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Biomedical subjects

A Schweitzer

Publications and source records attributed to A Schweitzer.

At least 37 records · Page 2Linked to original sources
PubMed1993

From somatostatin to Sandostatin: pharmacodynamics and pharmacokinetics.

Somatostatin and its octapeptide analogue octreotide (Sandostatin) have a similar high affinity for specific receptors with IC50s in the sub-nanomolar range. Hence, the striking superiority of octreotide in vivo, which includes duration of action, specificity, and potency, must originate from its different distribution, metabolism, and excretion behaviour. In animals and humans, investigations on their pharmacodynamic/pharmacokinetic relationship show plasma levels of 0.2-0.5 ng/ml (approximately 0.3 nM) to be therapeutically relevant for both peptides. The much lower clearance and improved metabolic stability in the circulation and in target organs of octreotide compared with somatostatin, result in much longer lasting, therapeutically relevant plasma and tissue levels and therefore in a longer duration of action. Their apparently specific inhibitory action of growth hormone when compared with that on insulin is pharmacodynamically based and may be exaggerated by physiological mechanisms of carbohydrate regulation. In summary, there is a distinct relationship between pharmacokinetic profiles and pharmacodynamic behaviour of somatostatin and its analogue Sandostatin.

Animals↗
PubMed1993

Constitutive expression of GM-CSF mRNA by CML blast cells is correlated with endogenous megakaryocytic colony formation.

Purified blast cells from peripheral blood of 12 patients, with chronic myelogenous leukemia (CML) in chronic phase, were analyzed for the constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) transcript. Seven out 12 patients exhibited the specific 1.0 kb GM-CSF mRNA. Six from these patients presented an increased level of spontaneous megakaryocytic colony formation. Using an immunocytochemical procedure, the presence of GM-CSF was detected in a large proportion (52% to 72%) of the blast cells of the three patients studied, who were selected for the high expression of GM-CSF mRNA transcripts. Because the role of GM-CSF in the regulation of human megakaryocytopoiesis is well documented, we investigated the inhibiting effect of anti-GM-CSF antibodies on the spontaneous megakaryocytic colony growth of three of the patients expressing the GM-CSF transcript. Addition of anti-GM-CSF had a high neutralizing effect ranging from 60% to 70% inhibition of endogenous megakaryocytic colony growth. As the GM-CSF synthesis by leukemic cells is often induced by interleukin-1 (IL-1), we also investigated the effect of anti-IL-1 antibody on the spontaneous megakaryocytic colony growth of the same three patients. No significant inhibiting effect was observed, showing that the role of GM-CSF in the spontaneous colony formation is not mediated by IL-1. In addition, patients who constitutively expressed the GM-CSF transcript and showed endogenous megakaryocytic colony growth were those having a significantly higher platelet count than the group of patients without GM-CSF transcript and with no endogenous megakaryocytic colonies. In conclusion, these results suggest that GM-CSF, but not IL-1, participates in the production of spontaneous megakaryocytic colony formation observed in some CML patients. The true autocrine or paracrine nature of this stimulation remains to be established.

Antibodies↗
PubMed1992

From somatostatin to sandostatin: pharmacodynamics and pharmacokinetics.

Somatostatin (SRIF) and its octapeptide analogue, octreotide (Sandostatin), have a similar high affinity for specific receptors with 50% inhibitory concentrations (IC50s) in the subnanomolar range. Hence, the striking superiority of octreotide in vivo, which includes duration of action, specificity, and potency, must originate from its different distribution, metabolism, and excretion behavior. In animals and humans, investigations of their pharmacodynamic/pharmacokinetic relationship show plasma levels of 0.2 to 0.5 ng/mL (approximately 0.3 nmol/L) to be therapeutically relevant for both peptides. The much lower clearance rates and improved metabolic stability in the circulation and in target organs of octreotide, compared with SRIF, result in much longer-lasting, therapeutically relevant plasma and tissue levels and therefore in a longer duration of action. Their apparently specific inhibitory action on growth hormone when compared with that on insulin is pharmacodynamically based, and may be exaggerated by physiological mechanisms of carbohydrate regulation. In summary, there is a distinct relationship between the pharmacokinetic profiles and pharmacodynamic behavior of SRIF and its analogue. Sandostatin.

Animals↗
PubMed1992

Lack of transcription and expression of the alpha IIb integrin in human early haematopoietic stem cells.

The glycoprotein IIb, the alpha subunit of the platelet integrin GPIIb-IIIa, is a marker of megakaryocyte, but the stage of its expression during haematopoiesis remains controversial. We have examined the expression of GPIIb protein and alpha IIb mRNA in early human normal stem cells. We have purified stem cell expressing the CD34 surface marker (CD34+ fraction) and selected among this population quiescent cells (CD34+ MF(R) fraction). We have failed to detect GPIIb protein and alpha IIb mRNA in the pluripotential (CD34+ MF(R)) cells, even with polymerase chain amplification. Therefore alpha IIb transcription and GPIIb protein expression seemed to follow the commitment of the pluripotential cell in the megakaryocyte lineage.

Antigens, CD↗
PubMed1991

Gene regulation in megakaryocyte.

Analysis of the mechanisms which control the differentiation of the megakaryocytic lineage is a major commitment to understand the production of circulating blood platelets. One way to approach this question is to examine the promoter domain of a marker gene which is expressed exclusively in the megakaryocytic lineage and at an early stage of the differentiation process. For this purpose the gene coding for the platelet specific glycoprotein IIb was isolated and its promoter was analysed. This promoter contains positive and negative DNA responsive elements that are responsible for the cell specific expression of the gene. With this promoter region it is now possible to direct the expression of heterologous genes in vivo using the transgenic approach.

Biomarkers↗
PubMed1989

Cryopreservation of human megakaryocytic progenitor cells (CFU-MK): influence of culture conditions.

The survival of human megakaryocytic progenitor cells (CFU-MK) after freezing using a two-step cooling technique was studied in a methylcellulose culture system, using different stimulating activities and their combinations. The best growth stimulating activity for CFU-MK was found in plasma from aplastic patients (PAP). PAP was roughly three times more potent than optimal doses of human recombinant interleukin 3 (IL3), itself two times more active than our batch of phytohemagglutinin stimulated leukocyte conditioned medium (PHA-LCM). The addition of erythropoietin (EPO) to PHA-LCM doubled the number of megakaryocytic colonies, but had no effect on the number of CFU-MK stimulated by IL3. Of the two batches of PAP used, one was optimal and the other was significantly improved by the addition of PHA-LCM. The percentage recovery of CFU-MK after freezing reached 70 to 80% in cultures stimulated by PHA-LCM and IL3 +/- EPO, and 58% in PAP-supplemented cultures. However, this last value was not significantly different from the previous ones. The percentage recovery of CFU-MK in each condition tested was similar to that obtained with the other myeloid progenitors, CFU-GM and BFU-E. However, the high CFU-MK stimulating activity of PAP is hindered by its high variability and shortage in supply. Thus it seems more appropriate to recommend the use of recombinant human IL3 because of its easily standardizable and consistent CFU-MK stimulating activity.

Cells, Cultured↗
PubMed1989

[Advantages of single-dose treatment of vaginal Candida albicans infection].

One-hundred forty women (60 pregnant and 80 non-pregnant women) with a history of Candida albicans infection were examined one month before treatment and were reexamined one month after treatment. Administration of a single agent consisting of 2,300 mg tablets of GynoTragoven (isoconazole nitrate, Schering, AG) resulted in immediate clinical improvement. One month after treatment, the success rate was 85-100 p. cent for non-pregnant women, and 83-100 p. cent for pregnant women. No side-effects were observed following therapy. According to studies published, a high percentage of infections develop during pregnancy, especially during the second (35 p. cent) and third (31.5 p. cent) trimesters. Because of the high rate of infections during pregnancy, preventive therapy should be considered during the final weeks of pregnancy, to prevent intrauterine infection during parturition.

Adult↗
PubMed1988

Immunophenotype of blast cells in chronic myeloid leukemia.

The immunophenotype of peripheral blood blast cells from 14 patients in the chronic phase of chronic myeloid leukemia (CML) was studied using a panel of monoclonal antibodies (McAb) directed against megakaryocytic, granulomonocytic, erythroid and lymphoid antigenic determinants. The blast cells were enriched by a simple bovine serum albumin (BSA) density-cut separation and cooled in liquid nitrogen. The study was done using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique on the thawed blast cells. A consistent pattern of reactivity with McAb was found in all patients, showing that blast cells were heterogeneous. A minor component of the blast cells react with platelet antibodies, most of them being labelled with anti-GPIIb-IIIa McAb. Anti-GPIb and Von Willebrand factor McAb detected 4 times fewer megakaryocytic blast cells, suggesting that these cells are located very early in the differentiation scheme. Two major blast cell compartments were labelled with early myelomonocytic (anti-CD13: MY7) and early erythroid (anti-CD36: FA6-152) McAb. The CD34 (My10) and DR antigens which are expressed by immature blast cells and myeloid progenitors of human bone marrow (BM) were present on more than 50% of the CML blast cells. Thus, the blast cells of chronic phase CML patients, showed the same cellular diversity as the increased progenitor cell compartment observed in this disease, and their differentiation stages seemed to be very closely related.

Antibodies, Monoclonal↗
PubMed1987

A simple method for the quantitation of 14C-whole-body autoradiograms.

A simple method for the quantitation of 14C-whole-body autoradiograms by comparative densitometry is described. If processed under the same conditions as the samples of tissues to be investigated, a radioactive blood scale can be used as standard, with the exception of samples from bones, eyes and fat. This method is demonstrated to be simple, accurate, reproducible and precise.

Animals↗
PubMed1987

Megakaryocytic development in liquid cultures of cryopreserved leukocyte stem cell concentrates from chronic myelogenous leukemia patients.

The proliferation and differentiation of human megakaryocytes in liquid culture has been obtained using cryopreserved light-density blood cell concentrates from chronic myelogenous leukemia (CML) patients. A large number of megakaryocytes, representing 20%-60% of total cells cultured, developed after 12-14 days in liquid cultures supplemented with human plasma, while fetal calf serum supported the development of cells of the megakaryocytic lineage poorly. Ploidy studies showed the presence of 8N and 16N cells in human plasma-supplemented cultures while very few cells with DNA content greater than 4N were found in those supplemented with fetal calf serum. Using the FACS IV cytofluorometer, 1-2 X 10(6) megakaryocytes/h were sorted after immunolabeling of the human plasma-cultured cells with a monoclonal antibody reacting against the platelet glycoprotein complex IIb-IIIa. Thus, cryopreserved CML blood stem cell concentrates seem to offer a reproducible source of human megakaryocytes that retain their capacity to proliferate and differentiate in liquid cultures. These megakaryocytes can be used for the study of platelet glycoprotein biosynthesis as well as the regulation of megakaryocytopoiesis.

Blood Specimen Collection↗
PubMed1983

[Respect for life].

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Conflict, Psychological↗
PubMed1983

Distribution of the acetyl compared with the salicyl moiety of acetylsalicylic acid. Acetylation of macromolecules in organs wherein side-effects are manifest.

The distribution in rats of the acetyl group of aspirin has been compared with that of the salicyl moiety with the objective of establishing if: (1) there are differences in their biodisposition which might be important in the development of side- or therapeutic effects of aspirin, and (2) the range of organs and biomolecules therein which are acetylated by aspirin. Using whole-body autoradiography and liquid scintillation counting techniques it was found that the acetyl group of 3H- or 14C-acetyl-labelled aspirin became bound to a wide variety of proteins, glycoproteins and lipids of the glandular and non-glandular region of the stomach, kidney, liver and to a lesser extent bone marrow, i.e. organs in which side-effects are frequently encountered. It is suggested that: (1) the acetylation of biomolecules may be a major factor in the development of side-effects in these organs, and (2) in addition to acetylation of prostaglandin synthetase, the acetylation of enzymes and other biomolecules may have a much wider bearing on the biochemical changes underlying the development of these side-effects. Acetylation of the protein/macromolecular components was especially pronounced in inflamed (c.f. control) hindpaws of carrageenan-injected rats. This could be a result of acetylation of the drug-carrier protein, albumin, and other proteins carried into inflamed tissues and this acetylation could have marked consequences for the functions of these proteins.

Acetates↗
PubMed1983

Cryopreservation of human bone marrow cells by a modification of the two-step cooling technique.

The first attempt to freeze human bone marrow cells with a two-step cooling method is reported. A simple and reliable way of obtaining stable first-step subzero freezing baths is described. One-milliliter samples each containing 20 X 10(6) bone marrow cells and 10% Me2SO were frozen in polypropylene cryotubes. Using these experimental conditions, the optimal freezing temperature was found to be in the range of -36 to 37.5 degrees C for BM progenitor cell (GM-CFC, CFUE, and BFUE) survival. Such temperatures were easily obtained in stable sludges of anisole or K2CO3 eutectic solution in water. The optimal holding time was 20 min before plunging tubes into liquid nitrogen. Similar or improved progenitor cell recoveries were observed compared with the conventional cooling technique. Adaptation of this two-step technique for the freezing of large volumes of BM cells for autografting is under investigation.

Anisoles↗
PubMed1982

Purification and cryopreservation of granulomonocytic colony forming cells (GM-CFC) from the blood of patients with chronic granulocytic leukemia (CGL) for autologous transplantation.

A simple density-cut separation technique is described for obtaining GM-CFC concentrates from the peripheral blood of patients with chronic granulocytic leukemia (CGL) for autografting at the acute blastic phase of the disease. Large numbers of granulomonocytic colony forming cells (GM-CFC) were recovered from a single procedure (68.4 X 10(6) GM-CFC). The cryopreservation of these concentrates in liquid nitrogen allowed the recovery of 46.6 +/- 33.8% viable GM-CFC. An improved yield of GM-CFC was obtained by avoiding washing the cells (65.2 +/- 41.1%). The separation technique resulted in a concentrated suspension of progenitors in a small volume of medium (mean = 15 ml) allowing a great reduction in the amount of the cryoprotective agent injected into the patient at autografting. Preliminary data obtained in 4 patients transfused in blastic crisis after chemotherapy, with or without TBI, indicated the capacity of stored concentrates to repopulate these patients.

Adult↗
PubMed1982

Similarity of CSF of media conditioned by different human tissues.

Conditioned media prepared using human placenta, spleen, bone marrow and peripheral blood leucocytes revealed a common pattern of two distinct species of colony-stimulating factors (CSF) separable by gel filtration. The peak of greatest activity, active against both human and mouse marrow, had an apparent molecular weight (MW) of 24,000-28,000 Daltons. A peak of low activity detected only against mouse marrow had an apparent MW of approximately 150,000 Daltons. The type of progenitor cells stimulated by the crude medium, by the low MW CSF species, and by the high MW species were similar for the four conditioned media despite their different origins. No difference was found in either the MW of the human active CSF present or the type of progenitor cells stimulated by media conditioned with cells of leukemic origin.

Animals↗
PubMed1981

Percutaneous absorption of griseofulvin and proquazone in the rat and in isolated human skin.

Ointments containing griseofulvin and proquazone, respectively, were made up of monoglycerides of medium chain length and an aprotic solvent, glycerinformal. The ointments were applied topically on the back of bile cannulated rats. The total amount absorbed percutaneously and the permeability constants of both drugs were considerably higher for the ointments than for simple solutions of the drugs without monoglycerides. Distribution of the labeled drugs in rat skin has been demonstrated by microautoradiography. Concentrations of the drugs in the different layers of human skin together with the medium flow rates have been determined 16 h after administration of the ointments onto isolated human skin. Monoglycerides of medium chain length enhance significantly the permeability of the stratum corneum for solutes.

Animals↗