Pharmacological distribution diagrams: a tool for de novo drug design

BACKGROUND: There is no empirical data available on attitudes concerning AIDS and habits towards HIV infected patients of physicians in general or private practice. In this study results of a self-evaluation are presented. METHODS: 178 physicians working with out-patients in different medical fields were randomly selected for a cross sectional study and interviewed using a standardised questionnaire. RESULTS: 89% think that they are sufficiently informed about AIDS (in the USA 20%). They regarded the risk of infection to be lower than the Anglo-American physicians. They believed there is a lack of interchange of information between colleagues regarding the degree of infectiousness of referred patients. A third of the physicians fear that other patients will go elsewhere if they find out that their physician is treating AIDS patients. 54% would hold special clinic sessions for HIV-patients outside the normal schedule for practice times. 89% believed that HIV patients were partly to blame for their illness. CONCLUSIONS: Although the physicians recognise the problem of HIV-infection, they partly deny the real necessities and facts. A reason for this could be the emotions underlying the general attitude to everything pertaining to HIV-disease. Attitudes to HIV-disease and the dealing with it in daily practice must be considered on the basis of individual emotional motives.     

Pathology of Toxoplasma gondii infection in the nude rat. An experimental model of toxoplasmosis in the immunocompromised host?

Genetically athymic nu/nu (nude) rats, deficient in T cells, die from infection with various Toxoplasma gondii strains, including RH and Prugniaud strains. In contrast, these strains cause chronic infections without apparent symptoms in immunocompetent non-nude rats. We show here that nude rats die in two to three weeks after RH infection and three to four weeks after Prugniaud infection. Histological examination of brains from nude rats at different time points after infection, revealed an absence of lesions after RH strain infection and cysts with usually no inflammation after Prugniaud infection. Lungs from nude rats developed a fibrin alveolitis using either strain, whereas myocarditis with focal areas of necrosis were observed only after Prugniaud infection. Cysts and, in some cases, tachyzoites in the necrotic lesions were easily identifiable. The two strains of T. gondii elicited in nude rats a granulomatous hepatitis that only differed in intensity. Spleen and mesenteric lymph nodes appeared totally non reactive in both cases. This model allows immunological and parasitological studies by comparison with immunocompetent rat infection. Published data concerning toxoplasma pathology in AIDS, therefore, suggest that acute toxoplasma infection in nude rats may be a useful model for studying disseminated forms of toxoplasma infection found in AIDS patients.     

Morphological and functional polymorphism within clonal thyroid nodules

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.     

A major isoform of the maize plasma membrane H(+)-ATPase: characterization and induction by auxin in coleoptiles

The plasma membrane (PM) H(+)-ATPase has been proposed to play important transport and regulatory roles in plant physiology, including its participation in auxin-induced acidification in coleoptile segments. This enzyme is encoded by a family of genes differing in tissue distribution, regulation, and expression level. A major expressed isoform of the maize PM H(+)-ATPase (MHA2) has been characterized. RNA gel blot analysis indicated that MHA2 is expressed in all maize organs, with highest levels being in the roots. In situ hybridization of sections from maize seedlings indicated enriched expression of MHA2 in stomatal guard cells, phloem cells, and root epidermal cells. MHA2 mRNA was induced threefold when nonvascular parts of the coleoptile segments were treated with auxin. This induction correlates with auxin-triggered proton extrusion by the same part of the segments. The PM H(+)-ATPase in the vascular bundies does not contribute significantly to auxin-induced acidification, is not regulated by auxin, and masks the auxin effect in extracts of whole coleoptile segments. We conclude that auxin-induced acidification in coleoptile segments most often occurs in the nonvascular tissue and is mediated, at least in part, by increased levels of MHA2.     

Oxygen dependency of retinal adhesion

PURPOSE: Normal retina is firmly attached to the retinal pigment epithelium, but the force of this adhesion drops precipitously within the first 2-3 min after enucleation. The purpose was to study metabolic factors that might be relevant to this postmortem failure of adhesion. METHODS: Dutch rabbit retina was manually peeled from the retinal pigment epithelium on strips of enucleated eyecup within a 37 degrees C bath. Retinal adhesiveness was measured by observing the amount of retinal pigment epithelium that remained adherent to the retina. RESULTS: Autologous whole blood in place of salt solution retarded the decrease in adhesiveness. A solution of hemoglobin alone was similarly effective, whereas methemoglobin solution failed to help the persistence of retinal adhesion. Bubbling oxygen into the salt solution and circulating it to avoid oxygen depletion at the tissue boundary also proved effective at sustaining retinal adhesiveness. Eyes made ischemic in vivo for 5 min or longer, by elevating intraocular pressure, showed virtually no retinal adhesion when enucleated immediately thereafter. However, eyes made ischemic for 10 min, but allowed to regain circulation for 5 min before enucleation, showed a return of retinal adhesiveness to 80% of normal. CONCLUSIONS: Oxidative metabolism is critical to the maintenance of retinal adhesiveness, and the effects of oxygen deprivation on adhesion are reversible within a certain time period.     

Aromatic nitrations by mixed acid. Slow liquid-liquid reaction regime

Aromatic nitrations by mixed acid have been selected as a specific case of a heterogeneous liquid-liquid reaction. An extensive experimental programme has been followed using adiabatic and heat-flow calorimetry and pilot reactor experiments, supported by chemical analysis. A series of nitration experiments has been carried out to study the influences of different initial and operating conditions such as temperature, stirring speed and sulphuric acid concentration. In parallel, a mathematical model to predict the overall conversion rate has been developed. In this paper the mathematical modelling and the implementation and experimental validation for benzene, toluene and chlorobenzene mononitration in the kinetic control regime (slow liquid-liquid reaction) are presented and discussed.     

In-laboratory removal of femoral sheath following protamine administration in patients having intracoronary stent implantation

Two hundred twenty-eight patients with successful coronary stent implantation were randomized either to protamine administration and femoral sheath removal (group I, n = 117) or no heparin neutralization and delayed sheath removal (group II, n = 111). The hospital stay after treatment was shorter in patients receiving protamine; therefore, protamine use for neutralizing circulating heparin may be safely administered immediately after stent implantation.