Ontogeny, differentiation and growth of the endocrine pancreas

The pancreas develops from the primitive foregut endoderm, which differentiates into ductal, acinar and endocrine cells. This complex process is probably replicated in the adult pancreas when endocrine cell renewal is required, as may be the case in diabetes mellitus. This review describes what is known about the morphogenesis of the endocrine pancreas during ontogeny and the mechanisms regulating its differentiation and growth. Received: 23 December 1999 / Accepted: 15 February 2000     

Cell biology and pathology of liver sinusoidal endothelial cells

Growing evidence revealed that liver sinusoidal endothelial cells (SEC) play several important roles in physiology and pathology of the liver. It has been well understood that their structural characteristics, such as the membrane sieve and lack of basement membrane, facilitate direct contact of soluble and insoluble serum substances with hepatic parenchymal cells, resulting in enhancement of hepatic metabolic activity. In addition, SEC is now regarded as a member of the scavenger endothelial cells, which have potential to eliminate a variety of macromolecules from the blood circulation by receptor-mediated endocytosis. It is reported that molecules preferentially eliminated by SEC are denatured or modified proteins such as advanced glycation end products, extracellular matrix components including hyaluronic acid, and some lipoproteins. The nature of the scavenger receptors corresponding to these molecules remains to be clarified. Recently, it was noted that SEC has an antigen-presenting function similar to dendritic cells. Taken together, it is suggested that SEC, cooperating with Kupffer cells and hepatic dendritic cells, may partake of immunoregulatory functions in the liver. SEC also plays a pivotal role in the pathological process of ischemia-reperfusion injury following liver surgery and liver transplantation. Thus, it is of importance to elucidate the mechanisms of apoptosis and proliferation of SEC. Recent results on the regulation of growth and apoptotic signaling of SEC are discussed.     

Maximal oxygen consumption,pulmonary function,body composition,and anthropometry of adolescent female athletes

Three groups of girl athletes — 10 gymnasts and 8 middle-distance swimmers averaging 14 years of age, and 8 middle-distance runners averaging almost 19 — were the subjects of this study. The maximal oxygen intake was determined by graded work load on a bicycle ergometer, certain pulmonary functions by spirometry, and total body potassium by wholebody counting of naturally radioactive⁴⁰K. The total body water was obtained from measurements of deuterium oxide and application of the dilution principle, and creatinine excretion was determined from urine collections. Fat-free mass was calculated from total body water, and the amount of body fat was obtained by subtracting fat-free mass from body weight. Cell mass was calculated from total body potassium. Supporting evidence of leanness or fatness was provided by anthropometric measurements.The runners and swimmers achieved significantly higher maximal oxygen consumption per kg of body weight, fat-free mass, and cell mass; and the runners excelled the gymnasts in certain other pulmonary functions. Total body potassium in milliequivalents per kg of body weight, total body water expressed in percentage of body weight, and creatinine coefficients were similar in all three groups of subjects. These results indicated no differences in body composition. Calculations of body fat, fat-free mass, and cellular mass verified that conclusion; and supporting evidence was obtained from subcutaneous fat folds and from appraisal of leanness by corrected limb diameters or volumes, which also were similar in all three groups.     

Growth hormone as an early embryonic growth and differentiation factor

In this review we consider the evidence that growth hormone (GH) acts in the embryo as a local growth, differentiation, and cell survival factor. Because both GH and its receptors are present in the early embryo before the functional differentiation of pituitary somatotrophs and before the establishment of a functioning circulatory system, the conditions are such that GH may be a member of the large battery of autocrine/paracrine growth factors that control embryonic development. It has been clearly established that GH is able to exert direct effects, independent of insulin-like growth factor-I (IGF-I), on the differentiation, proliferation, and survival of cells in a wide variety of tissues in the embryo, fetus, and adult. The signaling pathways behind these effects of GH are now beginning to be determined, establishing early extrapituitary GH as a bona fide developmental growth factor.     

Effects of vitamin A on proliferation of human distal airway epithelial cells in culture

Using a serum-free culture method, we investigated the effects of vitamin A on the proliferation of human distal airway epithelial cells. Outgrowth of epithelial cells from lung tissue explants was enhanced by treatment with all-trans retinol at concentrations of 10^–8 to 10^–7 M. The colony-forming activity of cells harvested from the primary culture and replated onto Swiss 3T3 fibroblastic feeders was, in contrast, significantly reduced by 10^–7 M to 10^–5 M retinol. When the primary cells were harvested and subcultured on Primaria plates, population expansion was also inhibited by retinol at 10^–10 to 10^–6 M. We further investigated the cells to determine whether there was any difference in sensitivity to the growth-inhibitory effects of vitamin A between cells from the primary culture incubated with and without retinol. The population increase in cells harvested from the primary culture was inhibited equally in retinol-treated and non-treated cells by subsequent treatment with retinol or retinoic acid, this inhibition being dose-dependent. DNA synthetic activity was also inhibited. Interestingly, both the growth rate and the colony-forming efficiency on feeders were greater in the subculture of cells from the retinol-treated primary culture than in those non-treated. When the cells in the secondary subculture were treated with retinoic acid and replated again, they showed a greater population increase rate than those non-treated. Our results showed that human distal airway epithelial cells isolated from lung tissue were sensitive to the growth-inhibitory effect of vitamin A, but the proliferative potential in some fraction of the epithelial cell population was possibly enhanced by vitamin A treatment.     

多囊卵巢综合征患者的生长分化因子9基因的突变分析

目的通过对多囊卵巢综合征（PCOS）妇女的生长分化因子9（GDF-9）基因的突变分析，探索GDF-9基因与PCOS的发病机制的关系。方法对120例PCOS患者釉80例正常对照的GDF-9基因进行聚合酶链反应（PCR）特异扩增，应用单链构象多态性（SSCP）分析和DNA测序方法检测基因突变。结果PCOS患者的GDF-9的所有外显予均未发现错义突变。结论GDF-9因子的DNA变异可能与PCOS的发病没有相关关系。研究PCOS患者的GDF-9的mRNA与蛋白表达水平与其发病的关系可能是今后的研究方向。     

Morphological characteristics of cultured olfactory bulb cells

Cultured olfactory bulb cells from embryonic mice had ultrastructural characteristics similar to those of many cell types in the intact adult mouse olfactory bulb. Identified cultured cells included mitral/tufted cells, granule cells, short-axon cells, and fibrous and protoplasmic astrocytes. Cultured neurons were found as individual cells, clusters or aggregates. Clusters consisted of a loose array of neurons that appeared to be densely interconnected by neurites. However, few neurites or fascicles emanated from clusters to adjoining areas. Aggregates consisted of many small, usually rounded, neurons piled on top of one larger neuron, or on more than one, with typically many neurites and fascicles projecting to adjacent aggregates, clusters or individual neurons. Neurites of cultured olfactory bulb cells were well developed, and some were several millimeters long. Synapses were very prominent in these cultures, especially in aggregates, clusters, and fascicles. Electron-lucent, dense-core, and coated vesicles were present. Polarity, shape, and length of the long axis (size) of 815 cultured neurons, identified by positive anti-microtubule-associated protein 2 staining, were documented. Cultured neurons varied in size from 9 to 27 m, with an average size of 16 m. Elliptical bipolar (35%), triangular multipolar (21%), and round unipolar (15%) were the most common polarity/shape combinations found in culture. Multipolar, triangular, triangular multipolar, and elliptical bipolar cells increased in size with increasing age of culture. The relative proportions of triangular, multipolar, elliptical multipolar, and triangular multipolar cells decreased, whereas the relative proportions of round, unipolar, and round unipolar cells increased with increasing age of culture. These changes in population subtypes and cell size may indicate continued differentiation and maturation of cultured neurons.     

碱性成纤维细胞生长因子对卵巢癌CAOV3细胞cyclin D1及GADDl53表达的影响

目的:研究碱性成纤维细胞生长因子(bFGF)对人卵巢癌CAOV3细胞细胞周期调节蛋白cyclinD1及GADD153表达的影响,探讨bFGF促进人卵巢癌CAOV3细胞增殖、抑制凋亡的信号机制。方法:利用无血清饥饿诱导卵巢癌CAOV3细胞凋亡。分为对照组、bFGF组。分别应用MTT、流式细胞术、琼脂糖凝胶电泳观察25、50、75μg/L bFGF对CAOV3细胞增殖率、细胞周期及细胞凋亡的影响。利用Western blotting检测bFGF对CA-OV3细胞cyclin D1、GADD153以及转录因子(c-Fos、c-Jun)表达的影响。结果:与对照组相比,bFGF呈剂量依赖性加速CAOV3细胞细胞周期进程,促进细胞增殖,抑制饥饿诱导的凋亡(P<0.01);呈时间依赖性促进cyclinD1、c-Fos、c-Jun,抑制GADD153蛋白表达(P<0.01)。结论:bFGF可能通过上调cyclin D1、c-Fos、c-Jun,下调GADD153表达促进细胞增殖,抑制饥饿诱导的卵巢癌CAOV3细胞凋亡。     

Growth failure in Crohn’s disease children: may the first treatment have a role?

Introduction: Growth failure in children is a frequent feature of childhood-onset Crohn’s disease (CD), and stunting can persist into adulthood. Growth is an important outcome by which to judge the effectiveness of therapies in children; currently available studies in CD children have focused on the short-term impact of treatments on growth, and there are limited data regarding the long-term effects of treatments upon growth.

Areas covered: We designed the present article to review whether the first treatment performed in newly diagnosed CD children may have a role on the future growth course. We conducted a systematic literature search to identify relevant studies published on the PubMed database from January 2002 up to now. We found only six surveys that documented mid-term growth course in newly diagnosed CD patients.

Expert commentary: In the last years there have been relevant advances in the clinical management of CD children; however, there is a lack of knowledge about the best strategy to reverse growth failure. Children treated with enteral nutrition have appropriate height and weight gain but do not reverse the growth course. Further surveys are required to better explore not only clinical outcomes but also long-term growth course following each therapeutic strategy.     

Secretion of growth hormone and thyroid-stimulating hormone in patients with dementia

We studied the growth hormone (GH) response to GH-releasing hormone (GHRH) and the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in four groups of patients with dementia and examined whether GH and TSH secretion is altered in patients with Alzheimer's disease. The four groups included those with Alzheimer's disease (n=28), parkinsonism with dementia (n=10), progressive supranuclear palsy with dementia (n=10), and dementia of vascular origin (n=28). The results showed no differences among the four groups in GH response to GHRH (12.2 ± 2, 10.7 ± 2, 8.9 ±1.1, and 9.9 ± 1.9 g/ml, respectively); there was no correlation between GH response to GHRH and sex, stage of the disease, or cerebral atrophy. The proportion of patients with exaggerated, normal, or lower GH response was similar in the four groups. There were also no differences among the groups in terms of TSH response to TRH (9.2 ±0.9, 11.1 ± 1, 11.1 ± 1, and 10.3 ± 1 mU/ml, respectively), nor was there a correlation between TSH response to TRH and sex, stage of the disease, cerebral atrophy, or GH response to GHRH. The proportion of those with exaggerated, normal, or lower TSH response was similar in the four groups. Cerebrospinal somatostatin levels were similar in Alzheimer's disease and vascular dementia patients. These findings indicate that neither GH response to GHRH nor TSH response to TRH provides a useful diagnostic adjunt in Alzheimer's disease patients.Abbreviations AD Alzheimer's disease - PD parkinsonism with dementia - PSP progressive supranuclear palsy - VD dementia of vascular origin - GH growth hormone - GHRH growth hormone releasing hormone - TRH thyrotropin releasing hormone - TSH thyroid stimulating hormone Correspondence to: J.M. Gomez