Guidelines for the collection, processing and storage of human bone marrow and peripheral stem cells for transplantation

SUMMARY. There are no current U.K. or international guidelines or regulations covering the production, processing and storage of haemopoietic cells such as to allow their engraftment following myeloablative therapy. This paper seeks to provide such guidelines. It enumerates how quality control and assurance can be applied to this area of transfusion medicine; procedural steps relating to bone marrow harvest on peripheral blood stem cell collection are outlined and recommended doses of nucleated cells suggested for both procedures. General specifications for identification, storage and transportation of bone marrow and peripheral blood stem cells are included and specific laboratory procedures related to the provision of haemopoietic cells for engraftment are outlined. Umbilical cord blood transplants and long-term bone marrow culture are alluded to but these are still in a research phase.     

Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes

Prolactin (PRL) has been shown to contribute to the development of lymphoid tissues and maintenance of physiological immune function. Here we show that the role of the hormone extends to the control of the effector phase of the immune response. In addition to triggering resting lymphocytes to cell division, the hormone can also control the magnitude of their response to polyclonal stimuli. Concentrations of PRL in the physiological range increased the [3H]thymidine, [3H]uridine, and [3H]leucine incorporation of unstimulated NK cells cultured in serum-free conditions. The same concentrations of the hormone increased the response of NK, T, and B cells to the mitogenic stimuli interleukin 2 (IL2), phytohemagglutinin (PHA), and staphylococcus aureus cowan, respectively, the effect being maximally evident in the presence of suboptimal concentrations of the mitogens. By contrast concentrations of PRL five- to tenfold the physiological levels inhibited the mitogenic response to IL2 and PHA. These data indicate a double-faceted regulatory role of this hormone in vivo.     

Glutamate receptors in striatum and substantia nigra: Effects of medial forebrain bundle lesions

We examined NMDA-sensitive [³H]glutamate, [³H]AMPA, [³H]kainate and metabotropic-sensitive [³H]glutamate binding sites in neostriatum and substantia nigra pars reticulata (SNr) in rats after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. One week after the lesion, NMDA, AMPA, kainate and metabotropic receptors were decreased in the ipsilateral neostriatum, whereas at three months NMDA receptors were increased while AMPA, kainate and metabotropic receptors were not changed. In the SNr at one week, only AMPA and metabotropic receptors were significantly decreased whereas three months after the lesion NMDA, AMPA and kainate binding sites were decreased. The early decrease of excitatory amino acid receptors in the striatum is likely to reflect degeneration of dopaminergic fibers, suggesting that specific subpopulations of excitatory amino acid binding sites are located on dopaminergic terminals.     

Randomised prospective study on renal effects of two different contrast media in humans: protective role of a calcium channel blocker

Contrast media affect renal hemodynamics. Hyperosmolality is regarded as the major factor responsible for renal hemodynamic changes. In this study, the role of osmolality was evaluated in 30 hospitalized patients without risk factors during intravenous pyelography. Contrast media with low and high osmolality were used. In addition, nifedipine was administered before infusion of high-osmolality contrast to evaluate the role of calcium ions in radiocontrast-induced changes of renal hemodynamics. Hyperosmolar contrast reduced renal plasma flow and glomerular filtration rate. Calcium channel blocker prevented changes of renal hemodynamics. Hyperosmolality appears the most likely factor affecting renal hemodynamics during hyperosmolar radiocontrast infusion. Calcium channel blocker may prevent renal changes due to hyperosmolar medium.     

Residual haemopoietic damage in the mouse after fractionated gamma-irradiation, down to 0.1 Gy per fraction

Residual damage in haemopoietic progenitor cell populations, spleen and granulocyte-macrophage colony-forming cells (CFU-S and GM-CFC) was detected in mice after 15 daily fractions where the dose per fraction was as low as 0.1 Gy. The injury was dose-dependent and after higher total fractionated doses of 7.5-10 Gy the CFU-S population recovered to about 50% of control between 2 and 12 months after irradiation. Residual damage was also detected in the stroma, in the form of reduced numbers of fibroblastoid colony-forming cells and of CFU-S in ossicles under the kidney capsule. The response to a second course of 15 fractions, given 3 weeks after the end of the first course, was similar and additive to the response to the first course in the short term. However, in the long term, recovery levels were similar after either one or two courses.     

Profile of in Vitro Binding Affinities of Neuroleptics at Different Rat Brain Receptors: Cluster Analysis Comparison with Pharmacological and Clinical Profiles

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.