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T Friedrich

Publications and source records attributed to T Friedrich.

At least 73 records · Page 4Linked to original sources

Search for novel redox groups in mitochondrial NADH:ubiquinone oxidoreductase (complex I) by diode array UV/VIS spectroscopy.

The proton-translocating NADH:ubiquinone oxidoreductase of mitochondria (complex I) is a large L-shaped multisubunit complex. The peripheral matrix arm contains one FMN and a number of iron-sulfur (FeS) clusters and is involved in NADH oxidation and electron transfer to the membrane intrinsic arm. There, following a yet unknown mechanism, the redox-driven proton translocation and the ubiquinone reduction take place. Redox groups that would be able to link electron transfer with proton translocation have not been found so far in the membrane arm. We searched for such groups in complex I isolated from Neurospora crassa. Under anaerobic conditions, the preparation was analyzed in different redox states by means of UV/VIS and EPR spectroscopy. Absorption bands in the UV/VIS redox difference spectra were found which cannot be attributed to the FMN or the EPR detectable FeS clusters. The existence of two novel groups is postulated and their possible locations in the electron pathway and their roles in proton translocation are discussed.

Electron Spin Resonance Spectroscopy↗

[Inflammatory pseudotumor of the lung in hilus lymph node histoplasmosis].

The article deals with the case of an inflammatory pseudotumour of the lung in conjunction with histoplasmosis of the hilar lymph glands in a 35-year-old immunocompetent woman in a non-endemic area. She had been suffering from headaches and painful swelling of the lower legs, reddening and hyperthermia for 1.5 years. In addition to the above-mentioned symptoms she also complained of a typical flush syndrome which had begun a year later. The main paraclinical finding was a round mass in the right lung in chest radiography. After considering various differential diagnostic possibilities, thoracotomy and resection of the upper lobe of the right lung were performed. The histological diagnosis of the material removed was that of an inflammatory pseudotumour of the lung, combined with histoplasmosis of the hilar lymph glands. Following a postoperative period without complications, antimycotic treatment was performed. The discussion includes whether the simultaneous occurrence of these two diseases is coincidental or whether there is a causal relation between the two. The authors also discuss various treatments with reference to the relevant literature.

Adult↗

Papillomavirus-induced genital warts in a girl--management by surgery and immunomodulating therapy.

A 4-year-old girl with condylomata acuminata of the vulva and papular warts of the surrounding skin is presented. The lesions were removed by surgery. Histologic investigation showed koilocytosis of the squamous epithelium and in-situ hybridization revealed human papilloma virus type 6 infection. There were no signs of sexual abuse or sexual transmission of the virus. After ablation, an interferon-containing ointment was applied. In order to prevent recurrence, a low-molecular-weight immunomodulating leucocyte fraction was given for more than 1 year, during which time no relapse was observed.

Adjuvants, Immunologic↗

Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure.

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.

Adult↗

[Idiopathic pulmonary ossification].

OBJECTIVE: Linear and round shadows are very often revealed on chest radiographs. A rare entity most commonly appearing as branching linear shadows of calcific density involving a limited area of the lung is the so-called disseminated pulmonary ossification (DPO). Only 141 cases have been reported worldwide up to now since the first description. MATERIAL AND METHODS: A study on 490 autopsies was performed to find out the frequency of DPO. In case of DPO we compared the structures with the chest radiographs and CT of the patients. Further, we evaluate clinical communities of patients with DPO. RESULTS: From a total of 490 lungs eight were identified with DPO (1.6%). The mean age of patients with DPO was 80.2 years, the male/female ratio seven to one (mean age of all patients: 64.6 years, male/female ratio one to one). All cases were associated with hypertension followed by extreme arteriosclerosis. In 5 cases there was a proven extrapulmonary carcinoma and a renal insufficiency. In 4 cases we found diabetes mellitus. At postmortem radiographs and CT, a collection of small rounded calcific nodules and further linear shadows arranged in a branching or net-like configuration was identified. This was compared with the chest radiographs of the patients. There were no dysfunctions of lungs due to DPO. CONCLUSIONS: In chest radiographs of elderly men the differential diagnosis "DPO" should be given more importance.

Aged↗

[Incidence of damage to the recurrent laryngeal nerve in surgical therapy of various thyroid gland diseases--a retrospective study].

UNLABELLED: We investigated the incidence of the recurrent laryngeal nerve (RLN) palsy after thyroid gland surgery in 725 cases. The incidence was correlated to the different diseases of the thyroid gland, to the operative procedure (subtotal resection, lobectomy, thyroidectomy), to the intraoperative exploration of the nerve and to the surgeons' state of training. RLN palsy was found in 7.6 per cent (4.8 per cent nerve at risk) five days after surgery. A permanent RLN damage was defined as a persisting paralysis of the vocal cord six months after surgery. Permanent nerve damage occurred in 2.1 per cent for euthyroid nodular goitre, for recurrent goitre in 11.7 per cent and for thyroid carcinoma in 10.1 per cent. There was a statistically significant difference between the number of RLN pareses occurring after nerve exposure with 4.2 per cent and that occurring after non-exposure with 1.1 per cent for subtotal lobectomy. 67.7 per cent of these pareses at day five were transient. The RLN palsy rate for Senior House Officers was 6.7 per cent but there where none for registrars and consultants. CONCLUSIONS: The RLN damage five days after thyroid gland surgery is mainly caused by the great number of recurrent goitre and thyroid cancer (16.1 per cent), the rate of procedures performed by younger surgeons and the near total resection of euthyroid goitre. The exposure of RLN is important for the training to manage thyroid gland surgery.

Cross-Sectional Studies↗

[Indications and surgical therapy of thyroid gland diseases--analysis of 725 operated patients].

Diseases of the thyroid gland are an important part of elective surgical procedures. The adequate surgical therapy is at present standardized and requires a permanent qualitative control to reduce avoidable complications. The relation between men and women in our patients (n = 725) was 1 to 5. The mean age was 51.2 years. 10% (n = 79) of the patients were hyperthyroid. 646 patients had benign disease; and 79 patients were found to have malignancy of the thyroid gland. The most common indication for an operation was bilateral multinodular goitre (n = 325) in combination with a cold nodule (n = 123), in 79 patients latent hyperthyroidism or Morbus Basedow (n = 22). Struma nodosa with retrosternal extension (n = 49), recurrence of goitre (n = 34), thyroiditis (n = 12) and dystopic goitre (n = 2) were rare in these patients. Patients with malignancy of the thyroid gland were always treated by thyroidectomy or completed thyroidectomy with lymphnode dissection. In the cases of benign disease the surgical methods were variable, although the bilateral subtotal resection (n = 413) predominated. While doing so the radical resection of parenchyma with a persistent functioning remnant of goitre of 5 cm3 was favoured. The resulting postoperative complications are discussed. An endocrinological appropriate follow-up of the patients is necessary.

Female↗

[Primary malignant melanoma of the esophagus].

Primary malignant melanoma of the esophagus is extremely rare. Less than 200 cases have been published worldwide up to now. We report a case of a 65-years old male suffering from dysphagia for four months. The endoscopy showed a polypoidal tumor of black colour in the distal part of the esophagus. The histological diagnosis of the initial biopsy specimen was melanoma. Partial esophagectomy and lymph node sampling were performed. The resected specimen showed a polypoid tumor with black pigmentation of 8 x 5 x 3 centimeter. Histopathology revealed a primary malignant melanoma of the esophagus stage pT2 pN1 M0 and grading three. The patient died 8 months after resection from general metastatic disease. Age, sex, symptoms, duration of symptoms and time of survival are similar as described in former cases.

Aged↗

[Genesis and importance so-called inflammatory infiltration of the placenta. II. Immunohistochemical findings].

We investigated the morphologically distinct forms of inflammatory infiltration of the placenta both histologically and immunohistologically (n = 24). Our material included cases of membraneous inflammation (chorioamnionitis), inflammatory infiltration of arteries in the chorionic membrane, basal and intervillous placentitis. NACE staining was used to detect myeloid cells and monoclonal antibodies (LCA, CD3, CD8, CD20, CD68). To detect lymphoid and macrophageal cells we also measured the proliferation activity with MiB 1. In cases of chorioamnionitis and subchorial demarcation and in the arteries of the chorionic membranes the main inflammatory cell is the myeloid cell (most often the mature neutrophil granulocyte). T-lymphocytes were only occasionally found. In cases of intervillous placentitis, on the other hand, lymphocytic infiltration predominates, consisting of T-lymphocytes which are mostly CD8 negative, and some monocytes and macrophages. Basal inflammation in the demarcation zone was characterized by T-lymphocytes. We interpret this as indicating basal demarcation. According to our histological and immunohistological observations, "asphyxial infiltrates" are abortive forms of a placental (bacteriological) inflammation, possibly infective in origin. We do not consider asphyxial infiltration to be a separate entity with its own causal pathogenesis.

Antigens, CD↗

A reevaluation of substrate specificity of the rat cation transporter rOCT1.

The substrate specificity of the previously cloned rat cation transporter rOCT1, which is expressed in kidney, liver, and small intestine, was reevaluated. rOCT1 is the first member of a new protein family comprising electrogenic and polyspecific cation transporters that transport hydrophilic cations like tetraethylammonium, choline, and monoamine neurotransmitters. Previous electrical measurements suggested that cations like quinine, quinidine, and cyanine 863, which have been classified as type 2 cations in the liver, are also transported by rOCT1, since they may induce inward currents in rOCT1 expressing Xenopus oocytes (Busch, A. E., Quester, S., Ulzheimer, J. C., Waldegger, S., Gorboulev, V., Arndt, P., Lang, F., and Koepsell, H. (1996) J. Biol. Chem. 271, 32599-32604). Tracer flux measurements with oocytes and with stably transfected human embryonic kidney cells showed that [3H]quinine and [3H]quinidine are not transported by rOCT1. The voltage dependence observed for the quinine- or quinidine-induced inward currents in rOCT1-expressing oocytes, and tracer efflux measurements indicate that the inward currents by type 2 cations are generated by the inhibition of electrogenic efflux of transported type 1 cations. Therefore, rOCT1 cannot contribute to transport of type 2 cations in the liver and the hepatic transporter for type 2 cations remains to be identified.

Animals↗

Na+,K(+)-ATPase pump currents activated by an ATP concentration jump. Comparison of studies with purified membrane fragments and giant excised patches.

The lipid bilayer and the giant patch technique were used to study the Na+,K(+)-ATPase. In excised patches from ventricular myocytes, Na+,K(+)-pump currents show a saturable ATP dependence with a Km of approximately 150 microM at 24 degrees C. Partial reactions in the transport cycle were investigated by generating ATP concentration jumps through photolytic release of ATP from caged ATP at pH 7.4 and 6.3. Transient outward currents were obtained at pH 6.3 with a fast rising phase followed by a slow decay to a stationary current. Experiments with purified pig kidney Na+,K(+)-ATPase attached to a planar lipid bilayer resulted in similar pump current signals and the same outcome. It was concluded that the fast rate constant of approximately 200 s-1 at 24 degrees C reflects a step rate limiting the electrogenic Na+ release.

Adenosine Triphosphate↗

Modular evolution of the respiratory NADH:ubiquinone oxidoreductase and the origin of its modules.

The proton-pumping NADH:ubiquinone oxidoreductase is the foremost of the respiratory chain complexes providing the proton motive force required for the synthesis of ATP. The complex is found in purple bacteria and in the mitochondria of most eukaryotes. The bacterial complex consists of 14 different subunits while the mitochondrial complex contains at least 28 accessory proteins which do not directly participate in the electron and proton transport function. A homologous complex which has 11 subunits in common with the respiratory complex I exists in cyanobacteria and chloroplasts. This complex might probably work as a NADPH:plastoquinone oxidoreductase being possibly involved in a cyclic photosynthetic electron transport. Homologues of the functional modules of the complex are also found in other bacterial electron transfer and ion transport proteins. The modular evolution of the complex and the possible origin of its modules are discussed in this paper.

Adenosine Triphosphate↗

Comparison of Na+/K(+)-ATPase pump currents activated by ATP concentration or voltage jumps.

Using the giant patch technique, we combined two fast relaxation methods on excised patches from guinea pig cardiomyocytes to compare the rate constants of the involved reaction steps. Experiments were done in the absence of intra- or extracellular K+. Fast ATP concentration jumps were generated by photolysis of caged ATP at pH 6.3 with laser flash irradiation at a wavelength of 308 nm and 10 ns duration, as described previously. Transient outward currents with a fast rising phase, followed by a slower decay and a small stationary current, were obtained. Voltage pulses were applied to the same patch in the presence or absence of intracellular ATP. Subtraction of the voltage jump-induced currents in the absence of ATP from those taken in the presence of ATP yielded monoexponential transient current signals, which were dependent on external Na+ but did not differ between intracellular pH (pHi) values 6.3 or 7.4. Rate constants showed a characteristic voltage dependence, i.e., saturating at positive potentials (approximately 200 s-1, 24 degrees C) and exponentially rising with increasing negative potentials. Rate constants of the fast component from transient currents obtained after an ATP concentration jump agree well with rate constants from currents obtained after a voltage jump to zero or positive potentials (pHi 6.3), and the two exhibit the same activation energy of approximately 80 kJ.mol-1. For a given membrane patch, the amount of charge that is moved across the plasma membrane is roughly the same for each of the two relaxation techniques.

Adenosine Triphosphate↗

Site-specific interaction of thrombin and inhibitors observed by fluorescence correlation spectroscopy.

We report on the application of fluorescence correlation spectroscopy (FCS) to observe the interaction between thrombin and thrombin inhibitors. Two site-specific fluorescent labels were used to distinguish between inhibitors directed to the active site, the exosite, or both binding sites of thrombin. For several well-known inhibitors of thrombin, the binding sites observed by FCS correspond to previous studies. The interaction of the recently discovered thrombin inhibitor ornithodorin from the tick Ornithodorus moubata with thrombin was investigated. It was found that this inhibitor, like hirudin and rhodniin, binds to both the active site and exosite of thrombin simultaneously. This study shows the feasibility of FCS as a sensitive and selective method for observing protein-ligand interactions. As an additional technique, simultaneous labeling with both fluorescent labels was successfully demonstrated.

Animals↗

Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators.

OBJECTIVES: This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide, a pure class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. BACKGROUND: Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation. These effects, and preliminary clinical data, suggest that it may be effective in the treatment of atrial fibrillation and flutter. METHODS: Ninety-one patients with sustained atrial fibrillation (75 patients) or flutter (16 patients) were entered into a double-blind, randomized multicenter study of one of two doses of dofetilide (4 or 8 micrograms/kg body weight) or placebo. RESULTS: Dofetilide effectively terminated the arrhythmia in 31% of patients receiving 8 micrograms/kg, a statistically significant difference from those receiving 4 micrograms/kg (conversion rate 12.5%, p < 0.05) or placebo (no conversion, p < 0.01). Patients with atrial flutter had a greater response to dofetilide (54% conversion rate) than those with atrial fibrillation (14.5% conversion rate, p < 0.001). CONCLUSIONS: Intravenous dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm. However, its efficacy is greater in flutter--a response that contrasts with the poorer response seen with class I agents. This finding potentially represents an important advance in the pharmacologic termination of atrial flutter.

Anti-Arrhythmia Agents↗

A gene involved in both protein secretion during growth and starvation-induced development encodes a subunit of the NADH:ubiquinone oxidoreductase in Myxococcus xanthus.

The secretion of numerous proteins during vegetative growth of Myxococcus xanthus, and the multicellular development cycle induced upon starvation of these bacteria, are partially interrelated in so far as mutants impaired in extracellular protein production are unable to undergo development. We have cloned and sequenced a gene in which a Tn5 insertion leads to a decrease in the production of most, if not all, extracellular proteins, and prevents development and sporulation. The deduced protein is homologous to the putative ubiquinone-binding subunit of bacterial and mitochondrial NADH:ubiquinone oxidoreductases (complex I). This is the first example of the presence of this complex in a bacterium from subclass delta of the proteobacteria. This gene is expressed during growth and during early development. As its disruption by Tn5 does not impair growth of the mutant strain, we assume the presence of a second alternative NADH oxidoreductase, and suggest that the phenotypic alterations caused by the mutation are due to a decrease in the proton-motive force.

Bacterial Proteins↗

[Atypical metastasis of stomach carcinoma].

We report a case of unusual metastases from a gastric cancer. In a 66 years old female with bone metastases a breast cancer was diagnosed. The patient was treated by ablative surgery and chemotherapy but died short time later. An autopsy was performed and showed a large signetring cell carcinoma of the stomach. Further a diffuse involvement of the spleen unknown until autopsy was diagnosed. Serial tissue sections of all metastatic localizations were made. Histopathology and immunostaining including oestroprogesterone receptors identified a gastric cancer as the primary malignancy. A review of the recent literature on breast metastases from gastrointestinal tumours, gastric metastases from breast cancer and the problem of second primary malignancies is given. Further we reviewed the occult metastatic spread of the spleen and the importance of splenectomy in case of total gastrectomy.

Aged↗