Clinical and immunological evaluation of 20 patients with advanced colorectal cancer treated with high dose recombinant leukocyte interferon-αA (rIFNαA)

Summary A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-A (rIFNA) either chronically (group I: twice a week up to 20×10⁶ IU/m² i.m.) or cyclically (group II: 1–4 periods of 8 consecutive days up to 20×10⁶ IU/m² i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was >25% (P=0.05), extrahepatic disease was extensive (P<0.005), alkaline phosphatase level was >2× normal (P<0.02), or performance status was <100% (P<0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFNA led to a short lived augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon- production capacity was significantly stimulated during rIFNA therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.This trial was supported in part by Hoffmann-La Roche, Basle     

On the Phospholipid Metabolism of Glial Cell Primary Cultures.

Abstract: Primary cultures were prepared from newborn rat brain. After 16-18 days, they consisted mainly of mature and immature astrocytes and oligodendrocytes, as judged by immunohistochemistry. To study the metabolism of ethanolamine glycerophospholipids, the cells were incubated with 1-[1-³H]alkyl- sn -glycero-3-phosphoethanolamine (1-alkyl-GPE), for 1–20 h. Five main products were formed: 1-alkyl-2-acyl-GPE; 1-alkyl-2-acyksn-glycero-3-phosphocholine (1-alkyl-2-acyl-GPC); 1-alkenyl-2-acyl-GPE (ethanolamine plasmalogen); 1-alkenyl-2-acyl-GPC (choline plasmalogen); and 1-alkyl-glycerol. Acylation of the substrate was the main reaction during the first 3 h of incubation, whereas desaturation to plasmaiogen reached a maximum after 12 h. Greater amounts of radioactivity were observed in the phosphatidylcholine fraction after longer incubation times. Only small amounts of choline plasmalogen were observed. The phosphatidylethanolamine fraction consisted of 26.5% diacyl-, 27.5% alkyl-acyl-, and 46.0% alkenyl-acyl- compounds, whereas the corresponding data for the phosphatidylcholine fraction were 78.5, 16.4, and 5.1%, respectively, after 20 h of incubation. Hydrolysis of the substrate to 1-alkyl-glycerol was a minor reaction.     

The recognition specificity of a murine helper T cell for hemagglutinin of influenza virus A/PR/8/34

Human large granular lymphocytes (LGL), which are known to be responsible for natural killer (NK) cell activity, also produced a variety of lymphokines including interleukin 2 (IL 2), colony stimulating factor (CSF), and interferon (IFN) in response to phytohemagglutinin (PHA) or concanavalin A (Con A). Human peripheral blood LGL, which were purified by removal of monocytes adhering to plastic flasks and nylon columns, followed by separation on a discontinuous Percoll gradient, and additional treatment with anti-OKT3 and Leu-M1 plus complement, were more potent producers of these lymphokines than unseparated mononuclear cells (MNC), nylon column-eluted cells, or purified T lymphocytes. Moreover, IL 2 production by LGL could be further distinguished in that it was not enhanced by the addition of macrophages or macrophage-derived factor, i.e., IL 1, whereas addition of macrophages did potentiate IL 2 production by T lymphocytes. Further analysis of cells in the LGL population using various monoclonal antibodies revealed that removal of cells with OKT11 or AF-10, a monoclonal antibody against human HLA-DR antigen, decreased IL 2 production, whereas removal of OKT8+, OKM1+, Leu-M1+, or Leu-7+ cells led to enhanced IL 2 production. The LGL population is therefore heterogeneous and includes at least three functionally and phenotypically distinct subsets. An atypical T cell subset (OKT3-, Leu-1-, OKT11+) rather than the myeloid subset of LGL (Leu-M1+ or OKMI+) was the source of LGL-derived IL 2, whereas the latter subset and/or another subset of OKT8+ cells appear to regulate this IL 2 production. In addition to performing NK activity, LGL on a per cell basis seem to be more effective than T lymphocytes in producing lymphokines, namely, IL2, CSF, and IFN.     

Hybrid enzyme molecules reconstituted from mixtures of wild-type and mutant Escherichia coli -galactosidase

Subunits in hybrid β-galactosidase reconstituted from wild type and a lac_aba⁻-mutant protein behave as independent units of activity. Under certain conditions for renaturation or denaturation of the hybrid enzyme molecules, subunits exert an influence on neighbouring subunits, rendering the whole hybrid molecule active or inactive.     

Über die Gefässe,die Faszikel und das Bindegewebe der Nerven während des Wachstums

Zusammenfassung Die Gefäße sprossen während zweier Wachstumsphasen in den Nerv ein: bei 11 cm langen Feten liegen 125 Gefäße innerhalb des N. tibialis (R. poplitea), auch bei 23 cm langen Feten finden sich etwa gleichviel Haargefäße im Endoneuralraum. Bei 39 cm langen Feten hat sich die Kapillarzahl etwa verdreifacht. Die Kapillarzahl pro Quadratmillimeter Endoneuralraum ist tabellarisch zusammengefaßt, die kritische Schichtdicke für einzelne Altersstufen errechnet worden.Bereits beim 11 cm langen Feten sind innerhalb des Nerven zarte Septen zu erkennen, aus denen sich bei 16 cm langen das Stratum lamellare perineurii entwickelt hat. Die Zahl der Lamellen vermehrt sich während des intrauterinen Lebens bis auf fünf. Das Stratum fibrosum perineurii et epineurii entwickelt sich erst beim über 35 cm langen Feten. Als erste Bindegewebsstruktur legen sich Teile des interfaszikulären Bindegewebes in Form von dreieckigen Zwickeln um die größeren Nervengefäße. Gleichzeitig runden sich die vorher eckig begrenzten Nervenfaserbündel ab. Während des intrauterinen Wachstums verdicken sich die Faszikel stetig. Allerdings schwanken Zahl und Durchmesser der Faszikel eines Nervs erheblich (Tabelle 2).Das Nervenbindegewebe nimmt während des Wachstums kontinuierlich zu (Tabelle 3). An der Umbiegungsstelle des N. tibialis sind die Faszikel vermehrt und verkleinert. Außerdem lassen sich mehr Bindegewebsanteile am Nervenquerschnitt ermitteln (Tabelle 4).In Injektionspräparaten von Nerven alter Menschen sind endoneurale Degenerationsherde (Renautsche Körperchen) aufgefunden worden. Da innerhalb der betroffenen Faszikel die Kapillarzahl um die Anzahl der Degenerationsherde vermindert ist, wird angenommen, daß diese Gebilde untergegangen und nekrobiotisch veränderten Kapillaren entsprechen.Diese Deutung wird gestützt durch Befunde an Kapillaren in der Umgebung der Degenerationsbezirke, deren Grundhäutchen verdickt und hyalinisiert sind.Im gelähmten Nerv nimmt das Bindegewebe relativ zur schrumpfenden Nervensubstanz zu.Herrn Professor Dr. Fritz Wassermann zum 80. Geburtstag in Verehrung gewidmet.     

Inhibition of Swarming of Proteus by Sodium Tetradecyl Sulfate, β-Phenethyl Alcohol,and p-Nitrophenylglycerine

The effects of sodium tetradecyl sulfate (STS), β-phenethyl alcohol (PEA), and p-nitrophenylglycerol (PNPG) on motility, swarming, flagellation, and growth of Proteus were examined. Growth-inhibitory concentrations (GIC) and swarming-inhibitory concentrations (SIC) were determined. A characterization of the swarming-inhibitory efficacy of these compounds was based on their GIC/SIC ratio and their concentration inhibition curves. Using the homologous series of sodium alkyl sulfates as a standard reference, we showed that PNPG was more effective than STS, which was the most effective of the homologous series. PEA was less effective than sodium decyl sulfate but more effective than sodium octyl sulfate. Motility tests in liquid medium and electron microscope investigations indicated that the modes of action of the three compounds, all of which effectively inhibit the swarming of Proteus, are different. Whereas STS and PEA inhibit swarming by inhibition of motility, PNPG seems to act on the swarming mechanism sensu strictori, without impairment of motility. STS immobilizes by inhibition of flagellum formation or by some lytic action on the flagella already synthesized. PEA acts by impairing flagellar function, but leaves the flagella morphologically intact.     

Über die reaktiven Veränderungen des Trabeculum corneosclerale im Primatenauge nach Einwirkung von Hyaluronidase

Zusammenfassung Einmalige Injektionen von 75–150 IE Hyaluronidase in die Augenvorder-kammer oder den Glaskörper führten am Trabekelwerk höherer Affen (Cercopithecus aeth.) in wenigen Tagen zur Auflösung der homogenen Substanzen des Lamellenkernes und zur Ablösung der Trabekelendothelien. Stellenweise wurden die Trabekel vollständig aufgelöst. Die abgelösten Trabekelendothelien zeigten elektronenmikroskopisch eine Vermehrung des Retikulum und der freien Ribosomen. Phagocytierte Zelleinschlüsse waren nachzuweisen. Die vergrößerten Kerne enthielten zahlreiche Nukleoli und wenig Chromatin. Inflammatorische Reaktionen waren nicht erkennbar. Stellenweise kam es zur Bildung größerer Symplasmen mit zahlreichen, aktivierten Kernen. Je nach Dosis regenerierte das Zell- und Lamellensystem des Trabekelwerkes in 7–10 Tagen vollständig.Durch mehrmalige Injektionen von Hyaluronidase in den Glaskörper konnten außer den beschriebenen Auflösungs- und Reparationsvorgängen erstmalig am Trabekelwerk auch proliferative Prozesse ausgelöst werden, die teilweise zur vollständigen Verlötung des Kammerwinkels und Obliteration des Schlemmschen Kanals führten. Der Mechanismus dieses Proliferationseffektes wird diskutiert.Ein Teil dieser Untersuchungen wurde in dankenswerter Weise durch die Deutsche Forschungsgemeinschaft unterstützt.