Effect of antihepatocytotoxic serum on DNA synthesis in the rat

Incorporation of thymidine-³H into parenchymatous and reticulo-endothelial cells of the liver was studied autoradiographically in adult female rats treated with small doses (0.06 g/100 g body weight per injection) of antihepatocytotoxic serum (AHTS), the -globulin isolated from it (AHTS), and the -globulin fraction of normal rabbit serum (NRS) to intact animals and to rats with liver damage caused by carbon tetrachloride (CCl₄). Following injection of AHTS and, to a lesser degree, of AHTS into intact animals the index of labeled nuclei of both the parenchymatous and the reticulo-endothelial cells was increased. When given after preliminary CCl₄ administration, AHTS stimulated reparative regeneration. The action of AHTS took place in phases: A period of increase in the index of labeled nuclei was followed by a period of decrease, and this again was followed by a fresh period of stimulation of proliferative processes.Department of Immunology and Cytotoxic Sera, A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Gorev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 75–78, July, 1978.     

Transmural distribution of antioxidant defences and lipid peroxidation in the rabbit left ventricular myocardium

The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, -glutamylcysteine synthetase and -glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H₂O₂-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocarium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury.     

Periodic administration of vitamin B2 and its effect on demand

Summary This experiment took 90 days and was performed on rats. It was established that when vitamin B₂ is introduced with the interval of one week in the dose of 20 per day, its action is decreased by four times in comparison with that when the vitamin is given daily. If the interval between the feedings equaled 2 weeks the action of vitamin B₂ decreased even more. Increase in weight was taken as a criterion of vitamin B₂ activity.The above data allow us to recommend systematic administration of vitamin B₂.Submitted by Active Member Acad. Med. Sci. USSR B.A. Lavrov     

Nachweis der Plasmocytom-γ-Globuline und ihrer Individualspezifität mit der Stärkegel-Elektrophorese

Zusammenfassung Mit der Stärkegel-Elektrophorese nachSmithies wurden an 76 _ss- und 30 _1A-Plasmocytom-Seren folgende Befunde erhoben:1. Plasmocytom--Globuline sind im Gegensatz zu den Befunden der Papierelektrophorese nicht homogen, sondern aus mehreren Komponenten zusammengesetzt. Anordnung, relative Konzentration und Lokalisation dieser Komponenten sind für den einzelnen Patienten konstant und charakteristisch, also individualspezifisch.2. Die Heterogenität des _1A-Plasmocytom-Globulins ist durch höhermolekulare Anteile bedingt, die sich als distinkte Banden im Stärkegel nachweisen und durch Cysteamin dissoziieren lassen.3. Bei _ss-Plasmocytom-Globulinen werden zwei Typen beobachtet: a) In der Mehrzahl der Fälle sieht man multiple, maximal sieben bis neun Komponenten, die im Einzelserum durch gleiche Breite und regelmäßige Abstände gekennzeichnet sind; sie können sich annäherungsweise in ihrer relativen Konzentration einer Gauss-Verteilung unterordnen oder zeigen in anderen Fällen eine kathodenwärts zunehmende Konzentration. b) Bei ca. 1/4 der Seren wurde keine Unterteilung in mehrere Komponenten erreicht.4. Auch die nach Papainspaltung⁴⁴ isolierter _ss-Globuline entstehenden Fragmente sind in mehrere Komponenten unterteilt; charakteristische und ebenfalls individualspezifische Unterschiede zwischen normalen und abnormen _ss-Globulinen sind im S-Fragment nachweisbar⁴⁵.5. Die Stärkegel-Elektrophorese kann als zuverlässiges und reproduzierbares Verfahren die Immunoelektrophorese in der Erkennung abnormer -Globuline ergänzen bzw. ersetzen. Dies gilt besonders für den Nachweis und die Identifizierung von Bence-Jones-Proteinen im Harn und Serum und von sog. -Plasmocytomen.6. Die Untersuchungen zeigen, daß erworbene Anomalien der Proteinsynthese individualspezifisch sind. Die Befunde werden im Hinblick auf die Proteinsynthese in den Plasmazellen diskutiert.

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Summary Report on starch-gel electrophoresis studies on 76 sera of _ss-myeloma and 30 sera of _1A-myeloma. Most myeloma-_ss-globulins are not homogeneous but heterogeneous. Concentration and localization of these components are individually different. Heterogeneity of _1A-myelomaglobulins is dependent on higher molecular species, lacking after dissoziation by 2-mercaptoethanol. There exist two types of _ss-myeloma-globulins: a) in most cases starch-gel electrophoreses reveals multiple bands characterized by regularity of closely spaced periodic intervals; relative concentration of the bands may be distributed in some cases like a Gauss-curve or may increase in other cases to the cathodic end of the starch-gel strip. b) A single band was found in about 1/4–1/5 of the _ss-myeloma sera. — The papain-fragments of _ss-myeloma globulin also are composed of multiple components; individually specific differences were found in the S-fragments whereas F-fragments were identical with those of normal _ss-globulin. -myeloma often reveals an abnormal component in the post-albumin region (between albumin and transferrin), corresponding to the Bence-Jones protein of the urine.The findings favor the possibility that the single clone of plasma cells in myeloma forms multiple protein components. Consequently we may assume that the single plasma cell synthesizes a group of closely related proteins.

     

Modulation of L-type Ca channel activity by P2-purinergic agonist in cardiac cells

The mechanism of enhancement of the L-type Ca current by a P₂-purinergic agonist adenosine-5-O-(3-thiotriphosphate) (ATPS) was studied by recording single channel activity from cell-attached patches on rat isolated ventricular cells using patch pipettes containing 110 mM Ba²⁺. The application of ATPS to the patch membrane through the pipette solution did not affect single channel activity. The addition of ATPS to the bath containing a depolarizing solution was ineffective due to the voltage dependence of the purinergic stimulation. Bath application of ATPS (100 M) to control 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES) solution increased the amplitude of ensemble average currents both by decreasing the probability of a blank sweep occurring and by increasing the number of openings per non-blank sweep. The single channel conductance (17 pS) was not changed by ATPS. Both activation and inactivation curves were shifted towards hyperpolarized potentials by about 10 mV under P₂-purinergic stimulation. Since ATPS increased channel activity when applied via the bath, it must be supposed that a diffusible messenger is involved.     

Inhibitory effects ofγ-interferon on bradykinin-induced bone resorption and prostaglandin formation in cultured mouse calvarial bones

The effects of mouse recombinant-interferon (-IFN) and indomethacin on bone resorption stimulated by bradykinin, Lys-bradykinin, Met-Lys-bradykinin, des-Arg⁹-bradykinin and prostaglandin E₂ (PGE₂) have been studied using cultures of neonatal calvarial bones and analyzing the release of⁴⁵Ca from prelabelled bones as a paramenter of bone resorption. In addition, the effects of-IFN and indomethacin on formation of PGE₂ in bone cultures stimulated by bradykinin was analyzed. Indomethacin (1 mol/l) totally abolished bradykinin (1 mol/l) induced⁴⁵Ca release. The inhibitory effect of indomethacin could be fully reversed by addition of PGE₂ (1 mol/l).-IFN (1000 U/ml) almost totally inhibited⁴⁵Ca release stimulated by bradykinin (1 mol/l), but the inhibitory effect could only be partially overcome by PGE₂.-IFN and indomethacin also inhibited the stimulatory effects of Lys-bradykinin, Met-Lys-bradykinin and des-Arg⁹-bradykinin (1 mol/l) on⁴⁵Ca release. The stimulatory effects of PGE₂ (1 mol/l) on radioactive calcium mobilization was partially inhibited by-IFN (1000 U/ml), whereas indomethacin (1 mol/l) was without effect. The inhibitory effect of-IFN on⁴⁵Ca release stimulated by bradykinin and PGE₂ was dose-dependent with threshold for action at 3–30 U/ml. Comparative dose-response curves showed that-IFN was most potent as inhibitor of bradykinin induced⁴⁵Ca release. Bradykinin (1 mol/l) significantly stimulated PGE₂ formation by a mechanism that was completely inhibited by indomethacin (1 mol/l).-IFN (1000 U/ml) partially inhibited the stimulatory effect of bradykinin on PGE₂ formation. These data show that i)-IFN is a potent inhibitor of bone resorption induced by bradykinin and bradykinin analogues and ii) that the mechanism of action can be mainly explained by an inhibition of kinin induced prostaglandin biosynthesis. The results, however, also show that-IFN can inhibit bone resorption by mechanisms unrelated to prostaglandin formation.     

Effect of antihepatocytotoxic serum on cellular and intracellular regeneration of the pathologically changed liver

Parameters of regeneration of the liver (mitotic index, DNA synthesis, volume of hepatocyte nuclei, and histological structure) were studied in experiments on adult male rats with liver damage induced by CCl₄ and receiving injections of antihepatocytotoxic serum (-AHCS) during regeneration of the liver after CCl₄ poisoning; cellular and intracellular forms were found to predominate at different times. -AHCS given in a dose of 0.06 g protein/100 g body weight per injection stimulates and prolongs regeneration of the liver at both cellular and intracellular levels.Department of Immunology and Cytotoxic Sera, A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Gorev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp 368–370, March, 1980.     

Prostaglandin E2 Downregulates Interferon-γ-Induced Intercellular Adhesion Molecule-1 Expression via EP2 Receptors in Human Gingival Fibroblasts

In the present study, the effect of prostaglandin E₂ (PGE₂) on intercellular adhesion molecule-1 (ICAM-1) expression in interferon- (IFN-)-stimulated human gingival fibroblasts (HGF) was investigated. Addition of PGE₂ to HGF inhibited ICAM-1 expression elicited by IFN-. As PGE₂ elevated intercellular cyclic AMP (cAMP) levels in HGF in a dose-dependent fashion, the effect of dibutyryl cAMP and 8-bromo-cAMP, cAMP analogues, on IFN--elicited ICAM-1 expression was examined. Both the agents downregulated ICAM-1 expression in IFN--stimulated HGF. Next, we examined which subtype(s) of the four PGE₂ receptor subtypes (EP₁, EP₂, EP₃ and EP₄) modulated the ICAM-1 expression elicited by IFN-, using subtype-specific agonists or antagonists. An EP₂/EP₄ agonist, 11-deoxy-PGE₁, attenuated IFN--elicited ICAM-1 expression in a concentration-dependent manner. A specific EP₄ antagonist, AH-23848B, showed no effect on inhibition of IFN--elicited ICAM-1 expression by PGE₂ and 11-deoxy-PGE₁. Butaprost, an EP₂-selective agonist, mimicked inhibition of IFN--elicited ICAM-1 expression by 11-deoxy-PGE₁. An EP₃ agonist, ONO-AP-324, was inert with respect to IFN--elicited ICAM-1 expression. Sulprostone, an EP₁/EP₃ agonist, showed stimulatory effect on ICAM-1 expression elicited by IFN-. From these results, we suggest that PGE₂ downregulates IFN--induced ICAM-1 expression in HGF, primarily via EP₂ receptors by cAMP-dependent signaling pathways.     

Cell cycle-dependent repair of double-strand DNA breaks in a γ-ray-sensitive Chinese hamster cell

A Chinese hamster cell mutant has been isolated which is extremely sensitive to killing by -irradiation in the G₁, and early S phases of the cell cycle (LD₅₀ of 20 vs. 250 rads for parent), but which has nearly normal resistance in late S. The mutant cell is able to repair single-stranded DNA breaks introduced by -radiation. However, in comparison to its parental cell, the mutant is deficient in the repair of double-stranded DNA breaks produced by -irradiation during the sensitive G₁-early S period, while in the resistant late S period, the repair is nearly the same for both cell types. This correlation between -ray sensitivity and repair strongly suggests that an inability to repair double-strand DNA breaks in G₁ is the basis for the hypersensitivity of the mutant to killing by -rays in this phase of the cell cycle. It also provides direct evidence in mammalian cells that the ability to repair double-strand DNA breaks induced by ionizing radiation is an important biochemical function in cell survival and supports the hypothesis that unrepaired double-strand breaks are a major lethal lesion in mammalian cells. A plausible explanation for the appearance of the cell cycle phenotype of the mutant is that in normal cells there are at least two pathways for the repair of double-strand breaks, one of which functions primarily in late S phase, and the other, either throughout the cell cycle or only in the G₁ and early S phases.     

Combined treatment with vitamin B12b and ascorbic acid causes in vitro DNA degradation in tumor cells

Incubation of Ehrlich ascites carcinoma and HEp-2 human epidermoid laryngeal carcinoma cells with hydroxycobalamin (vitamin B_12b) and ascorbic acid induced generation and accumulation of double-stranded DNA fragments (23,000 b.p. and longer) in cells. The same vitamins alone in the same concentrations produced no such effects. DNA degradation in HEp-2 cells caused by long-term (4 h) incubation with 5-25 M hydroxycobalamin and ascorbic acid (1:10-1:40 molar ratio) at 37°C was comparable with that induced by -irradiation in a dose of 150 Gy at 4°C.     

Chromatographische, sedimentationsanalytische, immunologische und st?rkegelektrophoretische Untersuchungen an Paraproteinen

Zusammenfassung Die Seren von A-, M- und G-Paraproteinen wurden vor und nach Behandlung mit Cysteamin an Sephadex G200 gelfiltriert. Die erhaltenen Fraktionen wurden sedimentationsanalytisch und immunologisch untersucht. Die II. Fraktionen nach Gelfiltration vor und nach Cysteamin wurden an den Anionenaustauschern Sephadex DEAE und TEAE rechromatographiert. Die so erhaltenen Unterfraktionen wurden ebenfalls sedimentationsanalytisch, immunologisch und in der Stärkegelelektrophorese untersucht.Durch das Cysteamin wird bei den A-Paraproteinen aus der I. Fraktion nach Gelfiltration ein Globulin mit der Sedimentationskonstanten S=6 bis 7×10^–13 abgespalten, das auf Grund des geringeren Molekulargewichtes in der II. Komponente eluiert wird. Bei dem abgespaltenen Globulin handelt es sich nach dem Agardiffusionstest um ein atypisches A-Globulin.Bei den -Makroglobulinen wird durch Cysteamin aus der I. Fraktion nach Gelfiltration ein immunologisch aktives M-Globulin abgespalten, das eine Sedimentationskonstante S=6,34×10^–13 aufweist und in der II. Komponente eluiert wird.Die Rechromatographie der II. Fraktionen nach Gelfiltration vor und nach Behandlung der Seren mit Cysteamin an Sephadex DEAE und TEAE zeigt gegenüber der Norm ein in quantitativer und qualitativer Hinsicht abweichendes Bild. Daraus wird auf eine veränderte Primärstruktur der Paraproteine geschlossen. Auch untereinander weichen die Chromatogramme der untersuchten Seren deutlich voneinander ab. Diese Komponenten nach Rechromatographie an Sephadex DEAE sind größtenteils in bezug auf die Sedimentationskonstante einheitlich, in der Stärkegelelektrophorese sind die Komponenten heterogen. Damit ist die Individualspezifität der Paraproteine erneut belegt.

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Summary Sera of _1A, _1M and _SS paraproteins were subjected to gel filtration on sephadex G200 before and after treatment with cysteamine. The fractions obtained were examined by ultrazentrifugation and by immunological methods. The second fraction after gelfiltration before and after cysteamine treatment were rechromatographed on sephadex DEAE and TEAE. The subfractions obtained by this procedure were examined by ultrazentrifugation, immunological methods and by starchgel-electrophoresis.Cysteamine treatment causes splitting off of a globulin from fraction I after gelfiltration with S=6 to 7×10¹³. This component is eluted with the fraction II due to its low molecular weight. According to the agar diffusion test the split off globulin behaves like an atypical _1A globulin.From the ₁ macroglobulin an immunological active _1M globulin is splitt off by cysteamine. This has a sedimentation constant of S=6.34×10^–13 and is eluted with the fraction II.The second fractions after gelfiltration of sera before and after cysteamine treatment show different chromatographic patterns on sephadex DEAE and TEAE, both, quantitatively and qualitatively. It is concluded, that this is caused by a chenged primary structure of the paraproteins compared to normale globulins. There are also differences in the chromatographic patterns of sera from different patientes.The compounds after sephadex DEAE and TEAE chromatography do not differ in their sedimentation constants but they prove to be heterogenous in starchgel-electrophoresis. So far the individual specifity of the paraproteins is proved.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Über den Effekt von γ-Aluminiumhydroxyd und γ-Aluminiumoxyd auf die antigene Wirksamkeit von Tetanus- und Diphtherietoxoid im Schutzversuch am Meerschweinchen

Zusammenfassung In zwei Versuchen mit je 600 Meerschweinchen wurde die Wirkung von-Al(OH)₃ und-Al₂O₃ auf Tetanus- bzw. Diphtherietoxoid untersucht. Die für beide Adjuvantien erzielten Werte sind vergleichbar. Der Schutzversuch wurde nach den zur Zeit gültigen deutschen staatlichen Prüfungsvorschriften durchgeführt. Für je eine Toxoidkonzentration der beiden Antigenarten wurden die wirksamkeitssteigernden Einflüsse der genannten Adjuvantien gemessen und dabei festgestellt, daß-Al₂O₃ gegenüber-Al(OH)₃ unterlegen ist. Vergleichende Versuche sprechen dafür, daß zwischen den verschiedenen-Al(OH)₃-Herstellungen keine Unterschiede hinsichtlich des adjuvierenden Effektes bestehen.     

Isoenzymes of γ-glutamyl transpeptidase in liver diseases

Summary A new method for the separation of isoenzymes of-glutamyl-transpeptidase is described, using electrophoresis on acetate cellulose gel and a developing solution composed by-glutamyl-naphthylamide, and a colored diazonium compound.The method permits the separation of up to four different isoenzymes, which we called-GT₁,-GT₂,-GT₃,-GT₄, the first two showing an electrophoretic migration similar to that of ₁- and ₂-globulins and the other two to that of-globulins.The present technique has proved its usefulness in detecting isoenzymes in serum with values of total-glutamyl-transpeptidase higher than 80 U/L.The application of this method in 52 patients with different types of biliary obstruction and hepatocellular damage has shown that it provides new possibilities in differential diagnosis.     

Conjugation of acetaldehyde with cysteinylglycine,the first metabolite in glutathione breakdown byγ-glutamyltranspeptidase

Glutathione and its metabolites were examined for reactivity to acetaldehyde. When acetaldehyde was incubated with glutathione alone, there was only a slight decrease of acetaldehyde, while an apparently equimolar reaction between acetaldehyde and free sulfhydryl was observed with the addition of -glutamyltranspeptidase. Cysteinylglycine, the first metabolite in the glutathione breakdown by -glutamyltranspeptidase, showed a rapid and equimolar reactivity to acetaldehyde and such was comparable to the reaction seen withl-cysteine ord-penicillamine. In light of the chemical structure, cysteinylglycine probably conjugates with acetaldehyde to form thiazolidinecarboxylic acid derivatives, 2-methyl-thiazolidine-4-carbonyl-glycine, and if so, the alteration of glutathione metabolism by acetaldehyde during ethanol intoxication warrants further attention.     

The dissociability of different poliovirus-antibody complexes as tested by hypertonic salt solutions

Summary The dissociability of complexes formed by poliovirus and early 19S₁and late 7S₂-globulin antibody respectively was studied by the use of hypertonic sodium chloride solutions (0.6–5.0 M). The effect of high ionic strength on the neutralization kinetics was also investigated. Complexes of poliovirus and early rabbit 19S₁-globulin antibody were dissociated by hypertonic salt solutions; the dissociation being proportional to the hypertonicity. Complexes of virus and late 7S₂-globulin antibody did not dissociate in the same hypertonic milieu. In a hypertonic environment the neutralization reaction rate was reduced and equilibrium was reached at high levels of surviving virus. Following a change from iso- to hypertonic milieu the reaction between virus and 19S₁-globulin antibody rapidly reached a new level of equilibrium equal to that established when the reaction proceeded in this hypertonicity from its start. The same change in tonicity evoked no shift in the state of equilibrium established by virus and late 7S₂-globulin antibody.The poliovirus-19S₁-globulin antibody reaction obeyed pseudounimolecular kinetics only during the initial 5–10 minutes while the reaction between virus and 7S₂-globulin antibody followed pseudofirst order kinetics for 1–1 1/2 hours.Dedicated to the Honor of the 60th birthday of ProfessorSven Gard. This investigation was supported in part by Research Grant E-4360 from the National Institute of Allergy and Infectious Diseases, United States Public Health Service.The term affinity (avidity) as used here refers to the firmness of the virusantibody complex as measured by the efficiency with which infectious virus can be recovered at high concentrations of hydrogen, sodium or chloride ions.     

Elevated monocyte interleukin-6 (IL-6) production in immunosuppressed trauma patients. I. Role of FcγRI cross-linking stimulation

This study demonstrates that immunodepressed trauma patients' monocytes produce elevated interleukin-6 to adherence, bacterial, and cytokine stimulation compared to immunocompetent trauma patients' or normals' monocytes, suggesting theirin vivo preactivation possibly mediated by the hyperimmunoglobulinemia which characterizes these patients. Furthermore, stimulation of monocytes through cross-linking their FcRI induces and augments interleukin-6 (IL-6) production to subsequent stimulation both in trauma patients' (P<0.001) and in normals' (P<0.001) monocytes. As we reported earlier, immunodepressed trauma patients have an increased proportion of FcRI-bearing monocytes in their total monocyte population and here we show that those FcRI⁺ monocytes produce significantly elevated interleukin-6, suggesting a relationship between elevated monocyte interleukin-6 production and FcRI triggering. Interleukin-6 induction by FcRI stimulation is not mediated solely by FcRI-induced MØ tumor necrosis factor alpha, IL-1, or IL-1 production and is independent of MØ prostaglandin E₂ levels. Therefore, FcRI stimulation-induced elevated MØ IL-6 might contribute to the increased immunoglobulin levels posttrauma.     

Action of single dynamic fusimotor neurones on cat soleus Ia afferents during muscle shortening

Summary 1. The ability of single dynamic fusimotor (d) fibres to sustain the firing of muscle spindle primary (Ia) afferents during shortening was investigated in soleus muscles of anaesthetised cats. 2. Of 11 d fibres, 10 could maintain Ia firing during 10 mm/s shortening. Of the 7 tested at greater velocities, 5 could maintain Ia firing during shortening at velocities greater than 50 mm/s. 3. This ability was, however, critically dependent upon the timing of the stimulation. In particular, it rapidly reduced with increasing duration of stimulation before the onset of shortening. Furthermore, if appreciable stretch occurred between the onset of _d stimulation and the onset of shortening, this could greatly reduce the ability of _d fibres to sustain Ia discharge. 4. If _d neurones are on occasion phasically activated during voluntary shortening movements, their action could be an important determinant of Ia firing, even in the presence of weak _s action. Therefore in chronic recordings, observation of Ia firing during muscle shortening is not an adequate criterion for inferring _d activity.     

Die optische Rotationsdispersion isolierter Paraproteine

Zusammenfassung Die aus dem optischen Drehungsvermögen abgeleiteten Konstanten elektrophoretisch isolierterA-Paraproteine werden mitgeteilt. Die Dispersionskonstante _c weist keine Unterschiede zwischen den 3 ParaproteingruppenG,A undM auf. Der nach dem Verfahren vonMoffitt undYang ermittelte Parameterb ₀ wurde zu Schätzung des-Helixgehaltes benutzt. Er betrug in den 7 untersuchten Paraproteinen 0. Für den Parameter —a ₀ ergab sich ein Mittelwert von 276,0±35,1. FürG-Paraprotein wurde in früheren Untersuchungen ein solcher von 312,8±20,8, fürM-Paraprotein 217,9±26,7 gefunden. Der Mittelwertsvergleich zeigte Signifikanz der Konstantea ₀ für jede der 3 Paraproteingruppen.a ₀ beschreibt demnach gruppenspezifische Eigenschaften von Paraproteinen. Die für den Wert vona ₀ maßgeblichen strukturellen Voraussetzungen sind kaum bekannt. Sie werden am ehesten die die spezifischen Antigendeterminanten tragenden H-Ketten des Paraproteinmoleküls betreffen.

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Summary The constants of the optical rotatory dispersion of electrophoretically isolatedA-paraproteins are communicated. There is no difference between theG,A andM-paraprotein group with respect to the dispersion constant _c . The parameterb ₀ was measured according toMoffitt andYang. The-Helix-content calculated fromb ₀ of 7A-paraproteins was sero (0).The mean value of the parameter —a ₀ was 276±35,1. In earlier experiments it was found that —a ₀ forG-paraproteins is 312,8±20,8 and forM-paraproteins 217,9±26,7. The parametera ₀ of each group differs significantly from the others; in other words,a ₀ is group specific. The structural implications of these findings are discussed.

     

Immunoelektrophoretische Studien an Myelomseren

Zusammenfassung 17 Seren von Kranken mit klinisch gesichertem Myelom wurden mit Hilfe der Papier- und der Immunoelektrophorese untersucht. Hierbei wurde jedes Serum 1. gegen ein Anti-Normalserum, 2. gegen ein Anti-Normalserum, aus welchem das -Globulin durch Absorption entfernt wurde, in 6 von den untersuchten Fällen auch 3. gegen das spezifische Antimyelomserum sowie 4. gegen das mit physiologischem -Globulin versetzte spezifische Antimyelomserum getestet.Es konnte festgestellt werden, daß sich Myelomfraktionen wie normale Globulinfraktionen verhalten, da sie I. bei Diffusion gegen Anti-Normalserum auspräcipitieren wie die entsprechenden physiologischen Fraktionen, und da II. der gegen die Myelomfraktionen gebildete Antikörper im entsprechenden Immunserum durch ein physiologisches Antigen — hier ein -Globulin — absorbiert wird, was darin zum Ausdruck kommt, daß Myelomfraktionen gegen ein Antimyelomserum nach Absorption durch -Globulinkeine Präcipitation mehr ergeben.Im einzelnen konnte die -Globulinfraktion von 9 papierelektrophoretisch reinen -Typen in 4 Fällen alseinheitliche, in weiteren 4 Fällen alsdoppelte und in einem Fall alsweitauslaufende Präcipitationslinie differenziert werden. Ferner waren zwei ₁-Myelome, ein ₂-, einM-Myelom, sowie drei ₂-Myelome immunoelektrophoretisch darstellbar. In einem papierelektrophoretisch normalen Serum konnte mit der hier angewandten immunologischen Methode eine im ₂-Bereich gelegene Präcipitationslinie nachgewiesen werden.Herrn Prof. Dr.H. Pette zum 70. Geburtstag.     

Cytokine polarization in miliary and pleural tuberculosis

Cytokines were measured in patients with pleural effusion and miliary tuberculosis (TB). Patients with pleural effusion had significantly higher interferon-gamma (IFN-) levels (P < 0.001) in their pleural fluid as compared to that of peripheral blood of the same patients, thus exhibiting localization of predominantly Th1-type immunity in the pleural fluid. On the contrary, patients with miliary TB had higher IFN- levels in the peripheral blood as compared to their bronchoalveolar lavage fluid. Moreover, the median IFN-:IL-4 ratio in the peripheral blood of miliary TB patients was two-fold higher as compared to bronchoalveolar lavage fluid, suggesting that the cytokine profile at the disease site is skewed toward a Th2-like bias. Further, flow cytometry data revealed a significantly higher (P < 0.001) percentage of CD4⁺ pleural fluid lymphocytes expressing IFN-, whereas in the miliary TB, a nine-fold higher percentage of lymphocytes in bronchoalveolar lavage fluid expressed IL-4 in comparison with their peripheral CD4 T cells. Our data indicate, respectively, a Th1-like and Th2-like response in tuberculous pleural effusion and miliary TB, suggesting that these clinical forms of extrapulmonary tuberculosis probably reflect the extreme ends of a Th1–Th2 spectrum of the disease.