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Biomedical subjects

M Braun

Publications and source records attributed to M Braun.

At least 181 records · Page 10Linked to original sources

Enzymatic properties of chorismate synthase isozymes of tomato (Lycopersicon esculentum Mill.).

Three plastidic chorismate synthase isozymes (CS1, CS2 and CS2 delta) of tomato were identified by isolation of the corresponding cDNAs. These three cDNAs are derived from only two genes (LeCS1 and LeCS2). This additional complexity results from differential splicing of the primary transcript of one of the genes (LeCS2) giving rise to two different transcripts (CS2 and CS2 delta transcripts). All three isozymes were individually expressed in Escherichia coli both as precursor proteins with N-terminal transit peptides and as mature proteins. Only the mature but not the precursor isozymes CS1 and CS2 were enzymatically active. The enzyme CS2 delta was unstable in E. coli. Both CS1 and CS2 were purified to near homogeneity and their enzymatic properties were analyzed. They differ substantially in their Km values for the substrate 5-enol-pyruvylshikimate 3-phosphate (11 and 80 microM for the mature forms of CS1 and CS2, respectively). The two isozymes appear to be active only as oligomers, and the potential physiological implications of this result are discussed.

Amino Acid Sequence↗

Pontine veins. MRI cross-sectional anatomy.

The pons is covered by a rich venous network offering numerous vascular landmarks in MRI and during surgery. We present an original study of the veins as they appear on MR multiplanar scans after gadolinium IV injection. This prospective study is based on 40 consecutive patients with normal posterior fossa structures. One of the major venous collectors follows the pons: the superior petrosal v. was identified on MRI in 95% of our cases. Its hooklike extremity drains into the superior petrosal sinus. The inferior petrosal v. was never identifiable. The superficial pontine venous network are identified in 72.5% of cases in the axial plane and were organised in longitudinal and transverse collectors, whose MR aspects are presented here.

Humans↗

The veins of the medulla oblongata: MRI cross-sectional anatomy.

Magnetic resonance imaging (MRI) has progressively become the major or even the only imaging procedure for displaying the vascular relationships of the brainstem in the context of infra-tentorial lesions. In order to assess the MR sectional anatomy of the bulbar vv. 40 normal patients were examined in the MR axial, frontal and sagittal planes after gadolinium i.v. injection. The bulbar venous networks were inconstantly visualised: anterior vv. (16%). posterior (3%), lateral (8%). The vein of the lateral recess of the fourth ventricle was constant in the three planes; the inferior petrosal sinus could be seen in 82% of cases. Their relation with the posterior fossa structures are emphasised and discussed.

Contrast Media↗

19F NMR spectroscopy of glass ceramics containing fluorapatites.

Glass ceramics which contain apatite crystals are used as implant materials in medicine. Because most of these glass ceramics are comprised of fluoride-containing glass compositions, the apatites should be fluoride-containing apatites. The fluorine content of these apatites is important for medical applications. The purpose of the current study was to determine the possibilities of measuring the fluorine content of these apatites. High resolution solid state 19F Magic Angle Spinning (MAS) Nuclear Magnetic Resonance (NMR) spectra of apatite-containing glass ceramics have been obtained. Using the correlation between the isotropic 19F chemical shift and the fluorine content, it was possible to determine the fluorine content of the apatites.

Apatites↗

Phase II trial of intravenous endotoxin in patients with colorectal and non-small cell lung cancer.

We report the immunological and clinical results of a phase II trial with intravenously administered highly purified endotoxin (Salmonella abortus equi) in patients with advanced cancer. 15 patients with non-small cell lung cancer and 27 with colorectal cancer were entered into the study. 37 evaluable patients received at least four injections of endotoxin (4 ng/kg body weight) and 1600 mg ibuprofen orally in 2-week intervals. Transient renal (WHO grade 0-1) and hepatic (WHO grade 0-4) toxicities occurred in several patients. Constitutional side-effects such as fever, chills and hypotension could not be prevented completely by pretreatment with ibuprofen. 3 patients in the colorectal cancer group demonstrated objective responses (1 complete remission (CR), 2 partial remission (PR)). The complete remission has been maintained for more than 3 years, while the partial remissions were stable for 7 and 8 months, respectively. Only marginal antitumour effects were seen in the lung cancer group. Tolerance of the macrophage system to the stimulatory effect of endotoxin, as measured by human necrosis factor alpha (TNF-alpha) release into serum, built up after the first administration and remained at a steady-state level after each subsequent injection. In constrast, rising CD4:CD8 ratio and release of tumour necrosis factor beta (TNF-beta) indicated the continuing activation of the lymphocyte system by repetitive injections of endotoxin.

Adult↗

Ochrobactrum anthropi endophthalmitis after uncomplicated cataract surgery.

PURPOSE: To treat a case of Ochrobactrum anthropi endophthalmitis after uneventful cataract surgery. METHODS: A 66-year-old patient in good general health underwent uncomplicated cataract surgery in his right eye. Seven weeks later, pars plana vitrectomy with removal of the intraocular lens became necessary because of progressive low-grade endophthalmitis resistant to topical and systemic erythromycin, cephalosporins, aminoglycosides, and colistin. RESULTS: Microbiologic examination of the vitreous biopsy, capsule, and anterior chamber fluid disclosed O. anthropi, a nonfermentative gram-negative bacillus sensitive to imipenem, amikacin, ciprofloxacin, and vancomycin. CONCLUSION: Ochrobactrum anthropi and its natural resistance against many antibiotics should be considered in the treatment of low-grade endophthalmitis after uneventful cataract surgery.

Aged↗

Enantioselective depletion of mitochondrial glutathione concentrations by (S)- and (R)-3-hydroxy-4-pentenoate.

(R,S)-3-Hydroxy-4-pentenoate rapidly and selectively depletes the mitochondrial glutathione pool in rat hepatocytes, but shows little cytotoxicity and does not induce mitochondrial dysfunction [Shan, X., et al. (1993) Chem. Res. Toxicol. 6, 75-81]. The objective of the present studies was to investigate the 3-hydroxybutanoate dehydrogenase-dependent oxidation of (R)- and (S)-3-hydroxy-4-pentenoate and the enantioselectivity of 3-hydroxy-4-pentenoate-induced depletion of mitochondrial glutathione concentrations in isolated rat liver mitochondria and hepatocytes. (S)-3-Hydroxy-4-pentenoate, but not (R)-3-hydroxy-4-pentenoate, was a substrate for 3-hydroxybutanoate dehydrogenase. Incubation of rat liver mitochondria or hepatocytes with (S)-3-hydroxy-4-pentenoate resulted in a time- and concentration-dependent depletion of mitochondrial glutathione concentrations, whereas (R)-3-hydroxy-4-pentenoate produced little depletion. These results show that (S)-3-hydroxy-4-pentenoate is a substrate for 3-hydroxy-butanoate dehydrogenase and is converted to the Michael acceptor 3-oxo-4-pentenoate, which reacts with glutathione and thereby depletes the mitochondrial glutathione pool. (S)-3-Hydroxy-4-pentenoate may find use in the study of mitochondrial glutathione homeostasis and the role of mitochondrial glutathione in cellular protection.

Animals↗

Saccharomyces cerevisiae chorismate synthase has a flavin reductase activity.

Chorismate synthase (CS) catalyses the conversion of 5-enolpyruvylshikimate 3-phosphate (EPSP) to form chorismate, which is the last common intermediate in the synthesis of the three aromatic amino acids phenylalanine, tyrosine and tryptophan. Despite the overall redox-neutral reaction, catalysis has an absolute requirement for reduced flavin. In the fungus Neurospora crassa, a flavin reductase (FR) activity able to generate reduced flavin mononucleotide in the presence of NADPH is an intrinsic feature of a bifunctional CS. In all bacterial and plant species investigated to date, purified CSs lack an FR activity and are correspondingly 8-10 kDa smaller than the N. crassa CS (on the basis of SDS-PAGE). The cloning of N. crassa CS and subsequent characterization of the purified heterologously expressed enzyme indicates that, surprisingly, the FR probably resides within a region conserved amongst both mono- and bifunctional CSs and is not related to non-homologous sequences which contribute to the larger molecular mass of the N. crassa CS. This information directed this work towards the smaller Saccharomyces cerevisiae CS, the sequence of which was known, although the protein has not been extensively characterized biochemically. Here the characterization of the S. cerevisiae CS is reported in more detail and it is shown that the protein is also bifunctional. With this knowledge, S. cerevisiae could be used as a genetic system for studying the physiological consequences of bifunctionality. The phylogenetic relationship amongst known CSs is discussed.

Amino Acid Sequence↗

[Juvenile open angle glaucoma with microcornea in oculo-dento-digital dysplasia (Meyer-Schwickerath-Weyers syndrome)].

HISTORY: An 8-year boy underwent bilateral repeat trabeculectomies with iridectomies at age 4 and 5 and cyclocryocoagulation of the right eye at age seven for glaucoma. FINDINGS: The first examination in our department revealed a visual acuity of OD light perception, OS 0.2. The right eye was exotropic and hypotropic. The intraocular pressure was 30 mm Hg in both eyes. The corneal diameters were OD 9.0 x 7.0 and OS 8.5 x 6.5 mm, while the axial length was OD 25.3 and OS 23.6 mm. Both eyes had slightly prominent filter blebs with uveal incarceration. The chamber angles were open in both eyes and partly covered with uveal tissue, the E/P ratio was OD 1.0, OS 0.9. Extraocular changes were: dysplastic teeth, dental enamel hypoplasia, thickened jaw, small nose with pronounced nose bridge. Both hands showed shortening of the metacarpals and of the IVth digits as compared to the IInd and IIIrd digits. Syndactylic digits IV and V had been surgically separated earlier. DIAGNOSIS: Our diagnosis was juvenile open-angle glaucoma in oculo-dento-digital dysplasia. THERAPY: After trabeculotomy and cyclocryocoagulation IOP remained around 10 mm Hg. CONCLUSIONS: Despite small corneal diameters, congenital glaucoma needs to be ruled out early in patients with oculo-dento-digital dysplasia. These patients should be treated in close cooperation with pediatric neurologists, orthopedic surgeons, dentists and otorhinolaryngologists.

Abnormalities, Multiple↗

[Band-like corneal degeneration as the initial sign of sarcoidosis].

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Ocular involvement has been reported in about 25% of patients (1). Band keratopathy is rare in sarcoidosis. PATIENT: A 31 year-old clerk presented to our clinic with a 10 months' history of foreign body sensation OU. Visual acuity was OD1.2, OS 1.0. Intraocular pressure was 10 mm Hg OU. We found a moderate band keratopathy OU (Fig. 1a, 1b). The rest of the ocular exam was unremarkable. 10 months before, the patient had experienced symmetrical swelling of his large joints and his creatinine and calcium levels had been elevated at that time. Therefore, we referred the patient to the internist to rule out primary hyperparathyroidism (2). The differential diagnosis included myeloma, paraneoplasia and sarcoidosis (3). The general medical examination was unremarkable. Calcium (2.5 mmol/l), creatinine (2.0 mg/dl) and ACE-levels (177 U/ml) were elevated, parathormone (< 1.4 pg/ml) was low. The chest x-ray showed reticular, small-nodular changes of both lungs. Pulmonary function tests and the bronchial mucosa were normal. The CD4/CD8-ratio was markedly elevated. Ultrasonography of the kidneys suggested nephrocalcinosis. This was confirmed by kidney biopsy. Histologic findings were consistent with the diagnosis of sarcoidosis. After initial symptomatic reduction of calcium levels by forced diuresis, calcium and creatinine levels were lowered by administration of 60 mg prednisolone daily. Six months after presenting to our clinic the patient is well on low-dose steroids and his calcium levels are normal. DISCUSSION: Primary hyperthyroidism was ruled out by low PTH-levels. Because of clinical, serologic and radiologic findings suggestive of sarcoidosis, bronchoscopy with bronchoalveolar lavage was performed. Since the CD 4/CD 8-ratio was increased, a kidney biopsy was performed which confirmed the diagnosis.

Adult↗

Monte Carlo and experimental evaluation of accuracy and noise properties of two scatter correction methods for SPECT.

Scatter correction is a prerequisite for quantitative SPECT, but potentially increases noise. Monte Carlo simulations (EGS4) and physical phantom measurements were used to compare accuracy and noise properties of two scatter correction techniques: the triple-energy window (TEW), and the transmission dependent convolution subtraction (TDCS) techniques. Two scatter functions were investigated for TDCS: (i) the originally proposed mono-exponential function (TDCSmono) and (ii) an exponential plus Gaussian scatter function (TDCSGauss) demonstrated to be superior from our Monte Carlo simulations. Signal to noise ratio (S/N) and accuracy were investigated in cylindrical phantoms and a chest phantom. Results from each method were compared to the true primary counts (simulations), or known activity concentrations (phantom studies). 99mTc was used in all cases. The optimized TDCS(Gauss) method overall performed best, with an accuracy of better than 4% for all simulations and physical phantom studies. Maximum errors for TEW and TDCS(mono) of -30 and -22%, respectively, were observed in the heart chamber of the simulated chest phantom. TEW had the worst S/N ratio of the three techniques. The S/N ratios of the two TDCS methods were similar and only slightly lower than those of simulated true primary data. Thus, accurate quantitation can be obtained with TDCS(Gauss), with a relatively small reduction in S/N ratio.

Air↗

Minimum cross-entropy reconstruction of PET images using prior anatomical information.

An algorithm is presented for the reconstruction of PET images using prior anatomical information derived from MR images of the same subject. The cross-entropy or Kullback-Leiber distance is a measure of dissimilarity between two images. We propose to reconstruct PET images by minimizing a weighted sum of two cross-entropy terms. The first is the cross-entropy between the measured emission data and the forward projection of the current estimate of the PET image. Minimizing this term alone is equivalent to the ML-EM reconstruction. The second term is the cross-entropy between the current estimate of the PET image and a prior image model which incorporates anatomical information derived from registered MR images. A weighting parameter determines the relative emphasis given to the emission data and the prior model in the reconstruction. Details of this algorithm are presented as well as test reconstructions for real and simulated data. The performance of the algorithm was evaluated with respect to errors in prior anatomical information. The algorithm provided significant improvement in the quality of reconstructed images as compared with the ML-EM reconstruction technique. The reconstructed images had higher resolution as compared with the images obtained from MAP-like reconstructions which do not utilize anatomical information. The algorithm displayed robustness with respect to errors in prior anatomical information.

Algorithms↗

Pharmacokinetic and pharmacodynamic interactions between omeprazole and amoxycillin in Helicobacter pylori-positive healthy subjects.

BACKGROUND: Omeprazole with amoxycillin has been used to treat Helicobacter pylori infection. It was speculated that omeprazole-induced hypoacidity enhances the antibacterial activity of amoxycillin. Limited information exists about intragastric pH and bioavailability of amoxycillin during combination therapy. No data are available about possible effects of the antibiotic on the pharmacokinetics and pharmacodynamics of omeprazole. METHODS: The study was performed in a three-way cross-over double-blind design. After a run-in period on placebo with a baseline intragastric pH-metry, 24 H. pylori-positive healthy subjects were randomly dosed with amoxycillin 750 mg b.d. + placebo, amoxycillin 750 mg b.d. + omeprazole 40 mg b.d. and omeprazole 40 mg b.d. + placebo for 5 days. On the last day of each regimen intragastric pH-metries were performed, and blood samples taken for omeprazole and amoxycillin serum profiles. RESULTS: Amoxycillin monotherapy had no acid-inhibiting effect. Median pH during combined dosing was significantly lower, compared to omeprazole monotherapy (P < 0.01). Mean serum concentrations of omeprazole and amoxycillin given alone or in combination were not different. CONCLUSIONS: High-dose omeprazole does not alter the pharmacokinetics of amoxycillin. The significantly lower intragastric pH during combination therapy might be due to the H. pylori-suppressive effect of this treatment.

Adult↗

Arteriovenous malformations of the corpus callosum--radioanatomic study and effectiveness of intranidus embolization.

Forty-three patients with arteriovenous malformations (AVMs) of the corpus callosum treated by embolization were reviewed. The following clinical and radioanatomic characteristics were found: 84% (36 patients) presented with intracranial hemorrhage, 43% (20 nidi) of the lesions were located in the posterior half of the corpus callosum, multiple nidi were more frequent (21%) than expected, 27 nidi (59%) were fed by branches of both the anterior and posterior cerebral arteries, AVMs mainly drained into the internal cerebral vein and/or interhemispheric superficial veins, and 19 (41%) had both draining pathways, 10 patients (23%) had impaired drainage through the straight sinus due to dysplasia. Staged embolization was performed in 245 feeders. Curative occlusion (more than 95%) was obtained in 17 patients (40%) and considerable occlusion (more than 75%) in 33 patients (77%). Large and giant, diffuse-type, and multifocal AVMs were difficult to completely embolize. Complications associated with embolization occurred in six patients, mostly during the first 5 years. Only two patients had a permanent deficit related to a complication. Overall morbidity and mortality were 7% and 2%, respectively. Nine patients were referred for stereotactic radiosurgery, three of whom were completely cured and five patients have not been assessed. Most AVMs in the corpus callosum are supplied by multi-axial feeders, so multi-target intranidus embolization is very important to prevent the development of other feeders secondary to the hemodynamic shift. Combined therapy using maximum embolization and subsequent radiosurgery may be the most effective method to treat AVMs in the corpus callosum.

Adolescent↗

Estimated versus predicted creatinine generation as an indicator of compliance with the prescribed dose of continuous peritoneal dialysis.

The expression (Estimated-Predicted)/Predicted creatinine generation ¿(E-P)/P¿ has been proposed as an index of compliance in continuous peritoneal dialysis (CPD). We attempted to define an (E-P)/P value that can be used as a cut-off for non-compliance and to characterize the relation of (E-P)/P to serum albumin. In 324 clearance studies, (E-P)/P had a normal distribution with a mean of +0.094 and an SD of 0.357. In these studies, there was a weak correlation between (E-P)/P and serum albumin (r = 0.12, P < 0.05), but (E-P)/P was not a predictor of serum albumin by logistic regression. In 34 CPD patients, who had an increase in the dose of CPD resulting in an increase in measured creatinine clearance from 43.8 +/- 14.0 to 66.1 +/- 17.6 L/1.73 m2 weekly (P < 0.001), (E-P)/P increased correspondingly from +0.018 +/- 0.284 to +0.153 +/- 0.369 (P = 0.018), although all subjects should be in a steady state of creatinine excretion in the second study. The rise in (E-P)/P was statistically significant in the subgroup of 17 subjects who had a decrease in serum albumin, but not in the subgroup of 14 subjects who had an increase in serum albumin from the first to the second clearance study. The (E-P)/P cut-off for a definitive diagnosis of CPD non-compliance may be around +0.400 or +0.500. The findings of this study suggest that non-compliance, as indicated by (E-P)/P, has an adverse effect on serum albumin and that non-compliance increases after a prescribed increase in the dose of CPD.

Creatinine↗

Impediment of basilar membrane motion reduces overload protection but not threshold sensitivity: evidence from clinical and experimental hydrops.

The mechanical function of the basilar membrane (BM) in the mammalian cochlea has been newly debated after the discovery of frequency selectivity of single hair cells. Decisive information on this matter can be expected from hydropic ears, since hydrops presumably alters cochlear mechanics by (1) impeding BM motion and (2) uncoupling outer hair cell (OHC) stereocilia from the tectorial membrane (TM). Therefore hearing in Menière's disease (MD) was examined analysing data on epidemiology of MD types and audiogram types, 2f thresholds, over-recruitment, loudness intolerance, and otoacoustic emissions. Further, hearing in experimental hydrops (XH) was examined analysing data on: morphological changes on TM and OHCs in relation to hydrops duration; morphological and electrophysiological changes upon acoustic overstimulation. The results were unequivocal on two points: (1) co-occurrence of hydrops and normal hearing thresholds can appear both in MD and XH, (2) co-occurrence of non-hearing-loss hydrops and loudness hypersensitivity is typical both in MD and XH. The conclusion is that BM motion apparently is no necessary element in the chain of cochlear sound transmission but obviously is an auxiliary element for overload protection through resonant absorption. The results are further indicative of audiometric methods for an early detection of incipient MD.

Animals↗