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排序方式: 共有1214条查询结果,搜索用时 15 毫秒
1.
C A Mathis J M Gerdes J D Enas J M Whitney S E Taylor Y Zhang D J McKenna S Havlik S J Peroutka 《The Journal of pharmacy and pharmacology》1992,44(10):801-805
The in-vitro inhibition constants (Ki) of 14 structural analogues of the potent 5-hydroxytryptamine (5-HT)-uptake inhibitor paroxetine were determined to assess the structure-affinity relationship of these derivatives. A goal of these studies was to determine those positions on paroxetine which could be derivatized without significantly decreasing the affinity of the drug for the binding site, so that radiolabels such as [18F]fluoroalkyl groups might be appended for future in-vivo imaging studies of the 5-HT uptake system. Using the methyl moiety as a steric probe for these studies, it was found that the rank order of potency of various methyl-substituted paroxetine analogues for inhibiting the binding of [3H]paroxetine to the 5-HT re-uptake site was: 4'-approximately equal to 3'-approximately equal to 2'- > 2'-approximately equal to 1- > 5'- > 6'-methyl. The in-vitro equipotent molar ratios (EPMR, Ki(analogue)/Ki(paroxetine)) of the analogues were determined, and the EPMRs of the 4'-, 3'-, and 2'-methyl derivatives were 1.9, 2.2 and 2.2, respectively. The 4'- and 2'-fluoromethyl and -fluoroethyl analogues were synthesized, and the EPMRs of the 4'- and 2'-fluoromethyl derivatives were determined to be 2.0 and 3.5, and those of the 4'- and 2'-fluoroethyl analogues were 5.2 and 6.2, respectively. The 2'-fluoromethyl analogue was unstable in aqueous solutions, and it is not a promising ligand for in-vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
2.
LEE JS IM HH JUNG Y JUNG IS JANG JY CHUN YK CHO YD KIM JO CHO JY KIM YS SHIM CS & KIM BS 《Neurogastroenterology and motility》2006,18(6):493-494
Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future. 相似文献
3.
4.
B Flott-Rahmel W Gerdes P A Pechan W Brysch K H Schlingensiepen W Seifert 《Neuroreport》1992,3(12):1077-1080
Basic FGF mRNA induction by bFGF was investigated in cell cultures from rat brain, i.e. postnatal day 2 cortex and embryonic day 18 hippocampus. In situ hybridization shows that after bFGF treatment (10(-10) M) for 14 h neurones and glial cells show a remarkable increase in bFGF mRNA production. Incubation of astrocytes with antisense bFGF phosphorothioate oligodeoxynucleotides (bFGF-PTOs) resulted in an inhibition of both bFGF induced and serum induced proliferation. The results indicate that bFGF is capable of inducing its own mRNA production. This induction, i.e. new synthesis of bFGF mRNA, seems to be essential for the mitogenic effect of both bFGF and serum components. 相似文献
5.
Lena Möbus Elke Rodriguez Inken Harder Agatha Schwarz Ulrike Wehkamp Dora Stölzl Nicole Boraczynski Sascha Gerdes Thomas Litman Andreas Kleinheinz Susanne Abraham Annice Heratizadeh Christiane Handrick Eva Haufe Jochen Schmitt Thomas Werfel Stephan Weidinger 《The Journal of allergy and clinical immunology》2021,147(5):1959-1965.e2
6.
7.
Tumor cell growth fractions in human malignant melanomas and the correlation to histopathologic tumor grading. 总被引:1,自引:1,他引:1
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P. Kaudewitz O. Braun-Falco M. Ernst M. Landthaler W. Stolz J. Gerdes 《The American journal of pathology》1989,134(5):1063-1068
The growth fraction (GF) of 72 human malignant melanomas was determined by immunostaining with monoclonal antibody Ki-67. A positive correlation of GF and histopathologically-assessed prognostic variables, such as tumor thickness, mitotic rate, and prognostic index, was found. Individual Ki-67 values were considerably scattered in all histologically defined groups of malignancy. Thus, GF as determined by Ki-67 was used to calculate a modified prognostic index. In contrast to the histologically defined prognostic index, the Ki-67 based prognostic index allows further subdivision of thin malignant melanomas with no or few mitotic figures. This may be of help in identifying tumors with a high recurrence potential. 相似文献
8.
Increased frequency of congenital chromosomal aberrations in female partners of couples undergoing intracytoplasmic sperm injection 总被引:3,自引:7,他引:3
van der Ven K; Peschka B; Montag M; Lange R; Schwanitz G; van der Ven HH 《Human reproduction (Oxford, England)》1998,13(1):48-54
We evaluated the frequency of congenital chromosomal aberrations in a
sample of 305 couples included in an intracytoplasmic sperm injection
(ICSI) programme. Twenty individuals (3.3%) with congenital chromosomal
abnormalities could be identified. The following types of abnormalities
were observed: reciprocal translocations (n = 7), Robertsonian
translocations (n = 3), inversions (n = 3), other structural aberrations (n
= 4) and sex chromosome aberrations (n = 3). The rate of chromosomally
abnormal males (10/305, 3.3%) lay within the expected range for patients
with reduced semen quality. Surprisingly, 50% (10/20) of all abnormal
karyotypes were contributed by the female partner of ICSI patients. These
data confirm the higher incidence of chromosomal aberrations in infertile
populations as compared with the baseline population risk. Additionally,
the data imply that in some cases of male factor infertility a hidden
female chromosomal factor may be present, which cannot be identified by
standard clinical evaluation. In conclusion, we recommend chromosomal
analysis in both partners of couples undergoing ICSI treatment.
相似文献
9.
Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP) 总被引:2,自引:2,他引:2
Roepman R; Bauer D; Rosenberg T; van Duijnhoven G; van de Vosse E; Platzer M; Rosenthal A; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(6):827-833
The gene for the most frequent from of X-linked retinitis pigmentosa
(XLRP), RP3, has been assigned by genetic and physical mapping to a segment
of less than 1000 kbp, which is flanked by the marker DXS1110 and the
ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have
screened the DNA of 30 unrelated patients with XLRP by employing a
representative set of YAC-derived DNA fragments that were generated by
restriction enzyme digestion and PCR amplification. In one of these
patients, a 6.4 kbp microdeletion was detected which was not present in the
DNA of 444 male controls. A cosmid contig spanning the deletion was
constructed and used to isolate cDNAs from retina-specific libraries. Exons
corresponding to these expressed sequences as well as other putative exons
were identified by sequencing more than 30 kbp of the critical region. So
far, no point mutations in these putative exon sequences have been
identified.
相似文献
10.
Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1 总被引:6,自引:7,他引:6
Roepman R; van Duijnhoven G; Rosenberg T; Pinckers AJ; Bleeker-Wagemakers LM; Bergen AA; Post J; Beck A; Reinhardt R; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(7):1035-1041
The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-
linked RP (XLRP), has been mapped previously to a chromosome interval of
less than 1000 kbp between the DXS1110 marker and the OTC locus at
Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization
(YRH)', we have recently identified a small XLRP associated microdeletion
in this interval, as well as several putative exons including the 3' end of
a gene that was truncated by the deletion. cDNA library screening and
sequencing of a cosmid centromeric to the deletion has now enabled us to
identify numerous additional exons and to detect several point mutations in
patients with XLRP. The predicted gene product shows homology to RCC1, the
guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our
findings suggest that we have cloned the long-sought RP3 gene, and that it
may encode the GEF of a retina-specific GTP-binding protein.
相似文献