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Biomedical subjects

T Ernst

Publications and source records attributed to T Ernst.

At least 73 records · Page 4Linked to original sources
PubMed1996

In vivo proton magnetic resonance spectroscopy of the normal aging human brain.

The effect of age on brain metabolite concentrations was evaluated using localized proton magnetic resonance spectroscopy. This technique allows in vivo measurements of N-acetyl compounds (NA), total creatine (CR), choline-containing compounds (CHO), myo-inositol (MI), glutamate and glutamine (GLX), as well as the percentage of cerebrospinal fluid (CSF) and the brain water content within the brain region studied. Frontal gray matter and frontal white matter brain regions were examined in 36 normal healthy volunteers (19-78 years of age). Using a rigorous absolute quantitation method, with an external reference and atrophy correction, we found relatively stable concentrations of NA, a neuronal marker. In contrast, CR, CHO, MI, and the percentage of CSF increased in the gray matter with age. However, the brain water content decreased significantly with age (r = -0.72; p < 0.0001). No significant age-related changes in metabolite concentrations, CSF or brain water content were observed in the white matter regions. These findings demonstrate that biochemical alterations are associated with aging in the frontal gray matter. There might be an increase in the brain density as indicated by increased metabolite concentrations and decreased brain water content with aging.

Adult↗
PubMed1996

Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations.

3,4-Methylenedioxymethamphetamine (MDMA) is a phenethylamine with potent effects on serotonergic neurotransmission which has been the object of controversy over its potential as a therapeutic adjunct versus its possible risks for causing neurotoxic injury. This paper discusses the background, methodology and preliminary findings of the first FDA approved Phase I study prospectively evaluating the effects of MDMA administration in humans. Six subjects with prior experience with MDMA were administered two different dosages of MDMA and an inactive placebo utilizing a randomized, double-blind methodologic design. Dosages from 0.25 to 1.0 mg/kg, p.o., were administered. All subjects tolerated the procedures without any overt evidence of physical discomfort or psychological distress. MDMA produced a modest increase in heart rate and blood pressure. The threshold dose for the stimulation of ACTH and prolactin appeared to be between 0.5 and 0.75 mg/kg, with the two higher doses clearly stimulating both ACTH and prolactin. Methodology for assessing MDMA's effects on serotonergic neurotransmission is discussed.

Adult↗
PubMed1995

Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL.

Paxillin is a 68-kDa focal adhesion protein that is phosphorylated on tyrosine residues in fibroblasts in response to transformation by v-src, treatment with platelet-derived growth factor, or cross-linking of integrins. Paxillin has been shown to have binding sites for the SH3 domain of Src and the SH2 domain of Crk in vitro and to coprecipitate with two other focal adhesion proteins, vinculin and focal adhesion kinase (p125fak). After preliminary studies showed that paxillin was a substrate for the hematopoietic oncogene p210BCR/ABL, we investigated the role of this protein in hematopoietic cell transformation and signal transduction. A full-length length cDNA encoding human paxillin was cloned, revealing multiple protein domains, including four tandem LIM domains, a proline-rich domain containing a consensus SH3 binding site, and three potential Crk-SH2 binding sites. The paxillin gene was localized to chromosome 12q24 by fluorescence in situ hybridization analysis. A chicken paxillin cDNA was also cloned and is predicted to encode a protein approximately 90% identical to human paxil-lin. Paxillin coprecipitated with p210BCR/ABL and multiple other cellular proteins in myeloid cell lines, suggesting the formation of multimeric complexes. In normal hematopoietic cells and myeloid cell lines, tyrosine phosphorylation of paxillin and coprecipitation with other cellular proteins was rapidly and transiently induced by interleukin-3 and several other hematopoietic growth factors. The predicted structure of paxillin implicates this molecule in protein-protein interactions involved in signal transduction from growth factor receptors and the BCR/ABL oncogene fusion protein to the cytoskeleton.

3T3 Cells↗
PubMed1995

Brain lesions in patients with AIDS: H-1 MR spectroscopy.

PURPOSE: To evaluate the role of proton (hydrogen-1) magnetic resonance (MR) spectroscopy in the differential diagnosis of focal brain lesions in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Twenty-six men with 35 AIDS-related brain lesions underwent MR imaging and localized H-1 MR spectroscopy. Lesions consisted of 11 toxoplasmic abscesses, 12 progressive multifocal leukoencephalopathic lesions, eight lymphomas, and four cryptococcomas. Metabolite peak areas in the lesions were compared with those in the contralateral hemisphere in each patient. RESULTS: H-1 MR spectroscopic findings showed significantly different biochemical profiles for each diagnostic group (P = .0001) with regard to N-acetyl compounds, total creatine pool, choline-containing compounds, myoinositol, and lactate. H-1 MR spectroscopy alone helped correctly diagnose 94% (84% with jackknifed classification) of the brain lesions, without overlap between toxoplasmosis and lymphoma. CONCLUSION: H-1 MR spectroscopy is a sensitive and potentially specific noninvasive adjunctive method for differential diagnosis of focal brain lesions in AIDS.

AIDS Dementia Complex↗
PubMed1994

Detection of brain activation using oxygenation sensitive functional spectroscopy.

A nonwater-suppressed localized spectroscopy experiment using the PRESS-sequence has been used to study the signal changes of the water resonance during cortical activation. Significant effects with an effect-to-noise ratio up to 50:1 for a single shot experiment have been observed upon photic stimulation. The exceedingly high signal-to-noise ratio of the experiment was used to demonstrate signal changes as low as 0.1% after electrical stimulation of the median nerve.

Cerebral Cortex↗
PubMed1994

Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease.

To establish whether recently described abnormalities of peak ratios are the result of changes in metabolite concentrations, quantitative 1H magnetic resonance spectroscopy was performed in 10 patients with Alzheimer disease (AD) and seven normal elderly. CSF volumes, metabolite T1 and T2 relaxation rates, ratios and concentrations of N-acetyl residues, creatine, choline residues, myo-inositol, glutamine plus glutamate (Glx), and glucose were obtained. Difference spectroscopy and quantitative assays showed a 50% increase in myo-inositol (6.4-9.8 mM; P < 0.005) and a decrease in N-acetyl in occipital gray matter. A reduction in beta, gamma-Glx and a significant increase in intracerebral [glucose], greater than attributable to CSF, were defined. Choline concentration increased with age, but was not elevated above normal in AD patients. These findings indicate the need for quantitative 1H MRS to substantiate metabolite ratios. The increased myo-inositol concentration in AD is demonstrated by these studies.

Aged↗
PubMed1994

Observation of a fast response in functional MR.

A spectroscopic MR technique was used to investigate the time course of the MR signal following a single visual stimulus. Gated experiments demonstrate there is an early response (500 ms after stimulus) leading to a reduction of the MR signal by -0.25% (P = 0.02), whereas a slower response (> 1500 ms after stimulus) results in a signal increase of +0.59% (P = 0.01). The fast negative response may be attributed to increased oxygen consumption, followed by a slower vascular response with overcompensation in blood oxygenation. This explanation would be in agreement with the blood oxygenation level dependent (BOLD) contrast mechanism considered the basis of functional MR. However, other physiological events might also be responsible for the signal drop observed.

Adult↗
PubMed1994

Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy.

BACKGROUND/AIMS: Recent in vivo studies using proton magnetic resonance (1H-MR) spectroscopy showed low levels of myo-inositol in the brain in hepatic encephalopathy; the pathogenetic relevance of this observation is unclear. METHODS: Myo-inositol and glutamine levels in the brain were studied in vivo by 1H-MR spectroscopy in patients with hypo-osmolarity and hepatic encephalopathy. RESULTS: A patient with severe plasma hypo-osmolarity (222 mOsm/L) had almost undetectable signals for myo-inositol and glutamine/glutamate in the brain. Both signals reappeared after normalization of plasma osmolarity, suggesting that both myo-inositol and glutamine were released as organic osmolytes from the brain. A decreased cerebral myo-inositol signal is also found in low-grade hepatic encephalopathy but is accompanied by an increased glutamine signal. Cirrhotics without hepatic encephalopathy have near-normal inositol signals, and patients with acquired immunodeficiency syndrome encephalopathy have increased inositol signals. CONCLUSIONS: The 1H-MR spectroscopic myo-inositol signal in the human brain predominantly reflects an osmosensitive inositol pool. It is hypothesized that its depletion in latent hepatic encephalopathy points to a disturbance of cell volume homeostasis in the brain as an early pathogenetic event. This may partly be caused by a hyperammonemia-induced glutamine accumulation in the brain.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Functional spectroscopy: the limits and potentials of a new method for the study of brain activation with MR tomography].

The possibility of examining brain activity by means of localised spectroscopy was studied in relation to its neurological basis. Measurements on 18 normals during optical stimulation showed an improvement in signal to noise ratio compared with functional imaging of almost one order of magnitude. Time dependent measurements during stimulation by a 500 ms light impulse showed definite delay of increased blood flow when compared with oxygen utilisation. The excellent signal to noise ratio and the inherent stability of the method permits reliable detection of weak effects such as are caused by finger tapping or electrical stimulation.

Artifacts↗
PubMed1994

Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities.

PURPOSE: To determine whether hydrogen-1 magnetic resonance (MR) spectroscopy of the brain allows detection of subclinical hepatic encephalopathy (SCHE). MATERIALS AND METHODS: In a double-blind study, overt hepatic encephalopathy (HE) and SCHE (defined with clinical and neuropsychiatric tests) were compared by means of H-1 MR spectroscopic criteria--reduction in cerebral myo-inositol (< 2 standard deviations [SDs] from normal) and choline (< 2 SDs from normal) with or without increased cerebral glutamine (> 1 SD from normal)--in 20 patients with cirrhosis. RESULTS: Concordance between MR spectroscopic and neuropsychiatric test results was 94% (kappa = 0.84). MR spectroscopy allowed diagnosis of SCHE in nine of nine patients (100%) and of HE in seven of eight (88%). Myo-inositol depletion alone had 80%-85% sensitivity for detection of HE and SCHE. CONCLUSION: H-1 MR spectroscopy allows accurate diagnosis of SCHE, and the results suggest an important role for myo-inositol in psychomotor and visuopractic functions.

Adult↗
PubMed1993

Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy.

Cerebral metabolite concentrations and water content were measured by means of localized proton magnetic resonance spectroscopy in 50 children, while metabolite peak ratios in short echo time spectra were evaluated in 173 examinations. Normative curves for normal development were established for two cerebral locations. The current report presents the first study of absolute metabolite concentrations and T1- and T2- relaxation as a function of age. Myo-inositol was found dominating the spectra at birth (12 mmoles/kg), while choline is responsible for the strongest peak in older infants (2.5 mmoles/kg). Creatine and N-acetyl groups are at significantly lower concentrations in the neonate than in the adult (Cr: 6, NA: 5 mmoles/kg). NA and Cr are determined by gestational age, whereas the concentration of ml correlates best with postnatal age. Quantitative 1H MRS is expected to be of particular value in diagnosis and monitoring of pathology in infants, since metabolite ratios are often misleading.

Brain↗
PubMed1993

Human brain tumors: assessment with in vivo proton MR spectroscopy.

To better understand variations in spectra of brain tumors, 122 in vivo proton spectra of brain tumors in 82 patients were analyzed. The changes in relative metabolite concentrations compared with those in normal spectra and the presence of any new metabolite were assessed. To evaluate the clinical usefulness of in vivo hydrogen-1 magnetic resonance (MR) spectroscopy in brain tumors, the authors looked for specific spectral changes on the basis of tumor grade. All tumor spectra showed differences from normal reference spectra. The differential diagnosis of the spectra was limited because intraindividual differences between spectra of one tumor at different locations were often larger than differences between spectra of tumors with different histologic characteristics. However, the variations in metabolite concentrations, and especially the presence or absence of aliphatic signals, were proved to be indicators of the histologic grade of tumor. The observed spectral patterns conformed to a four-compartment model, described herein, which is proposed to improve the interpretation of brain spectra.

Brain↗
PubMed1993

Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy.

To define altered metabolites in the brain of patients with probable Alzheimer disease (AD) of two brain regions, localized in vivo hydrogen-1 magnetic resonance (MR) spectroscopy was performed with a short echo time (30 msec) in 11 elderly patients and 10 healthy age-matched subjects. The patients had mild to moderate dementia, assessed with standard neuropsychological tests. Two abnormalities in the patients' cerebral cortex were defined: When compared with healthy subjects, the patients showed a 22% increase (P = .005) (approximately equal to 1.5 mmol/kg) in myo-inositol (MI) and an 11% decrease (P = .005) in residues of N-acetyl (NA), a putative neuronal marker. The elevation of MI in patients with mild to moderate AD suggests that abnormalities in the inositol polyphosphate messenger pathway occur early in the natural history of AD. The combination of high MI and low NA at examination with H-1 MR spectroscopy shows promise as an early diagnostic test for AD.

Aged↗
PubMed1991

Double-volume 1H spectroscopy with interleaved acquisitions using tilted gradients.

A method is presented by which volume selective in vivo 1H spectra of two different voxels can be acquired in an interlaced mode using PRESS or STEAM spectroscopy. Spatially tilted gradients are employed for voxel definition so as to avoid mutual saturation. Independent volume selective shimming of the voxels is possible. Two spectra of volumes as small as (1.5 cm)3 can be acquired from human brain within 14 min even from very disadvantageous locations close to air-borne interfaces.

Adenoma↗
PubMed1991

Coupling effects in volume selective 1H spectroscopy of major brain metabolites.

The effect of PRESS and STEAM sequences on the spectra of coupled substances are discussed using the examples of weakly coupled AX and A2X systems. Maximum differences compared to uncoupled spins occur if the RF pulses are applied to antiphase magnetization. In this case, the spin echo of the PRESS experiment shows a modified dependence on the refocusing flip angle, which may lead to an attenuation of the acquired signal. In STEAM spectroscopy the evolution within the middle interval tm is dominated by zero quantum coherences and longitudinal polarization, whose maximum efficiencies are 25 and 12.5%, respectively. Zero quantum coherences may lead to strong modulations when the tm value is varied. The effects on the spectra of important coupled metabolites of the human brain such as glutamate, GABA, inositol, and particularly lactate, are demonstrated. The observed modulations seem to make the quantification of the spectra rather difficult at echo times above 50 ms.

Aspartic Acid↗
PubMed1991

Karyotypic stability of serum-free mouse embryo (SFME) cells.

Mouse embryo cultures derived in serum-containing medium undergo growth crisis or senescence after fewer than 20 population doublings, followed by the emergence of genetically altered, polyploid 'immortalized' cells capable of growing indefinitely. Serum-free mouse embryo (SFME) cells, derived in medium in which serum is replaced with growth factors and other supplements, do not exhibit growth crisis or gross chromosomal aberrations when cultured for well over 100 population doublings and display other unique properties. We examined culture conditions and physiological factors affecting karyotypic stability in long term cultures of SFME cells derived from several mouse strains. Cloning SFME cells consistently isolated colonies with altered karyotype, even when the clones were derived from parent cultures with no karyotypic alterations. After 140-200 population doublings in vitro, the percentage of SFME cells showing hyperdiploidy or structural chromosomal abnormalities increased, although the modal chromosome number remained diploid. SFME cells transformed with molecularly cloned oncogenes did not show alterations in karyotype beyond that expected from the clonal origins of these cells, indicating that malignant transformation of SFME cells does not result in general karyotypic instability.

Animals↗