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Activation of the visual pigment rhodopsin involves both steric and electrostatic interactions between the chromophore and opsin within the retinal-binding site. Removal of the C9 methyl group of 11-cis-retinal inhibits light-dependent activation of the G protein, transducin, suggesting a direct steric contact. More recently, we have shown that steric interactions lead to receptor activation when Gly121 in the middle of transmembrane helix 3 is replaced by larger hydrophobic residues. In order to understand in more detail the role of the C9 methyl group of retinal in the structure and function of rhodopsin, we first studied the properties of recombinant 9-dm-Rho (opsin reconstituted with 11-cis-9-demethylretinal). The 9-dm-Rho pigment displayed a blue-shifted lambdamax, increased hydroxylamine reactivity, and decreased ability to activate transducin. These properties are consistent with the hypothesis that the C9 methyl group is a crucial structural anchor for the correct docking of the chromophore in its binding site. Next, we investigated the possible interaction between Gly121 of opsin and the C9 methyl group of retinal by characterizing recombinant pigments produced by combining mutant opsins (G121A, -V, -I, -L, and -W) with 11-cis-9-demethylretinal. Mutant opsins G121I, -L, and -W failed to bind the chromophore. However, the double mutant G121L/F261A bound 11-cis-9-demethylretinal to form a stable pigment with a lambdamax of 451 nm. When activity was assayed in membranes, the reduction in transducin activation by 9-dm-Rho caused by the lack of a C9 methyl group on the chromophore could be partially restored by replacing Gly121 with a bulky residue (leucine, isoleucine, or tryptophan). These results support a model of receptor activation that involves steric interaction between the C9 methyl group of the chromophore and the opsin in the vicinity of Gly121 on transmembrane helix 3. 相似文献
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K Fujinaga TP Cujec J Peng J Garriga DH Price X Gra?a BM Peterlin 《Canadian Metallurgical Quarterly》1998,72(9):7154-7159
146.
It is estimated that 49% to 74% of cases of contact lens-associated ulcerative keratitis could be prevented by eliminating overnight wear. Heavy alcohol consumption appears to be associated with all types of cataracts. Cigarette smokers have a nearly threefold greater risk of developing age-related macular degeneration than nonsmokers. 相似文献
147.
TP Piepponen J Katajam?ki T Kivastik A Zharkovsky L Ahtee 《Canadian Metallurgical Quarterly》1996,54(4):787-792
The sensitivity of dopamine D2-like receptors in morphine-withdrawn rats was studied using the selective agonist quinpirole. Morphine was administered twice daily increasing the daily dose from 20 to 50 mg/kg during 7 days. Twenty-four hours after the last morphine administration the rats were given quinpirole (0.01-1 mg/kg) and their behavior was assessed. Withdrawal from repeated morphine treatment enhanced yawning behavior and penile erections induced by small doses (0.01-0.1 mg/kg) as well as the intensity of stereotypy induced by a large dose (1.0 mg/kg) of quinpirole. In the morphine-withdrawn rats the dose of 1 mg/kg of quinpirole caused less yawning than in the control rats, whereas the number of erections induced by this dose was enhanced as compared with the control animals. In the control rats, the striatal and limbic concentrations of dopamine metabolites, 3,4-dihydroxphenylacetic acid (DOPAC), and homovanillic acid (HVA), were not clearly affected by the smallest dose of quinpirole. However, the small dose of quinpirole (0.01 mg/kg) significantly reduced the levels of DOPAC and HVA in the striatum and limbic forebrain of the rats withdrawn from morphine either for 24 or 48 h. These findings indicate that withdrawal from repeated morphine treatment enhances the sensitivity of dopamine D2-like receptors. 相似文献
148.
We report the outcome of 177 consecutive primary Charnley total hip arthroplasties inserted with Boneloc cement between November 1991 and November 1993. There were 107 women and 70 men. The mean age at the time of the operation was 71 years. 11 patients (13 hips) died during the follow-up period and 3 patients were too weak to attend a follow-up examination. Of the 161 remaining hips, 4 had been revised because of deep infection. The mean follow-up time for the remaining 157 hips was 2 (0.5-3) years. 24 hips had been revised and 6 are waiting for revision because of stem loosening. Of the remaining 127 hips, 72 showed radiographic signs of stem loosening and 2 hips were probably loose. Osteolysis was seen around the femoral component in 56 hips. 相似文献
149.
We describe an example of a rare benign intranodal haemorrhagic spindle cell tumour (also called intranodal myofibroblastoma), occurring in a lymph node of the right inguinal region of a 53 year-old male patient. This is the first documentation of this tumour in the Danish literature. The lesion presents typically as a unilateral, solitary, painless inguinal lump. The microscopic appearance is characterized by proliferating spindle-shaped cells, interstitial haemorrhage and amianthoid fibers. Differential diagnosis includes primary and secondary lymph node tumours, such as Kaposi's sarcoma; metastatic spindle cell carcinoma; melanoma; neurilemmoma and soft tissue sarcomas. The clinical behaviour of the tumour is benign and local excision is the treatment of choice. 相似文献
150.
OBJECTIVE: To describe the presentation and incidence of Kaposi's sarcoma (KS) in a cohort of women infected with HIV and to compare their clinical characteristics with men at the same institution. DESIGN: Retrospective chart and database review. SETTING: Adult clinical AIDS program outpatient clinics at a municipal teaching hospital. RESULTS: One hundred and seven people with KS were found of whom twelve (11.2%) were women. The prevalence of KS in women was 3.6% compared with 9.9% among men (P < 0.001). Women born outside the United States were at increased risk of developing KS (P < 0.05). At initial KS presentation, no difference in HIV stage or CD4 count was found between men and women. Women presented with more advanced KS than men, with increased incidence of non-cutaneous disease (P < 0.001), lymphedema (P < 0.0001), lymph-node disease (P < 0.0001) and visceral disease (P = 0.03). Women had decreased survival after KS diagnosis compared to men, although the difference was not significant (P = 0.41). CONCLUSIONS: KS is not a rare diagnosis in HIV-infected women followed at our institution. Although the increased risk of KS in men is most likely to be related to differences in exposure, the sex-related differences in presentation and course may be due in part to delay in diagnosis. KS should be considered in the spectrum of HIV-related complications in women as well as in men. 相似文献