摘要:

Abstract.The process of cancer metastasis is sequential and selective and contains stochastic elements. The growth of metastases represents the endpoint of many lethal events that only few tumour cells survive. Primary tumours contain cells with heterogeneous metastatic properties, and the outcome of metastasis depends on the interplay of tumour cells with various host factors. Collectively, then, our studies and most data reported by others have led us to conclude that metastasis is a highly selective process regulated by a number of mechanisms. This belief is contrary to the once widely accepted notion that neoplastic dissemination is the ultimate expression of cellular anarchy. In fact, suggesting that cancer metastasis is a selective process is a more optimistic view in terms of cancer therapy than the one that contends that tumour dissemination is an entirely random event. A selective biological process is regulated by the interaction of tumour cells with their host, and these complex interactions can be studied and manipulated. A better understanding of the complexity of the processes of tumour evolution, progression, and metastasis should lead to improvements in the treatment of cancer.

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01889.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.It has recently become apparent that several cytokines and growth factors are capable of modulating fibroblast proliferation and biosynthetic activity. To understand the role of these factors in connective tissue regulation, we examined the effects of the simultaneous addition of interferon‐γ (IFN‐γ) and transforming growth factor‐β (TGF‐β) on normal human dermal fibroblast collagen and fibronectin production. In addition,in vitrotranscription rates and steady‐state mRNA levels for these molecules were determined by nuclear run‐off assays and Northern and dot‐blot hybridization using specific human cDNA probes. Treatment of cultures with TGF‐β caused stimulation of collagen and fibronectin production. Addition of IFN‐γ to the TGF‐γ‐treated cultures abrogated the stimulatory effects of TGF‐γ on collagen production in a dose‐dependent manner and resulted in a net inhibition of collagen production. In contrast, the increase in fibronectin synthesis induced by TGF‐γ was augmented further by IFN‐γ. These changes in collagen and fibronectin production were accompanied by parallel changes in the steady‐state mRNA levels for these proteins. The effects of TGF‐γ plus IFN‐γ on fibronectin gene expression appeared to be mediated entirely by transcriptional mechanisms, whereas the effects on collagen gene expression resulted from a combination of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01890.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Time‐dependent serum concentrations of extracellular matrix proteins were studied in 32 patients with pancreatitis in order to find potential markers of the reparative response during the disease. Patients were subdivided by clinical and biochemical criteria: severe acute pancreatitis (n=10), moderate acute pancreatitis (n= 17), and acute attack of chronic pancreatitis (n= 5). Serum and plasma samples were collected on days 1–7, 10,14, and 21 for measurements of the aminoterminal propeptide of type III procolla‐gen (PIIINP), hyaluronic acid, laminin, fibronectin, and routine clinical‐chemical parameters. During an acute attack of chronic pancreatitis all parameters were within the reference range. In moderate acute pancreatitis concentrations of PIIINP, laminin, and hyaluronic acid fluctuated around the upper reference limit, but declined to mid‐normal levels at day 21. In severe acute pancreatitis all three parameters increased. In patients who died as a consequence of sepsis and multi‐organ failure the increase in PIIINP, laminin and hyaluronic acid was much more pronounced and paralleled by a decrease in plasma concentrations of fibronectin. In conclusion, this study revealed a relation between the severity of acute pancreatitis and the increase in serum concentrations of extracellular matrix components, especi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01891.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Endothelin‐1 is a recently described endothe‐lium‐derived vasoconstricting peptide. Plasma concentrations of immunoreactive (IR‐) endothelin were investigated in six healthy young men applying a radioimmunoassay after extraction of endothelin from plasma. In venous plasma a mean concentration of 1.3 pM; 0.4 pmol 1‐1was found, whereas the mean concentration in arterial plasma was 0.9 pM; 0.4 pmol 1‐1(p<0.005). During venous stasis for 10 min the mean plasma concentration of IR‐endothelin increased about twofold, from basal 1.1pM;0.3 pmol l‐1to 2.1pM;0.3 pmol 1‐1(p<0.01). This manoeuvre may prove helpful to investigate the control of endothelinin vivounder a variety of pathol

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01892.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Human jejunal tissue obtained by peroral biopsy was cultured in control medium and in medium containing 100 mmol 1‐1ethanol. Subsequently, the incorporation and metabolism of [3H]‐arachidonic and [14C]‐linoleic acid were evaluated. Of the two fatty acids a significantly higher amount of [3H]–arachidonic acid was incorporated into phospholipids and more [14C]–linoleic acid was incorporated into triacylglycer–ols. This preferential distribution of the labelled fatty acids was not affected by ethanol, but when ethanol was present in the tissue culture medium, there was a significant decrease in the incorporation of both fatty acids into tissue phospholipids. The study thus shows that ethanol in moderate concentrations can affect human jejunal absorption and metabolism of poly–enoic fatty acids, contributing to a decrease in the amount of eicosanoid precursors available in j

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01893.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.In 10 duodenal ulcer patients gastric juice was aspirated every 10 min for 20 min before and 200 min after sham feeding. One antacid tablet or placebo was given 80 min after the sham feeding. Analyses of the aspirates showed that antacids reduced mean hydrogen ion activity and pepsin concentration significantly for 40 and 60 min, respectively, and increased phospholipid concentration for 30 min, compared with placebo. Highest mean pH was 2.52. The percentage of pH readings at or above pH levels of 2, 3, and 4 during the 2 h period following antacid administration was 29, 10, and 2%, respectively. No significant differences between antacid and placebo were found regarding intragastric concentrations of bile acids and prostaglandin E2. When one antacid tablet was administered 80 min after a real meal, the effect on intragastric pH was similarly weak, but lasted slightly longer.Acid neutralization alone can hardly explain the ulcer‐healing effect of low‐dose antacids. Antacid‐induced increase in intragastric concentration of phos‐pholipids is a new and potentially important obse

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01894.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy‐proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti‐nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera were also negative for antibodies to double‐stranded DNA, anti‐mitochondrial antibodies, and antibodies to gastric parietal cells. Using sensitive enzyme‐linked immunosorbent assays with purified antigens and Western blotting with cytoskeletal proteins of human intestinal cells, the following antibodies could be demonstrated: cytokeratin 18 autoantibodies (IgG 20.0%; IgM 6.7%; IgA 13.3%), actin antibodies (IgG 36.7%; IgM 48.3%, IgA 26.7%), desmin antibodies (IgG 6.7%; IgM 15.08%; IgA 50%), vimentin antibodies (IgG 3.3%; IgM 16.7%; IgA 10.0%) and tropomyosin antibodies (IgG 3.3%; IgM 3.3%, IgA 5.0%). Statistically significant correlations could be found for levels of cytokeratin 18 antibodies (IgM‐type) and the BEST index of activity, and for levels of desmin antibodies (IgM‐type) and the van HEES index of activity. Highest levels could be measured for actin antibodies (IgG‐type) in patients with isolated disease manifestation in the colon. The mechanism of induction of autoantibodies against cytoskeletal components in Crohn's disease still remains obscure. Unmasking of hidden antigens after cell injury during the inflammatory process of disease might lead to sensitization and antibody production. The pattern of antibodies in patients with Crohn's disease seems to be different compared with that of connective

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01895.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.During an oral glucose tolerance test (oGTT) and an isoglycaemic intravenous glucose infusion, blood glucose and the responses of insulin and glucose‐dependent insulinotropic polypeptide (GIP) were measured in six healthy volunteers. On a subsequent occasion a constant infusion of human synthetic GIP (2 pmol kg‐1min‐1for 30 min and 0.5 pmol kg‐1min‐1for another 30 min was given to each subject, again with a simultaneous infusion of glucose to maintain isoglycaemia to the oGTT. During the oGTT, plasma GIP concentrations rose from 92pM18 pmol 1‐1to 257 pM42 pmol 1‐160 min after ingestion of glucose (meanpMSEM). When glucose was administered intravenously plasma GIP levels did not rise significantly over basal. The infusion of hGIP mimicked the physiological plasma GIP response after oral glucose during the first 60 min of the study. Plasma insulin concentrations were significantly lower between 45 and 60 min than during the oGTT (438 pM 67 vs. 200pM48 pmol l‐1p<0.02; 465pM96 vs. 207pM48 pmol 1‐1;p<0.01). However, the total and incremental integrated insulin responses during the first 60 min of the study were, though lower, not significantly different from the oGTT experiment when glucose and hGIP were infused simultaneously. Thus, in the presence of mild physiological hypergly‐caemia, human GIP is able to enhance the initial insulin response almost equivalently to the stimulus provided by oral glucose. Decreased insulin concentrations during porcine GIP infusions in previous experiments might be due to sequence differences between human and porcine GIP. In humans, GIP must be considered as an important factor in the

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01896.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Increased lipolysis in abdominal adipocytes has been suggested to be of importance for the insulin resistance typical for abdominal obesity. In order to differentiate between fat distribution, measured as waist/hip ratio (WHR), and amount of body fat, glucose disposal during a euglycaemic clamp as well as lipolysis in isolated cells from abdominal and gluteo‐femoral regions were studied in 20 obese and 20 lean postmenopausal women with a high (n= 10) and low (n= 10) WHR, respectively.The lipolytic response was increased in cells from obese women irrespective of region. Furthermore, lipolysis was enhanced in abdominal compared with the gluteo‐femoral cells in obese women with a high WHR. Fasting blood glucose and insulin were increased in both groups of obese women while the degree of insulin resistance was most pronounced in the obese women with a high WHR.It is concluded that increased body fat is associated with both insulin resistance and increased lipolysis, and that this relationship is stronger in the presence of a high WHR. A high WHR may increase the expression of obesity as a risk for insulin resistance and this may be mediated through an increased lipolytic r

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01897.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The present study compares the preservation of the porcine pancreas by the standard Euro‐Collins solution or the cardioplegic histidine‐trypto‐phan‐ketoglutarate solution (HTK). The explanted pancreas was stored at 4°C for 6 and 24 h respectively, following which organ quality was assessed in a reperfusion chamber measuring physiological and biomedical parameters. After 6 h ischaemia, the amount of lactate was significantly lower when HTK was used for protection. Other parameters like insulin release, amylase release, vascular resistance and oxygen consumption of the pancreas did not indicate a significant difference. Protection with HTK significantly improved pancreas preservation after 24 h ischaemia: lactate content in the reperfusate was lower (HTK: 64.0±7.2μmol 50 ml‐1n= 8, v. EC: 114.2pM1–7 μmol 50 ml‐1,n= 6), the arteriovenous flow rate was higher (HTK: 5.7pM0.91 ml min‐1v. EC: 3.0pM0.26 ml min‐1), and the pancreatic oxygen consumption was increased (HTK: 2.15pM0.22 μl O2min‐1g‐1v. 0.47pM0.08 μl O2min‐1g‐1). We conclude that pancreas preservation can be improvedin vitro

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01898.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY