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K Dörries

Publications and source records attributed to K Dörries.

At least 19 recordsLinked to original sources
PubMed2000

Clinical course and treatment of haemorrhagic cystitis associated with BK type of human polyomavirus in nine paediatric recipients of allogeneic bone marrow transplants.

UNLABELLED: Of a total of 117 bone marrow transplant (BMT) recipients in the period from August 1988 to November 1995, 9 (7.7%) developed haemorrhagic cystitis. This condition was characterized in all nine patients by late onset (day +24 to +50 post-BMT), long duration (1 to 7 weeks), and the excretion of BK virus in the urine, as confirmed by electron microscopy, DNA hybridization and PCR analysis. Adenovirus was not involved. The serological assessment of BK virus-specific IgM and IgG pre- and post-BMT is consistent with viral reactivation in all patients, although a primary infection cannot be absolutely excluded in a single patient. A significant correlation between the use of high-dose busulphan (16 mg/kg) in the preparative regimen and development of haemorrhagic cystitis (P = 0. 0003) was evident. The severe course of the disease in two patients resulted in bladder tamponade; bleeding could not be inhibited with coagulation and laser treatment. Deterioration was prevented by bladder irrigation via a suprapubic catheter. Remission occurred spontaneously in all patients. CONCLUSION: BK virus induced haemorrhagic cystitis in a paediatric bone marrow transplantation recipients is characterized by late onset, long duration, viral reactivation and correlates to high-dose busulphan. Severe bleeding could not be influenced by surgical intervention.

Adolescent↗
PubMed2000

Quantification of human polyomavirus JC in brain tissue and cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy by competitive PCR.

Activation of human polyomavirus JC (JCV) infection is the cause of the central nervous system (CNS) disease progressive multifocal leukoencephalopathy (PML). Previous studies with uncontrolled quantification systems suggested that the virus load in the CNS correlates with the state of disease and might reflect therapeutic effects. Therefore the aim of this study was the development of a competitive system with standard PCR techniques that allowed rapid detection of JCV subtypes, simultaneous differentiation of the two human polyomaviruses JCV and BKV and absolute quantification of the virus burden in initial diagnosis and progressive disease states. Subtype- and species-specificity of the PCR was achieved with the development of a degenerative PCR primer pair that detected JCV DNA in a range regularly found in PML samples, but did not amplify BKV DNA. The accuracy of the system was evaluated by quantification of known amounts of cloned JCV DNA with a competitive JCV-specific template that exhibited a comparable amplification rate to that of the native product. The calibration study demonstrated a linear correlation over a wide range of DNA concentrations on the background of buffer or JCV-negative diagnostic samples. The reliability of the system for PML diagnosis was analysed by calibration and determination of the virus burden in tissue and cerebrospinal fluid (CSF) of 11 PML patients confirming the accuracy in both types of samples under diagnostic conditions. Comparison of the JCV DNA concentration in tissue and CSF by a tightly controlled quantification technique revealed for the first time differences in a range of about four orders of magnitude and a variable virus load in CSF samples taken at comparable states of disease. This pointed to an individual course of virus shedding and demonstrates that a controlled competitive PCR system of high accuracy is essential for reliable quantification of virus DNA either in initial diagnosis, in progressive disease or for the evaluation of therapeutic effects.

AIDS-Related Opportunistic Infections↗
PubMed1999

Quantification of JC virus DNA in the cerebrospinal fluid of patients with human immunodeficiency virus-associated progressive multifocal leukoencephalopathy--a longitudinal study.

In progressive multifocal leukoencephalopathy (PML) the JC virus (JCV) load in the cerebrospinal fluid (CSF) is discussed as a parameter for disease progression. To investigate the evolution of viral shedding into the CSF, the JCV DNA concentration was quantified by competitive polymerase chain reaction (PCR) in multiple CSF samples from prior to and during an unsuccessful intrathecal salvage therapy in 2 human immunodeficiency virus-infected patients with biopsy-proven PML. With continuous clinical progression the virus load varied considerably intra- and interindividually, ranging from nondetectable to 1.2x108 genome equivalents/10 microliter CSF. Whereas an overall increase during progressive disease was confirmed, the virus burden was either constant or fluctuated irregularly during the intermediate stage of disease. This shows a variability of viral shedding during active disease that must be taken into account when the JCV load is measured by quantitative PCR for both the diagnosis of PML and monitoring under investigational treatment.

AIDS-Related Opportunistic Infections↗
PubMed1998

Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue.

The question of a possible role for JC virus (JCV) genomic rearrangements in the pathogenesis of progressive multifocal leukoencephalopathy (PML) was addressed by analysis of the genomic complexity and the transcriptional control region (TCR) of the JCV DNA population in persistently infected CNS and kidney tissue. After cloning of full-length viral DNA, no extensive changes were detected in the coding regions of the JCV genome by restriction analysis suggesting an intact JCV DNA population. For further analysis of the distribution of JCV subtypes, the non-coding region was amplified by PCR. Molecular analysis revealed homogeneous JCV TCR populations in almost 50% of the individuals. Heterogeneity was found in two CNS samples with three and five different JCV subtypes, respectively, and in four kidney specimens with two TCR subtypes. Altogether, seven TCR subtypes were identified. One in each group represented single promoter element TCRs without duplication of sequences. The TCR of the major variant JCV-W1 was comparable in sequence and structure to that of the PML prototype JCV Mad-1 DNA. The identification of dominant PML-derived JCV TCR subtypes in most persistently infected individuals suggests that rearrangements of the JCV TCR can be associated with the persistent state of infection. However, it appears unlikely that PML-associated JCV subtypes are generated anew in each individual host in the course of persistence. The findings rather suggest that a limited number of stable JCV subtypes circulate in different geographical regions of the world.

Adult↗
PubMed1998

Nucleic acid detection as a diagnostic tool in polyomavirus JC induced progressive multifocal leukoencephalopathy.

Procedures involved in the diagnosis of JC virus central nervous system infection range from detection of virus specific products in biopsy material to demonstration of viral DNA in cerebrospinal fluid by PCR. Despite the fact that PCR is the most sensitive method for the detection of virus in clinical specimens, diagnostic evaluation is increasingly difficult in view of the possible subclinical activation of persistent JCV infection in the central nervous system of high risk patients. Therefore, PML diagnosis by molecular detection of JCV DNA in biopsy material was compared with diagnosis by PCR on CSF of patients with and without PML. Evaluation of the diagnostic techniques revealed that stereotactic biopsy based PCR diagnosis at present combines speed and sensitivity with the highest specificity available. Although the non invasive technique of JCV detection in CSF by PCR is even more sensitive leading to detection of about 20 genome equivalents per 1 microl of CSF, the specificity of the method is limited by subclinical presence of JCV DNA in CSF of neurologically asymptomatic HIV infected patients. Additionally, autopsy proven PML cases remaining JCV negative in PCR on CSF become a common finding. Therefore, in cases where biopsy is not performed, diagnosis of PML can only be achieved in combination with neurological and radiological diagnosis.

Brain↗
PubMed1998

Molecular biology and pathogenesis of human polyomavirus infections.

The two human polyomaviruses JC and BK are ubiquitous in the human population. Primary infection leads to lifelong persistence in the kidney, the CNS and in lymphoid cells. Virus is shed into the urine and is transmitted at least in part by the oral route. Under limited changes of the immunological state persistent polyomavirus infection is activated to an asymptomatic virus production. However, in severe long-lasting immunosuppression, highly effective virus multiplication can be accompanied by extended cytolytic damage of viral target cells leading to fatal disease. Whereas BKV is associated with severe urogenital disorders, JCV affects the CNS, leading to progressive multifocal leukoencephalopathy (PML). Although the number of PML cases is steadily increasing because of the AIDS epidemic, the mechanisms responsible for the change from asymptomatic-activated to the diseased state are not yet understood. As a possible pathogenic factor, the role of genomic heterogeneity of the transcriptional control region in the induction of disease is discussed.

BK Virus↗
PubMed1997

Diagnostic criteria and clinical procedures in HIV-1 associated progressive multifocal leukoencephalopathy.

The diagnosis of definite progressive multifocal leukoencephalopathy (PML) has been a neuropathological domain. We reviewed all Human Immunodeficiency Virus Type 1 (HIV-1) seropositive patients in our institution between 01.01.1989 and 31.12.1994 and identified 20/823 cases with PML by clinical and imaging criteria. Diagnosis was neuropathologically confirmed in 5 cases. Diagnostic criteria included rapid onset (< 2 weeks) of multifocal neurological signs and symptoms, advanced immunosuppression and asymmetric uni- or multifocal white matter lesions without mass effect, contrast enhancement or cortical atrophy in magnetic resonance imaging (MRI). The overall incidence of PML was stable over the observation period (approximately equal to 2.5%). The mean age at onset (41.7 years) was significantly lower compared to HIV-1 seronegative PML patients (peak in the sixth decade of life), male patients prevailed (100%). Mean survival (3.9 months) was extremely short. Human polyoma virus JC (JCV) polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) demonstrated a considerable rate of possible cerebral co-infection with HIV-1 and JCV as well as subclinical infection with JCV. Therefore demonstration of JCV deoxyribonucleic acid by PCR in the CSF alone is not sufficient for clinical PML diagnosis. We present diagnostic criteria on the basis of epidemiological, neuroradiological and CSF parameters that allow us to make the clinical diagnosis of PML. Although quick and safe, routine stereotactic brain biopsy is not necessary to confirm the diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Virus-host interactions and diagnosis of human polyomavirus-associated disease.

Persistent human polyomavirus infection is asymptomatic with limited states of virus production in the healthy individual, in immunocompromised patients, however, infection may lead to uncontrolled virus growth and fatal disease. Predominantly the CNS and in rare cases the urogenital tract are affected. During the AIDS epidemic, the number of cases is steadily increasing, thus dictating the need for an early and fast differential diagnosis. Virological diagnosis is essentially based on the detection of virus products in tissue or body fluids. Although sensitive and specific diagnostic techniques are available for the diagnosis of polyomavirus infection, widely accepted standards are not yet reached. This is in part due to the low number of cases in the past, but also to asymptomatic viral activation in nondiseased patients. Thus, additional parameters have to be evaluated to provide complementary tools for differential diagnosis.

BK Virus↗
PubMed1995

Focal brain lesions in patients with AIDS: aetiologies and corresponding radiological patterns in a prospective study.

We report the results of a hospital-based study of 188 consecutive patients seropositive for the human immune deficiency virus type 1 (HIV-1) who presented in a 4-year period (1988-1991) with possible signs or symptoms of first-ever central nervous system disease. Confirmed diagnoses were cerebral toxoplasmosis in 47 patients (25.0%), HIV-1 encephalopathy in 19 (10.1%), progressive multifocal leucoencephalopathy (PML) in 9 (4.8%), cerebral lymphoma in 1 (0.5%), and other conditions in 9 patients (4.8%). Seventy-three subjects (38.8%) showed focal brain lesions on initial computed tomography or magnetic resonance imaging, which were assessed prospectively. Positive predictivity for toxoplasmosis was 100% if multiple lesions occurred in combination with mass effect or contrast enhancement (23 patients), or if at least one space-occupying or enhancing lesion was located in the basal ganglia or the thalamus (26 patients). Solitary lesions with mass effect or contrast enhancement were seen in 26 patients and were caused by cerebral toxoplasmosis in 22 (84.6%). Eight of the 9 PML patients presented with one or more non-enhancing, non-mass lesions, although the predictive value of this pattern was low (47.1% for PML). Thus, in our epidemiological context, certain imaging findings in HIV-1-seropositive patients were highly predictive of cerebral toxoplasmosis. This may differ from findings from other parts of the world where cerebral toxoplasmosis may be less prevalent among HIV-1-infected individuals.

AIDS Dementia Complex↗
PubMed1995

Expression of human polyomavirus JC T antigen by an adenovirus hybrid vector and its binding to DNA sequences encompassing the JC virus origin of DNA replication.

In the search for factors that influence the outcome of human polyomavirus JC (JCV) infection, the roles not only of host-related immunological control but also of virus-dependent regulatory steps have to be taken into account. Besides cell-specific control of early expression of the multifunctional virus protein large tumour antigen (T Ag), control mechanisms involve individual steps of the DNA replication process. For the analysis of T Ag DNA binding, the protein was expressed by an adenovirus hybrid vector in the 293 cell line to provide saturating amounts of JCV T Ag. After determination of the size and immunoreactivity, functional activity was analysed by specific DNA binding. To avoid the interference of cellular proteins, T Ag was immunoprecipitated prior to the reaction. Binding to T Ag-binding sites I and II within a 141 bp DNA segment in the control region was analysed using deletion mutants of a JCV subtype from brain tissue of a patient with fatal central nervous system disease. The specificity of the binding was confirmed by recombinant T Ag binding to origin of DNA replication (ori) sequences of wild-type JCV genomes. These data document that recombinant T Ag overexpressed by the adenovirus vector in eukaryotic cells was JCV-specific, had the expected length and exhibited specific ori-binding activity, thus providing the essential tool for future analysis of virus-host interactions at the level of viral DNA replication.

Adenoviridae↗
PubMed1994

Infection of human polyomaviruses JC and BK in peripheral blood leukocytes from immunocompetent individuals.

Widely disseminated infection with the human polyomaviruses JC and BK is followed by lifelong asymptomatic viral persistence that can be reactivated under prolonged immunosuppression to fatal CNS and urogenital disease. In an attempt to understand the pathogenesis of polyomavirus diseases, we asked whether leukocytes are involved in polyomavirus infection in the immunocompetent host. Peripheral blood leukocytes from 29 immunocompetent individuals and umbilical cord blood from 10 newborn children were analyzed for the presence of polyomavirus DNA. Southern blot analysis demonstrated the presence of JCV-specific full-length virus genomes and indicated involvement of the second human polyomavirus BK. In contrast to specimens from newborn children, PCR amplification of target DNA in the adult age group followed by species-specific hybridization provided evidence of concomitant JCV and BKV infection in almost all specimens. Nucleotide sequencing of virus-specific products representing DNA segments essential for virus multiplication confirmed presence of both virus species in leukocytes. The detection of a new virus subtype and single base changes or deletions in the noncoding DNA region from individual cases suggested widespread heterogeneity in the circulating virus population, although the structure of the transcriptional control elements in all cases was comparable to highly active elements found in lytically infected cells. Those findings and the localization of both virus types in the nuclei of blood cells by in situ hybridization demonstrate that JCV and BKV frequently infect peripheral leukocytes and give strong evidence that leukocytes are common sites of polyomavirus persistence in healthy individuals.

BK Virus↗
PubMed1993

Disseminated BK type polyomavirus infection in an AIDS patient associated with central nervous system disease.

A 27-year-old man with hemophilia type A and acquired immunodeficiency syndrome developed a subacute meningoencephalitis, associated with a normotensive internal hydrocephalus, 14 weeks before his death. From cerebrospinal fluid and brain autopsy material, a virus could be isolated and was classified by Southern blot analysis and restriction endonuclease reactions as the human polyomavirus BK. The postmortem findings of polyomavirus antigen and BK virus DNA in various cell types of the kidneys, lungs, and central nervous system strongly suggest that BK virus was the causative agent of a tubulointerstitial nephropathy, an interstitial desquamative pneumonitis, and a subacute meningoencephalitis with accentuation of the ventricular and meningeal surfaces of the brain. Besides distinctive cytopathic effects, the presence of intranuclear inclusions was a prominent histopathological feature. Therefore, the human polyomavirus BK should be regarded as a new candidate on the still growing list of opportunistic pathogens in acquired immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗
PubMed1992

Evidence of human polyomavirus BK and JC infection in normal brain tissue.

Infection with the polyomaviruses JC and BK is ubiquitous in the human population and JCV is the only virus associated with the central nervous system disease progressive multifocal leukoencephalopathy. In the attempt to analyze the pathogenesis of polyomavirus infections we asked whether human polyomaviruses invade the brain during persistence. Brain autopsy material from 67 individuals with disorders other than PML was examined for the presence of polyomavirus DNA. Southern blot analysis demonstrated JCV-specific full-length virus genomes in healthy brain tissue in about 20% of the patients. Type-specific analysis with polymerase chain reaction and sequencing confirmed these data. Additionally, the presence of BKV DNA sequences covering an early gene fragment and the control region with flanking early and late protein coding sequences was detected. Cloning of the complete BKV genome from two cases supported the assumption that not only full-length JCV DNA was present in those tissue specimens but also BKV genomes. The data obtained demonstrate that dual infection of the brain with the polyomaviruses JCV and BKV is a common event and give strong evidence that both viruses frequently establish a latent CNS infection.

BK Virus↗
PubMed1991

Nucleotide sequence and genome organization of the murine polyomavirus, Kilham strain.

The polyomavirus Kilham strain (KV) represents a second murine member of the polyomavirus family. However, in contrast to other polyomaviruses, KV exhibits a stringent host and cell specificity. To determine the relationship of these viruses, the complete DNA sequence of KV consisting of 4754 bp was determined. The predicted organization of K virus was found to be comparable to that of other members of the polyomavirus family with two strands coding in an opposite direction of an intergenic region harboring putative control elements for gene expression. These include consensus elements for the origin of DNA replication as well as predicted promoter protein binding domains. Inferred signal sequences for 3' and 5' end formation of mRNAs and splice/branch site consensus sequences resemble those found among the SV40 group of viruses. From the organization of the genome two nonstructural proteins, large T and small t antigen, are predicted, both of which share the same amino-terminal sequence. Three putative capsid proteins VP1, VP2, and VP3 are encoded by alternative open reading frames. The nucleotide sequence in the proposed origin of DNA replication and the inferred amino acid sequence of the viral proteins suggest an evolutionary relationship placing KV between the murine PyV and the SV40 group of viruses. In the region bearing putative transcriptional control elements less nucleotide similarity to that of other polyomaviruses is found and this may reflect the unique host and cell specificity of KV.

Amino Acid Sequence↗
PubMed1988

Morphological and immunohistochemical studies of the central nervous system involvement in papovavirus K infection in mice.

The murine papovavirus K causes fatal pneumonia in infant mice, but an asymptomatic infection in older mice. In order to establish whether the virus affects the central nervous system in the course of systemic infection, we carried out morphological and immunohistochemical studies on the experimentally infected mice. BALB/c mice, less than 4 days of age, were inoculated with K virus either intraperitoneally or intracerebrally. When the animals were moribund, usually 10 days or so, after inoculation, their brains were removed and examined. Acutely infected mice showed only minor changes: intranuclear eosinophilic inclusions in very rare capillary endothelial cells of the brain. However, immunoperoxidase studies, using specific antibody to K virus, revealed that a number of brain cells had positive nuclear staining. These nuclei were distributed throughout the brain, without an apparent site of predilection. Double-immunostaining showed that virtually all cells whose nuclei were positive for viral antigen were endothelial, because their cytoplasm was positive for factor-VIII or vimentin. There were no nuclei positive for viral antigen in astrocytes, as determined by positive staining for glial fibrillary acidic protein or glutamine synthetase. By electron microscopy, clusters of K virus particles were found only in the nuclei of brain capillary endothelial cells. Although these endothelial cells showed degeneration of varying degree, their basement membranes remained relatively intact and there was no disorganization in the endfeet of contiguous astrocytes. Neurons and glial cells had normal ultrastructures. Therefore, this study has demonstrated that there is involvement of central nervous system during systemic K virus infection and that the infection involves predominantly brain capillary endothelial cells.

Animals↗