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Biomedical subjects

A J Wu

Publications and source records attributed to A J Wu.

At least 19 recordsLinked to original sources
PubMed2000

Xerostomia--clinical evaluation and treatment in general practice.

Xerostomia is a common symptom with various causes that, if ignored, can lead to serious oral consequences. Clinical evaluation of patients complaining of dry mouth must include some additional history and specific examination of the salivary glands, oral mucosa, and teeth. Additional evaluation may include consultation with the patient's physician, request for microbial culture, or labial salivary gland biopsy. No one form of treatment for patients with chronic xerostomia is sufficient, but comprehensive treatment is effective in improving patient oral comfort and function and preventing unnecessary loss of teeth. This treatment must include ongoing dental caries prevention and treatment, salivary flow stimulation, recognition and treatment of oral candidiasis, selective use of saliva substitutes, and possible changes in the patients' prescription and nonprescription drug use.

Candidiasis, Oral↗
PubMed1998

Polyreactive antigen-binding B cells are the predominant cell type in the newborn B cell repertoire.

Polyreactive antibodies bind to a variety of different self and non-self antigens. The B cells that make these antibodies express the polyreactive lg receptor on their surface. To determine the frequency of polyreactive antigen-binding B cells in peripheral blood, we incubated two different antigens, one (insulin) labeled with fluorescein isothiocyanate and the other (beta-galactosidase) with phycoerythrin, with peripheral B cells. The percentage of cells that bound these antigens was determined with the fluorescence-activated cells sorter. Approximately 21% of adult B cells bound insulin, 28% bound beta-galactosidase, and 11% bound both antigens. In contrast to B cells in the adult repertoire, 49% of B cells in cord blood bound insulin, 54% bound beta-galactosidase, and 33% bound both antigens. The properties of polyreactive antigen-binding B cells in adult and cord blood were similar, except for the fact that almost all the polyreactive antigen-binding B cells in cord blood were CD5 positive (93%), whereas only 40% of the polyreactive antigen-binding B cells in adult peripheral blood were CD5 positive, indicating that the CD5 marker is not directly linked to polyreactivity. The percentage of polyreactive antigen-binding B cells in patients with Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis was equal to or slightly below that found in the normal adult B cell repertoire. It is concluded that polyreactive antigen-binding B cells are a major constituent of the normal adult B cell repertoire and are the predominant cell type in the newborn B cell repertoire.

Adolescent↗
PubMed1997

Modulation of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by interferon-gamma in a human salivary gland cell line.

Gelatinases have been shown to be regulated by many cytokines and growth factors, and have been implicated in the pathogenesis of certain autoimmune diseases via tissue destruction. High levels of several cytokines, including IFN-gamma and TNF-alpha, have been demonstrated in the salivary gland microenvironment of patients with Sjogren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of this disease is not well understood. We hypothesized that IFN-gamma with or without (+/-) TNF-alpha could be playing a role in the pathogenesis of SS via the regulation of matrix metalloproteinase (MMP) levels. This study examined the role of IFN-gamma and (+) TNF-alpha in the regulation of the matrix metalloproteinases, MMP-2 (72 kD gelatinase A) and MMP-9 (92 kD gelatinase B). A human salivary gland cell line (HSG) has been used as a possible in vitro model to study the role of IFN-gamma + TNF-alpha in the pathogenesis of SS. The HSG cell line, in the presence of IFN +/- TNF-alpha, displays increased MMP-2 and MMP-9 gelatinolytic activity, protein and RNA levels. The increase in MMP activity was partially blocked with an antibody against the IFN-gamma receptor, and this was associated with a complete inhibition of the previously described IFN-gamma +/- TNF-alpha antiproliferative effect. However, incubation of IFN-gamma treated HSG cells with the synthetic MMP inhibitor BB94 did not alleviate this antiproliferative effect. In addition, we demonstrate that there are very high levels of MMP-9 in the saliva of patients with SS when compared to healthy control subjects. These data suggest that cytokines could be regulating MMP production by salivary epithelial cells and thus indicate a potential role for these cells in the pathogenesis of SS.

Animals↗
PubMed1997

Interferon-gamma-induced JAK2 and STAT1 signalling in a human salivary gland cell line.

We have used a human salivary gland cell line (HSG) as a possible in vitro model to evaluate the effects of IFN-gamma on human salivary gland epithelium (Wu et al., 1994, 1996, 1997). In the present study, we examined the JAK-STAT signal-transduction pathway in IFN-gamma-treated HSG cells. We demonstrate that JAK2 and Stat1 are phosphorylated at tyrosine residues in a time- and concentration-dependent manner following exposure to IFN-gamma. In addition, we show that activation of this signalling pathway is decreased by the addition of a blocking antibody to the IFN-gamma receptor. The same maneuver is also able to reduce by approximately 50-70% the surface expression of two IFN-gamma-induced immunoregulatory molecules: HLA-DR and ICAM-1. These results demonstrate that the JAK2 and Stat1 signalling pathway is active in salivary-derived epithelial cells and may contribute to their immunopathologic destruction.

Antibodies↗
PubMed1997

Interferon-gamma induces a decrease in the intracellular calcium pump in a human salivary gland cell line.

Interferon-gamma (IFN-gamma) +/- tumor necrosis factor-alpha (TNF-alpha) induces antiproliferation and intracellular Ca2+ store depletion in a human submandibular ductal cell line (HSG), which can be reversed on cytokine removal [A. J. Wu, G. C. Chen, B. J. Baum, and I. S. Ambudkar. Am. J. Physiol. 270 (Cell Physiol. 39): C514-C521, 1996]. Here we have examined a possible mechanism for the IFN-gamma-induced intracellular Ca2+ store depletion. There was a time-dependent decrease in thapsigargin-dependent internal Ca2+ release after exposure of the cells to the cytokines. The intracellular Ca2+ pump [sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] protein in lysates and membranes of cells treated with IFN-gamma +/- TNF-alpha, but not with TNF-alpha alone, showed a similar time-dependent decrease (examined using a SERCA2 antibody). Removal of the cytokines, which resulted in recovery of cell growth and refill of internal Ca2+ stores, also increased the level of SERCA protein. The decrease in SERCA is not a result of decreased cell proliferation, since thapsigargin, 2,5-di-(t-butyl)-1,4-hydroquinone, or serum-free growth conditions induced antiproliferative effects on HSG cells without any corresponding decrease in SERCA. We suggest that the IFN-gamma-induced decrease in the level of SERCA accounts for the depleted state of internal Ca2+ stores in cytokine-treated HSG cells. These data suggest a novel mechanism for the inhibition of HSG cell growth by IFN-gamma.

Calcium↗
PubMed1996

Interferon-gamma induced cell death in a cultured human salivary gland cell line.

Increased levels of several cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), have been demonstrated in the salivary gland microenvironment of patients with Sjögren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of the disease is not well understood. This study examined the role of IFN-gamma +/- TNF-alpha on cellular death in a cultured human salivary gland cell line (HSG). Cells treated long-term with IFN-gamma +/- TNF-alpha demonstrate a profound antiproliferative effect with a decrease in cell number to below that initially plated. Treatment of HSG cells with TNF-alpha alone did not have any significant effects on growth but did increase the expression of the IFN-gamma receptor. Cells labelled with propidium iodide and anti-digoxigenin dUTP/dATP were examined by flow cytometry to determine the percentage of cells exhibiting low DNA content and DNA strand breaks. The percentage of cells exhibiting subdiploid DNA and DNA strand breaks increased with increased time of exposure to the cytokines. The maximum percentage of cells exhibiting DNA degradation at 12 days was 58% for cells treated with IFN-gamma + TNF-alpha, 31% for IFN-gamma treated cells, and < 5% for TNF-alpha-treated and untreated cells. The cells with subdiploid ( < 2n) DNA were subsequently demonstrated to represent two populations, both with evidence of increased DNA strand breaks but with differing light scatter characteristics. One population had features of cells undergoing necrosis, whereas the second population exhibited features of apoptosis. These findings were confirmed by transmission electron microscopy. Cells not exposed to cytokines did not exhibit significant evidence of either death process. We conclude that long-term exposure of a human salivary gland epithelial cell line to IFN-gamma +/- TNF-alpha leads to increased DNA degradation and subsequent cell death. This suggests a potential SS disease mechanism and implicates the role of the epithelial cell in this disease as an important area for future study.

Cell Count↗
PubMed1996

Interferon-gamma induces persistent depletion of internal Ca2+ stores in a human salivary gland cell line.

Interferon-gamma (IFN-gamma), in the presence of tumor necrosis factor-alpha (TNF-alpha), decreases proliferation of a human salivary gland ductal cell line, HSG (Wu, A., R. Kurrasch, J. Katz, P. Fox, B. Baum, and J. Atkinson. J. Cell. Physiol. 161:217-226, 1994). We examined the possible effects of these cytokines (1,000 U/ml IFN-gamma +/- 20 U/ml TNF-alpha for 7 days) on Ca2+ mobilization in HSG cells. In HSG cells, fetal bovine serum (10%) or carbachol (100 microM) stimulated rapid increases in cytosolic Ca2+ concentration ([Ca2+]i), apparently mobilized from different thapsigargin-sensitive intracellular Ca2+ stores. Serum induced a proliferative effect on HSG cells, which was suppressed (> 90%) by treatment with IFN-gamma +/- TNF-alpha, but not with TNF-alpha alone. Serum-, carbachol-, and thapsigargin-stimulated [Ca2+]i elevations were reduced by 90, 60, and > 65%, respectively, in cells treated with IFN-gamma +/- TNF-alpha and 30, 45, and 45%, respectively, in cells treated with TNF-alpha. Removal of the cytokines from the growth medium induced recovery of both cell proliferation and Ca2+ mobilization responses within 7 days. Treatment of HSG cells with thapsigargin (0.02-2 nM) induced a dose-dependent decrease in cell proliferation. Additionally, acute treatment (< 10 min) of cells with IFN-gamma did not affect [Ca2+]i or alter carbachol-, thapsigargin-, or serum-induced changes in [Ca2+]i. These data demonstrate that prolonged treatment of HSG cells with IFN-gamma +/- TNF-alpha leads to a persistent depletion of intracellular Ca2+ stores. We suggest that this may have a role in cell growth.

Blood Physiological Phenomena↗
PubMed1995

Extended stimulated parotid and submandibular secretion in a healthy young and old population.

BACKGROUND: Previous morphological studies have shown that both the human parotid and submandibular glands display age-related reductions in the proportion of fluid secreting acinar cells. In contrast, short-term functional studies of fluid secretion do not show such a consistent disparity among different-aged persons. This study compared the ability of a population of healthy young and old individuals to secret saliva from the parotid and submandibular glands for an extended period of time under conditions of intense gustatory stimulation. METHODS: Saliva was collected over 30 minutes from 30 healthy, unmedicated individuals using 10% citric acid as a gustatory stimulus. Of the 30 subjects, 15 were young (age range 27-40 years) and 15 were old (age range 60-97 years). Parotid salivary flow rates were determined every minute, and submandibular flow rates were determined at 2, 10, 20, and 30 minutes. A comparison was made between the slopes of the two groups. The slopes were derived from the average salivary flow rate at each time point. RESULTS: There was no difference in the ability of the parotid glands of young and old individuals to secrete saliva. In contrast, the submandibular glands of the elderly individuals did not show the same pattern of secretion when compared to their younger counterparts, who demonstrated increasing flow rates over the test period. CONCLUSIONS: The parotid glands of young and old persons are able to maintain high secretory ability under the stress of intense stimulation for an extended period of time. Conversely, the submandibular gland demonstrates an age-related, statistically significant difference in the pattern of fluid secretion with an intense gustatory stimulus.

Adult↗
PubMed1994

Effect of tumor necrosis factor-alpha and interferon-gamma on the growth of a human salivary gland cell line.

Interferon-gamma (IFN-gamma) is a product of activated T-lymphocytes, and tumor necrosis factor-alpha (TNF-alpha) is a product of both lymphocytes and macrophages. These cell types are often present at sites of tissue damage secondary to chronic infection or autoimmune disease. The purpose of this study was to characterize the effects of TNF-alpha and IFN-gamma on a human submandibular gland epithelial cell line (HSG). IFN-gamma caused a concentration-dependent decrease in HSG cell growth (approximately 70% in 6 days). Conversely, TNF-alpha alone had little effect on the growth of these cells. When these cytokines were added in combination (20 units/ml TNF-alpha and 1,000 units/ml of IFN-gamma), there was a synergistic antiproliferative effect; no apparent cell growth was observed. The cytokine-induced antiproliferative effect was reversible. After the apparent cessation of cell growth for 3-6 days, removal of the cytokines permitted complete growth recovery. Further, cells that recovered and exhibited growth patterns that were similar to control cells remained susceptible to the antiproliferative effects of the cytokines. Flow cytometry revealed that the percentage of cells in G0/G1 with the combination of cytokines was significantly increased by 24 h. The antiproliferative effect of IFN-gamma alone and that of IFN-gamma and TNF-alpha in combination were blocked completely using an antibody to the IFN-gamma receptor. A hypothesized mechanism of tissue damage in autoimmune inflammatory disorders is via up-regulation of cell surface markers such as intercellular adhesion molecule type I (ICAM-1) and histocompatibility antigen HLA-DR which can exacerbate the inflammatory process. Treatment of HSG cells with IFN-gamma, with or without TNF-alpha, resulted in increased levels of ICAM-1 and the acquisition of HLA-DR expression. These aggregate data suggest that IFN-gamma alone can regulate the expression of cell surface markers involved in the inflammatory process as well as cause a potent yet reversible inhibition of HSG cell growth that is modulated by the presence of TNF-alpha.

Antibodies↗
PubMed1994

Comparison of stimulated parotid salivary gland flow rates in normotensive and hypertensive persons.

Although hypertension is a prevalent condition among the elderly, little is known with respect to the influence of hypertension on oral health and function. Therefore a study was conducted that compared stimulated parotid salivary flow rates in elderly persons (65 years and older) from two diverse populations who are normotensive, mild, and severe hypertensive. The normotensive group consisted of 45 healthy subjects with systolic blood pressures of less than 140 mm Hg and diastolic pressures less than 90 mm Hg. The mildly hypertensive group consisted of 14 otherwise healthy subjects with either systolic pressures greater than 140 mm Hg or diastolic pressures greater than 90 mm Hg. The severely hypertensive group consisted of 10 otherwise healthy subjects with either systolic pressures greater than 180 mm Hg and/or diastolic pressures greater than 100 mm Hg. All three groups were not taking any prescription or nonprescription medications. Samples of 2% citrate-stimulated parotid saliva were collected from each subject. The results showed no significant differences in stimulated parotid flow between normotensive, mildly hypertensive, and severely hypertensive subjects. These results suggest that hypertension per se has no influence on stimulated parotid salivary gland flow rates in otherwise healthy, elderly unmedicated white and African-American persons.

Aged↗
PubMed1994

Stimulated parotid salivary flow rates in normotensive, hypertensive, and hydrochlorothiazide-medicated.

Stimulated parotid salivary flow rates were compared in elderly normotensive, hypertensive, and controlled hypertensive African-Americans, the latter group taking hydrochlorothiazide (HCTZ). The normotensive group consisted of 15 healthy unmedicated subjects with systolic blood pressures of less than 150 mm Hg and diastolic pressures less than 90 mm Hg. The hypertensive group consisted of 10 unmedicated subjects with systolic pressures greater than 160 mm Hg and diastolic pressures greater than 100 mm Hg. The controlled hypertensive group consisted of 20 subjects taking HCTZ (50 mg, daily) with controlled blood pressures similar to the normotensive control group. Stimulated parotid salivary samples were collected from each subject. A 2% citrate solution applied to the dorsum of the tongue was used for stimulation. The results showed no significant differences in stimulated parotid flow rates between normotensive and uncontrolled hypertensive subjects. However, the medicated, controlled hypertensive subjects had a significant reduction of stimulated parotid salivary flow rates compared to both the normotensive and hypertensive groups.

Aged↗
PubMed1994

Salivary gland dysfunction: causes, symptoms, treatment.

The three most common known causes of salivary gland dysfunction are medication usage, radiation therapy and Sjogren's syndrome. Current therapeutic options to treat salivary dysfunction are limited. Clinical considerations as well as the outlook for individuals experiencing salivary dysfunction are discussed.

Aged↗
PubMed1994

[Changes of enamel intake of fluoride amount while PH and fluoride concentration varies]

The four enamel pieces,which are from one bovine tooth,are treated individually by 2.7% NaF gel(pH4),2.7% NaF gel(pH7),1%NaF gel (pH7.0) and the control group gel.The fluoride amount in enamel pieces is measured by fluoride electrode.The aim of present study is to observe the changer of enamel intake of fluoride amount when the pH and fluoride concentration varies.In results the most fluoride amount in enamel pieces treated by 2.7% NaF gel(pH4) is measured.The more fluoride amount is measured in group of 2.7%NaF gel(pH7) than 1% NaF gel (pH7).The Results show lower pH and higher fluoride concentration can increase more fluoride amount in enamel.

Journal Article↗
PubMed1994

Sjögren's syndrome.

This article reviews the diagnostic criteria for Sjörgen's syndrome (SS), as well as some of the more common associated signs and symptoms. Dermatological manifestations associated with SS will be evaluated. Finally, general treatment strategies will be discussed.

Humans↗
PubMed1993

A characterization of major salivary gland flow rates in the presence of medications and systemic diseases.

The purpose of this study was to characterize the effects of medications and systemic diseases on major salivary gland flow rates. Unstimulated and 2% citrate-stimulated parotid and submandibular salivas were collected from 293 subjects of the oral physiology component of the Baltimore Longitudinal Study of Aging. The influence of the number of medications and diseases on salivary flow rates was determined by separate one-way ANOVA tests. There was an overall decrease in both parotid and submandibular flow rates with increasing numbers of medications and systemic diseases. However, this was significant (p < 0.05) only for unstimulated submandibular flow rates (with increasing numbers of systemic diseases) and stimulated submandibular flow rates (with increasing numbers of systemic diseases and medications). Unstimulated flow rates rapidly approached zero with increasing numbers of medications and diseases. These results suggest that the submandibular gland may be more sensitive to physiologic permutations than the parotid gland. In addition, individuals being treated for multiple systemic diseases and taking numerous medications may be more susceptible to salivary hypofunction.

Adult↗
PubMed1993

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↗
PubMed1992

Salivary gland function and aging: a model for studying the interaction of aging and systemic disease.

This review describes an approach to examining the interaction of aging and systemic disease on a key aspect of oral physiology, salivation. The approach requires several steps: defining general health, and a specific physiological function, at different ages; defining a disease of interest and the influence of the disease on the specific physiological function; and determining if the disease can affect performance of the physiological function with increased age.

Aging↗