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Biomedical subjects

P C Fox

Publications and source records attributed to P C Fox.

At least 37 records · Page 2Linked to original sources
PubMed1998

Salivary electrophoresis in the diagnosis of Sjögren's syndrome.

OBJECTIVE: The purpose of this study was to investigate the potential use of salivary electrophoresis for the diagnosis of Sjögren's syndrome. METHODS: Salivary protein profiles of 43 patients and 39 healthy control subjects were compared on three different gel electrophoresis systems: sodium dodecylsulfate-polyacrylamide gel electrophoresis, anionic polyacrylamide gel electrophoresis, and immobilized pH gradient gel electrophoresis (isoelectric point, 3.5-5.0). RESULTS: Most of the patients with Sjögren's syndrome exhibited an electrophoretic profile that was different from that of the healthy control subjects. Among the three gel electrophoresis systems examined, the immobilized pH gradient system appeared to be the most reliable for Sjögren's syndrome. Tests of accuracy revealed that the immobilized pH gradient system exhibits high specificity (97%), sensitivity (95%), positive predictive value (97%), and negative predictive value (95%) in the diagnosis of Sjögren's syndrome. CONCLUSIONS: Our results suggest that salivary electrophoresis is a potentially useful test for the diagnosis of Sjögren's syndrome.

Case-Control Studies↗
PubMed1998

Fas and Fas-mediated effects on a human salivary cell line in vitro: a model for immune-mediated exocrine damage in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune exocrinopathy characterized by mononuclear cell infiltration and loss of parenchymal tissue in salivary and lacrimal glands. The mechanisms for these histologic alterations are not known. Apoptotic cell death, induced by the ligation of Fas (APO-1/CD95) with Fas ligand (FasL/CD95L) may be an explanation for the tissue damage seen in SS. Fas and FasL were detected in minor salivary glands from SS patients and healthy individuals using immunohistochemical methods. There was increased expression of both Fas and FasL in the patients. The ability of the Fas-FasL pathway to influence epithelial cell growth and survival was demonstrated in vitro using a human submandibular cell line. The presence of Fas receptor was demonstrated on the cells. Anti-Fas antibody triggered cell death. Cells were also grown in the presence of gamma-interferon (IFN-gamma). IFN-gamma induced an upregulation of Fas receptor expression and pre-treatment of cells with IFN-gamma led to enhanced anti-Fas mediated cell death.

Cell Division↗
PubMed1998

Optical simulations of a noninvasive technique for the diagnosis of diseased salivary glands in situ.

A simulation experiment for three-dimensional (3D) imaging of exogenous fluorescinated antibodies that specifically bind to infiltrating lymphocytes in minor salivary glands was carried out. Small (approximately 1 mm3 volume) rhodamine targets, which mimic diseased minor salivary glands labeled with fluorescent antibodies to infiltrating lymphocytes in Sjøgren's syndrome, were embedded in a highly scattering tissue phantom consisting of a thick Delrin disk covered by index matched Delrin slabs of various thickness. In this way the variation of fluorescence profiles on the surface of tissue could be examined corresponding to the range of depths of the salivary glands in vivo. Surface images were obtained for different target depths and radial distances from laser excitation to target fluorophore. These images were analyzed and compared to calculations based on random walk theory in turbid media, using previously determined scattering and absorption coefficients of the Delrin. Excellent agreement between the surface profiles experimentally measured and those predicted by our random walk theory was obtained. Derivation of these theoretical expressions is a necessary step toward devising an inverse algorithm which may have the potential expressions to perform 3D reconstruction of the concentration distribution of fluorescent labels within tissue.

Diagnostic Imaging↗
PubMed1998

Sjögren's syndrome: a model for dental care in the 21st century.

The diagnosis and treatment of Sjögren's syndrome, which poses many severe complications, should be of critical interest to dentists, who are often the first practitioners to detect symptoms. Dentistry is an integral part of health care delivery for patients with this condition. Management of Sjögren's syndrome can be seen as a model for the expanded scope of dental care in the future.

Autoimmune Diseases↗
PubMed1998

Differential cytokine mRNA expression in human labial minor salivary glands in primary Sjögren's syndrome.

Cytokines are known to be involved in a number of autoimmune conditions and are increasingly viewed as key components in numerous aspects of normal and abnormal cell functions. The purpose of the present study was to investigate possible immunopathogenic mechanisms within the labial minor salivary glands of patients with primary Sjögren's syndrome (pSS) by examining differential cytokine gene expression in individual cell populations (acini, ducts, or lymphoid cells). A cell-specific microdissection technique in combination with reverse transcription-polymerase chain reaction (RT-PCR) and Southern hybridization using 32P-labeled cytokine gene-specific probes was utilized to measure cytokine messenger RNA expression in individual cell populations of patients and healthy controls. mRNAs for interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGF-beta1) were detected in the epithelial cells (acini and ducts) and lymphoid cells of the labial minor salivary glands of pSS patients. The expression levels of these mRNAs in the epithelial cells were either up- or down-regulated by adjacent focal infiltrating lymphoid cells. mRNAs for all of the above cytokines, with the exception of IFN-gamma, were detected in salivary tissues of healthy volunteers. The epithelial cells in the salivary glands are active participants in the autoimmune-mediated process of pSS, as evidenced by their ability to express a high frequency and wide variety of cytokines. The presence of an infiltrating lymphoid focus within the gland appeared to modulate cytokine gene expression by the salivary epithelial cells.

Blotting, Southern↗
PubMed1998

The mouth is a gateway to the body: gene therapy in 21st-century dental practice.

Gene therapy may become an integral tool in dental practice early in the 21st century. It and other biological therapies are expected to be applied to oral diseases and disorders during the midpractice lifetime of today's dental students. If the applications of oral gene transfer are expanded to systemic diseases, oral health care providers in the future could routinely be "gene therapists" with therapeutic targets well outside the oral cavity.

Animals↗
PubMed1997

Comparative molecular field analysis and molecular modeling studies of 20-(S)-camptothecin analogs as inhibitors of DNA topoisomerase I and anticancer/antitumor agents.

Conformational studies and comparative molecular field analysis (CoMFA) were undertaken for a series of camptothecin (CPT) analogs to correlate topoisomerase I inhibition with the steric and electrostatic properties of 32 known compounds. The resulting CoMFA models have been used to make predictions on novel CPT derivatives. Using the newly derived MM3 parameters, a molecular database of the 32 CPT analogs was created. Various point atomic charges were generated and assigned to the MM3 minimized structures, which were used in partial least-squares analyses. Overall, CoMFA models with the greatest predictive validity were obtained when both the R- and S-isomers were included in the data set, and semiempirical charges were calculated for MM3 minimized low-energy lactone structures. A cross-validated R2 of 0.758 and a non-cross-validated R2 of 0.916 were obtained for MM3 minimized structures with PM3 ESP charges for the 32 CPT analogs. The derived QSAR equations were used to assign topoisomerase I inhibition values for compounds in this study and compounds not included in the original data set. Prior to its appearance in the literature, an IC50 of 103 nM was predicted for the 10,11-oxazole derivative. This CoMFA predicted value compared favorably with the recently reported value of 150 nM. The CoMFA model was also evaluated by predicting the activities of recently reported 11-aza CPT and trione derivatives. The predicted activity (IC50 = 249 nM) for 11-aza CPT compared well with the reported value of 383 nM.

Antineoplastic Agents↗
PubMed1997

Irradiation-induced damage to the salivary glands: the role of redox-active iron and copper.

The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redoxactive metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue.

Ancitabine↗
PubMed1997

Salivary and serum interleukin 6 in primary Sjögren's syndrome.

OBJECTIVE: To measure interleukin 6 (IL-6) salivary and serum concentrations in primary Sjögren's syndrome (SS), to correlate these data with the clinical presentation in patients, and to determine if salivary IL-6 is reflective of local exocrine involvement or of the underlying autoimmune disorder. METHODS: Thirty-one patients with primary SS, 15 with primary biliary cirrhosis (PBC), and 14 healthy controls were studied. Parotid secretion was stimulated with 2% citric acid and collected using a Carlson-Crittenden collector. Concentrations of salivary and serum IL-6 were determined using a high sensitivity ELISA. Serologic autoimmune disease markers and salivary functional and histopathologic disease markers in the patients with SS were correlated with salivary and serum IL-6 levels. RESULTS: Mean serum IL-6 concentrations were elevated in both patient groups (SS = 3.05 pg/ml, PBC = 3.07 pg/ml, healthy subjects = 0.843 pg/ml). Mean stimulated salivary IL-6 concentrations were elevated only in the patients with SS (16.21 pg/ml) compared to the PBC (1.07 pg/ml) and healthy subjects (0.769 pg/ml). No correlation was found between serum and salivary IL-6 concentrations for any group. Positive correlations were found between salivary IL-6 concentrations and serum IgG concentrations and between salivary IL-6 and erythrocyte sedimentation rate. Higher IL-6 concentrations were associated with increased disease activity. CONCLUSION: Salivary IL-6 concentration is elevated in SS compared to healthy subjects and patients with another systemic autoimmune disease without salivary gland involvement. Elevated salivary IL-6 concentrations in SS are reflective of local exocrine involvement and may serve as a useful monitor of disease activity.

Adult↗
PubMed1997

Management of dry mouth.

Dry mouth is a common complaint and, when associated with salivary gland dysfunction, a significant problem. Accurate and complete diagnosis of the patient with complaints of xerostomia is essential. Management should be directed to relief of symptoms, control of oral disease, and improvement in salivary function. With a systematic approach and aggressive management, most dry mouth patients can achieve oral comfort and adequate oral function.

Aged↗
PubMed1996

A 2 week pair-fed study of early X-irradiation effects on rat major salivary gland function.

Salivary gland function is affected shortly after irradiation of the head and neck. An intense oral mucositis develops after exposure and may interfere with ingestion. The effects of restricted food and water intake on the secretory output of rat major salivary glands were examined. Parotid and submandibular salivary output and body weight were measured in rats at 4, 8, 11 and 14 days after 15 Gy X-irradiation of the head and neck. Comparisons were made with two groups: a non-irradiated group with food and water intake restricted to that of the irradiated group (pair-fed), and a non-irradiated, ad libitum-fed control group. Parotid saliva output was significantly decreased in the irradiated group at 4, 8, and 11 days compared with the control group. The pair-fed rats also had significantly decreased parotid output at these time points and their parotid function did not differ from that of the irradiated animals. At 14 days, all three groups demonstrated similar parotid function. Submandibular salivary output was not affected to the same extent. Only at a single time point (11 days) was flow significantly decreased in the irradiated group. Total body weight was less than that of control rats for both the irradiated and pair-fed animals at all time points. These results suggest that the early effects of radiation on salivary glands are due, in part, to limited intake of food and water during the immediate post-irradiation period.

Analysis of Variance↗
PubMed1996

Pilot study of controlled-release pilocarpine in normal subjects.

OBJECTIVES: Current systemic treatments with sialogogues for patients with xerostomia are limited because of minimal efficacy, short duration of activity, or problems with side effects. The purpose of this pilot study was an initial assessment of safety, efficacy, duration of action, multiple dose tolerance, and side effects of a controlled-release formulation of pilocarpine hydrochloride. STUDY DESIGN: Eight healthy hospitalized subjects were given 15 mg of a controlled-release pilocarpine formulation every 12 hours for three doses. Saliva and blood samples were collected at assigned intervals. Repeated measures analysis and paired t tests were used for statistical analyses. RESULTS: A significant (p < 0.05) increase in both parotid and whole saliva output followed all three doses beginning within 1 hour of dosing and lasting over 10 hours. Mean plasma pilocarpine concentration reached a maximum of 8.2 ng/ml at approximately 1 hour after the first dose, 11.5 ng/ml after the third dose, and declined to near baseline (0.06 ng/ml) 24 hours after the final dose. None of the participants showed evidence of adverse effects including complaints of sweating or gastrointestinal discomfort. CONCLUSIONS: A controlled-release formulation of pilocarpine may overcome the therapeutic weaknesses of current pilocarpine preparations by prolonging salivary secretion and reducing undesirable side effects.

Adult↗
PubMed1996

Ion transport systems in human labial acinar cells.

Human labial acini were assayed for the presence of ion transport systems associated with salivary fluid secretion using microfluorometric methods. Na(+)-K(+)-Cl- contransport and Na+/H+ exchange activities (determined by their bumetanide and amiloride sensitivities, respectively) were found at levels approximately 50% of those seen in similarly assayed rat parotid acini, but little, if any, C1-/HCO3-exchange activity was observed. Also, when human labial acini were stimulated with the muscarinic agonist carbachol, little evidence of the intracellular acidification associated with HCO3- secretion by other salivary glands was found. Na+/H+ exchange activity in human labial acini was downregulated (approximately 40%) by beta-adrenergic stimulation and upregulated (approximately threefold) by muscarinic stimulation. In contrast, beta-adrenergic stimulation produced only a marginally significant increase in Na(+)-K(+)-Cl- cotransport activity, and muscarinic stimulation was without effect. We include that basolateral Na(+)-K(+)-Cl- cotransport appears to be the dominant mechanism driving Cl- secretion and thereby fluid secretion in this tissue.

Adrenergic beta-Agonists↗
PubMed1996

Differentiation of dry mouth etiology.

Dry mouth is a common complaint. While it is often considered to be synonymous with the diagnosis of salivary gland disease, this is not the case. There are many causes of the symptomatic complaint of oral dryness, both salivary and non-salivary. This paper will review the causes of "dry mouth" and the means of establishing the underlying diagnosis.

Diagnosis, Differential↗
PubMed1996

Current concepts of autoimmune exocrinopathy: immunologic mechanisms in the salivary pathology of Sjögren's syndrome.

Sjögren's syndrome is a systemic autoimmune disorder characterized by symptoms of oral and ocular dryness and a chronic, progressive loss of salivary and lacrimal function. The exocrine involvement is the result of a focal, peri-ductal mononuclear cell infiltrate and the subsequent loss of secretory epithelial cells. The mechanisms of this autoimmune exocrinopathy are not understood fully. Many recent investigations have described alterations in a number of immune mediators within the salivary glands. These studies provide new insights into the immune regulation of normal salivary gland functions and the mechanisms of gland damage in Sjögren's syndrome.

Autoimmune Diseases↗
PubMed1995

Isolation and characterization of six heat shock transcription factor cDNA clones from soybean.

Thermal stress in soybean seedlings causes the activation of pre-existing heat shock transcription factor proteins (HSFs). Activation results in the induction of DNA binding activity which leads to the transcription of heat shock genes. From a soybean cDNA library we have isolated cDNA clones corresponding to six HSF genes. Two HSF genes are expressed constitutively at the transcriptional level, and the remaining four are heat-inducible. Two of the heat inducible genes are also responsive to cadmium stress. Comparative analysis of HSF sequences indicated higher conservation of the DNA binding domain among plant HSFs than those from yeast or other higher eukaryotes. The putative plant HSF oligomerization domain contains hydrophobic heptapeptide repeats characteristic of coiled coils and seems to exist in two structural variants. The carboxy-terminal domains are reduced in size and the C-terminal heptad repeat is degenerate.

Amino Acid Sequence↗