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Biomedical subjects

T Bergström

Publications and source records attributed to T Bergström.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mode of interaction between pseudorabies virus and heparan sulfate/heparin.

It has been demonstrated that the efficient attachment of pseudorabies virus (PrV) is mediated by an interaction between glycoprotein C (gC) and a cellular heparin-like substance (T. C. Mettenleiter, L. Zsak, F. Zuckermann, N. Sugg, H. Kern, and t. Ben-Porat, J. Virol. 64, 278-286, 1990). According to the prevalent concept, this interaction is likely to occur between clusters of basic residues of PrV gC and the negatively charged sulfate esters and carboxylate groups of heparan sulfate/heparin. To elucidate which of the three major types of sulfate groups of heparan sulfate/heparin are involved in the interaction with PrV, we used selectively N-, 2-O-, and 6-O-desulfated samples and other modified heparins as competitors in virus-attachment assays. PrV exhibited limited preference for the specific sulfate groups of heparan sulfate/heparin in accordance with a hierarchy of 6-O- > 2-O- > N-sulfates. In addition, since selective removal of any of the specific sulfates had only a slight effect on the competition capacity of heparin, it is likely that the combination of any two of three types of sulfate groups could contribute to an interaction with PrV with an efficiency nearly equal to native, fully sulfated heparin. When tested on different cell lines the pattern of PrV requirement for the specific O-sulfate groups, i.e., 6-O-sulfates > 2-O-sulfates, remained the same. However, different minimum lengths of heparin fragments were required to inhibit PrV attachment to different cell lines, suggesting a relative virus flexibility in accommodation to different forms of heparan sulfate.

Animals↗
PubMed1996

Rapid allelic diversification and intensified selection at antigen recognition sites of the Mhc class II DPB1 locus during hominoid evolution.

The evolution of polymorphism at the Mhc class II DPB1 locus was studied by comparison of chimpanzee (Pan troglodytes), pygmy chimpanzee (Pan paniscus), gorilla (Gorilla gorilla) and human DPB1 alleles. Extensive polymorphism was found in all hominoids. The clustering of sequences in the phylogenetic tree is consistent with rapid generation of the DPB1 polymorphism. Analysis of the substitution pattern for human alleles shows an excess of non-synonymous changes to synonymous changes at antigen recognition sites, indicating that the amino acid polymorphism at these sites is being maintained by selection. By contrast, no excess of nonsynonymous changes was found at the antigen recognition sites of nonhuman hominoid species. Thus, it appears that diversifying selection on the DPB1 polymorphism has intensified in the lineage leading to humans. No evidence was found for the existence of ancient allelic lineages predating the divergence of the hominoid species. The number of synonymous differences among DPB1 alleles is lower than among DQB1 and DRB1 alleles, indicative of a more recent origin for the DPB1 polymorphism and consistent with the more rapid evolution suggested by the phylogenetic tree.

Alleles↗
PubMed1996

Antigenic differences between HSV-1 and HSV-2 glycoproteins and their importance for type-specific serology.

The ability to discriminate between herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) infections by serological means is of increasing importance for clinical virological diagnostics. HSV type-specific serology has a number of applications, e.g. to guide duration and dosage of antiviral therapy, to allow for stringent epidemiological analyses, to evaluate efficacy of HSV vaccine candidates, and to help the clinician during counseling of couples where one has genital herpes. The genomes of the two HSV types appear to be sufficiently intratypically stable and intertypically discrepant to permit such a discrimination. Despite recent advances in methodology, the ideal HSV type-specific serological assays still remain to be developed. The viral antigens utilized for such an assay should evoke strong antibody responses, but only against unique determinants, in order to be able to combine high sensitivity and specificity. Of all the HSV envelope proteins, the most promising candidate antigens, i.e. HSV-1 glycoprotein G (gG-1) and its HSV-2 counterpart gG-2, contain relatively long type-unique stretches of amino acids. However, whether the type-specific determinants preferentially localize to the unique or homologous stretches of gG is still unknown. Paradoxically, type-specific monoclonal antibodies to the moderately type-specific antigen, HSV-1 glycoprotein C, have hitherto been mapped to homologous rather than to type-unique stretches. A definition of human type-specific epitopes on gG-1 and gG-2, as well as a broader search for new candidate HSV antigens, might be needed to fully discriminate dual infections from high titer single HSV-1 or HSV-2 infections.

Antigens, Viral↗
PubMed1996

Polymerase chain reaction for diagnosis of varicella zoster virus central nervous system infections without skin manifestations.

Varicella zoster virus (VZV) can cause disease in the central nervous system (CNS) during both primary infection and reactivation. Rapid and adequate diagnosis of VZV have previously been hampered by the shortcomings of standard virological methods, such as isolation and serology. Earlier reported cases of CNS manifestations of VZV infection have, therefore, mostly been noted in connection with, or shortly after, onset of vesicular rash. Several studies have recently been described of cases of VZV-induced CNS disease occurring as the only sign of viral reactivation, with the diagnosis aided by polymerase chain reaction (PCR) amplification and other methods of genome detection. A prospective study was performed using PCR on cerebrospinal fluid (CSF) and brain samples received for routine diagnosis of possible VZV infection during a 2-year period. Samples from 8 (7 from CSF, 1 from brain) of the 260 patients investigated (3.1%) were found to be positive for VZV-DNA. All 8 had a presumed reactivated VZV infection according to serological and clinical analysis. Their CNS manifestations ranged from meningitis to severe encephalitis, and only in 3 of these patients was a vesicular rash present. Thus, VZV-DNA detection in the CSF was an unexpected finding for the clinician and, in 2 cases, antiviral treatment with aciclovir was initiated only because of the PCR evidence of CNS infection. VZV should be considered as a possible causative agent of infection in patients with CNS disease of suspected viral origin, even in the absence of skin manifestations. Rapid diagnosis by PCR amplification of VZV-DNA from CSF might allow for early and adequate antiviral treatment.

Adolescent↗
PubMed1995

[Gene amplification in viral CNS infections. Rapid diagnostic identification of herpesviruses].

DNA amplification with the polymerase chain reaction (PCR) technique was used as a diagnostic test on cerebrospinal fluid samples in cases where herpesvirus infection of the central nervous system (CNS) was suspected. During the period, 1992-93, 47 (8.9%) of 528 patients tested were positive for one or another of the following herpesviruses: herpes simplex virus type 1 (n = 16) or type 2 (n = 9), cytomegalovirus (n = 16), varicella-zoster virus (n = 4), or Epstein-Barr virus (n = 2). The study showed PCR to be a rapid and useful diagnostic method in clinical routine, enabling early antiviral intervention in several cases with an atypical clinical picture. Moreover, cytomegalovirus was found to be an important CNS pathogen in addition to herpes simplex virus, especially during childhood.

Child↗
PubMed1995

Detection of cytomegalovirus DNA in cerebrospinal fluid in immunocompetent patients as a sign of active infection.

Detection of cytomegalovirus (CMV) DNA by the polymerase chain reaction (PCR) in samples of cerebrospinal fluid (CSF) has been shown to be a sensitive method of diagnosing CMV disease in the central nervous system. Since CMV causes latent infection in white blood cells, an unanswered question is whether detection of latent CMV DNA in the cell fraction of CSF samples by PCR is possible in seropositive patients. In a prospective study, the finding of CMV DNA in CSF of CMV seropositive patients with suspected viral infection of the central nervous system (CNS) was evaluated clinically. Fractionation of 64 CSF samples from seropositive patients was carried out before analysing the samples for CMV DNA by PCR. In four of the five patients who had CMV DNA in the cell pellet and/or supernatant, the clinical data suggested CMV-associated neurological disease. The remaining 59 samples were negative in both pellet and supernatant. In addition, 11 CSF samples with high cell counts from patients with bacterial meningitis were examined for CMV DNA and found to be negative in 10 patients and positive in 1. One hundred thirty two uncentrifuged CSF samples were used as negative controls. The results of the study indicate that detection of CMV DNA in CSF samples by PCR correlated well with disease and was not due to latent CMV infection.

Adolescent↗
PubMed1995

Epilepsy etiology with special emphasis on immune dysfunction and neurovirology.

The etiology of epilepsy remains in most cases an enigma. Based on the finding of a genetically dependent immune dysfunction in focal epilepsies, brain specimens from 16 patients, ranging in age from 6 to 39 years and operated on for therapy-resistant focal, mainly temporal lobe epilepsy were analyzed for the presence of viral DNA. The PCR technique was used for detection of viral DNA from the herpes virus group. HSV-1 was found in 44% CMV in 50%, and HHV-6 in 25%. Three patients were positive for more than one of these viruses. The control material, consisting of only 4 brain tissue samples, showed DNA from HSV-1 in one case. Until more brain samples from controls have been examined, caution must be taken before a viral etiology is applied to focal epilepsy.

Adolescent↗
PubMed1995

An evaluation of a hemagglutination-inhibition test for the detection of antibodies to herpes simplex virus type 1.

BACKGROUND: We have recently demonstrated the ability of herpes simplex virus type 1 (HSV-1) to agglutinate mouse red blood cells, and identified glycoprotein C (gC-1) as a major virus hemagglutinin. Based on this a classical hemagglutination-inhibition (HI) assay was developed. OBJECTIVES: Regarding significant structural differences between HSV-1 gC-1 and its herpes simplex virus type 2 (HSV-2) counterpart, gC-2, the possibility of application of a classical HI assay for the detection of HSV-1-specific antibodies was explored. STUDY DESIGN: HI antibody titers were compared with those of gC-1-specific enzyme-linked immunoassay (ELISA), and with the results of the standard gG-1- and gG-2-specific immunodot enzymatic assays for the detection of type-specific antibodies to HSV-1 and HSV-2 respectively. RESULTS: The sensitivity of HI test was 89% and 97% of that gC-1-ELISA and gG-1-immunodot respectively. Approximately 21% of serum specimens, defined as containing antibodies specific for only HSV-2, showed low HI titers. Heterotypic reactivity with purified gC-1 antigen was also observed in both ELISA and immunoblot assays. CONCLUSION: Antibodies detectable in HI assay were mainly HSV-1-specific; however, a limited degree of serologic reactivity between HSV-2-specific sera and HSV-1 hemagglutinin also occurred. Thus, our results confirmed prevalent opinion about the presence of a limited number of antigenic determinants shared by HSV-1 gC-1 and HSV-2 gC-2.

Journal Article↗
PubMed1995

Evolution of Mhc class II polymorphism: the rise and fall of class II gene function in primates.

The substitution rate at the codons implicated at ARS of Mhc class II genes has previously been shown to be heavily biased towards nonsynonymous substitutions, indicative of positive selection for polymorphism. Based on our analysis of the number of synonymous changes at codons outside putative ARS in primates, the average age of the polymorphism at class II loci was found to increase in the following order: DPB1, DRB3, DRB5, DRB1, DRB4, DQB1, DQA1. For DRB loci, nonsynonymous changes were found to exceed synonymous changes at HLA-DRB1, DRB3 and DRB5, while no evidence of deviations from equal rates of synonymous and nonsynonymous substitutions were found for DRB6. The pattern of substitutions at the DRB loci of most Catarrhini species indicates constant positive selection at ARS codons over the evolutionary period examined. An exception to the relatively stable selection pattern between species exhibited by most loci is the appearance of polymorphism under positive selection at DRB4 only in the regular chimpanzee. The ds/dn ratios for DQA1 and DQB1 alleles are lower than for the most polymorphic DRB genes. Since the dn/ds ratio of ARS codons may be positively correlated to the ds for non-ARS codons, at least for DQB1, caution must be exercised in interpreting the low ratio for the DQ genes as an indication of weaker selection. The DQA1 allelic lineages show different dn/ds ratios, consistent with the hypothesis that the lineages are constrained from evolving in relation to the diversity of the interacting DQB1 alleles. In contrast to all other class II loci, DPB1 appears to have been subjected to strong positive selection only in the human lineage, and may represent the most conspicuous example of an Mhc locus acquiring an altered function in antigen presentation.

Animals↗
PubMed1995

Detection of genital human papillomavirus by single-tube nested PCR and type-specific oligonucleotide hybridization.

Cervical cancer is, on a global scale, the second most common form of cancer in women. Development of cervical carcinoma is strongly associated with infection by certain types of human papillomavirus (HPV). To facilitate the detection and molecular typing of HPV in clinical samples, nested-PCR amplification systems were developed for regions of the E1 and L1 genes. The nested amplifications were performed in a single reaction tube, and shifting between inner and outer primer pairs was achieved by a two-phase amplification with different annealing temperatures. This method eliminates cross-contamination between samples during transfer from the first to the second amplification step. A set of type-specific oligonucleotide probes were designed for the E1 system and used to distinguish 19 genital HPV types. The sensitivities of our amplification systems compare favorably with that for the L1 system on the basis of the MY09-MY11 primer pair (M.M. Manos, Y. Ting, D. K. Wright, A. J. Lewis, T. R. Broker, and S. M. Wolinsky, Cancer Cells 7:209-214, 1989) and our systems can be used on materials such as HPV-infected cell lines, cytobrush samples, cancer biopsies, and recent as well as archival Papanicolaou (Pap) smears. The high sensitivity coupled with the effective elimination of contamination in the transfer between the two amplification steps of the nested PCR makes these systems suitable for research as well as clinical analyses.

Base Sequence↗
PubMed1994

Diagnosis of Epstein-Barr virus-induced central nervous system infections by DNA amplification from cerebrospinal fluid.

A nested polymerase chain reaction was used for the detection of Epstein-Barr virus DNA in 1 patient with encephalitis, and in 1 patient with myelitis. Epstein-Barr virus DNA was detected in cerebrospinal fluid samples obtained at the onset of neurological symptoms in both patients, and serological findings indicated ongoing Epstein-Barr virus infection. In the patient with encephalitis, herpes simplex virus type 1 DNA was transiently detected in the cerebrospinal fluid, while Epstein-Barr virus DNA was still present on day 44 after admittance. Single-photon emission computed tomography in this patient indicated a frontal bilateral hypoperfusion. The diagnostic value of polymerase chain reaction on cerebrospinal fluid and serum samples for Epstein-Barr virus infections of the central nervous system is emphasized.

Adolescent↗
PubMed1994

The cotton-top tamarin revisited: Mhc class I polymorphism of wild tamarins, and polymorphism and allelic diversity of the class II DQA1, DQB1, and DRB loci.

Cotton-top tamarins (Saguinus oedipus) in captivity are unusual in that they exhibit low levels of polymorphism and allelic diversity at the major histocompatibility complex (Mhc) class I loci. Since the polymorphism has previously only been examined in captive tamarins, we analyzed the Mhc class I alleles of a population of wild tamarins. These wild tamarins, like their captive counterparts, exhibited limited class I polymorphism. We also assessed the levels of polymorphism and allelic diversity at the Mhc class II DQA1, DQB1, DQB2, and the DRB loci in captive populations of cotton-top tamarins. In contrast to the extensive polymorphism in Old World monkeys, only two alleles were detected at each of DQA1 and DQB1. Also, the DQB2 locus was monomorphic and conserved between New and Old World monkeys. Sequences derived from four putative DRB loci were obtained, and extensive polymorphism was found at all four loci. Phylogenetic analysis did not indicate that any of the tamarin DRB loci, with the possible exception of Saoe-DRB3, were orthologous to the human DRB loci. At three of the DRB loci (Saoe-DRB11, Saoe-DRB*W12, Saoe-DRB*W22), the number of nonsynonymous changes was higher than the number of synonymous changes in the putative antigen recognition sites, indicative of positive selection. We found no support for a restriction on the polymorphism at the cotton-top tamarin class II loci. However, the allelic diversity at some of the Saoe-DRB loci is more limited than for the HLA-DRB1, consistent with a restriction imposed by the bone marrow-chimerical lifestyle.

Alleles↗
PubMed1994

Resistance of rat CNS to brain stem infection with herpes simplex virus type 1.

Infection of the CNS by herpes simplex type 1 (HSV-1) via the trigeminal route to the brain stem was elucidated in a rat model. In contrast to the earlier described cortical and hippocampal infection after intracranial injection, the CNS showed a profound resistance to HSV-1 infection when the virus was administered by nose inoculation, as judged by histopathology and immunohistochemistry. In contrast, when the distribution of HSV-1 in the brain was investigated after nose inoculation by polymerase chain reaction, viral DNA was detected at all levels from the ganglia to the cortex. When replication of HSV-1 was assayed in primary cell cultures of rat astrocytes derived from brain stem, striatum, hippocampus and cerebral cortex, significantly lower virus yields were obtained in brain stem-derived astrocytes cultures as compared with in cortex-derived astrocytes. This finding was independent of whether HSV-1 strains used originated from brains of patients suffering from herpes simplex encephalitis or from patients with oral cutaneous lesions and lacking neurological symptoms. Also, by immunocytochemistry of cultures after HSV-1 infection, a lower number of plaques were seen in brain stem-derived astrocytes as compared with cortex-derived astrocytes. The observed relative resistance of brain stem-derived astrocytes to replicate HSV-1 might contribute to the ability of the brain stem to withstand infection during reactivation of this virus in the trigeminal neurons.

Animals↗
PubMed1994

Clinical evaluation in organ transplant patients of a polymerase chain reaction test for CMV DNA applied on white blood cells and serum.

A polymerase chain reaction (PCR) test for CMV DNA was evaluated for clinical usefulness. Leukocytes and serum were sampled from 36 patients who had recently undergone organ transplantation. Clinical symptoms, virus culture, and IgG and IgM antibodies were used to identify, in retrospect, patients with CMV disease certified beyond all doubt, with probable disease, with asymptomatic infection, or without infection. PCR tests for CMV DNA in leukocytes (BC-PCR) and serum (SE-PCR) were then evaluated. BC-PCR was positive in all patients with certified CMV disease but also in 31% of the samples from patients without infection. SE-PCR was positive in 11/13 patients with certified disease and was concordant with CMV culture in 192/231 tests. Of the 39 discordant cases, 27 had a positive SE-PCR with a negative culture. The effect of ganciclovir treatment could not be predicted by any test. In conclusion, a negative BC-PCR is strong evidence against CMV disease and a positive SE-PCR strongly suggests CMV disease, but the opposite results are of little clinical help.

Adult↗
PubMed1994

Clinical, serological and PCR evidence of cytomegalovirus infection in the central nervous system in infancy and childhood.

Over a 3-year-period (Dec. 1990-Nov. 1993) 12 children were found PCR-positive for CMV-DNA in CSF and brain biopsies. Three of the patients were immunologically compromised. During the same period CSF samples from 10 shunt-operated children and 143 virological routine CSF samples were PCR CMV negative. Clinical association with positive PCR-CMV reaction was considered likely in 6 patients: two boys developed prolonged fever and meningoencephalitis following neurosurgery, one infant girl had a course compatible with congenital inclusion disease, and three had prolonged fever following transplantation. Clinical association was deemed probable in 3 infant girls: one had neonatal infection, meningitis and intraventricular haemorrhage, one had neonatal encephalitis and failure to thrive, and one with neonatal seizures and encephalitis developed brain atrophy. Clinical association was judged possible in 3 patients: one infant girl with no signs of encephalitis developed brain atrophy, one had an Aicardi Type 1 syndrome and one 2 1/2-year-old boy had an acute encephalitis with insufficient serological support for CMV but was 12 months later PCR positive for CMV. We conclude that CMV may be an overlooked infectious agent of the CNS also in immunocompetent children. PCR aids in rapid diagnosis of CMV infection in the immunocompromised. CMV may occasionally be disclosed with PCR in other conditions as a probably non-relevant observation.

Brain↗
PubMed1994

Localization of a functional site on herpes simplex virus type 1 glycoprotein C involved in binding to cell surface heparan sulphate.

The amino acid residues critical for interaction between herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) and cell surface heparan sulphate (HS) were localized to two separate regions within antigenic site II of this glycoprotein. These amino acids were Arg-143, Arg-145, Arg-147 and Thr-150 in one region and Gly-247 in the other. This conclusion is based on the following observations. (i) Monoclonal antibodies defining gC-1 antigenic site II, and not those reactive with antigenic site I, inhibited HSV-1-induced haemagglutination and virus binding to susceptible cells. (ii) A number of HSV-1 mar mutants, altered at these critical residues, were impaired in attachment to cells. (iii) Synthetic peptides, corresponding to these two regions inhibited virus attachment to cells and infectivity. In addition these peptides were found to agglutinate red blood cells. This agglutination was inhibited by soluble HS, and was prevented by the pretreatment of red blood cells with heparitinase suggesting that cell surface HS was a site of peptide binding. The same was observed with the polycationic substances neomycin and poly-L-lysine. In conclusion, we propose that the regions of gC-1 represented by the HS-binding peptides may form a functional site of a polycationic nature, active in attachment to the polyanionic glycosaminoglycan chain of cell surface HS.

Amino Acid Sequence↗
PubMed1994

Cytomegalovirus infection of the CNS in non-compromised patients.

Six non-compromised patients with cytomegalovirus (CMV) associated meningoencephalitis are described. CMV was isolated from the cerebrospinal fluid (CSF) in 2/4 cases, while the diagnosis was based on an 8-fold rise in CMV-specific serum IgG antibodies and intrathecal antibody production against CMV in one case. By the polymerase chain reaction (PCR) CMV DNA was detected in the CSF in 5/5 cases and in serum in 3/4 cases. In one patient who had an Influenza A infection, both CMV and Epstein-Barr virus DNA were detected by PCR in the CSF. In 4 patients possible triggering events could be identified. Symptoms and signs indicating a multifocal brain involvement were present in 4 patients. The outcome was generally favourable except for sequelae in form of slight dysphasia in one case.

Aged↗