ABSTRACT
Sjögren syndrome (SS), a chronic autoimmune disorder causing dry mouth, adversely affects the overall oral health in patients. Activation of innate immune responses and excessive production of type I interferons (IFNs) play a critical role in the pathogenesis of this disorder. Recognition of nucleic acids by cytosolic nucleic acid sensors is a major trigger for the induction of type I IFNs. Upon activation, cytosolic DNA sensors can interact with the stimulator of interferon genes (STING) protein, and activation of STING causes increased expression of type I IFNs. The role of STING activation in SS is not known. In this study, to investigate whether the cytosolic DNA sensing pathway influences SS development, female C57BL/6 mice were injected with a STING agonist, dimethylxanthenone-4-acetic acid (DMXAA). Salivary glands (SGs) were studied for gene expression and inflammatory cell infiltration. SG function was evaluated by measuring pilocarpine-induced salivation. Sera were analyzed for cytokines and autoantibodies. Primary SG cells were used to study the expression and activation of STING. Our data show that systemic DMXAA treatment rapidly induced the expression of Ifnb1, Il6, and Tnfa in the SGs, and these cytokines were also elevated in circulation. In contrast, increased Ifng gene expression was dominantly detected in the SGs. The type I innate lymphoid cells present within the SGs were the major source of IFN-γ, and their numbers increased significantly within 3 d of treatment. STING expression in SGs was mainly observed in ductal and interstitial cells. In primary SG cells, DMXAA activated STING and induced IFN-ß production. The DMXAA-treated mice developed autoantibodies, sialoadenitis, and glandular hypofunction. Our study demonstrates that activation of the STING pathway holds the potential to initiate SS. Thus, apart from viral infections, conditions that cause cellular perturbations and accumulation of host DNA within the cytosol should also be considered as possible triggers for SS.
Subject(s)
Membrane Proteins/genetics , Sjogren's Syndrome/genetics , Animals , Autoantibodies/blood , Cytokines/blood , Cytosol/immunology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression , Immunity, Innate , Interferon-gamma/genetics , Interferons/immunology , Mice , Mice, Inbred C57BL , Real-Time Polymerase Chain Reaction , Saliva/chemistry , Signal Transduction , Sjogren's Syndrome/immunology , XanthonesABSTRACT
Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF/SF is synthesized by prostate stromal cells (PrSC). Met is also expressed in localized and metastatic prostate cancers. Our results show that PrECs in in vitro culture maintain expression of Met at a level comparable to DU145 cancer cell expression. HGF/SF secreted by PrSC stimulates tyrosine phosphorylation of the Met receptor. In normal PrEC, HGF/SF causes growth inhibition, sustained phosphorylation of mitogen-activated protein kinase, and increased CK18 expression consistent with cell differentiation. In contrast, HGF/SF significantly stimulates the proliferation of DU145 prostate cancer cells. HGF/SF in the conditioned medium of PrSC specifically induces migration of both normal and malignant prostate epithelial cells through MatriGel-coated Transwell filters. HGF/SF depletion reduces cell migration by approximately 50%. The response of PrEC is specific for HGF/SF since the other growth factors tested do not significantly affect growth or migration of PrECs. These results support the in vivo importance of the prostate stroma and specifically of HGF/SF as a unique stromal derived factor in the development and progression of prostate cancer.
Subject(s)
Epithelial Cells/drug effects , Hepatocyte Growth Factor/genetics , Hepatocyte Growth Factor/pharmacology , Prostate/cytology , Prostatic Neoplasms/pathology , Animals , Cell Differentiation , Cell Division/drug effects , Cell Line , Cell Movement/drug effects , Cell Movement/physiology , Cells, Cultured , Collagen , Culture Media, Conditioned , Desmin/analysis , Desmin/genetics , Dogs , Drug Combinations , Epithelial Cells/cytology , Epithelial Cells/pathology , Hepatocyte Growth Factor/analysis , Humans , Immunohistochemistry , Keratins/analysis , Keratins/genetics , Laminin , Male , Prostate/drug effects , Prostate/pathology , Proteoglycans , Receptors, Androgen/analysis , Receptors, Androgen/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Vimentin/analysis , Vimentin/geneticsABSTRACT
The incidence of contralateral patent processus vaginalis (CPPV) is >50% in infants with clinical unilateral inguinal hernia (CUIH) and decreases only slowly with advancing age. Laparoscopy through the hernia sac (transinguinal laparoscopy) to detect suspected CPPV is a safe and efficient way to minimize routine contralateral inguinal exploration, but can be technically difficult. We used flexible urologic instruments and/or angled cystoscopic lenses to make transinguinal laparoscopy easier. Over a 3-year period, 37 patients (34 boys and 3 girls) ranging in age from 4 months to 12 years (mean age 59 months) with CUIH underwent ipsilateral groin exploration and diagnostic transinguinal laparoscopy. Laparoscopy was performed with flexible 17F cystoscopes (26 cases), flexible 9F ureteroscopes (2 cases), and rigid 70 degrees cystoscope lenses (9 cases). We detected eight CPPV (22%) in our series of 20 right and 17 left inguinal hernias, in a mean transinguinal laparoscopy time of 4.5 minutes. At 26-month mean follow-up, no patient whose contralateral inguinal ring was deemed closed had developed a hernia. Flexible fiberoptic urologic scopes and/or angled cystoscope lenses make transinguinal laparoscopy easy and efficacious in the pediatric population. Our series represents the longest longitudinal study of transinguinal laparoscopy for the diagnosis of CPPV.
Subject(s)
Diagnostic Techniques, Urological/instrumentation , Hernia, Inguinal/diagnosis , Laparoscopy/methods , Child , Child, Preschool , Diagnostic Techniques, Urological/trends , False Positive Reactions , Female , Humans , Infant , Inguinal Canal/abnormalities , Laparoscopes , Longitudinal Studies , Male , Sensitivity and SpecificityABSTRACT
An approximation variant of the 1-compartment model and its clinical application in routine work are described. It is demonstrated how quantity and distribution of the dialyses, clearance and duration of the dialysis are to be chosen in order to obtain in a patient a course of the urea concentration striven for. A probable residual dialysis is taken into consideration. By this means an adaptation of the management of dialysis to the protein balance of the patient and to the effect of the dialysis with regard to easily dialysable substances is possible. The system demonstrated stood the test in clinical routine work. It is simple in its application, since the connections can be brought in easily legible graphs. Decisions in practice on duration of the dialysis, type of dialyzer and frequency of dialysis get a quantifiable basis.
Subject(s)
Blood Urea Nitrogen , Kidney Failure, Chronic/therapy , Renal Dialysis , Glomerular Filtration Rate , Humans , Kidney Failure, Chronic/blood , KineticsABSTRACT
An equipment for the continuous recording of the oxygen consumption and other parameters in the awake rabbit is presented. Construction, function, advantages, and failings were described. More than 300 successful animal experiments were carried out by means of this equipment till now. It is characterized by a clear structure and a simple operation and has a stable function. Important indications are the course and the therapy of the shock, the energy transformation in the postoperative respectively the posttraumatic phase, and the influence of drugs on the metabolism.
Subject(s)
Oxygen Consumption , Animals , Carbon Dioxide/analysis , Energy Metabolism , Male , Methods , Rabbits , TechnologySubject(s)
Skin Transplantation , Tissue Banks , Tissue Preservation/methods , Freezing , Humans , NitrogenABSTRACT
A technically simple method for the continuous recording of the arterial blood pressure in the conscious rabbit is described. For the placement of the catheter it is not necessary to perform a temporally expensive preparation. The median auricular artery of the animal can be used repeatedly above all. In case the arterial mean pressure is needful as a control mechanism then this method is recommended especially.
Subject(s)
Blood Pressure Determination/veterinary , Rabbits/physiology , Animals , Animals, Laboratory , Arteries , Blood Pressure Determination/methods , Catheterization/veterinary , Ear, External/blood supplyABSTRACT
Regional function parameters under myocardial ischemia are frequently clearly changed when the parameters as the stroke volume, cardiac output, ejection fraction and the like are still unchanged by a compensation mechanism. Length changes can be measured regionally and phasically by means of a mercury wire strain gauge. The active shortening during the ejection time in relation to the total length change in this region is a possibility for the registration of the relative systolic shortening (delta LS%). Changes will be quantified still clearer and earlier if in the x-y display a vector representation of the regional displacements with the pressure in the left ventricle takes place. The plane of this vector decreased already a few seconds after the coronary occlusion. This is therefore a special early change in ischemia. The important for the estimation of therapeutic measures and other indirect measuring methods is accentuated.
Subject(s)
Coronary Disease/physiopathology , Vectorcardiography , Animals , Aorta , Blood Pressure , Heart Ventricles , Myocardial Contraction , SwineABSTRACT
The relatively rare complications developing under local anaesthesia may be due to various causes. The possibilities of the development of accidents under local anaesthesia are outlined; and prophylactic and therapeutic measures are deduced. A schematic premedication cannot prevent the development of complications with a sufficient degree of certainty; for instance, in certain cases the administration of atropine alone will still worsen the course of a complication. On the contrary, an individual premedication should be aimed at, especially in risk patients; the dosage must take into consideration all important factors. Consequently, atropine is of less importance than, for example, psychopharmaca and beta-receptor blockers.
Subject(s)
Anesthesia, Dental/adverse effects , Adrenergic beta-Antagonists/therapeutic use , Anesthesia, Local/adverse effects , Humans , Hypertension/complications , Psychotropic Drugs/therapeutic use , Shock, Cardiogenic/prevention & control , Stress, Psychological , Syncope/prevention & controlABSTRACT
The ventricle function can be established by the vectorial description of left-ventricular pressure parameters or flow sizes, respectively. The vector diagrammes result from the momentaneous pressure within the ventricle on the X-axis and the differentiated pressure curve or the aortic flow, respectively, on the Y-axis. Well surveyable from the vector loop received (LVP/dp/dt) are established dp/dtmax, dp/dtmin, LVPmax, LVEDP as well as the tg of the pressure increase speed or the pressure decrease speed, respectively, pro developed pressure. By way of example medicamentous changes of the vector diagrammes were induced and the parameters mentioned established. The vectorial demonstration of the left-ventricular haemodynamics seems to give additional informations concerning the phase of centraction and relaxation
