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At least 415 records · Page 23Linked to original sources
PubMed2005

Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction.

The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C. Delporte, B.C. O'Connell, X. He, H.E. Lancaster, A.C. O'Connell, P. Agre, B.J. Baum, Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc. Natl. Acad. Sci. U S A. 94 (1997) 3268-3273] and miniature pig [Z. Shan, J. Li, C. Zheng, X. Liu, Z. Fan, C. Zhang, C.M. Goldsmith, R.B. Wellner, B.J Baum, S. Wang. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol. Ther. 11 (2005) 444-451] salivary glands approximately 16 weeks following IR resulted in a dose-dependent increase in salivary flow to > or =80% control levels on day 3. A control Ad vector was without any significant effect on salivary flow. Additionally, after administration of Ad vectors to salivary glands, no significant lasting effects were observed in multiple measured clinical chemistry and hematology values. Taken together, the findings show that localized delivery of AdhAQP1 to IR-damaged salivary glands is useful in transiently increasing salivary secretion in both small and large animal models, without significant general adverse events. Based on these results, we are developing a clinical trial to test if the hAQP1 cDNA transfer strategy will be clinically effective in restoring salivary flow in patients with IR-induced parotid hypofunction.

Animals↗
PubMed2006

Salivary gland gene therapy.

Salivary glands have proven to be unusual but valuable target sites for multiple clinical gene transfer applications. Access to salivary glands for gene transfer is easy. Multiple studies in animal models have yielded proofs of concept for novel treatments for damaged salivary glands following therapeutic irraditation, in Sjögren's syndrome, and for gene therapeutics systemically by way of the blood-stream and locally in the oral cavity and upper gastrointestinal tract.

Animals↗
PubMed2005

Distinct profiles of Sjögren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF.

The formation of ectopic germinal centers (GC) has been described in Sjögren's syndrome (SS), although little is known about the molecular basis of this phenomenon. These structures are a focus of in situ autoantibody production and have been hypothesized to be involved in lymphomagenesis in SS patients. Serum cytokines also play an important role in SS pathogenesis in part via immune dysregulation and may therefore contribute to ectopic GC formation. Herein, highly multiplex cytokine screening of SS patients with (SSGC+) and without (SSGC-) GC formation was done to identify cytokine profiles that correlate with this phenomenon. Serum levels of B-cell activating factor (BAFF) were also screened as a potential biomarker of immune dysregulation in SS and SSGC formation. Univariate analysis demonstrated that serum levels of a broad spectrum of immune and inflammatory modulating cytokines are upregulated in SSGC+ and SSGC- patients relative to unaffected controls IL-1beta, IL-2, IL-6, IL-15, IFN-gamma and CCL4 (MIP-1beta). SSGC+ patients were distinguished from healthy individuals by higher levels of IL-4, IL-10, GM-CSF, IFN-alpha, CCL3 (MIP-1alpha), CCL11 (Eotaxin) and BAFF, while SSGC+ and SSGC- patients differed in CCL2 (MCP-1) expression. Discriminant function analysis (DFA), a multivariate discrimination method that uses observed differences to characterize groups when casual relationships are not well understood, was employed to identify a subset of these biomarkers that maximally discriminate among SSGC+, SSGC- and unaffected individuals. The biomarker having the strongest discriminatory power identified by DFA besides CCL11 (Eotaxin) and IFN-gamma was BAFF. The variables identified by DFA are interdependent and are often of mechanistic significance to the pathologic states they distinguish, suggesting that these factors modulate SS pathology and SSGC formation in a synergistic manner.

Adult↗
PubMed2006

Submandibular sialogram performed through a Wharton's duct fistula: technical adaptation of conventional technique.

We report a case of submandibular duct fistula in which a sialogram was performed through the fistulous opening after attempt of sialography through the Wharton's duct had failed. To our knowledge, this technical modification in obtaining a sialogram has not been described previously in scientific literature. Blunt-tipped needles and polythene catheters are commonly used for cannulation of the submandibular duct orifice for obtaining a sialogram. However, in this case, a larger gauge metallic cannula was employed to opacify the ductal system through the fistula.

Catheterization↗
PubMed1999

Trauma to the salivary glands.

Penetrating and blunt trauma to the salivary glands produces potential injury to the salivary tissue, salivary ducts, and to the facial nerve. This article presents a rationale of management for glandular and duct injury, emphasizing surgical and conservative therapy. It also presents management of neural injury including a discussion of surgical options and conservative management with electrical testing.

Fistula↗
PubMed1988

Primary B-cell lymphoma of salivary glands and its relationship to myoepithelial sialadenitis.

A detailed morphologic and immunohistochemical study has been carried out on salivary glands excised from 20 cases in which the initial histologic diagnosis was either myoepithelial sialadenitis (MESA) or salivary gland lymphoma (SGL). The results have shown that these cases, except one that had been diagnosed as MESA, showed a spectrum of changes ranging from focal lymphoid infiltrates, designated as early MESA, through established MESA with dense, extensive lymphoid infiltration, to lymphoma. The distribution of the lymphoid infiltrate in early MESA was related to ducts and mimicked Peyers patches. In established MESA, this infiltrate became confluent with the formation of prominent epimyoepithelial islands. The evolution of lymphoma was characterized by an expanded population of centrocyte-like (CCL) cells that showed light chain restriction. Like other lymphomas of mucosa-associated lymphoid tissue, to which they bear a striking resemblance, salivary gland lymphomas may remain localized for prolonged periods with a tendency to local recurrence rather than to distant spread. These properties may be explained by the histogenesis of these tumors from CCL cells that appear to be of similar lineage of splenic marginal zone cells.

Adult↗
PubMed1987

Epithelial membrane antigen as a marker of human salivary gland acinar and ductal cell function.

Monoclonal antibody to epithelial membrane antigen (EMA) from human milk fat globule membrane was used with the immunoperoxidase method to examine the distribution of EMA in normal human salivary glands and in their obstructive lesions. EMA staining in the normal salivary gland was limited to luminal and lateral borders of acinar cells. The antigen was also present in high concentration on the luminal side of ductal cells. In obstructive lesions or sialoadenitis, lateral border and luminal positive staining in atrophic acinar cells was reduced or absent, and the EMA staining in duct-like structures was also markedly decreased on even absent in chronic stage. The degree of reduction in EMA staining was dependent on the extent of degeneration. Expression of immunohistochemically detectable EMA in paraffin sections suggests the antigen to be useful as a new marker of salivary gland function, of either acinar compartments or ductal segments.

Antibodies, Monoclonal↗
PubMed1988

Immunoreactive prolactin in lesions and tumours of salivary glands.

The prolactin binding in obstructive lesions and tumours of salivary glands was described by use of the immunohistochemical PAP technique. Normal salivary glands had prolactin binding cells in the striated ducts only. Chronic obstructive lesions of submandibular glands showed negative immunoreaction for prolactin binding in ductal cells, but positive staining of the luminal surface of ductal segments. In pleomorphic adenomas, occasional neoplastic cells located along the luminal borders of tubular, ductal, or of duct-like epithelial structures were strongly reactive with anti-prolactin and 26.5% of cases pleomorphic adenoma were positive for anti-prolactin. Adenoid cystic carcinoma exhibited positive prolactin binding on the luminal surface of some of tumour foci, but not in the rest of the tumour. Warthin's tumour was devoid of detectable prolactin binding.

Humans↗
PubMed2002

Gene transfer to salivary glands.

This article provides a review of the application of gene transfer technology to studies of salivary glands. Salivary glands provide an uncommon target site for gene transfer but offer many experimental situations likely of interest to the cell biologist. The reader is provided with a concise overview of salivary biology, along with a general discussion of the strategies available for gene transfer to any tissue. In particular, adenoviral vectors have been useful for proof of concept studies with salivary glands. Several examples are given, using adenoviral-mediated gene transfer, for addressing both biological and clinical questions. Additionally, benefits and shortcomings affecting the utility of this technology are discussed.

Animals↗