Biomedical subjects

H Merkle

Publications and source records attributed to H Merkle.

At least 37 records · Page 2Linked to original sources

PubMed1998

Quantitative measurements of cerebral blood flow in rats using the FAIR technique: correlation with previous iodoantipyrine autoradiographic studies.

Flow-sensitive alternating inversion recovery (FAIR) is a recently introduced MRI technique for assessment of perfusion that uses blood water as an endogenous contrast agent. To characterize the FAIR signal dependency on spin tagging time (inversion time (TI)) and to validate FAIR for cerebral blood flow (CBF) quantification, studies were conducted on the rat brain at 9.4 T using a conventional gradient-recalled echo sequence. The T1 of cerebral cortex and blood was found to be 1.9 and 2.2 s, respectively, and was used for CBF calculations. At short TIs (<0.8 s), the FAIR signal originates largely from vascular components with fast flows, resulting in an overestimation of CBF. For TI > 1.5 s, the CBF calculated from FAIR is independent of the spin tagging time, suggesting that the observed FAIR signal originates predominantly from tissue/capillary components. CBF values measured by FAIR with TI of 2.0 s were found to be in good agreement with those measured by the iodoantipyrine technique with autoradiography in rats under the same conditions of anesthesia and arterial pCO2. The measured pCO2 index on the parietal cortex using the FAIR technique was 6.07 ml/100 g/min per mmHg, which compares well with the pCO2 index measured by other techniques. The FAIR technique was also able to detect the regional reduction in CBF produced by middle cerebral artery occlusion in rats.

Animals↗

PubMed1998

Inhibition of the development of spontaneous autoimmune thyroiditis in the obese strain (OS) chickens by in vivo treatment with anti-CD4 or anti-CD8 antibodies.

The involvement of CD4+ and CD8+ T cells in pathogenesis of spontaneous autoimmune thyroiditis (SAT) in obese strain (OS) chickens has not been studied in depth until now. We depleted CD4+ or CD8+ T cells in OS chickens by treatment with murine monoclonal anti-CD4 or anti-CD8 antibodies at 3 day intervals beginning at hatching. The birds were killed at 19-25 days of age. Treatment with anti-CD4 antibody completely prevented SAT development, while treatment with anti-CD8 antibody partially inhibited SAT. These results show the critical role of CD4+ T cells in the development of SAT in OS chickens, and indicate that CD8+ T cells are also involved in SAT pathogenesis.

Age Factors↗

PubMed1998

Resolution improvements in in vivo 1H NMR spectra with increased magnetic field strength.

The measurement of cerebral metabolites using highly homologous localization techniques and similar shimming methods was performed in the human brain at 1.5 and 4 T as well as in the dog and rat brain at 9.4 T. In rat brain, improved resolution was achieved by shimming all first- and second-order shim coils using a fully adiabatic FASTMAP sequence. The spectra showed a clear improvement in spectral resolution for all metabolite resonances with increased field strength. Changes in cerebral glutamine content were clearly observed at 4 T compared to 1.5 T in patients with hepatic encephalopathy. At 9.4 T, glutamine H4 at 2.46 ppm was fully resolved from glutamate H4 at 2.37 ppm, as was the potential resonance from gamma-amino-butyric acid at 2.30 ppm and N-acetyl-aspartyl-glutamate at 2.05 ppm. Singlet linewidths were found to be as low as 6 Hz (0.015 ppm) at 9.4 T, indicating a substantial decrease in ppm linewidth with field strength. Furthermore, the methylene peak of creatine was partially resolved from phosphocreatine, indicating a close to 1:1 relationship in gray matter. We conclude that increasing the magnetic field strength increases spectral resolution also for 1H NMR, which can lead to more than linear sensitivity gains.

Adult↗

PubMed1997

Imaging H2(17)O distribution in a phantom and measurement of metabolically produced H2(17)O in live mice by proton NMR.

Previously we suggested a method for indirect detection of H2(17)O via a combination of 1H spin-echo sequence and 17O decoupling. The method is based on the shortening of the water proton T2 due to the residual spin-spin coupling with the 17O nucleus, and on our finding that this shortening is abolished by applying an radio frequency field at the 17O resonance frequency. In the present work we demonstrate how the method can be used for imaging low concentrations of H2(17)O, and report for the first time an application of this method to in vivo detection of H2(17)O in live newborn mice, where the H2(17)O was introduced either directly i.p. or by inhalation of 17O2 where it was formed by oxidative metabolic activity.

Animals↗

PubMed1997

Detection of 13C-labeled metabolites in the in vivo canine heart by B1 insensitive heteronuclear coherent polarization transfer and comparison of signal enhancement with NOE.

A recently developed adiabatic coherent polarization transfer enhancement technique [H. Merkle, H. Wei, M. Garwood, K. Uğurbil. J. Magn. Reson, 99, 480-494 (1992)] was employed to perform 13C spectroscopy in the intact canine heart in vivo during [2-13C]-acetate infusion into the left descending coronary artery, the results were compared with 13C spectra obtained with conventionally employed nuclear Overhauser enhancement. The results demonstrate that both methods can be performed by using surface coils to obtain in vivo 13C spectra and that coherent polarization transfer provides better enhancement than NOE for [2-13C]-acetate but not for short T2 compounds.

Acetates↗

PubMed1997

Determination of deoxymyoglobin changes during graded myocardial ischemia: an in vivo 1H NMR spectroscopy study.

1H NMR spectroscopy was used to detect the proximal histidyl Ndelta proton signal of deoxymyoglobin from canine hearts in vivo during graded myocardial ischemia. The NMR signal intensity provided an indicator of intracellular oxygenation in myocardium. The relationship between the myocardial blood flow and the deoxymyoglobin concentration was successfully measured during resting, partial, and complete coronary artery occlusion conditions. The results demonstrate the feasibility to detect deoxymyoglobin using a 1H NMR spectroscopy technique in living hearts for the first time and the possibility to use this technique for investigating myocardial oxidative metabolism nondestructively and repetitively.

Animals↗

PubMed1997

Helper activity of chicken V beta 1+ and V beta 2+ alpha beta T cells for in vitro IgA antibody synthesis.

Chickens have only two T cell receptor variable beta gene families: V beta 1 and V beta 2 (1). In our previous work we found that IgA production was almost completely suppressed in chickens depleted of V beta 1+ alpha beta T cells by treatment with a TCR V beta 1-specific monoclonal antibody (2), while IgM and IgG production was not affected. Our present results indicate that, in vitro, both V beta 1+ and V beta 2+ chicken cecal tonsil T cells provide help for the differentiation of cecal tonsil IgA B cells, suggesting that the failure of V beta 1+ T cell-depleted chickens to produce IgA is not caused by the inability of V beta 2+ T cells to provide help for IgA production by B cells, but rather by the scarcity of these T cells in mucosal tissues (3), where most IgA responses are induced (4).

Animals↗

PubMed1997

Myocardial bioenergetics during acute hibernation.

During moderate reductions of blood flow, the myocardium downregulates contractile function and ATP utilization to result in reduced but stable ATP levels, recovery or stability of (reduced) creatine phosphate (CP), and preservation of myocyte viability. The intent of this study was to determine the influence of the level of ischemic blood flow and the major determinants of myocardial O2 consumption (MVO2) (heart rate and systolic blood pressure) on recovery of CP during prolonged moderate myocardial hypoperfusion. 31P-nuclear magnetic resonance spectroscopy was used to measure CP, ATP, and Pi in the subepicardium (Epi) and subendocardium (Endo) of 13 open-chest dogs. Wall thickening was measured with sonomicrometry. A coronary stenosis reduced mean myocardial blood flow (microspheres) from 1.10 +/- 0.07 to 0.71 +/- 0.06 ml.g-1.min-1 (P < 0.01) and the Endo-to-Epi blood flow ratio from 1.12 +/- 0.07 to 0.59 +/- 0.06 (P < 0.01), and dyskinesis developed. Coronary blood flow and systolic wall thickening did not change significantly during 4 h of hypoperfusion. Epi CP and ATP fell to 80 +/- 4% (P < 0.05) and 93 +/- 3% of control, respectively, at 30 min. Epi CP then recovered to 87 +/- 5% while ATP decreased further to 83 +/- 5% of baseline by the end of the 240-min ischemic period. Endo CP and ATP fell to 53 +/- 4 and 77 +/- 5% of control, respectively, at 30 min; then Endo CP recovered to 85 +/- 6% while ATP decreased further to 68 +/- 6% of baseline at 240 min of hypoperfusion. ADP levels were significantly increased at 30 min but recovered to baseline by 240 min of hypoperfusion. delta Pi/CP increased significantly (Endo > Epi) at the onset of ischemia and then progressively decreased. At 30 min, mild myocardial acidosis was observed in some hearts with variable pH recovery during continuing hypoperfusion. The data demonstrate that variations in blood flow cannot account for the magnitude of the initial fall in CP or for the final extent of recovery. However, the rate at which CP recovered was significantly correlated with the level of blood flow. Variations in the determinants of MVO2 did not account for differences in CP recovery.

Adenosine Diphosphate↗

PubMed1996

Relationships among lactate concentration, blood flow and histopathologic profiles in rat C6 glioma.

Increased capacity for glycolytic metabolism is a well-known characteristic of neoplastic cells. Because lactic acid is the end product of glycolysis, in vivo MRS measurements of tumor lactate concentration ([lac]t) may provide valuable information about tumor metabolism, which will aid the development of therapies and the clinical diagnosis and treatment of tumors. In the present study, several hemodynamic and histologic parameters were evaluated with respect to their influence on [lac]t. Pronounced differences in [lac]t in two distinct populations of tumors suggested a putative perfusion threshold. Above this threshold, [lac]t was independent of hemodynamic and histologic factors including tumor blood flow (measured using MRS and the method of D2O washout), extent of necrosis and inflammatory cell infiltrate. Thus, for most tumors, [lac]t was not determined by any one single factor such as hypoxia, venous clearance, glucose supply, extent of necrosis or degree of inflammatory cell infiltrate. Rather, [lac]t may be equilibrated, at least in part, by an interplay of forces involving hemodynamics and substrate supply. In general, the data are consistent with the hypothesis that elevated lactate in most tumors is related to the high glycolytic activity of adequately perfused, viable neoplastic cells.

Animals↗

PubMed1996

Broadband decoupled, 1H-localized 13C MRS of the human brain at 4 Tesla.

Broadband proton decoupling of the entire 13C spectrum was possible within power absorption guidelines and resulted in the detection of narrow (as low as 2-3 Hz), natural abundance signals from metabolites such as myo-inositol, glutamate, N-acetyl-aspartate, and glutamine from 72 cm3 volumes in the human brain. To overcome the chemical shift displacement error, three-dimensional localization on the 1H z magnetization was combined with polarization transfer. Efficiency of the heteronuclear localization method was demonstrated by the elimination of all scalp lipid resonances. A signal-to-noise ratio of 5:1 for 0.07 mM [13C] was achieved in 12 min, which is approximately a fivefold improvement over the sensitivity reported at 2.1 Tesla.

Aspartic Acid↗

PubMed1996

Prevention of spontaneous autoimmune thyroiditis in the obese strain (OS) chickens by treatment with a monoclonal anti-CD4 antibody.

Untreated control OS chickens develop spontaneous autoimmune thyroiditis (SAT). In contrast, OS chickens treated with a monoclonal anti-CD4 antibody failed to develop SAT. The preventive effect of anti-CD4 antibody on SAT was associated with the marked depletion of CD4+ T-cells by anti-CD4 treatment. These results indicate that CD4+ T-cells play a crucial role in SAT of OS chickens.

Animals↗

PubMed1995

Effect of left ventricular hypertrophy secondary to chronic pressure overload on transmural myocardial 2-deoxyglucose uptake. A 31P NMR spectroscopic study.

BACKGROUND: This study tested the hypothesis that 31P nuclear magnetic resonance (NMR)-detectable 2-deoxyglucose (2DG) uptake is increased in chronically pressure-overloaded hypertrophied left ventricular myocardium. METHODS AND RESULTS: 31P NMR spectroscopy was used to determine the transmural distribution of high-energy phosphate levels and 2-deoxyglucose-6-phosphate (2DGP) accumulation during intracoronary infusion of 2DG (15 mumol.kg body wt-1.min-1) in eight normal dogs and in eight dogs with severe left ventricular hypertrophy (LVH) produced by ascending aortic banding. The ratio of LV weight to body weight was 8.25 +/- 0.65 g/kg in the LVH group compared with 4.35 +/- 0.11 g/kg in the normal group (P < .01). Myocardial ATP content was decreased by approximately 40% and phosphocreatine (PCr) by approximately 60% in LVH hearts. ATP values were transmurally uniform in LVH and normal hearts, whereas PCr was lower in the subendocardium (Endo) than the subepicardium (Epi) of both groups. The PCr/ATP ratio was lower in LVH hearts (1.72 +/- 0.05, 1.64 +/- 0.07, and 1.53 +/- 0.10 in Epi, midwall, and Endo, respectively) compared with normal hearts (2.36 +/- 0.05, 2.09 +/- 0.06, and 1.96 +/- 0.06; each P < .01 normal versus LVH). Arterial blood levels of glucose, insulin, and free fatty acids were comparable between groups, whereas arterial lactate and norepinephrine levels were significantly higher in the LVH group. 2DG infusion did not affect systemic hemodynamics or myocardial high-energy phosphate or inorganic phosphate levels in either group. At the end of 60 minutes of 2DG infusion, there was no detectable accumulation of 2DGP in the normal hearts. However, seven of the eight LVH hearts showed time-dependent accumulation of 2DGP, which was linearly related to the severity of hypertrophy (r = .90 for subendocardial 2DGP versus LV weight/body weight). A transmural gradient of 2DGP was present, with greatest accumulation in the subendocardium (3.3 +/- 1.6, 5.8 +/- 2.3, and 7.9 +/- 2.2 mumol/g in Epi, midwall, and Endo of the LVH hearts, respectively; P < .05 Epi versus Endo). CONCLUSIONS: The pressure-overloaded hypertrophied left ventricle demonstrated increased accumulation of 2DGP detected with 31P NMR spectroscopy. Accumulation of 2DGP was positively correlated with the degree of hypertrophy and was most marked in the subendocardium.

Adenosine Triphosphate↗

PubMed1995

Myocardial tagging with B1 insensitive adiabatic DANTE inversion sequences.

A new technique, based on adiabatic delays alternating with mutations for tailored excitation (DANTE) inversion sequences, is presented for generating uniform contrast tags across the myocardial wall even in the presence of B1 inhomogeneities. The utility of this pulse was demonstrated using a surface coil for both transmission and signal reception in phantom and animal heart tagging studies. The experimental data demonstrated uniform grid contrast over a sixfold variation of B1 magnitude, sharp tagging profiles, and the ability to follow the cardiac wall motion through the deformation of the fine rectangular tagging grid at different phases throughout the cardiac cycle.

Animals↗

PubMed1995

Fast anatomical imaging of the heart and assessment of myocardial perfusion with arrhythmia insensitive magnetization preparation.

A new contrast preparation based on modified driven equilibrium Fourier transfer is introduced and evaluated for generation of T1-weighted images for assessment of the myocardial perfusion with contrast agent first-pass kinetics. The new preparation scheme produces T1 contrast with insensitivity to arrhythmias in prospectively triggered sequential imaging thereby eliminating one of the major sources of problems in potential patient studies with previously employed contrast preparations schemes.

Algorithms↗

PubMed1995

Transmural distribution of 2-deoxyglucose uptake in normal and post-ischemic canine myocardium.

This investigation was performed to determine (i) whether 31P spatially localized 31P NMR spectroscopy could be utilized to determine the transmural distribution of 2-deoxyglucose (2DG) uptake in the in vivo canine heart and (ii) whether transmural 2DG uptake would be affected by a preceding ischemic insult. 2DG was infused and the accumulation of 2-deoxyglucose-6-phosphate (2DGP) was monitored (by means of spatially localized 31P NMR) in control hearts, in pharmacologically hyperperfused hearts, and in hearts subjected to four (5 min) occlusions of the left anterior descending coronary artery. Myocardial blood flow was measured with radioactive microspheres. In control hearts, subendocardial (ENDO) 2DGP contents were significantly higher than those in the subepicardium (EPI) being 3.8 +/- 0.3 and 2.2 +/- 0.2 mumol/g, respectively; the ENDO/EPI ratio of 2DGP was 1.70 +/- 0.21. During hyperperfusion blood flow increased approximately four-fold but 2DGP accumulation was not altered. ATP levels in post-ischemic myocardium were significantly decreased (ENDO more than EPI) and 2DGP accumulation in each layer was increased (p < 0.01 vs control); however, the ENDO/EPI ratio of 2DGP was not altered. 2DG infusion induced a marked elevation of blood insulin and norepinephrine levels. These data demonstrate that in the presence of high blood levels of 2DG and insulin: (i) 2DGP accumulation can be measured in the in vivo canine heart; (ii) in normal hearts 2DG uptake is more pronounced in the inner layers of the left ventricular wall (this transmural 2DG uptake gradient is not due to subendocardial hypoperfusion); and (iii) 2DG uptake is greater in the post-ischemic heart but the ENDO/EPI gradient of 2DG uptake is not altered indicating that the more severe ischemic insult in the subendocardium does not result in a disproportionate increase in 2DG uptake in that region of the myocardium. Although 2DG uptake patterns in this model most probably reflect those of glucose (at comparable glucose and insulin levels), quantitative extrapolations with regard to the rate of glucose uptake are not possible from the present data.

Animals↗

PubMed1995

An in vivo 31P magnetic resonance spectroscopy study of uridine excess in rats fed orotic acid.

Spatially localized 31P NMR spectroscopy was used to assay in vivo the liver of intact rats fed orotic acid (OA) in a diet which produces hepatic steatosis. Twenty-three sets of multiple volume spectra were obtained from twenty-one 265- to 315-g female rats after 0-9 days of feeding either a 1% OA/64% sucrose diet (12 rats) or a 65% sucrose control diet (9 rats). The intensity of the in vivo diphosphodiester resonance ascribed to UDP-hexos(amin)es increased and the phosphomonoester resonance decreased in intensity prior to fatty infiltration. High resolution NMR spectroscopy of extracts of these livers indicated that the UDP-hexos(amin)e peak included four different UDP-sugars including UDP-N-acetylglucosamine (UDP-glcNAc), and that lower phosphocholine (P-Cho) accounted for the lower phosphomonoester resonance in vivo. Increased UDP-glcNAc is thought to reflect impaired lipoprotein glycosylation as a mechanism for hepatic steatosis in orotic acid feeding. P-Cho deficiency has been shown to be due to an increased rate of phosphatidylcholine synthesis. Low P-Cho concentration has been shown to be associated with lipid accumulation in a choline-deficient diet, but was not previously associated with hepatic steatosis in OA feeding. Changes in phosphorus metabolites were observed 2 days prior to development of fatty liver. HPLC assay of uridine nucleotides showed a good correlation between magnetic resonance spectroscopy and HPLC quantitation. In this study there were two biochemical correlates of impaired hepatic lipid secretion detectable by in vivo assay with 31P NMR spectroscopy. This method has application for noninvasive assays in ornithine transcarbamylase-deficient patients.

Animals↗

PubMed1995

Differential binding of two chicken beta-galactoside-specific lectins to homologous lymphocyte subpopulations and evidence for inhibitor activity of the dimeric lectin on stimulated T cells.

Plant lectins can be potent modulators of vertebrate immune functions. Biochemical characterization of lectins from animal tissues enables the determination of whether these endogenous activities display a comparable immunological potency. Focusing on chicken beta-galactoside-binding lectins, the monomeric intestinal (CL-14) and the dimeric liver lectin (CL-16) were purified and the lack of cross-contamination was ascertained. In very close agreement with the molecular masses of 14,974 and 14,976 calculated on the basis of the available sequence data (Y. Sakakura et al., J. Biol. Chem. 265, 21573-21579, 1990), electrospray mass spectrometric analysis yielded values of 14,969 (CL-14) and 14,972 (CL-16), the reasons for the deviation in gel electrophoretic behavior being unclear. Solid-phase assays with immobilized lactosylated poly-L-lysine demonstrated a comparatively lower affinity and higher extent of binding at saturation for the monomeric lectin than for the dimeric protein, whose properties were similar to those of an immunomodulatory plant lectin. Flow cytometry revealed homogeneous and strong binding of the dimeric lectin within the chicken peripheral blood lymphocyte population, whereas the monomeric lectin stained two subpopulations at different intensities. Two-color flow cytometry disclosed preferential binding of this lectin to B cells. When a B cell line was employed for determination of affinity constants and extents of binding at saturation, qualitatively comparable parameters to those for the solid-phase assays were obtained. The similar profile of lectin-binding glycoproteins in blots of cellular extracts underscored that accessibility to ligands, not qualitatively different ligand display, may explain the differences for the cell line. At up to a concentration of 10 micrograms/ml of the lectins no stimulation of [3H]thymidine incorporation was seen for blood and spleen cell populations. However, the dimeric lectin reduced stimulation of cells that were responsive to an anti-TcR2 antibody. Thus, this lectin can apparently exhibit inhibitory activity to this kind of T cell activation in vitro.

Animals↗

PubMed1995

A new localization method using an adiabatic pulse, BIR-4.

A new method is described for accomplishing localized spectroscopy with an adiabatic pulse, BIR-4. The method has advantages similar to previously described combinations of outer-volume suppression (OVS) and ISIS, with the additional advantages that localization is achieved with only three radiofrequency pulses and the localization remains accurate even in the presence of intense signals with short relaxation times. This new localization pulse sequence is referred to as integrated OVS-ISIS. Computer simulations, experimental images of the localized volumes, and in vivo 1H spectroscopy measurements demonstrate the high degree of localization achievable with integrated OVS-ISIS.

Animals↗