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Biomedical subjects

C Jost

Publications and source records attributed to C Jost.

At least 19 recordsLinked to original sources
PubMed2005

A new test of random walks in heterogeneous environments.

Environmental heterogeneities can change animal movement in two different manners. First, they can modify movement characteristics (move lengths or turning angles), in which case the movement remains of the diffusive kind. Second, they can bias displacement towards a particular direction in which case it becomes non-diffusive. We propose in this paper a simple method that only requires computing the mean length of a sample of trajectories in some bounded area to distinguish between these two kinds of movement. We show through simulations that the method allows to detect the presence of heterogeneities that orient animal movement. We apply it to experimental trajectories of Messor sancta ants engaged in corpse aggregation to show that their displacement is oriented at the contact of the formed corpse piles and that their trajectories become non-diffusive.

Animals↗
PubMed2004

Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: a quantitative in vivo 1H and 31P magnetic resonance study.

Creatine kinase (CK)-catalysed ATP-phosphocreatine (PCr) exchange is considered to play a key role in energy homeostasis of the brain. This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative magnetic resonance (MR) imaging and spectroscopy. MR imaging revealed an increase in ventricle size in a subset of B-CK-/- mice, but not in animals with UbCKmit or compound CK mutations. Mice lacking single CK isoenzymes had normal levels of high-energy metabolites and tissue pH. In the brains of CK double knockouts pH and ATP and Pi levels were also normal, even though PCr had become completely undetectable. Moreover, a 20-30% decrease was observed in the level of total creatine and a similar increase in the level of neuronal N-acetyl-aspartate compounds. Although CKs themselves are not evenly distributed throughout the CNS, these alterations were uniform and concordant across different brain regions. Changes in myo-inositol and glutamate peaks did appear to be mutation type and brain area specific. Our results challenge current models for the biological significance of the PCr-CK energy system and suggest a multifaceted role for creatine in the brain.

Animals↗
PubMed2003

Subjective quality of life and sexual functioning after germ-cell tumour therapy.

PURPOSE: To evaluate the influence of germ-cell tumour therapy on sexual functioning and subjective quality of life (QL). To investigate the communication about sexual problems between patients, their partners, and doctors. In all, 474 patients treated for germ-cell tumours at the Department of Internal Medicine III, Ludwig-Maximilians-University Munich, from 1979 to 2000 were asked to complete a self-report questionnaire concerning psychosocial dimensions and subjective QL (QLS; Henrich and Herschbach, 2000). In total, 341 patients returned a completed questionnaire (response rate, 71.9%). The median age at survey was 41.9 years and the median follow-up period after therapy was 9.6 years. Persisting sexual sequelae were lower than in the current literature: decreased sexual desire (7.1%), erection (10.0%), orgasm (10.2%), ejaculation (28.8%), sexual activity (8.5%), and sexual satisfaction (4.8%). In QL the satisfaction with 'friends/acquaintances' (P<0.001) and 'family life/children' (P<0.001), is lower than in the healthy population. Correlations between functional scales and subjective QL were highly significant. There is a strong correlation between sexual satisfaction and global life satisfaction (Spearman's Rho: 0.48; P<0.01). A total of 61.4% of patients were not offered communication about sexual problems by their doctors and 21.2% were unable to talk with their partner about sexual issues. In conclusion, moderating psychosocial variables (e.g. personality factors, cognitive processes) should be investigated to clarify the relationship between life satisfaction (subjective QL) and functional impairments. Communication about sexual problems should be offered as a standard to patients treated for germ-cell tumours.

Adult↗
PubMed2002

Circulating transforming growth factor beta1 (TGFbeta1) is elevated by extensive exercise.

Transforming growth factor beta1 (TGFbeta1) is a multifunctional growth factor involved in immune function, atherosclerosis, fibrotic disease, diabetic complications and bone turnover. It is synthesized in large quantities by bone cells in response to hormones and mechanical stimuli. Plasma contains inactive "latent" TGFbeta1, which consists of the precursor molecule and a TGFbeta1-binding protein. Platelets store latent TGFbeta1 in their alpha-granules, and serum therefore contains large amounts of latent TGFbeta1. We developed a technique for determining latent plasma TGFbeta1 and investigated whether circulating TGFbeta1 is affected by the stimulation of bone formation in response to strength training. Ten healthy students with low training activity participated in a heavy exercise programme over 4 weeks. Blood was drawn into citrate-filled syringes containing prostaglandin E(1) (PGE(1)) and immediately centrifuged at 4 degrees C. TGFbeta1 was determined with a sandwich ELISA standardized with National Institute for Biological Standards and Controls (NIBSC) materials. Six of the ten students completed the training. Highly reproducible values (500-600 pg/ml) of latent TGFbeta1 in plasma were determined. Baseline levels of TGFbeta1 were 525 (50) pg/ml [mean (SE)], which is in the range observed for young adults. TGFbeta1 concentrations rose significantly to 710 (65) pg/ml after 2 weeks of training and thereafter slowly declined to 650 (62) pg/ml after 2 weeks and 440 (33) pg/ml after 4 weeks, respectively. No active TGFbeta1 was detectable in citrate PGE1 plasma samples. Serum levels were between 6000 and 10,000 pg/ml and contained 200-400 pg/ml active TGFbeta1. In contrast to previous reports, plasma did not contain measurable amounts of circulating active TGFbeta1. We demonstrate that heavy exercise transiently elevates latent TGFbeta1 concentrations in plasma. TGFbeta1 is produced by osteoblasts in considerable amounts; therefore, we assume that the observed changes are partly due to enhanced TGFbeta1 production or release in bone, since the quantities of TGFbeta1 produced by other cells are comparably small.

Adult↗
PubMed2001

Analysis of TGFbeta3 gene expression and protein levels in human bone and serum.

Recent data indicate that TGFbeta3, one member of the TGFbeta-isoforms, has an important role in bone remodeling. Up to date little is known about the expression and regulation of TGFbeta3 in man. We established a highly specific ELISA for quantitative measurement of TGFbeta3 in bone and blood samples and a RT-PCR in combination with HPLC for detection and quantification of TGFbeta3 mRNA in 89 human bone samples. Levels of TGFbeta3 protein ranged between 30 and 66 pg/mg bone (mean 36,6 +/-1,03 pg/mg) and between 30 and 1910 pg/ml in serum (mean 128.9+/-38.9 pg/ml). TGFbeta3 mRNA expression as well as protein levels in serum and in bone declined age dependently. No specific load- or site-specific distribution of TGFbeta3 mRNA expression or protein content was detected at different sites indicating an absence of mechanical regulation. Protein levels of TGFbeta3 in serum correlated with TGFbeta3 mRNA expression in bone (p= 0.0027; r=0.49). By contrast, TGFbeta3 protein levels stored in the bone matrix were not related to TGFbeta3 mRNA reflecting the long term process of TGFbeta3 deposition during bone remodeling. Notably TGFbeta3 serum levels were highly correlated with IGF-I and osteocalcin levels in serum. We conclude that TGFbeta3 in man circulates in significant amounts which appears to be representative for TGFbeta3 expression in bone tissue and may be in part derived from bone. The high correlation of TGFbeta3 with IGF-I suggests parallel systemic principles of regulation.

Adolescent↗
PubMed2001

TGFbeta1 and TGFbeta2 mRNA and protein expression in human bone samples.

Transforming growth factor beta is one of the most abundant growth factors stored in bone. It is known as a potent regulator of osteoblast proliferation and differentiation as well as of production extracellular matrix. We established a highly specific RT-PCR in combination with HPLC for detection and quantification of TGFbeta1 and TGFbeta2 mRNA expression in 89 human bone samples. Levels of TGFbeta1 protein ranged between 27 and 580 ng/g bone (mean 188 +/- 15 ng/g; n=75) and for TGFbeta2 between 7.2 and 35 ng/g bone (mean 14.3 +/- 2.1 ng/g; n=57). TGFbeta1 and TGFbeta2 protein concentrations and TGFbeta isoform mRNA expression in bone were not significantly different between the sexes. TGFbeta isoform mRNA expression as well as protein content in bone declined age dependently. TGFbeta1 and TGFbeta2 protein and mRNA expression were different in bone samples from different sites of the skeleton indicating in part the regulation by mechanical stimuli. In contrast to TGFbeta1, TGFbeta2 mRNA expression was significantly enhanced in osteoarthritic bone compared to unaffected bone. These data are in concordance to previous results concerning the expression of TGFbeta3 in bone. In conclusion, the data suggest distinct patterns' of expression of the TGFbeta isoforms under physiological and pathological conditions in bone.

Adolescent↗
PubMed2000

Testing for predator dependence in predator-prey dynamics: a non-parametric approach.

The functional response is a key element in all predator-prey interactions. Although functional responses are traditionally modelled as being a function of prey density only, evidence is accumulating that predator density also has an important effect. However, much of the evidence comes from artificial experimental arenas under conditions not necessarily representative of the natural system, and neglecting the temporal dynamics of the organism (in particular the effects of prey depletion on the estimated functional response). Here we present a method that removes these limitations by reconstructing the functional response non-parametrically from predator-prey time-series data. This method is applied to data on a protozoan predator-prey interaction, and we obtain significant evidence of predator dependence in the functional response. A crucial element in this analysis is to include time-lags in the prey and predator reproduction rates, and we show that these delays improve the fit of the model significantly. Finally, we compare the non-parametrically reconstructed functional response to parametric forms, and suggest that a modified version of the Hassell-Varley predator interference model provides a simple and flexible function for theoretical investigation and applied modelling.

Animals↗
PubMed2000

Identifying predator-prey processes from time-series.

The functional response is a key element in predator-prey models as well as in food chains and food webs. Classical models consider it as a function of prey abundance only. However, many mechanisms can lead to predator dependence, and there is increasing evidence for the importance of this dependence. Identification of the mathematical form of the functional response from real data is therefore a challenging task. In this paper we apply model-fitting to test if typical ecological predator-prey time series data, which contain both observation error and process error, can give some information about the form of the functional response. Working with artificial data (for which the functional response is known) we will show that with moderate noise levels, identification of the model that generated the data is possible. However, the noise levels prevailing in real ecological time-series can give rise to wrong identifications. We will also discuss the quality of parameter estimation by fitting differential equations to such time-series.

Algorithms↗
PubMed2000

In vivo gene transfer of endothelial nitric oxide synthase to carotid arteries from hypercholesterolemic rabbits enhances endothelium-dependent relaxations.

BACKGROUND AND PURPOSE: Hypercholesterolemia is associated with abnormal endothelium-dependent vasorelaxation due to decreased nitric oxide bioavailability. Our aim was to examine the effect of adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) to the hypercholesterolemic rabbit carotid artery in vivo. In addition, we examined whether adenovirus-mediated gene transfer was associated with vascular dysfunction. METHODS: Rabbits were fed a 1% cholesterol diet for 4 weeks followed by a 0.5% cholesterol diet for 6 weeks. Vascular reactivity was assessed in nontransduced carotid arteries from chow- and cholesterol-fed animals. In addition, carotid arteries were surgically isolated, and 2 separate doses of adenoviral vectors encoding eNOS or beta-galactosidase (AdbetaGal) on the contralateral side were delivered to the lumen (1x10(10) and 5x10(10) pfu/mL). RESULTS: Abnormal acetylcholine-mediated endothelium-dependent vasorelaxation was detected in the carotid artery from cholesterol-fed animals, whereas responses to calcium ionophore A23187 and diethylamine NONOate were normal. Vascular reactivity was similar in nontransduced and AdbetaGal-transduced hypercholesterolemic vessels. In vessels transduced with eNOS, transgene expression was demonstrated by immunostaining in both the endothelium and the adventitia and by Western blot analysis. High-dose but not low-dose eNOS gene transfer enhanced endothelium-dependent relaxation in vessels from cholesterol-fed rabbits. CONCLUSIONS: Adenovirus-mediated gene transfer of eNOS to carotid arteries of cholesterol-fed animals improves endothelium-dependent relaxation when an optimal viral titer is administered.

Animals↗
PubMed1999

Mapping of a gene predisposing to familial thyroid tumors with cell oxyphilia to chromosome 19 and exclusion of JUN B as a candidate gene.

BACKGROUND: Familial nonmedullary thyroid carcinoma (FNMTC) is a clinical entity characterized by a more aggressive phenotype than the sporadic counterpart. The transmission of susceptibility of FNMTC is compatible with autosomal dominant inheritance. We report the identification of a new entity of FNMTC and the mapping of the responsible gene named TCO (for thyroid tumor with cell oxyphilia). METHODS: In one family, multinodular goiters were diagnosed in six individuals and papillary thyroid carcinoma was diagnosed in three. Eight patients were operated on. Blood samples were collected from the nine affected patients and from eight unaffected relatives. The gene was mapped by linkage analysis with a whole-genome panel of microsatellite markers. RESULTS: The neoplastic cells from all lesions showed characteristic faint to marked cytoplasmic oxyphilia. We found a logarithm of odd ratio (LOD) score of 2.41 at theta = 0 for marker D19S586. Additional markers were typed in the region and were found to be in linkage, with LOD scores peaking at markers D19S916 (Zmax = 3.01 at theta = 0) and D19S413 (Zmax = 2.95 at theta = 0). All these markers have been physically mapped to 19p13.2. CONCLUSIONS: TCO was mapped to chromosome 19p13.2. Interestingly, both the benign and malignant thyroid tumors in this family exhibit some degree of oxyphilia, which has not been described until now in the familial forms of NMTC.

Adenoma, Oxyphilic↗
PubMed1998

Intracellular storage and regulated plasma membrane expression of human complement receptor type 1 in rat basophil leukemia cell transfectants.

Polymorphonuclear neutrophils (PMN) contain multiple distinct secretory compartments that are sequentially mobilized during cell activation. Complement receptor type 1 (CR1) is a marker for a readily mobilizable secretory vesicle compartment, which can undergo exocytic fusion with the plasma membrane independently of secretion of traditional granule contents. The basis for the formation of these distinct compartments is incompletely understood. Primary and secondary granules are generated directly from the Golgi complex during different stages of development of the cell, obviating the need for sorting signals for proper packaging of their constituents. To determine whether the secretory vesicles are formed in a similar manner, we studied a stable rat basophilic leukemia cell line (RBL-CR1) transfected with a plasmid containing the cDNA of human CR1 driven by a viral promoter. The CR1 was present primarily intracellularly in small vesicles resembling the CR1 storage pools in resting PMN. Activation of RBL-CR1 resulted in translocation of intracellular CR1 to the plasma membrane, with mobilization requirements different from those of the classical RBL granules. Thus, in RBL-CR1, continuously synthesized CR1 is stored and upregulated in much the same way as in PMN. This suggests that differential timing of gene expression is not essential for proper storage of CR1 and that other sorting mechanisms are involved, which can be studied in RBL-transfectants.

Animals↗
PubMed1998

Comparative ethnoveterinary and serological evaluation of the Karimojong Community Animal Health Worker Program in Uganda.

The Karimojong CAHW program, in which members of the pastoral Karimojong community were trained as basic veterinary care providers, was evaluated using ethnoveterinary techniques. A serological study of rinderpest antibody titers was also completed to compare serological results with ethnoveterinary results in the case of one disease, rinderpest. An outbreak of rinderpest-like disease that occurred during the field phase of the study was also investigated. The results show that rinderpest does exist in Karamoja in an apparently endemic form. Given the significant value placed by Karimojong herders on vaccinated animals, it can be concluded that they would adequately vaccinate their herds if they could trust the vaccine and the vaccinator. Discrepancies between ethnoveterinary and serological results show that ethnoveterinary techniques do not provide numerically accurate data concerning protection from disease, but that they can, nonetheless, provide basic, cost effective indications of disease patterns.

Animal Husbandry↗
PubMed1998

Audit of the change of outcome of peptic ulcer disease following treatment of Helicobacter pylori.

In this audit we tried to assess the effect of the detection of Helicobacter pylori on the change of outcome and symptoms of peptic ulcer disease outside well defined prospective studies, and its influence on treatment praxis by general practitioners. The study was carried out in the canton of Uri, a geographically closed area of Switzerland. The records of all patients with peptic ulcer disease diagnosed from 1991 to 1994 were evaluated retrospectively. In addition, the patients were followed by contact through their family doctors who were asked to fill out questionnaires on the immediate and long-term treatment of acute peptic ulcer, H. pylori therapy, recurrence of ulcers in light of symptoms or endoscopy, and on any surgery performed for ulcer disease. We found 453 patients with peptic ulcer disease proven by endoscopy, 134 patients presented with signs of ulcer bleeding, 45% of these had used nonsteroidal anti-inflammatory drugs previously. Only 9 of 453 patients required surgery. In 430 patients follow-up was possible (median of 18 months). H. pylori eradication was the primary treatment in 24% of the patients in 1991 and in 79% in 1994. Long-term prophylaxis with histamine H2 antagonists had been selected in 22%. Recurrence of the ulcer disease was seen in 157 patients during the follow-up period. The recurrence rate was 8% (3/39) in patients with documented H. pylori eradication, 43% (62/145) in patients with H. pylori eradication therapy without documentation of the result, 57% (31/54) in H. pylori positive and 50% (14/28) in H. pylori negative patients on long-term treatment with histamine H2 antagonists. 33% of the patients still had substantial abdominal pain despite using long-term histamine H2 antagonists as prophylaxis against recurrence, but this was the case in only 5% (2/39) after successful H. pylori eradication. The rate of successful antibiotic treatment improved substantially during this audit. This follow-up study demonstrates that patients with successfully eradicated H. pylori remain largely free of symptoms and of ulcer recurrence. Control of the eradication result seems to be necessary outside controlled studies. In contrast, symptoms and ulcer recurrence are frequent despite long-term treatment with histamine H2 antagonists. Few patients need surgery for ulcer disease today. Audits like this are a valuable method to improve acceptance and success of a new treatment modality.

Aged↗
PubMed1998

High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization during a 20-fold normal oxalate load in humans.

BACKGROUND: The aim of the study was to test whether increasing dietary calcium intake lowers intestinal oxalate absorption and thereby prevents hyperoxaluria and urinary crystallization during a 20-fold normal oxalate load in healthy subjects. METHODS: Fourteen healthy male volunteers (age 23-44 years, BMI 21.5-27.7 kg/m2) collected 24-h urines while on free-choice diet as well as on two standardized diets. The latter contained 2545 kcal, 2500 ml of mineral water, 102 g of protein, 13.6 g of sodium chloride and 2220 mg of oxalate (approximately 20-fold content of an average diet). Subjects were studied twice while on the standardized diet, once while eating a normal amount of calcium (1211 mg/day, oxalate-rich diet), and once while eating 3858 mg of calcium/day (calcium and oxalate-rich diet). RESULTS: Compared with the free-choice diet (322+/-36 micromol/d), UOx x V increased to 780+/-72 micromol/d on the oxalate-rich diet (P=0.001) and fell again to 326+/-31 micromol/d on calcium and oxalate-rich diet (P=0.001 vs oxalate-rich diet). Urinary glycolate (a metabolic precursor of Ox) always remained below the upper limit of the normal range and did not change between different diets, indicating that changes in UOX x V reflect respective variations in intestinal absorption of Ox. Uca x V was 4.60+/-0.45 mmol/d on the free-choice diet and 3.20+/-0.32 mmol/d on the oxalate-rich diet (P=0.011 vs free-choice diet); it increased to 7.28+/-0.74 mmol/d on the calcium- and oxalate-rich diet (P=0.001 vs free-choice and oxalate-rich diets). As indicated by the AP (CaOx) index (Tiselius), urinary supersaturation did not vary significantly between the three diets. In freshly voided morning urines (studied in 8/14 subjects) on the oxalate-rich diet, CaOx crystals or crystal aggregates of up to 80 microm diameter were found in 5/8 urines, whereas this never occurred on the free-choice diet and only t once on the calcium- and oxalate-rich diet. CONCLUSION: . Increasing calcium intake while eating Ox-rich food prevents dietary hyperoxaluria and reduces CaOx crystallization in healthy subjects. This further illustrates that dietary counseling to idiopathic calcium-stone formers should ensure sufficient calcium intake, especially during oxalate-rich meals.

Adult↗
PubMed1998

Are Current Cardiovascular Stents MRI Safe?

The number of coronary stents may be over half a million world-wide. The neurologist and radiologist are frequently confronted with cardiac patients who have had a recent carotid or coronary stent implanted and present with an acute and unrelated stroke for which an MRI is recommended. We have reviewed and classified all the major stents currently available world-wide and discussed their interaction with MRI through their ferro-magneticity. All current stents are MRI safe and MRI can be done anytime.

Journal Article↗
PubMed1998

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK) mediated phosphocreatine (PCr) <==> ATP transphosphorylation in mitochondria and cytosol of skeletal muscle by knocking out the genes for the mitochondrial (ScCKmit) and the cytosolic (M-CK) CK isoforms in mice. Animals which carry single or double mutations, if kept and tested under standard laboratory conditions, have surprisingly mild changes in muscle physiology. Strenuous ex vivo conditions were necessary to reveal that MM-CK absence in single and double mutants leads to a partial loss of tetanic force output. Single ScCKmit deficiency has no noticeable effects but in combination the mutations cause slowing of the relaxation rate. Importantly, our studies revealed that there is metabolic and cytoarchitectural adaptation to CK defects in energy metabolism. The effects involve mutation type-dependent alterations in the levels of AMP, IMP, glycogen and phosphomonoesters, changes in activity of metabolic enzymes like AMP-deaminase, alterations in mitochondrial volume and contractile protein (MHC isoform) profiles, and a hyperproliferation of the terminal cysternae of the SR (in tubular aggregates). This suggests that there is a compensatory resiliency of loss-of-function and redirection of flux distributions in the metabolic network for cellular energy in our mutants.

Animals↗
PubMed1997

Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice. Contrary to expectation, the PCr level was only marginally affected, but the compound was rendered metabolically inert. Mutant muscles in vivo showed significantly impaired tetanic force output, increased relaxation times, altered mitochondrial volume and location, and conspicuous tubular aggregates of sarcoplasmic reticulum membranes, as seen in myopathies with electrolyte disturbances. In depolarized myotubes cultured in vitro, CK absence influenced both the release and sequestration of Ca2+. Our data point to a direct link between the CK-PCr system and Ca2+-flux regulation during the excitation and relaxation phases of muscle contraction.

Adenosine Triphosphate↗