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ID PMID Title PublicationDate abstract
10746444 Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of 2000 Mar PURPOSE: To compare the efficacy and short-term safety of diclofenac sodium, 0.1% (Voltaren Ophtha; Ciba-Vision) and of sodium chloride, 5% ophthalmic solution, in the treatment of filamentary keratitis (FK) in patients with dry-eye syndrome due to secondary Sjögren's syndrome. METHODS: Thirty-two patients (64 eyes) with dry-eye syndrome due to secondary Sjögren' syndrome were enrolled in a randomized study (patients and authors were aware of which medication was being used). All patients had FK. Sixteen patients were treated with sodium chloride, 5% drops, and 16 patients received diclofenac sodium, 0.1% eyedrops. Treatment regimen included instillation of 1 drop, 4 times a day for 28 days, for both groups. Clinical assessment was performed once a week during the study period. Data on the efficacy and safety of the different therapeutic regimens were collected and compared. RESULTS: Both medications achieved disappearance of filaments at the end of the study. Treatment with diclofenac sodium, 0.1%, revealed a significantly more rapid improvement of the clinical symptoms as compared with sodium chloride, 5%. No significant adverse effects were observed in both groups. CONCLUSION: Diclofenac sodium, 0.1%, may be an effective and safe topical therapy in patients with FK caused by secondary Sjögren's disease.
9682987 Minor salivary gland hyalinisation and amyloidosis in low-grade lymphoma of MALT. 1998 May Two patients with low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) arising in primary Sjögren's syndrome developed solitary nodules in their lips. Histologically both lesions showed enlargement and hyalinisation of single minor salivary glands with acinar atrophy, loss of most ducts and conversion into almost acellular sclerotic eosinophilic masses. In one case the lesion was shown to contain an amyloid component. No amyloid was detected in the second case but deposition of collagen and basement membrane and sclerotic neoplasm were excluded.
9569073 Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in Sjögren 1998 Feb The antigen receptor diversity of pathogenic T cells in Sjögren's syndrome (SS) may have important implications in the development of the disease; cytokines from these cells and other sources also play a role in the pathogenesis of this disease. Using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique, we have attempted to correlate the presence of restriction in the T-cell receptor (TCR) repertoire with cytokine profiles. We have analysed TCR V alpha family usage, and the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), in labial biopsies from 12 patients with SS and compared these with samples from three patients with chronic sialadenitis (CS). Only one of the SS biopsies showed evidence of V alpha restriction (three out of 18 gene families). Apart from this, expression patterns were similar in both patient groups. Four of the 12 SS samples demonstrated a 'limited heterogeneity' of the V alpha repertoire with 3-4 families predominantly expressed, in particular V alpha1 and V alpha3. Peripheral blood lymphocytes were unrestricted. The cytokine profiles of the SS and CS biopsies were generally similar. However both IFN-gamma and IL-1alpha were absent from CS, but present in SS samples. The expression of IFN-gamma in the majority of the samples, together with a lack of IL-4 and IL-13 mRNA, suggests the predominance of a Th1 response in SS. There was no clear association between the repertoire of V alpha genes expressed and the cytokine profile observed. However, the V alpha restriction in one SS sample did correspond with a limited diversity of cytokines detected.
11232635 Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögre 2001 Feb Patients with Sjögren's syndrome (SS) suffer from deficient secretion of saliva due to an autoimmune destruction of salivary glands, however, glandular dysfunction also occurs without destruction. Based upon its abnormal distribution in SS salivary glands, a potential role for the water channel protein aquaporin-5 (AQP5) is proposed in the pathogenesis of SS. The immunohistochemical distribution of AQP5 was compared in minor salivary gland biopsies obtained from women after informed consent: primary SS (53.2 +/- 14 years old, n = 10), healthy volunteers (46.2 +/- 17 years old, n = 10), patients with sarcoidosis (37 and 48 years old), and patients with non-specific sialoadenitis (54 and 61 years old). Biopsies from normal subjects revealed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, biopsies from SS patients revealed AQP5 primarily at the basal membranes of the acinus. The AQP5 distribution in biopsies from patients with other dry mouth disorders, such as non-specific sialoadenitis or sarcoidosis, was similar to biopsies from control subjects. Computer-assisted microscopy was performed to quantitatively evaluate AQP5 distribution in the immunoreactive acini of both SS and control subjects. Biopsies from SS patients had higher labeling indices (percentage of acinus area immunoreactive for AQP5) at the basal membrane when compared with biopsies from control subjects. In contrast, biopsies of SS patients exhibited lower labeling indices at the apical membrane when compared with biopsies from control subjects. To verify the specificity of the AQP5 antibody, Western blot analysis was performed on membranes from Xenopus oocytes injected with AQP5 cRNA or on membranes from minor salivary glands of control subjects and SS patients. In each case, the immunoblots had a 27 kd band, corresponding to the expected molecular weight of AQP5. Abnormal distribution of AQP5 in salivary gland acini is likely to contribute to the deficiency of fluid secretion, which is a defining feature of Sjögren's syndrome.
11202629 [Morphologic study of the microcirculation in connective tissue diseases]. 2000 Oct Capillaroscopy is a non-invasive diagnostic test used to study microvascular abnormalities which are present in many disorders, particularly some rheumatic pathologies, such as connective tissue diseases. In systemic sclerosis, capillaroscopy allows detection of pathognomonic microvascular alterations. In other connective tissue diseases, including systemic lupus erythematosus, dermatopolymyositis, undifferentiated connective tissue diseases, and mixed connective tissue disease, the capillaroscopic patterns, although non-specific, can provide a valid support for the diagnosis. In Raynaud's phenomenon, capillaroscopy enables detection of early microvascular abnormalities that are useful for preclinical diagnosis of secondary Raynaud's phenomenon.
11193326 [A case of primary Sjögren's syndrome with interstitial pneumonia showing bronchiolitis o 2000 Nov A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sjögren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sjögren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sjögren's syndrome.
11130833 Pathological features of lymphoid proliferations of the salivary glands: lymphoepithelial 2000 Dec Lymphoid proliferations of the salivary glands can be either reactive or neoplastic. Reactive lesions include the lymphoepithelial sialadenitis (LESA; also known as myoepithelial sialadenitis [MESA]) of Sjogren's syndrome. Lymphomas of the salivary glands are predominantly B-cell type and include extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. The spectrum of histopathologic features of LESA/MESA includes 1) "fully benign lymphoid infiltrate," with or without an associated lymphoid follicular structure, without immunoglobulin (Ig) light chain restriction in B-cells, and without any features of aggressive behavior, and 2) "lymphoproliferative lesions," with or without areas of Ig light chain restriction in B-cells, with the usual presence of centrocyte-like cells. A more or less pronounced lymphoepithelial aggressiveness may be present without definite evidence of malignancy. B-cell clones are detected in over 50% of cases of LESA/MESA by molecular genetic methods, but this does not correlate with morphological or clinical evidence of overt lymphoma. On the other hand, "marginal zone B-cell lymphoma of the MALT type" of the salivary glands produces a dense lymphoid infiltrate diffusely involving the gland, with obliteration of acini. The centrocyte-like cells form broad "halos" around the epithelial cell nests and broad strands between lymphoepithelial lesions, often linking together several lymphoepithelial lesions. Further, lymphoma cells express monotypic surface Ig, and in the majority of the cases, the plasma cells are also monoclonal. In conclusion, the diagnosis of LESA/MESA versus marginal zone B-cell lymphoma of the MALT type still relies on the evaluation of morphological features. It seems that molecular genetic analysis has little or no practical role in the clinical diagnosis of salivary gland lymphoma in a setting of LESA/MESA and Sjögren's syndrome.
10531746 Outcome of treatment with implant-retained dental prostheses in patients with Sjögren syn 1999 Sep The purpose of this investigation was to evaluate the outcome of treatment with implant-retained prostheses in patients suffering from Sjögren syndrome. Eight women were included in the study; all had suffered oral symptoms of Sjögren syndrome for many years. Seven patients were edentulous in both arches, and 1 patient was edentulous in the maxilla only. All patients reported poor or very poor comfort levels with their conventional dentures. It was the intention to treat each arch that showed subjective and objective denture problems with a complete fixed prosthesis after placement of 6 implants. In all, 54 Brånemark dental implants were placed in these patients. No implants were lost, but 7 implants in 4 patients were clinically not osseointegrated at the time of the abutment connection procedure. Because of nonosseointegrated implants and lack of jawbone, 3 arches were treated with an implant-retained overdenture. Fixed prostheses were made with a titanium framework of premachined components welded together (Procera) and acrylic resin teeth and flanges. Patients answered a questionnaire regarding their oral function before the onset of treatment and 1 month and 2 years after treatment. An average radiographic bone loss of 0.7 mm from the time of implant placement to 1 year after treatment was observed; additional bone loss of less than 0.6 mm was recorded 4 years after treatment. During the first year of function 2 implants lost osseointegration. No prostheses were lost or remade. Treatment with implant-retained prostheses considerably increased the prosthetic comfort and function of the patients. Two years after prosthetic treatment, only 1 patient indicated poor comfort of the prostheses, while the remaining patients reported good or very good comfort levels.
9775186 [A rare cause of intra-alveolar hemorrhage: a transfusion-related incident with leukoagglu 1998 Jun INTRODUCTION: Transfusion-related acute lung injury (TRALI) is an infrequent but life-threatening complication of hemotherapy, usually secondary to passive transfer of antibody from the donor's plasma to the recipient. TRALI is a diagnosis of exclusion often masked by underlying factors. EXEGESIS: We report a new case of TRALI in a patient with severe multinevritis associated with Sjögren's syndrome and cryoglobulinemia, who had received intravenous immunoglobulins. CONCLUSION: This case report underlines the difficulty to establish a diagnosis in both acute respiratory failure and intra-alveolar hemorrhage in patients with auto-immune disorders. This case report also emphasizes the necessity of taking precautions in these immunocompromised patients in whom hemoglobin transfusion is required.
9740997 Fine-needle aspiration of large cell lymphoma in a patient with agnogenic myeloid metaplas 1998 Sep We describe a patient with agnogenic myeloid metaplasia and Sjogren's disease who developed a large B-cell lymphoma. We discuss the differential diagnoses of fine-needle aspirations of a localized mass from such patients and review the literature of the association between agnogenic myeloid metaplasia and lymphoma.
9307859 Assessment of bromhexine as a treatment regimen in Sjögren's syndrome-like disease in the 1997 Sep OBJECTIVE: Bromhexine has been reported to alleviate the xerostomia and xerophthalmia associated with secondary Sjögren's syndrome. The aim of this study was to determine if it might prove useful in the treatment of Sjögren's syndrome-like disease of the NOD mouse model for autoimmune sialoadenitis. METHODS: Groups of mice were divided into sets receiving 60 mg/kg bromhexine in drinking water and control pair-fed animals. The efficacy of drug treatment was assessed by weekly measurement of stimulated saliva volumes, protein concentration, and amylase activity. At termination (20 weeks) submandibular and lacrimal glands were removed to assess the levels of lymphocytic infiltration by histological evaluation under light microscopy. RESULTS: Control and bromhexine-treated groups of mice showed no difference in the loss or rate of reduction in stimulated saliva flow over the 12 weeks of treatment. No differences were noted in the protein concentration and amylase loss with increasing age of the animals. Similar temporal changes in total protein profiles and aberrant expression of the 20 kDa parotid secretory protein isoform were observed by SDS-polyacrylamide gel profiles and Western bolt analysis. Histological evaluation of exocrine gland sections failed to detect any reduction in focal lymphocyte infiltration. CONCLUSION: Bromhexine therapy did not alter the development or severity of Sjögren's syndrome-like disease in the NOD mouse model for autoimmune sialoadenitis.
11581200 Cytokines in autoimmune lacrimal gland disease in MRL/MpJ mice. 2001 Oct PURPOSE: MRL/MpJ-+/+ (MRL/+) and MRL/MpJ-lpr/lpr (MRL/lpr) mice show spontaneous development of a T-cell-driven lacrimal gland inflammation that is a model for Sjögren syndrome. The lacrimal gland lesions in these mice were evaluated by quantitative RT-PCR for selected cytokine mRNA for the relative contributions of T-helper (Th)1 versus Th2 immune responses and by RT-PCR and immunohistochemistry for the contribution of the interleukin (IL)-2/IL-2 receptor (IL-2R) autocrine pathway. METHODS: RNA was isolated from lacrimal glands of MRL/+ mice ages 1 to 9 months and from MRL/lpr mice ages 1 through 5 months, and competitive RT-PCR was used to quantify mRNA for the cytokines IL-2, -4, -10, and -12 and interferon (IFN)-gamma. Frozen sections of lacrimal glands from MRL/+ and MRL/lpr mice ages 2 through 5 months were stained for the IL-2R. RESULTS: IL-2 and -12 mRNA transcripts were below the limit of detection (<10(-3) fg/pg hypoxanthine phosphoribosyl transferase gene; HPRT) in both MRL/+ and MRL/lpr mice of all ages. When detectable, IFN-gamma transcripts were present in low amounts and were below the limit of detection in most samples. IL-4 transcripts were present in 100- to 1000-fold greater amounts than IFN-gamma transcripts. IL-10 transcripts were detectable in both MRL/+ and MRL/lpr mice. IL-2R typically was detected on less than 10% of lymphocytes infiltrating lacrimal gland lesions in both substrains. CONCLUSIONS: On the basis of RT-PCR for cytokine mRNA, autoimmune lacrimal gland lesions in MRL/+ and MRL/lpr mice appear to be largely Th2-mediated. There does not appear to be a direct role for the IL-2/IL-2R autocrine pathway within the microenvironment of the lacrimal gland.
11472414 Functional heterogeneity of anti-endothelial cell antibodies. 2001 Jun While it has been claimed that some anti-endothelial cell antibodies (AECA) activate EC, there is also evidence that others trigger apoptosis. To address the issue of whether activation is a prerequisite for AECA-mediated apoptosis of EC, 23 AECA-positive sera were evaluated for their ability to induce activation and/or apoptosis. Activation was defined as an over-expression of E-selectin and intercellular adhesion molecule 1. Optical microscopy, annexin V binding, hypoploid cell enumeration, and determination of poly (ADP-ribose) polymerase cleavage-related products were used to assess apoptosis. Four functional profiles were defined: 10 sera promoted activation and apoptosis (act+/apo+), one was act+/apo-, six act-/apo+, and the remaining six act-/apo-. The reduced membrane expression of thrombomodulin was associated with apoptosis, rather than activation. Caspase-3 was implicated in the two models of apoptosis, the ratios of several survival proteins to Bax decreased, regardless of the ability of apo+ AECA to activate the cells, while radical oxygen species did not appear to be involved. Furthermore, it occurred that macrophages engulfed EC treated with apoptosis-promoting AECA, but not those incubated with AECA that did not induce apoptosis. Hence, AECA represent an extremely heterogeneous family of autoantibodies, not only because of the variety of their target antigens, but also the subsequent diversity of their effects.
11236777 High serum IgG4 concentrations in patients with sclerosing pancreatitis. 2001 Mar 8 BACKGROUND: Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract. METHODS: We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjögren's syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor. RESULTS: The median serum IgG4 concentration in the patients with sclerosing pancreatitis was 663 mg per deciliter (5th and 95th percentiles, 136 and 1150), as compared with 51 mg per deciliter (5th and 95th percentiles, 15 and 128) in normal subjects (P<0.001). The serum IgG4 concentrations in the other groups of patients were similar to those in the normal subjects. In patients with sclerosing pancreatitis, serum concentrations of immune complexes and the IgG4 subclass of immune complexes were significantly higher before glucocorticoid therapy than after four weeks of such therapy. Glucocorticoid therapy induced clinical remissions and significantly decreased serum concentrations of IgG4, immune complexes, and the IgG4 subclass of immune complexes. CONCLUSIONS: Patients with sclerosing pancreatitis have high serum IgG4 concentrations, providing a useful means of distinguishing this disorder from other diseases of the pancreas or biliary tract.
10924646 The health of mothers of children with cutaneous neonatal lupus erythematosus differs from 2000 Jun 15 PURPOSE: Neonatal lupus erythematosus is caused by the transplacental passage of maternal autoantibodies. The aim of this study was to determine the risk of connective tissue disorders in mothers of children with cutaneous neonatal lupus erythematosus, as compared with the risk in mothers of children with congenital heart block, which is also often caused by maternal autoantibodies. SUBJECTS AND METHODS: We prospectively studied all mothers of children with cutaneous neonatal lupus erythematosus during a 14-year period at the Hospital for Sick Children, Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for study. The health and antibody status of the mothers were determined at the birth of the child and at followup. RESULTS: All mothers had anti-Ro antibodies at the time of birth. Initially 10 mothers were healthy and 14 mothers had either a defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital heart block were asymptomatic at follow-up (P <0.005). CONCLUSIONS: The majority of mothers of children with cutaneous neonatal lupus erythematosus had a defined or undifferentiated autoimmune disorder at the time of the child's birth, and others developed these conditions during follow-up. The health of these mothers appears to differ from that of mothers of children with congenital heart block.
10765928 CD8+, CD57+ T cells from healthy elderly subjects suppress neutrophil development in vitro 2000 Apr OBJECTIVE: To investigate the ability of CD8+,CD57+ large granular lymphocytes (LGL) from normal individuals and from Felty's syndrome (FS) or LGL syndrome patients to suppress allogeneic neutrophil precursor development. METHODS: Six FS patients, 5 LGL syndrome patients, and 13 elderly controls were studied. CD8+,CD57+ T cells were cocultured with cord blood-derived stem cells, and percentage inhibition was calculated. Recombinant chemokines and Fas-stimulating molecules were used in separate cultures to address possible mechanisms of suppression. Proliferation after stimulation with interleukin-2 (IL-2) and anti-CD3 was assessed. RESULTS: Significant (79%) suppression of colony-forming unit-granulocyte-macrophage (CFU-GM) by the CD8+,CD57+ subset was shown by 1 FS patient. None of the CD8+,CD57+ cells from LGL syndrome patients had any effect. Six of 13 controls studied showed >40% inhibition of CFU-GM, and all but 2 showed at least some suppression. The suppressive effect was not mediated by Fas/Fas ligand interactions or by the chemokines macrophage inhibitory protein 1alpha or IL-8. LGL from both patients and controls were largely CD28- and had reduced proliferative capacity. CONCLUSION: In a subset of FS patients, expansion of CD8+,CD57+ T cells in the bone marrow may be responsible for neutropenia by suppressing neutrophil precursors. This effect is also seen with normal LGL, which are likely to have an important function in neutrophil homeostasis.
10364042 Primary hepatic lymphoma associated with primary biliary cirrhosis. 1999 Jun We report a case of primary hepatic lymphoma in a 55-yr-old female patient with primary biliary cirrhosis and Sjögren's syndrome. On July 1994, a tumor measuring 11 mm in diameter was detected in the right lobe of the liver by abdominal ultrasonography. A needle biopsy specimen showed the lesion to contain small- and medium-sized lymphoid cells without obvious atypia, and a provisional diagnosis of pseudolymphoma was made. About 2 yr later, the tumor increased to 15 mm in diameter, necessitating a second needle biopsy. Histological and genetic examinations confirmed non-Hodgkin's lymphoma of diffuse, mixed small and large cell, B-cell type. However, the size of the tumor remained almost stable (16 mm in diameter) over a period of 7 months after diagnosis, without any treatment for lymphoma, indicating a low grade malignancy. We document hepatic lymphoma as an additional complication of primary biliary cirrhosis.
9795778 Determinant spreading: lessons from animal models and human disease. 1998 Aug Spreading of the immune response is a common theme in organ-specific and systemic autoimmune diseases. We evaluated whether some of the mixed antinuclear antibody patterns characteristic of systemic autoimmunity might be the result of determinant spreading from a single initiating event. Immunisation of healthy mice with individual protein components of the La/Ro ribonucleoprotein (RNP) targeted in systemic lupus erythematosus and primary Sjögren's syndrome induced autoantibodies recognising Ro60 (SS-A), Ro52 (SS-A) and La (SS-B) and in some cases the molecular chaperones calreticulin and Grp78. The endogenous antigen(s) driving determinant spreading might be derived from physiological apoptosis which could explain the involvement of some chaperone proteins in the autoimmune response. Diversified anti-La/Ro antibody responses were initiated by challenge with a single subdominant T epitope of La even though some self epitopes of La were efficiently tolerised. The pattern of autoantibody responses in primary Sjögren's syndrome was strongly influenced by HLA class II phenotype which we speculate controls activation of T cells recognising defined peptides from the La/Ro RNP. In this way, HLA class II alleles may be critical in influencing initiation and spreading of systemic autoimmune reactions. Molecular mimicry of such determinants by exogenous agents might readily initiate spreading of an autoimmune response in genetically susceptible hosts.
9330934 Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor rec 1997 Oct OBJECTIVE: Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) affect cells through binding to a shared EGF receptor (EGF-R), which is a transmembrane protein with tyrosine kinase activity. They exert trophic effects on vascular endothelial, salivary acinar, and ductal and mucosal epithelial cells. In Sjögren's syndrome (SS) focal sialadenitis leads to salivary gland tissue damage, diminished salivary flow, and changes in the oral epithelium, a complex referred to as xerostomia. We compared the localization of EGF, TGF-alpha, and EGF-R in labial salivary glands in SS and in healthy controls. METHODS: Labial salivary gland tissues of 12 patients with SS and 7 healthy controls were stained with the immunohistochemical peroxidase-antiperoxidase method for EGF, TGF-alpha, and EGF-R. RESULTS: Immunoreactivity for both EGF and TGF-alpha was found in endothelial cells of blood vessels and in some ductal epithelial cells. TGF-alpha, but not EGF, was also found in some acinar cells. EGF-R was found in endothelial, acinar, and salivary duct epithelial cells. There was no difference in the expression of EGF-R between diseased and healthy specimens, but both EGF and TGF-alpha were diminished in SS. CONCLUSION: The interrelated localization of EGF-R and its ligands, EGF and TGF-alpha, suggests an autocrine, juxtacrine, and paracrine mitogenic/trophic role for them and thus a role in the maintenance of the secretory and excretory cells of the normal salivary glands. The trophic effects on acinar cells seem not to be mediated by EGF, but more likely by TGF-alpha. The diminished expression of EGF and TGF-alpha indicates a failure of this trophic system in SS, which may contribute to the acinar atrophy and secondary changes thereof, including atrophy of the oral mucosa.
9310949 Coexistence of different B-cell clones in consecutive lesions of low-grade MALT lymphoma o 1997 Sep Low-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the salivary gland are usually indolent diseases with a protracted clinical course. Recurrent multifocal disease has been shown to represent identical clones in some cases, and intraclonal variation resulting from continuing somatic hypermutation has been described, but emergence of novel, major clones upon recurrent disease has not been documented. We analyzed three consecutive biopsy specimens of parotid lymphoid infiltrates of a young woman with Sjögren's disease. The immunoglobulin heavy chain (IgH) gene rearrangements were first amplified using FR2/LJH-VLJH consensus primers. Then, the PCR products were cloned, sequenced, and compared. On the basis of the sequences of the complementarity determining region 3 (CDR3), clone-specific primers were designed and used to evaluate the presence of similar sequences in different biopsy specimens. Recurrent parotid lymphoid infiltrates during a span of 9 years showed histologically similar features consistent with low-grade MALT lymphoma. Polymerase chain reaction amplification showed a clonal pattern of IgH gene rearrangement in all of the lesions with similar product sizes, suggesting the identity of the clones, but two major clones with different CDR3 sequences were found. Intraclonal variation was seen among the sequences seen in the three lesions consistent with the occurrence of somatic hypermutations. Primers specific to the clone seen in the first two lesions failed to amplify products from the third lesion, but primers specific to the third clone showed similar products in the second clone in a small quantity, indicating that this clone persisted and expanded. Our results suggest that different B-cell clones might dominate during the course of low-grade MALT lymphoma of the salivary gland. This implies that in some cases, these processes can represent oligoclonal B-cell proliferations.