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Biomedical subjects

M Lehmann

Publications and source records attributed to M Lehmann.

At least 91 records · Page 5Linked to original sources
PubMed1999

Biochemical characterization of fungal phytases (myo-inositol hexakisphosphate phosphohydrolases): catalytic properties.

Supplementation with phytase is an effective way to increase the availability of phosphorus in seed-based animal feed. The biochemical characteristics of an ideal phytase for this application are still largely unknown. To extend the biochemical characterization of wild-type phytases, the catalytic properties of a series of fungal phytases, as well as Escherichia coli phytase, were determined. The specific activities of the fungal phytases at 37 degreesC ranged from 23 to 196 U. (mg of protein)-1, and the pH optima ranged from 2.5 to 7.0. When excess phytase was used, all of the phytases were able to release five phosphate groups of phytic acid (myo-inositol hexakisphosphate), which left myo-inositol 2-monophosphate as the end product. A combination consisting of a phytase and Aspergillus niger pH 2.5 acid phosphatase was able to liberate all six phosphate groups. When substrate specificity was examined, the A. niger, Aspergillus terreus, and E. coli phytases were rather specific for phytic acid. On the other hand, the Aspergillus fumigatus, Emericella nidulans, and Myceliophthora thermophila phytases exhibited considerable activity with a broad range of phosphate compounds, including phenyl phosphate, p-nitrophenyl phosphate, sugar phosphates, alpha- and beta-glycerophosphates, phosphoenolpyruvate, 3-phosphoglycerate, ADP, and ATP. Both phosphate liberation kinetics and a time course experiment in which high-performance liquid chromatography separation of the degradation intermediates was used showed that all of the myo-inositol phosphates from the hexakisphosphate to the bisphosphate were efficiently cleaved by A. fumigatus phytase. In contrast, phosphate liberation by A. niger or A. terreus phytase decreased with incubation time, and the myo-inositol tris- and bisphosphates accumulated, suggesting that these compounds are worse substrates than phytic acid is. To test whether broad substrate specificity may be advantageous for feed application, phosphate liberation kinetics were studied in vitro by using feed suspensions supplemented with 250 or 500 U of either A. fumigatus phytase or A. niger phytase (Natuphos) per kg of feed. Initially, phosphate liberation was linear and identical for the two phytases, but considerably more phosphate was liberated by the A. fumigatus phytase than by the A. niger phytase at later stages of incubation.

6-Phytase↗
PubMed1999

Human skeletal muscle HSP70 response to training in highly trained rowers.

Previous studies have demonstrated exercise-induced heat shock protein 70 (HSP70) in animals. The purpose of this study was to investigate human skeletal muscle HSP70 response to rowing training. Ten male rowers trained for 4 wk with different forms, durations, and intensities of exercise. Biopsy was performed in the right musculus vastus lateralis before training and at the end of each week. HSP70 in 5 microg of total protein from the muscle sample was determined by using Western blot and immunodetection with chemiluminescence technique, by means of laser densitometer referring to a series of known standard HSP70. Compared with pretraining (100%), HSP70 increased during training (181, 405, 456, and 363% from the first to fourth training week, respectively) with the maximum HSP70 production at the end of second training week. Thus HSP70 is induced in highly trained human muscle by long-term training.

Adolescent↗
PubMed1999

[Standards, options and recommendations (SOR) for clinical care of malignant thymoma. Groupe de Travail SOR].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration 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 outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of malignant thymoma in adult. METHODS: Data have been identified by literature search using Medline (december 1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for malignant thymoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and made from a biopsy, except in cases of well-encapsulated tumors which are completely resected. The biopsy, via anterior mediastinostomy, should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical resection must be complete including thymus and perithymic fat and performed by an experienced surgeon; 4) the therapeutic strategy for malignant thymoma is based on the three current staging systems and involves surgery with radiotherapy given if the capsule is invaded or penetrated. Radiotherapy should be given in experienced centres. Inclusion of patients in prospective clinical trials is recommended in order to determine the usefulness of neoadjuvant chemotherapy and multimodality approaches; 5) treatment of metastatic malignant thymoma is based on chemotherapy. Secondary surgery may be performed with the aim of achieving complete resection. Inclusion in clinical trials is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition. Because of late recurrence, follow-up should be long.

Adult↗
PubMed1999

[Predictive factors of the delivery method in women with cesarean section scars].

OBJECTIVE: To determine the independent effect of clinical and non clinical factors on the mode of delivery after previous cesarean section. METHODS: We performed a retrospective multicenter study of 579 women who had previously undergone a cesarean section and who delivered between January 1995 and June 1997. Maternal and perinatal morbidity associated with trial of labor and elective repeat cesarean was assessed. Multiple logistic regression was used to identify prognostic factors for the outcome of a trial of labor. The odds ratios provided indicate the risk of cesarean section when the factor is present. RESULTS: The rate of successful trial of labor was 74.5%. Overall morbidity was not increased in the trial of labor group. The variables of significant predictive value were the Bishop's score (OR = 15.2 for a score < 3; 95% CI: 5.54 to 41.9), an anomaly of the pelvis (OR = 5.89; 95% CI: 2.37 to 14.7), a previous vaginal delivery (OR = 0.27; 95% CI: 0.12 to 0.60), a fetal distress (OR = 4.11; 95% CI: 2.01 to 8.43), the weight gain during pregnancy (OR = 2.01; 95% CI: 1.10 to 3.68), a delivery between 11 p.m. and 7 a.m. (OR = 0.29; 95% CI: 0.13 to 0.66), a hypertension (OR = 3.10; 95% CI: 1.09 to 8.80) and the use of an intra-uterine pressure catheter (OR = 0.26; 95% CI: 0.11 to 0.57). CONCLUSION: A trial of labor should be allowed in most of the women with previous cesarean section. The Bishop's score is the best predictor of the mode of delivery. Induction of labor and a first cesarean for dystocia do not affect the chances of vaginal birth.

Adult↗
PubMed1999

Physical activity level during a round of golf on a hilly course.

BACKGROUND: Regular physical activity plays a role in preventive medicine. Our study aimed at establishing the duration of different levels of exercise intensity during a round of golf. METHODS PARTICIPANTS: we studied 21 male and 9 female golfers (mean age 53 +/- 11 and 54 +/- 13 years respectively) volunteering for a round of golf on a hilly course. MEASURES: we recorded mean heart rate (HR) of every 15 seconds. Blood pressure was taken on each tee. Maximum HR (HRmax) reserve of each subject was calculated from the difference between pre-exercise and maximum HR attained during a test to volitional exhaustion on a cycle ergometer. A percentage of this value was added to the resting HR and was expressed as a percentage of HRmax reserve. RESULTS: Before start mean HR (+/- SD) was 86 +/- 11 beats per minute (BPM), during play 113 +/- 18, and during rest after play 100 +/- 24 BPM. Mean maximal HR of holes were 135 +/- 21 BPM. Mean systolic blood pressure was 145 +/- 30 before play, 137 +/- 31 on tees during play and 119 +/- 15 mmHg after play. A mean of 82 +/- 51 minutes was spent at 50-74% of HRmax reserve. 21 +/- 27 and 23 +/- 38 minutes were spent in the two higher intensity classes. An average of 106 +/- 77 minutes were spent at or above the individual heart rate equivalent of 100 W, the mean heart rate for this time was 128 +/- 17 BPM. Creatine kinase (+47%; p < 0.001), uric acid (+9%; p < 0.001) and HDL-cholesterol (+6%; p < 0.05) increased, triglycerides decreased by 18% (p < 0.01). CONCLUSIONS: The HR level during the golfround not using an electric cart relative to the maximum attained on the ergometer reaches the exercise intensity of 50 to > 85% HRmax reserve for a mean of over 2 hours, much longer than the 20-60 min recommended for endurance training.

Adult↗
PubMed1998

The pipsqueak protein of Drosophila melanogaster binds to GAGA sequences through a novel DNA-binding domain.

Pipsqueak (Psq) belongs to a family of proteins defined by a phylogenetically old protein-protein interaction motif. Like the GAGA factor and other members of this family, Psq is an important developmental regulator in Drosophila, having pleiotropic functions during oogenesis, embryonic pattern formation, and adult development. The GAGA factor controls the transcriptional activation of homeotic genes and other genes by binding to control elements containing the GAGAG consensus motif. Binding is associated with formation of an open chromatin structure that makes the control regions accessible to transcriptional activators. We show here that Psq contains a novel DNA-binding domain, which binds, like the GAGA factor zinc finger DNA-binding domain, to target sites containing the GAGAG consensus motif. Binding is suppressed, as in the GAGA factor and other proteins of the family, by the associated protein-protein interaction motif. The DNA-binding domain, which we call the Psq domain, is identical with a previously identified region consisting of four tandem repeats of a conserved 50-amino acid sequence, the Psq motif. The Psq domain seems to be structurally related to known DNA-binding domains, both in its repetitive character and in the putative three-alpha-helix structure of the Psq motif, but it lacks the conserved sequence signatures of the classical eukaryotic DNA-binding motifs. Psq may thus represent the prototype of a new family of DNA-binding proteins.

Amino Acid Sequence↗
PubMed1998

Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides.

Nerve growth is regulated by attractive and repulsive factors in the nervous system. Microscopic gradients of Collapsin-1/Semaphorin III/D (Sema III) and myelin-associated glycoprotein trigger repulsive turning responses by growth cones of cultured Xenopus spinal neurons; the repulsion can be converted to attraction by pharmacological activation of the guanosine 3',5'-monophosphate (cGMP) and adenosine 3',5'-monophosphate signaling pathways, respectively. Sema III also causes the collapse of cultured rat sensory growth cones, which can be inhibited by activation of the cGMP pathway. Thus cyclic nucleotides can regulate growth cone behaviors and may be targets for designing treatments to alleviate the inhibition of nerve regeneration by repulsive factors.

Animals↗
PubMed1998

Effect of microtubule disruption on cell adhesion and spreading.

Microtubules have been involved in a variety of cellular processes. In this study, we examined the role of the microtubular system in the adhesion and spreading of the adenocarcinoma cell line HT29-D4. Disruption of microtubules by nocodazole or navelbine resulted in an increase in cell adhesion to purified ECM proteins. This enhanced cell adhesion is mediated by integrins, but is not attributable to quantitative changes in the number of integrin receptors at the cell surface, as determined by flow cytometric analysis. In contrast to attachment, spreading of HT29-D4 cells was reduced by nocodazole treatment in a dose-dependent manner. Thus, microtubule depolymerization appears to increase initial attachment of cells to extracellular matrix, while impeding subsequent cell spreading.

Adenocarcinoma↗
PubMed1998

Free plasma catecholamines in spinal cord injured persons with different injury levels at rest and during exercise.

Spinal cord lesion leads to an interruption of pathways from brain to the peripheral sympathetic nervous system, which results in pathological changes in sympathetic innervation. Free epinephrine (E), norepinephrine (NE) and dopamine (DA) were measured in 30 tetraplegics (TETRA), 15 high-lesion paraplegics (T1 and T4, HPARA), 15 paraplegics with injuries between T5 and T10 (MPARA), 15 low-lesion paraplegics (below T10, LPARA) and 16 non-handicapped control persons (C) at rest, at 60 and 100% of maximal oxygen consumption during graded wheelchair ergometry (WCE). The TETRA showed significant lower E and NE levels at rest and only slight increases during physical exercise. The E and NE concentrations of the paraplegics with a lesion below T5 were significantly higher than those of the high-lesion paraplegics, as well as those of the control persons at every point in the study. All paraplegics and the control persons showed, at submaximal and maximal exercise, a significant increase in NE. Only a slight increase in E in HAPRA was shown. No differences were found at rest and during exercise in E and NE levels in the MPARA and LPARA. No significant differences were found in the dopamine concentration at rest or during exercise for any of the groups. In summary, different levels of lesion and the resulting interruption to sympathetic pathways in the spinal cord are decisive factors in the degree of impairment of sympathetic innervation in SCI persons. Tetraplegics show less preganglionic resting activity because of interruption of impulses from central centers and no considerable stimulation of the sympathetic nervous system during maximal exercise. Individuals with high paraplegia have a partial impairment of catecholamine release, especially of epinephrine, at rest and during exercise. Paraplegics with a lesion level below T5 showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity in comparison to control persons.

Adult↗
PubMed1998

Comparison of the GAGA factor genes of Drosophila melanogaster and Drosophila virilis reveals high conservation of GAGA factor structure beyond the BTB/POZ and DNA-binding domains.

As a member of the trithorax-group, the Trithorax-like (Trl) gene of Drosophila melanogaster contributes to the expression of homeotic genes and many other genes. Trl encodes different isoforms of the GAGA factor which is thought to act as an "antirepressor" of transcription by remodelling chromatin structure and thereby rendering control regions accessible for transcriptional activators. A more global role of the GAGA factor in chromatin structure and function is suggested by various phenotypes of Trl mutations, such as modification of position effect variegation. To better define the molecular basis of these pleiotropic effects, we cloned cDNAs encoding the GAGA isoforms of D. melanogaster and a distantly related species, D. virilis. We also characterized the genomic organization of both the D. melanogaster and D. virilis genes, and analysed the expression patterns of isoform-specific mRNAs. The D. virilis GAGA isoforms show high similarity to their D. melanogaster counterparts, particularly within the BTB/POZ protein-interaction and the zinc finger DNA-binding domains. Interestingly, conservation clearly extends beyond the previously defined limits of these domains. Moreover, the comparison reveals a completely conserved block of amino acid residues located between the BTB/POZ and DNA-binding domains, and a high conservation of the C-terminus specific for one of the GAGA isoforms. Thus, sequences of as yet unknown functions are defined as rewarding targets for further mutational analyses. The high conservation of the GAGA proteins of the two species is in accord with the nearly identical genomic organization and expression patterns of the corresponding genes.

Amino Acid Sequence↗
PubMed1998

The transcriptional switch between the Drosophila genes Pig-1 and Sgs-4 depends on a SEBP1 binding site within a shared enhancer region.

The Drosophila genes Pig-1 and Sgs-4 are adjacent and oppositely transcribed genes which share a common enhancer region located in the intergenic region between the two transcription start sites. Both genes are transcribed in the same tissue, the larval salivary gland, but they are expressed at different times, the expression switching from Pig-1 to Sgs-4 expression during development of the third-instar larva. Here we describe partial purification and functional analysis of a DNA-binding protein, secretion enhancer binding protein 1 (SEBP1), from nuclear extracts of whole Drosophila larvae. SEBP1 binds to a single site within the Pig-1/Sgs-4 intergenic region. Point mutations that disrupt this site had no significant effect on activation of the Sgs-4 promoter in constructs lacking the Pig-1 promoter. However, if the Pig-1 promoter was present, the same mutations led to a strong attenuation of Sgs-4 promoter activity, suggesting that binding of SEBP1 is necessary for the Pig-1/Sgs-4 transcriptional switch. The data are consistent with a model in which the SEBP1 binding site acts as a transient silencing element that facilitates the reorganization of promoter-enhancer interactions by disrupting pre-existing interactions, thus enabling stage-specific activators of Sgs-4 to bind to their enhancer target sites.

Animals↗
PubMed1998

HCG secretion by peripheral mononuclear cells during pregnancy.

Peripheral mononuclear cells (MNC) in culture release a biologically active hCG. This effect is detectable during pregnancy with a maximum between the 9th and 16th wk. Peripheral MNC already secrete hCG between the 7th and 11th d after embryo transfer. The secretion of hCG is activated by the PKC-activator TPA. TPA induces hCG release into the medium, thus causing a decrease in intracellular hCG content. In contrast, db-cAMP inhibites hCG secretion into the medium. Protein synthesis inhibitors of transcription and translation suppress the production and secretion of hCG. Peripheral natural killer (NK) cells (CD56+/CD16+) and monocytes (CD14+) show the highest secretion rates. IL-1 beta, IL-4, IL-6, IL-10, TNF alpha, and GM-CSF stimulate, whereas IL-2 and INF gamma inhibit, the hCG secretion of mononuclear cells. Flow cytometric experiments with hCG antibody demonstrate a binding of hCG on the surface of monocytes more than lymphocytes. The binding capacity is improved during pregnancy. Different hCG bands are shown in the Western blot analysis. We could confirm the mRNA of beta hCG and alpha CG are in MNC as well in the placental control. Peripheral MNC, first and foremost NK cells and monocytes, produce and secrete hCG during pregnancy, which play an important role for the corpus luteum rescue during the early gestational age and possibly for the immunotolerance.

Animals↗
PubMed1998

Convergent effects of growth factors, hormones, and fibronectin are necessary for the enterocyte differentiation of a colon adenocarcinoma cell line (HT29-D4).

The aim of this work was to show in serum-free medium a convergent effect of physiological factors and extracellular matrix proteins on the differentiation process of enterocytes by taking as a model the HT29-D4 clone that has the feature of differentiating when subcultured in fetal bovine serum glucose-free medium. We show that triiodothyronine (T3) as well as insulin promotes limited cell growth and differentiation, whereas fibronectin or bovine serum albumin (BSA) induces cell growth and a low level of differentiation. However, insulin, T3, fibronectin, and BSA together with epidermal growth factor and transferrin promoted satisfactory growth and enterocyte morphology with epithelial electrophysiological properties in HT29-D4 cells. With these factors adequate protein targeting was achieved since cells apically expressed the carcinoembryonic antigen, and basolaterally transferrin and insulin receptors, beta 1 and alpha v beta 6 integrins, talin, vinculin, and focal adhesion kinase (FAK). Talin, vinculin, FAK, and alpha v beta 6 integrin, the fibronectin receptor, were clustered in focal contacts, which agrees with a possible role of fibronectin in final cell growth, the latter process mediating the final phase of differentiation. This level of differentiation can be maintained for a long time. Thus HT29-D4 cells appear to be a suitable model to study the implication of integrins in the differentiation process of human enterocytes.

Adenocarcinoma↗
PubMed1998

Effect of "living high-training low" on the cardiac functions at sea level.

Living high-training low (LHTL), living at high altitude and training at sea level, is reported to be beneficial in enhancing physical performance. Effect of LHTL on cardiac function which is one of major determinants in performance, however, was not examined. To address this issue, 21 well-trained triathletes divided into control (n = 10, living and training at sea level) and LHTL group (living at 1980 m altitude > or = 12 hrs/day and training at sea level) were Doppler echocardiographically examined before and at the end of the two-week program. Heart rate and blood pressure did not change in both groups. At end of the training, left ventricular endsystolic diameter of LHTL group was smaller than that of controls (32 vs 34 mm, P < 0.05). Shortening fraction and ejection fraction in LHTL group increased by 9% and 17 %, respectively, P < 0.05. Preejection period/ejection time was more greatly reduced in LHTL group (P < 0.05). Stroke volume and cardiac output in LHTL increased. Diastolic function was not significantly affected by LHTL. These results suggest that LHTL produced an improvement of systolic function underlined by incremented left ventricular contractility, which might be associated with increased beta-adrenergic receptor or an improved myocardial energy utilization.

Adult↗
PubMed1998

Repression of hybrid dysgenesis in Drosophila melanogaster by combinations of telomeric P-element reporters and naturally occurring P elements.

In Drosophila melanogaster, hybrid dysgenesis occurs in the germline of flies produced by crosses between females lacking P elements and males carrying 25-55 P elements. We have previously shown that a complete maternally inherited repression of P transposition in the germline (P cytotype) can be elicited by only two autonomous P elements located at the X chromosome telomere (cytological site 1A). We have tested whether P transgenes at 1A, unable to code for a P-repressor, may contribute to the repression of P elements. Females carrying a P-lacZ transgene at 1A ["P-lacZ(1A)"], crossed with P males, do not repress dysgenic sterility in their progeny. However, these P-lacZ(1A) insertions, maternally or paternally inherited, contribute to P-element repression when they are combined with other regulatory P elements. This combination effect is not seen when the P-lacZ transgene is located in pericentromeric heterochromatin or in euchromatin; however a P-w,ry transgene located at the 3R chromosome telomere exhibits the combination effect. The combination effect with the P-lacZ(1A) transgene is impaired by a mutant Su(var)205 allele known to impair the repression ability of the autonomous P elements at 1A. We hypothesized that the combination effect is due to modification of the chromatin structure or nuclear location of genomic P elements.

Animals↗
PubMed1998

The presence of chorionic gonadotrophin beta subunit in normal cyclic human endometrium.

The aim of the present study was to determine whether human endometrial cells are able to secrete beta-chorionic gonadotrophin (betaCG). Immunohistochemical studies and in-situ hybridization were performed in order to provide evidence for the occurrence of betaCG in the normal endometrium in 15 patients in the proliferative phase, two patients in the periovulatory phase and 13 patients in the secretory phase. Neither immunohistochemical nor hybridization reactions could be recognized during the proliferative phase. In contrast, both protein and betaCG mRNA were observed in the glandular cells of the endometrium during the secretory phase. The results were supported by Western blotting of secretory phase endometrium extracts and the assessment of the functional secretory capacity of primary endometrium cultures. In comparison with cultured and separated cell fractions, tissue extracts showed a higher betaCG, indicating a regulatory interaction. In conclusion, betaCG can be demonstrated in normal human cyclic endometrium, suggesting a paracrine role in endometrial physiology.

Cells, Cultured↗