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Biomedical subjects

C Boesch

Publications and source records attributed to C Boesch.

At least 19 recordsLinked to original sources

Observation of intramyocellular lipids by 1H-magnetic resonance spectroscopy.

Magnetic resonance (MR) methods are increasingly being used to investigate the physiology of human muscle. Although MR imaging (MRI) reveals the morphology of muscles in great detail, for example, for determining their volume and fiber orientation, MR spectroscopy (MRS) provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the observation of high-energy phosphates (31P-MRS), glycogen (13C-MRS), or intramyocellular lipids (1H-MRS), to give only a few examples. 1H-MRS of human skeletal muscle requires special techniques because 1H nuclei in water or adipose tissue are far more concentrated than in any other metabolite of human tissue. The strong signal from water can be suppressed by special prepulses, whereas large signals from fat in adipose tissue can be reduced by carefully selecting the region of interest. Until recently, it was presumed that only a few metabolites would be visible underneath the large resonances of water and subcutaneous fat. Meanwhile, it was clear that 1H-MR spectra of human muscle reveal much metabolic and structural information. The determination of intramyocellular lipids (IMCL) by 1H-MRS was initiated by the observation of two compartments of triacylglycerols with a resonance-frequency shift of approximately 0.2 ppm. The two resonances can be attributed to CH2 protons of lipids in fat cells, and to lipids inside muscle cells (IMCL). 1H-MRS examinations are noninvasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace biopsy to follow-up IMCL levels; however, biopsy still has the advantage that other methods, such as molecular biology, can be applied to the sample. It can be shown that IMCL levels (expressed in mMol/kg wet weight and volume %) are muscle specific and vary with diet and physical activity. In addition, it has been reported that IMCL levels are correlated with insulin sensitivity. A comparison of different methods for assessing IMCL levels, including MRS, chemical analysis, and morphometry, revealed a satisfactory correlation among them and a superior correlation of MRS with the average of the three methods. The observation of IMCL levels by means of 1H-MRS is extremely promising, but several methodological limitations and pitfalls need to be considered.

Adipose Tissue↗

Cultures in chimpanzees.

As an increasing number of field studies of chimpanzees (Pan troglodytes) have achieved long-term status across Africa, differences in the behavioural repertoires described have become apparent that suggest there is significant cultural variation. Here we present a systematic synthesis of this information from the seven most long-term studies, which together have accumulated 151 years of chimpanzee observation. This comprehensive analysis reveals patterns of variation that are far more extensive than have previously been documented for any animal species except humans. We find that 39 different behaviour patterns, including tool usage, grooming and courtship behaviours, are customary or habitual in some communities but are absent in others where ecological explanations have been discounted. Among mammalian and avian species, cultural variation has previously been identified only for single behaviour patterns, such as the local dialects of song-birds. The extensive, multiple variations now documented for chimpanzees are thus without parallel. Moreover, the combined repertoire of these behaviour patterns in each chimpanzee community is itself highly distinctive, a phenomenon characteristic of human cultures but previously unrecognised in non-human species.

Animals↗

Mitochondrial sequences show diverse evolutionary histories of African hominoids.

Phylogenetic trees for the four extant species of African hominoids are presented, based on mtDNA control region-1 sequences from 1,158 unique haplotypes. We include 83 new haplotypes of western chimpanzees and bonobos. Phylogenetic analysis of this enlarged database, which takes intraspecific geographic variability into account, reveals different patterns of evolution among species and great heterogeneity in species-level variation. Several chimpanzee and bonobo clades (and even single social groups) have retained substantially more mitochondrial variation than is seen in the entire human species. Among the 811 human haplotypes, those that branch off early are predominantly but not exclusively African. Neighbor joining trees provide strong evidence that eastern chimpanzee and human clades have experienced reduced effective population sizes, the latter apparently since the Homo sapiens-neanderthalensis split. Application of topiary pruning resolves ambiguities in the phylogenetic tree that are attributable to homoplasies in the data set. The diverse patterns of mtDNA sequence variation seen in today's hominoid taxa probably reflect historical differences in ecological plasticity, female-biased dispersal, range fragmentation over differing periods of time, and competition among social groups. These results are relevant to the origin of zoonotic diseases, including HIV-1, and call into question some aspects of the current taxonomic treatment and conservation management of gorillas and chimpanzees.

Animals↗

Non-invasive observation of acetyl-group buffering by 1H-MR spectroscopy in exercising human muscle.

The observation of a previously unidentified peak in localized 1H magnetic resonance (MR) spectra of human muscle during and after a work load is reported. Basic NMR properties of this resonance, as well as physiologic circumstances of its observation, suggest that it is due to the acetyl group of acetylcarnitine. The relatively large pool of muscular carnitine acts as a buffering system stabilizing the ratio of acetylated to free coenzyme A. Free carnitine can be acetylated to a large extent whenever a mismatch occurs between the fluxes through pyruvate dehydrogenase and the TCA cycle. Results of initial applications of 1H MR spectroscopy in several muscles and under different exercise regimens are in agreement with earlier invasive measurements of acetylcarnitine. It is demonstrated that the detailed dynamics of acetyl group formation are now likely to be observable non-invasively in humans by localized 1H magnetic resonance spectroscopy on standard MR imaging systems, and that acetylcarnitine buffering as a function of exercise type, oxygenation states, diet and pathology could thus be studied repeatedly and in various muscle groups with much improved temporal resolution.

Acetylation↗

Restoration of electrophysiological signals distorted by inductive effects of magnetic field gradients during MR sequences.

A generally applicable method for almost complete suppression of signal artifacts on electrophysiological signals caused by B0-gradient switching (gradient noise) is presented. The method is demonstrated for electrocardiograms (ECGs) but can also be used for other electrophysiological signals. It takes advantage of the fact that under certain conditions, the effect of switching the B0-field gradient upon an electrophysiological signal can be modeled as a linear time-invariant system and fully characterized by pulse response functions. It is shown how the system's pulse response functions of the X, Y, and Z gradients can be determined and how gradient noise can be eliminated efficiently. The elimination of gradient noise by the proposed method causes in the current arrangement a constant delay of 128 msec, which is acceptable for patient monitoring and magnetic resonance sequence triggering.

Artifacts↗

Methods and reproducibility of cardiac/respiratory double-triggered (1)H-MR spectroscopy of the human heart.

Localized (1)H-MR spectroscopy is sensitive to motion and has mostly been applied to the brain. For the human heart, cardiac and respiratory motion lead to displacements on the order of the localized voxel and lead to substantial variations of voxel content, lineshape, water suppression, and signal phase and amplitude. Combined respiratory and cardiac double triggering can avoid these complications to a large extent. Three methods of double triggering are evaluated, with reproducibility established in nine subjects for a method based on respiratory modulation of the ECG amplitude and a visual feedback mechanism. Quantitated with respect to water, within-subject reproducibilities for this setup were 9% for trimethylammonium compounds, 10% for creatine/phosphocreatine, and 13% for lipids. ANOVA showed significant differences between subjects which may relate to natural variability between subjects or exact location within the heart. Unresolved issues for this technique are its susceptibility to precise placement of ECG electrodes and the reasons for failure in 20% of examination. With this technique it is possible to investigate open questions in cardiac pathophysiology, such as the creatine content in chronic heart disease. Variants of this triggering method may also improve cardiovascular MRI methods relying on data acquired in several heartbeats. Magn Reson Med 42:903-910, 1999.

Adult↗

Female reproductive strategies, paternity and community structure in wild West African chimpanzees.

Although the variability and complexity of chimpanzee behaviour frustrates generalization, it is widely believed that social evolution in this species occurs in the context of the recognizable social group or community. We used a combination of field observations and noninvasive genotyping to study the genetic structure of a habituated community of 55 wild chimpanzees, Pan troglodytes verus, in the Taï Forest, Côte d'Ivoire. Pedigree relationships in that community show that female mate choice strategies are more variable than previously supposed and that the observed social groups are not the exclusive reproductive units. Genetic evidence based on nuclear microsatellite markers and behavioural obser-vations reveal that females in the Taï forest actively seek mating partners outside their social unit; noncommunity males accounted for half the paternities over 5 years. This female mating strategy increases male gene flow between communities despite male philopatry, and negates the predicted higher relatedness among community males. Kin selection seems unlikely to explain the frequent cooperation and sharing observed among group males in this population. Similarly, inbreeding avoidance is probably not the sole cause of permanent adolescent female dispersal as a combination of extragroup mating and avoidance of incest with home group males would allow females to avoid inbreeding without the hazards associated with immigration into a new community. Extragroup mating as part of chimpanzee females' reproductive strategy may allow them to choose from a wider variety and number of males, without losing the resources and support provided by their male social group partners. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Effect of exercise on the creatine resonances in 1H MR spectra of human skeletal muscle.

1H MR spectra of human muscles were recorded before, during, and after fatiguing exercise. In contrast to expectations, it was found that the spectral contributions of creatine/phosphocreatine (Cr/PCr) were subject to change as a function of exercise. In particular, the dipolar-coupled methylene protons of Cr/PCr were found to be reduced in intensity in proportion to the co-registered PCr levels. Recovery after exercise and behavior under ischemic conditions provide further evidence to suggest that the contributions of the CH2 protons of Cr/PCr to 1H MR spectra of human muscle in vivo reflect PCr rather than Cr levels. Variation of experimental parameters showed that this effect is not due to a trivial change in relaxation times. At present it can only be speculated about why the Cr resonances have reduced NMR visibility. If temporary binding to macromolecules should be involved, the free Cr concentration-important for equilibrium calculations of the creatine kinase reaction-might be different from what was previously assumed.

Adult↗

Observation of intramyocellular lipids by means of 1H magnetic resonance spectroscopy.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.

Diet↗

Ebola virus outbreak among wild chimpanzees living in a rain forest of Côte d'Ivoire.

An outbreak of Ebola in nature is described for the first time. During a few weeks in November 1994, approximately 25% of 43 members of a wild chimpanzee community disappeared or were found dead in the Taï National Park, Côte d'Ivoire. A retrospective cohort study was done on the chimpanzee community. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola-specific immunohistochemical staining was positive for autopsy tissue sections from 1 chimpanzee. Demographic, epidemiologic, and ecologic investigations were compatible with a point-source epidemic. Contact activities associated with a case (e.g., touching dead bodies or grooming) did not constitute significant risk factors, whereas consumption of meat did. The relative risk of meat consumption was 5.2 (95% confidence interval, 1.3-21.1). A similar outbreak occurred in November 1992 among the same community. A high mortality rate among apes tends to indicate that they are not the reservoir for the disease causing the illness. These points will have to be investigated by additional studies.

Animals↗

Histopathological and immunohistochemical studies of lesions associated with Ebola virus in a naturally infected chimpanzee.

Lesions caused by the Côte d'Ivoire subtype of Ebola virus in a naturally infected young chimpanzee were characterized by histopathological and immunohistochemical methods. The predominant lesions consisted of multifocal necrosis in the liver and diffuse fibrinoid necrosis in the red pulp of the spleen. In these sites, macrophages contained large eosinophilic intracytoplasmic inclusion bodies. Immunohistochemical staining indicated that macrophages were a major site of viral replication. The absence of bronchiolar and pulmonary lesions and the paucity of antigen-containing macrophages in the lung suggested that aerosol transmission by this animal was unlikely. There were necrotic foci and antigen-containing macrophages in intestinal lymph nodes, in association with lesions caused by intestinal parasites, suggesting the possibility of virus entry through the digestive tract.

Animals↗

Creatine supplementation--part I: performance, clinical chemistry, and muscle volume.

PURPOSE: Our purpose was to study the effects and side effects of creatine (Cr) supplementation on high-intensity, short-term muscle work, on biochemical parameters related to Cr metabolism in blood and urine, and on muscle volume of the lower limb muscles. METHODS: A cycling ergometer was used in a double-blind, cross-over study on 10 well-trained male physical education students to measure physical performance with 10 repetitive ergometer sprints (6-s duration, 30-s rest) before and after supplementation (5 d, 20 g x d(-1), washout period 61 +/- 8 d, mean +/- SEM, minimum 28 d) with Cr or placebo. Before and after supplementation, blood and urine were taken and the muscle volume of the lower limb was determined by magnetic resonance imaging (MRI). RESULTS: A significant (P << 0.05) increase in performance (+7%) at the end [4-6 s] of the later sprints (4-7 and 8-10) was observed combined with a lower production of blood lactate (-1 mmol x L(-1)) with Cr supplementation. The concentration of Cr was increased significantly in urine (P < 0.001) and serum (P = 0.005), whereas creatinine (Crn) was increased in serum (P < 0.001). Crn in urine and Crn clearance did not change significantly with Cr intake. There were no significant changes in the analyzed blood enzyme activities. A significant gain of body weight (pre-Cr 76.5 +/- 1.7 kg to 77.9 +/- 1.7 kg post-Cr) with Cr supplementation was measured, but no accompanying increase of muscle mass in a limited volume of the lower limb was observed by MRI. CONCLUSION: Cr supplementation is effective in improving short-term performance, and the methods used show no detrimental side effects with this supplementation protocol.

Adult↗

Creatine supplementation--part II: in vivo magnetic resonance spectroscopy.

PURPOSE: Our purpose was to study effects of creatine (Cr) supplementation on muscle metabolites noninvasively by means of magnetic resonance spectroscopy (MRS) before and after supplementation with Cr or placebo. METHODS: 1H-MRS was used in a comprehensive, double-blind, cross-over study in 10 volunteers to measure Cr in m. tibialis anterior and m. rectus femoris at rest. PCr/ATP was observed in m. quadriceps femoris by 31P-MRS at rest and after exercise. RESULTS: A significant increase in total Cr was observed with Cr intake in m. tibialis anterior (+9.6 +/- 1.7%, P = 0.001) and in m. rectus femoris (+18.0 +/- 1.8%, P < 0.001). PCr/ATP showed a significant increase (+23.9 +/- 2.3%, P < 0.001) in m. quadriceps femoris at rest with Cr supplementation. Post-Cr supplementation recovery rates from exercise were significantly lower (k = 0.029 s(-1), P < 0.01) compared with postplacebo consumption (k = 0.034 s(-1)) and presupplementation (k = 0.037 s(-1)). However, higher levels of PCr/ATP at rest compensate for this reduction of the recovery rate after Cr supplementation. The increase of PCr/ATP determined by 31P-MRS correlates with the increase of Cr observed by 1H-MRS (r = 0.824, P < 0.001). CONCLUSION: Noninvasive observation of Cr and PCr after Cr supplementation shows an increase in a muscle specific manner. Higher preexercise levels of PCr/ATP at rest compensate for significantly slower recovery rates of PCr/ATP after Cr supplementation.

Adenosine Triphosphate↗

Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria.

Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.

Adult↗

Neonatal body composition: dual-energy X-ray absorptiometry, magnetic resonance imaging, and three-dimensional chemical shift imaging versus chemical analysis in piglets.

An animal study to evaluate dual-energy x-ray absorptiometry (DXA) and magnetic resonance (MR) imaging and spectroscopy for measurement of neonatal body composition was performed. Twenty-three piglets with body weights ranging from 848 to 7550 g were used. After measuring total body water, animals were killed and body composition was assessed using DXA and MR (1.5 T; MR imaging, T1-weighted sagittal spin-echo sequence; MR spectroscopy, three-dimensional chemical shift imaging) as well as chemical carcass analysis (standard methods) after homogenization. Body composition by chemical analysis (percent of body weight, mean +/- SD) was as follows: body water, 75.3 +/- 3.9%; total protein, 13.9 +/- 8.8%; and total fat, 6.5 +/- 3.7%. Absolute content of fat and total ash was 7-674 and 35-237 g, respectively. Mean hydration of fat-free mass was 0.804 +/- 0.011 g/kg and decreased with increasing body weight (r2 = 0.419) independent of age. Using DXA, bone mineral content was highly correlated with calcium content (r2 = 0.992), and calcium per bone mineral content was 44.1 +/- 4.2%. DXA fat mass correlated with total fat (r2 = 0.961). Using MR, spectroscopy and chemical analysis were highly correlated with fat-to-water ratio (r2 = 0.984) and absolute fat content (r2 = 0.988). Total fat by MR imaging volumetry showed a lower correlation (r2 = 0.913) and overestimated total fat by a factor of 2.46. Conversion equations for DXA were developed (total fat = 1.31 x fat mass measured by DXA--68.8; calcium = 0.402 x bone mineral content + 1.7), which improved precision and accuracy of DXA measurements. In conclusion, both DXA and MR spectroscopy give accurate and precise estimates of neonatal body composition and may become valuable tools for the noninvasive assessment of neonatal growth and nutritional status.

Absorptiometry, Photon↗

[Late potentials in chronic alcoholics].

OBJECTIVE: Cardiac arrest is the most frequent cause of death in chronic alcoholics. Detection of late potentials in this population could be helpful in screening from early signs of myocardial disorders and identifying patients at risk of severe ventricular dysrythmia. PATIENTS AND METHODS: A prospective study of late potentials was conducted in 53 subjects (mean age 49 +/- 10 years) with a history of long-standing alcohol abuse (mean 13.6 +/- 8.5 years, mean daily alcohol intake 86 +/- 30 g). After a period of abstinence, the following explorations were performed: liver tests, liver biopsy, electrocardiogram, echocardiography, Holter recording. RESULTS: Among the 53 patients, 37% were positive for 2 of the 3 criteria for late potentials. There was a strong correlation between the duration of alcohol abuse and presence of late potentials (p = 0.006, r = 0.37). The percentage of hepatic steatosis was higher in alcoholic subjects with late potentials (34% versus 23%; p = 0.05) and was correlated with the number of positive criteria for late potentials (p = 0.05, r = 0.328). Finally, the presence of late potentials was also correlated with the following laboratory results: serum gamma glutamyltranspeptidase (p = 0.031), serum aspartate amino transferase (p = 0.033), serum alkaline phosphatases (p = 0.0025). CONCLUSION: Late potentials can be detected easily although their prognostic value remains to be determined. They could be an early marker of infraclinical myocardial lesions.

Adult↗

Effects of physiologic motion of the human brain upon quantitative 1H-MRS: analysis and correction by retro-gating.

Signal loss and absolute quantitation errors in 1H-MRS (localized proton MR spectroscopy) because of physiologic brain motion are analyzed quantitatively. Cardiac and respiratory related motion lead to substantial phase dispersion when using a standard, short echo-time STEAM sequence. The loss in signal area varies from 6-7% with TM (middle interval time in a STEAM sequence) = 13.7 ms, to 25-39% with TM = 100 ms. The variation in signal area because of motion-related phase dispersion is up to 16% for TM = 100 ms. The signal phase as a function of the position in the cardiac cycle is shown to be reproducible. Maximal differences in the signal phase are over 180 degrees for long TMs. ECG-gating reduces the phase dispersion considerably but introduces problems with variable repetition times. Using a phase calibration curve recorded with the water suppression turned off, it is possible to retrogate subsequent untriggered acquisitions with the water suppression activated, if the time points in the cardiac cycle are recorded for each acquisition. The gain in signal intensity is between 3 and 21%. For absolute quantification via brain water, this phase analysis has the important consequence that reference scans must be phased individually before co-adding, otherwise metabolite concentrations may be severely overestimated.

Brain↗