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A A Lackner

Publications and source records attributed to A A Lackner.

At least 55 records · Page 3Linked to original sources
PubMed1999

Identification and characterization of Kaposi's sarcoma-associated herpesvirus K8.1 virion glycoprotein.

Kaposi's sarcoma-associated herpesvirus (KSHV) has been consistently identified in Kaposi's sarcomas (KS), body cavity-based lymphomas (BCBL), and some forms of Castleman's disease. Previous serological tests with KS patient sera have detected lytic-cycle polypeptides from KSHV-infected BCBL cells. We have found that these polypeptides are predominantly encoded by the K8.1 open reading frame, which is present in the same genomic position as virion envelope glycoproteins of other gammaherpesviruses. The cDNA of K8.1 from BCBL-1 cells was found to encode a glycosylated protein with an apparent molecular mass of 37 kDa. K8.1 was found to be expressed during lytic KSHV replication in BCBL-1 cells and was localized on the surface of cells and virions. The results of immunofluorescence and immunoelectron microscopy suggest that KSHV acquires K8.1 protein on its virion surface during the process of budding at the plasma cell membrane. When KSHV K8.1 derived from mammalian cells was used as an antigen in immunoblot tests, antibodies to K8.1 were detected in 18 of 20 KS patients and in 0 of 10 KS-negative control subjects. These results demonstrate that the K8.1 gene encodes a KSHV virion-associated glycoprotein and suggest that antibodies to K8.1 may prove useful as contributory serological markers for infection by KSHV.

Amino Acid Sequence↗
PubMed1999

Clinicopathological study of canine oral epulides.

To clarify the clinicopathological features of canine epulides, 189 epulides were reviewed retrospectively. The incidence of the fibromatous, ossifying, acanthomatous and giant cell epulides were 56.6% (107/189), 23.3% (44/189), 18.0% (34/189) and 2.1% (4/189), respectively. The average ages of dogs with fibromatous, ossifying, acanthomatous and giant cell epulides were 8.8, 8.4, 7.8 and 8.7 years, respectively. The male/female ratio of dogs with the acanthomatous epulis (0.8) was lower than those of dogs with the fibromatous (1.9), ossifying (1.4) and giant cell epulis (3.0). There were slight breed differences among the types of epulides. The most noticeable result was that 38.2% of the acanthomatous epulis occurred in Shetland sheepdogs. 43.9% of the fibromatous epulis and 52% of the ossifying epulides arose around maxillary premolars, while 58.8% of the acanthomatous epulis arose around the mandibular canines. Dogs with the fibromatous and ossifying epulides had more severe dental plaque deposition than those with the acanthomatous epulides. Few of the fibromatous (6/104) or ossifying epulides (4/44) showed recurrence after excision, while the majority (21/23) of the acanthomatous epulides showed rapid and repeated recurrences after surgical excision. Epulides treated with hemimandibulectomy or bleomycin chemotherapy did not recur. Giant cell epulides showed no recurrence after surgical removal. These results indicate that the acanthomatous epulis differed from other types of epulides in biological and morphological features and poor prognosis.

Age Factors↗
PubMed1999

Proliferative potential of canine oral epulides and malignant neoplasms assessed by bromodeoxyuridine labeling.

The proliferative potential of canine oral lesions, including epulides, squamous cell carcinomas, a malignant melanoma, and a fibrosarcoma, was examined using a monoclonal antibody to bromodeoxyuridine (BrdU). Twenty-three dogs with oral masses were administered BrdU intravenously at a dose of 8 mg/kg 1 hour before surgery, and the BrdU labeling index (LI) of each lesion was determined immunohistochemically. The average BrdU LIs for the main proliferating elements in the fibromatous epulis (4 cases), ossifying epulis (2 cases), and acanthomatous epulis (10 cases) were 4.9, 3.0, and 8.8%, respectively. The squamous cell carcinomas (5 cases) had an average LI of 15.9%, and the LIs of the malignant melanoma and fibrosarcoma were 7.5 and 10.3%, respectively. All cases of acanthomatous epulides and squamous cell carcinoma treated with simple marginal surgical resection recurred within a short time. The higher LIs in the acanthomatous epulides, squamous cell carcinomas, and fibrosarcoma correlate well with their poor prognoses, reflected by rapid growth and frequent recurrence. Acanthomatous epulis is clearly distinguished from other epulides by its aggressive clinical behavior and high proliferative potential, which is equivalent to that of malignant tumors, despite a lack of cell atypia. The BrdU LI is a useful marker for evaluating the proliferative potential and prognosis of canine oral tumors.

Animals↗
PubMed1999

Nodular Pneumocystis carinii pneumonia in SIV-infected macaques.

Pneumocystis carinii (PC) pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome (AIDS) in humans and macaques. An unusual nodular type of PC pneumonia was observed in two simian immunodeficiency virus (SIV)-inoculated rhesus macaques (Macaca mulatta). These animals developed clinical signs of simian AIDS, including anorexia, weight loss, dyspnea, and collapse. Grossly, both animals had multifocal tan-white nodules 1-10 mm in diameter scattered throughout the lungs. One animal had similar nodules involving the diaphragm and thoracic wall. The lungs were characterized by severe PC pneumonia with numerous large nodules consisting of foamy material that compressed adjacent tissue. The nodules had central areas of necrosis and lysis of alveolar septa. Varying degrees of necrotizing vasculitis were observed in areas of nodular PC pneumonia. The presence of PC in intra-alveolar spaces and nodular lesions was confirmed by immunohistochemistry. No evidence of other agents, including viral inclusions, bacteria, fungi, and lung mites, was detected. The animal with the most severe nodular PC pneumonia had vascular involvement with extrapulmonary spread to the diaphragm, thoracic wall, and regional lymph nodes. This unusual type of nodular PC pneumonia has been rarely seen in human AIDS patients.

Animals↗
PubMed1998

Early regeneration of thymic progenitors in rhesus macaques infected with simian immunodeficiency virus.

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model of AIDS, we examined the early effects of SIV on the thymus. We found that thymic infection by SIV resulted in increased apoptosis 7-14 d after infection, followed by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte progenitors occurred by day 50 and was accompanied by increased levels of cell proliferation in the thymus. Our results demonstrate a marked increase in thymic progenitor activity very early in the course of SIV infection, long before marked declines in peripheral CD4(+) T cell counts.

Animals↗
PubMed1998

Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection.

Human and simian immunodeficiency virus (HIV and SIV) replicate optimally in activated memory CD4(+) T cells, a cell type that is abundant in the intestine. SIV infection of rhesus monkeys resulted in profound and selective depletion of CD4+ T cells in the intestine within days of infection, before any such changes in peripheral lymphoid tissues. The loss of CD4+ T cells in the intestine occurred coincident with productive infection of large numbers of mononuclear cells at this site. The intestine appears to be a major target for SIV replication and the major site of CD4+ T cell loss in early SIV infection.

Animals↗
PubMed1998

Characterization of the cutaneous exanthem in macaques infected with a Nef gene variant of SIVmac239.

The molecularly cloned viruses known as SIVmac239/R17Y and SIVmac239/YEnef cause extensive lymphocyte activation and induce an acute disease syndrome in macaque monkeys. One manifestation of this syndrome is a severe diffuse cutaneous maculopapular exanthem that is similar to the exanthem associated with HIV-1 infection. To examine the pathogenesis of this exanthem, biopsies obtained throughout the course of clinically evident rash were examined for the presence of virus by in situ hybridization and immunohistochemistry, and the cellular infiltrate was characterized with respect to cellular immunophenotype and chemokine receptor expression. The onset of rash was associated with abundant simian immunodeficiency virus nucleic acid and protein within perivascular dermal infiltrates and occasionally within intraepithelial cells. Analysis of cellular infiltrates showed that biopsies, obtained on the day of rash onset, were composed of equal numbers of CD4+ and CD8+ lymphocytes and abundant alphaEbeta7 positive cells surrounding vessels with upregulated endothelial E-selectin. Moreover, by examining virus expression in sequential skin biopsies from the same animal, the clearance of virus and the resolution of rash were associated with an increase in the percentage of cells expressing CD8, the chemokine receptor CXCR3, and GMP-17, a marker of cytotoxic granules. These results suggest that activated cytotoxic T cells are trafficking to sites of inflammation in the skin and directly or indirectly affect levels of viral replication at these sites.

Animals↗
PubMed1998

Localization of persistent Enterocytozoon bieneusi infection in normal rhesus macaques (Macaca mulatta) to the hepatobiliary tree.

Enterocytozoon bieneusi is the most common microsporidian parasite recognized in human patients with AIDS. Recently, we identified a virtually identical organism causing a spontaneous infection associated with hepatobiliary and intestinal disease in simian immunodeficiency virus (SIV)-infected macaques. To examine the natural history of the infection, we examined captive rhesus macaques for E. bieneusi by PCR, in situ hybridization, and cytochemical techniques. PCR performed on fecal DNA detected enterocytozoon infection in 22 (16.7%) of 131 normal rhesus macaques (Macaca mulatta), compared to 18 (33.8%) of 53 rhesus macaques experimentally inoculated with SIV. In normal rhesus macaques, persistence of infection was demonstrated for up to 262 days and was usually not associated with clinical signs. In six of seven normal rhesus animals, E. bieneusi was detected by PCR in bile obtained through percutaneous cholecystocentesis but not by in situ hybridization performed on endoscopic biopsies of duodenum and proximal jejunum.

Animals↗
PubMed1998

Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression.

Central nervous system (CNS) disease is a major feature of simian immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS lesions in SIV-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all animals. The incidence of SIVE correlated significantly with shortened survival (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors (animals that died within 200 days) compared to only 18% (16/89) of normal progressors (animals that lived longer than 200 days) (P=0.011). Animals with SIVE had higher viral loads in peripheral blood than those that did not, but this difference did not reach statistical significance. Similarly, while animals infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51) than animals infected with molecularly cloned SIVmac239 and its T-cell tropic derivatives (18.5%; 10/54) this difference was not statistically significant. In this study rapid disease progression and SIVE were highly correlated making separation of viral determinants of virulence from those of neurovirulence difficult.

Animals↗
PubMed1998

Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis.

Although the mechanisms of human immunodeficiency virus (HIV) neuroinvasion, neuronal injury, and subsequent development of HIV-1-associated AIDS dementia complex are not fully understood, a correlation between monocyte/macrophage infiltrates in the brain and neurological disease exists. In light of the many potential roles that chemokines and chemokine receptors may play in HIV neuropathogenesis, we sought to describe their pattern of expression in the SIV-infected rhesus macaque model of HIV encephalitis. We previously demonstrated elevated expression of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, and interferon-inducible protein (IP)-10 in brain of macaque monkeys with SIV encephalitis. In this study, we demonstrate that the corresponding chemokine receptors CCR3, CCR5, CXCR3, and CXCR4 are expressed in perivascular infiltrates in these same tissues. In addition, we detected CCR3, CCR5, and CXCR4 on subpopulations of large hippocampal and neocortical pyramidal neurons and on glial cells in both normal and encephalitic brain. These findings suggest that multiple chemokines and their receptors contribute to monocyte and lymphocyte recruitment to the brain in SIV encephalitis. Furthermore, the expression of known HIV/SIV co-receptors on neurons suggests a possible mechanism whereby HIV or SIV can directly interact with these cells, disrupting their normal physiological function and contributing to the pathogenesis of AIDS dementia complex.

Animals↗
PubMed1997

Characterization of gut-associated lymphoid tissue (GALT) of normal rhesus macaques.

This study characterizes the gut-associated lymphoid tissue (GALT) of normal healthy rhesus macaques and compares the percentages of T and B cell subsets to those of systemic lymphoid tissue. Lymphocytes from the systemic lymphoid tissue (spleen, axillary, and inguinal lymph nodes), mesenteric lymph nodes (MLN), and intestinal epithelium (IEL) and lamina propria (LPL) of the jejunum, ileum, and colon were examined from both adult and juvenile, normal rhesus macaques. Lymphocytes were analyzed for expression of CD2, CD3, CD4, CD8, CD25, gamma delta TCR, and CD20 by two- or three-color flow cytometric analysis. Sections of jejunum, ileum, and colon were examined for CD3, CD20, and CD103 expression by immunohistochemistry. Peyer's patches were also examined for CD3, CD4, CD8, and CD20 expression by immunohistochemistry. Most IEL and LPL were CD103+, CD3+ T cells with significantly fewer CD20+ B cells. The IEL were predominantly CD3+CD8+ (63-80%), with very few CD4+ cells, whereas CD4:CD8 ratios in the LPL ranged from 0.74 to 1.3. Three to 38% of the IEL were gamma delta TCR positive, but gamma delta expression was rare in the LPL and MLN. gamma delta TCR expression was also higher in the IEL of younger animals. LPL had higher expression of CD25 compared to IEL and systemic tissues, particularly in aged animals. CD4+CD8+, double-positive and CD3+CD4-CD8- double-negative cells were also observed in GALT. These results demonstrate that GALT of rhesus macaques is remarkably similar to that of humans, further justifying the use of these animals as models for various intestinal disorders.

Animals↗
PubMed1997

Resistance of neonatal monkeys to live attenuated vaccine strains of simian immunodeficiency virus.

A major safety concern of using live-attenuated vaccine strategies against AIDS is the potential exposure of neonates or fetuses to vaccine virus from the mother. Here we report that high viral loads and disease were observed in only 2 of 18 neonatal monkeys infected with gene-deleted vaccine strains of simian immunodeficiency virus. Pathogenicity was restricted to neonates born to unvaccinated mothers, that is, lacking maternal immunity, and that received extremely high doses of vaccine virus orally. No in utero transmission of vaccine virus was observed in four neonates born to mothers vaccinated during the second trimester. Our results suggest that the live attenuated vaccine approach should remain a viable option for preventing HIV infection and disease in high-risk human populations.

Animals↗
PubMed1997

Simian immunodeficiency virus-inoculated macaques acquire Mycobacterium avium from potable water during AIDS.

During the terminal stages of AIDS, Mycobacterium avium complex (MAC) infection is the most common disseminated bacterial infection in rhesus macaques (Macaca mulatta) experimentally inoculated with the simian immunodeficiency virus (SIV). The source of mycobacterial infection in 15 SIV-inoculated rhesus macaques housed in a biolevel 3 containment facility was investigated using a sensitive polymerase chain reaction typing technique. Six animal isolates had banding profiles identical to that of 1 environmental isolate obtained from the facility's water distribution system. An additional 6 isolates had banding profiles differing by the addition or loss of one or two bands from this and 1 other water isolate. These findings indicate that potable water may serve as a significant source of mycobacterial infection in SIV-inoculated macaques and suggest that strategies to prevent exposure to mycobacteria within potable water should be investigated as a method to prevent mycobacteriosis in human immunodeficiency virus-infected persons.

AIDS-Related Opportunistic Infections↗
PubMed1997

A herpesvirus of rhesus monkeys related to the human Kaposi's sarcoma-associated herpesvirus.

A herpesvirus that is related to but distinct from the Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) was isolated from rhesus monkeys. The sequence of 10.6 kbp from virion DNA revealed the presence of an interleukin-6 homolog similar to what is present in KSHV and a closer relatedness of the DNA polymerase and glycoprotein B reading frames to those of KSHV than to those of any other herpesvirus. This rhesus monkey herpesvirus replicated lytically and to high titers in cultured rhesus monkey fibroblasts. Antibody testing revealed a high prevalence for at least 10 years in our rhesus monkey colony and a high prevalence in two other colonies that were tested. Thus, rhesus monkeys naturally harbor a virus related to KSHV, which we have called RRV, for rhesus monkey rhadinovirus.

Animals↗
PubMed1997

Early cytokine and chemokine gene expression in lymph nodes of macaques infected with simian immunodeficiency virus is predictive of disease outcome and vaccine efficacy.

Competitive PCR was used to evaluate the expression of cytokine, granzyme B, and chemokine genes in lymph nodes of macaques recently infected with the simian immunodeficiency virus (SIV) pathogenic molecular clone SIVmac239 (n = 16), the nonpathogenic vaccine strain SIVmac239 delta nef (n = 8), and the nonpathogenic molecular clone SIVmac1A11 (n = 8). For both SIVmac239 and its nef-deleted derivative, strong expression was observed as early as 7 days postinfection for interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha, gamma interferon, and IL-13. The levels of gene induction were equally intense for both viruses despite a lower viral load for SIVmac239 deltanef compared with that for SIVmac239. However, the nature of the cytokine network activation varied with the viral inocula. Primary infection with SIVmac239 was characterized by a higher level of IL-4, IL-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES gene expression and a lower level of IL-12 and granzyme B gene expression compared with infection with SIVmac239 delta nef. Thus, infection with nef-deleted SIV was associated with a preferential Th1 versus Th2 pattern of cytokine production. Infection with SIVmac1A11 was characterized by a delayed immune response for all markers tested. The unique patterns of cytokine and chemokine gene expression in lymph nodes correlated nicely with the pathogenic potential of the SIV strains used as well as with differences in their ability to serve as protective vaccines.

Animals↗
PubMed1997

Induction of AIDS by simian immunodeficiency virus lacking NF-kappaB and SP1 binding elements.

Rhesus monkeys (Macaca mulatta) were infected with five strains of simian immunodeficiency virus (SIV) derived from SIVmac239 containing deletions (delta) or substitutions (subst) in NF-kappaB and Sp1 binding sites. We have shown previously that mutations in these regions still allow efficient SIVmac replication in primary lymphoid cell cultures (P. O. Ilyinskii and R. C. Desrosiers, J. Virol. 70:3118-3126, 1996). Two animals were inoculated intravenously with each mutant strain of SIVmac239: delta NFkappaB, delta Sp1234, delta NFkappaB delta Sp1234, substSp12, and substSp1234. All but one of the infected animals showed an early spike in plasma antigenemia, maintained high virus burdens, and had significant changes in lymphoid tissues, and six died with AIDS within the first 60 weeks of infection. One of the animals infected with the SIV strain delta NFkappaB delta Sp1234 showed lower levels of plasma antigenemia and lower virus burdens; the other animal infected with this same mutant strain died with AIDS 17 weeks after inoculation. No consistent novel mutations or reversions were detected in proviral sequences derived from the animals infected with the deletion mutants and the substSp12 mutant by 20 weeks postinfection. Point-mutated sequences were partially deleted in both animals infected with the substSp1234 strain. These results indicate that the NF-kappaB and Sp1 binding sites are not essential for the induction of AIDS by SIVmac239. They also provide indirect evidence for the importance of a novel enhancer element in the U3 region of the SIVmac long terminal repeat that is located immediately upstream of the NF-kappaB binding site within the C-terminal region of the nef coding sequence.

Animals↗
PubMed1997

Neuropathogenesis of simian immunodeficiency virus infection in macaque monkeys.

Patients infected with human immunodeficiency virus (HIV) develop immunologic dysfunction and multiorgan inflammatory diseases directly associated with HIV-1 infection. Of these inflammatory diseases, the most devastating to the HIV-infected patient is involvement of the central nervous system (CNS). The pathogenesis of the clinical syndrome observed in these patients, termed HIV-associated dementia, remains poorly understood. However, as most of the detectable virus in the CNS is in cells of monocyte/macrophage lineage, it is clear that penetration of the blood-brain barrier by HIV-1 and the subsequent influx of monocytes into the brain are crucial components in the neuropathogenesis of HIV-associated dementia. Using the SIV-infected macaque model of acquired immunodeficiency disease, much has been learned about viral neuroinvasion occurring soon after experimental infection. The aim of this review is to discuss these recent advances and provide insight into plausible mechanisms for monocyte entry into the CNS.

AIDS Dementia Complex↗