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Biomedical subjects

T Engel

Publications and source records attributed to T Engel.

At least 19 recordsLinked to original sources
PubMed2004

Fresh meniscal allograft transplantation and autologous ACL/PCL reconstruction in a patient with complex knee trauma following knee dislocation--a case report.

Instability of the knee joint, particularly in combination with the loss of one meniscus, regularly leads to the early development of arthritis. This paper describes the case of a 19-year-old male with ruptures of the anterior (ACL) and posterior cruciate ligament (PCL) along with the loss of the medial meniscus due to knee dislocation. Combined, time-delayed reconstruction of both the ACL and PCL and the allogenic fresh meniscal transplantation of the medial meniscus without bone plugs were performed. The control arthroscopy performed 6 months post-transplantation revealed good vitality and integration of the grafts as assessed both macroscopically and histologically. A small portion of the posterior horn had to be refixated, and the anterior horn was atrophic. At 24 months after trauma and 13 months following meniscal transplantation, the patient achieved a Lysholm score of 88 points and clinical examination indicated a stable knee. Fresh meniscal allograft transplantation, in combination with autologous ACL and PCL reconstruction, constitutes--in specialized centers--an alternative treatment option for complex trauma of the knee joint with loss of a meniscus.

Accidents, Traffic↗
PubMed2003

[Tibial plateau fracture--biodegradable bonecement-augmentation].

Between October 1996 and January 1999,29 patients (f:16,m:13,age: 22-86) with fractures of the lateral tibial plateau were operated on arthroscopic,fluoroscopic control or were treated with open reduction and internal fixation. 15 of them were retrospective and 14 prospective analysed. The metaphyseal defect after elevation of the depressed fragment was augmented in 11 cases with autologous spongeous bone grafting,in 9 cases with biodegradable bone cement (Norian SRS). Augmentation was unnecessary in 9 cases. The results according to the Lysholm score and the radiological results were good or excellent. Concerning the kind of augmentation no difference was noted. In the Norian SRS-group the duration of postoperative treatment was shorter than in the other group. The duration of partial weight bearing was shorter too. The results of the present study suggest that an injectable calcium phosphate cement may be a competent material for augmentation in lateral tibial plateau fractures because of the application form and the initial high mechanical stability.

Adult↗
PubMed2001

The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages.

Here we report the induction of gene expression of ABCG4, a member of the ABC transporter subfamily G, from human macrophages by oxysterols and retinoids, agonists of the nuclear receptors LXR and RXR. The cloned ABCG4 transcript has a size of 3.5 kb and contains an open reading frame which encodes a polypeptide of 646 amino acids. Structurally, the putative ABC transporter protein consists of a nucleotide binding fold followed by a cluster of six transmembrane-spanning domains and thus conforms to the group of half-size ABC transporters. Among the human ABC transporter subfamily G members the novel transporter shows highest protein sequence homology and identity to ABCG1 (84 and 72%, respectively). Analysis of the genomic organization demonstrates that the ABCG4 gene is composed of at least 14 exons which extend across a region of 12.6 kb in size on chromosome 11q23.3. Based on its structural features and an LXR/RXR-responsive regulation similar to the cellular lipid export protein ABCA1, we conclude that ABCG4 may be involved in macrophage lipid homeostasis.

ATP Binding Cassette Transporter, Subfamily G↗
PubMed2001

Conservative functional treatment of ankle fractures.

Thirty-eight patients (mean age 49 years; range 19-91 years; nine of them over 60 years; 28 women, 10 men) suffering from an isolated Weber B fracture with a dislocation of less than 1 mm underwent functional therapy using a pneumatic ankle brace and were included in a prospective study. The clinical outcome was measured according to the Olerud-Molander ankle score. Functional therapy was finished in 34 cases successfully. Twenty-one patients were scored after 17 months on average (range 8-27 months) with the Olerud-Molander ankle score. A very good result was seen in 18 patients, including 12 with 100 points, a complete remission. The remaining 3 patients showed good results (1 had 90, 2 had 85). However, functional treatment failed in 4 cases due to secondary dislocation. These patients underwent surgery without further complications. The control group, 31 operated patients, did not show as good results. Functional therapy of stable Weber-B ankle fractures appears to be superior to surgery. We were able to avoid surgery in 90% of our patients and got better results than with patients undergoing open reduction and internal fixation.

Adolescent↗
PubMed2001

Apolipoprotein E in macrophages and hepatocytes is eegraded via the proteasomal pathway.

Macrophage-derived apolipoprotein E (apoE) influences the susceptibility of the arterial wall to atherosclerosis. Previous studies have shown that production of apoE in these cells is regulated at a posttranscriptional level and is increased by inhibitors of proteasomal degradation. To further investigate this mechanism, we stably transfected RAW 264.7 macrophages and HepG2 cells with a construct overexpressing ubiquitin, the peptide targeting proteins to the proteasome, fused to an influenza virus hemagglutinin epitope tag. Ubiquitination of apoE was investigated by immunoprecipitation and Western blot analysis. In both cell types, apoE was ubiquitinated, and inhibition of proteasome function by lactacystin led to accumulation of ubiquitinated apoE. These studies provide strong evidence for proteasomal degradation of apoE in the two main cell types responsible for its production and indicate a possible new level of regulation of this important protein.

Acetylcysteine↗
PubMed2001

Genomic sequence and structure of the human ABCG1 (ABC8) gene.

The human ATP-binding cassette half transporter G1 (hABCG1) may play a role in cholesterol transport in macrophages. Using RACE assays we determined the structure of this gene. The hABCG1 gene spans more than 97 kb comprising 20 exons, 20 kb and 5 exons more than hitherto described. Four of the novel exons are upstream and one is downstream of previous exon 1, and they are predicted to encode at least five novel transcripts. We also detected two separate promoters, upstream of exons 1 and 5, respectively. The region 650 bp upstream of exon 1 was predicted to contain putative binding sites for SP1 and nuclear factor kappaB (NF-kappaB), but no sterol response elements (SREs) or retinoid X receptor (RXR) binding sites. The region 650 bp upstream of exon 5 contained 19 possible SP1 binding sites, one possible SRE, two possible NF-kappaB, and two putative RXR binding sites. Nevertheless, both promoters responded in macrophages to stimulation by hydroxycholesterol and retinoic acid.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages.

Apolipoprotein E (apoE) produced by macrophages in the arterial wall protects against atherosclerosis, but the regulation of its secretion by these cells is poorly understood. Here we investigated the contribution of the adenosine triphosphate binding cassette transporters ABCA1 and ABC8 to the secretion of apoE from either primary human monocyte-derived macrophages (HMDM) or human THP1 macrophages. During incubations of up to 6 h, apoE secretion from both THP1 macrophages and HMDM was stimulated by 8-Br-cAMP, which activates ABCA1 expression. The putative ABCA1 inhibitor glyburide and antisense oligonucleotides directed against ABCA1 mRNA significantly reduced apoE secretion from THP1 macrophages and HMDM. Antisense oligonucleotides directed against ABC8 mRNA also inhibited apoE secretion, although this inhibition was less pronounced and consistent than in the case of ABCA1. ApoE secretion from HMDM of ABCA1-deficient patients with Tangier disease was also decreased. ApoE mRNA expression was not affected by inhibition of ABCA1 or ABC8 in normal HMDM or the lack of functional ABCA1 in HMDM from Tangier disease patients. Inhibition of ABCA1 in HMDM prevented the occurrence of anti-apoE-immunoreactive granular structures in the plasma membrane. We conclude that ABCA1 and, to a lesser extent, ABC8 both promote secretion of apoE from human macrophages.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Functional architecture of an intracellular membrane t-SNARE.

Lipid bilayer fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, of which one is supplied by the v-SNARE and the other three by the t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and a SNAP-25 protein contributes the other two. Although there are numerous homologues of syntaxin on intracellular membranes, there are only two SNAP-25-related proteins in yeast, Sec9 and Spo20, both of which are localized to the plasma membrane and function in secretion and sporulation, respectively. What replaces SNAP-25 in t-SNAREs of intracellular membranes? Here we show that an intracellular t-SNARE is built from a 'heavy chain' homologous to syntaxin and two separate non-syntaxin 'light chains'. SNAP-25 may thus be the exception rather than the rule, having been derived from genes that encoded separate light chains that fused during evolution to produce a single gene encoding one protein with two helices.

Escherichia coli↗
PubMed2000

Anterograde flow of cargo across the golgi stack potentially mediated via bidirectional "percolating" COPI vesicles.

How do secretory proteins and other cargo targeted to post-Golgi locations traverse the Golgi stack? We report immunoelectron microscopy experiments establishing that a Golgi-restricted SNARE, GOS 28, is present in the same population of COPI vesicles as anterograde cargo marked by vesicular stomatitis virus glycoprotein, but is excluded from the COPI vesicles containing retrograde-targeted cargo (marked by KDEL receptor). We also report that GOS 28 and its partnering t-SNARE heavy chain, syntaxin 5, reside together in every cisterna of the stack. Taken together, these data raise the possibility that the anterograde cargo-laden COPI vesicles, retained locally by means of tethers, are inherently capable of fusing with neighboring cisternae on either side. If so, quanta of exported proteins would transit the stack in GOS 28-COPI vesicles via a bidirectional random walk, entering at the cis face and leaving at the trans face and percolating up and down the stack in between. Percolating vesicles carrying both post-Golgi cargo and Golgi residents up and down the stack would reconcile disparate observations on Golgi transport in cells and in cell-free systems.

Amino Acid Sequence↗
PubMed1999

[Bilateral posterior fracture-dislocation of the shoulder caused by an epileptic seizure - diagnostic, treatment and result].

The case of an 39-year-old man is presented, who sustained a bilateral locked fracture dislocation of the shoulders occurring during an epileptic seizure. Radiographs demonstrated a compression-fracture of the anteromedial aspect of the humeral head bilaterally (reversed Hill-Sachs-lesions). Additionally, fractures of the lesser and greater tuberosity were diagnosed at the right site. Open reduction and internal fixation was performed in both shoulders within 12 hours. 6 months later the patient has no complaints with a free range of motion. Diagnostics, treatment and result are discussed in context with the literature.

Adult↗
PubMed1998

Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function.

Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(-/-) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein.

Acetyl-CoA C-Acetyltransferase↗
PubMed1997

Hearing loss from combined exposures among petroleum refinery workers.

Workers from a refinery (n = 438) were interviewed, had their hearing tested and had their exposures to noise and solvents assessed. Measurements suggested that most exposures to noise and solvents were within exposure limits recommended by international agencies; however, the prevalence for hearing loss within the exposed groups ranged from 42 to 50%, significantly exceeding the 15-30% prevalence observed for unexposed groups. The adjusted odds ratio estimates for hearing loss were 2.4 times greater for groups from aromatics and paraffins (95% CI 1.0-5.7), 3 times greater for the maintenance group (95% CI 1.3-6.9) and 1.8 times greater for the group from shipping (95% CI 0.6-4.9), when compared to unexposed workers from the warehouse and health clinic. The results of acoustic reflex decay tests suggest a retrocochlear or central auditory pathway involvement in the losses observed in certain job categories. These findings indicate that factors in addition to noise ought to be considered when investigating and preventing occupational hearing loss.

Adult↗
PubMed1997

A cephalometric analysis of nasal septal growth.

In a study using lateral cranial radiographs of 454 males and 475 females (age 0-20 years) the anterior nasal spine-nasion (ANS-N) and ANS-posterior nasal spine (ANS-PNS) distance were measured and related to age and gender. The development of both dimensions is best described by negative exponential functions. ANS-PNS distance to the age of 5 and the ANS-N distance to the age of 2, develop linearly without gender difference. After this, deceleration, statistically more significant in females (P < 0.01, ANCOVA non-linear regression analysis) occurs for both parameters. Although a study of this type does not have maximal sensitivity, no significant calendar-age-related 'growth spurts' were detected.

Adolescent↗
PubMed1996

Porcine 80-kDa protein reveals intrinsic 17 beta-hydroxysteroid dehydrogenase, fatty acyl-CoA-hydratase/dehydrogenase, and sterol transfer activities.

Four types of 17beta-hydroxysteroid dehydrogenases have been identified so far. The porcine peroxisomal 17beta-hydroxysteroid dehydrogenase type IV catalyzes the oxidation of estradiol with high preference over the reduction of estrone. A 2.9-kilobase mRNA codes for an 80-kDa (737 amino acids) protein featuring domains which are not present in the other 17beta-hydroxysteroid dehydrogenases. The 80-kDa protein is N terminally cleaved to a 32-kDa fragment with 17beta-hydroxysteroid dehydrogenase activity. Here we show for the first time that both the 80-kDa and the N-terminal 32 kDa (amino acids 1-323) peptides are able to perform the dehydrogenase reaction not only with steroids at the C17 position but also with 3-hydroxyacyl-CoA. The central part of the 80-kDa protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-CoA hydratase reaction with high efficiency. The C-terminal part of the 80-kDa protein (amino acids 597-737) is similar to sterol carrier protein 2 and facilitates the transfer of 7-dehydrocholesterol and phosphatidylcholine between membranes in vitro. The unique multidomain structure of the 80-kDa protein allows for the catalysis of several reactions so far thought to be performed by complexes of different enzymes.

17-Hydroxysteroid Dehydrogenases↗
PubMed1995

Intrinsic sterol- and phosphatidylcholine transfer activities of 17 beta-hydroxysteroid dehydrogenase type IV.

Previous studies have shown that the 80 kDa 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) type IV comprises distinct domains, including an N-terminal region related to the short chain alcohol dehydrogenase multigene family and a C-terminal part related to the lipid transfer protein sterol carrier protein 2 (SCP2). In this study, we have investigated whether the SCP2-related part of the 80 kDa protein leads to an intrinsic sterol and phospholipid transfer activity, as shown earlier for the 60 kDa SCP2-related peroxisomal 3-ketoacyl CoA thiolase with intrinsic sterol and phospholipid transfer activity called sterol carrier protein x (SCPx). Our results indicate that a fraction rich in the 80 kDa form of 17 beta-HSD type IV exhibits high transfer activities for 7-dehydrocholesterol and phosphatidylcholine. In addition, a purified recombinant peptide derived from the SCP2-related domain of the 17 beta-HSD type IV has about 30% of the transfer activities for 7-dehydrocholesterol and phosphatidylcholine seen with purified recombinant human SCP2. We conclude that the 80 kDa type IV 17 beta-HSD represents a potentially multifunctional protein with intrinsic in vitro sterol and phospholipid transfer activity in addition to its enzymatic activity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

Sterol carrier protein X is peroxisomal 3-oxoacyl coenzyme A thiolase with intrinsic sterol carrier and lipid transfer activity.

Sterol carrier protein 2 (SCP2; also called nonspecific lipid transfer protein) is a small basic sterol carrier and lipid transfer protein assumed to participate in the intracellular transport of sterols and certain other lipids. Upon cloning and sequencing SCP2-encoding cDNAs, we and others found cDNAs containing unexpected in-frame 5'-extensions of up to 1,250 nucleotides upstream of the initiator ATG of the cDNA encoding pre-SCP2. The corresponding transcripts are primarily expressed in the liver and are predicted to encode a previously undescribed fusion protein containing a 143-amino acid C-terminal domain completely identical to pre-SCP2 and a 404-amino acid N-terminal domain with unknown biochemical activity or function (named sterol carrier protein x, SCPx). Here, we show that purified recombinant SCPx cleaves 3-oxoacyl(n)-CoA to yield acetyl-CoA and acyl(n-2)-CoA. Like SCP2, recombinant SCPx also stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol from small unilamellar vesicles to acceptor membranes in vitro. Furthermore, SCPx epitopes are primarily detected within peroxisomes. These findings suggest that SCPx is a previously undescribed peroxisomal 3-ketoacyl-CoA thiolase (EC 2.3.1.16) with intrinsic sterol carrier and lipid transfer activity (suggested name: SCP2/3-oxoacyl-CoA thiolase).

Acetyl-CoA C-Acetyltransferase↗