Biomedical subjects
D Petzoldt
Publications and source records attributed to D Petzoldt.
Retraction: evidence for genetic HIV variants from detection of HIV-DNA.
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T4+ cell numbers are correlated with plasma glutamate and cystine levels: association of hyperglutamataemia with immunodeficiency in diseases with different aetiologies.
Human immunodeficiency virus type 1 (HIV-1) seropositive individuals suffer from a depletion of T4+ T cells and have elevated plasma glutamate levels. Glutamate is also elevated in cancer patients, and several authors have shown that elevated extracellular glutamate levels inhibit competitively the membrane transport of cystine and cause a decrease of intracellular cystine. We, therefore, tested the hypothesis that high glutamate and/or low cystine levels may generally be associated with low lymphocyte reactivity or low T4+ counts. In three independent studies we tested (i) serum amino acid levels (AAL) versus T4+ counts in healthy individuals, (ii) plasma AAL versus lymphocyte responses in healthy individuals, and (iii) plasma AAL versus T4+ counts in HIV-1 seropositive individuals. When the individuals in each study were divided into four subgroups as defined by median glutamate and cystine levels, the results showed that persons with a combination of low glutamate and high cystine level (LGHC subgroups) had the highest mean T4+ count or highest lymphocyte reactivity. Moreover, the LGHC subgroup in a study of lung cancer patients had a much longer mean survival time than the other three subgroups. In HIV-1 infected patients, hyperglutamataemia is associated with hypocystinaemia and hypocysteinaemia. Azidodeoxythymidine (AZT) treated HIV patients had, on average, lower glutamate levels than patients without AZT.(ABSTRACT TRUNCATED AT 250 WORDS)
Subclinical Epstein-Barr virus infection of both the male and female genital tract--indication for sexual transmission.
Epstein-Barr Virus (EBV) can infect B lymphocytes as well as epithelial cells of the oral cavity. Recently, infection of epithelial cells of the inflamed uterine cervix has been demonstrated, and EBV-DNA has been detected in urethral discharge of men suffering from genital infection. We investigated whether EBV can be found in the genital tract of both sexes independently from inflammatory disease states. Genital specimens of men and women of a sexually transmitted diseases outpatient clinic after excluding sexually transmitted diseases and clinically apparent signs of inflammation were investigated using the polymerase chain reaction to screen for EBV-DNA. In 13 of 47 samples (27.7%) swabbed from the uterine cervix, EBV-DNA could be detected. Similarly, 6 of 45 samples (13.3%) scraped from the sulcus coronarius contained EBV-DNA. Our study shows that the female genital tract and likewise the male genital tract can subclinically harbor EBV. These findings suggest i) that in addition to the oral cavity, the female and the male genital tract may be a reservoir for EBV and ii) that sexual transmission of this virus associated with an epidemiology different from that of oral infection may be possible.
[Epstein-Barr virus infection--a lympho- and epitheliotropic infection].
Epstein-Barr virus (EBV) has long been thought to be primarily a B-lymphotropic virus. This tropism becomes obvious in the association of the virus with diseases that become manifest in lymphoproliferative conditions, such as acute infectious mononucleosis or endemic Burkitt's lymphoma. In the course of mononucleosis, however, viraemia cannot be detected and B-lymphocytes infected with EBV in vitro produce only small amounts of the virus. In contrast, recent studies document that EBV replicates in the epithelial cells in the mouth, and pronounced secretion of virus can also be detected. Cells of the basal layer of the epithelium can be infected via the EBV-specific CR2 receptor. Upon mitosis of the cells of the basal layer, EBV genome in episomal form is partitioned to the daughter cell. On the other hand, differentiation and maturation of the epithelial cells is paralleled by active virus production. Thus, there is evidence that the epithelial EBV infection is the main factor in the persistence and production of EBV. Accordingly, the EBV infection of epithelial cells which can result in diseases, seems to be the primary process, leading to the infection of B-lymphocytes and then to other diseases. Diseases associated with infection of epithelial cells by EBV and diseases involving B-lymphocytes are discussed with reference to this idea.
[Hodgkin's disease in HIV infection--detection of Epstein-Barr virus DNA in tongue epithelium and lymphoma].
We present an HIV-infected patient with lymphadenopathy syndrome in whom an unusually aggressive case of Hodgkin's disease developed. Examination of tissue excised from the lymphoma and of epithelial cells scraped from the tongue of the patient revealed Epstein-Barr virus (EBV). The relationship between an enhanced replication of EBV in the epithelium of the tongue and the elevated frequency of Hodgkin's lymphomas containing EBV-DNA among HIV-infected patients is discussed.
Alpha 2-macroglobulin and alpha 2-macroglobulin/proteinase complexes in human seminal fluid.
OBJECTIVE: To determine the broad-spectrum proteinase inhibitor alpha 2-macroglobulin (alpha 2M) and its functional subforms, i.e., free alpha 2M and alpha 2M/proteinase complexes, in human seminal fluid by using specific enzyme immunoassay systems. SETTING: The study has been performed in the Andrology Department of the Dermatology Clinics and the Laboratory of Immunopathology of the Institute of Immunology. PATIENTS, PARTICIPATES: Routine patients attending the Andrology Department. INTERVENTIONS: The data have been obtained without particular interventions before or after collection of seminal fluid. MAIN OUTCOME MEASURES: The aim of the study was to determine whether alpha 2M or alpha 2M/proteinase complexes are present in human seminal fluid. RESULTS: The concentration of total alpha 2M in human seminal fluid ranged from 1 to greater than 1,000 ng/mL, and between 56% and 85% of the inhibitor was complexed with proteinases. CONCLUSIONS: These findings show that alpha 2M and alpha 2M/proteinase complexes have to be considered as functionally relevant biomolecules in male genital tract secretions.
[Local and systemic humoral immune response to protein I of Neisseria gonorrhoeae].
Knowledge of the immune response to natural infection with Neisseria gonorrhoeae is presupposition for the development of a gonococcal vaccine. Pili and protein I have gained importance for a subunite vaccine. A pilus vaccine proved to be ineffective in a field trial due to extensive pilus variability. According to an alternative strategy protein I may represent an important vaccine candidate for a gonococcal vaccine. To study the local and systemic, humoral immune response to N. gonorrhoeae cervical secretion, vaginal fluid and serum from prostitutes and family planning patients were compared by the use of a protein I ELISA. In local secretions and in serum patients in the study group showed significantly higher anti-protein-I-IgA-levels than patients in the control group. In cervical secretion immune response to an acute gonococcal infection consisted of a short lived, significant increase of anti-protein-I-IgA, while anti-protein-I-IgG showed a lower, but longer lasting significant increase. The course of the immune response in vaginal fluid reflected the immune response of cervical secretion at a lower level. In serum antigenic stimulus of a local gonococcal infection resulted in a significant but short lived protein I specific IgG immune response. In local infection with N. gonorrhoeae protein I represents a target antigen of the local and systemic immune response. Clear differences exist between local and systemic humoral immune response in the protein I reactive immunoglobulin class and in the course of reactivity. In the future it may be possible to define epitopes on protein I which induce protective immunity.
Evidence for genetic HIV variants from detection of HIV-DNA.
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Detection of Epstein-Barr virus-DNA in tongue epithelium of human immunodeficiency virus-infected patients.
Oral hairy leukoplakia is a lesion on the lateral part of the tongue that contains replicating Epstein-Barr virus (EBV) and presages progression from human immunodeficiency virus (HIV) infection to AIDS. To clarify the role of EBV in the development of the lesions, we used filter in situ DNA hybridization to determine the prevalence of EBV and of human papillomavirus (HPV) in epithelial cells obtained on swabs from the tongue of HIV-infected patients who had hairy leukoplakia, HIV-infected patients who did not have hairy leukoplakia, and healthy uninfected control persons. In samples collected from the 35 uninfected control persons, EBV DNA could not be detected except at low concentrations in three people. In contrast, all but one of the samples from 11 HIV-infected patients who had hairy leukoplakia contained EBV DNA. Of greatest interest, in 19 of 32 HIV-infected patients who had no signs of hairy leukoplakia, EBV DNA was also detected on the epithelium of the tongue. DNA filter in situ hybridization for the detection of HPV serotypes 6, 11, 16, and 18 in all cases yielded negative results. Statistical analysis showed that the presence of EBV DNA was significantly correlated with the clinical status of the HIV-infected persons, as determined by Walter Reed staging classification, whereas hairy leukoplakia was not. It is concluded that detection of EBV DNA in oral epithelium may be an earlier and more powerful predictor of progression to AIDS than is hairy leukoplakia.
Serovar distribution of urogenital C trachomatis isolates in Germany.
Using monoclonal antibodies in a microimmunofluorescence test the distribution of C trachomatis serovars isolated in the STD out-patient clinic of the Department of Dermatology of the University of Heidelberg was determined. Of 56 isolates investigated the most frequent was serovar E with 35.7%, followed by serovar D with 28.6% and serovar F with 26.8%. This shows that the distribution of C trachomatis in Germany is very similar to that in other Western countries.
Detection of C trachomatis in urogenital specimens by polymerase chain reaction.
OBJECTIVE: To establish a polymerase chain reaction (PCR) protocol for the detection of urogenital C trachomatis infection and to compare it with the detection in cell culture. SPECIMENS: Urethral specimens were collected from 62 male patients and cervical specimens from 106 female patients. SETTING: Department of Dermatology and Venereology, Ruprecht-Karls-Universität, Heidelberg. METHODS: Urogenital specimens were simply boiled for 15 minutes and subsequently subjected to amplification without prior extraction of nucleic acid. The DNA sequence selected for amplification is located in the third open reading frame of the ubiquitous C trachomatis plasmid pCTT1. The amplified products were demonstrated by agarose gel electrophoresis followed by Southern blot hybridization. In addition, specimens were investigated with cell culture. MAIN OUTCOME MEASURES: Results of PCR and cell culture. RESULTS: PCR detected all C trachomatis serovars relevant for urogenital infections (D-L2). Serial dilution experiments revealed that the PCR procedure was 100 fold more sensitive than cell culture. The investigation of 168 urogenital specimens showed that the PCR confirmed all 30 cell culture positive results, however, out of the 138 cell culture negative specimens 16 were positive using the PCR. CONCLUSIONS: A substantial number of urogenital C trachomatis infections detectable by PCR may be missed by the cell culture technique.
[Serotyping of Chlamydia trachomatis isolates].
Antigens can be used in the classification of microorganisms and can give information about the biological behaviour of the infectious agent and the spread of the infection. Starting with the mouse toxicity prevention test, followed by the two-step and then the one-step micro-IFT using polyclonal antibodies, C. trachomatis serovars are now typed with monoclonal antibodies. Worldwide, serovars D, E and F are found with the highest prevalence. No differences have been found between women and men in the prevalence of serovars. In addition, symptomatic and asymptomatic courses of the disease were not correlated with distinct serovars. The persisting technical difficulties of for large-scale typing could be overcome by the use of the polymerase chain reaction followed by treatment with endonucleases.
[The value of symptoms and clinical findings in cervical Chlamydia trachomatis infection].
The frequency of symptoms in the case histories of 68 female patients with and of 313 without Chlamydia trachomatis infections was investigated. Dysuria, vaginal discharge and/or burning/itching in the genital region were reported by 50% (n = 34) of chlamydia-positive women and 53.7% (n = 168) of chlamydia-negative women. Clinical investigation of the chlamydia-positive patients revealed discharge in 83.8% (n = 57), contact bleeding in 38.3% (n = 26) and ectopia in 27.9% (n = 19). The corresponding investigations in chlamydia-negative women disclosed discharge in 72.8% (n = 228) women, contact bleeding in 19.8% (n = 62) and ectopia in 16.8% (n = 52). The results were significantly different as far as contact bleeding and ectopia were concerned. Only when yellow or whitish yellow discharge was distinguished from clear discharge was the difference between the two groups significant (66.7% vs 43.9%). Significant numbers of polymorphonuclear leucocytes (greater than 4 per high power field with oil immersion) were found in 52.9% of the chlamydia-positive women, as against 23% of the chlamydia-negative women. Overall, 48.7% of the women with a C. trachomatis infection were found to have notes of symptoms in the history and signs of cervicitis revealed by clinical investigation. Symptoms only were found in 1 woman, while in 36.8% of the patients signs only were found. Neither symptoms nor signs were mentioned by 13.3% of the women. These results indicate that microbiological detection of the infectious agent is obligatory for the diagnosis of C. trachomatis cervicitis.
[Detection of proviral HIV DNA with polymerase chain reaction in the epidermis].
The infection of cells of the epidermis with HIV can still not be taken as proved, since the demonstration of HIV in Langerhans cells has not been universally accepted. In our study, the polymerase chain reaction was used to look for proviral HIV-DNA in epidermal cells collected by the suction blister technique. The primers flanked sequences of the gp41-encoding region of the env gene and hybridized with highly conserved HIV-DNA sequences. Amplified sequences were detected by the dot-blot technique. The PCR revealed HIV-DNA in epidermals cells of four HIV patients. In addition, HIV-DNA was detected in the mononuclear cells of the blood in the same patients by the PCR. These results strongly support the notion that in addition to blood cells, epidermal cells of HIV patients are also infected with HIV.
[Chlamydia trachomatis serovars and the clinical picture of urogenital infections].
A total of 56 Chlamydia trachomatis strains isolated from female and male patients in the STD outpatient clinic of the Department of Dermatology, University of Heidelberg, were serotyped by means of monoclonal antibodies in an indirect immunofluorescence test. The most prevalent serovar was serovar E, with 35.7%, followed by serovar D, with 28.6%, and serovar F, with 26.8%. No double or multiple infections with different C. trachomatis serovars were found. The first epidemiological study of C. trachomatis serovars in Germany shows that the distribution of distinct serovars is not essentially different from that found in other western countries. The distribution of serovars was similar in women and men. There was no demonstrable correlation between asymptomatic or symptomatic courses of the infections with distinct serovars. In addition, the presence of polymorphonuclear leucocytes in urethritis or cervicitis was not associated with distinct serovars. These results indicate that the antigens used as a criterion in the classification of C. trachomatis are not correlated with the biological behaviour of this infections agent.
[The value of symptoms and findings in urethral Chlamydia trachomatis infection].
The history and the results of clinical investigations in 74 patients with and 262 men without urethral Chlamydia (C.) trachomatis infection were evaluated: symptoms such as dysuria, discharge and/or burning/itching in the genital region were reported by 77% (n = 57) of the patients with an infection and 63.4% (n = 166) of the men without an infection. Upon clinical investigation, discharge was found in 55.4% (n = 41) of the chlamydia-positive patients and in 47.7% (n = 125) of the chlamydia-negative men. Only when yellow, whitish yellow and clear discharge were distinguished from one another was the difference between the two groups of patients (56.1% versus 12%) significant. Microscopic signs of urethritis, i.e. significant numbers of polymorphonuclear leukocytes (greater than 4 per high-power field and oil immersion) were detectable in the smears of 59.5% (n = 44) of the chlamydia-positive patients, in contrast to 15.6% (n = 41) in the smears of chlamydia-negative men. Overall, 67.6% (n = 50) of the patients with a C. trachomatis infection reported symptoms in the anamnesis combined with signs of urethritis upon clinical and microscopic investigation. There were 9.5% (n = 7) of the patients who either mentioned symptoms or showed clinical signs, and 13.5% (n = 10) who neither mentioned symptoms nor showed clinical signs. These results indicate that microbiological detection of the infectious agent is obligatory for diagnosis of urethral infection with C. trachomatis.
[Preventive use of AZT in occupational HIV exposure].
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