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Biomedical subjects

H Seitz

Publications and source records attributed to H Seitz.

At least 19 recordsLinked to original sources

Small non-coding RNAs and genomic imprinting.

Experimental and computer-assisted approaches have led to the identification of hundreds of imprinted small RNA genes, mainly clustered in two chromosomal domains (human 15q11-->q13 and 14q32 loci). The genes are only detected in placental mammals and belong to the C/D RNA and microRNA gene families. These are small non-coding RNAs involved in RNA-guided post-transcriptional RNA modifications and RNA-mediated gene silencing, respectively. Here, we discuss their potential functions and report the identification of novel small RNA genes lying within (or nearby) known imprinted chromosomal domains.

Animals↗

Electromagnetic hypersensitivity (EHS) and subjective health complaints associated with electromagnetic fields of mobile phone communication--a literature review published between 2000 and 2004.

Literature published between 2000 to 2004 concerning electromagnetic fields (EMF) of mobile communication and electromagnetic hypersensitivity (EHS) or unspecific symptoms of ill health, respectively, is reviewed. Basically, literature from established databases was systematically searched for. For each study, the design and quality were evaluated by means of a criteria list in order to judge evidence for causality of exposures on effects. Finally, 13 studies of sufficient quality were considered for this review. In only one provocation study, individuals with self-reported electromagnetic hypersensitivity were exposed to EMF. Their perception of field status was no better than would have been expected by chance. Results of five randomised cross-over studies on impaired well-being due to mobile phone exposure were contradictory. Even though these studies would allow more reliable exposure assessment, they are limited due to short exposure period and the small study size. No firm conclusion could be drawn from a few observational epidemiological studies finding a positive association between exposure and unspecific symptoms of ill health due to methodological limitations. Causality of exposure and effect was not derivable from these cross-sectional studies as field status and health complaints were assessed at the same time. In addition, exposure assessment has not been validated. In conclusion, based on the limited studies available, there is no valid evidence for an association between impaired well-being and exposure to mobile phone radiation presently. However, the limited quantity and quality of research in this area do not allow to exclude long-term health effects definitely.

Anxiety↗

Computer aided surgical reconstruction after complex facial burn injuries -- opportunities and limitations.

In severe facial burn injuries with extensive destruction of anatomical structures, cosmetic and functional outcome of treatment are frequently not satisfactory. Although operative therapy is being continuously refined, the variety and proximity of structures in the facial region is considered a major challenge in reconstructive surgery. We present the case of a 16-year-old patient with a severe facial burn injury. In planning the reconstructive procedures, we used a multimodal approach employing data from computerized tomography imaging, as well as from surface laser scanning, which provided three-dimensional visualization of facial soft tissues. Amount and pattern of structural loss could thus be determined more precisely and studied more vividly than by inspection of two-dimensional imaging alone. Anatomical features to be reconstructed could be projected onto the skin area of the prelaminated vertical rectus abdominis muscle (VRAM) flap that has been chosen to cover the defect. Prior to surgery, correction of the defects was simulated and the results of the virtual procedure superimposed on a three-dimensional head model of the patient. Tissue elasticity and thickness of the flap, however, could not be ascertained in advance, indicating the limitations of the method.

Adolescent↗

Fast generation of stereolithographic models.

In this paper we present a work-in-progress method for fast and efficient generation of stereolithographic models. The overall approach is embedded in our general software framework Julius, which runs on high-end-graphic systems as well as on low-level PCs. The design of the support structures needed for the stereolithographic process will allow semiautomatic generation of the model. We did produce support structures for stereolithographic models with this fast data processing pipeline and will show future perspectives in this paper.

Computer Graphics↗

A hybrid bacterial replication origin.

We constructed a hybrid replication origin that consists of the main part of oriC from Escherichia coli, the DnaA box region and the AT-rich region from Bacillus subtilis oriC. The AT-rich region could be unwound by E. coli DnaA protein, and the DnaB helicase was loaded into the single-stranded bubble. The results show that species specificity, i.e. which DnaA protein can do the unwinding, resides within the DnaA box region of oriC.

Bacillus subtilis↗

The diagnostic dilemma of traumatic rupture of the diaphragm.

BACKGROUND: Traumatic rupture of diaphragm is caused by blunt or penetrating trauma. Early diagnosis is difficult, and complications such as visceral herniation may arise. A 10-year evaluation of all diagnostic procedures used in patients with surgically proved traumatic rupture of the diaphragm is presented. METHODS: A review of all patients with surgically proved diaphragmatic injury from 1988 to 1998 was conducted. All diagnostic methods were analyzed in terms of their ability to identify diaphragmatic rupture. RESULTS: During the study period, 31 patients with a mean age of 34 years were treated. Of these patients, 20 sustained blunt trauma and 11 experienced penetrating trauma. The initial chest x-ray was diagnostic for 6 of the 31 patients, nonspecific for 15 of the patients, and normal for 10 of the patients. In no case was sonography diagnostic. Thoracoabdominal computed tomography (CT), performed in 22 of the patients, led to diagnosis for 5 patients and unspecific findings for 17 patients. Statistical analyses showed no significant difference between initial chest x-ray and thoracoabdominal CT. No significant difference between blunt or penetrating trauma or between left-side and right-side ruptures could be recognized with any diagnostic tool. CONCLUSIONS: All the diagnostic methods investigated in this study showed unsatisfying results, and traumatic rupture of the diaphragm seems to remain a diagnostic dilemma. Endoscopic techniques not tested in this study and discussed controversially may offer a good chance for early diagnosis and repair of the injured diaphragm.

Abdominal Injuries↗

Bacterial replication initiator DnaA. Rules for DnaA binding and roles of DnaA in origin unwinding and helicase loading.

We review the processes leading to the structural modifications required for the initiation of replication in Escherichia coli, the conversion of the initial complex to the open complex, loading of helicase, and the assembly of two replication forks. Rules for the binding of DnaA to its binding sites are derived, and the properties of ATP-DnaA are described. We provide new data on cooperative interaction and dimerization of DnaA proteins of E. coli, Streptomyces and Thermus thermophilus, and on the stoichiometry of DnaA-oriC complexes of E. coli.

Bacterial Proteins↗

Parvovirus B19 DNA in plasma pools and plasma derivatives.

BACKGROUND AND OBJECTIVES: Human parvovirus B19 (B19) has been transmitted by various plasma-derived medicinal products. The aim of this study was to determine the frequency and the level of B19 DNA contamination in plasma pools destined for fractionation and in a broad range of plasma derivatives. In addition, removal of B19 DNA by the manufacturing process was investigated in cases where corresponding samples from plasma pool and product were available. MATERIALS AND METHODS: Plasma pool samples and blood products were tested for B19 DNA by nested polymerase chain reaction (PCR), and the viral DNA content was determined by TaqMan quantitative PCR. RESULTS: Two-hundred and twenty two of 372 plasma pools for fractionation contained B19 DNA at concentrations of 10(2)-10(8) genome equivalents/ml (geq/ml). While approximately 65% of the DNA-positive plasma pools were only moderately contaminated (< 10(5) geq/ml), 35% contained > 10(6) geq/ml. High frequencies of contamination were detected in Factor VIII (79 of 91), prothrombin complex concentrates (38 of 43) and Factor IX (41 of 62), where the concentration of B19 DNA ranged between 102 and 107 geq/ml. A lower level of B19 DNA contamination was found in antithrombin III (five of 26 samples), in anti-D immunoglobulins (three of 37 samples) and in albumin (four of 51 samples), with levels ranging between 10(2) and 10(3) geq/ml. Furthermore, investigation of plasma pools for solvent/detergent plasma (S/D plasma), from two manufacturers, revealed B19 DNA in 15 of 66 batches at concentrations of 10(2)-10(8) geq/ml. Similar concentrations were detected in the corresponding final S/D plasma products. Anti-B19 immunoglobulin G (IgG) was found in plasma pools and S/D plasma at concentrations of approximately 40 IU/ml. CONCLUSION: Although positive PCR results do not necessarily reflect infectivity, these data show that B19 is a common contaminant in plasma pools and in plasma-derived medicinal products. Considering the resistance of animal parvoviruses to inactivation by heat and chemical agents, and the absence of specific information for B19, the risk of B19 transmission by plasma products should be considered. Physicians should be aware of this problem when treating patients of B19-related risk groups. The plasma fractionation industry should continue their efforts to avoid B19 contamination of plasma derivatives and develop methods which are effective in removing/inactivating parvovirus B19.

Blood↗

Binding of human lipoproteins (low, very low, high density lipoproteins) to recombinant envelope proteins of hepatitis C virus.

Heterogeneities in the density of hepatitis C virus (HCV)-RNA-carrying material from human sera (1.03-1.20 g/ml) are partially due to the binding of lipoproteins [low density (LDL), very low density (VLDL), high density (HDL) lipoproteins] and immunoglobulins. In this study we demonstrate the binding of recombinant HCV envelope protein (El/E2) to human LDL, VLDL and HDL on a molecular basis. The binding of lipoproteins was restricted to the middle part of the El gene product (amino acids 222-336) and the C-terminal part of the E2 protein (amino acids 523-809). Lipoproteins did not bind to recombinant HCV core protein.

Animals↗

The interaction domains of the DnaA and DnaB replication proteins of Escherichia coli.

The initiation of chromosome replication in Escherichia coli requires the recruitment of the replicative helicase DnaB from the DnaBC complex to the unwound region within the replication origin oriC, supported by the oriC-bound initiator protein DnaA. We defined physical contacts between DnaA and DnaB that involve residues 24-86 and 130-148 of DnaA and residues 154-210 and 1-156 of DnaB respectively. We propose that contacts between DnaA and DnaB occur via two interaction sites on each of the proteins. Interaction domain 24-86 of DnaA overlaps with its N-terminal homo-oligomerization domain (residues 1-86). Interaction domain 154-210 of DnaB overlaps or is contiguous with the domains known to interact with plasmid initiator proteins. Loading of the DnaBC helicase in vivo can only be performed by DnaA derivatives containing (in addition to residues 24-86 and the DNA-binding domain 4) a structurally intact domain 3. Nucleotide binding by domain 3 is, however, not required. The parts of DnaA required for replication of pSC101 were clearly different from those used for helicase loading. Domains 1 and 4 of DnaA, but not domain 3, were found to be involved in the maintenance of plasmid pSC101.

Bacterial Proteins↗

Giant-cell tumor of the synovial membrane: localized nodular synovitis in the knee joint.

Giant-cell tumor of the synovia is a benign neoplasm characterized histologically by proliferating histiocytes bearing lipids and hemosiderin intermingled with a variable number of multinuclear giant cells. Areas of predilection are the hand, and in the case of synovial joints, the knee joint is particularly affected. Clinically, patients have signs of mechanical derangement and, with the knee joint, meniscal symptoms and locking are often present. Joint effusion without previous trauma is another typical finding. Diagnosis is carried out by radiographic tools and has to be confirmed histologically. Giant-cell tumor of the synovia is treated by local excision either by arthroscopy or by arthrotomy. To our knowledge, the case we present is the largest giant-cell tumor of the synovia in the knee joint ever described in literature.

Adolescent↗

Distal femoral fracture through the screw hole of a ligament augmentation device fixation.

SUMMARY: Complications associated with fixation of artificial ligaments in augmented repair of the anterior cruciate ligament (ACL) have been reported throughout the literature. However, fractures following ligament augmentation device (LAD) fixation appear to be rare. We report the case of a 43-year-old woman, injured in a road accident, who sustained a depressed fracture of the tibial plateau and knee instability. The fracture was reduced and the medial collateral ligament and the menisci were sutured. The torn ACL was repaired using the Marshall technique and augmented with an LAD in an over-the-top technique. Twenty-five months postoperatively, the patient sustained a distal femoral fracture through the screw hole of the former LAD fixation after a simple fall on the street.

Accidental Falls↗

Timing of developmentally programmed excision and circularization of Paramecium internal eliminated sequences.

Paramecium internal eliminated sequences (IESs) are short AT-rich DNA elements that are precisely eliminated from the germ line genome during development of the somatic macronucleus. They are flanked by one 5'-TA-3' dinucleotide on each side, a single copy of which remains at the donor site after excision. The timing of their excision was examined in synchronized conjugating cells by quantitative PCR. Significant amplification of the germ line genome was observed prior to IES excision, which starts 12 to 14 h after initiation of conjugation and extends over a 2- to 4-h period. Following excision, two IESs were shown to form extrachromosomal circles that can be readily detected on Southern blots of genomic DNA from cells undergoing macronuclear development. On these circular molecules, covalently joined IES ends are separated by one copy of the flanking 5'-TA-3' repeat. The similar structures of the junctions formed on the excised and donor molecules point to a central role for this dinucleotide in IES excision.

Animals↗

Is stage conversion the initiating event for reactivation of Toxoplasma gondii in brain tissue of AIDS patients?

Reactivation of chronic toxoplasmosis resulting in Toxoplasma encephalitis (TE) is a common event in acquired immune deficiency syndrome (AIDS) patients. Conversion from Toxoplasma gondii bradyzoites to tachyzoites is a prerequisite for reactivation. Until recently, the study of stage conversion in human tissue was not possible due to the lack of antibodies that recognize stage-specific epitopes after long-term formaldehyde fixation. Using the combination of a polyclonal anti-T. gondii antibody, the cyst-stage-specific monoclonal antibody CC2, and a tachyzoite-specific polyclonal antibody (anti-SAG1, recombinant), we tried to demonstrate parasite differentiation in the brain tissue of 10 AIDS patients with clinically suspected TE. Double labeling of the stage-specific antibodies enabled us to demonstrate interconversion between tachyzoites and bradyzoites for the first time in human tissue. The study confirmed that the transformation process is nonsynchronous and that the manifestation of TE depends on the degree and site of tissue destruction caused by invading tachyzoites. The original source of tachyzoites could never be located, but a few samples suggested that tachyzoites may invade by dissemination across the blood-brain barrier. Cyst rupture as the first event in the process of reactivation was not seen. We conclude that the initial site(s) of reactivation will be destroyed by tissue-destructive tachyzoites long before clinical symptoms occur.

AIDS-Related Opportunistic Infections↗

The mycosubtilin synthetase of Bacillus subtilis ATCC6633: a multifunctional hybrid between a peptide synthetase, an amino transferase, and a fatty acid synthase.

Bacillus subtilis strain ATCC6633 has been identified as a producer of mycosubtilin, a potent antifungal peptide antibiotic. Mycosubtilin, which belongs to the iturin family of lipopeptide antibiotics, is characterized by a beta-amino fatty acid moiety linked to the circular heptapeptide Asn-Tyr-Asn-Gln-Pro-Ser-Asn, with the second, third, and sixth position present in the D-configuration. The gene cluster from B. subtilis ATCC6633 specifying the biosynthesis of mycosubtilin was identified. The putative operon spans 38 kb and consists of four ORFs, designated fenF, mycA, mycB, and mycC, with strong homologies to the family of peptide synthetases. Biochemical characterization showed that MycB specifically adenylates tyrosine, as expected for mycosubtilin synthetase, and insertional mutagenesis of the operon resulted in a mycosubtilin-negative phenotype. The mycosubtilin synthetase reveals features unique for peptide synthetases as well as for fatty acid synthases: (i) The mycosubtilin synthase subunit A (MycA) combines functional domains derived from peptide synthetases, amino transferases, and fatty acid synthases. MycA represents the first example of a natural hybrid between these enzyme families. (ii) The organization of the synthetase subunits deviates from that commonly found in peptide synthetases. On the basis of the described characteristics of the mycosubtilin synthetase, we present a model for the biosynthesis of iturin lipopeptide antibiotics. Comparison of the sequences flanking the mycosubtilin operon of B. subtilis ATCC6633, with the complete genome sequence of B. subtilis strain 168 indicates that the fengycin and mycosubtilin lipopeptide synthetase operons are exchanged between the two B. subtilis strains.

Adenosine Monophosphate↗

Acetabular fractures: operative management and long term results.

INTRODUCTION: While the undisplaced acetabular fractures have a good prognosis after conservative treatment, the management of the displaced fractures has been a controversial issue over the last decades with variable results in their treatment and prognosis. Anatomical reduction can be only achieved operatively. The long term outcome of 209 patients with displaced acetabular fractures treated by open reduction and internal fixation was presented. MATERIAL AND METHODS: Between 1972 and 1996, 209 patients with a mean age of 38 years (15-62a) were treated for displaced acetabular fractures operatively. 161 patients could be followed up over a period of 2 to 20 years. The function of the hip joint in correlation with radiological results was evaluated according to the scheme of Merle d'Aubinge. RESULTS: Patients with single column fractures showed 90% good or excellent results followed by 55% good or excellent results in patients with transverse fractures. The highest rates of complication (20% osteoarthritis, 6% femoral head necrosis, 9% heterotopic ossification) were observed in both column fractures and in transverse and posterior wall fractures. Deep infection was observed in 6 cases (4%), superficial wound infection in 8 cases (5%). Primary sciatic nerve palsy was seen in 10 cases (6%) and postoperative peroneal nerve palsy in 6 cases (4%), all of which improved during the rehabilitation period. CONCLUSION: Displaced acetabular fractures of the weight bearing part of the dome, i.e. transtectal fractures, should be treated operatively. The operation should preferably be performed within one week after the injury.

Acetabulum↗

The N-terminus promotes oligomerization of the Escherichia coli initiator protein DnaA.

Initiation of chromosome replication in Escherichia coli is governed by the interaction of the initiator protein DnaA with the replication origin oriC. Here we present evidence that homo-oligomerization of DnaA via its N-terminus (amino acid residues 1-86) is also essential for initiation. Results from solid-phase protein-binding assays indicate that residues 1-86 (or 1-77) of DnaA are necessary and sufficient for self interaction. Using a 'one-hybrid-system' we found that the DnaA N-terminus can functionally replace the dimerization domain of coliphage lambda cl repressor: a lambdacl-DnaA chimeric protein inhibits lambda plasmid replication as efficiently as lambdacI repressor. DnaA derivatives with deletions in the N-terminus are incapable of supporting chromosome replication from oriC, and, conversely, overexpression of the DnaA N-terminus inhibits initiation in vivo. Together, these results indicate that (i) oligomerization of DnaA N-termini is essential for protein function during initiation, and (ii) oligomerization does not require intramolecular cross-talk with the nucleotide-binding domain III or the DNA-binding domain IV. We propose that E. coli DnaA is composed of largely independent domains - or modules - each contributing a partial, though essential, function to the proper functioning of the 'holoprotein'.

Amino Acid Sequence↗

Comparison of femoral and tibial pullout forces in bone-patellar tendon-bone anterior cruciate ligament reconstructions with a new interference fixation device.

Interference screws have become the standard method for fixing bone-patellar tendon-bone (BPTB) grafts. To avoid the inherent pitfalls and complications of interference screws, a 28-mm long and from 5 to 7 mm spreadable metal bolt with nontapping threads was developed for this study. The technical applicability and biomechanical characteristics of this new BPTB interference fixation device were investigated by dissection or tensile testing of 48 cadaveric knee specimens from young donors. No problems occurred with respect to bone plug anchoring during insertion of the spreading bolts. The clinically important linear load was 920+/-283 N for the femoral and 635+/-247 N for the tibial fixation site. Bone plug pullout was the mode of failure in all specimens. The results of this study indicate that the spreading bolt is a reasonable alternative to interference screws.

Adult↗