[...]... targeted to mammary epithelial SCs The first evidence to support the notion of mammary SCs came from murine transplantation experiments Mammary gland tissue was removed from a donor mouse and transplanted into the cleared mammary fat pad of a recipient mouse, regenerating a fully functional mammary gland (Deome et al 1959) More recently, transplantation of mammary epithelia marked with mouse mammary. .. inhibitory factor is able to modulate the Wnt/β- Progesterone and Wnt Signalling 13 Fig 2a, b The Wnt/β-catenin signalling pathway a In mammary epithelium, progesterone (Pg) binds to its receptor (PR) within the cell nucleus Wnt proteins are in turn expressed, activated and secreted from the cell These secreted extracellular Wnt proteins are then able to bind to the transmembrane receptor Frizzled and. .. cells from this subpopulation had the ability to produce the normal heterogeneous structure of the gland, suggesting that these cell markers are not sufficient to completely mark the SC (Shackleton et al 2006) The subpopulation can be further enriched using a CD49f+ sort with 1 in 20 R Lamb, H Harrison, R.B Clarke 8 mouse mammary cells from this population having the ability to regenerate the entire gland. .. that the dye Hoechst 33342 is toxic to cells; perhaps cells that can efflux the dye are able to form mammary glands and mammospheres simply because they are left unharmed when compared to the cells which are unable to efflux the dye This method, therefore, may not be the most suitable for the identification of mammary SCs (Smalley and Clarke 2005) 7 Cell Surface Markers A more appropriate method may be the. .. through the Wnt pathway to increase SC self-renewal 2 Mammary Gland Development Mammary gland development begins during embryogenesis, with the formation of a rudimentary ductal system and remains virtually unaltered throughout childhood (Naccarato et al 2000) During puberty, hormonal changes induce the formation of networks of epithelial ducts which grow outwards from the nipple and divide into primary and. .. receptors and low-density lipoprotein receptor protein 5/6 (LRP5/6) (Bejsovec 2005; Bhanot et al 1996) Binding of Wnt to Frizzled receptor results in the phosphorylation of the cytoplasmic mediator Dishevelled, and the inhibition of the multifunctional serine/ threonine kinase GSK3β (Doble and Woodgett 2003) When GSK3β is inactive, β-catenin accumulates within the cytoplasm and translocates to the nucleus... observed with the use of exogenous ovarian hormones in the form of the oral contraceptive pill or hormone replacement therapy (Clemmons and Gross 2001; Travis and Key 2003) Ovarian hormones have been shown to exert their effects through ligand-activated steroid receptors in the mammary epithelium Approximately 10%–15% of the cells within the epithelium coexpress oestrogen receptor alpha (ERα) and progesterone... be detected from the early stages of embryonic mammary development The Pituitary Gland and Hypothalamus The Pituitary Gland and Hypothalamus Bởi: OpenStaxCollege The hypothalamus–pituitary complex can be thought of as the “command center” of the endocrine system This complex secretes several hormones that directly produce responses in target tissues, as well as hormones that regulate the synthesis and secretion of hormones of other glands In addition, the hypothalamus–pituitary complex coordinates the messages of the endocrine and nervous systems In many cases, a stimulus received by the nervous system must pass through the hypothalamus–pituitary complex to be translated into hormones that can initiate a response The hypothalamus is a structure of the diencephalon of the brain located anterior and inferior to the thalamus ([link]) It has both neural and endocrine functions, producing and secreting many hormones In addition, the hypothalamus is anatomically and functionally related to the pituitary gland (or hypophysis), a bean-sized organ suspended from it by a stem called the infundibulum (or pituitary stalk) The pituitary gland is cradled within the sellaturcica of the sphenoid bone of the skull It consists of two lobes that arise from distinct parts of embryonic tissue: the posterior pituitary (neurohypophysis) is neural tissue, whereas the anterior pituitary (also known as the adenohypophysis) is glandular tissue that develops from the primitive digestive tract The hormones secreted by the posterior and anterior pituitary, and the intermediate zone between the lobes are summarized in [link] 1/12 The Pituitary Gland and Hypothalamus Hypothalamus–Pituitary Complex The hypothalamus region lies inferior and anterior to the thalamus It connects to the pituitary gland by the stalk-like infundibulum The pituitary gland consists of an anterior and posterior lobe, with each lobe secreting different hormones in response to signals from the hypothalamus Pituitary Hormones Pituitary lobe Associated hormones Chemical class Effect Anterior Growth hormone (GH) Protein Promotes growth of body tissues Anterior Prolactin (PRL) Peptide Promotes milk production from mammary glands Anterior Thyroid-stimulating hormone (TSH) Glycoprotein Stimulates thyroid hormone release from thyroid Anterior Adrenocorticotropic hormone (ACTH) Peptide Stimulates hormone release by adrenal cortex Anterior Follicle-stimulating hormone (FSH) Glycoprotein Stimulates gamete production in gonads Anterior Luteinizing hormone (LH) Glycoprotein Stimulates androgen production by gonads Posterior Antidiuretic hormone (ADH) Peptide Stimulates water reabsorption by kidneys 2/12 The Pituitary Gland and Hypothalamus Pituitary Hormones Pituitary lobe Associated hormones Chemical class Effect Posterior Oxytocin Peptide Stimulates uterine contractions during childbirth Intermediate Melanocyte-stimulating Peptide zone hormone Stimulates melanin formation in melanocytes Posterior Pituitary The posterior pituitary is actually an extension of the neurons of the paraventricular and supraoptic nuclei of the hypothalamus The cell bodies of these regions rest in the hypothalamus, but their axons descend as the hypothalamic–hypophyseal tract within the infundibulum, and end in axon terminals that comprise the posterior pituitary ([link]) Posterior Pituitary Neurosecretory cells in the hypothalamus release oxytocin (OT) or ADH into the posterior lobe of the pituitary gland These hormones are stored or released into the blood via the capillary plexus 3/12 The Pituitary Gland and Hypothalamus The posterior pituitary gland does not produce hormones, but rather stores and secretes hormones produced by the hypothalamus The paraventricular nuclei produce the hormone oxytocin, whereas the supraoptic nuclei produce ADH These hormones travel along the axons into storage sites in the axon terminals of the posterior pituitary In response to signals from the same hypothalamic neurons, the hormones are released from the axon terminals into the bloodstream Oxytocin When fetal development is complete, the peptide-derived hormone oxytocin (tocia- = “childbirth”) stimulates uterine contractions and dilation of the cervix Throughout most of pregnancy, oxytocin hormone receptors are not expressed at high levels in the uterus Toward the end of pregnancy, the synthesis of oxytocin receptors in the uterus increases, and the smooth muscle cells of the uterus become more sensitive to its effects Oxytocin is continually released throughout childbirth through a positive feedback mechanism As noted earlier, oxytocin prompts uterine contractions that push the fetal head toward the cervix In response, cervical stretching stimulates additional oxytocin to be synthesized by the hypothalamus and released from the pituitary This increases the intensity and effectiveness of uterine contractions and prompts additional dilation of the cervix The feedback loop continues until birth Although the mother’s high blood levels of oxytocin begin to decrease immediately ...Open Access Available online http://arthritis-research.com/content/11/1/R18 Page 1 of 12 (page number not for citation purposes) Vol 11 No 1 Research article Impaired vascular responses to parasympathetic nerve stimulation and muscarinic receptor activation in the submandibular gland in nonobese diabetic mice Ellen Berggreen 1 , Krister Nyløkken 1 , Nicolas Delaleu 2 , Hamijeta Hajdaragic-Ibricevic 3 and Malin V Jonsson 4,5 1 Department of Biomedicine, Jonas Liesvei 91, Bergen 5009, Norway 2 Broegelmann Research Laboratory, Gade Institute, Haukeland Hospital, Bergen 5021, Norway 3 Ministry of Health, Amiri Dental Center, PO Box 472, Dasman 15455, Kuwait 4 Department of Medicine, Section for Rheumatology, Gade Institute, Haukeland Hospital, Bergen 5021, Norway 5 Section for Pathology, Gade Institute, Haukeland Hospital, Bergen 5021, Norway Corresponding author: Ellen Berggreen, ellen.berggreen@biomed.uib.no Received: 15 Aug 2008 Revisions requested: 12 Sep 2008 Revisions received: 22 Jan 2009 Accepted: 6 Feb 2009 Published: 6 Feb 2009 Arthritis Research & Therapy 2009, 11:R18 (doi:10.1186/ar2609) This article is online at: http://arthritis-research.com/content/11/1/R18 © 2009 Berggreen et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Decreased vascular responses to salivary gland stimulation are observed in Sjögren's syndrome patients. We investigate whether impaired vascular responses to parasympathetic stimulation and muscarinic receptor activation in salivary glands parallels hyposalivation in an experimental model for Sjögren's syndrome. Methods Blood flow responses in the salivary glands were measured by laser Doppler flowmeter. Muscarinic receptor activation was followed by saliva secretion measurements. Nitric oxide synthesis-mediated blood flow responses were studied after administration of a nitric oxide synthase inhibitor. Glandular autonomic nerves and muscarinic 3 receptor distributions were also investigated. Results Maximal blood flow responses to parasympathetic stimulation and muscarinic receptor activation were significantly lower in nonobese diabetic (NOD) mice compared with BALB/ c mice, coinciding with impaired saliva secretion in nonobese diabetic mice (P < 0.005). Nitric oxide synthase inhibitor had less effect on blood flow responses after parasympathetic nerve stimulation in nonobese diabetic mice compared with BALB/c mice (P < 0.02). In nonobese diabetic mice, salivary gland parasympathetic nerve fibres were absent in areas of focal infiltrates. Muscarinic 3 receptor might be localized in the blood vessel walls of salivary glands. Conclusions Impaired vasodilatation in response to parasympathetic nerve stimulation and muscarinic receptor activation may contribute to hyposalivation observed in nonobese diabetic mice. Reduced nitric oxide signalling after parasympathetic nerve stimulation may contribute in part to the impaired blood flow responses. The possibility of muscarinic 3 receptor in the vasculature supports the notion that muscarinic 3 receptor autoantibodies present in nonobese diabetic mice might impair the fluid transport required for salivation. Parasympathetic nerves were absent in areas of focal infiltrates, whereas a normal distribution was found within glandular epithelium. Trial registration The trial registration number for the present study is 79-04/BBB, given by the Norwegian State Commission for Laboratory Animals. Introduction Sjögren's syndrome (SS) is a systemic autoimmune disease mainly affecting the exocrine glands, resulting in severe impair- ment of saliva and tear production. The histopathological hall- marks of the disease are T-cell-dominated and B-cell- dominated Introduction Sjögren’s syndrome (SS) is a chronic inflammatory disease preferentially involving the lacrimal and salivary glands. Patients with SS are characterized by keratocon- junctivitis sicca and xerostomia. Although the cause of the disease is unknown, histopathologic findings suggest an essential role of lymphocytic infiltrates that accumulate in the affected glands. Exogenous antigens and autoantigens have been suggested as potential trig- gers of the immune response in the salivary glands in genetically and hormonally susceptible individuals [1,2]. Whereas glandular tissue destruction has been shown to be mediated by activated CD4 + T cells that home into the lacrimal gland [3], autoantibodies directed against Ro(SS-A) and La(SS-B) autoantigens as well as IgG (rheumatoid factor) are detectable in high titers in about 80–95% of sera from SS patients. This suggests an important role for autoantibodies in this disease [4]. Moreover, a 44-fold increased risk for the development of lymphoid malignancy, almost exclusive of B-cell origin, has been documented in SS, emphasizing the intimate role of activated proliferating B cells in this condition [5]. Whether B-cell activation is a primary cause or a sec- ondary effect in SS is not known. CDR = complementary determining regions; FACS = fluorescence-activated cell sorting; FR = framework regions; H & E, hematoxylin and eosin; PBS = phosphate-buffered saline; PCR = polymerase chain reaction; RF = rheumatoid factor; R/S ratio = replacement to silent ratio; SS = Sjögren’s syndrome; Th = T helper cells; Vκ = variable kappa chain gene; Vλ = variable lambda chain gene. Available online http://arthritis-research.com/4/4/R4 Research article Analysis of immunoglobulin light chain rearrangements in the salivary gland and blood of a patient with Sjögren’s syndrome Annett M Jacobi 1 , Arne Hansen 2 , Olaf Kaufmann 3 , Axel Pruss 4 , Gerd R Burmester 1 , Peter E Lipsky 5 and Thomas Dörner 1 1 Department of Internal Medicine/Rheumatology and Clinical Immunology, Charite University Hospital, Berlin, Germany 2 Outpatients’ Department, Charite University Hospital, Berlin, Germany 3 Institute of Pathology, Charite University Hospital, Berlin, Germany 4 Institute of Transfusion Medicine, Charite University Hospital, Berlin, Germany 5 NIAMS, National Institutes of Health, Bethesda, Maryland, USA Corresponding author: Thomas Dörner (e-mail: thomas.doerner@charite.de) Received: 19 February 2002 Revisions received: 7 May 2002 Accepted: 13 May 2002 Published: 11 June 2002 Arthritis Res 2002, 4:R4 © 2002 Jacobi et al., licensee BioMed Central Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913) Abstract Patients with Sjögren’s syndrome (SS) have characteristic lymphocytic infiltrates of the salivary glands. To determine whether the B cells accumulating in the salivary glands of SS patients represent a distinct population and to delineate their potential immunopathologic impact, individual B cells obtained from the parotid gland and from the peripheral blood were analyzed for immunglobulin light chain gene rearrangements by PCR amplification of genomic DNA. The productive immunglobulin light chain repertoire in the parotid gland of the SS patient was found to be restricted, showing a preferential usage of particular variable lambda chain genes (Vλ2E) and variable kappa chain genes (VκA27). Moreover, clonally related V L chain rearrangements were identified; namely, VκA27–Jκ5 and VκA19–Jκ2 in the parotid gland, and Vλ1C–Jλ3 in the parotid gland and the peripheral blood. Vκ and Vλ rearrangements from the parotid gland exhibited a significantly elevated mutational frequency compared with those from the peripheral blood (P < 0.001). Mutational analysis revealed a pattern of somatic hypermutation similar to that found in normal donors, and a comparable impact of selection of mutated rearrangements in both the peripheral blood and the parotid gland. These data indicate that there is biased usage of V BioMed Central Page 1 of 3 (page number not for citation purposes) Journal of Medical Case Reports Open Access Case report Direct spread of thyroid follicular carcinoma to the parotid gland and the internal jugular vein: a case report Ahmed Alzaraa* 1 , Jason Stone 2 , Glyn Williams 3 , Irfan Ahmed 1 and Mohammed Quraishi 1 Address: 1 Department of Otolaryngology, Doncaster Royal Infirmary, Doncaster, UK, 2 Department of Histopathology, Doncaster Royal Infirmary, Doncaster, UK and 3 Department of Radiology, Doncaster Royal Infirmary, Doncaster, UK Email: Ahmed Alzaraa* - ahmedwahabf@gmail.com; Jason Stone - jason.stone@dbh.nhs.uk; Glyn Williams - glynn.williams@dbh.nhs.uk; Irfan Ahmed - irfanuk@yahoo.co.uk; Mohammed Quraishi - shquraishi@hotmail.com * Corresponding author Abstract Introduction: The parotid gland and the great cervical veins are very rarely involved in a metastatic thyroid cancer. Case presentation: We report an interesting case of an unusual metastasis of a thyroid follicular carcinoma including the histopathological and radiological findings. A woman was seen in the otolaryngology clinic with a mass at the angle of the left side of her jaw. Clinical examination and investigations confirmed a thyroid follicular carcinoma with metastases to the parotid gland and the internal jugular vein. Conclusion: This is an educational case which highlights the importance of close communication between clinicians, histopathologists and radiologists to ensure that such rare cases are not missed. Introduction Thyroid carcinoma sometimes shows a microscopic vas- cular invasion, but gross angioinvasion with intraluminal thrombosis is extremely rare. Very few cases about metas- tasis of thyroid cancer to the internal jugular vein, and fewer cases about metastasis to the parotid gland have been separately reported. Our patient has both these organs involved by direct spread from a thyroid follicular carcinoma. Case presentation A 78-year-old woman was seen in the otolaryngology clinic in June 2006 with a painless swelling at the angle of the left side of her jaw which had been present for 9 months. The mass had slightly increased in size over this period. The patient had tinnitus but no other complaints. Her weight was stable. Clinical examination revealed a smooth, soft lesion in the tail of the left parotid gland. There was no cervical lymphadenopathy. The ears, nose and throat were normal and the facial nerve was intact. Ultrasound of the neck showed swellings in the left parotid gland and the left thyroid lobe. Fine needle aspi- ration (FNA) of the left parotid gland showed thyroid fol- licular cells. A magnetic resonance imaging (MRI) scan of the neck confirmed both soft tissue masses with extensive thrombosis of the left internal jugular vein contiguous with the primary tumour (Figure 1A and 1B). A computed tomography (CT) scan of the chest was normal. Subse- quent FNA of the left thyroid lobe and the internal jugular Published: 9 September 2008 Journal of Medical Case Reports 2008, 2:297 doi:10.1186/1752-1947-2-297 Received: 29 November 2007 Accepted: 9 September 2008 This article is available from: http://www.jmedicalcasereports.com/content/2/1/297 © 2008 Alzaraa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Journal of Medical Case Reports 2008, 2:297 http://www.jmedicalcasereports.com/content/2/1/297 Page 2 of 3 (page number not for citation purposes) vein (IJV) revealed thyroid follicular cells similar to those seen in the first FNA. The cells were positive for thyroglob- ulin and thyroid transcription factor 1 and negative for chromogranin and synaptophysin on immunohisto- chemistry, confirming the diagnosis of a thyroid follicular carcinoma (Figure CHAPTER 56 ENDOCRINE SYSTEM Disorders of the Pituitary Gland PG. 947 Acromeg aly (Hype rpituitaris m): A condition in which an over secretion of GH (gro wth hormone ) occurs after the epiphyses of the long bones have sealed Results of hyperplasia (increase in the number of cells) or a tumor of the anterior pituitary. S/S of Acromegaly S/S: coarse features, a huge lower jaw, thick lips, a thickened tongue, a bulging forehead, a bulbous nose, and feet (fig 56-1) The heart, liver, and spleen may be enlarged. Despite enlarged tissues, muscle weakness is common, and hypertrophied joints may become painful and stiff Osteoporosis of the spine and joint pain develop. Acromegaly Medical Management Treated by surgical removal of the pituitary gland or by radiation therapy with consequent destruction of the pituitary. Even if the disease is arrested successfully, physical changes are irreversible. If the tumor is removed or destroyed by radiation therapy, replacement therapy with thyroid hormone, corticosteroids, and sex hormones is necessary Simmond’s Disease (Panhypopituitarism) PG. 949 Simmond’s dis e as e is a rare disorder caused by destruction of the pituitary gland followed by an absence of pituitary hormonal activity. Events such as postpartum emboli, surgery, tumor, and TB can destroy pituitary function. S/S Simmond’s Disease The gonads and genitalia atrophy. S/s of hypothyroidism, hypoglycemia, and adrenal insufficiency are apparent. The client ages prematurely and becomes extremely cachectic. Medical Management Administration of substitute hormones for the glands that depend on the pituitary for stimulation. If untreated, the disease is fatal. Assess the client’s mental status, emotional state, energy level, and appetite. Diabetes Insipidus pg 950 An endocrine disorder that develops when there is insufficient antidiuretic hormone (ADH) from the posterior pituitary gland. Can be caused by head trauma that damages the pituitary and by primary or metastatic brain tumors. S/S Urine output for a 24 – hour period may be as high as 20 liters (20,000 mL) The urine is dilute, with a specific gravity of 1.002 or less. The excretion of urine cannot be controlled by limiting the intake of fluids The need for drinking and voiding frequently limits activities Weakness, dehydration, and weight loss develop. [...]... used to block the synthesis of thyroid hormones A corticosteroid may be given IV to replace depletion that results from overstimulation of the adrenals during the hypermetabolic state Thyrotoxic Crisis IV sodium iodide prevents the release of thyroid hormones by the thyroid gland Inderal, a beta blocker, reduces the effect of thyroid hormones on the cardiovascular system Supportive therapy includes... respects to those of hyperthyroidism The metabolic rate and physical and mental activity are SLOWED!! Lethargic, lacks energy, dozes frequently during the day, is forgetful, and has chronic headaches The face takes on a mask like unemotional expression, yet the client often is irritable S/S The tongue may be enlarged and the lips swollen, and there may be edema of the eyelids The temperature... and oxygen therapy Thyrotoxic Crisis Nurs ing Manag e me nt: Pt is ac ute ly ill!! Monitor V/S esp the temperature (may require measures other than antipyretics such as cooling blankets or the application of ice) Hypothyroidism pg 954 Occurs when the thyroid gland fails to secrete an adequate amount of thyroid hormones May originate within the thyroid (primary) or within the pituitary, in... hyponatremia is ... thyroid gland? 10/12 The Pituitary Gland and Hypothalamus Chapter Review The hypothalamus pituitary complex is located in the diencephalon of the brain The hypothalamus and the pituitary gland are.. .The Pituitary Gland and Hypothalamus Hypothalamus Pituitary Complex The hypothalamus region lies inferior and anterior to the thalamus It connects to the pituitary gland by the stalk-like... and contrast the anatomical relationship of the anterior and posterior lobes of the pituitary gland to the hypothalamus The anterior lobe of the pituitary gland is connected to the hypothalamus