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2.
Tetsuhiko Nagao Seizo Sadoshima Takao Ishitsuka Kenji Kusuda Osamu Shiokawa Setsuro Lbayashi Masatoshi Fujishima 《Clinical and experimental pharmacology & physiology》1992,19(7):489-493
1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke-prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia. 2. The resting cerebral blood flow was comparable between the control and denervated animals. 3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham-operated control and denervated animals during ischaemia. 4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp. 相似文献
3.
4.
The property of aerobic glycolysis commonly possessed by malignant cells points to a weakness in oxidative metabolism which has been equated in some tumours with partial uncoupling of oxidative phosphorylation. The suggestions are made, first, that this endogenous defect may account for spontaneous cell death
, and, second, that its accentuation would inflict extensive tumour injury upon sensitive neoplasms. Certain drugs not in current use for the treatment of malignant disease are known to be able to interfere selectively with energy metabolism in sensitive tumours to such an extent that widespread necrotisation ensues. The drugs activate an endogenous destructive mechanism that appears to require oxygen. Liminal therapy, the maintenance of continuous destructive pressure on sensitive growths in such a manner that maximal anti-tumour activity in terms of interference with energy production is not achieved at any one time, and under conditions in which the oxygen supply is only partly depleted, is put forward as a possible means of achieving complete and selective tumour destruction
. 相似文献
5.
Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis 总被引:3,自引:0,他引:3
Ichiki Y Selmi C Shimoda S Ishibashi H Gordon SC Gershwin ME 《Clinical reviews in allergy & immunology》2005,28(2):83-91
Several factors point toward an auto-immune pathogenesis for primary biliary cirrhosis (PBC), mostly based on the presence
of serum auto-antibodies to mitochondrial antigens (AMAs) and autoreactive T cells (both helper and cytotoxic). Interestingly,
epitopes recognized by AMA and T-cell clones are located within overlapping areas of the antigens. Moreover, a role for an
imbalance in cytokine pattern and for natural-killer lymphocytes has also been proposed. Despite several experimental reports,
no clear evidence is available regarding the interaction of these factors leading to bile duct destruction. This article reviews
the current reports regarding the auto-immune reaction against mitochondrial auto-antigens in PBC. 相似文献
6.
N. Zurgil R. Bakimer M. Kaplan P. Youinou Y. Shoenfeld 《Journal of clinical immunology》1991,11(5):239-245
Antimitochondrial antibodies (AMA) may be detected in 95% of patients with primary biliary cirrhosis (PBC). The target autoantigens for the AMA were recently identified as four closely related metabolic enzymes located in the mitochondria. We have purified the pyruvate dehydrogenase (PDH) enzyme from bovine heart, showing that all PBC sera reacted with a 74-kd band. PDH was utilized to establish an ELISA assay for detecting the relevant antibodies. One hundred twelve of 120 sera from patients with PBC (95%) reacted with the PDH but none of the 201 control sera, including normal subjects and a panel of sera from other patients with liver diseases, showed similar reactivity. In 77% of the PBC sera the anti-PDH antibody isotype was identified as a combination of IgG and IgM, while in 18% only IgM was detected. In 5% of the sera the isotype was confined to IgG. PBC sera specifically inhibited the PDH enzyme activity. The enzyme inhibition correlated with the anti-PDH antibody titers. Thus, PDH seems to be one of the major target epitopes for AMA observed in sera of patients with PBC. 相似文献
7.
Previous studies have shown that xenobiotic compounds such as the environmental pollutant -hexa-chlorocyclohexane (-HCH) and the synthetic sex steroid cyproterone acetate (CPA) induce growth of rat liver by hypertrophy and hyperplasia. After withdrawal of the growth stimuli, liver hypertrophy was usually found to be readily reversible. Conflicting observations were made concerning the fate of liver hyperplasia: hepatic hyperplasia persisted when induced by -HCH but was found to be partially reversible when induced by CPA. The present study confirms the reversibility of hepatic hyperplasia induced by CPA in rats: about 30% of liver DNA present at maximal liver enlargement disappeared within 6 days after cessation of CPA treatment. Simultaneously, a dramatic increase in the rate of cell elimination by apoptosis was found. Glutamate-pyruvate transaminase and alkaline phosphatase in serum did not show major increases, suggesting that cell death was not due to lytic membrane damage. Furthermore, if treatment with CPA was continued or resumed, the enhanced DNA content persisted and the number of apoptotic bodies was greatly reduced. These observations suggest that the occurrence of cell death is due to withdrawal of the growth stimulus CPA. It may reflect a regulatory phenomenon serving to maintain homeostasis of cell number.Further studies showed that CPA is rapidly eliminated from rat liver and serum: t 1/2 in the liver is about 11 h. In contrast, -HCH was previously found to be eliminated more slowly: t 1/2 approximately 144 h. The present study revealed that -HCH, CPA and nafenopin lower the number of apoptotic bodies. This suggests that inducers of liver growth can inhibit hepatocellular death by apoptosis. It is concluded that the regression of hyperplasia after CPA withdrawal may be due to its rapid elimination. On the other hand the relatively long persistence of -HCH may result in inhibition of cell death and thereby stabilize hepatic hyperplasia.Abbreviations CPA
cyproterone acetate
- -HCH
-hexachlorocyclohexane
- PB
phenobarbital
- NAF
nafenopin
- AB
apoptotic body
- b.w.
body weight
- p. admin.
post-administration
- GPT
glutamate-pyruvate transaminase
- ALP
alkaline phosphatase
Dedicated to Professor W. Koransky on the occasion of his 65th birthday 相似文献
8.
张丹 《中国卫生标准管理》2021,(6):95-98
目的探究肿瘤M2型丙酮酸激酶检测在结肠癌诊断中的临床价值。方法选取本院经病理诊断确诊为结肠癌的50例患者与结肠腺瘤的60例患者分别设为结肠癌组与结肠腺瘤组,选择90例健康人设为正常组,分别使用ELISA、化学发光法(CL)检测血浆M2-PK数值及癌胚抗原(CEA)水平。结果结肠癌组及Dukes C、D期肿瘤M2-PK水平与结肠腺瘤组、正常组及Dukes A、B期相比更高(P<0.05),肿瘤M2-PK结肠癌诊断敏感性与CEA相比更高。结论肿瘤M2型丙酮酸激酶检测在结肠癌诊断中具有较高的临床价值,且肿瘤M2-PK的敏感性高于CEA,与肿瘤分期之间具有十分密切的联系,能够有效应用于结肠癌的筛查与诊断工作当中。 相似文献
9.
Sotiria Tavoulari Maximilian Sichrovsky Edmund R. S. Kunji 《Acta physiologica (Oxford, England)》2023,238(4):e14016
The mitochondrial pyruvate carrier (MPC) resides in the mitochondrial inner membrane, where it links cytosolic and mitochondrial metabolism by transporting pyruvate produced in glycolysis into the mitochondrial matrix. Due to its central metabolic role, it has been proposed as a potential drug target for diabetes, non-alcoholic fatty liver disease, neurodegeneration, and cancers relying on mitochondrial metabolism. Little is known about the structure and mechanism of MPC, as the proteins involved were only identified a decade ago and technical difficulties concerning their purification and stability have hindered progress in functional and structural analyses. The functional unit of MPC is a hetero-dimer comprising two small homologous membrane proteins, MPC1/MPC2 in humans, with the alternative complex MPC1L/MPC2 forming in the testis, but MPC proteins are found throughout the tree of life. The predicted topology of each protomer consists of an amphipathic helix followed by three transmembrane helices. An increasing number of inhibitors are being identified, expanding MPC pharmacology and providing insights into the inhibitory mechanism. Here, we provide critical insights on the composition, structure, and function of the complex and we summarize the different classes of small molecule inhibitors and their potential in therapeutics. 相似文献
10.
C. W. M. van Veelen H. Verbiest K. J. Zülch B. van Ketel M. J. M. van der Vlist A. M. C. Vlug G. Rijksen G. E. J. Staal 《Acta neurochirurgica》1982,61(1-3):145-159
Summary Pyruvate kinase isozyme distribution was studied in 101 intracranial tumours of various nature and origin, and in normal human brain (both foetal and adult). In foetal brain, five different forms could be detected by electrophoresis (K4, K3M, K2M2, KM3, and M4). In adult brain, the M4 type, K3M hybrid, and K4 are present; the M type is largely predominant. Alanine inhibition of pyruvate kinase can be used to discriminate between M and K-type pyruvate kinase. The results obtained in an alanine inhibition test are in agreement with the electrophoretic pattern. Pyruvate kinase from foetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. In adult brain a high residual activity of pyruvate kinase is found in the presence of alanine. Well differentiated neuroepithelial tumours,i.e., astrocytomas, oligodendrogliomas, and ependymomas showed also relatively high residual activities, though less than in normal adult brain. On the contrary, in poorly differentiated gliomas low residual activity was found. Alanine inhibition of pyruvate kinase correlates well with degree of differentiation of these tumours. There is also a strong correlationship between alanine inhibition of pyruvate kinase and one year survival after total or subtotal resection of gliomas in adults.When in gliomas the residual activity is determined not in the centre of the tumour but more towards the periphery, much higher residual activity is found. It is suggested that brain biopsies in which a residual activity higher than 70% is found probably contain no tumour in the paraffin slides.Poorly differentiated gliomas were characterized by the presence of type K, and the hybrids K3M. In well differentiated gliomas, besides K4 and K3M, M4 was also present. Alanine inhibition was in agreement with the electrophoretic pattern in all tumours. In children (age 1–11 years) gliomas showed no correlation between the distribution of pyruvate kinase isozymes and the histological classification and grading. Of the non-neuro-epithelial tumours studied relatively high residual activities were found for pyruvate kinase in haemangioblastomas, chromophobe adenomas, and craniopharyngiomas. This was also found in an arteriovenous malformation. Other non-neuroepithelial tumours showed much less residual activity. These included benign tumours, meningiomas, neurilemmomas, malignant metastatic tumours, and fibrosarcomas. It was also found in cavernomas. The determination of pyruvate kinase activity in the presence of alanine may be useful for the diagnosis and treatment of intracerebral tumours, in particular gliomas of adults.The alanine inhibition test is a reliable quantitative procedure. It can be performed in 10 minutes, and may well fit in the scope of a surgical procedure. 相似文献