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Biomedical subjects

K Brecht

Publications and source records attributed to K Brecht.

At least 19 recordsLinked to original sources
PubMed2006

Toxicity of statins on rat skeletal muscle mitochondria.

We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin, fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin). In L6 cells (rat skeletal muscle cell line), the four lipophilic statins (100 micromol/l) induced death in 27-49% of the cells. Pravastatin was not toxic up to 1 mmol/l. Cerivastatin, fluvastatin and atorvastatin (100 micromol/l) decreased the mitochondrial membrane potential by 49-65%, whereas simvastatin and pravastatin were less toxic. In isolated rat skeletal muscle mitochondria, all statins, except pravastatin, decreased glutamate-driven state 3 respiration and respiratory control ratio. Beta-oxidation was decreased by 88-96% in the presence of 100 micromol/l of the lipophilic statins, but only at higher concentrations by pravastatin. Mitochondrial swelling, cytochrome c release and DNA fragmentation was induced in L6 cells by the four lipophilic statins, but not by pravastatin. Lipophilic statins impair the function of skeletal muscle mitochondria, whereas the hydrophilic pravastatin is significantly less toxic.

Animals↗
PubMed2005

Upregulation of alpha globin promotes apoptotic cell death in the hematopoietic cell line FL5.12.

The function of alpha globin in the context of oxygen transport in erythroid cells is well described. Recently the expression of alpha globin was shown to be upregulated upon specific apoptotic stimuli like cytokine deprivation or cisplatin treatment in the hematopoietic pro-B cell line, FL5.12. In contrast to alpha globin, beta globin or globin-like genes were expressed at a very low level or were not expressed at all. Further, we found that alpha globin was not associated with heme. Apoptotic cells neither produced hemoglobin nor displayed a phenotype of cells differentiating down the erythroid lineage. Also other cell lines of variable differentiation status (NIH3T3, HeLa, K562) upregulated alpha globin during treatment with apoptosis-inducing agents. Under IL-3-deprived conditions GFP-alpha globin accelerated the progression of apoptosis comparable to GFP-Bax. GFP-alpha globin was expressed at a low level and enrichment of FL5.12 cells expressing GFP-alpha globin was difficult even in the presence of IL-3. Caspase-8, -9 and -3 as well as the proapoptotic factor Bax and cytochrome c were activated. Antisense alpha globin downregulated the expression of endogenous alpha globin und reduced caspase activity. Taken together these data indicate that alpha globin is a new and crucial factor in apoptosis especially supporting the mitochondrial pathway.

Amino Acid Chloromethyl Ketones↗
PubMed2005

Hematopoietic transcription factor GATA-2 promotes upregulation of alpha globin and cell death in FL5.12 cells.

Recently we showed that alpha globin is a novel pro-apoptotic factor in programmed cell death in the pro-B cell line, FL5.12. Alpha globin was also upregulated in various other cell lines after different apoptotic stimuli. Under withdrawal of IL-3, overexpression of alpha globin accelerated apoptosis in FL5.12. Here, we have studied how transcription of alpha globin is placed in the broader context of apoptosis. We used Affymetrix chip technology and RT QPCR to compare expression patterns of FL5.12 cells growing with or without IL-3 to search for transcription factors which were concomitantly upregulated with alpha globin. The erythroid-specific transcription factor GATA-2 was the earliest and most prominently upregulated candidate. GATA-1 was expressed at low levels and was weakly induced while GATA-3 was completely absent. To evaluate the influence of GATA-2 on alpha globin expression and cell viability we overexpressed GATA-2 in FL5.12 cells. Interestingly, high expression of GATA-2 resulted in cell death and elevated alpha globin levels in FL5.12 cells. Transduction of antisense GATA-2 prevented both increase of GATA-2 and alpha globin under apoptotic conditions and delayed cell death. We suggest a role of GATA-2 in apoptosis besides its function in maintenance and proliferation of immature hematopoietic progenitors.

Animals↗
PubMed1996

Otocephalus: histopathology and three-dimensional reconstruction.

Otocephaly is a lethal malformation of the first and second branchial arches, which consists of ventromedial displacement of the external ear structures (synotia), mandibular aplasia (agnathia), absence of the tongue (aglossia), and microstomia. We present the first complete description of the temporal bone findings in a case of otocephalus. A three-dimensional computer-assisted reconstruction of the right temporal bone was performed, allowing a unique graphic analysis. An extremely low-lying middle fossa tegmen was noted with malrotation of the middle ear structures. Severe ossicular malformations were also found. An anomalous course of the internal carotid artery was noted with indentation of the basal turn of the cochlea. All three layers of the otic capsule were incompletely developed. Cochlear bony dehiscences were noted. These findings are consistent with early arrest of fetal development and malrotation caused by lack of growth pressure from the mandibular arch. Implications of these findings in the embryologic development of the ear are discussed.

Abnormalities, Multiple↗
PubMed1990

Hepatic subcellular localization of cresylbenzodioxaphosphorin oxide (CBDP)-sensitive soman binding sites.

The toxicity of the organophosphorus poison soman (pinacolylmethylphosphonofluoridate) is attributable to its irreversible inhibition of the enzyme acetylcholinesterase. In addition, soman binds irreversibly to a number of noncholinesterase tissue binding sites which appear to be its major means of in vivo detoxification. This study was conducted to determine the hepatic subcellular localization of these sites. Subcellular fractions of liver from male Sprague-Dawley rats (200-250 g) were prepared by differential and isopycnic density gradient centrifugation. The binding of [14C]soman to these subcellular fractions was determined in the presence and absence of cresylbenzodioxaphosphorin oxide (CBDP), a compound that binds irreversibly to the noncholinesterase soman binding sites. Crude fractionation of liver homogenates into nuclear, mitochondrial, microsomal, and soluble fractions revealed that 78% of the total CBDP-sensitive binding activity was localized in the nuclear and microsomal fractions. Further purification of these fractions indicated that all of the homogenate binding activity could be accounted for in the purified microsomal fraction. When purified liver microsomes were solubilized and fractionated on linear sucrose gradients, 90% of the CBDP-sensitive soman binding activity cosedimented with carboxylesterase activity which suggests that these binding sites are carboxylesterase.

Animals↗
PubMed1988

[Psychoanalysis in Germany under nazi rule: the adjustment to the institution and the relationships between Jewish and non-Jewish psychoanalysts].

The process of institutional adaptation of the German Psychoanalytic Society (Deutsche Psychoanalytische Gesellschaft--D.P.G.) to National Socialism and the relationship between Jewish and non-Jewish psychoanalysts are described step by step. In a second paragraph, based on new documents, the "case of Edith Jacobson" is represented, and a dilemma of the I.P.A. regarding National Socialism shown. In a last paragraph the struggle between defense, return of the repressed and remembrance is developed from institutional reconstruction of both psychotherapy and psychoanalysis, the founding of the German Psychoanalytical Association (Deutsche Psychoanalytische Vereinigung--D.P.V.) in 1950, its separation from the D.P.G., and group processes within the D.P.V. before the Hamburg Congress.

Germany↗
PubMed1986

Myocardial infarction with topical cocaine anesthesia for nasal surgery.

Cocaine, the active alkaloid in coca leaf, is widely used as local anesthetic for otolaryngologic procedures. Our patient suffered an acute nontransmural myocardial infarction following clinical use of cocaine as topical anesthesia for nasal surgery, the first such case to be documented, to our knowledge. Although evidence documenting its cardiovascular toxicity is listed in contemporary pharmacologic literature, clinical cardiac injury has been reported to date only with the recreational use of cocaine. Authentic documentation of drug composition when received through the intervention of illicit vendors is always difficult. The literature is reviewed, justifying the use of cocaine as the most popular topical anesthetic in otolaryngologic practice. However, we hope that awareness of this possible complication will create a resurgence of research interest in topical cocaine anesthesia.

Adult↗
PubMed1985

Complete mandibular agenesis. Report of a case.

A child had complete mandibular agenesis, with associated anomalies of microstomia, left choanal stenosis, and a cleft soft palate. This child had evidence of disruption in development at about the four-week stage by the persistence of several developmental remnants, specifically, the buccopharyngeal membrane, tongue remnants, and the laryngotracheal groove. The etiology of this condition is unclear at this time.

Abnormalities, Multiple↗
PubMed1980

Effect of potassium on isolated bovine facial and human saphenous veins.

A moderate elevation of external (K0+) (5--10 mM) induces relaxation in bovine facial and human saphenous veins. A further increase of (K0+) leads to biphasic reactions (relaxation followed by contraction). Concentrations of (K0+) higher than about 15 mM cause contractions only. The potassium-induced relaxation may be explained by the stimulation of an electrogenic sodium pump.

Animals↗
PubMed1979

Reactivity of isolated bovine facial vessels to electric stimulation and to drugs.

The effects of electric stimulation on isometric force generation of isolated helical strips of bovine facial arteries (BFA) and veins (BFV) were investigated. Whereas BFA always contracted, electrically stimulated BFV showed a biphasic response, i.e. a small, transient contraction followed by an intense relaxation. The findings presented suggest a neurogenic response for the vasodilator component of BFV response to electric stimulation. Exogenous catecholamines and serotonin dilated the veins; the effects were antagonized by propranolol and dihydroergotamine, respectively. Dopamine-induced relaxations were only partially inhibited by propranolol; the residual relaxations were antagonized by chlorpormazine and haloperidol. Relaxations of the veins after electric stimulation or after administration of noradrenaline were accompanied by an increase of the cAMP content. In the BFA catecholamines, serotonin and histamine increased the tension, whereas isoprenaline was ineffective. Acetylcholine contracted the veins and relaxed the arteries; both effects were antagonized by atropine.

Acetylcholine↗
PubMed1975

Cyclic AMP and the potassium-induced vasodilation.

The cAMP concentration of bovine facial arteries (helical strips) increased from 0.84 +/- 0.14 to 1.51 +/- 0.24 nmole/g wet weight, when the strips were relaxed by exposure to a physiological salt solution containing 10 instead of 2.7 mM KCl. A similar result (increase from 1.13 +/- 0.15 to 2.07 +/- 0.29 nmole cAMP/g wet weight) was obtained in strips pretreated with 10(-7) g/ml beta-methyldigoxin. These strips reacted to 10 mM KCl with a constriction. Addition of the phosphodiesterase activator N-methyl-imidazole (3 - 10(-3)M) did not affect the mechanical response to 10 mM KCl. It is concluded that for the potassium-induced vasodilation cAMP does not have a mediating function comparable to that in beta-adrenergic relaxation of vascular smooth muscle.

Animals↗