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Biomedical subjects

C H Fox

Publications and source records attributed to C H Fox.

At least 55 records · Page 3Linked to original sources
PubMed1993

Isolation and characterization of a novel B cell activation gene.

Using subtractive cDNA cloning, we have isolated a series of cDNA clones that are differentially expressed between B and T lymphocytes. Whereas some of the isolated cDNA are from known B cell-specific genes, many of them represent previously uncharacterized genes. One of these unknown genes was denoted as BL34. Northern blot analysis performed with the BL34 cDNA revealed a 1.6-kb mRNA transcript that was present at low levels in RNA extracted from resting B lymphocytes, but whose expression was markedly increased in RNA prepared from mitogen-activated B cells. Similarly, RNA prepared from several B cell lines treated with phorbol myristate acetate (PMA) contained high levels of BL34 mRNA. In contrast, RNA from purified T cells treated with phytohemagglutinin and PMA had undetectable amounts of BL34 mRNA. In addition, high levels of BL34 mRNA were detected in RNA purified from PBMC of a patient with B cell acute lymphocytic leukemia. Southern blot analysis of human DNA from various tissues and cells lines demonstrated that BL34 is a single-copy gene without evidence of rearrangement. Two full length BL34 cDNA were sequenced, and an open reading frame of 588 bp was identified that was predicted to encode for a 196 amino acid protein. Searches of several protein data bases failed to find any homologous proteins. To directly analyze the expression of BL34 mRNA in lymphoid tissues in situ, hybridization studies with human tonsil tissue sections were performed. BL34 mRNA was detected in a portion of the cells in the germinal center region and adjacent to the mantle region. Further characterization of the BL34 gene and its protein should lead to insights to its role in B cell function and the consequences of its over-expression in acute lymphocytic leukemia.

Amino Acid Sequence↗
PubMed1993

HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease.

Primary infection with the human immunodeficiency virus (HIV) is generally followed by a burst of viraemia with or without clinical symptoms. This in turn is followed by a prolonged period of clinical latency. During this period there is little, if any, detectable viraemia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells. We have analysed viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. Here we report that in early-stage disease there is a dichotomy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency, even at times when minimal viral activity is demonstrated in blood.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Subtractive cDNA cloning of a novel member of the Ig gene superfamily expressed at high levels in activated B lymphocytes.

Using subtractive cDNA cloning we have isolated a series of cDNA clones that are exclusively or selectively expressed in B lymphocytes. mRNA transcripts from one such cDNA clone, referred to as BL11, were found to be expressed at low levels in RNA from normal B lymphocytes, but at very high levels in RNA from in vitro activated B lymphocytes. One major 2.5-kb BL11 mRNA transcript was detected, while low levels of 4.8-, 1.8-, and 1.6-kb transcripts were also found. BL11 mRNA transcripts were absent or present at low levels in RNA prepared from resting or mitogen activated T cells, a variety of lymphoid cell lines including several B-cell lines, and several different tissues. Low levels of BL11 transcripts were found in poly(A) RNA purified from brain and lung. A study of the kinetics of BL11 mRNA accumulation in B lymphocytes stimulated in vitro with Staphylococcus aureus Cowan strain I showed a rapid induction of BL11 mRNA within 2 hours of stimulation with peak expression by 16 hours and a mild decrease with time following the peak levels. Consistent with the in vitro data, in situ hybridization using antisense BL11 RNA probes and human tonsillar tissue localized BL11 transcripts in B-cell-enriched areas. Multiple BL11 cDNA and genomic clones were isolated and sequenced to complete and verify the BL11 cDNA sequence (2,404 bp). A 615-nucleotide open reading frame predicted to encode for a 205-amino acid protein with a molecular weight of 23 Kd was identified. Search of protein data bases with the predicted BL11 protein showed homologies to several members of the Ig superfamily. Analysis of the predicted protein showed a likely signal peptide, a single membrane spanning region, and one V-like Ig domain with three predicted n-glycosylation sites. Southern blot analysis of human genomic DNA suggested that BL11 is a single copy gene without evidence of rearrangement. Primer extension and S1 nuclease mapping identified four tightly clustered transcriptional start sites approximately 40 bp upstream of the predicted translation start site. The first 270 bp of the promoter region were sequenced and found to contain a CATAA box rather than a TATAA box and several DNA motifs found in activation genes. BL11 should prove to be an interesting gene that likely encodes for a protein involved in B-cell activation.

Amino Acid Sequence↗
PubMed1993

Oral health status of the elderly in New England.

The New England Elders Dental Study (NEEDS) reports the prevalence, extent and severity of oral diseases and conditions among a representative sample of community-dwelling elders age 70 and older residing throughout the six New England states. In-home, full-mouth examinations were conducted by four calibrated dentists who used National Institute of Dental Research (NIDR) standardized disease measures plus additional diagnostic codes on all tooth surfaces. Only 37.6% of elders age 70 and older were edentulous, while dentate elders had a mean number of teeth per person ranging from 21.5 to 17.9 across age and gender cohorts. The prevalence of untreated coronal decay in elders with teeth was 28% in female elders and 34% in male elders. More than 90% of all elders with teeth had coronal fillings and 22% exhibited untreated root caries. Periodontal destruction was substantial, with 66% of dentate elders exhibiting moderate periodontal pockets (4-6 mm) while 21% exhibited severe periodontal pocketing (> 6 mm). Comparisons with national surveys suggest that periodontal disease prevalence and severity appear to have been underestimated in previous national studies of the elderly. Because of aging and tooth retention trends, the periodontal disease problem of the elderly may be increasing in the face of dentists' tendency to underdiagnose the periodontal diseases, legal constraints on dental hygienists to independently treat them, and inadequate funding for conservative nonsurgical therapies.

Aged↗
PubMed1993

An improved enrichment method for functionally competent, highly purified peripheral blood dendritic cells and its application to HIV-infected blood samples.

Dendritic cells (DC) were purified from human peripheral blood using a rapid and simple method based on magnetic depletion of phagocytes with carbonyl iron, followed by centrifugation of nonphagocytic cells on a Percoll density gradient and depletion of lymphocytes and macrophages/monocytes with a panel of MoAbs and immunomagnetic beads. Enriched DC were obtained with > 99% purity as judged by non-specific esterase (NSE) staining. After isolation, these cells, representing 0.4% of the starting mononuclear cell population, still function as potent antigen-presenting cells for purified T lymphocytes. The present results confirm the ability of human peripheral blood DC to present soluble antigens to T cells including microbial antigens and show, further, that DC are more potent soluble antigen-presenting cells than monocytes. The method was successfully applied to the purification of DC from the blood of HIV-infected individuals. We could not detect decreased numbers of DC in four individuals with early HIV infection and no replicating HIV was detected by in situ hybridization in the DC.

Antigen-Presenting Cells↗
PubMed1993

Beneath the surface of coronal caries: primary decay, recurrent decay, and failed restorations in a population-based survey of New England elders.

A cross-sectional study was conducted of the oral health status of a random sample of community dwelling elders, aged 70 and older, living within the six New England states. Four examining teams, each composed of a trained and calibrated dentist and a field technician, collected data during an in-home oral examination. The prevalence of carious, filled, recurrent decayed, and non-carious but failed restored coronal surfaces was recorded. For the 1,151 respondents, the mean DFT was 6.16 (SD = 6.96) and the mean DFS was 18.83 (SD = 23.37), with 37.6 percent of the sample edentulous. Eleven percent of the population had 70 percent of the coronal decay. Males (OR = 2.2, CI = 1.3-3.8) and elders with less education (OR = 1.8, CI = 1.0-3.0) were at higher risk for three or more surfaces of coronal decay. Recurrent decay was present in 16 percent of the dentate population. However, more noncarious but failed restored coronal surfaces (332) were recorded in the population of New England elders than were surfaces of recurrent decay (234). The New England elders have higher rates of decay than New England children, although the rates matched those of previous national studies. The findings signal a need to develop targeted preventive regimens for older adults and greater understanding of dental treatment needs of elders.

Aged↗
PubMed1993

Cross-sectional studies in periodontal disease: current status and implications for dental practice.

This paper reviews the cross-sectional national studies of periodontal disease conducted over the past 30 years. Studies included are the 1960-62 HES study (NCHS), the 1971-74 NHANES I study (NCHS), the 1981 RTI study (HRSA), and the 1985-86 Employed Adults study (NIDR). For each of these surveys, the population studied, the general sampling strategy, the periodontal measures collected, and the periodontal findings are compared in this paper. Compared with the first three studies, the NIDR 1985-86 findings appear markedly lower, implying that there has been a decline in the prevalence of periodontal disease. Two possible inferences from these studies are that: (1) there has been a decline in the prevalence of periodontal disease in recent years or (2) the sampling and measurement methods may be sufficiently different for these lower numbers to result. Each inference is explored, with the authors concluding that the latter is more plausible. The implications for future treatment needs are then estimated, given the marked trends in the size of the aging population. The number of older adults over age 55 who will need periodontal services will increase. The adequacy of the number, type, and distribution of dental care providers to meet these increasing needs is discussed.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗