Influence of gender and the endocrine environment on the distribution of androgen receptors in the lacrimal gland

Androgens are known to regulate both the structure and function of lacrimal tissue in a variety of species. To explore the endocrine basis for this hormone action, the following study was designed to: (1) determine the cellular distribution of androgen receptors in the lacrimal gland; and (2) examine the influence of gender and the endocrine environment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular location of androgen receptors was evaluated by utilizing an immunoperoxidase protocol, in which a purified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of epithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as compared to females; (3) orchiectomy or hypophysectomy, but not sham-surgery or diabetes, lead to a dramatic reduction in the immunocytochemical expression of androgen receptors; and (4) testosterone administration to orchiectomized rats induces a marked increase in androgen receptor content, relative to that in placebo-exposed glands. Our results also reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland. Overall, these findings demonstrate that gender and the endocrine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors.     

Primary ductal adenocarcinoma of the lacrimal gland

The morphological similarity of salivary and lacrimal gland tumors is known. Many clinicopathological studies and characteristics of salivary duct carcinoma, which bears histological similarities to mammary duct carcinoma, have been recently reported; however, only one case of lacrimal duct carcinoma is reported. A second case of lacrimal duct carcinoma is presented. A 67-year-old male with a painless mass in the right upper eyelid underwent total removal of the tumor mass. Microscopic examination of the tumor mass revealed ductal adenocarcinoma of the lacrimal gland, which was the equivalent of salivary duct carcinoma. The immunohistological studies of the lacrimal duct carcinoma showed similar results to those reported for salivary duct carcinoma. The recurrent tumor in the subdural spaces was removed 2 years after the initial surgery and the patient is followed as an outpatient.     

Tumors arising in the palpebral lobe of the lacrimal gland

PURPOSE: Tumors arising in the palpebral lobe of the lacrimal gland are uncommon. There have been only eight reported patients, all of whom had pleomorphic adenomas. The authors present another six patients with primary palpebral lobe tumors. METHODS: The clinical presentation, computed tomographic, and pathologic findings of these six patients were reviewed. RESULTS: Tumor types include three pleomorphic adenomas, one well-differentiated adenoid cystic carcinoma, one carcinoma in pleomorphic adenoma, and one carcinoma ex pleomorphic adenoma. All six patients presented with a painless mass in the upper outer eyelid without significant displacement of the globe, but the superficial location of these lesions led to early detection. The tumors were localized to the lacrimal gland, predominantly anterior to the orbital rim. In all six patients, the involved palpebral lobe was removed, five via a direct anterior subcutaneous approach and one by superolateral orbitotomy. In two patients (adenoid cystic carcinoma and carcinoma ex pleomorphic adenoma), repeat surgery via superolateral orbitotomy was necessary to achieve complete removal of the lacrimal gland and surrounding tissue. No recurrences were detected during follow-up (range, 6 months to 7 years; mean, 26 months). CONCLUSION: Palpebral lobe tumors of the lacrimal gland are more common and consist of a greater variety of histologic types than previously described. In our series, these tumors comprise 17% of all epithelial lacrimal gland lesions. These are the first reported cases of malignancy in this location. A longer follow-up period is necessary to determine the true recurrence rate of these tumors.     

Adenoid cystic carcinoma of the lacrimal gland in a six-year-old girl

A 6-year-old white female was found to have an adenoid cystic carcinoma originating in a lacrimal gland. Eighteen months following diagnosis, the tumor recurred. Conservative surgery has been the sole mode of therapy. To date, after four operations and quadrimenstral imaging surveillance, there is no sign of disease progression. Our purpose is to record the unusual occurrence of an adenoid cystic carcinoma of the lacrimal gland in a child. An interim report, 32 months after diagnosis, is presented.     

Localization of glycosaminoglycans and CD44 in the human lacrimal gland

Recent analyses of tears indicate the presence of glycosaminoglycans as their components, but their origin remains unknown. To further understand the origin of these tear components, we investigated by immunohistochemical techniques the localization of glycosaminoglycans and CD44 human lacrimal glands obtained from 20 cadavers at autopsy. Monoclonal antibodies to CD44, a receptor for hyaluronic acid, dermatan sulfate, chondroitin sulfate, and keratan sulfate were applied to the tissue. Hyaluronic acid binding region was also used for the staining of hyaluronic acid. By light microscopy, immunoreactivity for CD44 was mostly detected on the baso-lateral membrane of acinar and ductal cells, and the vascular endothelium in the interstitium. Positive staining of hyaluronic acid was associated intensely with the basal membrane of acinar and ductal cells and weakly, faintly or not at all with their lateral membrane. Positive staining of hyaluronic acid and immunoreactivity for dermatan sulfate were detected in interstitial fibrous structures; particularly, the former was intense in the perivascular fibrous structures, and the latter along the periparenchimal fibrous structures. Immunoreactivity for chondroitin sulfate and keratan sulfate was seen in some acinar cells and the acinar and ductal lumen. By electron microscopy, immunogold particles indication chondroitin sulfate sulfate or keratan sulfate labeled secretory granules of the acinar cells. Considering the fact that CD44 is a receptor molecule for hyaluronic acid, the association of hyaluronic acid with the basal membrane and weakly or faintly with the lateral membrane of acinar and ductal cells may be attributed to the expression of CD44 on the baso-lateral membrane of the cells. Moreover, the presence of immunoreactivity for chondroitin sulfate and keratan sulfate in secretory granules of acinar cells and their lumens suggests that tears from the lacrimal gland contain these glycosaminoglycans.     

Immunolocalization of myoepithelial cells in isolated acini of rat exorbital lacrimal gland: cellular distribution of muscarinic receptors

The secretion of proteins and fluids from the exorbital lacrymal gland of rat is mainly controlled by muscarinic receptors. In a recent pharmacological study. Mauduit et al (Am J Physiol (1993) 264, C1550-C1560) identified a homogeneous population of M3 muscarinic receptors in preparations of acini from these tissues. In order to define the cellular composition of these acini and localize the muscarinic receptors, we have performed an immunofluorescent labelling study combined with confocal scanning microscopy. Antibodies raised against components of the different cytoskeletal networks (alpha-smooth muscle actin, cytokeratin peptide 14 and alpha-tubulin) revealed the presence of two different cell types. Cells with a stellate form are identified as myoepithelial cells, whereas rounded cells are secretory acinar cells. Both cell types are reactive with an antibody specifically directed against the muscarinic receptor. However, myoepithelial cells appear more intensely labelled than acinar cells. The roles of myoepithelial cells and secretory cells in the physiological function of the gland are discussed in terms of the distribution of muscarinic receptors.     

Ectopic lacrimal gland in the orbit identified by computerized axial transverse tomography

A case of ectopic lacrimal gland within the orbit causing progressive exophthalmos and visual loss is presented. The orbital mass, identified by computerized axial transverse tomography, had characteristics which were different from other orbital tumors identified to date by this technique.     

Characterization of an inwardly rectifying potassium channel in the rabbit superior lacrimal gland

We have investigated the underlying assumptions in estimating cross-correlation rates between chemical shift anisotropy (CSA) and dipolar coupling mechanisms in a scalar-coupled two-spin IS system, from laboratory frame relaxation experiments. It has ben shown that for an arbitrary relaxation delay, the difference in relaxation rates of the individual components of an in-phase (or antiphase) doublet is not related to the CSA-dipolar coupling cross-correlation rate in a simple way. This is especially true in the case where the difference in the decay rates of the in-phase and antiphase terms of the density matrix becomes comparable to the magnitude of the scalar coupling between the two spins. Improved means of extracting cross-correlation rates in these cases are presented.     

Immunohistochemical study of leucine-enkephalin and its secretory effects in the isolated pig lacrimal gland

BACKGROUND: In our previous studies immunohistochemical studies have demonstrated the presence of leucine-enkephalin (Leu-Enk) in the intrinsic nerves of the pig lacrimal gland, which are discernible in the interlobular and interacinar areas from where branches that innervate the acinar tissues are sent. Since the intrinsic nerves have been shown to contain Leu-Enk, this study aimed to investigate the secretory effects of this neuropeptide in isolated segments of the pig lacrimal gland and to reconfirm its presence in the neuronal tissue of the lacrimal gland. METHODS: Leu-Enk was identified using immunohistochemical techniques, while total protein output was measured in the effluent samples by an automated on-line colorimetric method. The Ca2+ and Mg2+ concentrations in the effluent samples were determined using an atomic absorbance spectrophotometer. RESULTS: Leu-Enk (10(-12)-10(-7) M) evoked marked increases in total protein output from superfused lacrimal gland segments. The secretory effect of Leu-Enk was not blocked by pretreatment of the tissue with atropine but was substantially reduced by a combination of phentolamine and propranolol. The competitive antagonist, naloxone, has no effect on basal protein output, but when combined with Leu-Enk it caused a significant reduction in total protein output. Combining theophylline (10(-3) M) with Leu-Enk resulted in a marked potentiation of total protein output. In superfused lacrimal gland segments Leu-Enk (10(-8) M) evoked a net efflux of magnesium (Mg2+ release) and a net influx of calcium (Ca2+ intake). CONCLUSION: The results indicated a physiological role for Leu-Enk in the regulation of protein secretion in the pig lacrimal gland.     

Age-related changes in morphology and secretory responses of male rat lacrimal gland

This study investigates the differences in the outward appearance and morphology of lacrimal glands, the morphology within the lacrimal acinar cells and the secretion of protein from acinar cells of young (3-5 months) and aged (20 and 24 months) male rats. The appearance of the glands, as seen by the naked eye, differed between the three age-groups. The lacrimal gland of young animals was a smooth pink tissue, while the tissue from aged animals appeared lobular and white in colour, thought to result from infiltration of fatty/connective tissue. Glands from 24 month old animals had a more pronounced lobular appearance than the glands from 20 month old animals. Light microscopy studies revealed that as the animals aged there was evidence of progressive morphological changes. These changes included thickening of the connective tissue sheath, chronic inflammation with increased infiltration by mast cells, patchy destruction of ductal and vascular tissues, enlargement of lacrimal ducts, luminal swelling of the acini, and changes in acinar type. Electron microscopy (EM) studies revealed the presence of 3 types of acini in the rat lacrimal gland: acini which contained only protein secretory granules (serous acini), acini which contained protein and mucous secretory granules (seromucous acini), and acini which contained only mucous secretory granules (mucous acini). In young glands the majority of acini were serous with a few seromucous acini and even fewer mucous acini. In aged glands there were significant reductions in serous acini (ANOVA; P < 0.01) when compared to the young glands. In 20-month-old glands, there were marked increases in the percentage occurrence of seromucous acini, while in 24 month old glands, there were large increases in the relative number of mucous acini. Qualitative EM studies demonstrated that the typical acini from young glands contained numerous protein secretory granules. Ageing was associated with a progressive loss of protein (serous) secretory granules. Furthermore, marked changes and patchy destruction of the endoplasmic reticulum and Golgi apparatus were observed in acini of glands from aged rats when compared to acini of glands from young rats. Measurement of total protein output from acini revealed a significant (Student's t-test, P < 0.05) decrease in protein secretion from aged glands compared to glands from young animals. These results suggest that not only is there considerable structural damage, chronic inflammation and mast cell infiltration to the lacrimal gland with ageing, but also possible redifferentiation of acini from serous to seromucous and then to mucous acini. Furthermore, the results also suggest a reduction or an inability of the acini to synthesise and to secrete protein from glands of aged animals compared to glands of young rats. All of these changes appear to occur more rapidly as the rats mature between 20 and 24 months. These findings provide a morphological basis to explain the phenomenon of reduced tear/protein secretion with ageing.     

Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD-scid mice

Reactive gliosis, which occurs in response to any damage or disturbance to the central nervous system, has been recognized for many years, but is still not completely understood. The hallmark is the increased expression of glial fibrillary acidic protein (GFAP), yet studies in GFAP knockout mice suggest that GFAP may not be required for an astrocyte to become hypertrophic. In this review, we describe a series of tissue culture models that have been established in order to address: 1) the biochemical phenotype of reactive astrocytes; 2) the factor and/or cell responsible for induction of gliosis; 3) the mechanisms by which one might block the induction. These models range from cultures of astrocytes, both neonatal and adult, to co-cultures of astrocytes with either neurons or microglia, to organ cultures. None is ideal: each addresses a different set of questions, but taken together, they are beginning to provide useful information which should allow a better understanding of the plasticity response of astrocytes to brain injury.     

Adenoid cystic carcinoma of the lacrimal gland simulating a dermoid cyst in a 9-year-old boy

Adenoid cystic carcinoma of the lacrimal gland is a malignant neoplasm that is generally found in adults and is usually managed by orbital exenteration and supplemental external beam irradiation or chemotherapy. A recent report has suggested that the tumor may have a less malignant course in children. We describe a case of adenoid cystic carcinoma of the lacrimal gland that simulated a dermoid cyst clinically and radiographically in a 9-year-old boy. The patient was treated with local surgical resection of the mass, followed by orbital plaque brachytherapy. Based on a review of the literature and our recent experience, the advisability of a more conservative approach to this tumor in selected cases is discussed. Although no prognostic conclusions can be drawn on the basis of a single case report with short follow-up, the relatively earlier detection of this tumor made possible by modern orbital imaging studies may allow total removal at an earlier stage and prevent orbital exenteration in a patient with normal vision. Recent developments suggest that there may be a basis for reassessing the advisability of a radical approach to the management of adenoid cystic carcinoma of the lacrimal gland in selected cases.     

The modified Schirmer tear test in birds--a method for checking lacrimal gland function

A treatment against osteoporosis can be considered efficacious only when its beneficial effects on bone remodeling, bone mass, and osteoporotic fracture incidence are proven. As for any treatment, proven efficacy must be combined with proven safety. This review analyzes published data on efficacy and safety of alendronate, clodronate and etidronate, the bisphosphonates currently marketed in Italy for osteoporosis treatment. Different studies have shown that alendronate, clodronate and etidronate reduce bone turnover, and increase bone mineral density in postmenopausal osteoporotic patients. Prospective, double blind, multicenter studies reported a reduction in osteoporotic fracture incidence for alendronate and etidronate. Fracture incidence reduction by clodronate, on the other hand, was shown only in an open label study. Finally, a reduction in fracture incidence by etidronate was shown in a large retrospective postmarketing study. Postmarketing surveillance evidenced that osteomalacia, a suspected side effect of etidronate treatment, does not occur at the currently used dose regimens. Postmarketing surveillance of alendronate has recently raised some concern regarding possible severe esophageal damage during alendronate treatment, especially when the drug is not taken according to the manufacturer's instructions.     

Sarcoidosis with orbital tumor outside the lacrimal gland: initial manifestation in 2 elderly white women

Two elderly white women (aged 72 and 87 years) were first seen with painless, unilateral orbital swelling. Orbital scanning revealed masses infiltrating the soft tissue around the eye. Biopsy results showed nodular, noncaseating granulomas consistent with sarcoidosis. One patient's workup revealed systemic manifestations of sarcoidosis at the time of examination with hilar lymphadenopathy noted on gallium scan; the other refused a complete systemic workup. The orbital tumors resolved with systemic prednisone therapy. To our knowledge, our 87-year-old patient is the oldest to be seen with orbital sarcoidosis. These 2 patients demonstrate that this diagnosis must be considered with orbital tumors in the elderly and in unusual locations, such as these which occurred outside the lacrimal gland.     

Augmented expression of CD44 splice variants in lymphoproliferative disorder of the lacrimal gland in Sj?gren's syndrome

We explored the involvement of CD44 isoforms in lymphoproliferative disorder (LPD) of the lacrimal gland of a Sj?gren's syndrome patient with unilateral LPD. The CD44 variant with the v6 exon was selectively detected from infiltrating lymphocytes in the gland with LPD, but not from infiltrating lymphocytes in the normal lacrimal gland, suggesting that the CD44 v6 variant exon may be closely associated with the development of LPD in Sj?gren's syndrome.