Neuropathology in non-human immunodeficiency virus-infected drug addicts: hypoxic brain damage after chronic intravenous drug abuse

Neuropathological studies were carried out on 180 human immunodeficiency virus-seronegative intravenous drug addicts. The findings in victims of acute heroin intoxication (n = 116) were congestion (99.1%), capillary engorgement (68.1%), and/or perivascular bleeding (68.1%) – hemodynamic processes attributable to toxic primary respiratory failure. In a high percentage of these cases (88%), cerebral edema was also present. In 18 cases of acute heroin intoxication who survived for periods of hours or days, the sole postmortem finding was ischemic nerve cell damage, resembling that typically seen in systemic hypoxia. Semiquantitative analysis revealed nerve cell loss in the hippocampal formation and/ or Purkinje cell layer in 26% of the 162 chronic drug abusers. By contrast, in nearly 80% of these cases, the hippocampus showed enhanced expression of glial fibrillary acid protein by astrocytes and/or a proliferation of microglia, demonstrated by CD68 expression. Since such reactive processes are produced by primary neuronal damage, it can be assumed that chronic intravenous drug abuse results in obviously ischemic nerve cell loss. This could be demonstrated in the hippocampus, but it must also occur throughout the whole brain. The demonstration of ischemic nerve cell damage and neuronal loss or secondary reactive alterations has not been described previously. Received: 31 March 1995 / Revised, accepted: 27 November 1995     

Thoracic outlet syndrome: a comprehensive evaluation

Using various modalities, 480 patients were evaluated for thoracic outlet compression syndrome. Of this group, 300 patients were eventually diagnosed as having thoracic outlet syndrome after extensive evaluation. Ninety of these patients underwent a total of 103 operative procedures for thoracic outlet decompression. Nerve conduction velocities and directional Doppler studies were the most useful adjuncts in making the diagnosis. Surgical therapy after proper selection yielded an 80.6 per cent long-term "good" operative result and an additional 6.9 per cent long-term "fair" operative result in follow-up to 12 years.     

Presynaptic regulation of the electrically evoked release of endogenous dopamine from the isolated neurointermediate lobe or isolated neural lobe of the rat pituitary gland in vitro

Summary Isolated neurointermediate lobes (NILs) or isolated neural lobes (NLs) of the rat pituitary gland were incubated in Krebs-HEPES solution which contained pargyline and the dopamine uptake inhibitor GBR 12921. The release of endogenous dopamine was determined by HPLC with electrochemical detection. Electrical stimulation of the pituitary stalk induced a frequency-dependent release of dopamine.The release of dopamine from the combined NIL evoked by stimulation at 15 Hz was increased by 130% in the presence of the dopamine D2 receptor antagonist, (–)-sulpiride; the (+)-enantiomer of sulpiride had virtually no effect. When the stimulation frequency was 3 Hz (–)-sulpiride caused an increase in dopamine release by 230%. A similar increase was observed in the presence of domperidone, another dopamine D2 receptor antagonist.The dopamine receptor agonists, apomorphine and quinpirole, had no significant effects on the evoked release of dopamine indicating that under the present incubation conditions endogenous dopamine may have been maximally activating the autoinhibition. However, in the presence of 1 mol/l (–)-sulpiride, apomorphine as well as quinpirole reduced the evoked release of dopamine in a concentration-dependent manner.The dopamine D1 receptor selective antagonist, SCH 23390, had no effect on the evoked release of dopamine at a concentration of 1 mol/1. Only at a concentration of 10 mol/l did SCH 23390 cause a small increase in dopamine release; this effect was, however, abolished in the presence of 1 mol/1(–)-sulpiride.In the presence of 1 mol/l (–)-sulpiride neither clonidine, yohimbine, 5-methoxytryptamine nor metitepine significantly affected the release of dopamine from the NIL evoked by stimulation at 3 Hz.In the NL, the release of dopamine is inhibited by endogenous opioids. For this reason, naloxone 1 or 10 mol/1 was present in the experiments on isolated NLs. Domperidone and (–)-sulpiride, but not (+)-sulpiride, increased the release of dopamine from the NL evoked by electrical stimulation at 15 Hz by about 90%. SCH 23390 caused a significant increase in dopamine release at 10 mol/l, but not at 1 mol/lIn conclusion, the release of endogenous dopamine from the neurons terminating in the intermediate and neural lobe of the pituitary gland is inhibited via dopamine receptors of the D2 type.Abbreviations DOPAC dihydroxyphenylacetic acid - 5-HT 5-hydroxytryptamine - HPLC high performance liquid chromatography - IL intermediate lobe - NIL neurointermediate lobe - NL neurallobe Send offprint requests to K. Racké at the above address     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.     

Cyclosporin A-mediated killing of <Emphasis Type="Italic">Leishmania major</Emphasis> by macrophages is independent of reactive nitrogen and endogenous TNF-α and is not inhibited by IL-10 and 13

Murine macrophages were treated with various doses of cyclosporin A (CsA) to enhance the killing of Leishmania major parasites. CsA reduced the rate of infected cells from 75% in non-treated controls to less than 15% with 1 micro g CsA/ml in a dose-dependent manner. The leishmanicidal effect was also observed when CsA was added 48 h after the infection of macrophages. In contrast, FK506, another structural non-related immunosuppressive drug with antiparasitic activities, showed no effect on the ability of macrophages to kill intracellular Leishmania parasites. Since nitric oxide has been identified as a key molecule for the leishmanicidal function of macrophages, we analyzed the role of this molecule. There was no influence on the leishmanicidal effect of CsA when L- N-(1-iminoethyl)lysine, a potent and selective inhibitor of mouse inducible nitric oxide synthase, was added. Furthermore, the presence of the macrophage-inhibiting cytokines interleukin (IL)-10 and IL-13 simultaneously or prior to CsA did not inhibit leishmania killing, while both cytokines completely prevented parasite killing by macrophages activated with gamma interferon and tumor necrosis factor (TNF). CsA was fully active on macrophages from TNF-receptor p55 knockout mice arguing against autocrine activation by TNF. We therefore conclude that the antileishmanial effect of CsA is independent of effector mechanisms employed by macrophage-activating cytokines.     

Tissue distribution of the T cell activation antigen Ta1. Serological, immunohistochemical and biochemical investigations.

The recently described Ta1 antigen is expressed by activated T cells in vitro and in vivo, as observed in patients with certain immune-mediated diseases, such as multiple sclerosis. In this paper we report on the tissue distribution of the Ta1 antigen. Serological testing of human tumour cell lines and immunohistochemical analysis of human tissue sections revealed a reactivity of the anti-Ta1 antibody with normal and malignant tissues of the upper gastro-intestinal tract, the biliary tract, exocrine pancreas and kidney. SDS-PAGE analysis of immunoprecipitates from 125I-labelled cells, employing the anti-Ta1 antibody, yielded a 113-115 kD band from three serologically Ta1 positive tumour cell lines, from a serologically Ta1 negative human EBV-transformed B lymphoblastoid cell line, from peripheral blood mononuclear cells (PBMC) and, as previously described, a 105 kD band from PHA activated T cells (Fox et al., 1984). After endoglycosidase F treatment similar bands of 85 kD were precipitated from activated T cells and from tumour cell lines. It is therefore likely that very similar glycoproteins, which differ only modestly in the size of carbohydrate chains, bear the Ta1 epitope on Ta1 positive tissues.     

Familie mit multipler endokriner Adenomatose (MEA TypI) und einigen zusätzlichen Besonderheiten

Zusammenfassung 3 Generationen mit 37 Mitgliedern einer Familie mit multipler endokriner Adenomatose Typ I (MEA Typ I) wurden anamnestisch und katamnestisch erfaßt. Klinische, biochemische und histologische Befunde wurden zusammengestellt: 20 Personen hatten Erkrankungen oder Befunde, die für eine MEA Typ I charakteristisch sind.Ein Patient (II 1) hatte ein chromophobes Hypophysenadenom, Epithelkörperchen- und Inselzelladenome, eine knotige Kolloidstruma und eine bilaterale knotige Nebennierenrindenhyperplasie. Dies ist das voll ausgeprägte Bild einer MEA Typ I (Wermer-Syndrom). Außerdem hatte er ein medulläres Schilddrüsencarcinom.Bei 14 Familienangehörigen ergaben sich Hinweise auf primären Hyperparathyreoidismus (pHPT), darunter waren 5 Patienten mit Nierensteinen. Die bei 3 Personen exstirpierten Epithelkörperchen erlaubten eine histologische Bestätigung der Diagnose pHPT. Die nach Möglichkeit mehrmals durchgeführte Bestimmung des Calcium- und Phosphatspiegels im Serum spielte eine Hauptrolle bei der Entdeckung von asymptomatischen Trägern des Gens.6 Patienten hatten Magen-Darmulcera: darunter waren 5 Patienten mit sicherem oder wahrscheinlichem pHPT, von denen aber nur einer (II 1) ein Gastrinom und eine Inselzelladenomatose hatte. Drei Patienten hatten eine Pankreatitis, bei zwei von ihnen nachweislich kombiniert mit pHPT. — Zweimal fand sich eine euthyreote Struma, einmal eine hyperthyreote Struma. Zwei Familienangehörige hatten erhöhte Plasmacortisolwerte; Lipome im Unterhautfettgewebe hatten ebenfalls zwei Patienten. Der Befund eines Alpha-1-Antitrypsinmangels (ZZ Phänotyp) bei zumindest 2 Patienten mit pHPT läßt an eine genetisch bedingte Verknüpfung des Defektallels Z mit der MEA Typ I denken. Weitere Familienuntersuchungen sind für eine Beweisführung notwendig.Ein Polyp im Jejunum mit heterotoper Magenschleimhaut (Fundus- und Pylorusdrüsen) ausgekleidet und blutend wurde bei diesem Syndrome noch nicht beschrieben. Der Befund wird von uns als Entwicklungsstörung des Entoderm aufgefaßt. Das bei einem Patienten (II 1) gefundene medulläre Schilddrüsencarcinom zeigt, daß die Trennlinie zwischen MEA Typ I und MEA Typ II nicht immer scharf gezogen ist.