Hepatotrophic factors in liver growth and atrophy.

The hepatotrophic effect of portal blood was studied in rats with portal branch ligation (PBL) simultaneously subjected to mesocaval shunt or total hepatic arterialization. A direct supply of the nonligated liver lobes with pancreatic effluent did not improve DNA synthesis or mitotic response compared to arterialized rats, in which the portal-borne hepatotrophic factors reached the same lobes after systemic recirculation. A comparison with shunted but Sham-PBL rats showed that restorative capacity of the liver was not seriously impaired. In rats with PBL alone the lobes with portal occlusion showed extensive necrosis. In contrast, in PBL + shunt rats necrosis was significantly inhibited, indicating a hepatoprotective role of portal blood during hepatic arterial recirculation. Thus, the study suggests that quality of hepatic blood supply is of vital importance in maintenance of hepatocellular integrity. Hemodynamical factors seem to be of importance, but more in a sense of increased or decreased accessibility of humoral hepatotrophic factors in the blood.     

Mechanisms of muscle growth and atrophy in mammals and Drosophila

Background: The loss of skeletal muscle mass (atrophy) that accompanies disuse and systemic diseases is highly debilitating. Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. Results: In this review, we highlight the outstanding unsolved questions that may benefit from a combination of studies in both flies and mammals. In particular, we discuss how different environmental stimuli and signaling pathways influence muscle mass and strength and how a variety of disease states can cause muscle wasting. Conclusions: Studies in Drosophila and mammals should help identify molecular targets for the treatment of muscle wasting in humans. Developmental Dynamics 243:201–215, 2014. © 2013 Wiley Periodicals, Inc.     

Hepatotrophic activity in mouse serum infected with plerocercoids ofSpirometra erinacei

To investigate the mechanism by which liver weight increases during plerocercoid infections as well as the possible existence of a hepatocyte-growth-factor (HGF)-like substance in the serum of mice infected withSpirometra erinacei plerocercoids, liver DNA synthesis was measured in vivo and in vitro. Infection withS. erinacei plerocercoids significantly stimulated DNA synthesis in mouse parenchymal hepatocytes prior to the increase in liver weight, at least partly by stimulating the induction of the salvage pathways of pyrimidine biosynthesis. Furthermore, infected mouse serum directly stimulated DNA synthesis in cultured mouse parenchymal hepatocytes. These results suggest that an HGF-like substance is present in the serum of mice infected withS. erinacei plerocercoids.     

Endocrinology of growth and growth factors

This review discusses normal growth patterns and the appropriate use of preprinted growth curves. The important roles of thyroid and growth hormone in the modulation of growth are delineated. I present an approach to the evaluation and proper management of children and adolescents with short stature and poor growth.     

Oncogenes and growth factors

Certain polypeptide gene products regulate mitosis, differentiation, and other basic biologic functions of cells. These genes and their products are well preserved throughout evolution. Other sets of genes encode receptors for these polypeptides. Polypeptide growth factors can stimulate the cells that express receptors for them. Autocrine growth occurs when a cell produces a growth factor and also expresses receptors for it. When certain genes remain in a permanently switched-on position or are amplified, excessive amounts of growth factors are produced and receptor-positive cells continuously respond, thus achieving illegitimate growth advantage over other cells. Permanently switched-on and/or point-mutated receptor-encoding genes direct the synthesis of truncated receptors that do not need to capture their ligand for signaling receptor activation, thus their cells remain in a permanently activated state. When immortalization and/or malignant transformation results from these activities, the gene is recognized as a protooncogene-oncogene. Acutely transforming retroviruses contain close derivatives of these cellular genes (c-onc----v-onc) obtained through transduction. Genes encoding the synthesis of nontransforming growth factors (angiogenesis factors, colony-stimulating factors, interleukins, etc.) imitate protooncogenes in stimulating the growth and differentiation-dedifferentiation on nonimmortalized cells. Immortalized and malignantly transformed cells may retain receptors to regulatory growth factors that may induced differentiation and/or cessation of mitosis. Growth factors or receptors produced in excess by transformed cells may be neutralized by monoclonal antibodies (McAb) breaking the chain of autocrine or paracrine growth. Protooncogenes-oncogenes may be deactivated by biological response modifiers (dexamethasone, interferons, bacterial toxins, etc.). These interventions may lead to a new treatment modality for the malignant process.     

Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy

BACKGROUND. Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation of unknown pathogenesis. Transforming growth factor (TGF) beta 1 induces the production of extracellular matrix proteins by liver cells and has been implicated in the pathogenesis of hepatic fibrosis in laboratory animals. TGF alpha is a hepatocyte mitogen that participates in liver regeneration. METHODS. Using Northern blot analysis, we studied the expression of TGF beta 1 messenger RNA (mRNA) in liver specimens from 42 patients with chronic hepatitis and cirrhosis and 12 subjects with either normal or fatty livers. The results were correlated with measurements of procollagen Type I mRNA in liver tissue, procollagen Type III peptide in serum, and the degree of histologic injury. We also investigated whether TGF alpha mRNA would be detectable in biopsy specimens of livers with proliferative activity. RESULTS. TGF beta 1 mRNA expression correlated closely with the expression of procollagen Type I mRNA (r = 0.94) and serum procollagen Type III peptide (r = 0.89) and with the histologic activity index (r = 0.73). All patients with increased fibrogenic activity (serum procollagen Type III peptide level, greater than 11.9 micrograms per liter) had increased levels of TGF beta 1 mRNA (2 to 14 times the levels in the control group or in patients with normal fibrogenic activity), and both TGF alpha and H3 histone (a marker of DNA synthesis) mRNAs were detectable in patients with regenerative nodules. Six of eight patients with hepatitis C treated with interferon alfa for one year had sustained clinical responses with normalization of serum procollagen Type III peptide and aminotransferase activity. All these patients had normal levels of TGF beta 1 mRNA in liver specimens obtained at the end of the year. CONCLUSIONS. TGF beta 1 may have an important role in the pathogenesis of fibrosis in patients with chronic liver disease, and TGF alpha expression may be associated with liver regeneration in these patients.     

人胎肝中肝细胞生长因子的纯化及某些生物学特性的研究

人胎肝细胞裂解后,胞液分别经分子量6万Da、3万Da,1万Da的滤膜超滤,在分子量1—3万Da组分中可检测出肝细胞生长因子(hHGF)活性。此样品再经DEAE离子交换层析,FPLCmonoQ色谱及HPLC分子排阻色谱,已将hHGF纯化为单体,相对活性提高5万倍。在HPLC-TSK2000SW柱上hHGF蛋白峰的分子量为11,100Da,纯hHGF在SDS-PAGE上为一条分子量14,900Da的条带。纯hHGF的生物活性、细胞特异性及理化性质与hHGF粗品一致,也与再生或断乳动物肝中初步纯化的肝生长刺激物相似,而与体液来源的肝生长因子不同。这两种肝细胞生长因子可能共同参与肝细胞生长调控。     

Compensatory hyperplasia in the rat liver as a result of cytoplasmic atrophy

A protracted process of hepatocyte atrophy was induced in the anterior lobes of the rat liver by portal vein ligation (PVL), and within 3 days the combination of atrophy in the anterior lobes and compensatory hyperplasia of the posterior lobes had resulted in the anterior lobes comprising only about 20% of the total liver weight. Apart from an initial fall in the total liver weight due to atrophy of the anterior lobes without any corresponding growth reaction in the posterior lobes, the total liver weight remained close to normal throughout the first 3 days. Surprisingly, increases in posterior lobe DNA synthesis after PVL were triggered almost as rapidly (15-18 h post-operatively) as occurs after anterior lobe resection, though subsequently the level of proliferative activity was generally lower than is found after partial hepatectomy. The rapidity of the proliferative response to PVL suggests the proliferative signal is generated by a minimal cytoplasmic deficit and/or the increased rate of portal blood perfusion.     

Keratinocyte growth factor and epidermal growth factor can reverse the intestinal atrophy associated with elemental diets in mice

Elemental diets are associated with intestinal atrophy and reduced intestinal integrity. Growth factors such as keratinocyte growth factor (KGF) and epidermal growth factor (EGF) have considerable potential for the therapeutic reversal of such atrophy and may have greater actions if given in combination. We examined the effects of recombinant human KGF (rHuKGF), EGF and their combination on tissue mass, cell proliferation and crypt fission throughout the intestine of mice fed elemental diets. rHuKGF significantly increased the relative wet weight of the intestine, with EGF having a lesser effect. Cell proliferation of the stomach, small intestine and colon were significantly increased by rHuKGF, but EGF only increased proliferation in the small intestine. Crypt fission in the small intestine and colon was significantly decreased by rHuKGF. An interactive effect of rHuKGF and EGF on the weight of stomach and the proliferation of the fundus and antrum was observed. Moreover, an interactive effect of the agents was also seen on crypt fission in the colon. We concluded that (1) rHuKGF and EGF have significant trophic effects on the stomach, small intestine and colon, (2) these actions vary between different sites in the gastrointestinal tract, and (3) interactive effects occur.     

Curative factors in psychotherapeutic and growth groups

A 60-item Q-sort that represented 12 “curative factors” regarded as crucial to the efficacy of psychotherapeutic groups by Yalom (1970) was administered to volunteer undergraduate participants after the end of 20-hour (2 hours weekly) personal growth groups. The Q-sort items were ranked very similarly for Helpfulness in the group experience by the growth groupers and by Yalom's successful group psychotherapy outpatients. Members of both kinds of groups linked Helpfulness strongly with Yalom's Interpersonal Input and Catharsis measures. The content of these variables' salient items closely resembled two broader dimensions of interpersonal behavior, Acceptance vs. Rejection of Others and Self-Acceptance vs. Rejection, which appear prepotent (Hurley, 1976) in a wide variety of group settings.     

Cytokines and growth factors in atherogenesis.

The development of laboratory techniques for the culturing of vascular endothelial and smooth-muscle cells during the 1970s, followed by the rapid advances in molecular and cell biology during the 1980s, provided the foundation for the identification of growth factor and cytokine networks involved in maintenance of the normal vasculature as well as participating in diverse pathologic processes involving blood vessels. Vascular cells can produce and respond to a vast array of biochemical messengers that control cell replication, differentiation, and many specific cell functions. Investigators are beginning to explore the changes in the patterns of messengers exchanged between the vascular cells and infiltrating leukocytes during the initiation and progression of atherosclerosis. A variety of in vitro and in vivo studies have indicated that growth factors and cytokines that mediate the critical processes of inflammation and wound healing also play a central role in vascular disease. Indeed, many view atherosclerosis as the result of excessive or prolonged chronic inflammation and wound healing in response to diverse injurious stimuli to cells of the vessel wall. Vascular injury may result from many varied and interacting forces, including nutritional and metabolic abnormalities such as hyperlipidemias or elevated homocysteine, mechanical forces associated with hypertension, exogenous toxins including those found in cigarette smoke, abnormally glycated proteins associated with diabetes mellitus, oxidatively modified lipids or proteins, and, possibly, viral infections. Ultimately, a greater understanding of the activated cytokine and growth factor networks within the vascular wall following injury and during atherogenesis will allow clinical scientists to identify steps susceptible to therapeutic intervention using recombinant cytokines, antibodies, soluble receptors, or receptor antagonists. Other therapeutic strategies may involve the transfection of specific genes, which may inhibit atherosclerosis, into vascular cells at sites prone to lesion formation.     

成纤维细胞生长因子与器官发育

背景：成纤维细胞生长因子能够影响多种器官组织的形态发生、分化及功能,对多种器官的发育具有决定性作用。 目的：综述近年来关于成纤维细胞生长因子在器官发育中所起的作用,为进一步研究器官发育提供理论基础。 方法：检索Pubmed(1995/2010)和CNKI(2001/2010)数据库,检索关键词分别为“fibroblast growth factor, tooth development, kidney development, lung development, salivary gland development”,“成纤维细胞生长因子、牙齿发育、肾脏发育、肺发育、涎腺发育”。纳入与成纤维细胞生长因子结构、功能及其与器官发育相关的研究,同一领域研究则选择近期发表及发表在权威杂志的文章。 结果与结论：共收集文献850篇,排除发表时间较早及重复研究文献,共纳入37篇英文文献和2篇中文文献。目前研究发现,牙齿、肺、肾脏、羽毛、毛发、心脏、涎腺的发育都是从上皮与间充质相互作用开始的。成纤维细胞生长因子能够促进上皮和间充质细胞之间的相互作用,诱导两种细胞的增殖并抑制其凋亡,成纤维细胞生长因子与器官发育紧密相关。