Dissipative processes during cyclic hardening of spheroidal graphite cast iron

The hardening of spheroidal graphite cast irons alloyed by vanadium via chemical dispersion has been studied. Strain hardening is experimentally found to effectively occur in a cast iron with a relatively low vanadium content (0.5 wt %). Dissipative processes in cast irons with dispersed vanadium carbide inclusions are analyzed. An increase in the degree of dispersion of vanadium carbide inclusions is shown to favor more complete dissipation of the supplied energy into heat and decreases the level of damage in the material.     

Loss of ovarian function promotes angiogenesis in human ovarian carcinoma

We show here that elevated levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), as found in menopause or after ovariectomy, promote growth of human ovarian carcinoma by induction of tumor angiogenesis. Human epithelial ovarian cancer tumors progressed faster in ovariectomized mice. This induced growth could be attributed to the elevated levels of gonadotropins associated with loss of ovarian function because direct administration of gonadotropins also was effective in promoting tumor progression in vivo. On the other hand, gonadotropins had no direct effect on the proliferation of human ovarian cancer cells in vitro. Using MRI, we demonstrated that ovariectomy significantly (P < 0.02) induces neovascularization of human ovarian carcinoma spheroids implanted in nude mice. Moreover, conditioned medium of gonadotropin-treated human ovarian carcinoma cells showed increased mitogenic activity to bovine endothelial cells, and this activity could be blocked by neutralizing antibodies against luteinizing hormone and against vascular endothelial growth factor. Accordingly, gonadotropin stimulation resulted in a dose-dependent-induced expression of vascular endothelial growth factor in monolayer culture as well as in the outer proliferating cells of human ovarian cancer spheroids. These results demonstrate the significance of the elevated levels of gonadotropins, as found in menopause and in all ovarian cancer patients, on the progression of ovarian cancer and could explain the protective effect of estrogen replacement therapy. Based on these results, we suggest that hormonal therapy aimed at lowering the circulating levels of gonadotropins may possibly prolong remission in ovarian cancer by extending tumor dormancy.     

Intrafollicular insulin-like growth factor-binding protein levels in equine ovarian follicles during preovulatory maturation and regression

The profiles of insulin-like growth factor-binding proteins (IGFBPs) in follicular fluid have been characterized in a number of mammals (rats, pigs, sheep, cattle, humans) and are good indicators of follicular status. We studied the IGFBP profiles of equine serum and ovarian follicular fluid recovered at various stages of the follicular phase. The levels of IGFBPs were related to the morphology and the steroidogenic activity of the follicles. Follicular fluids were recovered by ultrasound-guided follicular aspiration. In the first experiment, the dominant follicles of 10 mares were partly punctured (aspiration of 0.5-2.2 ml of fluid) once at the early dominant stage (22-25 mm in diameter) and a second time at the preovulatory stage (PO), 34 h after induction of ovulation. Among these 10 PO follicles, 5 were classified as healthy whereas the other 5 were classified as hemorrhagic, as assessed by ultrasonic morphology and subsequent ovulation or not. In another group of mares (n = 5), the largest follicle was punctured once at the late dominant stage (33-35 mm in diameter) and then at the PO stage, 34 h after induction of ovulation. Serum was prepared at each puncture session. In the second experiment, follicular fluid was recovered from the dominant and contemporary cohort subordinate follicles (n = 5 mares). Samples were individually assayed for estradiol-17beta and progesterone content by RIA, and IGFBPs were studied by using Western ligand blotting and densitometry. Equine serum and follicular fluid displayed IGFBP at 42-44 kDa (likely corresponding to IGFBP-3), 28-32 kDa (likely corresponding to IGFBP-5), 24 kDa (likely corresponding to IGFBP-4), and 35 kDa, identified as IGFBP-2 by immunoblotting, plus one band at 120 kDa. IGFBP were clearly more abundant in serum than in fluid from healthy follicles. In the follicular fluid, 42-44-kDa IGFBP was the major binding protein, and its level was almost constant at the various physiological statuses studied. Follicular development of the dominant follicle in each mare was characterized by a decrease in intrafollicular IGFBP-2 and 28-32-kDa IGFBP levels before LH stimulation and by an increase in IGFBP-2 after LH stimulation. Follicular regression of large follicles, as well as subordinate ones, was characterized by a low level of intrafollicular estradiol-17beta and was associated with an increase in IGFBP-2, 24-kDa IGFBP, and 28-32-kDa IGFBP intrafollicular levels. Taking these results together, we have demonstrated clear correlations between the intrafollicular levels of estradiol-17beta and IGFBP-2 and 28-32-kDa IGFBP. Therefore, follicular growth and regression in the mare are associated with specific changes in IGFBP levels. These changes could be of crucial importance for follicular development in ovulation or atresia.     

Hydrogen-involved tensile and cyclic deformation behavior of low-alloy pressure vessel steel

The temperature- and strain-rate-dependent tensile behavior of hydrogen-charged low-alloy pressure vessel steel ASTM A508 C1.3 has been investigated. The fatigue crack initiation and propagation behavior of the steel in high-temperature water environments has also been evaluated. It was found that hydrogen played significant roles in both tensile and cyclic deformation processes, especially in the temperature and strain-rate region of dynamic strain aging (DSA). The presence of hydrogen resulted in a distinct softening in tensile strength and a certain loss in tensile ductility in the DSA region. Remarkable degradation in fatigue crack initiation and propagation resistance in high-temperature water environments was observed in the DSA strain-rate region. Typical hydrogen-induced cracking features also appeared on the corresponding fatigue fracture surfaces. The interactions between hydrogen and DSA in tensile and cyclic deformation processes are discussed as well as their combined effects on the environmentally assisted cracking (EAC) mechanism of pressure vessel steels in high-temperature water environments.     

Usefulness of Dallon prostheses for blood vessel reconstruction

Experimental and clinical results of the application of Dallon prostheses in vascular surgery are presented. Dallon prostheses are produced in the Medical Materials Department of the Research Development Centre of the Knitting Industry in ?ód?. They are contained in disposable radially sterilized wrappings. The experiments were performed on 17 mongrel dogs and the process of healing in was observed after three and six months. The process was similar to the healing in of other porous, synthetic prostheses. In 37 patients operated because of the artheromasia bypasses or vascular flaps of Dallon prostheses were implanted. The results of experimental and clinical research proved that the radially sterilized Dallon prostheses have similar properties like the prostheses produced be well known foreign firms, and are very useful in arterial reconstruction.     

The frequency of cyclic processes in biological multistate systems

Cyclic processes in stochastic models of macromolecular biological systems are considered. The diagram solution of the model equations (master equation) gives rise to special functions of the rate constants, called the circuit (or one-way cycle) fluxes. As Hill has shown, these functions are the fundamental theoretical components of the operational fluxes, i.e., of the rates of reaction, of transport, of energy conversion, etc. Evidence recently has been found by Monte Carlo simulations that the circuit fluxes can be interpreted as the frequencies of circuit completions. Making use of the theory of graphs, we prove that this physical interpretation of the circuit fluxes is generally valid.     

Ultrastructural alterations of collagen fibrils in blood vessel walls

With increasing concern for elucidation of the role of connective tissues in degenerative diseases of blood vessels, an ultrastructural study was conducted on collagen fibrils of intimal proliferation in experimental autogenous venous pouch aneurysms in rabbits and in atherosclerotic human arteries. The fibrils were compared morphometrically with adventitial collagen as controls. In intimal proliferation from both species intimal collagen fibrils displayed increased variation in shape and size when compared to adventitial collagen fibrils. The abnormal fibrils resembled those of inherited connective tissue diseases, indicating that the changes in collagen fibrils can be acquired and that hemodynamic stress is likely to contribute to their occurrence.     

适量献血可以避免心脑血管疾病

自1998年10月1日<中华人民共和国献血法>颁布实施以来,无偿献血人数有了较大提高,尤其是街头无偿献血者,特别是外五县的居民,文化层次不算太高,但在献血的概率上确挺高.约占献血者的60%以上.他们对无偿献血的知识、态度及行为只是从义务献血制度,实际上还是属于有偿献血制度到实施无偿献血制度这个跨度中.他们只认为献血就可以改善心脑血管疾病,防止血稠,不得脑血栓,而踊跃献血.从国内心血管专家对127名多次献血者、87例高血压者、60例缺血性中风者,进行血液流变学的对照研究,结果表明,证实了这一点.适量献血可减少或避免心脑血管疾病的发生.     

The degree of nonlinearity and anisotropy of blood vessel elasticity

Blood vessel elasticity is important to physiology and clinical problems involving surgery, angioplasty, tissue remodeling, and tissue engineering. Nonlinearity in blood vessel elasticity in vivo is important to the formation of solitons in arterial pulse waves. It is well known that the stress-strain relationship of the blood vessel is nonlinear in general, but a controversy exists on how nonlinear it is in the physiological range. Another controversy is whether the vessel wall is biaxially isotropic. New data on canine aorta were obtained from a biaxial testing machine over a large range of finite strains referred to the zero-stress state. A new pseudo strain energy function is used to examine these questions critically. The stress-strain relationship derived from this function represents the sum of a linear stress-strain relationship and a definitely nonlinear relationship. This relationship fits the experimental data very well. With this strain energy function, we can define a parameter called the degree of nonlinearity, which represents the fraction of the nonlinear strain energy in the total strain energy per unit volume. We found that for the canine aorta, the degree of nonlinearity varies from 5% to 30%, depending on the magnitude of the strains in the physiological range. In the case of canine pulmonary artery in the arch region, Debes and Fung [Debes, J. C. & Fung, Y. C.(1995) Am. J. Physiol. 269, H433-H442] have shown that the linear regime of the stress-strain relationship extends from the zero-stress state to the homeostatic state and beyond. Both vessels, however, are anisotropic in both the linear and nonlinear regimes.     

Vascular events responsible for thrombotic occlusion of a blood vessel

In summary, the sequence of endothelial plaque disruption, platelet activation, and thrombogenic factors--that is, the balance between the thrombolytic system and the coagulation system--determine which blood vessel will thrombose and which vessel will remain patent. It seems to me that although the soft plaque with the thin cap and lipid core laden with oxidized LDL-activated macrophages is more prone to rupture than the calcified, hard plaque, it is also the plaque that may regress when the patient is treated aggressively with lipid-lowering or antioxidant therapy. In addition, drugs that lower blood pressure and heart rate may also decrease the tendency of the "vulnerable" plaque to rupture by attenuating fatigue failure. Current and future research should be directed at identifying vulnerable plaques in the individual patient, so that measures can be taken to prevent plaque rupture.     

Morphological profiles of mouse ovarian follicles: extensive accumulation of a strongly negative-charged substance at specific foci in follicular tissue during oocyte maturation

Structural changes in cumulus-oocyte complexes and granulosa cells were induced by administering pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to female mice. Three and 9 h after hCG administration, dissolution of the germinal vesicle (GVBD) and progression to the second metaphase occurred respectively in oocytes. The number of cumulus cells associated with the granulosa cell layer decreased significantly 1 h after hCG administration. Expansion of cumulus cell investment was due to the abundant deposition of intercellular materials in the cumulus-oocyte complexes during oocyte maturation. A strongly negative-charged (colloidal iron-positive) substance was detected in the intercellular spaces of follicular tissue, especially in the cumulus mass. Moreover, cells located where the cumulus mass and granulosa cell layer intertwined became enlarged during the resumption of the meiosis of oocytes. Colloidal iron-positive substances accumulated extensively within the intercellular spaces of the enlarged cells.     

The assessment of ovarian tumor angiogenesis: what does three-dimensional power Doppler add?

A new approach to defining and calculating accuracy and uncertainty in external dosimetry is described. It is more comprehensive and mathematically rigorous than other approaches currently in use, while at the same time being practical to implement. The type testing required to demonstrate the performance of a dosimeter is described, and an example of the calculation of accuracy and uncertainty is given. The paper concludes with some recommendations concerning performance testing and independent testing.     

Regulation of angiogenesis by hypoxic stress: from solid tumours to the ovarian follicle

The preovulatory follicle provides a unique physiological example of rapid growth accompanied by neovascularization, two processes that are generally characteristic of pathologies such as wound repair or malignancy. During the hours preceding ovulation, follicular growth is accompanied by elevated levels of messenger RNA for vascular endothelial growth factor (VEGF). Angiogenic activity, mediated by VEGF, is manifested in the peripheral blood vessels surrounding the follicle, that show capillary sprouting and increased vascular permeability. Following ovulation, rapid infiltration of capillaries through the follicular wall is essential for the formation of the corpus luteum. In this review we compare the preovulatory follicle with a popular model of avascular solid tumour growth, namely the multicellular tumour spheroid, in particular the role of hypoxic stress in the regulation of angiogenesis in both systems.     

Preoperative assessment of blood vessel involvement in patients with pancreatic cancer

The major prerequisite for resection of a pancreatic tumor is non-involvement of large blood vessels. Preoperative assessment of blood vessel infiltration may prevent unnecessary surgery. The aim of our study was to investigate the accuracy of endoscopic ultrasonography (EUS) in diagnosis of pancreatic cancer and in preoperative staging. Thirteen patients (7 females, 6 males; mean age 64 years) with a pancreatic tumor, but no evidence of distant metastases, underwent EUS and computerized tomography (CT) in order to assess blood vessel involvement by the tumor. The results were compared with intraoperative findings in 12 patients and with postmortem findings in 1 patient. A tumor was demonstrated by EUS in 12 patients and was confirmed at surgery in all 12 patients. In one patient no tumor was demonstrated by EUS, although a tumor was visible by CT; no tumor was found at surgery. In two patients CT failed to demonstrate a pancreatic tumor that was demonstrated by EUS; at surgery a tumor was detected in both patients. EUS detected blood vessel involvement in seven patients, which was confirmed at surgery in six of them. In the other six patients surgery confirmed the EUS finding of no blood vessel involvement. CT detected blood vessel involvement in two patients only. The overall accuracy of EUS and CT for detecting the tumor was 100% and 77% respectively, and for blood vessel involvement 92% and 61% respectively. In conclusion, EUS is an accurate procedure for preoperative assessment of blood vessel involvement in patients with pancreatic cancer. This procedure may enable the selection of those patients who may benefit from surgery, and should be part of the evaluation of patients with pancreatic cancer who are candidates for curative surgery.     

Differential release of proteoglycans during human B lymphocyte maturation

Proteoglycans interact with soluble proteins such as growth factors and thereby regulate extracellular signals. During B lymphocyte maturation, secretion of proteoglycans may be functionally related to the different requirements of the respective maturation stage. In order to address this question we compared structures of proteoglycans released by three B lymphocyte lines which correspond to different maturation stages. Plasma-cell type U266 cells secreted the largest proteoglycans (150 kDa), followed by mature B cells JOK-1 (130 kDa) and pre-B cells Nalm 6 (90 kDa). On average, secreted proteoglycans carried four glycosaminoglycan chains with molecular masses ranging each from 32 kDa (U266) to 23 kDa (Nalm 6). All three cell lines secreted more than 90% of their proteoglycans possessing chondroitin sulfate chains having chondroitin-4-sulfate (delta Di-4S) as the prevalent disaccharide unit. In these proteochondroitin sulfates, unsulfated chondroitin (delta Di-0S) was present in smaller quantities and chondroitin-6-sulfate (delta Di-6S)-containing proteoglycan was released only by Nalm 6 and U266 cells. Cell line Nalm 6 exclusively produced proteochondroitin sulfate, whereas in culture medium of JOK-1 and U266 a small amount of proteoheparan sulfate was found also. In all three cell lines, treatment with chondroitinase ABC released a protein of 30 kDa and chemical deglycosylation resulted in a core protein of 21 kDa. In addition to pure proteochondroitin sulfate, a small portion of proteoheparan sulfate with a protein moiety of 30 kDa was detected after heparitinase treatment in supernatants of JOK-1 and U266. Thus, our results indicate that released proteoglycans may undergo modulations in their glycosaminoglycan moieties during B-cell differentiation. This may have functional consequences at the level of growth factor regulation.     

Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins during sperm maturation

The majority of gene therapy protocols have used or plan to use retroviral vectors based upon murine leukaemia virus. These vectors are able to infect many different cell types, and the retroviral promoter, which is often used to control the expression of a therapeutic gene, is active in a wide range of different cell types. Safe and efficient gene transfer systems, whether based upon retroviruses or other agents, should deliver beneficial genes only to cells that require their therapeutic action, and these genes ideally should be expressed exclusively in such cells. In this paper, strategies for redirecting the infection spectrum of retroviral vectors in order to obtain cell-targeted gene delivery are discussed. These strategies include the engineering of the retroviral envelope protein, which, together with the availability of its cognate receptor, determines infectivity, and the use of proteins from other enveloped viruses of both retroviral and nonretroviral origin in the cell lines used to produce retroviral vector virus particles. Expression targeting can be achieved by limiting the expression of therapeutic genes to the cell type(s) of interest using promoters from genes that are normally active in these cells. This approach to targeting is illustrated using promoters from genes expressed in either the liver, the pancreas or the mammary gland as a means to limit gene expression specifically to the cell types that make up these organs. The successful utilization of new generations of targeted retroviral vectors in the clinic may well pave the way for superior gene delivery systems of the future that seek out their target cell, delivering a therapeutic gene to and expressing it only in such cells.     

Non-histone chromatin proteins during maturation of avian erythroid cells

1. In chicken erythroid cells (erythroblast, reticulocyte and erythrocyte) maturation was accompanied by a decrease in the content of non-histone chromatin proteins. 2. Phenol-soluble non-histone chromatin proteins (phosphoproteins) from the three cell populations studied, showed differences in the behavior on sodium dodecyl sulphate polyacrylamide-gel electrophoresis, and isoelectric focusing. Phosphoprotein of immature cells had a higher content of fractions of about 86 000 and 23 000 daltons than the phosphoproteins of erythrocytes.     

The source of NMR-detected motional anisotropy of water in blood vessel walls

2H Double quantum-filtered (DQF) NMR spectroscopy of deuterated water is sensitive to the presence of order in biological systems. This is because the only nuclei that are detected are those with residual quadrupolar interactions due to their anisotropic motion. In the present study, samples of aorta, coronary and carotid arteries, and vena cava were studied in parallel by 2H DQF NMR and by light microscopy. The average quadrupolar splitting, calculated from the NMR data, varies considerably among the different blood vessels, with high reproducibility for each type of vessel. Polarization microscopy examinations using collagen-specific staining with picrosirius red, have shown a variety of color profiles for the different blood vessels. These reflect different physical modes of aggregation (packing and thickness) of collagen fibers. A correlation was found between the NMR parameters and the color profiles of the picrosirius red-stained sections. Treating the blood vessels with 90% formic acid resulted in the elimination of the 2H DQF NMR signal. Histological analysis demonstrated a complete degradation of collagen and muscle, whereas the elastin filaments were preserved. Evidence is given that the 2H DQF NMR signal is dominated by the contribution of water molecules interacting with the collagen fibers.     

Development of calcium signalling mechanisms during maturation of human oocytes

Sperm-induced Ca2+ signals mediate the events of oocyte activation at fertilization. In this study, the development of mechanisms involved in the generation of Ca2+ signals in human oocytes was investigated. The thiol reagent, thimerosal, which induces oscillations of intracellular Ca2+ ([Ca2+]i) similar to those seen during fertilization, was used to mobilize Ca2+ in in-vivo matured, immature and in-vitro matured human oocytes. There was an increase in the sensitivity to thimerosal during maturation of human oocytes, with oocytes from small antral follicles being relatively insensitive, compared with those from luteinized follicles, which displayed a large spike followed by sustained oscillations in [Ca2+]i. These oscillations were inhibited by caffeine which suggests that they were mediated by the inositol trisphosphate receptor Ca2+ release system. When immature oocytes were cultured in vitro they acquired the capacity to undergo a single large spike in [Ca2+]i, however, subsequent sustained oscillations were not observed, indicating that these oocytes failed to develop fully competent Ca2+ signalling mechanisms during culture in vitro. This finding may be a key factor in the poor developmental competence of in-vitro matured human oocytes.