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61.
Bisphosphonates are a group of chemical substances which have been used in medicine for thirty years in the treatment of skeletal diseases and disorders of calcium metabolism. Bisphosphonates are derived from pyrophosphate by substitution of an O atom for a C atom. This structure makes possible a number of variants by changing the side-chains of the C atom. The basic P-C-P bond is very thermostabile and completely resistant to enzymatic hydrolysis. The basic biological property of bisphosphonates is inhibition of bone resorption but has not been completely elucidated so far. The prerequisite is the inhibitory action of bisphosphonates on osteoclast activity. The latter are inhibited only when they are in contact with bone surfaces which contain bisphosphonates. Another possible mechanism of action of bisphosphonates is their action on osteoblasts: osteoblasts produce local growth factors which inhibit osteoclasts and thus osteoresorption is inhibited. So far it is not exactly known whether the direct effect on osteoclasts, the indirect effect via osteoblasts or a combination of both are the most important effect of bisphosphonates on the resorption of bone.  相似文献   
62.
Orthotopic heart transplantation (OHT) with bicaval and pulmonary venous anastomoses avoids the large atrial anastomoses of the standard biatrial technique. To determine whether the bicaval technique improves atrial performance, we used Doppler echocardiography to study 13 patients with bicaval OHT, 15 with biatrial OHT, and 8 normal subjects. All were in sinus rhythm and free of rejection. Left atrial size, transmitral (M) and late diastolic (A) mitral flow velocity integrals were measured. Atrial transport (A/M, %) and atrial ejection force (kilodynes, calculated from peak A-wave velocity and mitral orifice area) were assessed. Left atrial dimensions in the bicaval (4.3 +/- 0.5 cm) and biatrial groups (4.9 +/- 0.9 cm) were larger than in controls (3.3 +/- 0.8 cm, p < 0.05). Left atrial transport (37% +/- 12% and 35% +/- 12%) and ejection force (14.1 +/- 6.9 kdyne and 10.2 +/- 7.8 kdyne) were similar in the bicaval group and controls (p not significant) but were significantly lower in the biatrial group (20% +/- 19% and 3.6 +/- 4.0 kdynes, p < 0.05). The bicaval and pulmonary venous technique of OHT produces more physiologic atrial function compared with the biatrial technique as evidenced by greater atrial ejection force and more normal atrial transport.  相似文献   
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64.
Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantitatively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus results in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.  相似文献   
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66.
A feasibility study is carried out on a 1.6 μm continuous-wave modulation laser absorption spectrometer system for measurement of global CO(2)concentration from a satellite. The studies are performed for wavelength selection and both systematic and random error analyses. The systematic error in the differential absorption optical depth (DAOD) is mainly caused by the temperature estimation error, surface pressure estimation error, altitude estimation error, and ON wavelength instability. The systematic errors caused by unwanted backscattering from background aerosols and dust aerosols can be reduced to less than 0.26% by using a modulation frequency of around 200 kHz, when backscatter coefficients of these unwanted backscattering have a simple profile on altitude. The influence of backscattering from cirrus clouds is much larger than that of dust aerosols. The transmission power required to reduce the random error in the DAOD to 0.26% is determined by the signal-to-noise ratio and the carrier-to-noise ratio calculations. For a satellite altitude of 400 km and receiving aperture diameter of 1 m, the required transmission power is approximately 18 W and 70 W when albedo is 0.31 and 0.08, respectively; the total measurement time in this case is 4 s, which corresponds to a horizontal resolution of 28 km.  相似文献   
67.
68.
The clinical utility of doxorubicin, an antineoplastic agent, is limited by its cardiotoxicity. Our objective was to determine whether expression of genes encoding proteins that affect Ca2+ homeostasis were altered in the hearts of rabbits chronically treated with doxorubicin. Twelve male New Zealand white rabbits received an injection of doxorubicin (2.5 mg/kg i.v.) once a week for 8 weeks. Eight rabbits were similarly injected with saline as controls. The cardiac function of both groups was evaluated 8 weeks after the final injection, as were the levels of expression of mRNA for Ca2+ transport proteins in the sarcoplasmic reticulum and plasma membrane. The amount of the sarcoplasmic reticulum Ca2+-ATPase and the Ca2+ uptake capacity of the protein were also quantitated. Cardiac output was significantly decreased in the doxorubicin-treated group (71+/-21 ml/min, P<0.05) compared with the control group (118+/-15 ml/min). The mRNA levels for the sarcoplasmic reticulum proteins were significantly diminished in the doxorubicin-treated hearts: ryanodine receptor-2 (relative expression level compared with controls, 0.35+/-0.13, P<0.01), sarcoplasmic reticulum Ca2+-ATPase (0.56+/-0.13, P<0.01), phospholamban (0.62+/-0.20, P<0.01) and cardiac calsequestrin (0. 57+/-0.26, P<0.01). In addition, both relative amount of sarcoplasmic reticulum Ca2+-ATPase protein (doxorubicin-treated group, 69+/-17% of control, P<0.01) and the Ca2+ uptake capacity (46. 9+/-9.8 nmol Ca2+/mg protein-5 min in doxorubicin group v 63.2+/-10. 4 in the control group, P<0.01) were concomitantly decreased with its mRNA expression level. Conversely, the mRNA levels for the plasma membrane proteins did not differ from those of control rabbits: the dihydropyridine receptor (relative expression level, 1. 03+/-0.30, N.S.), plasma membrane Ca2+-ATPase (0.93+/-0.33, N.S.) and the Na+/Ca2+ exchanger (0.87+/-0.34, N.S.). These findings suggest that a selective decrease in mRNA expression for sarcoplasmic reticulum Ca2+ transport proteins is responsible for the impaired Ca2+ handling, and thus, for the reduced cardiac function seen in the cardiomyopathy induced in rabbits by the long-term treatment with doxorubicin.  相似文献   
69.
The Escherichia coli exonuclease III (AP endonuclease VI) is a DNA-repair enzyme that hydrolyzes the phosphodiester bond 5' to an abasic site in DNA. To study how the enzyme recognizes the abasic site, we used oligonucleotides containing a synthetic abasic site at any desired position in the sequence. We prepared oligonucleotides containing an abasic residue such as 2'-deoxyribosylformamide, 2'-deoxyribose, 1',2'-dideoxy ribofuranose or propanediol. Duplex oligonucleotides containing an abasic residue used in this study were cleaved on the 5' side of the abasic site by exonuclease III in spite of the varieties of the bases opposite and adjacent to the abasic site. In addition, we observed that the enzyme cleaved single-stranded oligonucleotides containing an abasic site on the 5' side of the abasic site. These findings suggest that the enzyme may principally recognize the DNA-pocket formed at an abasic site. The indole ring of the tryptophan 212 residue of the exonuclease III is probably intercalated to the abasic site. The tryptophan in the vicinity of the catalytic site is conserved in the type II AP endonuclease from various organisms.  相似文献   
70.
Two patients with uterine cervical adenocarcinoma received two courses of intra-arterial cisplatin administration. In the specimens of cervix 24 or 48 h after chemotherapy, marked apoptosis were observed. These bulky cervical tumors almost disappeared, and good PRs were confirmed by CT before operation. Apoptosis which is observed in the tissues of cervical adenocarcinoma 24 or 48 h after intra-arterial infusion of cisplatin, might be a new criterion of this chemotherapy effect.  相似文献   
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