Murine epidermal Langerhans cells do not express inducible nitric oxide synthase

In Leishmania-infected macrophages (MΦ), the formation of reactive nitrogen intermediates by the inducible isoform of nitric oxide synthase (iNOS) is critical for the killing of the intracellular parasites. We have recently shown that, in addition to MΦ, epidermal Langerhans cells (LC) can phagocytose Leishmania major, but they do not allow parasite replication. Therefore, we analyzed whether LC and MΦ display the same leishmanicidal effector mechanism. Unlike MΦ, stimulation of unselected epidermal cells with interferon-γ/lipopoly-saccharide did not lead to the release of nitric oxide (NO), and inhibition of NO production had no effect on the rate of infection of LC. iNOS mRNA was clearly detectable in MΦ as well as unselected epidermal cells (the majority of which consists of keratinocytes) after stimulation with different cytokines. In contrast, pure LC obtained by single-cell picking from cytokine-activated or L. major-infected epidermal cells did not express iNOS mRNA. Addition of the NO donor S-nitroso-N-acetylpenicillamine to already-infected LC did not alter their rate of infection, indicating that LC do not utilize exogenous NO for the control of intracellular Leishmania. These results suggest that in the L. major-infected skin, activated MΦ and keratinocytes, but not LC have the ability to express iNOS activity. Therefore, an as yet unidentified, NO-independent mechanism appears to be responsible for the control of parasite replication in LC.     

Liposome-mediated gene transfer to fetal human ventral mesencephalic explant cultures

To clarify how Abeta deposits induce secondary tauopathy, the presence of phosphorylated tau, glycogen synthase kinase 3alpha (GSK3alpha), GSK3beta, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and fyn were examined in the Tg2576 brain showing substantial brain Abeta amyloidosis and behavioral abnormalities. Phosphorylated tau at Ser199, Thr231/Ser235, Ser396 and Ser413 accumulated in the dystrophic neurites of senile plaques. The major kinase for tau phosphorylation was GSK3beta. Smaller contributions of GSK3alpha, CDK5 and MAPK were suggested. Thus, brain Abeta amyloidosis has a potential role in the induction of tauopathy leading to the mental disturbances of Alzheimer's disease.     

Determination of Dissolved Oxygen in Heterogenous Systems Particularly in Emulsions and Oily Liquids

The content of dissolved oxygen was determined by four independent methods in a series of non-aqueous or heterogenous systems. The Lex-O₂-Content Analyzer represents a fast and simple apparatus that employs a coulometric oxygen assay with Hersch cell detection. A comparison of the results with different methods demonstrates the reliability of the Lex-O₂ in the determination of oxygen dissolved in heterogeneous or non-aqueous systems. Therefore, this apparatus can be recommended for the measurement of oxygen in oxygenator or perfusion fluids, as well as in blood substitutes or other oxygen transporting systems.     

Treatment of severe chronic insomnia with L-tryptophan: results of a double-blind cross-over study

Thirty-nine subjects with chronic insomnia were treated with L-tryptophan (L-TRP) in a double-blind, cross-over study. Instead of a placebo, a very low dose of 0.04 g L-TRP was used. The subjects suffered from a sleeping disorder classified as "psychophysiological, persistent". In the subgroup taking the full L-TRP (2 g) dose first, there was a significant difference between the treatment period with the full L-TRP dose and the ineffective dose (placebo). If the placebo was given first, however, there was no significant difference between the two treatment periods. It is suggested that psychological factors are responsible for the diverging results in the two subgroups of patients. On the basis of subjective ratings, it appears that L-TRP is effective in promoting sleep in cases of chronic insomnia.     

Nosology of osteochondrosis dissecans of the trochlea of the talus

The histories of 56 patients with the diagnosis "osteochondrosis dissecans tali" were retrospectively analyzed with regard to etiology, localization, therapy, course, and prognosis. Some of the patients were reexamined. In 33 patients it is highly probable that the osteochondrosis dissecans was not associated with the sequelae of osteochondral fractures. The typical X-ray image is that of a medial, deep osteolysis on the trochlea of the talus, close to the margin, with one or more roundish dissections. There are usually no degenerative or posttraumatic changes. The history and frequent bilateralism tend to rule out trauma as the cause. In the authors' opinion, therefore, the term "osteochondrosis dissecans" should not be used for osteochondral fractures and their sequelae. A number of borderline cases are critically discussed.     

106. Kriterien zur Biostatistik bei der Chirurgie des Magencarcinoms

Zusammenfassung Es wird auf die Problematik von Aussagen über Radikalität der Operation und Prognose beim Magencarcinom aus retrospektiven oder prospektiven Beobachtungsstudien hingewiesen. Einige Gründe für sich widersprechende oder nicht reproduzierbare Resultate in Subgruppen werden aufgezeigt. Insbesondere wird auf das Problem der Suche nach signifikanten Ergebnissen durch multiple Testanwendungen in den verschiedensten Subgruppen aufmerksam gemacht. Bei offenen Fragen erscheinen nach den Kriterien des statistischen Schliessens randomisierte Studien angebracht.     

Stability of drug metabolizing enzymes during the incubation conditions of the liver microsomal assay with non-induced and induced mouse liver S-9 fractions

The purpose of this work was to study the relative activitiesand stabilities of phase-I and phase-II drug metabolizing enzymesin incubation mixtures used in in vitro genotoxicity testingin order to optimize the conditions of the assay, increase sensitivityand eliminate false negative results. Cytochrome P-450, NADPH-cytochromeP-450 (cytochrome c) reductase activity and various phase-Iand phase-II enzyme activities of the drug-metabolizing systemwere determined in incubation mixtures used in liver microsomalassays. The behaviour of aminopyrine N-demethylase and p-nitroanisoleO-demethylase activities as phase-I markers have been reportedpreviously. Other activities measured were glutathione S-transferase,glutathione S-epoxide transferase and epoxide hydrase, and lipidperoxidation (LP) was determined. The experiments were carriedout on liver S9 fractions derived from non-induced mice or miceinduced with sodium phenobarbital (PB), and/or ß-naphthoflavone(ß-NF). The phase-II enzymes were much more stable(70–90% residual activity) than phase-I enzyme activities(35–60%) in all conditions tested. The residual cytochromeP-450 was 70% stable and the remaining activity of NADPH-cytochromec-reductase about 80%, indicating that this latter enzyme doesnot limit the rate of the monooxygenase system in these conditions.Phase-II enzymes were induced to a smaller extent (about 2 times)than in phase-I enzymes (5–6 times) by ß-NF+ PB. NADPH-cytochrome c-reductase behaved as phase-II enzymesin this respect as well as for stability. LP was appreciablyhigher in non-induced than in induced animals. Treatment withthe ß-NF + PB mixture, however, showed that inducedenzymes were more stable than those obtained by simple inductionwith either ß-NF or PB alone. These results lead tothe conclusion that prolonged incubation times in mutagenicityassays are unnecessary when considering the relative stabilitiesof the various phase-I and phase-II enzyme activities in thedrug-metabolizing system.     

Seeing but not recognizing

Visual recognition disturbances are caused by lesions that affect visual cortex as well as white matter connections between visual cortex and temporal and parietal cortex. Homonymous visual field defects are often present but do not explain the recognition difficulty. In "alexia without agraphia" (pure alexia), the intact right visual cortex is disconnected from the left parietal language center by a lesion in the splenium. In "prosopagnosia," visual cortex is disconnected bilaterally from temporal cortex. In simultanagnosia, visual association cortex is damaged. The first condition is most commonly caused by left posterior cerebral artery occlusion, the second by bilateral posterior cerebral artery occlusion or head trauma, and the third by watershed infarction, tumors, abscesses, head trauma, leukoencephalopathies and Alzheimer's disease. When such disorders are suspected, the examiner should supplement the routine visual examination with suggested screening maneuvers.     

The influence of radiation therapy on T-lymphocyte subpopulations defined by monoclonal antibodies

We studied the influence of radiation therapy on lymphocyte subpopulations in 17 patients undergoing adjuvant radiation therapy for primary breast cancer, and eight patients receiving brachytherapy and external beam irradiation for primary cancer of the uterus. Radiation therapy reduced B- and T-lymphocytes in proportion to the total lymphocyte population so that their percentages remained unchanged. Determination of helper and suppressor T-lymphocytes before, during and 6 months after completion of radiotherapy revealed that in both groups of patients suppressor T-lymphocytes were more resistant to and recovered faster after radiotherapy. This resulted in a decline of the "immunoregulatory balance" (helper/suppressor ratio). Although this ratio had been higher in both groups of patients than in healthy age- and sex-matched controls before therapy, it became normal and subnormal during and after radiotherapy. The clinical significance of the differential influence of radiotherapy on T-lymphocyte subpopulations remains to be determined.