Positive Individual Research Articles

A single‐nucleotide polymorphism in the human ITGB3 gene is associated with the platelet‐specific alloantigen Vaa (HPA‐17bw) involved in fetal maternal alloimmune thrombocytopenia

The previously reported platelet (PLT)-specific antigen, Va(a), was defined by an alloantibody detected in the serum sample of a mother who delivered an infant displaying symptoms of severe fetal maternal alloimmune thrombocytopenia (FMAIT). This PLT antigen was localized to the integrin alphaIIbbeta3 (GPIIbIIIa) but its genetic basis was not defined. Genomic ITGA2B (alphaIIb) and ITGB3 (beta3) DNA from a Va(a)-positive individual were sequenced to identify potential polymorphisms underlying the Va(a) antigen. Recombinant beta3 integrin carrying the putative mutation was then used to assess serologic reactivity with the original maternal Va(a) antiserum. A single-nucleotide polymorphism (SNP; C622>T) in exon 5 of ITGB3 resulting in the replacement of threonine with methionine at residue 195 of the mature beta3 was identified. Calmodulin-tagged soluble recombinant beta3 encoding Met195 was produced in S2 cells and found to react specifically with the Va(a) antiserum. With the use of a combination of DNA sequencing and recombinant antigen expression, the molecular basis of the PLT-specific Va(a) antigen (HPA-17bw), a low-frequency antigen implicated in FMAIT, has been resolved. These data further demonstrate the value of using recombinant beta3 peptides for the detection of rare but clinically relevant antibodies.

The impact of low- and moderate-wealth homeownership on parental attitudes and behavior: Evidence from the community advantage panel

Considerable research has suggested that homeownership imparts a variety of positive individual, family, neighborhood, and community effects. Yet, much of the research to date has failed to examine such effects by level of income [Dietz, R.D., & Haurin, D.R. (2003). The social and private micro-level consequences of homeownership. Journal of Urban Economics, 54(3), 401–450.]. This study adds to the limited research on the impact of assets on parental attitude and behavior among low- and moderate-income (LMI) families. Data used in this study are from the evaluation of Self-Help's Community Advantage Home Loan Secondary Market Program. Specifically, we focus on the differences in the demographic and financial backgrounds, and parental attitudes and behavior between LMI homeowners and a comparison group of renters ( n = 815 owners; n = 333 renters). Logistic regression analyses are used to model parental attitude and behavior outcomes on tenure, controlling for a variety of household characteristics. Results show that the overall differences between homeowners and renters on parental outcomes are statistically nonsignificant. This finding implies that tenure per se is not associated with parental attitudes and behavior. Explanations for the possible reasons for the lack of a tenure effect are discussed. Policy implications are forwarded.

SCN2A Mutations and Benign Familial Neonatal‐Infantile Seizures: The Phenotypic Spectrum

Mutations of the sodium channel subunit gene SCN2A have been described in families with benign familial neonatal-infantile seizure (BFNIS). We describe two large families with BFNIS and novel SCN2A mutations. The families had 12 and 9 affected individuals, respectively, with phenotypes consistent with BFNIS. Two mutations were discovered in SCN2A (E430Q; I1596S). Both families had individuals with neonatal onset but the typical age of onset was in the early infantile period (mean 3.0 months). One mutation positive individual, with an otherwise typical clinical pattern, had seizures beginning at 13 months. Two individuals with SCN2A mutations were identified with seizures in later life. In each family a single individual with infantile seizures was mutation negative and thus represented phenocopies. This study extends the age range of presentation of BFNIS, confirms that neonatal and early infantile onsets are characteristic, and emphasizes the role of molecular diagnosis to confirm the etiology.

Staphylococcus lugdunensis Early Prosthetic Valve Endocarditis in a Young HIV Positive Patient

Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that causes skin and soft tissue infections and occasionally life threatening endocarditis of native valves. Prosthetic valve infection due to this pathogen is very rare and has not been described in HIV infected individuals. We report on the first case of early prosthetic valve endocarditis in an HIV-1 positive individual.

Prevalence of stigmatizing attitude among urban middle class in Maharashtra: Implications for HIV/AIDS education strategy

People living with HIV/AIDS received negative response from community largely because of misconceptions and lack of knowledge about the disease. Stigma acts as a major obstruction in the rehabilitation of people infected and affected by HIV in India. A persistently negative societal response plays a critical role in the experiences of individuals infected with the virus. Therefore stigma and discrimination are of concern to AIDS programmes. According to the UNAIDS report in 2006 nearly 5.2 million people in the age group of 15-49 years are living with HIV in India. Denial by the society or health care system will pose a serious threat to the ongoing prevention support and care strategies. The stigma related to HIV has been well documented in the past; however this study attempts to understand the perceptions opinions and attitudes of the urban educated and middle-income community members towards HIV positive individuals. HIV-related stigma has been categorized into four specific areas. The operational definitions are (i) attribution of blame which is defined as blaming the HIV positive individual for his/her condition (ii) violation of rights which is defined as denial of rights to employment health care and maintaining confidentiality about the HIV status (iii) stigma in interaction which is prevalent when respondents answer negatively to formal interactions or communication with HIV positive individuals (e.g. handshake buying grocery being served in a restaurant etc.) and (iv) stigma at workplace which is demonstrated by respondents by refusing to share or work with HIV positive individuals in a formal set-up and insisting on compulsory testing of the disease prior to employment and termination from jobs upon testing positive. (excerpt)

Neuroborreliosis in an HIV-1 Positive Patient

Simultaneous co-infections of Borrelia burgdorferi sensu lato and HIV-1 are rare events, with only six published cases. A case of acute neuroborreliosis with facial palsy, meningoradiculitis (Bannwarth's syndrome) in an HIV-1 positive individual is described. Diagnosis was confirmed by Western immunoblot analysis of serum and CSF and by proof of intrathecal production of antibodies against B. garinii. The patient was successfully treated with cefotaxime. In all published HIV+ cases, the course of borreliosis did not differ from that of the HIV negative population and the prognosis in properly treated patients was good.

Syphilitic myeloradiculopathy and pupillary light near disassociation: An overlap syndrome in a HIV positive individual

Syphilitic myeloradiculopathy and pupillary light near disassociation: An overlap syndrome in a HIV positive individual

Immortalized HLA Class I Negative Daudi B Cells Coated with HLA/Peptide Monomers Promote Efficient In Vitro Expansion of Antigen Specific CD8+ T Cells.

Monocyte derived dendritic cells (DCs) have historically been used to stimulate antigen specific T cells in vitro for both experimental and clinical applications. However, this is a time consuming procedure that is restricted by the limited number of DC precursors within peripheral blood. We developed an alternative source of antigen presenting cells (APCs) exploiting the immortalized HLA class I negative human B cell line Daudi. A fusion protein comprising the variable region of an anti CD20 antibody linked to streptavidin was used to target recombinant biotinylated HLA class I peptide complexes to Daudi cells via the cell surface antigen CD20. These alternative APCs were used to induce in vitro proliferation of memory T cells specific for Cytomegalovirus (CMV). CD8+ T cells from an HLA-A*0201 positive, CMV positive individual were stimulated with irradiated Daudi cells coated with HLA-A*0201 monomers presenting a peptide epitope from the CMV coat protein pp65. Staining with fluorescent-labelled HLA class I tetramers showed a 40-fold expansion of pp65 peptide specific CD8+ T cells after 14 days of culture that was comparable to expansion produced by stimulating with peptide antigen presented by DCs. The alternative APCs were also used to induced proliferation of allo-restricted peptide specific CD8+ T cells from an allo-naive individual yielding a population in which 78% bound tetramers representing the HLA-A*0201/peptide combination used for stimulation. Functional specificity of the expanded CD8+ T cells was demonstrated using HLA class I monomer coated Daudi cells as targets in cytolytic killing assays and to stimulate cytokine production that was measured by intracellular staining. Our results show these easy to prepare novel APCs induce efficient in vitro expansion of functional peptide specific CD8+ T cells.

The R563Q mutation of the β-subunit of the Epithelial Sodium Channel (ENaC) strongly associates with hypertension

We have previously reported the association of the R563Q mutation in the β subunit of the ENaC in black and mixed ancestry patients with hypertension, and Liddle's syndrome in the minority. The purpose of the study was to investigate the association of hypertension and Liddle's syndrome, and the mutation within affected families. The study was approved by the Research Ethics Committee of the University of Cape Town. After informed consent family members of index patients had their the blood pressure (BP) measured according to standard guidelines, and bloods drawn for K+, renin, aldosterone and DNA analysis. DNA was extracted from whole blood and the β-subunit of the ENaC was sequenced for the R563Q mutation. Only first degree relatives ≥ 20 years were included. Hypertension was defined by a BP > 140 systolic or 90 mmHg diastolic, or the use of antihypertensive medication. Fourteen families were studied totalling 69 individuals, of whom 37 were heterozygous for the R563Q mutation and 32 negative. The mean age of the R563Q positive individuals was significantly greater than the negatives, but there was no difference in renin, aldosterone and K+ levels (table 1). Demographics of R563Q positive and negative family members Demographics of R563Q positive and negative family members Of the 37 affected persons with the R563Q mutation 29 (78.3%) had hypertension and 11 (34.3%) of the negatives (p=0.0002). Both the mean systolic and diastolic BP was higher in the R563Q positive individuals than negatives (table 1). Only 1 positive individual had unprovoked hypokalaemia. In conclusion the R563Q mutation strongly associates with hypertension in family members, but not Liddle's syndrome. Further research is needed to define the prevalence of this mutation in our hypertensive population.

994. E1 Adenovirus Gene Transfer Vectors Inhibit HIV-1 Replication in Human Alveolar Macrophages

E1 adenovirus (Ad) vector infection of human alveolar macrophages (AM) inhibits HIV-1 replication independently of any transgene (Rice et al, Am J Respir Cell Mol Biol 2002; 27: 214-219) when the AM are infected with HIV-1 in vitro. We have previously shown that deletions of E4, Ad DNA polymerase or preterminal protein had no effect on the ability of Ad to block HIV-1 replication, empty Ad capsids do not block HIV-1 replication, and Ad acts, in part, by suppressing transcription from the HIV-1 long terminal repeats (LTR). The inhibition of HIV-1 replication by Ad is dose-dependent. We hypothesized that Ad would cause a similar dose-dependent inhibition of endogenous HIV-1 replication in AM obtained from HIV-1+ individuals. To address this question, we examined the shape of the dose-response curve for submaximal Ad inhibition of HIV-1 replication in AM. AM (6|[times]|105 cells/well) from a normal individual were infected with AdNull (0 to 2.5 |[times]| 104 pu/cell) or treated with azidothymidine (AZT, 10 |[mu]|g/ml), prior to infection with HIV-1 (103 TCID50/well). Conditioned media was collected twice weekly, and HIV-1 replication was quantified by measuring p24 in the conditioned media by ELISA. On day 16 post-infection, at a time of linear increases in p24, indicating active HIV-1 replication, p24 levels were (ng/ml) No Ad: 19.4; Ad doses in pu/cell: 102: 17.2 ; 5|[times]|102: 12.5; 103: 5.2; 5|[times]|103: 0.72; 104 0.11; 2.5|[times]|104: 0.04; AZT: 0.04. We compared these results with Ad effects on HIV-1 spontaneously elaborated from AM recovered from an HIV-1 positive individual. AM (8 |[times]| 105 cells/well) were infected with AdNull (0 to 2.5 |[times]| 104 pu/cell) or treated with AZT. p24 levels in the culture increased linearly over 4 days. On day 4 post-infection with Ad, p24 levels were No Ad: 44.2; 102: 32.4 ; 5|[times]|102: 24.7; 103: 10.7; 5|[times]|103: 1.70; 104: 0.27; 2.5|[times]|104: 0.08; AZT: 0.08. The dose-response for inhibitory effects of Ad on HIV-1 replication was similar under both conditions over several logs of Ad doses. In a separate experiment, Ad inhibition of HIV-1 replication in AM obtained from another HIV+ individual was evaluated as a function of Ad dose in half-log increments spanning the range from 102 |[minus]|3|[times]|104 pu/cell and yielding a range of p24 levels on day 4 ranging from 1.1-26.2. When the percent inhibition of HIV-1 replication was plotted as a function of log [Ad dose], the relationship was nearly linear, R2=0.96 over a 2 log range of doses. These data indicate that Ad inhibits endogenous HIV-1 replication in AM with a dose-response relationship similar to that observed when normal AM are infected with HIV-1 in vitro.

HIV/AIDS in Cuba: a model for care or an ethical dilemma?

HIV/AIDS in Cuba: a model for care or an ethical dilemma?

Old and New World arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by Lassa virus-specific human CD4+ T-cell clones

Data from human studies and animal experiments indicate a dominant role of T-cells over antibodies in controlling acute Lassa virus infection and providing immunity to reinfection. Knowledge of the epitopes recognized by T-cells may therefore be crucial to the development of a recombinant Lassa virus vaccine. In order to study human T-cell reactivity to the most conserved structural protein of Lassa virus, the glycoprotein 2 (GP2), seven GP2-specific CD4+ T-cell clones (TCCs) were generated from the lymphocytes of a Lassa antibody positive individual. All TCC displayed high specific proliferation, showed DR-restriction, and produced IFN-γ upon stimulation with recombinant GP2. The epitope of four of the clones was localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (aa 289–301, numbering according to sequence of GPC). This epitope is conserved in all strains of Lassa virus and lymphocytic choriomeningitis virus (LCMV), shows >90% similarity in all New World arenaviruses of clade B, and overlaps with the proposed fusion domain of GP2. Peptides with conservative aa exchanges, as they naturally occur in the epitope 289–301 of the Old World arenavirus Mopeia and some New World arenaviruses, continued to effectively stimulate the Lassa-GP2-specific T-cell clones tested. The finding of a human T-helper cell epitope, which is highly conserved between Old and New World arenaviruses, is of importance for the design of arenavirus vaccines.

Ramifications of ostracism as a consequence of revelation of HIV positive status: its effect o individuals and families in Botswana

Using primary data and a combination of qualitative and quantitative methods the study looks into ramifications of ostracism as a factor influencing people’s behavior towards the spread of HIV/AIDS, which have devastating effects on the structure and composition of the family in Botswana. The study showed that the highest proportion of respondents who would abandon an HIV positive partner (58.4%) occurs among young people aged 15 to 19 years; and that the propensity to abandon an HIV positive partner diminishes with advancement in age. In-depth inquiries on why HIV positive partners would be abandoned produced responses that revolved around fear of exposure, vulnerability and association with an HIV positive individual. The study showed that the highest proportion of respondents who would not reveal their HIV positive status occurs among those who have lost a relative or a friend to AIDS. Fear of being isolated, rejected, stigmatized and unwanted featured among the top reasons why respondents would not reveal their HIV positive status. Society’s reaction towards HIV positive individuals and families with HIV/AIDS patients appeared strong enough to drive individuals to hide their positive status and to go ahead and take the risk of onward transmission of the virus.

Living with HIV/AIDS seropositivity: from concept to preconceptions

This is an interactive study which aimed at identifying the reactions and feelings of nurses/clients in relation to positive serum for HIV/AIDS. From the nurses's narratives emerged the following meanings: to have difficulty in interacting due to the fear of infection and death; to treat the client as a non-person; to act as an "informed" professional. From the individuals with positive serum, the following meanings were extracted from their discourses: to be non-equal; to accept victimization/self-exclusion; to impress by the use of manipulation and to be a normal deviant. This data served as groundwork for a reflection about their significances in light of the work Stigma: notes about the manipulation of the deteriorated identity, by Erwing Goffman and of the Resolution COFEn--160/93. The understanding of this phenomenon signals to defensive and excluding practices on both parts, based on the fear of death. The results indicate the need to carry out training and awareness workshops for health professionals in order to qualify them for a more holistic and humanitarian care that favors the (re)socialization of the positive serum individual.

A qualitative evaluation of HIV and AIDS education to senior school children in Lothian Region, Scotland

In response to the high incidence of HIV and AIDS in Lothian Region Scotland the Education Department has funded a development team to work in the schools. The main focus of this team is a conference day aimed at 15-16-year-old school pupils run by external facilitators. The day comprises an educational input a question-and-answer session role playing and a plenary session led by an HIV positive individual. This paper evaluates the programme using qualitative methods at three schools. The views of the pupils were sought using focus groups both before and after the conference day. The programme was well received giving pupils the opportunity to raise personal issues surrounding HIV and AIDS. In general the pupils were well informed about the subject but lacked confidence in their knowledge and their ability to implement safer sex practices. This conference day appears to have underlined the importance of HIV and AIDS in the pupils lives and clarified related issues. It is a good model of practice. (authors)

Scientific facts and their public: the history of the diagnosis of syphilis

In the 1910's and 1920', thanks to the conjunction of scientific views concerning the specificity of anti-bacterial antibodies, of lay ideas about the existence of anti-bacterial antibodies and of the perceived importance of developing a syphilis test for public health officials, the community of serologists collectively transformed a relatively inefficient diagnostic test described by Wassermann in 1906 into an "incontestable scientific fact". This "scientific fact" established the equivalence: Wassermann positive individual=person infected with the germ Treponema pallidum, the etiological agent of syphilis. It modified the boundaries of the nosologic entity "syphilis", medical practices, professional attitudes, lay perceptions of syphilis, and health policies. In the 1950's, however, discrepancies between Wassermann test data and epidemiological data and, on the other hand, the development of specific anti-treponemal tests, destabilized the previously stabilized "scientific fact". A high percentage of Wassermann positive individuals were redefined as "biological false positifs", that is persons who suffered from chronic affections able to induce positive results of the Wassermann test. The equivalence Wassermann positive person=individual infected by Treponema pallidum was replaced by the equation: Wassermann positive person=individual infected by Treponema pallidum or biological false positive. The new perception of the Wassermann test again changed scientific views, professional practices and lay beliefs. The history of the Wassermann reaction illustrates the complicated interaction between "scientific facts" and "social facts", and the mutual shaping of both.

Willingness of male homosexuals to perform mouth-to-mouth resuscitation

Background: Providing mouth-to-mouth resuscitation (MMR) during cardiopulmonary resuscitation (CPR) is a proven effective lifesaving procedure. However, the perceived risk to the rescuer of contracting infectious diseases, especially acquired immunodeficiency syndrome (AIDS), by performing MMR on a possibly human immmunodeficiency virus (HIV) positive individual is probably affecting the number of people willing to perform MMR. Physicians and nurses constitute a major part of citizen cardiopulmonary resuscitation (CPR) responders and serve as CPR educators and resource personnel. Currently, the fear of physicians and nurses of contracting infectious disease has dampened their willingness to perform MMR, and thus has reduced the number of strangers who will receive MMR. Homosexual males, like the medical community, have an increased perceived risk of acquiring infectious diseases, especially AIDS, and have been the target of intense educational efforts concerning the transmission of HIV. By (a) determining the willingness of various groups to perform MMR, (b) elucidating the factors which affect their willingness to perform MMR, and (c) comparing this willingness to the actual, not perceived, risk of acquiring HIV by performing MMR, either appropriate changes can be made to educate people in the performance of MMR, by informing them of the actual risks of contracting infectious diseases, or alternative methods of resuscitation, involving ‘lay-on’ masks, can be recommended. Thus the willingness of homosexual males to perform MMR was determined and compared to the previously determined actual reluctance of the medical community to perform MMR in similar hypothetical scenarios. Methods: During interviews, 200 male homosexuals in Los Angeles were asked to assume that they knew how to perform CPR and MMR and to indicate how they would respond to four hypothetical cardiac arrest scenarios. These scenarios included cardiac arrests of a child, a trauma victim, a young man in a gay neighbourhood, and a victim of unknown history. Demographical data concerning the respondents was also obtained. Results: Of the homosexual men surveyed, 93 and 85% stated they would perform MMR on a stranger of unknown history, if they, the rescuer, were HIV negative or positive, respectively, ( P < 0.001). Similarly, a high percentage of the presumed HIV negative and HIV positive respondents stated a high willingness to perform MMR in response to hypothetical cardiac arrest scenarios involving a trauma victim, a child, and a young man in a gay neighbourhood. Conclusions: The willingness of male homosexuals to perform MMR is high, in contrast to the general reluctance of internists and medical nurses to perform MMR in the same outpatient scenarios. The different perceived risks of male homosexuals and physicians acquiring infectious diseases by performing MMR is probably responsible for the difference in willingness of these two groups to perform MMR. The high perceived risk of acquiring infectious diseases due to performance of MMR currently held by physicians in general may be lowered by increasing educational efforts. CPR courses should (a) discuss actual and perceived risks of acquiring infectious diseases by MMR, (b) discuss and weigh a small, and possibly not valid, risk of contracting an infectious disease while performing MMR on a victim, and (c) emphasize techniques involving ‘lay-on’ barrier masks. The availability of effective ‘lay-on’ barrier masks' should also be increased.

Generation of HLA-B55 restricted T lymphocyte mediated cytotoxicity against autologous LCL

The lymphocytes of one HLA-A11 positive individual (A1, A11, B49, B55) were stimulated in vitro with the autologous EBV transformed lymphoblastoid cell line (LCL). The culture contained HLA-A1, A11 and B55 restricted, LCL selective cytotoxic T cells (CTLs). In the T cell culture stimulated four times, the lysis of A11 and B55 carrying targets suggested that the subsets of the two latter CTL types had similar size. After further stimulations the B55 restricted CTLs were enriched in the culture. Earlier results suggested that in HLA-A11 positive individuals the All-restricted LCL-selective CTL subset dominates. The sensitivity of a target panel including Burkitt lymphoma (BL) lines suggested that the peptide presented by the B55 molecule differs in A and B type EBV strain carrying cells.

HBsAg Taşıyıcılarının Yakın Aile Çevresindeki Bireylerde ELISA ile HbsAg’ın AraştırılmasI

DETECTION OF HBSAG BY ELISA IN THE FAMILY MEMBERS OF HBSAG CARRIERS. ✓In this study, by Elisa and by using Wellcozyme HBsAg kits, Hi sAg was detected in the same environment living family members of 84 HBsAg positive people. It was observed that HBsAg was positive by the ratio of 41/243 (16.9 %) in the environmen of HBsAg carriers. This ratio was compared with the control group having no medical problems and study groups's % 16,9 positi-vity rate showed significant difference (p<0.001) against 11/140 (7.85 %) ratio (control group). It was noted that of the 84 families, HBsAg was positive in one in 52 families, in two in 23 families, in 3 in 9 families. Our these findings show that, the HBsAg positive individual is an important risk factor for his near environment. Bu calismada, HBsAg pozitif 84 olgu ile ayni aile ortaminda yasayan 243 kiside, Elisa ile, Wellcozyme HBsAg kitleri kullanilarak, HBsAg aranmistir. HBsAg tasiyicisinin cevresinde 41/ 243 (%16.9) oraninda HBsAg pozitifligi gozlenmistir. Bu oran, hicbir saglik sorunu bulunmayan kontrol grubu HBsAg bulgulariyla karsilastirilmis ve 11/140 (%7.85) oraninin, calisma grubu¬nun % 16.9 pozitiflik oram ile p<0.01 duzeyinde anlamlilik gosterdigi saptanmistir. Bu 84 aile¬den 52'sinde HBsAg 1 olguda pozitif bulunurken, 23 ailede 2'ser, 9 ailede 3'er bireyde HBsAg varligi not edilmistir.

Enhancing Self‐esteem and Confidence

Managers need to know how to recognise when low esteem and lack of confidence are contributing to a worker′s performance problems and how to promote development of self‐image in this individual. This process can be encouraged by providing a positive supportive atmosphere where the individual can achieve success and build his or her own self‐image. Careful attention must be given to task organisation, feedback, reinforcement and appropriate interpersonal communication.