RESUMEN
When measurements are made with a magnetometer, it is usually assumed that the sample produces a pure dipolar magnetic field. This is only true if the sample is a sphere. If the sample is not a sphere, the magnetic field produced by it will also contain higher order multipoles. These components of the magnetic field depend not only on the volume and magnetization but also on the sample's shape and size. Ideally the measured moment of a sample is only proportional to the sample's magnetization and volume. This paper explains why a sample's shape and size affects the response of a magnetometer, shows results illustrating this effect, and discusses conditions that will minimize these effects.
RESUMEN
The recent advice on vaccination against cervical cancer from the Health Council of the Netherlands and the decision by the Minister of Health, Welfare and Sport to implement the vaccination within the National Immunisation Programme by September 2009, has been criticized by a group of authors because five of seven criteria for vaccination in public programmes are considered not to have been met; notably with respect to efficacy and safety. It appears that the available scientific data have been weighted differently by the Health Council committee and the criticising group of authors. In the original advisory report, the committee of the Health Council lists all uncertainties, and argues that a linked monitoring programme will provide public vaccination with sufficient warranties for efficacy and safety. Thus, new opportunities for primary prevention can be taken, and a significant health benefit is likely to be gained. On the other hand, postponing a decision until all uncertainties have been resolved will postpone a significant potential health benefit for many years.
Asunto(s)
Papillomaviridae/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Seguridad , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Medicina Basada en la Evidencia , Femenino , Humanos , Infecciones por Papillomavirus/complicaciones , Vacunas contra Papillomavirus/efectos adversos , Salud Pública , Neoplasias del Cuello Uterino/virologíaRESUMEN
--Each year, 600-700 women in the Netherlands are diagnosed with cervical cancer. Over the last 10 years, an average of 250 women have died annually due to cervical cancer. --Gardasil, the first vaccine for Human papillomavirus (HPV), was recently approved in Europe for the prevention of cervical cancer. --The availability of a vaccine for HPV prompts the question whether it should be included in the Dutch National Immunisation Programme. --At the end of 2006, the Medicines Evaluation Board, the Health Council of the Netherlands and the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment organised a workshop for experts in the field to answer that question. --The HPV vaccine provides protection against HPV-16 and HPV-18, which cause approximately 70% of cervical cancers. --Because the efficacy of vaccination is only evident after many years, preserving good participation in the screening programme is essential. --The current screening could be improved by introducing an HPV test combined with self-sampling for women who do not participate in screening. --Vaccination is unarguably an important development. However, there are still several unanswered questions regarding vaccination and its actual protection, duration of protection, long-term safety and cost-effectiveness. --April 1st, 2008, the Health Council of the Netherlands had recommended including HPV vaccination in the National Immunisation Programme.
Asunto(s)
Programas de Inmunización , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Enfermedades Virales de Transmisión Sexual/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Niño , Análisis Costo-Beneficio , Femenino , Humanos , Tamizaje Masivo , Países Bajos , Vacunación/normasRESUMEN
The Dutch Ministry of Health asked the Health Council for advice on how to prepare for a possible influenza pandemic. In two advisory reports the Committee responsible indicated the measures that it believes would need to be taken if such a pandemic were to reach the Netherlands. During a pandemic, the Committee recommends that every resident of the Netherlands with influenza-like illness should be treated with neuraminidase inhibitors such as antiviral agents. This approach serves to mitigate the course of the disease, to reduce infectivity and to allow patients to build up immunity to the virus. Since up to 30% of the population could become ill, the Committee anticipates that a stock of five million courses of the neuraminidase inhibitor oseltamivir is sufficient. If a pandemic were to occur at a time that the stock does not exceed the present 225,000 courses, the committee advises restricting treatment to three specified groups of patients. If the first few patients are traced shortly after they fall ill, the Committee recommends treatment of the patient and postexposure prophylaxis for his/her close contacts. The Committee does not advocate prophylaxis in general, but it can envisage prophylaxis for particular groups of patients or under particular circumstances. The Committee believes that in order to reduce rapid spread of the virus, schools should be closed and events where large numbers of people gather in a confined space should be cancelled. Because this recommendation would have major social and economic consequences, the Committee understands that its implication will depend on the anticipated severity and extent of the pandemic. The Committee regards vaccination against influenza as the best means of protecting the population. The development of a vaccine should be the absolute priority.
Asunto(s)
Antivirales/uso terapéutico , Brotes de Enfermedades/prevención & control , Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Gripe Humana/prevención & control , Neuraminidasa/antagonistas & inhibidores , Acetamidas/uso terapéutico , Guanidinas/uso terapéutico , Humanos , Gripe Humana/epidemiología , Países Bajos , Oseltamivir , Guías de Práctica Clínica como Asunto , Piranos/uso terapéutico , Riesgo , Ácidos Siálicos/uso terapéutico , ZanamivirRESUMEN
A Committee of the Health Council of The Netherlands has expressed its opinion on introducing testing of blood products for parvovirus B19 (B19). Although infections with B19 generally run their course without any serious health problems, for some groups, such as pregnant women, patients with underlying haematological problems and patients with immunodeficiency, infections with B19 can result in serious complications. For cellular blood products, which are derived either from a single donor or a limited number of donors and are administered either to a single patient or to a limited number of patients, the Committee recommends that a risk-group approach be adopted and that 'Big-virus safe' blood products be administered to the risk groups mentioned above. The Committee defines as 'Big-virus safe' cellular blood products from a donor in which IgG antibodies against B19 have been detected in two separate blood samples, one taken at least six months after the other. Patients other than those in the risk groups should continue to receive cellular blood products that have been produced in accordance with current safety criteria. For plasma products, which are prepared from plasma pools and are administered to large numbers of patients, the measures must be aimed at cutting down the levels of B19 infectivity in such pools. For plasma pools, the Committee proposes a maximum permissible limit of 104 genome copies of Bl9 per ml.
Asunto(s)
Donantes de Sangre , Sangre/virología , Parvovirus B19 Humano/aislamiento & purificación , HumanosRESUMEN
To assess the value of laboratory investigations for the diagnosis and treatment of cytomegalovirus-induced upper gastrointestinal tract ulcerations, the medical records and biopsy material from HIV-infected patients were reviewed retrospectively during a 12-month period. Clinical diagnosis of cytomegalovirus (CMV) ulceration, based on characteristic endoscopic appearance of extensive ulceration of the mid- to distal esophageal or gastric mucosa and responsiveness to anti-CMV therapy, was compared with laboratory investigations of biopsies. Laboratory procedures consisted of both histopathological examination of the biopsy specimens and viral culture. Twenty episodes in 12 HIV-infected patients could be evaluated. Clinical diagnosis of CMV ulceration appeared to be justified in 14 of 20 episodes (70%), which were confirmed by laboratory investigations. Of the remaining six episodes, which showed partial or no response to anti-CMV therapy, laboratory investigations were negative in two episodes and discrepant in four episodes (histopathology or viral culture positive). A good response to anti-CMV therapy was more frequent in patients whose biopsies proved positive by histopathological examination and/or viral culture than in patients with negative tests (82% versus 0%), which indicates the importance of both investigations. In conclusion, laboratory diagnosis of CMV-induced upper gastrointestinal tract ulcerations supported the diagnosis and decisions on treatment of CMV-induced upper gastrointestinal tract ulcerations.
Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Enfermedades del Esófago/virología , Infecciones por VIH/complicaciones , Úlcera Gástrica/virología , Úlcera/virología , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/complicaciones , Enfermedades del Esófago/complicaciones , Enfermedades del Esófago/patología , Infecciones por VIH/virología , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Úlcera Gástrica/complicaciones , Úlcera Gástrica/diagnóstico , Úlcera/complicaciones , Úlcera/diagnósticoAsunto(s)
Papillomaviridae/genética , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Secuencia de Aminoácidos , Cromosomas Humanos Par 11 , Femenino , Regulación Viral de la Expresión Génica , Humanos , Datos de Secuencia Molecular , Mutación , Fosfoproteínas Fosfatasas/genética , Proteína Fosfatasa 2 , Neoplasias del Cuello Uterino/genéticaRESUMEN
Previous results indicated that SV40 small t is essential for SV40-induced transformation of diploid cells but dispensable for the transformation of cells with a deletion on the short arm of chromosome 11 (del-11 cells). From these results we concluded that del-11 cells contain a cellular 'SV40 small t-like' factor, which is able to transactivate the HPV16 long control region (LCR) and to complement SV40 large T in transformation. Since SV40 small t and the regulatory 55 kDa subunit (PR55) of protein phosphatase 2A (PP2A), have been shown to inhibit the enzyme activity of PP2A, the PR55 beta subunit could be the putative 'small t-like' factor. In accordance with this hypothesis, we show that the PR55 beta subunit is highly expressed in del-11 but not in diploid cells and is able to trans-activate the HPV16 LCR in diploid cells. Moreover, inhibition of PP2A by okadaic acid resulted in trans-activation of the HPV16 LCR in diploid cells. Alignment of PR55 and SV40 small t showed a common four amino acid motif DKGG. We present evidence that the integrity of this motif is necessary for the PP2A-mediated ability of SV40 small t to trans-activate the HPV16 LCR.
Asunto(s)
Cromosomas Humanos Par 11 , Eliminación de Gen , Papillomaviridae/genética , Fosfoproteínas Fosfatasas/metabolismo , Activación Transcripcional , Secuencia de Aminoácidos , Western Blotting , Transformación Celular Viral , Células Cultivadas , Diploidia , Elementos de Facilitación Genéticos , Éteres Cíclicos/farmacología , Genes Virales , Humanos , Datos de Secuencia Molecular , Ácido Ocadaico , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosfoproteínas Fosfatasas/genética , Plásmidos , Regiones Promotoras Genéticas , Proteína Fosfatasa 2 , ARN Mensajero/genética , Virus 40 de los Simios/genéticaRESUMEN
The early region of bovine polyomavirus (BPyV) was tested for its cell transformation potential employing an assay of dense focus formation. Dense foci of morphologically transformed cells were observed upon transfection of primary rodent cells with a plasmid construct encoding the complete early region of BPyV under the transcriptional control of the long terminal repeat of Rous sarcoma virus. No transformation of primary rodent cells was observed upon transfection of these cells with a plasmid encoding the complete early region of BPyV under the control of its own transcriptional regulatory sequences. In BPyV-transformed cells, the viral sequences had become integrated into the cellular genome, and expression of large T antigen could be detected in a high percentage of cells. The transformed cells were demonstrated to be capable of anchorage-independent growth and to be oncogenic in immunocompromised newborn rats. Therefore BPyV should be considered as a potentially tumorigenic polyomavirus. Since many commercial batches of calf serum have been shown to be contaminated with BPyV, our observations may have implications for the use of calf serum in cell culture.
Asunto(s)
Transformación Celular Viral , Poliomavirus/genética , Infecciones Tumorales por Virus/veterinaria , Secuencia de Aminoácidos , Animales , Antígenos Transformadores de Poliomavirus/aislamiento & purificación , Virus del Sarcoma Aviar/genética , Línea Celular , Núcleo Celular/metabolismo , ADN Viral/genética , Inmunohistoquímica , Ratones , Datos de Secuencia Molecular , Plásmidos/genética , Ratas , Secuencias Reguladoras de Ácidos Nucleicos/genética , Secuencias Repetitivas de Ácidos Nucleicos , TransfecciónRESUMEN
The genetic organization of the early region of bovine polyomavirus (BPyV) was studied by analysis of the splice sites used in early mRNA maturation, using reverse transcription-polymerase chain reaction and DNA sequencing techniques. When compared to other polyomaviruses, the BPyV early region appears to have an uncommon organization. In the major early mRNA molecule two small intron sequences of 71 and 77 nucleotides, separated from one another by an 80 nucleotide exon sequence, were identified. Through splicing out both introns, a mRNA molecule is generated that contains an open reading frame with the capacity to encode 619 amino acids. Comparisons with the simian virus 40 large T antigen suggested that this mRNA molecule encodes the BPyV large T antigen. Remarkably, no mRNA product encoding a protein with a size comparable to that of the small t antigens of other polyomaviruses was detected. Another transcript was observed from which only the 77 nucleotide intron sequence had been removed, thereby creating a mRNA molecule with the capacity to encode only 45 amino acids. Whether this mRNA product represents a mature transcript which is translated in BPyV-infected cells or is an intermediate in the formation of the large T mRNA molecule is not known. Analysis of BPyV-specific early mRNA products isolated from BPyV-transformed murine cells revealed only the amplification product representing the putative large T antigen transcript.
Asunto(s)
Antígenos Transformadores de Poliomavirus/genética , Poliomavirus/genética , Poliomavirus/metabolismo , Empalme del ARN , ARN Mensajero/biosíntesis , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos/microbiología , Genoma Viral , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Viral/genética , ARN Viral/metabolismo , ADN Polimerasa Dirigida por ARN/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
The human papillomavirus (HPV) type 16 enhancer-promoter has been shown to be active in human fibroblasts with a deletion on the short arm of one chromosome 11 (karyotype 46,del(11)(p11.11p15.1)) but is virtually inactive in diploid human fibroblasts (Smits, Smits, Jebbink, and ter Schegget, 1990b, Virology, 176, 158-165). In diploid human embryonic fibroblasts, activation of the HPV16 enhancer-promoter could be achieved by expression of the SV40 small t. By cotransfecting SV40 small t cDNA together with HPV16 DNA into diploid cells, it was possible to increase the transforming activity of HPV16 by 10- 15-fold. Furthermore, SV40 small t was essential for the SV40 large T-induced morphological transformation of human diploid fibroblasts, whereas SV40 small t was dispensable for transformation of del-11 cells. We propose that, as a result of the deletion of loci on the short arm of chromosome 11 in del-11 cells, functions are expressed that mimic those of SV40 small t in transformation and trans-activation.
Asunto(s)
Antígenos Transformadores de Poliomavirus/metabolismo , Transformación Celular Viral , Cromosomas Humanos Par 11 , Papillomaviridae/genética , Transactivadores/metabolismo , Transcripción Genética , Línea Celular , Deleción Cromosómica , Diploidia , Elementos de Facilitación Genéticos , Humanos , Regiones Promotoras GenéticasRESUMEN
In order to determine the sensitivity of herpes simplex virus (HSV) isolates from immunocompromised patients treated with antiviral compounds, a retrospective study was carried out in the Clinical Virology Department of the University Medical Centre, Amsterdam. Virus isolates from four AIDS patients and one bone marrow transplant recipient were examined for their sensitivity for the antiviral compounds used by means of plaque reduction assay. In some of the virus isolates, from patients in whom resistance was assumed on clinical grounds, in vitro resistance of the HSV to acyclovir (ACV) could be demonstrated, both after oral and after parenteral administration. There was a clear correlation between the clinical course of the HSV infection and in vitro resistance. ACV resistant virus isolates were sensitive to foscarnet, both clinically and in vitro. In immunocompromised patients treated for some time with ACV for HSV infection, resistance should be considered at lack of results or progression of the lesion and when necessary be demonstrated in vitro. Alternative therapy then consists of intravenous foscarnet treatment.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Aciclovir/farmacología , Herpes Simple/microbiología , Adulto , Antivirales/uso terapéutico , Trasplante Óseo/inmunología , Farmacorresistencia Microbiana , Femenino , Foscarnet , Herpes Simple/tratamiento farmacológico , Humanos , Masculino , Ácido Fosfonoacético/análogos & derivados , Ácido Fosfonoacético/uso terapéutico , Estudios Retrospectivos , Simplexvirus/efectos de los fármacos , Simplexvirus/aislamiento & purificaciónRESUMEN
Twenty commercial batches of calf serum, obtained from several suppliers, were tested for the presence of bovine polyomavirus (BPyV) DNA and antibodies against the virus. Using polymerase chain reaction (PCR) technology, BPyV DNA was detected in 70% of the batches; no BPyV was detected in any of the negative control samples. The specificity of the amplification reactions was proven by hybridization. PCR results were confirmed by virus isolation experiments performed with five PCR-positive and five PCR-negative serum batches. The results indicate that the use of calf serum to supplement tissue culture media involves a serious risk of contaminating cell cultures with BPyV. No correlation was observed between the presence or absence of anti-BPyV immunoglobulins and the detection of BPyV-specific DNA sequences in the serum batches.
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Bovinos/microbiología , ADN Viral/sangre , Poliomavirus/aislamiento & purificación , Animales , Anticuerpos Antivirales/sangre , Secuencia de Bases , Técnica del Anticuerpo Fluorescente , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
We describe two rapid, simple, and reliable procedures for routine purification of hepatitis B virus (HBV) DNA from serum. HBV DNA could be purified from 24 serum samples in 1.5 to 2 h and was recovered in the initial reaction vessel. Both procedures have in common that HBV DNA is complexed with silica particles in the chaotropic agent guanidinium thiocyanate (GuSCN) but differ in lysis conditions and in the conditions used to elute HBV DNA from the silica particles after purification of the silica-DNA complexes. In one procedure (protocol H), serum HBV lysis was mediated by sodium dodecyl sulfate-proteinase treatment and HBV DNA was subsequently complexed with silica particles in the presence of GuSCN. After washing and drying of the silica-DNA complexes, HBV DNA was eluted from the silica particles in a low-salt buffer. In the other procedure (protocol Y*), serum HBV was directly lysed in GuSCN and HBV DNA was simultaneously complexed with silica particles. After washing and drying of the complexes, HBV DNA was eluted by proteinase treatment in low-salt buffer. Omission of proteinase treatment prevented efficient elution, presumably because of copurification of the protein which is covalently bound to the HBV DNA genome. We show, by Southern blot analysis, that HBV DNA could be reproducibly purified from human serum with the same yields by either procedure (30 to 50% relative to a classic procedure) and apparently independent of serum composition. HBV DNA purified by either method was a good substrate in the polymerase chain reaction compared with DNA purified by the classic procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
ADN Viral/sangre , Virus de la Hepatitis B/aislamiento & purificación , Secuencia de Bases , ADN Viral/genética , Estudios de Evaluación como Asunto , Hepatitis B/sangre , Hepatitis B/diagnóstico , Hepatitis B/microbiología , Virus de la Hepatitis B/genética , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Factores de Tiempo , Virología/métodosRESUMEN
The complete sequence of the genome of bovine polyomavirus (BPyV), formerly known as the CK isolate of the stump-tailed macaque virus, is presented. The genomic organization of BPyV is similar to that of the non-rodent polyomaviruses. With a genome size of 4697 bp, BPyV has the smallest polyomavirus genome known so far. When compared to simian virus 40 (SV40), the shortness of the BPyV genome is due mainly to differences in the coding capacity of the BPyV early region. The first exon of the proposed large T antigen encodes only 35 amino acids; also, a coding region corresponding to the C-terminal 64 amino acids of the SV40 large T antigen is absent in BPyV. It is proposed that the nucleotide sequence encompassing the small t antigen coding sequence contains an intron sequence of 71 nucleotides. Together the two exon sequences encode a 124 amino acid protein. We conclude that this may be the first example of a polyomavirus that has a small t antigen which is translated from two exon sequences. The enhancer region of BPyV does not show homology to the SV40 enhancer sequences. An agnogene is present with a coding capacity of 118 amino acid residues. The highest degree of homology to SV40 and PyV is present in the VP1 molecule.
Asunto(s)
Genes Virales , Poliomavirus/genética , Secuencia de Aminoácidos , Animales , Antígenos Virales , Antígenos Virales de Tumores/genética , Secuencia de Bases , Bovinos , ADN Viral/genética , Datos de Secuencia Molecular , Procesamiento Postranscripcional del ARN , Empalme del ARN , ARN Viral/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Homología de Secuencia de Ácido Nucleico , Proteínas Virales/genética , Proteínas Reguladoras y Accesorias ViralesRESUMEN
We utilized the RNA polymerase chain reaction (PCR) to analyse the transcripts of the E6/E7 open reading frames of human papillomavirus type 16 (HPV-16). Total RNA was isolated from 14 cervical squamous carcinomas, nine cervical intraepithelial neoplasias and from human fibroblasts transformed with different HPV-16 constructs. In all specimens two spliced transcripts were detected. Sequence analysis of the cloned PCR products showed that both transcripts were generated by splicing out an intron in E6, from nucleotides (nt) 226 to 409 in one transcript and from nt 226 to 526 in the other. The major transcript present in all RNA specimens had the smallest intron in E6. The RNA PCR described here is the method of choice for analysing splice and donor sites in tissue specimens where a limited amount of RNA is available. Results obtained with transformed cells revealed no difference in splicing whether HPV-16 was controlled by its homologous promoter or by a heterologous promoter, the Rous sarcoma virus long terminal repeat.
Asunto(s)
Transformación Celular Viral , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Empalme del ARN , Neoplasias del Cuello Uterino/microbiología , Secuencia de Bases , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/microbiología , Células Cultivadas , Femenino , Fibroblastos , Humanos , Datos de Secuencia Molecular , Proteínas E7 de Papillomavirus , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/genética , Lesiones Precancerosas/microbiología , ARN Viral/genética , Transcripción Genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
We have developed a simple, rapid, and reliable protocol for the small-scale purification of DNA and RNA from, e.g., human serum and urine. The method is based on the lysing and nuclease-inactivating properties of the chaotropic agent guanidinium thiocyanate together with the nucleic acid-binding properties of silica particles or diatoms in the presence of this agent. By using size-fractionated silica particles, nucleic acids (covalently closed circular, relaxed circular, and linear double-stranded DNA; single-stranded DNA; and rRNA) could be purified from 12 different specimens in less than 1 h and were recovered in the initial reaction vessel. Purified DNA (although significantly sheared) was a good substrate for restriction endonucleases and DNA ligase and was recovered with high yields (usually over 50%) from the picogram to the microgram level. Copurified rRNA was recovered almost undegraded. Substituting size-fractionated silica particles for diatoms (the fossilized cell walls of unicellular algae) allowed for the purification of microgram amounts of genomic DNA, plasmid DNA, and rRNA from cell-rich sources, as exemplified for pathogenic gram-negative bacteria. In this paper, we show representative experiments illustrating some characteristics of the procedure which may have wide application in clinical microbiology.
Asunto(s)
ADN/aislamiento & purificación , ARN/aislamiento & purificación , ADN/sangre , ADN/orina , ADN Circular/sangre , ADN Circular/aislamiento & purificación , ADN de Cadena Simple/sangre , ADN de Cadena Simple/aislamiento & purificación , Electroforesis en Gel de Agar , Eucariontes , Vidrio , Humanos , Microesferas , ARN/sangre , ARN/orina , ARN Ribosómico/aislamiento & purificación , ARN Ribosómico/orina , Dióxido de SilicioRESUMEN
Eighteen asymptomatic men with persistent human immunodeficiency virus type 1 (HIV-1) p24 antigenemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and thereafter with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 92 weeks. Six additional HIV-1 p24 antigenemic subjects were treated with zidovudine 500 mg 12-hourly for 76 weeks. Disease progression occurred in 4 subjects, despite sustained reduction of serum HIV-1 p24 antigen levels: Pneumocystis carinii pneumonia was diagnosed after 60, 80, 90 and 93 weeks, respectively. The median CD4+ cell count of these 4 men at study entry was 0.2 x 10(9)/l, and it declined to 0.07 x 10(9)/l at the moment AIDS was diagnosed. In 20 subjects no disease progression occurred. The median CD4+ cell count of these 20 men at study entry was 0.4 x 10(9)/l and it was 0.45 x 10(9)/l at the end of the study period. Median serum HIV-1 p24 antigen levels at the end of the study period were 42% lower than at study entry in these 20 subjects. In 5/20 men, an initial decline was followed by a rise in antigen levels to above pretreatment value. Treatment with zidovudine was well tolerated. Anemia caused symptoms in 3/24 men, but prolonged leucopenia or neutropenia did not occur. None developed clinical or convincing biochemical evidence of zidovudine-associated myopathy.