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M Schäffer

Publications and source records attributed to M Schäffer.

35 records · Page 2Linked to original sources
PubMed1997

Michellamines D-F, new HIV-inhibitory dimeric naphthylisoquinoline alkaloids, and korupensamine E, a new antimalarial monomer, from Ancistrocladus korupensis.

New monomeric (korupensamine E, 6) and dimeric (michellamines D-F, 7-9) naphthylisoquinoline alkaloids have been isolated from exracts of the tropical liana Ancistrocladus korupensis. Structures were determined by spectroanalytical methods, and stereochemistry was defined through NOE correlations, chemical degradation, and CD spectroscopy. Michellamines D-F exhibited in vitro HIV-inhibitory activity comparable to michellamine B, and korupensamine E exhibited in vitro antimalarial activity comparable to korupensamines A-D.

Anti-HIV Agents↗
PubMed1997

N,N-dimethyldioncophyllinium A iodide: synthesis, stereoanalysis, and antimalarial activity of the first N-quaternary naphthylisoquinolinium salt.

The first synthesis of an N-quaternary salt of a naphthylisoquinoline alkaloid, N,N-dimethyldioncophyllinium A iodide, is described. For this potential natural product, a degradative procedure for the unambiguous stereoanalysis of the stereogenic centers has been elaborated. It shows enhanced anti-plasmodial activity in vitro towards Plasmodium falciparum erythrocytic forms, as compared to its less methylated precursors.

Animals↗
PubMed1997

Comparative assessment of the activity of beta-carotene, retinoyl-beta-D-glucuronide and retinoic acid on growth and differentiation of a human promyelocytic leukemia cell line HL-60.

We compared the ability of all-transretinoic acid (RA), all-trans-retinoyl-beta-D-glucuronide (RAGL), and all-trans-beta-carotene (BC) to inhibit growth and to induce differentiation of the human promyelocytic leukemia cell line HL-60 into morphologically mature granulocytes. BC was made water-soluble by the solutol-solvent-system. RA (1 microM) could induce differentiation of 85% of the HL-60 cells after a total incubation time of 180 hours, RAGL (5 microM) induced 64% of the cells, whereas 33% of the HL-60 cells were differentiated after incubation with BC (10 microM), which was determined by assessing cell functional capacity to reduce nitroblue tetrazolium dye in response to phorbolesters. The absence of RA in RAG and BC treated cells gives strong evidence that RAG and BC exert intrinsic biological effects.

Antioxidants↗
PubMed1997

Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines.

Binding of interleukin-6 to its receptor (IL-6R) induces the association of the IL-6R alpha chain (IL-6Ralpha) with a 130-kDa transmembrane glycoprotein, gp130. This event activates tyrosine kinases of the Janus kinase (JAK) family and transduces signals to the cytosol or nucleus. To further characterize the biochemical mechanisms by which IL-6 promotes cell proliferation, we investigated the effects of IL-6 on the growth and transmembrane signaling of several lymphoid cell lines. In the IL-6-dependent cell line B-9, IL-6 induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of several cytosolic proteins as detected by antiphosphotyrosine immunoblots. The molecular weight of major bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 44, 65, 70, 80, 137, 148, 184, and 190 kDa, respectively. Similar effects of IL-6 on tyrosine phosphorylation were observed in the human multiple myeloma cell line LP-1. Because JAKs were unlikely to mediate all the biological effects of IL-6, we investigated whether members of the Src family of tyrosine kinases were also activated in B-9 or LP-1 cells. IL-6 induced the activation and tyrosine phosphorylation of p59Fyn, p56/59Hck, and p56Lyn. Coprecipitation experiments with anti-Hck, anti-Lyn, anti-Fyn, and anti-gp130 antibodies revealed a physical association with gp130 of p56/59Hck and p56Lyn, but not p59Fyn, in LP-1 cells. Together, these results show for the first time that several Src kinases may become activated by IL-6 (p59Fyn, p56/59Hck, and p56Lyn) and associate with gp130 (p56/59Hck and p56Lyn).

B-Lymphocytes↗
PubMed1994

Anti-HIV michellamines from Ancistrocladus korupensis.

Here we report details of the isolation and determination of the absolute configurations and comparative anti-HIV activities of novel, atropisomeric naphthylisoquinoline alkaloid dimers, michellamines A, B, and C, from a newly described species of Ancistrocladus from the Korup rainforest of Cameroon. We further provide a more extensive analysis of the range of anti-HIV activity of michellamine B, the most potent and abundant member of the series. Michellamine B inhibited HIV-induced cell killing and viral replication in a variety of human cell lines, as well as in cultures of human peripheral blood leukocytes and monocytes. Michellamine B was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6 and the pyridinone-resistant strain A17; the compound also inhibited several strains of HIV-2.

Africa↗
PubMed1993

Mechanism of galanin's inhibitory action on pancreatic enzyme secretion: modulation of cholinergic transmission--studies in vivo and in vitro.

This study examined the inhibitory mechanism of galanin, a 29 amino acid polypeptide on pancreatic enzyme secretion in anaesthetised rats, isolated pancreatic acini, and lobules. Urethane anaesthetised rats with pancreatic fistulas pretreated with 3-0-methyl-glucopyranose (500 mg/kg/h) were stimulated with an intravenous bolus of 2-deoxyglucose (2-DG) (75 mg/kg). Maximal amylase secretion was mean (SEM) 274 (19)% of basal secretion. Atropine (150 micrograms/kg/h) and galanin (10 nmol/kg/h) almost completely inhibited 2-DG stimulated amylase secretion suggesting an inhibition of cholinergic transmission. To further test this possibility this study investigated the effect of galanin on carbachol and cholecystokinin stimulated amylase release from isolated pancreatic acini. Galanin did not suppress carbachol or cholecystokinin stimulated amylase release, indicating that galanin inhibits exocrine secretion by indirect mechanisms. The cholinergic pathway was assessed by using pancreatic lobules containing intrapancreatic neurons. Veratridine, a sodium channel activator, dose dependently stimulated amylase release. Veratridine (100 microM) stimulated amylase release by 411 (10)% of basal secretion. Atropine (1 microM) or tetrodotoxin (1 microM) almost completely blocked veratridine stimulated amylase release. Galanin (1 microM) significantly inhibited veratridine stimulated amylase release with a maximal inhibition of 50% (p < 0.05). In addition, when lobules were incubated with [3H]-choline, galanin significantly (p < 0.05) inhibited veratridine stimulated release of newly synthesised [3H]-acetylcholine. Thus galanin inhibits pancreatic secretion by inhibiting cholinergic transmission. These studies show that galanin inhibits rat pancreatic enzyme secretion by an indirect mechanism by reducing cholinergic transmission.

Acetylcholine↗
PubMed1992

[Type-2B multiple endocrine neoplasms with diffuse liver metastases as the cause of chronic diarrhea].

During examination before surgical correction of pes valgus a 20-year-old man reported having 3-5 pasty, foul smelling diarrhoeic motions per day for the past 3 years. He was noted to have rather thick lips and Marfan-like body build. Erythrocyte sedimentation rate was 18/34 mm, serum activity of GOT 22.5 U/l, GPT 35.7 U/l. Faecal weight was increased to 640 g/d, fat content to 12 g/d. Serum levels of the carcinoembryonic antigen (2494 ng/ml; normal: < 2.5) and of calcitonin (1,619,760 pg/ml; normal < 100) were elevated. Gastroscopy, partial coloscopy, colon-contrast imaging, ultrasonography and computed tomography of the neck and abdomen, as well as magnetic nuclear imaging of the neck were all normal. But laparoscopy revealed the liver to be infiltrated by small whitish nodules which immunohistologically proved to be metastases of a C-cell carcinoma. Total thyroidectomy was performed and the diagnosis of a C-cell carcinoma of the thyroid confirmed intra-operatively. After the operation the diarrhoea was stopped with codeine (9 mg/d). In case of tumour progression, therapy with octreotide, a somatostatin analogue, will be carried out. The concomitant occurrence of C-cell carcinoma, Marfan-like body build, thick lips and skeletal changes is typical of multiple endocrine neoplasia type 2B, which is caused by a chromosomal defect.

Adult↗
PubMed1992

[Detection of mutated ras-oncogene in pancreatic cancers: improved diagnostic possibilities using molecular biology techniques?].

C-Ki-ras oncogenes have been detected by polymerase chain reaction in the majority of pancreatic carcinomas. The biological role of ras oncogenes in pancreatic carcinogenesis is unknown. This review summarizes the current knowledge of ras oncogenes in pancreatic carcinomas, the different techniques for oncogenes and their possible diagnostic value.

Cell Division↗
PubMed1991

Molecular cloning of the human histamine H2 receptor.

We utilized the technique of polymerase chain reaction with oligonucleotide primers based upon the nucleotide sequence of the canine H2 histamine receptor gene which we recently isolated to clone its human homologue. Transfection of a construct of this gene in Colo-320 DM cells led to the expression of a receptor that bound to [methyl-3H] tiotidine and was linked to 3',5'cyclic adenosine monophosphate (cAMP) generation in response to histamine. Both cAMP generation and [methyl-3H] tiotidine binding were inhibited with the H2 histamine receptor selective antagonist cimetidine but not diphenhydramine or thioperamide which are, respectively, H1 and H3 histamine receptor antagonists. These data confirm that we have successfully cloned a novel gene encoding the human H2 histamine receptor.

Amino Acid Sequence↗
PubMed1991

Molecular cloning of a gene encoding the histamine H2 receptor.

The H2 subclass of histamine receptors mediates gastric acid secretion, and antagonists for this receptor have proven to be effective therapy for acid peptic disorders of the gastrointestinal tract. The physiological action of histamine has been shown to be mediated via a guanine nucleotide-binding protein linked to adenylate cyclase activation and cellular cAMP generation. We capitalized on the technique of polymerase chain reaction, using degenerate oligonucleotide primers based on the known homology between cellular receptors linked to guanine nucleotide-binding proteins to obtain a partial-length clone from canine gastric parietal cell cDNA. This clone was used to obtain a full-length receptor gene from a canine genomic library. Histamine increased in a dose-dependent manner cellular cAMP content in L cells permanently transfected with this gene, and preincubation of the cells with the H2-selective antagonist cimetidine shifted the dose-response curve to the right. Cimetidine inhibited the binding of the radiolabeled H2 receptor-selective ligand [methyl-3H]tiotidine to the transfected cells in a dose-dependent fashion, but the H1-selective antagonist diphenhydramine did not. These data indicate that we have cloned a gene that encodes the H2 subclass of histamine receptors.

Amino Acid Sequence↗
PubMed1991

Determination of various molecular forms of cholecystokinin from canine mucosa by radioimmunoassay and bioassay.

Bioassays using amylase release from isolated pancreatic acini measure only cholecystokinin (CCK) forms with an intact carboxyl terminus ending with phenylalanine amide, but it cannot be excluded that peptides not structurally related to CCK are also responsible for CCK-like bioactivity. CCK exists in several molecular forms in intestinal mucosa which are released into the circulating blood. We studied the molecular forms of CCK in canine intestinal extracts after separation by high performance liquid chromatography by bioassay and compared them with those detected by radioimmunoassay. For the radioimmunoassay, an antibody was used which needs the carboxyl terminal phenylalanine amide for recognition. Three immunoreactive peaks were reproducibly seen in HPLC eluates which eluted in the regions of synthetic CCK-8, purified porcine CCK-33-39 (which co-elute using this gradient) and purified canine CCK-58. All these peaks were bioactive for amylase release from isolated pancreatic acini. No further bioactive peaks were detected in the HPLC eluates. When an antibody was used which recognizes the midregion of CCK-58, an additional peak was detected which eluted between CCK-33-39 and CCK-58. This form presumably represents an amino terminal fragment of CCK lacking the carboxyl terminus. It can be concluded that bioassays of CCK measure only CCK bioactivity in intestinal mucosal extracts, whereas radioimmunoassays may detect biologically inactive forms depending on the antibody recognition site.

Amylases↗
PubMed1990

[Plant scale optimization of the oxygen content of distilled water for injection].

Before dissolving oxygen sensible drugs, water for injection is boiled and flowed through with nitrogen gas in order to reduce the amount of dissolved oxygen. The aim was to optimize the amount of oxygen of water for injection in manufacturing vessel for production. A 2(2)-1 type fractional factorial design was selected to study the parameters which can influence the amount of oxygen in water for injection. The following parametes were studied: gas pressure of nitrogen (X1), flowing time of nitrogen gas (X2), boiling time of water (X3) and amount of water (X4). Performing the factorial studies the coefficients were calculated and controlled by mathematical-statistical methods. Knowing the coefficients the factorial area was left the optimum was found by Box--Wilson method.

Hot Temperature↗
PubMedDate not supplied

The mast cell-nerve axis in wound healing: a hypothesis.

Beyond their classic roles in allergic reactions and defence against parasites, mast cells can now be viewed as key players in regulating connective tissue homeostasis. There is good evidence that mast cells are in close morphological and functional contact with the peripheral nervous system. Although substantial differences exist between mast cells of different tissues and different species, they produce a wide range of agents, including cytokines, growth factors, and other regulatory molecules, and they respond to an equally wide range of substances, including neuropeptides. At our current level of understanding wound healing, inflammation plays a central role in this process, with macrophages being central protagonists at the cellular level. There is now increasing evidence that mast cells are also involved in wound healing, in health and disease. They produce and secrete histamine, heparin, and multifunctional cytokines and growth factors, which represent important agents in the wound-healing process. Reviewing the recent literature supporting this hypothesis, we also outline the clinical importance of this work to help close the gap between basic research and clinical application.

Animals↗
PubMedDate not supplied

[Hodgkin's disease in pregnancy--case report and literature review].

We report the case of a 24-year-old Gravida II/Para I who was diagnosed with Hodgkin's disease (stage 2A) at week 28 of pregnancy. Due to clinical progression, a dose-reduced adriamycin, bleomycin, vincristin, dacarbazine chemotherapy was started at week 32. After unsuccessful induction of labor at week 35, secondary cesarean section with a healthy newborn was performed. Chemotherapy was continued with full dose 10 days postpartum. We discuss clinical management as well as diagnostic and therapeutic options with respect to the available literature.

Adult↗