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Biomedical subjects

C H Fox

Publications and source records attributed to C H Fox.

At least 19 recordsLinked to original sources

Use of an animal model for the study of the role of human immunodeficiency virus 1 in the human intestine.

The gastrointestinal manifestations of human immunodeficiency virus (HIV)-1 disease have centered on identifiable causes of intestinal dysfunction such as parasitic and bacterial pathogens. The lamina propria of the intestine contains cell that harbor HIV-1, but the significance of this observation remains unknown. Because limited animal models are available to evaluate the gastrointestinal effects of this infection, a system that uses human fetal intestine transplanted subcutaneously onto the back of an immunodeficient mouse was developed. After 8 weeks, fetal tissues mature into an adult-appearing tissue with a lumen. Cell-free HIV-1 was inoculated into the explants, an evidence for infection was evaluated by histological evaluation, in situ hybridization, and polymerase chain reaction. No evidence for HIV-1 incorporation into epithelial cells could be found. It was concluded that this model provides a system in which intestinal HIV-1 interaction can be evaluated. In this model, cell-free HIV-1 does not appear to infect the epithelial cell.

Animals

Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.

Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.

Adult

The pathobiology of HIV infection.

The follicular dendritic cells (FDCs) of the germinal center are known to absorb antigens in the form of immune complexes and to express them on the cell surface for long periods of time. Here, Cecil Fox and Michele Cottler-Fox propose that, as a result of FDC binding of immune-complexed viruses, lymphoid organs are the major reservoirs of HIV, and that FDCs play a key role in infection of CD4+ T cells.

Antigen-Antibody Complex

Chronic idiopathic esophageal ulceration in the acquired immunodeficiency syndrome. Characterization and treatment with corticosteroids.

Study objectives were to characterize the clinical syndrome of chronic idiopathic esophageal ulceration in patients with acquired immunodeficiency syndrome (AIDS), to determine the extent of local human immunodeficiency virus (HIV) infection, and to evaluate the effect of corticosteroid therapy upon symptoms and healing. Twelve AIDS patients with chronic esophageal ulcers whose etiology remained unknown after clinical evaluation were the subjects. All patients complained of severe odynophagia, chest pain, and weight loss. Barium radiography and endoscopy demonstrated large, undermined ulcers with severe acute inflammation. No evidence of herpes simplex viruses I or II, cytomegalovirus, fungi, or tumors were found histologically. Evidence of HIV was found in all ulcers using a combination of RNA in situ hybridization, immunohistochemistry, and quantitative antigen capture enzyme-linked immunosorbent assay of tissue homogenates. Steroid therapy by the oral or intravenous routes or by direct intralesional injection resulted in pain relief, weight gain in 10 patients, and ulcer healing in five patients. A characteristic clinical syndrome of chronic idiopathic esophageal ulceration may occur in patients with AIDS, related to local HIV infection in the esophagus. Corticosteroids relieve symptoms and may promote healing of the ulcer.

Acquired Immunodeficiency Syndrome

Human immunodeficiency virus (HIV) and HIV infected cells in saliva and salivary glands of a patient with systemic lupus erythematosus.

A young woman with systemic lupus erythematosus (SLE) was infected with human immunodeficiency virus 1 (HIV-1) and about 6 years later developed persistent bilateral parotid gland enlargement. It was unclear whether this represented salivary gland involvement as a component of her SLE (secondary Sjögren's syndrome) or the initial clinical manifestation of her HIV-1 infection. HIV proviral DNA was found in individual salivary glandular secretions and in whole saliva. Additionally, cells positive for HIV RNA were isolated from whole saliva. A parotid gland biopsy revealed infiltrating lymphocytes containing large amounts of HIV RNA.

Adult

New considerations in the prevalence of periodontal disease.

International surveys demonstrate that the prevalence of pocketing of 6 mm or more is between 5% and 20% for much of the world's population. A recently completed national survey of employed adults found the prevalence of gingival bleeding was 44%, the prevalence of pocketing of 4 mm or more was 14%, and the prevalence of attachment loss of 3 mm or more was 44%. Risk indicators for a higher prevalence of periodontal disease include increasing age, poor education, lack of professional dental care, previous periodontal destruction, tobacco use, and diabetes. African-Americans show a higher prevalence of juvenile periodontitis and adult periodontitis than whites. The female-to-male ratio in juvenile periodontitis may be close to 1:1. Another report during the review period suggests that periodontal disease in adults may have a strong genetic component. A doctoral dissertation demonstrated that the sensitivities of methods used in a national survey to detect pocketing and attachment loss range from 0.24 to 0.87 in a high-prevalence population.

Adolescent

Recombinant gp120 specifically enhances tumor necrosis factor-alpha production and Ig secretion in B lymphocytes from HIV-infected individuals but not from seronegative donors.

The effect of recombinant protein from the envelope (gp120) of the HIV on B lymphocytes purified from either HIV-infected individuals or healthy seronegative controls was examined. B cells from peripheral blood and lymph nodes of HIV-infected individuals spontaneously secreted TNF-alpha; this secretion was augmented by the presence of gp120, whereas B cells from healthy seronegative donors failed to secrete significant levels of TNF-alpha in the presence or absence of gp120. In a coculture system of B cells and chronically HIV-infected T cells (ACH-2), where viral expression is largely mediated by TNF-alpha, gp120 increased virus expression only if the B cells were obtained from HIV-infected individuals. The effects of gp120 on viral expression in this system were not mediated via CD4 receptor binding or FcR binding of anti gp120-gp120 immune complexes. Besides its effect on cytokine production, gp120 also stimulated Ig secretion in B cells from HIV-infected individuals, but not from normal donors. Finally, it was demonstrated by in situ hybridization that germinal centers of lymph nodes from HIV-infected individuals contain large amounts of HIV RNA that is in close proximity to germinal center B cells. These findings suggest that the hyperplastic germinal centers of lymph nodes provide an unique environment for virus expression and accumulation where gp120 stimulates B cells to secrete HIV inductive cytokines, such as IL-6 and TNF-alpha, and thereby further enhances virus expression in infected cells in a paracrine manner.

Antibody Formation

Name of the game?

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Ethics, Professional

cDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell interactions.

We have cloned a full-length cDNA for the B cell membrane protein CD22, which is referred to as B lymphocyte cell adhesion molecule (BL-CAM). Using subtractive hybridization techniques, several B lymphocyte-specific cDNAs were isolated. Northern blot analysis with one of the clones, clone 66, revealed expression in normal activated B cells and a variety of B cell lines, but not in normal activated T cells, T cell lines, Hela cells, or several tissues, including brain and placenta. One major transcript of approximately 3.3 kb was found in B cells although several smaller transcripts were also present in low amounts (approximately 2.6, 2.3, and 1.6 kb). Sequence analysis of a full-length cDNA clone revealed an open reading frame of 2,541 bases coding for a predicted protein of 847 amino acids with a molecular mass of 95 kD. The BL-CAM cDNA is nearly identical to a recently isolated cDNA clone for CD22, with the exception of an additional 531 bases in the coding region of BL-CAM. BL-CAM has a predicted transmembrane spanning region and a 140-amino acid intracytoplasmic domain. Search of the National Biological Research Foundation protein database revealed that this protein is a member of the immunoglobulin super family and that it had significant homology with three homotypic cell adhesion proteins: carcinoembryonic antigen (29% identity over 460 amino acids), myelin-associated glycoprotein (27% identity over 425 amino acids), and neural cell adhesion molecule (21.5% over 274 amino acids). Northern blot analysis revealed low-level BL-CAM mRNA expression in unactivated tonsillar B cells, which was rapidly increased after B cell activation with Staphylococcus aureus Cowan strain 1 and phorbol myristate acetate, but not by various cytokines, including interleukin 4 (IL-4), IL-6, and gamma interferon. In situ hybridization with an antisense BL-CAM RNA probe revealed expression in B cell-rich areas in tonsil and lymph node, although the most striking hybridization was in the germinal centers. COS cells transfected with a BL-CAM expression vector were immunofluorescently stained positively with two different CD22 antibodies, each of which recognizes a different epitope. Additionally, both normal tonsil B cells and a B cell line were found to adhere to COS transfected with BL-CAM in the sense but not the antisense direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Influence of surface characteristics on bone integration of titanium implants. A histomorphometric study in miniature pigs.

The purpose of the present study was to evaluate the influence of different surface characteristics on bone integration of titanium implants. Hollow-cylinder implants with six different surfaces were placed in the metaphyses of the tibia and femur in six miniature pigs. After 3 and 6 weeks, the implants with surrounding bone were removed and analyzed in undecalcified transverse sections. The histologic examination revealed direct bone-implant contact for all implants. However, the morphometric analyses demonstrated significant differences in the percentage of bone-implant contact, when measured in cancellous bone. Electropolished as well as the sandblasted and acid pickled (medium grit; HF/HNO3) implant surfaces had the lowest percentage of bone contact with mean values ranging between 20 and 25%. Sandblasted implants with a large grit and titanium plasma-sprayed implants demonstrated 30-40% mean bone contact. The highest extent of bone-implant interface was observed in sandblasted and acid attacked surfaces (large grit; HCl/H2SO4) with mean values of 50-60%, and hydroxylapatite (HA)-coated implants with 60-70%. However, the HA coating consistently revealed signs of resorption. It can be concluded that the extent of bone-implant interface is positively correlated with an increasing roughness of the implant surface.

Animals

Human intestine matures as nude mouse xenograft.

This report describes a novel system for the study of the development and function of human intestine. Human fetal bowel transplanted into a subcutaneous tunnel on the back of athymic nude (nu/nu) mice develops a new microcirculation within 4 weeks. Tissues undergo morphological development, become similar to adult human bowel tissue, and may survive for 6 months after transplantation. Monoclonal antibody immunoperoxidase staining shows that the epithelial and some endothelial elements are of human phenotype, but the circulating blood cells and migrating mucosal lymphocytes are of mouse origin.

Animals

Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA.

When radiolabeled RNA was used for in situ hybridization, human immunodeficiency virus type 1 (HIV-1) RNA was found in high concentrations in germinal centers of lymphoid tissues from patients with HIV-1 infection. Most of the signal from hybridized probe was independent of specific cells, being found in the extracellular space of germinal centers in all lymphoid tissues examined from adult patients with Centers for Disease Control (CDC) class II and III disease or pediatric patients with CDC class P-2A disease. Lymphoid tissues from adult patients with CDC class IV infections or pediatric patients with CDC class P-2D disease (including autopsy material) lacked intact germinal centers, and HIV-1 RNA was then found only in rare, isolated cells, with some tissues having no detectable HIV-1 RNA. Thus, in the early stages of HIV infection, germinal centers serve as important reservoirs of free virus in the interstitial spaces, and this reservoir disappears as the germinal centers involute with advancing disease.

Adenoids

Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs.

The purpose of this study was to evaluate the early wound healing events of bone around press-fit titanium implants inserted with and without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-I). Nine months prior to implant placement all mandibular premolar teeth were extracted in 8 beagle dogs. Subsequently, 40 specially manufactured titanium implants with 2 transverse holes in the apical section were press fit into precise recipient sites in the dogs' mandibles. The dogs were sacrificed at 7 and 21 days following implant placement yielding 12 PDGF-B/IGF-I treated and 8 control (placebo gel or non-treated) implants for each observation period. Coded undecalcified sections were analyzed for: 1) percentage of implant surface in contact with new bone; 2) percentage of peri-implant space filled with new bone; and 3) percentage of implant hole filled with new bone. An analysis of variance was used to determine significant differences among the treatment groups. At 7 days, the percentage of bone fill in the peri-implant spaces and the percentage of implant surface in contact with new bone were both significantly increased in PDGF-B/IGF-I treated sites (P less than 0.01 for both groups). There was less than 1.5% fill of the implant holes in both treated and control sites (no significant differences). At 21 days the percentage of bone fill in the peri-implant spaces was significantly increased in the PDGF-B/IGF-I treated sites (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance