2-Carboxyethylgermanium sesquioxide,a synthetic organogermanium compound,as an inducer of contrasuppressor T cells

2-Carboxyethylgermanium sesquioxide (Ge-132), a synthesized organogermanium compound with immunomodulaing activities, was shown to be an inducer of anti-suppressor T cells in normal mice. The suppressor cell activity of T6S cells, a clone of burn-induced CD8⁺ IL-4-producing suppressor T cells, was clearly inhibited when a mixed lymphocyte-tumor cell reaction of the clone was conducted with splenic mononuclear cells from mice treated orally with a 100 mg/kg dose of Ge-132. The activity of anti-suppressor cells was demonstrated in spleens of mice 2 days after treatment with Ge-132 and reached its peak on day 3. The anti-suppressor cells induced by the compound were of a contrasuppressor T cell-linage, because they were characterized as CD4⁺ CD28⁺ TCR/⁺ Vicia villosa lectin-adherent T cells. These cells produced IFN- but did not produce IL-2, IL-4, IL-6 or IL-10 in their culture fluids. CD4⁺ anti-suppressor T cells induced by Ge-132 may be different from other subsets of CD4⁺ T cells because Th1 and Th2 cells generated in our laboratory did not adhere toVicia villosa lectin-coated petri dishes, and each produced specific cytokines. Th1 cells produced IFN- and IL-2 while Th2 cells produce IL-4 and IL-10 in vitro. These results suggest that Ge-132 may be useful as an inducer of contrasuppressor T cells in immunocompromised individuals bearing suppressor T cells. To eliminate suppressor T cells from immunocompromised hosts may result in improved resistance from various opportunistic infections.     

Two cell-free systems for the assay of virus-specific polymerase

, - : - No 199. , ( 3- ) , .     

Comparative analysis of human milk and human blood plasma by means of diffusion-in-gel methods

Zusammenfassung Mit Hilfe von Immunoelektrophorese und Doppeldiffusiontechnik wurden in Humanmilch an Blutplasmaproteinen serologisch identifiziert: Praealbumin, Albumin, Acid Seromucoid, ₁-Glykoprotein (3·5 S), Coeruloplasmin, Haptoglobin, ₂- oder-Lipoprotein, Transferrin, Fibrinogen, _2A-Globulin, _2M-Globulin und-Globulin.     

Fusimotor effects on position and velocity sensitivity of muscle spindles

Zusammenfassung Primäre und sekundäre Muskelspindelendigungen der Katze wurden mit sowie ohne statische und dynamische -Aktivierung, bei periodischer Dehnung und Entspannung über einen weiten Geschwindigkeitsbereich untersucht. Es wurde die Lage- und Geschwindigkeitsempfindlichkeit bestimmt; dabei wurden 2 Typen statischer -Effekte bei den primären wie auch sekundären Endigungen beobachtet.

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This work was supported by the Swedish Medical Research Council (Project No. 14X-544-02), and by Karolinska Institutet (Reservationsanslaget för främjande av ograduerade forskares vetenskapliga verksamhet).     

Der Einfluss der γ-Globuline auf die Viskosität

Summary Depending on concentration of fibrinogen, increasing concentrations of -globulines cause an exponential increase of viscosity, which is more pronounced, the higher the basic concentration of fibrinogenis. Fibrinogen that is dependent on -globulines and albumin, -globulines that is dependent on albumin, or albumin that is dependent on fibrinogen and -globulines do not show this behaviour.

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Für die zuverlässige Mitarbeit sei der biochem.-techn. Assistentin, Fräulein Ilse Stelter, gedankt.     

HCN channels contribute to the intrinsic activity of cochlear pyramidal cells

A hyperpolarization-activated current recorded from the pyramidal cells of the dorsal cochlear nucleus was investigated in the present study by using 150- to 200-m-thick brain slices prepared from 6- to 14-day-old Wistar rats. The pyramidal neurones exhibited a slowly activating inward current on hyperpolarization. The reversal potential of this component was –32 ± 3 mV (mean ± SE, n = 6), while its half-activation voltage was –99 ± 1 mV with a slope factor of 10.9 ± 0.4 mV (n = 27). This current was highly sensitive to the extracellular application of both 1 mM Cs⁺ and 10 M ZD7288. The electrophysiological properties and the pharmacological sensitivity of this current indicated that it corresponded to a hyperpolarization-activated non-specific cationic current (I_h). Our experiments showed that there was a correlation between the availability of the h-current and the spontaneous activity of the pyramidal cells, suggesting that this conductance acts as a pacemaker current in these neurones. Immunocytochemical experiments were also conducted on freshly isolated pyramidal cells to demonstrate the possible subunit composition of the channels responsible for the genesis of the pyramidal h-current. These investigations indicated the presence of HCN1, HCN2 and HCN4 subunits in the pyramidal cells.Received 15 May 2003; received after revision 26 June 2003; accepted 21 July 2003     

Aminoacidi della Perilinfa

Summary The following aminoacids have been detected in the perilymph from horses by filter paper chromatography: aspartic acid, glutamic acid, phosphocolamine, glycine, serine, taurine, threonine, alanine, glutamine, lysine, arginine,-aminobutyric acid, proline, valine, leucine, tyrosine, phenylalanine, cystine.A comparative study of chromatograms obtained from blood, perilymph and liquor showed that the perilymph is much more similar to the blood than to the cerebrospinal fluid either for qualitative and for quantitative content in aminoacids.     

Gewinnung präzipitierender Insulin-Antikörper von der Ziege,Caper domesticus

Summary Antiserum was produced against beef insulin in male goats (goat anti-insulin-serum). It contains precipitating insulin antibodies; they were identified by immunelectrophoresis as a fraction of-globulin.     

Bovine microvascular endothelial cells of separate morphology differ in growth and response to the action of interferon-γ

Five cell types recently isolated from the bovine corpus luteum differed in their epithelioid morphology and their cytoskeleton, but shared common criteria of microvascular endothelial cells^1,2. To give strong evidence for the separate entity, the growth rate of the 5 phenotypically different cells was studied. They were seeded at low density on day 0. Most of these cells were treated with 200 to 1000 U recombinant bovine interferon- (IFN-) for 3 days. The untreated remainder served as controls. Cell counts were made for all cultures on days 4, 7, 10 and 13. morphology: 13 d after treatment with IFN- senescent cells as well as intact cells occurred in cultures of cell types 1 to 4. Cultures of cell type 5 were apparently unchanged and resembled their untreated counterparts. Desminpositive cells in cultures of cell type 2 developed cell processes. Growth rate: In the absence of IFN-, the growth rate was high for cell types 3 and 4, moderate for cell type 1, and low for cell types 2 and 5. The presence of IFN- caused anti-proliferative effects. These were higher for cell types 3 and 4 than for cell types 1 and 2. IFN- could be cytotoxic on cell type 3. In contrast, the cytokine tended to support the cell growth of cell type 5. These findings substantiate the postulate that endothelial cells exhibiting separate morphology in culture also function differently.     

Chromatography of mast cell sensitizing antibodies in guinea-pigs

Résumé L'inoculation intraveineuse d'albumine humaine (HA), provoque chez le cobaye l'apparition d'un anticorps (-1) sensibilisant les cellules mast (CM) homologues. L'inoculation dans le coussinet plantaire (HA et adjuvant de Freund complet) fait apparaître deux anticorps: l'un (-2) sensibilisant les CM hétérologues, l'autre (dans le-1 ainsi que dans le-2) sensibilisant les CM homologues.

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We thank Mrs.Nava Raz, Mrs.Tamar Minai and Mr.I. Ofek for technical assistance.     

The molecular mechanisms of congenital hypofibrinogenaemia

Congenital hypofibrinogenaemia is characterized by abnormally low levels of fibrinogen and is usually caused by heterozygous mutations in the fibrinogen chain genes (, and ). However, it does not usually result in a clinically significant condition unless inherited in a homozygous or compound heterozygous state, where it results in a severe bleeding disorder, afibrinogenaemia. Various protein and expression studies have improved our understanding of how mutations causing hypo- and afibrinogenaemia affect secretion of the mature fibrinogen molecule from the hepatocyte. Some mutations can perturb chain assembly as in the 153 Cys Arg case, while others such as the B Leu Arg and the B414 Gly Ser mutations allow intracellular hexamer assembly but inhibit protein secretion. An interesting group of mutations, such as 284 Gly Arg and 375 Arg Trp, not only cause hypofibrinogenaemia but are also associated with liver disease. The nonexpression of these variant chains in plasma fibrinogen is due to retention in the endoplasmic reticulum, which in turn leads to hypofibrinogenaemia.Received 17 December 2003; received after revision 19 January 2004; accepted 21 January 2004     

A new type of antigen induced by chemical linkage ofMycobacterium tuberculosis and γ-globulin

Zusammenfassung Mit Hilfe derPauly'schen Diazo-Reaktion wird humanes -Globulin an humanpathogene, virulenteMycobacterium tuberculosis-Stämme (M) gekoppelt. Das Zustandekommen der chemischen Bindung wurde mit gefärbten Präparaten, elektronenmikroskopischen und immunelektrophoretischen Untersuchungen der Bakterien bewiesen. Die mit-Globulin gekoppeltenM haben ihre Virulenz eingebüsst. In den Versuchstieren wurden Antikörper sowohl gegen -Globulin als auch gegenM gebildet. Durch ersteres wurde das Allergisierungsvermögen vonM gesteigert.     

Reaction of pyridoxal-5′-phosphate with γ-carboxyglutamic acid

Summary Pyridoxal-5-phosphate (PLP) reacts with -carboxyglutamic acid (Gla) to form a stable complex absorbing at 325 nm. It is suggested that a condensation occurs in which the formyl group of PLP reacts with the -amino group and the carbon atom of Gla to give a pyrrolidine derivative.     

Radioprotective effects of the immunostimulating lauroylpeptide LtriP (RP 56142)

The lipopeptide lauroyl-L-Ala--D-Glu-L,L-A₂pm (LtriP) increased the resistance of mice to the lethal effect of -ray irradiation. The radioprotective effect was dependent on the doses of LtriP and of radiation. Maximum survival was observed when the lipopeptide was injected on two successive days before irradiation. This activity seems to be related to immunostimulating functions, since the non-immunostimulating analog lauroyl-L-Ala--D-Glu-D,D-A₂pm-Gly, containing D,D-diaminopimelic acid, was not radioprotective. The protective activity might result from an induction of cytokines, such as IL-1, TNF and M-CSF, since LtriP induced the mRNA expression and the secretion of these immunomodulators.     

Das Prinzip der Äthylogie in der organischen Chemie

Summary The concept of ethylogy is introduced to correlate reactions of compounds of the typea-C-X and those of their ethyloguesa-C-C-C-X,a being a group capable of electron donation andX an electron-accepting leaving group.Besides normal substitution and elimination ofX ina-C -C -C -X, the latter type of compound may undergo cleavage of the C -C bond. This fragmentation produces an olefin in addition to the products also derivable from the simpler compounda-C-X. A number of such fragmentation reactions are reviewed.In the case of-halo amines, there are indications that, depending on structure and stereochemistry, fragmentation can occur by a one-step or two-step process. It is considered likely that the duality and merging of mechanism encountered in simple systemsa-C-X will also prevail in the fragmentation of their ethylogues.     

Structure specificity of some immunoadjuvant synthetic glycopeptides

Summary The immunoadjuvant activity of muramyl dipeptide seems to be critically dependent on the type of substitution of the -carboxyl group of the D-isoglutamine residue. Moreover the nonapeptide L-Ala-D-isoGlu-L-Lys-D-Ala-(Gly)₅-OME also shows a definite effect.     

Cardenolide glycosides from the adults and eggs ofChrysolina fuliginosa (Coleoptera: Chrysomelidae)

Besides the known sarmentogenin 3-O--D-allopyranoside (1) and digitoxigenin-3-O-[-D-xylopyranosyl-(14)-2, 3-di-O-acetyl--D-allopyranoside] (4), four new cardiac glycosides (2, 3, 5 and6) have been isolated from the defensive glands of adults ofChrysolina fuliginosa. The structures of the new compounds were determined by¹H NMR at 600 MHz and FABMS. Compounds1–6, present in the adults ofC. fuliginosa, have also been identified in the eggs.     

Development of γ-glutamylcysteine synthetase and oxoprolinase in rat kidney

Summary -Glutamylcysteine synthetase is present in barely detectable amounts in foetal kidney. Its activity starts to increase in postnatal life. In contrast, oxoproline is already found in significant quantities in the foetal tissue. Both enzymes show marked elevation in activities during the weaning period.Acknowledgment. The work was supported by a research grant awarded by the Committee on Research and Conference Grants, University of Hong Kong.     

Effect of dibutyryl cAMP and theophylline on cultured rat embryonic shields

Summary Effects of N⁶, O² dibutyryl adenosine 3,5-cyclic monophosphate (db-cAMP) and theophylline (Th) on cultured rat embryonic shields were studied. After addition of db-cAMP to the culture medium, an increase of the weight of explants and of the incidence of the skeletal muscle was observed. Theophylline seems to be ineffective.