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PubMed2005

[Clinical and morphological features of alcoholic steatohepatitis].

48 patients with alcoholic steatohepatitis (ASH) were examined and divided into 3 groups according to the degree of fatty liver infiltration. It was minimal in 8 (16. 6%) patients, moderate in 10 (20.8%) and severe in 30 (62.5%) patients. The higher the degree of the fatty infiltration, the more pronounced dystrophic alterations and the more often necrosis, fibrosis and cell infiltration focuses were found in liver biopsy material. Morphologic changes in biopsy samples from ASH patients were much more pronounced in comparison with those in non-alcoholic steatohepatitis (NASH). The latter is characterized mostly by lymphocyte infiltration, while leukocyte infiltration is more typical of ASH. The study found prominent alterations in serum lipoprotein spectrum, triglyceride (TG) and saturated fatty acid concentrations in patients with ASH. High concentrations of chylomicrons, low-density lipoproteins and TG were registered together with low levels of high-density lipoproteins and albumin complex.

Biomarkers↗

PubMed1992

[Erythrocyte aggregation and clinical course stages of venous insufficiency of the legs].

A double vicious circle at the venule and capillary level had already been pointed out by J. Dormandy and G. Nash as a pathophysiologic mechanism of rheological disorders associated with venous insufficiency of the lower limbs. Afterwards, such disorders were found by many authors when ex vivo analysis were performed on venous insufficient patients. However the time of their onset and their evolution in the course of the disease remain unknown. We studied red cell aggregation and plasma fibrinogen in 67 patients depending on the evolutive stage: 1st stage: isolated functional disorders, 2nd stage: trunk varicose vein linked to ostial incompetence, 3rd stage: trunk varicose vein linked to ostial incompetence with chronic trophic skin changes. The results showed that red cell aggregation and fibrinogen values are increased with the severity of the diseases. The rheological parameters increase when compared to controls from the first stage. Within the studied population, we avoided skewed results due to age and fibrinogen level by covariance analysis. Therefore recorded differences were practically linked with erythrocyte aggregability. Thus, red cell aggregation appears to be both an aggravating factor and a severity marker of the disease, proving the relevance of a rheological treatment in the lower limb insufficiency.

Adult↗

PubMedDate not supplied

Attraction and growing interest for the fatty liver by the scientific associations.

NAFLD is considered to be the most common cause of liver test abnormalities among adults, up to the 10-24% of the general population being affected by NAFLD, with a prevalence rising up to the 50-90% among obese. These data determined a significant interest in the scientific communities. The publications regarding NAFLD increased of 3 folds between 1987 and 1990, of 4,5 folds between 1991 and 1993, of 6,5 folds between 1994 and 1996, of 20 folds between 1997 and 1999 and of 63 and 67 folds in the 2000-2002 and 2002-2004 periods. Approximately the 60% of the published papers appeared in gastroenterological journals, while the 25% of the papers were published on diabetologic journals and the 10% on cardiovascular disease journals. This growing interest has led the most important international scientific associations to organize monotematic conferences specifically on NAFLD and NASH.

Congresses as Topic↗

PubMedDate not supplied

Nonalcoholic fatty liver disease: defining a common problem.

Non Alcoholic Fatty Liver Disease (NAFLD), with prevalence of 10-51% in general population involving all ages, is the major cause of elevation of ALT and a common finding by ultrasound screening and may range from simple steatosis, to Non Alcoholic Steatohepatitis (NASH) and its clinical consequences as cirrhosis and hepatocellular carcinoma. In this review will be analyse factors influencing the onset of the disease. NAFLD, primarly associated with insulin resistance, is in fact considered the hepatic manifestation of the metabolic syndrome: a cluster of disorder that includes obesity, diabetes mellitus, dyslipidaemia, arteriosclerosis and hypertension. The increased incidence and prevalence of obesity and diabetes may explain growing interest in NAFLD. Racial, ethnic, enviromental and behaviour models are also reviewed.

Alanine Transaminase↗

PubMedDate not supplied

The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a condition of increasing incidence in western Countries seldom associated to other diseases of high prevalence in general population (i.e. diabetes and obesity). NAFLD ranges from simple fatty liver to steatohepatitis (NASH), which may lead to cryptogenic cirrhosis and in some cases hepatocellular carcinoma (HCC). Natural history of NAFLD in humans is poorly understood and progression of liver disease seems to be due to interaction between hosting (i.e. genetic, gut flora, insulin resistance) and environmental factors (social and eating behaviours) that should be responsible of increased oxidative stress within hepatocytes. Even if we need non-invasive markers able to describe the progression of liver disease, only meaning of liver biopsy is useful to characterize the stigmata of worsening such as inflammation and fibrosis.

Animals↗

PubMedDate not supplied

Steatosis and portal hypertension.

Non Alcoholic Fatty Liver Disease (NAFLD) is characterized by histologically macrovesicular steatosis in the absence of alcohol consumption. Portal hypertension (PH) is a severe complication of liver cirrhosis leading to a higher risk to develop gastro-esophageal varices, ascites, hepatorenal syndrome, and hepatic encephalopathy. The definition of portal hypertension is based on a pressure measurement. It may be performed directly through portal vein punction or by subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP). The hepatic venous pressure gradient (HVPG) reflects the degree of PH in the majority of liver diseases. The hepatic vein catheterization with measurement of the HVPG is considered the golden standard for portal pressure evaluation. The mechanisms by which steatosis could induce PH are not fully understood. It is not clear whether the degree of PH differs between patients with viral and alcoholic cirrhosis, and between patients with mild vs severe steatosis, In the majority of the studies subjects with alcoholic cirrhosis were included. Among patients with NASH, the portal hypertensive syndrome appears only in those with advanced cirrhosis. Further, although weight reduction decreases steatosis grade and fibrosis score, it is not clear whether it improves PH in patients with cirrhosis. In contrast, other studies found a correlation between the severity of steatosis and clinical or lab parameters of PH. We can conclude that up to now it is not actually clear whether steatosis in itself might affect portal pressure.

Cholesterol↗

PubMed2005

Parameter precision in the HBV-NP model and impacts on nitrogen scenario simulations in the Rönneå river, southern Sweden.

The HBV-NP model is a newly developed water quality model that describes the turnover and fluxes of both nitrogen and phosphorous. It is based on the conceptual precipitation/runoff HBV model. The HBV-NP model was applied for simulation of nitrogen for the Rönneå catchment in southern Sweden. The catchment was divided into 64 subcatchments in the model. Discharge measurements from six stations and nitrogen measurements from 12 stations were used in the calibration of parameters in the model. Eight automatic calibrations were performed with different combinations of time periods, objective functions, and levels of the nitrogen load in the model. A regionally extended interpretation of the Nash-Sutcliffe R2 criterion was used in the calibration. In the evaluation of the criterion, the errors were summed over both time steps and sampling points. Scenario simulations of combined measures for reduction of nitrogen load into the sea by 30% were thereafter performed with the eight sets of parameters established by calibration. The model parameters were not uniquely defined by the calibration. However, the simulated relative reduction of nitrogen load into the sea was relatively insensitive to the choice of parameter set, given the available input sources, variables, and data.

Computer Simulation↗

PubMed2006

[Adipokine interrelationship with the liver].

Recent progress in adipocyte biology delineates that adipocytes not only store excess energy, but also respond to metabolic signals by secreting proteins that exert local, central, and peripheral effects. Among these adipokines are free fatty acids, plasminogen activator inhibitor-1, angiotensinogen, TNFa, leptin and adiponectin. Dysregulation of production of these adipokines and/or imbalance of their actions lead to a wide array of liver and systemic pathophysiology related to NASH such as 1) development of systemic and hepatic insulin resistance, 2) progression from benign fatty liver to steatohepatitis and 3) activation of hepatic fibrogenesis. This review deals with the emerging concept of the adipokine interrelationship with the liver.

Adipocytes↗

PubMed2006

Hospitals' dirty secret. New reports on hospital patient safety and infections reveal pattern of deadly and expensive, yet preventable, medical errors.

They "will be met with skepticism by some, shock by others and incredulity by the remainder", says David Nash, left, editor of the American Journal of Medical Quality, about three new reports published in the journal that question patient safety in the nation's hospitals. The reports use different methods but all come to same conclusion: Poor practices at hospitals lead to deadly, costly infections.

Catheterization, Central Venous↗

PubMed2006

[Effects of resolving phlegm method on fibrinolytic status in non-alcoholic steatohepatitis patients of phlegm and blood-stasis syndrome].

OBJECTIVE: To observe the effect of resolving phlegm method (RPM) on fibrinolytic status in non-alcoholic steatohepatitis (NASH) patients of phlegm blood-stasis (PBS) syndrome type. METHODS: Sixty-two patients were randomly assigned to 2 groups, namely the treated group (n = 34) treated with Chinese herbs for resolving phlegm and dampness, smoothing liver and gallbladder, promoting blood circulation and removing blood stasis (composition: Indigo Naturalis 10 g, Alumen 3 g, Semen Cassiae 15 g, Fructus Crataegi 15 g, vinegar prepared Radix Bupleuri 10 g, Radix Curcumae 10 g, Radix Salviae Miltiorrhizae 12 g, Herba Lycopi 12 g, talc 12 g and Radix Glycyrrhizae 2 g), one dose twice per day orally, and the control group (n = 28) with ursodeoxycholic acid tablet (UAT) 150 mg three times per day. The treatment course for both groups was 12 weeks. Liver function (ALT, AST, ALP), insulin resistance (IR) index represented by homeostasis model-IR (HOMA-IR) and insulin (Ins), levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1), as well as main symptoms and physical signs were assessed before and after treatment. RESULTS: (1) Compared with those before treatment, levels of ALT, AST, HOMA-IR, t-PA, PAl-1 and main symptoms were all improved in the treated group (P < 0.05 or P < 0.01); (2) There was significant difference in ALP, HOMA-IR, t-PA and PAI-1 between the treated group and the control group (P < 0.05 or P < 0.01); (3) The improvement in liver function related indexes in the control group was mainly the level of ALT, t-PA (P < 0.01), and also shown on HOMA-IR, Ins and PAI-1. CONCLUSION: RPM could effectively improve liver function and fibrinolytic status. Its effect was better than that of UAT.

Adult↗

PubMed1991

Selected risk factors in adolescent suicide attempts.

This study examined stress, depression, attempted suicide, and knowledge of common signs of potential suicide in Alabama adolescents. A modified version of the National Adolescent Student Health Survey (NASHS) was administered to 3,803 eighth- and tenth-grade public school students during the fall of 1988. The incidence of stress, depression, and attempted suicide was analyzed by gender, ethnicity, locale (urban vs. rural), and participation in sexual intercourse and use of alcohol. Chi-square tests were used to determine if there were significant differences between groups. Findings indicated that females were at greater risk than were males. Both males and females who engaged in sexual intercourse and alcohol consumption were at greater risk than were abstainers. When analyzed by ethnicity, white adolescents who engaged in these behaviors were at significantly greater risk than were those who abstained; differences were not as pronounced for black youth. Comparisons on the knowledge scale indicated that females scored better than males, whites scored better than blacks, and urban students scored better than rural students. The data suggest that many adolescents are having difficulty coping with stress and depression, and that those who are engaging in various types of risk-taking behavior are at greater risk for depression and suicide.

Adolescent↗

PubMed1990

An alternatively processed mRNA specific for gamma-glutamyl transpeptidase in human tissues.

Human gamma-glutamyl transpeptidase (GGT)1 is composed of two subunits derived from a single precursor (Nash, B., and Tate, S.S. (1984) J. Biol. Chem. 259, 678-685; Finidori, J., Laperche, Y., Tsapis, R., Barouki, R., Guellaën, G., and Hanoune, J. (1984) J. Biol. Chem. 259, 4687-4690) consisting of 569 amino acids (Laperche, Y., Bulle, F., Aissani, T., Chobert, M.N., Aggerbeck, M., Hanoune, J., and Guellaën, G. (1986) Proc Natl. Acad. Sci. U.S.A. 83, 937-941). In the present study we report the cloning of an altered form of this precursor from human liver. We have isolated two clones, one 2,632 base pairs (bp) long from a fetal liver cDNA library and one 926 bp long from an adult liver cDNA library, each containing a 22-bp insertion that introduces a premature stop codon and shortens the open reading frame to 1,098 bp when compared with known human cDNA sequences specific for GGT. Sequence analysis of a human genomic GGT clone shows that this insertion of 22 bp is generated by a splicing event involving an alternative 3'-acceptor site. By polymerase chain reaction experiments we demonstrate that the alternatively spliced mRNA is present in polysomes from the microsomal fraction of a human hepatoma cell line (Hep G2) and thus could encode an altered GGT molecule of 39,300 Da (366 amino acids) encompassing most of the heavy subunit which is normally 41,500 Da (380 amino acids). The altered mRNA is detected in various human tissues including liver, kidney, brain, intestine, stomach, placenta, and mammary gland. This report is the first demonstration of an alternative primary sequence in the mRNA coding for GGT, a finding that could be related to the presence of some inactive forms of GGT detected in human tissues.

Adult↗

PubMed1990

Idiopathic scoliosis: correction of lateral and rotational deformities using the Cotrel-Dubousset spinal instrumentation system.

The Cotrel-Dubousset instrumentation (CDI) system developed between 1982 and 1984 is now being used extensively for the posterior correction of idiopathic scoliosis. In this study we compared the lateral and rotational correction obtained with CDI to that obtained with Harrington rod instrumentation and Drummond wiring. We matched 14 patients who had had CDI by age and sex with 14 patients who had had either Harrington rod instrumentation (n = 5) or Drummond wiring (n = 9). Average lateral curve correction was significantly better with CDI than with the combination of the other systems (71.9% and 56.4%, respectively; P less than .01). Average rotational correction was studied using the methods of Mehta, and Nash and Moe; all patients having CDI showed a median rotational improvement of 30 degrees; 57% of the comparison group had minimal improvement (P less than .01). These results suggest that CDI may offer a significant alternative to the Harrington and Drummond spinal instrumentation systems in the surgical management of adolescent idiopathic scoliosis.

Adolescent↗

PubMed1985

The phi 80 and P22 attachment sites. Primary structure and interaction with Escherichia coli integration host factor.

Although the lambdoid bacteriophage phi 80 and P22 possess site-specific recombination systems analogous to bacteriophage lambda, they have different attachment (att) site specificities. We have identified and determined the nucleotide sequences of the att sites of phi 80 and P22 and have examined the interaction of these sites with purified Escherichia coli integration host factor (IHF). The sizes of the homologous core regions of the att sites vary greatly: P22 has a 46-base pair core, while phi 80 and lambda have 17- and 15-base pair cores, respectively. The core sequences of the three phage show no significant homology, although dispersed regions of homology in arm sequences indicate that the three phage att sites are related. All three att sites have a high A + T composition, and restriction fragments carrying these sites migrate anomalously upon polyacrylamide gel electrophoresis. IHF binds to a site to the left of the common core in the phi 80 and P22 phage att sites (attP) and to a site to the right of the core in P22 attP and attB (the bacterial att site). In the lambda system, IHF interacts with three regions on attP (designated H1, H2, and H') and none on attB (Craig N., and Nash, H.A. (1984) Cell 39, 707-716). Alignment of the IHF sites of all three phage results in a consensus sequence for IHF binding, Pyr-AANNNNTTGATAT. Among the three phage, the number of IHF sites differs; however, the location and orientation of the binding sites in relation to the respective core regions are well conserved. An IHF site analogous to lambda H2 is present in both phi 80 and P22 attP, while a site analogous to lambda H' is present in P22 attP. This conservation suggests that IHF plays a very similar role in the site-specific recombination pathways of all three phage, and that the flanking arm sequences are necessary for phi 80 and P22 attP function, as is the case for lambda attP function. These structural similarities presumably reflect a conservation of the mechanism of site-specific recombination for the three phage.

Bacteriophage lambda↗

PubMed1987

[Radiographic estimation of vertebral rotation].

Although there are various methods such as that of Nash and Moe, to measure the degree of vertebral rotation in patients with scoliosis, no decisive method has been established to date. In the present study, a formula for estimation of the pedicle rotation ratio (PRR) was obtained, based on the results of measurements of 5 dry cadaver vertebrae to establish a reasonably accurate quantitative determination of the degree of vertebral rotation on a routine antero-posterior roentgenogram of the spine. The formula could be written as: Y = AX - B(X: PRR, Y: a degree of vertebral rotation, A and B: variable according to the level of the vertebrae). The degree of vertebral rotation was obtained on antero-posterior roentgenograms of 150 vertebrae from 29 patients with idiopathic scoliosis, and was also measured on computerized tomograms of these patients for comparison. There was statistically significant relationship between the results of two methods. The present appears to be useful for clinical evaluation of scoliosis.

Adolescent↗

PubMed1983

Glucosamine-derived phospholipids in Escherichia coli. Structure and chemical modification of a triacyl glucosamine 1-phosphate found in a phosphatidylglycerol-deficient mutant.

Certain Escherichia coli mutants defective in phosphatidylglycerol biosynthesis accumulate novel glucosamine-derived phospholipids. We previously demonstrated that the simplest of these substance (lipid X) is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3 (Takayama, K., Qureshi, N., Mascagni, P., Nashed, M. A., Anderson, L., and Raetz, C. R. H. (1983) J. Biol. Chem. 258, 7379-7385). We now report the structural characterization of a triacylglucosamine 1-phosphate (designated lipid Y) that is also found in these mutants. Hydrolyzates of Y contain 2 mol of beta-hydroxymyristate and 1 mol of palmitate/mol of glucosamine. In the lipid, one of the beta-hydroxymyristates is amide-linked at position 2, while the two other fatty acyl groups are ester-linked. Fast atom bombardment mass spectrometry is used to confirm that Y is a monosaccharide derivative and that the molecular weight of Y as the free acid (C50H96NO13P) is 950.29. Analysis of Y by proton NMR spectroscopy at 200 MHz reveals that the anomeric configuration is alpha. Further, one of the esterified fatty acid residues is attached to the 3 OH of the sugar, while the second is linked to an OH moiety of a hydroxymyristate. The 4 and 6 OH groups of the sugar are unsubstituted, as in E. coli lipid X. To establish the precise location of each esterified fatty acyl residue, we subjected Y to a very mild alkaline hydrolysis in the presence of triethylamine. This resulted in the selective removal of a single hydroxymyristoyl group. The triethylamine-treated derivative (lipid Y) has a molecular weight of 723. NMR spectroscopy of Y shows that the 3 OH of the sugar is no longer substituted, while the beta OH of the remaining amide-linked hydroxymyristate is still esterified with palmitate. On the basis of these findings, we propose that lipid Y has the same fundamental structure as lipid X, except for the additional presence of a palmitoyl moiety on the N-linked hydroxymyristate. Presumably, lipid Y is synthesized from X by a selective acylation reaction.

Endotoxins↗

PubMed1984

The biosynthesis of gram-negative endotoxin. Identification and function of UDP-2,3-diacylglucosamine in Escherichia coli.

Escherichia coli mutants defective in the pgsB gene are phosphatidylglycerol-deficient in certain genetic settings and accumulate novel, glucosamine-derived phospholipids (Nishijima, M., and Raetz, C. R. H. (1979) J. Biol. Chem. 254, 7837-7844). The simplest of these compounds is 2,3-diacylglucosamine 1-phosphate (2,3-diacyl-GlcN-1-P) ("lipid X" of E. coli), in which beta-hydroxymyristoyl moieties are the sole fatty acid substituents (Takayama, K., Qureshi, N., Mascagni, P., Nashed, M. A., Anderson, L., and Raetz, C. R. H. (1983) J. Biol. Chem. 258, 7379-7385). We now report a sensitive radiochemical method for detection of 2,3-diacyl-GlcN-1-P in wild type E. coli and demonstrate that there are about 4000 molecules/cell (0.02% of the total CHCl3-soluble phosphorus). In mutants bearing the pgsB1 lesion, the levels are 100- to 300-fold higher. In addition, we have discovered a novel liponucleotide, UDP-2,3-diacyl-GlcN, that also accumulates in conjunction with the pgsb1 mutation. This material represents 0.005% of the wild type phospholipid and accumulates 50- to 100-fold in the mutant. The identification of UDP-2,3-diacyl-GlcN in E. coli is based on: 1) migration of a minor 32P-labeled lipid from wild type and mutant cells with a UDP-2,3-diacyl-GlCn standard during two-dimensional thin layer chromatography; 2) susceptibility of this 32P-labeled material to cleavage by a liponucleotide-specific pyrophosphatase; and 3) chromatographic identification of [32P]UMP and [32P]2,3-diacyl-GlcN-1-P (lipid X) as the sole products of the enzymatic degradation. As shown in the accompanying article, this novel nucleotide is crucial for biosynthesis of lipid A disaccharides in extracts of E. coli and Salmonella typhimurium.

Endotoxins↗

PubMed1980

[The myocardfunction in chronic obstructive lung diseases with different pathogenesis (author's transl)].

The results of an investigation of the myocardial function are given. Described as contractility, ability of hypertrophy and reagibility in patients with chronic obstructive lung diseases under definate ergometric conditions. The patients are divided in three groups according to the proposition of Dornhorst and Nash: pink puffer or typ A, blue bloater or Typ B and mixing Typ M. Concerning contractility and hypertrophy differences between the groups are apparent significantly. The patients of typ B and M have the highest load by hypertrophy and contractility. The patients of typ A have only a small reserve of load. They are also not well adapted on exercise and have a high risk for cardiac insufficiency.

Adult↗