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Biomedical subjects

D Meier

Publications and source records attributed to D Meier.

At least 73 records · Page 4Linked to original sources

True myocardial motion tracking.

Myocardial tagging is a powerful tool for the assessment of in-plane cardiac motion. However, for previous myocardial tagging techniques, the imaged slice is fixed with respect to the magnet coordinate system. Thus, images acquired at different heart phases do not always represent the same slice of the myocardium. A new myocardial tagging technique is presented, which takes the through-plane motion into consideration. It involves tagging of the desired myocardial slice and applying a subtraction imaging technique to image just that part of the myocardium. The examination time can be reduced considerably by the acquisition of two one-dimensionally tagged images. To increase the signal-to-noise ratio especially at later heart phases, variable imaging RF excitation flip angles are applied. To reduce motion artifacts a repetitive breathhold scheme was applied. In vivo results demonstrate that the tags can be accurately tracked within the entire heart period with a temporal resolution of 35 ms, even at a top basal level of the heart and right ventricle.

Algorithms↗

Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part II: Muscle, liver, kidney.

Absolute metabolite concentrations were assessed in the muscle, the liver, and the kidney of healthy human volunteers by 31P MRS. Fully relaxed in vivo spectra were acquired with a surface coil and were localized with an adiabatic ISIS pulse sequence. The spectra were quantified with a subsequent measurement of a calibration phantom and were processed iteratively in the time domain. The following mean metabolite concentrations (mmol/liter) were measured in the resting male calf muscle (n = 9), in the fasting liver (n = 12), and in the orthotopic kidney (n = 5): [PME] = 2.0 +/- 0.6, 3.8 +/- 0.7, and 2.6 +/- 0.9, [Pi] = 2.9 +/- 0.3, 1.8 +/- 0.3, and 1.6 +/- 0.4, [PDE] = 3.8 +/- 0.8, 9.7 +/- 1.5, and 4.9 +/- 1.1, [PCr] = 22.0 +/- 1.2, 0, and 0, [NTP] = 5.7 +/- 0.4, 2.9 +/- 0.4, and 2.0 +/- 0.3, respectively. Several interesting findings are to be emphasized: The concentrations of Pi, PCr, and NTP were 20% lower in the muscle of women than of men. In addition, the pHi was significantly lower in female muscle (6.99 +/- 0.03) than in male muscle (7.05 +/- 0.03). The pHi in the liver (7.12 +/- 0.09) and in the kidney (7.09 +/- 0.08) were higher than in the muscle of both genders. The free magnesium concentration (mmol/liter) was higher in the liver (1.40 +/- 0.64) than in the kidney (0.79 +/- 0.39) and in the muscle (0.52 +/- 0.10).

Adult↗

Flow pattern analysis of the Baylor total artificial heart.

To obtain an optimal design of the left blood chamber of the total artificial heart (TAH), flow visualization studies were performed. Information on velocities in critical areas of the left chamber was gathered using sectional pulsed laser light. The flow patterns on the entire pumping duration were photographed frame by frame. The inflow port, the opposite of the inflow and outflow of the pump (bottom area), and the diaphragm/housing junction were the focal areas. The pump conditions, such as chamber pressure, preload and afterload pressure, pumping rate and roller screw, and displacement were recorded. Major stagnations and a low washout effect were observed in the bottom region. The closing of the inflow valve was irregular. In order to solve this problem, the inflow valve angle was changed 20 degrees. A comparison study showed a better valve closing characteristic, and no stagnation areas were observed with this new valve angle. Various velocity profiles confirmed the results. The valve closing characteristics is described in relationship to back flow.

Blood Flow Velocity↗

Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy.

A novel 31P magnetic resonance spectroscopy procedure allows the estimation of absolute concentrations of certain phosphorus-containing compounds in liver. We have validated this approach by measuring ATP, phosphomonesters, and inorganic phosphate (Pi) during fasting and after an i.v. fructose bolus in healthy adults and in three adults with disorders of fructose metabolism and by comparing results with known metabolic concentrations measured chemically. During fasting, the ATP concentration averaged 2.7 +/- 0.3 (SD, n = 9) mmol/L, which, after due correction for other nucleoside triphosphates, was 2.1 mmol/L and corresponded well with known concentrations. Fructose-1-phosphate (F-1-P) could not be measured during fasting; its concentration after fructose was calculated from the difference of the phosphomonester signals before (2.9 +/- 0.2 mmol/L) and after fructose. Pi was 1.4 +/- 0.3 mmol/L and represented the one fourth of Pi visible in magnetic resonance spectra. In the three healthy controls after fructose (200 mg/kg, 20% solution, 2.5 min), the fructokinase-mediated increase of F-1-P was rapid, reaching 4.9 mmol/L within 3 min, whereas the uncorrected ATP decreased from 2.7 to 1.8 mmol/L and the Pi from 1.4 to 0.3 mmol/L. The subsequent decrease of F-1-P, mediated by fructaldolase, was accompanied by an overshooting rise of Pi to 2.7 mmol/L. In the patient with essential fructosuria, the concentrations of F-1-P, ATP, and Pi remained unchanged, confirming that fructokinase was indeed inactive. In the patient with hereditary fructose intolerance, initial metabolic changes were the same as in the controls, but baseline concentrations were not yet reestablished after 7 h, indicating weak fructaldolase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Age distribution and iron dependency of the T2 relaxation time in the globus pallidus and putamen.

Heavily T2-weighted spin echo sequences of the brain show age-dependent low signal intensity in many extrapyramidal nuclei. Although it has been suggested that this low intensity results from non-haem iron, the specific influence of non-haem iron on the T2 relaxation time has not been quantified and remains controversial. The T2 relaxation times of the globus pallidus and putamen were measured from MRI at 1.5T in 27 healthy patients, by using a mathematical model. They were then plotted as a function of age and compared to the curve of age-dependent iron concentration determined post mortem. The curves of T2 relaxation time in the basal ganglia are congruent with published curves of iron concentration, indicating a high probability that the changes in T2 relaxation times and the low signal in the basal ganglia result from the local, age-dependent iron deposition. Individual measurements of T2 relaxation time show less variation before than after 45 years of age, indicating the influence of a second, more individual factor.

Adolescent↗

T2 relaxation time in patients with Parkinson's disease.

Postmortem studies of patients with Parkinson's disease (PD) reveal an increase in iron concentration in the substantia nigra. Iron content in the brain is associated with decreased signal intensity on T2-weighted MRI. We measured in vivo the T2 relaxation time in 30 PD patients and 33 healthy volunteer subjects, using a 1.5-T whole-body MRI system. In comparison with healthy controls, T2 values in PD patients were reduced in the following brain regions: substantia nigra, caudate nucleus, and putamen. Due to the overlap between patients and control subjects, we could not differentiate, in a given patient, healthy from diseased state on the basis of T2 relaxation time. Our findings support the notion of increased iron deposition in the substantia nigra of patients with PD. However, the shortening of T2 values in the substantia nigra did not correlate with disease duration nor with clinical severity.

Adult↗

The impact of the ISIS experiment order on spatial contamination.

When performing volume-localized spectroscopy measurements, the amount of spatial contamination is an important quality criterion. With the ISIS localization technique contamination cannot only arise from the transition regions around the volume of interest, but also from remote regions of the sample. The latter contamination component is a consequence of inhomogeneous excitation pulses, if short repetition times TR are used. Its severity depends both on the order of the eight phase cycling experiments needed for an ISIS measurement, and on the ratio TR/T1. Here it is theoretically discussed from which regions of the sample contamination can arise for a specific phase cycling order. For the worst orders the contaminating regions are almost three times as large as for the optimal orders. The ratio for the effectively measured contamination, however, can be moderated in real experiments, because cancellation effects occur due to the phase distribution of the contaminating signals. 31P phantom experiments clearly demonstrate that contamination is present even if adiabatic excitation pulses are applied and that spatial contamination can be reduced to about a third by an optimal choice of the phase cycling order.

Brain↗

Visualization and quantification of the human blood flow by magnetic resonance imaging.

Magnetic Resonance Imaging (MRI) offers new possibilities for the visualization and the noninvasive quantification of the blood flow in human vessels. By the application of conventional gradient echo sequences with electrocardiographic gating on a 1.5 Tesla whole body MRI system the flow induced phase shifts in the ascending and the abdominal aorta are analyzed. The instantaneous two-dimensional velocity profiles and the instantaneous flow rates are determined in a series of subsequent images with high temporal resolution throughout the cardiac cycle. For the flow analysis in further vessels and for the analysis of more complex flow patterns, as they occur in bifurcations or stenoses, a new MR flow imaging technique called FAcE with extremely short echo times is introduced and the first results of flow examinations in a bifurcation phantom and in the carotid artery are presented.

Aorta, Abdominal↗

Divergence between GLUT4 mRNA and protein abundance in skeletal muscle of insulin resistant rats.

Hyperglycemia and skeletal muscle insulin resistance coexist in uncontrolled type 2 diabetes mellitus. Similar defects in insulin action were observed in glucose-infused, normal rats, a model of glucose toxicity. In these rats insulin-stimulated glucose uptake by skeletal muscle was decreased due to a post-receptor defect. We investigated whether the impaired glucose uptake resulted from a decrease in the abundance of the predominant muscle glucose transporter (GLUT4) mRNA and/or protein. GLUT4 protein abundance in the hyperglycemic rats was not different from the control group despite a 50% decrease in muscle glucose uptake. GLUT4 mRNA abundance was 2.5-fold greater in the hyperglycemic rats as compared to the control animals. We conclude that the coexistence of hyperglycemia and hyperinsulinemia results in (1) a defect in GLUT4 compartmentalization and/or functional activity and (2) a divergence between GLUT4 mRNA levels and translation.

Animals↗

Is there really a "lack of natural tolerance to allotypic gamma-globulins in rabbits"?

We present data of extended studies on the possibility of maternally derived allotype Ig inducing a state of natural immunological tolerance to a non-inherited allotype in the offspring. Rabbits homozygous at the a locus, encoding allotypes in the variable region of immunoglobulin heavy chains, and rabbits homozygous at the unliked b locus, encoding allotypes of the constant region of kappa 1 chains, were immunized at the age of 2 months against the non-inherited allotype of their heterozygous mothers to which they had been exposed in utero and in early life. As control, we immunized rabbits of the same Ig phenotype but born to homozygous mothers, and therefore not exposed to that allotype. Immunization was done in a3/a3 offspring of either a1/a3 or a3/a3 mothers, by injecting a 1 IgG, and in b6/b6 offspring of b4/b6 or b6/b6 mothers, by injecting b4 IgG. The IgG was injected either in a soluble form or emulsified in adjuvant. Injection of soluble IgG elicited only a low response, if any, revealing no differences between the various groups. All rabbits responded upon immunization with IgG in adjuvant. We have not found any good evidence for natural tolerance to a non-inherited allotype, although progeny of a1/a3 mothers had slightly decreased responses to a1. On the contrary, progeny of b4/b6 mothers responded even better than offspring of b6/b6 mothers, upon such immunization with b4. To induce tolerance experimentally, we injected newborn rabbits, either from heterozygous a1/a3 or from homozygous a3/a3 mothers, with a1 serum or IgG. Newborn of heterozygous b4/b6 or of homozygous b6/b6 mothers were injected with b4 serum or IgG in the same way. Such treatment resulted in partial tolerance to each allotype. In an attempt to amplify the tolerizing effect of the maternal a1 Ig, we injected newborn rabbits of a1/a3 mothers with the serum of their mother. The response upon subsequent immunization with a1 allotype of another individual did not differ significantly from the response of control rabbits. The response was much poorer when rabbits were injected with nonmaternal tolerogen at birth, and when the same Ig preparation was used as immunogen. In a control experiment, neonatal injection of xenogeneic proteins, human IgG or bovine serum albumin, clearly resulted in tolerance. We speculate that tolerance to allotypes is established in the T cell repertoire only but bypassed by recognition of idiotypic determinants on antigen molecules by helper T cells, which trigger anti-allotype antibody formation by allotype-specific B cells. The end result of it is a lack of natural tolerance.

Animals↗

Molecular analysis of recombination sites within the immunoglobulin heavy chain locus of the rabbit.

Previously, recombinations involving genes of the rabbit immunoglobulin heavy chain locus have been documented serologically. These data indicated that the sites at which the causative recombination events occurred could have been anywhere from within the VH gene cluster up to, or 3' of, C mu. Since these sites could not be localized further by serological methods, we attempted to do this using techniques of molecular biology. DNAs from homozygous recombinant rabbits and from the appropriate non-recombinant parental haplotypes were characterized using Southern blots hybridized with a panel of probes derived from cloned regions of the rabbit immunoglobulin heavy chain gene complex. In all three recombinants, the site was downstream of the entire VH cluster and upstream of the JH cluster within an approximately 50 kilobase (kb) region containing expanses of repetitive-sequence DNA as well as DH genes. DH-specific probes further showed that in two of the recombinants, the recombination appears to have occurred within or 5' of DH1 and 5' of DH2 genes; in the third it occurred 3' of the DH2 genes but at least approximately 5 kb 5' of the JH region.

Animals↗

Left ventricular wall thickness measurements by magnetic resonance: a validation study.

Left ventricular (LV) wall thickness was determined by magnetic resonance (MR) in 15 patients (7 controls and 8 patients with coronary artery disease). End-diastolic (ed) and end-systolic (es) wall thickness were measured in a short axis view perpendicular to the LV long axis. Wall thickness measurements were compared to data obtained by digital subtraction angiography (DSA) and M-mode echocardiography (Echo). End-diastolic and end-systolic wall thickness were significantly overestimated by MR (34% and 37%, respectively) when compared to DSA. In contrast, LV end-diastolic and end-systolic chamber diameter were significantly underestimated by MR (25% and 30%, respectively) when compared to DSA. However, fractioned shortening was similar (all NS) for MR (48 +/- 22%), DSA (54 +/- 15%) and Echo (44 +/- 10%), respectively. The mean difference (= accuracy) and the standard deviation of difference (= precision) for LV wall thickness was 0.4 +/- 0.2 cm between MR and DSA, 0.4 +/- 0.3 cm between MR and ECHO and 0.03 +/- 0.1 cm between DSA and ECHO. The correlation of wall thickness between MR and DSA (correlation coefficient r = 0.74, p less than 0.001) and between MR and Echo (r = 0.70, p less than 0.001) was good although the standard error of estimate (SEE) was 17% for MR vs. DSA and 21% for MR vs. Echo. The corresponding SEE for chamber diameter was 16% between MR and DSA and 19% between MR and Echo, respectively. Intraobserver variability for wall thickness determination by MR was excellent (correlation coefficient r = 0.99, p less than 0.001) SEE of 4%. Interobserver variability was also good (correlation coefficient r = 0.90, p less than 0.001) with a SEE of 12%. It is concluded that LV wall thickness and chamber diameter (short axis plane) can be determined by MR with good precision but only satisfactory accuracy. LV wall thickness is significantly overestimated probably due to signals from static blood which might be indistinguishable from the subendocardium.

Angiography, Digital Subtraction↗

Propofol and spontaneous movements: an EEG study.

Spontaneous movements during induction of anesthesia with propofol were studied in 21 children aged 6-12 yr. The children were randomly assigned to group A (propofol 3 mg.kg-1), B (propofol 5 mg.kg-1), or C (thiopental 5-7 mg.kg-1). A baseline electroencephalogram (EEG) was recorded during 10 min in children awake, supine with eyes closed and opened, and then from the beginning of induction until 5 min after tracheal intubation. Spontaneous movements were observed in all children in group A but only in 14% in groups B and C. The induction EEG sequences were similar for the three groups: after a mean latency of 12 s, the tracing showed an increase in frequency from 9 to 10 Hz (alpha waves) to more than 14 Hz (beta waves). This transition lasted approximately 2 s, followed by delta waves (2-3 Hz) that continued for 1-2 min. Finally, beta waves reappeared and progressively but incompletely replaced delta waves during the next 5 min. Neither spikes, spike-wave patterns, rhythmic theta waves, nor burst suppressions were observed. Spontaneous movements were recorded on videotape and analyzed after the completion of the study by a neurologist unaware of patient treatment. Videotape analysis of the periinduction period showed spontaneous movements to be dystonic and choreiform with flexion, twisting, or extension movements of all extremities. All movements occurred coincident with the appearance of delta waves on the EEG. Their dystonic nature and the absence of EEG abnormalities suggest a subcortical origin and argue against associated cortical epileptic activity.

Anesthesia↗

Phytoalexins as part of induced defence reactions in plants: their elicitation, function and metabolism.

Microbial infection of plants or elicitation of cell cultures initiates substantial metabolic changes directed at the induction of defence reactions. The antimicrobial phytoalexins deserve special attention because they represent one essential component of plant resistance. The great structural diversity of phytoalexins and possible cellular sites for their toxic activity are discussed. Pterocarpan phytoalexin biosynthesis in Cicer arietinum is an example of the induction of extended biosynthetic pathways, their modes of regulation and metabolic links with constitutive secondary product formation. Elicitation of plant tissues represents a technique to induce simultaneously the formation of phytoalexins and increased levels of constitutive or other secondary products that do not normally accumulate. The biological function of phytoalexins and the pathways of their degradation by pathogenic fungi are outlined. Detoxification of phytoalexins by fungi may have important consequences for the practical application of these defence compounds and for the genetic transformation of fungi and plants. Phytoalexins accumulate in plants or cell cultures only transiently, because they are readily degraded or polymerized by extracellular peroxidases.

Fungi↗

Limited number of immunoglobulin VH regions expressed in the mutant rabbit "Alicia".

A unique feature of rabbit Ig is the presence of VH region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear the VHa allotypic specificities, al, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack VHa allotypic specificities and are designated VHa-. A mutant rabbit designated Alicia, in contrast, has predominantly serum immunoglobulin molecules that lack the VHa allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of VHa- molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six of the clones appeared to encode VHa- molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has been seen in only 2 of 54 sequenced rabbit VH genes. The similarity of the sequences of the six VHa- clones to each other and their dissimilarity to most other VH genes leads us to suggest that the VHa- molecules in Alicia rabbits are derived predominantly from one or a small number of very similar VH genes. Such preferential utilization of a small number of VH genes may explain the allelic inheritance of VH allotypes.

Amino Acid Sequence↗

Altered phenotypic expression of immunoglobulin heavy-chain variable-region (VH) genes in Alicia rabbits probably reflects a small deletion in the VH genes closest to the joining region.

Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression.

Animals↗