Reproductive studies of C57B/6 male mice treated with TCDD-contaminated soils from a 2,4,5-trichlorophenoxyacetic acid manufacturing site

Reproduction was studied in male C57B/6 mice treated with contaminated soils from a 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) manufacturing site in Newark, New Jersey, and a metal scrap yard where equipment from the manufacturing site was recycled. The soils contained a wide variety of contaminants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Treated males were mated to females given decontaminated soil. No acute toxicity was observed in treated males. 2,3,7,8-TCDD (up to 90 g/kg) or 2,3,7,8-TCDD from the contaminated soils (up to 288 g/kg) had no adverse effect on reproduction when the male mouse was treated. However, treatment of males with soil from the 2,4,5-T manufacturing site was associated with a marked decrease in viable litters at whelping and a decrease in pup survival. This toxicity may be associated with TCDD in combination with other toxic compounds that are present on the soil.     

The Alkaloids of Melodinus acutiflorus. Rhyzicine N-Oxide

From the leaves of MELODINUS ACUTIFLORUS a new alkaloid, rhazicine N-oxide ( 2), and two known compounds, deacetylakuammiline ( 3) and 16- EPI-rhazinaline ( 4) were isolated. The structure of 2 was determined by spectral analysis and chemical correlation with rhazicine ( 1).     

ACTH increases noradrenaline release in the rabbit heart

Summary The effects of ACTH on the release of noradrenaline and the increase of heart rate produced by sympathetic nerve stimulation (1 Hz) were studied in isolated perfused rabbit hearts. ACTH-(1–24) 0.1–100 nmol/l increased the stimulation-evoked overflow of noradrenaline concentration-dependently, reversibly and up to two-fold. The basal outflow of noradrenaline, the basal heart rate and the stimulation-evoked increase in heart rate were not changed. Human ACTH-(1–39) also increased the evoked overflow of noradrenaline. The effect of ACTH-(1–24) 0.3 nmol/l persisted after blockade of -adrenoceptors with propranolol and blockade of neuronal catecholamine uptake by cocaine. ACTH-(1–24) 3 nmol/l did not change the removal of noradrenaline from the perfusion fluid, when hearts were perfused with medium containing 59 nmol/l noradrenaline. The results show that ACTH increases the action potential-evoked release of noradrenaline from cardiac postganglionic sympathetic neurones, probably by activating specific presynaptic ACTH receptors. The high potency of ACTH suggests that these presynaptic receptors may be activated in vivo by circulating ACTH under certain pathophysiological conditions.Send offprint requests to B. Szabo at the above address     

Zum Reaktionsmechanismus der Oxygenierung von Naphtholen mit dem System CuCl/O2

Mechanism of the CuCl/O₂-mediated Oxygenation of Naphtholes The mechanism of the oxygenation of 1- and 2-naphthole derivatives in the system $\left[ {\mathop {\rm C}\limits^{+} \mathop {\rm u}\limits^{1} {\rm L}_4 } \right]^{+} + {\rm O}_2 \rightleftharpoons \left[ {\mathop {\rm C}\limits^{+} \mathop {\rm u}\limits^2 {\rm L}_3 {\rm O}_2^{^.} } \right]^{+} + {\rm L}$ depending on solvent (L) and temp., is studied. It was possible to distinguish between reactions via the radical ion pair type (L = CH₃CN) and hydrogen abstraction via free radicals (L = CH₃OH). There is a marked difference between the oxygen transfer to the naphthole derivatives and the oxygenation of 2, 6-di-tert.-butylphenol ( 6 ), which does not depend characteristically on L and temp.     

Expression of selectin ligands on murine effector and IL-10-producing CD4+ T cells from non-infected and infected tissues

Endothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL-10-producing T cells displayed the highest frequency of ligand-positive cells in general. Within the inflamed tissues, the frequencies of P-selectin-binding cells increased in the dominant subset, either Th1 or Th2. Up-regulation was also found for E-selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P-selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu.     

Immunohistochemical detection of VEGF in the bone marrow of patients with acute myeloid leukemia. Correlation between VEGF expression and the FAB category

We studied vascular endothelial growth factor (VEGF) expression in bone marrow sections obtained from 3 healthy donors and 41 patients with acute myeloid leukemia (AML) of various French-American-British (FAB) subtypes by immunohistochemical analysis using an anti-VEGF antibody. In normal bone marrow, the anti-VEGF antibody reacted with myeloid progenitor cells and megakaryocytes but not with erythroid cells or mature granulocytic cells. High levels of VEGF were found in the bone marrow in patients with AML-M1, -M2, -M3, -M4, -M4Eo, and -M5. In these leukemias, the vast majority of myeloblasts (> 90%) expressed VEGF. By contrast, in AML-M0, the percentage of VEGF-positive blasts was lower in most cases (median, 42%), and if at all detectable, these blast cells contained only trace amounts of VEGF. In AML-M3 and -M4Eo, maturing granulocytes failed to express VEGF similar to granulocytes in normal bone marrow. In AML-M6, myeloblasts exhibited VEGF, whereas erythroid cells did not. In AML-M7, blast cells and megakaryocytes were identified as major sources of VEGF. In summary, VEGF expression in the bone marrow is restricted to certain stages of differentiation and maturation of myeloid cells and correlates with the FAB category.     

Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.     

Taste bud development in the zebrafish, Danio rerio.

Taste buds are chemosensory endorgans consisting of modified epithelial cells. Fish and other vertebrates use their taste bud cells to sample potential food, either selecting or rejecting substances according to their edibility. The adult gustatory system in fish has been studied thoroughly, including regeneration experiments. Taste buds occur in the epithelia of the lips, the mouth cavity, the oropharyngeal cavity, and also in the skin of the barbels, the head, and sometimes even all over the body surface. Despite its importance for feeding, little is known about the ontogeny of the fish taste system. We examined the development of taste buds in the zebrafish on the light microscopical and the scanning and transmission electron microscopical levels. Taste buds develop later than the olfactory organ and the solitary chemosensory cells, two other chemosensory systems in aquatic vertebrates. The first few taste bud primordia are visible within the epithelia of lips and gill arches 3 to 4 days after fertilization, and the first few taste buds with open receptor areas appear on the lips and simultaneously on the gill arches 4-5 days after fertilization, which coincides with the onset of feeding. Taste buds in the mouth cavity, on the head, and on the barbels are formed later in development. As seen in other fish, zebrafish taste buds contain elongate dark and light cells, termed according to their electron density. Dark cells with a cell apex of many short microvilli appear first, followed by the light cells with one large microvillus. In addition, the zebrafish has a third fusiform cell type, which appears last. This cell type is low in electron density and has a brush-like apical ending with several small microvilli. This cell type has not been described previously. Furthermore, in zebrafish, the ontogenetic processes of taste bud formation differ from regenerative processes described in the literature.     

Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques

Summary Different regions of human aorta and of other human arteries obtained at autopsy were analyzed with regard to their topography and to the different stages of arteriosclerosis. Material was studied by immunocytochemical techniques with antibodies specific for either desmin (D) or for vimentin (V), the two types of intermediate filament proteins present in vascular smooth muscle cells. In normal arteries endothelial cells as well as the adjacent intimal cells were D–V+. In the media D+V+ as well as D–V+ cells were present, with the relative numbers of each cell type dependent on the particular blood vessel. When cells in arteriosclerotic plaques at different stages of development were examined an occasional plaque showed cells of the D+V+ type. In the majority of plaques however the cells were V– D+. In plaques where severe ulceration and necrotic material was present D–V+ cells were found at the border of the lesion: foam cells when they could be identified appeared to be D–V+.     

Paired-pulse transcranial magnetic stimulation protocol applied to visual cortex of anaesthetized cat: effects on visually evoked single-unit activity

In this study, we tested the paired-pulse transcranial magnetic stimulation (ppTMS) protocol – a conditioning stimulus (CS) given at variable intervals prior to a test stimulus (TS) – for visually evoked single-unit activity in cat primary visual cortex. We defined the TS as being supra-threshold when it caused a significant increase or decrease in the visually evoked activity. By systematically varying the interstimulus interval (ISI) between 2 and 30 ms and the strength of CS within the range 15–130% of TS, we found a clear dependence of the ppTMS effect on CS strength but little relation to ISI. The CS effect was strongest with an ISI of 3 ms and steadily declined for longer ISIs. A switch from enhancement of intracortical inhibition at short ISIs (2–5 ms, SICI) to intracortical facilitation (ICF) at longer ISIs (7–30 ms), as demonstrated for human motor cortex, was not evident. Whether the CS caused facilitation or suppression of the TS effect mainly depended on the strength of CS and the polarity of the TS effect: within a range of 60–130% a positive correlation between ppTMS and TS effect was evident, resulting in a stronger facilitation if the TS caused facilitation of visual activity, and more suppression if the TS was suppressive by itself. The correlation inverted when CS was reduced to 15–30%. The ppTMS effect was not simply the sum of the CS and TS effect, it was much smaller at weak CS strength (15–50%) but stronger than the sum of CS and TS effects at CS strength 60–100%. Differences in the physiological state between sensory and motor cortices and the interactions of paired synaptic inputs are discussed as possible reasons for the partly different effects of ppTMS in cat visual cortex and human motor cortex.