Effect of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of adhesion molecules on human neutrophils

The effects of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of CD11b/CD18, CD11c/CD18 integrins and l-selectin on human neutrophils were studied by flow cytometry in a whole blood assay. None of these compounds had any effect on the basal expression of CD11b, CD11c, or l-selectin in the concentration range of 20–100 μM. However, linoleic acid at a concentration of 1000 μM slightly up-regulated CD11b and CD11c by a factor of 2.1 and 1.7, respectively. Linoleic acid, linoleic acid anilide, and arachidonic acid did not affect the formyl-methionyl-leucyl-phenylalanine induced up-regulation of CD11b or CD11c. However, linoleic acid and linoleic acid anilide slightly inhibited the phorbol myristate acetate (PMA)-induced expression of CD11b, which was decreased by 27 and 21% at concentrations of 100 and 1000 μM, respectively. Likewise, arachidonic acid at 40 μM inhibited the PMA-induced expression of CD11b by 19%. Our results suggest that linoleic acid, linoleic acid anilide, and arachidonic acid do not dramatically affect the expression of leukocyte adhesion molecules in a whole blood assay. Received: 17 February 1997  / Accepted: 5 May 1997     

Location of motoneurones projecting to the cat distal forelimb. II. Median and ulnar motornuclei

The position of the motornuclei projecting through the median (Mn) and ulnar (Ul) nerves to the cat distal forelimb has been investigated. Horseradish peroxidase (HRP) and fluorescent (Fl) compounds have been used as retrograde tracers. They were either injected into forelimb muscles or applied to the proximal end of transected forelimb nerves. Limb muscles that were not investigated were carefully denervated. The position and the architecture of the individual motornuclei were traced with HRP. The topographical relations between the nuclei were established with application of up to three different Fl compounds in the same animal. The Mn motoneurones had a bimodal distribution in the brachial spinal cord. The motoneurones to the pronator teres and flexor carpi radialis muscles were located in C7 and the other Mn motoneurones were located in C8 and Th1. In C7 the Mn motoneurones occupied a single representation area, which is located some distance medially of the lateral funiculus. In C8 and Th1 two Mn representation areas were found: A dorsal one that contacts the lateral funiculus and is located at the level of the central canal; a ventral one that is located ventrally in the ventral horn. The dorsal area is occupied by the motornuclei projecting to the intrinsic hand muscles and the ventral one by the nuclei projecting to the limb. The Ul motoneurones extend with an unimodal distribution from the caudal C7 to the caudal Th1 segments. They occupy a single, broad representation area. The dorsal part, which contacts the lateral funiculus, is located at the level of the central canal and harbours the nuclei to the intrinsic hand muscles. The other Ul nuclei are located ventromedially deep in the ventral horn. These results, together with those from the companion paper on the location of the deep radial motornuclei, provide important anatomical information for the investigation of the cat brachial enlargement.     

Second nonocular tumors in cured unilateral retinoblastoma patients

Summary According to recent data the incidence of second tumors in cured hereditary unilateral retinoblastoma patients is 20% within 10 years, 50% after 20 years and rises to 90% after 30 years. Nonhereditary unilateral retinoblastoma patients have not been regarded as susceptible for second nonocular tumors so far. A case is reported of such a patient having developed a second presacral retroperitoneal tumor after successful treatment of a nonhereditary unilateral retinoblastoma group V without intracranial extension or pulmonary metastases. Consequently all (hereditary and non-hereditary) retinoblastoma patients should receive at least quarterly intensive follow-up examinations after primary ophthalmologic treatment.     

Protective genes expressed in endothelial cells of second hamster heart transplants to rats carrying an accommodated first graft

Abstract: Accommodation refers to survival of a xenograft despite the presence of anti-donor organ antibodies and complement. We have recently shown that accommodation of a hamster heart transplanted to a rat receiving short-term cobra venom factor (CVF) and continuing cyclosporine A (CyA) therapy is associated with i) the expression in the endothelial cells (EC) and smooth muscle cells of the graft of a number of "protective" genes, ii) a prominent intragraft Th2 cytokine profile, and iii) the relatively heavy deposition of IgG2c antibodies on the EC of the graft. In contrast, rejecting grafts do not express the protective genes, have a Th1 cytokine profile, and apparently have lesser amounts of IgG2c. These findings are consistent with host factors (Th2 cytokines and IgG2c) contributing to xenograft accommodation. To test whether these host factors may predispose to the development of accommodation, we placed a second hamster heart into each of 12 rats carrying a surviving first heart; recipients were, at the time, receiving only CyA. Whereas first grafts transplanted to rats receiving only CyA survive for 3 to 4 days, 11 out of 12 second transplants survived more than 20 days, and the other survived for 7 days. Nine of the twelve were not rejected: of these, four were removed between day 35 and 132 for study, and the remainder are still beating at 35 to 52 days. The surviving second hearts we studied had accommodated in that the picture on immunopathology was the same as for surviving first hearts. We suggest that the Th2 cytokines and perhaps the IgG2c response are factors in allowing prolonged survival of the second grafts and, further, that these factors contribute to the expression in the EC and smooth muscle cells of the surviving second hearts of the protective genes.     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995     

Substantiating hazardous exposure to asbestos by examination of pulmonary dust

Summary Substantiation of relevant asbestos risks by microscopic examination sets a lower detection limit at fibres longer than 5 to 10 m and thicker than 0.5 m Such microscopically detectable fibres are, of course, in respect to total quantity the insignificant part of the overall dust burden, but apparently a necessary part of the whole fraction when assessing the relevance of exposure. Until now, no epidemiologically conclusive asbestos risks resulting from occupational exposure have been made known solely with fibre fraction below the microscopic detection limit. Demands for supplementary electromicroscopic examination on the basis of case reports of lung parenchyma damage by fibres of a lower calibre than the microscopic detection limit are, therefore, presently without foundation. The subject examinations reveal that substantiation of asbestos risks with light-optical means, using different methods, provides comparable results. Initially, of course, it is surprising to obtain fluctuations in results of 100000 to 600000 asbestos particles for the same case. However, one must realize that calculations based on intermediate results are responsible for this range of fluctuation, due to the varying degree of asbestos fibre dispersion in the different sections of the lung and, depending on the method of detection used. Interest on the part of everyday occupational medicine and expert opinion is determined by the need to categorize individual cases into different basic classes of risk by referring to relevant morphological facts, such as substantiation of asbestosis or drawing a borderline between persons with occupational risk and those with a non-occupational risk. The subject examinations reveal, using different methods of analysis, equally significant results, which correspond with those published by other authors who used a method which, in terms of expenditure for material and manpower, is also suitable for routine analysis.     

Effects of trapidil-derivatives on calcium channel currents in isolated ventricular cells from mice

Summary A single glass micropipette voltage clamp technique with intracellular dialysis was used to study the effects of the trapidil derivatives AR 12–456 and AR 12–463 on Ca channel currents carried by Bat+ in isolated ventricular cells from mice hearts. Inspite of a more potent inhibition of the cAMP phosphodiesterase from heart (Bartel et al. 1985) a reversible Ca channel blocking action of both compounds could be observed. The concentration of half maximal block was calculated to about 50 mol/l for both derivatives tested. Neither a shift in the current-voltage relationships nor a significant change in the potential for half maximal activation was found. The maximal Ba²⁺ -conductance was reduced. The steady state inactivation was shifted towards more negative potentials by application of 100 mol/l AR 12–463. The decay of the Ba currents was accelerated in the range of the applied test potentials between –20 and +20 mV. It is concluded that the new trapidil derivatives with more potent inhibitory action on cardiac phosphodiesterase than trapidil can block myocardial Ca channels. Send offprint requests to B. Nilius     

The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy

Two iliac crest needle biopsies were taken from a 43-year-old lead-poisoned woman during and after completion of a Ca-EDTA treatment. By atomic absorption spectroscopy the first and second biopsy were found to contain 56, respectively 41.6 g lead/g wet tissue. In both biopsies 36% of the lead was extractable in 0.1 N HCl. Electron microbeam X-ray analysis proved to have too low sensitivity for quantitation of the lead in these biopsies. Laser microbeam mass analysis (LAMMA), performed only on the second biopsy, revealed a high and fairly constant residual lead concentration in all bone marrow cell nuclei (approximately 55 g/g) and a low lead concentration in the cytoplasm of the same cells (4–12 (g/g). The extracellular bone matrix lead was greatly concentrated in the superficial 3–6 m osteoid zone of the bony trabeculae and totally absent from deeper parts of the mineralized matrix. The LAMMA results are in good agreement with those of subcellular fractionation experiments and atomic absorption spectroscopy, provided that the relative volume fraction of nucleus and cytoplasm is accounted for. The high residual osteoid lead after completed chelation therapy indicates that lead has a stronger affinity for the organic than the mineral components of bone matrix.     

Die Rassenfrage bei Culex pipiens in Deutschland

Zusammenfassung Auch für Deutschland müssen wenigstens 2 verschiedene Rassen vonCulex pipiens als bewiesen gelten, die mit den vonRoubaud aufgestellten RassenC. p. pipiens undC. p. autogenicus identisch sein dürften. Die letztere Rasse, die in Hamburg unter anderem in einem Kinderkrankenhaus gefunden wurde, ist vor allem dadurch gekennzeichnet, da\ sie zur Entwicklung der Eier keine Blutnahrung benötigt, sondern allein auf Grund der im Larvalleben gespeicherten Reservestoffe reife Eier zu bilden vermag. Diese Eigenschaft ist auch an dem Entwicklungszustand des Ovars erkennbar. Da bei der autogenen Rasse das Ovar nach dem Schlüpfen und vor der Eiablage fast stets wesentlich weiter als bei der nichtautogenen Rasse vor der Blutaufnahme entwickelt ist, lassen sich die beiden Rassen hierdurch leicht unterscheiden. Dieses Merkmal hat für die Diagnose der Rassen und der autogenen Eigenschaft bei Mischpopulationen deshalb besondere Bedeutung, weil in autogenen StÄmmen (wenigstens im Laboratorium) nur ein Teil der Vollreife Eier bildet, bei den übrigen aber die Entwicklung des Ovars stehen bleibt, sofern der Mücke nicht Gelegenheit zum Blutsaugen geboten wird. ZÄhlt man in einer Zucht oder Population nur die autogenen Gelege, so erfa\t man damit nur einen Teil der wirklich autogenen . Die Unterschiede im Entwicklungszustand des Ovars reichen bis in das letzte Larvenstadium zurück. Die beiden Rassen verhalten sich auch sonst physiologisch (Begattungs- und überwinterungsgewohnheiten, Form und Grö\e der Gelege usw.), wie die vonRoubaud beschriebenen. Im Anschlu\ wird ein erfolgreiches Kreuzungsexperiment zwischen der autogenen und der typischen Rasse beschrieben und die Vererbung der autogenen Eigenschaft in den nÄchstfolgenden Generationen analysiert.