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PubMed2003

Conversion disorder and its subtypes: a need for a reclassification.

Four subtypes of conversion disorder were described in DSM-IV. There are few publications concerning studies aimed at separating the subtypes of the conversion disorder. Usually, pseudoseizures are in focus and attempts are made to differentiate these seizures from other disorders. The aim of the present study has been to investigate differences between the four subtypes of the conversion disorder and to discuss the possibilities for a reclassification. Ninety-five patients were seen by two researchers and diagnosed as conversion disorders. The subtypes were determined according to DSM-IV criteria. All completed the Patients Information Form, developed by the researchers, and the Dissociative Experience Scale (DES). Twenty-four (25.2%) of the patients had motor symptoms or deficits (Type 1), 5 (5.2%) sensory symptoms or deficits (Type 2), 23 (24.2%) seizures or convulsions (Type 3) and 43 (47.3%) had mixed presentations (Type 4). There were statistically significant differences between the subtypes as concerns occupation, family history of psychiatric disorders, hospitalizations and place of settlement. Furthermore, the DES scores were statistically different between the groups of patients with different subtypes of conversion disorder.

Adult↗
PubMedDate not supplied

Risk factors and stroke subtypes: results of five consecutive years of the Perugia Stroke Registry.

To understand the etiopathogenetic mechanisms of stroke and to target prevention, we need to know how risk factors differ among etiological subtypes. Our aims were to determine the different profile of risk factors for ischemic and hemorrhagic stroke subtypes in our cohort from the Perugia Hospital-Based Stroke Registry. We analyzed the characteristics and the different risk factors of 2,395 first-ever consecutive stroke patients admitted to the Perugia Hospitals in the period between January 1, 1998 and December 31, 2002. The prevalence of cerebrovascular risk factors in each stroke subtype was analyzed independently and compared with other subtypes of stroke pooled together by means of univariate analysis and logistic regression models. Hypertension occurred in 61% of patients; familial history of stroke in 41.6%; vascular disease in 27.2%; embolic heart disease in 22.3%; cigarette smoking in 21.6%. Different potentially modifiable risk factors profiles were identified for each ischemic subtype of stroke, while in hemorrhagic lobar stroke subtypes, only male gender was an independent risk factor.

Adult↗
PubMed1993

Different HLA-B27 subtypes present the same immunodominant Epstein-Barr virus peptide.

An immunological basis has been postulated for the strong association between at least five subtypes of the HLA-B27 allele (B27.01, .02, .04, .05, and .06) and ankylosing spondylitis, namely that cytotoxic T lymphocyte (CTL) responses are induced against an "arthritogenic" peptide that these different subtypes can all present. This requires a degree of overlap between the peptide binding repertoires of different B27 molecules. The present work, using CTL responses to Epstein-Barr virus (EBV) as a model system in which to identify B27-restricted epitopes, provides the first direct evidence that different disease-related alleles can present the same immunodominant peptide. We first noted that EBV-specific CTL clones, whether from B27.05-, B27.02-, or B27.04-positive donors, were largely subtype-specific in their restriction, recognizing only EBV-transformed B cell lines of the relevant B27 subtype. However, when tested against targets expressing individual EBV proteins from recombinant vaccinia virus vectors, all B27.05-restricted, all B27.02-restricted, and a proportion of B27.04-restricted clones were reactive to the same viral nuclear antigen, Epstein-Barr nuclear antigen (EBNA)3C. In subsequent peptide sensitization assays, all the EBNA3C-specific clones tested and also the EBNA3C-specific component within polyclonal CTL preparations from B27.05-, B27.02-, or B27.04-positive donors recognized the same immunodominant viral peptide RRIYDLIEL (EBNA3C residues 258-266). This sequence accords well with the proposed B27.05 peptide motif and clearly must be accommodated within the different peptide binding grooves of B27.05, B27.02, and B27.04 molecules. Clonal analysis revealed a second component of the B27.04-restricted response that was not shared with other subtypes. This was directed against an EBV latent membrane protein LMP2 epitope whose sequence RRRWRRLTV satisfies some but not all requirements of the B27.05 peptide motif. We conclude that there is indeed a degree of functional overlap between different B27 subtypes in their selection and presentation of CTL epitopes.

Amino Acid Sequence↗
PubMed1995

HLA-A2 subtypes are functionally distinct in peptide binding and presentation.

Nearly half of HLA-A2-positive individuals in African populations have a subtype of HLA-A2 other than the A*0201 allele. We have isolated the common African HLA-A2 subtype genes from Epstein-Barr virus-transformed B cell lines and have established stable class I reduced transfectants expressing these alleles. We have studied the peptide binding and presentation properties of A*0201, A*0202, A*0205, A*0214, and A*6901 by a combination of approaches: assaying direct binding of labeled synthetic peptides, studying the ability of antigen-specific cytotoxic T lymphocytes to recognize peptide-pulsed cells, and sequencing peptide pools and individual ligands eluted from cells. We find that A*0201-restricted peptides can also bind to A*0202 but do not bind strongly to the other alleles in this study. We show that some cytotoxic T lymphocytes can recognize all subtypes capable of binding an antigenic peptide, whereas others are subtype specific. Sequencing of eluted peptides reveals that A*0202 has a similar peptide motif to A*0201, but that A*0205, A*0214, and A*6901 have different motifs. These data strongly support a model in which residue 9 (Phe or Tyr) of the A2/A68/A69 molecules is a critical factor in determining the specificity of the B pocket of the major histocompatibility complex and the position 2 anchor residue of associated peptides. We conclude that a single-amino acid difference in the major histocompatibility complex can be sufficient to cause a dramatic change in the nature of bound peptides, implying that individuals with closely related HLA subtypes may present very different repertoires of antigenic peptides to T cells in an immune response. It is likely to be a general phenomenon that very similar class I subtypes will behave as functionally distinct HLA allotypes.

Alleles↗
PubMed2000

Elevated tumor necrosis factor-alpha activation of human immunodeficiency virus type 1 subtype C in Southern Africa is associated with an NF-kappaB enhancer gain-of-function.

The human immunodeficiency virus type 1 (HIV-1) epidemic within southern Africa is predominantly associated with the HIV-1C subtype. Functional analysis of the enhancer region within the long terminal repeat (LTR) indicates that HIV-1C isolates have >/=3 NF-kappaB binding sites, unlike other subtypes, which have only 1 or 2 sites. A correlation was shown between NF-kappaB enhancer configuration and responsiveness to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha within the context of naturally occurring subtype LTRs, subtype-specific NF-kappaB enhancer regions cloned upstream of an isogenic HXB2 core promoter or a heterologous SV40 minimal promoter, and full-genome subtype clones. In all cases, TNF-alpha activation was correlated with the subtype configuration of the NF-kappaB enhancer. Whether the naturally occurring gain-of-function in the NF-kappaB enhancer of HIV-1C observed in this study can provide a selective advantage for the virus in vivo remains to be determined and warrants further study.

Binding Sites↗
PubMed2001

Molecular subtyping of Treponema pallidum in an Arizona County with increasing syphilis morbidity: use of specimens from ulcers and blood.

A molecular-based subtyping system for Treponema pallidum was used during an investigation of increasing syphilis in Maricopa County, Arizona. Genital ulcer or whole blood specimens from patients with syphilis were assayed by a polymerase chain reaction (PCR) amplification of a T. pallidum DNA polymerase I gene. Positive specimens were typed on the basis of PCR amplification of 2 variable genes. In all, 41 (93%) of 44 of ulcer specimens and 4 (27%) of 15 blood specimens yielded typeable T. pallidum DNA. Twenty-four (53%) of 45 specimens were subtype 14f; other subtypes identified included 4f, 4i, 5f, 12a, 12f, 14a, 14d, 14e, and 14i. Only 2 specimens were from epidemiologically linked patients. This investigation demonstrates that multiple subtypes of T. pallidum can be found in an area with high syphilis morbidity, although 1 subtype (14f) was predominant. Four typeable specimens were from blood, a newly identified specimen source for subtyping.

Arizona↗
PubMed2002

Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial.

The association between virologic response and human immunodeficiency virus type 1 (HIV-1) subtype was investigated in 113 HIV-1-infected children randomly assigned to receive zidovudine plus lamivudine, zidovudine plus abacavir, or lamivudine plus abacavir in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. Symptomatic children (n=68) also received nelfinavir; asymptomatic children (n=45) were randomly assigned to receive nelfinavir or placebo. HIV-1 subtypes A, B, C, D, F, G, H, A/E, and A/G were found in 15%, 41%, 16%, 9%, 5%, 2%, 1%, 5%, and 7% of the children, respectively. Resistance assay failure rates were higher for non-B subtypes than for B subtypes (genotype, P=.01; phenotype, P=.02). HIV-1 subtype was not associated with virologic response at 24 and 48 weeks after initiation of treatment. No differences were observed in the frequency of development of resistance mutations L90M (P=1.00) and D30N (P=.61) in B and non-B viruses. In conclusion, no evidence that subtype determined virologic response to therapy was found.

Antiviral Agents↗
PubMed2001

Presence and chromosomal subtyping of Legionella species in potable water systems in 20 hospitals of Catalonia, Spain.

OBJECTIVE: To investigate the presence and clonal distribution of Legionella species in the water supply of 20 hospitals in Catalonia, Spain. SETTING: 20 hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain. METHODS: Environmental cultures of 186 points of potable water supply and 10 cooling towers were performed for the presence of Legionella species. Following filtration and acid treatment, the samples were seeded in selective MWY (modified Wadowsky Yee)-buffered charcoal yeast extract-alpha agar. All isolates obtained were characterized microbiologically and genotyped by SfiI pulsed-field gel electrophoresis (PFGE). RESULTS: 73 of 196 water samples, representing 17 of the 20 hospitals included in the study, were positive for Legionella pneumophila (serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to 74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each hospital had its own Legionella DNA subtype, which was not shared with any other hospitals. CONCLUSIONS: Legionella was present in the water of most of the hospitals studied; each such hospital had a unique, dominant chromosomal DNA subtype. The verification of several genomic DNA restriction profiles in such a small geographic area demonstrates the great genetic diversity of Legionella in the aquatic environment.

Bacterial Typing Techniques↗
PubMed2006

Carriage of multiple subtypes of methicillin-resistant Staphylococcus aureus by intensive care unit patients.

OBJECTIVE: To determine how consistently patients are colonized with methicillin-resistant Staphylococcus aureus (MRSA) at various sites and how many subtypes can be carried simultaneously by a single patient. SETTING: A 28-bed Intensive care unit in a tertiary-care referral hospital. METHODS: A total of 1,181 patients were screened by culture of swab specimens obtained from the nose, throat, groin, and axilla on admission to the intensive care unit (ICU), twice weekly during their ICU stay, and at discharge. RESULTS: MRSA was isolated at least once from 224 patients. Of these isolates, 359 were selected from 32 patients to be subtyped using pulsed-field gel electrophoresis. The rate of compliance with collection of swab specimens was 79.9%. The combination of sites colonized varied frequently over time for many patients. Of patients who had swab specimens obtained twice in 1 day, 8.7% had discordant results from the 2 swab sets. No patient had a clinical isolate that was not of an identical subtype to an isolate from an anatomical site that was sampled for screening. Half the patients carried multiple subtypes during their stay, with up to 4 subtypes per patient. CONCLUSIONS: The findings of this study may indicate that these patients have been colonized with MRSA on more than one occasion, possibly because of multiple breaches in infection control procedure. In MRSA-colonized patients, anatomical sites were intermittently colonized and carriage of multiple subtypes was common. These findings indicate that MRSA carriage is not a fixed state but may vary over time.

Axilla↗
PubMed1998

Glycoprotein B subtyping of cytomegalovirus (CMV) in the vitreous of patients with AIDS and CMV retinitis.

A 550-bp region of the cytomegalovirus (CMV) glycoprotein B (gB) gene was amplified by polymerase chain reaction (PCR) from 141 vitreous specimens of 120 patients with AIDS and CMV retinitis from three different metropolitan centers. The distribution of gB subtypes I, II, III, and IV were 19%, 43%, 12%, and 21%, respectively, based on restriction enzyme digestion patterns of PCR-amplified DNA. Two patients had simultaneous infection with two different gB subtypes. The ratio of gB subtypes was similar among the three geographically distinct patient populations. Two of 14 patients with bilateral vitreous specimens had different viral subtypes in each eye. In addition, different gB subtypes were observed in 1 of 6 patients with serial specimens. The ratio of different gB subtypes in the vitreous of patients with CMV retinitis is similar to that previously reported in the peripheral blood of patients with advanced AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Evidence of a high frequency of HIV-1 subtype F infections in a heterosexual population in Buenos Aires, Argentina.

We analyzed HIV-1 genetic variability, phylogenetic relationships, and association with transmission modes among 58 HIV-1-infected patients from Buenos Aires City, Argentina. The 58 strains were classified as env(gp41) HIV-1 group M subtype B (n = 34) and subgroup F1 of subtype F (n = 24). Potential recombinants combining parts of viral regions from different subtypes, B(prot)/F(env) and F(prot)/B(env), were found in two patients, and a dual infection with HIV-1 prot subtypes B and F was identified in one individual. Epidemiologic analysis of behavioral risks revealed that the frequency of infection with subtype F viruses was significantly higher (p < 0.0001) among heterosexual patients (71%) compared with homosexual patients (11%). The spread of non-B subtypes into heterosexual populations may be more common than previously thought. Our findings provide important information for monitoring the transmission of HIV-1 strains among different risk groups in Argentina as well as for vaccine development.

Adult↗
PubMed2000

A comparison of full-length glycoprotein 120 from incident HIV type 1 subtype E and B infections in Bangkok injecting drug users with prototype E and B strains that are components of a candidate vaccine.

Complete gp120 sequence information was obtained from eight persons with incident HIV-1 infections (four subtype E and four subtype B) who were part of a prospective injecting drug user (IDU) cohort in Bangkok, Thailand, during 1996-1998. The incident subtype E strains were similar to the prototype subtype E strain CM244 isolated in 1992 in northern Thailand. The incident subtype B strains displayed divergence, in both overall genetic distance and other significant gp120 characteristics, from the prototype North American subtype B strain HIV-MN. Recombinant gp120s derived from CM244 and HIV-MN strains are components of a vaccine that is undergoing phase III efficacy testing, begun in March 1999, among Bangkok area IDUs. The information presented here will be important in the evaluation of any breakthrough HIV-1 infections occurring among vaccinees during the vaccine trial and in ongoing vaccine development efforts in Thailand.

AIDS Vaccines↗
PubMed2002

HIV-1 subtypes in Yugoslavia.

To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.

Adult↗
PubMed2002

Consistent subtype-specific anti-HIV type 1 T lymphocyte responses in Indian subjects recently infected with HIV type 1.

Anti-HIV-1-specific T cell responses in early HIV-1 infection have been found to be important in deciding the course of disease progression. But there are few data concerning nonsubtype B HIV infection. HIV-1 subtype C is the most prevalent subtype in India. HIV-1 Gag-specific T cell responses in 12 Indian subjects with recent HIV-1 infection were characterized by an ELISpot assay at two consecutive visits and their correlation with plasma viral load and CD4(+) T lymphocyte counts was studied. Ten of the 12 subjects demonstrated T cell responses to either one or both Gag B and C peptides, on at least one visit. Five of 10 responders showed a consistent response (response at both visits): 4 exhibited a Gag C-specific consistent response and 1 showed a consistent response to Gag B. The remaining five patients, showing response at only one of the two visits, were considered inconsistent responders. None of the individuals showed a consistent response to both B and C Gag peptides. Marginally significant correlation was observed between consistency of the response and lower plasma viral load (p = 0.062). The subtype-specific Gag C response was also found to be correlated with lower viral load as compared with the response to Gag B (r = -0.336, p = 0.054 for subtype C and r = -0.234, p = 0.13 for subtype B). The data suggest that the patients exhibiting consistent subtype-specific responses to HIV-1 Gag might have better control of viral replication in early HIV infection.

CD4-Positive T-Lymphocytes↗
PubMed2002

Characterization of the South African HIV type 1 subtype C complete 5' long terminal repeat, nef, and regulatory genes.

Human immunodeficiency virus type 1 (HIV-1) subtype C has become the major etiological agent in the global and especially African epidemic. To gain better understanding of the genetic diversity and rapid transmission of HIV-1 subtype C, we have characterized the complete 5' long terminal repeat (LTR) region along with the regulatory genes tat and rev as well as the accessory gene nef of 14 South African HIV-1 subtype C isolates. Phylogenetic analysis revealed a subtype C 5' LTR cluster, as well as subclustering of our nef sequences with various subtype C strains separate from the India and China subclusters. At least 3 NF-kappaB sites were present in the 5' LTR of most isolates and 13 isolates had the subtype C-specific Rev truncation. Some length variation in exon 2 and the absence of a critical cysteine were found in Tat. Residue variation in the myristoylation signal and motifs involved in CD4 and MHC-I downregulation was recorded in our nef gene sequences.

Africa, Southern↗
PubMed2002

Full-length genome analysis of HIV-1 subtype C utilizing CXCR4 and intersubtype recombinants isolated in South Africa.

The HIV-1 epidemic in South Africa is largely due to subtype C viruses, which preferentially use CCR5 as a coreceptor for infection. We describe full-length genome sequences of two CXCR4-utilizing HIV-1 subtype C viruses and two intersubtype recombinants from South Africa. Three of the viruses (99ZACM4, 99ZACM9, and 99ZASW7) were isolated in 1999 from AIDS patients in Johannesburg, and a fourth virus (98ZADu178) was isolated in Durban in 1998 from an asymptomatic female sex worker. Isolates 99ZASW7 and 99ZACM9 from Johannesburg were subtype C throughout the genome, 99ZASW7 used the CXCR4 coreceptor, and 99ZACM9 used both CCR5 and CXCR4. Isolate 98ZADu178 from Durban was a novel recombinant between subsubtype A2 and subtype C. The third isolate from Johannesburg, 99ZACM4, was a complex, novel recombinant with multiple breakpoints and contained segments of subtypes A, C, D, G, and K. These results establish the presence of intersubtype recombinants in South Africa, indicating that ongoing surveillance for other subtypes and recombinants is necessary.

Female↗
PubMed2003

Longitudinal study of humoral immune responses in HIV type 1 subtype CRF01_AE (E)-infected Thai patients with different rates of disease progression.

Identification of immune correlates associated with disease progression will provide information for HIV-1 vaccine design in countries such as Thailand, where the prevalent subtypes (B and CRF01_AE [E]) are characterized. In this study, plasma viral load and humoral immune responses were measured in 20 HIV-1 subtype E-infected Thai patients with different rates of disease progression, based on CD4(+) T cell decline and clinical symptoms. Nine progressors (PRs) and 11 slower progressors (SPs) were evaluated. CD4(+) T cell counts were inversely correlated with viral load (p = 0.004) and positively correlated with p24 Ab (p = 0.022). In progressors, p24 Ab showed a significant decrease (p < 0.001) over time. V3 and gp41 Ab did not change significantly in either group. Both CD4-binding site (CD4/gp120BS) and gp120 titers correlated positively with neutralizing antibody (NAb) against both a subtype E cell line-adapted virus (NP03) and a primary isolate (TH023). However, V3 Ab correlated only with NAb against NP03 (p < 0.001). Increased NAb over time was observed more frequently in SPs as compared with PRs, against both the TH023 (p = 0.004) and NPO3 (p = 0.004) viruses. Cross-clade antibody-dependent cellular cytotoxicity was demonstrated in both groups. These data suggest that in HIV-1 subtype E infection, declining p24 Ab titer is a predictive marker of disease progression, as described for subtype B. Furthermore, in subtype E-infected patients, slower progressors retain the immune competence to develop new antibody responses to Env over time; these evolving responses may contribute to prolonged survival during HIV-1 disease progression.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2003

Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice.

Codon usage optimization of human immunodeficiency virus type 1 (HIV-1) structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo; however, all optimized genes reported thus far are derived from HIV-1 (group M) subtype B viruses. Here, we report the generation and biological characterization of codon usage-optimized gag, pol, env (gp160, gp140, gp120), and nef genes from a primary (nonrecombinant) HIV-1 subtype C isolate. After transfection into 293T cells, optimized subtype C genes expressed one to two orders of magnitude more protein (as determined by immunoblot densitometry) than the corresponding wild-type constructs. This effect was most pronounced for gp160, gp140, Gag, and Pol (>250-fold), but was also observed for gp120 and Nef (45- and 20-fold, respectively). Optimized gp160- and gp140-derived glycoproteins were processed, incorporated into virus particles, and mediated virus entry when expressed in trans to complement an env-minus HIV-1 provirus. Mice immunized with optimized gp140 DNA developed antibody as well as CD4+ and CD8+ T cell immune responses that were orders of magnitude greater than those of mice immunized with wild-type gp140 DNA. These data confirm and extend previous studies of codon usage optimization of HIV-1 genes to the most prevalent group M subtype. Our panel of matched optimized and wild-type subtype C genes should prove valuable for studies of protein expression and function, the generation of subtype-specific immunological reagents, and the production of DNA-based sub-unit vaccines directed against a broader spectrum of viruses.

AIDS Vaccines↗