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PubMed2004

Utilizing endocrine secretory pathways in salivary glands for systemic gene therapeutics.

Mammalian salivary glands are commonly used models of exocrine secretion. However, there is substantial experimental evidence showing the physiological existence of endocrine secretory pathways in these tissues. The use of gene transfer technology in vivo has allowed the unambiguous demonstration of these endocrine pathways. We and others have exploited such findings and evaluated salivary glands as possible target tissues for systemic applications of gene therapeutics. Salivary glands present numerous advantages for this purpose, including being well encapsulated, which limits extra-glandular vector dissemination, and having the luminal membranes of almost all parenchymal cells accessible via intraoral delivery of vectors through the main excretory ducts. Existing studies suggest that clinical benefits will result from salivary gland targeted systemic gene therapeutics.

Animals↗

PubMed1999

Lymphoid proliferations of the salivary glands.

Lymphoid proliferations of the salivary glands can be either reactive or neoplastic. Reactive lesions include cystic lymphoid hyperplasia--a multicystic ductal proliferation with reactive germinal centers, seen most often in intravenous drug users infected with HIV--and the lymphoepithelial sialadenitis of Sjögren's syndrome (so-called benign lymphoepithelial lesion [BLEL] or myoepithelial sialadenitis [MESA]). This lymphoid proliferation involves infiltration of ductal epithelium by lymphocytes of marginal zone or monocytoid B-cell type, forming lymphoepithelial lesions (epimyoepithelial islands). Patients with lymphoepithelial sialadenitis have a 44-fold increased risk of developing salivary gland or extrasalivary lymphoma, of which 80% are marginal zone/MALT type. Broad strands of marginal zone or monocytoid B cells around lymphoepithelial lesions and monotypic immunoglobulin detection by immunohistochemistry are considered diagnostic of MALT lymphoma. B-cell clones are detected in over 50% of cases of MESA by molecular genetic methods, but this does not correlate with overlymphoma. "Nodal" type B-cell lymphomas of the salivary glands are either follicular lymphoma (35%), which may arise in intrasalivary gland lymph nodes and behave similarly to follicular lymphoma in other sites, or diffuse large B-cell lymphoma (30%), which may arise de novo or secondary to either MALT or follicular lymphomas.

Diagnosis, Differential↗

PubMed2006

Comparison of preoperative fine-needle aspiration cytology diagnosis and histopathological diagnosis of salivary gland tumors.

We investigated 115 patients with salivary gland epithelial tumors who had undergone preoperative fine needle aspiration cytology (FNAC) of salivary glands and had been diagnosed by postoperative histopathological examination. We compared the findings of preoperative FNAC with their histopathological types in salivary gland tumors, and discuss the results and problems. The diagnostic accuracy, sensitivity, and specificity of preoperative FNAC of salivary glands were 98.2%, 88.2%, and 100%, respectively. The percentage of inadequate specimens was 6.1%. The rates of agreement in the diagnosis of pleomorphic adenoma, Warthin tumor, and basal cell adenoma were 96%, 92.9%, and 55.5%, respectively. The rate of agreement of histopathological types in the malignant tumors was 30%. We realized again not only that the diagnostic accuracy of preoperative FNAC for salivary gland tumors was high, but also that it was a safe, easy-to-perform, clinically very useful diagnostic procedure. However, this study exposed several problems which are the inadequate sampling rate and the difficulty in diagnosing malignant tumors. We have been making efforts to take appropriate specimens by writing comments on the cytological report indicating a re-examination, or by the presence of the clinical laboratory technician at the FNAC procedure. We consider it necessary to adequately re-aspirate the solid portion after cyst fluid aspiration, or to re-perform FNAC at a later date, and to improve the diagnostic accuracy by further experience with more patients.

Biopsy, Needle↗

PubMed1985

[Adenocarcinoma of the salivary glands. The pathohistology and subclassification of 77 cases].

Seventy-seven adenocarcinomas of the salivary glands recorded in the Salivary Gland Register between 1965 and 1984 were analysed and classified histopathologically. The following results were obtained: 1. 2% of all salivary gland tumours and 10% of all malignant epithelial salivary gland tumours were allotted to the group of adenocarcinomas. The age peak lies in the 7th to 8th decade. 60% occurred in women, 58.5% were localized to the parotid gland, 28.5% to the minor salivary glands (palate, lips, and cheek), 11.5% to the submandibular gland and only 1.5% to the sublingual gland. 2. Solid, tubular and papillary adenocarcinomas can be distinguished. Additional criteria are microcysts, mucus production and grade of differentiation. 3. The solid adenocarcinoma (13%) is predominantly localized in the parotid gland and characterized by a low differentiation, invasive growth and metastases. 4. 62.5% of tubular adenocarcinomas (52%) are localized in the parotid gland, 27.5% to the minor salivary glands and 10% to the submandibular gland. Most of the tumours are highly differentiated. A distinct mucus production is present in 40% of the cases. Microcysts are very frequent. 5. Papillary adenocarcinomas (28.5%) are localized in almost 50% of cases to the minor salivary glands, 45% to the parotid and only 5% to the submandibular gland. Microcysts and mucus production can be observed in 50% of the cases. 6.5% of the cases have a mixed tubular papillary structure. 6. In differential diagnosis, thyroid gland carcinomas and metastases of other adenocarcinomas must be distinguished, the former by negative result of the thyroglobulin reaction, and absent mucus production. 7. Adenocarcinomas arise from the salivary duct system. Solid or tubular adenocarcinomas imitate stages of the embryonal development of the salivary ducts.

Adenocarcinoma↗

PubMed2000

Chrysoptin is a potent glycoprotein IIb/IIIa fibrinogen receptor antagonist present in salivary gland extracts of the deerfly.

Salivary gland lysates of the deerfly (genus Chrysops) contain chrysoptin, an inhibitor of ADP-induced platelet aggregation, which presumably assists the fly in obtaining a blood meal. Chrysoptin has now been isolated, and its cDNA has been cloned and expressed. Chrysoptin was purified to homogeneity using anion exchange and hydrophobic interaction chromatography and found to be a protein with a molecular mass of 65 kDa as determined by gel electrophoresis. N-terminal amino acid sequencing allowed for the synthesis of degenerate oligonucleotides that led to cloning, from salivary gland specific mRNA, of the cDNA encoding this platelet inhibitor. No RGD sites are present in the predicted sequence. A search of GenBank(TM) did not reveal significant sequence homology between chrysoptin and other proteins. The molecular mass predicted from the cDNA was 59 kDa. Predicted glycosylation and phosphorylation sites may account for this difference in molecular mass, as recombinant chrysoptin expressed in Sf21 cells had a molecular mass of 65 kDa, matching that of the natural protein. Chrysoptin functions by inhibiting the binding of fibrinogen to the fibrinogen/glycoprotein IIb/IIIa receptor on platelets with an IC(50) of 95 pmol. These results reveal that insect salivary glands are a source of fibrinogen receptor antagonists.

Adenosine Diphosphate↗

PubMed1996

Submandibular salivary gland fibrosis.

Although the salivary glands are the primary participants in the first stage of digestion, they are discussed infrequently by clinicians of every category. Rarely, are they mentioned in the physical examination of a patient's medical record. Nonetheless, these glands are of clinical significance and worthy of diagnostic evaluation. A brief review is given of submandibular salivary gland fibrosis concerning the anatomy, physiology, pathology, clinical aspects diagnosis, and its treatment.

Fibrosis↗

PubMed2002

The superficial mandibular gland of the rabbit: a new experimental model for scintigraphic evaluation of salivary glands.

The aim of this study was to provide an appropriate experimental model to study functional changes in salivary glands using scintigraphy. Although the rabbit was frequently used for laboratory experiments, there are only a few studies that describe the exact position of its different salivary glands on the sialoscintigram. Twenty rabbits were used for the study; ten of them were anatomically dissected to provide the required topographic anatomy on the different salivary and lacrimal glands. The remaining ten animals underwent a static scintigraphy after extirpation of a particular salivary gland. Changes in the pattern of tracer uptake indicated the exact position of every gland allowing its evaluation. The results show that the 99mTcO4- uptake can only be selectively evaluated in two salivary glands, the superficial mandibular gland and the parotid gland. The superficial mandibular gland was proved to be a particularly useful model to evaluate functional changes of salivary gland parenchyma due to its well defined and high enhanced structure which allows a precise detection and measurement of the tracer uptake. Additionally, the good surgical accessibility of this gland and the existence of a well defined capsule facilitate associated histological studies of its parenchyma.

Animals↗

PubMed2000

Sialography of sheep parotid and mandibular salivary glands.

The anatomy of ovine salivary glands was studied on cadaver heads. The mandibular duct enters the oral cavity on the ventral surface of sublingual caruncles, which are located medial to the orifice of the ventral sublingual gland duct. The parotid gland duct enters the oral cavity on the cheek opposite the upper 2nd molar. Prior to applying sialography to live animals, the procedure was carried out on cadaver heads then the live animals were sedated, the mandibular and parotid ducts catheterized and contrast medium was injected into each gland. Lateral radiographs were made immediately after the injection. The normal sheep mandibular and parotid salivary glands have a multilobular appearance in cadaver heads, but in live animal only the ducts and their smaller branches could be identified. The mean diameter of mandibular and parotid duct were 1.4+/-0.3 mm and 3. 1+/-1.0 mm respectively. The monostomatic sublingular gland had a slender shape in the sialogram. In conclusion sialography of mandibular, parotid and sublingual salivary glands in sheep is practical and can be helpful in diagnosis of pathological conditions of these glands.

Animals↗

PubMed1989

Myoepithelial cells in salivary gland neoplasms.

Archival paraffin sections from normal salivary gland tissue and salivary gland neoplasms were stained by immunoperoxidase technique with a well characterized cytokeratin antibody (PKK1). In normal parotid tissue, myoepithelial cells and peripheral cells of larger ducts were selectively stained. In pleomorphic adenomas, most cells were stained, the staining being somewhat stronger towards the duct lumina. In basal cell adenomas, only cells adjacent to the duct lumina were stained where a differentiation of cells into peripheral and ductal was seen. In adenolymphomas basal cells were stained, and in oncocytomas small elongated cells reacted with the PKK1 antibody. Only a few duct cells in an acinic cell carcinoma were reactive and in mucoepidermoid carcinoma, peripheral epidermoid cells were strongly stained. In adenoid cystic carcinoma, mostly duct cells were stained whereas the peripheral ones remained unstained. Although the intermediate filament protein expression is very stable during tumorigenesis, the staining with the presently used monoclonal antibody in salivary gland neoplasms differed markedly from what could be expected according to current views on the participation of this cell type. This supports our view that cells in tumors should be characterized on the basis of their staining, i.e. state of differentiation and not on their presumed histogenesis.

Adenoma↗

PubMed2006

Salivary gland carcinoma of the larynx.

BACKGROUND: Salivary gland carcinomas of the larynx are rare, and account for < 1% of laryngeal malignancy. The purpose of this study is to review our management experience of salivary gland carcinomas of the larynx in Taipei Veterans General Hospital and to compare it with other major existing series. METHODS: From 1981 to 2000, 11 patients with laryngeal salivary gland carcinomas treated in Taipei Veterans General Hospital were included in this study. Their demographic data, treatment modalities, survival, and failure pattern, obtained by review of medical records, were analyzed. RESULTS: All 11 patients were male. Median follow-up period was 95 months (range, 18-181 months). The 5-year overall survival rate of all patients was 71%, and the 5-year disease-specific survival rate was 83%. CONCLUSION: The mainstay treatment of laryngeal salivary gland carcinomas in these cases was surgery or surgery with postoperative radiotherapy. The survival rate was satisfactory and similar to that of squamous cell carcinoma of the larynx.

Aged↗

PubMed1995

Depletion of total salivary gland protein in blood-fed Anopheles mosquitoes.

Reduction in total salivary gland protein from four anopheline vectors of human malaria, Anopheles stephensi Liston, An. albimanus Wiedmann, An. gambiae Giles, and An. freeborni Aitken, was quantified after mosquitoes blood-fed to repletion on human volunteers, hamsters or through a Baudruche artificial membrane. Total salivary gland protein from pools of six unfed mosquitoes ranged from 4.33 to 7.91 micrograms/ml. The difference between the total protein of glands from unfed and blood-fed mosquitoes for all species ranged from 1.77 to 3.12 (micrograms/ml for six pooled salivary glands. Total salivary gland protein for mosquitoes blood-fed to repletion was significantly less than that of unfed controls from the same cohort. Reduction in total salivary gland protein for An. freeborni and An stephensi blood fed to repletion on human volunteers, hamsters, and a Baudruche membrane ranged from 24 to 46%, from 43 to 56%, and from 24 to 51%, respectively. An. stephensi mosquitoes were allowed to blood feed on humans for 0 (unfed), 0.5-, 1.0-, 2.0-min time periods or to repletion (> 2-5 min). As feeding time increased, there was a significant decrease in total amount of protein in the salivary glands. This decrease was proportional over time, indicating that salivation occurred continuously from the beginning (probing) of blood feeding to withdrawal of the mosquito mouthparts at repletion. These data indicate that during blood feeding there difference between species in the salivary gland output measured as amount of protein depleted from the salivary glands and that depletion of salivary protein from the glands occurred continuously as mosquitoes fed to repletion.

Animals↗

PubMed2000

First insights into the molecular basis of pleomorphic adenomas of the salivary glands.

Pleomorphic adenoma, or mixed tumor of the salivary glands, is a benign tumor originating from the major and minor salivary glands. Eighty-five percent of these tumors are found in the parotid gland, 10% in the minor (sublingual) salivary glands, and 5% in the submandibular gland. It is the most common type of salivary gland tumor, accounting for almost 50% of all neoplasms in these organs. In fact, after the first observation of recurrent loss of chromosome 22 in meningioma, this was the second type of benign tumor for which non-random chromosomal changes were reported. The rate of malignant change with the potential to metastasize has been reported to be only 2 to 3%, and only a few cases of metastasizing pleomorphic salivary gland adenomas have been described to date. The fact that these tumors arise in organs located in an ontogenetic transitional zone, a region where endoderm and ectoderm meet, might be one of the reasons for the often-problematic histopathological classification. This type of benign tumor has been cytogenetically very well-characterized, with several hundreds of tumors karyotyped. In addition to the cytogenetic subgroup with an apparently normal diploid stemline (making up approximately 30% of the cases), three major cytogenetic subgroups can be distinguished. In addition to a subgroup showing non-recurrent clonal abnormalities, another subgroup is various translocations involving 12q15. By far the largest cytogenetic subgroup, however, consists of tumors with chromosome 8 abnormalities, mainly showing translocations involving region 8q12. The most frequently encountered aberration in this group is a t(3;8)(p21;q12).

Adenoma, Pleomorphic↗

PubMed1995

Histological and functional changes in the salivary glands in thalassaemia major.

Oral salivary secretion and oral histology in 15 multi-transfused adult thalassaemia homozygotes was studied. Iron stores of minor salivary glands were also histochemically determined. Salivary secretion in multi-transfused thalassaemia patients was subclinically decreased, but no clear correlation was evident between salivary secretion impairment and salivary gland destruction by iron deposition, lymphocyte infiltration and fibrosis. The underlying mechanism remains to be determined.

Adolescent↗

PubMed1977

Puffing activity in the salivary gland chromosomes of Rhynchosciara under experimental conditions.

By using the techniques of ligation of the larvae (brain and endocrine glands extirpation) and salivary gland implantation, the hormonal dependence of the activity of certain puffs of Rhynchosciara was investigated. Our results have shown that the puffing behaviour--activation and deactivation--varies according to the developmental stage in which the larvae were ligated. When the larvae were ligated just before the drastic changes in the puffing pattern, which occur prior to pupation, these changes fail to occur. When the larvae were ligated after the onset of these changes we have observed: a) some of the puffs active at the time of the ligature regress promptly, earlier than their normal timing observed in controls; b) others remain active indefinitely and c) there are still some which regress accordingly to the normal timing. The puff B2 which behaves as those in b was double checked by means of implantation experiments. Salivary glands which had puff B2 at its maximum expansion were implanted into younger larvae and that puff also remained active in the body cavity of these larvae. Hypotheses to explain the results obtained are discussed.

Animals↗

PubMed2006

SAGE analysis of mosquito salivary gland transcriptomes during Plasmodium invasion.

Invasion of the vector salivary glands by Plasmodium is a critical step for malaria transmission. To describe salivary gland cellular responses to sporozoite invasion, we have undertaken the analysis of Anopheles gambiae salivary gland transcriptome using Serial Analysis of Gene Expression (SAGE). Statistical analysis of the more than 160000 sequenced tags generated from four libraries, two from glands infected by Plasmodium berghei, two from glands of controls, revealed that at least 57 Anopheles genes are differentially expressed in infected salivary glands. Among the 37 immune-related genes identified by SAGE tags, four (Defensin1, GNBP, Serpin6 and Cecropin2) were found to be upregulated during salivary gland invasion, while five genes encoding small secreted proteins display induction patterns strongly reminiscent of that of Cecropin2. Invasion by Plasmodium has also an impact on the expression of genes involved in transport, lipid and energy metabolism, suggesting that the sporozoite may exploit the metabolism of its host. In contrast, protein composition of saliva is predicted to be only slightly modified after infection. This study, which is the first transcriptome analysis of the salivary gland response to Plasmodium infection, provides a basis for a better understanding of Plasmodium/Anopheles salivary gland interactions.

Animals↗

PubMed1986

Ultrastructure of the angularis oris salivary gland in the house sparrow.

The angularis oris gland, an avian salivary gland that lies beneath the zygomatic arch, was studied in the house sparrow by means of light and electron microscopy. The gland consists of lobules composed of epithelial tubules and folds on a delicate connective tissue framework. The lobules are drained by large channels to form an intraglandular duct, which becomes the main extraglandular duct. The tubules, folds, and all ducts are covered by pseudostratified epithelium that shows progressive changes from the blind ends of tubules to the duct system. At the closed end of the tubules, the tall cells contain an aggregation of closely packed mucous droplets; their mitochondria are long and slender. As the epithelium nears the duct system, the mucus content of the tall cells is reduced and the mitochondria, which are increased in number, are ovoid. The lateral borders of the cells are complexly interlocked. In the ducts, mitochondria-rich cells with extensive lateral interfoliation comprise the major cell type; some of these cells contain a few mucous droplets at their apices. The basal cells of the pseudostratified epithelium have the same basic structure regardless of their location. These pyramidal cells have abundant cytofilaments and are joined to the basal lamina by many hemidesmosomes. Despite the absence of clear-cut morphological zonation, the angularis oris may function in a manner that is analogous to mammalian salivary glands: secretory cells produce the organic component of the saliva, mucus, while the mitochondria-rich cells with their extensive lateral membranes probably resorb electrolytes to render the final saliva hypotonic.

Animals↗

PubMed2001

Morphological pattern of salivary gland tumours.

OBJECTIVE: To delineate the spectrum of salivary gland tumors in our setup. SETTING: The Aga Khan University Medical Centre, Karachi. METHOD: Tumors were analysed considering histological type, age and sex of the patients and anatomic location. The diagnosis of individual tumours was based on the 1991 World Health Organisation Classification. RESULTS: During the span of eight years (1991-1998), 379 cases of salivary gland tumours were diagnosed. Of these, 205 (65.7%) were male and 174 (34.3%) were female. The median age at the time of diagnosis was 35 years. The median age for patients with malignant lesions (44 years) was 12 years older than those with benign tumours (34 years). Overall, malignant tumours were seen more frequently in males, however benign tumours were distributed equally between the two sexes. The most common site was parotid gland (82.85%). Only five cases of minor salivary gland tumours were seen. The most frequently diagnosed benign salivary gland neoplasm was pleomorphic adenoma (84.5%), followed by Warthin's tumours (6.18%), Mucoepidermoid carcinoma was the most commonly encountered malignant lesion (56.9%), followed by adenoid cystic carcinoma (19.6%). CONCLUSION: Plemorphic adenoma was the most common benign salivary gland tumour and mucoepidermoid carcinoma was the most frequent malignant neoplasm. Parotid gland was the most common site of origin in both benign and malignant tumours. The overall relative frequency of salivary gland tumours in this series correlates with that reported in the international literature.

Adenoma, Pleomorphic↗

PubMed1995

Identification of anticoagulant activities in the salivary glands of the soft tick, Ornithodoros savignyi.

Salivary gland extracts of the sand tampan, Ornithodoros savignyi, prolonged the activated partial thromboplastin time (APTT) and prothrombin time (PT) significantly in a concentration-dependent manner. There was also a pronounced inhibition of human activated factor Xa (fXa) by salivary gland extracts. The salivary gland extracts inhibited chromogenic assays specific for both fXa and thrombin. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of the salivary gland proteins followed by elution of specific areas or bands from a polyvinylidene difluoride (PVDF)-membrane, showed that various anticoagulant factors are present when screened by means of the APTT assay. The most active component was associated with a band of M(r) of 14 kDa. Partial purification of this component was achieved using isoelectric focusing (IEF) and size-exclusion high-performance liquid chromatography (HPLC).

Animals↗