Immunization of macaque monkeys with low- and high-dose regimens of SIVmac results in different immune responses.
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Animals↗
Biomedical subjects
W Bodemer
Publications and source records attributed to W Bodemer.
HIV-2-specific immune status of an HIV-2-exposed but uninfected cynomolgus monkey offspring.
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Animals↗
Moclobemide twice daily in the treatment of major depressive episode: a double-blind, multicenter comparison with different three-times-daily dosage schedules.
Data on a twice-daily dosage schedule with moclobemide in the treatment of depression is limited. In this study, moclobemide 150 mg twice daily (b.i.d.) was compared to two different three-times-daily (t.i.d.) regimens with total daily dosages of 300 and 450 mg, respectively, over a 6-week period. The study was randomized, double-blind, and conducted at three university centers. Efficacy was measured on the Hamilton Depression and Anxiety Rating Scales, on the Zung Scale, and on clinical global impression. Tolerability and safety were assessed through adverse events and vital signs and on clinical global impression. One hundred seventy-eight depressed outpatients were included, and 158 completed the study. The treatment groups were comparable at baseline. No clear differences between the treatment groups could be shown with respect to efficacy. There was, however, a slightly larger decrease in the total HAM-A score in the groups receiving 150 mg b.i.d. and t.i.d. than in the third group. There were no marked differences between the groups with respect to tolerability and safety. Tolerability was rated "good" or "excellent" in 94% of patients, and there was no appreciable change in vital signs in any of the treatment groups. Moclobemide 150 mg b.i.d. is the optimal initial schedule for treatment of depression.
Adult↗
Dopamine increases platelet intracellular calcium in bipolar affective disorder and controls.
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Adult↗
Early helper T-cell dysfunction in simian immunodeficiency virus but not in human immunodeficiency virus type-2-infected macaques.
Both naive and vaccinated macaques acquired a virus-specific proliferative helper T-cell reactivity in response to infection with the nonpathogenic human immunodeficiency virus type 2 (HIV-2). In contrast, macaques infected with the pathogenic simian immunodeficiency virus of the macaque strain (SIVmac) did not develop a helper T-cell response. Furthermore, a vaccine-induced preexisting T-cell reactivity was abrogated after SIVmac infection in vaccine failures. These differences may reflect the different pathogenicity of the two closely related viruses.
AIDS Vaccines↗
Comparison of humoral immunity and induction of proliferating T lymphocytes in vaccinia virus-infected rabbits and rhesus macaques.
Vaccina virus (VV) infection induces specific antibodies and cytotoxic T cells in various animal species. Therefore, helper T cells also should be induced that stimulate the humoral and cellular immune responses. We determined such helper T-cell activity in 2 species after VV infection. Rabbits and rhesus macaques were infected with the Copenhagen strain of VV or with recombinant VV expressing retroviral proteins. Animals of both species developed antibodies and specific proliferative T-cell response. This reactivity could be enhanced by booster infection with VV. The proliferating macaque cells were CD4+ and major histocompatibility complex class II-restricted. These data confirm the broad immunogenicity of VV. Expression of additional polypeptides expressed from a recombinant VV does not lead to altered immune response to VV antigens. However, strength of the helper T-cell response, as well as clinical reactions, differed between macaques and rabbits. Infection with recombinant VV as delivery vectors offers the opportunity for combined vaccination against recombinant proteins and does not diminish cellular and humoral immune responses to VV itself.
Animals↗
Personality traits, brief recurrent depression and attempted suicide.
This study investigated the relationship between attempted suicide, personality factors and brief recurrent depression. Over a period of 1 year, the demographic and psychiatric factors of 307 patients who had attempted suicide and subsequently been hospitalised at H. F. Verwoerd Hospital and referred to its Department of Psychiatry were recorded. Their personality traits were evaluated clinically. After 5 years, 205 respondents were traced to complete a follow-up questionnaire and, where possible, a personality assessment was completed on clinical grounds. They were also evaluated for brief recurrent depression. Among the men, antisocial, dependent and histrionic personality traits, in that order, were most commonly noted and among the women, histrionic, dependent and antisocial traits. A clear relationship between suicidal behaviour and the syndrome of brief recurrent depression was established. The latter was also found to be related to histrionic personality traits in women. This underscores the relationship between suicide attempts and histrionic personality traits.
Depression↗
Immunization with virion-derived glycoprotein 130 from HIV-2 or SIV protects macaques against challenge virus grown in human or simian cells or prepared ex vivo.
We have compared in the macaque model the efficacy of the virion-derived glycoprotein of HIV-2ben (HIV-2 gp130) with that of SIVmac251/32H (SIV gp130). The latter vaccination trial was in part combined with vaccinia virus (VV) priming. Both antigen preparations induced a strong humoral, but a weak cellular, immune response. The first challenge was performed with autologous virus grown on a human T cell line. More than 50% of the monkeys immunized with HIV-2 gp130 (five of nine) and 63% of the monkeys immunized with SIV gp130 (five of eight) were protected. All such protected animals received one or two booster immunizations before they were rechallenged either with heterologous HIV-2SBL6669 grown on monkey peripheral blood mononuclear cells or with an ex vivo stock of SIVmac251/32H prepared from the spleen of an SIV-infected macaque and not passaged in vitro. Immunization with HIV-2 gp130 did not protect against the second challenge, but one animal showed limited infection as indicated by positive PCR only. Challenge of the SIV gp130-immunized monkeys with the spleen-derived virus led to infection of three animals; remarkably, one of these was only PCR positive. Two animals were completely protected. Thereby we can exclude the influence of cellular proteins on protective immunity. Priming with VV was not superior to immunization with gp130 alone. Neither at the first nor at the second challenge were the virus-specific humoral and cellular immune responses of the vaccinees clearly correlated with protection. However, neutralizing antibodies may have been important in the SIV gp130-immunized animals at first challenge.
AIDS Vaccines↗
Psychiatric classification--an ongoing process.
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Humans↗
High level expression of active human prothrombin in a vaccinia virus expression system.
We have worked out an efficient and time saving procedure for the expression of recombinant human prothrombin. The glycoprotein was expressed in the vaccinia virus expression system in several mammalian cell lines. The kidney cell lines Vero and BHK and the human cell line Hela were found to efficiently secrete prothrombin. Expression level of 3-4 micrograms of factor II per 10(6) cells per day corresponding to 18-23 mU per 10(6) cells per day were achieved. Since the expression levels obtained with the vaccinia virus/Vero cell system were comparable to those obtained in amplified transformed CHO cells it provides an alternative system for the efficient expression of human prothrombin and may allow to further elucidate structure-function relationships of (pro)thrombin and its various effectors.
Amino Acid Sequence↗
[Suicide in schizophrenic patients].
Suicide is a serious and extensive problem in the clinical management of schizophrenic patients. A retrospective empirical study was conducted on 33 white schizophrenic patients who committed suicide between 1978 and 1989. 'Psychological autopsy' and psychiatric interviews were used for gathering information. A group of 33 schizophrenic patients with a high suicide risk were used as control group. The two groups were correlated as far as possible with regard to age, duration of illness and sex. A statistical analysis was made of the findings. Risk factors revealed by this study, which may be of use in the clinical situation to help prevent suicide in schizophrenic patients, are discussed and include sociodemographic data, depressive and psychotic symptomatology and the misuse of Cannabis. Suggestions are also made regarding future research on schizophrenia and suicide. It is concluded that the clinician should be conservative in his assumptions when identifying schizophrenic patients with a high risk of suicide and should not overestimate his abilities in this field.
Adult↗
Human papillomavirus in cervix carcinoma and condylomata acuminata--identification of HPV-DNA by improved dot-blot-hybridization.
Using the benzoylated naphthoylated DEAE cellulose method (BND-method) we have designed a more efficient approach for the detection of human papillomavirus-DNA (HPV-DNA) via dot-blot and hybridization. Biopsy material from anogenital warts (40 patients), invasive carcinoma uteri (12 patients) and normal controls (20 patients) were studied for the presence of HPV-DNA. Phenol extracted DNA from representative lesions was loaded onto a pretreated nitrocellulose filter, was incubated under stringent conditions with 32-P-dCTP labelled HPV-DNA and exposed to a Kodak X-OMAT film. DNA of HPV types 11, 16, 18 were cloned into plasmid vectors. The common, time-consuming caesium-chloride density-gradient centrifugation used for purification of plasmid DNA (20-36 h), was substituted by the BND-method (15 min). Complete HPV genomes were excised using the restriction endonucleases Eco RI and Bam HI. The HPV-DNA fragments obtained were then electroeluted using the 'Bio-Trap' method and subsequently labelled with 32P-dCTP by nick translation. Without resorting to more complex and sensitive technology, such as the polymerase chain reaction, efficiency of specific analysis of large numbers of cervical samples and condylomata was achieved without loss of accuracy or increased costs. The time required for HPV identification from biopsy or sample receipt was shortened considerably (approximately 50%).
Blotting, Southern↗
A new vaccinia recombinant plasmid pSC-O.
A new plasmid pSC-O for generation of recombinant vaccinia virus was constructed. It offers additional advantages when compared with other widely used insertion vectors. This plasmid allows the expression of coding sequences lacking codons for the initiation as well as for termination of translation. Additional sequences modulating translation, but also transcription or affecting intracellular processing can be introduced. Sequences flanking the transcription unit of the gene of interest are complementary to SP6/T7 sequencing primers and thus may allow rapid sequencing (amplification) of the inserted DNA.
Base Sequence↗
[Psychiatric aspects of family killings].
There has been very little research done on family slayings in the RSA. The concept is defined and a short survey of the literature is provided. Five case studies of patients who were referred to Weskoppies Hospital after being involved in family killings are described; a diagnosis of depression was made in all 5 cases. The clinical implications of manslaughter and depression are discussed, and suggestions are offered for future research into psychiatric factors involved in family killings.
Adult↗
DNA dot-blot hybridization implicates human papillomavirus type 11-DNA in epithelioma cuniculatum.
Epithelioma cuniculatum is a rare, low-grade squamous cell carcinoma, belonging to the group of verrucous carcinomas. Evidence is presented that suggests that human papilloma virus type-11 may be involved in the pathogenesis of epithelioma cuniculatum. HPV-DNA was detected by dot-blot hybridization with 32P-labelled probe DNA. Plasmids containing HPV-DNA were isolated by the benzoylated naphthoylated DEAE cellulose method (BND-method), an improved procedure for routine detection of HPV-DNA.
Aged↗
Organization of terminal reiterations in the virion DNA of herpesvirus saimiri.
The population of herpesvirus saimiri (HVS) genomes extracted from extracellular virions are double-stranded, linear DNA molecules of about 160 kilobase pairs (kbp) each composed of a central segment of 110 to 112 kbp and 36% (G + C) (i.e. 'light' or L-DNA) linked to direct reiterations of a 1.44 kbp repeat unit of 71% (G + C) (i.e. 'heavy' or H-DNA) at each terminus. In this paper, we show that the population of HVS DNA molecules contains approximately equal concentrations of genomes with all possible integral numbers of complete repeat units (i.e. from greater than 30 to 1) at either 'left' or 'right' ends but that all molecular ends are derived by a unique cleavage at a site close to the single ApaI restriction endonuclease site of the H-DNA repeat unit. Junctions of proximal H-DNA repeat units with L-DNA occur at, or very close to, the sequence present at the molecular ends. The transition from L- to H-DNA occurs abruptly at this site at the 'right' end of the L-DNA component but some rearranged restriction enzyme cleavage sites typical of H-DNA are found within the first 0.8 kbp of the L-DNA sequences at the 'left' H-L DNA junction. HVS appears to provide an extreme example of the general process whereby herpesvirus DNAs are matured from concatemeric intermediates by a site-specific cleavage/recombination process involving random choice between equivalent sites for the initiation of the process and with choices between alternative termination sites being limited by a headful packaging mechanism.
Base Composition↗
The 160,000-Mr virion protein encoded at the right end of the herpesvirus saimiri genome is homologous to the 140,000-Mr membrane antigen encoded at the left end of the Epstein-Barr virus genome.
The sequence of 4.4 kilobase pairs (kbp) from the conventional right terminus of the A + T-rich light-DNA (L-DNA) sequences of the herpesvirus saimiri (HVS) genome contains a leftward-directed open reading frame (ORF) for a 1,299-residue protein. The molecular weight predicted for the protein (143,000) is in good agreement with the estimates of 150,000 to 160,000 for the major nonglycosylated polypeptide of the virion tegument (the 160K polypeptide), previously shown to be encoded by this region of the genome. The first initiation codon of the ORF is only 250 nucleotides from the junction of the L-DNA component with the G + C-rich terminal reiterations (i.e., heavy or H-DNA) of the genome. An unusually A + T-rich sequence (43 of 45 nucleotides are A or T, relative to a mean composition of 40% G + C for the ORF) occurs some 75 bp 5' to this initiation codon, and the first adenylation signal (AATAAA) on this DNA strand occurs 18 bp 3' to the termination codon. The amino acid sequence predicted for the 160K protein of HVS is homologous over most of its length to the 1,318-residue protein encoded by the leftmost major ORF of the G + C-rich genome of Epstein-Barr virus (BNRF1, the 140K nonglycosylated membrane antigen). No homology to either of these proteins is evident among the products predicted from the complete sequence of the alpha herpesvirus varicella-zoster virus. Thus gamma herpesviruses with coding sequences which differ in mean nucleotide composition by some 20% G + C have homologous proteins encoded at similar positions with respect to genome termini, with the right end of HVS being homologous to the left end of Epstein-Barr virus.
Amino Acid Sequence↗
[Molecular biology of human T-lymphotropic retroviruses (HTLV)].
The first human retroviruses have been discovered during the past seven years. They cause two diseases which involve disturbances of the growth of the T4-lymphocyte. This target cell type, which is central to the regulation of the immune system is induced by human T-lymphotropic virus type I (HTLV-I) to excessive proliferation (leukaemia) and by HTLV-III/LAV (lymphadenopathy associated virus) to premature death (acquired immune deficiency syndrome [AIDS]). Both also seem to be indirectly involved in several other disorders. The genetic structures of these retroviruses and the mechanisms by which they usurp host-cell functions are novel among retroviruses. The continuous increase in the number of AIDS cases for whom no effective therapy is currently possible mandates attempts at developing primary prevention by a vaccine. Based on past attempts at developing vaccines against retroviruses, the most feasible configuration will be the glycoprotein linked to its transmembrane protein. Any virus preparation containing nucleic acids could be considered less safe. Potential problems exist in that there is extensive heterogeneity among various HTLV-III isolates, particularly in the env-gene. This fact and the known relationship of HTLV-III to some Lentiviruses suggest that functional antigenic variation could be encountered. The methodology of developing a vaccine against the retroviruses causing AIDS should also be helpful in designing vaccine strategies against human leukaemia and lymphomas caused by other members of this virus family.
Acquired Immunodeficiency Syndrome↗