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Biomedical subjects

M Lehmann

Publications and source records attributed to M Lehmann.

At least 109 records · Page 6Linked to original sources
PubMed1998

Circulating oxyntomodulin-like immunoreactivity in healthy children and children with celiac disease.

BACKGROUND: The aim of the study was to evaluate the new hormonal entity oxyntomodulin-like immunoreactivity in malabsorption states, and to assess its potential in celiac disease management. METHODS: We measured basal and postprandial oxyntomodulin-like immunoreactivity values in 35 children divided into 3 groups: group 1 was composed of 13 children with celiac disease, either under a gluten-free diet (8 patients) or normal diet (5 patients); group 2 was composed of 8 children hospitalized for gastroenteritis or chronic diarrhea, without biological evidence of malabsorption nor abnormal jejunal mucosa; group 3 was composed of 22 control subjects. RESULTS: Fasting and meal-stimulated levels in the control group were 71+/-10 and 130+/-26 pmol/l, respectively. Mean concentrations were elevated in patients with celiac disease (basal = 349+/-254 pmol/l, postprandial = 446+/-332 pmol/l) and in the group 2 (basal = 139+/-58 pmol/l, postprandial = 218+/-85 pmol/l), but the difference with control subjects did not reach statistical significance. In children with celiac disease, basal and stimulated values correlated with the degree of malabsorption as assessed by hemoglobin (p = 0.006 and p = 0.01, respectively) and serum folate concentrations (p = 0.03 and p = 0.02, respectively). CONCLUSIONS: Oxyntomodulin-like immunoreactivity is noticeably higher in healthy children than previously measured in healthy adult subjects. This hormonal parameter is not an adequate diagnostic tool in celiac disease. Nevertheless, in the context of celiac disease, its elevation reflects the degree of malabsorption and may provide a quantitative approach of the extent of mucosal damage.

Biomarkers↗
PubMed1998

Autonomic imbalance hypothesis and overtraining syndrome.

PURPOSE: The parasympathetic, Addison type, overtraining syndrome represents the dominant modern type of this syndrome. Beside additional mechanisms, an autonomic or neuroendocrine imbalance is hypothesized as underlying. METHODS/RESULTS: Several findings support this thesis. During heavy endurance training or overreaching periods, the majority of findings give evidence of a reduced adrenal responsiveness to ACTH. This is compensated by an increased pituitary ACTH release. In an early stage of the overtraining syndrome, despite increased pituitary ACTH release, the decreased adrenal responsiveness is no longer compensated. The cortisol response decreases. In an advanced stage of overtraining syndrome, the pituitary ACTH release also decreases. In this stage, there is additionally evidence for decreased intrinsic sympathetic activity and sensitivity of target organs to catecholamines. This is indicated by decreased catecholamine excretion during night rest, decreased beta-adrenoreceptor density, decreased beta-adrenoreceptor-mediated responses, and increased resting plasma norepinephrine levels and responses to exercise. However, this complete pattern is only observed subsequent to high-volume endurance overtraining at high caloric demands. CONCLUSION: The described functional alterations of pituitary-adrenal axis and sympathetic system can explain persistent performance incompetence in affected athletes.

Adrenocorticotropic Hormone↗
PubMed1998

Training of rowers before world championships.

In rowing, static and dynamic work of approximately 70% of the body's muscle mass is involved for 5.5 to 8 min at an average power of 450 to 550 W. In high load training phases before World Championships, training volume reaches 190 min.d-1, of which between 55 and 65% is performed as rowing, and the rest is nonspecific training like gymnastics and stretching and semispecific training like power training. Rowing training is mainly performed as endurance training, rowing 120 to 150 km or 12 h.wk-1. Rowing at higher intensities is performed between 4 and 10% of the total rowed time. The increase in training volume during the last years of about 20% was mainly reached by increasing nonspecific and semispecific training. The critical borderline to long-term overtraining in adapted athletes seems to be 2 to 3 wk of intensified prolonged training of about 3 h.d-1. Sufficient regeneration is required to avoid overtraining syndrome. The training principles of cross training, alternating hard and easy training days, and rest days reduce the risk of an overtraining syndrome in rowers.

Adult↗
PubMed1998

Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson's disease with autonomic failure.

OBJECTIVE: To selectively investigate postganglionic sympathetic cardiac neurons in patients with Parkinson's disease and autonomic failure. MATERIAL AND METHODS: Metaiodobenzylguanidine (MIBG) is a pharmacologically inactive analogue of noradrenaline, which is similarly metabolized in noradrenergic neurons. Therefore the uptake of radiolabelled MIBG represents not only the localization of postganglionic sympathetic neurons but also their functional integrity. Ten patients with Parkinson's disease and autonomic failure underwent standardized autonomic testing, assessment of catecholamine plasma levels and scintigraphy with [123I]MIBG. RESULTS: The cardiac uptake of MIBG, as demonstrated by the heart/mediastinum ratio, was significantly lower in patients in comparison with controls. Scintigraphy with MIBG allowed the selective in-vivo investigation of postganglionic sympathetic cardiac efferents in patients with autonomic failure, a procedure which was previously confined to post-mortem examination. CONCLUSION: These findings point to a relevant postganglionic pattern of involvement of the autonomic nervous system (ANS) in Parkinson's disease and autonomic failure.

3-Iodobenzylguanidine↗
PubMed1998

Beta interferon is produced by Chlamydia trachomatis-infected fibroblast-like synoviocytes and inhibits gamma interferon-induced HLA-DR expression.

Infection of fibroblast-like synovial cells with Chlamydia trachomatis (serotype D strain IC Cal 8) in culture induced the secretion of beta interferon (IFN-beta). Chlamydial infection inhibited IFN-gamma-induced expression of HLA-DR antigen in the cells. Addition of IFN-beta antibody directly to infected cultures mitigated HLA-DR inhibition, suggesting involvement of produced IFN-beta.

Cells, Cultured↗
PubMed1998

Catecholamines, heart rate, and oxygen uptake during exercise in persons with spinal cord injury.

The purpose of this study was to investigate the influence of different injury levels in persons with spinal cord injury (SCI) on epinephrine (Epi) and norepinephrine (NE) at rest and during graded wheelchair exercise and the related changes in heart rate and O2 uptake (VO2). Twenty tetraplegics (Tetra), 10 high-lesion paraplegics (HLPara), 20 paraplegics with SCI below T5 (MLPara), and 18 able-bodied, nonhandicapped persons (AB) were examined. Because of the higher level of interruption of the sympathetic pathways, Tetra persons showed lower Epi and NE at rest and only slight increases during exercise compared with all other groups; the Tetra subjects' impaired cardiac sympathetic innervation caused restricted cardioacceleration and strongly reduced maximal VO2. When compared with AB persons, HLPara had comparable NE but lower Epi levels as a result of partial innervation of the noradrenergic system and denervation of the adrenal medulla. MLPara subjects showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity compared with AB subjects. The increase in heart rate in relation to VO2 was higher in HLPara because of a smaller stroke volume as a result of venous blood pooling. The different exercise response in persons with SCI is a result of the interruption of pathways in the spinal cord to the peripheral sympathetic nervous system in addition to the motor paralysis.

Adult↗
PubMed1998

Microsensor-aided measurements of cellular signalling and metabolism on tumor cells. The cell monitoring system (cms(R)).

Microsensors provide instruments particularly suited for the rapid, noninvasive and on-line analysis of cell and tissue cultures. The microsensor system presented in this paper is a modular arrangement of various planar and nonplanar sensor elements for the measurement of physiological parameters of cell cultures. An optic access to the cultures (e.g. for light microscopy and spectrophotometric techniques) is also provided for a parallel and comparative data acquisition. The system was originally designed for biomedical research in chemotherapy (predicative chemotherapy assays) and pharmacology but it turned out to be also an effective tool for toxicological and environmental research.

Biosensing Techniques↗
PubMed1998

Blood flow of the middle cerebral artery with sleep-disordered breathing: correlation with obstructive hypopneas.

BACKGROUND AND PURPOSE: Epidemiological data link heavy snoring to an increased risk for stroke, an association often ascribed to hypertension and/or sleep apnea. The aim of this study was to determine whether obstructive hypopneas, central apneas, or obstructive apneas during sleep alter blood flow of the middle cerebral artery (MCA). METHODS: Doppler sonography of the MCA was performed in conjunction with nightly polysomnography in 11 men and one woman. RESULTS: A significant decline in blood flow occurred in 76% (169/223) of obstructive hypopneas and in 80% (98/123) of obstructive apneas, compared with only 14% (13/96) of central apneas (P<.0001). While duration of events was not significantly different, MCA blood flow reductions were associated only with the duration of the obstructive hypopneas (P< or =.01) and not with the duration of central (P=.17) or obstructive (P=.07) apneas. The magnitude of fall in arterial oxygen saturation from baseline correlated with a reduced blood flow with obstructive hypopneas but not with obstructive or central apneas. CONCLUSIONS: With obstructive hypopneas and obstructive apneas, MCA blood flow is more often decreased in comparison to central apneas. MCA blood flow reductions occur with longer obstructive hypopneas and with those hypopneas with greater falls in oxygen saturation. These observations indicate pathophysiology relevant to an increased risk for stroke in heavy snorers and patients with obstructive hypopneas and apneas.

Adult↗
PubMed1998

Deficient processing and activity of type I insulin-like growth factor receptor in the furin-deficient LoVo-C5 cells.

To investigate endoproteolytic processing of the type I insulin-like growth factor receptor (IGF-IR), we have examined its structure and activity in the furin-deficient LoVo-C5 cell line. Immunoprecipitation experiments using the monoclonal anti-IGF-IR antibody (alpha-IR3) showed that LoVo-C5 cells expressed a major high molecular mass receptor (200 kDa) corresponding to the unprocessed alpha/beta pro-receptor. A small amount of successfully cleaved alpha/beta heterodimers was also produced, indicating a residual endoproteolytic cleavage activity in these cells. In vitro, a soluble form of recombinant furin was able to cleave the pro-IGF-IR (200 kDa) into alpha-subunit (130 kDa) and beta-subunit (97 kDa). Measurement of IGF binding parameters in LoVo-C5 cells indicated a low number of typical type I IGF-binding sites (binding capacity, 5 x 10(3) sites/cell; Kd, 1.9 nM for IGF-I and 7.0 nM for IGF-II). These findings in LoVo-C5 contrast with those in HT29-D4 cells, which have active furin, and where IGF-IR (2.8 x 10(4) sites/cell) was fully processed. Moreover, the 200-kDa pro-IGF-IR of LoVo-C5 was unable to induce intracellular signaling, such as beta-subunit tyrosine autophosphorylation and insulin-related substrate-1 tyrosine phosphorylation. Flow immunocytometry analysis using alpha-IR3 antibody indicated that LoVo-C5 cells expressed 40% more receptors than HT29-D4 cells, suggesting that in LoVo-C5 cells only the small amount of mature type I IGF-IR binds IGFs with high affinity. To provide evidence for this idea, we showed that mild trypsin treatment of living LoVo-C5 cells partially restored alpha/beta cleavage of IGF-IR, and greatly enhanced (6-fold) the IGF-I binding capacity of LoVo-C5 cells, but did not restore IGF-IR signaling activity. Moreover, LoVo-C5 cells were totally unresponsive to IGF-I in terms of cell migration, in contrast to fully processed IGF-IR-HT29-D4 cells. Our data indicate that furin is involved in the endoproteolytic processing of the IGF-IR and suggest that this posttranslational event might be crucial for its ligand binding and signaling activities. However, our data do not exclude that other proprotein convertases could participate to IGF-IR maturation.

ADP Ribose Transferases↗
PubMed1998

Integrin ligation and PKC activation are required for migration of colon carcinoma cells.

The activation of protein kinases C (PKCs) is an essential step in integrin-dependent cell adhesion and spreading. In this report we examined the effect of the phorbol ester PMA, a PKC activator, on adhesion, spreading and migration of a colon carcinoma cell line, HT29-D4. Treatment with PMA increased the rate of cell spreading and induced the migration of these cells towards purified matrix proteins in haptotaxis assays on Boyden chambers. PMA-induced effects were the result of PKCs activation, as shown by using the inactive isomer 4alpha-PMA and PKCs inhibitors. The involvement of integrins in the phorbol ester-induced cell migration was demonstrated both by the absence of migration of cells plated on membranes coated with poly-L-lysine and by the use of function blocking antibodies. Thus, interactions between alpha 2beta1, alpha3beta1, alpha6beta4, alpha vbeta5, alphavbeta6 integrins and their specific ligands are necessary for the PKC-mediated migration. However, adhesion, immunoprecipitation and immunocytofluorometry experiments clearly showed that HT29-D4 cell haptotaxis induced by PKC activation is not a consequence of quantitative or qualitative changes in the cell surface integrins. We also demonstrated that PKCs were able to activate the MAP kinase pathway and that the impediment of MAP kinase activation resulted in the loss of cell migration. Moreover, stimulation of the insulin-like growth factor I signalling pathway led to MAP kinase activation and to the induction of cell migration. In addition, the growth factor-induced motility of HT29-D4 cells was affected both by PKC and MAP kinase cascade inhibitors. It thus appears that both integrin ligation and MAP kinase activation by PKCs are required to promote the migration of HT29-D4 cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Lung diffusing capacity and exercise in subjects with previous high altitude pulmonary oedema.

Subjects with a history of high-altitude pulmonary oedema (HAPE) have increased pulmonary artery pressure and more ventilation-perfusion (V'A/Q') inhomogeneity with hypoxia and exercise. We used noninvasive methods to determine whether there are differences in the pulmonary diffusing capacity for carbon monoxide (DL,CO) and cardiac output (Q') during exercise, indicative of a more restricted pulmonary vascular bed in subjects with a history of HAPE. Eight subjects with radiographically documented HAPE and five controls with good altitude tolerance had standard pulmonary function testing and were studied during exercise at 30 and 50% of normoxic maximal oxygen consumption (V'O2) at an inspiratory oxygen fraction of 0.14 and 0.21. DL,CO and Q' were measured by CO and acetylene rebreathing techniques. HAPE-resistant subjects had 35% greater functional residual capacity than HAPE-susceptible subjects. Vital capacity and total lung capacity were also 7-10% greater. There were no differences in airflow rates or resting diffusing capacity. However, DL,CO in HAPE-susceptible subjects was lower in hypoxia and with exercise, and showed less increase (32 versus 49%) with the combined stimulus of hypoxic exercise. HAPE-susceptible subjects had smaller increases in stroke volume, Q', and ventilation during exercise. The findings are consistent with lower pulmonary vasoconstriction, greater vascular capacitance and greater ventilatory responsiveness during exercise in subjects who are resistant to high-altitude pulmonary oedema. Their larger lung volumes suggest a constitutional difference in pulmonary parenchyma or vasculature, which may be a determinant of high-altitude pulmonary oedema resistance.

Adult↗
PubMed1998

Ultra-triathlon-related blood-chemical and endocrinological responses in nine athletes.

BACKGROUND: Objective of this study was to get more insight in hematology, biochemistry, and endocrinology of ultra-endurance exercise, to improve knowledge in this field, supplementation, and medical care of affected athletes. METHODS: A large body of individual hematological, biochemical, and endocrinological parameters was analyzed in the blood taken from ultra-athletes before and after completing the 1993 Colmar ultra triathlon covering 7.5 km swimming, 360 km cycling, and approximately 85 km running. PARTICIPANTS: Nine experienced ultra-athletes participated in the study. A follow-up was not possible since the athletes left Colmar within 24 hrs after the contest. RESULTS: The athletes finished the ultra-contest at rankings 4, 5, 7, 8, 9, 11, 18, 22, 23 in a total time between 23:38:53 and 27:54:30 hr:min:sec. Their final body mass (68.6 +/- 1 kg) was significantly lower than at baseline (71.9 +/- 4.2 kg). Non of the athletes made use of medical care. Data after this contest reflect mild hyponatremia, intravascular hemolysis, increased triglyceride turnover, acute-phase reaction, hyperaldosteronemia 2061 +/- 1013 pmol.L-1), hypercortisolemia 971 +/- 486 nmol.L-1), hyper-growth-hormonemia (median 6.8 ng.ml-1), hypoinsulinemia, hypo-free-testosteronemia (42 +/- 17 pmol.L-1), protein catabolism, depressed testicular function, oliguria, and muscle cell leakage. CONCLUSIONS: In our opinion, data presented do not reflect any acute health risks in healthy athletes who are well prepared and carefully supplied during such a contest.

Adult↗
PubMed1998

[Biological perspectives].

The tumour biology of non-small cell bronchial cancer integrates recent developments and a dynamic schema of the phenomena of tumour progression and diffusion of the metastatic disease. There is no leap of known biological disruption between Stage II and Stage III. The latter is defined by anatomical criteria and is a transition in the continuum of the natural history of these cancers. The moto for the tumour progression is the genotypic instability and phenotypic diversification. Metastatic microscopic disease constitutes the first cause of failure in the treatment of Stage III non-small cell bronchial cancer. Among prognostic factors for survival emphasis is placed on the alterations of p53 expression, different types of aneuploidy, anomalies of the expression of cellular adhesion molecules and finally, tumour diversification towards a metastatic phenotype.

Aneuploidy↗
PubMed1998

[Standards, Options, and Recommendations for the management of patients with malignant mesothelioma of the pleura. Fédération Nationale des Centres de Lutte Contre le Cancer].

The "Standards, Options and Recommandations" (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. The objectives are to develop a clinical practice guideline with definitions of Standards. Options and Recommendations for the clinical care of malignant pleural mesothelioma. Data have been identified by literature search using Medline (1966-June 1997) and personal references lists. The main criteria considered were incidence, risk factors, pronostic factors and efficacy of cancer treatment. Once the guideline was defined, the document was submitted to 40 independent reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement. The results are: 1) systematic assessment of (professional) exposure to asbestos is based on a standardized interrogatory, completed by specific consultation for professional disease; 2) diagnostic and clinical staging is based on multiple biopsies under thoracoscopy and thoracic scanner; 3) there is no indication for extemporaneous examination, immunocytochemistry should use cytokeratine, EMA, vimentine, ACE, Leu-M1; 4) clinical care: the recommended staging classification is the IMIG (International Mesothelioma Interest Group) classification; 5) validated, independent pronostic factors are stage of disease patient's functional status and histologic type (i.e. epithelial lesions are of better prognosis); 6) treatment is based on symptomatic and palliative treatment options. Anticancer treatments (surgery, chemotherapy, immunotherapy, radiotherapy) did not show significant improvement of survival. The inclusion of patients in clinical trials is recommended.

Humans↗
PubMed1998

Monitoring intensive endurance training at moderate energetic demands using resting laboratory markers failed to recognize an early overtraining stage.

BACKGROUND: Aim was to answer the question whether resting laboratory parameters are suitable for monitoring intensive endurance training at moderate energetic demands. This was designed since markers of overtraining at high energetic demands, e.g. mild anemia, leukopenia, iron deficiency, reduced serum albumin, glucose, triglyceride, triglyceride-rich cholesterol (LDL, VLDL), free fatty acid, increased plasma noradrenaline levels, and decreased basal catecholamine excretions were recommended. METHODS: A prospective 6-wk, 6-dys/wk intensive steady state and interval cycle ergometer training of 40-60 min/dy was performed. Total load was about 6-time pretraining activities followed by a 2-wk, 2-hour/wk regenerative training period. Six recreational athletes (VO2max 51.5 +/- 4.5 ml.kg-1.min-1) participated and finished the study. A large pattern of resting hematological, blood-chemical, and hormonal parameters was tested regarding suitability for monitoring overtraining. RESULTS: After 3 wks, submaximum and maximum performance were significantly increased, stopped improving between wk 3 and 6, or deteriorated. No supercompensation occurred after regeneration, but a decrease in work output. Lack of progression and supercompensation, and decreased maximum work output indicate a critical stage in the training process. CONCLUSIONS: All examined resting laboratory parameters failed to reflect this critical stage except for a significant decrease in serum glucose, ferritin, and free fatty acid concentrations.

Adult↗
PubMed1997

Impact of a clinical guidelines program for breast and colon cancer in a French cancer center.

CONTEXT: Between 1993 and 1994, the 80 physicians in the French comprehensive cancer center, Léon Bérard, developed and implemented a Clinical Practice Guidelines (CPGs) project based on an analysis of the literature and a consensus of intrainstitutional experts. OBJECTIVE: The aims of this project are to assist community-based oncologists in their decision making and to minimize inappropriate variation in practices. A study was designed to assess the impact of CPGs on management of breast and colon cancer. DESIGN: A "before-after" study, using institutional computerized records of patients with breast or colon cancer. SETTING: Records for 100 women with localized breast cancer were randomly selected from those available in 1993 and 1995, and those for all patients newly referred with colon cancer in 1993 and 1995 (77 and 81 patients, respectively). Medical decisions on these records were analyzed to assess their compliance with the CPGs. (A systematic search of the literature was performed to determine the scientific evidence for noncompliant decisions.) RESULTS: Of 375 available medical decisions, 350 were assessable. The compliance rate with CPGs for breast cancer was significantly higher in 1995 compared with 1993, 54% (54/99; 95% confidence interval [CI], 44%-64%) vs 19% (18/95; 95% CI, 11%-27%) (P<.001). The compliance rate for colon cancer was also significantly higher in 1995 than in 1993, 70% (62/88; 95% CI, 60%-80%) vs 50% (34/ 68; 95% CI, 38%-62%) (P=.009). In 1993, 42% (40/95; 95% CI, 32%-52%) of medical decisions for breast cancer and in 1995, 68% (67/99; 95% CI, 59%-77%) conformed with the CPGs or were judged to be based on "scientific evidence." In 1993, 71% (48/68; 95% CI, 60%-81%) of medical decisions for colon cancer, and in 1995 81% (71/88; 95% CI, 73%-89%) conformed with the CPGs or were judged to be based on scientific evidence. CONCLUSIONS: Compliance rates were significantly higher in 1995 for both cancers. The development and implementation of CPGs for cancer management seem to result in significant changes in medical practice, although a causal relationship between changes and CPGs is not demonstrated in this study.

Adult↗
PubMed1997

Anti-CD4 monoclonal antibody-induced allograft tolerance in rats despite persistence of donor-reactive T cells.

Although CD4-targeted therapy abrogates acute rejection and may induce permanent graft acceptance in rodents, little is known about the mechanisms of long-term graft survival in these models. Recently, we have shown that treatment with a nondepleting anti-CD4 monoclonal antibody (mAb) (RIB-5/2) induces long-term survival of renal, heart, and skin allografts in strong major histocompatibility complex I/II incompatible rat strains. Here, we demonstrate that the development of major histocompatibility complex-specific and tissue-nonspecific tolerance rather than graft adaptation is responsible for long-term anti-CD4 mAb-induced transplant survival. Donor-specific but not third-party heart and pancreatic islet grafts were accepted permanently without adjunctive therapy in long-term kidney allograft recipients, and infusion of naive or alloimmune splenocytes failed to break the tolerant state. Interestingly, alloreactive T cells were not depleted in these long-term survivors, as ex vivo donor-specific mixed lymphocyte reaction was largely unaffected. The reverse transcriptase-polymerase chain reaction analyses of long-term renal allografts before and after donor-specific antigen challenge revealed no changes in CD3 mRNA level, but showed up-regulation of CD25, interleukin (IL) 2, interferon (IFN) gamma, IL-4, and IL-10 mRNA in the early phase, suggesting the presence of alloreactive T cells in tolerant rats. At later time points, the expression of IFN-gamma declined rapidly, whereas IL-4 persisted, resulting in a reversal of IFN-gamma/IL-4 ratio. Our data demonstrate the stability of anti-CD4 mAb-induced tolerance despite persistence of alloreactive T cells, suggesting the role of active tolerance-maintaining mechanisms. The T helper (Th) 1/Th2 shift may be involved in this regulatory process, as anti-CD4 mAb prevents acute graft-deteriorating rejection by effectively blocking Th1 responses, and well-functioning grafts may tolerize themselves by inducing regulatory cells.

Animals↗