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PubMed2006

The advantages of submandibular gland resection in anterior retropharyngeal approach to the upper cervical spine.

Anterior surgery to the upper cervical spine, although rare, several successful approaches were described in the literature. To avoid the risks and limitations of transoral approach, the anterior retropharyngeal approach was developed. In this study, we describe our experience with anterior retropharyngeal approach to the upper cervical spine and discuss the significance of resecting the submandibular gland. From July 2001 to July 2004, we performed six anterior prevascular retropharyngeal approaches to the upper cervical spine. The series included five males and one female, ranging in age from 26 to 60 years (mean = 46). All six patients were intubated with nasotracheal cannula. The submandibular gland was mobilized and removed in all patients allowing adequate exposure of the arch of C1, C2, and C3 vertebral bodies. The anterior retropharyngeal approach permitted an adequate access to anteriorly situated lesions from C1 to C3 in all six patients, without the risks and limitations of transmucosal surgery. This approach allowed us to perform decompression of the spinal cord and reconstruction of the anterior column of the spine with bone graft and internal fixation. Careful removal of the submandibular gland provided better visualization of the arch of C1 and C2. No facial nerve palsy was seen in any of the six patients. Anterior retropharyngeal approach to the upper cervical spine combined with removal of the submandibular gland permits exposure of the anterior spine similar to that obtained by the transmucosal route, and provides a safe simultaneous arthrodesis and instrumentation during the primary surgical procedure without the potential contamination of the oropharyngeal cavity. Removal of the submandibular gland allows better exposure with less retraction and thus avoids severe injury to the mandibular branch of the facial nerve.

Adult↗
PubMed1981

Ultrastructure and histochemistry of the submandibular gland of the Japanese wood mouse (Apodemus ainu ainu Tokuda).

The submandibular glands of adult female and male Japanese wood mice (Apodemus ainu ainu Tokuda) were studied histochemically using toluidine blue (pH 2.5, 4.1 and 7.0, McIlvaine), PAS reaction, Millon's reaction for tyrosine, p-dimethylaminobenzaldehyde for tryptophan, and substrate film techniques for amylase and protease. The glands were also examined ultrastructurally and ultracytochemically by the periodic acid-thiocarbohydrazide-silver proteinate technique (PA-TCH-SP staining) for glycoprotein. The submandibular gland consisted of the striated ducts (SDs), the convoluted granular tubules (CGTs), the intercalated ducts and the terminal portions. In both sexes the acinar cells were seromucous in secretory nature, and the secretory granules contained glycoproteins and were negative to amylase and protease activities. By the PA-TCH-SP staining, the distribution of glycoproteins and fine structural alternations corresponding to the maturation of the secretory granules were demonstrated. The granules of the CGT cells contained tryptophan, tyrosine and neutral mucopolysaccharides. The granules showed negative reactions to acid mucopolysaccharides, protease and amylase activities, and glycoproteins. Glycogen particles in the apocrine processes were intensely positive to PA-TCH-SP staining. Dark and clear cells were distinguished in the SDs. The apical cytoplasm of the SD cells contained two types of vesicles. One type may represent reabsorption vesicles and the other secretory vesicles. Some of the SD cells had both microvilli, associated with reabsorption vesicles and apocrine process containing abundant glycogen particles on their luminal surface. From the statistical analysis of the average values, the CGT diameter of the male mice was significantly larger than that of the female mice.

Animals↗
PubMed1998

Expression of an allozyme of prorenin-converting enzyme in the submandibular gland of DBA/2N mice.

A protein product of the tissue kallikrein gene family was isolated from the submandibular gland of DBA/2N mice. Amino acid sequencing showed this protein to be highly homologous to two tissue kallikreins, mK13 and mK26, also known as prorenin-converting enzymes PRECE and PRECE-2, respectively. The cDNA corresponding to the present enzyme was cloned, and its complete nucleotide sequence was determined. The cloned cDNA was different in 6 and 12 bases out of 783 nucleotides from those of mK1k-13 and mK1k-26 cDNAs, respectively, the homologies being 99.2 and 98.5% (nucleotide), or 98.3 and 96.2% (amino acid). Upon incubation with either bovine kininogens or mouse Ren 2 prorenin, this tissue kallikrein generated bradykinin and renin, respectively, as judged by Western blotting and protein sequence analysis. Isoelectric focusing analysis of the submandibular gland tissue kallikreins suggested that the present enzyme was not expressed in CD-1 or ICR mice and that no mK13 protein was present in DBA/2N mice. These data suggest that the enzyme is an allozyme of mK13, a prorenin-converting enzyme highly expressed in the submandibular gland of DBA/2N mice. The mK1k-13 gene in mice is therefore suggested to be polymorphic, having at least two allelic forms with a high sequence homology. The designation mK13(b) and mK1k-13(b) for the protein and gene of this tissue kallikrein is proposed.

Amino Acid Sequence↗
PubMed1994

Submandibular gland with multiple ducts.

A morphological peculiarity was observed in the form of a submandibular gland having three ducts. These ducts opened separately into the oral cavity. Only the upper and the largest of these three ducts was in the usual position and had the expected relation to the lingual nerve. Such a condition is to be kept in mind by a surgeon or a radiologist performing sialography. Unless each of the duct in instilled he may miss pathological findings.

Adult↗
PubMed1995

Immunohistochemical evidence that tumors elicit the synthesis of estrogen receptors in the submandibular gland of female rats.

We have demonstrated the presence of estrogen receptor mRNA and the mature protein in the cytoplasm and nucleus, respectively, of a 9,10-dimethyl-1,2-benzathracene-induced submandibular gland tumor in female rats. We have previously shown that progesterone receptors are also present in human salivary gland tumors. These results suggest that endocrine therapy may be effective in treatment of submandibular gland tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Protein breakdown in submandibular glands rendered hypertrophic by amputation of lower incisor teeth in rats.

Protein breakdown in submandibular glands rendered hypertrophic by amputation of the lower incisor teeth in rats was investigated. Reduced protein breakdown was observed in the hypertrophic gland tissues, and was found to be inhibited by 20 mM epsilon-amino-n-caproic acid, an inhibitor of serine protease, and 50 microM leupeptin, an inhibitor of trypsin, plasmin, papain and cathepsin B, but not by 2 mM PMSF (phenylmethylsulfonyl fluoride), an inhibitor of serine protease, 10 microM pepstatin, an inhibitor of cathepsin D and 20 microM antipain, an inhibitor of cathepsin A and B. These results suggest that some serine proteases and leupeptin-sensitive proteases (presumably cathepsin B) participate in protein breakdown in hypertrophic gland tissues, and that hypertrophy of the submandibular glands is closely related to the reduced protein breakdown in these tissues.

Aminocaproic Acid↗
PubMed1978

Sex difference in L-glutamine D-fructose-6-phosphate aminotransferase activity of mouse submandibular gland.

L-Glutamine D-fructose-6-phosphate aminotransferase (2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase (amino-transferring), EC 5.3.1.19) activities in the three main salivary glands of male and female mice were measured. It was found that the activity in the submandibular gland was about 10 times more in females than in males, whereas the activities in the sublingual and parotid glands of males and females were similar. The activity in the submandibular gland of female mice was not affected appreciably by ovariectomy but it decreased to the level in males on injection of testosterone. The activity in males was not affected appreciably by injection of progesterone or 17beta-estradiol, but it increased to the level in females after castration. The increased activity in castrated male mice was decreased again to the normal level by testosterone injection. Thus, this sex difference is caused by androgen, not by female hormones. On the basis of in vivo experiments using actinomycin D, it was suggested that testosterone produced an "enzyme inhibitor", which suppressed the enzyme activity in the submandibular glands of androgen-rich animals.

Animals↗
PubMed1994

Effect of chronic insulin administration on mouse parotid and submandibular gland function.

Chronic (six-day) injection of insulin (im, 50 microM/animal) into BALB/c mice resulted in changes in secretory function, hypertrophy and hyperplasia of the parotid and submandibular glands. There were no significant changes in the flow rate or concentrations of proline-rich proteins, TGF alpha, or amylase in saliva when measured against constant protein levels. However, amylase enzyme activity and total saliva protein content were reduced when measured against constant saliva volume. In contrast, EGF synthesis and secretion from the submandibular gland was increased. Both the parotid and submandibular gland showed evidence of gland hypertrophy and increased rates of DNA synthesis as indicated by [3H]-thymidine incorporation in response to insulin treatment. Chronic injection of insulin did not effect the level of receptor in the plasma membrane of either gland.

Animals↗
PubMed2000

Sonographic analysis of rat submandibular glands in experimentally-induced sialadenitis.

OBJECTIVES: To correlate the sonographic features of experimentally-induced obstructive sialadenitis in rat submandibular glands with the histopathological changes. MATERIALS AND METHODS: Changes in sonograms of ligated and non-ligated rat submandibular glands were compared with the wet weight and histopathology. Sonograms were obtained at 1, 2, 3, 4, 5, 7 and 21 days after duct ligation at 13 and 14 MHz for B-mode and for power Doppler mode respectively. Changes in gland size, echo intensity, distribution of internal echoes and vascularity were evaluated both qualitatively and quantitatively. RESULTS: Changes in size of the ligated glands were very similar to changes in wet weight. The ligated glands showed lower echo intensity than the non-ligated glands. The ligated glands showed higher echo intensity in the central portion at 4-7 days after duct ligation which resulted in heterogeneity of the glands. Vascularity of the ligated glands increased in the acute phase, and then decreased to the level of the non-ligated glands. CONCLUSIONS: The three phases in the changes in ligated glands identifiable histopathologically can be differentiated by B-mode sonography. Power Doppler can differentiate the acute phase. Sonography therefore appears useful for the diagnosis of the degree of gland damage.

Acute Disease↗
PubMed2005

Chemoradiation-induced cell loss in human submandibular glands.

OBJECTIVES: Chemoradiation-induced xerostomia affects approximately 40,000 head and neck cancer patients annually in the United States. No human histopathologic or immunohistochemical data exist that characterize chemoradiation-related salivary gland damage. The objective of this study was to describe the histopathologic and immunohistochemical features of the non-acute phase of human submandibular gland damage after chemoradiation therapy. METHODS: Pathologic materials were retrieved from patients who had undergone neck dissection after protocol-driven chemoradiotherapy for stage IV head and neck cancer at a tertiary head and neck cancer institute. Histologic and immunohistochemical analyses were performed on representative sections of chemoradiated submandibular glands, and findings were compared to age- and sex-matched, untreated control glands. RESULTS: Forty patients were identified who had undergone neck dissection an average of 11 weeks after treatment with induction chemotherapy and chemoradiation therapy for non-oral head and neck cancer. In the chemoradiated glands, light microscopic findings included pronounced acinar cell loss with accompanying ductal metaplasia and ductal proliferation and increased fibrosis, chronic inflammation, nuclear atypia, and cytoplasmic vacuolization when compared with controls. Microvascular density was marginally affected by chemoradiation; cytokeratin staining showed preservation of ductal epithelium when compared to controls. CONCLUSIONS: Nonacute changes seen in human submandibular glands after chemoradiation therapy are compared to those seen in previously described irradiated animal and human models. Primary dysfunction in humans appears to be related to a reduction in function and number of submandibular gland acinar cells. The ductal system appears to be preserved after chemoradiation therapy. Implications for management of xerostomia are discussed.

Aged↗
PubMed1998

Abnormally high levels of cystatin S in submandibular glands, saliva, and gingiva of plaque-resistant rats.

To identify salivary biomarkers of periodontal diseases, we used plaque-resistant and -susceptible rats as animal models. The levels of salivary cystatin S in saliva, salivary glands, and gingiva were tested in Nembutal-anesthetized young and adult plaque-resistant and -susceptible rats of both sexes with and without chronic treatment with isoproterenol. Isoproterenol was injected i.p. once a day for 4 or 6 consecutive days. Isoelectric focusing electrophoresis by the PhastSystem and the western blotting method were used to separate different proteins and to identify a salivary cystatin S band in these samples. The expression of salivary cystatin S mRNA was also determined by the northern blotting method. Depending upon the types of agonists, a few differences were observed in secretory functions between both strains of rats in both sexes, but the levels of salivary cystatin S in saliva elicited from the submandibular gland and in the extracts of the submandibular glands and gingiva were significantly higher in plaque-resistant rats when compared with those of plaque-susceptible rats in both sexes. However, no significant difference was seen between the strains after chronic treatment with isoproterenol. The N-terminal 26-amino-acid sequence of salivary cystatin S purified from submandibular saliva of plaque-resistant rats was identical with that purified from submandibular saliva of Sprague-Dawley rats subjected to chronic treatment with isoproterenol. The expression of salivary cystatin S mRNA was dramatic in the submandibular glands of the plaque-resistant rats and in the submandibular glands of Wistar rats subjected to chronic treatment with isoproterenol, but not in those of plaque-susceptible rats. These results suggest that salivary cystatin S might be a good biomarker in distinguishing between the two strains of rats and that its concentration is correlated with plaque resistance.

Amino Acid Sequence↗
PubMed2000

Microvascular submandibular gland transfer for severe cases of keratoconjunctivitis sicca.

Free submandibular salivary gland transfer was investigated as a surgical method for the treatment of severe keratoconjunctivitis sicca. In an animal model, we examined the tolerance of warm ischemia of the submandibular gland. After temporary interruption of the blood supply (1 to 6 hours), the morphologic changes in the submandibular gland were analyzed histologically and immunohistochemically in 41 rabbits. From 1.5 hours ischemia onward, an increasing structural damage of the parenchyma with emphasis on the secretory cells was seen. Six hours of ischemia caused total necrosis of the salivary gland. Our clinical experience includes 24 highly selected patients suffering from keratoconjunctivitis sicca, in whom we transferred 31 autologous submandibular glands to the temple for permanent autologous tear substitution within the past 4 years. The glands were implanted into a pocket prepared in the temporalis muscle, and the nourishing vessels were anastomosed to the superficial temporal artery and vein. The submandibular duct was implanted into the upper lateral conjunctival fornix. The transferred glands were left denervated. In addition to the clinical examination, scintigraphy with Tc 99m pertechnetate was used to document the graft's viability after the transfer. Viable incorporation with longstanding secretory function occurred in 26 of the 30 transplanted denervated salivary glands. The resulting lubrication of the treated eyes was irregular for up to 3 months in almost even case. One year after surgery, all patients with a viable transplant developed at least occasional epiphora, which was surgically managed by reducing the size of the graft in 10 patients. No severe side effects were seen in this series. The ophthalmologic evaluation of the method included the assessment of dry eye symptoms and of the volume and quality of ocular lubrication (Schirmer test, fluorescein break-up time), the pathology of the ocular surface (rose bengal staining), and the need for pharmaceutical tear substitutes. One year after surgery, 18 of 27 cases assessed were judged as significantly improved by these tests.

Adolescent↗
PubMed1998

Expression and localization of HGF mRNA in monkey submandibular gland.

We investigated the characteristics and mRNA expression of hepatocyte growth factor (HGF) in the adult female monkey submandibular gland using Western blot analysis and the reverse-transcriptase PCR (RT-PCR) technique, and observed HGF mRNA localization using the in situ RT-PCR technique. HGF was extracted with PBS containing protease inhibitors, and purified partially by heparin affinity chromatography. With Western blot analysis, the HGF fraction showed an immunopositive protein band of 69-kDa corresponding to the alpha-subunit of HGF. The gene expression for HGF was revealed in the monkey submandibular gland using RT-PCR, and the PCR products showed high homology to cDNA for human HGF. Furthermore, the mRNA signal for HGF was localized in the striated and excretory ductal cells. These results unequivocally confirmed both the synthesis and existence of HGF in monkey submandibular glands.

Animals↗
PubMed2005

Sympathectomy-induced increases in calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide (VIP)-levels in parotid and submandibular glands of the rat.

The neuropeptide contents of rat salivary glands were increased four weeks after sympathetic postganglionic denervation (but not after preganglionic denervation): calcitonin gene-related peptide (CGRP) by 400 and 65% in the parotid and submandibular glands, respectively; substance P by 30% in the submandibular gland; and vasoactive intestinal peptide (VIP) by 30% in the parotid gland. The sensory neurotoxin capsaicin prevented the expected increases of CGRP and substance P in the submandibular glands and of VIP in the parotid glands. The CGRP-increase in the parotid gland was, however, only reduced (by 65%). Parasympathetic otic ganglionectomy reduced the peptide levels in the parotid glands (CGRP--50%, VIP--98% and substance P--99%). From these residual levels, CGRP increased almost 8-fold and substance P 3-fold in response to the sympathetic denervation, while VIP was unaffected. In the parasympathetically denervated glands, the capsaicin-sensitive contribution to the CGRP-response to sympathetic denervation was roughly estimated to be more than 25% but less than 40%, while the corresponding contribution to the substance P-response was roughly estimated to be more than 6% but less than 58%. Most likely not only CGRP/substance P-containing sensory C-fibres (submandibular and parotid glands) but also parasympathetic VIP-containing secretomotor and vasomotor fibres (parotid glands) contributed to the capsaicin-sensitive response to sympathetic denervation.

Animals↗
PubMed1986

Purification and characterization of a serine protease (esterase B) from rat submandibular glands.

A new protease has been purified to homogeneity from rat submandibular gland homogenate by using DEAE-Sephadex chromatography, chromatofocusing, aprotinin-Sepharose affinity chromatography, and high-performance liquid chromatography. The enzyme has been named esterase B, since it represents the second major esterolytic peak on DEAE-Sephadex chromatography of submandibular gland homogenate. It is an acidic protein (pI = 4.45) with an apparent molecular weight of 27 000. It is heat-stable and has an optimum pH of 9.5. Esterase B hydrolyzed the synthetic substrates tosyl-L-arginine methyl ester and Val-Leu-Arg-p-nitroanilide (S2266). It also cleaved dog plasma kininogen to produce a kinin, identified as bradykinin on reverse-phase high-performance liquid chromatography. Esterase B, however, is only a weak kininogenase, since it had only 5% of the kininogenase activity of equimolar concentrations of glandular kallikrein and had no effect on rat mean blood pressure or on the isolated rat uterus. Esterase B activated plasminogen and had caseinolytic activity. It was inhibited by aprotinin, soybean trypsin inhibitor, lima bean trypsin inhibitor, phenylmethanesulfonyl fluoride, antipain, leupeptin, and p-tosyl-L-lysine chloromethyl ketone. On double immunodiffusion, when reacted with kallikrein and tonin antisera, esterase B showed partial identity with kallikrein but not with tonin. On immunoelectrophoresis against kallikrein antisera, esterase B formed a precipitin arc at a position different from that of kallikrein. Esterase B appears to be a trypsin-like serine protease having some homology with glandular kallikrein.

Amino Acids↗
PubMed1988

Epidermal growth factor content of submandibular glands is increased in rats with experimentally induced gastric lesions.

Occurrence and growth-promoting effect suggest that epidermal growth factor (EGF) is involved in the maintenance of the gastrointestinal mucosa. The aim of this study was to ascertain whether rats with gastric lesions, induced by cold-water stress, ethanol, or indomethacin, have altered EGF levels in their gastrointestinal tract compared with controls. For this purpose we established a solid-phase enzyme immunoassay and measured the amount of immunoreactive EGF (IR-EGF) in extracts of the submandibular gland, stomach, duodenum, jejunum, ileum, and colon. In the submandibular glands of control rats the IR-EGF content was 100-400 times higher than in the gastrointestinal tract. In animals with experimentally induced ulcer the IR-EGF content was increased in the submandibular glands (1480 versus 423 ng/g), duodenum (11.4 versus 5.8 ng/g), and colon (4.1 versus 1 ng/g), whereas no change was observed in the stomach and jejunum. When the formation of lesions was prevented by omeprazole (stress) or prostaglandin E2 (ethanol and indomethacin), the IR-EGF increase in submandibular glands and duodenum was abolished. This indicates that mechanisms regulating the synthesis and secretion of submandibular EGF might be of importance in the development of gastric and duodenal ulcers.

Animals↗
PubMed1994

Substance P (SP) and neurokinin A (NKA) in developing submandibular glands of the rat.

The effect of isoprenaline, carbachol, substance P (SP) and neurokinin A (NKA) on peroxidase and total protein secretion was studied in the developing postnatal submandibular glands of the rat using in vitro methods. Submandibular glands of 1, 5, 12 and 30 day-old rats were stimulated by 10(-5) M isoprenaline and carbachol, and 10(-6) M SP and NKA. The stimulatory effects of these compounds were compared to the basic release of peroxidase and total amount of protein from submandibular gland fragments in incubation solution with no added transmitter substances. Indirect immunohistochemical methods were used to study these developing glands from SP- and NKA-immunoreactive (IR) nerve fibers. The distributions of SP-IR and NKA-IR nerve fibers closely resembled each other, being most abundantly spread around the developing acini and ducts. The number of these fibers was high on the 1st, 5th and 12th days, but was decreased on the 30th day. On peroxidase release, isoprenaline was the most effective, causing a maximal response of 47 times the basic release on the first postnatal day, after which it gradually decreased. The effects of carbachol, SP and NKA on peroxidase release were clearly weaker and, unlike isoprenaline, their strongest response was on the 5th postnatal day (carbachol, 4.3; SP 5.2; NKA, 4.5). The total protein secretion effect patterns of the studied substances resembled each other more, showing their strongest response on the 5th day (isoprenaline, 5.0; carbachol, 4.5; SP, 4.2; NKA, 3.4) and decreasing thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗