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Biomedical subjects

P C Fox

Publications and source records attributed to P C Fox.

At least 73 records · Page 4Linked to original sources

Cross-sectional and longitudinal analyses of stimulated parotid salivary constituents in healthy, different-aged subjects.

BACKGROUND: Salivary gland dysfunction has traditionally been associated with old age, and complaints of xerostomia are common in an elderly population. Measurement of certain salivary constituents can provide information about the functional ability of discrete areas of the salivary gland. To our knowledge, this is the first longitudinal study to examine levels of salivary constituents in stimulated parotid saliva in a population of different-aged persons. METHODS: The levels of five salivary constituents (total protein, lactoferrin, proline-rich proteins, sodium, and potassium) were measured in stimulated parotid saliva of 47 healthy, unmedicated men and women over a 10.5 year period. RESULTS: There were no significant age-related decreases in the presence of total protein, lactoferrin, proline-rich proteins, sodium, and potassium in this exocrine secretion. CONCLUSIONS: These data confirm and extend previous cross-sectional studies of salivary constituents, indicating that parotid gland function is maintained in healthy aging individuals.

Adult↗

Salivary autoantibodies in HIV-associated salivary gland disease.

A subset of HIV-positive patients develops salivary gland disease (HIV-SGD), characterized by salivary gland enlargement and/or decreased salivary flow. While clinical symptoms are similar to Sjögren's syndrome (SS), patients with HIV-SGD lack circulating anti-SS-A/Ro and anti-SS-B/La. Occasionally, SS patients lacking circulating anti-SS-A/Ro and anti-SS-B/La have these antibodies in their saliva. Salivas from 11 patients with HIV-SGD, 13 HIV+ patients without HIV-SGD, 14 HIV-negative men controls, and 11 patients with SS were screened for autoantibodies. Five HIV-SGD salivas had antibodies recognizing the cytoplasm of a salivary cell line. No HIV+ controls showed reactivity. Ten of 11 SS patients had salivary autoantibodies, and one HIV-negative control was positive for them. Salivary anti-SS-A/Ro was present in 8/11 SS patients, and 7 also contained anti-SS-B/La. No HIV-SGD salivary samples had these specific autoantibodies. These findings suggest that while glandular polyclonal expansion occurs in both HIV-SGD and SS, different autoantibodies are produced.

Autoantibodies↗

Diagnosis and management of salivary dysfunction.

Salivary gland dysfunction may occur as a result of common medications, cancer therapy, or Sjögren's syndrome. Affected patients may develop significant oral, dental, and upper gastrointestinal sequelae. This article reviews the basic elements in diagnosis of salivary dysfunction, including initial evaluation and specialized diagnostic procedures. Patient management depends primarily on the severity of salivary dysfunction. More severe permanent forms of dysfunction, such as radiation-induced and Sjögren's syndrome, require long-term care, with preventive measures to maintain the dentition and therapeutic attempts to increase oral fluids.

Humans↗

Sjogren's syndrome: oral and dental considerations.

Patients with Sjogren's syndrome have many oral health needs. Due to the extensive oral involvement, dentists may be the first to recognize this condition. Characteristics and treatment options for this disorder are discussed and three case histories are presented.

Adult↗

Acute effects of X irradiation on the function of rat salivary glands.

Radiation-induced damage to salivary glands has been recognized for over 80 years. However, the mechanisms responsible for the destruction of gland parenchyma are still not known. The purpose of this study was to describe alterations in salivary function in the rat within the first 24 h after irradiation. Saliva was collected from the parotid and submandibular glands during radiation treatment and at four times (0.5, 1, 4, and 24 h) after 15 Gy X irradiation delivered to the head and neck. Total body weight, submandibular gland weight, and food and water intake were monitored and the total protein, sodium, and potassium content of the salivas was analyzed. The effects of radiation on salivary glands of the rat could be demonstrated by 24 h. Parotid salivary flow was reduced and the sodium concentration was significantly less than that in control animals. Submandibular gland weights declined markedly by 24 h. These effects appear to be influenced significantly by the animals' limited intake of food and water during this period, as well as the anesthesia administered.

Animals↗

Effects of X irradiation on the function of rat salivary glands at 3 and 40 days.

The purpose of this study was to examine the effects of different doses of X irradiation on the major rat salivary glands. The flow rates of the salivary glands were measured simultaneously in both parotid and submandibular glands of mature male Wistar rats at 3 and 40 days after head and neck irradiation with single doses of 2.5, 5, 7.5, 10, or 15 Gy. The parotid and submandibular glands were weighed at the time of saliva collection and total body weight was obtained weekly. Significant reductions in parotid salivary flow at 3 days and parotid and submandibular flow at 40 days were found. Diminished saliva output was dose-dependent and significantly reduced at radiation exposures of 7.5 Gy and greater. Submandibular function deteriorated between 3 and 40 days and the extent of hypofunction was comparable to the parotid gland at the latter time. Parotid and submandibular gland weights were reduced by irradiation in a dose-dependent manner at both 3 and 40 days. The effects were similar for both glands at the latter time. Total body weight was also reduced by the head and neck irradiation in a dose-dependent manner. There was significant mortality in the group receiving 15 Gy irradiation between 7 and 14 days after irradiation. The results demonstrate that parotid and submandibular glands may be affected comparably by equal doses of head and neck irradiation when examined at later times. In the period immediately after irradiation, there are significant differences in the responses of the major salivary glands.

Animals↗

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↗