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Biomedical subjects

T Friedrich

Publications and source records attributed to T Friedrich.

At least 37 records · Page 2Linked to original sources
PubMed2001

Histopathology in rabbit Achilles tendon after operative tenolysis (longitudinal fiber incisions).

The surgical treatment (tenolysis) of chronic Achilles tendinopathy is often successful. However, little is known about the postoperative intratendinous changes after this procedure. The study group consisted of 21 rabbits. Operative tenolysis was done in each case on one Achilles tendon (AT). The ATs of both legs were studied histologically and immunohistochemically using antibodies against collagen types I and III 2, 4 and 6 weeks postoperatively. Nine rabbits without operation served as controls. A significant uniform hypervascularization was noted in the entire operated tendon postoperatively, and this concurred with the contralateral nonoperated AT, but neither side showed changes in collagen fiber structure as judged by immunohistochemistry. We conclude that the tenolysis procedure triggers neoangiogenesis at the AT followed by increased blood flow and improved nutrition in the same. These changes could, at least partly, explain the often seen clinical success in surgically treated tendinopathy.

Achilles Tendon↗
PubMed2001

Soft tissue infection caused by Kingella kingae in a child.

During the last years an increasing number of reports concerning Kingella kingae infections in children has been published. Most cases were osteoarticular infections. The authors report the clinical and laboratory findings from a 3-year-old child with a presternal soft tissue infection due to K kingae. After surgical excochleation and antibiotic treatment there was an uneventful recovery. J Pediatr Surg 36:946-947.

Child, Preschool↗
PubMed2001

A 23-year experience with malignant renal tumors in infancy and childhood.

A retrospective analysis of 77 children treated between 1974 and 1996 was undertaken to evaluate morbidity and the evolution of therapy. A Wilms' tumor (WT) was present in 73 children. 74% of patients (pats.) with WT survived (54 of 73 pats.). Histological specimens of 67 patients were re-evaluated, including 4 children with non-WT histology. Among patients with Wilms' tumors (WT), nephroblastoma (NB) of intermediate risk predominated (73%; 46 of 63 pats.). Low-risk tumors occurred in 5 of 63 children (8%; mesoblastic nephroma 3, cystic partially diff. NB 1, completely necrotic NB 1). High-risk WT were diagnosed in 12 of 63 patients (19%) (NB with anaplasia 10, clear cell sarcoma 1, malignant rhabdoid tumor 1). Nephrogenic rests were present in 14 cases. We observed 3 children of school age with renal carcinoma and one patient with an intrarenal neuroblastoma. WT histology was the most important factor determining prognosis (p = 0.018). The risk for relapses was 2.6-fold higher in patients with high-risk WT compared to the standard risk group. Stages were re-evaluated according to SIOP 93-01. Comparing relapse-free survival of stages I, II and III, respectively, there was a reduced survival rate for stage III (p=0.019). According to the SIOP/GPOH protocol in 1989, the regimen was switched from primary surgery to preoperative chemotherapy without biopsy in 1989 (11 pats.). Compared to earlier years, survival improved (n.s.). In 3 patients preoperative diagnosis by means of imaging failed. During preoperative chemotherapy a venous occlusive disease of the liver occurred in 2 patients. Preoperative chemotherapy led to an impressive tumor shrinkage in the majority of patients. 2 patients of the preoperative group died (focal anaplastic NB). Long-term morbidity was analysed in 49 patients and included radiation-induced scoliosis (35), chest-wall deformity (3), congestive cardiomyopathy after relapse (1) and arterial hypertension (2). Over the years there was a trend to reduce frequency and dose of irradiation. Prognosis of WT is excellent but unfavorable histology (high risk) predicts a poor prognosis. In our experience, reduction of tumor volume due to preoperative chemotherapy facilitates tumor removal by surgery and may prevent tumor spillage and the deleterious effects of radiation in young children. Surgery without delay is necessary if the diagnosis is unclear or the tumor fails to respond to preoperative chemotherapy.

Antineoplastic Agents↗
PubMed2001

[Myxoid uterine leiomyoma with focal lymphangioma-like pattern].

Myxoid leiomyomas of the uterus are uncommon. They are characterised by a myxoid stroma, no mitotic activity and a myogenic phenotype. We present a case with focal lymphangioma-like pattern. The solid compartiment showed positive immunoreactivity with muscular markers and but no CD 34-immunostaining. Contrary, the endothelial-like cells of the cystic part were positive with antibodies against CD 34, CD 31 and factor VIII, indicating vascular differentiation. The lack of infiltrative growth patterns excluded myxoid leiomyosarcoma as the major differenzial diagnosis.

Adult↗
PubMed2001

Non-specific activation of the epithelial sodium channel by the CFTR chloride channel.

The genetic disease cystic fibrosis is caused by mutation of the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Controversial studies reported regulation of the epithelial sodium channel (ENaC) by CFTR. We found that uptake of (22)Na(+) through ENaC is modulated by activation of CFTR in oocytes, coexpressing CFTR and ENaC, depending on extracellular chloride concentration. Furthermore we found that the effect of CFTR activation could be mimicked by other chloride channels. Voltage- and patch-clamp measurements, however, showed neither stimulation nor inhibition of ENaC-mediated conductance by activated CFTR. We conclude that the observed modulation of (22)Na(+) uptake by activated CFTR is due to the effect of CFTR-mediated chloride conductance on the membrane potential. These findings argue against the notion of a specific influence of CFTR on ENaC and emphasize the chloride channel function of CFTR.

Animals↗
PubMed2000

An internalization signal in ClC-5, an endosomal Cl-channel mutated in dent's disease.

The ClC-5 chloride channel resides mainly in vesicles of the endocytotic pathway and contributes to their acidification. Its disruption in mice entails a broad defect in renal endocytosis and causes secondary changes in calciotropic hormone levels. Inactivating mutations in Dent's disease lead to proteinuria and kidney stones. Possibly by recycling, a small fraction of ClC-5 also reaches the plasma membrane. Here we identify a carboxyl-terminal internalization motif in ClC-5. It resembles the PY motif, which is crucial for the endocytosis and degradation of epithelial Na(+) channels. Mutating this motif increases surface expression and currents about 2-fold. This is probably because of interactions with WW domains, because dominant negative mutants of the ubiquitin-protein ligase WWP2 increased surface expression and currents of ClC-5 only when its PY motif was intact. Stimulating endocytosis by expressing rab5 or its GTPase-deficient Q79L mutant decreased WT ClC-5 currents but did not affect channels with mutated motifs. Similarly, decreasing endocytosis by expressing the inactive S34N mutant of rab5 increased ClC-5 currents only if its PY-like motif was intact. Thus, the endocytosis of ClC-5, which itself is crucial for the endocytosis of other proteins, depends on the interaction of a carboxyl-terminal internalization signal with ubiquitin-protein ligases containing WW domains.

Amino Acid Sequence↗
PubMed2000

FT-IR spectroscopic characterization of NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli: oxidation of FeS cluster N2 is coupled with the protonation of an aspartate or glutamate side chain.

The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the first energy-transducing complex of many respiratory chains. It couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. One FMN and up to nine iron-sulfur (FeS) clusters participate in the redox reaction. So far, complex I has been described mainly by means of EPR- and UV-vis spectroscopy. Here, we report for the first time an infrared spectroscopic characterization of complex I. Electrochemically induced FT-IR difference spectra of complex I from Escherichia coli and of the NADH dehydrogenase fragment of this complex were obtained for critical potential steps. The spectral contributions of the FMN in both preparations were derived from a comparison using model compounds and turned out to be unexpectedly small. Furthermore, the FT-IR difference spectra reveal that the redox transitions of the FMN and of the FeS clusters induce strong reorganizations of the polypeptide backbone. Additional signals in the spectra of complex I reflect contributions induced by the redox transition of the high-potential FeS cluster N2 which is not present in the NADH dehydrogenase fragment. Part of these signals are attributed to the reorganization of protonated/deprotonated Asp or Glu side chains. On the basis of these data we discuss the role of N2 for proton translocation of complex I.

Alkanesulfonic Acids↗
PubMed2000

Characterization of two novel redox groups in the respiratory NADH:ubiquinone oxidoreductase (complex I).

The proton-pumping NADH:ubiquinone oxidoreductase is the first of the respiratory chain complexes in many bacteria and mitochondria of most eukaryotes. The bacterial complex consists of 14 different subunits. Seven peripheral subunits bear all known redox groups of complex I, namely one FMN and five EPR-detectable iron-sulfur (FeS) clusters. The remaining seven subunits are hydrophobic proteins predicted to fold into 54 alpha-helices across the membrane. Little is known about their function, but they are most likely involved in proton translocation. The mitochondrial complex contains in addition to the homologues of these 14 subunits at least 29 additional proteins that do not directly participate in electron transfer and proton translocation. A novel redox group has been detected in the Neurospora crassa complex, in an amphipathic fragment of the Escherichia coli complex I and in a related hydrogenase and ferredoxin by means of UV/Vis spectroscopy. This group is made up by the two tetranuclear FeS clusters located on NuoI (the bovine TYKY) which have not been detected by EPR spectroscopy yet. Furthermore, we present evidence for the existence of a novel redox group located in the membrane arm of the complex. Partly reduced complex I equilibrated to a redox potential of -150 mV gives a UV/Vis redox difference spectrum that cannot be attributed to the known cofactors. Electrochemical titration of this absorption reveals a midpoint potential of -80 mV. This group is believed to transfer electrons from the high potential FeS cluster to ubiquinone.

Electrochemistry↗
PubMed2000

The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases.

The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the first of the respiratory complexes providing the proton motive force which is essential for energy consuming processes like the synthesis of ATP. Homologues of this complex exist in bacteria, archaea, in mitochondria of eukaryotes and in chloroplasts of plants. The bacterial and mitochondrial complexes function as NADH dehydrogenase, while the archaeal complex works as F420H2 dehydrogenase. The electron donor of the cyanobacterial and plastidal complex is not yet known. Despite the different electron input sites, 11 polypeptides constitute the structural framework for proton translocation and quinone binding in the complex of all three domains of life. Six of them are also present in a family of membrane-bound multisubunit [NiFe] hydrogenases. It is discussed that they build a module for electron transfer coupled to proton translocation.

Archaea↗
PubMed2000

Specificity of DNA binding and methylation by the M.FokI DNA methyltransferase.

The M.FokI adenine-N(6) DNA methyltransferase recognizes the asymmetric DNA sequence GGATG/CATCC. It consists of two domains each containing all motifs characteristic for adenine-N(6) DNA methyltransferases. We have studied the specificity of DNA-methylation by both domains using 27 hemimethylated oligonucleotide substrates containing recognition sites which differ in one or two base pairs from GGATG or CATCC. The N-terminal domain of M.FokI interacts very specifically with GGATG-sequences, because only one of the altered sites is modified. In contrast, the C-terminal domain shows lower specificity. It prefers CATCC-sequences but only two of the 12 star sites (i.e. sites that differ in 1 bp from the recognition site) are not accepted and some star sites are modified with rates reduced only 2-3-fold. In addition, GGATGC- and CGATGC-sites are modified which differ at two positions from CATCC. DNA binding experiments show that the N-terminal domain preferentially binds to hemimethylated GGATG/C(m)ATCC sequences whereas the C-terminal domain binds to DNA with higher affinity but without specificity. Protein-protein interaction assays show that both domains of M.FokI are in contact with each other. However, several DNA-binding experiments demonstrate that DNA-binding of both domains is mutually exclusive in full-length M.FokI and both domains do not functionally influence each other. The implications of these results on the molecular evolution of type IIS restriction/modification systems are discussed.

Base Sequence↗
PubMed2000

Effects of intravenous dofetilide in patients with frequent premature ventricular contractions: a clinical trial.

BACKGROUND: Although suppression of premature ventricular contractions (PVCs) is not a predictor of mortality over the long term, the extent of PVC suppression is an important characteristic of any antiarrhythmic drug. HYPOTHESIS: This study was undertaken to determine whether intravenous (i.v.) dofetilide has the ability to suppress PVCs in patients who have frequent occurrences. METHODS: Subjects were men and women, aged 18 to 75 years, with > 30 PVCs/h on two consecutive 24-h Holter recordings while drug free, and > 50 PVCs/h during a 2-hour telemetric electrocardiogram. The study was randomized, double-blind, and placebo controlled. Subjects received a single-blind, i.v. infusion of placebo and were randomized (3:1) to receive a double-blind second infusion of placebo or an infusion of dofetilide (a 15-min loading infusion of 4 g/kg followed by a 60-min maintenance infusion of 3.5 g/kg, for a total dose of 7.5 g/kg). RESULTS: Dofetilide produced an 82.6% and placebo a 2.9% median reduction in PVCs. Drug responder rate, defined as 80% reduction in PVCs, was 50% in the dofetilide group and 0% in the placebo group. CONCLUSION: Intravenous dofetilide significantly reduced PVCs in patients who had > 30 PVCs/h at baseline, and it produced > or = 80% reduction in PVCs in 50% of all subjects.

Adult↗
PubMed2000

[Recurrent laryngeal nerve paralysis as intubation injury?].

INTRODUCTION: Vocal cord paralysis is a important complication in thyroid gland surgery. A prospective study was conducted ascertain the frequency of laryngeal nerve palsy not caused by surgical trauma. PATIENTS AND METHODS: Two hundred and ten patients were investigated laryngoscopically pre- and postoperatively after short-term intubation in the course of operations far removed from thorax or neck region. We noted the inner diameter of the tube, intubation problems, the qualification of the anaesthesiologist and the positioning of the patient. RESULTS: Preoperatively we found previously unknown unilateral laryngeal nerve palsy in 1.9% of cases. Postoperatively there were pathological findings of vocal cords in 13 patients (6.2%). In 10 patients a direct lesion (oedema, rubor, haematoma, granuloma) was established. Three patients (1.4%) were found to have a movement disorder caused by a neural lesion without morphological findings, leading to restitutio ad integrum in two of three cases after 6 months. CONCLUSION: The frequency of intubation-related recurrent nerve palsy is 1.4% transiently and 0.5% permanently. The reasons are discussed. Preoperative laryngoscopic investigation of vocal cords should be carried out before intubation.

Adolescent↗
PubMed2000

Evaluation of ultracision in lung metastatic surgery.

BACKGROUND: There are very few studies on the histological outcome of lung metastatic surgery using the Ultracision particularly in deeper areas of the lung. METHODS: In a prospective study, we resected 24 lung metastases from 18 patients using the Ultrasonic scalpel (Ethicon Endo-Surgery, Norderstedt, Germany). We analyzed the risk of bleeding and air leakage as well as the histopathological features of the resection area. RESULTS: There was no intraoperative bleeding and, in 72%, no intraoperative air leakage. The resection surface was closed with a suture. In 8 cases, the metastases were located deeply, near the hilus of the lobe which did not necessitate a lobectomy. Histologically, occluded blood vessels as well as occluded small bronchioli under 0.1 cm were observed. There was no evidence of deep tissue destruction. No postoperative complications occurred. CONCLUSIONS: Ultracision in metastatic lung surgery is an appropriate method of treatment with minimum risk of bleeding or air leakage. This procedural approach allows for adequate resection of lung metastases while sparing a generous amount of healthy lung tissue.

Adult↗
PubMed2000

Formate protects stationary-phase Escherichia coli and Salmonella cells from killing by a cationic antimicrobial peptide.

For a sustained infection, enteric bacterial pathogens must evade, resist or tolerate a variety of antimicrobial host defence peptides and proteins. We report here that specific organic acids protect stationary-phase Escherichia coli and Salmonella cells from killing by a potent antimicrobial peptide derived from the human bactericidal/permeability-increasing protein (BPI). BPI-derived peptide P2 rapidly halted oxygen consumption by stationary-phase cells preincubated with glucose, pyruvate or malate and caused a 109-fold drop in cell viability within 90 min of addition. In marked contrast, O2 consumption and viability were not significantly affected in stationary-phase cells preincubated with formate or succinate. Experiments with fdhH, fdoG, fdnG, selC and sdhO mutants indicate that protection by formate and succinate requires their oxidation by the Fdh-N formate dehydrogenase and succinate dehydrogenase respectively. Protection was also dependent on the BipA GTPase but did not require the RpoS sigma factor. We conclude that the primary lesion caused by this cationic peptide is not gross permeabilization of the bacterial cytoplasmic membrane but may involve specific disruption of the respiratory chain. Because P2 shares sequence similarity with a range of other antimicrobial peptides, its cytotoxic mechanism has broader significance. Additionally, protective quantities of formate are secreted by E. coli and Salmonella during growth suggesting that such compounds are important determinants of bacterial survival in the host.

Amino Acid Sequence↗
PubMed2000

[Therapeutic management of postoperatively diagnosed bilateral recurrent laryngeal nerve paralysis].

UNLABELLED: Bilateral vocal cord paralysis is a rare but potentially dangerous postoperative complication in thyroid gland surgery. There is a controversial discussion about therapeutic management of postoperative bilateral vocal cord paralysis. METHODS: We analysed the frequency of bilateral nerve palsy in 985 operations. The disease of thyroid gland, the operative procedure, the exposure of laryngeal nerve, the mobility of vocal cord detected by an otolaryngologist, clinical symptoms and therapy of patients with bilateral paralysis were analysed. All patients were examined immediately postoperatively and 5 days, 14 days, 6 and 12 months after resection. RESULTS: The overall transient bilateral palsy rate was 0.7%, the permanent 0.3%. The palsy rate depended on the disease of thyroid gland. After resection of simple goitre we found a 0.2% transient injury rate (0.1% permanent), after operation of thyroid cancer 2.0% transient (1.0% permanent) and in cases of recurrent goitre 5.9% transient (1.9% permanent) palsies. The immediate postoperative symptoms are also very different. There are patients suffering from stridor and dyspnoea, patients with dysphonia without dyspnoea and those without any symptoms. These different clinical symptoms are due to the different grade of laryngeal nerve damage and the resulting position of vocal cords. The bilateral paralysis was completely temporary in 4 cases. 12 months later 4 patients suffered from dysphonia. Only in 3 patients with thyroid cancer and a preoperative unilateral vocal cord paralysis tracheostomy was necessary after operation. The vocal cord mobility did not recover in these 3 cases after 12 months and the patients are not decannulated. DISCUSSION: Bilateral paralysis is only relevant in thyroid cancer and recurrent goitre. The symptoms varies and no patient should leave the hospital without examination of the vocal cords by an otolaryngologist. Because vocal cord paralysis is temporary in most cases an emergency tracheostomy is seldom indicated.

Adult↗