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PubMed2005

Experience of Mars therapy with and without transplantation in 101 patients with liver insufficiency.

Liver support devices are used to treat life-threatening organ dysfunction until a hepatic graft is available or recovery of the native liver. We used a blood purification system--molecular adsorbent recycling system (MARS)--that is based on removal of both protein-bound and water-soluble substances and toxins. Within 2.5 years we treated 101 patients, who were stratified to three subgroups: acute liver failure (ALF; n = 56), acute decompensation in chronic liver failure (AcOCh; n = 35) and liver graft failure (n = 10). MARS seems to be a promising therapy for ALF, allowing the patient's own liver to recover or to gain enough time to find a liver graft. The most promising results, namely the highest number of livers to recovery were observed among acute patients with liver failure due to a toxic etiology. However, we did not discover much benefit of MARS for patients with AcOCh without liver transplantation.

Alanine Transaminase↗
PubMed1986

Detection of autoimmunity to sperm: mixed antiglobulin reaction (MAR) test or sperm agglutination? A study on 537 men from infertile couples.

Two different ways of testing for antisperm antibodies were compared: the mixed antiglobulin reaction (MAR) test for demonstration of antibodies of the IgG and IgA classes bound in vivo to the sperm membrane antigens and the gelatin agglutination test for detection of nonbound antisperm antibodies in serum and seminal plasma. Samples from 537 men from infertile couples were investigated. Antibodies bound to the sperm membrane were detected in 49 men (9.1%), IgG in 44 (8.2%), and IgA in 38 cases (7.1%). Sperm agglutinins were recorded in seminal plasma from 30 men (5.6%) and in serum (titer greater than or equal to 16) from 43 men (8.0%). The investigation revealed a very close correlation between the results of MAR testing and the occurrence of sperm agglutinins in serum and seminal plasma. However, if one focuses on antisperm antibodies of the IgA class, which seem to play the major role in male immune infertility, the MAR test offered the advantage that a minor group of patients with pure IgG responses could be distinguished, and rare cases with mainly or exclusively locally produced IgA antibodies could be detected.

Autoantibodies↗
PubMedDate not supplied

[MARS (Molecular Adsorbents Recirculating System). New technique of extracorporeal depuration in liver failure].

MARS (Molecular Adsorbent Recirculating System) is a new technique as a system of liver detoxification in patients with severe acute or acute on chronic hepatic failure. Also, it has shown its usefulness in the control of resistant pruritus in the primary biliary cirrhosis. Due to the fact that this technique is often delivered in Intensive Care Units (ICUs), we have reviewed the literature 1999 until now to describe this technique, its benefits and its mains complications. The technique was developed in Germany, where in 1999 was first used in clinical practice. It was used for the first time in Spain in 2000 and in the Clínica Universitaria of Navarra in July of 2001. Despite the short clinical experience using MARS its obvious beneficial effects such as decrease of hepatic toxins and the improvement of encephalopathy and hemodynamic situation, makes it a very useful technique in these patients. MARS has been shown to be a safe procedure, well tolerated by patients and accessible to the use by specialised nurses. Despite the encouraging clinical results, its used is still limited. Moreover its high cost precludes it widespread use and requires further studies.

Clinical Trials as Topic↗
PubMed2000

Use of matrix attachment regions (MARs) to minimize transgene silencing.

Matrix attachment regions (MARs) are operationally defined as DNA elements that bind specifically to the nuclear matrix in vitro. It is possible, although unproven, that they also mediate binding of chromatin to the nuclear matrix in vivo and alter the topology of the genome in interphase nuclei. When MARs are positioned on either side of a transgene their presence usually results in higher and more stable expression in transgenic plants or cell lines, most likely by minimizing gene silencing. Our review explores current data and presents several plausible models to explain MAR effects on transgene expression.

Animals↗
PubMed2002

Improvement in central nervous system functions during treatment of liver failure with albumin dialysis MARS--a review of clinical, biochemical, and electrophysiological data.

The Molecular Adsorbent Recirculating System (MARS) is a nonbiological liver support method based on the principles of dialysis, filtration, and adsorption. It allows the safe and efficient removal of both albumin-bound and water-soluble toxic metabolites, including ammonia, aromatic amino acids, tryptophan, and related phenolic and indolic products, as well as benzodiazepines. A well-documented effect of the treatment is the improvement of the hemodynamic situation of decompensated chronic patients. Systemic vascular resistance, mean arterial pressure, cerebral blood flow, and cerebral oxygen consumption increased significantly. The degree of hepatic encephalopathy decreased significantly. Increased intracranial pressure could be normalized in both chronic and fulminant liver failure. In three randomized clinical trials significant improvement of survival could be demonstrated. In a model of murine neuronal networks cultured on multi-microelectrode array plates and incubated with plasma from liver failure patients, a normalization of the spike and burst pattern could be observed, if plasma samples from MARS-treated patients before and after treatment were compared. In conclusion, MARS significantly improves central nervous system functions. It can serve as a model for the further investigation of the role of protein-bound substances in hepatic encephalopathy and cerebral hemodynamics.

Brain↗
PubMed2003

A 3-year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusion.

In our 3-year experience, we treated 63 patients with Molecular Adsorbent Recirculating System (MARS). The patients were divided as follows: 10 primary non-function (PNF) 16%, 10 delayed non-function (DNF) 16%, 16 Fulminant hepatitis (FH) 24%, 23 acute decompensation of chronic liver disease (ACLF) 38%, and 4 hepatic resection 6%. All patients who underwent MARS treatment had bilirubin >15 mg/dL, Glasgow Coma Score between 9 and 11, ammonium >160 microg/dL and non-coagulability. The determining factors taken into consideration for the continuation of MARS treatment were: an improvement in Glasgow Coma Score, and a decrease in ammonium and bilirubin. We also monitored hemodynamic parameters, acid-base equilibrium, and blood gas analysis before and after each treatment. In order to determine patients' neurological conditions, we not only took into account the Glasgow Coma Score, which does not give mathematically precise results but also took into account the fact that patients with hepatic coma had lower cerebral mean velocity in the cerebral arteries than patients without encephalopathy. For this reason, in the last 22 patients we monitored cerebral perfusion, determined by mean flow velocity (Vmean) in the middle cerebral artery. Our results were expressed as mean +/- SD and we analyzed the differences between mean values for each variable, before and after treatment by means of Student's t-test. At the end of treatment, we obtained significant P-values for bilirubin, ammonium, Glasgow Coma Score and creatinine. In 16/20 patients, we could demonstrate a clear correlation between the improvement in clinical conditions (especially neurological status) and improvement in cerebral perfusion, measured by color Doppler US.

Adult↗
PubMed2002

MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure.

As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P < 0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our study, we believe that MARS can be applied with high tolerance for a very long period of time. In addition, its repeatability allows it to be used in patients with DNF and FH as a bridge to transplant. In patients with DNF, it is used while waiting for complete recovery of the transplanted organ.

Adult↗
PubMed2004

Partitioning of oxygen during core formation on the Earth and Mars.

Core formation on the Earth and Mars involved the physical separation of metal and silicate, most probably in deep magma oceans. Although core-formation models explain many aspects of mantle geochemistry, they have not accounted for the large differences observed between the compositions of the mantles of the Earth (approximately 8 wt% FeO) and Mars (approximately 18 wt% FeO) or the smaller mass fraction of the martian core. Here we explain these differences as a consequence of the solubility of oxygen in liquid iron-alloy increasing with increasing temperature. We assume that the Earth and Mars both accreted from oxidized chondritic material. In a terrestrial magma ocean, 1,200-2,000 km deep, high temperatures resulted in the extraction of FeO from the silicate magma ocean owing to high solubility of oxygen in the metal. Lower temperatures of a martian magma ocean resulted in little or no extraction of FeO from the mantle, which thus remains FeO-rich. The FeO extracted from the Earth's magma ocean may have contributed to chemical heterogeneities in the lowermost mantle, a FeO-rich D" layer and the light element budget of the core.

Journal Article↗
PubMed2002

Review article: the molecular adsorbents recirculating system (MARS) in liver failure.

In recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. The molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialysed across an albumin-impregnated membrane against a recirculated albumin-containing solution, seems to be effective in removing albumin-bound toxins, such as fatty acids, bile acids and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. Data regarding MARS experience in acute liver failure and in primary graft dysfunction are encouraging but limited. Its real usefulness in these settings is, at present, under evaluation in randomized controlled clinical trials.

Humans↗
PubMed1999

Viable heterotrophic bacteria in water and sediment in 'Mar Piccolo' of Taranto (Ionian Sea, Italy).

Samples of water and sediment were collected from October 1996 to September 1997 in 'Mar Piccolo' of Taranto (Ionian Sea, Italy). Mar Piccolo is a semi-enclosed basin subject to pollution and receives a considerable amount of sewage and industrial waste. Qualitative and quantitative analyses of the composition of the microbial flora were conducted on samples from six stations. The highest bacterial densities, in water and in sediment samples, were found in summer and the lowest, in autumn. Among Gram-negative bacteria, the predominant genus was Aeromonas; Photobacterium and Pseudomonas were also found. Gram-positive bacilli were abundant at all sampling points. Faecal contamination indicators demonstrated that all the stations examined in Mar Piccolo are influenced by anthropogenic pollution throughout the year.

Colony Count, Microbial↗
PubMed1999

Two MAR DNA-binding proteins of the pea nuclear matrix identify a new class of DNA-binding proteins.

Four MAR-binding proteins of 60, 65, 70 and 72 kDa have been detected by South-Western blotting and isolated from pea nuclear matrices. Two cDNAs encoding the 60 and 65 kDa proteins (MARBP-1 and MARBP-2) were isolated from a pea leaf cDNA library by screening with a PCR product obtained using degenerate primers based on an amino acid sequence from the 60 kDa protein. The proteins of 560 and 550 amino acids are 86% identical and contain several KKD/E repeats near the C-terminus. Escherichia coli-expressed MARBP-1 specifically binds A/T-rich MAR DNA. The interaction of MARBP-1/MARBP-2 with MAR DNA involves novel DNA-binding motifs. The MARBP-1 and MARBP-2 genes are expressed in a range of pea tissues and are encoded by genes at different loci. MARBP-1 and MARBP-2 are homologous to yeast nucleolar proteins Nop56p and Nop58p, which are involved in ribosome biogenesis, and to similar highly conserved proteins in other eukaryotes and in archaebacteria. MARBP-1 and MARBP-2 may have multifunctional roles in chromatin organisation and ribosome biogenesis.

Amino Acid Sequence↗
PubMed2002

The multiple antibiotic resistance (mar) locus and its significance.

Chromosomally encoded systems involved in low level resistance of bacteria to different classes of antibiotics (mainly beta-lactams, chloramphenicol, quinolones and tetracycline), disinfectants and in resistance to organic solvents have been the focus of considerable interest in recent years. The multiple antibiotic resistance (mar) locus of Escherichia coli and Salmonella is perhaps the best described system involved in this type of resistance which is induced by MarA, the activator protein encoded by the marRAB locus. The mar -locus is reported to mediate resistance primarily by up-regulating efflux of some antibiotics, disinfectants and organic solvents via the AcrAB-TolC efflux pump and down regulating influx through Outer Membrane Protein F (OmpF). Whilst the level of antibiotic resistance conferred by marRAB is only low level, there are increasing data to suggest that marRAB and related systems are important in clinical antibiotic resistance, possibly as a 'stepping stone' to higher levels of resistance. Other related systems include up-regulation of RobA, SoxS and AcrAB which give rise to a similar resistance phenotype to that conferred by up-regulation of MarA. The aim of this paper is to review the function and significance of the mar -locus and related systems with a particular focus on its implications in veterinary medicine.

Animals↗
PubMed2002

Drainage basins and channel incision on Mars.

Measurements acquired by the Mars Orbiter Laser Altimeter on board the Mars Global Surveyor indicate that large drainage systems on Mars have geomorphic characteristics inconsistent with prolonged erosion by surface runoff. We find the topography has not evolved to an expected equilibrium terrain form, even in areas where runoff incision has been previously interpreted. By analogy with terrestrial examples, groundwater sapping may have played an important role in the incision. Longitudinally flat floor segments may provide a direct indication of lithologic layers in the bedrock, altering subsurface hydrology. However, it is unlikely that floor levels are entirely due to inherited structures due to their planar cross-cutting relations. These conclusions are based on previously unavailable observations, including extensive piece-wise linear longitudinal profiles, frequent knickpoints, hanging valleys, and small basin concavity exponents.

Journal Article↗
PubMed2000

Specific interaction of mouse major satellite with MAR-binding protein SAF-A.

A DNA-binding activity specific to the major mouse satellite (satMa) has been detected in a nuclear matrix protein extract by electrophoretic mobility shift assays (EMSA) after fractionation by ion exchange chromatography. An antibody raised against the satMa-protein complexes recovered from preparative EMSA recognizes on Western blots one major polypeptide with an apparent molecular mass of 120 kDa. The protein also has a similar affinity for a matrix-associated region (MAR) fragment. We demonstrate that the protein is a murine homologue of SAF-A which has been shown to bind selectively to MARs and is responsible for the satMa-binding activity in the chromatographic fractions. SatMa has significant homology to the mouse minor satellite fragments, but its binding of SAF-A shows much less affinity. No protected regions of significant length were found by footprinting, but multiple T residues scattered within the satMa sequence are protected, indicating that the whole fragment is involved in the binding to SAF-A. Combined immunofluorescence (SAF-A) and FISH (satMa) with in situ nuclear matrix procedures reveal that SAF-A and satMa colocalize. SAF-A appears as bright dots in interphase nuclei, presumably associated with MARs, predominantly surrounding and covering heterochromatic areas. A scheme based on morphological observations and biochemical data of SAF-A double satMa/MAR specificity is discussed.

Animals↗
PubMed2001

Role of the molecular adsorbent recycling system (MARS) in the treatment of patients with acute exacerbation of chronic liver failure.

OBJECTIVE: To test the efficacy of the molecular adsorbent recycling system (MARS) in patients with acute exacerbation of chronic liver disease. DESIGN: A prospective case analysis. SETTING: A university-affiliated tertiary medical center. PATIENTS AND METHODS: We applied MARS to treat a consecutive series of eight patients with acute exacerbation of chronic liver disease. RESULTS: The overall survival rate was 62.5%. All patients demonstrated improvement with regard to their degree of encephalopathy. In three patients, intracranial pressure and jugular bulb oxygen saturation decreased and cerebral perfusion pressure increased after treatment institution. Patients' hyperdynamic state was attenuated, as demonstrated by elevation of systemic vascular resistance, mean arterial pressure, and parallel reduction in cardiac index. A prompt reduction in serum ammonia, bilirubin, and lactate levels was observed. There were no complications during the treatment period. CONCLUSIONS: Applying MARS treatments to patients with acute exacerbation of chronic liver disease can detoxify blood, improve cerebral circulation, and reduce brain edema, as reflected by the reduction in intracranial pressure and jugular bulb oxygen saturation values in our patients. A partial reversal of the characteristic hyperdynamic circulation was also achieved. Despite our encouraging results, further testing is needed to determine the reliability of the system.

Adsorption↗
PubMed1995

The MAR-Mediated Reduction in Position Effect Can Be Uncoupled from Copy Number-Dependent Expression in Transgenic Plants.

To study the role of matrix-associated regions (MARs) in establishing independent chromatin domains in plants, two transgenes were cloned between chicken lysozyme A elements. These transgenes were the neomycin phosphotransferase (NPTII) gene under control of the nopaline synthase (nos) promoter and the [beta]-glucuronidase (GUS) gene controlled by the double cauliflower mosaic virus (dCaMV) 35S promoter. The A elements are supposed to establish an artificial chromatin domain upon integration into the plant DNA, resulting in an independent unit of transcriptional regulation. Such a domain is thought to be characterized by a correlated and position-independent, hence copy number-dependent, expression of the genes within the domain. The presence of MARs resulted in a higher relative transformation efficiency, demonstrating MAR influence on NPTII gene expression. However, variation in NPTII gene expression was not significantly reduced. The selection bias for NPTII gene expression during transformation could not fully account for the lack of reduction in variation of NPTII gene expression. Topological interactions between the promoter and A element may interfere with the A element as a domain boundary. In contrast, the GUS gene on the same putative chromatin domain showed a highly significant reduction in variation of gene expression, as expected from previous results. Surprisingly, no copy number-dependent GUS gene expression was observed: all plants showed approximately the same GUS activity. We concluded, therefore, that dCaMV 35S-GUS gene expression in mature tobacco plants is regulated by some form of dosage compensation.

Journal Article↗
PubMed1994

MAR, a novel high-incidence Rh antigen revealing the existence of an allelic sub-system including Cw (Rh8) and Cx (Rh9) with exceptional distribution in the Finnish population.

We present new genetic evidence obtained from population studies on Finns and from the studies on Finnish blood donors as well as their selected families using an antibody that defines a novel high-incidence Rh antigen MAR. Anti-MAR antibody shows an antithetical relationship to both anti-Cw and anti-Cx. The Rh antigens Cw (RH8) and, more strikingly, Cx (RH9) have each an exceptionally high frequency in Finns. Our studies on their genetic relationship indicate that the three antigens Cw, Cx and MAR behave as if being determined by alleles of the same Rh sub-system. Furthermore, we conclude that this sub-system manifests an inheritance pattern that is distinct from but analogous to that of the two well-known allelic sub-systems of C/c and E/e antigens.

Adult↗
PubMed1983

The value of the mixed antiglobulin reaction (MAR test) as an addition to routine seminal analysis in the evaluation of the subfertile couple.

A mixed erythrocyte-spermatozoa antiglobulin reaction (MAR test) for IgG antibodies has been done on semen specimens supplied by the male partners in 720 subfertile couples during a two-year period. The test was possible in all except 69 patients (9.5%). Antisperm antibodies were detected in 48 (10%) of 484 men with normal sperm counts, 18 (23%) of 78 with low sperm motility, and 19 (15%) of 128 with low counts. In 204 patients, antisperm antibodies were also measured by serum sperm-agglutination tests: The results showed a highly significant correlation with the results of MAR testing. It is concluded that the MAR test should be a routine part of seminal analysis, since the presence of IgG antisperm antibodies can be established in about 10% of men who might otherwise be passed as normal, and such antibodies can be positively excluded in a further 78% of the male partners of infertile marriages.

Autoantibodies↗