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Biomedical subjects

L Hofmann

Publications and source records attributed to L Hofmann.

18 recordsLinked to original sources

Quantitative 1H-magnetic resonance spectroscopy of human brain: Influence of composition and parameterization of the basis set in linear combination model-fitting.

Localized short-echo-time (1)H-MR spectra of human brain contain contributions of many low-molecular-weight metabolites and baseline contributions of macromolecules. Two approaches to model such spectra are compared and the data acquisition sequence, optimized for reproducibility, is presented. Modeling relies on prior knowledge constraints and linear combination of metabolite spectra. Investigated was what can be gained by basis parameterization, i.e., description of basis spectra as sums of parametric lineshapes. Effects of basis composition and addition of experimentally measured macromolecular baselines were investigated also. Both fitting methods yielded quantitatively similar values, model deviations, error estimates, and reproducibility in the evaluation of 64 spectra of human gray and white matter from 40 subjects. Major advantages of parameterized basis functions are the possibilities to evaluate fitting parameters separately, to treat subgroup spectra as independent moieties, and to incorporate deviations from straightforward metabolite models. It was found that most of the 22 basis metabolites used may provide meaningful data when comparing patient cohorts. In individual spectra, sums of closely related metabolites are often more meaningful. Inclusion of a macromolecular basis component leads to relatively small, but significantly different tissue content for most metabolites. It provides a means to quantitate baseline contributions that may contain crucial clinical information.

Adolescent↗

Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy.

Biochemical maturation of the brain can be studied noninvasively by (1)H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short-TE (1)H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32-43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, gamma-aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo-inositol, macromolecular contributions, N-acetylaspartate, N-acetylaspartylglutamate, o-phosphoethanolamine, scyllo-inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N-acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight.

Aspartic Acid↗

Characterization of the macromolecule baseline in localized (1)H-MR spectra of human brain.

Short-echo-time magnetic resonance spectra of human brain contain broad contributions from macromolecules. As they are a priori of unknown shape and intensity, they pose a problem if one wants to quantitate the overlying spectral features from low-molecular-weight metabolites. On the other hand, the macromolecular contributions may provide relevant clinical information themselves, if properly evaluated. Several methods, based on T(1), T(2), or spectral shape, have previously been suggested to suppress or edit the macromolecule contributions. Here, a method is presented based on a series of saturation recovery scans and that allows for simultaneous recording of the macromolecular baseline and the fully relaxed metabolite spectrum. In comparison to an inversion recovery technique aimed at nulling signals from long-T(1) components, the saturation recovery method is less susceptible to T(1) differences inherent in signals from different metabolites or introduced by pathology. The saturation recovery method was used to quantitate the macromolecular baseline in white and/or gray matter locations of the human brain in 40 subjects. It was found that the content and composition of MR visible macromolecules depends on cerebral location, as well as the age of the investigated subject, while no gender dependence could be found.

Adult↗

Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission.

To explore the role of endogenous GABA in NMDA antagonist induced dopamine (DA) release, we used in vivo microdialysis to study the effects of pretreatment with gamma-vinyl GABA (GVG) on phencyclidine (PCP)-induced DA release in terminal regions of midbrain DA neurons. GVG, an irreversible inhibitor of the GABA catabolizing enzyme GABA-AT, significantly reduced the DA response to PCP (7.0 mg/kg) in freely moving animals. Preferential increases in PCP-induced DA release in the PFC (four-fold those of NAcc) were dose-dependently inhibited by acute pretreatment with GVG at doses of 150 (51% inhibition), 300 (68% inhibition), and 500 (82% inhibition) mg/kg, whereas NAcc PCP-induced DA activity was unresponsive to 150 mg/kg and only partially inhibited by 300 and 500 mg/kg. Subchronic treatment with GVG did not enhance the inhibitory capacity of the GABAergic system. While GVG evidently modulates PCP-induced increases in mesocorticolimbic DA transmission, the character of this modulation is regionally specific, with cortical NMDA-antagonist induced increases appearing more sensitive to inhibition by endogenous GABA than subcortical areas.

Animals↗

Malignant external otitis: a case report and review.

Malignant external otitis is an unusual but serious and potentially fatal condition that has only recently been described. It is an invasive pseudomonal infection of the external auditory canal and deep periauricular tissues that characteristically involves the bone and adjacent cartilaginous structures, and it may lead to osteomyelitis of the base of the skull. It typically occurs in elderly diabetic patients. Malignant external otitis can cause severe pain, necrosis of the external auditory canal and progressive palsies of the facial and cranial nerves. Treatment consists of debridement of external auditory canal granulation tissue and long-term therapy with an antipseudomonal cephalosporin or an antipseudomonal penicillin plus an aminoglycoside.

Aged↗

[Patient-controlled administration of alfentanil during interventional measures--an alternative to general anesthesia].

OBJECTIVE: In 360 patients undergoing extracorporal shock wave lithotripsy (ESWL) the effects of an opioid analgesia with alfentanil (Rapifen) were investigated. METHODS: Starting with an intravenous bolus injection of 30 micrograms/kg repetitive injections of 15 micrograms/kg were administered when pain recurred. In 12 patients arterial blood samples were taken to determine alfentanil serum concentrations and blood gases. The pharmacokinetics of alfentanil were described by an open two-compartment model. RESULTS: In spite of multiple applications of the opioid no relevant cumulation could be seen. Although the patients received 3 l/min of oxygen via nasal tube, a significant decrease in paO2 was observed. pH was decreased and there was a significantly increased paCO2. No significant changes in arterial blood pressure were observed. Two patients developed rigidity of the chest wall. CONCLUSION: For short operations with only mild noxious stimuli opioid analgesia with alfentanil is a suitable procedure if applied by an experienced anaesthesiologist.

Adolescent↗

Company sponsored clinical research--it can be trusted.

Clinical research provides the basis for product claims in company literature, in submissions to the Food and Drug Administration (FDA), and in publications. Checks and balances before, during, and after research which safeguard the public are 1) regulatory control of clinical studies by FDA; 2) internal company procedures governing the conduct of clinical studies; and 3) peer and competitor review of published clinical results and product claims.

Clinical Trials as Topic↗

Irreversible inactivation of Saccharomyces cerevisiae fructose-1,6-bisphosphatase independent of protein phosphorylation at Ser11.

The fructose-1,6-bisphosphatase gene was used with multicopy plasmids to study rapid reversible and irreversible inactivation after addition of glucose to derepressed Saccharomyces cerevisiae cells. Both inactivation systems could inactivate the enzyme, even if 20-fold over-expressed. The putative serine residue, at which fructose-1,6-bisphosphatase is phosphorylated, was changed to an alanine residue without notably affecting the catalytic activity. No rapid reversible inactivation was observed with the mutated enzyme. Nonetheless, the modified enzyme was still irreversibly inactivated, clearly demonstrating that phosphorylation is an independent regulatory circuit that reduces fructose-1,6-bisphosphatase activity within seconds. Furthermore, irreversible glucose inactivation was not triggered by phosphorylation of the enzyme.

Base Sequence↗

Isolation and primary structure of the gene encoding fructose-1,6-bisphosphatase from Saccharomyces cerevisiae.

The gene encoding Saccharomyces cerevisiae fructose-1,6-bisphosphatase (FBP1) was isolated. Constructed fbp1::HIS3 null mutants were unable to grow with ethanol, and growth was restored after transformation with the cloned fbp gene. The gene codes for a protein of 347 amino acid residues with an Mr of 38131. Homology with the pig kidney cortex and the sheep liver enzyme is 47.7% and 46.6%, respectively, within a central core of 328 amino acid residues. The cloned promoter size was 318 bp and allowed only low level expression of the gene. This indicates a positive activation site (UAS) upstream of the cloned DNA fragment.

Alleles↗

Persistent infection of human fibroblasts by hepatitis A virus.

Infection of human embryo fibroblasts with hepatitis A virus (HAV), a picornavirus, leads to an inapparent, persistent infection; cultures can be passed serially with consistent recovery of the virus in the supernatant. All of the cells of a HAV carrier culture are infected and proliferate. Subcultivation under HAV-immune serum cannot achieve a cure or even a reduction in the number of infected cells in HAV carrier cultures. No interferon activity can be detected during HAV infection and persistence. Addition of exogenous interferon eliminates HAV infection in vitro. Persistence of HAV in vitro appears to contradict the clinical course of HAV infection in vivo. The system presented offers the possibility of evaluating the role of immunological injury of HAV-infected cells, an injury which may lead to damage of these cells and to elimination of HAV during an HAV infection in vivo.

Carrier State↗

[A new model of multiple sclerosis. Experimental vaccinia infection in the monkey].

Experimental vaccinia infection in immunosuppressed and immunocompetent Rhesus monkeys has been studied for two years. The results show that vaccinia virus induces two forms of infection in the central nervous system, i.e. choriomeningitis and demyelination disease. The first form occurs in immunologically competent animals; the latter can develop in animals with defective immune response associated with an incomplete clearance of virus. These animals exhibit a noncytocidal persistent infection of glial cells, inducing a complex of potentially pathogenic immune mechanisms. Their direct, or by mediators mediated action is capable of damaging myelin sheaths.

Animals↗