Biomedical subjects
Ann A Kiessling
Publications and source records attributed to Ann A Kiessling.
Isolation of human immunodeficiency virus type 1 from semen and vaginal fluids.
Semen and vaginal fluids transmit HIV infection. The virus is present as cell-free particles and as infected cells. Isolation of infectious virus from both genital tract fluids poses unique problems. Vaginal fluids are heavily contaminated with normal bacterial flora, and seminal plasma is cytotoxic to peripheral blood mononuclear cells. Adaptations of routine laboratory procedures have been developed to largely overcome these problems, allowing the culture and characterization of genital-tract HIV.
Detection of drug-resistant HIV-1 strains.
Human immunodeficiency virus (HIV-1) encodes proteins essential to its replication cycle. Reverse transcriptase, protease, and viral envelope gp120 are three proteins that have been targeted for antiviral drug development. Eleven inhibitors of reverse transcriptase, seven inhibitors of protease, and one inhibitor of viral envelope binding have been approved for use. Antiretroviral therapy has reversed the mortality rate of HIV-infected persons, but over time, therapy-resistant virus variants may outgrow. A large body of information is now available to relate specific amino acid sequences in the resistant variants to specific drug regimens. Designing therapy to compensate for virus resistance results in improved patient outcomes. The advent of microsequencing technologies paved the way for direct sequencing of DNA products generated by polymerase chain reactions, thus dramatically lowering the cost of HIV gene sequencing. Designing therapy according to genetic analysis of HIV variants will not only also improve clinical outcome, but will also deter the transmission of drug-resistant strains.
What is an embryo?
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Tissue-specific populations of leukocytes in semen-producing organs of the normal, hemicastrated, and vasectomized mouse.
Semen HIV is separate and distinct from blood HIV and work has revealed that seminal plasma HIV particles do not arise from infected cells in semen. These findings indicate that semen-producing organs contain multiple, separate populations of HIV host cells. To test this hypothesis, we have examined leukocytes in semen-producing organs of male mice. Cells expressing F4/80 (tissue-specific macrophage marker) were abundant in testicular interstitium and as dendritic-like cells in the lumenal epithelium of the epididymis, especially the initial segment. Cells expressing CD45 (panleukocyte marker) were found rarely in the testicular interstitium, commonly in epididymal epithelium, were most abundant in the interstitium of the epididymis, and were more readily released from minced tissues than were F4/80(+) cells. Unlike the testis and epididymis, F4/80(+) cells in seminal vesicles also appeared to be CD45(+). Seminal vesicle leukocytes were restricted to the epithelium surrounding the lumen and were not released by mincing. CD11b (monocyte/B cell marker) was detected in testicular and seminal vesicle interstitium, but not in the epididymis. Hemicastration and vasectomy caused a limited redistribution of the leukocytes. These findings confirm the existence of tissue-specific populations of leukocytes in semen-producing organs and indicate that some populations are highly tissue adherent. The regionalized, tissue-adherent macrophages in the testicular interstitium, the initial segment of the caput epididymis, and the seminal vesicle epithelium suggest the existence of reservoirs of HIV-infected cells in humans that could contribute virus particles, but not infected cells, to semen and possibly blood.
Seminal plasma induces programmed cell death in cultured peripheral blood mononuclear cells.
Immunosuppressive properties of seminal plasma inhibit the recovery of infectious HIV from semen, and led to the view early in the pandemic that semen HIV was transmitted principally by infected semen cells. More recent studies have revealed significant titers of HIV RNA in seminal plasma, however, even from men receiving successful antiviral therapy. Thus, studies of infectious HIV in seminal plasma are important to understanding sexual transmission and response to therapy. The present studies were undertaken to determine whether seminal plasma immunosuppression is mediated by the induction of programmed cell death (PCD). Peripheral blood mononuclear cells (PBMCs) were cultured without or with phytohemagglutinin and seminal plasma from normal donors, or men postvasectomy, or seminal vesicle protein collected at surgery. PBMC survival was measured at 3, 6, and 18 hr of culture; cells were examined for evidence of PCD by uptake of the fluorescent dye YO-PRO, and for fragmented nuclear DNA by the TUNEL assay. Approximately 90% of PBMCs cultured with seminal plasma from intact or vasectomized men were lost during 18 hr of culture; seminal vesicle protein did not induce cell loss. PCD assays were positive for PBMCs exposed to the seminal plasma, and negative for PBMCs cultured with seminal vesicle protein. Serum was not required for PCD induction. A 3-hr pulse with seminal plasma was sufficient to initiate PCD. These findings indicate that PCD induction accounts for the cytotoxic properties of semen, that the PCD is not the result of semen amine oxidases, and either that substances produced by seminal vesicles only at ejaculation, or by the prostate, are responsible for PCD induction.
Overseeing research on therapeutic cloning: a private ethics board responds to its critics.
Advanced Cell Technology's Ethics Advisory Board has been called window dressing for a corporate marketing plan. But the scientists and managers have paid attention, and the lawyers have gone along.