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Biomedical subjects

P C Fox

Publications and source records attributed to P C Fox.

At least 19 recordsLinked to original sources

Serum anti-SS-B/La and IgA rheumatoid factor are markers of salivary gland disease activity in primary Sjögren's syndrome.

OBJECTIVE: To identify serologic markers of salivary gland disease activity in 43 patients with primary Sjögren's syndrome. METHODS: Comparison of salivary gland biopsies (focus scores) and flow rates with serum concentrations of IgA and IgM rheumatoid factor (RF), total serum IgG, serum anti-SS-B/La antibodies, and the erythrocyte sedimentation rate. RESULTS: Serum anti-SS-B/La antibody levels correlated with focus scores (rs = 0.477, P < 0.0025). Serum IgA-RF concentrations correlated inversely with stimulated parotid gland salivary flow rates (rs = -0.394, P < 0.01). CONCLUSION: Measuring serum levels of anti-SS-B/La and IgA-RF would be useful when monitoring salivary responses in therapeutic trials, especially in patients with minimal salivary function.

Adult

Multiple ocs-like elements required for efficient transcription of the mannopine synthase gene of T-DNA in maize protoplasts.

Regulatory elements controlling transcriptional activity of the mannopine synthase 2' promoter (mas 2') were defined by analysis of deletion mutants in transient expression assays in maize protoplasts. Deletion of the region between -305 and -290 containing sequence similarity to the octopine synthase (ocs) promoter element reduced activity by 67% compared to wild type activity. Less than 1% of the activity remained in 5' deletions downstream of -153. Inclusion of various heterologous enhancer-like sequences immediately upstream of position -325 increased activity by up to 7.5-fold. Insertion of the -325 to -275 sequence alone, or in combination with heterologous enhancer-like elements, restored activity of some of the 5'-deletion mutants. Restoration of activity was not obtained with mutants deleted past position -127. Our results suggest that a single class of nuclear proteins from maize interact with high affinity at elements designated mas b (-306 to -275; mas 1' element), d (-127 to -108), and e (-82 to -39; mas 2' element) as well as the 20 bp element from the ocs promoter. Although the binding site at mas d only appears to accommodate a single protein, this element has the potential to make a weak, but positive, contribution to the activity of the mas 2' promoter. The binding of nuclear proteins could not be demonstrated at mas a and c, both of which showed limited homology to the ocs element. Mutational evidence suggested that mas a and c may also contribute to mas 2' transcription.

Agrobacterium tumefaciens

Salivary gland involvement in HIV-1 infection.

After infection with human immunodeficiency virus (HIV)-1, virus can be recovered from both whole saliva (the total fluid contents of the mouth) and individual major salivary gland secretions. The concentration of virus is low, and recovery is infrequent. Antibodies (primarily of the IgA class) to HIV-1 are found in saliva. Despite the presence of virus, the oral cavity does not appear to be a route of transmission for HIV-1. This may relate to protective properties of saliva. It has been reported that whole saliva and mixed submandibular/sublingual secretions inhibit the infectivity of the virus in vitro. HIV infection also induces alterations in salivary gland function. Both salivary output and composition may be affected.

HIV Antibodies

Salivary gland 99mTc-scintigraphy: a grading scale and correlation with major salivary gland flow rates.

Sequential salivary gland scintigraphy with 99mTc-technetium pertechnetate (Tc-99) is a safe, minimally invasive test for study of major salivary glands. However, its relationship to salivary function has not been investigated in detail. We have investigated the relationship between major salivary gland flow rates and Tc-99 scans and developed a new rating scale using scans of a control group with normal salivary function. Salivary flow rates and Tc-99 scans were obtained from healthy, non-medicated subjects (n = 33) and from xerostomic patients (n = 22). There were significant differences between the groups for salivary flow rates and Tc-99 ratings. Significant correlations were found between salivary flow rates and Tc-99 ratings in the control and xerostomic groups. The Tc-99 rating scale proved reliable in assessing salivary dysfunction, and showed a high inter-examiner correlation. These results demonstrate the usefulness of salivary gland scintigraphy in assessing major salivary gland flow rates and the utility of a new rating scale.

Adult

Effect of ionizing radiation on sympathetic nerve function in rat parotid glands.

Ionizing radiation (IR) irreversibly damages salivary glands. The pathologic mechanism is unknown. Previously we reported that parotid serous acinar cells may not be the primary site of damage by IR. The purpose of this study was to determine if IR alters sympathetic nerve function in rat parotid glands. Male adult rats received a single dose of radiation (20 Gy) to the head and neck. Three days after IR, parotid saliva secretion induced by norepinephrine (NE) was completely blocked. Catecholamine uptake and metabolism were studied by injecting [3H] dopamine ([3H]DA) into irradiated rats, as a bolus. After 60 min, animals were sacrificed and the parotid gland, submandibular gland, and left ventricle removed. Tissue contents of [3H]DA and [3H]NE, identified by HPLC, were unaffected by IR. The results indicate that IR abolishes acinar responsiveness to NE without affecting parotid sympathetic nerve function.

Animals

Absence of hepatitis C viral RNA from saliva and semen of patients with chronic hepatitis C.

Body fluids from 14 patients with chronic hepatitis C were analyzed for the presence of hepatitis C viral RNA using the polymerase chain reaction. Nucleic acids were extracted from serum, saliva, and semen in guanidinium thiocyanate, subjected to reverse transcription, and then amplified by a double polymerase chain reaction technique using "nested" primers from the highly conserved 5' non-coding region of the hepatitis C virus genome. Hepatitis C viral RNA was found in the serum of all patients in titers ranging between 10(-1) and 10(-3). The hepatitis C viral genome was not detected in any saliva or semen sample. These findings suggest that body fluids of patients with chronic hepatitis C are rarely, if ever, contaminated with the hepatitis C virus. This may help to explain the infrequent transmission of this disease by sexual or close physical contact.

Adult

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

Salivary and oral components of Sjögren's syndrome.

The intraoral symptoms and signs of SS are not specific to SS, being shared with other conditions in which salivary function is diminished. The decrease in saliva causes chronic oral discomfort and functional problems and predisposes patients to dental caries and oral candidiasis. Many methods have been used to assess SGs in SS objectively, but at present a labial salivary gland biopsy specimen showing focal lymphocytic sialadenitis provides the best diagnostic criterion for the salivary component of SS, in terms of its disease specificity, convenience, availability, and low risk. The treatment of xerostomia in patients with SS consists of (1) preventing new and recurrent dental caries by frequent and regular application of topical fluoride, careful dental supervision, and avoidance of sucrose and other metabolizable carbohydrates between meals; (2) reducing oral symptoms by diagnosing and treating oral candidiasis (repeatedly if necessary); and (3) attempting to replace lost saliva by stimulating salivary secretion with physiologic sialogogues or pilocarpine, or if adequate amounts of saliva cannot be stimulated, using some form of saliva substitute, especially for patients wearing complete dentures.

Dental Caries

Salivary gland dysfunction.

Clinically significant declines of salivary output are not a function of aging. Complaints of oral dryness (xerostomia) are common in the elderly patient, however. This complaint is most often a consequence of medications; tricyclic antidepressants, certain antihypertensives, and anticholinergics can cause marked decreases in salivary flow rates. Other medications such as diuretics may cause xerostomia without decreasing salivary output. Systemic diseases such as Sjögren's syndrome can destroy salivary glands. Specific serologic, ophthalmologic, and salivary findings are necessary for the diagnosis of Sjögren's syndrome. Radiation therapy for treatment of head and neck cancers also can damage salivary glands permanently. Infectious agents such as mycobacteria, Epstein-Barr virus, and various oral bacteria can infect human salivary glands. Diminished salivary output can lead to serious oral sequelae. Rapidly progressing dental caries and oral candidiasis are found frequently in this age group. Close supervision of the geriatric patient's oral and dental health is essential.

Aged

Further studies of salivary inhibition of HIV-1 infectivity.

An HIV-1/ATH8-cell cytopathic system was used to characterize the previously reported anti-HIV-1 activity of human saliva. Inhibitory activity was demonstrated by monitoring viable cell counts, HIV-1 p24 core antigen, and reverse transcriptase levels. Nonfiltered whole saliva, sterilized by irradiation, protected the ATH8 cells from HIV-1 infection. When HIV-1/saliva mixtures were filtered following incubation, the quantity of virus was significantly less (approximately 50%) than in HIV-1/media-filtered controls, suggesting that salivary aggregation and/or agglutination may be involved in the inhibitory activity. However, a sufficient number of apparently morphologically intact viral particles were still present in the HIV-1/saliva filtrates to lead to infection. When saliva was filtered prior to incubation with HIV-1, these filtrates showed substantial inhibitory activity, although reduced compared with that of non-prefiltered saliva. We conclude that saliva likely has several means by which to inhibit HIV-1 infectivity.

Adult

Sialochemistry in human immunodeficiency virus associated salivary gland disease.

Human immunodeficiency virus (HIV) associated salivary gland disease is defined as the presence of enlargement of one or more major salivary glands and/or diminished salivary function in an HIV infected individual. It has a number of similarities to, as well as differences from, Sjögren's syndrome (SS). We studied the sialochemistry of stimulated parotid saliva of 11 patients with HIV associated salivary gland disease and bilateral parotid gland enlargement, and compared these findings with those of 15 HIV negative controls, 13 HIV positive individuals with no salivary gland involvement and 18 individuals with SS. The patients with HIV associated salivary gland disease had a significant decrease in the level of salivary protein, with increases in salivary IgA, lysozyme and albumin compared to the HIV negative controls. There were no changes in concentration of electrolytes. The sialochemistry among the patients with HIV associated salivary gland disease was unrelated to the degree of immune suppression and did not change over a 6 month period. The observed changes were similar to those of SS but less pronounced. The similar clinical, histologic and sialochemical features of HIV associated salivary gland disease and SS suggest that these conditions share common pathogenetic mechanisms, which may be modified in the former by the HIV infection.

Acquired Immunodeficiency Syndrome

Effects of ionizing radiation and beta-adrenergic stimulation on the expression of early response genes in rat parotid glands.

There is little known about the regulation of gene expression in rat parotid glands after exposure to ionizing radiation. The present studies investigate the effects of in vivo ionizing radiation, with subsequent stimulation of beta-adrenergic receptors by isoproterenol, on parotid gland function and on the expression of the early response genes, c-fos, c-jun, and jun B. Ionizing radiation diminished parotid gland weight and saliva output. Treatment of irradiated rats with isoproterenol increased the gland weight to levels similar to those in nonirradiated rats. However, such treatment had no effect on saliva output as indicated by measurements of parotid salivary flow rate. Irradiation alone increased the expression of c-fos, c-jun, and jun B. The combination of irradiation and isoproterenol had an additional effect on the levels of c-fos and jun B mRNAs and proteins particularly at earlier experimental times (1 to 8 h). Isoproterenol alone induced high levels of c-fos and jun B mRNA but not of c-jun mRNA. However, c-jun mRNA was induced markedly by radiation and 8 h of isoproterenol treatment, indicating a combined effect on c-jun gene expression. These observations suggest that the expression of the proto-oncogenes c-fos, c-jun, and jun B is probably regulated through differential signal transduction pathways which may be activated by these external stimuli and may be associated with functional changes induced in the rat parotid gland by ionizing radiation and by ionizing radiation and isoproterenol.

Animals

c-myc mRNA expression in minor salivary glands of patients with Sjögren's syndrome.

c-myc protooncogene is implicated in the pathogenesis of B cell lymphoid malignancies and high levels of c-myc mRNA expression are observed in activated blood mononuclear cells. Sjögren's syndrome (SS) is characterized by lymphocytic infiltrates of exocrine glands, remarkable B cell hyperreactivity and a strong predisposition to B cell neoplasia. In this study, c-myc protooncogene mRNA expression in 29 labial minor salivary gland biopsies from patients with primary SS and 15 controls was examined using in situ hybridization histochemistry. Two 40mer oligonucleotides from the 1st and the 2nd exon of the c-myc gene, labeled with 35S, were used as probes. To detect the origin of the cell hybridized with a c-myc probe, a combined immunochemistry in situ hybridization histochemistry technique was used. High c-myc mRNA expression was detected on acinar epithelial cells. c-myc did not correlate with c-fos and c-jun protein expression. Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration (p less than or equal to 0.002) and more intense T lymphocyte infiltrates (p less than 0.05) although these patients revealed no hypergammaglobulinemia. No correlation was observed between c-myc mRNA and B lymphocyte monoclonicity or lymphoma. In conclusion, strong c-myc mRNA expression was observed on epithelial cells of labial salivary glands from patients with primary SS. Our findings may indicate the presence of a reactivated virus hosted in these cells.

Adult

Oral mucosal appearance is unchanged in healthy, different-aged persons.

Oral mucosal status in 182 different-aged, healthy, community-dwelling persons was evaluated. Ninety-four men and 88 women, ranging in age between 20 and 95 years, participated in this study. Oral mucosal status was assessed according to both subjective complaints and a semiquantitative clinical rating scale. No changes in either criterion were detected with increasing age. Oral mucosal status of the older subjects of this study was comparable to that found in a previous study with a randomly enrolled, noninstitutionalized older population in Iowa. The results of this study suggest that aging per se does not lead to changes in the appearance of oral mucosa.

Adult

Magnetic resonance imaging of canine salivary glands after ductal ligation and stimulation by pilocarpine.

We performed magnetic resonance imaging in six dogs after submandibular ductal ligation on one side, followed by secretory stimulation with intraperitoneal injection of pilocarpine (5 mg/kg). On the images obtained after ductal ligation but before stimulation, there was no significant change in signal intensity on either side. After injection of pilocarpine the signal intensity of the ligated gland increased significantly (p less than 0.01) in T2-weighted images and nonsignificantly in inversion recovery images, and remained constant in T1-weighted images. Significant (p less than 0.01) volume increases of the glands after ligation and stimulation were measured for the T1, T2, and inversion recovery protocols. These findings likely reflect the retention of saliva caused by pilocarpine stimulation and the absence of drainage through the obstructed duct. The results indicate that the T2-weighted images obtained after pilocarpine stimulation may be useful for studying patients with disturbance of major salivary gland function and may provide an objective basis for the noninvasive diagnosis of unilateral stenosis.

Animals

An investigation of parotid gland function and histopathology in autoimmune disease-prone mice of different age groups.

This work aimed to characterize parotid gland function in autoimmune disease-prone murine strains (MRL/n, MRL/l and NZB/W) in relation to increasing age and to relate the extent of functional impairment to the intensity of histopathologic changes observed at the different ages. Pilocarpine-stimulated parotid saliva was collected to assess salivary flow rate and composition. Parotid tissue was then removed for histopathologic assessment. Parotid flow rates were not significantly reduced in autoimmune strains compared to controls but were reduced with age in NZB/W mice and in males of the C57 (control) strain. Age-related salivary compositional changes were present in MRL/l mice and in male NZB/W mice. Focal lymphocytic adenitis increased with age in prevalence and intensity in both sexes. The functional and histopathologic changes were not closely correlated. These results suggest that the parotid gland of autoimmune disease-prone mice provides only a poor replication of the salivary changes in human Sjögren's syndrome. Nevertheless, both the functional and histopathological changes developing in these strains, even though of limited extent, are significantly influenced by age.

Aging

Interactions of the salivary and gastrointestinal systems. I. The role of saliva in digestion.

Considerable evidence now demonstrates that saliva and its components have multiple functions in the GI tract. Saliva aids in bolus formation; it lubricates, protects and cleanses the pharyngeal and esophageal mucosa. Salivary bicarbonate buffers esophageal acid in common reflux. Normal salivary flow decreases the duration of acid contact with esophageal mucosa, an important factor in the development of GERD. If salivary flow is depressed or if the esophagosalivary reflex is lost, a patient may be predisposed to develop GERD. Salivary EGF stimulates GI mucosal proliferation via a direct lumenal effect in the esophagus and stomach. The salivary enzymes LL and salivary amylase initiate fat and starch digestion. They are particularly significant in patients with pancreatic insufficiency such as neonates and patients with cystic fibrosis.

Amylases