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Biomedical subjects

M Lehmann

Publications and source records attributed to M Lehmann.

At least 19 recordsLinked to original sources

Implication of the alpha v beta 3 integrin in the adhesion of the ovarian-adenocarcinoma cell line IGROV1.

Accumulating evidence suggests that integrins, which participate in many complex cellular processes, are important for tumor progression and metastasis. In order to understand the role of these cell-surface receptors and of their ligands in the biological behavior of ovarian tumor cells, we have examined the expression of integrins in the human ovarian-adenocarcinoma cell line IGROV1. These cells expressed the alpha v sub-unit and used it to attach on vitronectin (Vn). A monoclonal antibody (MAb) (69-6-5) specific to alpha v blocked the attachment of IGROV1 cells on Vn and fibrinogen (Fg), but not on fibronectin (FN) and other adhesive ligands. Immunoprecipitation of surface biotinylated cells followed by Western blotting showed that the alpha v sub-unit was associated with beta 3, but not with beta 1, beta 5 or beta 6. When cells were cultivated on glass coverslips or on Vn sub-stratum in serum-free medium, immunofluorescence staining with MAb 69-6-5 revealed the presence of alpha v at cell-cell contacts and at focal contacts, supporting its active participation in adhesion as part of a functional heterodimer. Furthermore, immunofluorescence data showed the presence of Vn as a fibrillar network in IGROV1 cells cultivated on FN-coated slides. These results suggest that alpha v beta 3 and its Vn ligand may play a important role in the behavior of ovarian epithelial tumors.

Adenocarcinoma

Unaccustomed high mileage compared to intensity training-related neuromuscular excitability in distance runners.

The influence of a 4-week unaccustomed average 103% mileage increase (ITV, increase in training volume; n = 8; average baseline mileage 85.9 km.week-1, final mileage 174.6 km.week-1) on performance and neuromuscular excitability (NME) was tested in experienced distance runners and controlled 1 year later by a 4-week unaccustomed average 152% increase in tempo-pace and interval-runs (ITI, increase in training intensity; n = 9; baseline 9 km.week-1 final 22.7 km.week-1) with an average total mileage of 61.7 km.week-1 (week 1) to 84.7 km.week-1 (week 4). Seven athletes participated in ITV as (week 4). Seven athletes participated in ITV as well as in ITI. During incremental treadmill test performance at a lactate concentration of 2 mmol.1-1 (2 LP) increased, and at 4 mmol.1-1 (4 LP) performance did not change, whereas total running distance (TD) during the incremental test decreased in ITV compared to an increase in 2 LP, 4 LP and TD during ITI which may indicate that there was an ITV-related overtraining. The NME of the reference muscles vastus medialis and rectus femoris deteriorated in ITV (day 28 compared to 0) compared to constant values during ITI, reflecting an ITV-related overload of neuromuscular structures.

Adult

Comparison between exact and parametric distributions of multiple inter-raters agreement coefficient.

The Global Kappa statistic can be used for measuring the degree of agreement between more than two raters. In this paper, we give simple computation formulas in the case of dichotomic and no missing responses in order to describe the exact distribution of Kappa for various sets defined by the number of raters, of different examinations and of positive responses. By programming those computations with the SAS software package, we were able to compare the exact and parametric distributions of Kappa. Although the correlation between parameters is high, a linear regression analysis shows that a strong imbalance between positive and negative responses can lead to misinterpretation of the results when using the parametric method.

Humans

Serum amino acid concentrations in nine athletes before and after the 1993 Colmar ultra triathlon.

The amino acid imbalance hypothesis should explain the fatigue originating in the brain during sustained exercise or over-training as a branched-chain (BCAA)/aromatic amino acids (AAA) imbalance with increased brain tryptophan uptake and 5-hydroxytryptamine synthesis. The serum amino acid profile was determined in 9 ultra-triathletes before and after completing the 1993 Colmar ultra-triathlon to additionally analyse the extent of this amino acid imbalance during such an extreme prolonged contest lasting more than 23 hours. The summed serum concentration of 25 amino acids decreased by 18% from 3962 +/- 846 to 3255 +/- 694 umol.l-1 likely reflecting a catabolic state of the organism with a decrease in 18 individual amino acids by 9-56%, an increase in cystine (+38%), methionine (+24%), tyrosine (+10%), phenylalanine (+12%), free tryptophan (+74%), and constant glutamine, leucine and total tryptophan levels. Since plasma volume increased by approximately 7.6% with a 3.3 kg body mass decrease in the athletes during the ultra triathlon, a decrease in intra-cellular water with an extra-cellular fluid increase is hypothesized. This decrease in cellular hydration state is seen as a protein-catabolic signal.

Adult

Delay in corneal allograft rejection due to anti-CD4 antibody given alone and in combination with cyclosporin A and leflunomide.

Anti-CD4 monoclonal antibodies (mAbs) have been shown to inhibit in vitro T-cell activation and proliferation to both antigens and mitogens. Animals studies have demonstrated the immunosuppressive potency of anti-CD4 mAbs given in vivo for therapy of autoimmune disease and following allografting. Similarly, leflunomide (LF), a new potent immunosuppressive, has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplant rejection. LF is thought to antagonize cytokine activity, thereby interfering with T-helper-cell-dependent B- and T-lymphocyte proliferation. A new anti-CD4 antibody (RIB 5/2) was investigated alone and in combination with cyclosporin A (CsA) and LF for the treatment of corneal allograft rejection in the rat. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA at 1.5 mg/kg; (3) RIB 5/2 at 2.5 mg/kg; (4) RIB 5/2 at 2.5 mg/kg and CsA at 1.5 mg/kg; (5) RIB 5/2 at 2.5 mg/kg, CsA at 1.5 mg/kg and LF at 10 mg/kg; (6) RIB 5/2 at 4 mg/kg; (7) RIB 5/2 at 4 mg/kg and CsA at 1.5 mg/kg; and (8) RIB 5/2 at 4 mg/kg, CsA at 1.5 mg/kg, and LF at 10 mg/kg. RIB 5/2 was given intraperitoneally at 24 h before surgery, on the day of grafting, and on postoperative day 1 and was continued every 2nd day until the rat had received ten doses in all (postoperative day 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Co-mutagenic effect of tannic acid on ring-X chromosome loss induced by mitomycin C in sperm cells of Drosophila melanogaster.

To investigate the effects of tannic acid (TA) on ring-X chromosome loss, Drosophila melanogaster females exposed to different TA concentrations were crossed with untreated, methyl methanesulfonate (MMS)- or mitomycin C (MMC)-treated males which carried a ring-X chromosome. Progeny were analyzed for loss of the ring-X. The results of this in vivo study showed that TA had no suppressing effect on chromosome loss occurring spontaneously or after induction by MMS in mature spermatozoa. In contrast, TA caused a significant increase in the frequency of MMC-induced ring-X loss. The increase caused by this co-mutagenic effect reached values of 34, 33 and 40% at TA concentrations of 10, 25 and 50 mM, respectively. These increments may reflect the action of TA on a uvrABC-type enzyme which, by increasing the double-strand breaks (DSBs), somehow interferes with the post-replicational repair responsible for the final DSB correction.

Animals

A monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon carcinoma cell line and recognizes the integrins alpha v beta 3, alpha v beta 5, and alpha v beta 6.

Using whole viable human colon carcinoma HT29 cells as immunogen, we produced a monoclonal antibody (mAb) termed 69-6-5. The antibody was functionally selected on its anti-cell-spreading activity. By immunoprecipitation of surface radiolabeled cell lysates from HT29-D4 cells (an HT29 cell clone), mAb 69-6-5 recognized a molecular complex resembling integrin heterodimers. Sequential immunodepletions with mAb to the integrin alpha v subunit demonstrated that this complex was composed of alpha v-containing integrins. Accordingly, mAb 69-6-5 reacted with integrin alpha v beta 3 immunopurified from melanoma cells and integrins alpha v beta 5 and alpha v beta 6 immunopurified from pancreatic carcinoma cells. In cell adhesion assays, the 69-6-5 mAb was able to inhibit strongly in a dose-dependent manner arginine-glycine-aspartic acid-mediated adhesion of HT29-D4 cells to vitronectin, fibronectin, or ProNectin F but not to laminin or collagen. Immunoprecipitations with beta chain-specific antisera indicated that these cells express integrins alpha v beta 5 (receptor for vitronectin) and alpha v beta 6 (receptor for fibronectin) but neither alpha v beta 1 nor alpha v beta 3. In summary, these results indicated that mAb 69-6-5 reacts with several alpha v integrins and that it can effectively interfere with the adhesive functions of at least alpha v beta 5 and alpha v beta 6, which represent the major receptors on HT29-D4 cells responsible for their adhesion on vitronectin and fibronectin.

Amino Acid Sequence

Suppressing effect of vanillin on chromosome aberrations that occur spontaneously or are induced by mitomycin C in the germ cell line of Drosophila melanogaster.

In order to investigate the anticlastogenic effect of vanillin on ring-X loss, D. melanogaster females exposed to different vanillin concentrations were crossed with non-treated, MMC- or MMS-treated males. The results obtained with this in vivo investigation showed a significant inhibition of vanillin in the frequencies of spontaneous ring-X loss--59, 56, 38 and 36%--at the different concentrations used. In addition, vanillin treatment caused a significant suppression of MMC-induced ring-X loss. This decrease was observed only in the first 3 days after the interruption of vanillin treatment and at the concentrations of 0.5 and 1% of this flavoring agent. In contrast, vanillin did not show any effect on chromosome loss provoked by MMS. Therefore, the ring-X loss-decreasing effect of vanillin seemed to depend on the quality of DNA lesions and consequently on a specific enzymatic repair process present in the oocytes of D. melanogaster.

Animals

Training-overtraining: influence of a defined increase in training volume vs training intensity on performance, catecholamines and some metabolic parameters in experienced middle- and long-distance runners.

The influence of an increase in training volume (ITV; February 1989) vs intensity (ITI; February 1990) on performance, catecholamines, energy metabolism and serum lipids was examined in two studies on eight, and nine experienced middle- or long-distance runners; seven participated in both studies. During ITV, mean training volume was doubled from 85.9 km.week-1 (pretrial phase) to 174.6 km within 3 weeks. Some 96%-98% of the training was performed at 67 (SD 8)% of maximal performance. During ITI, speed-endurance, high-speed and interval runs increased within 3 weeks from 9 km.week-1 (pretrial phase) to 22.7 km.week-1 and the total training distance from 61.6 to 84.7 km.week-1. The ITV resulted in stagnation of running velocity at 4 mmol lactate concentration and a decrease in total running distance in the increment test. Heart rate, energy metabolic parameters, nocturnal urinary catecholamine excretion, low density, very low density lipoprotein-cholesterol and triglyceride concentrations decreased significantly; the exercise-related catecholamine plasma concentrations increased at an identical exercise intensity. The ITI produced an improvement in running velocity at 4 mmol lactate concentration and in total running distance in the increment test; heart rate, energy metabolic parameters, nocturnal catecholamine excretion, and serum lipids remained nearly constant, and the exercise-related plasma catecholamine concentrations decreased at an identical exercise intensity. The ITV-related changes in metabolism and catecholamines may have indicated an exhaustion syndrome in the majority of the athletes examined but this hypothesis has to be proven by future experimental studies.

Adult

Decreased nocturnal catecholamine excretion: parameter for an overtraining syndrome in athletes?

The effectiveness of high performance training should be examined at short intervals in order to recognize overtraining promptly. Field or laboratory tests can usually not be performed with such frequency. Easy-to-measure biological, training-relevant parameters are being sought to use in their place. Since the importance of the sympathetic nervous system for adaptation of stress and the relationship between physical training and the activity of the sympathetic nervous system are well accepted, and since an impairment of the sympathetic nervous system is assumed in an overtraining syndrome, we examined the relevance of nocturnal "basal" urinary excretion of free catecholamines with respect to its practical application: 1. during a pilot study (training of road and track cyclists before the 1988 Olympic Games in Seoul), 2. through a 4-week prospective, experimental study in 1989 and 1990 (middle- and long-distance runners), 3. during the competitive season and winter break of a soccer team between August 1990 and April 1991. The following hypothesis was made: An overtraining or exhaustion syndrome in athletes may usually be accompanied by at least a 50% decrease in basal dopamine, noradrenaline and adrenaline excretion. When training is effective or the athletes are not exhausted, the decrease of the excretion rate--with the exception of dopamine--is more likely to be lower (noradrenaline, adrenaline). Generalization of these results requires further expansion of the experimental basis.

Adult

Induction of long-term survival of rat skin allografts by a novel, highly efficient anti-CD4 monoclonal antibody.

The new monoclonal antirat CD4 antibody RIB 5/2, which detects another epitope than those covered by W3/25 and MRC OX35, was tested for its immunosuppressive potency following skin allografting by using strain combinations with different genetic barriers in the MHC and genetic low- or high-responder background. High-dose and long-term therapy of the grafted rats led to a significant delay of the acute rejection (P < 0.01) in the strain combination Wistar Furth-to-BDX as well as in LEW1W-to-LEW1A. No significant prolongation of the mean allograft survival time was obtained for the high-responder rats (LEW1A-to-LEW1W). Cytofluorometric analysis revealed that RIB 5/2 exerts the immunosuppressive activity predominantly by modulation of the CD4 glycoprotein. Furthermore, the dependence of the humoral immune response against the mouse-globulins upon the administered protein quantity could be demonstrated.

Animals

[Detection of lectin binding sites in the trophoblast of cattle during early pregnancy].

In the present study we report on the histotopographical distribution of lectin binding sites in the trophoblasts of day 18 to day 40 bovine embryos, using the FITC-labeled lectins BPA, Con A, DBA, GS I, GS II, MPA, PNA, SBA, UEA I and WGA. Lectin binding sites localized in giant binucleate cells differ from those localized in uninucleate cells, indicating changes in the biochemical structure of cell surfaces taking place during differentiation. In the trophoblast of the day 40 embryo, a distinct staining of uninucleate cells was seen after incubation with GS I, Con A and MPA, demonstrating N-acetylgalactosamine (GS I), Mannose (Con A) and Galactose (MPA) moieties, whereas giant binucleate cells showed intense reactions after incubation with DBA and WGA, indicating presence of N-acetylgalactosamine (DBA) and N-acetylglucosamine (WGA). GS II (specific for N-acetylglucosamine), SBA (specific for N-acetylgalactosamine) and UEA I (specific for L-Fucose) showed no affinity toward any of the examined tissues. We assume, that carbohydrate moieties in trophoblast cells play an important role in fetomaternal cell-cell adhesion and cell migration during implantation and placentation period.

Animals

[The development of the yolk sac in ruminants (sheep and cattle)].

Yolk sac development was investigated in 69 ovine and 10 bovine embryos from the blastocyst stage to the 7th week of gestation. Light and electron microscopical findings are reported. The yolk sac in sheep and cattle is composed of an enlarged sac-like portion lying below the embryo and two ends which follow the elongated course of the trophoblast. In sheep, an open connection exists between the intestines and the yolk sac up to a crown-rump length (CRL) of 9 mm. It is closed by 12 mm CRL. The wall of the yolk sac is especially well vascularized in the enlarged, sac-like portion. Primary erythropoiesis occurs within the blood capillaries. In the blastocyst, the yolk sac entoderm is made up of elongated, flat cells. It becomes cuboidal in the 3 mm embryo (ovine) and later columnar. The up to 20 microns tall cells stain darkly and contain numerous light-colored vesicles. At 4.5 mm CRL light cells appear between the dark ones. Both cells are rich in rough endoplasmic reticulum (rER). The increased staining of the darker cells is due to an osmophilic cytoplasm and numerous, often parallel lamella of rER. The rER of the light cells is enlarged to irregularly-shaped cisternae, which nearly fill the entire cytoplasm and give them a rounded appearance. The dark cells contain polygonal nuclei, whereas those in the light cells are round with one or two nucleoli. The oval mitochondria have only a few peripheral cristae. Golgi fields are not very common. Cells of the entoderm are connected to one another over zonulae occludentes. They possess microvilli on the luminal surface and are supported by a basement membrane. From 5 mm CRL onwards (ovine), the yolk sac entoderm folds itself between the capillaries, thereby becoming stratified. The intercellular space between the cells expands as projections between neighboring cells interlock. Canaliculi arise between adjacent epithelia. The wall of the yolk sac thickens as a result of this infolding and the densely packed capillaries. Infoldings are especially predominant in the sac-like portion of the yolk sac, and only suggested in the ends. Involution of the yolk sac begins in the peripheral end segments and proceeds centripetally. Numerous glycogen particles appear in the yolk sac entoderm cells of the ovine fetus at a CRL of 36 mm, and by a CRL of 42 mm, the sac-like portion has also begun to show signs of degeneration. Mesenchyme is very sparse within the wall of the yolk sac throughout the entire period of development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Training-overtraining: performance, and hormone levels, after a defined increase in training volume versus intensity in experienced middle- and long-distance runners.

Performance and hormones were determined in eight middle- and nine long-distance runners after an increase in training volume (ITV, February 1989) or intensity (ITI, February 1990). Seven runners participated in both studies. The objective was to cause an overtraining syndrome. The mean training volume of 85.9 km week-1 increased within 3 weeks to 176.6 km week-1 during ITV and 96-98% of training volume was performed as long-distance runs at mean(s.d.) 67(8)% of maximum capacity. Speed endurance, high-speed and interval runs averaging 9 km week-1 increased within 3 weeks to 22.7 km during ITI, and the total volume increased from 61.6 to 84.7 km. A plateau in endurance performance and decrease in maximum performance occurred during ITV, probably due to overtraining, with performance incompetence over months. Nocturnal catecholamine excretion decreased markedly (47-53%), contrary to exercise-related plasma catecholamine responses, which increased. Resting and exercise-related cortisol and aldosterone levels decreased. Improvement in endurance and maximum performance occurred during ITI indicating a failure to cause an overtraining syndrome in ITI. Decrease in noctural catecholamine excretion was clearly lower (9-26%), exercise-related catecholamine responses showed a significant decrease, cortisol and aldosterone levels remained almost constant, exercise-related prolactin levels decreased slightly. There were no differences in insulin, C-peptide, free testosterone, somatotropic hormone (STH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), tri-iodothyronine (T3) and thyroxine (T4). The decrease in nocturnal catecholamine excretion during ITV might indicate a decrease in intrinsic sympathetic activity in exhausted sportsmen. But it remains open whether this reflected a central nervous system incompetence.

Adult

[Secretion of hCG by mononuclear cells--a specific and essential reaction in pregnancy?].

Mononuclear cells in peripheral blood secrete immunoreactive hCG (ir-hCG) when they are stimulated in in-vitro culture with the proteinkinase C - activator phorbol-myristat-acetate (TPA). We examined the ir-hCG secretion in 61 fertile and 191 pregnant women and 38 men. Mononuclear cells of pregnant women secrete after TPA stimulation significantly more ir-hCG than mononuclear cells on non-pregnant but fertile women. This effect can be detected as early as 23rd days of a menstrual cycle which is accompanied by conception and persisted over the entire duration of a pregnancy. Maximal effects were observed in the 7th to 19th and 30th to 34th weeks of pregnancy. An artefact caused by adhesive serum-hCG could be excluded. The elevated potential of the mononuclear cells to be stimulated remained intact for about 14 days after termination of a normal pregnancy in the first trimester. An ir-hCG secretion similar to that seen in nonpregnant women was found in patients with early abortion. The possible physiological importance of the in-vivo secretion of beta-HCG during pregnancy is discussed.

Abortion, Incomplete

[Interval resistance exercise in comparison with bicycle ergometry stress. Studies with resistance endurance training in coronary patients].

UNLABELLED: In the rehabilitation of coronary patients there is an increased interest in using complementary resistance exercise training. Therefore, we studied nine patients (males; age: 51 +/- 7 years) with chronic stable coronary heart disease during extensive resistance exercise (ex RE) (legpress, abduction, adduction) (60-s work: 60-s rest; contraction intensity: 65% of 1 RM) and during intensive resistance exercise (int. RE) (legpress) (30-s work: 45-s rest) with 85% of 1 RM. Non-invasive continuously measured blood pressure, heart rate, norepinephrine, epinephrine, lactic acid, and glucose were compared with values from maximal bicycle ergometry (3-min steps, each 25 w; max. performance: mean 156 w; range 125-200 w). RESULTS: 1) Comparing ex RE and int RE with bicycle ergometry there were no differences in blood pressure (systolic: 206 and 204 vs. 210 mm Hg; ns; diastolic: 98 and 104 vs. 92 mm Hg; ns). Heart rates (104 and 103 vs. 125/min; p < .01), norepinephrine (3.8 and 3.3 vs. 8.8 nmol/l; p < .01) and epinephrine (0.7 and 0.6 vs. 1.4 nmol/l; p < .01) were considerably lower. 2) The most significant increase and decrease of blood pressure and heart rate occurred within 15-30 s after the beginning and end, respectively, of isometric exercise. CONCLUSIONS: 1) ex RE is suitable for patients with stable CHD and cardiac exercise tolerances of 1.5-2 W/kg = 125-150 watts. 2) Blood pressure monitoring by the cuff method (RR) immediately after RE did not reflect blood pressure during RE. 3) Controlling RE by the training heart rate prescribed for endurance exercise is not possible.

Adult

Sympathetic autonomic dysfunction. Programmed subcutaneous noradrenaline administration via microdosing pump.

Sympathetic dysfunction is characterized by postural hypotension, decreasing blood pressure without compensatory tachycardia during graded supine ergometric exercise, impaired catecholamine metabolism, and hypersensitivity to catecholamines. We report on eight patients, seven with sympathetic dysfunction, of whom three patients were treated for the first time with programmed subcutaneous noradrenaline administration by means of a microdosing pump over a time period of 1.5-13 months. A clear improvement in blood pressure values, orthostasis tolerance, and exercise capacity has been observed in these three patients which permit them to extend their action radius. Adjustment of the noradrenaline dose to the wide range of everyday stress and the possible occurrence of adrenoreceptor desensitization, however, remains a severe problem.

Adult