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Biomedical subjects

C Muhr

Publications and source records attributed to C Muhr.

40 records · Page 3Linked to original sources

Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study.

Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-[11C]methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells.

Adenoma↗

Macroprolactinomas: serial MR imaging in long-term bromocriptine therapy.

PURPOSE: To study the changes in macroprolactinomas during long-term bromocriptine therapy by means of serial MR imaging, and to correlate the findings to the serum prolactin (S-PRL) levels. PATIENTS AND METHODS: Thirteen patients with macroprolactinomas were studied before and during bromocriptine therapy; six to 11 MR examinations were performed with a duration of follow-up of 22 to 74 months. Tumor size, extension, relationship to adjacent structures, and signal intensity patterns were evaluated. Signal intensity ratios and T2 values were calculated in areas of apparently solid tumor tissue. RESULTS: Bromocriptine effectively reduced the size of all tumors; the size reduction was already significant at 1 week, but often continued for several years. Reenlargement during therapy was seen in three cases. The development of chiasmal herniation parallel to increasing cisternal invagination into the sella was a common finding, but was not correlated to visual symptoms. Signal intensity patterns corresponding to hemorrhage, cysts or necrosis were frequently observed, and transitions from one pattern to another were common. Hemorrhage occurred mainly in tumors corresponding to high initial serum prolactin levels. After 1 year of therapy, there was a significant increase in T2 values, indicating an increased water content in residual solid tumor tissue. CONCLUSIONS: MR is valuable for follow-up in bromocriptine therapy of macroprolactinomas, and provides new information on the tumor size changes, the inner structure of the tumors, and the optic chiasm.

Bromocriptine↗

Leukotriene and 5-lipoxygenase inhibitor induced variations in thymidine uptake in a human glioma cell line cultured as monolayers or as multicellular spheroids.

Effects of exogenous leukotrienes and/or treatment with the 5-lipoxygenase inhibitor, AA-861, on the 3H-thymidine uptake were investigated in a human glioma cell line, U-343MGa, growing as monolayers or multicellular spheroids. The spheroids contained about four times more endogenous leukotrienes than the monolayers. Administration of 0.1 microM exogenous leukotriene D4 increased the 3H-thymidine uptake in the spheroids while it gave a decrease in the monolayers. Inhibition of 3H-thymidine uptake was induced in the spheroids by 10 microM AA-861 and this inhibition was only seen during the period at which central necrosis develops in the spheroids. This drug showed an inhibitory effect on monolayers one day after subculture but gave no measurable effect on the monolayers two days later. It seemed that AA-861 exerted an inhibitory action at culture conditions associated with "cellular stress" such as subculture (trypsinization) of monolayers and induction of necrosis in spheroids. Induction of "cellular stress" with heat or exposure to a Ca(2+)-ionophore also gave an inhibitory action of AA-861 and the inhibition could be counteracted by administration of exogenous B4 leukotrienes. The observed effects are probably related to the activation of the arachidonic acid cascade and indicate that leukotrienes in some way interact with "cellular stress" and induce acute changes in 3H-thymidine uptake. Further research is necessary to reveal the detailed molecular mechanisms.

Antineoplastic Agents↗

Interferon-alpha inhibits the DNA synthesis induced by PDGF and EGF in cultured meningioma cells.

The growth of meningioma in vivo may be mediated by a growth factor. We evaluated inhibitory effect of IFN-alpha on DNA synthesis promoted by PDGF and EGF on meningioma cell cultures. Eight cases of meningioma were tested for the expression of PDGF receptor. The effects of PDGF AA, PDGF BB, EGF and TGF-beta1 on five meningioma cell cultures were investigated by measuring 3H-thymidine incorporation during 24 hours of incubation with the growth factors under serum-free culture conditions. The incorporation of 3H-thymidine was elevated in all of the five tested tumor cell cultures after the addition of PDGF BB and EGF. Maximal stimulation was observed on three cultures with EGF and two cultures with PDGF BB. Under the same culture conditions, simultaneous incubation with IFN-alpha inhibited the 3H-thymidine incorporation promoted by PDGF and EGF. Our results indicate the inhibitory effect of IFN-alpha both on DNA synthesis promoted by PDGF and EGF, and on the meningioma cell proliferation. The present study also demonstrates the inhibitory effect of TGF-beta 1 in meningioma cell culture.

Adult↗