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1.
Finite Element Method (FEM) using 26-node isoparametric finite elements was applied for modeling saddle-shaped head coils used in Magnetic Resonance Imaging (MRI) generating linearly polarized radiofrequency (RF) pulses at 64 MHz. The human head was modeled from MR scans of a volunteer and additional information were taken from Atlas of Sectional Human Anatomy. The physical dimensions of the head coil and the head permit a calculation of the outside magnetic field by a quasistatic approach. Of course, a full-wave approach was applied within the head. Values of specific energy--specific absorption (SA)--as well as of specific power--specific absorption rate (SAR)--were calculated by the method, simulating the real exposure conditions during MRI. Although the results of the used numerical method were compared previously to the results of the analytical solution with homogeneous sphere and to the results of RF measurements on heterogeneous phantom, a comparison between the numerical results of the modeled human head and in vivo measurements performed on the human head of the volunteer was made once more. Since the results are in excellent agreement, they argue for the correctness of the numerical method. The "worst-case" temperature elevations delta theta of the "hot-spots" were calculated, as well. Finally, the results of SA, SAR, and delta theta are compared to the existing recommendations.  相似文献   

2.
We have studied the effect of a gamma-linolenic acid (18:3 n-6, GLA)-supplemented diet on the growth of a human lung mucoepidermoid carcinoma (HLMC) implanted in athymic mice and on its uptake of human low density lipoproteins labeled with 99mTc (99mTc-LDL). Mice bearing the HLMC were divided into two experimental groups. One of them was administered a control diet (C diet) and the other one was given a diet supplemented with 25 mg GLA/g pellet (GLA diet) for three weeks (Table 1). A tumor growth inhibition with the GLA diet was evident at the second week of treatment, and a marked inhibition (56%) was reached at the end of the third week (Fig. 1). The GLA diet produced some changes in the total fatty acid composition of tumor, plasma and liver of host mice: GLA and arachidonic acid (20:4 n-6, AA) induced significant increases, whereas oleic (18:1 n-9, OA) and linoleic acids (18:2 n-6, LA) were decreased (Table 2). Tumors of those animals fed both diets were labeled by 99mTc-LDL, and no difference was observed in the ratio of tumor/liver and tumor/kidney uptake of host animal (Table 3). Results obtained using this experimental model suggest that the inhibitory effect of GLA on tumor growth is not related to the LDL tumor uptake.  相似文献   

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Although enormous progress has been made in the detection and treatment of localized (nonmetastatic) breast cancer, there has been relatively moderate progress toward the effective treatment of advanced disease. This study investigates the antitumor efficacy of a potent MHC nonrestricted cytotoxic human T cell line (TALL-104) upon transfer into a clinically relevant mouse model of metastatic breast cancer. Fragments from a surgical specimen of a patient with infiltrating ductal carcinoma were implanted s.c. in the flank region of severe combined immunodeficient (SCID) mice. One hundred % of the animals developed a local tumor mass that metastasized to subaxillary and inguinal lymph nodes, bones, lungs, liver, kidneys, ovaries, and brain, very closely mimicking the human disease. Multiple i.p. transfers of gamma-irradiated (nonproliferating) TALL-104 cells into mice bearing low tumor burden (the primary tumor mass weighed only 150 mg) completely arrested local tumor growth and prevented systemic spread into local lymph nodes and distant organs. Remarkably, cell therapy administered in an advanced disease stage (when the tumor weighed 2 g) induced a significant or total regression of established metastasis with no obvious effects on the primary tumor mass. Profound antitumor effects against both local and systemic disease were instead seen in mice that received cell therapy after surgical excision of the primary tumor. The implications of these data in adjuvant breast cancer therapy are discussed.  相似文献   

5.
To determine when and how the dystrophin-positive muscle fibers are formed after myoblast transplantation into dystrophin-negative muscles, the tibialis anterior (TA) muscle from mdx nude mouse was chronologically examined after C2 myoblast transplantation by immunohistochemical and glucose 6-phosphate isomerase (GPI) isoenzyme analyses. The host TA muscle transplanted with C2 myoblasts became necrotic with accumulation of basic fibroblast growth factor in the necrotic areas. This may stimulate concomitant proliferation of the host satellite cells and C2 myoblasts. Small dystrophin-positive muscle fibers appeared in the necrotic areas 3 days after transplantation. This TA muscle contained two different kinds of homodimer GPI isoenzymes but did not contain the heterodimer, suggesting rare fusion of host and donor cells. The dystrophin-positive muscle fibers in the necrotic areas rapidly increased in number and in size by 7 days, but they were smaller than the original host muscle fibers. They had central nuclei, indicating that they were regenerating fibers. The presence of heterodimer GPI isoenzyme in these muscles indicated that the regenerating fibers were mosaic host/donor muscle fibers. The dystrophin-positive muscle fibers are probably formed first by fusion of donor cells with each other and then later by the fusion of host satellite and donor cells.  相似文献   

6.
Improvement of symptoms and, accordingly, quality of life, as well as prolongation of life, are the objectives of drug therapy in congestive heart failure patients. Diuretics are most effective in relieving symptoms related to congestion, and angiotensin converting enzyme inhibitors improve exercise capacity, reduce the incidence of decompensations and hence hospitalizations, and prolong life. Angiotensin type-1 receptor antagonists also seem to improve survival, while digoxin improves symptoms and morbidity but not survival in patients in sinus rhythm. The value of prophylactic antiarrhythmic therapy with amiodarone and oral anticoagulation in the presence of sinus rhythm is not established, and the role of newer dihydropyridine calcium antagonists and betablockers is also not precisely defined. These agents should only be considered in selected cases after careful consideration of potential advantages and risks, and should usually be used as an addition to established therapy. Better understanding of the pathophysiology of congestive heart failure will lead to the development of new treatment concepts, the clinical relevance of which will have to be tested in appropriately designed clinical trials.  相似文献   

7.
Asthma is a common, potentially serious medical complication during pregnancy. Optimal clinical and pharmacologic management is necessary to mitigate maternal and fetal complications. Mild asthma may be managed in most cases with inhaled beta 2-mimetics. Anti-inflammatory therapy is recommended for the treatment of moderate and severe asthma. Based on limited human experience, beclomethasone is currently the recommended inhaled corticosteroid during pregnancy. However, other inhaled corticosteroids may have advantages compared to beclomethasone because of reduced systemic absorption, which may adversely affect intrauterine growth. Based upon theoretic considerations, theophylline is now considered a secondary therapy, but data demonstrating the superiority of inhaled corticosteroids versus theophylline during pregnancy are lacking.  相似文献   

8.
One of the main causes of cardiovascular death is the sudden death which is most frequently caused by malign arrhythmias: ventricular tachycardia (VT) and ventricular fibrillation (VF). These fatal disorders of rhythm are not manageable effectively by surgery, catheter ablation and pharmacology which cannot be thus widely used. Automatic implantable cardiovertors-defibrillators (AICD) have been used since 1980 in the therapy of malign ventricular disorders of rhythm. Modern AICD in more severe ventricular arrhyhmias have reduced the frequency of sudden death from 10-30% yearly to 1%. Our objective was to use preferentially the best therapy possible with the least demanding output and the smallest postoperative risk, i.e. therapy with transvenous AICD. This was enabled by new apparatuses-Phylax 03 and Phylac 06 which are able to give the defibrillation shock by iridium covered electrodes also without subcutaneous so called "patch" electrodes. These circumstances result in a suitable defibrillation threshold. (Fig. 2, Ref. 14.)  相似文献   

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To develop a therapeutic modality for overcoming multidrug-resistant (MDR) cancer with anti-MDR1 antibody, we examined the effect of macrophage colony-stimulating factor (M-CSF) gene transfection into MDR AD10 cells on therapy of MDR cancer with anti-MDR1 antibody (MRK17) in nude mice. MDR human ovarian cancer (AD10) cells were transduced with the human M-CSF gene inserted into an expression vector to establish gene-modified cells capable of producing low (ML-AD10), intermediate (MM-AD10) nd high (MH-AD10) amounts of M-CSF. Systemic administration of MRK17 resulted in significant dose-dependent inhibition of subcutaneous growth of ML-AD10 tumors. In contrast, systemic administration of recombinant M-CSF in combination with MRK17 did not augment the therapeutic efficacy of MRK17 alone, but rather promoted the growth of the parent AD10 cells. To test the efficacy of in vivo M-CSF gene therapy combined with antibody, we mixed the parent AD10 cells with MH-AD10 cells producing a large amount of M-CSF, and inoculated the mixed cells subcutaneously. Treatment with MRK17 inhibited growth of the mixed cells more than that of the parent cells alone. Thus, combined therapy with anti-MDR1 mAb and M-CSF gene modification of MDR cancer cells may provide a new immunotherapeutic modality for overcoming MDR in humans.  相似文献   

11.
Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/- nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.  相似文献   

12.
Recombinant retroviral vectors represent an attractive means of transferring genes into the liver because they integrate in the host cell genome and result in permanent gene expression. However, efficient gene transfer is limited by the requirement of active cell division for integration. Surgical partial hepatectomy has been the traditional method of inducing hepatocellular proliferation, but this invasive approach would be difficult to justify in clinical gene therapy. As an alternative, we used a recombinant adenovirus expressing a nonsecreted form of urokinase plaminogen activator (Ad.PGKmuPA), which results in liver regeneration over a period of 8 days. When a high-titer retroviral vector was continuously infused into the portal vein of mice during this period of hepatocyte proliferation, 33.5% of hepatocytes were stably transduced. In addition, high-level expression of a secreted transgene reporter was sustained for at least 48 weeks (length of experiment). We investigated the influence of vector titer on the in vivo transduction efficiency in our system, and found that the total number of infectious retroviral particles delivered per target cell is a critical factor. The results presented here demonstrate the ability to obtain a high gene transfer efficiency and long-term gene expression in hepatocytes in vivo without the need for surgical hepatectomy. The two-vector system described here may be of clinical relevance, as the level of hepatic gene transfer achieved has potential to be curative for a large number of genetic liver diseases.  相似文献   

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To address the question whether calretinin (CR) may protect cells against Ca2+ overload or trophic factor deprivation, PC12 cells were transfected with plasmids containing a CR coding region under control of a cytomegalovirus promoter. Nerve growth factor (NGF) treatment induced differentiation, increased transfection efficiency (at least 10-fold) and activated the CR gene (as found by RNase protection method and immunohistochemistry). Exogenous CR expression was identified either in living cells by fluorescence of green fluorescent protein (when the CR coding region was fused to this protein) or in fixed cells by CR immunoreactivity. Undifferentiated and NGF-differentiated populations of transfected cells were incubated in the presence of a Ca(2+)-ionophore or in media deprived of serum or NGF. Expression of exogenous CR in undifferentiated or NGF-treated cells (due to transfection) or endogenous CR (due to gene activation by NGF) did not render PC12 cells more resistant to insults such as Ca(2+)-overload and trophic factor deprivation.  相似文献   

15.
Atrial fibrillation is associated with a resting heart rate in excess of age-matched subjects in sinus rhythm, and there is an additional steep rise in rate during exertion. This article reviews the factors responsible for this tachycardia, the pharmacologic agents commonly used for heart rate control, and the effects of atrial antiarrhythmic agents on the heart rate during paroxysmal atrial fibrillation.  相似文献   

16.
With the advent of gene-targeting in mouse embryonic stem (ES) cells, the use of knockout mice to study the physiological effects of loss of gene function has become increasingly prevalent. However, there are several drawbacks with conventional gene-targeting approaches which may make phenotyping of the resultant mice difficult, if not, impossible. Conventional gene-targeting results in the loss of function of the targeted gene in all cells and tissues, which can be problematic for genes which are required developmentally, which exhibit a wide tissue-specific expression pattern, or are part of complex paracrine systems. As with mice that lack the angiotensinogen or endothelin-1 gene, loss of gene function may lead to a lethal phenotype which can be manifested during embryonic development, at birth or postnatally. These limitations could potentially be circumvented by using a system in which the loss of gene function is placed under spatial and/or temporal control. We will discuss how the cre-loxP recombinase system can be applied to delete a gene in a tissue- and developmentally regulated fashion.  相似文献   

17.
The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver metastasis and peritoneal dissemination of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2 and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was prevented significantly by early treatment of TNP-470. In particular, early treatment of MT-2 completely inhibited the development of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer.  相似文献   

18.
Previous rodent studies have demonstrated the capacity of cerebellar transplants to organize into trilaminar cell layers typically observed in the normal cerebellum. In Purkinje Cell (PC)-deficient animals, PCs will migrate into the host and form synaptic connections. Recently, fetal cerebellar grafts transplanted into the Purkinje cell degeneration (pcd) mutant mouse were shown to result in an improvement of motor behaviors. These studies indicate the potential therapeutic use of neural transplantation in patients with cerebellar degeneration. In the present study, human fetal cerebellar tissue (8.5 wk postconception) was dissociated and transplanted into the normal cerebellum of nude mice. Six months following transplantation, histological analysis revealed donor cells in recipient mice. Immunostaining for the 28 kDa calcium-binding protein (calbindin) revealed the presence of donor PCs that were organized in discrete cellular layers within the transplant neuropil. In most cases the dendritic processes were oriented in a planar fashion perpendicular to the transplant cell layer. Human neurofilament immunostaining revealed bundles of donor fibers within the core of the transplant and/or at the periphery. These bundles were found to be calbindin positive (PC fibers). Three animals provided evidence of donor PC axon growth ventrally into host white matter, and in one case, this ventral migration reached the deep cerebellar nuclei. Most notable was the development of a pronounced folia-like organization by the implanted cell suspensions. Glial processes within the grafts were aligned perpendicular to the long axis of the transplant folia. These results demonstrate the capacity of human fetal cerebellar cell suspension to reorganize into cell layers typical of the normal cerebellum following transplantation into the rodent cerebellum, and develop an organotypic folia-like organization.  相似文献   

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Nine subjects ranging in muscle fiber composition (m, vastus lateralis) from 38% to 100% slow twitch (ST) were filmed while running on a treadmill at a speed corresponding to the onset of blood lactate accumulation (VOBLA). The film analysis concentrated on several kinetic features of running, such as mechanical work (W) and average power output (W) for the total step cycle including the positive and negative work phases. The results indicated that %ST was related significantly (r = 0.78) with VOBLA and with the average speed of a marathon race (Vm; r = 0.80), which followed the treadmill test. The values of VOBLA and Vm were 4.27 +/- 0.51 and 3.74 +/- 0.64 m x s-1, respectively. Capillary density as calculated from amylase PAS staining of the muscle samples demonstrated also a significant relationship with Vm (r = 0.80). The value of W was not significantly related to either %ST or VOBLA. However, the average mechanical power output at VOBLA (WOBLA) demonstrated high correlations with %ST (r = 0.75), VOBLA (r = 0.90), Vm (r = 0.92), and with capillary density (r = 0.77). The findings suggest that mechanical power at VOBLA is an important parameter, which indicates the maximum power output of the runner under pure aerobic conditions.  相似文献   

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