Biomedical subjects

A Krol

Publications and source records attributed to A Krol.

At least 55 records · Page 3Linked to original sources

PubMed1998

An essential non-Watson-Crick base pair motif in 3'UTR to mediate selenoprotein translation.

The SECIS element is an RNA hairpin in the 3'UTR of selenoprotein mRNAs required for decoding UGA selenocysteine codons. Our experimentally derived 2D structure model for the SECIS RNA revealed the conservation of four consecutive non-Watson-Crick base pairs, with a central G.A/A.G tandem. The present study was dedicated to gaining insight into the role of this quartet of base pairs. The effects of mutations introduced into the SECIS quartet of the glutathione peroxidase (GPx) cDNA, an enzyme with selenocysteine in its active center, were reported in vivo by the GPx activity. The detrimental consequence of an all-Watson-Crick mutant quartet disclosed the paramount importance of the non-Watson-Crick base pairs for GPx activity. Next, structure probing established that base pair changes in the central G.A/A.G tandem, predicted by the model to be structurally unfavorable, effectively led to local opening of the helix at the quartet. A concomitant abolition of GPx activity was observed, arising from translational impairment of full-length GPx. In contrast, an isosteric base pair replacement in the tandem did not affect base pairing in the quartet, leading to an almost wt GPx activity. Collectively, the data provided conclusive evidence for the functional relevance of these non-Watson-Crick base pairs in vivo, thus identifying a noncanonical RNA motif crucial to SECIS function in mediating selenoprotein translation. Within the quartet, the prominent requirement for the central G.A/A.G tandem is highlighted, our previous structural model and the mutagenesis data presented here strongly arguing in favor of a sheared arrangement for the G.A base pairs. The SECIS RNA is therefore another member to be added to the growing list of RNAs containing building blocks of non-Watson-Crick base pairs, required for structure and/or function.

Amino Acid Sequence↗

PubMed1997

Staf, a promiscuous activator for enhanced transcription by RNA polymerases II and III.

Staf is a zinc finger protein that we recently identified as the transcriptional activator of the RNA polymerase III-transcribed selenocysteine tRNA gene. In this work we demonstrate that enhanced transcription of the majority of vertebrate snRNA and snRNA-type genes, transcribed by RNA polymerases II and III, also requires Staf. DNA binding assays and microinjection of mutant genes into Xenopus oocytes showed the presence of Staf-responsive elements in the genes for human U4C, U6, Y4 and 7SK, Xenopus U1b1, U2, U5 and MRP and mouse U6 RNAs. Using recombinant Staf, we established that it mediates the activating properties of Staf-responsive elements on RNA polymerase II and III snRNA promoters in vivo. Lastly a 19 bp consensus sequence for the Staf binding site, YY(A/T)CCC(A/G)N(A/C)AT(G/C)C(A/C)YY-RCR, was derived by binding site selection. It enabled us to identify 23 other snRNA and snRNA-type genes carrying potential Staf binding sites. Altogether, our results emphasize the prime importance of Staf as a novel activator for enhanced transcription of snRNA and snRNA-type genes.

Animals↗

PubMed1997

Laser-based microfocused x-ray source for mammography: feasibility study.

A laser-produced plasma (LPP) x-ray source with possible application in mammography was created by focusing a laser beam on a Mo target. A Table-Top-Terawatt (TTT) laser operating at 1 J energy per pulse was employed. A dual pulse technique was used. Maximum energy transfer (approximately 10%) from laser light to hot electrons was reached at a 150 ps delay between pulses and the conversion efficiency (hard x-ray yield/laser energy input) was approximately 2 x 10(-4). The created LPP x-ray source is characterized by a very small focal spot size (tens of microns), Gaussian brightness distribution, and a very short pulse duration (a few ps). The spectral distribution of the generated x rays was measured. Images of the focal spot, using a pinhole camera, and images of a resolution pattern and a mammographic phantom were obtained. The LPP focal spot modulation transfer function for different magnification factors was calculated. We have shown that the LPP source in conjunction with a spherically bent, high throughput, crystal monochromator in a fixed-exit Rowland circle configuration can be used to created a narrow band tunable mammography system. Tunability to a specific patient breast tissue thickness and density would allow one to significantly improve contrast and resolution (exceeding 20 lp/mm) while lowering the exposure up to 50% for thicker breasts. The prospects for the LPP x-ray source for mammographic application are discussed.

Biophysical Phenomena↗

PubMed1997

Solution structure of SECIS, the mRNA element required for eukaryotic selenocysteine insertion--interaction studies with the SECIS-binding protein SBP.

Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally incorporated at UGA codons which usually act as translation stop codons. In eukaryotes, decoding of selenocysteine necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3'-untranslated region of selenoprotein mRNAs. A detailed experimental study of the secondary structures of the SECIS elements of rat and human type 1 iodothyronine deiodinases and rat glutathione peroxidase was performed. Enzymatic and chemical structure probing led us to propose a secondary structure model, supported by sequence comparison of 23 SECIS mRNAs. The secondary structure model revealed the existence of a novel type of RNA motif composed of four consecutive non-Watson-Crick base-pairs. Using gel shift experiments, we identified in several mammalian cell type extracts the protein SBP, for SECIS-binding protein, that specifically recognizes the iodothyronine deiodinases and glutathione peroxidase SECIS elements. The structural model that we derived for the SECIS RNAs discloses RNA features possibly implicated in the binding of SBP and/or SECIS function.

Animals↗

PubMed1996

Euthanasia and physician-assisted suicide in homosexual men with AIDS.

BACKGROUND: In the Netherlands a nationwide study has shown that, in 38% of deaths, there have been medical decisions concerning the end of life (MDEL); 2.1% of all deaths were brought about by euthanasia or physician- assisted suicide (PAS). We investigated the incidence of MDEL in homosexual men with AIDS, suspecting that it might be higher, and studied the effect of euthanasia/PAS on survival time. METHODS: The patients were 131 male homosexual participants in a cohort study in Amsterdam, diagnosed between 1985 and 1992 as having AIDS; all had died before Jan 1, 1995. Clinical and laboratory data and information on mode of death were obtained from their physicians and by review of hospital records. Those who died by euthanasia/PAS or in whom there had been other MDEL were then compared with those who died naturally. FINDINGS: 29 men (22%) had died by euthanasia/PAS and in 17 (13%) another MDEL had been made; thus, more than one-third of these men had made medical decisions concerning the end of life. The greatest difference between the groups was in age at time of diagnosis-72% aged 40 or more in the euthanasia/PAS group compared with 38% in the natural death group. The likelihood (relative risk) of euthanasia/PAS increased with duration of survival after AIDS diagnosis. Comparison of the groups in terms of three laboratory markers (CD4+ and CD8+ cells and phytohaemagglutinin responses) in the two years before death, and estimates of these markers at the time of death, did not indicate any substantial shortening of life by euthanasia/PAS; in the judgment of the physicians, most of these patients would have died naturally within one month. INTERPRETATION: A possible reason for the high incidence of MDEL in this cohort was a good knowledge of the characteristics of AIDS acquired through long-term awareness of HIV infection. The higher rate of euthanasia in those with long survival from AIDS diagnosis could reflect either additional suffering or the greater opportunity to discuss this option with friends and physicians. Our findings indicate that euthanasia and other MDEL did little to shorten life; rather, they were an extreme form of palliation, applied in the terminal phase of a lethal disease.

Acquired Immunodeficiency Syndrome↗

PubMed1996

A protein binds the selenocysteine insertion element in the 3'-UTR of mammalian selenoprotein mRNAs.

Several gene products are involved in co-translational insertion of selenocysteine by the tRNA(Sec). In addition, a stem-loop structure in the mRNAs coding for selenoproteins is essential to mediate the selection of the proper selenocysteine UGA codon. Interestingly, in eukaryotic selenoprotein mRNAs, this stem-loop structure, the selenocysteine insertion sequence (SECIS) element, resides in the 3'-untranslated region, far downstream of the UGA codon. In view of unravelling the underlying complex mechanism, we have attempted to detect RNA-binding proteins with specificity for the SECIS element. Using mobility shift assays, we could show that a protein, present in different types of mammalian cell extracts, possesses the capacity of binding the SECIS element of the selenoprotein glutathione peroxidase (GPx) mRNA. We have termed this protein SBP, for Secis Binding Protein. Competition experiments attested that the binding is highly specific and UV cross-linking indicated that the protein has an apparent molecular weight in the range of 60-65 kDa. Finally, some data suggest that the SECIS elements in the mRNAs of GPx and another selenoprotein, type I iodothyronine 5' deiodinase, recognize the same SBP protein. This constitutes the first report of the existence of a 3' UTR binding protein possibly involved in the eukaryotic selenocysteine insertion mechanism.

Animals↗

PubMed1996

Comparison of measured and calculated dose for asymmetric x-ray beams defined by independently movable collimators.

Linear accelerators with x-ray collimators that move independently are becoming increasingly common for treatment with asymmetric fields. In an asymmetric field, the center of the treatment field is away from the true central axis where dosimetric data are normally obtained. In this paper we present a simplified approach to the calculation of dose for asymmetric fields. We use central axis tissue-maximum ratio, off-axis factor in phantom and relative field-size factor in phantom to calculate dose. The accuracy of our calculations has been compared with ion-chamber measurements for 6 and 15 MV x-ray beams. Measurements were made at 5, 10, and 15 cm off-axis for a 20 cm x 20 cm asymmetric field at dmax and 6 cm depths in a solid-water phantom using a 0.6 cc Farmer chamber. Agreement within 3% was found at the measurement points.

Equipment Design↗

PubMed1996

RNAs mediating cotranslational insertion of selenocysteine in eukaryotic selenoproteins.

Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. Its biosynthesis and cotranslational insertion into selenoproteins is performed by an outstanding mechanism, implying the participation of several gene products. The tRNA(Sec) is one of these. In eukaryotes, its transcription mode by RNA polymerase III differs from that of classical tRNA genes, both at the level of the promoter elements and transcription factors involved. In addition, enhanced transcription is afforded by a newly characterized zinc finger activator. Not only transcription of the gene, but also the tRNA(Sec) itself is atypical since its 2D and 3D structures exhibit features which set it apart from classical tRNAs. Decoding of eukaryotic selenocysteine UGA codons requires a stem-loop structure in the 3'UTR of mRNAs, the selenocysteine insertion sequence (SECIS) element. Structure probing and sequence comparisons led us to propose a 2D structure model for the SECIS element, containing a novel RNA motif composed of four consecutive non-Watson-Crick base-pairs. A 3D model, rationalizing the accessibility data, was elaborated by computer modeling. It yields indicative or suggestive evidence for the role that could play some conserved residues and/or structural features in SECIS function. These might act as signals for interaction with SBP, the SECIS binding protein that we have characterized.

Animals↗

PubMed1996

Complications of varicella zoster virus reactivation in HIV-infected homosexual men.

OBJECT: To study the complication rate of varicella zoster virus (VZV) reactivation and the relationship between complications, presentation and localization of zoster and immune function in HIV disease. DESIGN AND METHODS: A total of 142 episodes of VZV reactivation in 113 out of 544 HIV-1-infected participants in the Amsterdam Cohort Study of homosexual men were studied. Persistent hyperkeratotic or necrotic skin lesions, post-herpetic neuralgia, other neurological events, ocular events and pneumonitis occurring within 6 months of the onset of the last episode of VZV reactivation were defined as complications, provided that other possible diagnoses were excluded and the event had been previously described in the literature as related to VZV reactivation. RESULTS: Twenty-four complications occurred in 15 (11%) of these 142 episodes. Complications occurred exclusively in the 40 episodes with either multidermatomal or disseminated presentation, or a trigeminal localization, or both. In the group of episodes of unidermatomal zoster at a non-trigeminal localization no complications occurred. Twenty-one episodes of herpes zoster were localized in the trigeminal area. Localization was not significantly associated with the level of immune function. Compared to unidermatomal presentation (n = 120), multidermatomal (n = 15) and disseminated presentation (n = 7) occurred at lower median CD4+ cell counts (330, 240 and 50 x 10(6)/l, respectively; P = 0.003) and significantly lower levels of CD3 monoclonal antibodies or phytohaemagglutinin-induced T-cell reactivity in vitro. Complications were related to CD4+ cell counts, but in the cases of disseminated, multidermatomal or trigeminal zoster a CD4+ cell measurement provided no additional information on the risk of complications. CONCLUSION: In HIV-infected individuals the extent of the clinical presentation and the occurrence of complications of VZV reactivation are related to the degree of immunodeficiency. In episodes of VZV reactivation with either multidermatomal or disseminated presentation or a trigeminal localization, or both the complication rate was high. CD4+ cell counts provided no additional information on the complication risk. Oral acyclovir appears to be sufficient as therapy for unidermatomal zoster at a non-trigeminal localization.

Acyclovir↗

PubMed1996

Scatter reduction in mammography with air gap.

Scatter reduction by air gaps in mammography was investigated. We have experimentally demonstrated that, independently of the imaging geometry, scatter in air-gap mammography can be well described by a virtual source of scatter (VSS) model. This model postulates that scatter radiation originates from a virtual point source of scatter placed on the central axis between the x-ray source and the exit surface of a patient at distance delta and utilizes only two parameters: delta and (S/P)0. The (S/P)0 parameter represents scatter-to-primary ratio without an air gap and delta is the distance from the exit surface of a patient to the virtual source of scatter. We have experimentally determined the analytical form of the two independent parameters of the VSS model; delta exhibits a linear increase proportional to the radiation field size, does not depend on patient thickness, and is in the 10-30 cm range, while (S/P)0 increases with the field size as a power function and is in the 0.4-1.3 range. In the framework of the VSS model the selectivity, the contrast improvement factor, and the signal-to-noise improvement factor were employed to evaluate performance of air-gap mammography systems. We have demonstrated that selectivity of an air gap rapidly deteriorates at some well-defined critical value of scatter fraction that has profound consequences on air-gap performance. Assuming fixed patient exposure, the results shows that, if a contrast limited detection system (such as film/screen mammography) is used, an air gap system can outperform a grid system only if a very large source-to-patient (SPD) distance is utilized, which might be possible with new laser-based x-ray sources. For the noise limited detection systems (such as digital mammography) even a small SPD (70 cm) and a small air-gap (20 cm) system will outperform a grid system.

Air↗

PubMed1996

A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs.

In eukaryotes, co-translational insertion of selenocysteine into selenoproteins necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3'-untranslated region of selenoprotein mRNAs. We report a detailed experimental study of the secondary structures of the SECIS elements of three selenoprotein mRNAs, the rat and human type I iodothyronine deiodinase (5'DI) and rat glutathione peroxidase (GPx). Based on RNase and chemical probing, a new secondary structure model is established. It is characterized by a stem-loop structure, comprising two helices (I and II) separated by an internal loop, with an apical loop surmounting helix II. Sequence comparisons of 20 SECIS elements, arising from 2 5'DI, 13 GPx, 2 selenoprotein P, and 1 selenoprotein W mRNAs, confirm the secondary structure model. The most striking finding of the experimental study concerns a set of conserved sequences in helix II that interact to form a novel RNA structural motif consisting of a quartet composed of non-Watson-Crick base pairs 5'UGAY3': 5'UGAU3'. The potential for forming the quartet is preserved in 15 SECIS elements, but three consecutive non-Watson-Crick base pairs can nevertheless form in the other five SECIS, the central G.A tandem being invariant in all cases. A 3D model, derived by computer modeling with the use of the solution data, suggests that the base pairing interactions in the G.A tandem are of the type found in GNRA loops. The 3D model displays the quartet lying in an accessible position at the foot of helix II, which is bent at the internal loop, suggesting that the non-Watson-Crick base pair arrangement provides an unusual pattern of chemical groups for putative ligand interaction.

Animals↗

PubMed1995

Native bovine selenocysteine tRNA(Sec) secondary structure as probed by two plant single-strand-specific nucleases.

Two single-strand-specific nucleases, discovered in plants, have been used to investigate the secondary and tertiary structures of the native bovine liver selenocysteine tRNA(Sec). To check the possible influence of nucleotide modifications on these structures, we compared the results obtained with the fully modified tRNA to the unmodified transcript prepared by in vitro T7 transcription of the Xenopus laevis tRNA(Sec) gene. We found that the structures in solution of the native tRNA(Sec) and the transcript are very similar despite some differences in accessibility to the enzymatic probes. Indeed, the modified anticodon-loop of native bovine tRNA(Sec), containing 5-methylcarboxymethyluridine (mcm5U34) and N6-isopentenyladenosine (i6A37), is less accessible to Rn nuclease than that of the transcript: the intensity of bands representing cuts at A36 and A38 is much lower as compared to those of the transcript, whereas no cuts were found at the level of i6A37 in the anticodon loop of the native molecule. Surprisingly, the variable arm of the native molecule has been found to be more susceptible to single-strand-specific nuclease action, suggesting a looser structure of the variable arm in native bovine tRNA(Sec) than in the transcript.

Animals↗

PubMed1995

Selenocysteylation in eukaryotes necessitates the uniquely long aminoacyl acceptor stem of selenocysteine tRNA(Sec).

Selenocysteine synthesis is achieved on a specific tRNA, tRNA(Sec), which is first charged with serine to yield seryl-tRNA(Sec). Eukaryotic tRNA(Sec) exhibits an aminoacyl acceptor stem with a unique length of 9 base pairs. Within this stem, two base pairs, G5a.U67b and U6.U67, drew our attention, whose non-Watson-Crick status is maintained in the course of evolution either through U6.U67 base conservation or base covariation at G5a.U67b. Single or double point mutations were performed, which modified the identity of either or both of the base pairs. Serylation by seryl-tRNA synthetase was unaffected by substitutions at either G5a.U67b or U6.U67. Instead, and quite surprisingly, changing G5a.U67b and U6.U67 to G5a-C67b/U6.G67 or G5a-C67b/C6-G67 gave rise to a tRNA(Sec) mutant exhibiting a gain of function in serylation. This finding sheds light on the negative influence born by a few base pairs in the acceptor stem of tRNA(Sec) on its serylation abilities. The tRNA(Sec) capacities to support selenocysteylation were next examined with regard to a possible role played by the two non-Watson-Crick base pairs and the unique length of the acceptor stem. It first emerges from our study that tRNA(Sec) transcribed in vitro is able to support selenocysteylation. Second, none of the point mutations engineered at G5a.U67b and/or U6.U67 significantly modified the selenocysteylation level. In contrast, reduction of the acceptor stem length to 8 base pairs led tRNA(Sec) to lose its ability to efficiently support selenocysteylation. Thus, our study provides strong evidence that the length of the acceptor stem is of prime importance for the serine to selenocysteine conversion step.

Acylation↗

PubMed1995

Staf, a novel zinc finger protein that activates the RNA polymerase III promoter of the selenocysteine tRNA gene.

The selenocysteine tRNA gene (tRNA(Sec)) is atypical. Though transcribed by RNA polymerase III like all other tRNA genes, its basal promoter elements are distinct and reside essentially upstream of the coding region. In addition, transcription from the basal promoter is activated by a 15 bp activator element. In this report we describe the cloning and functional characterization of Staf (selenocysteine tRNA gene transcription activating factor), a novel Xenopus laevis transcription factor which binds to the tRNA(Sec) activator element and mediates its activation properties. The 600 amino acid Staf protein contains seven zinc fingers and a separate acidic activation domain. Seven highly conserved regions were detected between Staf and human ZNF76, a protein of unknown function, thereby aiding in predicting the locations of the functional domains of Staf. With the use of a novel expression assay in X.laevis oocytes we succeeded in demonstrating that Staf can activate the RNA polymerase III promoter of the tRNA(Sec) gene. This constitutes the first demonstration of the capacity of a cloned factor to activate RNA polymerase III transcription in vivo.

Amino Acid Sequence↗

PubMed1995

Age at menarche and breast cancer risk in nulliparous women.

Early age at menarche is a known risk factor for breast cancer, some inconsistency in the literature not withstanding. Relative risks for an early menarcheal onset as compared to a late onset vary from 1.0 to 1.9. To avoid (residual) confounding by parity-related factors a case-control study was conducted among nulliparous women. 135 cases and 540 controls were selected from two population-based screening projects for breast cancer in The Netherlands. Four controls were matched to each case for year of birth, for screening-centre, and for number of screening examinations. Women with a menarcheal age of 10 or 11 years showed a 2.2 times (95% confidence interval: 1.2-4.0) higher risk for breast cancer compared to women who had their first menstrual period at 12 years of age or older.

Adolescent↗

PubMed1995

Transmission maximum-likelihood reconstruction with ordered subsets for cone beam CT.

An iterative algorithm is presented for accelerated reconstruction of cone beam transmission CT data (CBCT). CBCT supplies an attenuation map for SPECT attenuation compensation and anatomical correlation. Iterative algorithms are necessary to reduce truncation artifacts and 3D reconstruction artifacts. An existing transmission maximum-likelihood algorithm (TRML) is accurate but the reconstruction time is too long. The new algorithm is a modified EM algorithm, based on ordered subsets (OSEM). OSEM was evaluated in comparison to TRML using a thorax phantom and a 3D Defrise phantom. A wide range of image measures were evaluated, including spatial resolution, noise, log likelihood, region quantification, truncation artifact removal, and 3D artifact removal. For appropriate subset size, OSEM produced essentially the same image as TRML, but required only one-tenth as many iterations. Thus, adequate images were available in two to four iterations (20-30 min on a SPARC 2 workstation). Further, OSEM still approximately maximizes likelihood: divergence occurs only for very high (and clinically irrelevant) iterations. Ordered subsets are likely to be useful in other geometries (fan and parallel) and for emission CT as well. Therefore, with ordered subsets, high-quality iterative reconstruction is now available in clinically practical reconstructions times.

Algorithms↗

PubMed1995

The predictive value of T cell function in vitro and pre-AIDS zidovudine use for survival after AIDS diagnosis in a cohort of homosexual men in Amsterdam.

The best independent predictors of survival after AIDS diagnosis were determined in 160 homosexual men from the Amsterdam Cohort Study (1987 CDC case definition). In a Cox model, all pre-AIDS laboratory markers gathered during follow-up in the study did not independently predict survival after AIDS. A second analysis, using data available only at AIDS diagnosis, revealed that T cell reactivity after stimulation with phytohemagglutinin and monoclonal CD3 antibodies and the CD4+ cell count at diagnosis were independent predictors of survival. In an interval-based Cox model, the predictive value of pre-AIDS zidovudine use was determined. One year after AIDS diagnosis, participants with pre-AIDS zidovudine use had a worse survival probability (relative hazard = 3.99). In conclusion, the survival probability of homosexual men with AIDS can be estimate adequately using information obtained at clinical AIDS diagnosis. Analysis revealed the important predictive value of T cell function tests in vitro.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Herpes zoster, immunological deterioration and disease progression in HIV-1 infection.

OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. RESULTS: The incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositives the incidence was 31.2 per 1000 PY at CD4+ cells > or = 500 x 10(6)/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (CI), 0.78-2.94] at CD4+ cells 200-499 x 10(6)/l and 97.5 per 1000 PY (RR, 3.13; 95% CI, 1.54-6.32) at CD4+ cells < 200 x 10(6)/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% CI, 1.1-2.4) and for death 1.7 (95% CI, 1.1-2.5), but these were not independent from CD4+ cell counts. CONCLUSION: In HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.

Adult↗