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Biomedical subjects

V Müller

Publications and source records attributed to V Müller.

At least 19 recordsLinked to original sources
PubMed2003

Incisional hernia repair after orthotopic liver transplantation: a technique employing an inlay/onlay polypropylene mesh.

BACKGROUND: The literature provides no data on the incidence and operative management of incisional hernias developing after orthotopic liver transplantation. The use of high-dose immunosuppressive agents results in an appreciable delay in wound healing. There is thus a need for a procedure for the reconstruction of the abdominal wall for patients on immunosuppression. The aim of this retrospective study was to establish the incidence of incisional hernias and an analysis of the results after implantation of a polypropylene mesh in inlay-onlay technique after liver transplantation is given. METHODS: The basis for the present retrospective investigations was a total of 207 liver transplantations carried out in 192 patients (15 re-transplantations). After performing tensiometry, a polypropylene mesh (Marlex) was implanted to close the hernias using the inlay/onlay technique or a direct closure of the fascia was done. All treated hernias were followed up for a median of 18 months. RESULTS: Among 184 patients, 17 developed incisional hernias after primary direct closure of the abdominal wall, giving an incidence of 9%. In an additional 8 patients an incisional hernia was seen where an absorbable mesh was used to close the abdominal wall after liver transplantation. In addition, there were 25 incisional hernias after 207 liver transplantations (12%). One of 15 (7%) of the surgically repaired hernias with implantation of a polypropylene mesh (Marlex) developed a recurrence. All the 3 patients after direct apposition of the fascia without using a polypropylene mesh suffered a recurrence (3 of 3; 100%). Significant risk factors for developing an incisional hernia were the amount of ascites and the stay in the ICU after transplantation. Neither severe deep nor superficial wound infection nor bowel fistulas were observed after implantation of a inlay/onlay mesh. CONCLUSION: In patients after liver transplantation, the implantation of a polypropylene mesh proved to be an efficient and safe method of treating incisional hernias. Implantation of a mesh was not associated with an increased infection rate, despite the use of immunosuppression. In view of the high recurrence rate associated with primary closure, mesh implantation should be given preference.

Female↗
PubMed2003

ATP synthases: structure, function and evolution of unique energy converters.

A-, F- and V-adenosine 5'-triphosphatases (ATPases) consist of a mosaic of globular structural units which serve as functional units. These ion-translocating ATPases are thought to use a common mechanism to couple energy of ATP hydrolysis to ion transport and thus create an electrochemical ion gradient across the membrane. In vitro, all of these large protein complexes are able to use an ion gradient and the associated membrane potential to synthesize ATP. A-/F-/V-type ATPases are composed of two distinct segments: a catalytic sector, A1/F1/V1, whose three-dimensional structural relationship will be reviewed, and the membrane-embedded sector, Ao/Fo/Vo, which functions in ion conduction. Recent studies on the molecular biology of the Ao/Fo/Vo domains revealed surprising findings about duplicated and triplicated versions of the proteolipid subunit and shed new light on the evolution of these ion pumps.

Adenosine Triphosphate↗
PubMed2002

Experience with 123I-iomazenil SPECT in acute cerebral infarction.

Neuronal cells are susceptible to cerebral ischaemia. As gamma-aminobutyric acid(A) (GABA(A)) receptors are specific for neurones, functional receptor imaging using I-iomazenil (IMZ), a ligand to the GABA benzodiazepine receptor, has been proposed as an imaging modality for the assessment of neuronal integrity. However, there is only limited experience with IMZ in patients with acute cerebral infarction. Therefore, the aim of this study was to evaluate IMZ single photon emission computed tomography (SPECT) in patients with acute cerebral ischaemia. IMZ SPECT was performed in 21 patients with acute cerebral infarction 7-10 days after stroke onset. Eleven patients underwent systemic thrombolysis within 6 h after symptom onset (group 1), whereas 10 patients were treated conservatively (group 2). IMZ (150-200 MBq) was injected intravenously and imaging was performed using a dedicated four-head SPECT camera at 5 min (perfusion) and 90 min (receptor distribution) post-injection, with an acquisition time of 50 min each. Images were analysed by visual inspection. Four patients showed normal IMZ distribution, and 17 patients showed abnormalities of IMZ uptake on both early and late images. In six patients with regional uptake deficits, a crossed cerebellar diaschisis was observed on early images. Cerebellar inhomogeneity of tracer uptake was absent at the time of late images in all six patients. In eight patients, areas of hypoperfusion corresponded exactly to the regions of receptor deficiency (match). In five patients, preserved neuronal integrity was present in hypoperfused areas (mismatch). In four patients, normally or even hyperperfused areas exhibited regional receptor deficiency (inverse mismatch). In conclusion, IMZ SPECT demonstrated differences between regional perfusion and receptor distribution in about one-half of patients 7-10 days after acute cerebral ischaemia. Interesting patterns between the early phase (perfusion) and the late phase (receptor distribution) were found. These patterns are indicative of the heterogeneous development of cerebral ischaemia where, even days after stroke onset, areas of hypoperfusion but preserved neuronal integrity may be present. However, the evaluation of the potential clinical and therapeutic impact of individual IMZ distribution patterns requires further investigation.

Adult↗
PubMed2002

Identification of a salt-induced primary transporter for glycine betaine in the methanogen Methanosarcina mazei Gö1.

The salt adaptation of the methanogenic archaeon Methanosarcina mazei Gö1 was studied at the physiological and molecular levels. The freshwater organism M. mazei Gö1 was able to adapt to salt concentrations up to 1 M, and the addition of the compatible solute glycine betaine to the growth medium facilitated adaptation to higher salt concentrations. Transport studies with cell suspensions revealed a salt-induced glycine betaine uptake activity in M. mazei Gö1, and inhibitor studies argue for a primary transport device. Analysis of the genome of M. mazei Gö1 identified a homolog of known primary glycine betaine transporters. This gene cluster was designated Ota (osmoprotectant transporter A). Its sequence and gene organization are very similar to those of the glycine betaine transporter OpuA of Bacillus subtilis. Northern blot analysis of otaC revealed a salt-dependent transcription of this gene. Ota is the first identified salt-induced transporter for compatible solutes in Archaea.

Amino Acid Sequence↗
PubMed2001

The Na(+) cycle in Acetobacterium woodii: identification and characterization of a Na(+) translocating F(1)F(0)-ATPase with a mixed oligomer of 8 and 16 kDa proteolipids.

The homoacetogenic bacterium Acetobacterium woodii relies on a sodium ion current across its cytoplasmic membrane for energy-dependent reactions. The sodium ion potential is established by a yet to be identified primary, electrogenic pump connected to the Wood-Ljungdahl pathway. Reactions possibly involved in Na(+) export are discussed. The electrochemical sodium ion potential generated is used to drive endergonic reactions such as flagellar rotation and ATP synthesis. Biochemical and molecular data identified the Na(+)-ATPase of A. woodii as a typical member of the F(1)F(0) class of ATPases. Its catalytic properties and the hypothetical sodium ion binding site in subunit c are discussed. The encoding genes were cloned and, surprisingly, the atp operon was shown to contain multiple copies of genes encoding subunit c. Two copies encode identical 8 kDa proteolipids, and a third copy arose by duplication and subsequent fusion of two genes. Furthermore, the duplicated subunit c does not contain the ion binding site in hair pin two. Biochemical and molecular data revealed that all three copies of subunit c constitute a mixed oligomer. The evolution of the structure and function of subunit c in ATPases from eucarya, bacteria, and archaea is discussed.

Adenosine Triphosphatases↗
PubMed2001

Arterialization of the portal vein in liver transplantation: a new microsurgical model in the rat.

BACKGROUND: A preexisting thrombosis of the portal vein and the deep splanchnic bed can make it extremely difficult to reestablish the portal blood flow in orthotopic liver transplantation in man. Complete arterialization of the liver transplant, including the donor portal vein, might be a viable therapeutic option. A new rat transplantation model is described, in which the liver is completely arterialized. METHODS: The outflow of the portal blood in the recipient was secured via a portocaval shunt. Hepatectomy was then performed and the liver transplant placed in orthotopic position. An interposed aortic segment was used for direct arterialization of the donor portal vein. RESULTS: The laboratory parameters determined in the serum at the end of the observation period of 28 days revealed normal functioning of the transplant. The histological examinations showed largely normal cellular architecture, with no signs of necrosis, but incipient fibrosis. CONCLUSIONS: Using this new surgical technique in the rat liver transplantation model, long-term morphological and functional changes in a completely arterialized liver graft, and the regenerative capability of liver tissue perfused in this way, can be investigated.

Anastomosis, Surgical↗
PubMed2001

Structural Insights into the A1 ATPase from the archaeon, Methanosarcina mazei Gö1.

The low-resolution structure and overall dimensions of the A(3)B(3)CDF complex of the A(1) ATPase from Methanosarcina mazei Gö1 in solution is analyzed by synchrotron X-ray small-angle scattering. The radius of gyration and the maximum size of the complex are 5.03 +/- 0.1 and 18.0 +/- 0.1 nm, respectively. The low-resolution shape of the protein determined by two independent ab initio approaches has a knob-and-stalk-like feature. Its headpiece is approximately 9.4 nm long and 9.2 nm wide. The stalk, which is known to connect the headpiece to its membrane-bound A(O) part, is approximately 8.4 nm long. Limited tryptic digestion of the A(3)B(3)CDF complex was used to probe the topology of the smaller subunits (C-F). Trypsin was found to cleave subunit C most rapidly at three sites, Lys(20), Lys(21), and Arg(209), followed by subunit F. In the A(3)B(3)CDF complex, subunit D remained protected from proteolysis.

Adenosine Triphosphatases↗
PubMed2001

Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach.

Steady-state levels of HIV-1 viraemia in the plasma vary more than a 1,000-fold between HIV-positive patients and are thought to be influenced by several different host and viral factors such as host target cell availability, host anti-HIV immune response and the virulence of the virus. Previous mathematical models have taken the form of classical ecological food-chain models and are unable to account for this multifactorial nature of the disease. These models suggest that the steady-state viral load (i.e. the set-point) is determined by immune response parameters only. We have devised a generalized consensus model in which the conventional parameters are replaced by so-called 'process functions'. This very general approach yields results that are insensitive to the precise form of the mathematical model. Here we applied the approach to HIV-1 infections by estimating the steady-state values of several process functions from published patient data. Importantly, these estimates are generic because they are independent of the precise form of the underlying processes. We recorded the variation in the estimated steady-state values of the process functions in a group of HIV-1 patients. We developed a novel model by providing explicit expressions for the process functions having the highest patient-to-patient variation in their estimated values. Small variations from patient to patient for several parameters of the new model collectively accounted for the large variations observed in the steady-state viral burden. The novel model remains in full agreement with previous models and data.

HIV Infections↗
PubMed2001

Selective extraction of subunit D of the Na(+)-translocating methyltransferase and subunit c of the A(1)A(0) ATPase from the cytoplasmic membrane of methanogenic archaea by chloroform/methanol and characterization of subunit c of Methanothermobacter thermoautotrophicus as a 16-kDa proteolipid.

Chloroform/methanol was applied to cytoplasmic membranes of the thermophilic methanogens Methanothermobacter thermoautotrophicus and Methanothermobacter marburgensis as well as to the mesophile Methanosarcina mazei Gö1. In any case, the chloroform/methanol extraction yielded only two proteins, subunit D (MtrD) of the Na(+)-translocating methyltetrahydromethanopterin:coenzyme M methyltransferase and the proteolipid of the A(1)A(0) ATPase. Both polypeptides are assumed to be directly involved in ion translocation in their respective enzymes, but have not been studied in detail due to lack of simple isolation procedures. The rapid and selective isolation by chloroform/methanol offers a new way to obtain the large quantities of material required for biochemical analyses. As a first result, molecular and biochemical data suggest that the proteolipid from M. thermoautotrophicus is a duplication of the 8-kDa proteolipid usually present in other archaea, but it retained the conserved glutamate involved in proton translocation in every copy. This is the first 16-kDa proteolipid found in archaea.

Adenosine Triphosphatases↗
PubMed2001

Chloride dependence of glycine betaine transport in Halobacillus halophilus.

Growth of Halobacillus halophilus is strictly chloride-dependent but the physiological basis for the chloride dependence remains to be elucidated. To address the function of Cl(-) in H. halophilus, a physiological study was performed. It was found that uptake of the compatible solute glycine betaine under isoosmotic conditions was stimulated by increasing salt concentrations. Uptake of glycine betaine required both, Na(+) and Cl(-). Cl(-) could be substituted by nitrate and bromide, but not by sulfate. Glycine betaine transport was optimal at around 0.7 M Cl(-). Cells responded to an osmotic upshock by accumulating glycine betaine, but only in the presence of chloride. These studies revealed the first chloride-dependent glycine betaine transporter in a prokaryote.

Betaine↗
PubMed2001

Investigation of brain dynamics in Parkinson's disease by methods derived from nonlinear dynamics.

EEGs were recorded from patients in early stages of Parkinson's disease (17 patients, 9 females) and healthy controls (12 subjects, 8 females) during rest and during execution/imagining of a complex motor task. The prediction that Parkinson's disease patients compared to controls would show more complex brain dynamics during performance of a complex motor task and imagination of the movements was confirmed by methods derived from nonlinear dynamics. In the resting state, analysis of correlation dimension of EEG time series revealed only slight topographical differences between the groups. During performance of a complex motor task, however, data from Parkinson's disease patients showed higher dimensionality than data from controls, indicating more complex EEG time series. The same difference was found when subjects did not perform any motor movements but imagined the complex movements they had just performed. The data are consistent with the hypothesis that the disturbances in Parkinson's disease result in the recruitment of superfluous cortical networks due to failed inhibition of alternative motor programs in the striatum and thus increase the complexity of cortical representation in motor conditions.

Aged↗
PubMed2001

Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model.

alpha-Synuclein (alpha-SYN) is deposited in intraneuronal cytoplasmic inclusions (Lewy bodies, LBs) characteristic for Parkinson's disease (PD) and LB dementias. alpha-SYN forms LB-like fibrils in vitro, in contrast to its homologue beta-SYN. Here we have investigated the solubility of SYNs in human LB diseases and in transgenic mice expressing human wild-type and PD-associated mutant [A30P]alpha-SYN driven by the brain neuron-specific promoter, Thy1. Distinct alpha-SYN species were detected in the detergent-insoluble fractions from brains of patients with PD, dementia with LBs, and neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden-Spatz disease). Using the same extraction method, detergent-insolubility of human alpha-SYN was observed in brains of transgenic mice. In contrast, neither endogenous mouse alpha-SYN nor beta-SYN were detected in detergent-insoluble fractions from transgenic mouse brains. The nonamyloidogenic beta-SYN was incapable of forming insoluble fibrils because amino acids 73 to 83 in the central region of alpha-SYN are absent in beta-SYN. In conclusion, the specific accumulation of detergent-insoluble alpha-SYN in transgenic mice recapitulates a pivotal feature of human LB diseases.

Amino Acids↗
PubMed2001

Duration and frequency of every day activities in total hip patients.

Little knowledge about frequency and duration of daily activities in patients after total hip arthroplasty is available. Such information is required for the definition of realistic load collectives for pre-clinical testing of prostheses. It could also be helpful for the quantitative evaluation of surgery outcome with different prosthesis types. The purpose of this study was to develop and apply a system for the determination of frequency and duration of patient activities in their habitual environment and to compare the results to a clinical outcome score (Harris hip score).A portable activity monitoring system (weight 1.6 kg including batteries) was designed using a Palm top computer, 2 inclination sensors for the thigh and calf and one goniometer positioned at the knee joint. An algorithm was developed to identify frequency and duration of the activities lying, sitting, standing, walking and stair climbing from the signals of the 3 sensors. 42 patients participated in the study and were equipped with the system in the morning at their home. Datasets of 31 patients (age 62.5+/-11.5 y) covered more than 6h (9.8 +/- 1.6 h) and were included in the analysis. Prosthesis specific data as well as the Harris hip score were collected. The most frequent patient activity was sitting (44.3% of the time), followed by standing (24.5%), walking (10.2%), lying (5.8%) and stair climbing (0.4%). The median number of steps/stairs was 6048/164. The number of step cycles representing one year in vivo use should, consequently, be increased to 1.1 million. The Harris hip score (91.4 +/- 9.8) correlated significantly with the number of stairs (r(2) = 0.26, p = 0.003) and showed a positive tendency with the number of steps per day. No differences in activity levels between prosthesis specific factors were found.

Activities of Daily Living↗
PubMed2001

Surgical treatment of HELLP syndrome-associated liver rupture -- an update.

In some 2% of the cases of the HELLP syndrome, severe spontaneous bleeding into the liver accompanied by haemorrhagic liver cell necrosis and rupture of the organ occurs and represents one of the main cause of death. On the basis of our own experience with four cases, a review of the literature is presented with particular focus on a therapeutic concept based on appropriate surgery. Within a MEDLINE search covering the period 1990-1999, the case reports of this kind of liver complication in the literature were analysed in terms of clinical course and outcome.In addition to our own four patients, a total of 49 cases with rupture of the liver were found in the literature. Despite surgical interventions, HELLP syndrome-associated liver rupture carried a mortality of 39%. Most patients died of haemorrhagic shock and organ failure. In order to improve survival, patients with ruptured liver or hepatic failure should be transferred to a centre with the necessary experience in liver surgery including liver transplantation. An interdisciplinary approach is required, including the use of temporary packing of the liver to control the bleeding, and during the further course of the condition, possibly even liver transplantation, as in one of our own cases.

Adult↗
PubMed2001

Overproduction of a functional A1 ATPase from the archaeon Methanosarcina mazei Gö1 in Escherichia coli.

Single subunits of the A1 ATPase from the archaeon Methanosarcina mazei Gö1 were produced in E. coli as MalE fusions and purified, and polyclonal antibodies were raised against the fusion proteins. A DNA fragment containing the genes ahaE, ahaC, ahaF, ahaA, ahaB, ahaD, and ahaG, encoding the hydrophilic A1 domain and part of the stalk of the A1AO ATPase of M. mazei Gö1, was constructed, cloned into an expression vector and transformed into different strains of Escherichia coli. In any case, a functional, ATP-hydrolysing A1 ATPase was produced. Western blots demonstrated the production of subunits A, B, C, and F in E. coli, and minicell analyses suggested that subunits D, E, and G were produced as well. This is the first demonstration of a heterologous production of a functional ATPase from an archaeon. The A1 ATPase was sensitive to freezing but lost only about 50% of its activity within 18 days on ice. Inhibitor studies revealed that the heterologously produced A1 ATPase is insensitive to azide, dicyclohexylcarbodiimide and bafilomycin A1, but sensitive to diethylstilbestrol and its analogues dienestrol and hexestrol. The expression system described here will open new avenues towards the functional and structural analyses of this unique class of enzymes.

Archaeal Proteins↗