Effect of butaclamol enantiomers on hypothalamic tyrosine hydroxylase in the rat brain

The authors demonstrate stereospecificity of the action of butaclamol enantiomers on substrate inhibition of hypothalamic tyrosine hydroxylase (TH) and regulation of the tyrosine hydroxylase response by the presynaptic membrane (presynaptic receptors) of rat hypothalamus synaptosomes under membrane activation with dopamine. The effect of (+)-butaclamol on the substrate inhibition of TH was noticeable at a concentration of 10(-8)M, reaching a maximum at 10(-5)M. (-)-Butaclamol administered at the same concentrations did not influence the substrate inhibition of the enzyme. (+)-Butaclamol added to the incubation medium containing hypothalamic synaptosomes concurrently with dopamine (10(-5)M) completely blocked the regulatory action of the latter on TH, with this action mediated via presynaptic receptors. (-)-Butaclamol (10(-5)M) antagonized the action of dopamine under the same conditions. The data obtained indicate high stereo-specificity of butaclamol enantiomers as regards their effect on presynaptic regulation of TH, suggesting that elimination of the substrate inhibition of hypothalamic TH is a stereoselective effect of neuroleptics and can be a prognostically important criterion in the appraisal of compounds with potential neuroleptic activity.     

New Approach to Information Handling in General Practice

In this paper we describe the use of punched feature cards in a general practice for 18 months. Its advantages are the low cost, speed of information retrieval, visible statistics, computer compatibility, accuracy, confidentiality, flexibility, and simplicity of setting up and collection of information. The system encourages the doctor to ask questions about his practice, and could readily be adopted in other practices.     

Functional activation of immune lymphocytes by antigenic stimulation in cell-mediated immunity. III. A soluble factor released from LPS-stimulated peritoneal adherent cells effective in antigenic activation of sensitized lymphocytes.

Antigen-induced production of migration inhibitory factor (MIF) by sensitized lymphocytes requires macrophages to effectively stimulate lymphocytes with soluble antigen in vitro. The present study showed that macrophage-depleted lymphocytes of sensitized guinea pigs could be activated with antigens when the culture supernatant of peritoneal adherent cells pulse-stimulated with a macromolecular fraction of bacterial lipopolysaccharide (LPS) was added to the lymphocyte culture. The apparent macrophage-replacing activity was found in the fraction which emerged slightly ahead of serum albumin upon gel filtration of the culture supernatant, and the activity was shown to be destroyed by heating at 65 °C for 30 min or by trypsin digestion. These results appeared to show that the activity was due to a protein component, most probably released from macrophages. Two-step culture experiments revealed that the soluble factor should be present in the early stage of the culture to activate the macrophage-depleted immune lymphocytes with antigen, as well as in the later stage when the presence of antigen in the medium is no longer required. Furthermore, the factor was shown to act in the activation of a T-cell-enriched fraction of immune lymphocytes. The factor appeared to be playing some essential role in making an antigenic stimulus effective for the activation of immune lymphocytes.     

MutantHFE genotype leads to significant iron overload in patients with liver diseases from western Romania

The present study aimed at assessing the frequency ofHFE mutations (C282Y, H63D and S65C) in western Romanian patients with liver disease of diverse aetiologies suspected of iron overload. A total of 21 patients, all Romanian residents hospitalized with clinical suspicion of iron overload and liver disease, were assayed for C282Y, H63D and S65C mutations, serum ferritin and viral hepatitis markers. Overall, 9 out of the 21 patients (42.86%) were found to harbour mutations in theHFE gene: 4 homozygotes C282Y (19.0%), 1 compound heterozygote C282Y/H63D (4.8%), 1 single heterozygote C282Y (4.8%), 2 single heterozygotes H63D (9.5%), 1 single heterozygote S65C (4.8%), and 12 wild-type cases (57.1%). Among the subgroup of 10 patients with the most prominent signs of iron overload (hyperferritinaemia and/or hepatocyte iron score ≥ 1), without hepatocellular carcinoma, theHFE genotypes were conclusive in 5 cases (50%). They had significantly increased ferritin levels compared to wild-type cases (P = 0.029). The inclusion of iron studies during routine clinical visits, coupled with the availability ofHFE genotyping for family and population studies, should facilitate the early detection of hereditary haemochromatosis in Romania.     

Stem cell function during plant vascular development

While many regulatory mechanisms controlling the development and function of root and shoot apical meristems have been revealed, our knowledge of similar processes in lateral meristems, including the vascular cambium, is still limited. Our understanding of even the anatomy and development of lateral meristems (procambium or vascular cambium) is still relatively incomplete, let alone their genetic regulation. Research into this particular tissue type has been mostly hindered by a lack of suitable molecular markers, as well as the fact that thus far very few mutants affecting plant secondary development have been described. The development of suitable molecular markers is a high priority in order to help define the anatomy, especially the location and identity of cambial stem cells and the developmental phases and molecular regulatory mechanisms of the cambial zone. To date, most of the advances have been obtained by studying the role of the major plant hormones in vascular development. Thus far auxin, cytokinin, gibberellin and ethylene have been implicated in regulating the maintenance and activity of cambial stem cells; the most logical question in research would be how these hormones interact during the various phases of cambial development.