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Biomedical subjects

D Schäfer

Publications and source records attributed to D Schäfer.

At least 19 recordsLinked to original sources
PubMed1997

Functional and morphological outcome of knee joint transplantation in dogs depends on control of rejection.

BACKGROUND: The reconstruction of massive osteochondral defects extending to weight-bearing joints remains a surgical challenge. Total knee joint transplantation has been performed experimentally, but these studies lacked prospective evaluation of functional outcome, graft vascularization, and graft viability. METHODS: Replantation and transplantation of vascularized knee joints was performed in dogs (n=4 per group), comparing functional and morphological results during a 6-month follow-up. RESULTS: All replant recipients and three transplant recipients survived the 6-month follow-up period. At this time, duplex sonography and angiography revealed patent anastomoses in all animals. Increases in volumetric flow rates and vascular collateralization were observed in allografts, as compared with replanted joints (100+/-16 ml/min vs. 31+/-15 ml/min at 6 months after transplantation). Bone fusion at the graft-host interface was verified by fluorography in all animals at 3 months after transplantation. Six months after transplantation, microradiographies and computerized tomographies revealed spongialization of the cortical bone and filling of the medullary space by trabecular bone in transplanted joints. Such alterations were not detectable in replanted joints. Chondrocyte viability exceeded 80% in all but one transplanted joint. Lymphocyte infiltration of synovia and arterial walls was detected in all transplanted joints, suggesting the presence of chronic rejection. Weight-bearing capacity recovered in all replanted animals (weight-bearing index before transplantation: 0.499+/-0.080; 6 months after transplantation: 0.38+/-0.16) but only in two of four transplanted animals (weight-bearing index 6 months after transplantation: 0.37, 0.28, and 0.00). CONCLUSIONS: These data demonstrate the potential of joint grafting and the critical dependence of allotransplantation on the control of rejection.

Angiography↗
PubMed1997

Redox-regulated expression of glycolytic enzymes in resting and proliferating rat thymocytes.

Resting rat thymocytes partially degrade glucose aerobically to CO2 and H2O and produce reactive peroxide anions. In contrast proliferating cells, due to enhanced induction of glycolytic enzymes, degrade glucose almost completely to lactate thus minimizing the production of reactive oxygen species. In this paper we show that under conditions of oxidative stress the induction of the glycolytic enzymes in cultured rat thymocytes is markedly reduced. Furthermore, transfection assays with a rat hepatoma cell line and Drosophila Schneider cells revealed that reactive oxygen intermediates dramatically decrease the transcriptional activities of the Sp1-dependent aldolase A and pyruvate kinase M2 promoters leading to reduced reporter gene expression. These results indicate that cellular redox changes can regulate gene expression by reversible oxidative inactivation of Sp1 binding.

Animals↗
PubMed1996

The aldolase A promoter in proliferating rat thymocytes is regulated by a cluster of SP1 sites and a distal modulator.

In mitogen-stimulated rat thymocytes the activities and mRNA levels of aldolase A increase remarkably during proliferation pointing to a transcriptional regulation of this enzyme. By DNAse I footprinting and mobility shift competition assays five binding sites for the activating transcription factor Sp1 and one site for an AP-1 like nuclear factor could be identified in the core activating region of the proximal aldolase AH1 promoter downstream of -400. Transfection data and differences found in nuclear protein binding of resting and proliferating cells to DNA sites suggest that Sp1 is an integral part of the mechanism by which the AH1 promoter achieves high level transcription during proliferation. Moreover we demonstrate that an element between positions -1066/-731 significantly attenuates the AH1 promoter driven transcription as well as transcription regulated by the heterologous SV40 promoter. From this effect a functional linkage between the distal muscle-restricted M1 promoter and the active AH1 promoter can be suggested.

Animals↗
PubMed1996

Differences in DNA-binding efficiency of Sp1 to aldolase and pyruvate kinase promoter correlate with altered redox states in resting and proliferating rat thymocytes.

Thymocytes induce their glycolytic enzymes as they undergo transition from the resting to the proliferating state. Corresponding increases in mRNA levels point to a transcriptional regulation. Electrophoretic mobility shift assays revealed that the DNA-binding efficiency of Sp1 is increased when nuclear extracts from proliferating compared to resting rat thymocytes were used. Here we demonstrate that hydrogen peroxide, added to nuclear extract from proliferating cells, decreases the Sp1 DNA-binding activity, whereas in nuclear extracts from resting cells dithioerythritol fully restores DNA-binding efficiency. Moreover we show that in contrast to resting thymocytes, production of reactive peroxide anions upon priming with phorbol 12-myristate 13-acetate is nearly abolished in the proliferating cells. From these results we propose that reactive oxygen intermediates affect the interaction of the Sp1 transcription factor with its consensus sequence and subsequently regulate glycolytic gene expression.

Animals↗
PubMed1996

Repression of c-Jun-induced mouse major histocompatibility class I promoter (H-2Kb) activity by the Adenovirus type 12-unique 52R E1A protein.

Down-regulation of major histocompatibility (MHC) class I gene expression by protein products of the early region 1A (E1A), which might allow transformed cells to escape the host immune system, is discussed as one cause for the oncogenicity of Adenovirus (Ad) subtype 12-transformed cells. The MHC class I promoter is activated through several cellular-transcription factors among them AP-1, whose target sequences are located in the enhancers A and B, and NF kappa B. In this report we present evidence that the Ad12-unique 52R E1A protein inhibits c-Jun-induced activation of MHC class I gene expression. Repression occurs through both AP-1 recognition sequences with the AP-1 binding site of Enhancer A, which can be bound by c-Jun dimers in vitro, being the main target for c-Jun activation as well as 52R-mediated down-regulation. Furthermore our data revealed that both promoter elements of Enhancer A, the AP-1 and NF kappa B binding sites, are necessary for full promoter activity. As NF kappa B is down-regulated by the 266R protein of Ad12 E1A our results suggest a model in which two Ad12 E1A proteins co-operate in the repression of MHC class I gene expression.

Adenovirus E1A Proteins↗
PubMed1996

Arthroscopic assessment of the chronic unstable ankle joint.

The purpose of this study was to evaluate prospectively the findings during arthroscopy in patients with chronic instability of the ankle joint. One hundred and ten consecutive patients who had suffered at least two ankle sprains and were symptomatic for at least 6 months were included in this study. A complete rupture of the anterior talofibular ligament was found in 64%, of the calcaneofibular ligament in 41% and of the deltoid ligament in 6%. Cartilage lesions of the talus were seen in 54% of the joints, more of them medial (56%) than lateral (15%) or ventral (20%). Other frequently observed findings were synovialitis (38%), rupture of the syndesmosis (7%), and ventral scarring (6%). While cartilage damage was found independently of the lateral ligament injuries, all complete tears of the deltoid ligament were associated with cartilage injury of the talus. Medial instability was assessed in five ankles clinically and found arthroscopically in 23 ankle joints. Our arthroscopic findings show that chronic instability of the ankle joint is associated with various pathological conditions of ligaments, capsule and cartilage. It can therefore give essential information about the status of the chronic unstable joint with regard to the choice of operative or conservative treatment.

Adolescent↗
PubMed1996

Local therapy of rectal tumors.

PURPOSE: The aim of the study is to outline the rising importance of local treatment of rectal tumors and a changing strategy in therapy of early rectal cancer. METHODS: As the surgical procedure, transanal endoscopic microsurgery was used. Indications for the local procedure were pT1 low-risk tumors and tumors of higher stages in patients with severe risk factors and of those who refused the operation according to oncologic guidelines. RESULTS: A total of 236 rectal adenomas and 98 carcinomas were locally excised using the transanal endoscopic microsurgery technique. Mortality rate was 0.3 percent, and rate of complications requiring surgical reintervention was 5.5 percent in adenomas and 8 percent in carcinomas. Final histology of removed carcinomas revealed 56 pT1, 27 pT2, and 15 pT3 stages. After an average follow-up time of 24 months, two recurrences were observed in the group of patients with pT1 low-risk carcinomas who only underwent local therapy. In both cases, a second intervention for cure was undertaken but for tumors in a late stage. CONCLUSIONS: In selected cases, local therapy of rectal carcinoma avoids high morbidity and mortality of the classical operation. Quality of life will be improved, especially if an artificial anus can be avoided. In case of recurrence, the chance of a secondary procedure for cure is not to be underestimated.

Adenoma↗
PubMed1996

[Diagnostic imaging of ankle joint instability].

The value of the available diagnostic methods for the evaluation of the unstable ankle joint still is under discussion. This is a result of the increasing knowledge of basic biomechanics. It has been demonstrated that ankle instability is not restricted to two planes, but can be multidirectional or rotatory. There is also a trend to conservative treatment of acute unstable ankle joints. This paper presents the actual diagnostic tools for evaluation of the unstable ankle joint with regard to their efficiency. Stress views, sonography, MRI and arthrography will be discussed.

Ankle Injuries↗
PubMed1996

[Arthroscopic findings in the unstable upper ankle joint].

The purpose of this prospective study was the assessment of the chronic unstable ankle joint. With regard to cartilage and ligament lesions this was done arthroscopically. 99 consecutive arthroscopies were performed in patients with symptomatic chronic ankle instability. There were 67 complete ruptures of the anterior talofibular ligament and 45 complete ruptures of the calcaneofibular ligament. A complete rupture of the deltoid ligament was found in 6 cases, always combined with lesions of the lateral ligaments. Cartilage damage of the talus was noted in 51 cases and of the tibial pilon in 12 cases. While all complete lesions of the deltoid ligament were associated with talar cartilage damage, this was different for lateral ligament lesions. 11/22 ruptures of the talofibular ligament were associated with cartilage damage of the talus and 11/22 ruptures presented with an intact talar cartilage. Combined ruptures of the talofibular and the calcaneofibular ligament were associated with talar cartilage damage in 21 cases and presented with intact cartilage in 24 cases. This study demonstrated a near equal distribution of intact and damaged articular cartilage in the presence of lateral ligament lesions indicating that the status of the ligaments allows no conclusion with regard to the cartilage. Arthroscopy therefore can give essential information about the status of the unstable ankle joint concerning operative or conservative treatment.

Adolescent↗
PubMed1996

Distribution of marker-Y chromosome containing cells in different tissues of a Turner mosaic patient with mixed gonadal dysgenesis.

We here describe a 12-year-old girl with numerous Turner stigmata and virilized external genitalia. Chromosome analysis of PHA stimulated lymphocytes using different banding techniques revealed a 45,X/46,X,+mar Turner mosaicism with the prominent marker present in about 90% of the blood cells. A PCR-based analysis using a set of 9 STS from different regions of the human Y chromosome indicated the presence of Y chromosomal material with a deletion breakpoint most likely within deletion interval 6. Because of the risk of gonadoblastoma for Turner patients carrying Y chromosomal material, and clinical indications of functional testicular tissue, a gonadectomy in addition to surgical correction of the external genitalia was performed. The histological analysis of the gonads showed a mixture of testicular tissue and ovarian stroma, thus indicating mixed gonadal dysgenesis. Fibroblasts from skin and different parts of the gonads were cytogenetically analyzed and showed a variable distribution of the Y-derived marker between 4% in skin, 11-31% in gonadal tissue and up to 90% in peripheral lymphocytes.

Child↗
PubMed1996

Effect of prostaglandin E2 on eicosanoid release by human bronchial biopsy specimens from normal and inflamed mucosa.

BACKGROUND: Eicosanoids such as prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and peptidoleukotrienes (pLT) are known to be biologically highly active lipid mediators, especially in human lung epithelium. PGE2 is thought to have mostly bronchoprotective effects, whereas pLT and TXA2 are bronchoconstrictive. This study was undertaken to assess the release and interaction of eicosanoids in human bronchial biopsy specimens of normal and inflamed mucosa. METHODS: Bronchial biopsy specimens were obtained from 16 patients, seven controls without signs of inflammation and nine patients with severe inflammatory processes in the epithelium. The release of pLT, TXA2 (measured as TXB2), and PGE2 was investigated using a "functional in vitro test" and the addition of several stimuli. RESULTS: Specimens incubated with arachidonic acid released higher amounts of pLT, TXB2, and PGE2 than unstimulated specimens. Preincubation with PGE2 revealed significant inhibition of arachidonic acid-induced release of pLT and TXB2 (> 50%). The inhibitory effect was higher in normal than in inflamed epithelium. CONCLUSIONS: Exogenous PGE2 has inhibitory effects on the release of pLT and TXB2 in human bronchial biopsy specimens. This finding could explain the bronchoprotective effect of inhaled PGE2 in normal subjects and asthmatic subjects as direct eicosanoid interactions. It also supports the concept of PGE2 as a bronchoprotective endogenous substance. The complex effects of PGE2 as a modulating mediator in inflammation may be worth investigating.

Adult↗
PubMed1996

Eicosanoids from biopsy of normal and polypous nasal mucosa.

In order to clarify the influence of inflammatory mediators of the arachidonic acid cascade in the mechanism of nasal polyp growth, peptido-leukotriene (pLT), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) synthesis was investigated. In addition to several stimuli, functionally intact human biopsy specimens of polypous and normal tissue were incubated. Especially remarkable was the significantly increased release of pLT by polypous tissue upon arachidonic acid stimulation, in contrast to only slightly elevated PGE2 release compared to normal tissue. Basic release of pLT and PGE2 was similar for polypous and normal tissue. Examining TXB2 release, no significant difference was observed with regard to the origin of tissues. These data support an altered pattern of the lipoxygenase and cyclo-oxygenase pathways when tissue becomes irritated and suggest their involvement in the aetiopathogenesis of nasal polyps.

Biopsy↗
PubMed1996

[Sleep and breathing disorders in patients with brain stem lesions].

Most information about the structures within the brain stem that modulate respiration and sleep are gathered from animal experiments. Therefore we examined 10 patients several weeks after an infarction of the brain stem by means of polysomnography and tested the chemosensitive drives of respiration. None of these patients complained about symptoms of sleep disordered breathing. In each case polysomnographic measurements and ventilatory response curves revealed pathologic findings. The respiratory response to CO2 was diminished or completely abolished in each patient. In some cases hypoventilation or disturbances of the respiratory rhythmicity could be seen. In several cases missing REM sleep, sleep fragmentation or the reduction of slow wave sleep were observed. The study indicates that on the base of results from animal research the comparison of morphological and pathophysiological data is helpful to gain a better understanding on the coupling of the respiratory system with sleep at the brain stem level as well as on the pathomechanism of sleep related breathing disorder.

Adult↗
PubMed1995

[Tendon cysts].

We report two cases of intratendinous cysts of the Achilles tendon, which occurred after treatment of tendon ruptures. Intratendinous cysts develop in the Achilles tendon and patellar ligament. The clinical diagnosis should be confirmed by sonography or magnetic resonance imaging. Surgical excision of the necrosis is the therapy of choice.

Achilles Tendon↗