Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinico-laboratory and radionuclide (radio-hepatography with 131I-rose bengal and liver scanning with 198Au colloid solution) investigation of liver function was performed in 110 patients with polycythemia vera during exacerbation, in 16 patients with symptomatic erythrocytosis (10--chronic pulmonary disease, 3--polycystic kidney, 2--obesity, 1--peptic ulcer), and in 11 patients with a polycythemic form of myelofibrosis. The results of the radionuclide method showed disturbed liver function in 51 (46.3%) patients with polycythemia, in 4 patients with myelofibrosis and in 3 with erythrocytosis which were characterized by a decrease in hepatocytic absorptive-excretory function and a decrease in the activity of the reticulo-histiocytic stroma. Liver changes depended on a stage of disease and were detected earlier than with the use of biochemical methods. As distinct from erythrocytes, one-type disorders were noted in the patients with myelofibrosis. Correlation in the lever of RP accumulation in the spleen, its sizes and stage of disease was established. Liver function returned to normal after cytostatic therapy in the patients with stage IIA polycythemia, partially IIB stage, during remission.
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PMID:[Radionuclide study of liver function in polycythemia vera and other types of polycythemia]. 282 15

In children with pancreatic disease, computed tomography (CT) has a primary role in the evaluation of pancreatitis, trauma, and malignancy. At CT, pancreatic abnormalities may manifest as pancreatic enlargement (tumor, acute pancreatitis), pancreatic atrophy (cystic fibrosis, chronic pancreatitis), cystic lesions (pseudocysts, congenital simple cysts, autosomal dominant polycystic kidney disease, von Hippel-Lindau disease, cystic fibrosis, cystic neoplasms), or fatty replacement (cystic fibrosis, Shwachman-Diamond syndrome, history of steroid therapy, Cushing syndrome, Johanson-Blizzard syndrome, obesity). CT is the best modality for evaluation of pancreatitis, allowing detection of pancreatic abnormalities as well as abnormal extrapancreatic fluid collections. In children who have undergone blunt abdominal trauma, CT has been shown to be the best initial imaging study, being more sensitive than ultrasound for detection of pancreatic injury. In neoplastic conditions, CT demonstrates the extent of disease, enables characterization of the tissue components of the tumor, and allows accurate posttreatment follow-up. Although the various diseases of the pancreas may have overlapping appearances at CT, the correct diagnosis can often be made on the basis of the CT findings in combination with the clinical history, laboratory data, and the patient's age.
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PMID:Pancreatic disease in children and young adults: evaluation with CT. 974 14

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by postaxial hexadactyly, obesity, mental retardation, pigmented retinopathy, hypogonadism, and renal disease. Morphological changes are present in all areas of the kidney, the renal medulla being the most frequently affected site. Cystic and dysplastic changes are prevalent. Seven children from five families were followed from birth through their 5th birthday. Serial renal sonography revealed a number of characteristic features. Bilateral renal enlargement and increased parenchymal echogenicity were present at birth. The usual corticomedullary differentiation was absent. Pyramids were either not seen or deformed. With high-resolution ultrasonography, small cysts were detected at the corticomedullary junction. After the 3rd month of life, there was a striking inversion of normal echogenicity, the inner medulla became more echogenic and was demarcated from the less-echogenic cortex. After 12 months, the kidney size regressed significantly. Fetal lobulation persisted in some patients. In conclusion, ultrasonography is a useful tool to evaluate the extent of renal lesions, but more importantly to differentiate bilateral polycystic kidney diseases in the newborn period.
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PMID:Early sonographic aspects of kidney morphology in Bardet-Biedl syndrome. 976 54

The recent identification in Chlamydomonas of the intraflagellar transport machinery that assembles cilia and flagella has triggered a renaissance of interest in these organelles that transcends studies on their well-characterized ability to move. New studies on several fronts have revealed that the machinery for flagellar assembly/disassembly is regulated by homologs of mitotic proteins, that cilia play essential roles in sensory transduction, and that mutations in cilia/basal body proteins are responsible for cilia-related human disorders from polycystic kidney disease to a syndrome associated with obesity, hypertension, and diabetes.
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PMID:Cilia and flagella revealed: from flagellar assembly in Chlamydomonas to human obesity disorders. 1518 71

Defects in cilia are associated with several human disorders, including Kartagener syndrome, polycystic kidney disease, nephronophthisis and hydrocephalus. We proposed that the pleiotropic phenotype of Bardet-Biedl syndrome (BBS), which encompasses retinal degeneration, truncal obesity, renal and limb malformations and developmental delay, is due to dysfunction of basal bodies and cilia. Here we show that individuals with BBS have partial or complete anosmia. To test whether this phenotype is caused by ciliary defects of olfactory sensory neurons, we examined mice with deletions of Bbs1 or Bbs4. Loss of function of either BBS protein affected the olfactory, but not the respiratory, epithelium, causing severe reduction of the ciliated border, disorganization of the dendritic microtubule network and trapping of olfactory ciliary proteins in dendrites and cell bodies. Our data indicate that BBS proteins have a role in the microtubule organization of mammalian ciliated cells and that anosmia might be a useful determinant of other pleiotropic disorders with a suspected ciliary involvement.
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PMID:Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. 1532 45

Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance. Therefore, elucidating the mechanisms that regulate GIP release is important. GIP is produced by K cells, a specific subtype of small intestinal enteroendocrine (EE) cell. Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo. We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells). Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells. In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling. Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD. Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity. Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion. Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release. Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself. These results strongly suggest that K cells in vivo independently respond to neuronal vs. nutritional stimuli via two distinct signaling pathways.
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PMID:Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells. 1538 72

Biologists have long known that humans experience their environment through cilia. Light, odorant, and sound perception depend on these microtubule-filled, complex organelles present on cells in primary sensory tissues. Recently, discoveries on the mechanism of assembly of cilia (flagella) in the lowly, biflagellated, eucaryotic green alga Chlamydomonas have triggered a renaissance of interest in the organelles along with a recognition of their key sensory roles in nonsensory tissues. Chlamydomonas researchers uncovered an entirely new set of cellular machinery essential for transporting the protein components of cilia and flagella in all ciliated/flagellated eukaryotic cells between their site of synthesis in the cell body and their site of assembly at the tip of the flagellum (intraflagellar transport: IFT). Prompted by the surprising observations that disruption of IFT genes in mice led to polycystic kidney disease (PKD) and that PKD proteins are present on the sensory cilia of Caenorhabditis elegans, researchers have made a direct connection between PKD and cilia. At least five (and possibly all) of the seven identified human genes disrupted in PKD and a related disorder nephronophthisis encode proteins expressed in the primary cilia that project into the lumen from the epithelial cells that line renal tubules. Moreover, the renal cilia are flow sensors and at least two of the PKD genes encode ciliary transmembrane proteins essential for mechanosensation. Although their roles have not yet been as clearly identified, cilia also are at the center of a rare human disorder, Bardet-Biedl syndrome (BBS), in which patients exhibit phenotypes of common human diseases, including obesity and increased incidence of hypertension and diabetes. Five of the eight known BBS genes encode basal body or cilia proteins in mice or humans, and homologues of two of the remaining genes are present in basal bodies/cilia of model organisms. Here we briefly describe the biology of cilia and flagella, we outline how studies on model organisms have led to our current understanding of the roles of these organelles and their proteins in health and disease, and we highlight the notion that the primary cilia present on cells throughout the body, even those on brain neurons, may be essential for as yet undiscovered cilium-generated signaling functions.
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PMID:Cilium-generated signaling and cilia-related disorders. 1572 88

ADP-ribosylation factor-like 3 (Arl3) is a member of a small subfamily of G-proteins involved in membrane-associated vesicular and intracellular trafficking processes. Genetic studies in Leishmania have shown that the Arl3 homolog is essential for flagellum biogenesis. Mutations in a related human family member, Arl6, result in Bardet-Biedl syndrome in humans, which is characterized by genital, renal, and retinal abnormalities, obesity, and learning deficits. As part of our large-scale phenotypic screen, mice deficient for the Arl3 gene were generated and analyzed. Arl3 (-/-) mice were born at a sub-Mendelian ratio, were small and sickly, and had markedly swollen abdomens. These mutants failed to thrive, and all died by 3 weeks of age. The (-/-) mice exhibited abnormal development of renal, hepatic, and pancreatic epithelial tubule structures, which is characteristic of the renal-hepatic-pancreatic dysplasia found in autosomal recessive polycystic kidney disease. Absence of Arl3 was associated with abnormal epithelial cell proliferation and cyst formation. Moreover, mice lacking Arl3 exhibited photoreceptor degeneration as early as postnatal day 14. These results are the first to implicate Arl3 in a ciliary disease affecting the kidney, biliary tract, pancreas, and retina.
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PMID:ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor development. 1656 2

Cilia are microtubule-based organelles that project like antennae from the surface of most cells in the body. Motile cilia move fluid past cells, for example mucus in the airway. Non-motile primary cilia, however, transduce a multitude of sensory stimuli, including chemical concentrations of growth factors, hormones, odorants, and developmental morphogens, as well as osmolarity, light intensity, and fluid flow. Cilia have evolved a complex ultrastructure to accommodate these diverse functions, and an extensive molecular machinery has developed to support the assembly of these organelles. Defects in the cilia themselves, or the machinery required to assemble them, lead to a broad spectrum of human disease symptoms, including polycystic kidney disease, nephronophthisis, hydrocephalus, polydactyly, situs inversus, retinal degeneration, and obesity. While these diseases highlight the pivotal roles of cilia in physiology and development, the mechanistic link between cilia, physiology, and disease remains unclear.
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PMID:Cilia: tuning in to the cell's antenna. 1689 May 22

Aquaporins (AQPs) are a family of small hydrophobic, integral membrane proteins that are expressed in all living organisms and play critical roles in controlling the water flow into and out of cells. So far, 13 different AQPs have been identified in mammals (AQP 0-12). AQPs have recently been implicated in various diseases such as cancer, cataract, brain oedema, gallstone disease and nephrogenic diabetes insipidus, as well as in the development of obesity and polycystic kidney disease. Interfering with the expression of AQPs will undoubtedly have therapeutic applications. Hence, in this review, the authors look at each AQP and its association with various pathological conditions in humans and demonstrate that they form potential targets for the treatment of such diseases.
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PMID:Aquaporins: a promising target for drug development. 1710 75


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