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Biomedical subjects

F Rapp

Publications and source records attributed to F Rapp.

At least 19 recordsLinked to original sources
PubMed1999

[Arthroscopic therapy of patellar dislocation. Surgical technique and clinical results].

Between January 1986 and August 1995, we treated 86 patients suffering from lateral displacement of the patella with arthroscopic medial tightening and lateral release after a conservative functional treatment remained unsuccessful. 49 patients were available for follow-up studies. 29 patients were treated after primary dislocation of the patella, and 20 patients after recurrent dislocations (2-20). The lateral release was performed by arthroscopy in 28 patients and in 21 patients in an open procedure. The mean follow-up time was 47.3 months. The rate of reluxation was 8%. In the opinion of the patients, 44 (90% of the follow-up) operations were evaluated as good/very good, the average Lysholm score was 87.3 +/- 13.9. The clinical results were influenced by the point of time of the operation. Patients with monoluxation showed a lower rate of reluxation (3% vs. 15%) and superior functional and subjective results than those with recurrent dislocation. However, there were no significant differences between the open and closed performed lateral release. We recommend the technique presented here as a minimal-invasive method especially for patients with monoluxation of the patella.

Adolescent↗
PubMed1991

Role of latency-associated transcript in herpes simplex virus infection.

Herpes simplex virus (HSV)-specified RNA transcript has been detected by in situ hybridization and by RNA blot analyses in latently infected peripheral nerve ganglia in experimentally infected mice and humans. Physical analysis of the nucleotide sequence, approximately 2,500, indicates possible splicing of the transcript into two overlapping open reading frames (ORF) and the presence of potential promoter elements. The latency-associated transcript, probably, is involved in the maintenance of latent herpes simplex virus infection; however, recent findings indicate that latent-phase transcription is involved in some in vivo reactivation.

Animals↗
PubMed1991

Selection of L cell sublines resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine.

A mouse thymidine kinase (TK) deficient L cell subline and L cell sublines biochemically transformed by herpes simplex virus TK were cultured in the presence of increasing concentrations of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) which inhibited the growth of all sublines, and resistant sublines were isolated. Their growth properties were dependent on the medium condition used for selection. One subline had lost viral TK activity, while another retained viral TK activity with altered sensitivity of TK to BVDU in comparison with that of the original subline. Growth characteristics and TK activity of sublines are discussed.

Animals↗
PubMed1990

Effects of cellular fixatives on human immunodeficiency virus production.

Effects of cell fixation procedures appropriate for flow cytometric analysis on the infectivity of human T lymphoblastoid H9 cells infected with human immunodeficiency virus-1 (HIV-1) were evaluated to provide guidelines for choosing cell treatments for potentially infectious samples. H9 cells experimentally infected with HIV-1 were treated by the test fixation procedure, washed, and cocultured with equal numbers of live, uninfected H9 cells. To estimate the reduction in infectivity due to the fixation procedure, dilution series of live infected H9 cells in uninfected H9 cells were simultaneously established in culture. Cell cultures were incubated 8-10 d, harvested, and evaluated for evidence of HIV-1 infection by the presence of cell-associated HIV-1 antigens and/or by the presence of particle-associated reverse transcriptase activity in cell culture supernatants. Thirty-minute fixation with formaldehyde (1.85%), methanol (absolute), methanol:acetone (1:1), or paraformaldehyde (0.5%) reduced the infectivity of HIV-1-infected H9 cells by greater than 99.99%. To the same degree, a multi-step fixation procedure utilizing formaldehyde and ethanol was effective in reducing HIV-1 infectivity. Conversely, the erythrocyte fixative dimethylsuberimidate at 3 micrograms/ml was ineffective in reducing HIV-1 infectivity.

Fixatives↗
PubMed1990

Circulating human immunodeficiency virus (HIV) p24 antigen-positive lymphocytes: a flow cytometric measure of HIV infection.

Asymptomatic individuals seropositive for human immunodeficiency virus (HIV) progress in a heterogeneous fashion toward AIDS. To facilitate monitoring of disease progression and response to therapy, a rapid, new flow cytometric assay (FCA) lymphocyte p24-FCA, has been devised to quantify peripheral blood lymphocytes expressing cell-associated HIV-1 p24 antigen. Results from 55 asymptomatic, HIV-1-seropositive, serum p24 antigen-negative individuals ranged from undetectable (less than 0.1%) to 13.6% p24+ lymphocytes (mean, 2.0%). Mean values for three other groups studied were 0.1% for seronegative, viral culture-negative laboratory workers (n = 24); 4.2% for untreated patients with AIDS (n = 16); and 0.3% for AIDS patients receiving zidovudine (n = 11). Lymphocyte p24-FCA values were inversely related to the number of days to positive viral cultures and to levels of CD4+ lymphocytes. The ratio of p24+ lymphocytes to CD4+ lymphocytes may reflect the fraction of infected CD4+ lymphocytes. Lymphocyte p24-FCA determination may provide a method for monitoring response to antiretroviral therapy regardless of serum p24 antigen status.

CD4-Positive T-Lymphocytes↗
PubMed1990

Suppression of herpes simplex virus type 1 reactivation from latency by (+-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) in vitro.

Latent herpes simplex virus type 1 (HSV-1) infection was induced in human embryonic lung cells in vitro by using a combination of viral replication inhibitors and elevated temperature. Under reactivating conditions (superinfection by human cytomegalovirus or temperature manipulation), a nonantiviral thymidine kinase inhibitor (L-653,180) was found to suppress or delay reactivation of HSV-1 from latently infected human embryonic lung cells. L-653,180 alone or in combination with interferon was ineffective as a primary or acute viral replication inhibitor and was unable to induce latent HSV-1 infection in cell culture. These data suggest that initial or acute virus replication and replication resulting from reactivation from latency are separate events.

Antiviral Agents↗
PubMed1990

Tropism of human immunodeficiency virus 1 isolates for H9 cells and U937 cells.

Human immunodeficiency virus 1 (HIV-1) produced in the human T lymphoblastoid H9 cell line infected cells of that line more readily than cells of the human monocytoid U937 line. While both cell lines expressed detectable levels of the CD4 molecule on their surfaces, the H9 and U937 cell lines differed in expression of major histocompatibility complex class I and class II antigens. Both H9 and U937 cells were infected initially with HIV-1 derived from H9 cells. Cell-free culture supernatants were harvested after the cells had been infected for at least 1 month. Culture supernatant from HIV-infected H9 cells was used to infect H9 and U937 cells. Conversely, culture supernatant from HIV-infected U937 cells was used to infect H9 and U937 cells. The percentages of cells infected at each of several time points during the first few days after infection were determined by flow cytometric analysis of cell-associated HIV-1 major core protein p24. Infection of each cell line was more efficient when the cell type infected was identical to that in which the infecting supernatant was produced. However, this difference in tropism was not generated early after infection of each cell line, as might have been expected if this effect were mediated by cell surface molecules acquired during the process of budding through the cell membrane.

Antigens, Surface↗
PubMed1990

Anti-interferon antibody inhibits natural killer cell activity in HSV-2 genital infection in C57BL/6J mice.

We reported previously that the administration of anti-alpha/beta murine interferon antibody (anti-IFN-Ab) to C57BL/6J mice genitally infected with herpes simplex virus type 2 (HSV-2) dramatically increases morbidity and mortality. The effect of anti-IFN-Ab is visible early postinfection and it is more evident when low virus doses are used. This report describes our study of the mechanism of action of anti-IFN-Ab. We found that anti-IFN-Ab did not affect peripheral multiplication of the virus at the site of infection. The T-cell cytotoxic activity of spleen and lymph node cells of HSV-2 genitally infected C57BL/6J mice was dependent on the virus dose and peaked 7 days postinfection and, therefore, was excluded as a possible mechanism for the effect of anti-IFN-Ab. Natural killer (NK) cell activity paralleled the effect of anti-IFN-Ab closely; the activity peaked early postinfection, and there was no correlation between NK cell activity and virus dose. We have now observed that in mice treated with anti-IFN-Ab, the NK cell activity was significantly lower than in mice infected and not treated with anti-IFN-Ab. The lack of effect of anti-IFN-Ab on local multiplication of HSV-2 coupled with the decrease in NK cell activity indirectly point to a non-antiviral mechanism of action of endogenous IFN in vivo.

Animals↗
PubMed1990

Viral oncogenesis and the immune system.

Oncogenic transformation of normal cells and the establishment of transformed cells to form malignant tumors is a complex, multistep process influenced by viruses in multiple ways. The relationship between viruses and the immune system manifests itself, in part, through various roles of viruses in transformation of host cells, including cells of the immune system. A large number of viruses participate in oncogenic transformation of cells in many animal species. Candidates for oncogenic transformation in man are human T lymphotropic viruses I and II, certain human papillomavirus types, hepatitis B virus, and Epstein-Barr virus. Various mechanisms, which may overlap with one another, have been proposed to account for viral oncogenesis. These include introduction of a directly transforming viral gene, retroviral transduction of protooncogenes, mutagenesis, uncoupling of cellular protooncogene expression from normal regulatory controls, overexpression of normal cellular genes resulting from effects of viral cis- or trans-acting factors, and inactivation of tumor suppressor genes. A second critical area of interaction between viruses and the immune system is in the selection of transformed cells. When cell transformation is accompanied by expression of tumor antigens, the immune system may influence tumor cell establishment and selection of transformed cells for metastatic outgrowth. Finally, host well-being may be severely compromised when viruses infect cells of the immune system, leading to an inability to mount immunological responses specific for opportunistic microorganisms and for cells transformed by viruses or nonviral agents. Human immunodeficiency virus infection exemplifies this phenomenon, although other viruses also negatively affect the immune system. The role of normal immune responses in limiting tumor cell growth is evident from the increased incidence of malignancies in immunocompromised hosts.

Cell Transformation, Neoplastic↗
PubMed1989

Protein analysis of herpes simplex virus latency in vitro established with cycloheximide.

Herpes simplex virus (HSV)-specific protein synthesis was examined during establishment of HSV latency and reactivation of virus in human embryonic lung cells treated with cycloheximide and incubated at 40.5 degrees. Eight viral proteins, identified during the first two days of establishment of latency at 40.5 degrees, were undetectable by Day 3. At least two synthesized proteins were present during the maintenance phase of latency. Reactivation of HSV (viral protein 135K) was first detected in latently infected cultures between 2 and 3 hr after superinfection with human cytomegalovirus (HCMV). During this period an 82K protein with the same molecular weight as one of the HCMV immediate-early proteins (82 and 75K) was detected in the immunoprecipitates of latently infected cultures with anti-HSV serum. Thus, this HSV latency system can be used to analyze protein synthesis and clarify reactivation of HSV by HCMV superinfection.

Antigens, Viral↗
PubMed1989

Analysis of viral proteins in human cytomegalovirus-infected cells during impaired lytic replication of herpes simplex virus.

Herpes simplex virus (HSV) latency can be established in vitro following arrest of virus replication and survival of infected cells in culture. Human cytomegalovirus (HCMV) has been shown to interact with HSV, resulting in reactivation of latent HSV. In addition, impaired replication of superinfecting HSV occurs in HCMV-infected human cells. HCMV-infected human embryonic lung cells inhibit production of infectious HSV despite replication of HSV DNA at levels comparable to those in control cultures infected only with HSV. Using radioimmunoprecipitation techniques, we found that the synthesis of HSV type 1 proteins of the alpha, beta/gamma, and gamma kinetic classes was impaired during the restricted replication of HSV in HCMV-infected HEL cells. However, synthesis of the HSV beta protein ICP-8 and HCMV alpha and beta proteins was not significantly affected in superinfected cell cultures.

Cells, Cultured↗
PubMed1989

Kinetics of infected cell appearance as a determinant of number of human immunodeficiency virus-1 infectious units.

In order to optimize detection of human immunodeficiency virus-1 (HIV-1)-infected cells, the temporal appearance of virus antigens in newly infected H9 cell cultures was examined. Analyses were accomplished by indirect immunofluorescence labeling with each of 10 monoclonal antibodies and evaluation by flow cytometry. Of the antibodies examined, those specific for HIV-1 capsid protein p24, matrix protein p17, or their precursor molecule p55 allowed the earliest and most sensitive detection in infected cells fixed to allow detection of intracellular antigen. Discrimination of infected cells from uninfected cells was much less sensitive when three antibodies specific for HIV-1 glycoproteins were used to detect intracellular or cell surface antigen. In several experiments involving the time course of infection, we observed no differences in cell numbers between infected and uninfected H9 cultures initiated at identical cell concentrations. We hypothesized that it might be possible to quantitate infectious HIV-1 virions from the kinetics of infected cell appearance. Straight-line relationships between the log p24-positive cells and the time after infection were observed. These quantitative observations were employed to calculate the number of infectious units originally added to the culture that were capable of infecting H9 cells. The production of infectious virus, but not of cytopathic effects, was required. The results of this novel approach to the titration of infectious HIV-1 particles agreed well with those from median cell culture infective dose determination. This method could be employed with other infectious agents for which detection of cell-associated antigens is possible in cell cultures not destroyed by infection.

Antibodies, Monoclonal↗
PubMed1989

The Friend legacy: from mouse to man.

The origins of retrovirology began in the primordial laboratories of Ellermann and Bang and of Rous in the first decade of the twentieth century. More than 40 frustrating years were to elapse before this early work with chickens was to lead to experiments with mice, made possible by the use of inbred strains and catalyzed by the observations of Dalldorf and of Gross that newborn animals were susceptible targets for pathogenesis by, respectively, Coxsackie viruses, and polyoma and retroviruses. Seminal observations by Charlotte Friend that retroviruses caused neoplasia in adult mice and her studies investigating the properties and pathogenesis of the Friend leukemia virus, as well as the role of the host immune response in development of disease, helped lay the groundwork of modern retrovirology. The use of retroviruses to study cell differentiation became the foundation on which many more recent discoveries rest. Above all, the information supplied by Friend and her colleagues and investigators in other laboratories finally enabled unequivocal isolation of the first human retroviruses long after most investigators had given up hope of finding such agents in man. Moreover, the techniques developed and the rapid characterization of these newly discovered human pathogens enabled the isolation of human immunodeficiency virus, the cause of acquired immunodeficiency syndrome. It is a challenge to current investigators to extend and expand upon the original work of Friend concerning the pathogenesis of retroviruses, as only a fuller understanding of the complex virus-host disease patterns induced by these viruses will ultimately lead to their control and prevention.

Genetics↗
PubMed1989

Transcriptional activity of the herpes simplex virus genome during establishment, maintenance, and reactivation of in vitro virus latency.

We previously have described a model of in vitro herpes simplex virus (HSV) latency in which latent infection was (i) established with human leukocyte interferon (IFN-alpha) in combination with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) or 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir); (ii) maintained after termination of combined inhibitor treatment by incubation at 40.5 degrees, and (iii) reactivated by either reducing the incubation temperature to 37 degrees or by superinfecting at the elevated temperature with human cytomegalovirus (HCMV). We now report the use of this system to examine the transcriptional activity of the HSV genome during establishment, maintenance, and reactivation of HSV latency in vitro. Numerous species of virus-specific polyadenylated RNAs were present during the first 3 days of combined BVDU and IFN-alpha treatment of HSV type 1 (HSV-1)-infected human fetus lung fibroblast cells. However, after 7 days of combined inhibitor treatment, only a very small quantity of virus-specific RNA could be detected utilizing the short unique region of the HSV-1 genome as probe. After terminating combined BVDU and IFN-alpha treatment and increasing the temperature from 37 to 40.5 degrees on day 7 after infection, virus-specific RNA was undetectable by RNA blot hybridization analysis; however, a small amount of HSV-specific RNA was detected in 2% of the cells by in situ hybridization. The HSV-1 transcriptional products produced after HCMV superinfection in the presence of selected inhibitors of macromolecular synthesis also were examined and demonstrated that the efficient activation of HSV-1 immediate-early gene transcription required the expression of not only immediate-early HCMV gene product(s), but also at least a subset of early-late gene products.

Blotting, Northern↗
PubMed1988

A human cytomegalovirus function inhibits replication of herpes simplex virus.

Human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of herpes simplex virus type 1 (HSV-1). A delay in HSV replication of 15 h as well as a consistent, almost 3 log inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 h after superinfection were observed compared with controls infected with HSV alone. Treatment of HCMV-infected HEL cells with cycloheximide (100 micrograms/ml) for 3 or 24 h, conditions known to result in accumulation of HCMV immediate-early and early mRNA, was demonstrated effective in blocking HCMV protein synthesis, as shown by immunoprecipitation with HCMV antibody-positive polyvalent serum. Cycloheximide treatment of HCMV-infected HEL cells and removal of the cycloheximide block before superinfection inhibited HSV-1 replication more efficiently than non-drug-treated superinfected controls. HCMV DNA-negative temperature-sensitive mutants restricted HSV as efficiently as wild-type HCMV suggesting that immediate-early and/or early events which occur before viral DNA synthesis are sufficient for inhibition of HSV. Inhibition of HSV-1 in HCMV-infected HEL cells was unaffected by elevated temperature (40.5 degrees C). However, prior UV irradiation of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HSV-2 replication was similarly inhibited in HCMV-infected HEL cells. However, replication of adenovirus, another DNA virus, was not restricted in these cells under the same conditions. Superinfection of HCMV-infected HEL cells with HSV-1 labeled with [3H]thymidine provided evidence that the labeled virus could penetrate to the nucleus of cells after superinfection. Evidence for penetration of superinfecting HSV into HCMV-infected cells was also provided by blot hybridization of HSV DNA synthesized in cells infected with HSV alone versus superinfected cell cultures at 0 and 48 h after superinfection. In addition, superinfection with vesicular stomatitis virus ruled out a role for interferon in restriction of HSV replication in this system.

Cell Line↗