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Biomedical subjects

M Braun

Publications and source records attributed to M Braun.

At least 109 records · Page 6Linked to original sources

Inferior colliculus as candidate for pitch extraction: multiple support from statistics of bilateral spontaneous otoacoustic emissions.

The fibrodendritic laminae of the central nucleus of the inferior colliculus (ICC) constitute a frequency map in stacked sheets that are consistently related to the psychoacoustic critical bandwidth (CB) [Schreiner and Langner, 1997. Nature 388, 383-386]. The recently observed co-occurrence of the CB and the double CB (2CB) suggested an adaptation of the ICC frequency map to the extraction of the fundamental frequency f(0) [Braun, 1999. Hear. Res. 129, 71-82]. The present study examined a possible influence of this frequency map upon efferent signaling towards the cochlea. The f(0) distribution of 2890 monaural and 2604 binaural pairs of human spontaneous otoacoustic emissions was analyzed by three statistical methods and in each case showed non-random behavior in the CB-2CB range. Single results were (1) a bias of right ear f(0) (mode at 349 Hz) and left ear f(0) (mode at 262 Hz) towards different ranges of speech f(0) (P<0.02); (2) a bias of binaural, but not monaural, f(0) towards five of 12 semitone bins, C-G-D-A-E, representing the most frequent tones in music (P<0.003); (3) a bias of binaural, but not monaural, f(0) fine-distribution towards the exact pitch frequencies used in music, according to the international standard A4=440 Hz (P=0.03). The results support a model of lamina-based f(0) extraction in the ICC and suggest a specific colliculo-cochlear feedback for f(0) enhancement.

Humans↗

[Head and brain injuries. Place of imaging].

This article considers the various mechanisms of brain injury and specifies the most efficient radiologic technique for assessing patients, depending on clinical presentation. The brain injuries include either extracerebral and intracerebral lesions. The former require rapid diagnosis and therapy and the latter determine management in an intensive therapy, unit and outcome. Standard X-rays are obsolete. The CT, rapidly performed, is the most relevant imaging procedure for surgical lesions. Cortical contusions and diffuse axonal injuries are underestimated by CT and best depicted by MRI. Only late MRI has a strong correlation with neuropsychological outcome. In terms of prognosis, MRI needs to be evaluated. The indications include: a) unstable neurological status: CT; b) moderate head injury: CT may help to decide hospital admission; c) severe head injury: initial CT may be followed by MRI; d) long-term consequences: MRI. Special Indications: a) angio-MRI: suspicion of vascular lesion; b) CT with thin slices and bone window: depressed skull fracture; c) teleradiology (image transfer): to decide a patient transport from a peripheral hospital to a neurosurgical centre. In conclusion, CT remains the first-line examination to detect immediately life-threatening lesions. MRI is the examination of choice for full assessment of brain lesions.

Brain Injuries↗

Comparison of cryofixation and aldehyde fixation for plant actin immunocytochemistry: aldehydes do not destroy F-actin.

For walled plant cells, the immunolocalization of actin microfilaments, also known as F-actin, has proved to be much trickier than that of microtubules. These difficulties are commonly attributed to the high sensitivity of F-actin to aldehyde fixatives. Therefore, most plant studies have been accomplished using fluorescent phallotoxins in fresh tissues. Nevertheless, concerns regarding the questionable ability of phallotoxins to bind the whole complement of F-actin necessitate further optimization of actin immunofluorescence methods. We have compared two procedures: (1) formaldehyde fixation and (2) rapid freezing and freeze substitution (cryofixation), both followed by embedding in low-melting polyester wax. Actin immunofluorescence in sections of garden cress (Lepidium sativum L.) root gave similar results with both methods. The compatibility of aldehydes with actin immunodetection was further confirmed by the freeze-shattering technique that does not require embedding after aldehyde fixation. It appears that rather than aldehyde fixation, some further steps in the procedures used for actin visualization are critical for preserving F-actin. Wax embedding, combined with formaldehyde fixation, has proved to be also suitable for the detection of a wide range of other antigens.

Actins↗

Epidemiology of erectile dysfunction: results of the 'Cologne Male Survey'.

The last few decades have seen a marked increase in mean life expectancy in Central Europe. This has made elderly people and their quality of life a matter of ever-increasing medical concern. Available data from the United States and Scandinavia relating to erectile dysfunction (ED) do not enable us to draw valid conclusions about the current situation in Germany. The aim of the present study was to evaluate the epidemiology of male sexuality in Germany, and the proportion of men who need medical treatment because of increased suffering from this.A newly developed and validated questionnaire on male erectile dysfunction was mailed to a representative population sample of 8000 men, 30-80 y of age in the Cologne urban district. The response included 4489 evaluable replies (56.1%). The response rates in different age groups ranged from 49.2% to 68.4%. Regular sexual activity was reported by 96.0% (youngest age group) to 71.3% (oldest group). There were 31.5%-44% of responders who were dissatisfied with their current sex life. The prevalence of ED was 19.2%, with a steep age-related increase (2.3-53.4%) and a high co-morbidity of ED with hypertension, diabetes, pelvic surgery and 'lower urinary tract symptoms'. When treatment need was defined by co-occurrence of ED and dissatisfaction with sex life, 6.9% men required treatment for ED. Oral treatment of ED was preferred by 73.8% of respondents. There were 46.2% respondents who were willing to contribute more than DM 50 (25 Euro) per month for ED treatment. We conclude that regular sexual activity is a normal finding in advanced age. ED is a frequent disorder, contributing to dissatisfaction with sex life in a considerable proportion of men. The high burden of ED is reflected in willingness to pay for treatment. ED is frequently associated with chronic diseases. Therefore adequate diagnostic workup is essential, to offer patients individually adapted treatment. General non-reimbursability of treatment for ED appears to be unacceptable.

Adult↗

The C5a receptor is expressed by human renal proximal tubular epithelial cells.

The C5a receptor is expressed by a variety of cell types. These studies demonstrate by immunohistochemistry that the receptor is present on the surface of proximal and distal tubular epithelial cells from normal kidney. In addition, the receptor was detected on transitional epithelial cells of the ureter and bladder. Primary proximal tubular cultures and a proximal tubular cell line both also expressed the C5a receptor, as demonstrated by immunofluorescence and by FACS analysis. The presence of mRNA encoding the receptor was confirmed by reverse transcriptase-polymerase chain reaction analysis. As opposed to its effect on glomerular mesangial cells, the receptor did not mediate a proliferative response by the proximal tubular cells. C5a also did not enhance the synthesis/secretion of transforming growth factor-beta 1, monocyte chemoattractant protein-1, platelet-derived growth factor-AB or tumour necrosis factor-alpha by cultured proximal tubular cells. Therefore, although the C5a receptor clearly is expressed by proximal tubular cells, clarification of its functional relevance on this cell type awaits further studies.

Antigens, CD↗

Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes.

The expression of CR2 (CD21) by synovial B and T lymphocytes of patients suffering from various forms of arthritis was analysed with cytofluorometry and with reverse transcriptase-polymerase chain reaction. CR2 (CD21) cell surface protein was detected in normal quantities on peripheral B cells, but was almost absent on synovial B lymphocytes of the same patients. This reduction was most severe in patients with rheumatoid arthritis, but also observed in all other cases. CR2 (CD21) did not reappear after in vitro culture. CR2 (CD21) mRNA was also strongly reduced in synovial B and T lymphocytes. Synovial fluid B lymphocytes were larger than peripheral blood B lymphocytes, while T cells from the same patients showed no size differences. We conclude that synovial fluid B lymphocytes have undergone an irreversible step towards terminal differentiation. The presence or absence of CR2 (CD21) mRNA in peripheral versus synovial T cells indicates that CR2 (CD21) is also differentially expressed by T lymphocytes.

Adult↗

Plant cells on earth and in space.

Two quite different types of plant cells are analysed with regard to transduction of the gravity stimulus: (i) Unicellular rhizoids and protonemata of characean green algae; these are tube-like, tip-growing cells which respond to the direction of gravity. (ii) Columella cells located in the center of the root cap of higher plants; these cells (statocytes) perceive gravity. The two cell types contain heavy particles or organelles (statoliths) which sediment in the field of gravity, thereby inducing the graviresponse. Both cell types were studied under microgravity conditions (10(-4) g) in sounding rockets or spacelabs. From video microscopy of living Chara cells and different experiments with both cell types it was concluded that the position of statoliths depends on the balance of two forces, i.e. the gravitational force and the counteracting force mediated by actin microfilaments. The actomyosin system may be the missing link between the gravity-dependent movement of statoliths and the gravity receptor(s); it may also function as an amplifier.

Actins↗

Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.

Granzyme B is the prototypic member of the granzymes, a family of trypsin-like serine proteinases localized in the dense cytoplasmic granules of activated natural killer cells and cytotoxic T lymphocytes. Granzyme B directly triggers apoptosis in target cells by activating the caspase pathway, and has been implicated in the etiology of rheumatoid arthritis. Human granzyme B expressed in a baculovirus system has been crystallized without inhibitor and its structure has been determined to 3.1 A resolution, after considerably improving the diffraction power of the crystals by controlled humidity changes. The granzyme B structure reveals an overall fold similar to that found in cathepsin G and human chymase. The guanidinium group of Arg226, anchored at the back of the S1-specificity pocket, can form a salt bridge with the P1-Asp side chain of a bound peptide substrate. The architecture of the substrate binding site of granzyme B appears to be designed to accommodate and cleave hexapeptides such as the sequence Ile-Glu-Thr-Asp-/Ser-Gly present in the activation site of pro-caspase-3, a proven physiological substrate of granzyme B. These granzyme B crystals, with fully accessible active sites, are well suited for soaking with small synthetic inhibitors that might be used for a treatment of chronic inflammatory disorders.

Amino Acid Sequence↗

Molecular characterisation of pancreatic zymogen granule ion channel and regulator proteins involved in exocytosis.

In pancreatic acinar cells Ca(2+)-dependent secretagogues promote the fusion of zymogen granules (ZG) with the apical plasma membrane (PM) and exocytosis of digestive enzymes. In addition to exocytotic fusion complexes between SNARE proteins in the ZG membrane (ZGM) and the apical PM, enzyme secretion elicited by Ca(2+)-dependent secretagogues requires cytosolic Cl and K+ and is inhibited by blockers of Cl- and K+-channels. We have identified a Cl-conductance activated by ATP, and a K+-conductance (with properties similar to ATP-sensitive K+-channels), regulated by the granule matrix protein Zg-16p in the ZGM. Both conductances are inversely regulated by a 65-kD mdr1 gene product. We have also identified a novel Ca(2+)-activated anion conductance in ZGM, the Ca(2+)-sensitivity of which increases 50-fold when Cl is replaced by 1. This conductance is blocked by micromolar H2-DIDS or DTT, reminiscent of a family of epithelial Ca(2+)-activated Cl -channels (CaCC). Expression of a CaCC in exocrine pancreas has been confirmed by RT-PCR analysis, and by immunoblotting and immunogold labeling of ZG membranes. These data suggest that ion channels in the ZGM are essential elements in pancreatic exocytosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Photoaffinity labeling and purification of ZG-16p, a high-affinity dihydropyridine binding protein of rat pancreatic zymogen granule membranes that regulates a K(+)-selective conductance.

In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyridine derivative (-)-[(3)H]BZDC-DHP, a recently developed high-affinity ligand for Mdr1, binds with similar affinity to ZG membranes (ZGM) (K(d) = 6.2 nM). Binding was inhibited by nanomolar concentrations of the L-type Ca(2+) channel blockers azidopine and verapamil and by micromolar concentrations of the K(+) channel blockers glibenclamide and quinidine. Inhibition by glibenclamide was noncompetitive. The Mdr1 modulators cyclosporin A and vinblastine did not inhibit binding, which is different from Mdr1. In addition, only (+/-)-BZDC-DHP, azidopine, and verapamil selectively inhibited the K(+) conductance in ZGs, whereas the Cl(-) conductance was not affected. In photoaffinity labeling experiments, (-)-[(3)H]BZDC-DHP surprisingly specifically and selectively labeled a approximately 19-kDa protein in ZGM with a pharmacological profile identical with the high-affinity binding site but did not label a 65-kDa protein. The 19-kDa protein was purified by ion exchange chromatography and SDS-polyacrylamide gel electrophoresis and sequenced. The sequence obtained corresponds to ZG-16p, a recently cloned ZG protein with no apparent homology to Mdr1. The identity of the 19-kDa protein was confirmed by immunoprecipitation of (-)-[(3)H]BZDC-DHP-labeled ZGM with an anti-ZG-16p antibody. Furthermore, it is shown that ZG-16p is associated with the ZGM. We propose that ZG-16p, as part of the submembranous granule matrix, regulates the ATP-sensitive K(+) conductance of ZGs.

Adenosine Triphosphate↗

[Exploration of visual memory by functional MRI].

PURPOSE: The aim of our study was to evidence the location of the cortical area triggered by visual memory tasks by he mean of functional magnetic resonance imaging examination (fMRI). METHODS: Twelve healthy volunteers underwent fMRI examination on a 1.5 Tesla magnet with echoplanar imaging sequence during figurative and non-figurative memory tasks. An area was considered to be activated if at least 10 contiguous voxels activation was noted. Activated areas were defined for both tasks and the brain mapping was realized according to Talairach atlas. RESULTS: For all examinations a bilateral activity was evidenced (area 17 and 18). In addition, a frontal activation was also noted in 83% of the cases for both tasks. However, frontal activation was bilateral in 9/10 cases for the figurative task and 6/10 cases for the non-figurative task. CONCLUSION: FMRI was able to evidence activation of cerebral areas during visual memory tasks in all our study cases. Frontal activation was not discriminative of figurative or non figurative memory. This might be probably explain by inappropriate non-figurative tests. FMRI should allow a better knowledge of memory mechanisms as well as an enhancement of functional cerebral mapping before surgery.

Adult↗

It takes two.

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Education, Medical↗

[Radioanatomy of the cerebral cortex. Practical guide of identification].

Cerebral sulci identification process is based on several formal rules: it consists a series of steps allowing the identification of the major sulci. The process may be variable for each of us and we propose to read the images in certain order starting with the frontal lobe and its superior frontal gyrus than precentral and central gyri followed by the lateral fissure. Then the insular, lateral parietal and medial hemispheric regions. Finally the major sulci within the temporal and occipital lobes are described in the frontal plane. This presentation indicates the principal rules of cerebral lobes'identification, the basis of variability perception and the localization of small lesions allowing an accurate correlation with clinical findings and a suitable therapeutic procedure.

Cerebral Cortex↗

Factor Xa acts as a PDGF-independent mitogen in human vascular smooth muscle cells.

This study investigates the mitogenic effect of the coagulation factor Xa in smooth muscle cells (SMC) from human saphenous vein and the procoagulant activity of these cells. Factor Xa elicited a concentration-dependent increase in [3H]thymidine incorporation. This mitogenic effect of factor Xa was inhibited by DX-9065a and BABCH, indicating the requirement of proteolytic activity of the enzyme. Factor Xa activated the MAP kinases ERK1/2 concentration- and time-dependently. PDGF-neutralizing antibodies neither inhibited the increase in [3H]thymidine incorporation nor ERK-1/2 phosphorylation in factor Xa-stimulated cells, suggesting that factor Xa-induced signaling and mitogenic activity in human venous SMC are independent of PDGF. Exposure of SMC to recalcified plasma resulted in a significant thrombin generation which was inhibited by anti-tissue factor antibody, tissue factor pathway inhibitor, inactivated factor VIIa and DX-9065a. These data indicate that interaction of SMC with the clotting system may contribute to venous graft disease, i.e. thrombus formation and intimal hyperplasia.

Blood Coagulation↗

[The mesorectum: improvement and anatomy of a semantic error].

AIMS: The cancer of the rectum touches 10,000 patients per year in France. Its treatment is mainly surgical. 50% of the treated patients will die of their cancer, either by loco-regional recurrence, or by metastatic disease. The rates of local recurrence vary from 10 to 40%. Heald is first who brought back recurrence rates lower than 4%, results obtained by the only surgical treatment. This treatment included the total exeresis of cellulo-fatty tissue surrounding the rectum, tissue which was baptized mesorectum. The aims of this work is to define and describe this space, and to discuss its Christian name. MATERIAL AND METHODS: The anatomical study carries on the dissection of 2 frozen pelvis of fresh man, one cut transversely on the level of L4, the other half-compartment sagittaly, then defrosted for the dissection. RESULTS: The mesorectum is defined and its various structures, fascia, vessels and nerves, are detailed. CONCLUSION: The mesorectum is an anatomical and surgical structure individualisable. Its recognition and its importance were born from the understanding of the fascia and the rectal anatomy. Its exeresis decreases the rate of the local recurrence (18). The technique of exeresis of the mesorectum must be validated, standardized, in order to be reproducible in the treatment of the cancer of the rectum.

Female↗

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Animals↗

A rapid method to separate endosomes from lysosomal contents using differential centrifugation and hypotonic lysis of lysosomes.

Here we describe a fast and efficient subcellular fractionation procedure that permits lysosomes to be separated from endosomes. Differential centrifugation is used to isolate a subcellular fraction containing both endosomes and lysosomes. Because lysosomes are sensitive to osmotic stress, hypotonic conditions destroy them, whereas endosomes, which are osmotically insensitive, stay intact. We demonstrate that hypotonic lysis of an endosome-lysosome-pool releases 85% of the lysosomes into the supernatant as measured by the activity of the lysosomal marker enzyme N-acetyl-beta-D-glucosaminidase (beta-AGA). The endosomal fraction is thoroughly characterised using a variety of subcellular markers. After pulsing cells with fluorescein isothiocyanate labelled transferrin (FITC-Tf), only about 12% of the marker is released under hypotonic conditions. A typical fractionation procedure takes about 1-2 h from initial cell homogenisation. The fractionation gives a pure lysosomal fraction (fraction L) containing high activities of lysosomal enzymes and an endosomal fraction (fraction E) reflecting different stages of endosomes.

Antigens, Differentiation, B-Lymphocyte↗

The stimulatory action of tolbutamide on Ca2+-dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein.

Intracellular application of the sulfonylurea tolbutamide during whole-cell patch-clamp recordings stimulated exocytosis >5-fold when applied at a cytoplasmic Ca2+ concentration of 0.17 microM. This effect was not detectable in the complete absence of cytoplasmic Ca2+ and when exocytosis was elicited by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The stimulatory action could be antagonized by the sulfonamide diazoxide, by the Cl--channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), by intracellular application of the antibody JSB1 [originally raised against a 170-kDa multidrug resistance (mdr) protein], and by tamoxifen (an inhibitor of the mdr- and volume-regulated Cl- channels). Immunocytochemistry and Western blot analyses revealed that JSB1 recognizes a 65-kDa protein in the secretory granules. This protein exhibited no detectable binding of sulfonylureas and is distinct from the 140-kDa sulfonylurea high-affinity sulfonylurea receptors also present in the granules. We conclude that (i) tolbutamide stimulates Ca2+-dependent exocytosis secondary to its binding to a 140-kDa high-affinity sulfonylurea receptor in the secretory granules; and (ii) a granular 65-kDa mdr-like protein mediates the action. The processes thus initiated culminate in the activation of a granular Cl- conductance. We speculate that the activation of granular Cl- fluxes promotes exocytosis (possibly by providing the energy required for membrane fusion) by inducing water uptake and an increased intragranular hydrostatic pressure.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗