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Biomedical subjects

G Haas

Publications and source records attributed to G Haas.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hopelessness and first-episode psychosis: a longitudinal study.

Hopelessness has not been adequately studied in first-episode psychotic patients, although it is already present at the early stages, especially in schizophrenic patients. We have studied 96 neuroleptic-naive psychotic patients (49 schizophrenic patients and 47 other non-affective psychotic patients) over a period of 12 months after their first admission. The total score on the Hopelessness Scale (HS) at first admission was higher in the schizophrenic patients, and correlated with younger age and with negative symptoms. High HS scores at baseline predicted poor short-term outcome in schizophrenic patients, as evidenced by worse global functioning at the 12-month follow-up. These correlations were not observed in the other psychoses group. Our results suggest that young, severely affected schizophrenic patients who experience hopelessness might be at higher risk of poor outcome.

Adolescent↗
PubMed1996

Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo.

The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points. Two distinct patterns for dynamics of CTL responses to viral variation were observed: 1) temporary amplification of viral variants followed by expansion of variant-specific CTL, ultimately leading to the disappearance of 12 out of the 14 initial epitope variants within two years. A second set of viral variants that had replaced the initial ones could also stimulate specific CTL precursors in the context of the same or an alternative HLA molecule; and 2) persistence of 2 viral variants in relatively conserved epitopes despite specific CTL recognition. Therefore, a remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.

Amino Acid Sequence↗
PubMed1996

Synthetic peptides coupled to the lipotripeptide P3CSS induce in vivo B and Thelper cell responses to HIV-1 reverse transcriptase.

To evaluate the ability of the lipotripeptide P3CSS to increase peptide-specific immune responses in vivo, we immunized mice from different inbred strains (BALB/c, C3H/HeJ, C57BL/6) with the 22-mer lipopeptide conjugates P3CSS-[RT-(522-543)] and P3CSS-[RT-(528-549)] of HIV-1 reverse transcriptase (RT) which included an immunodominant Th epitope [i.e. RT-(528-543)] characterized previously. Analysis of T and B cell responses to these lipopeptide conjugates indicated that specific Th responses could be readily induced in vivo. The peptide segments could also efficiently prime mice for secondary recognition of native RT. The use of shorter peptides permitted a delineation of the minimal T cell recognition site of this RT C-terminal region [i.e. RT-(528-540)]. Close to this T cell epitope we identified a B cell determinant containing the motif EQVD [RT-(546-549)] which was recognized in three different strains of mice (H-2b, H-2d and H-2k). A comparison with X-ray analysis of the C-terminal region of HIV-1 reverse transcriptase indicated exposed positions of these Th and B cell epitopes. Both the presence of T and B cell sites and its limited polymorphism make the region RT-(528-549) a promising candidate for vaccine design. The use of the P3CSS adjuvant/carrier principle as a nontoxic adjuvant may be of major importance in the development of vaccines applicable to humans.

Adjuvants, Immunologic↗
PubMed1996

Evolution and plasticity of CTL responses against HIV.

Exceptionally potent cytotoxic T lymphocyte responses are generated after HIV invasion and probably control the primary infection as well as the asymptomatic phase of HIV infection. The chronic phase appears as a quasi-equilibrium between waves of new HIV variants and variant-specific CTLs, thus sustaining continuous CTL activation which eventually fails to eradicate HIV disease progression and the reascension of viral replication. Meanwhile, both the host and the virus develop various strategies either to stop or to evade this potentially deleterious permanent CTL activity. The transient effectiveness of CTLs opens perspectives for understanding disease progression generally as well as for immune therapeutic strategies.

Carrier State↗
PubMed1995

CTLs from lymphoid organs recognize an optimal HLA-A2-restricted and HLA-B52-restricted nonapeptide and several epitopes in the C-terminal region of HIV-1 Nef.

In a previous analysis of HIV-1-specific CTLs in lymphoid organs from HIV-seropositive patients, we reported high frequencies of in vivo differentiated CTLs directed against two immunodominant regions in the central and in the C-terminal part of the HIV-1 Nef protein. The present study analyzes the epitopes recognized by CTLs in the carboxyl terminus of Nef (amino acids 182-205). In addition to several epitopes that are recognized in association with different HLA molecules (A1, A2, A25(10), B35, B52), we defined an optimal nonapeptide (190-198). This nonapeptide was recognized by CTLs down to nanomolar concentrations in the context of at least two HLA molecules, HLA-B52 and HLA-A2, including three HLA-A2 subtypes: HLA-A2.1, -A2.2, and -A2.4. We also determined the relative frequencies of effector CTLs directed against peptide 190-198 to be as high as 10(-4), as opposed to lower frequencies ranging between 5 x 10(-5) and 5 x 10(-6) observed for the other peptides recognized in the same region, thus confirming the optimal presentation of this nonapeptide in vivo. Molecular modeling of the interactions between HLA-A2.1 and Nef peptide 190-198 suggests the formation of a stable complex and allowed us to study sequence motifs that are important for the binding of the HIV-1 peptide in the pockets of the HLA-A2.1 molecule.

Base Sequence↗
PubMed1995

Bilateral spastic cerebral palsy--a collaborative study between southwest Germany and western Sweden. III: Aetiology.

In this third report from the collaborative study of children with bilateral spastic cerebral palsy born between 1975 and 1986, aetiology was analysed. Evidence for a prenatal aetiology increased with gestational age, whereas evidence for a peri-/neonatal aetiology decreased. The largest subgroup, the leg-dominated subtype, showed the same distribution of aetiology as the total group. A prenatal aetiology was found mainly among term and moderately preterm children with a four-limb-dominated subtype; a peri-/neonatal aetiology among very preterm children with a three- or four-limb-dominated subtype or among term children with a dyskinetic-spastic subtype. The findings support the hypothesis generated from the authors' epidemiological results of a peri-/neonatal aetiology being predominant among preterm, and a prenatal aetiology among term, children with bilateral spastic cerebral palsy.

Cerebral Palsy↗
PubMed1995

Sleep EEG changes in psychotic disorders: gender and age effects.

The aim of this study was to examine gender-related differences in electroencephalographic (EEG) sleep in inpatients with psychotic disorders. We investigated the effects of gender and age as well as gender-by-age interactions on sleep continuity, architecture and intranight distributions in 38 male and 23 female patients with functional psychoses. No gender effects were seen for any sleep parameters. However, older psychotic males had less slow-wave sleep than older psychotic females. On the other hand, female psychotic patients showed a significant decline in automated REM counts with age. It is possible that gender-related differences in neurodevelopment and/or aging could account for these findings.

Adolescent↗
PubMed1995

Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation.

A prospective evaluation of neoadjuvant hormonal downsizing in patients with localized carcinoma of the prostate was undertaken to assess its effect on normal tissue irradiation. Twenty patients with stage T1 or T2 (A, B) carcinoma of the prostate received 3 months of Lupron prior to definitive radiotherapy. The volumes of the prostate, seminal vesicles, bladder, and rectum from both the pre- and posthormone treatment planning CT were entered onto a 3-D treatment-planning system. The treatment planning parameters were standardized to facilitate comparison of the pre- and posthormonal volumes. Following the three monthly injections of Lupron, the average volume of the prostate was reduced by 37%. As a consequence, the volume of the bladder receiving at least 40, 52, and 64 Gy was reduced by an average of 15, 18, and 20%, respectively. In addition, the volume of the rectum receiving at least 40, 52, and 64 Gy was reduced by an average of 13, 20, and 34%, respectively. In conclusion, in patients with localized prostate cancer, downsizing of the prostate resulted in a reduction in the volume of bladder and rectum receiving high radiation doses. This approach may result in an improvement in the therapeutic ratio by reducing the morbidity of treatment.

Adenocarcinoma↗
PubMed1994

Human immunodeficiency virus-1 reverse transcriptase immunodominant CD4+ T cell epitopes: a peptide-based multiparametric assessment in the mouse.

We previously identified an immunodominant CD4+ T cell determinant in the carboxy-terminal region of HIV-1 reverse transcriptase (RT528-543). The present study aimed at enumerating all the potential sites of HIV-1 RT recognized by Th cells in the BALB/c (H-2d) mouse model. To achieve this we used a panel of 62 overlapping 15-mer synthetic peptides covering the whole RT sequence to assay the following parameters: (i) immunogenicity in naive BALB/c mice injected either with peptides pools or individual peptides; (ii) antigenicity, as detected by their ability to restimulate in vitro T cells from BALB/c mice primed with native RT; (iii) MHC class II (Ad)-binding capacity as measured by the inhibition of the antigen-specific, Ad-restricted presentation of unfolded apamin (4-Acm) by fixed antigen-presenting cells to Ad/4-Acm-specific, interleukin-2-producing T hybridoma cells; and (iv) the presence of typical or degenerate consensus Ad-binding motifs. The results in this study permitted identification of three novel immunodominant RT mouse CD4+ T cell sites (RT276-290, RT375-389 and RT411-425) located in regions of limited polymorphism among RT from several HIV isolates. Some of these RT segments were found to be in the vicinity of B cell or H-2Kk- or HLA-A2-restricted cytotoxic T lymphocyte epitopes. Finally, the approach used in this study was found to be very efficient for enumerating most T cell recognition sites in a complex protein, a result that would have not been achieved by a single parameter-based analysis.

Amino Acid Sequence↗
PubMed1994

Bilateral spastic cerebral palsy--a comparative study between southwest Germany and western Sweden. II: Epidemiology.

Epidemiological data of a collaborative study on children with bilateral spastic cerebral palsy (BSCP) between south-west Germany and western Sweden are reported. The study period covered the birth years 1975 to 1986. Overall, the rate of BSCP increased during the birth year periods 1975-77 and 1978-80, but decreased thereafter. The rise was due to an increase of BSCP in low-birthweight (LBW) children, especially very LBW (VLBW) children. Mortality rates in LBW, and particularly VLBW, children decreased significantly during the whole study period in both countries. The BSCP rate, after the initial increase, showed a decrease during the second half of the study period in LBW children. Results are interpreted in favour of a predominantly prenatal aetiology in normal-birthweight and of a predominantly peri- and neonatal aetiology in LBW children.

Cerebral Palsy↗