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Salivary gland ultrasonography in the evaluation of primary Sjögren's syndrome. Comparison with minor salivary gland biopsy.

OBJECTIVE: To evaluate the diagnostic accuracy of ultrasonography (US) of the salivary glands versus histologic examination in detection of salivary gland involvement in primary Sjögren's syndrome (SS). METHODS: Thirty female patients with primary SS diagnosed according to the European criteria and 30 female subjects of similar age with dry mouth (symptomatic controls) due to other selected disorders were studied. Evaluation of salivary involvement was by 2 independent observers for both the parotid and submandibular glands using US score (range 0 to 4) that assigns points to the different degree of glandular inhomogeneity. Lip salivary gland (LSG) biopsies were graded according to the Chisholm and Mason classification system and by morphometric analysis. The area under receiver operating characteristic (ROC) curve was employed to evaluate the screening method's performance. RESULTS: Through ROC curves salivary gland US arose as the best performer, followed by the volume percentage of inflammatory cells and by the semiquantitative focus score. The difference between area under ROC curve of salivary gland US and lymphocytic focus score was significant (p = 0.044), reflecting the accuracy of the imaging diagnostic assessment. No differences arise between areas under the ROC curve of salivary gland US and volume percentage of inflammatory cells (p = 0.610) and between volume percentage of inflammatory cells and semiquantitative focus score (p = 0.081). Attempts to assess the independent contribution of the fractional composition of the LSG biopsy as the predictor of US score showed a significant contribution of both the fractional composition of inflammatory infiltrate (p = 0.01) and intralobular ducts (p = 0.02). These findings indirectly suggest that the US abnormalities we found were strongly related to SS. CONCLUSION: These results conclusively indicate that quantitative assessment of salivary gland ultrasonography is a very useful method fdr evaluating salivary gland involvement in SS and can replace other diagnostic techniques, such as sialography or salivary scintigraphy.

Adult↗

Meibomian gland dysfunction. I. Keratin protein expression in normal human and rabbit meibomian glands.

The expression of keratin proteins from meibomian glands and their correlation with skin epidermal keratins were determined. Keratin proteins were localized in both human and rabbit meibomian glands by indirect immunofluorescence using mouse monoclonal antibodies AE1, AE2 and AE3, which are known to react with human epidermal keratins as well as with keratins from other sources. Keratin proteins from rabbit meibomian glands were further isolated and characterized by SDS-PAGE and immunoblot using mouse monoclonal antibodies AE1 and AE3. Meibomian glands from human and rabbit showed similar immunofluorescent staining with each monoclonal antibody. AE1 antibody, which stains human basal epithelial cells of skin, stains all duct epithelial cells in the human but only the superficial duct epithelial cells in the rabbit meibomian gland. AE2 antibody, which stains human suprabasal epithelial cells of skin and is a marker for fully keratinized epithelia, stains the suprabasal epithelial cells of the central duct and ductules in both the human and rabbit meibomian gland. AE3 antibody, which stains all human epithelial cells of skin, stains all epithelial cells of the duct and ductules, as well as the basal epithelial cells of the acinus in both the human and rabbit meibomian gland. Keratins isolated from whole rabbit meibomian glands contained a 65-67 kD and 58 kD AE3-positive, and a 56.5 kD and 50 kD AE1-positive keratin protein. Expression of 65-67 kD/56.5 kD keratin proteins, and the immunofluorescent staining of the duct epithelium by the AE2 antibody, indicate that the meibomian gland duct epithelium is committed to the process of keratinization.

Animals↗

Microfluorometric measurements of cytoplasmic calcium in chief and oxyphil parathyroid cells of adenomatous and hyperplastic glands and of normal-sized glands associated with adenomas.

The effects of extracellular calcium on the cytoplasmic Ca2+ concentration (Ca2+i) were studied by dual-wavelength microfluorometry in individual human parathyroid cells obtained from adenomatous glands and normal-sized glands associated with adenomas in hypercalcemic hyperparathyroidism (HPT), as well as from enlarged glands of patients with uremia with HPT. In comparison with the normal parathyroid tissue, chief cells of the adenomatous and hyperplastic glands showed significantly lower Ca2+, and also right-shifted responses of Ca2+i to increases in the extracellular calcium concentration within the 0.5 to 3.0 mmol/L range. This pathophysiologic disturbance apparently was independent of the cell size. Oxyphil cells of nodules from the hyperplastic glands had lower Ca2+i and responded less to increments in extracellular Ca2+ than the chief cells from the surrounding parts of the same glands. Also the chief cells from the normal-sized glands associated with single adenomas exhibited a disturbance of the regulation of Ca2+i, which was less pronounced than that in the cells of the adenomas. These findings support the presence of relative calcium insensitivity of Ca2+i in chief and oxyphil parathyroid cells from adenomatous and hyperplastic glands. This derangement may also be found in all parathyroid glands of individuals with adenomatous HPT.

Adenoma↗

Differential regulation of alpha 2u globulin gene expression in liver, lachrymal gland, and salivary gland.

The alpha 2u globulins, products of a highly homologous multigene family, are synthesized in the liver and submaxillary salivary glands of the rat. Although their precise function has not been ascertained, they are of interest because of the complex developmental and hormonal regulation of their tissue levels. We now report that alpha 2u globulin is synthesized in a third tissue of the rat, the extraorbital lachrymal gland. Immunocytochemical studies indicate that the distribution of alpha 2u globulin is more homogeneous in the lachrymal gland than in the liver or submaxillary gland. In situ hybridization to alpha 2u globulin RNA reveals specific signal only over the acinar cells of the lachrymal gland. Several different isoelectric forms of alpha 2u globulin are encoded by lachrymal gland mRNA. The major lachrymal and salivary gland isoforms are indistinguishable from one another, but more acidic than the hepatic isoforms. In addition, analysis of double-stranded cDNAs with a diagnostic restriction-enzyme pair detects no differences between the alpha 2u globulin mRNAs of lachrymal and salivary gland, but clearly distinguishes these from their hepatic counterparts. In spite of the similarity between the lachrymal and salivary gland alpha 2u globulin gene products, we find that the hormonal and developmental regulation of alpha 2u globulin expression differs markedly in these two tissues. In the liver, where a different subset of alpha 2u globulin genes is expressed, a third regulatory phenotype is observed.

Alpha-Globulins↗

Expression of a glycoprotein of the carcinoembryonic antigen family in normal and neoplastic sebaceous glands. Limited role of carcinoembryonic antigen as a sweat gland marker.

BACKGROUND: Carcinoembryonic antigen (CEA) is a well-known marker for sweat gland differentiation in adnexal neoplasms. OBJECTIVE: The aim of this study was to examine the expression of glycoproteins of the CEA family, that is, CEA-180, nonspecific cross-reacting antigens (NCAs), and biliary glycoprotein (BGP), in sebaceous glands and in neoplasms with sebaceous differentiation. METHODS: Normal adult and fetal skin, hyperplasias, hamartomas, and neoplasms with sebaceous or follicular differentiation were stained immunohistochemically with a panel of polyclonal and monoclonal antibodies highly specific for CEA-180, NCAs, and BGP. Double immunostaining was performed to correlate the CEA expression with that of epithelial membrane antigen (EMA), a glycoprotein consistently found in differentiating sebocytes. RESULTS: Whereas sweat glands coexpressed CEA, NCAs, BGP, and EMA, sebaceous glands were exclusively labeled with the antibodies recognizing BGP or EMA. Staining of the sebaceous glands was restricted to mature sebocytes, sparing immature cells. At the ultrastructural level immunoreactivity for BGP and EMA was demonstrable in the golgi area, in small vesicles, and along the cell membranes. During fetal development BGP was not found until the sebaceous glands matured. The expression of BGP and EMA was highly conserved in reactive, hamartomatous, and neoplastic proliferations of adnexal structures with sebaceous differentiation. CONCLUSION: The expression of BGP, a CEA glycoprotein, in differentiating sebocytes accounts for the reactivity of many anti-CEA antibodies with sebaceous glands and thus disqualifies the CEA family as a monospecific marker for sweat gland differentiation.

Adolescent↗

T-cell adherence to lacrimal gland: the event responsible for IgA plasma cell predominance in lacrimal gland.

The majority of immunoglobulin in tears in various species is of the IgA isotype and is produced mainly by plasma cells of the lacrimal gland. The mechanism responsible for lodging of IgA committed cells in lacrimal gland is unknown, but could occur as a result of retained T helper cells in the lacrimal gland. The present experiments use an in-vitro adherence assay to examine the interaction of various murine lymphocyte populations with frozen sections of mouse lacrimal gland. Splenic and Peyer's Patch lymphocytes, as well as T-cell enriched and T-cell depleted lymphocyte populations were incubated with thin sections of lacrimal gland. Adherent lymphocytes were counted in randomly selected fields for each experiment. Each lymphocyte population was tested at least three times. It was found that more Peyer's Patch cells adhered to lacrimal gland than did spleen cells, and this increase was due to T-cells. The T-cell population responsible for adherence was localized to the helper T-cell population which appeared greater with Peyer's Patch T helper cells than splenic T helper cells. The data suggest that a lacrimal gland-T-cell interaction could retard the migration of a subpopulation of T helper cells as they migrate through the lacrimal gland. It is speculated that such T helper cells could be responsible for the terminal differentiation of IgA B cells to plasma cells, thus explaining the predominance of IgA plasma cells in the lacrimal gland.

Animals↗

Pathobiology of salivary glands. IV. Histogenetic concepts and cycling cells in human parotid and submandibular glands cultured in floating collagen gels.

Localization of cells with proliferative capacity in human major salivary glands lacks extensive study. Minced fragments of human parotid (n = 3) and submandibular (n = 3) glands embedded in a floating collagen gel matrix and cultured for up to 28 days allowed maintenance of the three-dimensional relationship of the various cell types in these glands. Immunocytochemistry and electron microscopy of a time-dependent series of cultured gland fragments showed gradual cytologic modification of acinar cells so that acini became duct-like but also established that even after 28 days of culture certain cellular features allowed continued identification of acinar cells. Serial section immunostaining for amylase, cytokeratins, and proliferating cell nuclear antigen (a specific marker for cycling cells) revealed that acinar, intercalated duct, and excretory duct (both basal and luminal) cells are all capable of entering the cell cycle. At day 5 of culture, the number of cycling cells increased 16-fold in the parotid gland and 9-fold in the submandibular gland over that in the respective in situ gland. In this in vitro system, which perhaps simulates regenerative processes in human salivary glands, none of the samples showed cycling cells localized only to segments of intercalated duct or the basal cells of excretory duct as suggested by current histogenetic concepts.

Cell Adhesion↗

Malignant salivary gland tumors: squamous cell carcinoma of the submandibular gland in a child.

PURPOSE: Malignant neoplasms of the salivary glands are extremely unusual in the pediatric age group. METHODS: We report an 11-year-old boy who presented with a mass in the left submandibular region and a second mass in the jugularfacial venous angle. RESULTS: Histologic evaluation determined that this was a squamous cell carcinoma of the submandibular gland with metastasis to a cervical node. Review of the literature was undertaken to identify the rate of malignant salivary gland tumors in children. Malignant salivary gland tumors are extremely rare in children. When malignancy does occur, nearly 90% are present in the parotid gland. The submandibular gland is effected in 7.7% of cases. The most common malignancy in salivary glands of children is the mucoepidermoid carcinoma. Squamous cell carcinoma occurs in less than 2% of cases. CONCLUSIONS: Salivary gland tumors are very rare in children in contrast to adults. The proportion of malignant tumors in children is higher than that observed in adults; however, it is not possible to draw conclusions concerning treatment from the few case reports that exist. A higher rate of local recurrence and cervical lymph node metastasis may be expected in children.

Carcinoma, Squamous Cell↗

Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis.

The proliferation of mouse submandibular gland carcinoma YT-12 cells was stimulated by endothelial cell growth factor (ECGF)/bovine brain-derived acidic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the effect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 were injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received bovine brain-derived aFGF and Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen weeks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2. Immunohistochemical study indicated that ducts in the normal submandibular glands and carcinomas showed positive staining with anti-aFGF antibody. Immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. These findings suggest that bovine brain-derived aFGF stimulates the proliferation of submandibular gland carcinoma cells and promotes mouse submandibular gland carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Uptake index and stimulated salivary gland response in 99Tcm-pertechnetate salivary gland scintigraphy in normal subjects.

With a view to improve the diagnosis of salivary gland diseases (in particular, Sjögrén's syndrome) associated with decreased salivary gland function and decreased stimulated salivary gland response, the normal range of radionuclide uptake function and the stimulated salivary gland response were established in 27 subjects without any known salivary gland disease. Following injection of 99Tcm-pertechnetate, sequential images were recorded for 40 min with oral administration of citric acid at 30 min. The total uptake index (TUI) was calculated as the sum of the background corrected count rates over the parotid and submandibular glands at 3 min divided by the injected dose. The TUI, expressed as a percentage of dose, was 0.55 +/- 0.12 (mean +/- S.D.). The stimulated salivary gland response (SSGR) was calculated as the difference between the rate constants (min-1) of monoexponential fits to the time-activity curves over the four salivary glands immediately after and before the administration of citric acid. The lower significance limit (P < 0.05) of the SSGR was a 2.4% decrease per min. The parameters TUI and SSGR can be used as a diagnostic tool in, for example, early Sjögren's syndrome.

Administration, Oral↗

[Histological study on gland tissue in the median region of the lingual root--morphology of the foramen cecum and posterior lingual gland].

The lingual root is an area where the thyroid gland develops and small salivary glands composed of both serous and mucous glands are distributed in the submucosa. In this paper the foramen cecum and mucous glands at the root of the tongue were histologically investigated in serial sagittal sections of the medial portion of the lingual root. The materials were obtained from 59 autopsied cases, excluding the cases with metabolic disease, brain tumor and neck tumor in whom the original disease might exert direct or indirect effects to the gland tissue. The frontal end was determined to be the line which connects the right and left palatoglossal arch junctions with the tongue, and the rear end the line of transition of the vallecula to the epiglottis. The specimen was cut in half along the median lingual sulcus and median glossoepiglottic fold. Each serial section of 4 microns in thickness was cut from the median plain to the lateral and stained with Hematoxylin-Eosin or Pas-Alcian blue at pH 2.5. The results of the study were summarized as follows. 1) The foramen cecum was histopathologically confirmed in 12 cases out of 59 (20%). The ratio of the detection did not show any difference between both sexes and in the groups of different age. 2) The mucous gland opening into the mucosal epithelium, which were located at the side of the lingual apex from the Ebner's gland or serous gland, were detected in 45 out of 59 (76%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗