Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of specific morphogens is well established in the determination of body plans in development. A variety of morphogens have been identified; others are suspected. Pathways have been delineated. In complex tissues, the ability to maintain fidelity of microarchitectural structure is crucial. Microarchitecture is a consequence of relationships among cells, not a function of single cells. Epithelial layers, in particular, are able to maintain their microarchitecture with remarkable accuracy over many decades despite recurrent damage, regular cell turnover, and complexity of structure. Nonetheless, metaplasia and transdifferentiation (change in tissue structure without cell dysplasia) do occur, suggesting that there is the possibility of loss of control or change of control of the microarchitecture. A strong inference to be derived from the above is that there are control systems and molecules and that these are derived from cells that are outside, but plausibly adjacent to, the respective epithelia. It is postulated is that there are morphogen-like controller molecules with morphogen-like functions in adult epithelial tissues. These are responsible for the maintenance of normal tissue microarchitecture. Because the function of these putative molecules is maintenance of tissue structure, I have chosen to call them morphostats by analogy with morphogens. It seems plausible that morphostats and morphogens may constitute overlapping families of molecules. Evidence for the existence of morphostats can be derived from a variety of in vivo and in vitro data and from studies of normal tissue, precancer, and cancer, including: (a) the existence but rarity of metaplasia and transdifferentiation; (b) the fact that metaplasias are multicentric and are only one step from normal but do not show any consistent epithelial mutation; (c) the genesis of animal cancers by simple transplantation of tissues into the wrong environment and the evidence that epithelial mutation is not a feature of such transplantation carcinogenesis; (d) the fact that carcinogenesis occurs frequently at the junctions of different epithelial types, e.g., squamocolumnar junctions in gastrointestinal and genital tracts; (e) the fact that cancer-associated fibroblasts can stimulate proliferation in transformed cells but not influence normal cells; and (f) the failure to grow most epithelial organs in a fully differentiated structural pattern in monolayer culture. It is suggested that morphostats may function like morphogens inasmuch as they may act via a diffusion gradient from source mesenchymal cells and provide architectural instruction for complex adult epithelia. Morphostats may influence architecture via control of cell adhesion, apoptosis, and proliferation. Some specific predictions follow from this hypothesis, most notably, a new two-hit model of cancer: one mutation in an epithelial cell resulting in disruption of cell function and structure (e.g., dysplasia); and the other in a mesenchymal or other supporting cell resulting in disruption of tissue microarchitecture. The corollary of this is that there will be mesenchymal mutations producing microarchitectural abnormalities without epithelial dysplasia and vice versa. Disruption of the functions of morphostats may result in a variety of abnormalities. Such disruption may be a key event in carcinogenesis.
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PMID:Morphostats: a missing concept in cancer biology. 1130 83

Squamous epithelial dysplasia is frequently encountered in the cancerous esophagus. However, its biological and clinical significance have not yet been fully elucidated. Investigations in squamous cell dysplasia of the esophagus have been performed to date in our department. We consider dysplasia to be the earliest malignancy of the esophagus based on such biologic features as the histopathologic findings, the proliferative activity, and the altered expression of cancer-associated genes. It is essential to detect and treat these early lesions endoscopically. Hopefully the findings of further studies of dysplasia can help to elucidate the mechanism of carcinogenesis in esophageal squamous cell carcinoma.
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PMID:Biologic and clinical significance of squamous epithelial dysplasia of the esophagus. 1182 83

Diastrophic dysplasia (DD) is a rare skeletal dysplasia characterized by short-limbed short stature, contractures and early degeneration of joints, and spinal deformities such as scoliosis. Mortality is increased in the neonatal period, in part due to tracheo- and bronchomalacia. Additionally, spinal deformities are very rigid, decreasing mobility of the chest cage. The aim of our study was to evaluate lung volumes and airway flow dynamics in patients with DD. A total of 31 patients (12 males, 19 females) underwent a detailed clinical examination measurements of standing height PA-radiography of the spine, flow-volume spirometry, and body plethysmography. The patients were assigned to two groups: children and adolescents (0-18 years, n = 18) and adults (over 18 years, n = 13). The mean spirometric parameters were mostly within the predicted value range, although the variation was wide. At least one abnormally low spirometry parameter was found in 6 (33%) of the children and adolescents and in 7 (54%) of the adults. Mean forced vital capacity (FVC) was 104% (range 48-163%) of predicted values in the children and adolescents and 95% (58-140%) of the adults. Peak expiratory flow (PEF) values were abnormal in 4 (22%) of the children and adolescents and in 5 (39%) adults. The mean plethysmographic parameters were all within the predicted value range. At least one abnormal plethysmographic value was found in 6 (33%) of the children and adolescents and in 4 (31%) of the adults. Airway resistance (Raw) was significantly higher in the adults than in the children and adolescents (P = 0.016), and was abnormally high in 3 (23%) of the adults. The angle of thoracic or thoracolumbar scoliosis correlated with the percentages of the predicted values of FVC (r(s) = - 0.66), forced expired volume in 1 sec (FEV(1)) (r(s) = - 0.56), and total lung capacity (TLC) (r(s) = - 0.67). Age correlated with the FEV(1)/FVC ratio (r(s) = - 0.41), with the maximal expired flow at 50% FEV (MEF(50)) values (r(s) = - 0.55), with the residual volume (RV) values (r(s) = - 0.47), and with the RV/TLC ratio (r(s) = - 0.43). Variable bronchial obstruction was found in 1 (6%) child and in 2 (17%) adults. Although the patients with DD had, on average, normal lung volumes, large individual variation occurred. Airway resistance was increased in adults. The angle of scoliosis correlated inversely with lung volume parameters.
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PMID:Lung function in diastrophic dysplasia. 1192 57

We report two cases of thanatophoric dysplasia (TD) with detailed neuropathologic evaluation. One case was representative of TD type I and the other TD type II. The case with TD type I showed macrocephaly, narrow thoracic cage, pulmonary hypoplasia and bowed limbs. Radiological study showed flat vertebral bodies, short curved appendicular skeleton and flaring of metaphyses. The other case (TD type 2) showed macrocephaly, cleft palate, short limbs and cloverleaf skull. Radiological findings were generalized platyspondy with excessive intervertebral disc space heights and a large head. Microscopic examination of both cases revealed temporal lobe polymicrogyria, abnormalities of the hippocampus and heterotopic neuroglial tissue within the meninges. There were no noticeable differences in CNS abnormalities between TD type I and II.
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PMID:[Thanatophoric dysplasia: report of 2 cases with neuropathological study]. 1196 23

Acampomelic campomelic dysplasia is a rare variant of campomelic dysplasia syndrome affecting bone and connecting tissue. This syndrome is implicated by the absence of bowed limbs. Affected children have a characteristically smooth facial profile and are born with respiratory distress. A 15 day old Turkish boy presented with a small flat face, dolicocephalic head, proptotic eyes, short neck, low-set ears and a small thoracic cage. Limbs were mesomelically short and bilateral talipes equinovarus was present. The radiological findings indicated hypoplastic scapulae, narrow ribs, small thorax, thin claviculaes, and small iliac wings. Angulation of the femur, tibia and humerus was not observed. Our case, suited to acampomelic campomelic dysplasia, is discussed with differential diagnosis and compared with previously reported cases of the syndrome.
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PMID:A case of acampomelic campomelic dysplasia. 1201 34

Helicobacter pylori may protect against the development of dysplasia in Barrett's epithelium of patients with gastroesophageal reflux disease. The aim of this study was to determine whether H. pylori preferentially induces apoptosis in Barrett's-derived cancer cells compared to normal cells. A Barrett's-derived adenocarcinoma cell line (OE33) was grown. H. pylori wild-type, isogenic vacA-, cagA(-), and picB-/cagE- mutant strains were grown on agar plates. Intact or sonicated bacteria were used to treat normal and OE33 cells for 24 hours, and Hoechst dye binding was performed to measure apoptosis. FAS protein expression was determined by Western immunoblotting. OE33 cells treated with intact H. pylori wild-type strains produced significant (P < 0.05) dose-dependent increases in apoptosis compared to normal esophageal cells. H. pylori wild-type and vacA- isogenic strains were more effective than cagA- and picB-/cage- isogenic strains in inducing apoptosis in OE33 cells. In OE33 cells, H. pylori sonicates produced lower levels of apoptosis than intact bacteria. Wild-type H. pylori strains increased Fas protein expression in OE33 cells at 18 hours. H. pylori induced apoptosis at a higher rate in the Barrett's-derived human esophageal adenocarcinoma cells than in normal esophageal cells. The H. pylori-induced apoptosis was primarily dependent on intact bacteria and the presence of the cagA and picB/cagE gene products. H. pylori-induced apoptosis may involve the Fas-caspase cascade.
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PMID:Helicobacter pylori induces apoptosis in Barrett's-derived esophageal adenocarcinoma cells. 1255 87

Jarcho-Levin syndrome, also known as spondylothoracic dysplasia and characterized by short trunk dwarfism, "crab-like" rib cage, with ribs and vertebral defects; it is not uncommon in Puerto Ricans. Many patients die in early infancy due to respiratory compromise associated to lung restriction and the reported cases emphasize mostly the skeletal malformations associated to the syndrome. We report the autopsy findings in a newborn with isolated Jarcho-Levin syndrome emphasizing pulmonary pathology. He was a pre-term male who died of respiratory failure at three hours old and, autopsy findings confirmed the clinical diagnosis. Internal examination showed hypoplastic lungs with normal lobation. The histological structure appeared normal and relatively mature; the diaphragm showed eventration and unilateral absence of musculature. This case shows the worst spectum of the Jarcho-Levin syndrome: pulmonary hypoplasia not compatible with extrauterine life. Since thoracic restriction is present during the fetal period, the degree of pulmonary hypoplasia probably defines survival beyond the neonatal period.
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PMID:Pulmonary hypoplasia in Jarcho-Levin syndrome. 1512 21

We report a newly recognized bone disorder consisting of polyostotic expansile osteolysis affecting long bones and iliac bones; hyperostosis of the skull, thoracic cage, and medial portion of both clavicles; pectus carinatum; gigantiform synovial masses of the elbows and knees; atrial septal defect; cardiomegaly; unilateral cryptorchidism; and mental deficiency. Affected bones can be grouped into four general types of skeletal pathology: (1) expansile osteolysis, (2) osteolysis without expansion, (3) expansion without osteolysis, and (4) hyperostosis. Some bones remained unaffected. We have named the condition "polyosteolysis/hyperostosis syndrome." It is clearly at variance with any previously reported bone disorder, including familial expansile osteolysis, juvenile Paget disease, and McCune-Albright syndrome (and polyostotic fibrous dysplasia). Because our patient shared some features in common with juvenile Paget disease, we thought that mutational analysis of TNFRSF11B was indicated, even though our patient had some manifestations not found in juvenile Paget disease. Direct sequencing failed to identify a TNFRSF11B mutation. Because the parents of our propositus were first cousins suggests that polyosteolysis/hyperostosis syndrome may possibly have autosomal recessive inheritance.
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PMID:A newly recognized polyosteolysis/hyperostosis syndrome. 1700 72

Thanatophoric dysplasia is the most common neonatal lethal skeletal dysplasia with an estimated incidence of 1 in 20,000 live births. This condition shares some similarity of radiological findings with other types of lethal skeletal dysplasias. Definite diagnosis is necessary for accurate medical and genetic counseling. The authors describe a male neonate who had characteristic features of thanatophoric dysplasia type I including severe shortening of limbs with redundant skin folds, large head, frontal bossing, depressed nasal bridge, and narrow thoracic cage with severe respiratory insufficiency. Postmortem radiographs revealed short ribs, flat vertebral bodies (platyspondyly), hypoplastic iliac bones, marked shortening of long bones including short and mild bowing of both femora, oval radiolucent area of proximal femur. Molecular analysis of Fibroblast Growth Factor Receptor 3 (FGFR3) gene identified a de novo mutation, p.R248C, in exon 7.
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PMID:Thanatophoric dysplasia: roentgenographic findings and detection of a de novo mutation of FGFR3 gene in a Thai patient. 1704 42

Campomelic dysplasia (CD; OMIM #114290) is an autosomal dominant, frequently lethal dysplasia syndrome whose primary features include angular bowing and shortening of the limbs, and sex reversal in the majority of affected XY individuals. Most CD cases have heterozygous de novo mutations in the coding region of the transcription factor gene SOX9 (SRY-related high-mobility group [HMG] box 9) in chromosome 17q. Here, we report a novel mutation of SOX9 in a female neonate with CD with autosomal sex reversal. Respiratory distress and cyanosis were noted at birth, and endotracheal intubation with mechanical ventilation was performed due to respiratory failure. The presenting phenotypes included dysmorphic face with macrocephaly, prominent forehead, low nasal bridge, cleft palate and micrognathia. Skeletal deformities characteristic of CD were observed, including narrow thoracic cage, hypoplastic scapulae, scoliosis and short limbs with anterolateral femoral and tibial bowing. The karyotype was 46,XY despite female external genitalia. SOX9 gene analysis revealed frameshift mutation (at nucleotide position 1095G-->AT) in the open reading frame, resulting in a frameshift with 211 new amino acids.
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PMID:Novel SOX9 gene mutation in campomelic dysplasia with autosomal sex reversal. 1718 44


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