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ID PMID Title PublicationDate abstract
11916964 Reactive oxygen species differentially affect T cell receptor-signaling pathways. 2002 May 31 Oxidative stress plays an important role in the induction of T lymphocyte hyporesponsiveness observed in several human pathologies including cancer, rheumatoid arthritis, leprosy, and AIDS. To investigate the molecular basis of oxidative stress-induced T cell hyporesponsiveness, we have developed an in vitro system in which T lymphocytes are rendered hyporesponsive by co-culture with oxygen radical-producing activated neutrophils. We have observed a direct correlation between the level of T cell hyporesponsiveness induced and the concentration of reactive oxygen species produced. Moreover, induction of T cell hyporesponsiveness is blocked by addition of N-acetyl cysteine, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, and catalase, confirming the critical role of oxidative stress in this system. The pattern of tyrosine-phosphorylated proteins was profoundly altered in hyporesponsive as compared with normal T cells. In hyporesponsive T cells, T cell receptor (TCR) ligation no longer induced phospholipase C-gamma1 activation and caused reduced Ca(2+) flux. In contrast, despite increased levels of ERK1/2 phosphorylation, TCR-dependent activation of mitogen-activated protein kinase ERK1/2 was unaltered in hyporesponsive T lymphocytes. A late TCR-signaling event such as caspase 3 activation was as well unaffected in hyporesponsive T lymphocytes. Our data indicate that TCR-signaling pathways are differentially affected by physiological levels of oxidative stress and would suggest that although "hyporesponsive" T cells have lost certain effector functions, they may have maintained or gained others.
11832727 Diurnal cortisol variations and symptoms in patients with interstitial cystitis. 2002 Mar PURPOSE: Little attention has focused on systemic factors that may allow a state of chronic bladder inflammation to be established and maintained in interstitial cystitis cases. Abnormalities of the hypothalamic-pituitary-adrenal feedback system result in poorer regulation of the inflammatory response and are present in many chronic inflammatory and pain conditions, of which some have high co-morbidity with interstitial cystitis. MATERIALS AND METHODS: A total of 48 patients with interstitial cystitis and 35 healthy, age matched controls collected 24-hour urine samples and 3 days of salivary samples at 7 to 8 a.m., 4 to 5 p.m. and 8 to 9 p.m. for cortisol analysis. In addition, they completed a concurrent symptom questionnaire. Prospective symptom diaries also were completed in the month before sampling. RESULTS: Mean urinary or salivary cortisol did not differ in patients and controls. However, patients with interstitial cystitis and higher morning cortisol had significantly less pain and urgency, while those with higher urinary free cortisol reported less overall symptomatology (p <0.05). Relationships with morning cortisol were also observed when controlling for co-morbid conditions known to be affected by the hypothalamic-pituitary-adrenal axis, such as fibromyalgia, chronic fatigue and rheumatoid arthritis. Patients with morning cortisol less than 12.5 nmol./l. were 12.8 times more likely to report high urinary urgency than those with values above this cutoff. CONCLUSIONS: These findings imply that regulation of the hypothalamic-pituitary-adrenal axis may be associated with interstitial cystitis symptomatology and there may be different diurnal hypothalamic-pituitary-adrenal patterns in patients with interstitial cystitis who do and do not have co-morbid conditions. These findings may have treatment implications for patients with interstitial cystitis who have early morning cortisol deficiencies.
23785733 Al(18)F-1,4,7-Triazacyclononane,1-glutaric acid-4,7-acetic acid-Glu-[cyclo(Arg-Gly-Asp-d-P 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of α(v)β(3) are being studied as antitumor and antiangiogenic agents, and the agonists of α(v)β(3) are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). Extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) contain a tripeptide sequence consisting of Arg-Gly-Asp (RGD), which binds to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for use with the imaging of tumors and tumor angiogenesis (10). Most cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD (c(RGD)) peptides exhibit selective inhibition of binding to α(v)β(3) (inhibition concentration (IC(50)), 7–40 nM) but not to integrins α(v)β(5) (IC(50), 600–4,000 nM) or α(IIb)β(3) (IC(50), 700–5,000 nM). Various radiolabeled c(RGD) peptides have been found to have high accumulation in tumors in nude mice (12). Dijkgraaf et al. (13) reported the evaluation of Al(18)F-1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid-Glu-[cyclo(Arg-Gly-Asp-d-Phe-Lys)](2) (Al(18)F-NODAGA-E-[c(RGDfK)](2)) for use with positron emission tomography (PET) imaging of α(v)β(3) in tumors.
21491703 (68)Ga-1,4,7-Triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-d-T 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. The α(v)β(3) antagonists are being studied as antitumor and antiangiogenic agents, and the agonists are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). The peptide sequence Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most of the cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to α(v)β(3) (IC(50), 7–40 nM) but not to α(v)β(5) (IC(50), 600–4,000 nM) or α(IIb)β(3) (IC(50), 700–5,000 nM) integrins. Various radiolabeled cyclic RGD peptides have been found to have high accumulation in tumors in nude mice (12). Jeong et al. (13) used 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4-7-triacetic acid (SCN-Bz-NOTA) as a bifunctional chelator for labeling c(RGDyK) to form (68)Ga-1,4,7-triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-d-Tyr-Lys) ((68)Ga-NOTA-RGD) for positron emission tomography (PET) imaging of α(v)β(3) receptors in nude mice bearing tumor xenografts.
20641723 (111)In-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Glu-{Glu-[cyclo(Arg-Gly-Asp-D 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of α(v)β(3) are being studied as antitumor and antiangiogenic agents, and the agonists of α(v)β(3) are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). Extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) contain a tripeptide sequence consisting of Arg-Gly-Asp (RGD), which binds to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to α(v)β(3) (inhibition concentration (IC(50)), 7–40 nM) but not to integrins α(v)β(5) (IC(50), 600–4,000 nM) or α(IIb)β(3) (IC(50), 700–5,000 nM). Various radiolabeled cyclic RGD peptides have been found to have high accumulation in tumors in nude mice (12). Dijkgraaf et al. (13) reported the development of (111)In-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Glu-{Glu-[cyclo(Arg-Gly-Asp-D-Phe-Lys)](2)}(2) ((111)In-DOTA-E-{E-[c(RGDfK)](2)}(2)) for imaging α(v)β(3) receptors in nude mice bearing ovarian carcinoma tumors.
20641712 (99m)Tc(CO)(3)-Bipyridine-cyclo-(Arg-Gly-Asp-D-Tyr-Lys). 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell-cell and cell-matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. α(v)β(3) antagonists are being studied as antitumor and antiangiogenic agents and the agonists as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most of the cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to α(v)β(3) (IC(50), 7-40 nM) but not to α(v)β(5) (IC(50), 600-4,000 nM) or α(IIb)β(3) (IC(50), 700-5,000 nM) integrins. Various radiolabeled cyclic RGD peptides have been found to have high accumulation in tumors in nude mice (12). The ready availability and low cost of (99m)Tc led to the development of (99m)Tc-RGD peptides for targeting α(v)β(3) integrins in tumor angiogenesis. (99m)Tc(CO)(3)-Bipyridine-cyclo-(Arg-Gly-Asp-D-Tyr-Lys) ((99m)Tc(CO)(3)-BPy-c(RGDyK)) has been prepared as a single-photon emission computed tomography (SPECT) tracer for imaging α(v)β(3) integrins in tumor (13).
12239673 Analgesic benefit, functional outcome, and patient satisfaction after partial wrist denerv 2002 Sep Partial wrist denervation is a useful palliative procedure for chronic wrist pain when reconstructive procedures are not feasible or desirable. We reviewed 19 patients who had 20 isolated anterior and posterior interosseous neurectomies with no previous or concurrent wrist surgery in a 5-year period at our institution. At an average of 2.5 years postoperatively, 80% of patients reported a decrease in pain, 45% reported normal or increased grip strength, and 73% of employed patients had returned to work. Three patients required additional procedures for pain relief (2 arthrodesis, 1 radial styloidectomies). Failure tended to occur in the first postoperative year. Poor preoperative range of motion and workers' compensation status were predictive of failure. Failure also occurred in the single patient with rheumatoid arthropathy. Two patients had subsequent arthrodeses. There were no complications related to the surgery. Overall, 85% of patients reported satisfaction with this procedure; 90% retrospectively would choose the same treatment for their chronic wrist pain. Partial denervation of the wrist via the anterior and posterior interosseous nerves is a technically easy procedure and may provide pain relief sufficient to markedly delay the need for more extensive salvage procedures in patients with wrist arthritis.
15081254 Autoantibodies against cerebral muscarinic cholinoceptors in Sjögren syndrome: functional 2004 May Previous studies have demonstrated that antibodies against muscarinic acetylcholine receptors (mAChRs) from exocrine glands, correlates with Sjögren syndrome (SS) in the majority of patients. The aim of the present investigation was to establish if serum IgG antibodies present in SS interacts with cerebral mAChRs. Results show that anti-cerebral IgG are present in the sera of 40% SS patients studied. Autoantibodies were able to interact with mAChRs of cerebral frontal cortex membranes inhibiting the [(3)H]QNB binding to its specific receptor. Moreover, tested by ELISA and dot blot they recognized the synthetic peptides corresponding to the second extracellular loop of human M(1) and M(3) mAChR. In addition, the corresponding affinity-purified anti-M(1) and anti-M(3) peptide IgGs displayed an agonistic activity, stimulating phosphoinositide hydrolysis. The results support the notion that serum IgG autoantibodies in SS patients target cerebral mAChRs may have some role in the pathogenesis of higher cognitive dysfunction present in SS patients.
15188366 Abnormalities in peripheral B cell memory of patients with primary Sjögren's syndrome. 2004 Jun OBJECTIVE: To delineate disturbances in peripheral B cell memory in primary Sjögren's syndrome (SS). METHODS: Isotype-specific immunoglobulin (Ig) heavy-chain transcripts were analyzed in single-sorted CD19+,CD27- naive and CD19+,CD27+ memory B cells from patients with primary SS and normal healthy control subjects. RESULTS: A significantly higher frequency of B cells expressing mu-, alpha-, and/or gamma-chain transcripts were found in patients with primary SS compared with controls (58.0% versus 14.3%; P < 0.0001). Notably, 30.5% of individual B cells (for primary SS, 38.7%; for controls, 12.7% [P < 0.0001]) simultaneously expressed transcripts for different Ig heavy-chain isotypes using identical V(H)-D-J(H) rearrangements. However, these cells lacked surface expression of more than one of the respective Ig heavy-chain isotypes as well as messenger RNA (mRNA) transcripts for 2 germinal center markers, activation-induced cytidine deaminase, and Bcl-6. In contrast with the findings in normal healthy controls, peripheral B cell memory in patients with primary SS was characterized by 1) circulating CD27+ B cells expressing heavily mutated Ig V(H) transcripts (mutational frequency 8.6% versus 4.3%; P < 0.0001), 2) significantly enhanced mutational frequencies of C mu transcripts (9.6% versus 2.5%; P < 0.0001), 3) a high proportion (61.2%) of CD27+ B cells expressing transcripts for multiple Ig heavy-chain isotypes, and 4) a CD27- memory-type B cell subpopulation expressing mutated C mu transcripts. CONCLUSION: Altogether, both B cell hyperactivity and striking abnormalities in peripheral B cell memory are indicated at the single-cell mRNA level in patients with primary SS. Detection of multiple Ig heavy-chain transcripts in peripheral CD19+,CD27+ memory B cells of patients with SS may represent the abnormal retention of pre-switch mRNA transcripts in circulating post-switch B cells.
15030576 Antibodies raised against the second extracellular loop of the human muscarinic M3 recepto 2004 Mar Functional antimuscarinic M3 receptor (M3R) autoantibodies have been shown to inhibit cholinergic neurotransmission at the postsynaptic level and appear to mediate parasympathetic dysfunction, including sicca symptoms in Sjögren's syndrome (SS). The precise epitope(s) involved in the inhibition of M3R-mediated cholinergic neurotransmission has not been defined. In this study, an active immunization approach to raise antibodies with functional activity against the second extracellular loop of the M3R was used and their functional properties were compared with those of human autoantibodies. Peptides corresponding to the second extracellular loop of the M3R were used as immunogens in rabbits, and antisera were tested for inhibition of carbachol-evoked colon smooth muscle contraction in parallel with immunoglobulin G from a patient with SS. Anti-M3R antibodies were affinity purified on a peptide representing a dominant functional epitope at the COOH terminus of the second extracellular loop of the M3R and tested for concentration-dependent inhibition. Experimentally raised anti-M3R antibodies, like the human autoantibodies, showed concentration-dependent and noncompetitive inhibition of carbachol-evoked colon contractions. Inhibitory activity was detected by functional assays at concentrations as low as 3 ng/ml, which was below the threshold of detection of antibody by peptide enzyme-linked immunosorbent assay. It is concluded that the experimentally raised anti-M3R antibodies share the functional properties of autoantibodies in patients with SS.
12367562 Cardiac 5-HT(4) serotoninergic receptors, 52kD SSA/Ro and autoimmune-associated congenital 2002 Aug It was recently reported that sera from patients with systemic lupus erythematosus contain antibodies reactive with the second extracellular loop of the serotoninergic 5-HT(4) receptor expressed in the human heart. This antibody response was associated with antibodies to 52kD SSA/Ro, a reactivity prevalent in mothers of children with congenital heart block (CHB). The current study was undertaken to determine whether the 5-HT(4) receptor is a target of the immune response in these mothers. Initial experiments demonstrated mRNA expression of the 5-HT(4) receptor in the human foetal atrium. Electrophysiologic studies established that human foetal atrial cells express functional 5-HT(4) receptors. Sera from 116 mothers enrolled in the Research Registry for Neonatal Lupus, whose children have CHB, were evaluated. Ninety-nine (85%) of these maternal sera contained antibodies to SSA/Ro, 84% of which were reactive with the 52kD SSA/Ro component by immunoblot. None of the 116 sera were reactive with the peptide spanning aa165-185 of the serotoninergic receptor. Rabbit antisera which recognized this peptide did not react with 52kD SSA/Ro or peptide aa365-382 in the C terminus. Although 5-HT(4) receptors are present and functional in the human foetal heart, maternal antibodies to the 5-HT(4) receptor are not associated with the development of CHB.
11989843 Diagnosis of a gastric mucosa-associated lymphoid tissue lymphoma by endoscopic ultrasonog 2002 Apr We report the case of a 32-year-old man with a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland associated with Sjögren syndrome. He underwent an upper endoscopy as part of the screening of a gastric localization which showed a diffuse non-specific gastritis. However, endoscopic ultrasonography (EUS) evidenced a focal wall thickening of the vertical portion of the smaller curvature. EUS-guided biopsies of this area disclosed a MALT lymphoma, whereas biopsies under endoscopy concluded to mild chronic gastritis. The search for Helicobacter pylori infection remained negative. Four months after treatment with anti-CD20 antibodies, EUS showed a diminution of the abnormal thickening of the second layer. Regression was confirmed histologically on new EUS-guided biopsies. MALT lymphoma is usually considered a localized disease; however, dissemination is probably more frequent than initially believed. Our case reflects the importance of a systematic screening for a gastric localization in patients with MALT lymphoma of the salivary glands. In this situation, association to autoimmune disease such as Sjögren syndrome is more likely to explain the gastric location than infection with H. pylori. Endoscopic ultrasonography has a major impact for the staging of gastric MALT lymphoma, but may also help diagnose focal infiltration by the disease.
15470032 E2f1 mutation induces early onset of diabetes and Sjögren's syndrome in nonobese diabetic 2004 Oct 15 E2f1 is an important regulator of T cell proliferation, differentiation, and apoptosis that controls the transcription of a group of genes that are normally regulated at the G1 to S phase transition in the cell cycle. Insulin-dependent diabetes mellitus (IDDM) and Sjogren's syndrome (SS) are highly regulated autoimmune diseases that develop spontaneously in NOD mice. The aim of the present in vivo study was to explore the functional importance of the E2f1 molecule in IDDM and SS, in the context of whole animal physiology and pathophysiology, using E2f1-deficient NOD mice. For the experiment, we produced NOD mice homozygous for a nonfunctional E2f1 allele onto a NOD background. E2f1-deficient NOD mice developed an early and increased onset of diabetes as compared with their littermates. These mice also exhibited a defect in T lymphocyte development, leading to excessive numbers of mature T cells (CD4+ and CD8+), due to a maturation stage-specific defect in the apoptosis of thymocytes and peripheral T cells. We also found that they also exhibited a more rapid and increased entry into the S phase following antigenic stimulation of spleen cells and thymocytes in vitro. Furthermore, E2f1-deficient mice showed a profound decrease of immunoregulatory CD4+CD25+ T cells, while the spleen cells of NOD mice lacking E2f1 showed a significant increase of the proinflammatory cytokine IFN-gamma following antigenic stimulation in vitro. Consistent with these observations, E2f1 homozygous mutant NOD mice were highly predisposed to the development of IDDM and SS.
14740974 Matched-control retrospective study of the acute and late complications in patients with c 2003 Nov BACKGROUND: Controversy surrounds the potential complication rate of patients with collagen vascular diseases (CVD) after radiation. We assess the acute and late complications (based on Radiation Therapy Oncology Group criteria) by a matched-control retrospective study. PATIRNTS/METHODS: The charts of 12,000 patients treated with radiation therapy at the University of Louisville from 1982 to 2001 were reviewed for CVD. A total of 38 patients with documented CVD were compared with a matched-control group of 38 patients without CVD. Median follow-up for patients with CVD was 35 months. The patients were matched on the basis of site treated, age, dose, date of treatment, sex, treatment goal, follow-up, tumor site and histology, therapeutic technique, and general treatment method. The patients with CVD included 21 patients with systemic lupus erythematosus (55%), two with scleroderma (5%), four with Raynaud's phenomena (11%), three with fibromyalgia (8%), three with polymyalgia rheumatica (8%), three with Sjögren's syndrome (8%), and two with polymyositis-dermatomyositis (5%). Twenty-nine patients received curative doses, and nine patients received palliative doses. RESULTS: No difference was observed in the incidence of acute or late complications between the two groups. For CVD and matched-control patients receiving curative doses, the incidence of acute reaction for grade II was 49% versus 58% and for grade III was 7% versus 7%, respectively. The incidence of late reactions for patients with CVD and the matched control patients for grade I was 3% versus 7%, for grade II was 7% versus 3%, and for grade III was 7% versus 7%, respectively. The patients treated with palliation had a similar incidence of acute reaction in the CVD and the matched-control groups. No patients in the CVD or matched-control group had fatal complications. Only patients with scleroderma had a slight increase in acute and late complications. CONCLUSION: This is the largest matched-control study thus far in the literature. In the comparison between the patients with CVD and the matched-control patients, there was no significant difference in the incidence of acute or late complication. However, there was a higher incidence of radiation complications in patients with scleroderma. Importantly, no fatal complication was noted in any of the patients with CVD.
12951278 A rare case of autoimmune polyglandular syndrome type 3. 2003 Aug A 57-year-old female was admitted to our hospital suffering from a lower lip tumor, small ulcers in the arms and alopecia of the head. Because she had type 2 diabetes mellitus (DM) for the past 3 years, she was referred to our department of internal medicine for its treatment. Her endogenous insulin secretion was much decreased despite the short duration of diabetes. Glutamic acid decarboxylase antibodies (GADA) and islet cell antibodies (ICA) were both positive. Therefore, she was diagnosed as having slowly progressive form of type 1 DM. Type 1 DM is sometimes complicated with autoimmune disorders. After further examinations, she was diagnosed as having Sjögren's syndrome, Graves' disease and autoimmune neutropenia (AIN). According to the histological examinations of the lip tumor and peripheral site of the skin ulcer, the patient was diagnosed as having carcinoma spinocellulare and chronic cutaneous lupus erythematosus. The examination also showed positive anti-intrinsic factor and anti-ribonucleoprotein (RNP) antibodies. She is a rare case of an autoimmune polyglandullar syndrome (APS) type 3 simultaneously manifesting these seven diseases with multiple autoimmune antibodies.
12888052 Abnormal protein profiles in tears with dry eye syndrome. 2003 Aug PURPOSE: To verify the hypothesis that protein concentrations, such as lactoferrin, epidermal growth factor (EGF), and aquaporin 5 (AQP5), in tears are abnormal in patients with dry eye. DESIGN: Prospective case-control study. METHODS: One hundred three dry eye patients were divided into three groups: dry eye not associated with the Sjögren syndrome (non-SS; n = 71), Sjögren syndrome (SS; n = 23), and Stevens-Johnson syndrome (SJS; n = 9). Sixteen normal control subjects were also checked. The concentrations of lactoerrin, EGF, and AQP5 were measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of lactoferrin was significantly decreased in tears of non-SS (P =.0001), SS (P =.00005), and SJS (P =.0006) patients compared with control subjects. The concentration of EGF was significantly decreased in non-SS (P =.0005), SS (P =.00002), and SJS (P =.0001) patients compared with control subjects. The concentration of AQP5 was significantly increased in tears of only SS patients (P =.01) compared with control subjects and increased in tears of only SS patients compared with non-SS patients (P =.007). CONCLUSIONS: The decrease in both lactoferrin and EGF was found not only in SS patients but also in non-SS patients, indicating that tear components in dry eyes differ in their quantity and quality. Quantification of AQP5 increased only in SS patients, suggesting that AQP5 protein leaks into the tears when acinar cells of the lacrimal gland are damaged by lymphocytic infiltration.
12714620 Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft- 2003 May PURPOSE: To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS: Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical analysis of lacrimal gland biopsy specimens obtained from nine patients with cGVHD and five with Sjögren's syndrome (SS). The regions of interest were further assessed by transmission electron microscopy. RESULTS: CD4(+) and CD8(+) T cells were mainly detected in the periductal areas of the glands of patients with cGVHD, but were distributed throughout the acinar areas in patients with SS. In the periductal areas of patients with cGVHD, a subpopulation of CD4(+) and CD8(+) T cells expressed the activation marker CD154. In addition, CD4(+) and CD8(+) T cells were colocalized with mononuclear infiltrates and stromal fibroblasts expressing the full component of surface molecules necessary for antigen presentation, including HLA-DR, CD54, CD40, CD80, and CD86. Electron microscopy revealed activated fibroblasts that embraced lymphocytes and macrophages with their processes. Also, there were more CD8(+) T cells in the glandular epithelia of patients with cGVHD than in those with SS. Intraepithelial T cells were attached to epithelial cells by several primitive contacts and colocalized with dead cells. CONCLUSIONS: The results strongly suggest that CD4(+) and CD8(+) T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.
12533681 Apoptosis and apoptosis-related molecules in the submandibular gland of the nonobese diabe 2003 Jan Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the exocrine glands. Pathogenetic aspects of the disease can be studied in the nonobese diabetic (NOD) mouse strain, a spontaneous model for Sjögren's syndrome. Apoptosis may play a role in the initation phase and in the effector phase of autoimmune diseases. Here, we have examined the role of apoptosis in the development of sialoadenitis in the NOD mouse. Apoptotic cells and the expression of apoptosis-related molecules were studied in submandibular glands (SMG) of NOD and NOD-scid mice before and after the onset of sialoadenitis. Numbers of apoptotic cells were not increased as compared with control mice, at any age. By immunohistochemistry, we demonstrated increased expression of Fas, Fas ligand (FasL), and bcl-2 on SMG epithelial cells of NOD and NOD-scid mice, as early as 3 days of age. mRNA expression of Fas and FasL was also examined in SMG by RQ-PCR. Low-level expression of Fas and FasL mRNA was observed in all mouse strains, from 1 day of age onward. We conclude that increased protein expression of Fas and FasL on SMG epithelial cells of NOD and NOD-scid mice probably indicates a genetically programmed abnormality in these cells that may form a trigger for the development of sialoadenitis in NOD mice. Because increased numbers of apoptotic cells were not observed, a role for actual apoptosis in the initiation or effector phase of sialoadenitis in the NOD mouse is unlikely.
15056403 Nasal manifestations of systemic illnesses. 2004 May This article is focused on the nasal and sinusal manifestations of systemic diseases, such as infections, immunodeficiencies, chronic multisystemic disorders, inflammatory bowel diseases, deposition diseases, hematologic diseases, respiratory diseases, and smell and taste disorders. A concise review of some of the systemic diseases that commonly present complaints in the nose and paranasal sinuses, including their prevalence, sinonasal manifestations, diagnosis, and treatment, is provided.
14735010 Thoracic manifestations of the less common collagen diseases. A pictorial essay. 2003 Nov Systemic autoimmune diseases include different forms of vasculitides and collagen diseases. Among collagen diseases, the rarer entities include: Sjögren syndrome, dermatopolymyositis, ankylosing spondylitis, relapsing polychondritis and mixed connective tissue disorders. The diagnosis of these entities requires an integrated multidisciplinary approach. The radiological findings of collagen diseases are well known; however, the introduction of HRCT studies provides additional information and enable an early diagnosis. The more common thoracic manifestations of collagen diseases include interstitial pneumonia (usual, nonspecific and lymphocytic), bronchiolitis obliterans organizing pneumonia (BOOP), airway diseases (bronchiectasis, obliterative and constrictive bronchiolitis, follicular bronchiolitis), pleural abnormalities, diaphragmatic dysfunction, apical fibrosis. The aim of this pictorial essay is to present the main radiological and HRCT patterns related to the less common collagen diseases.