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Ultrastructure of the binary parotid glands in the free-tailed bat, Tadarida thersites. II. Accessory parotid gland.

BACKGROUND: Many bat species have an extra set of major salivary glands. In some species, the accessory glands are quite similar to the principal one, but in others they may be radically different. Accessory glands usually are associated with the submandibular gland, but the free-tailed bat, Tadarida thersites, also has an accessory parotid gland. In the present study, we compared the accessory parotid gland with its principal counterpart. METHODS: Salivary glands were removed from two specimens of free-tailed bats, one of each sex, that had been live-trapped in western Kenya and immersion-fixed in a specially formulated mixture designed for field fixation. Once back in the laboratory, the tissue was further prepared for electron microscopy by conventional means. RESULTS: The secretory endpieces consist of serous tubules composed of typical serous cells that contain numerous dense granules. In contrast, the intralobular duct system shows a radical departure from normal. These ducts are enormous in caliber, their lumina measuring greater than 100 microm in diameter. They appear to arise by amalgamation of the homologues of intercalated and striated ducts into macroducts. The walls of the macroducts consist of intermingled patches of simple cuboidal and simple columnar epithelia that occasionally include a tuft cell and are underlaid by an almost continuous layer of myoepithelium. A few cells have some modified basal striations, but most cells display a cytological organization that differs radically from either of their two putative ancestral cell types. Both tall and short epithelial macroduct cells have a paranuclear collection of ovate mitochondria and aggregates of what presumably are peroxisomes. Macroduct cells in both the female and male are pervaded by a system of tubular smooth endoplasmic reticulum (SER). In the female, the SER gives rise to membranous whorls that consist of numerous plies. As the macroducts approach their termini, a single row of small dense secretory granules appears just beneath their luminal surface. At the lobular periphery, the ducts taper down to become excretory ducts of normal dimensions. CONCLUSIONS: An accessory parotid gland occurs in T. thersites, but apparently is absent in the related species, T. brasiliensis. The ultrastructural data are consistent with a possible steroidogenic function, although other features of the gland might relate to the elaboration of a secretory product associated with feeding on chitinous beetles. The macroducts conceivably function as reservoirs of preformed saliva.

Animals↗

The effect of the transplanted pineal gland on the sympathetic innervation of the rat sublingual gland.

We investigated the effect of the pineal on sympathetic neurons that normally innervate the sublingual gland of the rat. When the pineal gland was transplanted into the sublingual gland, it remained as a distinct mass that was innervated by sympathetic axons. Injection of the retrograde tracer, Fast Blue, into the sublingual gland labelled sympathetic neurons in the ipsilateral superior cervical ganglion (SCG). Thirty per cent of all neurons labelled retrogradely by Fast Blue injection into transplanted pineal glands were immunoreactive for both neuropeptide Y (NPY) and calbindin. This combination is characteristic of sympathetic neurons innervating the pineal gland in its normal location, but not the sympathetic vasoconstrictor neurons normally innervating the sublingual gland. This, and our previous study in which the pineal gland was shown to similarly influence the phenotype of salivary secretomotor neurons, suggests that a range of different functional classes of sympathetic neuron are able to change their phenotype in response to signals released by the pineal gland.

Amidines↗

Metamorphosis of the corpus allatum and degeneration of the prothoracic glands during the larval-pupal-adult transformation of Drosophila melanogaster: a cytophysiological analysis of the ring gland.

The degeneration of the prothoracic glands of Drosophila melanogaster during pupal-adult metamorphosis was analyzed by light microscopy, scanning, and transmission electron microscopy. The ultrastructural observations were correlated with the ability of the ring gland to synthesize ecdysteroids in vitro. The ring gland is prominent during larval life and is identifiable until just before adult eclosion but undergoes dramatic changes in location, shape, size, ultrastructure, and function during pupal-adult development. Prothoracic gland degeneration is characterized by: a gradual decrease in its ability to synthesize ecdysteroids; a decreasing quantity of smooth endoplasmic reticulum (SER) and mitochondria; the absence of intercellular channels; cytoplasmic fragmentation; and the separation of the prothoracic gland from the corpus allatum and corpus cardiacum. An ultrastructural analysis of the corpus allatum during larval-pupal-adult metamorphosis and adult life was also correlated with function, i.e., juvenile hormone biosynthesis, using a radiochemical assay of ring glands and adult corpora allata in vitro. A relatively high concentration of SER, mitochondria, and mitochondrion-scalariform junction complexes are typical features of an active corpus allatum cell. The migration of the corpus allatum from the ring gland to its position as a separate gland in the adult fly was studied in detail. The capacity of the corpus allatum to synthesize juvenile hormone is at its peak in the ring gland of the early wandering third instar larva, whereas the corpus allatum of 2-day-old female adults displayed the greatest synthetic activity during adult life. The physiological significance of the alterations in gland activity is discussed.

Animals↗

Pathologic observations of intrahepatic peribiliary glands in 1,000 consecutive autopsy livers: IV. Hyperplasia of intramural and extramural glands.

Hyperplastic changes of intrahepatic peribiliary glands have rarely been reported, with the exception of hepatolithiasis. To determine whether there are any hyperplastic changes in the glands in livers without hepatolithiasis, we examined 1,000 consecutive autopsy liver specimens that had no hepatolithiasis. The glands were divided into intramural mucous glands and extramural seromucous glands. The hyperplastic changes were found in "normal" livers and in livers with various hepatobiliary diseases, and they were classified into three categories: hyperplasia of intramural glands (49 cases; 4.9%), hyperplasia of extramural serous acini (35 cases; 3.5%), and hyperplasia of extramural mucous acini (92 cases; 9.2%). Two or more of these three hyperplastic changes occasionally coexisted in the same liver. Hyperplasia of intramural glands was seen rather evenly in normal livers and in livers with various hepatobiliary diseases. Prevalence of hyperplasia of extramural serous acini was high in intrahepatic cholangitis and submassive hepatic necrosis. Prevalence of hyperplasia of extramural mucous acini was high in cirrhosis, submassive hepatic necrosis, cholangitis, systemic infection, and extrahepatic biliary obstruction. The hyperplastic intramural glands and mucous acini of extramural glands contained more neutral, carboxylated, and sulfated mucin than normal glands. Although their pathogenesis is unclear, these hyperplastic changes may enhance seromucous secretion into biliary lumens and may lead to biliary dysfunctions such as retardation of bile flow and increased bile viscosity. These hyperplastic changes may be preexisting conditions predisposing to hepatolithiasis.

Autopsy↗

Assessment of salivary gland dysfunction following chemoradiotherapy using quantitative salivary gland scintigraphy.

PURPOSE: To assess chemoradiotherapy-induced salivary gland dysfunction using quantitative salivary gland scintigraphy (QSGS), and whether QSGS is capable of predicting the grade of persistent salivary dysfunction after chemoradiotherapy. METHODS: From a time-activity curve using a stimulation test, the washout rate (WR) calculated was assessed. All glands (n = 155) were classified into four groups: a no-therapy group (n = 18), a chemotherapy alone group (n = 31), a radiotherapy alone group (n = 50), and a chemoradiotherapy group (n = 56). Subjective descriptions of xerostomia were recorded 1 year after the completion of the treatment period, and the 32 glands subjected to irradiation with or without chemotherapy were assessed. RESULTS: The WR values were significantly lower in glands that received chemoradiotherapy than in glands treated with radiotherapy alone (mean: 0.75 x 10(-3), n = 40 vs. 0.22, n = 36, p < 0.015), but there was no significant difference in the WR values between the no-therapy group and the chemotherapy alone group. The mean values of WR were lower in the chemoradiotherapy glands than in the radiotherapy alone glands in each of cumulative dose ranges of 1-20, 21-30, and 31-60 Gy. With regard to recovery from xerostomia, the WR values at a cumulative dose range of 20 to 40 Gy were significantly lower in the not improved group (-0.418, n = 16) than in the improved group (0.245, n = 16) (p < 0.0001). CONCLUSION: Chemotherapy per se has no or little adverse effect on salivary function, but combination chemotherapy can deteriorate radiation-induced injury of the salivary glands. QSGS appears useful in predicting the grade of persistent xerostomia following chemoradiotherapy.

Adolescent↗

Harderian gland: regulation of sexual "type" by gonads and pineal gland.

The sexual dimorphism of the Harderian glands of golden hamsters is regulated by a complex interaction of the gonads and pineal gland. Ovariectomy was shown to prevent the conversion to male-type gland which normally follows blinding. Testosterone administration in combination with blinding and ovariectomy promoted the male type. Ovariectomy after 8 wk of blinding was ineffective in reversing the effects of blinding on the Harderian glands, but ovariectomy and pinealectomy caused complete reconversion to the female type. To our knowledge, this is the first report to demonstrate an influence of the ovaries on the Harderian gland of the hamster. In males, administration of testosterone for 7 days after 8 wk of castration was shown to have little effect on the conversion to the female type which normally attends castration, whereas testosterone injection followed by a period of blinding completely reversed the effects of castration on the Harderian gland. These studies, along with previously published reports, strongly suggest that the male-type Harderian gland is expressed whenever significant androgen levels are present, or when the glands are exposed to androgen priming during or just prior to a period of blinding-induced pineal activation. The probable role of ovarian androgens in mediating conversion to the male-type gland is discussed.

Animals↗

Morphological changes of the adrenal gland following soft-laser irradiation of the pineal gland.

We present the results obtained in the adrenal gland of white rats (average weight 220 g) following irradiation of the pineal gland with laser light. Irradiation was carried out with a 5 mW Politec 750 Helium-Neon laser. Total irradiation time was 5 min, with rest intervals of 1 min for every minute of irradiation. Pineal gland irradiation was done under "open sky", i.e., directly at the gland. The effects of the suprarenal gland were studied 3, 7 and 10 d postirradiation. Morphological signs of an increasing activity have been observed in all layers of the cortex and in the medulla of the gland. The highest increase was found 7 d after irradiation in the fascicular zone and in the medulla, and after 3 d in the glomerular and reticular zone. We suggest that laser light induces an inhibitory effect observed at the suprarenal gland. This effect is similar to that found following pinealectomy, showing once again that the pineal gland exerts control on the suprarenal gland, mediated by luminous stimuli.

Adrenal Glands↗

Molecular anatomy of an endodermal gland: investigations on mucus glycoproteins and cell turnover in Brunner's glands of Didelphis virginiana using lectins and PCNA immunoreactivity.

Brunner's glands are located in the submucosa of the proximal duodenum and are unique to mammalian species. The North American opossum (Didelphis virginiana) is generally regarded as a prototype marsupial that closely resembles fossil didelphids which can be placed at the beginning of mammalian evolution. The current investigation provided an opportunity for the analysis of secretory products from these glands in a species thought to be more closely related to earlier evolutionary forms. Extracts of Brunner's glands were subjected to SDS-PAGE and Western blotting. The results indicate the presence of two high molecular weight PAS-positive glycoprotein bands. In addition to these two PAS-positive bands, several other glycoprotein bands were detected in the high molecular weight range that bind several lectins which typically recognize O-linked carbohydrates indicative of mucus type glycoproteins. The same lectins bind to glandular structures in tissue sections. Comparison of lectin binding sites with the pyloric glands of the stomach and duodenal goblet cells indicates that Brunner's glands carbohydrate residues resemble those of the pyloric glands more closely than those of the duodenal goblet cells. The low cell turnover rate in Brunner's glands is in contrast to the rapid turnover rate of goblet cell precursors in the duodenal crypts. The mucus composition and the cell turnover rate correlate well with embryological data and suggest that Brunner's glands of Didelphis evolved from an epithelium more closely associated with the stomach than that of the duodenum as the topography of the gland would suggest.

Animals↗

Side gland of Suncus murinus as a new model of sebaceous gland: 5 alpha-reductase, androgen receptor, and nuclear androgen content in male and female animals.

The side gland of Suncus murinus is composed of well-developed sebaceous glands in both males and females. We measured the 5 alpha-reductase activity, androgen receptor content, and the intranuclear concentrations of testosterone and dihydrotestosterone in this side gland taking it as a new experimental model of human sebaceous glands. Lineweaver-Burk plot analysis suggested the presence of two classes of 5 alpha-reductase with different Km for testosterone in the homogenate. The enzyme activity was slightly higher in males than in females in the presence of a high concentration of testosterone. The levels of androgen receptors were approximately 40 and 30 fmol/mg protein in the cytosol and nuclei, respectively. The values did not differ significantly between males and females. The intranuclear concentration of dihydrotestosterone in the side gland was higher than that of testosterone in each sex. The intranuclear level of each of these two androgens in the female side gland was comparable to that in the male side gland despite the fact that the serum level of testosterone was much lower in the female. These data clearly indicate that the side gland is a typical target tissue for androgens in the female as well as in the male. Androgens other than testosterone may serve as precursors of dihydrotestosterone in the female side gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Development and properties of the secretory response in rat sweat glands: relationship to the induction of cholinergic function in sweat gland innervation.

Previous studies suggest that the sympathetic innervation of the sweat glands in the rat is initially noradrenergic and during development undergoes a transition in neurotransmitter phenotype to become cholinergic. To characterize this system and its development further, we have examined the adrenergic and cholinergic components of the secretory response in adult and immature rats and have studied the onset of sweating in the plantar sweat glands of developing rats. Stimulation of the sciatic nerve in adult rats elicited a secretory response which was completely blocked by the cholinergic antagonist, atropine, and was unaffected by adrenergic antagonists, indicating that nerve-evoked secretion was cholinergic. In adult rats, the sweat glands were quite sensitive to cholinergic agonists. In addition to acetylcholine, the mature sweat gland innervation contains vasoactive intestinal peptide (VIP). In some rats, the injection of VIP alone elicited a secretory response which was blocked by atropine, suggesting that the response to VIP was mediated cholinergically. In contrast to cholinergic agonists, the glands responded relatively infrequently and with reduced volumes of sweat to the alpha- and beta-adrenergic agonists 6-fluoronorepinephrine and isoproterenol. However, when VIP, which is a potent vasodilator, was simultaneously injected with adrenergic agonists, glands in many of the injected footpads exhibited a secretory response. The response to adrenergic agonists in combination with VIP was reduced by atropine and by phentolamine plus propranolol, but was blocked completely only by a combination of the three antagonists, indicating that both adrenergic and cholinergic mechanisms were involved. In immature rats, sweating evoked by nerve stimulation first appeared at 14 days of age in 25% of the rats tested. Both the percentage of rats sweating and the number of active glands increased rapidly. At 16 days, 50% of the rats tested exhibited some active glands, and by 21 days all rats tested exhibited a secretory response. In 16-day-old rats, nerve-evoked sweating was almost completely inhibited by local injection of 1 microM atropine, but was unaffected by phentolamine and propranolol in concentrations up to 10 microM. Similarly, the glands were sensitive to 10 microM muscarine, but they exhibited no secretory response to the alpha-adrenergic agonists, clonidine and 6-fluoronorepinephrine, nor to the beta-adrenergic agonist, isoproterenol, at concentrations up to 50 microM. The simultaneous injection of VIP with adrenergic agonists did not reveal an adrenergically mediated secretory response in 16-day-old animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: implications for future trials.

PURPOSE: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. METHODS AND MATERIALS: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H&N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion of radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. RESULTS: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to < or =25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. CONCLUSIONS: Stimulated flow measurements using Lashley cups, with a complication defined as flow < or =25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.

Head and Neck Neoplasms↗

Heterogeneous gland size in sporadic multiple gland parathyroid hyperplasia.

BACKGROUND: The success rate for bilateral exploration in patients with primary hyperparathyroidism approaches 95%. Multiglandular parathyroid hyperplasia accounts for approximately 10% to 30% of primary hyperparathyroidism. The incidence of recurrent or persistent hyperparathyroidism is highest in familial forms of the disease, in which multiglandular disease is more common; this may be due to asymmetric enlargement of parathyroid glands. Because of improvements in tumor-imaging capability, some surgeons are now advocating unilateral exploration for primary hyperparathyroidism, but there is limited experience concerning how often these imaging methods fail. STUDY DESIGN: The outcomes of 7 patients who had sporadic primary hyperparathyroidism with multigland hyperplasia were reviewed. We gathered demographic data and laboratory values and reviewed radiologic tests, surgical findings, pathologic findings, and postoperative followup. RESULTS: All patients underwent preoperative localization with ultrasonography and technetium/sestamibi scans. The sensitivity of these two tests for the dominantly enlarged gland was 100% for both, but dropped to 0% and 5%, respectively, for all other enlarged glands. The sensitivity of CT and MRI for the dominant tumor was 67% (2 of 3) and 50% (1 of 2), respectively. Six of 7 patients underwent subtotal (3(1/2) gland) parathyroidectomy. The mean volume of all glands was 1.51+/-5.89 cm3 compared with a mean of 5.66+/-11.4 cm3 for all dominant glands and 0.123+/-0.1 cm3 for all nondominant hyperplastic glands. There was a large amount of variability between the volumes of dominant and other glands as demonstrated by large SDs from the mean. CONCLUSIONS: There is a marked heterogeneity in gland size in patients with sporadic multigland hyperplasia, which is similar to that found in multiple endocrine neoplasia type I. This heterogeneity may result in failure to recognize multigland disease if a unilateral neck exploration is performed. Intraoperative parathyroid hormone assay may prove to be an important adjunct in this population of patients who have unsuspected multigland disease.

Adult↗

Tear lysozyme activity in frozen Schirmer strips and salivary gland biopsy as parameters of lacrimal gland function.

PURPOSE: The lysozyme concentration in human tears is an important parameter for tear gland function. The decline of lysozyme in tears reflects lacrimal gland destruction. In Sjögren's patients, lacrimal gland destruction parallels labial salivary gland destruction. The objective of this study was to determine whether human tear lysozyme that was frozen on Schirmer strips at -20 degrees C for several years maintained activity and whether there was a linear relation with inflammatory changes in labial salivary glands. METHODS: A total of 200 frozen Schirmer strips were processed. They were collected from 20 randomly selected patients each year of five consecutive years, all attending the UCSF Sjögren's Clinic. The tear lysozyme in the Schirmer strips was measured by a colorimetric assay. The average lysozyme concentration each year was calculated and compared. One third of the patients underwent labial salivary gland biopsy. The correlation was calculated between the tear lysozyme concentration and the lymphocytic focus scores in biopsy specimens. RESULTS: No significant difference of average lysozyme concentration in the Schirmer strips was found when the five different years of collection were compared. The linear relation between the tear lysozyme concentrations and the focus score in labial salivary gland biopsies showed a coefficient of r = -0.41. The linear relation between other diagnostic measurements, like Schirmer test, tear breakup time, or rose bengal staining pattern, and the focus score was lower. CONCLUSIONS: Human tear lysozyme in Schirmer strips can be stored at -20 degrees C for at least five years. There is little difference in lysozyme activity of frozen compared to unfrozen specimens. The lysozyme concentration in tears correlates better with the lymphocytic focus score in labial salivary gland biopsy than does clinical assessment and is therefore a parameter for the actual degree of tear gland destruction.

Biopsy↗

Adrenomedullin in mammalian and human skin glands including the mammary gland.

Adrenomedullin is a peptide that has been ascribed numerous functions. In the present paper, adrenomedullin has been localized immunhistochemically in a variety of skin glands of humans, elephants and impalas: apocrine scent glands, eccrine sweat glands, holocrine glands and mammary glands. In the apocrine glands expression of adrenomedullin varied with respect to staining intensity and intracellular localization. In general, glands which appeared to be actively secreting were more strongly stained than quiescent glands. However, within a single glandular tubule, individual cells differed considerably in the staining intensity of adrenomedullin. Adrenomedullin was present in both non-lactating and lactating mammary secretory epithelia, both ducts and alveoli reacted positively. In human mammary glands displaying apocrine metaplasia, the apical protrusions were strongly positive. Furthermore, positive immunostaining was found in endothelium and often in smooth muscle cells of small arteries and veins and in mast cells as well. Many of the adrenomedullin-positive epithelial cells were most strongly stained in the area of the Golgi apparatus, the cellular apex and particularly close to the basal side of the cell membrane. This pattern suggests packaging of adrenomedullin into secretory granules and secretion both at the apex of cells and at their basis. The first form of secretion suggests exocrine secretion, the latter form endocrine secretion of adrenomedullin. A possible hormonal function is in line with basally located electron dense small secretory granules, which have been found by electron microscopy in the glandular epithelia studied.

Adrenomedullin↗

Morphological and immunohistochemical characteristics of the heterogeneous prostate-like glands (paraurethral gland) seen in female Brown-Norway rats.

Morphological and immunohistochemical characteristics of the prostate-like glands (paraurethral gland) seen spontaneously in female Brown-Norway (BN) rats were investigated by gross, and light and electron microscopic examination. At 9- to 10-weeks-old, the paraurethral gland was detected in 50 out of 52 female animals examined (96.2%), and it was observed as single or paired structures located ventrolaterally in the urethra just caudal to neck of the urinary bladder. Microscopically, the glandular acini consisted of flat to cuboidal secretory epithelium surrounded by the smooth muscle. The glands displayed modest secreting activity, and a few secreting materials were observed in the acinar lumens. The main peripheral ducts were located in the urethral wall, and drained into the urethra on both sides. Ultrastructurally, abundant rough endoplasmic reticulum (RER), numerous mitochondria and lysosomes, and secretory granules in the apical portion of the epithelial cells were noted, and basal cells were also observed. These gland epithelial cells showed positive reactions when stained for androgen receptor (AR), prostate specific antigen (PSA), or prostate specific acid phosphatase (PSAP). The nature of this paraurethral gland resembled that of the prostate gland in male rats. Thus, the paraurethral glands seen in the females were considered homologous to the prostate gland in males.

Acid Phosphatase↗

Radiation induced cell loss in rat submandibular gland and its relation to gland function.

PURPOSE: To understand early and late radiation-induced loss of function of the submandibular gland, changes in cell number were documented and correlated with data on gland function. Modulation of the radiation effect by sialogogues was used to investigate possible mechanisms of action. MATERIALS AND METHODS: Rats were irradiated with a single dose of 15 Gy of X-rays after pre-treatment with either saline, the muscarinic receptor agonists methacholine or pilocarpine, the adrenergic receptor agonist phenylephrine or methacholine plus phenylephrine. Before and 1-240 days after irradiation, submandibular saliva flow rate was measured. At the same time points and from comparable animals submandibular glands were carefully extirpated, weighed and prepared for light microscopic examination. RESULTS: Soon after irradiation (<30 days) no significant loss of cells was observed, whereas the gland function was severely compromised. Sialogogue pre-treatment attenuated the radiation-induced loss of gland function. At later intervals a considerable loss of acinar cells and to a lesser extent loss of granular convoluted tubule cells were observed. Gland function subsequently declined slowly. Pre-treatment with sialogogues gave transient protection against cell loss and loss of gland function. CONCLUSIONS: The lack of cell loss observed soon after irradiation indicates that the observed reduction in gland function was caused by a compromised functioning of the acini. The later loss of cells is probably due to death of cells that normally proliferate, leading to a further reduced secretory capacity. Protection of gland morphology and function by sialogogues at later times must therefore involve resistance of progenitor cells to radiation-induced cell death.

Adrenergic alpha-Agonists↗

Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS.

Amino Acid Sequence↗

Influence on rabbit submandibular gland injury by stimulation or inhibition of gland function during irradiation. Histology and morphometry after 15 gray.

The loss of salivary gland function after a single dose of 15 Gy was correlated to loss of gland weight and degeneration of seromucous acini and serous tubules at 10 months postirradiation. The serous tubules were degranulated rather early, but regenerated after some months in an abnormal way as adenomatous structures. Striated ducts were mainly unaffected by irradiation. Arterioles showed slight to moderate narrowing of the lumina. There was an increased amount of plasma cells in the gland lobules at 10 months postirradiation. Histologic and morphometric criteria and changes in gland weight showed less pronounced radiation injury in glands irradiated during inhibition of the gland function by biperiden (Akineton) compared to glands irradiated during stimulation of the gland function by pilocarpine. This finding may offer a clinically important means to reduce salivary gland dysfunction after radiation treatment of tumors in the head and neck regions.

Animals↗