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Biomedical subjects

G Brehm

Publications and source records attributed to G Brehm.

At least 19 recordsLinked to original sources
PubMed1992

Inhibitory and excitatory muscarinic receptors modulating the release of acetylcholine from the postganglionic parasympathetic neuron of the chicken heart.

The effects of muscarinic receptor antagonists on ACh release were studied in the absence or presence of cholinesterase (ChE) inhibition using the isolated perfused chicken heart. Presynaptic inhibitory muscarinic autoreceptor were characterized by determining the potency of various antagonists to enhance [3H]-ACh release evoked by field stimulation (3 Hz, 1 min). The order of potencies was: (+/-)-telenzepine > atropine > 4-DAMP > silahexocyclium > pirenzepine > hexahydro-siladifenid-ol > AF-DX 116. The comparison with known pA2 values for M1-, M2- and M3-receptors revealed that the presynaptic autoreceptor meets the criteria of an M1-receptor. Basal, not electrically evoked overflow of unlabelled ACh into the perfusate was caused by 'leakage' release (non-exocytotic), as it was independent of extracellular Ca2+. Muscarinic receptor antagonists failed to enhance basel overflow. In contrast, when ChE activity was inhibited by 10(-6) M tacrine or pretreatment with 10(-4) M DFP, the ACh overflow was partially Ca(2+)-dependent and was reduced by tetrodotoxine. Moreover, block of the inhibitory muscarinic autoreceptors by (+/-)-telenzepine or pirenzepine caused a several-fold enhancement of the ACh release. The potencies of these antagonists were identical to those found for the electrically evoked [3H]-ACh release. The rate of ACh release enhanced by ChE inhibition plus telenzepine corresponds to about 12% of the total ACh pool per min, which is about the maximum amount of ACh that is available for any kind of stimuli. The release was dependent on the presence of exogenous choline. Hence elevation of ACh release led to a correspondingly enhanced ACh synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

[Pregnancy with an extremely rare P blood group with anti-PP1Pk].

The authors report on a successful pregnancy in a young Turkish patient with p and anti-PP1Pk-antibodies. Anti-PP1Pk is considered to cause haemolytic diseases in the newborn and habitual abortions. The patient was treated via plasma exchange and substitution with intravenous immunoglobulin. At 31 weeks of gestation the patient underwent Caesarean section due to growth retardation and pathological signs in the fetal CTG. The child has developed well up to two years after the delivery. Based on our data and a review of the literature, the effectiveness of therapy by plasmapheresis and/or immunoglobulin is discussed.

Abortion, Habitual↗
PubMed1990

Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.

Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras.

Adult↗
PubMed1990

[Plasmapheresis and/or intermediate high dosage immunoglobulin therapy--effective measures in threatened premature labor and intrauterine hemolysis in anti-PP1Pk (-Tja)?].

Anti-PP1Pk developed by women has been associated with abortion early in pregnancy and hemolytic disease of the newborn. The case of a 19-year-old woman who had had 2 spontaneous abortions in the first trimester is presented. When treated with plasma exchange and substituted with 5% albumin and intravenous immunoglobulin begun at six weeks' gestation and continued until the 30th week, she delivered a viable female infant without anemia. According to our data and review of literature, the effectiveness of therapy by plasmapheresis and/or immunoglobulin is discussed.

Combined Modality Therapy↗
PubMed1989

Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation.

Severe microangiopathy has been reported as a rare complication of cyclosporine A (CsA) prophylaxis in allogeneic bone marrow transplantation (BMT). We found morphological and biochemical changes indicative of generalized endothelial damage in 49 of 66 allogeneic marrow graft recipients receiving cyclosporine, but none in 11 patients treated with methotrexate for prophylaxis of graft-v-host disease (GVHD). Changes occurred after engraftment of bone marrow and consisted of intravascular hemolysis with red cell fragmentation and de novo thrombocytopenia. They were preceded by a decrease in activated partial thromboplastin time and fibrinogen indicating activation of coagulation. Endothelial damage as the central lesion of microangiopathy was confirmed by a simultaneous increase of factor VIII related antigen. Severe microangiopathy was observed in ten patients and was fatal in seven. Risk factor analysis revealed a highly significant association of microangiopathy with severity of acute GVHD (aGVHD) (P less than .001) and use of CsA prophylaxis (P less than .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of a aGVHD, which is not inhibited by CsA prophylaxis.

Adult↗
PubMed1989

Myeloablative conditioning for marrow transplantation in myelodysplastic syndromes and paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplastic syndromes (MDS) are disorders of pluripotent stem cells resulting in haematopoietic insufficiency which can be cured by marrow transplantation. The extent of myeloablative conditioning necessary for elimination of the non-malignant and premalignant clones is not known. We report our results of marrow transplantation with and without myeloablative conditioning in two patients with PNH and seven patients with MDS. Conditioning was not used in a patient with PNH and a monozygotic twin as donor. In this patient the disease remained unchanged. Myeloablative treatment with busulphan (BUS) in addition to immunosuppression with cyclophosphamide (CY) was used for conditioning in a patient with PNH and a 2-year-old boy with chronic myelomonocytic leukaemia (CMML). Fractionated total body irradiation (FTBI) and CY was used in six patients with refractory anaemia with excess of blasts (RAEB) and RAEB in leukaemic transformation (RAEB-T). Haematopoiesis was fully restored in all patients conditioned with myeloablative treatment except for a patient in leukaemic transformation with myelofibrosis and a HLA-DR-incompatible donor. Chimerism was complete in all patients except for the 2-year-old boy conditioned with BUS and CY. Our results and those reviewed in the literature indicate that myeloablative conditioning with either BUS or FTBI is advantageous for marrow transplantation in PNH and MDS.

Adult↗
PubMed1986

Unsaturated platelet-activating factor: influence on aggregation, serotonin release and thromboxane synthesis of human thrombocytes.

Unsaturated platelet-activating factor (paf-acether) aggregated thrombocytes of healthy male volunteers like saturated paf-acether. Unsaturated paf-acether released serotonin in the presence of imipramine. Within one minute the release increased depending on the concentrations of unsaturated paf-acether up to 45% of the serotonin. Human thrombocytes synthesized only a small amount of thromboxane B2 (TXB2) after aggregation induced by unsaturated paf-acether. Unsaturated paf-acether prevented the binding of radiolabelled saturated paf-acether to intact washed thrombocytes in the same extent as saturated paf-acether.

Blood Platelets↗
PubMed1986

Activation of C57BL/6 spleen cells by the mitogenic principle derived from mycoplasma arthritidis.

A T cell mitogen derived from the supernatant of cultured mycoplasma arthritidis (MAS) has been recently discovered. Here we show that among a variety of strains, mycoplasma arthritidis was the only one elaborating the mitogen. Pools of MAS obtained at different occasions were quite variable in their biologic activity. Thus, in an attempt to obtain a more uniform preparation, MAS was semi-purified by Sephadex G-150 columns. Biologic activity eluted in a single peak in the molecular weight range of 13,000 daltons. "Nonresponsive" C57BL/6 spleen cells could be reconstituted to respond to MAS by the addition of 2-mercaptoethanol (2-ME). This reconstitutive effect was seen even when 2-ME was added 12 h after MAS. In further experiments, the lymphocyte culture technique was modified. Adherent spleen cells (AC) were grown and repeatedly washed before the simultaneous addition of nylon-purified T cells and MAS. Also in this experimental set-up, 2-ME could be added after the T cells. Finally, AC were cultured in the presence of MAS and after 4 h washed repeatedly. Subsequently, T cells and 2-ME were added. Also under these conditions, C57BL/6 spleen cells were capable of responding to MAS. These data suggest that 2-ME does not act on AC but on T cells. However, nylon-purified T cells in the complete absence of AC did not respond to MAS even in the presence of 2-ME. Thus, in order for the response to MAS to occur in "nonresponsive" C57BL/6 spleen cells, both AC and 2-ME are required. So far, our experiments have failed to conclusively unravel the mode of action of 2-ME. Yet, experiments using monoclonal antibodies against I-E have suggested that the response of "non-reacting" C57BL/6 spleen cells to MAS in the presence of 2-ME is not restricted by the molecule on the cell surface coded for by the I-E region.

Animals↗
PubMed1986

Analysis of the interferons induced in mice in vivo and in macrophages in vitro by Newcastle disease virus and by polyinosinic-polycytidylic acid.

C57BL/6 mice or pure cultures of their macrophages were inoculated with Newcastle disease virus (NDV) or poly(I).poly(C) to induce interferons (IFNs) that were separated on CH-Sepharose 4B columns. The elution profiles of different activity peaks were compared. All preparations induced in vivo showed the same pattern but the relative proportions of the IFN activities varied. In vitro poly(I).poly(C)-induced IFN showed two peaks after separation by the column, and three peaks were found when NDV-induced IFNs were separated. When IFN induced by NDV in vitro was used to determine the molecular weight, activities were observed in three molecular weight ranges. The smallest one with 18,000 daltons was neutralized by anti-IFN-alpha and represented about 7% of the total activity. The activities of molecular weights 24,000 daltons and 29,000-31,000 daltons were neutralized by anti-IFN-beta. Poly(I).poly(C)-induced IFN in vitro showed two molecular weight ranges, 26,000 daltons and 40,000 daltons, and both were neutralized by anti-IFN-beta. IFN induced in serum by NDV at 3 h had molecular weights of 18,000 daltons neutralized by anti-IFN-alpha and 26,000-30,000 daltons neutralized by anti-IFN-beta. Both IFN subtypes were represented at equal quantities. Serum IFN found in the serum after 8 h had three molecular weight ranges: 18,500-19,500 daltons neutralized by anti-IFN-alpha containing 80% of the total IFN amount, 26,000-27,000 daltons, and 38,000 daltons both neutralized by anti-IFN-beta and containing 20% of the IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Critical evaluation of platelet aggregation in whole human blood.

Platelet aggregation studies generally are performed in platelet-rich plasma (PRP) by the turbidometric method. The authors compared this technic with the recently introduced impedance aggregometry in PRP and whole blood (WB). In healthy controls there was a good correlation between the two technics when aggregation was induced by ADP or collagen. As compared with PRP, platelets in WB were more sensitive to the aggregating effect of thrombin, ristocetin, and arachidonic acid. Platelet sensitivity to prostacyclin was increased in WB. The anti-platelet effect of a single oral dose of aspirin could be detected for a longer period in WB than in PRP. Platelet aggregation tests in WB from patients with platelet dysfunctions showed the same response pattern to different aggregating agents as in PRP. In contrast to turbidometry, the impedance method in PRP and WB enabled registration of platelet aggregation in a dose-dependent fashion in a sample from a patient with severe hyperlipoproteinemia. It is concluded that platelet aggregation can be studied conveniently with the impedance method in the more physiologic medium of WB. Providing the same information as the well-established turbidometry, the time-sparing impedance method needs less citrated blood. Moreover, our results show an increased sensitivity of the WB system to some aggregating and anti-platelet agents.

Adenosine Diphosphate↗
PubMed1986

Production of interferon-beta by murine T-cell lines induced by 10-carboxymethyl-9-acridanone.

Besides the established T-cell property of producing gamma interferon (IFN-gamma), murine T cells additionally possess the ability to produce IFN-alpha and IFN-beta when appropriate inducers such as 10-carboxymethyl-9-acridanone (CMA) or Newcastle disease virus (NDV) are used. Interleukin 2 (IL-2)-dependent murine T-cell lines, but not purified resting splenic T cells, responded to CMA and NDV with production of IFN-alpha, beta. The IFN production by these T cells was not restricted to a special subset, since T cells expressing the Lyt 1+2- and the Lyt 1-2+ phenotype responded to these inducers with IFN production. After prolonged passaging of the T-cell lines in IL-2-containing medium, the ability to respond to CMA with production of antiviral activity was sustained longer than the ability for concanavalin A-induced IFN-gamma production. Whereas the NDV-induced T-cell supernates contained both IFN-alpha and IFN-beta, the induction with CMA resulted exclusively in the synthesis of IFN-beta by the T-cell lines.

Acridines↗
PubMed1986

Biochemical characterization of the T-cell mitogen derived from Mycoplasma arthritidis.

A biochemical procedure is described to purify the T-cell mitogen in the supernatant of cultured Mycoplasma arthritidis organisms. The mitogenic material was bound on an affigel blue column. The eluate of this column was then acylated at 0 degrees C for 1.5 h and subsequently chromatography on a Sepharose Cl 6B and a Superose 12HR column were performed. SDS-PAGE showed a major band at MW 26,000 and some minor bands at 50,000. With this material biological tests were performed, including induction of lymphoproliferation and interferon induction in murine spleen cell cultures. Purified Mycoplasma arthritidis supernatant (MAS) vigorously stimulated spleen cell cultures of A/J, CBA, C3H/He, and DBA/2 mice, whereas a low-grade but definitive response was observed in C57BL/6 spleen cells. Cultures of Balb/c nu/nu mice, in contrast to those of their euthymic littermates, were non-reactive. When induction of interferon was tested, a marked response to purified MAS was observed in CBA and C3H/HeJ spleen cell cultures, whereas C57BL/6 spleen cells were non-reactive.

Animals↗
PubMed1986

Characterization of interferon induced in murine macrophage cultures by 10-carboxymethyl-9-acridanone.

Pure murine macrophages were induced by 10-carboxymethyl-9-acridanone to produce interferon. The supernatants were partially purified by a three-column procedure including a DEAE-Biogel A, a CM-Biogel A, and a CH-Sepharose 4B column. The specific activity achieved was about 10(5) IU/mg. Two different activities were detected after the third step and designated activity 1 and activity 2. The determination of the molecular weight was in the range of 24,000-27,000 dalton for activity 1 and in the range of 32,000-34,000 dalton for activity 2. Both were neutralized by antibodies against mouse interferon-beta, indicating that two different moieties were produced both representing interferon-beta. When macrophages were induced in the presence of tunicamycin, only one activity of a molecular weight of about 19,000 dalton was found which again was neutralized by anti-interferon-beta.

Acridines↗
PubMed1983

[Bone marrow transplantation in adults in acute leukemia, aplastic anemia and paroxysmal nocturnal hemoglobinuria. Results of the Medical Clinic IIi of LMU (Ludwig-Maximilians University) Munich].

Eleven adults have been transplanted for various reasons between July 1979 and July 1982: 2 with aplastic anemia (AA), 1 with paroxysmal nocturnal hemoglobinuria (PNH), 8 with acute leukemia (AL). Four patients suffered from acute lymphocytic leukemia (ALL) and four from acute non-lymphocytic leukemia (ANLL). Two of them were transplanted in relapse, 1 in a partial remission, and 5 in complete remission. All patients were in their late stage of disease. The PNH-patient had an identical twin, 8 patients had an HLA- and MLC compatible sib, 1 an unrelated donor, and 1 was transplanted from his father. Four patients are alive, 2 more than 3 years: 1 with AA and 1 with ALL who was transplanted in relapse. Six patients died of infectious complications (4 of interstitial pneumonia, 1 of a candida sepsis, 1 of acute toxoplasmosis). Patients living more than 3 weeks had a take. Acute graft-versus-host (GvH) disease did not present a major problem. All patients received methotrexate for GvH-prophylaxis, in three instances the marrow was additionally pre-incubated with anti-T-cell globulin.

Acute Disease↗
PubMed1981

[Bone marrow transplantation for aplastic anaemia (author's transl)].

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

Adolescent↗
PubMed1980

Plasma-separation in myasthenia gravis: a new method of rapid plasma exchange.

A patient with myasthenic crisis was successfully treated with a new method of plasma exchange using a hollow-fiber filter connected to a standard dialysis pump. The filter allows PE to be performed at more clinical centers and probably at lower costs than current methods applying blood cell separators.

Acetylcholine↗
PubMed1979

[The significance of determining antibodies to acetylcholine receptor in myasthenia gravis (author's transl)].

The sera of 65 patients with myasthenia gravis (MG) were analysed for antibodies against the nicotinic acetylcholine receptor (ACh-R) using an immunoprecipitation assay (125I-alpha-bungarotoxin bound to human ACh-R as antigen). In 91% of MG sera elevated antibody titers were found ranging up to 500 times reference values. A control group of 77 patients showing various autoimmunological phenomena had ACh-R antibody concentrations within the reference range. The demonstration of antibodies against ACh-R provides a sensitive and highly specific tool for the diagnosis of MG. In addition, the test is helpful in following patients under treatment with immunosuppressive drugs or plasmapheresis. Antibodies against striated, smooth, or heart muscle (indirect immunofluorescence test) are much less sensitive and nonspecific for the diagnosis of MG.

Acetylcholine↗