Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease.
 ...
PMID:A comparison of starvation and elastase models of emphysema in the rat. 656 48

Protein degradation was measured as tyrosine release rate from proteins of extensor digitorum longus (EDL) muscles and as urinary excretion of 3-methylhistidine in freely fed adult nongrowing C57BL/6J mice with sarcomas, to study protein degradation in cancer-induced wasting of skeletal muscles. Whole muscle protein breakdown rate was unchanged, whereas protein synthesis was depressed, leading to an increased net degradation of skeletal muscles with loss of soluble, myofibrillar, and collagen proteins. Starvation for 24 hours elevated whole muscle protein breakdown in mice with and without sarcomas. Subsequent refeeding for 24 hours normalized the degradation. Adaptation to anorexia in pair-fed controls was achieved by a decrease in muscle protein turnover evaluated by urinary excretion of 3-methylhistidine over 5 days. The measurement of "catabolic decrease" of muscle protein breakdown protected the muscle mass in mice without tumors, but it was ineffective in tumor-bearing animals. The unchanged rate of breakdown of proteins in whole EDL muscles from tumor-bearing mice was accompanied by increased maximum cathepsin D activity and by elevated autolytic activity at acid pH in some muscles. Therefore, cathepsin D activity and net protease activities did not reflect whole muscle protein degradation in tumor-induced malnutrition. The results demonstrate that wasting of skeletal muscles in experimental cancer was not dependent on increased degradation but was dependent on depressed protein synthesis.
 ...
PMID:Lack of evidence for elevated breakdown rate of skeletal muscles in weight-losing, tumor-bearing mice. 657 91

Following either standardized stapled resection of an ileal blind loop terminus (17 beagles) or construction of a colorectal anastomosis (10 beagles), half the subjects immediately were fed an elemental diet (Vivonex HN). Gastrointestinal (GI) motility and absorption were maintained by exclusion of swallowed air. Controls received the same rate of feeding solution containing only the electrolyte components. Four days postoperatively, the fed beagle's colorectal anastomosis had over double the bursting pressure of the control, 303 +/- 46 mm Hg (p less than 0.001). At this time, the mature collagen content of the fed subjects' ileal wound was undiminished from that of normal ileum 2,223 +/- 336 versus 2,250 +/- 577, contrasting with the 45% decrease of this structural component (OHP) in the wounds of the unfed controls, 1,237 +/- 820 microgram/g of tissue (p less than 0.001). Similarly, the wounds of fed but not unfed subjects had a doubling (p less than 0.001) in concentration of collagen precursors and "new" collagen. The "catabolic" and "lag" phases, as noted in unfed experimental animals, appeared to be reflections of the relative starvation that accompanied the intestinal wounding. With maintenance of GI function and immediate full enteral nutrition, "accelerated healing" was noted relative to the previously considered "norm".
 ...
PMID:Maintenance of GI function after bowel surgery and immediate enteral full nutrition. I. Doubling of canine colorectal anastomotic bursting pressure and intestinal wound mature collagen content. 678 Jul 4

A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species.
 ...
PMID:Isolation and characterization of a large, neurite-associated glycoconjugate from neuroblastoma cells. 683 76

Previously asymptomatic aneurysms in ten patients ruptured within 36 days (mean, ten days) of a prior laparotomy. The laparotomy and associated intra-abdominal disease may have precipitated rupture of the unresected abdominal aneurysms by reduction of the collagen content of the aneurysm wall, thus making the wall weaker. The scar-like collagen fibers of an aneurysm wall provide the strength that permits the wall to resist rupture. There is a dynamic equilibrium between synthesis and lysis of this collagen. Lysis of collagen is enhanced by injury, such as laparotomy, and by nutritional depletion and local inflammation. Collagen lysis is greatest in the area adjacent to the injury, but also occurs at remote sites as well. Lysis is greatest during the first postoperative week, after which, in the absence of sepsis or starvation, synthesis exceeds lysis and the equilibrium is restored. A thin aneurysm wall may be weakened enough during this period of negative collagen balance to allow rupture.
 ...
PMID:Laparotomy as a precipitating factor in the rupture of intra-abdominal aneurysms. 735 84

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that modulates type I collagen synthesis. In addition, IFN-gamma also exerts potent effects on cellular tryptophan levels by inducing the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase. Because recent evidence indicates that IDO-mediated oxidative tryptophan catabolism is important in cellular responses to IFN-gamma, we investigated the role of IDO in the IFN-gamma-induced modulation of type I collagen gene expression. IFN-gamma ( > or = 50 U/ml) stimulated IDO expression in human dermal fibroblasts in vitro, resulting in a > 90% depletion of tryptophan in the culture media following incubation for 48 h. Higher concentrations of IFN-gamma ( > or = 500 U/ml) caused a marked decrease in type I collagen mRNA levels. Time-course studies indicated that maximal induction of IDO mRNA expression in IFN-gamma-treated fibroblast cultures (24 h) preceded the maximal decrease in collagen mRNA (96 h). Type I collagen mRNA levels were also markedly and selectively decreased in fibroblasts maintained in tryptophan-depleted cultures. Addition of exogenous tryptophan (up to 2500 microM) to IFN-gamma-treated fibroblasts restored "normal" concentrations of tryptophan in the culture media, but did not abrogate the IFN-gamma-induced decrease in collagen mRNA. Addition of the tryptophan metabolite kynurenine, in concentrations similar to those generated in fibroblast cultures following IFN-gamma treatment for 48 h, had no significant effect on type I collagen mRNA levels. These results indicate that although IFN-gamma causes activation of IDO and enhanced tryptophan catabolism in fibroblast cultures, neither the ensuing tryptophan starvation nor the accumulation of kynurenine in the culture media can fully account for the inhibitory effects of IFN-gamma on type I collagen mRNA expression.
 ...
PMID:Inhibition of type I collagen mRNA expression independent of tryptophan depletion in interferon-gamma-treated human dermal fibroblasts. 766 18

Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been analyzed for their capability to adhere to different extracellular matrix (ECM) components. The GI-CA-N cells adhered to all the tested substrates: laminin (LN), type I and type IV collagen (Coll I, Coll IV), vitronectin (VN), and fibronectin (FN). Conversely LAN-5 cells weakly attached to FN and VN, whilst adhesion on LN and Coll I and IV was strong and induced a rapid elongation of cell processes. By means of RT-PCR and immunoprecipitation we showed that the integrin pattern of these two lines was different and could explain their diversity in adhesion capability. Both cell lines express a large amount of the beta 1 integrin subunit, associated with different alpha chains, probably responsible for their adhesion to some ECM proteins. After treatment of LAN-5 cells with biological differentiating agents, such as gamma-interferon, alone or in combination with tumour necrosis factor-alpha (TNF-alpha), or retinoic acid, the levels of alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 integrin expression were enhanced, while the amount of alpha v remained constant. In contrast, treatment of LAN-5 cells with TNF-alpha, that did not induce any maturation, or starvation in 2% foetal calf serum, that inhibited cell proliferation without affecting neural differentiation, did not induce any change in the integrin assessment. Messenger-RNAs for the two alpha 6 isoforms, A and B, were present in both cell lines. However, in LAN-5 cells, the protein product was neither detectable nor inducible by differentiation. Our results confirm the specific modulation of the alpha 1 beta 1 integrin expression in human neuronal development, and show, for the first time, the involvement of alpha 2 beta 1 and alpha 3 beta 1 heterodimers in this maturational process.
 ...
PMID:Modulation of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrin heterodimers during human neuroblastoma cell differentiation. 769 64

Overexpression of the B cell leukemia/lymphoma-2 (bcl-2) gene has been shown to confer a survival advantage on cells by inhibiting apoptosis. In epithelia, the bcl-2 gene is also related to development and differentiation, and the protein is strongly expressed in the embryo in the epithelial cells of the developing mammary gland. To investigate directly the effect of bcl-2 on human epithelial cells, we used an amphotropic recombinant retrovirus to introduce the gene into nontumorigenic cell lines developed from luminal epithelial cells cultured from milk. Here we demonstrate that while bcl-2 overexpression does not directly induce the tumorigenic phenotype, it provides a survival advantage to the mammary epithelial cells by inhibiting cell death at confluence or under conditions of serum starvation, bcl-2 can also affect the phenotype of the original epithelial cells, and promote epithelial-mesenchymal conversion, accompanied by loss of the cell adhesion molecules E-cadherin and alpha 2 beta 1 integrin. The extent of the epithelial-mesenchymal conversion varies with small differences in the phenotype of the parental line and with the level of expression of Bcl-2 and in some cases cell lines emerge with a mixed phenotype. The increased survival of Bcl-2-expressing cells at confluence results in multilayering, and the development of three- dimensional structures. Where a mixed phenotype is observed these structures consist of an outer layer of polarized epithelial cells separated by a basement membrane-like layer from an inner mass of fibroblastoid cells. Branching morphogenesis of bcl-2 transfectants is also observed in collagen gels (in the absence of fibroblast growth factors). The results strongly indicate that by increasing their survival under restrictive growth conditions, and by modifying the epithelial phenotype, bcl-2 can influence the specific morphogenetic behavior of mammary epithelial cells.
 ...
PMID:bcl-2 overexpression inhibits cell death and promotes the morphogenesis, but not tumorigenesis of human mammary epithelial cells. 777 80

Previous investigations have shown that culture of freshly isolated hepatocytes under conventional conditions, i.e., on dried rat tail collagen in the presence of growth factors, facilitates cell growth but also causes an extensive down-regulation of most liver-specific functions. This dedifferentiation process can be prevented if the cells are cultured on a reconstituted basement membrane gel matrix derived from the Englebreth-Holm-Swarm mouse sarcoma tumor (EHS gel). To gain insight into the mechanisms regulating this response to extracellular matrix, we are analyzing the activities of two families of transcription factors, C/EBP and AP-1, which control the transcription of hepatic and growth-responsive genes, respectively. We demonstrate that isolation of hepatocytes from the normal quiescent rat liver by collagenase perfusion activates the immediate-early growth response program, as indicated by increased expression of c-jun, junB, c-fos, and c-myc mRNAs. Adhesion of these activated cells to dried rat tail collagen augments the elevated levels of these mRNAs for the initial 1 to 2 h postplating; junB and c-myc mRNA levels then drop steeply, with junB returning to normal quiescence and the c-myc level remaining slightly elevated during the 3-day culture period. Levels of c-jun mRNA and AP-1 DNA binding activity, however, remain elevated from the outset, while C/EBP alpha mRNA expression is down-regulated, resulting in a decrease in the steady-state levels of the 42- and 30-kDa C/EBP alpha polypeptides and C/EBP alpha DNA binding activity. In contrast, C/EBP beta mRNA production remains at near-normal hepatic levels for 5 to 8 days of culture, although its DNA binding activity decreases severalfold during this time. Adhesion of hepatocytes to the EHS gel for the same period of time dramatically alters this program: it arrests growth and inhibits AP-1 DNA binding activity and the expression of c-jun, junB, and c-myc mRNAs, but, in addition, it restores C/EBP alpha mRNA and protein as well as C/EBP alpha and C/EBP beta DNA binding activities to the abundant levels present in freshly isolated hepatocytes. These changes are not due merely to growth inhibition, because suppression of hepatocyte proliferation on collagen by epidermal growth factor starvation or addition of transforming growth factor beta does not inhibit AP-1 activity or restore C/EBP alpha DNA binding activity to normal hepatic levels. These data suggest that expression of the normal hepatic phenotype requires that hepatocytes exist in a G0 state of growth arrest, facilitated here by adhesion of cells to the EHS gel, in order to express high levels of hepatic transcription factors such as C/EBP alpha.
 ...
PMID:Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors. 806 19

Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia). Diseases of the connective tissues discussed include those of nutritional origin (scurvy, lathyrism, starvation, and protein deficiency), the genetic diseases (dermatosparaxis, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, homocystinuria, alcaptonuria, epidermolysis bullosa, rheumatoid arthritis in humans, polyarthritis in swine, Aleutian disease of mink, and the several types of systemic lupus erythematosus) and the acquired diseases of connective tissues (abnormal calcification, systemic sclerosis, interstitial lung disease, hepatic fibrosis, and carcinomas of the connective tissues). Several of the diseases of connective tissues may prove to be useful models for determining the relationship of collagen to meat tenderness and its other physical properties. Several other promising models for studying the nutrition-related disorders and the quality-related characteristics of meat are also reviewed.
 ...
PMID:Diseases and disorders of muscle. 839 47


<< Previous 1 2 3 4 5 6 7 8 Next >>