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PubMed1979

Changes in Harderian gland activity in the female golden hamster during the oestrous cycle, pregnancy and lactation.

The Harderian gland, which is situated within the bony orbit, is usually thought of as a source of lubrication for the eye. However, recent studies have suggested links with reproductive function. In the male golden hamster, both gland histology and activity are known to be under hormonal influence, and the present experiment was undertaken to examine gland weight and activity (as measured by the production of porphyrins) over the oestrous cycle and during pregnancy and early lactation in the female hamster. Gland weight, the number of solid intraluminal porphyrin accretions, and concentrations of copro- and proto-porphyrin were all maximal on day 1 of the cycle (oestrous) and at their lowest on day 2 (or jointly on days 2 and 3), rising gradually thereafter. Porphyrin concentrations are considerably higher during pregnancy and early lactation than during the cycle, and the solid porphyrin accretions, although diminished in number, are larger. Although there is no indication of either the function or the physiological basis of these changes during the cycle or pregnancy, these findings do suggest that in the female golden hamster, as in the male, there is a link between Harderian gland activity and reproductive function.

Animals↗
PubMed2006

Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study.

AIM: To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population. METHODS: Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data. RESULTS: Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as "transitional MALT lymphoma," being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45-95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%. CONCLUSIONS: DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.

Aged↗
PubMed1980

Functional structure in lymphoepithelial cooperation.

With the help of electron microscopic investigations the morphological and functional connection of the epithelialial and lymphoid elements was examined in the lymphoepithelial organs (thymus, bursa of Fabricius, tonsils, Peyer's patches, gland of Harder). In all these organs special receptor cells were demonstrated, which may play a role in the uptake and transfer of the antigen. In the cytoplasm they all contain characteristic flattened vacuoles, with walls similar to the structure of the cell membrane. Formation of these bodies is identified with the striated bodies of micropinocytosis vermiformis and it was observed that the endocytosis start with a disintegration of the cell membrane which enters with the absorbed antigen in characteristic form into the cytoplasm of the epithel cell and induces the process of cellular immunity. Besides the function of lacrimal secretion the Harder's gland, as a lymphoepithelial organ is full of plasma cells, which constitutes the main lymphoid elements of this organ.

Animals↗
PubMed1989

The harderian gland of the frog, Rana esculenta, during the annual cycle: histology, histochemistry and ultrastructure.

The Harderian gland in Rana esculenta has been studied during the annual cycle at the histological, histochemical and ultrastructural levels. The Harderian gland has an acinar structure and is the only orbital gland in anuran amphibia. It develops at the medial corner of the orbit from the conjunctival epithelium at the premetamorphic stage. In the adult the glandular secretion reaches a maximum during the months of July and August, drops in September and resumes slowly from October onwards. The secretion is seromucoid and the secretory granules are released into the acinar lumen, mainly by exocytosis. Porphyrins were not detected. No sexual dimorphism was observed in the glandular cells. The resumption of secretory activity in October and the enhancement of secretion in May are marked by the appearance of "blue nuclei" (Mallory stain) in a relatively high percentage of glandular cells. This unusual blue colour, using the Mallory stain (by which nuclei stain red), disappears after digestion of paraffin sections with RNAase, but not with DNAase and trypsin. The blue staining may, therefore, indicate an increased amount of nuclear RNA. The Harderian gland in the frog most probably serves to lubricate and moisten the eye in the absence of the lacrimal gland. However, the gland may also represent an immunoactive organ owing to the presence of numerous mast cells and plasma cells in the interacinar spaces.

Animals↗
PubMed1997

Role of T cells in the pathogenesis of autoimmune lacrimal gland disease in MRL/Mp-lpr/lpr mice.

PURPOSE: MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop an autoimmune disease, including lacrimal gland lesions, which are a model for Sjögren's syndrome. Target organ lesions in MRL/lpr mice are composed largely of CD4+ T cells, and treatment with monoclonal antibodies (mAb) against CD4 improves in the systemic autoimmune disease but not the lacrimal gland inflammation. In anti-CD4 mAb-treated MRL/lpr mice, the lacrimal gland lesions are composed largely of CD8+ T cells. The effects of depletion of: (1) all T cells; (2) both CD4+ and CD8+ T cells, and (3) only CD8+ T cells on the lacrimal gland disease were investigated. METHODS: MRL/lpr mice underwent neonatal thymectomy and were treated with weekly injections of 6 mg of anti-Thy 1 mAb from age one week until sacrifice at age five months. Control nonthymectomized mice underwent similar treatment with either saline or normal rat immunoglobulin (rIg) injections. In a second experiment, MRL/lpr mice were treated with weekly injections of either: (1) 2 mg anti-CD4 mAb and 5 mg anti-CD8; or (2) 5 mg anti-CD8 alone. Control mice underwent similar treatment with either saline or rIg injections. RESULTS: Combined treatment with neonatal thymectomy and anti-Thy 1 mAb was effective in reducing the lacrimal gland disease in both frequency (50% > or = grade 3 vs. 100% in controls, P < 0.002) and extent (median 0% of lacrimal gland area involved by inflammation vs. 14.8% in controls; P = 0.01). Combined anti-CD4 and anti-CD8 therapy also was effective in reducing the lacrimal gland disease in terms of frequency (25% grade 3 vs. 93% in controls; P = 0.002) and extent (median 0% of lacrimal gland involved by inflammation vs. 12.9% in controls; P = 0.0005). Treatment with anti-CD8 mAb therapy alone was ineffective. The systemic autoimmune disease was also improved by T cell depletion and by combined anti-CD4 and anti-CD8 mAb therapy but not by anti-CD8 mAb therapy alone. CONCLUSIONS: Suppression of both CD4+ and CD8+ T cells is required to suppress lacrimal gland inflammation in MRL/lpr mice.

Animals↗
PubMed2003

Gene delivery by viral vectors in primary cultures of lacrimal gland tissue.

PURPOSE: To test the feasibility of gene transfer into lacrimal gland tissue in primary culture, using different viral vectors. METHODS: Lacrimal glands were dissected from adult Sabra rats and divided by pincers to 0.3-0.4 mm fragments. Tissue was maintained under primary organ culture conditions using the "raft" technique. The ability of three different viral vectors to conduct beta-galactosidase (beta-gal) gene delivery was examined: adenovirus (Ad5CMVLacZ), vaccinia (VSC9), and herpesvirus (tkLTRZ(1)). Tissue fragments were incubated for 60 minutes with one of the viral vectors and transferred to fresh medium. After 3 and 7 days, beta-gal expression was examined by X-gal staining in gross preparations and in histologic sections. RESULTS: At 3 days, beta-gal expression was observed in 33% of tissue fragments exposed to the vaccinia vector and in 18% and 14% of fragments exposed to the adenoviral and herpes vectors, respectively. After 7 days in culture, successful gene delivery occurred in 77% of vaccinia, 41% of adenovirus, and only 13% of herpesvirus applications. Vector-specific reporter gene expression patterns were observed: With the vaccinia vector, lacrimal duct cells were predominantly stained; in contrast, the adenoviral vector tended to transduce the interacinar areas, with beta-gal expression mainly occurring within the myoepithelial cells. CONCLUSIONS: Vaccinia and adenovirus are efficient vectors for gene transfer into lacrimal gland tissue in primary culture. The specific expression pattern obtained by the vaccinia vector probably reflects its characteristic tissue tropism to lacrimal duct cells. The results presented in this ex vivo system may be a first step toward expressing genes with products that could be continuously delivered to the eye through the tears. Such proteins could include anti-inflammatory, anti-angiogenic, anti-herpetic, anti-bacterial, or anti-glaucomatous agents, among others.

Adenoviridae↗
PubMed1983

Light microscopic detection of sugar residues in glycoconjugates of salivary glands and the pancreas with lectin-horseradish peroxidase conjugates. I. Mouse.

Mouse salivary glands and pancreases were stained with a battery of ten horseradish peroxidase-conjugated lectins. Lectin staining revealed striking differences in the structure of oligosaccharides of stored intracellular secretory glycoproteins and glycoconjugates associated with the surface of epithelial cells lining excretory ducts. The percentage of acinar cells containing terminal alpha-N-acetylgalactosamine residues varied greatly in submandibular glands of 30 male mice, but all submandibular acinar cells contained oligosaccharides with terminal sialic acid and penultimate beta-galactose residues. The last named dimer was abundant in secretory glycoprotein of all mucous acinar cells in murine sublingual glands and an additional 20-50% of these cells in all glands contained terminal N-acetylglucosamine residues. In contrast, terminal alpha-N-acetylgalactosamine was abundant in sublingual serous demilune secretions. Serous acinar cells in the exorbital lacrimal gland, posterior lingual gland, parotid gland and pancreas exhibited a staining pattern unique to each organ. In contrast, the apical cytoplasm and surface of striated duct epithelial cells in the submandibular, sublingual, parotid and exorbital lacrimal gland stained similarly. A comparison of staining with conjugated lectins reported biochemically to have very similar carbohydrate binding specificity has revealed some remarkable differences in their reactivity, suggesting different binding specificity for the same terminal sugars having different glycosidic linkages or with different penultimate sugar residues.

Animals↗
PubMed2003

Imaging of high-energy midfacial trauma: what the surgeon needs to know.

UNLABELLED: Treatment goals in severe midfacial trauma are restoration of function and appearance. Restoration of function is directed at multiple organ systems, which support visual acuity, airway patency, mastication, lacrimation, smelling, tasting, hearing, and facial expression. Victims of blunt facial trauma expect to look the same after surgical treatment as before injury. Delicate soft tissues of the midface often make cosmetic reconstructive surgery technically challenging. Generally, clinical evaluation alone does not suffice to fully characterize facial fractures associated with extensive swelling, and the deeper midface is not accessible to physical examination. Properly performed computed tomography (CT) overcomes most limitations of presurgical examination. Thus, operative approaches and sequencing of surgical repair are guided by imaging information displayed by CT. Restoration of function and appearance relies on recreating normal maxillofacial skeletal anatomy, with particular attention to position of the malar eminences, mandibular condyles, vertical dimension and orbital morphology. Due to its pivotal role in surgical planning, CT scans obtained for the evaluation of severe midfacial trauma should be designed to easily depict the imaging information necessary for clinical decision making. LEARNING OBJECTIVES: 1. Understand the facial skeletal buttress system; 2. Understand how the pattern of derangement of the buttress system determines the need for and choice of operative approach for repair of fractures in the middle third of the face; 3. Understand the role and importance of CT and CT reformations in the detection and classification of the pattern of buttress system derangement.

Humans↗
PubMed2000

[Hematological abnormalities of primary Sjogren's syndrome].

Sjogren's syndrome (SS) is an autoimmune disease characterized by a chronic inflammatory response mainly localized to the lacrimal and salivary glands. However, it sometimes involves extraglandular organs culminating in systemic disorders. Hematological abnormalities are not uncommon, although they rarely have clinical significance. In this study we examined 99 patients with primary SS who visited our hospital during 1989 to 1999. Patient's mean age was 54.1 years and 95 out of 99 were female. Lymphopenia and leukopenia was noted in 35 patients (35.3%) and 26 patients (26.2%) respectively, and 7 patients (7.1%) had thrombocytopenia. 43 patients (43.4%) had either of these hematological abnormalities. Patients with lymphopenia showed significantly low frequency of arthralgia and anti-SS-A/B antibody was more common in this group. Only one patient in this group required prednisolone therapy because of polyarthritis and general fatigue while others needed no specific therapy. Patients with thrombocytopenia were significantly younger and a male/female ratio was higher than those without this abnormality. They had higher tendency to accompany with skin eruption, positive anti-SS-B antibody, anti-nuclear antibody and rheumatoid factor. Three out of 8 patients with thrombocytopenia were treated with prednisolone according to the protocol for idiopathic thrombocytopenic purpura. All of 3 patients had positive PA-IgG and normocellular bone marrow. Autoimmune mechanism such as polyclonal B cell activation may play a role in the pathogenesis of thrombocytopenia.

Female↗
PubMed1990

Morphology and anatomy of the olfactory organs of the marine fish Thynnus thunnina (Cuv. et Val.).

The authors studied the morphology and anatomy of the olfactory organs of the marine fish Thynnus thunnina. The fish has a single nasal orifice. The round olfactory rosette has a central axis surrounded by radially oriented lamellae. The olfactory rosette (olfactory organ) is provided with two accessory nasal sacs - a lacrimal and an ethmoidal sac. Thynnus thunnina was classified in Teichmann's (1954) group II, i.e., the "eye-fishes", whose vision is better developed than their olfaction.

Animals↗
PubMed2002

Autoantigens and Sjögren syndrome.

PURPOSE: To review recent experimental evidence on the involvement of autoantigens and autoantibodies in the pathogenesis of organ-specific autoimmunity in Sjögren syndrome (SS). METHODS: Among candidate autoantigens in SS, we investigated the role of alpha-fodrin in the lacrimal gland using a mouse model and a lacrimal gland cell line established in p53 knockout mice. We also tried to identify a novel organ-specific autoantigen by screening the human salivary gland cell line (HSG) against sera from SS patients. The specificity and sensitivity of this autoantigen to SS patient sera, its cellular localization, and the gene encoding the protein were analyzed. RESULTS: In addition to the previously identified 120-kd alpha-fodrin in the salivary gland, a shorter fragment was detected, indicating that there may be a distinct apoptosis-related protease that cleaves alpha-fodrin in the lacrimal gland. A novel salivary gland-specific autoantibody was detected in 50.9% of sera from SS patients. The antigen recognized by this antibody may be a 45-kd nucleus protein not recognized in its native form. CONCLUSION: The precise roles of autoantigens in organ-specific autoimmunity are still unclear, although accumulated evidence suggests that they may be associated with disease progression. Further studies of alpha-fodrin and the 45-kd antigen may contribute to the understanding of the pathogenesis of SS and may provide a new strategy for organ-specific therapy, such as vaccination with analogue peptides.

Animals↗
PubMed2001

cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland.

Multiple extracellular factors are hypothesized to promote the differentiation of unstimulated and/or stimulated secretory pathways in exocrine secretory cells, but the identity of differentiation factors, particularly those organ-specific, remain largely unknown. Here, we report on the identification of a novel secreted glycoprotein, lacritin, that enhances exocrine secretion in overnight cultures of lacrimal acinar cells which otherwise display loss of secretory function. Lacritin mRNA and protein are highly expressed in human lacrimal gland, moderately in major and minor salivary glands and slightly in thyroid. No lacritin message or protein is detected elsewhere among more than 50 human tissues examined. Lacritin displays partial similarity to the glycosaminoglycan-binding region of brain-specific neuroglycan C (32 % identity over 102 amino acid residues) and to the possibly mucin-like amino globular region of fibulin-2 (30 % identity over 81 amino acid residues), and localizes primarily to secretory granules and secretory fluid. The lacritin gene consists of five exons, displays no alternative splicing and maps to 12q13. Recombinant lacritin augments unstimulated but not stimulated acinar cell secretion, promotes ductal cell proliferation, and stimulates signaling through tyrosine phosphorylation and release of calcium. It binds collagen IV, laminin-1, entactin/nidogen-1, fibronectin and vitronectin, but not collagen I, heparin or EGF. As an autocrine/paracrine enhancer of the lacrimal constitutive secretory pathway, ductal cell mitogen and stimulator of corneal epithelial cells, lacritin may play a key role in the function of the lacrimal gland-corneal axis.

Amino Acid Sequence↗
PubMed2005

Effect of inflammation on lacrimal gland function.

The lacrimal gland is the main contributor to the aqueous layer of the tear film. It secretes proteins, electrolytes and water, which helps to nourish and protect the ocular surface. Lacrimal gland secretion is primarily under neural control, which is achieved through a neural reflex arc. Stimuli to the ocular surface activate afferent sensory nerves in the cornea and conjunctiva. This in turn activates efferent parasympathetic and sympathetic nerves in the lacrimal gland to stimulate secretion. Sex steroid hormones are also important regulators of lacrimal gland functions. A decrease or lack of lacrimal gland secretion is the leading cause of aqueous tear deficient dry eye syndrome (DES). It has been suggested that DES is an inflammatory disorder that affects the ocular surface and the lacrimal gland. In several pathological instances, the lacrimal gland can become a target of the immune system and show signs of inflammation. This can result from autoimmune diseases (Sjögren's syndrome), organ transplantation (graft versus host disease), or simply as a result of aging. The hallmarks of lacrimal gland inflammation are the presence of focal lymphocytic infiltrates and increased production of proinflammatory cytokines. The mechanisms leading to lacrimal gland dysfunction are still poorly understood. Apoptosis, production of autoantibodies, hormonal imbalance, alterations in signaling molecules, neural dysfunction, and increased levels of proinflammatory cytokines have been proposed as possible mediators of lacrimal gland insufficiency in disease states.

Animals↗
PubMed1996

[Relationship between expression of P21ras and cellular DNA in pleomorphic adenoma of lacrimal gland].

BACKGROUND: The pleomorphic adenoma is the most frequent tumor of the human lacrimal gland comprising about 50% of the epithelial tumors of this organ. Although being benign, local recurrences can occur when the first removal was incomplete and malignant transformation is also not in frequent. It is well known that many sorts of cellular oncogene products are involved in the initiation, promotion and progression of the human neoplasm. Our purpose was to know whether there is abnormal expression of P21ras in pleomorphic adenoma. METHODS: We have undertaken a study of the expression of P21ras in 5 normal tissues and 32 pleomorphic adenoma of lacrimal gland by immunohistochemical means using the monoclone antibody F-132-62 and the nuclear DNA content in the tumor was assayed by image analysis technique. RESULTS: Normal tissues of lacrimal gland were negative, 12 tumors were stained positively with the antibody. The DNA content of 14 cases of tumor was increased. Their DNA ploidy distribution pattern showed two or several peaks. Good correlation has been found between the expression of P21ras and DNA ploidy distribution pattern, the DNA ploidy distribution pattern of tumor which expressed p21ras showed mainly two or several peaks. P< 0.05. CONCLUSIONS: The result of our studies may suggest that there are increased expression of p21ras in pleomorphic adenoma and the expression of p21ras is related to the promotion and progression of pleomorphic adenoma of lacrimal gland.

Adenoma, Pleomorphic↗
PubMed2004

Clinical manifestations and early diagnosis of Sjögren syndrome.

Sjögren syndrome (SS) is a common autoimmune disease evidenced by broad organ-specific and systemic manifestations, the most prevalent being diminished lacrimal and salivary gland function, xerostomia, keratoconjunctivitis sicca, and parotid gland enlargement. Primary SS presents alone, and secondary SS occurs in connection with autoimmune rheumatic diseases. In addition, symptoms do not always present concurrently. This diversity of symptomatic expression adds to the difficulty in initial diagnosis. Armed with the recently refined criteria for diagnosis, specialists, such as rheumatologists, primary care physicians, ophthalmologists, and dentists, who would otherwise focus only on those symptoms that encompass their areas of expertise, can get a comprehensive image of the presenting patient, leading to earlier identification and treatment of SS.

Humans↗
PubMed1995

Androgens and estrogens markedly inhibit expression of a 20-kDa major protein in hamster exorbital lacrimal gland.

We report here for the first time a 20-kDa hamster lacrimal gland major protein whose expression is markedly inhibited by physiological levels of both androgens and estrogens. This novel protein was present in adult females but not in males. In females, its level was several fold elevated on ovariectomy to apparently 20% of total soluble proteins. Castration in males induced this 20-kDa protein from undetectable to ovariectomized female levels. Administration of only androgens or estrogens to gonadectomized hamsters of both sexes obliterated this major lacrimal protein and estrogens were more potent than androgens. The 20-kDa lacrimal protein was secreted only in female tears. This lacrimal 20-kDa protein of yet unknown function is a useful marker to study the hormonal regulation of the lacrimal gland and it provides a model system to study how both androgens and estrogens mediate inhibition of a specific protein's expression.

Animals↗