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1.
GP SCHWAB AL BLUM E BODNER B DALLEMAGNE K GLASER H KOOP F PACE W RÖSCH JR SIEWERT G WETSCHER 《Journal of gastroenterology and hepatology》1997,12(12):785-789
Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper. 相似文献
2.
Purpose. This paper compares unsteady-state and steady-state methods for estimating dermal absorption or analyzing dermal absorption data. The unsteady-state method accounts for the larger absorption rates during short exposure times as well as the hydrophilic barrier which the viable epidermis presents to lipophilic chemicals.
Methods. Example calculations for dermal absorption from aqueous solutions are presented for five environmentally relevant chemicals with molecular weights between 50 and 410 and log10Kow between 0.91 and 6.8: chloromethane, chloroform, chlordane, 2,3,7,8-TCDD, and dibenz(a,h)anthracene. Also, the new method is used to evaluate experimental procedures and data analyses of in vivo and in vitro permeation measurements.
Results. In the five example cases, we show that the steady-state approach significantly underestimated the dermal absorption. Also, calculating permeability values from cumulative absorption data measured for exposure periods less than 18 times the stratum corneum lag time will overestimate the actual permeability.
Conclusions. In general, steady-state predictions of dermal absorption will underestimate dermal absorption predictions which consider unsteady-state conditions. Permeability values calculated from data sets which include unsteady-state data will be incorrect. Strategies for analyzing in vitro diffusion cell experiments and confirming steady state are described. 相似文献
3.
4.
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1) 总被引:10,自引:1,他引:10
Rousseau F; el Ghouzzi V; Delezoide AL; Legeai-Mallet L; Le Merrer M; Munnich A; Bonaventure J 《Human molecular genetics》1996,5(4):509-512
Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with
micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced
thoracic cavity. In the most common subtype (TD1), femurs are curved, while
in TD2, straight femurs are associated with cloverleaf skull. Mutations in
the fibroblast growth factor receptor 3 (FGFR3) gene were identified in
both subtypes. While TD2 was accounted for by a single recurrent mutation
in the tyrosine kinase 2 domain, TD1 resulted from either stop codon
mutations or missense mutations in the extracellular domain of the gene.
Here, we report the identification of FGFR3 mutations in 25/26 TD cases.
Two novel missense mutations (Y373C and G370C) were detected in 8/26 and
1/26 TD1 cases respectively. Both mutations created cysteine residues in
the juxta extramembrane domain of the receptor. Sixteen cases carried the
previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon
FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically
homogeneous condition and give additional support to the view that newly
created cysteine residues in the extracellular domain of the protein play a
key role in the severity of the disease.
相似文献
5.
Previous studies have demonstrated that individual neurons from neonatal rat superior cervical ganglion express a mixed adrenergic-cholinergic phenotype when grown under certain tissue culture conditions.9,14,15,29,30 The expression of this phenotype is critically influenced by a number of undefined components present in the culture medium.18,23,33 In the present study, we have examined whether superior cervical ganglion neurons grown on a chemically defined serum-free medium similarly develop dual transmitter expression, or if under these conditions, neurons express only those properties characteristic of their adrenergic heritage. To address this issue, we established that superior cervical ganglion neurons could be maintained in culture for extended periods on the defined medium described by Bottenstein & Sato4 in the absence of supporting cells. We then studied the biochemical, immunocytochemical and ultrastructural characteristics of these neurons. We found that in defined medium, superior cervical ganglion neurons continued to express, in a modified form, certain of their expected adrenergic properties, including the development of tyrosine hydroxylase and dopamine-β-hydroxylase activities, stores of endogenous norepinephrine, synaptic vesicles with dense cores and tyrosine hydroxy lase-immunoreactive staining properties. Superior cervical ganglion neurons grown on a defined medium did not, however, acquire cholinergic traits in culture. In this paper we show that choline acetyltransferase activity did not reach detectable levels; the companion paper13 documents that cholinergic synapses were not formed.We conclude that superior cervical ganglion neurons, grown under serum-free culture conditions, develop certain properties characteristic of adrenergic neurons and do not express a mixed adrenergic cholinergic phenotype. A companion paper13 describes the electrophysiological properties of these neurons and demonstrates the frequent occurrence of electrotonic synapses in these cultures. 相似文献
6.
7.
Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1 总被引:10,自引:0,他引:10
Lemmens I; Van de Ven WJ; Kas K; Zhang CX; Giraud S; Wautot V; Buisson N; De Witte K; Salandre J; Lenoir G; Pugeat M; Calender A; Parente F; Quincey D; Gaudray P; De Wit MJ; Lips CJ; Hoppener JW; Khodaei S; Grant AL; Weber G; Kytola S; Teh BT; Farnebo F; Thakker RV 《Human molecular genetics》1997,6(7):1177-1183
8.
Yang GC; Croaker D; Zhang AL; Manglick P; Cartmill T; Cass D 《Human molecular genetics》1998,7(6):1047-1052
Lethal white foal syndrome (LWFS) is a congenital anomaly of horses
characterized by a white coat colour and aganglionosis of the bowel, which
is similar to Hirschsprung disease (HSCR). We decided to investigate
possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as
recent studies in mutant rodents and some patients have demonstrated EDNRB
defects. First, we identified a full-length cDNA for horse EDNRB . This
cDNA fragment contained a 1329 bp open reading frame which encoded 443
amino acid residues. The predicted amino acid sequence was 89, 91 and 85%
identical to human, bovine and mouse as well as rat EDNRB respectively, but
only 55% identical to the human, bovine and rat endothelin A receptor
(EDNRA). Secondly, sequence analysis, together with allele-specific PCR and
the amplification- created restriction site (ACRS) technique, revealed a
dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in
the predicted first transmembrane domain of the EDNRB protein. This was
associated with LWFS when homozygous and with the overo phenotype when
heterozygous.
相似文献
9.
Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome) 总被引:4,自引:0,他引:4
Bunge Susanna; Steglich Cordula; Zuther Cornelia; Beck Michael; Morris C. Phillip; Schwinger Eberhard; Schinzel Albert; Hopwood John J.; Gal Andreas 《Human molecular genetics》1993,2(11):1871-1875
Mutations of the iduronate-2-sulfatase gene were identifiedin 16 patients with mucopolysaccharidosis type II (Hunter syndrome).Together with another 10 cases reported by us earlier it emergesthat about 20% of the patients have deletions of the whole geneor other major structural alterations. One, two or three basepair deletions are found in about 23% of the cases while theremaining about 57% carry point mutations predicting amlno acidreplacement, premature termination of translation, or aberrantsplicing. Molecular analysis of mRNA in splice site mutantsshowed that these latter defects frequently resulted in useof cryptic splice sites in exons or introns. 62% of the smalldeletions and point mutations have occurred in 3 of the 9 iduronate-2-sulfatasegene exons. Knowledge of the primary genetic defect allows fastand reliable carrier detection and prenatal diagnosis as wellas insight into the relationship between genotype and phenotype. 相似文献
10.
Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase 总被引:2,自引:0,他引:2
We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice. 相似文献