[Noradrenaline clearance in human urine]. The urinary clearance for DL-[3H] noradrenaline has been measured in four human subjects. The mean ratio of noradrenaline clearance over glomerular filtration rate was 0.93, the confidence limit for the mean at the 5% level being 0.81-1.06. These results are in perfect agreement with those obtained in dogs with the same experimental procedure. It is concluded that the urinary excretion of noradrenaline is strictly proportional to the glomerular filtration rate.


Effect of various ions on ATP determinations using the "luciferine-luciferase" system. Various salts and buffers used in routine as part of the ATP extraction procedues induce an important inhibition of the peak light emission produced by the "luciferine-luciferase" system. The nature of the anion is more important in determining the inhibitory effect than the nature of the cation. The series obtained when placing the anions studied by order of increasing effectiveness is as follows Ac- less than Cl- less than I- less than ClO4-. KClO4 appears thus as a strong inhibitor of the enzyme activity. It appears moreover to act competitively with respect to ATP, one mole of inhibitor binding per mole of ATP active site. These results are discussed in connection with the use of the "luciferine-luciferase" system for ATP and other energy-rich compounds' concentration measurements.


[Effect of prolonged glucidic starvation on the contents of starch and tannins of Blechnum brasiliense L. gametophytes]. Some Blechnum brasiliense gametophytes have been maintained in darkness, in a purely mineral medium, for the purpose of investigating the effect of prolonged glucidic starving on the amount of tannins and starch that they contain. During the first two months the tannin contents undergoes a fast decrease. The starch variations are different : a transitory increase simultaneous with the fall in tannin; a decrease after the disappearance of 3/4 of the tannin contents; and lastly, a new amylogenese which precedes the prothallus necrosis. It seems that the gametophytes, in order to survive, degrade first their tannoidic reserves, and they utilize the starch that they contain only with difficulty. This behaviour can be explained by the distribution of the two metabolites; by the acid pH of the medium, which is not very propitious to the phosphorylases activity and lastly by the presence of chlorogenic acids, which are inhibitors of those enzymes.


Release of prostaglandin-like material from isolated cat tracheal muscle by electrical and mechanical stimulation. Release of PGE-like material has been studied on the isolated continuously-superfused cat tracheal muscle using dynamic bioassay methods. The effluent of transmural electrically-stimulated cat tracheal muscle induced a contraction when superfused over the rat stomach fundus strip. This response did not alter with atropine, methysergide, phentolamine and propranolol but was inhibited by aspirin and Sc 19220. The same myotropic activity in the effluent was found when trachea was mechanically stimulated by an additional increase in tension. The effluent from mechanically- and electrically-stimulated tracheal muscle caused a definite relaxation when superfused over a second cat tracheal muscle contracted by serotonin and pretreated with propranolol. Electrically-stimulated cat trachea itself gave a relaxant response which was blocked by propranolol but potentiated by aspirin. From these results it was concluded that both electrical and mechanical stimulation can elicit a release of PGE-like material from isolated cat tracheal muscle.


[The possible protective effect of cysteine during acute alcohol intoxication]. In the experimental conditions used, cysteine administered per os together with ethanol reduces the blood alcohol levels, but does not modify significantly the rate of alcohol oxidation. No effect of cysteine administration is however observed when ethanol is injected intraperitoneally. Cysteine addition in vitro enhances ethanol consumption by liver slices and reduces at the same time 14CO2 production from [2-14C] ethanol. This effect is only observed with a high cysteine/ethanol molar ratio. The changes in the blood alcohol level resulting from cysteine administration do not appear to result from such an interaction with ethanol oxidation, but seem to be due to a delayed ethanol absorption from the gastrointestinal tract.


[Intensive albumin therapy and pressure modifications during acute coronary ischemia in the dog]. The influence, on left ventricular pressure, of an intensive human albumin administration, has been studied in eight open chest dogs, during a second myocardial ischemia produced by coronary occlusion. After elevation of plasmatic proteins, the systolic and telediastolic left ventricular pressure, the dP/dt and the cardiac rate are measured. Any hypotensive effect was not observed in the human albumin-perfused dogs, nor in another control groups of six animals.


Modification of testicular steroid metabolism in the rat during gonadotrophin administration. The administration of human chorionic gonadotrophins to adult rats stimulates the formation of testosterone, 7alpha-hydroxy-testosterone and 5alpha-androstanediol in incubated testes. When the gonadotrophins are injected for several days, the testosterone formation is maintained at a high level; however, the transformation to 7alpha-hydroxy-testosterone decreases progressively to subcontrol levels, while 5alpha-androstanediol is produced in greater amounts.


[Decrease in maximum consumption of oxygen after blockage of beta-andrenergic receptors]. VO2 max, maximum oxygen uptake, has been measured in 4 normal young men, before and after beta-adrenergic blockade (0.5 to 5 mg Pindolol by mouth). Pindolol induces bradycardia and reduces VO2 max. A statistically significant positive correlation appears between posology of Pindolol and bradycardia, this posology and reduction of VO2 max, and finally between bradycardia and reduction of VO2 max. These correlations indicate that the reduction of VO2 max is best explained by a circulatory limitation of oxygen supply to active muscles.


Voltage-current relationships in skeletal muscles of rats. (1) Thin sheets of fibres from gastrocnemius and lumbricalis muscles of rats were washed in Tris-proponiate solutions containing 0.67 to 60 mM K. The voltage-current relationship was measured by the two microelectrode technique. (2) The V-C curve was S-shaped. The steep region, sometimes including a "forbidden" voltage zone, occurred between about -40 and -70 mV when the solution contained 2 mM K. In some fibres the steep region was found to occur at more positive currents and voltages in "upward" runs (steps of increasing depolarizing currents) then in "downward" runs. The V-C curves thus revealed hysteresis loops presumably covering a negative conductance region. (3) The voltage at which the steep region occurred was a function of [K]0. The mid-point of the steep region was 50 to 60 mV more positive than EK for a particular [K]0 was about 6 mM the steep region of the V-C relationship was not conspicuous. The steep V-C region is considered to reflect depolarizing K inactivation. The near disappearance of the phenomenon at 6 mM K is thought to result from an interference of delayed rectification and depolarizing K inactivation.


Effect of sodium on voltage-current relationships in rat muscles. (1) Replacement of Tris by Na in propionate solution causes depolarizations (3-10 or more than 30 mV) in rat muscles. As a result, the resting potentials are distributed in two groups, one at about -70 mV and the other at about -40 mV. Small inward or outward currents are often sufficient for the membrane potential to switch from one level to the other. The change from the low (more positive) to the high (more negative) resting potential can also be provoked by small increases in [K] and vice versa. (2) High frequency, low-amplitude oscillations are produced by gradually repolarizing the membrane at the low resting potential level. The frequency decreases (from a high 2/sec to 5/min or less) and the amplitude increases (up to 30 mV) with further repolarization. Low amplitude oscillations are sinusoidal, high amplitude oscillations resemble pacemaker potentials in other tissues. (3) The voltage-current relationship in Na propionate solutions containing 2 mM K frequently displays pronounced hysteresis presumably covering a negative conductance region. Hysteresis is about the same in Na and Tris containing solutions at high (more than 20 mM) [K]. The results are discussed in terms of an interaction between depolarizing K inactivation and gNa activation, possibly in a channel not involved in spike production.


Relationships between eupnoeic pattern of breathing and ventilatory control in man: I. Response to airways occlusion during active lung inflation. The apnoeic response following interruption of the air flow at different levels of the inspiratory capacity (deltaVL) was studied in conscious children and adults. Changes in mouth pressure were used to measured the duration of the apnoe. The total duration of the interrupted breath (T1) was compared to mean value of the ventilatory period of the five preceding breaths (T0). A monoexponential regression could be fitted to the relationship between T1/T0 ratio and change in lung volume (deltaVL) measured at the onset of interruption: T1/T0=k-exp (S-deltaVL), S begin the sensitivity of the response to lung inflation. When T1/T0=1, the intrathoracic lung volume was called threshold volume (VTh.L.). The parameters S and VTh.L. were used for characterization of the individual importance of the Breuer-Hering inspiratory-inhibitory reflex (B.H. reflex). The high reproducibility of the T1/T0 vs. deltaVL relationship in many subjects showed the light influence of voluntary control on apnoea's duration. In each subject, S and VTh.L. were compared with ventilatory variables measured during eupnoea. A fast pattern of breathing (i.e. small inspired volume and short inspiratory duration) was associated with high value of S and low VTh.L. Moreover VTh.L. was near the tidal volume range in subjects where the B.H. reflex was the more potent. Thus, vagal afferents relating to this reflex could modulate the eupnoeic pattern of some subjects.


Relationships between eupnoeic pattern of breathing and ventilatory control in man II. Early response to transient hypercapnia. The individual importance of peripheral chemosensitive afferents was studied using a transient hypercapnia (inhalation of a 5% or a 10% CO2 in air gas mixture respectively during 4 or 2 breaths) in human conscious subjects chosen for their different eupnoeic ventilatory patterns. Calculation of the speed of change in end-tidal CO2 pressure in tracheal gas (sPETCO2) and of the rate of change in tidal volume (sVI) gave assessment for quantifying the sensitivity of arterial chemoreceptors to hypercapnia (sCO2=SVI/SPETCO2). Our results showed that, independently of any outside influence of the eupnoeic ventilatory pattern on the components of the chemical stimulus, sVI and sCO2 were found to be much smaller in subjects whose pattern of breathing was slow (i.e. having a large tidal volume). The possible causes of the weak importance of peripheral chemosensitive afferents in such subjects were discussed.


[Free amino acids in sera of Cymothoidae (crustacean, isopods, parasites of fishes) and some teleosts]. The free amino-acid composition of the sera of 4 species of Isopods Cymothoidae (Meinertia oestroides, Meinertia parallela, Emetha audouini, Anilocra physodes) are very similar, and present the same characteristics, both quantitatively and qualitatively, as those of free marine Isopods of the family Sphaeromatidae and Idoteidae. Five amino acids are preponderant (serin, prolin, glycin, alanin and taurin). The total concentration is relatively high (154.6-356.4 mg/100 ml) with respect to Decapods. In the parasites studied so far, the free amino-acid pattern (except prolin) is rather like that of the Teleost Fishes, whether they are potential hosts of Cymothoidae or not. The free amino-acid concentration of the blood of the Fishes does not seem to be impaired by the Cymothoidae parasitism.


[Free amino acids of hemolymph of marine isopods, Sphaeroma hookers Sphaeroma serratum (Flabellifera) and Idotea balthica (Valvifera)]. The total concentration of the free amino acids in the hemolymph is higher (about twice the amount in three species of marine Isopods (Sphaeroma hookeri, S. serratum and Idotea balthica) than in Decapods. In the three species so far studied, the proportions of glycine and taurine are always rather high. In the Sphaeromatidae, serine is the most concentrated amino acid while the proline concentration is comparatively low. The situation is reversed in Idotea balthica. In Crustaceans, the free amino acid composition of the hemolymph thus appears, both quantitatively and qualitatively, to be a biochemical character of marine Isopods when compared to Oniscoids Isopods and to Decapods.


Excretion of sodium and water by kidneys in situ and by transplanted kidneys following isotonic, hypotonic, iso-oncotic and hyperoncotic intravenous infusions in sodium-loaded and sodium-deprived dogs. The excretion of sodium and water following isotonic, hypotonic, iso-oncotic and hyperoncotic intravenous infusions has been investigated in the kidneys in situ and in transplanted kidneys of narcotized dogs previously submitted to sodium-enriched or-deprived diets. The fractional excretion of sodium depended basically on the cumulative effect on the kidney of the changes in plasma oncotic pressure, plasma sodium concentration, and haematocrit. The differences in excretory responses of sodium-loaded or-deprived animals did not depend on differences in the distribution of infused fluids between intra- and extravascular compartments, but to the sensitivity of the kidney itself to the direct cumulative effect of these non-specific changes in blood composition.


[Quantitative determination of blood-plasma protein fractions using micro-agar gel electrophoresis in highly pregnant dairy cows close to the day of delivery]. Ten clinically intact Jersey dairy cows in advanced pregnancy were examined and tested over a span of three hours before to seven hours after parturition. Blood was sampled from them in intervals of ten tp 20 minutes, and the blood plasma was checked total protein and the "classical" fractions. The average total protein value of the plasma samples was 6.5 g/100 ml. The albumin and alpha 1-fractions were inversely proportional the psi-globulin concentrations before, during, and after parturition. The albumin values were on a declining trend three hours prior to parturition and recommenced to rise ten minutes prior to parturition. They were relatively constant after parturition. The pri-globulins went up slightly prior to parturition, but that rise remained statistically unsecured. It is assumed that in a certain period of time from before to somewhen after parturition change of the fractions is caused by the corticoids and sexual hormones.


[Surgical treatment of gastric cancer-personal results (author's transl)]. In the years from 1964 to 1973, 672 patients with gastric cancer were treated in the Surgical Department of Medical Academy Dresden. Tumors were located in the gastric antrum in 28.9%, in the cardia-fundus region in 28,1%, in the corpus ventriculi in 18.3%, and had involved the stomach totally in 18.6%. A resection was performed in 268 cases or 50.0%. Postoperative fatality rate was 20.1% but amounted to 30% in resection of the proximal part of the stomach and in total gastrectomy. The 5-year relative survival rate was 35.0% in distal partial gastrectomy, 10.4% in proximal partial gastrectomy, 8.2% in total gastrectomy, and 20.1% for all resections. Prognosis depends on local extension and on lymph node metastasis. Results are compared with data from the literature.


Presence of the p27 antigenicity and absence of the gp52 antigenicity and leukemia virus antigens in intracytoplasmic A particles (iAp) of mouse mammary tumour origin. Using the Ouchterlony immunodiffusion method and indirect immunofluorescence tests on tissue slices the antigenic structure of iAp of mouse mammary tumour origin has further been investigated. Antisera against iAp, MTV-B particles, B particle polypeptide p27 and glycoprotein gp52, and leukemia C-type particles were used in these studies. The most prominent antigen of iAp in mammary tumours was found to be identical to the p27 antigen of B particles. This finding was not unexpected in view of recently published data by other authors showing the presence of p27 in iAp of leukemia cells and Leydig cell tumours. The p27 polypeptide is considered to be a group-specific antigen of mouse mammary tumour viruses associated with iAp of different tissue sources and inner structural components of mature B particles. On the other hand, the gp52 antigen and leukemia virus antigens were shown to be absent from iAp of mammary carcinomas. Therefore, the assumption is confirmed that the gp52 glycoprotein represents a group-specific antigen of B type viruses, presumably located at the virion surface. The failure to demonstrate leukemia virus antigens in iAp supports the suggestion that this kind of particles is not related to C type viruses.


Osmium dependent argentaffin reaction in the pancreatic islet. By applying at the ultrastructural level the silver methenamine impregnation method to glutaraldehyde-osmium fixed pancreatic tissue of Snell-Bagg mice it was found that two islet cell types show deposition of reduced silver on their secretory granules: B cells and another cell type. Histochemical analyses indicate that very likely the osmium dependent argentaffinity is due to S-S groups. After alkaline treatment the reactivity of B cells is lost, while that of the other cells remains unaffected. It is suggested that the third cell type stores the pancreatic somatostatin, an S-S containing polypeptide hormone.


Ultrastructural and cytochemical studies on the calcification of the tendon-bone joint. Ultrastructural and cytochemical studies on developing tendon-bone joints (fibrocartilage) of rats indicated that the initial calcification loci were, as in some other calcifying tissues, matrix vesicles. These membrane-bounded vesicular structures were concentrated in the spaces between the longitudinal cell columns of the fibrocartilage. Where calcification was going to start, the vesicles became denser and more osmiophilic in appearance. The first identifiable needles of apatite crystals were deposited in and close to the matrix vesicles. Where calcification was more extensive and crystals radiating from each calcification center formed a calcified spherule, the matrix vesicles were no longer deposits of minerals was noticed at the site of the initial calcification. Alkaline phosphatase activity was demonstrated in the matrix vesicles as well as in the plasma membrane of fibrocartilage cells, most intensely at the initiating site of calcification. Following potassium pyroantimonate fixation to produce electron opaque deposits of calcium, the deposits were located mainly in the mitochondria and plasma membrane of fibrocartilage cells as well as in matrix vesicles. The closer to the initial site of calcification, the stronger the cells and vesicles reacted. In the area where calcification was in progress, however, calcium was gradually lost from the cell and reversely accumulated in the matrix vesicles. The ultrastructural and cytochemical findings from this study suggested that they were of cellular origin and liberated into the matrix from cells, partly by way of budding off and partly by cell disintegration. The possible roles of matrix vesicles at the initiating sites of calcification in fibrocartilage were discussed.


A reversed jejunal segment interposition as feeding gastrostomy. Permanent feeding gastrostomies are needed for prolonged alimentation in some patients with foregut obstruction. The usual gastric flap or tube may be limited in patients with previous gastric surgery or with a small stomach. In these patients, interposition of a short, vascularized jejunal segment between the anterior wall of the stomach and the outside may be valuable. Periodic intubation is easy. Tested initially in dogs and then applied to selected patients, we have not seen ulcers, regurgitation, soiling, pain, or other complications.


The pathogenesis of optic nerve drusen. A hypothesis. Myriads of tiny perivascular drusen were found at histologic examination of the eyes of a 19-year-old patient who had pseudopapilledema and who died of a ruptured intracranial aneurysm. The possibility that they arose from constituents leaking from abnormal blood vessels prompted a review of 53 fluorescein retinal angiograms of patients with optic nerve drusen. As compared to a control group, many of these angiograms revealed the following abnormalities: (1) an abnormal branching pattern on the disc; (2) the presence of relatively large blood vessels connecting the superficial and deep disc circulations; and (3) increased disc capillarity. We believe that the tendency to develop optic nerve drusen results, at least in part, from a congenitally abnormal disc vasculature that allows transudation of plasma proteins that in turn serve as a nidus for the deposition of extracellular materials.


"Physiological interaction" does not explain the H-2 requirement for recognition of virus-infected cells by cytotoxic T cells. B10.A (H-2Kk, H-2Dd) ectromelia-immune T cells from secondary responses in vitro were protent killers of both infected L929 (H-2Kk H-2Dk) and infected P-815 (H-2Kd, H-2Db) target cells. Specific competition with unlabelled targets showed that two separate T cell subsets were responsible for lysis of infected L929 and infected P-815 cells. One hypothesis to account for this (a form of "physiological interaction") is that T cells which kill one target e.g. infected L929) display only one out of two possible self-complementary recognition structures, in this example the H-2Kk alloantigen, not H-2Dd, whereas T cells that lyse infected P-815 targets display only H-2Dd, not H-2Kk. This hypothesis was tested and seems untenable because of the following results: A.TH (H-2Ks, H-2Dd) ectromelia-immune, secondary cytotoxic T cells which killed infected SJL/J (H-2Ks, H-2Ds) targets were themselves inactivated by pre-incubation with SJL/J cytotoxic T cells generated in one-way mixed lymphocyte reaction (MLR) against BALB/c (H-2Kd, H-2Dd). A.TL (H-2Ks, H-2Dd) ectromelia-immune secondary cytotoxic T cells which killed infected BALB/c targets were themselves inactivated by BALB/c cytotoxic T cells generated in MLR against SJL/J. Thus, virus-immune T cells which lyse infected targets by virtue of shared H-2K are also displaying H-2D alloantigen, and vice versa.


Pharmacodynamic actions of midodrine, a new alpha-adrenergic stimulating agent, and its main metabolite, ST 1059. Pharmacodynamic actions of alpha-(2,5-dimethoxyphenyl)-beta-glycinamido-ethanol-hydrochloride (midodrine, Gutron) and alpha-(2,5-dimethoxy-phenyl)-beta-aminoethanol (ST 1059), the main metabolite of midodrine, were investigated in various experimental procedures. Midodrine raises arterial blood pressure both after parenteral and enteral administration in animal experiments. Midodrine increases peripheral vascular tone when given in doses still ineffective in raising blood pressure. The d(+)-isomer of midodrine is by far less effective than the racemic mixture. Pretreatment with atropine, reserpine, guanethidine or hexamethonium has no influence on midodrine activity. Midodrine effects are greatly reduced by phentolamine but rather enhanced by propranolol pretreatment. Midodrine raises blood pressure in pithed rats, too; in the experiments performed the drug is devoid of central effects even when high doses are given. Chronic pretreatment with midodrine over a longer period reduces the effect of a subsequent single injection of this substance. Because of the results cited above midodrine may be classified as a direct peripheral alpha-adrenergic stimulating agent. alpha-Adrenergic receptor stimulation induced by midodrine can be demonstrated in various smooth muscle organs (blood vessels, nictitating membrane, intestine, pupil, urinary bladder, bronchi). In contrast to other pressor sympathomimetic agents, midodrine is of long duration of action and good efficacy after enteral administration. ST 1059, the main metabolite of midodrine, is an active alpha-adrenergic stimulating agent with a shorter duration of action than midodrine. It is suggested that midodrine is the well-absorbed "transport form", from which ST 1059, the actural pressor agent, is formed enzymatically in organism.


Immunogenicity of macrophage RNA and its properties. Date on the ability of ribonucleic acid, extracted from antigenically stimulated macrophages, to transform normal spleen cells into immunocompetent cells are reported, along with some properties of the same ribonucleic acid. It was observed that: 1 - RNA isolated from antigenically stimulated macrophages may transform normal spleen cells into immunocompetent cells.2 - Antibodies formed by these cells belong to the IgM class.3 - The average value of the ribonucleic acid from normal and stimulated macrophages is of about 5 mug/10(6) cells. 4 - RNA isolated from stimulated macrophages is richer in guanidine, but it contains less uracil in comparison with the ribonucleic acid isolated from the normal (not stimulated) macrophages. 5 - The curves obtained after sedimentation and fractionation of the ribonucleic acid isolated from normal and stimulated macrophages on the methylalbumin column are equal (identical) and contain 3 fractions with sedimentation constants 4-5S, 16S and 28S.6 - The antigenic determinants of the IgG are attached exclusively on the adenylic nucleotide of macrophagic ribonucleic acid, less on the guanidylic and cytidylic nucleotide and are not bound to uracyl nucleotide. The role of macrophagic ribonucleic acid, in the mechanism of antibody formation is discussed.


Serum alpha-fetoprotein in viral hepatitis and its complications. Alpha-fetoprotein levels were measured by radioimmunoassay in 40 cases of acute viral hepatitis, 5 cases of chronic persistent hepatitis, 15 cases of chronic aggressive hepatitis and 5 cases of hepatic coma from fulminant viral hepatitis. Serum concentrations were increased in 55% of patients with acute viral hepatitis and in about 33% of patients with chronic aggressive hepatitis. Levels resulted markedly raised among the patients with coma from fulminant viral hepatitis who survived. The high aplha-fetoprotein values may reflect liver cell regeneration after necrosis of a critical mass of hepatic tissue.


[Clinical and immunological study of 2 cases of systemic candidiasis]. Two cases of chronic systemic candidiasis of the infancy are presented and their immunity in vivo and in vitro is studied. The clinical course, the negative intradermal tests to Candida extract and the absence of lymphoblastic transformation to the same antigen, suggest an immunological deficit of the cell mediated immunity. The positive response to intradermal test of bacterial antigens, the clinical recovery from infections different from Candida albicans and the positivity of the patch test to DNCB suggest the possibility of a selective immunological reponse (macrophage inability of precessing Candida albicans). The authors give a pathogenic hypothesis of the two different clinical cases (granuloma and erythematous-scaly sesions), based on the different capacity in producing MIF.


Alpha-fetoprotein in fetal skin and muscle. The skin and muscles of human fetuses were used to obtain extracts of alpha-fetoprotein (AFP). Fetuses up to sixteen weeks gestation gave the highest yields. Rabbits immunized by concentrates from this source made anti-AFP of a quality suitable for use in radioimmunoassay systems.


Fatty acid synthesis in Escherichia coli is indirectly inhibited by phenethyl alcohol. Experiments were performed to determine how phenethyl alcohol inhibits phospholipid synthesis in E. coli. At a nonbacteriostatic concentration, the drug reduces the rate of de novo fatty acid and phospholipid synthesis by 60 to 70%. The inhibition of fatty acid synthesis was found to be a secondary consequence of the inhibition of phospholipid synthesis. Phenethyl alcohol reduces the rate of incorporation of exogenous fatty acids into the phospholipids of a fatty acid auxotroph by 60%. These results indicate that this drug controls phospholipid synthesis beyond the level of fatty acid synthesis. Phenethyl alcohol inhibits the synthesis of phospholipids containing saturated fatty acids to a greater extent than it does the synthesis of phospholipids containing unsaturated fatty acids. It controls the synthesis of phospholipids containing saturated fatty acids at both the level of fatty acid synthesis and the level of incorporation of the saturated fatty acids into phospholipids. The synthesis of phospholipids containing unsaturated fatty acids is inhibited at the level of incorporation of the fatty acids into phospholipids.


pH dependence of progesterone interaction with progesterone-binding globulin. Kinetic and equilibrium studies. The kinetics of binding and dissociation for the progesterone-binding globulin (PBG)-progesterone complex have been measured as a function of pH. The association rate constant appears to be independent of pH from pH to 10 with an average value of kon = 8.5 X 10(7)M-1 S-1. The dissociation rate constant is strongly pH dependent with the dependency defined by: koff = k0 (1 + [H+]/K1 + K2/[H+])(1 + K3*/[H+])/(1 + K3/[H+]). The best values for the various parameters were k0 = 0.0785 s-1, pK1 = 5.30, pK2 = 10.54, pK3* = 7.41, and pK3 = 7.21. Simpler expressions were inadequate to fit the data, and it was concluded that at least three ionizing residues are responsible for the stability of the PBG-progesterone complex. The affinity constant was determined by equilibrium dialysis over the range of pH 3 to 12. The ratio of the association and dissociation rate constants is in agreement with the affinity constant from pH 6.5 to 10.5. The influence of pH on the conformation and binding activity of PBG was also investigated. Denaturation by acid, base, or guanidine hydrochloride leads to a reversible loss of binding activity. Regain of binding activity in all cases is slow with half-times of 0.5 to 2.7 h, depending on conditions. The rate of acid denaturation was found to be incompletely protonated at pH 1.4, suggesting a buried carboxylic acid residue. The slow renaturation of PBG might be due to the difficulty of burying a charged residue in the protein's interior coupled with steric hindrance by the large carbohydrate moiety of PBG.


Estimation of chlorophyll a distribution in the photosynthetic pigment systems I and II of the blue-green alga Anabaena variabilis. Chlorophyll a distribution in pigment systems I and II was estimated with the blue-green alga Anabaena variabilis by two methods: first, with intact cells using delayed light emission as an index reaction; second, by measuring the 2,6-dichlorophenolindophenol-Hill reaction and the cytochrome c photooxidation in membrane fragments. The first estimation indicated that 0.053+/-0.014 of total chlorophyll a functions as a component of pigment system II, and the second method 0.086+/-0.012. Though the values were somewhat different in the two methods, both estimations indicated that pigment system II chlorophyll a occupies a very small fraction of total chlorophyll a.


Isolation and characterization of alpha-fetoprotein from the mouse hepatoma BW7756. Purification of alpha-fetoprotein from mouse hepatoma BW7756 extracts was performed using ammonium sulfate precipitations, gel filtration, ion-exchange chromatography and isoelectric focusing. These procedures produced a 5.6% yield of alpha-fetoprotein with 96% purity. Polyacrylamide slab gel electrophoresis, extended agarose electrophoresis and immunoelectrophoresis demonstrated that mouse hepatoma alpha-fetoprotein migrated at pH 8.6 as a rapid alpha1, or postalbumin globulin. Crossed antibody electrophoresis of the agarose zone containing alpha-fetoprotein failed to demonstrate microheterogeneity. Molecular weight analysis of the mouse hepatoma alpha-fetoprotein on a calibrated Sephadex G-200 column yielded a value of 72 000-73 000 for the native protein. Sodium dodecyl sulfate gel electrophoresis subsequently demonstrated a single polypeptide chain with a molecular weight of 72 000. Amino acid analysis showed the alpha-fetoprotein to be an acidic protein dominated by hydrophobic residues. The total carbohydrate content was 5.5%, and 3 mol of sialic acid were detected per mol of alpha-fetoprotein. Although neutral sugars were the principal class present, galactosamine was the most abundant single sugar detected.


[Isolation and immunochemical study of monomer and dimer forms of IgA human globulins]. Monomer and dimer of myeloma IgA human globulins are isolated by means of electrophoresis, ionic exchange chromatography, gel filtration and immunoadsorbtion. They are shown to be homogenous (using analytical ultracentrifugation and immunochemical analysis) and to differ in their antigenic specificity. Dimeric form of IgA has additional antigenic determinants, which depend on the intactness of a polymer structure and which are destroyed after protein dissociation into subunits in the presence of beta-mercaptoethanol. Reconstructed polymers are polydispersed subunit aggregates, they do not have polymeric determinants inherent to native polymers.


The effects of certain immunity systemic advuvants, PHA, and human gamma globulin on the thymic cortex of mice: a light and electron microscope study. Thymus of (C57Bl/6 x DBA/2) F1 mice was examined histologically, histochemically and ultrastructurally, seven days after intravenous injection of BCG, pertussis vaccine, lipopolysaccharide or human gamma globulin, or intraperitoneal injection of complete or incomplete Freund's adjuvants or of phytohemagglutinin. Only BCG induced a marked increase of the secretory activity of the thymic epithelium at all histological sites (cortex, corticomedullary junction and medullar). Only with this adjuvant was the epithelial hyperplasia associated with marked mitotic activity and high percentage of cells with cytoplasmic pyroninophilia among cortical lymphoid cells. The other substances tested produced different changes in the thymic epithelial cells according to the histologic zones. These results suggest that the epithelial cells of the cortex, the corticomedullary junction and the medulla respond differently to the agents tested and that the action of these substances upon thymus-dependent lymphoid cells may be indirect perhaps involving factors secreted by the epithelial cells.


Detection of homocytotropic human antibodies by passive sensitization "in vitro" of monkey lung tissue. II. Technique. Results on 295 patients (215 with possible drug allergy). Anti-drug serum human IgE can be detected by passive sensitization "in vitro" of monkey lung tissue. This technique gives reproducible results which are not quantitative. It is sensible; there are no false positive results and the number of false negative results has been strongly decreased. This technique is really an anaphylaxis and IgE only are detected. The results concern the study of 215 patients which possible drug allergy. The most frequent drugs come from groups of penicillins, sulfonamides, salicylates and malonylurea derivates. In 54% of cases, anti-drug IgE have been detected.


[Properties and the protein composition of lymph and blood in burns]. Experiments conducted on 25 dogs demonstrated that burn was accompanied by a regular redistribution of plasma proteins between the fluid media of the organism and an intensification of lymphogenic resorption. Properdin, albumin, and alpha2-globulin retardation in tissues in case of burn was demonstrated indirectly. The degree of burn proved to depend on the initial properdin level.


[Effect of uncouplers of oxidative phosphorylation on ATP concentration in frog striated muscle following changes in the buffer capacity of the solution]. Uncouplers of oxidative phosphorylation--gramicidin D, tetrachloro-2-trifluoromethylbenzimidasole (TTFB) and carbonylcyanide-m-trichlorphenylhydrazone (CCCP)--reduced ATP concentration in muscle. An increase of the buffer capacity of solution was without effect on uncoupling action of TTFB and CCCP but increased that of gramicidin D. The results can be explained by a different mechanism of the transfer of ion carriers through the membrane. It has been shown that ATP is not directly concerned with the membrane potential.


[Thrombocyte antigens of dogs].

[Thrombocyte antigens of dogs]. Four platelet-specific antigens were identified in dogs by means of the platelet agglutination test; these antigens were not connected with the erythrocyte or leukocyte antigens, they were inherited by the mendelian type and controlled by several recessive genes.


[Coexistence of reactive and nonreactive endocrine cells in the fundal mucosa in the rabbit]. Whether the same endocrine like cells are reactive towards different staining methods has been examined in normal and L-Dopa treated rabbits for distinction of cell types. Correlation with electron microscopy is proposed. It seems likely that SM cells (poorly reactive with Sevier-Munger technic) include two cell types: cells having around medium size and dense granules; cells having small round dense granules (D1?). X cells may correspond to a well defined group at the electron or photonic microscopic level. Insertion of D cells (according to Solcia and coworkers nomenclature) is not satisfactory but true non Apud cells are described. The signification of Jt (dim yellow) cells remains unknown.


Classification and audiovisuals.

Classification and audiovisuals. The University of Connecticut Health Center Library's substantial investment in audiovisuals has prompted careful examination of its organization of the AV collection and its effectiveness in answering user needs. While an accession number system worked for a small collection, increased size quickly generated access problems, especially because shelves are open to users. With the present collection of over 2,500 audiovisual items, adoption of the NLM classification promises convenient and continued flexibility in the future.


Immunofluorescent staining of Treponema pallidum and Treponema pertenue in tissues fixed by formalin and embedded in paraffin wax. The main problems in identifying Treponema pallidum in tissues are optical definition contrast, and specificity. In general, fluorochrome staining provides optical definition and contrast superior to that obtained by ordinary tinctorial staining, and in theory improved resolution. Specificity is lacking however, as with other stains. In contrast, immunofluorescence should combine the optical advantages of fluorochrome staining with the immunological advantages of specificity. Since the validity of such staining depends in part upon the integrity of the antigenic components of the micro-organisms, it is customary to avoid such drastic procedures as are involved in routine fixation and paraffin embedding. The manipulation, however, of unfixed cryostat material, in contrast with that of paraffin sections suffers from two disadvantages--namely, friability and infectivity. Published and unpublished work has shown antigenic stability in T. pallidum to a variety of procedures, both physical and chemical. Consideration of these facts led in this work to successful immunofluorescent staining after routine formalin fixation and paraffin embedding of tissues infected with T. pallidum or Treponema pertenue. Optical definition and contrast, were superior to that obtained with silver methods, but it was not possible to differentiate between these two organisms. Nevertheless immunofluorescence applied as described to paraffin sections should supply a convenient safe, and sensitive means of reappraising the histopathology of treponemal disease in patients, necropsy material, and experimental animals.


Selective trans-synaptic migration of tetanus toxin after retrograde axonal transport in peripheral sympathetic nerves: a comparison with nerve growth factor. Adult rats were injected unilaterally into the anterior eye chamber and the submandibular gland with either [125I]tetanus toxin or [125I]nerve growth factor (NGF). Fourteen and 24 h later in electron microscopic autoradiographs of the superior cervical ganglia of the injected side the labeling was confined to a limited number (15-20%) of adrenergic ganglion cells and the silver grains were localized over axons, perikarya and dendrites providing evidence for a retrograde intraaxonal transport of the two macromolecules. Moreover, after injection of [125]tetanus toxin there was a very marked labeling of the presynaptic cholinergic nerve terminals. In contrast, after [125I]NGF these terminals were free of label. In both cases no specific labeling could be detected over glia and extracellular space. In the postganglionic axons the radioactivity seemed to be mainly associated with vesicles and smooth endoplasmic reticulum, in the perikarya and dendrites of the adrenergic neurons with secondary lysosomes, vesicles and smooth endoplasmic reticulum. The Golgi cisternae and the nuclei were free of radioactivity. The specific labeling of presynaptic terminals after injection of [125I]tetanus toxin together wirans-symaptic migration of [125I]tetanus toxin from the adrenergic ganglion cell to its innervating presynaptic terminals following retrograde intraaxonal transport.


Analysis of intracellular recordings from salamander olfactory epithelium. Intracellular recordings have been obtained from provisionally identified olfactory receptor and sustentacular cells in the salamander olfactory epithelium. Two categories of membrane potential transients were recorded intracellularly in response to odor stimulation. The first category of responses, presumably recorded from receptor cell somas, were monophasis positive spikes 10-50 mV in amplitude which were superimposed on a depolarizing slow potential which ranged from 4 to 8 mV in amplitude. Graded and differential responses were recorded in response to odor stimulation. The second category of responses were depolarizing and hyperpolarizing slow membrane potential transients presumably recorded from sustentacular cells. Spiking was not observed in response to odor stimulation. Pysiological criteria and Procion dye marking in several instances have provided evidence that responses in the first category were recorded from olfactory receptors and that certain of the other responses were recorded from sustentacular cells.


Axonal transport of labeled material into sensory nerve ending of cat carotid body. The origin of nerve endings on glomus cells in the carotid body has been the subject of much controversy in recent years. Specifically, the problem is whether these nerve endings, which contain clear-core ("synaptic") vesicles and mitochondria arise from sensory neurons in the petrosal ganglion or from efferent neurons located in the brain stem or elsewhere. To study this problem, [3H]proline was applied to cat petrosal ganglia, the animals were allowed to survive for 3 h-7 days, and the peripheral distribution of the label was analyzed by sample oxidation/scintillation counting and by EM autoradiography. The time courses of distribution of label along the nerves and the accumulation of label in the carotid body indicated the presence of fast, intermediate and slow components of axonal flow. EM autoradiographs of carotid bodies showed the label localized almost exclusively to nerve fibers and to nerve terminals on glomus cells. As much as 60--90% of the nerve terminals were labeled in a given ultrathin-section autoradiograph. Passive movement of label from the injection site, or fibers of passage (efferent) through the ganglion, did not contribute to the labeled material since administration of [3H]proline onto the desheathed nerve away from the ganglion was ineffective in labeling the carotid body. The results suggest that most, if not all, nerve terminals on glomus cells in cat carotid body arise from neurons in the petrosal ganglion.


Acute anterior uveitis and HLA-B27 in families. To determine the hereditary pattern of acute anterior uveitis (AAU) 12 families with 2 cases of AAU in each family were given a routine eye examination which included serological determination of HLA antigens. Members of four families underwent x-ray examination of the lumbosacral spine. Of the 23 cases with AAU examined, 19 had the antigen B27. The genes determining B27 and a2 were inherited together in 14 instances and the gene determining Cwl in 10 of these 14. The lymphocytes of the HLA identical siblings of the three families studied by the mixed lymphocyte culture test did not react against each other. Sacroilities was seen in 62.5% of cases with familial AAU and in 58.6% of their relatives. It is concluded that HLA-B27 is linked with genes predisposing the carrier to familial AAU, which is closely related to the rheumatic group of diseases.


Mean velocity of optically detected intraaxonal particles measured by a cross-correlation method. A method which uses by the cross correlation of optical signals is described for the determination of the mean velocity of somatopetally moving particles within nerve fibers. The method was validated by simulation experiments and by comparing the results with those obtained by averaging collections of velocities of individual particles. The significant contribution of the method is that it allows objective and rapid serial evaluation of mean particle velocity within individual nerve fibers with good accuracy and precision. A series of results from normal myelinated nerve fibers from Xenopus laevis is presented. Considerable variation (up to 50%) in mean velocity was found between individual nerve fibers. The mean of all determinations indicates that the mean velocity of somatopetally moving particles in axons with diameters greater than 10mum is in the region of 1.14 mum/s at a temperature of 22-24 degrees C. The findings are compared with small collection of such determinations which have been reported in the literature.


Uridine kinase activities in normal and neoplastic lymphoid cells. Both adult (I) and embryonic (II) forms of uridine kinase have been identified in the transplantable EL-4 leukemia of C57BL/6 mice and in the P815Y mastocytoma of DBA/2 mice. Only Species I is found in primary tumor cells of lymphoid orgin (virus-induced feline lymphosarcoma, human acute and chronic lymphocytic leukemia) and in normal calf thymocytes and porcine peripheral blood lymphocytes; Species I was induced 4-fold upon stimulation of the normal blood lymphocytes with phytohemagglutinin. The level of uridine kinase activity in the feline lymphosarcoma of thymus-dependent lymphocyte orgin and childhood lymphocytic leukemia of possible thymus-dependent lymphocyte or null-cell origin was similar to the induced level in phytohemagglutinin-stimulated normal lymphocytes, i.e., thymus-dependent lymphocytes. In contrast lymphocytes of a patient with chronic lymphocytic leukemia of thymus-independent lymphocyte origin had a level of uridine kinase activity comparable to that of the unstimulated normal lymphocytes or thymocytes. The uridine kinase activity in the EL-4 tumor cells was repressed by acute treatment of the mice with 5-azacytidine.


Origin, destination and mapping of tritocerebral neurons of locust. The connectivities of the tritocerebrum of locust (Locusta migratoria L., Schistocerca gregaria (Forsk.)) were studied histologically and by means of cobalt chloride infusion. Its neuropil consists partly of fibers which traverse the tritocerebrum and areas consisting of neuropilar agglomerizations ("glomeruli"). The following direct connections between the tritocerebrum and other regions were observed: connections to 1) dorsal and lateral brain regions (mushroom body, optic lobe), 2) the ventral nerve cord, 3) the stomatogastric nervous system (here the protocerebrum and the subesophageal ganglion are also involved in these connections), 4) the retro-cerebral glands (corpora cardiaca, corpora allata), and 5) muscles of the foregut.


Suppression of premature ventricular contractions by acebutolol. The antiarrhythmic action of the beta-blocking drug, acebutolol, was evaluated in patients with frequent premature ventricular contractions (PVCs). In the 12 hours following administration of a single 300 mg oral dose, 8 of 10 patients showed a greater than 50% reduction in PVC frequency, and statistical analysis indicated that PVC reduction persisted for 10 hours after the single dose. Analysis of plasma concentrations of acebutolol and an acetyl metabolite indicated that after single oral doses of plasma concentrations of the metabolite exceed those of unchanged acebutolol. When patients were studied during periods of 300 mg doses every 8 hours, eight of 11 showed a 70% reduction in PVC frequency, and analysis showed that the therapeutic effect was present throughout the 24-hour monitoring period. Acebutolol slowed the heart rate and prolonged the PR interval without affecting the QT interval. Significant clinical or laboratory toxicity was not encountered. In the small group studied, acebutolol was found to be safe and effective for short-term administration to patients with frequent PVCs and possessed a relatively long duration of antiarrhythmic action.


New approach to evaluation of proteinuric states. We evaluated the use of immunonephelometric methods for measuring specific urinary proteins. Using a nephelometer to detect light scattering (angle, 31 degrees), we measured some proteins immunonephelometrically in serum and aliquots of 24-h urines from 50 apparently healthy children, ages 2-17 years. The mean urinary excretion rate (mg/24h) and the range of values was: for albumin 5.5 (range, 0-13.3), for transferrin 0.5 (0-1.9, for IgG 3.3 0-12), and for alpha 2-macroglobulin 0.6 (0-2.3). Direct comparison of the values for pathological urines with those for a reference population may offer more meaningful information concerning the integrity of the glomerular basement membrane than is provided by protein selectivity indices, and measuring a plasma protein such as albumin in urine may better define pathological proteinuria.


Identification of alpha1-acid glycoprotein, alpha2-macroglobulin and antithrombin III as components of normal and malignant human tissues. alpha1-Acid glycoprotein, alpha2-macroglobulin, and antithrombin III have been identified, by immunological means, as components of the 90000 X g supernatant fraction of malignant and adjacent normal human breast, colon, and anal tissues, as well as malignant stomach and ileum. Malignant lung tissue only contained alpha1-acid glycoprotein. These protease inhibitors are immunologically equivalent to those present in human plasma.


Enhancement of Tb3+ fluoresence induced by serum proteins other than apotransferrin. When Tb3+ ions are incubated with human serum, there is a large enhancement in the fluorescence of the Tb3+ ions as revealed by the excitation and emission wavelength pair 288 and 545 nm. The fluorescence enhancement represents the binding of Tb3+ ions not only to (apo)transferrin, but to albumin and gamma-globulins as well. Spectrophotometric evidence indicate involvement of tyrosyl residues at the cation binding site(s). The ion fluorescence induced by albumin and gamma-globulins invalidates the usefulness of the fluorometric determination of transferrin in the routine laboratory.


Splitting of human thyroglobulin. IV. The antigenicity of the pepsin-derived fragments. Purified human thyroglobulin (Tg) was hydrolysed by pepsin. After completion of hydrolysis the pepsin hydrolysate was passed through a Sephadex G-200 column to remove undigested Tg. Further isolation of the enzymatic fragments was effected by passage through a Sephadex  G-75 column. Two discrete fragments, termed pep I and pep II, were separated. The two fragments had sedimentation coefficients of 1-0 and 0-6, respectively. These fragments retained antigenic determinants reactive with both hetero-and auto-antibodies to Tg. The larger fragment, pep I, possessed all antigenic determinants to intact Tg while pep II lacked some determinants. Neither fragment contained novel determinants resulting from proteolytic degradation.


Antigen specific lymphocyte activity in vitro by peripheral blood leucocytes from Mantoux positive and negative human beings. I. Comparison of quantitative and qualitative differences in the PPD-specific lymphoproliferative response of lymphocytes from the two kinds of donors. Lymphocytes from some PPD (purified protein derivative from tubercle bacillus) skin test negative (Mantoux negative=Mx--) human beings reacted against PPD in the lymphoproliferative assay with a time course and dose response very similar to those of lymphocytes from Mantoux positive (Mx+) individuals. Other Mx-- persons were PPD non-responsive in the lymphoproliferative assay. The PPD response of (immunoglobulin=Ig) Ig anti-Ig column passed lymphocytes (T-cells) from Mx--/LP+ (LP+=lymphoproliferative) persons was significantly reduced whereas the in vitro PPD response of T-lymphocytes from Mx+/LP+ was the same or increased. Purified B-lymphocytes from all kinds of tested individuals did not respond in vitro against PPD. Serological investigations indicated that one of the reasons for the negative skin reaction of individuals whose lymphocytes gave a positive lymphoproliferative response against PPD in vitro, is that such individuals had recirculating PPD of high molecular weight (greater than 900,000) and/or PPD anti-PPD antibody complexes in the serum. These substances could block the PPD-specific T-lymphocytes.


Cytostatic effector cells generated in vivo against M locus determinants. Cytostatic effector cells against M-locus (Mls) determinants were generated in mice by immunization with Mls incompatible lymphocytes. A post-labelling assay of 14C-labelled uridine uptake by macrophage targets was employed to meaure the inhibitory activity of the effector cells. Using lymphocytes from Mls pseudocongenic mice to immunize donors of effector cells, it was confirmed that the cytostatic effect was via the Mls determinants expressed on the macrophage targets. Cytotoxic effector cells against M-locus (Mls) determinants were not detected by the cell-mediated lympholysis assay (CML) in a five day mixed lymphocyte culture (MLC) between Mls incompatible lymphocytes. Specificity of cytotoxic cells generated by culturing in vivo preimmunized responder cells and Mls incompatible stimulator lymphocytes did not correlate with the Mls determinant of the stimulator lymphocytes.


Ethylenediamine sensitivity from exposure to epoxy resin hardeners and Mycolog cream. Sensitivity to ethylenediamine and to epoxy resin hardeners was found in three patients with long standing contact dermatitis. In one patient, a young man, the sensitivity was elicited by occupational contact with epoxy resin hardeners and subsequently sustained by use of Mycolog cream. In two patients, both elderly women, the condition was only due to use of Mycolog cream. These case histories and test results indicate that use of Mycolog cream can result in occupational disease viz. contact dermatitis from epoxy hardeners.


Conservative treatment of benign prostatic hyperplasia. A study was carried out in 30 male patients with benign prostate hyperplasia to assess the effectiveness of treatment with a progestational agent, gestonorone caproate (200 mg), given intramucularly every 7 days over a period of 2 to 3 months. The results showed definite subjective and objective improvement after treatment. Residual urine determination diminished significantly after therapy in 78% of the cases completing the study; uroflometry also showed improvement. There appeared to be some reduction in the degree of occlusion of the urethral lumen in at least 13(65%) out of 20 patients given follow-up cystopanendoscopy after 6 months. This result was further supported by improvement in urinary flow rates and uroflometrograms in the same patients. The only adverse effect of treatment noted was the development of impotency in 21 patients.


The treatment of Hodgkin's disease: emphasizing programs at the Clinic Center, National Institutes of Health. During the past 10--15 years there has been a dramatic improvement in the prognosis of patients with Hodgkin's diases. More than 80% of all patients now will live 5+ years, many of them free from disease. The well-recognized immediate complications of therapy discussed above, are insignificant compared to the tremendous improvement in patients' survival. The fact that they now probably will survive long enough to potentially be at risk of such long-term complications is a testament to the efficacy of modern-day aggressive therapy.


[Relationship between digoxin-induced cardiac arrhythmias and serum-digoxin levels (author's transl)]. The serum-digoxin level was measured by radio-immunoassay (Immutope) on 245 patients in a coronary care unit. Cardiac arrhythmias were assumed to be digoxin-induced if they disappeared after the drug had been stopped. Patients who had received digitoxin or spironolactone were excluded. The results indicated a normal digoxin range of 1.52 +/- 0.2 ng/ml and a toxic one of 2.78 +/- 0.38 ng/ml. First degree A-V block, atrial ectopic beats and ventricular ectopics with variable coupling intervals were frequently associated with serum-digoxin levels of 1.5-2.5 ng/ml, while higher grade A-V block, atrial tachycardia, bigeminy and atrial tachycardia with block were more frequent with higher serum-digoxin levels (greater than 3.0 ng/ml). Atrial arrhythmias were especially frequent with serum levels above 3.0 ng/ml. This suggests different sensitivities of atrial and ventricular myocardium. Atrial arrhythmias thus in general indicate a higher degree of toxicity at high serum levels, while ventricular ectopic beats occur both with high serum levels and also with increased digoxin sensitivity of the ventricles.


[Studies on the surgical and chemotherapeutic management of oral cancer]. Of the 101 patients who have been treated with bleomycin since 1971 two groups were formed: Group I: Preoperative chemotherapy with 345 mg bleomycin, followed by radical operation. Group II: 200 mg bleomycin preoperatively, followed by radical operation and postoperative chemotherapy up to a total dose of 345 mg bleomycin. 1. Bleomycin- induced cellular alterations showed a dose-time relation. 2. The treatment plan for group II with 200 mg bleomycin preoperatively plus postoperative cytostatic therapy up to a total of 345 mg resulted in less recurrences and fewer distant metastases than the sole preoperative application of the full dose of 345 mg bleomycin. 3. In all cases, preoperative microscopic examination after administration of the full dose of 345 mg still showed tumor cells with possible growth potential.


[Audiovisual programmed teaching].

[Audiovisual programmed teaching]. On the basis of the teaching program example "The taking of alginate impressions in patients", some viewpoints are reported which should be taken into consideration when establishing a teaching program. The choice of the medium or media, for example, is determined by the instructional objective and the type of learning targets which underlie the program. In a preliminary study, not only the first draft of the above-mentioned teaching program was examined, but at the same time it was also found out which factors should be considered in addition to those that are program inherent; e. g., how to integrate the teaching program into the organization of other instructional courses and how to make time and personnel plans for the quality checks of the nonpersonal program.


Correlation analysis of delta activity generated in cerebral hypoxia. 1. Differences in spatial and temporal characteristics between polymorphous delta activity (PDA) and "standard slow complexes" (SSCS) resulting from grave cerebral hypoxia have been demonstrated by means of digital correlation analysis and on line recording of correlograms. 2. PDA observed in the human EEG and the ECoG of dogs is characterized by the absence of periodic organization (high extinction indices of auto- and crosscorrelation functions) and absence of spatial synchronization when recorded from widely separated areas of the hemispheres (low correlation coefficients, significant and variable time shifts), with bilateral symmetry of slow waves being preserved. 3. Delta waves recorded from nucleus amygdalae, nucleus caudatus, thalamus, hypothalamus and midbrain in the dog differ from cortical PDA by a more synchronous and rhythmically arranged process. 4. During the establishment of SSC activity correlograms show a synchronous process common to all cortical aand subcortical areas characteized by very high values of correlation coefficients. 5. It is suggested that the unorganized slow wave PDA process could arise under conditions of hypoxic dysfunction of distant cortico-cortical relationships, accompanied by weak subcortical pacemaker influences. The process reflects local coexcitation of relatively limited cortical areas. The particular statistical characteristics of SSCs generated during further increase in oxygen deficit can be accounted for by simultaneous generation of responses in some subcortical areas to single volleys of impulses from a hypothetical pacemaker, accompanied by a passive wave propagation towards a cortex completetly depressed by hypoxia


Far field somatosensory potentials in the rat. Averaged somatosensory evoked potentials (SEPs) in the rat were recorded from skull electrodes. The cortical component of the SEP was preceded by at least three low amplitude potentials. Surface distribution of these potentials, correlation with depth recording from posterior columns, posterior column nuclei, inferior cerebellar peduncle, medial lemniscus, ventral posterior thalamus and sensory radiation, and the effect of brain stem and medullospinal transections on these potentials showed that: (1) All potentials preceding the cortical SEP are far field reflections of activity generated at a distance from the site or recording. (2) Component I originates in posterior columns. (3) Component II reflects summated activities in posterior column nuclei and medial lemniscus. (4) Anterior component III reflects summated activities in the ventral posterior thalamus and sensory radiation. (5) Posterior component III probably reflects activities originating in cerebellar pathways and cerebellum.


Computerized evaluation of electroencephalographic changes accompanying exchange transfusion in Reye's syndrome. The EEGs of 7 children with Reye's syndrome (fatty liver and encephalopathy) were continuously recorded on magnetic tape for times ranging from 12 to 80 h. During these times the major therapy consisted of exchange blood transfusions. The tapes were automatically processed on a LINC-8 computer using a peak-detection algorithm. The main parameters investigated were the delta and theta indices, the mean EEG frequency, the mean peak-to-peak amplitude, and the frequency versus amplitude characteristics of the delta waves. In 5 patients who responded to therapy, a marked decrease in the delta activity and an increase in mean frequency were noted subsequent to exchange transfusions. In all 5 cases the delta waves exhibited a similar pattern of decreasing amplitude and increasing frequency following therapy. However, in 2 patients with a fatal outcome, no favorable EEG response was observed during treatment, and a simultaneous decline in both delta frequency and delta amplitude was noted as the clinical condition worsened. The results of this study indicate that continuous EEG monitoring in Reye's syndrome may be an important clinical adjunct in evaluating the effectiveness of exchange transfusion therapy and in signaling the need for further treatment.


The penicillin focus. I. Distribution of potential at the cortical surface. The potential field of a penicillin focus of controlled size was recorded from a rectangular array of 12 electrodes occupying a 4 X 6 mm area on the exposed anterior sigmoid gyrus of the cat. The array was made with 2 mm interelectrode spacing of 0.4 mm I.D. glass capillary tubes filled with Ringer's in agar, excepting one containing penicillin to create the focus. Early in the development of the focus a negative spike appears at the penicillin electrode reaching amplitudes of as high as 3,000 muV while all of the other electrodes showed no synchronous activity of more than 100 muV. Within the first 15 min spike activity becomes visible at about 100 muV at all the electrodes and after 30 min, waveforms of all activity become quite stable. At the penicillin-containing electrode, at intervals of 2--10 sec each, a negative sharp wave of up to 4 mV occurs, having a shorter rise time than fall time. A smaller positive spike of about 30 msec duration which showed marked variations in amplitude often preceded the stable negative sharp wave. During the rise of the negativity at the penicillin electrode, practically all the surrounding electrodes showed a predominantly positive spike. This was occasionally followed by negativity during the falling phase at the penicillin electrode. Displays of potential surfaces interpolating the average values at the 12 recording points on the cortex at 4 msec intervals demonstrate a relationship between the field of the sharp wave at the penicillin focus which is less than 2 mm in diameter and that of the surrounding electrode which indicates that symmetrically located synaptic inhibitory processes are strongly activated in areas adjacent to the small simultaneous excitation at the penicillin electrode. Degrees of attenuation of interictal spikes that take place between cortex and scalp are estimated from the measured potential distributions. Explanation is offered for the reported apparent discrepancies between the findings at the cortex and the scalp EEG.


Identification and separation of acoustic frequency following responses (FFRS) in man. Frequency following responses (FFRs) to monaural tone bursts were recorded in normal and hearing impaired subjects as the potential difference between an ipsilateral earlobe electrode and a scalp vertex electrode. Whenn the rubber tube coupler between the earphone and the subject's ear was clamped, a stimulus artefact FFR was occasionally recorded. The "biological" FFR had a latency of about 1 msec and an irregular wave form which was made more sinusoidal by the addition of white noise. When the responses to tone bursts of opposite onset phases were added together, a "double frequency" FFR was obtained which had a latency of about 6 msec and whose amplitude was appreciably reduced by white noise. In some hearing impaired subjects (with no neural responses to clicks), this longer latency double frequency component could not be recorded, while in those cases in which the cochlear microphonic potential could be recorded, the shorter latency FFR was also present. It is concluded that the FFR in normally hearing subjects is made up of a short latency cochlear microphonic component and a longer latency neural component.


Movement-related forebrain and midbrain multiple unit activity in rats. In 16 rats multiple unit activity was recorded simultaneously from ventral forebrain and dorsal midbrain areas, with continuous monitoring by sensitive head movement and body movement recorders, along with careful observations of ongoing behaviors. Both forebrain and midbrain multiple unit activity were significantly correlated with head and body movements: recordings from both brain areas showed significant declines corresponding to decline in recordings head and body movement. The declines in midbrain multiple unit activity were significantly greater than those in forebrain multiple unit activity. The significant correlation of forebrain multiple unit activity with continuous recordings of bodily activity is, to the best of our knowledge, a new finding. The correlations between brain activity and bodily activity found in these experiments indicate the importance of monitoring brain recordings of awake animals with sensitive recordings of head and body movement. In addition, these findings represent a further demonstration of the need to analyze the operation of the brain in terms of its motor output.


Effects of atropine upon the hippocampal electrical activity in rats with special reference to paradoxical sleep. In freely moving male rats with implanted electrodes, the influence of atropine sulphate (5-30 mg/kg, i.p.) on the hippocampal theta activity was studied with special emphasis on paradoxical sleep (PS). In accordance with previous work with cats and rabbits, atropine was found to inhibit PS, in delaying its first appearance as well as in decreasing the duration of the first PS episode. The hippocampal theta activity during PS was also changed after atropinization. In particular, when REM occurred often, theta activity was increased not only in frequency but also in amplitude; however, with no or little REM, theta frequency was not changed but the regularity of theta rhythms was markedly disturbed. These findings are in contrast with the theta activity associated with gross body movement, which was not affected by atropine as was previous reported by Vanderwolf (1975). Thus, in contrast to commonly held views, the hippocampal theta activity during gross body movement may be different in its underlying mechanisms from that during PS.


The results of penicillin G Administration of chronic unrestrained cats: electrographic and behavioral observations. Intramuscular administration of penicillin G was carried out in a series of 27 chronic cat preparations. In addition to the EEG, the high frequency components of cerebral electrical activity were also recorded from cortical and deep structures. Videotape recordings using split-screen technique allowed correlations of the animal's clinical state with the EEG. The results showed that 'spike-wave' type activity occurred earliest in the cortex. The discharges were also best formed in cortical and thalamic structures. The other deep structures showed characteristic bursting, but not of the 'spikewave' type variety. The cerebellum showed also early participation. Clinical expressivity of the bursts depended upon the state of alertness of the animal, the height of the spike components and the extent of depth participation. The high frequency recordings revealed characteristic alternation of decrease and increase in activity mostly in cortical structures and to a lesser extent in thalamus. Pontine and medullary reticular formation areas showed usually no changes in the high frequency records during the bursts. When major seizures were induced, they were always of focal onset rather than of the primary generalized type as one sees with pentylenetetrazol. Different cortical or deep structures served as the initiating site in different animals. It was concluded that systemic penicillin adminstration does not lead to a truly primary generalized form of epilepsy, but produces its effects by multifocal activation of various cerebral structures, with cortex and cerebullum usually showing earliest involvement.


The scalp topography of potentials in auditory and visual discrimination tasks. Averaged event-related cortical potentials (ERPs) were obtained from an array of scalp electrodes overlying the left hemicranium in response to regularly presented visual or auditory stimuli (non-signals)and to infrequent random replacements by different stimuli (signals) in the same modality. A motor response was required to the signals. Non-signal ERPs were subtracted from signal ERPs and the topographic distributions of the negative (N2 delta) and positive (P3 delta) components were plotted as isopotential maps. N2 delta distributions differed for the auditory and visual modalities, whereas P3delta was modality unspecific. These topographic data were compared to those from the previous study of missing stimulus potentials (Simson et al. 1976) using maps representing the contributions from unilateral cerebral sources. The N2 delta and negative missing stimulus potential distributions ascribed to cortical activity within the secondary auditory and visual regions, whereas the late positive component (positive missing stimulus potential or P3 delta) were considered to derive principally from inferior parietal association cortex.


Electrophysiological correlates of optokinetic and reversed postoptokinetic nystagmus in the rabbit. Six rabbits with implanted electrodes in visual cortex, lateral geniculate body, superior colliculus and the mesodiencephalic nystagmogenic centres were exposed to 90 min optokinetic stimulation, followed by 30 to 60 min observation of reversed postoptokinetic nystagmus (RPN) in darkness. The oculographically recorded nystagmus was used to trigger a LINC 8 computer programmed for perisaccadic EEG averaging and for examination of excitability of visual centres by flashes applied at different intervals after the saccade onset. Whereas optokinetic nystagmus (OKN) was accompanied by marked electrical potentials appearing at all recording sites during and for about 100 msec after the saccade, these potentials were considerably attenuated or absent during RPN. Visual evoked responses to flashes applied during the OKN saccades were considerably smaller than responses to flashes delayed by 130-200 msec. No saccadic suppression was observed when the same visual stimuli were applied during RPN saccades in darkness. It is concluded that eye movements generated in the absence of external stimuli during RPN elicit only weak corollary discharge.


The stability of synergy in agonists during the execution of a simple voluntary movement. The characteristics of muscular synergy between the main elbow flexors (biceps brachii, brachialis, brachoradialis were considered. The activities of these different muscles were recorded simultaneously with surface and wire electrodes. A quantitative analysis of the activity of each of these muscles and of their excitation levels was carried out during movements performed at various velocities and against different inertias. It was shown that: (1) the onset as well as the cessation of activity in the different muscles occur practically simultaneously and independently of the velocity and inertia of the movement; (2) the well-known linear relation between the integrated EMG of biceps brachii and the work can be extended to the other main flexors. This implies that the relation between the activities of the main flexors remains constant whatever the velocity and inertia may be. These results confirm the notion of 'Flexor Equivalent'. They also demonstrate a stability of the synergy between agonist muscles which must be distinguished particularly from the synergy between agonists and antagonists.


Characteristics of the experimental reflex sleep induced by vago-aortic nerve stimulation. 1. Electrical stimulation of the baroceptive fibres of the vago-aortic trunks (VA St) reflexly induces, in the Ecéphale isolé (EI) cat preparation, a complete sleep cycle characterized by a progression of all stages of sleep previously described in chronic preparations (slow wave sleep, phasic slow wave sleep, paradoxical or REM sleep). Some qualitative and quantitative characteristics of this "vago-aortic" (VA) sleep are analysed and compared with those obtained in EI cats previously deprived of REM sleep. 2. VA sleep is not simply the consequence of chance occurrences, but the consequence of VA St. It is stimulus-bound, even if the interval between successive stimuli is as short as 7.5 min. Thus it is possible to impose an artificially regular cycle much shorter than the normal one. one. 3. VA St. precipitates the onset of the differrent sleep cycle episodes in the non-REM-deprived EI cat as well as in the REM-deprived EI cat. 4. REM sleep begins rapidly after stimulus onset, so that an experimental reflex REM narcolepsy may be obtained. This effect is particularly noteworthy in REM-deprived cats. In this situation, REM sleep episodes with cataplexy (muscular atonia and areflexia) can immediately follow the onset of stimulation.


Temporo-spatial pattern of subcortical spike activity in kindling epilepsy. A statistical approach. Recording electrodes were implanted stereotaxically in limbic and thalamic structures and the mesencephalic reticular formation in twelve cats. The animals were submitted to daily stimulation of the left amygdaloid nucleus following the technique for the kindling procedure, always combined with 5 h 30 min post-stimulation monitoring. After about 18 days, generalized convulsive activity was established. The following results concerning the quantitative evolution of spontaneously occurring interictal spikes were obtained. Amygdaloid nuclei, the hippocampus and the thalamic nucleus ventralis lateralis (VL) demonstrated an increase of discharge activity during the kindling procedure, following by a significant decrease after convulsions had been elicited. Thalamic nucleus centrum medianum (CM) was the only recording site investigated where the amount of interictal discharge increased and remained at a high level even after generalized convulsions had been established. Fourier analysis of slow oscillations in discharge generation yielded two main types of significant periodicity. A 165 min oscillation could be detected in all structures tested except reticular formation, which developed a 110 min cycle shared only with the thalamic CM. Significant correlations in spike activity were obtained from various structures. Stimulated amygdala seemed to have alternating relations with thalamic CM and VL, whereas stimultaneous oscillations excisted between MRF and CM. The occurrence of high voltage spikes in both contralateral and ipsilateral amygdalae was shown to be significantly correlated.


New sphenoidal electrode assembly to permit long-term monitoring of the patient's ictal or interictal EEG. A new sphenoidal wire electrode is described which greatly increases the clinical and diagnostic usefulness of sphenoidal electrode recordings. These very fine wire electrodes are easy to insert; they are comfortable and acceptable to the patient. In contrast to sphenoidal needle electrodes they expose the patient to no risk should he have a seizure during recording. These electrodes also allow one to extend the recording time to several days, thus increasing the chances of recording a spontaneous seizure, for instance while the patient's  EEG is being recorded with a telemetry system. The extended recording time also allows for continuous automatic sampling of the interictal EEG over a period of several days. The quality and the reliability of the EEG record are also enhanced. The new sphenoidal electrodes have been used on over 100 patients and are now being used routinely on suspected temporal lobe epileptics recorded with conventional techniques, while 50 of the patients have also been recorded with a cable-telemetry seizure monitoring system which has captured 65 spontaneous seizures.


Intracellular recording from pulsating cerebral cortex. An instrument has been developed for recording intracellulary from cortical neurons in an exposed pulsating brain. The electrode moves with the brain pulsations maintaining the electrode within the impaled cell. Stable recordings have been obtained for up to 20 min.


Early events in the steroidal regulation of alpha2mu globulin in rat liver. Evidence for both androgenic and estrogenic induction. 1. A double-antibody radioimmunoassay for alpha2mu globulin has been developed. With the help of this highly sensitive radoimmunoassay the early effects of both androgen and estrogen treatments on the hepatic synthesis of alpha2mu globulin in the rat have been investigated. 2. Results show that the earlier observation of the long lag period in the androgenic induction of alpha2mu globulin is more apparent than real. 3. Single injections of either 5alpha-dihydrotestosterone(5alpha-dihydro-17beta-hydroxy-4-androsten-3-one) or its physiological antagonist estradiol-17beta (1,3,5(10)-estratriene-3,17beta-idol) to castrated female rats resulted in the induction of alphamu globulin reaching maximum hepatic level of the protein between 6--9 h after the hormone administration. Administration of cycloheximide 15 prior to hormone treatment blocked both androgenic andestrogenic induction of alpha2mu globulin. 4. Daily pretreatments with 5alphamu-dihydrotestosterone increased the sensitivity of subsequent androgenic response to alpha2muglobulin synthesis. On the other hand, daily pretreatments with estradiol 17beta decreased and ultimately abolished the estrogenic induction of alpha2mu globulin. 5. The possible mechanism of both androgenic and estrogenic induction of alpha2mu globulin in rat liver mediated through a sex-hormone-binding protein with dual affinity for both dihydrotestosterone and estradiol has been suggested.


An immunofluorescent study of alpha-fetoprotein. I. Its ontogenic development in human conceptus. A development of alpha-fetoprotein-producing tissues was investigated in 52 cases of human conceptuses ranging from 2 to 7 months in gestation by a fluorescent antibody technique. It is synthesized in endodermal cells of the yolk sac, hepatocytes including the cells of large bile canaliculi, and some gland epithelial cells of the stomach, while its accumulation also occurs in mesenchymal cells of the yolk sac and Kupffer cells of the liver. A mode of its localization in individual tissues was described and possible explanation on the origin of its producers was discussed.


Evidence for quasi-silent germline genes coding for phylogenetically ancient determinants of the rabbit a locus allotypes. Anti-a2 sera raised in a3 rabbits are shown to detect determinants on a2 molecules which are different from those detected by anti-a2 sera raised in a1 animals. The former determinants are occasionally observed at a low level in rabbits of the a1 allotype and at a high level in sera of Leporidae of different genera. The two types of anti-a2 sera are shown to compete for the same sterical region of the a2 molecules. All homogeneous a2 molecules which have been tested show both types of determinants.


The expression and relation of HLA, beta2-microglobulin and receptor for marmoset red blood cells on man/mouse and man/Chinese hamster hybrid cells. The expression of HLA, human and mouse beta2-microglobulin (beta2m), P red blood cell antigen and a receptor for marmoset red blood cells (MaRBC) were studied on 18 man/mouse and man/Chinese hamster hybrids. A positive correlation was found between the expression of HLA, P, and the receptor for MaRBC, which we interpret as a possible synteny between these different loci. We studied 3 hybrid clones where HLA antigens are still expressed despite the absence of human beta2m and where redistribution experiments demonstrate that HLA is associated with mouse beta2m. Synteny between HLA and the receptor for MaRBC can be a useful tool to select HLA-positive hybrid clones.


Immunoglobulin-like messenger RNA in a mouse T cell lymphoma. RNA-driven complementary DNA (cDNA) hybridization experiments have been carried out in order to detect complementary sequences in RNA prepared from a mouse T cell lymphoma line (EL4). In conditions where efficient hybridization of L-chain cDNA with homologous P3 myeloma mRNA was observed, poor hybridization was observed with EL4 mRNA unless a low criterion of hybrid formation was employed (i.e. hydroxyapatite fractionation). The hybrid formed between EL4 mRNA and L-chain cDNA was found to melt about 5 degrees C below the homologous hybrid indicating that the sequence detected in EL4 mRNA is similar but not identical with the P3 mRNA sequence. However, a similar sequence was detectable in a Clambda-producing myeloma cell line but in this line the concentration of the sequence was found to be an order of magnitude lower than in EL4 cells.


Relationship between phosphatidylserine and cromolyn in histamine release. The opposing actions of phosphatidylserine (PS) and cromolyn on histamine release were studied in rat peritoneal mast cells in vitro. Histamine-releasing drugs could be separated into 2 groups on the basis of whether they were potentiated by PS and inhibited by muM cromolyn (dextran, antigen (BSA), concanavalin A) or neither potentiated by PS nor inhibited by muM cromolyn (48/80, polymyxin, phospholipase C and ATP). Compound 48/80 and polymyxin chemically combined with PS, but this could be circumvented by preincubating the mast cells in PS for one hour, and then washing them free of PS in solution prior to addition of the drugs. These data define at least 2 pathways for induction of histamine release: (1) a PS-potentiated pathway inhibited by muM cromolyn, and (2) a PS-independent pathway unaffected by muM cromolyn. Dose-response curves of the muM cromolyn inhibition of PS-potentiated release revealed a parallel shift, suggesting that cromolyn may compete with PS.


[On the classification of experimental brain tumours (author's transl)]. The classification of experimental brain tumours is essential for mutual understanding and for comparison with human CNS tumours. The histogenetic principle of human neurooncology should be applied to the classification of experimental tumours, too. In rats different quantities of experimental tumours have been classified as ependymonas by various authors. The aim of our morphological investigation is to elucidate the reasons of the differences. The tumours were induced with ethyl- or methylnitrosourea in newborn or adult rats or by trnasplacentar application. Serial sections through the cerebrum of 57 rats were performed to detect early tumour stages and to study their localization within the brain. In other rats the brain and spinal cord were investigated in selected areas. 174 small tumours, most of them less than 2 mm in diameter were found. Early tumour stages never involved the ependyma of the ventricular walls or of the central canal of the spinal cord. These tumours exhibited a strong activity of acid phosphatase whereas the ependymal cells were inactive. No true rosettes, cilia or blepharoblasts were seen in the tumours. No perivascular zones, free of nuclei were found. In literature the experimental ependymomas have been diagnosed on grounds of row-like arrangements of tumour cells. We found similar peculiar structures in large experimental oligodendrogliomas and glioblastomas. Our findings suggest that the classification of experimental brain tumours as ependymomas is not justified in many of the cases published in literature. To avoid misinterpretation of experimental results in their significance for human neurooncology the criteria of the histogenetic classification should be applied thoroughly.


Immune responses to environmental antigens absorbed through the gastrointestinal tract. Foods, food additives, beverages, drugs, and intestinal microorganisms are potentially important sources of environmental antigens. While proteins taken orally ordinarily are absorbed to only a limited extent, under appropriate circumstances enough absorption occurs to produce an immune response. Acute allergic reactions to foods are not uncommon and as a rule are mediated by IgE antibodies. The possibility that small quantities of food antigens absorbed over a period of years without acute symptoms of allergy might produce a cumulative systemic or local immunological toxicity remains to be convincingly demonstrated.


[Antigenic properties of the proteolytic enzymes of the gastrointestinal tract]. Antigenic properties of crystalline pepsin, trypsin and chymotrypsin were studied in 9 rabbits immunised with these enzymes. Production of antibodies and their titres were investigated by means of the reaction of the precipitation in testing tubes and immunoelectrophoresis. The most clear antigenic properties were revealed in trypsin, and they were the weakest in pepsin. Low titres of the antibody to pepsin were, probably, due to denaturation of its molecule at physiological values of pH immunisation. Absence of cross-reactions of antisera to trypsin and chymotrypsin with pepsin solutions may be due to considerable structural differences of the antigenic determinants of pepsin from those of trypsin and chemotrypsin. However, antisera to trypsin and chemotrypsin do develop cross-reactions with respective enzymes and there were may be due to a similarity between structures of their antigenic determinants.


Immunoprecipitation and radioimmunological studies of a lymph node activating factor released during contact of H-2-or HLA-different lymphocytes. Immunoprecipitation studies showed that the supernatants from the 4-hour mixed cultures of allogeneic mouse lymphoid cells contained a specific component with the alpha2-globulin electrophoretic mobility which can correspond to, or to which a "lymph node activating factor" can be bound. In addition, during allogeneic cell culture serum proteins with the prealbumin mobility were released into the culture medium and in the control culture of cells from only one donor proteins with the albumin mobility predominated. In the supernatants from the 4-hour cultures of human HLA-identical and HLA-diferent lymphocytes beta2-microglobulin was determined by immunodiffusion and radioimmunologically.


Correlation between inhibition of indicator cell migration and tuberculin hypersensitivity in patients with suspected tuberculous inflammation of the uveal tissue. Peripheral blood lymphocytes from patients with suspected tuberculous inflammation of the uveal tissue were examined for their capacity to produce in vitro a migration inhibition factor in the presence of specific antigen. Three modifications of the capillary tube migration technique were used to demonstrate MIF. The indicator cells were guinea pig peritoneal macrophages and human peripheral blood leucoytes. A correlation was found between the migration of indicator cells influenced by lymphocytes from Mantoux-positive donors in the presence of specific antigen and the tuberculin sensitivity. The possible uses of the in vitro tests as a correlate to cellular hypersensitivity in vivo in the human system are discussed.


Antigens on boar spermatozoa and the effect of antibodies against the spermatozoa and the accessory sexual gland fluids on boar spermatozoa. Antigens on the acrosomes of boar spermatozoa could be detected by the anti-complement immunofluorescence test, using antisera against spermatozoa and against seminal vesicle and epididymis fluids. Weak fluorescence was observed even on the tail and no fluorescence in the postnuclear segment. Adequate absorption of the complement allowed the sperm-immobilizing test to be used with boar spermatozoa. Using this test, the specificity of the sperm-immobilizing effect on antispermatozoal antibodies was confirmed. The sperm-immobilizing effect and damage to the acrosomes was prevented by absorption of the sera with spermatozoa. Antibodies against the fluid of the boar prostate did not react with antigens on boar spermatozoa.


Serum alpha-fetroprotein concentration in adult patients under corticoid, estroprogestative or androgen therapy. The serum alpha-fetoprotein concentration was measured by radioimmunoassy in 41 women with or without hormonal contraception, 21 patients with rheumatoid arthritis given corticosteroids or not, and 6 patients under androgen therapy for aplastic anemia. None of these therapies induced any significant variation of the serum alpha-fetoprotein level. More extensive studies are needed to investigate the possible effect of these hormones on the metabolism of this protein at a cellular level.


Development of chronic liver disease after acute non-A, non-B post-transfusion hepatitis. Role of gamma-globulin prophylaxis in its prevention. Progression of acute type B hepatitis to chronic liver disease and cirrhosis is well recognized, whereas no progression of acute type A hepatitis has as yet been documented. The natural history of acute non-A, non-B hepatitis has not been previously characterized. Ten cases of chronic liver disease were identified in 44 cases of acute non-A, non-B post-transfusion hepatitis. Age, sex, severity of acute illness, and prevalence of preoperative antibodies to known hepatitis-producing agents did not differ between the group whose hepatitis progressed to chronicity and the group whose hepatitis resolved. Less progression of acute hepatitis to chronic liver disease was seen in those patients receiving immune serum globulin preoperatively than in those receiving an albumin placebo (P = 0.009). Only 3 patients had clinical symptoms of hepatitis at the time of liver biopsy, and elevations of liver enzymes and gamma-globulin were mild. However, liver biopsy specimens in 8 of 10 patients showed chronic active hepatitis and an additional biopsy specimen showed cirrhosis. Acute non-A, non-B post-transfusion hepatitis often progresses to chronic active hepatitis. Preoperative gamma-globulin prophylaxis significantly reduces this progression. Identification and characterization of this viral agent(s) will further aid in the prevention of this undesirable complication of blood transfusion.


[Genetic counseling, a contribution to family planning]. Since introduction of oral contraceptives "family planning" is mostly understood as birth control. In contrast the gynecologist and the genetic counselor are often confronted with the desire of proconceptive methods. The counselor has different possibilities in family planning: reduction of the age of reproduction; consideration of "safety interval" between the birth of children: a. in families affected with a hereditary disease with late manifestation, b. after exposition to x-rays, cytotoxic or immunosupressant agents; warning against reproduction in case of high genetic risk and missing of prenatal diagnostic procedures; application of modern diagnostic procedures, i.e. detection of carrier in affected families, i.e. prenatal diagnostics. Genetic counseling is a way to help to plan his family, specially in families affected with hereditary diseases and other risks.


Short and long term effects of radioiodine and antithyroid drugs on T4 binding proteins, free T4 and T3, during Graves' disease therapy. Ninety five patients with Graves' disease were studied before and at three months intervals after antithyroid drugs (ATD) (31 cases) or radioiodine (64 cases) therapy until recovery. Before treatment, the T4 maxima binding capacity of TBPA was significantly decreased 253.5 +/- 11.4 mug/100 ml)(mean + se) (control values: 287 +/- 10.4 mug/100 ml) (alpha = 0.04), especially in 53.7% of patients (m = 177 +/- 8 mug/100 ml). The mean of TBG (m = 20.7 +/- 0.9 mug/100 ml) was not different from euthyroid subjects (m = 19.7 +/- 1.7 mug/100 ml) except in 51.2% of patients who had a low TBG (m = 14.3 +/- 1.1 mug/100 ml). An inverse linear correlation was found between TBG-DFT4 (alpha = 0.05) and DF T 3 (alpha = 0.002), TBPA-log DF T4 (alpha = 0.05) but not between TBG and TBPA. The physiological relationship between DFT3, DFT4, TT3, TBG and TBPA was studied in vitro; after adding increased quantities of T4 to a pool of sera collected from eu, hypo or hyperthyroid patients, DFT4, DFT3, FT3 index increased in linear positive relationship with TT4 concentrations, the kinetic of this phenomena was inversely correlated with T4 maximal binding capacity of TBG or TBPA for T4. Addition of T3 to the same sera did not show any effect on the previous parameters. DFT3 depended on the level of T4 in serum more than T3 concentration and was in inverse relationship with the maximal binding capacity of TBG. This data might explain the paradoxal normal or slightly increased values of DFT3 found in T3 thyrotoxicosis. In patients treated with ATD or radioiodine, TBPA but not TBG increased significantly on year after. However, in subjects with an initial very low TGB or TBPA, this phenomenon occurred on the third month after radioiodine or ATD. During the same period, DF T4 and DF T3 were inversely correlated to TBG and TBPA. In conclusion, important changes in T4 binding proteins and free fractions of thyroid hormones were observed in Graves' disease but were corrected by antithyroid therapy. All these data were in good agreement with the normalisation of thyroid function.


From ovulation to blastocyst attachment. A review of early embryonic life in the mouse. The development of the blastocyst from ovulation to implantation is discussed with particular reference to control mechanisms that enable the embryo to attach to the uterine wall, using the mouse as a laboratory model. The physical and chemical changes in the uterus and within the blastocyst are seen as essential steps towards implantation. Evidence that the oestrogen plays a fundamental part in the overall control of these changes is demonstrated. The interrelationship between the hormones of early pregnancy and the uterine production of histamine and cycle AMP is viewed in conjunction with the development of the blastocyst and the decidual changes that occur in the uterus which are essential for nidation.


The relationship between DNA replication and chromosome structure. The results obtained by acridine orange staining of chromosomes, after BrdU treatment, during one or two cell cycles, are described. The alterations of chromosome structure do not depend only on BrdU incorporation into DNA. Some other mechanisms are necessarily involved, and it is postulated that they are disturbances of protein-DNA association, occurring in G1 and in S- or  G2-phase.  The aspect of metaphase chromosomes then appears as the result of several metabolic steps, all occurring during interphase.