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Biomedical subjects

C Richter

Publications and source records attributed to C Richter.

At least 91 records · Page 5Linked to original sources
PubMed1998

Nitric oxide and its congeners in mitochondria: implications for apoptosis.

Apoptosis is an evolutionarily conserved form of physiologic cell death important for tissue development and homeostasis. The causes and execution mechanisms of apoptosis are not completely understood. Nitric oxide (NO) and its congeners, oxidative stress, Ca2+, proteases, nucleases, and mitochondria are considered mediators of apoptosis. Recent findings strongly suggest that mitochondria contain a factor or factors that upon release from the destabilized organelles, induce apoptosis. We have found that oxidative stress-induced release of Ca2+ from mitochondria followed by Ca2+ reuptake (Ca2+ cycling) causes destabilization of mitochondria and apoptosis. The protein product of the protooncogene bcl-2 protects mitochondria and thereby prevents apoptosis. We have also found that NO and its congeners can induce Ca2+ release from mitochondria. Thus, nitrogen monoxide (.NO) binds to cytochrome oxidase, blocks respiration, and thereby causes mitochondrial deenergization and Ca2+ release. Peroxynitrite (ONOO-), on the other hand, causes Ca2+ release from mitochondria by stimulating a specific Ca2+ release pathway. This pathway requires oxidized nicotinamide adenine dinucleotide (NAD+) hydrolysis to adenosine diphosphate ribose and nicotinamide. NAD+ hydrolysis is only possible when some vicinal thiols are cross-linked. ONOO- is able to oxidize them. Our findings suggest that NO and its congeners can induce apoptosis by destabilizing mitochondria via deenergization and/or by inducing a specific Ca2+ release followed by Ca2+ cycling.

Animals↗
PubMed1998

Oxidative stress, mitochondria, and apoptosis.

This article emphasizes the importance of mitochondria, the cellular ATP level, and the liberation of certain mitochondrial proteins for the execution phase of apoptosis. Destabilization of mitochondria results in release of these proteins. Oxidative stress and altered cellular Ca2+ homeostasis, considered to be mediators of apoptosis, synergistically decrease the mitochondrial membrane potential and lower the cellular ATP level. Conversely, stabilization of the mitochondrial membrane potential, e.g., by the protooncogene bcl-2, prevents cell death. An important process underlying mitochondrial destabilization is oxidant-induced mitochondrial Ca2+ release followed by re-uptake ("Ca2+ cycling"). Tumor necrosis factor-a induces oxygen radicals in mitochondria through ceramides, and the recently discovered mitochondrial nitric oxide synthase profoundly stimulates Ca2+ release from mitochondria through formation of nitrogen monoxide and peroxynitrite.

Journal Article↗
PubMed1998

[Aspects of preoperative management of biliary surgical procedures].

Difference between open cholecystectomy and laparoscopic cholecystectomy are described. General preparations and pre-operative work up in Austria, Switzerland, Germany and East German quality assurance study at compared. The importance of antibiotic and thrombembolic prophylaxis increased.

Antibiotic Prophylaxis↗
PubMed1998

[Intraoperative neuromonitoring of the recurrent laryngeal nerve--routine use in thyroid gland surgery].

We present a simple and reliable method for identification of the recurrent nerve by intraoperative stimulation. An electromyographic record from the vocal muscle is obtained using a bipolar needle electrode inserted through the cricothyroid membrane. The recurrent nerve could be easily identified in 176 cases out of 181 nerves at risk (97.2%). We have not seen any cases of recurrent nerve paralysis and discuss the advantages of intraoperative neuromonitoring as a routine procedure.

Electrodes, Implanted↗
PubMed1997

Photosensitization of isolated rat liver mitochondria by tetra(m-hydroxyphenyl)chlorin.

Tetra(m-hydroxyphenyl)chlorin (mTHPC) is used as a photosensitizer in photodynamic therapy (PDT), a novel modality for cancer treatment. Since little is known about mTHPC-mediated damage in vitro, we chose isolated rat liver mitochondria as a model system to study its photodynamic effects. Incubation of isolated mitochondria with mTHPC plus irradiation with light of a wavelength of 652 nm resulted in protein oxidation and lipid peroxidation, as measured by the mitochondrial content of carbonyl groups and thiobarbituric acid-reactive substances, respectively. Type I and type II photochemical reactions contribute to this oxidative damage as shown by the use of scavengers. Photodynamically treated mitochondria had a reduced membrane potential, and their Ca2+ uptake was impaired. Oxygen consumption of complex I of the respiratory chain was stimulated at a low concentration of mTHPC plus irradiation, but decreased at higher concentrations, whereas oxygen consumption at complex II and IV decreased with all mTHPC concentrations offered. No mitochondrial changes were seen with mTHPC in the absence of irradiation. Our results confirm the sensitivity of mitochondria to PDT and may help to understand the mechanisms by which PDT using mTHPC kills cells.

Adenosine Diphosphate↗
PubMed1997

Nitric oxide synthase activity in mitochondria.

In the present study we show the existence of a functional nitric oxide synthase (NOS) in rat liver mitochondria. The enzyme uses L-arginine (L-arg) to produce nitric oxide (NO) and L-citrulline, and is Ca2+-dependent. L-Arg analogues, N(omega)monomethyl-L-arg and N(omega)-nitro-L-arg, inhibit the enzyme, and D-arginine is not a substrate for it. We found mitochondrial NOS (mtNOS) activity associated with the inner mitochondrial membrane but not with the matrix fraction. In intact, succinate-energized mitochondria, the enzyme is constitutively active and exerts substantial control over mitochondrial respiration and membrane potential. The activity is further stimulated when Ca2+ is taken up by mitochondria. We suggest that the existence of mtNOS and its Ca2+ dependence are highly relevant for mitochondrial functioning.

Animals↗
PubMed1997

[Lymphomatoid granulomatosis--remission induction with interferon-alpha 2b].

HISTORY AND ADMISSION FINDINGS: A 72-year-old woman was admitted to hospital because of nonproductive cough, acrodistal sensorimotor axonal polyneuropathy, fatigue and 10 kg weight loss over the preceding 9 months. INVESTIGATIONS: Chest radiogram showed multiple round foci in both lungs. No organs other than the lungs and the peripheral nervous system were affected. Open lung biopsy revealed a pleomorphic angioinvasive lymphocytic infiltrations. DIAGNOSIS, TREATMENT AND COURSE: The findings indicated lymphomatoid granulomatosis (LG). Wegener granulomatosis was excluded on the basis of the clinical, serological and histopathological findings. Treatment with alpha-interferon (IFN-alpha) produced complete remission within 4 months. Interruption of treatment immediately resulted in a recurrence. CONCLUSION: Together with previously reported cases this patient's response to IFN-alpha suggests that IFN-alpha is a less toxic alternative to cyclophosphamide and corticosteroid administration in the early stages of LG.

Aged↗
PubMed1997

Quantification of wild-type mitochondrial DNA and its 4.8-kb deletion in rat organs.

Oxidative damage to mitochondrial DNA (mtDNA) is considered a major contributor in aging. An age-dependent increase of oxidative damage and of the quantity of partially deleted mtDNA was reported for several rat and human organs. Here, a systematic investigation of ten different tissues and organs of 20-months-old rats was performed. The amount of mtDNA and age-dependent 4.8 kb deletion (delta mtDNA4834) was determined by competitive polymerase chain reaction, along with the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). The data were related to the corresponding metabolic rates. MtDNA content was highest in heart and lowest in spleen. delta mtDNA4834 was detected in all ten tissues and organs, and its amount was highest in liver and lowest in intestine. In heart, lung, muscle, and bone-marrow the deletion could not be quantified because of a point mutation, an A-->T transition at position 8107. Activities of SOD and GSHPx were highest in liver and lowest in intestinal mucosa. A negative correlation between mtDNA content and delta mtDNA4834, and a positive correlation between metabolic rate, GSHPx, and the deletion was found. These results suggest that the occurrence of delta mtDNA4834 in rat is related to oxidative stress.

Animals↗
PubMed1997

MRI of the nasal cavity, the paranasal sinuses and orbits in Wegener's granulomatosis.

The purpose of this study was to evaluate diagnostic MRI criteria in Wegener's granulomatosis of the nasal cavity, the paranasal sinuses and orbits. Between March 1991 and January 1996, 62 patients with biopsy-proven Wegener's granulomatosis were studied with T1- and T2-weighted spin-echo (SE) sequences. In 32 patients coronal postcontrast T1-weighted images were obtained. Mucosal thickening of the nasal cavity and paranasal sinuses was demonstrated as high-intensity lesions on T2-weighted SE sequences in 57 patients (92%). Of this group, inflammatory granulomatous tissue was found on biopsy in 30 patients (48%) in the nasal cavity and in 4 patients (6%) in the paranasal sinuses. In 23 patients (37%) biopsy revealed unspecific inflammatory changes without evidence of granulomatous tissue. In 14 patients (23%) granulomas were depicted as low-signal intensity lesions on T1- and T2-weighted SE sequences in the paranasal sinuses and orbits. In 5 patients (8%) osseous destruction was found. After gadolinium injection, 12 of 14 granulomas showed inhomogeneous signal enhancement. In two granulomas no enhancement was found. The MRI technique is helpful in the diagnosis of patients with Wegener's granulomatosis. In the initial inflammatory process of Wegener's granulomatosis, it is not possible to differentiate between mucosal inflammation and granulomatous tissue in MRI. In the later stage of granulomatous transformation, granulomas can be depicted as low-signal-intensity lesions. Therefore, Wegener's granulomatosis should be included in the differential diagnosis of patients with low-signal-intensity lesions on T1- and T2-weighted SE sequences of the nasal cavity, paranasal sinuses and orbits.

Adult↗
PubMed1997

Reactive oxygen and nitrogen species regulate mitochondrial Ca2+ homeostasis and respiration.

The reduction of molecular oxygen to water provides most of the biologically useful energy. However, oxygen reduction is a mixed blessing because incompletely reduced oxygen species such as superoxide or peroxides are quite reactive and can, when out of control, cause damage. In mitochondria, where most of the oxygen utilized by eukaryotic cells is reduced, the dichotomy of oxygen shows itself best. Thus, reactive oxygen is a threat to them, as is evident from oxidative damage to mitochondrial lipids, proteins, and nucleic acids. Reactive oxygen, in the form of peroxides, also serves useful functions in mitochondria. This is exemplified by the control of mitochondrial and cellular calcium homeostasis, whose understanding has improved greatly during the last few years. An exciting new aspect is the discovery that nitric oxide and congeners have an enormous impact on mitochondria. Physiological concentrations of nitrogen monoxide (NO) at physiological cellular oxygen pressure inhibit cytochrome oxidase and thereby respiration. A transient inhibition of cytochrome oxidase by NO appears to be used in at least some forms of cell signalling. Peroxynitrite, the product of the reaction between superoxide and NO, can stimulate the specific calcium release pathway from mitochondria by oxidizing some vicinal thiols in mitochondria. There is evidence mounting that mitochondrial calcium handling and its modulation by reactive oxygen and nitrogen species is important for necrotic and apoptotic cell death.

Aging↗
PubMed1997

The ftsH gene of Bacillus subtilis is involved in major cellular processes such as sporulation, stress adaptation and secretion.

The ftsH gene of Bacillus subtilis has been identified as a general stress gene which is transiently induced after thermal or osmotic upshift. The FtsH protein exhibits 70.1% homology to FtsH of Escherichia coli which constitutes an essential ATP- and Zn(2+)-dependent protease anchored in the cytoplasmic membrane via two N-terminal transmembrane domains. This paper describes the isolation and functional characterization of an ftsH null mutant which was obtained by integration of a cat-cassette near the 5' end of ftsH, thereby preventing the synthesis of FtsH protein. In contrast to the situation in E. coli, ftsH is dispensable in B. subtilis but results in a pleiotropic phenotype. While the mutant cells grew mostly as large filaments under physiological conditions, they turned out to be extremely sensitive to heat and salt stress. Although ftsH is necessary for adaptation to heat, it is not involved in the regulation of the heat-shock response. The induction profiles of representative genes of the CIRCE and sigma-B regulon and class III heat-shock genes ion and clpC were identical in the wild type and the ftsH null mutant. Furthermore, the ftsH knockout strain was unable to sporulate, and this failure was probably due to the absence of Spo0A protein which is essential for entry into the sporulation programme. In addition, secretion of bulk exoproteins was severely impaired in the ftsH null mutant after entry into stationary phase. The alpha-amylase and subtilisin activity in the supernatant was specifically tested. Whereas the activity of alpha-amylase increased after entry into stationary phase in both the wild type and the ftsH mutant strain, that of subtilisin encoded by aprE was prevented at the level of transcription in the mutant. Most of these results can be explained by the failure to synthesize appropriate amounts of Spo0A protein in the ftsH null mutant and point to ftsH as a developmental checkpoint.

ATP-Dependent Proteases↗
PubMed1997

Mannan-binding lectin in the sub-Saharan HIV and tuberculosis epidemics.

Inherited deficiency of mannan-binding lectin (MBL) has been shown to predispose to infections. Conversely, it has also been suggested that MBL might facilitate the uptake of certain intracellular microbes. The aim of this study was to investigate whether MBL plays a role in the HIV and tuberculosis epidemics in Africa. Thus, the authors determined the MBL serum concentration in 173 HIV infected patients (150 with concomitant tuberculosis), 94 patients with tuberculosis without being HIV infected, and 113 controls from Tanzania. The frequency of MBL deficiency was significantly increased in HIV infected patients compared with controls (12.1% and 3.5%, respectively). The frequency of patients deficient of MBL did not differ between controls and HIV negative patients with tuberculosis. However, HIV negative patients with tuberculosis had significantly higher MBL levels than both controls and HIV infected patients with or without tuberculosis. These results indicate that low levels of MBL are associated with increased risk of sexually transmitted HIV infection in Africans. By contrast, high levels of MBL may be involved in the pathogenesis of tuberculosis in immunocompetent individuals.

Adolescent↗
PubMed1997

Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis.

BACKGROUND: Pneumonitis is a rare but potentially life threatening side effect of methotrexate treatment for rheumatoid arthritis which needs to be distinguished from interstitial lung disease due to rheumatoid arthritis. METHODS: To examine the value of bronchoalveolar lavage (BAL) in diagnosing methotrexate pneumonitis, the BAL cell profile of four patients with methotrexate pneumonitis was compared with findings in 16 patients with rheumatoid arthritis treated with methotrexate without clinical or radiological evidence of lung disease and eight patients with interstitial lung disease secondary to rheumatoid arthritis treated with methotrexate. RESULTS: Methotrexate pneumonitis was associated with an increase in the lymphocytes in the BAL fluid to 33-68% of total BAL cells. BAL lymphocytosis was also found in five patients in each of the two control groups. The four patients with methotrexate pneumonitis had a disproportionate increase in CD4+ cells to 72-84% of total lymphocytes and in the CD4/CD8 ratio to 17.0, 6.6, 8.7, and 4.0, respectively, figures which exceeded those of the two control groups. CONCLUSIONS: Methotrexate pneumonitis was associated with lymphocytic alveolitis with a preferential increase in CD4+ cells. This pattern differs from that in interstitial lung disease due to rheumatoid arthritis and may therefore assist in making an early diagnosis of methotrexate pneumonitis.

Aged↗
PubMed1996

Stimulation of Ca2+ release from rat liver mitochondria by the dithiol reagent alpha-lipoic acid.

Rat liver mitochondria contain a Ca(2+)-specific release pathway stimulated by Ca(2+)-dependent hydrolysis of oxidized intramitochondrial pyridine nucleotides to ADP ribose and nicotinamide. We have previously shown that NAD+ hydrolysis and subsequent Ca2+ release are inhibited by cyclosporine A and that they are only possible when some critical thiols are cross-linked or oxidized, e.g. by phenylarsine oxide, gliotoxin, or peroxynitrite. We now report that the antioxidant alpha-lipoic acid stimulates Ca2+ release from intact mitochondria, i.e. with preservation of the mitochondrial membrane potential and without large-amplitude swelling. The release stimulated by alpha-lipoic acid is inhibited by cyclosporine A and is more effective when the pyridine nucleotides are oxidized. The results strongly suggest that alpha-lipoic acid stimulates the Ca(2+)-specific release pathway from intact mitochondria by oxidizing some vicinal thiols, thereby stimulating hydrolysis of oxidized pyridine nucleotides. These observations further corroborate that intact rat liver mitochondria contain a specific Ca2+ release pathway stimulated by modification of vicinal thiols. Prolonged stimulation of Ca2+ release by lipoic acid followed by its re-uptake (Ca2+ "cycling") may contribute to the detrimental, prooxidant-like effects seen with higher concentrations of lipoic acid.

Animals↗
PubMed1996

Direct observation of iron-induced conformational changes of mitochondrial DNA by high-resolution field-emission in-lens scanning electron microscopy.

When respiring rat liver mitochondria are incubated in the presence of Fe(III) gluconate, their DNA (mtDNA) relaxes from the supercoiled to the open circular form dependent on the iron dose. Anaerobiosis or antioxidants fail to completely inhibit the unwinding. High-resolution field-emission in-lens scanning electron microscopy imaging, in concert with backscattered electron detection, pinpoints nanometer-range iron colloids bound to mtDNA isolated from iron-exposed mitochondria. High-resolution field-emission in-lens scanning electron microscopy with backscattered electron detection imaging permits simultaneous detailed visual analysis of DNA topology, iron dose-dependent mtDNA unwinding, and assessment of iron colloid formation on mtDNA strands.

Animals↗
PubMed1996

Peroxynitrite stimulates the pyridine nucleotide-linked Ca2+ release from intact rat liver mitochondria.

Rat liver mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolyzed in a Ca2+-dependent manner to ADP-ribose and nicotinamide. We have previously shown that NAD+ hydrolysis is inhibited by cyclosporin A and is possible only when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxynitrite (ONOO-), which can form from nitric oxide (nitrogen monoxide, NO.) and superoxide anion (O2-), at low concentrations stimulates the specific Ca2+ release pathway. Both peroxynitrite-induced pyridine nucleotide hydrolysis and Ca2+ release are inhibited by cyclosporin A, and peroxynitrite is ineffective when pyridine nucleotides are kept reduced. Ca2+ release induced by peroxynitrite occurs with maintenance of the mitochondrial membrane potential and is not accompanied by entry of sucrose into mitochondria. The results suggest that peroxynitrite stimulates the specific Ca2+ release from intact mitochondria by modifying critical mitochondrial thiols other than glutathione in such a way that hydrolysis of oxidized pyridine nucleotides is achieved. These findings provide further insight into the regulation of Ca2+ release from mitochondria by nitric oxide and its congeners.

Animals↗