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Biomedical subjects

M Birk

Publications and source records attributed to M Birk.

At least 19 recordsLinked to original sources
PubMed2004

GB virus C coinfection and vertical transmission in HIV-infected mothers before the introduction of antiretroviral prophylaxis.

OBJECTIVES: To investigate the prevalence of GB virus C (GBV-C) viraemia and GBV-C antibodies in a cohort of HIV-infected mothers and their infants between 1987 and 1994. METHODS: GBV-C viraemia and antibodies were determined by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in 52 HIV-infected mothers and their 53 infants, who were born before antiretroviral prophylaxis for reduction of HIV transmission was introduced at the end of 1994. Ten of these children acquired HIV. RESULTS: Mothers of three children had GBV-C viraemia and mothers of another 14 children carried antibodies against GBV-C. No mother had GBV-C antibodies and GBV-C viraemia simultaneously. GBV-C viraemia was detected in only one infant. This child was delivered by the vaginal route to a mother with GBV-C viraemia, and was not HIV-infected. No vertical transmission of GBV-C occurred from mothers with GBV-C antibodies. However, four of 10 children who were infected with HIV had a mother with past or ongoing GBV-C infection. CONCLUSION: Our findings suggest that the risk of vertical transmission of GBV-C is not elevated in HIV-infected mothers. Furthermore, although the number of HIV-1-infected children was low, we saw no evidence that the presence of ongoing or past GBV-C infection influenced the probability of vertical HIV transmission.

Adolescent↗
PubMed2001

Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy.

OBJECTIVE: To study the kinetics of HIV-1 RNA and drug-induced mutations after cessation of antiretroviral therapy (ART). DESIGN AND METHODS: Successive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by sequencing of the pol gene. RESULTS: After cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6 to more than 29 days, was followed by a rapid viral increase, which slowed down before a plateau corresponding to pre-treatment levels or higher was reached in most cases (14/19 patients). In one patient virus was still undetectable at 4 weeks. Also, a significantly larger number of primary protease inhibitor (PI)-associated mutations reverted to wild-type, as compared with secondary PI-, and primary reverse transcriptase inhibitor (RTI)-associated mutations. During the rapid viral increase no mutations disappeared, which instead happened during the slower viral increase preceding the viral plateau level. CONCLUSION: After discontinuation of ART large individual variations were found for the time period until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1 specific immunity. The more rapid loss of primary PI mutations suggests that they might cause a more impaired viral fitness than primary RTI mutations. However, the persistence of drug mutations during the initial viral load increase indicates that mutated strains may still replicate efficiently.

Adult↗
PubMed2001

Initiation of therapy during primary HIV type 1 infection results in a continuous decay of proviral DNA and a highly restricted viral evolution.

A latent pool of HIV-1 is established early in memory CD4+ T lymphocytes and persists during antiretroviral therapy. Also, viral replication may continue in subjects despite undetectable viremia. However, it remains unclear whether this residual replication results in any significant sequence evolution. We were therefore interested in studying the viral evolution and HIV-1 DNA dynamics in subjects with primary infection receiving or not receiving early potent antiretroviral therapy. In 16 subjects, HIV-1 DNA load was monitored from 1 to 23 days, up to 1253 days, after onset of symptoms. Extensive sequential cloning and sequence analysis of the V3 region was performed in four subjects. In the treated subjects a continuous decline in the proviral load was found, corresponding to a half-life of about 6 months. As expected in newly infected individuals the founder virus populations showed high intrasubject sequence similarity. Also, a limited increase in the viral divergence was detected during the first 6 months in three treated subjects. Thereafter, no significant sequence changes were found despite analysis of a large number of clones. Our data thus suggest that early and successful therapy in compliant subjects with primary HIV-1 infection results in a highly restricted viral evolution and a decline in the proviral load close to the decay rate of human memory T lymphocytes.

DNA, Viral↗
PubMed2000

Proviral HIV-1 dynamics and evolution in patients receiving efficient long-term antiretroviral combination therapy.

OBJECTIVES: Different experimental approaches have shown that, despite plasma viral loads under the threshold of detection, HIV-1 frequently continues to replicate in patients receiving potent antiretroviral therapy. However, whether this low-grade viral replication is sufficient for the generation of new major quasispecies has not been studied. Thus, in order to evaluate the extent of variation in the major proviral HIV-1 population, we monitored proviral DNA sequences in such patients over a time period of up to 30 months. METHODS: DNA was extracted from peripheral blood mononuclear cells (PBMC) and the V3 region was amplified by nested polymerase chain reaction (PCR) and directly sequenced. Additionally, both HIV-1 RNA and DNA levels and CD4+ T-lymphocyte counts were monitored. RESULTS: Analysing the V3 gene sequences of 17 patients, we observed a sequence evolution in nine patients. Interestingly, the majority of these changes (77%) occurred in the first interval following the initiation of therapy and despite signs of ongoing replication the proviral DNA levels continued to decrease in all patients. CONCLUSIONS: Our data suggest that, although available data report that HIV-1 continues to replicate in patients with undetectable viraemia, the extent of viral replication in many of these patients is not sufficient to result in changes in the major viral population.

Adult↗
PubMed2000

Variability and immunogenicity of human immunodeficiency virus type 1 p24 gene quasispecies.

Despite the conserved nature of the human immunodeficiency virus type 1 (HIV-1) gag gene, multiple quasispecies of the p24 gene coexist in HIV-1-infected patients. We cloned and sequenced 31 p24 genes from four HIV-1-infected patients. The intrapatient homology between the p24 genes ranged from 97.1 to 99.1%, whereas the interpatient homology ranged from 91.5 to 93.8%, suggesting a host-specific evolution. Synonymous and nonsynonymous nucleotide changes were evenly distributed in the p24 gene, with 27 and 28%, respectively, located within host human leukocyte antigen class I recognition sites. This would suggest only a minor influence from the host cytotoxic T-cell response on the evolution of the p24 gene. The importance of minor variations within p24 was analyzed by designing DNA-based immunogens from two distinct p24 quasispecies genes simultaneously derived from one patient. In plasmid-immunized H-2(b), H-2(d), and H-2(k) haplotype mice, a clear influence from the host major histocompatibility complex was noted on the immune responses, fully consistent with those noted when a recombinant p24 protein is used as the immunogen. The two p24 DNA immunogens did not differ in their immunogenicity, indicating that the limited genetic variability (<1%) had little influence on the immune responses.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Short-term effect of amantadine sulphate on motor performance and reaction time in patients with idiopathic Parkinson's disease.

In thirty patients with idiopathic Parkinson's disease (PD) we examined in a prospectively designed study the effect on motor performance and cognitive functions of amantadine sulphate, applied intravenously over a period of 14 days. Prior to the introduction of amantadine and post infusionem the motor function was measured by the Unified Parkinson Disease Rating Scale (UPDRS) and the Motor Performance Test Series (MPS); the simple and the choice reaction time were assessed using the Vienna Reaction Unit (VRU). The primary endpoint of efficacy was the change in the UPDRS part III (motor examination) after 14 days of amantadine sulphate administration compared with baseline. Secondary end-points were changes in the variables of-the MPS and VRU at the end of administration interval compared with baseline. Overall, after 14 days of intravenous amantadine administration (200mg/ day), a significant improvement was obtained in motor performance with respect to the semiquantitative motor scores of the UPDRS (p = 0.002) and the quantitative motor variables in the pertinent subtests of the MPS, reflecting precision and speed of arm-hand movement as well as manual and finger dexterity, for the right (p < 0.01) and the left hand (p < 0.05). However, all patients being viewed collectively, it was observed that there was a widely differing time delay of efficient motor response to amantadine from 4 to 9 days between individuals, whilst the quality of motor response remained stable for the follow-up period. Although simple reaction time showed no significant improvement, choice reaction time shortened significantly in less affected PD patients staging Hoehn and Yahr I to III (p < 0.05). We conclude that apart from efficacy on motor performance, amantadine sulphate - applied intravenously - has a positive effect on cognitive functions, particularly in less affected PD patients.

Adult↗
PubMed1998

Variations in HIV-1 pol gene associated with reduced sensitivity to antiretroviral drugs in treatment-naive patients.

OBJECTIVE: Various drugs against the HIV-1 enzymes reverse transcriptase (RT) and protease have been introduced in the last few years: protease inhibitors, nucleoside RT inhibitors (NRTI) and non-NRTI (NNRTI). Several sequence variations associated with reduced drug sensitivity have been described in the HIV-1 pol gene. DESIGN: To analyse the occurrence of mutations associated with drug resistance in treatment-naive individuals. METHODS: RNA was extracted from sera of treatment-naive individuals, who were first diagnosed to be HIV-1 infected between August 1996 and February 1998. The pol region was amplified by RT-PCR and directly sequenced. Data on mutations associated with resistance to antiretroviral drugs were obtained from literature. RESULTS: Fifty protease genes and 53 RT genes from 57 individuals were sequenced. In the RT we analysed 20 amino-acid positions associated with resistance to NRTI and NNRTI. In total, 1054 amino acids at critical positions were analysed and three (0.3%) mutations known to contribute to RTI resistance were detected. In the protease, 16 amino-acid positions associated with resistance to protease inhibitors were analysed. By analysing a total of 768 amino acids at key positions in the protease, 50 (7%) mutations were detected that were associated with reduced drug sensitivity. Thirty-one (61%) patients showed between one and six mutations at the analysed protease amino-acid positions. In eight out of 16 analysed amino-acid positions, up to 44% of all patients carried mutations associated with resistance to protease inhibitors. CONCLUSIONS: Very few pre-existing mutations to RTI were found, suggesting that the transmission of RT-resistant strains is still uncommon. However, about two-thirds of the patients had one or more mutations associated with resistance to protease inhibitors. In addition, at some amino-acid positions up to almost half of the patients carried variations claimed to contribute to protease inhibitor resistance. Most of these mutations are likely to reflect the natural polymorphism of the protease. Their impact on the long-term effect of antiretroviral treatment should be evaluated in future studies.

Adolescent↗
PubMed1998

Coexisting members of HIV-1 p17 gene quasispecies represent proteins with distinct antigenicity and immunogenicity.

BACKGROUND: Despite the comparatively conserved nature of the HIV-1 gag gene, countless quasispecies of the p17 gene coexist in HIV-1-infected patients. It is not known if the minor genetic differences in quasispecies will affect immune recognition. OBJECTIVE: To characterize the antigenicity and immunogenicity of three different members of HIV-1 p17 quasispecies. METHODS: Three members of HIV-1 p17 gene quasispecies, one from patient A (clone 9; qsA9) and two from patient E (clones 5 and 8; qsE5 and qsE8), were expressed and purified from Escherichia coli. The antigenicity of the p17 proteins was analysed using sera from HIV-1-infected individuals, and the immunogenicity was evaluated using sera and lymphocytes from primed mice of three different haplotypes. RESULTS: The antigenicity of the qsE5 and qsE8 p17 recombinant proteins were distinct when tested for reactivity with human p17 antibodies. The qsE5 and qsE8 p17 were equally immunogenic in H-2d mice, but not in H-2b and H-2k mice. In H-2b mice the qsE8 protein induced higher levels of anti-p17 IgG2a, IgG2b and IgG3 than the qsE5 protein. Corroborating the IgG subclass pattern, H-2b-restricted qsE5-specific T cells produced higher in vitro levels of interferon-gamma, but not of interleukin (IL)-4, IL-5 and IL-6, than qsE8-specific T cells, suggesting a more pronounced T-helper (TH)1-like response. CONCLUSIONS: The p17 gene quasispecies coexisting in the same patient at the same time may represent antigenically and immunogenically distinct proteins despite sequence homologies of above 90%. Subsequently, subtle differences between two p17 protein quasispecies are enough to prime different TH1/TH2 subsets. These findings will have implications for therapeutic HIV-1 immunizations.

Amino Acid Sequence↗
PubMed1998

Nonsynonymous mutations within the human immunodeficiency virus type 1 p17 gene are clustered to sequences binding to the host human leukocyte antigen class I molecules.

We have analyzed the relation between intrapatient variabilities of the p17 gene and the location of known host p17 cytotoxic T lymphocyte (CTL) epitopes in five patients infected with human immunodeficiency virus type 1 (HIV-1). All patients were typed with respect to the human leukocyte antigen (HLA) class I type. One to seven previously fine-mapped p17 CTL epitopes corresponded to the HLA class I restriction elements of each patient. An average of 28+/-16% of the p17 gene of each patient encoded CTL epitopes corresponding to the HLA restriction elements of the host. Twenty full-length p17 gene clones were sequenced from each patient. The intrapatient homology between the p17 sequences ranged from 96.4 to 98.9%. The interpatient homology between the consensus sequences of each patient ranged from 83.1 to 91.6%. A total of 246 nucleotide differences within the 100 p17 clones was noted. Fifteen (16%) of 96 synonymous substitutions were found within host CTL epitopes, whereas 72 (48%) of 150 nonsynonymous nucleotide changes were found within CTL epitopes corresponding to the HLA restriction elements of the host (p < 0.0001; Fisher's exact test). Subsequently, variable residues indicating the evolution of at least two major p17 species (i.e., >20% of the clones) were determined to be more common at positions contained within these CTL epitopes (p < 0.01). The present data suggest that the evolution of the p17 gene is influenced by contact areas with the host HLA class I molecules.

Adult↗
PubMed1998

The Far Infrared Spectrum of HOCl: Line Positions and Intensities.

The far infrared spectrum of HOCl has been recorded at high resolution between 20 and 360 cm-1 by means of Fourier transform spectroscopy, and it was possible to observe pure rotation lines involving rotational levels with high Ka quantum numbers (up to Ka = 9). These lines combined with microwave and tunable far infrared data available in the literature were least squares fitted using a Watson-type Hamiltonian. The fitting leads to precise sets of rotational and centrifugal distortion constants for the ground states of both isotopomers HO35Cl and HO37Cl. Also relative line intensities were measured and their fitting allowed the determination of rotational corrections to the b-component of the permanent transition moment. Finally, to get Hamiltonian constants consistent with the newly determined ground state constants for the (100), (010), (001) vibrational states, available data concerning the nu1, nu2, and nu3 bands were refitted. Three interesting points are to be stressed. For the (001) state, we were able to complete the existing data with rotation lines observed in our spectra up to rather high Ka values (Ka = 7). For HO35Cl, we were able to show that some (010) and (100) levels are perturbed by levels of the (002) and (030) states, respectively, through Coriolis-type interactions. This allows the determination of the band centers of these two dark states. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Human immunodeficiency virus type 1 disease progression, CCR5 genotype, and specific immune responses.

The correlation among the presence of a 32-bp deletion in the CC-chemokine receptor 5 (CCR5) gene, disease progression, and human immunodeficiency virus type 1 (HIV-1)-specific immune responses was analyzed for a cohort of 79 Caucasian HIV-1-infected patients. The CCR5 genotype (CCR5/CCR5 = wild type/wild type or delta32CCR5/CCR5 = 32-bp deletion/wild type) in peripheral blood mononuclear cells was determined by PCR, followed by sequencing of both wild-type and delta32CCR5 gene fragments. HIV-1-specific humoral responses to gp41 and V3MN peptides were determined by enzyme immunoassays. The prevalence of the delta32CCR5 allele was lower among 37 patients with rapid progression (progression to AIDS or to a CD4 cell count of <200 x 10(6)/liter in less than 9 years; P < 0.01) compared to that for 42 patients with slow progression (no AIDS and CD4 cell count of >200 x 10(6)/liter after at least 9 years from infection) or to that for 25 non-HIV-1-infected Swedish blood donors (P < 0.05). No differences were observed in the wild-type CCR5 sequences between the different groups of patients. For three analyzed patients, the 32-bp delta32CCR5 gene deletions were identical. The antibody titers against gp41 and a V3MN peptide in patients with the delta32CCR5/CCR5 genotype were not significantly different from those in pair-matched CCR5/CCR5 controls. However, in 13 analyzed patients, a stronger serum neutralizing activity was associated with the delta32CCR5/CCR5 genotype. Thus, a CCR5/CCR5 genotype correlates with a shortened AIDS-free HIV-1 infection period and possibly with a worse neutralizing activity, without an evident influence on the antibody response to two major antigenic regions of HIV-1 envelope.

Amino Acid Sequence↗
PubMed1997

The Rotational Spectrum and Anharmonic Force Field of Chlorine Dioxide, OClO

The rotational spectra of O35ClO and O37ClO in their (000), (100), (010), (001), and (020) states have been reinvestigated in selected regions between 130 and 526 GHz. About 800 newly measured lines spanning the quantum numbers 2 </= N </= 65 and 0 </= Ka </= 17 have been analyzed together with data from two previous microwave and millimeter wave studies. In particular, the spectroscopic constants in the ground vibrational states have been improved enabeling precise predictions of line positions into the submillimeter region. The newly derived ground state rotational and quartic centrifugal distortion constants, their vibrational changes, and the sextic centrifugal distortion constants were used together with data from infrared studies in a calculation of the quartic force field. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1994

[Increasing the reliability of anamnestic data by increasing the length of the interview].

In accordance with the theory of mental tests in this study it was tried to improve the reliability of diagnostic interview data by enhancing the number of items concerning the same biographical topic (= homogeneous items). Reliability was defined as stability of the statements in repeated interviews. The reliabilities of three interview items concerning different topics were calculated. The interviews were carried out under two different conditions: Under the experimental condition (30 subjects) the item, of which the stability was calculated, was the last in a series of ten homogeneous items, under the control conditions (30 subjects) the item was the last in a series of ten heterogeneous items. Under the experimental condition the reliabilities of two items, concerning the diseases of children and concerning the school record, were significantly improved. Not improved was the reliability of the appraisal of parent's educational methods. The reliabilities of the interview data not seemed to depend on the age of the subjects.

Adult↗
PubMed1981

[Investigations in animal experiments into the influence of the beta-1-selective blocking agent metoprolol on the cardiovascular and metabolic side effects of the tocolytic fenoterol].

The influence of the highly selective beta-1-adrenergic blocker Metoprolol on cardiovascular and metabolic side effects of the beta-mimetic Fenoterol, used for labour inhibition, was investigated in anesthetized mongrel dogs. In a dosage of 1.5 microgram/kg BW/min Metoprolol antagonized the positive inotropic and chronotropic cardiac effects of Fenoterol (0.06 microgram/kg BW/min) thus compensating the impaired energetic balance of the myocardium. As expected, there was no influence on the beta-mimetic mediated metabolic alterations. Taking into account its pharmacologic actions, the additional application of Metoprolol in labour inhibition with beta-mimetics seems to be advantageous. On account of the proven results a reduction of the more or less considerable missensations and a cardioprotective effect may be expected.

Animals↗