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.

Dynamic interaction between CD4+ T cells and parasitic helminths: mathematical models of heterogeneity in outcome.

Potential mechanisms of immunoregulation have been investigated for the capacity to generate heterogeneity in the outcome of infection with helminth parasites. We have developed a mathematical model of the interaction between T cell and parasite populations, based on the assumption that activation of a Th1 CD4+ T cell response is required for host resistance. Antigen dose-dependent inhibition of Th1 cell proliferation generates heterogeneity in the outcome of host response to infection, with relatively low levels of exposure inducing resistance, and high levels of exposure associated with host susceptibility.

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).

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.

Alternative patterns of MHC-restricted antibody responsiveness following intraperitoneal immunization of inbred mice with different preparations of an 86 kilodalton antigen of Schistosoma mansoni.

The investigation of MHC restricted antibody responses to an 86 kDa antigen (p86) during chronic Schistosoma mansoni infection has been extended to immunization with this antigen. In the absence of adjuvant, a similar pattern of responsiveness by mice expressing H-2k and H-2d but not H-2b was observed following immunization with unpurified adult worm homogenate. Adjuvant selectively abrogated the capacity of H-2d mice to respond and this was also the case when purified p86 with adjuvant was injected.

The regulation of immunological responses to parasitic infections and the development of tolerance.

It is well established that specific unresponsiveness to immunization can be induced by prolonged exposure to antigenic proteins. More generally, many parasitic infections, such as the helminth worms and the Leishmania parasites, appear to be able to persist in some of their human hosts over long periods of time, via what appears to be an ability to induce defective or inappropriate T-cell responses (= tolerance). Recent research has suggested that cytokines, produced by specific subsets of CD4+ T-cells (characterized by cytokine secretory profiles and growth properties), have an important, and often complex, role in promoting or inhibiting host protective immunity to parasitic infections.

MHC-restriction of antibody responses to an 86 kilodalton antigen of Schistosoma mansoni.

The previously observed MHC-restriction of the antibody response to an 86kDa S. mansoni antigen has been investigated in more detail. The I-A locus of the H-2 complex has been implicated as conferring responder or non-responder status on mice expressing the k and b alleles respectively.

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.

Voyager planetary radio astronomy at neptune.

Detection of very intense short radio bursts from Neptune was possible as early as 30 days before closest approach and at least 22 days after closest approach. The bursts lay at frequencies in the range 100 to 1300 kilohertz, were narrowband and strongly polarized, and presumably originated in southern polar regions ofthe planet. Episodes of smooth emissions in the frequency range from 20 to 865 kilohertz were detected during an interval of at least 10 days around closest approach.

Disposition of sandostatin, a new synthetic somatostatin analogue, in rats.

The distribution, excretion, and metabolism of Sandostatin, a long-acting octapeptide analogue of somatostatin, have been studied in the rat after iv administration. Similar plasma levels and excretion values were observed by using radioimmunoassay and HPLC-liquid scintillation techniques. For the latter technique Sandostatin was radiolabeled with either 14C or 3H.

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).

[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.

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.

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.

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.

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.

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.

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).

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.

Autoradiographic and biochemical observations on the distribution of non-steroid anti-inflammatory drugs.

A comparison has been made of the distribution of some new radioactively-labelled non-steroid anti-inflammatory (NSAI) drugs or pro-drugs with their respective progenitors and/or standard acidic NSAI drugs (i.e. aspirin, indomethacin and phenylbutazone), using whole body autoradiography and scintillation counting.

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.