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81.
目的构建大鼠维生素D受体(VDR)蛋白表达载体,测定并分析遗传性高钙尿性结石(GHS)大鼠VDRcDNA序列。方法采用半定量逆转录-聚合酶链反应(RT—PCR)方法扩增含VDR蛋白编码基因序列,将扩增产物克隆至真核表达载体pcDNA3.1/Zero(+),对5只GHS大鼠和4只正常尿钙对照(NC)大鼠十二指肠VDRcDNA序列进行测序分析。结果琼脂糖凝胶电泳示PCR扩增产物碱基数目与目的片段大小一致。对重组质粒的分析表明,插入片段的序列与发表的VDR基因编码序列相同。5只GHS鼠和4只NC鼠肠VDR cDNA序列均有3个相同的位点不同于已公布的大鼠肠VDR cDNA序列:在256bp位点:C取代G;569bp位点:G代替A;1658位点:A替代G。另外,GHS鼠在1795bp位点发生改变,G取代A,而NC鼠则无改变。结论大鼠维生素D受体蛋白编码序列被成功地克隆至表达载pcDNA3.1/Zero(+)上。GHS大鼠基因编码区的序列组成同NC大鼠相一致,但GHS鼠1795bp位点的碱基改变未见于NC鼠。 相似文献
82.
K. OKAMURA I. KOBAYASHI K. MATSUO T. KIYOSHIMA K. YAMAMOTO A. MIYOSHI & H. SAKAI 《Histopathology》1997,31(6):540-548
Aims:
The purpose of this study is to examine the relationship between immunohistochemical localization of cathepsin D (CD), proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGF-R) in 65 cases of breast carcinoma in Japanese women and traditional prognostic factors such as histological grade, lymph node status, mitotic rate and clinical stage, in order to possibly identify some indicator(s) that may be specifically associated with prognosis.
Methods and results:
Serial sections of 5-μm thick were cut from the archival formalin-fixed, paraffin-embedded tissue blocks, and processed for CD, PCNA and EGF-R immunostaining. The results were analysed by computer-based image analysis system. All samples showed a positive immunoreaction for cathepsin D in both the parenchyma and stroma. However, the staining area and intensity varied from cell to cell in the parenchyma and stroma as well as among samples. Subsequently, the evaluation of immunostaining for CD was separately performed in both the parenchyma and stroma (CDpar and CDstr, respectively) and the combination of both components (CDtotal). PCNA and EGF-R showed positive immunostaining almost exclusively in the parenchymal component of the carcinoma tissue specimens. CDtotal significantly correlated with the histological grade, PCNA index (PI), mitotic rate (MR), EGF-R and lymph node metastasis. Significant correlation was also demonstrated between CDpar and the histological grade, EGF-R and lymph node metastasis, or between CDstr and MR, EGF-R and lymph node metastasis. EGF-R correlated highly with the histological grade, MR score, lymph node metastases and recurrence-free survival.
Conclusions:
Both the CD parameters and EGF-R are valuable indicators for predicting the biological behaviour of human breast carcinoma. 相似文献
83.
Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine 总被引:1,自引:0,他引:1
L. C. Kirkwood R. L. Nation & A. A. Somogyi 《British journal of clinical pharmacology》1997,44(6):549-555
Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
84.
Diminished effect of etidronate in vitamin D deficient osteopenic postmenopausal women 总被引:7,自引:0,他引:7
J. C. Koster W. H. L. Hackeng H. Mulder 《European journal of clinical pharmacology》1996,51(2):145-147
Objective: The effects of vitamin D deficiency in osteopenic postmenopausal women treated with intermittent cyclical etidronate have
been studied. Bone mass and biochemical parameters as bone markers were measured before and after one year of therapy with
intermittent cyclical etidronate.
Results:
In 30 patients without vitamin D deficiency, bone mass in the lumbal spine and femoral neck was significantly increased compared
to 28 vitamin D deficient patients. After cyclical intermittent etidronate therapy, serum osteocalcin and PTH were significantly
increased in the vitamin D deficient patients, whereas in non-vitamin D deficient patients they did not change.
Conclusion:
It is worthwhile measuring serum vitamin D before starting etidronate therapy and, in case of deficiency, to give vitamin
D.
Received: 6 April 1995/Accepted in revised form: 23 April 1996 相似文献
85.
Nicotine has been found to improve memory performance in a variety of tests including the radial-arm maze. Nicotine may have effects mediated by promoting the release of dopamine. The present study was conducted to determine the interactions of nicotine with D1 and D2 agonists. Rats were acutely administered nicotine, the D1 agonist SKF 38393, and D2/D3 agonist quinpirole, and nicotine together with each of these agonists. Nicotine significantly improved choice accuracy in the radial-arm maze. The D1 agonist SKF 38393 significantly impaired choice accuracy. Nicotine was effective in reversing this effect. The D2/D3 agonist quinpirole showed a trend toward potentiating the improvement in choice accuracy caused by 0.2 mg/kg (0.43 μmol/kg) of nicotine. These data show that, as with the nicotinic antagonist mecamylamine, there are significant interactions of dopamine systems with nicotine effects. © 1994 Wiley-Liss, Inc. 相似文献
86.
Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of a palatable (1%) sucrose solution, and to attenuate food-induced place preference conditioning. In this study the effects of pramipexole (SND-919), a dopamine D2 agonist, were studied during 7–9 weeks of chronic treatment. Pramipexole (1.0 mg/kg per day) reversed the suppression of sucrose intake in stressed animals, increasing sucrose intakes above the levels seen in untreated nonstressed controls. Pramipexole also increased sucrose intake in nonstressed animals; these effects were accompanied by increases in water intake and tended to correlate with weight loss. Drug-treated stressed animals also lost weight, but in this case water intake was unaffected. A second group of animals received a higher dose of pramipexole (2.0 mg/kg per day). The effects of the two doses were very similar. After three weeks of treatment, these animals were switched to a lower dose of pramipexole (0.1 mg/kg per day). Increases in sucrose intake were maintained over three weeks of treatment at the lower dose, with significant recovery of body weight. Two further groups received the same doses of pramipexole (1.0 mg/kg for 6 weeks or 2.0 mg/kg for 3 weeks followed by 0.1 mg/kg thereafter), but received intermittent (twice-weekly) drug treatment. Intermittent pramipexole treatments also tended to increase sucrose intakes, but the results were less consistent from week to week. Following 6–8 weeks of pramipexole treatment, food-induced place preference conditioning was studied in all animals. Untreated stressed animals showed no evidence of place conditioning. Normal conditioning was seen in both groups of stressed animals treated daily with pramipexole (at 1.0 and 0.1 mg/kg) and in the group treated twice weekly at the higher dose (1.0 mg/kg); intermittent treatment at the lower dose (0.1 mg/kg) was ineffective. The results indicate that pramipexole exerts rapid anti-anhedonic effects in the chronic mild stress model. This conclusion is complicated, but not undermined, by drug-induced weight loss and by the presence of significant drug effects in nonstressed control animals. 相似文献
87.
Hiroshi Ujike Kazuo Tsuchida Kazufumi Akiyama Yutaka Fujiwara Shigetoshi Kuroda 《Pharmacology, biochemistry, and behavior》1995,50(4):613-617
The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56–60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21–25 or 28–32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later. 相似文献
88.
D. Thiébaud P. Burckhardt M. Costanza D. Sloutskis D. Gilliard F. Quinodoz A.-F. Jacquet B. Burnand 《Osteoporosis international》1997,7(5):457-462
The relative importance of vitamin D deficiency, secondary hyperparathyroidism, nutritional deficiency and low bone mineral
density (BMD) as risk factors for hip fracture is not definitely established. In the framework of a case-control study of
risk factors for hip fractured, biochemical markers of bone metabolism and nutrition and femoral BMD data were compared in
136 female and 43 male hip fracture patients, 126 female and 44 male age-matched hospitalized controls, and 47 healthy elderly
women (8 men). Patients with hip fracture had lower albumin (−10%9 and 25(OH)-vitamin D (25(OH)D; −19%) compared with hospitalized
controls, and lower albumin (−28%) and 25(OH)D levels (−52%) compared with the elderly controls. Serum values of IGFBP-3 were
also significantly lower (−33%) in hip fracture patients than in community controls. BMD of femoral neck was lower (p < 0.001) in patients than in hospitalized and community controls. In hip fracture patients, parathyroid hormone (PTH) correlated
weakly with BMD (neck: r = −0.19, trochanter: r = −0.17; both p < 0.05). When all women were pooled (n = 233), albumin correlated significantly (age-adjusted) with BMD at all sites (neck: r = 0.27, trochanter: r = 0.25; all p < 0.001). Albumin, but not 25(OH)D, also correlated with skinfold thickness (r = 0.19, p < 0.0025) and with body mass index (BMI) (r = 0.14, p < 0.05). Male patients with hip fracture had lower BMD and albumin (both p < 0.001), 25(OH)D (p = 0.02) and IGFBP-3 levels (p <: 0.005) compared with the controls. When male patients and controls were pooled together, albumin, skinfold thickness and
BMI were significantly correlated with each other, but not with BMD. IGFBP-3 was highly correlated with albumin (p < 0.0001), 25(OH)D (p < 0.005) and, less significantly, with PTH (p < 0.05), but not with BMI or skinfold thickness. IGFBP-3 was significantly correlated with BMD at all sites (neck: r = 0.27, p < 0.05); trochanter: r = 0.40, p < 0.0005). In conclusion, low albumin and low BMD were both important risk factors for hip fracture. Low serum albumin was
the strongest independent variable correlated with hip fractures. In men, IGFBP-3 was correlated with BMD. The femoral BMD
depended only weakly on PTH and 25(OH)D, but was correlated at all sites with albumin, a non-specific parameter of nutrition
and general health. 相似文献
89.
Summary Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia.
Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid
hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary.
We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D
deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric
studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia
but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became
normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings
indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other. 相似文献
90.
M. V. Lareu C. Pestoni A. Carracedo M. Schürenkamp S. Rand B. Brinkmann 《International journal of legal medicine》1996,109(3):134-138
A total of 103 fragments in the STR D12S391 locus were sequenced. 24 different alleles were found which can be grouped into 12 allelic classes based on the total number of repeats. The structure of this compund STR consists of blocks of (AGAT) and (AGAC) repeats with a consensus structure (AGAT)8–l7 (AGAC)6–10 (AGAT)0–1. Whereas shorter alleles only have (AGAT) repeats, > 225 bp alleles are more complex, having two motifs (AGAT) and (AGAC). Population data showed that this to be a highly polymorphic STR with a heterozygosity of 0.9. This fact together with its simple structure make this STR very suitable for forensic and genetic purposes. 相似文献