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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of chronic treatment with cystic fibrosis (CF) fibroblast medium on rat submandibular gland and pancreas was investigated. Rats were injected for 8 days with conditioned medium from normal or CF fibroblasts. The elemental content of the acinar cells was measured by X-ray microanalysis of cryosections. A significant increase in cellular calcium, and a decrease in cellular sodium concentrations were found after treatment with CF medium. The ultrastructure of the submandibular acinar cells was not affected by the conditioned CF fibroblast culture medium. No effect of treatment with CF medium on ultrastructure and elemental content of pancreatic acinar cells could be demonstrated. The response to alpha-adrenergic, beta-adrenergic, cholinergic, and peptidergic stimulation in submandibular gland acinar cells of rats injected with normal or CF medium was investigated in vitro. With regard to changes in elemental composition after stimulation, no significant differences in response between the two groups could be found. Apparently, a factor in conditioned medium from cultured CF fibroblasts induces a net increase in calcium content of rat submandibular gland acinar cells. Possibly, this factor acts in a similar way in CF patients and may cause elevated calcium levels in CF cells.
Exp Mol Pathol 1985 Aug
PMID:Effect of chronic treatment with cystic fibrosis fibroblast medium on rat submandibular gland acinar cells. 400 40

The chronically pilocarpine-treated rat has been proposed as an animal model for the disease cystic fibrosis, a generalized exocrinopathy. The effect of chronic pilocarpine treatment on structure, composition, and function of the acinar cells of rat submandibular gland and pancreas was investigated by electron microscopy, X-ray microanalysis, and biochemical analysis. The morphological effects of chronic pilocarpine treatment were most pronounced in the pancreas. The number and size of the zymogen granules was increased, and the granules had a less electron-dense appearance. X-ray microanalysis at the cellular level showed in both the submandibular gland and the pancreas a significant increase in calcium and a decrease in sodium. The increase in cellular calcium concentrations can be explained by an increase in the relative volume of secretory material in the cell (assessed by morphometry) and an increase in the local calcium concentration in the secretory material (assessed by X-ray microanalysis at the subcellular level). Chronic pilocarpine treatment caused a disturbance of glycolysis and energy metabolism in the submandibular gland, but no significant effects in this respect were noted in the pancreas. On the other hand, a nearly twofold increase of the pancreatic amylase activity was noted. The pancreas appeared somewhat hyperreactive towards cholinergic stimulation.
Exp Mol Pathol 1985 Aug
PMID:The chronically pilocarpine-treated rat in the study of cystic fibrosis: investigations on submandibular gland and pancreas. 400 43

A human genomic clone containing a portion of the structural gene for the third component of complement (C3) was used as a hybridization probe to DNA from two genetically informative families in which cystic fibrosis (CF) occurs. Several restriction fragment length polymorphisms (RFLPs) can be identified using the C3 probe, which appears to detect a high level of sequence variation in the general population. The inheritance of C3 RFLP was found to be independent of the inheritance of the CF phenotype. Assuming that CF is caused by a mutation affecting a single genetic locus, the demonstration that an allele of the C3 gene does not segregate with CF proves that a defect of complement C3 cannot be the cause of the disease.
Mol Biol Med 1983 Sep
PMID:Cystic fibrosis is not caused by a defect in the gene coding for human complement C3. 609 50

Immature rats were reserpinized to determine whether the model used for adults may be suitable for the study of pancreatic exocrine insufficiency seen in infants with cystic fibrosis. Rats were reserpinized by injections either into pregnant dams or into newborn rats. The dose of reserpine used by others was lethal to immature rats, so lower doses were used. Pancreas from 1-day-old fetal-treated pups was hypoplastic, but concentration of chymotrypsinogen was elevated. At age 7 days hyperplasia was seen. When rats were reserpinized as neonates, hypoplasia and decrease in all parameters measured was observed at age 7 days. Progressive recovery occurred during the following 2 weeks in both groups. Electron microscopic study of the fetal-treated 24-hr-old pancreas revealed evidence of acinar cell degeneration with the presence of abnormal zymogen granules. At age 7 days the pancreas from neonatal-treated rat pups appeared to have a reduced number of granules. At ages 14 and 21 days the pancreas was similar to that seen at age 7 days except that the granules were larger and some acinar lumina were filled with a finely granular, homogeneously dense material. It is concluded that prenatal and neonatal reserpinization of rats induces changes in pancreas similar to those found in cystic fibrosis.
Exp Mol Pathol 1983 Aug
PMID:Pancreatic structure and function in the immature reserpinized rat. 619 12

The chronically isoproterenol-treated rat has been proposed as an animal model for cystic fibrosis. Ultrastructural studies showed enlarged cells with abnormally large mucus granules that were more often fused than in control animals. X-ray microanalysis of mucous acinar cells showed a significant increase in calcium levels, but unaffected magnesium levels. Combined treatment with isoproterenol and reserpine caused a very large increase in cellular calcium levels that appeared to be an addition of the single effects and increased magnesium levels (as in glands of rats treated with reserpine only). Chronic treatment with isoproterenol, reserpine, or both substances tended to decrease cellular potassium levels. Chronic exposure to the specific beta 1-agonist prenalterol or the specific beta 2-agonist terbutaline did not affect cellular calcium or potassium levels. It is concluded that chronic isoproterenol treatment affects the elemental composition of mucous acinar cells of rat submandibular gland differently from chronic reserpine treatment. The increase in cellular calcium concentration after chronic isoproterenol treatment does not appear to be due to an effect via beta-adrenergic receptors.
Exp Mol Pathol 1984 Jun
PMID:The chronically isoproterenol-treated rat in the study of cystic fibrosis: X-ray microanalysis of the submandibular gland. 672 39

Burkholderia cepacia (basonym Pseudomonas cepacia), the type species of the new genus Burkholderia, is of interest, not only because of its broad catabolic capacity and its ability to antagonize soil-borne plant pathogens, but also because of its causative role in infections in man, which are particularly evident in patients with cystic fibrosis. A physical map of the 8.1 Mb genome of the B. cepacia type-strain ATCC 25416 was constructed by applying two-dimensional pulsed-field gel electrophoresis techniques. Placed onto the macrorestriction map were 38 SpeI, 11 SwaI, 11 PacI, 11 PmeI and six I-CeuI sites, resulting in an average resolution of 105 kbp. Random single-hit linearization by irradiation and restriction mapping uncovered the presence of four circular replicons of 3.65 Mb, 3.17 Mb, 1.07 Mb and 200 kbp in size. The largest replicon harbours four rrn operons while the other two Megabase-size replicons each contain a single rrn operon, suggesting that the genome has three chromosomes and a large plasmid. Within the beta subdivision of proteobacteria, the existence of multiple replicons is not confined to B. cepacia. The phylogenetically related species Burkholderia glumae, Burkholderia pickettii, Burkholderia solanacearum, Alcaligenes eutrophus and the so far unassigned Pseudomonas glathei were also found to harbour more than one Megabase-size replicon.
Mol Microbiol 1995 Jul
PMID:A physical genome map of the Burkholderia cepacia type strain. 747 9

Two novel CFTR mutations were detected in Greek cystic fibrosis patients. One was a missense mutation, A46D, and the other a splice mutation, 296 + 1G-C. Neither was detected on normal chromosomes.
Mol Cell Probes 1995 Aug
PMID:Identification of two novel mutations (296 + 1G-C and A46D) in exon 2 of the CFTR gene in Greek cystic fibrosis patients. 747 25

Mice with a termination codon mutation in exon 2 of the cystic fibrosis (CF) gene were generated using homologous recombination in embryonic stem cells. Animals homozygous for the mutant allele display a severe intestinal phenotype similar to that previously reported for CF mutant mice. The null nature of this allele was demonstrated by the absence of detectable wild-type mRNA, by the absence of detectable CFTR in the serous gland collecting ducts of salivary tissues, and by the lack of cAMP-mediated short-circuit current responses in colonic epithelium of mutant animals.
Somat Cell Mol Genet 1995 May
PMID:Severe phenotype in mice with termination mutation in exon 2 of cystic fibrosis gene. 748 32

In 545 Pseudomonas aeruginosa strains, mainly collected from patients with cystic fibrosis, SpeI-DraI macrorestriction fragment length diversity was scanned for using probes of known map position on the P. aeruginosa PAO chromosome. Southern analysis of the 60 unrelated clones uncovered a gradient of macrorestriction fragment length polymorphisms (RFLPs) from the origin of replication towards the auxotroph-poor region of the P. aeruginosa genome. Linkage disequilibrium between macrorestriction sites was conserved in the P. aeruginosa population in the region encompassed by the rrn operons. The oriC-reactive SpeI fragment was conserved in nearly all isolates examined. Few fragment length classes were seen for the alg60-, algR- and toxA-encoding SpeI fragments. Fragment size varied within one class by up to 20 kb. Two probes from the auxotroph-poor region detected a broad size range for the SpeI fragment, suggesting extensive genomic diversity in these regions. Subclonal variation of fragment size was detected at all investigated loci in at least one of the analysed clones, but within one particular clone, SpeI-RFLPs were found at only few loci.
Mol Microbiol 1995 Jul
PMID:Gradient of genomic diversity in the Pseudomonas aeruginosa chromosome. 749 81

To develop an animal model for cystic fibrosis (CF), targeted gene disruption in embryonic stem (ES) cells was used to generate a duplication of exon 3 (cftrm1Bay allele) of the mouse CF gene. ES cells containing this mutation were used to generate chimeric animals that transmitted the mutant allele through the germline. Homozygous mutant animals display a severe phenotype, with approximately 40% dying within 1 week from intestinal obstruction. RNAase protection analysis of the cftrm1Bay allele did not detect any normal mRNA (< 1-2% of wild-type) in mutant animals. Pathologic changes in the intestines from mutant mice included mucus accumulation in the crypts and intestinal lumen, dilatation of the bases of the crypts, enlargement of goblet cells, and the presence of concretions in the crypts or between the villi. Changes were also present in the mucosal glands of the pharynx and the minor sublingual glands, where dilatation of acini and accumulation of eosinophilic material were evident. Atrophy of acinar cells that may be secondary to nutritional deficiency and mild inflammation in the main pancreatic duct were present in the pancreas of mutant animals. No changes were noted in the lung, trachea, liver, or male reproductive tract of mutant animals, and mutant males were fertile. Homozygous mutant mice showed defects in cAMP-mediated ion transport both in ileum and in cultured fetal tracheal explants. Thus, an additional mouse model for CF has been generated that should prove useful for the understanding of the pathogenesis and the development of treatments for CF.
Hum Mol Genet 1993 Oct
PMID:A severe phenotype in mice with a duplication of exon 3 in the cystic fibrosis locus. 750 91


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