Constant and continuous growth reduction as a possible cause of ageing

Post-embryonic growth is characterized by a constant reduction of some growth parameters in relation to other growth parameters. Comparison of growth in chickens, rats and nematodes reveals an identical growth pattern, so a theory about the growth process in general is presented. It is presumed that the same growth promoting and growth inhibiting substances regulate not only growth but also ageing and that it is the equilibrium between growth promoters and growth inhibitors which is constantly changed.     

Heparin-binding growth factor/prostatropin attenuates inhibition of rat prostate tumor epithelial cell growth by transforming growth factor type beta

Summary Normal rat prostate epithelial cell growth requires both epidermal growth factor and heparin-binding growth factor/prostatropin. In contrast, epithelial cells derived from the transplantable Dunning R3327H rat tumor require either epidermal growth factor or heparin-binding growth factor/prostatropin. Transforming growth factor type beta inhibited normal epithelial cell growth. Transforming growth factor beta inhibited epidermal growth factor-dependent growth of tumor epithelial cells, independent of epidermal growth factor concentrations. Transforming growth factor beta increased the effective dose of heparin-binding growth factor type 1 required to support tumor epithelial cell growth by 10-fold but saturating levels of heparin-binding growth factor type 1 (290 pM) completely attenuated the inhibitory effect of transforming growth factor beta. These results suggest that prostate tumor epithelial cells may escape the inhibitory effect of transforming growth factor beta as a consequence of alteration of the concurrent requirement for both epidermal growth factor (or homologues) and heparin-binding growth factors. This work was supported by NCI Grant CA37589. Editor’s Statement The observation that heparin-binding growth factor/prostatropin can counteract the inhibitory effect of transforming growth factor beta in prostate epithelial cells may help explain how some cancers avoid the action of growth inhibitors and provides a model for studying how inhibitory peptides overcome the stimulatory signals generated by growth factors.     

营巢类型、巢捕食和窝卵数对高寒草甸雀形目雏鸟生长期的影响

根据1998—2001年高寒草甸10种雀形目鸟类的窝卵数、雏期和巢捕食数据,以Logistic方程拟合雏鸟生长过程,并计算出有关生长率参数;根据营巢类型将10种雀形目鸟划分为开放或半开放类群(GOB)和全封闭穴居类群(HCB)两类,将把雏鸟的生长过程划分为3个生长期(缓增期、快增期和渐增期)。3个生长期占雏期的比例因营巢类型而异,GOB类群快增期>渐增期>缓增期;HCB类群渐增期>快增期>缓增期。分析营巢类型、巢捕食和窝卵数与各生长期之间的关系,结果表明3个生长期的体重积累占离巢时体重的比例因巢型不同而有显著差异;营巢类型和巢捕食显著影响各生长期占雏期的比例和体重积累占离巢时体重的比例;窝卵数影响快增期和渐增期长度,而不影响缓增期长度。快增期体重积累与渐增期的生长率不相关,但与渐增期长度显著相关。因此,前期的能量积累不影响后期生长率,而影响后期生长的长度。该结果进一步印证在晚成鸟中不存在补偿性生长。     

Polypeptide growth factors in embryogenesis and tumor growth

Polypeptide growth factors, which belong to different families (epidermal growth factors, insulin-like growth factors, fibroblast growth factors, transforming growth factors-beta, and some others), were characterized regarding their specific role in embryogenesis and tumor growth. Differences and parallels of the functioning of growth factors in these processes have been noted. Potential significance of the described characteristics of growth factors for directed modulation of embryogenesis and tumor growth is discussed.     

Platelet-derived growth factor or basic fibroblast growth factor induce anchorage-independent growth of human fibroblasts

Anchorage-independent growth, i.e., growth in semi-solid medium is considered a marker of cellular transformation of fibroblast cells. Diploid human fibroblasts ordinarily do not exhibit such growth but can grow transiently when medium contains high concentrations of fetal bovine serum. This suggests that some growth factor(s) in serum is responsible for anchorage-independent growth. Much work has been done to characterize the peptide growth factor requirements of various rodent fibroblast cells for anchorage-independent growth; however, the requirements of human fibroblasts are not known. To determine the peptide growth factor requirements of human fibroblasts for anchorage-independent growth, we used medium containing serum that had had its peptide growth factors inactivated. We found that either platelet-derived growth factor (PDGF) or the basic form of fibroblast growth factor (bFGF) induced anchorage-independent growth. Epidermal growth factor (EGF) did not enhance the growth induced by PDGF, or did so only slightly. Transforming growth factor beta (TGF-beta) decreased the growth induced by PDGF. EGF combined with TGF-beta induced colony formation in semi-solid medium at concentrations at which neither growth factor by itself was effective, but the combination was much less effective in stimulating anchorage-independent growth than PDGF or bFGF. This work showed that PDGF, or bFGF, or EGF combined with TGF-beta can stimulate anchorage-independent growth of nontransformed human fibroblasts. The results support the idea that cellular transformation may reduce or eliminate the need for exogenous PDGF or bFGF.     

Differential dissociation kinetics explain the binding preference of insulin-like growth factor binding protein-6 for insulin-like growth factor-II over insulin-like growth factor-I

Insulin-like growth factor binding protein-6 binds insulin-like growth factor-II with a marked preferential affinity over insulin-like growth factor-I. The kinetic basis of this binding preference was studied using surface plasmon resonance. Binding of insulin-like growth factor-I and insulin-like growth factor-II to immobilized insulin-like growth factor binding protein-6 fitted a two-site binding kinetic model. Insulin-like growth factor-I and insulin-like growth factor-II association rates were similar whereas the dissociation rate was approximately 60-fold lower for insulin-like growth factor-II, resulting in a higher equilibrium binding affinity for insulin-like growth factor-II. The equilibrium binding affinities of a series of insulin-like growth factor-II mutants were also explained by differential dissociation kinetics. O-glycosylation had a small effect on the association kinetics of insulin-like growth factor binding protein-6. The insulin-like growth factor binding properties of insulin-like growth factor binding protein-6 are explained by differential dissociation kinetics.     

Acute Regulation of the Epidermal Growth Factor Receptor in Response to Nerve Growth Factor

PC12 cells possess specific receptors for both nerve growth factor and epidermal growth factor, and by an unknown mechanism, nerve growth factor is able to attenuate the propagation of a mitogenic response to epidermal growth factor. The differentiation response of PC12 cells to nerve growth factor, therefore, predominates over the proliferative response to epidermal growth factor. We have observed that the addition of nerve growth factor to PC12 cells rapidly produces a decrease in surface 125I-epidermal growth factor binding capacity. Unlike previously described nerve growth factor effects on 125I-epidermal growth factor binding capacity, which required several days of nerve growth factor exposure, the decreases we report occur within minutes of nerve growth factor addition: A 50% decrease in 125I-epidermal growth factor binding capacity is evident at 10 min. This rapid nerve growth factor response is concentration dependent; inhibition of 125I-epidermal growth factor binding is detectable at nerve growth factor levels as low as 0.2 ng/ml and is maximal at approximately 50 ng/ml, consistent with known ranges of biological activity. No demonstrable differences in the rate of epidermal growth factor receptor synthesis or degradation were observed in cells acutely exposed to nerve growth factor. Scatchard analysis revealed that acute nerve growth factor treatment decreased the number of both high- and low-affinity 125I-epidermal growth factor binding sites, while the receptor affinity remained unchanged. We have also investigated the involvement of various potential intracellular mediators of nerve growth factor action and of known intracellular modulatory systems of the epidermal growth factor receptor for their capacity to participate in this nerve growth factor activity.     

Linking marine and freshwater growth in western Alaska Chinook salmon Oncorhynchus tshawytscha

The hypothesis that growth in Pacific salmon Oncorhynchus spp. is dependent on previous growth was tested using annual scale growth measurements of wild Chinook salmon Oncorhynchus tshawytscha returning to the Yukon and Kuskokwim Rivers, Alaska, from 1964 to 2004. First-year marine growth in individual O. tshawytscha was significantly correlated with growth in fresh water. Furthermore, growth during each of 3 or 4 years at sea was related to growth during the previous year. The magnitude of the growth response to the previous year's growth was greater when mean year-class growth during the previous year was relatively low. Length (eye to tail fork, L _ETF) of adult O. tshawytscha was correlated with cumulative scale growth after the first year at sea. Adult L _ETF was also weakly correlated with scale growth that occurred during freshwater residence 4 to 5 years earlier, indicating the importance of growth in fresh water. Positive growth response to previous growth in O. tshawytscha was probably related to piscivorous diet and foraging benefits of large body size. Faster growth among O. tshawytscha year classes that initially grew slowly may reflect high mortality in slow growing fish and subsequent compensatory growth in survivors. Oncorhynchus tshawytscha in this study exhibited complex growth patterns showing a positive relationship with previous growth and a possible compensatory response to environmental factors affecting growth of the age class.     

黄土丘陵半干旱区柠条林株高生长过程新模型

黄土丘陵半干旱区柠条林的株高生长不随时间单调增加,在生长末期因生长动力小于生长阻力,株高随时间小幅度减小。采用宁夏固原上黄生态站柠条林的生长观测资料,以经典Logistic方程为基础,添加了生长阻力因素,建立了柠条林生长的改进模型,使得生长速率在生长末期出现负值;并以高密度柠条成林多年生长观测数据为依据,建立了连年生长模型。用数学建模和统计检验的方法对数据进行处理,其结果表明,改进模型较Logistic方程具有更高的拟合度和相关系数。建立的模型与传统生长方程不同,由于微分方程中引入了阻力因子,故生长曲线中存在极值坐标且不具有严格单调性。将多年的株高生长曲线综合到一个坐标系内后,新模型中位置参数a与内禀生长率b的比值随着生长呈现逐渐增大的趋势。改进模型的生长顶点出现在8月,与柠条林株高的实际生长过程吻合;计算了新模型的生长顶点与生长期结束时的株高的差值,并将该值记为生长损失。由于柠条林的灌丛较为矮小,在越冬时干梢现象对株高的影响不可忽略,该过程导致生长方程中第二年初始点小于第一年最末点;在考虑了该现象后所建立的连年生长模型中,2002年和2003年干稍现象的终止点位于2月,与植物生长的节律吻合。本研究为描述半干旱区灌木林生长过程提供了依据。     

Polypeptide growth factors in gastroenteropancreatic neuroendocrine tumours

Polypeptide growth factors form a potent class of extracellular signal molecules in the regulation of cellular differentiation and proliferation. Disturbances in the expression of growth factors influence the normal pathway of differentiation and lead to cellular transformation and tumour progression. Contemporary medical studies report that various growth factors such as those for platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor, hepatocyte growth factor and insulin-like growth factor are expressed in gastroenteropancreatic neuroendocrine tumours (GEP/NET). Polypeptide growth factors have great significance in the growth, progression and development of metastases by various tumours. We describe the role of growth factors in GEP/NET on the basis of the available reports of medical research.     

单叶省藤苗期的生长规律

通过有序样品聚类分析单叶省藤生长规律,将苗木生长分为5个阶段:出苗期4月4日～5月21日,生长速生期5月22日～6月22日,二次速生期6月23日～7月22日,生长后期7月23日～11月22日,生长停止期11月23日～2月22日。其生长阶段缺少生长初期,而是直接进入速生期,并且有一个二次速生期。除了在两个速生期加强水肥管理外,在生长后期适当管理也能增加其生长量。     

Axis differentiation in two South American Nothofagus species (Nothofagaceae)

An analysis was carried out on the length, diameter and number of leaves, and the ratios between these variables for current-year growth units (sibling growth units) derived from different nodes of previous-year growth units (parent growth units) of young Nothofagus dombeyi and Nothofagus pumilio trees. Changes in sibling growth unit length, diameter, and number of leaves with position on the parent growth unit were assessed. In both species, sibling-growth unit morphology varied according to both the axis type of the parent growth unit and the position of the sibling growth unit on its parent growth unit. For the largest parent growth units, the length, diameter and number of leaves of their sibling growth units decreased from distal to proximal positions on the parent growth unit. Distal sibling growth units had a more slender stem and longer internodes than proximal sibling growth units. Sibling growth units in equivalent positions tended to have a more slender stem for N. dombeyi than for N. pumilio. Long main-branch growth units of N. pumilio had longer internodes than those of N. dombeyi; the converse was true for shorter growth units. The growth unit diameter/leaf number ratio was consistently higher for N. pumilio than for N. dombeyi. Nothofagus pumilio axes would go through a faster transition from an 'exploring' morphology to an 'exploiting' morphology than N. dombeyi axes. Within- and between-species variations in growth unit morphology should be considered when assessing the adaptive value of the branching pattern of plants.     

Polypeptide Growth Factors in Embryogenesis and Tumor Growth

Polypeptide growth factors belonging to different families (epidermal growth factors, insulin-like growth factors, fibroblast growth factors, transforming growth factors-, and some others), were characterized regarding their specific role in embryogenesis and tumor growth. Differences and parallels in the functioning of growth factors in these processes have been noted. The potential significance of the described characteristics of growth factors for directed modulation of embryogenesis and tumor growth is discussed.     

Differential effects of growth factors on [3H]thymidine incorporation and [125I]iodine uptake in FRTL-5 rat thyroid cells

We studied the effect of several growth factors on DNA synthesis and function of FRTL-5 rat thyroid cells by simultaneous measurement of [3H]thymidine incorporation and [125I]iodide uptake. Endothelial cell growth factor, fibroblast growth factor, platelet-derived growth factor, and insulin-like growth factor I stimulated thymidine incorporation in a dose-dependent manner without the parallel increase of [125I]iodide uptake. These growth factors had an additive effect with thyroid-stimulating hormone (TSH) on thymidine incorporation, but they inhibited TSH-stimulated iodide uptake. Bombesin stimulated thymidine incorporation and inhibited TSH-stimulated iodide uptake; epidermal growth factor and gastrin-releasing peptide 10 had neither effect. None of the growth factors studied affected iodide uptake in the absence of TSH. Of the growth factors tested, endothelial cell growth factor, fibroblast growth factor, insulin-like growth factor bombesin, and platelet-derived growth factor all share similar differential effects on FRTL-5 cells: stimulation of DNA synthesis, potentiation of the effects of TSH on DNA synthesis, and attenuation of the effects of TSH on cell function. The data suggest that these growth factors may play important roles in regulation of thyroid function.     

Long-range signaling in growing neurons after local elevation of cyclic AMP-dependent activity

Cyclic AMP-dependent activity at the growth cone or the soma of cultured Xenopus spinal neurons was elevated by local extracellular perfusion of the neuron with culture medium containing 8-bromoadenosine 3',5'-cyclic monophosphate (8-br-cAMP) or forskolin. During local perfusion of one of the growth cones of multipolar neurons with these drugs, the perfused growth cone showed further extension, while the distant, unperfused growth cones were inhibited in their growth. Local perfusion of the growth cone with culture medium or local perfusion with 8-br-cAMP at a cell-free region 100 microns away from the growth cone did not produce any effect on the extension of the growth cone. Reduced extension of all growth cones was observed when the perfusion with 8-br-cAMP was restricted to the soma. The distant inhibitory effect does not depend on the growth of the perfused growth cone since local coperfusion of the growth cone with 8-br-cAMP and colchicine inhibited growth on both perfused and unperfused growth cones, while local perfusion with colchicine alone inhibited only the perfused growth cone. The distant inhibitory effect was abolished when the perfusion of 8-br-cAMP was carried out together with kinase inhibitor H- 8, suggesting the involvement of cAMP-dependent protein kinase and/or its downstream factors in the long-range inhibitory signaling. Uniform exposure of the entire neuron to bath-applied 8-br-cAMP, however, led to enhanced growth activity at all growth cones. Thus, local elevation of cAMP-dependent activity produces long-range and opposite effects on distant parts of the neuron, and a cytosolic gradient of second messengers may produce effects distinctly different from those following uniform global elevation of the messenger, leading to differential growth regulation at different regions of the same neuron.     

Growth inhibitory polypeptides in the regulation of cell proliferation

The growth of cells in culture and in vivo is modulated by different effectors, some of which are called growth factors. This designation is given to polypeptides that have the ability to enhance cellular growth. Other important growth regulatory molecules are the growth inhibitory polypeptides. The balance between stimulatory and inhibitory signals is evidently essential for normal control of cell proliferation. Disturbances of cellular growth thus presumably result from quantitative alterations between stimulatory and inhibitory signals that the cells get from their environment via their cell surface receptors. Thus, either enhanced amounts of stimulatory or decreased inhibitory signals can contribute to augmented, cancerous growth. An important growth regulator appears to be transforming growth factor-beta (TGF beta), which has both stimulatory and inhibitory effects on cells. The significance of growth inhibitors in the regulation of cellular growth and differentiation is becoming an important research field of modern biology.     

The use of biological assays for detection of polypeptide growth factors

Polypeptide growth factors can be identified and quantified with high accuracy by the use of specific biological assays. In general these bioassays are highly sensitive for detection of growth factor activity, and enhanced specificity can be obtained by a proper choice of selective culture conditions for the target cells involved. In this paper sensitive and selective bioassays are described for growth factors acting on substrate-attached cells, in particular members of the epidermal growth factor, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor, and heparin-binding growth factor families. A cross-reactivity scheme has been worked out to identify possible contaminations in growth factor preparations.     

Growth estimates from otolith increment widths of juvenile chinook salmon (Oncorhynchus tshawytscha) reared in changing environments

For otolith increments to provide useful estimates of fish growth, otolith growth must covary closely with somatic growth. We reared groups of juvenile chinook salmon ( Oncorhynchus tshawytscha Walbaum) for 70 days, changing ration or temperature during a 20-day treatment period. Restricted rations halted somatic growth, however increment widths decreased gradually; somatic growth was overestimated from increment width. Otolith growth followed changes in water temperature more closely than changes in ration, supporting a hypothesized effect of metabolic rate on otolith growth. Increment growth was only loosely coupled to fish growth rate, and may also be affected by past growth histories. For juvenile fish, increment widths may not be sensitive indicators of short-term changes in growing conditions.     

COMPARATIVE ANALYSIS OF ANIMAL GROWTH: A PRIMATE CONTINUUM REVEALED BY A NEW DIMENSIONLESS GROWTH RATE COEFFICIENT

The comparative analysis of animal growth still awaits full integration into life‐history studies, partially due to the difficulty of defining a comparable measure of growth rate across species. Using growth data from 50 primate species, we introduce a modified "general growth model" and a dimensionless growth rate coefficient β that controls for size scaling and phylogenetic effects in the distribution of growth rates. Our results contradict the prevailing idea that slow growth characterizes primates as a group: the observed range of β values shows that not all primates grow slowly, with galago species exhibiting growth rates similar or above the mammalian average, while other strepsirrhines and most New World monkeys show limited reduction in growth rates. Low growth rate characterizes apes and some papionines. Phylogenetic regressions reveal associations between β and life‐history variables, providing tests for theories of primate growth evolution. We also show that primate slow growth is an exclusively postnatal phenomenon. Our study exemplifies how the dimensionless approach promotes the integration of growth rate data into comparative life‐history analysis, and demonstrates its potential applicability to other cases of adaptive diversification of animal growth patterns.