Biomedical subjects

G Hartmann

Publications and source records attributed to G Hartmann.

At least 91 records · Page 5Linked to original sources

PubMed1993

Relationship between the monoamine, progesterone and estradiol content in follicular fluid of preovulatory graafian follicles after superovulation treatment.

We measured the progesterone, estradiol (E2), serotonin (5-HT), noradrenaline (NA) and dopamine (DA) contents of follicular fluid (FF) samples obtained from 35 patients undergoing in vitro fertilization and embryo transfer. Progesterone and E2 were determined by radioimmunoassay, and monoamines were measured by a spectrofluorimetric method. Significantly higher progesterone and NA levels were found (p < 0.01) in FF from cycles in which the oocyte cleaved and resulted in pregnancy compared to FF containing uncleaved oocytes. NA and DA contents were significantly higher in FF from cycles resulting in pregnancy than in FF containing cleaved oocytes not resulting in pregnancy (p < 0.01). There were significantly lower NA and 5-HT levels in FF containing uncleaved oocytes compared to the latter group (p < 0.05). Significant positive correlations were found between progesterone and 5-HT (r = 0.67) and between NA and DA (r = 0.93) in the pregnant group; between progesterone and E2 (r = 0.84) in FF containing uncleaved oocytes; between progesterone and E2 (r = 0.71) and between NA and DA (r = 0.62) in FF from cycles in which the oocyte cleaved but did not result in pregnancy. The results suggest that the follicular hormonal changes associated with oocyte maturation may be locally modulated by monoamines.

Biogenic Monoamines↗

PubMed1993

Properties and functions of scatter factor/hepatocyte growth factor and its receptor c-Met.

Scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. The receptor for SF/HGF has recently been identified as the c-Met proto-oncogene product, a transmembrane receptor tyrosine kinase. Depending on the target cells and culture conditions, SF/HGF has several distinct activities in vitro, i.e., it induces cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. In vivo, SF/HGF might be involved in tissue regeneration, tumor progression, and embryological processes.

Amino Acid Sequence↗

PubMed1993

Molecular characteristics of HGF-SF and its role in cell motility and invasion.

Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and other cells, and is thought to play a role in liver regeneration. We have presented structural and functional evidence that human SF and human HGF are identical proteins encoded by a single gene, since (i) no differences could be found by protein sequencing, by cDNA analysis, or by immunological comparison, and (ii) SF acts as a hepatocyte growth factor--i.e., stimulates DNA synthesis of primary hepatocytes and is a morphogen of kidney epithelial cells--whereas HGF exhibits SF activity--i.e., dissociates and induces invasiveness of various epithelial cells. Furthermore, there exists only one gene for human HGF-SF which is located on chromosome 7, bands q11.2-21 (Weidner et al., Proc. Natl. Acad. Sci. USA 88, 7001-7005, 1991). HGF-SF has been found to be the ligand of the c-met receptor tyrosine kinase (Naldini et al., EMBO J. 10, 2867-2878, 1991b). We have recently used transient expression of naturally occurring and in vitro mutagenized cDNAs of HGF-SF in order to delineate the protein domains necessary for biological activity and c-met receptor activation. (i) A single-chain HGF-SF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg494 to Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A HGF-SF splice variant encoding a protein with a 5 amino acid deletion in the first kringle domain was as highly active as the wild type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N-terminus and the first two kringle domains bound the met receptor, stimulated its tyrosine phosphorylation, and induced dissociation of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N-terminal region and/or the first two kringle domains of HGF-SF is sufficient for binding to and activation of the met receptor (Hartmann et al., Proc. Natl. Acad. Sci. USA, in press).

Animals↗

PubMed1992

A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis.

We recently found that scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. SF/HGF is the ligand of the c-Met receptor tyrosine kinase. Here we used transient expression of naturally occurring and in vitro mutagenized cDNAs of SF/HGF to delineate the protein domains necessary for biological activity and binding to the c-Met receptor. (i) A single-chain SF/HGF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg-494--> Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A SF/HGF splice variant encoding a protein with a 5-amino acid deletion in the first kringle domain was as highly active as the wild-type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N terminus and the first two kringle domains bound the c-Met receptor, stimulated tyrosine auto-phosphorylation, and induced scattering of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N terminus/first two kringle regions of SF/HGF is sufficient for binding to the Met receptor and that this leads to the activation of the downstream signal cascade involved in the motility response. However, the complete SF/HGF protein seems to be required for mitogenic activity.

Amino Acid Sequence↗

PubMed1992

Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor.

The extracellular protease urokinase is known to be crucially involved in morphogenesis, tissue repair and tumor invasion by mediating matrix degradation and cell migration. Hepatocyte growth factor/scatter factor (HGF/SF) is a secretory product of stromal fibroblasts, sharing structural motifs with enzymes of the blood clotting cascade, including a zymogen cleavage site. HGF/SF promotes motility, invasion and growth of epithelial and endothelial cells. Here we show that HGF/SF is secreted as a single-chain biologically inactive precursor (pro-HGF/SF), mostly found in a matrix-associated form. Maturation of the precursor into the active alpha beta heterodimer takes place in the extracellular environment and results from a serum-dependent proteolytic cleavage. In vitro, pro-HGF/SF was cleaved at a single site by nanomolar concentrations of pure urokinase, generating the active mature HGF/SF heterodimer. This cleavage was prevented by specific urokinase inhibitors, such as plasminogen activator inhibitor type-1 and protease nexin-1, and by antibodies directed against the urokinase catalytic domain. Addition of these inhibitors to HGF/SF responsive cells prevented activation of the HGF/SF precursor. These data show that urokinase acts as a pro-HGF/SF convertase, and suggest that some of the growth and invasive cellular responses mediated by this enzyme may involve activation of HGF/SF.

Animals↗

PubMed1992

Measurement of noradrenaline, dopamine and serotonin contents in follicular fluid of human graafian follicles after superovulation treatment.

We measured the noradrenaline (NA), serotonin (5-HT) and dopamine (DA) contents of 47 normally maturated and 16 cystically degenerated follicular fluid samples obtained from patients involved in the in vitro fertilization and gamete transfer program. The patients were given human menopausal gonadotropin (HMG), as a superovulation treatment, and 7,500 IU human chorionic gonadotropin (HCG) to induce ovulation 34-36 h prior to the follicular puncture done by laparoscope. The NA content of the normally developed follicles was 11.4 + 8.4 micrograms/100 ml on average. For cystically degenerated follicles, the following data were obtained: 1.1 + 0.7 micrograms/100 ml (p less than 0.001). 5-HT and DA contents in the preovulatory follicles are 14.3 +/- 8.9 and 19.3 +/- 8.2 micrograms/100 ml, respectively; at the same time, 5-HT and DA contents in the cystically degenerated follicles were 12.2 +/- 6.2 and 12.7 +/- 6.8 micrograms/100 ml, respectively. They suggest that the higher amount of NA in the follicular fluid might play an important role in the mechanism of ovulation, the regulation of postovulatory tubal motility and the release of progesterone from granulosa cells.

Dopamine↗

PubMed1992

Prolactin and dopamine concentrations in the cerebrospinal fluid during the neonatal period.

UNLABELLED: Prolactin (PRL) has been detected in the cerebrospinal fluid (CSF) in humans and the absolute level appears to reflect the serum PRL concentration. Because PRL is thought to be involved in the regulation of brain water and electrolyte content attempt has been made to determine CSF and plasma PRL and dopamine (DA) concentrations, osmolality, and sodium level in 21 newborn infants undergoing lumbar punction because of apneic spells, fever, or perinatal asphyxia. The mean of gestational age was 36.5 weeks (range: 31-41) and birthweight was 2572 g (range: 1140-3550). The lumbar puncture was performed at the 8.3 postnatal day (range: 1-38). The plasma concentration of PRL was 106.52 +/- 14.43 ng/ml, significantly higher than the CSF PRL level (43.24 +/- 7.39 ng/ml, p < 0.01). This elevated level was observed in all individual cases. DA concentration in the plasma was much higher than the value detected in the CSF (64.75 +/- 13.83 vs 8.64 +/- 0.72 ng/ml, p < 0.01). No difference was observed between the sodium content of the CSF and plasma (138.94 +/- 1.28 vs 138.04 +/- 1.03 mmol/l), however, the osmolality of the plasma tended to be higher than the CSF osmolality (286.7 +/- 3.81 vs 276.76 +/- 2.19 mosm/kg, p < 0.05). In the CSF osmolality, PRL, DA, and sodium concentrations did not show any correlation. IN CONCLUSION: in the CSF PRL probably does not play a primary role in controlling the osmolality and sodium content. PRL in CSF seems to be independent from CSF DA concentration.

Dopamine↗

PubMed1991

[Analysis of noradrenaline, dopamine and serotonin levels in follicular fluid following superovulatory treatment].

The authors measured the noradrenaline (NA), serotonin (5-HT) and dopamine (DA) content of 47 normally maturated and 16 cystically degenerated follicular fluid samples obtained from patients involved in the in vitro fertilisation and gamete transfer program. The patients were given human menopausal gonadotropin (HMG) as a superovulation treatment, and they were given 7500 IE human Chorionic Gonadotropin (HCG) to induce ovulation 34-36 hours prior to the follicular puncture done by laparoscope. The NA content of the normally developed preovular follicles is 11.4 +/- 8.4 micrograms/100 ml on average. For the cystically degenerated follicles the data are following: 1.1 +/- 0.7 micrograms/100 ml (p less than 0.001). 5--HT and DA for the preovulatory follicles are 14.3 +/- 8.9 micrograms/100 ml and 19.3 +/- 8.2 micrograms/100 ml respectively; at the same time for the cystically degenerated follicles they are 12.2 +/- 6.2 micrograms/100 ml, and 12.7 +/- 6.8 micrograms/100 ml respectively. They presume that the higher amount of NA in the follicular fluid might play an important role in the mechanisms of ovulation, the regulation of postovulatory tubal motility, and the release of progesterone from granulosa cells.

Adolescent↗

PubMed1991

Evidence for the identity of human scatter factor and human hepatocyte growth factor.

Amino Acid Sequence↗

PubMed1991

[Pleural empyema--rational diagnosis and therapy].

A pyothorax is a relatively rare occurrence in a general hospital and is posing a number of problems. Among these the long mean duration of hospitalisation is of note lasting 47 days for 24 patients at our clinic. The course and the mortality rate are influenced by early detection and judicious use of interdisciplinary treatment. Small effusions accompanying pneumonia are frequent and likely to disappear after treatment of the underlying disease. In these instances a precipitate punction may lead to secondary infection. In case of a sterile punctate the pH value and consideration of glucose and LDH values determine further measures. Computed tomography is of great value since it yields decisive information not available from conventional radiography. If the empyema is not segregated in compartments a closed drainage with a large caliber chest-tube ist the method of choice. Limited thoracotomy is advised when several empyema chambers develop after short duration of the illness. Persistent disease or widespread scarring necessitate decortication in most cases.

Adolescent↗

PubMed1991

[Unsuccessful inoculation against hepatitis B].

Explore the source record for details and available documents.

Hepatitis B↗

PubMed1991

Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor.

Scatter Factor (SF) is a fibroblast-secreted protein which promotes motility and matrix invasion of epithelial cells. Hepatocyte Growth Factor (HGF) is a powerful mitogen for hepatocytes and other epithelial tissues. SF and HGF, purified according to their respective biological activities, were interchangeable and equally effective in assays for cell growth, motility and invasion. Both bound with identical affinities to the same sites in target cells. The receptor for SF and HGF was identified as the product of the MET oncogene by: (i) ligand binding and coprecipitation in immunocomplexes; (ii) chemical crosslinking to the Met beta subunit; (iii) transfer of binding activity in insect cells by a baculovirus carrying the MET cDNA; (iv) ligand-induced tyrosine phosphorylation of the Met beta subunit. SF and HGF cDNA clones from human fibroblasts, placenta and liver had virtually identical sequences. We conclude that the same molecule (SF/HGF) acts as a growth or motility factor through a single receptor in different target cells.

Animals↗

PubMed1991

Long-term effect of immunization with neural and nonneural antigens on the noradrenaline and serotonin levels of discrete brain areas in mice and the relationship between neurotransmitter levels and antibody production.

The effect of immunization with neural and nonneural antigens on hypothalamic and mesencephalic neurotransmission and antibody response have been investigated. Treatment of SJL/N mice with bovine myelin basic protein (BMBP), mouse spinal cord homogenate (MSCH) or bovine serum albumin (BSA) produced no significant changes in the average hypothalamic and mesencephalic noradrenaline (NA) or serotonin (5-HT) content. In Balb/c mice, however, treatment with BMBP caused a significant increase in mesencephalic NA, and treatment with MSCH caused a significant increase in hypothalamic 5-HT 3 weeks after the first antigenic challenge. The SJL/N strain showed a high antibody response to BMBP and BSA, and a moderate one to MSCH, while in Balb/c mice, there was a low response to BMBP, a moderate one to MSCH and a high response to BSA. Significant, positive correlations were found between the level of antigen-specific serum antibodies and the following neurotransmitters: hypothalamic NA in the BMBP and MSCH-treated groups, hypothalamic 5-HT in the MSCH-treated group, mesencephalic NA and 5-HT in the BMBP-treated group, and mesencephalic 5-HT in the MSCH-treated SJL/N animals. No significant correlations between the levels of antibodies and neurotransmitters have been found either in the BSA-immunized SJL/N animals, or in any of the groups of Balb/c mice treated with BMBP, MSCH or BSA.

Animals↗

PubMed1990

The glucose-induced insulin release after adrenalectomy in the rat.

Plasma glucose and insulin levels following glucose loading were investigated in adrenalectomized rats. Both oral and intravenous administration of glucose induced an elevation in plasma glucose and insulin level. The increases of plasma glucose and insulin concentrations were significantly higher in the adrenalectomized rats compared with the controls. We conclude, that corticoid hormones are capable of inhibiting glucose-induced insulin release in the rat.

Adrenalectomy↗

PubMed1990

Lack of inhibitory effect of verapamil on glucose-induced insulin release in the rat.

The effect of the calcium-antagonist Verapamil was investigated on the blood glucose and insulin release in rats. Verapamil induced a significant elevation of the blood glucose and increased the insulin release too, however, it was not able to inhibit the glucose-induced insulin release. The authors suggest, that the effect of glucose is not restricted for the calcium turnover of the islets of the pancreas, and may be there are other cellular mechanisms apart from the effect on the calcium movements by which glucose induces insulin release.

Analysis of Variance↗

PubMed1990

[Long time hospitalization in pediatric surgical intensive care units].

If the great majority of children stay in intensive care unit only for few days, a small group of patients stay for a long period of time, varying from 3 months to five years or even more. The small group include two very different entities. On the one hand, newborns with a congenital malformation, often digestive e.a. with a short small intestine, need a long time parenteral nutrition. In such cases, the family disturbance, the opening of the unit to the parents, the awakening of the infant, his psychomotor and affective attainments are as many problems for the whole medical team. On the other hand, children severely injured in accidents, that occurred on public thoroughfares or in domestic house holds, most of the time are older than 3 years. These children may present important central neurologic sequelae, or other major sequelae (multiple trauma, burn injuries, hypoxic cervical spinal cord injury). Their education, activities, games, and family relations must be actively supported. Does the hospital structure, and particularly the intensive care unit, meet such requirements in very long time hospitalization?

Adolescent↗

PubMed1989

[Non-healing foot wound].

A young man from Sri Lanka developed a suppurative chronic wound on the right foot after a minor trauma. In spite of several surgical interventions a closure of the ulcer did not occur. Only six months later after serious miliary tuberculosis had developed the correct diagnosis was established and tuberculostatic therapy initiated. This manifestation of tuberculosis--rare in recent times--is reviewed. Emphasis is placed on the causal relation between trauma and reactivation of tuberculosis as well as the pathogenesis of secondary miliary tuberculosis.

Adult↗

PubMed1989

Adaptation of tendon collagen to exercise.

We report an experimental study on the effect of exercise on tendon structure in mice. After one week of physical training an increase in mean diameter, in number, and in cross-sectional area, as well as a change in mean fibril diameter distribution, was demonstrated. In the long-term, there was an increase in fibril number, a fall in mean diameter, but no statistically significant changes in the relative cross-sectional area per unit compared with the control tendons.

Animals↗