 2008 Wiley-Liss, Inc. [source] HLA,B27 heavy chains distinguished by a micropolymorphism exhibit differential flexibilityARTHRITIS & RHEUMATISM, Issue 4 2010Heinz Fabian Objective Although the products of the HLA subtypes B*2705 and B*2709 differ only in residue 116 (Asp versus His) within their peptide-binding grooves, they are differentially associated with inflammatory rheumatic diseases such as ankylosing spondylitis (AS): B*2705 occurs in AS patients, whereas B*2709 is only rarely encountered. The reasons for this distinct association are still unclear but could include subtype-specific conformational and dynamic properties of these antigens. The present study was undertaken to investigate structural and dynamic differences between B*2705 and B*2709 and their possible relationship to subtype-specific disease association. Methods The membrane-distal segments of the B*2705 and B*2709 heavy chains were expressed in vitro and reconstituted together with ,2 -microglobulin and a peptide. HLA,B27 complexes loaded with 2 self peptides (TIS [RRLPIFSRL] and pVIPR [RRKWRRWHL]) and a sequence-related viral peptide (pLMP2 [RRRWRRLTV]) were studied by isotope-edited infrared spectroscopy to detect differences in their structure and flexibility at physiologic temperature. Results Our analyses revealed the existence of subtype-specific conformational differences between the 2 HLA,B27 heavy chains at physiologic temperature, which are undetectable using x-ray crystallography. Irrespective of the bound peptide, the heavy chain of the B*2705 complex exhibited higher conformational flexibility than the B*2709 heavy chain. Conclusion The present study demonstrates the existence of previously undetected systematic conformational and dynamic differences between the heavy chains of the 2 HLA,B27 subtypes. Since effector cell recognition of cells expressing HLA antigens is dependent on the dynamic properties of the interacting cell surface molecules, this HLA,B27 subtype,specific heavy chain flexibility could have a role in the distinct association of HLA,B27 subtypes with spondylarthritides. [source] | |||||||||||||