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At least 757 records · Page 42Linked to original sources
PubMed1992

New specific assays for tonin and tissue kallikrein activities in rat submandibular glands. Assays reveal differences in the effects of sympathetic and parasympathetic stimulation on proteinases in saliva.

At least fourteen separate bands of proteinase activity, labelled A-N, were identified by an enzyme overlay membrane technique, using oligopeptide-7-amino-4-trifluoromethylcoumarin (AFC) substrates in rat submandibular gland extracts fractionated on pH 4-6.5 isoelectric focusing gels. The proteinases were eluted into an ammonium bicarbonate buffer pH 9.8 containing 0.1% Triton X-100 and the relative contribution of each band to total activity evaluated using D-Val-Leu-Arg-AFC (DVLR-AFC) and Z-Val-Lys-Lys-Arg-AFC (ZVKKR-AFC) as substrates. Immunoblotting of band eluants run on sodium dodecyl sulphate gels with antibodies showed that band A was identical with tonin and bands K-N contained tissue kallikrein. Tonin was found to hydrolyse ZVKKR-AFC but not DVLR-AFC. Estimates of the Km values of tissue kallikrein for DVLR-AFC and tonin for ZVKKR-AFC were found to be similar (approx. 20 microM) yet the former enzyme hydrolysed its substrate five times faster. Tonin was inhibited by soybean trypsin inhibitor (SBTI) but not by aprotinin. Tissue kallikrein, on the other hand, was inhibited by aprotinin but was considerably more resistant to inhibition by SBTI. In tissue extracts 95% of the ZVKKR-AFC lytic activity in the presence of 1 microM aprotinin is due to tonin and a similar percentage of the DVLR-AFC hydrolysing activity in the presence of 10 microM SBTI is due to tissue kallikrein. These findings were used for the specific measurement of these two proteinases in submandibular gland extracts and in saliva without prior purification. Using these inhibitor based assays we revealed qualitative differences in the composition of proteinases secreted into saliva during parasympathetic versus sympathetic stimulation of the submandibular gland. The distribution of proteinases in sympathetic saliva is very similar to that found in submandibular extracts but on parasympathetic stimulation, although much less proteinase is released, the contributions of the more acidic isomers of tissue kallikrein are increased and that of tonin and other proteinases dramatically decreased. The data suggest that parasympathetic and sympathetic nerves induce proteinase secretion via different pathways.

Amino Acid Sequence↗
PubMed1990

Observation of tissue prokallikrein activation by some serine proteases, arginine esterases in rat submandibular gland.

Two serine proteases, arginine esterases (esterases I and II) which showed the activity of tissue prokallikrein activation were identified in rat submandibular gland. These enzymes were separated from the homogenate of rat submandibular gland by two successive DEAE-cellulose chromatographies and were further purified and characterized. Esterases I and II were found to be identical with tonin and esterase B-like enzyme, respectively. Both enzymes activated rat urinary prokallikrein at near neutral pH. Esterase B-like enzyme activated rat urinary prokallikrein better than tonin.

Amino Acid Sequence↗
PubMed2004

Evaluation of acetaminophen P-glycoprotein-mediated salivary secretion by rat submandibular glands.

The constant ratio between saliva and plasma acetaminophen concentrations (S/P) during the elimination phase is assumed to result from the equilibrium established among the free-drug concentrations in the arterial blood, venous blood and saliva. Salivary secretion of acetaminophen is assumed to result from a passive diffusion of the drug to saliva from the blood that supplies the salivary glands. However, the constant S/P ratio during acetaminophen disposition and the finding that P-glycoprotein (P-gp), a protein recognized to pump substrates out of the cell, is expressed in duct cells of the submandibular glands questions the mechanisms involved in acetaminophen salivary secretion. Thus, we intended to evaluate the existence of a P-glycoprotein-mediated transport of acetaminophen in rat submandibular glands. Acetaminophen (30 mg/kg, i.v.) pharmacokinetics was assessed in controls and in rats pre-treated with erythromycin (100 mg/kg) as a P-glycoprotein inhibitor. Acetaminophen pharmacokinetic parameters were calculated from saliva and plasma levels considering a non-compartmental analysis. Mean plasma and salivary profiles of control and pre-treated animals were almost superimposable. No difference could be found in S/P ratios in control and erythromycin pre-treated animals (P > 0.05). Moreover, no statistical difference could be found in the kinetic parameters calculated from saliva or plasma drug level (P > 0.05). These observations indicate that acetaminophen salivary secretion in rat submandibular glands is not related to P-glycoprotein-mediated transport under the experimental conditions of the present work.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1984

[Immunopathologic reactions in chronic sialadenitis of the submandibular gland (so-called Küttner tumor)].

The aim of this study was to investigate immunological aspects of the inflammatory reaction in the submandibular gland during chronic sialadenitis. Specimens of 54 patients registered at the Institute of Pathology at the University of Hamburg were stained according to the indirect immunoperoxidase method. The distribution patterns of Ig-secreting plasma cells (IgA, IgG, IgM) and of the enzymes lactoferrin, lysozyme, and secretory component were analysed. The formation of lymph follicles was also examined. The results were as follows: Stage 1 of the chronic sialadenitis starts as a simple inflammation with an increase of IgA-secreting plasma cells around the ducts. During stage 2 the unspecific, humoral part of the immune system is stimulated. The production of lactoferrin and lysozyme is enhanced. The titer of IgA rises due to activation of the local, specific immune system. The simultaneous rise of the IgG titer is probably caused by production at different sites. During the course of stage 3--4, the cells involved in the local, unspecific immune system are destroyed. The number of IgG secreting plasma cells also decreases. The formation of lymph follicles and the infiltration of the gland by lymphocytes is interpreted as a transition to the cellular immune response. Stage 4 of the Küttner tumor shows similarities to the autoimmune disease of Sjögren's syndrome.

Chronic Disease↗
PubMed1984

Diurnal variation of sialomucin concentration in female mouse submandibular glands measured by radioimmunoassay.

The validity of a radioimmunoassay (RIA) for the predominant sialomucin from female mouse submandibular glands was confirmed by immunological and non-immunological approaches. The maximum sensitivity was in the low nanogramme range. The RIA did not cross-react with parotid, sublingual, trachea, stomach or colon tissues, but showed incomplete cross-reactivity with duodenal tissue. An analysis of protein, sialic acid and mucin contents of submandibular glands obtained during diurnal samplings, indicated that mean sialic acid and mucin concentrations, relative to protein in sample groups, decreased overnight approx. 30 per cent and showed a net increase during the day. Sialic acid per gland showed a 3-fold variation among individuals in the population; mucin showed greater than 20-fold variation. An analysis of variation indicated that influence by time of day was the greatest factor affecting sialic-acid concentrations and was statistically significant but, variation in mucin concentration was not. Variation between individuals accounted for more than 90 per cent of the total population variation in mucin concentrations and in sialic acid to mucin ratios. Regression analyses of the sialic acid to mucin ratios at different times of day suggested that the rates of replenishment of sialic acid and mucin may be co-ordinated.

Animals↗
PubMed2004

Neural regulation of submandibular gland blood flow in the streptozotocin-diabetic rat: evidence for impaired endothelium-dependent vasodilatation.

Functional changes in vascular tone and reactivity arise early in diabetes, and endothelial dysfunction plays a central role in the development of these microvascular abnormalities. Blood flow in the rat submandibular gland is mainly under neural regulation, which is mediated in part via endothelium-dependent mechanisms. Given the role of the endothelium in regulating blood flow and the deleterious effects of diabetes on endothelial cell function, we hypothesised that diabetes would significantly impair neural regulation of submandibular gland vascular perfusion. Three weeks after the induction of streptozotocin diabetes continuous 2 Hz sympathetic stimulation resulted in a similar degree of vasoconstriction (as measured by a decrease in perfusion) in both diabetic (-31+/-17%) and control rats (-22+/-7%). However, the magnitude and the duration of the after-dilatation were significantly less in diabetic animals. The same number of impulses delivered at 20 Hz in bursts (1s in every 10s) also resulted in vasoconstriction with each burst, but unlike the effects of burst stimulation in control rats the initial vasoconstriction was not converted to a net vasodilatation between bursts. Parasympathetic stimulation (2, 5 and 10 Hz) caused a marked vasodilatation in both control and diabetic rats, but the initial responses were delayed in diabetic animals, the maintained phases were smaller in magnitude (P<0.02) and it took longer to return to resting levels. In conclusion, submandibular gland vascular responses are altered in streptozotocin-induced diabetic rats. Vasoconstrictor responses evoked by sympathetic impulses were unaffected, but vasodilatory responses, particularly those associated with endothelium-dependent mechanisms, were significantly reduced.

Animals↗
PubMed2002

Influence of age on circadian rhythms of adrenoceptors in brain cortex, heart and submandibular glands of BALB/c mice: when circadian studies are not only useful but necessary.

In the present paper we study circadian rhythm variation of alpha1-adrenoceptors (alpha(1)ARs) and beta-adrenoceptors (betaARs) characteristics during aging. Experiments have been performed on mice's whole brain cortex, heart and submandibular glands, which have physiologically relevant regulatory functions at different ages. We used 36 young (4 months) and 36 old (26 months) mice; six animals from each group were sacrificed every 4h, starting at 8.00 a.m. Both the alpha(1)ARs and betaARs density in heart and brain and the betaARs of submandibular glands are significantly lower in old mice with respect to the young ones. The difference, however, if the comparison is performed only at a particular time, for example 8.00 a.m., is not always significant. The alpha(1)ARs density in submandibular glands does not show significant difference with aging, but opposite phases are observed. This study demonstrates that in dynamical systems such as receptors, single point analysis is not so suitable for a correct estimate of adrenoceptors density variation between young and old mice.

Aging↗
PubMed2006

Cost efficiency analysis for fine-needle aspiration in the workup of parotid and submandibular gland nodules.

The utility and cost effectiveness of salivary gland fine-needle aspiration (FNA) is controversial. Some authorities argue FNA has no added value over clinical-radiographic study because most salivary gland nodules occur in the parotid and the tumor's relationship to the facial nerve determines the operative procedure rather than the histology. Other experts contend FNA is of value by reducing the overall number of operative procedures performed. We studied 306 salivary gland nodules (214 parotid and 92 submandibular gland) undergoing FNA. One hundred and seventy one were subsequently surgically resected and the remaining 135 followed clinically. A 16% error rate was associated with the nonoperative group, necessitating later surgical resection. The cost of the FNAs and surgical resections (when performed) was calculated based on Medicare reimbursement rates. Costs were based on all cases undergoing initial FNA. The expense of initial resection was based on the observed percentage of patients undergoing resection in our series. The costs of resections related to erroneous FNA diagnoses were based on the error rate associated with FNA diagnoses clinically followed (i.e., chronic sialadenitis). Costs of FNAs, initial resections, and subsequent resections related to FNA errors were summed and compared with the cost which would have occurred if all nodules had been primarily resected.FNA reduced the number of operative procedures by approximately 65% for submandibular nodules and 35% for parotid nodules. Diagnoses which resulted in nonsurgical management included chronic radiation-induced sialadenitis, intraparotid lymph node, recurrent lymphoma, and accessory nodules or lobes of the parotid gland. Pure surgical management was associated with a cost of $275,750.00 per 100 patients. FNA management was associated with an expenditure of $206,632.00 per 100 patients, representing a savings of $69,118.00 (33% savings over surgical management alone). Based on these data, FNA appears to be cost effective in addition to supplying preoperative diagnoses helpful in counseling, operative planning, and allaying patient anxiety.

Biopsy, Fine-Needle↗
PubMed1997

Field emission SEM, conventional TEM and HVTEM study of submandibular gland in prenatal and postnatal aging mouse.

The development of acinar and ductal cells of the mouse submandibular gland was studied using field emission SEM, conventional TEM and HVTEM methods. The specimens, at 15 and 18 days of gestation and 1, 3, 7, 14, 21, 30, 90 and 180 postnatal days were fixed in 2.5% glutaraldehyde solution in 0.1 M sodium phosphate buffer (pH 7.3). At 15 and 18 days of gestation, the structure of mouse submandibular gland contains acinar and ductal cells in proliferation. The cytoplasmic organelles such as mitochondria, granular endoplasmic reticulum and Golgi apparatuses are scattered in the cytoplasm. At 18 prenatal days only several acinar cells present immature secretory granules in the apical portion. In this stage the acinar and ductal cells are enveloped by bundles of fine collagen fibrils disposed in several directions. There are also numerous capillaries located closely to the acinar cell membranes. In the aging stages of 1, 3, 7, 14, 21, and 30 postnatal days, the histo-differentiation of acinar, intercalated and ductal cell components are observed. At newborn day one the cytoplasmic organelles start to place themselves around the nucleus. Several immature secretory granules are observed at day one, however, they increase in the aging days. At postnatal day 30, the cytoplasms of acinar and ductal cells are filled with a large number of secretory granules of different sizes. The stacks of granular endoplasmic reticulum and Golgi apparatus and some vesicles and free ribosomes are noted. The intercellular membranes are attached by desmosomes and cytoplasmic interdigitations. The luminal surface shows several small projections of microvilli. An electron-dense line of basement membranes followed by fine collagen fibrils are recognized. Delicate capillaries are found in the outer surface of acinar cells. At postnatal day 90 and 180 the acinar, intercalated and striated ductal cells reveal numerous secretory granules in the apical portion. The acinar cells showed basal nuclei and the parallel arrangement of granular endoplasmic reticulum. The mitochondria are located at the base of ductal cells showing a typical pattern of cristae. In these stages the intercellular digitations of cytoplasmic protrusions and desmosomes are also noted. The cytoplasm of myoepithelial cells are seen along the cell membranes. The spongy-like structures constituting the basement membrane are followed by bundles of fine collagen fibers.

Animals↗
PubMed1976

Immunocytochemical localization of nerve growth factor (NGF) in the submandibular gland of adult mice by light and electron microscopy.

Nerve growth factor (NGF) was localized in the submandibular gland of adult male mice by a direct immunocytochemical method using highly purified antibodies against NGF coupled to horseradish peroxidase. In light microscopic sections the reaction product was entirely confined to the cells of the secretory tubules. The acinar part of the gland was free of reaction product. This finding was confirmed by electron microscopy. Within the cells NGF was localized exclusively in the apical secretory granules. No reaction was observed in the rough endoplasmic reticulum, the Golgi region or in the granules of the basal part of the cells. This observation favours the assumption that NGF is derived from a precursor molecule and that the precursor is transformed into immunologically active NGF within the secretory granules during their transport from the basal to the apical part of the tubular cells. Stimulation of the submandibular gland with carbachol (2 mg/kg) led to a massive release of the content of the secretory granules, including NGF, into the salivary duct.

Animals↗
PubMed1993

Production of alpha-fetoprotein by human submandibular gland.

Alpha-fetoprotein (AFP) is a 590 amino acid polypeptide that was initially defined as an embryonal serum globulin. The yolk sac endoderm, fetal liver and fetal gut were shown to be the main sites of AFP synthesis in the embryo (Gitlin and Boesman, J. Clin. Invest. 46: 1010-1016, 1967). AFP synthesis is still continued in human adults (Ruoslahti and Seppala, Int. J. Cancer 8: 374-383, 1971) although the physiological level of serum AFP is lower than 10 ng/ml. AFP was also demonstrated in certain tumors and in various diseases or conditions such as yolk sac tumor, hepatoma, hepatoblastoma, acute and chronic liver cirrhosis, pregnancy and so on (Abelev, Adv. Cancer Res. 14: 295-358, 1971; Ruoslahti and Seppala, Cancer Res. 29: 275-346, 1979). Salivary glands have not been implicated in AFP synthesis. We investigated the expression of AFP in normal human salivary glands by immunohistochemistry with a monoclonal antibody against AFP, and documented immunoreactivity in intercalated and striated ducts of adult human submandibular glands.

Adult↗
PubMed1984

The effect of chronic isoproterenol administration on the plasma membrane of acinar cells in rat submandibular gland.

The effect of chronic administration of isoproterenol on the plasma membrane of acinar cells in the rat submandibular gland was studied by biochemical and immunohistochemical methods, using dipeptidyl peptidase (DPP) IV as a marker enzyme. Chronic isoproterenol treatment led to a marked reduction of DPP IV activity as well as of its immunoreactivity in the gland. Its effect progressively increased with the age of the animals. The present study showed that chronic treatment with isoproterenol caused a qualitative alteration of the plasma membrane of the luminal surface in acinar cells of the rat submandibular gland, and that the effect of the drug on the plasma membrane was dependent on the developmental stage of the acinar cells of the gland.

Age Factors↗
PubMed2003

[Gene expression and pathological changes of rat submandibular glands after adenovirus-mediated gene transfer].

OBJECTIVE: To investigate luciferase gene expression and pathological changes of submandibular glands (SMG) of rats after adenovirus-mediated gene transfer. METHODS: Adenovirus-mediated luciferase gene (AdCMVLuc, 10(8) pfu in 50 microl) was injected in to SMG of forty wistar rats. The SMGs were harvested for gene expression measurement and pathological study after 3 days, 1,2,4 and 8 weeks. RESULTS: Peak expression was observed in three days following administration of the vector however, gene expression in submandibular glands decreased rapidly. the pathological changes induced by retrograde injection of AdCMVLuc included: after 3 days to one week, compression of acini, dilation of terminal ducts; after two weeks, slight atrophy of a part of acini, increase of iteracinar distance and focal lymphocyte infiltration in lobules and interlobular ducts; after 4 weeks, recovery evidence was found in acini; after 8 weeks, normal acini and ducts were found. The ultrastructural changes included: 3 days, much more rough endoplasmic reticulum was found both in acini and duct epithelial cell; a lot of mucus drops were found in acini; after 1 week, microvillus decreased in duct epithelial cells, mitochondria increased significantly in acini; intercellular space was enlarged. CONCLUSIONS: Adenovirus-mediated gene transfer can produce biological proteins and induce marked inflammatory changes in rat SMG. The ultrastructural changes suggest high protein synthesis activity in the acinar cells after gene transfer.

Adenoviridae↗
PubMed1980

Immunocytochemical evidence for the presence of somatostatin-like immunoreactivity in scattered cells of the duct system of the submandibular glands in the monkey, Macaca irus.

Using the indirect immunofluorescent technique with anti-somatostatin serum, the distribution of scattered cells in the duct system of submandibular glands in the Monkey, Macaca irus has been assessed. In both males and females, these cells are located only in some portions of the duct system, e.g. striated ducts and excretory ducts. No immunoreactive cells were observed in the intercalated ducts or in secretory endpieces. The lymphatic node constantly adjacent to the submandibular gland did not contain immunoreactive cells. In the parotid glands, no immunoreactive cells to antisomatostatin immuneserum were ever observed.

Animals↗
PubMed2002

Enhanced immunocytochemical expression of antioxidant enzymes in rat submandibular gland after normobaric oxygenation.

In order to clarify the role of antioxidant enzymes in the male rat submandibular gland against short-term normobaric oxygenation, we performed immunocytochemical staining of manganese-containing superoxide dismutase (Mn-SOD), copper- and zinc-containing SOD (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase, and glutathione S-transferases (GST alpha, GST mu, and GST pi) between days 1 and 7 after normobaric oxygenation. Ultrastructural alterations and immunoreactivities for malondialdehyde (MDA), a lipid peroxidation-related molecule, of the acinar and ductal cells after the oxygenation were also investigated. Immunoreactivity for MDA was exhibited in the acinar cells throughout the experiment. On the other hand, immunoreactivity for the SODs, CAT, and GSTs was not altered, when compared to that of controls, but was significantly elevated in the granular, striated, and excretory ductal cells. Since an increase of lipid peroxidation as indicated by enhanced immunoreactivity for MDA was detected in the acinar and intercalated ductal cells, the results indicate that the enhanced antioxidant enzymes in the granular, striated, and excretory ductal cells play a crucial role in the self-defense system of the male rat submandibular gland against normobaric oxygenation.

Animals↗
PubMed2004

Adenoid cystic carcinoma of the submandibular gland: a 35-year review.

OBJECTIVES: To evaluate the treatment results of adenoid cystic carcinoma (ACC) of the submandibular gland at a single institution during a 35-year period. STUDY DESIGN & SETTING: A retrospective review was performed by examining the records and reviewing the pathology of 22 patients with ACC of the submandibular gland treated at UCLA Medical Center from June 1963 to December 1997. RESULTS: Seven men and 15 women with an age range of 23 to 85 years (median, 48 years) were treated. Surgical intervention was performed in 21 patients. All patients with advanced tumor size, perineural invasion, microscopically positive surgical margins, or regional neck metastases received postoperative adjunctive therapy, primarily radiotherapy. Follow-up varied from 6 months to 181 months (median, 67 months). Disease-free survival at 3, 5, and 10 years was 66%, 57%, and 41% respectively, whereas overall survival was 76%, 70%, and 37%, respectively (note: 5- and 10-year survival rates are not statistically conclusive due to the small sample size). CONCLUSIONS: We report fairly high disease-free survival rates in this patient population and a number of prognostic trends are evident. Early diagnosis, wide surgical intervention, and postoperative radiation are associated with a favorable prognosis. Advanced tumor size, positive surgical margins, perineural invasion, and local recurrence of the tumor are associated with an unfavorable prognosis. EBM RATING: C.

Adult↗
PubMed1993

Parenchymal cell proliferation and mechanisms for maintenance of granular duct and acinar cell populations in adult male mouse submandibular gland.

To evaluate proliferation as a factor in maintenance of parenchymal cell populations in adult male mouse submandibular glands, a variety of surveys were conducted following a pulse with 3H-thymidine. Striated granular duct (SGD) cells had the highest labeling index, followed by intercalated duct (ID) cells, then acinar (AC) cells, and granular duct (GD) cells had the lowest. These cell types showed from 30% to 60% completion of mitosis by 24 hr, with SGD, AC, and GD showing a likely second wave of mitosis sometime between 2 and 7 days after the pulse. About 40% of the pulse-labeled cells still remained as single cells at 42 days after the pulse. Repeat divisions in daughter cells of the primary labeled cells were very rare. A shift in the pattern of labeled cells at the ID-GD junction indicates that ID and SGD cells in this compartment are differentiating to GD cells. Further comparison of the magnitude of this conversion with the amount of noncompartmental GD cell proliferation provided a basis for calculating that approximately 70% of GD cell population maintenance occurs by self-proliferation, and the remaining 30% is contributed by differentiation from ID and SGD cells. A similar survey at the ID-acinus junction showed no evidence of conversion of ID cells to AC cells indicating that most, if not all, proliferative activity leading to AC cell population maintenance occurs by self-proliferation. Finally, based in part on structural changes at the ID-GD junction during the survey period, a pattern of cell conversion described as "in situ differentiation" is proposed. When this pattern is carried to fruition, this explains several structural features of the secretory complex typical to the male pattern submandibular gland. The proposed mechanism is supported by a three-dimensionally reconstructed sequence of likely intermediate structures.

Animals↗