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Biomedical subjects

K K Knox

Publications and source records attributed to K K Knox.

32 records · Page 2Linked to original sources
PubMed1994

Disseminated active HHV-6 infections in patients with AIDS.

Human herpesvirus 6 (HHV-6) infected cells were detected in all lung, lymph-node, spleen, liver, and kidney tissues obtained at necropsy from an unselected series of nine patients with AIDS. This infection rate was significantly higher than that for cytomegalovirus. Lung infection with HHV-6 was extensive enough in one patient to account for fatal pneumonitis. In other tissues increased numbers of HHV-6 infected cells were related to the presence of lymphocytes infiltrates or residual lymphoid tissue, with lymphocytes being predominantly infected. Thus HHV-6 is an important pathogen in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1994

Human herpesvirus-6-associated malignant lymphoma in a bone marrow transplant recipient.

BACKGROUND: Human herpesvirus-6 (HHV-6), the sixth member of the herpesvirus family, can infect and replicate in human hematopoetic cell lines and can cause various illnesses in humans. HHV-6 has been suggested to be linked to various lymhoproliferative disorders. In vitro studies have demonstrated the oncogenic potential of HHV-6. The role of HHV-6 in human lymphomas needs to be examined. OBJECTIVE: To determine the involvement of HHV-6 in an immunoblastic lymphoma which developed in a bone marrow transplant patient, who had HHV-6 viremia. STUDY DESIGN: Paraffin-embedded lymphoma tissues were examined for the presence of HHV-6 by immunohistochemistry, PCR and in-situ hybridization. This is a case report investigation. RESULTS: An acute myelogenous leukemia patient received an allogeneic bone marrow transplant. He developed human herpesvirus-6 (HHV-6) viremia approximately 6 weeks after transplantation and HHV-6 was concurrently isolated from his bone marrow. Soon afterward, a large cell immunoblastic lymphoma was diagnosed. Complications of this tumor subsequently resulted in the patient's death. Periaortic lymph nodes and tumor cells infiltrating the liver and kidneys showed the presence of HHV-6 by immunohistochemistry and polymerase chain reaction (PCR). Southern blot analysis of the PCR amplified DNAs confirmed the presence of transforming pZVH14 DNA sequences of HHV-6 in the tumor tissues. Lymph nodes of 6 immunologically intact individuals were negative for HHV-6 by immunohistochemistry and PCR analysis. Tumor tissues were negative for EBV DNA by in situ hybridization with DNA probes specific for the EBV EBER RNAs. CONCLUSION: Our data suggest that HHV-6 may be involved in the pathogenesis of some immunoblastic lymphomas.

Journal Article↗
PubMed1993

Human herpesvirus-6-associated suppression of growth factor-induced macrophage maturation in human bone marrow cultures.

Cultures of marrow mononuclear cells were exposed to medium derived from cell cultures infected with several different strains of human herpesvirus-6 (HHV-6) immediately before the addition of either of two growth factors, granulocyte-macrophage colony-stimulating factor and interleukin-3. Exposure to any of the viral preparations suppressed the outgrowth of nonspecific esterase-positive adherent macrophages induced by the factors by more than 90%. The nonadherent cell populations in the infected cultures were numerically similar to those in uninfected control cultures, demonstrating the absence of a nonspecific cytotoxic effect of the viral materials. Infectious virus was not necessary for the macrophage outgrowth suppression. These findings suggest that HHV-6 either encodes or induces a soluble mediator or mediators that can interfere with the responses of bone marrow to growth factors and possibly block the normal differentiation of macrophages from marrow precursors.

Animals↗
PubMed1993

Human herpesvirus-6 (HHV-6) infection in allogeneic bone marrow transplant recipients: evidence of a marrow-suppressive role for HHV-6 in vivo.

Sixteen adults were studied for the first 100 days after allogeneic bone marrow transplant to assess the pathogenic role of human herpesvirus-6 (HHV-6) infection in patients with unexplained febrile illnesses. HHV-6 was directly isolated from the blood of 6 patients. Analysis of the clinical courses of these 16 patients revealed otherwise unexplained posttransplant marrow suppression in 5 patients. Idiopathic marrow suppression occurred more frequently in patients with concurrent HHV-6 viremia (4/6) than in those from whom HHV-6 was not isolated from peripheral blood (1/10, P < .05). An etiologic role for the virus was also supported by isolation of HHV-6 from the bone marrow of all 4 patients at the time of marrow suppression and by in vitro colony-forming unit (cfu) assays that demonstrated that HHV-6 could inhibit cfu-granulocyte-macrophage and burst-forming unit-erythroid growth from human bone marrow. By restriction enzyme mapping, all clinical isolates were type B, suggesting that bone marrow transplant recipients may be preferentially infected with and reactivate this HHV-6 subtype. This study implicates HHV-6 as a novel cause of bone marrow suppression in marrow transplant recipients.

Adult↗
PubMed1992

In vitro suppression of bone marrow progenitor cell differentiation by human herpesvirus 6 infection.

Suppression of marrow function may be one of the most serious effects of human herpesvirus 6 (HHV-6) infection in marrow transplant patients. In this study, normal bone marrow mononuclear cells were infected in vitro with HHV-6, and a methylcellulose-based colony formation assay was used to evaluate the impact of the infection on marrow cell differentiation and proliferation. Results demonstrated that the outgrowth of colony-forming units of granulocyte and macrophage lineages (cfu-GM) was decreased by approximately 43%, that growth of cfu of granulocyte, erythrocyte, macrophage, and megakaryocyte lineages (cfu-GEMM) was inhibited by an average of 71%, and that the erythroid burst-forming unit (bfu-E) was decreased by approximately 73%. Further, outgrowth of the marrow stromal layer was reduced 74%. Direct infection of bone marrow monocytes was observed, although cell-free virus could not be detected in infected culture supernatants. Addition of a neutralizing monoclonal antibody specific for interferon-alpha to the infected cultures resulted in an almost complete reversal of the viral suppressive effects.

Bone Marrow↗
PubMed1991

Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation.

Severe interstitial pneumonitis in 2 marrow-transplant recipients was associated with human herpesvirus-6 (HHV-6) infection. The virus was repeatedly detected in respiratory specimens from 1 patient, and HHV-6-infected cells were shown in lung tissue from both patients by immunohistochemical staining. The infected cells were primarily intra-alveolar macrophages, although infected lymphocytes were seen. HHV-6 should be considered as a cause of unexplained lung disease in marrow-transplant recipients and other immunocompromised patients.

Adult↗
PubMed1991

Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult.

The authors report a case of pneumonitis in a young healthy man caused by coinfection with human herpesvirus 6 (HHV-6) and Legionella pneumophila. The patient's course was complicated by severe respiratory, renal, hepatic, and central nervous system dysfunctions, which were believed to be primarily the results of his Legionella infection. Aggressive antibiotic treatment produced no response, and Legionella remained isolatable from lung tissue throughout several weeks of antimicrobial therapy. Human herpesvirus 6 was isolated from a sample of peripheral blood during the acute stage of the patient's illness, and numerous HHV-6--infected macrophages and lymphocytes were detected by immunohistochemical staining of biopsy-derived lung tissue. Paradoxically treatment of the patient with high-dose corticosteroids resulted in dramatic improvement of his condition, including clearance of the Legionella infection. The demonstration that corticosteroids efficiently inhibit HHV-6 replication in vitro suggests that the virus may have contributed to the patient's pneumonitis by enhancing tissue inflammation, by compromising the function of pulmonary macrophages, and, perhaps, by destroying the patient's CD4+ T lymphocytes. Human herpesvirus 6 may be able to function as a synergistic cofactor in lung infections by Legionella and other pathogens.

Adrenal Cortex Hormones↗
PubMed1990

Suppression of human immunodeficiency virus type 1 replication by human herpesvirus-6.

The pathogenesis of AIDS is complex and poorly understood despite intensive research efforts. One of the most puzzling aspects of the disease is the long interval between primary infection with human immunodeficiency virus (HIV) and the production of antiviral antibodies and onset of overt disease. Probably the most important factor that determines the length of these intervals is the rate at which HIV replicates within the infected host. Molecular studies have suggested that the replication of HIV can be enhanced by concurrent infection with other viruses, especially herpesviruses such as cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. Presumably the presence of those viruses would serve to accelerate the progression of HIV-mediated disease. In contrast, studies reported here indicate that coinfection of cell populations with HIV and human herpesvirus-6 (HHV-6) leads to a near total suppression of HIV replication. The replication of HHV-6 is unaffected or minimally enhanced by the presence of HIV. These findings suggest that HHV-6 might serve to slow the progression of disease in some HIV-infected individuals.

Cells, Cultured↗
PubMed1990

Identification of interferon-resistant subpopulations in several strains of measles virus: positive selection by growth of the virus in brain tissue.

Subacute sclerosing panencephalitis (SSPE) is a chronic and usually fatal central nervous system disease caused by a persistent infection with measles virus. The pathogenic mechanisms of the disease are poorly understood, but restricted expression of viral antigens within the infected tissue appears to be involved. We have previously proposed that interferon (IFN) plays a role in the pathogenesis of SSPE by interacting with viral subpopulations that are relatively resistant to IFN-mediated inhibition. Such IFN-resistant viral subpopulations have now been identified in six independent strains of measles virus, two derived from patients with measles and four derived from patients with SSPE. By means of a replicative-plating procedure, these IFN-resistant viruses were found to be heterogeneous with respect to their growth in the presence of high levels of IFN. One viral form replicates fully, with complete destruction of the infected-cell culture, whereas the other form induces a restricted, self-limited form of cytopathic effect, similar to that seen with cell-associated strains of measles virus isolated from SSPE patients. Passage of a virus stock containing both of these viral forms through the central nervous system tissue of newborn hamsters strongly selects for the viral form associated with the self-limiting type of cytopathic effect. The presence of this form of IFN-resistant virus coupled with chronic production of IFN within the central nervous system may account for viral persistence in SSPE patients.

Animals↗
PubMed1986

Antigenic variation among Borrelia spp. in relapsing fever.

Seven antigens of Borrelia hermsii, B. parkeri, and B. turicatae with isoelectric points in the range of 4.4 to 5.0 and molecular masses of 40 to 43 kilodaltons played a role in the relapse phenomenon of relapsing fever. Based upon location of the antigens in the outer envelope, the molecular weight, and Western blot analysis, the antigens from each phase of spirochetemia appeared to be a mixture of the serotype-specific antigens of cloned B. hermsii.

Animals↗
PubMed1986

Comparison of cerebrospinal fluid C-reactive protein and lactate for diagnosis of meningitis.

Levels of C-reactive protein and lactate were determined on 562 consecutive cerebrospinal fluid (CSF) samples from adult patients with a wide variety of central nervous system diseases to compare the sensitivity and specificity of CSF lactate and C-reactive protein for the rapid diagnosis of bacterial meningitis. Neither test alone, together, or in combination with elevated CSF leukocyte count and protein had a predictive value over 60% for a positive test in this group of patients with diverse central nervous system problems. Neither test is useful as a screening test for bacterial or mycotic meningitis. Also, in patients with partially treated bacterial meningitis, the tests are often negative. CSF lactate may be useful in differentiating aseptic from septic meningitis in selected patients.

Bacterial Infections↗