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PubMed2006

Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies.

BACKGROUND: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson's disease (PD). AIMS: (1) To examine rates of cognitive and motor decline over two years in PD (n=40), PDD (n=42) and DLB (n=41) subjects, compared with age matched controls (n=41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. RESULTS: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE -4.5 and -3.9, respectively), compared with PD (-0.2) and controls (-0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (chi2=6.7, Fisher's exact test p<0.05). CONCLUSION: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.

Aged↗
PubMed1999

Viral subtype and heterosexual acquisition of HIV infections diagnosed in Scotland.

OBJECTIVE: As at December 1998, 87% of the estimated 33 million people living with HIV throughout the world resided in Africa and South East Asia. In Scotland (and the United Kingdom), a major public health concern has been that non-B subtypes of HIV which predominate in the regions above might enter the country and spread heterosexually among the indigenous population. The authors conducted an investigation to determine if, and to what extent, such transmission had occurred. METHODS: Stored blood samples from people who were diagnosed as HIV positive in central Scotland during 1995-7 and who were reported to have acquired their infection heterosexually, were identified. Sequence data were sought from each sample and, where obtained, viral subtype was assigned. For each case, viral subtype was linked to corresponding epidemiological details on heterosexual risk. RESULTS: Viral sequence was obtained from specimens for 53 of 59 cases. For 43 of the 53 cases, information on region of sexual contact was known. All 19 cases who had a sexual risk in Africa or Asia had a non-B subtype (A, C, or E) while 20 of 24 cases who did not report sexual contact in these regions had a B subtype (p < 0.0001). Of the remaining 10 cases, nine had a subtype B and one a subtype C virus. CONCLUSION: There is no evidence that non-B viral strains from developing countries have yet disseminated appreciably among indigenous heterosexual men and women within Scotland. Continuing to collect both demographic and molecular data from indigenous heterosexuals who are newly diagnosed with HIV would improve the chances of detecting rapidly any appreciable dissemination of non-B subtypes among this population if it were to occur. Such information would be helpful in informing HIV prevention strategies.

DNA, Viral↗
PubMed2004

Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots.

Fat depots vary in function and size. The preadipocytes that fat cells develop from exhibit distinct regional characteristics that persist in culture. Human abdominal subcutaneous cultured preadipocytes undergo more extensive lipid accumulation, higher adipogenic transcription factor expression, and less TNF-alpha-induced apoptosis than omental preadipocytes. We found higher replicative potential in subcutaneous and mesenteric than in omental preadipocytes. In studies of colonies arising from single preadipocytes, two preadipocyte subtypes were found, one capable of more extensive replication, differentiation, and adipogenic transcription factor expression and less apoptosis in response to TNF-alpha than the other. The former was more abundant in subcutaneous and mesenteric than in omental preadipocyte populations, potentially contributing to regional variation in replication, differentiation, and apoptosis. Both subtypes were found in strains derived from single human preadipocytes stably expressing telomerase, confirming that both subtypes are of preadipocyte lineage. After subcloning of cells of either subtype, both subtypes were found, indicating that switching can occur between subtypes. Thus proportions of preadipocyte subtypes with distinct cell-dynamic properties vary among depots, potentially permitting tissue plasticity through subtype selection during development. Furthermore, mesenteric preadipocyte cell-dynamic characteristics are distinct from omental cells, indicating that visceral fat depots are not functionally uniform.

Adipocytes↗
PubMed1992

Analysis of angiotensin II receptor subtypes in individual rat brain nuclei.

Previous studies have used new angiotensin II (AII) receptor subtype selective compounds to localize AII receptor subtypes within discrete rat brain nuclei. The purpose of this autoradiographic study was to extend these preliminary findings and provide a comprehensive analysis of AII binding sites in 22 rat brain nuclei and the anterior pituitary, to include estimates of the binding affinity for 125I sar1 ile8 AII (125I SIAII) at each nucleus, and determine the fractional distribution of each subtype at each nucleus. Estimates of KD in separate experiments revealed that AT1 nuclei had a consistently higher affinity for 125I SIAII than AT2 nuclei (0.66 vs. 2.55 nM). Displacement of subsaturating concentrations of 125I SIAII by 10(-8)-10(-4) M DuP753 (selective for the AT1 subtype) or PD123177 (selective for the AT2 subtype) indicated that approximately half of the brain regions surveyed contained predominantly AT1 sites and half contained predominantly AT2 sites. Binding was partially displaced by both compounds in several regions and two site analyses were performed to estimate the distribution of subtypes within each nucleus. The data were then corrected for differential occupancy by 125I SIAII. Brain nuclei associated with cardiovascular or dipsogenic actions of AII, e.g., subfornical organ, organum vasculosum of the lamina terminalis, median preoptic nucleus, nucleus of the solitary tract and area postrema, contained pure, or almost pure, populations of AT1 receptors. The functions of AII in brain regions containing predominantly AT2 binding sites, e.g., thalamus, colliculi, inferior olive and locus ceruleus, remain undefined. Thus, AII binding sites in the rat brain have been differentiated into two subtypes with similar characteristics to those reported in peripheral tissues. However, the unexpected finding that they can be differentiated on the basis of their affinity for 125I SIAII raises questions concerning their coidentity with peripheral receptor subtypes.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1981

Selectivity of dobutamine for adrenergic receptor subtypes: in vitro analysis by radioligand binding.

The cardiovascular responses elicited by dobutamine are distinctly different from those produced by other adrenergic or dopaminergic agonists. To test the hypothesis that dobutamine could have differential affinities for adrenergic receptor subtypes, and that such subtype selectivity could be related to its relatively unique pharmacologic properties, we assessed the ability of dobutamine to displace adrenergic radioligands from membrane receptors in a number of tissues of previously characterized adrenergic receptor subtype. For beta adrenergic receptors identified by (-) [(3)H]dihydroalprenolol (DHA), dobutamine had significantly greater affinity for the beta(1) subtype (K(D) = 2.5 muM in rat heart and 2.6 muM in turkey erythrocyte) than for the beta(2) subtype (K(D) = 14.8 muM in frog heart and 25.4 muM in rat lung) (P < 0.001). For alpha adrenergic receptors, dobutamine had markedly greater affinity for the alpha(1)-subtype identified by [(3)H]prazosin (K(D) = 0.09 muM in rat heart and 0.14 muM in rabbit uterus) than for the alpha(2)-subtype identified by [(3)H]dihydroergocryptine (DHE) (K(D) = 9.3 muM in human platelet) or by [(3)H]yohimbine (K(D) = 5.7 muM in rabbit uterus) (P < 0.001). Like other beta(1)-agonists, in the absence of guanine nucleotide, dobutamine competition curves for DHA binding in rat heart demonstrated two classes of binding sites, with one site of significantly higher affinity (K(D) = 0.5 muM, P = 0.008) than the single class of binding sites (K(D) = 5.2 muM) identified in the presence of guanine nucleotide. However, unlike beta(2)- or alpha(2)-agonists, dobutamine displacement of DHA binding in rat lung or of DHE binding in human platelets demonstrated only a single class of binding sites, and guanine nucleotide had only minimal effects. We conclude that dobutamine is selective for beta(1) as opposed to beta(2), and for alpha(1) as opposed to alpha(2) adrenergic receptors. Furthermore, guanine nucleotide effects on dobutamine binding, and biochemical response data in vitro suggest that dobutamine is a beta(1)-agonist, but has little intrinsic activity at beta(2) and alpha(2)-receptors. This selectivity for adrenergic receptor subtypes may be part of the basis for dobutamine's distinctive pharmacologic properties in vivo.

Animals↗
PubMed2006

HIV-1 subtype A infection in a community of intravenous drug users in Pakistan.

BACKGROUND: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. METHODS: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA). RESULTS: We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. CONCLUSION: Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country.

HIV Infections↗
PubMed2006

First report of an HIV-1 triple recombinant of subtypes B, C and F in Buenos Aires, Argentina.

We describe the genetic diversity of currently transmitted strains of HIV-1 in men who have sex with men (MSM) in Buenos Aires, Argentina between 2000 and 2004. Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B, 3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The 3 BF recombinants were 3 different unique recombinant forms. Full genome analysis of one strain that was subtype F when sequenced in pol was found to be a triple recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B; there were regions of subtype C interspersed throughout. The young man infected with this strain reported multiple sexual partners and sero-converted between May and November of 2004. This study reported for the first time the full genome analysis of a triple recombinant between subtypes B, C and F, that combines in one virus the three most common subtypes in South America.

Adult↗
PubMed1998

Heterogeneous dopamine D2 receptor subtype messenger ribonucleic acid expression in clinically nonfunctioning pituitary adenomas.

Little is known about differences in the expression, localization, and function of the two dopamine D2 receptor subtypes, D2short and D2long (D2s and D2l), in either normal or adenomatous pituitary. We investigated the messenger RNA (mRNA) expression of the D2 receptor (D2R) subtypes in clinically nonfunctioning pituitary adenomas by in situ hybridization using subtype-specific oligonucleotides. The five normal pituitaries studied expressed similar ratios of D2R subtypes mRNA with a predominant expression of the D2l isoform. In 2 of 18 clinically inactive adenomas no D2R mRNA was found, whereas in 16 a heterogeneous expression of D2R isoforms was observed. Six adenomas expressed only the D2l and 2 adenomas only the D2s subtype mRNA; the remaining 8 expressed extremely varying proportions of the two subtypes. The D2R was found only in a subset of the nonfunctioning adenoma cells. In gonadotropin-immunopositive adenomas, the D2R was mainly localized in LH- and FSH-immunopositive cells. Probably because of the heterogeneous D2R subtype expression, suppression of cell proliferation was observed in only 3 of 9 adenoma cell cultures in which the growth inhibitory effect of bromocriptine was studied. Although there is some evidence that the presence of the D2s receptor subtype favors the growth inhibitory response to bromocriptine, further studies with a larger number of inactive adenomas are needed to confirm this speculation.

Adenoma↗
PubMed2005

Temporal and spatial changes in the expression pattern of multiple red and green subtype opsin genes during zebrafish development.

Zebrafish have two red, LWS-1 and LWS-2, and four green, RH2-1, RH2-2, RH2-3 and RH2-4, opsin genes encoding photopigments with distinct absorption spectra. Occurrence of opsin subtypes by gene duplication is characteristic of fish but little is known whether the subtypes are expressed differently in the retina, either spatially or temporally. Here we show by in situ hybridization the dynamic expression patterns of the opsin subtypes in the zebrafish retina. Expression of red type opsins is initiated with the shorter-wavelength subtype LWS-2, followed by the longer-wavelength subtype LWS-1. In the adult retina, LWS-2 was expressed in the central to dorsal area and LWS-1 in the ventral and peripheral areas. Expression patterns of green type opsins were similar to those of the red type opsins. The expression started with the shortest wavelength subtype RH2-1 followed by the longer wavelength ones, and in the adult retina, the shorter wavelength subtypes (RH2-1 and RH2-2) were expressed in the central to dorsal area and longer wavelength subtypes (RH2-3 and RH2-4) in the ventral and peripheral areas. These results provide the framework for subsequent studies of opsin gene regulation and for probing functional rationale of the developmental changes by using the power of zebrafish genetics.

Animals↗
PubMed1995

Pharmacological characterisation and autoradiographic localisation of dopamine receptor subtypes in the cardiovascular system and in the kidney.

Combined radioligand binding and light microscope autoradiography techniques were used for investigating the pharmacological profile and the microanatomical localisation of dopamine receptor subtypes in the cardiovascular system and in the kidney. In superior mesenteric and renal arteries the predominant dopamine D1-like receptor belongs to the D5 (or D1b) subtype. This site is located within smooth muscle of the tunica media. The same receptor subtype predominates in the kidney, where it has a vascular and tubular localisation. The dopamine D2-like receptor subtype expressed by systemic arteries belongs to the D2 receptor subtype. It has a prejunctional and endothelial localisation. In the kidney the predominating dopamine D2-like receptor belongs to the dopamine D3 subtype. Atria but not ventricles express dopamine D2-like receptors belonging to the D4 receptor subtype. The above results suggest that in spite of the emerging complexity of the dopamine receptor profile demonstrated by molecular biology techniques, radioligand binding and autoradiographic techniques, if performed with appropriate radioligands and/or in the presence of compounds active on specific receptor subtypes, may represent a useful tool for better understanding the biological significance of peripheral dopamine receptors.

Animals↗
PubMed2006

Molecular dynamics simulations applied to the study of subtypes of HIV-1 protease common to Brazil, Africa, and Asia.

Africa accounts for the majority of HIV-1 infections worldwide caused mainly by the A and C viral subtypes rather than B subtype, which prevails in the United States and Western Europe. In Brazil, B subtype is the major subtype, but F, C, and A also circulate. These non-B subtypes present polymorphisms, and some of them occur at sites that have been associated with drug resistance, including the HIV-1 protease (PR), one important drug target. Here, we report a Molecular Dynamics study of the B and non-B PR complexed with the inhibitor ritonavir to delineate the behavior of each subtype. We compare root mean squared deviation, binding free energy by linear interaction energy approach, hydrogen bonds, and intermolecular contact surface area between inhibitor and PR. From our results, we can provide a basis to understand the molecular mechanism of drug resistance in non-B subtypes. In this sense, we found a decrease of approx 4 kcal/mol in deltaG of binding between B and non-B subtypes. This corresponds to the loss of one hydrogen bond, which is in agreement with our H-bond analysis. Previous experimental affinity studies reported analogous results with inhibition constant values for non-B PR.

Africa↗
PubMed1997

Recent advances in the identification of alpha1- and alpha2-adrenoceptor subtypes: therapeutic implications.

The cloning of multiple subtypes of both alpha1- and alpha2-adrenoceptors has renewed interest in the therapeutic application of agents interacting with these receptors. Effort has primarily been directed towards the design of uroselective alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia (BPH). Evidence is accumulating for the involvement of a novel alpha1-adrenoceptor, designated as alpha1L-adrenoceptor, in alpha1-adrenoceptor-mediated smooth muscle contraction in prostatic and other urogenital tissues. While several antagonists showing a high degree of uroselectivity in animal models have been identified, their clinical superiority over the currently available alpha1-adrenoceptor antagonists has not yet been demonstrated. It is possible that the interaction with alpha1-adrenoceptors, as yet uncharacterised subtypes, at non-prostatic sites contributes to the therapeutic activity of this drug class in BPH. The alpha1-adrenoceptor subtypes involved in the control of vascular tone are currently being evaluated, and the profile of interaction with the various alpha1-adrenoceptor subtypes may play a key role in the efficacy of cardiovascular drugs such as carvedilol. Alpha2-adrenoceptor agonists are now being employed for a variety of therapeutic applications, most involving actions on receptors within the central nervous system (CNS). These agents are useful in the treatment of hypertension, glaucoma, opiate withdrawal and attention deficit hyperactivity disorder (ADHD), and as analgesics and adjuncts to general anaesthesia. While subtype selectivity has not yet been applied to the design of new alpha2-adrenoceptor agonists for these applications, recent gene mutation/knock-out experiments have identified the alpha2-subtypes involved in some of these actions, and optimisation of a therapeutic profile may be possible. Furthermore, the design of agents combining affinities for multiple adrenoceptor subtypes, or the combination of a specific adrenoceptor affinity profile with another pharmacological action, may offer advantages over molecules selective for an individual adrenoceptor subtype.

Journal Article↗
PubMed2003

Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI) in humans from General Belgrano island, Formosa, Argentina.

This work presents the results of the detection of antibodies (immunoglobulin G) for subtypes I and VI of VEE viruses complex (Togaviridae family) in people from the General Belgrano island, Formosa province (Argentina). The prevalence of neutralizing (NT) antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI) was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

Adolescent↗
PubMedDate not supplied

Geographic distribution of HBsAg subtypes in Brazil.

HBsAg positive serum samples (896) from five brazilian regions were analysed for HBsAg subtypes. The presence of five different subtypes (ayw2, ayw3, ayw4, adw2 and adw4) was detected. In Northern region subtypes adw4 (41.2%) and adw2 (37.2%) were predominant. In the North East only subtype adw2 was encountered. In Central West, South-East and South, subtypes ayw2, ayw3, adw2 and adw4 were present, with predominance of adw2 in Central West and South East (84.3% and 69.4% respectively) whereas in the South the predominant subtype was ayw3 (41.9%) followed by ayw2 (36.4%). Subtypes ayw1, ayr and adr were not found among the samples studied. These results show the difference in the incidence of HBsAg subtypes in the different regions of Brazil and their significance in relation to the colonization and migrations in this country.

Brazil↗
PubMed2002

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test.

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

Adolescent↗
PubMed2001

Genotypic resistance mutations to antiretroviral drugs in HIV-1 B and non-B subtypes from Cuba.

OBJECTIVES: To determine the prevalence of drug resistance and to analyze the subtyping in HIV-1 samples from Cuba. METHODS: From an estimated total number of 1,950 HIV-1-infected persons in Cuba, a sample of 103 patients were studied, 76 of whom had received drug treatment for HIV and 27 who had not. The RNA plasma viral load was measured, and automated sequencing was used to assess resistance mutations to reverse transcriptase inhibitors (RTIs) and to protease inhibitors (PIs). Subtyping in the V3 region was performed using heteroduplex mobility assay (HMA). In order to corroborate the HMA results, sequencing of env (C2-V3-C3) was done with one-third of the samples in each of the subtype groups detected by HMA. RESULTS: Out of the 103 samples, 81 of them (78.6%) were classified as subtype B, 19 (18.5%) as subtype A, and 3 (2.9%) as subtype C. The prevalence of resistance mutations was 26.2% to RTIs, none to PIs alone, and 3.9% to both categories of drugs. The prevalence of resistance to nucleoside RTIs (NRTIs) was 27.6% in treated patients and 7.4% in the untreated patients, and for nonnucleoside RTIs (NNRTIs) it was 5.3% and 0%, respectively. Among treated patients a low frequency (2.6%) of dual resistance to zidovudine (ZDV) plus lamivudine (3TC) and abacavir (ABC) was detected, and multidrug resistance to NRTIs was not found. In relation to PIs together with RTIs, the prevalence of resistance was 5.3% for treated patients and 0% for untreated patients. CONCLUSIONS: Even though Cuba is generally considered an area where subtype B is dominant, we detected a high proportion of non-B subtype viruses. The low prevalence of resistance mutations to RTIs and PIs reflects the delay in introducing these drugs to Cuba. Multidrug resistance to RTIs was not found, so, as of now, the use of these drugs continues to be an option for Cuban patients.

Anti-HIV Agents↗
PubMedDate not supplied

Light microscope autoradiography of peripheral dopamine receptor subtypes.

Radioligand binding assay techniques associated with light microscope autoradiography were used for investigating the pharmacological profile and the micro anatomical localization of peripheral dopamine receptor subtypes. In systemic arteries, the predominant dopamine D1-like receptor belongs to the D5 (or D1B) subtype. It is located within smooth muscle of the tunica media. In pulmonary arteries, dopamine D1-like receptors have primarily an endothelial localization and belong to the dopamine D1 (or D1A) receptor subtype. Both systemic and pulmonary arteries express a dopamine D2-like receptor belonging to the D2 receptor subtype. It has a prejunctional localization in the majority of vascular beds investigated. In cerebral, coronary and mesenteric arteries, it has also an endothelial localization. In the heart, a dopamine D4 receptor was identified. It is expressed by atrial tissue and has a widespread distribution overall atrial musculature. The kidney expresses both dopamine D1-like and D2-like receptors. Renal dopamine D1-like receptors have a vascular and tubular localization. The majority of these sites belongs to the D5 receptor subtype. A smaller D1 receptor population has primarily a tubular localization. Renal dopamine D2-like receptors belong to the dopamine D3 subtype and in lesser amounts to the D2 and D4 receptor subtypes. Renal dopamine D3 receptor has to a greater extent a tubular localization, whereas the D4 receptor is located within glomerular arterioles. The above results suggest that radioligand binding assay and autoradiographic techniques, if performed in the presence of compounds displaying specific receptor subtype selectivity, may contribute to characterize, mainly from a quantitative point of view, peripheral dopamine receptors.

Animals↗
PubMed2003

Allospecific T cell epitope sharing reveals extensive conservation of the antigenic features of peptide ligands among HLA-B27 subtypes differentially associated with spondyloarthritis.

HLA-B*2702, B*2704, and B*2705 are strongly associated with spondyloarthritis, whereas B*2706 is not. Subtypes differ among each other by a few amino acid changes and bind overlapping peptide repertoires. In this study we asked whether differential subtype association with disease is related to differentially bound peptides or to altered antigenicity of shared ligands. Alloreactive CTL raised against B*2704 were analyzed for cross-reaction with B*2705, B*2702, B*2706, and mutants mimicking subtype changes. These CTL are directed against many alloantigen-bound peptides and can be used to analyze the antigenicity of HLA-B27 ligands on different subtypes. Cross-reaction of anti-B*2704 CTL with B*2705 and B*2702 correlated with overlap of their peptidic anchor motifs, suggesting that many shared ligands have similar antigenic features on these three subtypes. Moreover, the percent of anti-B*2704 CTL cross-reacting with B*2706 was only slightly lower than the overlap between the corresponding peptide repertoires, suggesting that most shared ligands have similar antigenic features on these two subtypes. Cross-reaction with B*2705 or mutants mimicking changes between B*2704 and B*2705 was donor-dependent. In contrast, cross-reaction with B*2702 or B*2706 was less variable among individuals. Conservation of antigenic properties among subtypes has implications for allorecognition, as it suggests that shared peptides may determine cross-reaction across exposed amino acid differences in the MHC molecules and that the antigenic distinctness of closely related allotypes may differ among donors. Our results also suggest that differential association of HLA-B27 subtypes with spondyloarthritis is more likely related to differentially bound peptides than to altered antigenicity of shared ligands.

Amino Acid Substitution↗