Purification and properties of a ribonuclease in human urine that hydrolyses polycytidylic acid. Human urine RNase was purified about 2000-fold. The preparation is free from phosphatase, phosphodiesterase and DNase activities. On electrophoresis through polyacrylamide gel at pH 8.3, it migrates toward the anode and stains with periodic acid-Schiff reagent, suggesting that it is acidic and glycoprotein in nature. Its isoelectric point is at pH 4.1. It has a molecular weight of about 21,500. It is thermostable at pH 4.2 and thermolabile at pH 8.5. It has a pH optimum at 6.5. It exhibits highest preference for cytidine 3'-phosphate linkages. Its activity on poly (C) is endonucleolytic. It cleaves poly (C) via intramolecular transphosphorylation. It has no action on cytidine 2': 3'-cyclic phosphate or uridine 2':3'-cyclic phosphate. Its rate of hydrolysis of poly (U) is less than 2% of that of poly C). Poly (A) and poly (G) are totally inert to its action. Its action on poly (C) is inhibited by poly (G), poly (A) and poly (U). It differs from bovine pancreatic Rnase A in its physical, chemical and catalytic properties. It is, however, similar to human serum and pancreatic RNase in all its properties, suggesting that pancreas is its likely source.


Kinetics of drug decomposition. Part 48. Specific acid-base hydrolysis of rolitetracycline. Using chromatographic-spectrophotometric method, the effect of H+ and OH- ions on the rate of hydrolysis of rolitetracycline (RT) to tetracycline (T) at 20degreeC was investigated. The advantage of this analytical procedure over the direct fluorescence or UV absorption measurements of RT solutions during the kinetic investigations in HCl medium was demonstrated. The catalytic rate constants (kH+ and kOH-) for the hydrolytic degradation of RT under oxygen-free conditions are given.


[Properties of urease immobilized by chemical binding to a derivatives of cellulose]. A comparative study of properties of soluble urease and urease immobilized by its binding to cellulose derivatives was carried out. Upon chemical binding of urease to cellulose derivatives the Mikhaelis constant and pH optimum for the enzyme action changed insignificantly. Maximum enzymic activity of soluble and immobilized urease occurred at 50 degrees C. The energy of activation of urea hydrolysis by urease during enzyme immobilization also changed insignificantly.


Primary photochemical event in vision: proton translocation. Picosecond studies of rhodopsin in low-temperature glasses have been carried out in order to observe directly the risetime of prelumirhodopsin, the first intermediate in the visual pathway. Only at 20 K or below can the risetime of this intermediate be resolved and even at 4 K it is astoundingly rapid, about 36 psec. An examination of the Arrhenius dependence on temperature of the rate of formation of prelumirhodopsin shows a strong deviation from linearity at low temperatures, i.e., non-Arrhenius behavior. This marked non-linear behavior is characteristic of a quantum mechanical tunneling event such as the translocation of hydrogen. An excellent candidate for the tunnelling process is the hydrogen of the protonated Schiff base formed between opsin and its retinal chromophore. Deuterium-exchanged rhodopsin, in which the Schiff base hydrogen is replaced by a deuterium, also shows a marked non-Arrhenius temperature dependence at low temperatures, consistent with tunneling. The rate of formation of prelumirhodopsin in deuterium-exchanged samples is much slower and a deuterium isotope effect kH/kD approximately or equal to 7 is observed. The data support a model in which the formation of prelumirhodopsin involves translocation of a proton toward the Schiff base nitrogen of the retinal chromophore.


[Denaturation of the alpha-amylase of Bacillus subtilis in an acid medium]. By fractionation of purine compounds (sorbtion on the cation exchange resin KU-2 (H+), extraction, precipitation of purine compounds as Ag-complexes) a "purine fraction" of the culture liquid epiphytic bacteria No. 703 isolated from barley overground organs was obtained. The presence of isopentenyl cytokinins was demonstrated by quality reactions of the purine fraction with aromatic amines and phenols as well as by the values of Rf and UV spectrum of individual compounds examined by paper chromatography of the purine fraction.


Sodium-stimulated glutamate uptake in membrane vesicles of Escherichia coli: the role of ion gradients. Membrane vesicles prepared from Escherichia coli B/r grown on glutamate as a sole source of carbon and energy require sodium for glutamate accumulation when energized by D-lactate oxidation. Glutamate uptake can also be driven by a prearranged sodium gradient (out to in) in the absence of an energy source or a protonmotive force. Sodium ions are exchanged rapidly in respiring vesicles and the sodium gradient may be large enough under certain conditions to drive glutamate uptake after the protonmotive force is abolished with m-chlorocarbonylcyanide phenylhydrazone. Glutamate uptake due to a prearranged sodium gradient or lactate oxidation is inhibited by monensin but not by nigericin. Transport does not occur in response to valinomycin-induced membrane potential. We interpret these results to indicate that glutamate transport is obligately coupled to sodium transport and can only occur when there is a net flux of sodium ions. This flux is driven by a chemical gradient of sodium that is created by the protonmotive force generated by respiration.


[Metabolism of sex steroid hormones in neuroendocrine organs. I. In vitro androgen metabolism in the hypophyses and epiphyses of rats during the puberal period]. Metabolism of tritium-labeled testosterone, delta4-androstane-3, 17-dion, dihydrotestosterone. 5alpha-androstane-3alpha, 17beta-diod and 5alpha-androstane-3beta, 17beta-dion by the isolated hypophyses and epiphyses of male and female 30-day rats was studied. The glands were incubated in Eagle's medium containing the mentioned androgens with the concentration of 1-2.10(-8) M for 90 min at 37 degrees C. As revealed, restoration of testosterone and delta4 androstane-3, 17-dion by 5alpha-reductase occurred in  the epiphyses and hypophyses; under conditions of incubation androgen hydroxylation was realized only in the 3alpha- and 17beta-positions. Organ and sexual specificity of the androgen metabolism in the hypophyses and the epiphyses was quantitative in character: the metabolism level of all the androgens was greater in female rats than in the male both in the hypophysis and in the epiphyses; the activity of 5-reductase was lower in the epiphyses of animals of the both sexes than in the hypophyses. It appeared that in the process of biotransformation androgens in the organs under study served as precursors of the polar unidentified metabolites poorly retained by the tissues and eliminated from the organs into the incubation medium during the incubation.


Fatty acid synthetase from Brevibacterium ammoniagenes: formation of monounsaturated fatty acids by a multienzyme complex. A multienzyme fatty acid synthetase complex isolated from Brevibacterium ammoniagenes has been purified to a specific activity of 1440 nmol of malonyl-CoA incorporated per min/mg. The enzyme is homogeneous, as judged by gel electrophoresis on agarose gels, and has a molecular weight of 1.2 X 10(6). Both NADPH and NADH are required for activity. In contrast to other fatty acid synthetase complexes, the enzyme catalyzes the synthesis of both long-chain saturated and monounsaturated fatty acids from malonyl-CoA and acetyl-CoA. The formation of unsaturated fatty acids is oxygen-independent and sharply reduced by 3-decynoyl-N-acetylcysteamine, a known inhibitor of Escherchia coli beta-hydroxydecanoyl thioester dehydrase (EC 4.2.1.60).


Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations. Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue preparations and was greatest (19- to 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal muscle, adrenal, and epididymal fat. Activation was also observed with partially purified preparations of guanylate cyclase. Activation of rat liver supernatant preparations was augmented slightly with reducing agents, decreased with some oxidizing agents, and greater in a nitrogen than in an oxygen atmosphere. After activation with NO, guanylate cyclase activity decreased with a half-life of 3-4 at 4 degrees but re-exposure to NO resulted in reactivation of preparations. Sodium azide, sodium nitrite, hydroxylamine, and sodium nitroprusside also increased guanylate cyclase activity as reported previously. NO alone and in combination with these agents produced approximately the same degree of maximal activation, suggesting that all of these agents act through a similar mechanism. NO also increased the accumulation of cyclic GMP but not cyclic AMP in incubations of minces from various rat tissues. We propose that various nitro compounds and those capable of forming NO in incubations activate guanylate cyclase through a similar but undefined mechanism. These effects may explain the high activities of guanylate cyclase in certain tissues (e.g., lung and intestinal mucosa) that are exposed to environmental nitro compounds.


Unequivocal demonstration of fructose-1,6-bisphosphatase in mammalian brain. Fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase; EC 3.1.3.11) has been found in rat brain and identified unequivocally. The enzyme has been purified to 95% homogeneity by standard procedures, including adsorption to a phosphocellulose column followed by elution with substrate. The purified enzyme exhibits a broad optimum above pH 7.6. Both fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate are substrates of this enzyme; the hydrolysis of the latter occurs at about 20% of the rate of the former, and the Km for fructose 1,6-bisphosphate is approximately 1.32 X 10(-4) M. 5'-AMP, an inhibitor of other mammalian-fructose-1,6-bisphosphatases, is without effect, and in further contrast with the other enzymes there is no metal requirement for activity. Purified brain enzyme fails to crossreact with the antibody prepared against the purified liver fructose-1,6-bisphosphatase. On the other hand, antiserum produced against the brain fructose-1,6-bisphosphatase quantitatively precipitates the enzyme activity and forms precipitin bands with preparations of brain fructose-1,6-bisphosphatase.


Resonance Raman spectroscopy of arsanilazocarboxypeptidase A: determination of the nature of the azotyrosyl-248-zinc complex. Resonance Raman spectra of arsanilazotryosyl-248 carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.12.2) exhibit only the vibrational bands of its chromophoric azotyrosyl-248 residue uncomplicated by background interference from either water or other components of the protein. The resonance Raman spectra contain multiple, discrete bands which change as a function of pH, thereby demonstrating the existence of interconvertible species of the azotyrosine probe in solution. Spectra of model azophenols and of the apoazoenzyme establish the identity of these species. All conclusions about the azoenzyme based on the resonance Raman spectra, including the apparent pK values for the interconversion of these species, are in complete agreement with those drawn earlier from studies by absorption spectroscopy. In addition, the properties of resonance Raman bands that have been identified with the motions of specific atoms of azotyrosyl-248 provide details of the interactions of specific atoms of this chromophore with the catalytic zinc atom at the active site. In particular, this has allowed elucidation of the structure of the azotyrosyl-248-zinc coordination complex. Such experiments are also providing information on the effects of crystallization on the enzyme and on its interaction with inhibitors. The important potential of resonance Raman spectroscopy for the study of the structure of chromophoric components of active enzymatic sites and of metal complex ions is discussed.


Selective inhibition of gamma-glutamyl-cycle enzymes by substrate analogs. Substrate analogs have been obtained that selectively inhibit the reactions of the gamma-glutamyl cycle or that are susceptible to only limited metabolism by the cycle. Thus, glutathione synthesis may be inhibited and analogs of glutathione may be synthesized that do not participate in transpeptidation. Specific inhibitors of gamma-glutamylcyclotransferase and 5-oxoprolinase have been obtained. The findings offer new approaches to the in vivo study of the cycle and also to the design of more specifically directed analogs of inhibitors such as methionine sulfoximine and 6-diazo-5-oxonorleucine.


Quantum efficiency of photosynthetic energy conversion. The quantum efficiency of photosynthetic energy conversion was investigated in isolated spinach chloroplasts by measurements of the quantum requirements of ATP formation by cyclic and noncyclic photophosphorylation catalyzed by ferredoxin. ATP formation had a requirement of about 2 quanta per 1 ATP at 715 nm (corresponding to a requirement of 1 quantum per electron) and a requirement of 4 quanta per ATP (corresponding to a requirement of 2 quanta per electron) at 554 nm. When cyclic and noncyclic photophosphorylation were operating concurrently at 554 nm, a total of about 12 quanta was required to generate the two NADPH and three ATP needed for the assimilation of one CO2 to the level of glucose.


Embryologic development of a mouse sympathetic ganglion in vivo and in vitro. The morphologic and biochemical development of the embryonic mouse superior cervical ganglion was characterized in vivo and in tissue culture. From 13 days of gestation, when the superior cervical ganglion was first visible, to birth at 19 days, tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] activity increased 100-fold in vivo. Explants of ganglia from 14-day embryos exhibited abundant neurite outgrowth in basal medium without added nerve growth factor (NGF), and increases in tyrosine hydroxylase activity paralleled that observed in vivo. Ganglia from 14-day embryos elaborated neurites and exhibited 3-fold increases in enzyme activity in vitro in the presence of antiserum to NGF (anti-NGF) or NGF + anti-NGF. In direct contrast, ganglia from 18-day fetuses failed to grow without added NGF or in medium containing anti-NGF or NGF + anti-NGF: virtually no axon outgrowth occurred and tyrosine hydroxylase activity decreased by half. These observations suggest that developmental regulatory mechanisms change radically during embryologic and fetal life of mammalian superior cervical ganglion.


Thyrotropin-releasing hormone-like material in the rat retina: changes due to environmental lighting. Material reacting with an antibody to thyrotropin-releasing hormone (TRH) has been found to be present in the rat retina. The compound present in the retina cochromatographed with authentic TRH and most of its activity was lost when incubated with pyroglutamate aminopeptidase (L-pyroglutamyl-peptide hydrolase, EC 3.4.11.8), an enzyme that degrades TRH. The TRH-like activity in the rat retina was low during the night and high during the day. There was a 4-hr lag period after the lights were turned on before peak TRH levels were attained. A decrease in TRH was seen after 2 hr of darkness and the level of TRH was lowest after 4 hr of darkness. Retinal TRH is elevated by environmental lighting regardless of the time of the day. These findings suggest that TRH may be involved in retinal photorecptive mechanisms.


Stimulation of human platelet guanylate cyclase by unsaturated fatty acid peroxides. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity of human platelet homogenates was stimulated by the addition of phospholipase A2 or unsaturated fatty acids such as oleic, vaccenic, linoleic, linolenic, eicosenoic, eicosadienoic, and arachidonic acids. The addition of lipoxidase potentiated the fatty acid-induced stimulation of guanylate cyclase purified by DEAE-cellulose column chromatography. The extent of the stimulation was dependent on the concentration of the oxidized form of these fatty acids (peroxides). Saturated fatty acids such as stearic and arachidic acids had no effect on the guanylate cyclase activity in the presence or absence of lipoxidase, indicating that human plateletguanylate cyclase is stimulated by unsaturated fatty acid peroxides rather than by fatty acids. Hemoglobin prevented the enzyme stimulation produced by low concentrations of fatty acid peroxides, but enhanced stimulation of the enzyme activity with high concentrations of fatty acid peroxides. 2-Mercaptoethanol, dithiothreitol, and N-ethylmaleimide inhibited the guanylate cyclase activities both in the presence and absence of unsaturated fatty acidperoxide. The stimulation of guanylate cyclase activity by unsaturated fatty acid peroxidesis attributed to oxidation of sulfhydryl residues of the enzyme protein.


Purification and properties of human erythrocyte pyrimidine 5'-nucleotidase. A 250,000-fold purification of pyrimidine 5'-nucleotidase from human erythrocytes has been achieved using a combination of DEAE-cellulose chromatography, ammonium sulfate fractionation, gel filtration, and isoelectric focusing. Polyacrylamide disc and starch gel electrophoresis of the purified material show two strong protein bands. On starch gel these bands exhibited pyrimidine 5'-nucleotidase activity. Two faint protein bands devoid of enzyme activity were also found in the case of polyacrylamide electrophoresis. The enzyme has a pH optimum at 7.5 and is most stable between pH 6 and 7.5. The enzyme has pI of 5.0 and a molecular weight of 28,000 by gel filtration. The Km of the purified enzyme was 10 muM, compared to 40 muM when measured in hemolysate. The higher Km in the hemolysate is due to the presence of an inhibitor. Inorganic phosphate was shown to be a competitive inhibitor of pyrimidine 5'-nucleotidase and inorganic phosphate in the hemolysate may be responsible for increasing the Km of the enzyme for the substrate cytidine monophosphate.


Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. [3H]Diazepam appears to bind specifically to a single, saturable, binding site located on rat brain membranes, with an affinity constant near 3 nM at pH 7.4. Specific binding constitutes more than 90% of total binding at 0 degrees and less than 10% of total binding at 37 degrees. Arrhenius plots suggest a sharp conformational change in the diazepam receptor near 18 degrees. Mitochondrial fractions from rat kidney, liver, and lung exhibit some [3H]diazepam binding that can be displaced by nonradioactive diazepam and several other benzodiazepines. However, Ro-4864, which is almost inactive in displacing [3H]diazepam from brain membranes, is extremely potent in displacing it from kidney mitochondria. Conversely, clonazepam, the most potent inhibitor of brain binding, is an extremely weak inhibitor of kidney binding. Furthermore, diazepam binding to kidney mitochondria has an affinity constantof 40 nM, about 15 times higher than that in brain. No specific diazepam binding was detected in intestine or skeletal muscle. Thus, specific [3H]diazepam binding to membranes appears to be restricted to brain, where it is unevenly distributed: the density of diazepam receptors is about five times higher in cortex (the highest density) than in pons-meddula (lowest density). Trypsin and chymotrypsin completely abolished specific [3H]diazepambinding in brain and kidney.


Kinetics of the alkaline tetramer leads to dimer dissociation in liganded human hemoglobin: a laser light-scattering stopped-flow study. The first-order dissociation of tetrameric HbCO to the dimer has been studied overthe pH range 10.30-11.57 in a light-scattering stopped-flow apparatus using argon-ion laser excitation. The first-order dissociation rate constant varies from 0.25 sec-1 to 24.0 sec-1over this pH interval. A semilogarithmic plot of k versus pH has a slope of 2.56 at pH 11.07, the midpoint. The pH dependence of the dissociation of the tetramer is consistent with progressive titration of alpha1-alpha2 and beta1-beta2 salt bridges. At pH 10.66, the dissociation rates of HbO2, HbCO, methemoglobin, and HbCN vary less than 20% from their mean value. A study of the dissociation kinetics as a function of protein concentration allows one to obtain both association and dissociation rate constants, and hence equilibrium constants, for the tetramer in equilibrium dimer reaction. In this manner, equilibrium constants were obtained on protein solutions with less than 15 sec of exposure to dissociating conditions.


Antimuscarinic properties of antidepressants: dibenzepin (Noveril). The antimuscarinic potency of dibenzepin (Noveril) was estimated by measuring (a) central in vivo effects in mice (antihypothermia and antitremor, both induced by oxotremorine), (b) peripheral in vivo activity (mydriasis caused by systemic administration of the drug), (c) the effects of dibenzepin on isolated smooth muscle from guinea pig ileum, and (d) in vitro determination of the affinity constant of dibezepine toward the muscarinic binding sites in whole mouse-brain homogenate. The data allowed the construction of a normalized antimuscarinic potency scale for some of the common tricyclic antidepressants. With a value of 1 for scopolamine, the following relative anticholinergic potencies were calculated: dibenzepin--1/600, nortriptylne--1/300, imipramine - 1/200, and amitriptyline - 1/75. These values suggest an explanation for the absence of clinically detectable anticholinergic side effects during treatment of depression with high doses of dibenzepin. Structural and spatial interrelations among various tricyclic antidepressants and scopolamine are discussed.


[Stability of tetracycline during fermentation]. The stability of tetracycline was studied at pH 6.0 and 1.5. The thermal inactivation constant at the lower pH was found to vary between 1.62 min-1 (40 degrees C) and 65.83 min-1 (100 degrees C). A degradation mechanism was proposed in the light of the variation of entropy and steric factors.


beta-blocking agents and human fat cell adenylate cyclase. The effects of various beta-blocking agents upon the catecholamine-activated adenylate cyclase of human fat cell ghosts were studied. Both non-selective and cardio-selective beta-blocking drugs are capable in inhibiting the human enzyme system. The concentrations of the non-selective beta-blockers (bupranolol, alprenolol, propranolol, 4-hydroxypropranolol, prindolol and oxyprenolol) required to produce half maximal inhibition of isoproterenol-stimulated rates of cAMP-formation were found to be in a narrow range (5X10(-7) M-3X10(-6) M).The cardioselective beta-blocking agents, however, were only 1/100 (methypranol) to 1/1000 (atenolol, practolol) as potent as the non-selective drugs.


[The effect of sympathomimetric drugs on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)]. This study reports on effects of beta-sympathomimetic drugs on the exocrine function of the isolated cat pancreas. The injection of these drugs resulted in an increase of pancreatic protein and enzyme secretion, the excretion of calcium into the juice and the rate of volume output were not changed. The enzyme secretion was inhibited by different adrenolytic drugs (phenoxybenzamine, practolol, butoxamine), by tetracain, hemicholinium, and atropine. The pancreatic function of cats pretreated by reserpine or 6-hydroxydopamine was not altered. It is concluded, that beta-sympathomimetic drugs influence the pancreatic protein and enzyme secretion in a cholinergic way. These results are consistent with those of other investigators showing a suppressibility of the isoproterenol-induced pancreatic amylase secretion by atropine.


Quantifying drugs influence on cardio-respiratory synchronism. The paper concerns the situation in which, for a considerable time, the onset of each respiratory cycle coincides with one and the same section of a cardiac cycle. A standardized procedure is described with which, in anesthetized rabbits, the potentiality of the biological mechanisms responsible for the phenomenon may be quantified. The procedure consists of progressively prolonging the cardiac cycles by selectively cooling the sinus node. Care is taken that during such procedure a situation is passed in which the respiratory cycles are a multiple of the cardiac cycles. The synchronizing kybernetic system, if any, must click in, then. As the prolonging of the cardiac cycles continues, the synchrony will get lost the sooner the weaker the potentialities of the kybernetic system and vice versa. Four drugs are tested as to their potential action on the kybernetic system. Nikethamide and methylphenidate tend to decrease its efficacy, allobarbital and benzoctamine tend to increase it, none of them, however, being conclusively effective.


A placebo-controlled, double-blind trial of Benorylate tablets in the treatment of bursitis and synovitis due to sports injury. In this two-week study, Benoral tablets, at a 4.5 g daily dosage were compared with a matching placebo in 20 patients suffering from sports injury. Four assessments were made: pain at rest, pain on movement, tenderness and soft tissue swelling. In each case the active treatment group (benorylate) was statistically greater than that in the placebo group at one week and after two weeks' treatment.


Labeling immunoelectrophoresis: a general method for increasing the sensitivity of rocket immunoelectrophoresis with 125I-labeled anti-antibodies. In a new procedure, rocket immunoelectrophoresis is performed at pH 8.7 with rabbit antibodies and 5% polyethyleneglycol 6000 in the agarose gel. After the pH in the gel has been changed to 5 the nonprecipitated immunoglobulins are electrophorsed out of the gel simultaneously with the electrophoresis of 125I-labeled swine antibodies against rabbit IgG into the gel. The latter antibodies tag the rabbit IgG, which is not present only in the precipitates. The radioactive precipitates are visualized by autoradiography. The method permits quantification of antigens down to an amount of approximately 0.5 ng; well-defined rockets are not formed below this limit. Compared to conventional protein staining with Coomassie brilliant blue, this represents an increase in sensitivity of up to 20 times.


[Therapy of childhood schizophrenia].

[Therapy of childhood schizophrenia]. Due to the multifacet genesis and variability of clinical phenomenology, the therapy of childhood schizophrenia must be multidimensional. Formerly applied techniques like electroshock- and insulin-therapy are now replaced by pharmaco-therapy, primarily with phenothiazines, butyrophenones and chlorprothixens. The dosage depends on age, body weight or body surface. Because of extrapyramidal motor side effects, combinations with anticholinergic drugs may be necessary. Psychopharmaco-therapy alone, however, is insufficient. High emphasis must be placed on psychotherapy and educational guidance and counselling of the psychotic child. Participation in play groups, sports, muscial activities, arts and crafts, and acting helps make it possible to improve communication behaviour and to transform aggressive anxiety defense into stabilized control of emotions and impulses. In addition to successive integration of the psychotic child into small groups, play therapy with the single child is meaningful. In this case, a constant and confidential relation between therapist and child is extremely important and only possible if the therapist attempts to place himself into the magic-animistic phantasies of the psychotic child. He has first to learn the psychotic language of his patient in order to support more reality-oriented behaviour processes of the child's thinking, preceiving and performing later on. In this manner, the magic-omnipotent phantasies can be dissolved and an increasing orientation of the child toward reality can be encouraged. This involves strengthening and support of non-pathological ego-functions and initiation of a new level of ego-functioning. Such an integrated developmental concept can best be realized through play therapy.


Metallic contamination of food during preparation and storage: development of methods and some preliminary results. A chemical procedure for studying trace metals leached from metallic cooking utensils and preserving cans used in the preparation and storage of food has been developed. The method consists in the destruction of the major part of organic matter with HNO3-vapour followed by a complete mineralization of residues with small amounts of HNO3 in Teflon bombs at 150-160 degrees C under a pressure of 3-12 kg/cm2, depending on the amount and composition of the samples. Subsequently, an ion-exchange step removes major components and concentrates the trace elements in a dilute HNO3-solution, suitable for analysis. The ion-exchange separation, which is performed with an automatic ion-exchange separator, is practically free from blank level problems, e.g., typically a mean of less than 2 per cent of the sample levels of the elements being determined. Preliminary results show that large amounts of aluminium are released from vessels to the water during boiling at the same pH-range which exist for most drinking water in Sweden.


Folate conjugase: two separate activities in human jejunum. Previous perfusion studies of the human jejunum suggested that conjugated folate is hydrolyzed on the mucosal surface. The techniques of cell fractionation and DEAE and gel chromatography led to the identification of two separate folate conjugase activities in human jejunal mucosa: one membrane-bound and concentrated in the brush border, the other soluble and intracellular. These enzyme activities exhibit different pH optima, molecular weights, and inhibition characteristics. Folate conjugase in the brush border may accomplish the initial digestion of dietary pteroylpolyglutamates.


Memory formation: evidence for a specific neurochemical system in the amygdala. beta-Adrenergic antagonists injected into the amygdala complex of rats trained in a passive avoidance task produced time-dependent and dose-dependent decreases in retention of the task. In addition, the effects observed with beta-adrenergic antagonists were both stereospecific and reversed by norepinephrine. The results support a role for an amygdala beta-adrenergic system in memory processes.


Biogenic amine synthesis defect in dihydropteridine reductase deficiency. In the enzymatic hydroxylation of aromatic amino acids, tetrahydrobiopterin is the essential cofactor. Regeneration of tetrahydrobiopterin requires dihydropteridine reductase, without which there should be a deficiency of hydroxylated amino acids and their products, biogenic amines. Assay of biopsied brain cortex of a patient with a deficiency of dihydropteridine reductases showed low concentrations of serotonin and dopamine, and this was reflected in the concentrations of their major metabolites measured in cerebrospinal fluid from lumbar, ventricular, and subarachnoid spaces. The metabolite concentrations were restored to normal, or above normal, by treatment with specific amino acids which bypass the metabolic block at the hydroxylation step. It is postulated that the seizures and neurological deterioration of the patient were related to a deficiency in the synthesis of biogenic amine neurotransmitters.


[Measurement of plasma renin activity, blood volume and exchangeable sodium: an aid in the orientation of treatment of essential arterial hypertension]. 95 patients with essential uncomplicated hypertension were mostly submitted to measurement of plasma renin activity, plasma volume and exchangeable sodium. According to the results of the plasma renin activity, we noted variations in blood volume and exchangeable sodium in order to determine the best possible treatment based on these data. Single treatment, based either on diuretics or beta-blockaders was rarely sufficient to bring the blood pressure down to normal. Association of these two types of drug was often very useful. Finally, a critical study of these 3 parameters was made in an economic view of investigations of the blood pressure. The plasma volume seemed to us the most useful investigation, after which came the measurement of plasma renin activity. for the exchangeable sodium seemed of little interest.


[Persistant danger of smallpox and necessity of continuing mandatory smallpox vaccination in France]. The WHO stated a short time ago that the total eradication of smallpox would occur shortly. This announcement has been contradicted by an epidemic of smallpox in Somaila which in spite of the energetic measures taken, remained in the capital from August 1976 to January 1977 then extended to 10 regions out of 16 with from January 1977 to 18 June 1977, 1 567 cases of smallpox. This is only a provisional estimation as it is increasing every week. In view of the ease and rapidity of airline communication, it is very possible that infected subjects or products arrive in France, it is necessary for doctors to be warned and counteract the present tendancy to neglect the legal requirement for smallpox vaccination.


Premedication with flunitrazepam in gastro-intestinal endoscopy. Administration of 2 mg flunitrazepam (Rohypnol; Roche) to patients before gastro-intestinal endoscopy caused significantly less anxiety and achieved significantly greater sedation than diazepam (Vallium; Roche). No differences were found between any of the trial groups with respect to ease of intubation, tolerance of the procedure, gastric peristalsis, and the state of the pylorus. Memory of the procedure was significantly less vivid in the groups who received 2 mg flunitrazepam, than in the other groups. The patients who received 2 mg flunitrazepam showed a significantly greater willingness to undergo a repeat procedure, both when asked immediately after the procedure, and when asked on the next visit. Pulse rate increased in all groups during the procedure. No change in respiratory rate or in systolic and diastolic blood pressure occurred in any group.


Pediatric plastic surgery.

Pediatric plastic surgery. Each section of this article has been discussed in severe brevity. Potential pitfalls have been expanded in an attempt to be helpful to the general surgeon who attends patients with these clinical problems. Making the relatives aware of a potential complication in its broadest sense is the responsibility of the surgeon and can only be done if there is cognizance of these problems. The author hopes that this article has accomplished this purpose, albeit in a brief format.


The effect of (+) --cyanidanol on lysosomal enzymes of I-cell fibroblasts. (+)--Cyanidanol, a water-soluble flavonoid, when added to cultured skin fibroblasts of a patient with I-cell disease raised the intracellular concentration of beta-galactosidase but did not affect the distribution of arylsulfatase. A, alpha-mannosidase or beta-glucuronidase. The elevated accumulation of 35SO4 by I-cell, Hunter and Maroteaux-Lamy fibroblasts was decreased by the addition of (+)--cyanidanol to the culture medium, but the degradation of previously labeled, intracellular glycosaminoglycans was not. It is concluded that (+)--cyanidanol does not produce a biochemical correction of the enzymic abnormalities existing in I-cell fibroblasts.


Structure-activity relationships of some selected beta-adrenergic blocking agents--oxidation with N-bromosuccinimide. A relationship between in vitro rate of oxidation by N-bromosuccinimide (NBS) and the pharmacologic activity (pA2) of different beta-adrenergic blockers for different blocking agent-tissue combinations has been studied. The rates of oxidation of the alcoholic group in the drugs by NBS, as well as their molecular conformations as represented by molecular models, were studied in order to determine requirements for selectivity and potency of action of beta-adrenergic blocking agents. Using data from all 7 drugs studied--both nonselective and selective blocking agents--no significant correlation between pA2 and -log k2 (k2 is the second order rate constant for the oxidative reaction) was found. If data from only the 4 nonselective agents were used (16 drug-tissue combinations), a correlation significant at p less than 0.01 was found. Hypotheses are presented to account for the selective action of some beta-adrenergic blocking agents.


Fine structural localization of phosphatases in cilia and basal bodies of Tetrahymena pyriformis. Cytochemical localization of ATPase activities in cilia and basal bodies of Tetrahymena pyriformis revealed a number of possible sites of ATPases. In basal bodies, reaction product was localized on the periphery of basal body microtubules, in the core of the B-microtubules, on the dense basal body core, and on the basal plate; some reaction product was associated with the postciliary and basal microtubules. In the cilium, reaction product was associated with the ciliary membrane, the basal granule, the periphery of the outer doublet microtubules, in the core of the B-microtubules, and on the arms and either the central microtubules or the radial spoke heads. Reaction product deposition required ATP and either Ca2+ or Mg2+ or ADP and Mg2+. When incubated in the presence of ATP and Na+, reaction product was only found at the base of the cilium in the region of the ciliary necklace. Implications of the various sites of activity are discussed with respect to possible mechanisms of ciliary motility.


Treatment of detrusor hyperreflexia in multiple sclerosis: a double-blind, crossover clinical trial comparing methantheline bromide (Banthine), flavoxate chloride (Urispas) and meladrazine tartrate (Lisidonil). 34 patients suffering from detrusor hyperreflexia due to multiple sclerosis entered the trial and 32 patients accomplished. The patients received each drug for a period of 14 days. The patients made records of relevant symptoms, urgency and urge incontinence and compared the treatment periods according to these symptoms. Registration of the number of micturitions was also made. Furthermore, the patients underwent cystometric studies. The following parameters were recorded and compared: residual urine, volume at the first bladder contraction, effective volume and amplitude of the first bladder contraction. The study showed that the patients preferred methantheline bromide. The entire cystometric pattern changed statistically significant with methantheline bromide, but only with concordance to the patients preferences in 60%. Decrease in number of micturitions and volume at the first bladder contraction were the only parameters showing accordance with the preferences. The drugs caused many various side effects. 12 treatment periods were discontinued due to side effects of meladrazine tartrate. The cystometric recordings seem to be of little use in evaluation of a drugs therapeutic effect, and it is difficult to find parameters which reflect the patients preference of the drugs.


[Urologic symptoms in the abdominal muscle deficiency syndrome (author's transl)]. The abdominal muscle deficiency syndrome ("prune belly syndrome"(, a symptom triad of aplasia of the abdominal wall musculature, malformations of the urinary tract, and cryptorchism, is described from the urologist's point of view, citing nine cases. With modern diagnostic procedures the early detection of the correct diagnosis in the usually very young patients is possible. While the urologic symptomatology is due to the malformations in the urinary tract, the life expectancy depends mainly on the degree of renal function impairment. Combat of infection together with proper operative repairs are the treatments of choice to date. Instrumental procedures should be limited as much as possible. The survival changes following kidney transplantation appear promising.


Platelet adhesion to foreign surfaces under controlled conditions of whole blood flow: human vs rabbit, dog, calf, sheep, pig, macaque, and baboon. Our results reveal significant differences between mammalian species with respect to platelet adhesion to foreign surfaces exposed to heparinized, flowing blood. In particular, we have demonstrated the following: 1) At a surface shear rate characteristic of shear rates in mammalian arteries, human platelet adhesion (and that of calf, baboon, macaque, hog or sheep) is negligible in comparison to dog or rabbit platelet adhesion after 10 mins of blood flow. 2) The species differences are biomaterial dependent: the human-dog difference is present with Cuprophan or Avcothane, but absent with compressed Gore-Tex or fluorinated ethylcellulose. (The platelets of humans and dogs adhere to comparable degrees on the latter 2 biomaterials.) 3) With Cuprophan and recirculated blood, the human-dog difference persists at 30 and 180 mins. 4) By means of videomicroscopy, the species differences are unlikely only to be an artifact of the possible formation and embolization of surface-adherent aggregates. Tests for the thromboresistance of candidate biomaterials and for platelet adhesion under controlled flow conditions must therefore begin to take into account differences between humans and other species.


[Characteristics of the ecology of the eastern equine encephalomyelitis virus in the Republic of Cuba]. Virologic and serological surveys of wild vertebrates carried out in various provinces of Cuba demonstrated definitely that birds were the main hosts of eastern equine encephalomyelitis (EEE) virus in this territory. Fifteen strains of this virus were isolated from 8 species of birds belonging to 5 orders. Isolation of EEE virus from the blood of the endemic genus of iguanas indicates a certain role of cold-blooded animals in the ecology of this agent. Active EEE virus foci have been found in 4 provinces of the Republic of Cuba: Pinar del Rio, Havana, Matanzas and Las Villas. Isolation of a number of EEE virus strains from sick horses during an epizootic in the latter province confirmed the importance role of this agent in the infectious pathology of domestic animals in Cuba. The experimental results suggest that in Cuba there occur at least two types of foci of this infection: forest and water-littoral (fresh-water swamps and lakes, and sea coast with mangrove forests).


[Inhibiting action of glycomacropeptide on stomach secretion induced by various humoral stimulants]. Tests staged on dogs demonstrated the action of GMP to differ depending upon the nature of the gastric secretion stimulant actually used. The inhibition of the gastric juice secretion occurring against the background of multiple introduction of histamine or gastrin tetrapeptide amide was quite spectacular: the secretion dropped down to zero and the action was more prolonged than following administration of pentagastrin with which the secretion was not inhibited to such a sharp degree and the effect of GMP was less protracted. The mechanism of the GMP action of the gastric secretion and the causes of described differences require further investigations.


[The acid-alkaline equilibrium of the organism and the age (author's transl)]. In 90 patients (three aging groups: from 20 to 29 years, from 60 to 69 years, from 80 to 89 years) with a physiologic aged status are investigated parameters of acid-alkaline equilibrium. There are no essential aging changes of the blood pH and other parameters, which characterize the acid-alkaline balance of the organism. The investigations in rats show, that with increasing age the possibilities of reserve of regulating mechanism in relation to the acid-alkaline equilibrium decrease.


[The water-electrolyte-change and the age (author's transl)]. In 403 healthy probands between 20 and 103 years old the ionogram of the erythrocytes and of the plasma was analysed. In the one part of the test persons (75 probands) also the water spaces of the organism was examinated. It was established, that the electrolyte composing of the blood is changing with increasing age. In the erythrocytes the content of potassium, magnesium decreases, the content of sodium and chloride increases; in the blood plasma the content of potassium, calcium, magnesium and acid carbonates decreases, the content of acid radical groups--sulphates, phosphates, chlorides and organic acid increases. In an examination of the water spaces was an age depended decreasing of the quantity of total and of the intracellular fluid remarked. The changes probably show the state of the metabolic processes in the age, which is characterized by decreasing of the total metabolism and decreasing of insufficient oxydised products.


[The proximal gastric vagotomy in the treatment of uncomplicated duodenal ulcer (author's transl)]. Of 97 patients, who had a PGV since July 1971, 86 were checked intraoperatively on completeness of vagotomy with various methods, including Kongo-red-staining, pH-electrode and Burge-test. On theoretical grounds, the Burge-test combined with pH-measurement seems the most reliable procedure. In 14 cases an incomplete Vagotomy could such be avoided. 72 patients, who met the critiria of more than 6 months follow-up, were graded according to VISICK with 89% good results (I, II) and 11% VISICK III, IV. Two Patients needed reoperation, one with recurrent ulcer. Our results confirm the good impression we had initially, regarding the low postoperative morbidity, effective reduction of acidity and recurrence rate, but longterm follow-up studies are still required to form a final judgement.


The assay of protein-bound nitrite in meat products. An improved procedure for the determination of protein-bound nitrite (PBN) in meat products, based on Mirna's method, is described. The results obtained with this modification are significantly higher, and have a lower variation coefficient, than those provided by the old procedure. This is demonstrated by comparison of the analytical results.


[Studies on the growth of the width in seminiferous tubules of eutopic and congenitally dystopic testes in children and adolescents]. The average diameter of the seminiferous tubules is to be regarded as a criterion for the estimation of the morphological value of testicles. By means of 89 autoptically got preparations of regularly descended testicles the breadth-growth of the tubules depending on age in children was judged. Of 55 untreated congenital dystopic testicles morphometric determinations of the diameters of the seminiferous tubules were performed. At the same time 79 unilaterally and 78 bilaterally operatively dislocated, congenital dystopic testicles and 78 contralateral eutopic gonades were evaluated. The average diameter of the tubule of untreated dystopic testicles is significantly (p less than 0.001) smaller than the diameter of the orthotopic gonades corresponding to age. The average diameter of the tubule of operatively dislocated congenital dystopic testicles is, however, larger than the diameter of the untreated gonades corresponding to age. The earlier the treatment of congenital dystopic testicles is performed the larger are the chances of a development of the tubules corresponding to age.


[Length-growth of seminiferous tubules of untreated and as surgically displaced, congenitallydystopic testes in children and adolescents]. The total length of the seminiferous tubules of congenital dystopic testicles was calculated from bioptical preparations. 55 untreated testicles, 79 unilaterally and 78 bilaterally operatively displaced testicles as well as 78 contralaterally eutopic testicles were evaluated. During the whole prepuberal phase of life in the congenital dystopic testicles a nearly continuous growth of the length of the seminiferous tubules takes place. The total length of the intrascrotally displaced testicles is larger than the length of untreated testicles corresponding to age. After the operative correction of the position of congenital dystopic testicles an acceleration of the growth of the length of the tubule begins.


Gamma-radiolysis of aqueous solution of histidine. The dependence of Gi(-M) values of histidine on the concentration of irradiated 10(-4) - 10(-1)M solutions, pH and the presence of O2, N2O and sec-butyl alcohol was investigated. In oxygen-free medium the maximum radiation sensitivity of histidine was found at pH 5--8; in oxygenated solutions it was shifted to the 6--1 pH range. The formation of radiation products was also studied. The course of radiation decomposition of histidine depends on the presence of oxygen and on the pH of irradiated solution.


On the influence of aromatic residues on the interaction of copper (II) with small peptides containing aromatic amino acids: ESR and optical studies. The complexation behaviour of Cu(II) with di- and tripeptides containing the aromatic amino acids phenylalanine or typtophan has been investigated at different pH-values and compared with results obtained with di- and triglycine. The results obtained by means of ESR and optical absorption spectroscopy show an influence of the two different aromatic entities on the magnetic and optical parameters. A significant decrease of the g11-value and, concomittantly, an increase of the energy of the d-d transition was measured when an aromatic entity is present in the peptide. A possible explanation for this observation is given.


Dehydrogenase activity and microbial population in a red sandy soil amended and unamended with incubation. Incubation of single bulk sample of freshly collected red sandy soil in trays showed immediate response to added nutrients both in dehydrogenase activity and bacterial and fungal populations. The prevailing acidic pH might have been responsible for the observed response of fungi as well. Actinomycetes population did not fluctuate. It was therefore suggested that TTC dehydrogenase technique for measuring the biological activity could be applicable to coarse-textured and more open soils. There were indications that fungi contributed to the soil dehydrogenase activity as well.


[Purification of protease from staphylococcus aureus (author's transl)]. 380 (80%) of 475 Staphylococcus aureus cultures isolated from humans, cattle and dogs were proteolytically active either on casein or gelatin or both (table 1). Protease-activity could also be demonstrated in experimental body-cavities of rabbits (fig. 1). The enzyme-activity was estimated with azocasein. Protease from S. aureus, M 135 precipitated from the culture supernatant with ammonium sulfate at 65% saturation (table 2). It was purified by 2 filtrations on Ultrogel AcA 44 (fig. 2,3) and subsequent isoelectric focusing between pH 3.5-7.0 (fig. 4). The purified protease yielded only 1 line in the SDS-polyacrylamidegel-electrophoresis, in the gelatin-polyacrylamidegel-electrophoresis and in the double immuno-diffusion test (fig. 5). Its isoelectric point was at pH 4.6, and its highest proteolytic activity between pH 7.5-8.3. The molecular weight was estimated by SDS-polyacrylamidegel-electrophoresis to be near 29.000. The protease-activity was completely inhibited in the presence of EDTA, partially inhibited by Cu2+ and Zn2+ and increased by Mn2+ (table 3).


[On the determination of chlorine with a polarographic probe. 1st communication: Examination of the physical properties of the new instrument (author's transl)]. A new chlorine measuring device for the field use in the water plant praxis was tested. The portable instrument supplied with a selectively permeable membrane works basing on the polarographic principle and shall allow an easy and accurate measurement of the "disinfectingpower" of a water chlorination. In the 1st note most important possibilities of meter-default as dependence on streamvelocity of water, pH and temperature are described. Furter the phenomenon of hysteresis is demonstrated.


Local hyperalimentation of experimental granulation tissue. The effect of local hyperalimentation on developing granulation tissue was studied in rats. Cylindrical hollow viscose cellulose sponge implants were used subcutaneously as an inductive matrix fro the growth of granulation tissue. In the first, control group the implants were kept untouched while the second, "sham" group was treated daily by withdrawing 1 ml of wound fluid from the central dead space of the implant and then injecting the fluid back. In the third, hyperalimentation group the aspirated wound fluid was substituted with a corresponding volume of sterile, nonpyrogenic solution containing a mixture of amino acids (Le-7402 A) and glucose, electrolytes and vitamins (Le-7402 B). Within the first week of tissue growth daily application of these nutritional substances caused a changeover of local tissue from predominantly anaerobic towards more oxidative metabolism. Measurement of nucleic acid and hydroxyproline contents indicated enhanced accumulation of cells and collagen in tissues receiving local hyperalimentation. The results combined with earlier data from our laboratory strongly suggest that several types of wounds, especially those containing a marked dead space or large regenerative area, exist in chronic lack of oxygen and other nutrients. Therefore, the healing process in these wounds can be stimulated, to a certain extent, by exposure to increased oxygen tension and/or by local hyperalimentation.


Diazepam and flunitrazepam as induction agents for cardiac surgical operations. Diazepam and flunitrazepam were compared in equipotent doses as induction agents for premedicated patients having cardiac surgery. Both drugs caused a significant fall in arterial blood pressure, a rise in Paco2 and a fall in Pao2. There was no significant difference between the two drugs in onset time of anaesthesia, cardiovascular or respiratory depression, or quality of induction. There was also no significant difference from induction with thiopentone in these respects. Diazepam, over a 0.2 to 0.6 mg/kg range of doses showed no difference in toxicity, although induction was clinically smoother with the higher dose.


The effects of PaCO2 reduction on regional cerebral blood flow in the acute phase of brain injury. In 26 unconscious patients with brain injuries, regional cerebral blood flow (rCBF) was measured with a 16-channel Cerebrograph before and after acute reduction of PaCO2. The intra-arterial 133xenon washout technique was used, and CBF was calculated regionally as initial slope index or stochastic flow. The CO2 reactivity was calculated as deltaln CBV/deltaPaCO2. In supratentorial cortical lesions, an acute fall in PaCO2 increased the homogeneity of the regional flow pattern (decrease in the standard deviation of the regional flow values), and reduced the number of focal hyperaemic regions (tissue peaks). The CO2 reactivity in tissue peak regions was generally higher than in regions without tissue peaks. In severely injured patients with a poor outcome (dementia, vegetative survival or death), inverse steal reaction was accounted for in 11% of all regions, but only in 3% of the regions in patients who survived without dementia. Inverse steal reaction was most frequently seen during the first 3 days after the trauma. In repeated CBF studies, an increase in the CO2 reactivity with time was observed after the acute trauma. In comparison with the CO2 reactivity found in normocapnic awake subjects, this increase was higher than expected in several cases.


Parkinsonian tremor: a neuropharmacological study. In the Parkinsonian syndrome tremor is the symptom which still eludes pharmacological therapy. The authors report the results of nine cases of Parkinsonian tremor in which agonist and antagonist drugs acting on the receptors were employed. These were dopaminergics, acetylcholinergics, serotoninergics, histaminics, and alpha- and beta-adrenergics. The data obtained demonstrate the involvement of all the neurotransmitters studied, some directly through quantitative modifications, others indirectly through their involvement in reciprocal functional equilibria. A sytem of equilibria is hypothesized in which the histamine: serotonin ratio is given greater emphasis. (Acta neurol belg., 1977, 77, 213-229).


Evidence of decarboxylation of lysine by mammalian ornithine decarboxylase. In enzymic preparations from mouse kidney stimulated with the anabolic steroid Durabolin (nandrolone phenpropionate) lysine and ornithine were shown to inhibit the decarboxylation of each other competitively. The Michaelis constants for the decarboxylations were approximately equal to the inhibition constants of the two amino acids. The pH optima of the decarboxylation of lysine and ornithine were found to be identical. Chromatographic studies of the enzyme preparation on a Sephadex G-150 Superfine column did not bring about a separation of the two enzyme activities. The ratio of the decarboxylating activities was practically the same during the elution. Lysine decarboxylating activity was also shown to be present in growth hormone stimulated rat liver. The results are in agreement with the assumption that the decarboxylation of lysine and ornithine is carried out by the same enzyme.


New amino acid derivatives formed by alkaline treatment of proteins. Intense heat treatment of proteins at high pH favors formation of transient, reactive intermediates derived from serine and cystine. The postulated dehydroalanine intermediate reacts further with the epsilon-amino groups side chains and sulfhydryl groups of cysteine residues to form derivatives of lysinoalanine and lanthionine. Recent studies indicate that besides these crosslinked products, several others are formed, by reaction of histidine, arginine, and possibly other residues. For this reason, caution should be exercised in assigning the prelysine peak(s) of an amino acid chromatogram to lysinoalanine. These results suggest that unnatural amino acid derivatives, other than lysinoalanine, may also contribute to the toxic effects reported from studies in which alkali-treated protein was fed to rats.


35S-Sulfide incorporation during alkaline treatment of keratin and its relation to lanthionine formation. Cattle hair exposed to solutions of 35S-sulfide ions at pH 12.5, hydrolyzed with acid, and analyzed for amino acids with simultaneous measurement of the radioactivity of the eluate from the analytical column showed 87 percent of the radioactivity incorporated in the hair in three amino acids: cysteic acid, lanthionine, and cystine. This and other evidence presented lend further support to the intermediacy of dehydroalanyl residues formed by a beta-elimination reaction in the conversion of cystinyl residues to lanthionyl residues in proteins. The presence of radioactively labelled cystine in the hydrolyzate indicates that the dehydroalanyl residues are also capable of reforming cystinyl residues under these same conditions through a series of reversible reactions.


Treatment of the "syndrome of doubles".

Treatment of the "syndrome of doubles". An account of the response to biological treatment of 20 patients with the syndrome of doubles (syndrome of Capgras, syndrome of Frégoli, syndrome of Intermetamorphosis, syndrome of subjective doubles) is presented. Our observations indicate that: a) the syndrome of doubles may respond to various biological treatment methods; b) in the setting of depression it responds to tricyclic antidepressants; c) in the setting of schizophrenia or organic psychosis it usually responds to neurolytics; d) in a schizophrenic setting it has more chances of responding to trifluoperazine either given alone or in association with other psychopharmaca, and, e) in certain cases combination of antipsychotic treatment with treatment of co-existing organic dysfunction appears to be important.


Lysinoalanine formation in wool after treatments with some phosphate salts. Treatment of wool with solutions of sodium tripolyphosphate, potassium tetrapyrophosphate, and sodium phosphate results in the formation of lysinoalanine, the amount of which increases from the first to the last reagent. As this may be due to the different pH, solutions of the three salts of the same pH were also tried. This series of experiments suggests that although the hydroxyl ions contribute to the formation of lysinoalanine, the governing factor is the kind of the anions concerned, as the sodium phosphate acts in a more rigorous may than the two other salts, in spite of the smaller concentration and the faster reduction of the pH of the solution during treatment.


The formation and cleavage of lysinoalanine crosslinks. Treatment of lysinoalanine (LAL) with methyl iodide at pH-values above 8 leads to cleavage to dehydroalanine (DHA) and Nepsilon-di- or/and trimethyllysine, as was shown by ultraviolet spectra and amino acid analysis. This reaction is due to methylation of the crosslinking NH group of LAL to the quaternary ammonium compound; nucleophilic beta-elimination follows. By this reaction, the epsilon-amino groups of polylysine and its copolymers can be methylated to form di- and/or trimetryl-lysine residues. Chemically modified polypeptides containing Nepsilon-dimethyllysine can be made in this way.


On the specific cleavage of cysteine containing peptides and proteins. Addition of cysteine to the double bonds of polydehydroalanine and copolymers of dehydroalanine (DHA) and methylcysteine, alanine, leucine or gamma- methyl-L-glutamate is accompanied by increased solubility and decreased molecular weight. This result is due to a peptide bond cleavage caused by formation of a thiazolidine as a consequence of nucleophilic attack by the sulfur atom on the preceding C=O group and subsequent splitting of the peptide bond by nucleophilic attack of an OH ion. This mechanism is predominant in alkaline media; in acid another mechanism is favoured; carbonyl-oxygen attacks the carbonyl-C-atom of the cysteine residue, forming a second ring system. Addition of one water molecule then yields two peptide fragments, one of them a terminal cysteine residue. Both mechanisms could be confirmed in the case of gamma-L-glutamyl-dehydroalanyl-glycine by adding cysteine. Furthermore, it could be shown that SH-glutathione is decomposed at alevated temperatures according to the two mechanisms mentioned. This SH-induced peptide bond cleavage can be used for selective peptide chain splitting of cysteine-containing polypeptides and proteins under relatively mild conditions.


Reactions of proteins with dehydroalanines. Reactions of proteins with dehydroalanine or derivatives of dehydroalanine were studied as models for protein crosslinking. Treatment of casein, bovine serum albumin, lysozyme, wool or polylysine with acetamido- and phenylacetamido acrylic acid methyl esters at pH 9-10 converted varying amounts of lysine to lysinoalanine residues. Howver, complete transformation was not achieved. Incomplete reaction is atributed to partial hydrolysis of the esters to the less reactive acrylic acids under the reaction conditions. Similar studies were made of the reactivities of protein SH groups generated by reduction of disulfide bonds by tributylphosphine. The SH groups could be completely alkylated at pH 7.6 in aqueous propanol, as shown by nearly quantitative recovery of lanthionine. Such a procedure might therefore be used to estimate cystine contents of proteins.


The formation, isolation and importance of isopeptides in heated proteins. The separation and resolution of the isopeptides Nepsilon (gamma-L-glutamyl)-L-lysine and Nepsilon (beta-aspertyl)-L-lysine, formed in heated proteins, has been successfully achieved. The method demands a well characterised ion-exchange column and the use of pH 3.40 lithium citrate buffer (O.2N Li+). Due to variations in particle size and percentage crosslinkages in the ion-exchange resin a computer assisted buffer gradient system has been developed. This system affects resolution of both isopeptides in 7h. The use of leucyl-glycine as an internal standard facilitates quantitative estimation of the isopeptides. This separative method has been used to analyse a series of heated protein samples and to estimate the quantities of isopeptides formed. The ability of a protein to form isopeptides links is discussed as well as the implication of such links on the reactivity and digestibility of proteins.


Cross-linking of protein by peroxidase.

Cross-linking of protein by peroxidase. The reaction products of peroxidase, a hydrogen donor and hydrogen peroxide decreased the amount of lysine recovered from proteins after acid hydrolysis. Oxidation of peroxidase treated proteins with performic acid prior to hydrolysis formed alpha-amino adipic acid indicating that the peroxidase or the quinones formed by peroxidase had oxidatively deaminated some lysyl residues of the protein to form lysyl aldehyde. Gel filtration and polyacrylamide gel electrophoresis revealed dimers, trimers and higher protein polymers that were not detected when peroxidase was omitted. Since some of the protein polymers were not dissociated by gel electrophoresis in the presence of dodecyl sulfate, urea and mercaptoethanol, it suggests that the free radicals or quinones formed by peroxidase had interacted with or cross-linked protein molecules by the formation of covalent bonds. Oxidative enzymes like peroxidase and polyphenol oxidase may lower the nutritive value of proteins by the oxidative deamination of lysine, reaction with cysteine and methionine and by cross-linking protein molecules to reduce their susceptibility to enzymatic hydrolysis.


Biological effects of alkali-treated protein and lysinoalanine: an overview. The renal alterations induced by alkali-treated protein and lysinoalanine are reviewed and their biological implications discussed. Alkali-treated proteins and lysinoalanine, an unusual amino acid formed in proteins during alkali treatment, have been shown to produce a renal alteration characterized by nuclear and cytoplasmic enlargement, with alterations in DNA synthesis, mitotsis and nucleoprotein. These changes are localized in the straight portion of the proximal renal tubule and have been observed in rats but not in several other species. The nephrotoxic effect of synthetic lysinoalanine has been consistently demonstrated, but the ability of alkali-treated protein to induce renal alterations is apparently modified by factors other than lysinoalanine content. Factors which may influence the development of the kidney lesions in animals fed alkali-treatment protein are discussed, including nutritional factors, the chemical form of lysinoalanine in the protein, species differences, and metabolic fate. Other clinical and experimental conditions that result in similar renal alterations are presented for comparison with the lysinoalanine induced lesion, and possible functional consequences are considred.


Some chemical and nutritional properties of feather protein isolates containing varying half-cystine levels. Feather (keratinous) protein isolates containing 2.8 and 7.2% half-cystine were prepared. Solubility of the former increased to 100% between pH 6 and 12, whereas, that of the latter reached only 2.5% at pH 12. Tests showed that mixtures of sodium dodecyl sulfate and 2-mercaptoethanol were needed to completely solubilize the high half-cystine protein, and that sodium dodecyl sulfate alone or in combination with urea and/or 2-mercaptoethanol increased solubilization of the low half-cystine product. The rates of these reactions are further increased by heat. Dry heat denatured the  low half-cystine isolate more readily than the high half-cystine product; moist heat denatured both at a similar rate. Gel electrophoretic properties were unique for each keratinous product. Only the low half-cystine isolate ahd desirable functional properties in that it formed thick, viscous mayonnaise-like emulsions and desirable foams. Functional properties of this isolate were improved dramatically by adjusting the pH from 5.0 to 8.2 or by a two-step change from pH 5.0 to 4.0 to 8.2. Apparent nitrogen digestibility of the two keratinous isolates was greater than 90% as measured by rat growth and by pepsin-HCl digestion.


Protected proteins in ruminant nutrition. In vitro evaluation of casein derivatives. Chemical treatment of proteins in feeds can, by crosslinking protein chains or other chemical effects, decrease their solubility and microbial degradation in the rumen. A need exists to modify proteins systematically under well-defined conditions with inexpensive reagents and to evaluate the treated products nutritionally for possible beneficial effects on wool growth and quality as well as production of meat and milk. As a first step toward this goal we evaluated many derivatives of casein treated at pH 9-10 with various acylating and alkylating agents. Initial tests indicate that all treatments decreased protein digestion by rumen microorganisms. Potentially crosslinking reagents are usually more effective than similar ones that cannot crosslink. A few treatments gave ruminal protection that approached or exceeded that obtained with formaldehyde. This result shows that systematic evaluation of ruminal in vitro digestibility of protein derivatives may disclose new products deserving tests of post-ruminal digestibility and practical nutritive value.


Inhibitory effect of mercaptoamino acids on lysino-alanine formation during alkali treatment of proteins. Alkali treatment of food proteins converts some amino acid residues to the unnatural amino acid lysinoalanine which has been found to cause kidney damage when fed to rats. Formation of lysinoalanine was essentially prevented when isolates of soy protein and casein were exposed to alkali in the presence of thio-alamino acids such as cysteine. The results suggest that added thiols minimize the formation of potentially toxic lysinoalanine.


Structural proteins of infectious bovine rhinotracheitis virus. Infectious bovine rhinotracheitis (IBR) virus grown in bovine embryo kidney cell cultures was concentrated and purified in Ficoll density gradients. The polypeptide composition of the virus was studied by polyacrylamide gel electrophoresis. The mature virion was found to contain 18 structural proteins with molecular weights from 250,000 to 29,000 daltons; 8 of them were glycosylated. The similarity of IBR virus protein composition to proteins of other herpetoviruses is discussed.


Investigation on the mechanisms of the failure of human influenza virus to replicate in chick embryo cell cultures. Thirteen strains of human influenza virus producing in chick embryo cell (CEC) cultures either virions with low infectivity or no virions were studied. In CEC, most of the strains induced synthesis of viral RNA, polypeptides, and ribonucleoprotein and produced functionaly active haemagglutinin, neuraminidase and virions lower infectivity. The low infectivity of virions produced by strains of this functional group was due to disturbed cleavage of a polypeptide, haemagglutinin precursor, formed in CEC, into a heavy a light haemagglutinin chain. Two strains belonging to another functional group induced no synthesis of virus-specific macromolecules in CEC, but were able to adsorb onto the cells. With one of these viruses, no transcription of parental RNA could be detected in CEC. There was no relationship between the grouping of the studied strains into a certain functional group with their antigenic characteristics, the year of isolation, the passage history in chick embryos and human pathogenicity.


Suppressive effect of Newcastle disease virus on the primary and secondary immune responses of hamsters. The effect of Newcastle disease virus (NDV) on the formation of 19 S haemolytic plaque-forming cells (HPFC) in the secondary immune response and on the formation of 7 S HPFC in both primary and secondary immune responses of hamsters to sheep red blood cells (SRBC) was studied. The 19 S and the 7 S HPFC in the spleens of hamsters injected with SRBC were demonstrated by the direct and indirect Jerne's method, repectively. A single intraperitoneal injection of NDV 5 days prior to primary immunization markedly depressed the number of 7 S HPFC. NDV administered 5 days prior to the second injection of SRBC resulted in a significant decrease in the number of both 19 S and 7 S HPFC. It is asssumed that interferon induced by NDV is responsible for the suppressive effect of the virus on both the primary and secondary immune responses of hamsters to SRBC.


Concentration and purification of tick-borne encephalitis virus grown in suspensions of chick embryo cells. Tick-borne encephalitis (TBE) virus grown in suspensions of chick embryo cells was precipitated by various concentrations of polyethylene glycol (PEG) 6000. Quantitative recovery was obtained at PEG concentrations of 5% and higher. As precipitation of contaminating non-viral protein increases with increasing PEG concentrations, best results with respect to purity and recovery were obtained at 5% PEG 6000. Analysis of virus concentrates by rate zonal centrifugation revealed two peaks--rapidly sedimenting haemagglutinin (RHA) associated with infectivity and slowly sedimenting haemagglutinin (SHA)--characteristic of Flaviviruses. Purification factors after PEG precipitation followed by rate zonal centrifugation in sucrose density gradients ranged from 50 to 200 for HA activity and from 40 to 50 for infectivity.


Characterization of tick-borne encephalitis virus and immunogenicity of its surface components in mice. Tick-borne encephalitis (TBE) virus grown in chick embryo cells and purified by rate-zonal centrifugation was shown to have a density of 1.195 g/cm3 in sucrose density gradients. Under the conditions used, CsCl centrifugation caused disruption of the virus and less than 5% of input infectivity could be recovered from the virus peak at 1.23 g/cm3. As in other fiaviviruses, three polypeptides (V1, V2, V3) were detected by polyacrylamide gel electrophoresis in radioactively labelled purified TBE virus. After disruption of TBE virus with Nonidet P-40, Tween-80/Tri-(n-butyl)-phosphate or sodium deoxycholate, a 120--130 S nucleoprotein could be separated by rate zonal centrifugation from more slowly sedimenting haemagglutinins. Immunization of mice with these haemagglutinins showed that they induced haemagglutination inhibiting, neutralizing and complement fixing antibodies. A pronounced increase in immunogenicity could be observed by the use of Al(OH3) as an adjuvant.


Potentiation of langat virus infection by lead intoxication--influence on host defenses. Pathogenesis was studied in mice with moderate levels of lead intoxication after Langat virus infection. Both lead chloride and lead nitrate increased mortality by 40--50%. This increase was associated with decreased in vivo interferon and neutralizing antibody synthesis. The increased mortality was associated with enhancement of viral growth in peripheral tissues as evidenced by early appearing and long-lasting high titer viremia following lead intoxication. This resulted in early penetration of blood brain barrier and led to much higher virus titers in the brain. The data strongly suggest that lead increased mortality following infection by complex means, the most important being the enhacement of encephalitogenic potential of Langat virus.


Non-infectious antigen for laboratory diagnosis of Japanese encephalitis. Sucrose-acetone suckling mouse brain antigens of Na-kayama NIH, JaGAr-01 and Peking-1 strains of Japanese encephalitis (JE) virus treated with beta-propiolactone (BPL) retained their ability to specifically react in haemagglutination inhibition (HI) tests with antibody to JE virus, as demonstrated with convalescent sera. BPL treatment abolished the infectivity but did not affect the haemagglutinating activity of the virus of the pH optimum of the haemagglutination (HA) test.


Measles antibodies in nasal secretions and sera of children with measles. Measles antibodies were determined, in the course of measles, in sera and nasal secretions of 54 and 27 children, respectively. The examinations were performed on the 3rd or 4th day (1st period) and between the 10th and 14th day (2nd period) after onset of rash in both sera and nasal secretions and after 25 to 60 days (3rd period) in sera only. Geometric mean titres of antibodies in sera determined by haemmagglutination inhibition (HI) and neutralization tests in the 1st period were 126.3 and 115.3 respectively. For the 2nd period the respective figures were 318.4 and 396.1 and for the 3rd period--388.0 and 445.6. Fractionation on Sephadex G-200 of sera from the 1st period revealed HI and neutralizaing antibodies associated mainly with the IgM serum globulin class. Measles HI and neutralizing antibodies were also found in nasal secretions of all 27 children, but their titres were much lower than in serum. The antibodies determined by indirect immunofluorescence in nasal secretions were associated with IgA in 26 and with IgG immunoglobulin in 15 of the 27 subjects. No IgM antibodies were found.


Comparison of interferon-inducing activities and antiviral effects of tobacco mosaic virus, tilorone and sodium nucleinate. Endogenous interferon was produced in animals in response to the administration of tobacco mosaic virus (TMV), tilorone and sodium nucleinate. The relationship between interferon production and the kind of inducer and the route of its administration was studied. TMV was completely innocuous for Macaca rhesus monkeys and mice and caused no untoward effects in humans upon peroral administration. TMV, tilorone and sodium nucleinate given per os exerted a marked protective effect in mice against tick-borne encephalitis, eastern and western equine encephalomyelitis and influenza virus infections.


Transmission of alfalfa mosaic virus through Nicandra physaloides seeds and its localization in embryo cotyledons. Alfalfa mosaic virus (AMV) was found to be transmitted through seeds of Nicandra physaloids L. The average seed transmission rate of the AMV isolates T6, LMBG-4 and ST amounted to 23, 4 and 0 per cent, repectively. In the cytoplasm of parenchyma cells of embryo cotyledons of seeds from plants infected with the T6 isolate, electron microscopy revealed AMV aggregates of type 2A and aggregations of irregularly viral particles with a tendency to subparallel alignment, representing early stages of type 2A aggregates.


Simple method for preparation of immune sera to envelope and nucleocapsid antigens of Semliki Forest virus. Immune sera to the envelope and nucleocapsid components of Zaisan 260 and R 16225 strains of Semliki Forest virus (SFV) were prepared with the use of disrupted, partially purified virus.


Chemical interactions between thiamin and tannic acid. II. Separation of products. Bio Rex 70 column chromatography and high voltage paper electrophoresis were used to fractionate and define the reaction products of thiamin-tannic acid and thiamin-tea mixtures. Fractions separated indicated the presence of (a) thiamin-tannic acid adduct(s) and several modified forms of thiamin among the products. Using radioactive thiamin and determining the intact form by scintillation counting, the extent of thiamin modification under various conditions was compared with previous results as determined by the thiochrome method. The elution profile of the thiamin-tea mixture and the electrophoretogram showed features similar to those of the thiamin-tannic acid mixture. The effectiveness of the tea extract and tannic acid in modifying thiamin was compared. Ascorbic acid was found to protect the modification of thiamin by tannic acid, not only at acidic pH as previously found, but also at neutral pH, thus making vitamin C a strong candidate for the protection of thiamin in the alimentary system.


Binding of zinc and iron to wheat bread, wheat bran, and their components. Wholemeal wheat bread decreases the availability and intestinal absorption of divalent metals. To define this action further, binding of zinc in vitro to a wheat wholemeal bread (Tanok), dephytinized Tanok, and cellulose was determined at pH 5.0 to 7.5. Zinc binding by each was highly pH-dependent and reached a maximum at pH 6.5 to 7.5. Removal of phytate from Tanok did not reduce its binding capability. Wheat bran at pH 6.5 and 6.8 bound 72% of iron (0.5 microgram/ml of solution) and 82.5% of zinc (1.43 microgram/ml solution), respectively. Lignin and two of the hemicellulose fractions of wheat bran and high binding capabilities for zinc (85.6, 87.1, and 82.1%, respectively) whereas a third had a lower zinc-binding capability (38.7%). Binding of zinc to various celluloses and dextrans is also demonstrated. Formation of complexes of these metals with wheat fiber can explain, at least in part, the decreased availability of dietary iron and zinc in wholemeal wheat bread.


Ionic flux across canine duodenum. Movement of bicarbonate. Effect of isosmotic biocarbonate-rich solutions on the Brunner's gland area were studied by means of proximal duodenal explants in eight anesthetized dogs. Volume gain occurred with all instillates and varied indirectly with the concentration of the bicarbonate in the instilled solutions. Net bicarbonate gain occurred with instillate of 40 mEq./1.; net insorption occurred with instillates of higher bicarbonate concentration, the rate of which was dependent on the instillate concentration. Insorption of chloride occurred with the lower bicarbonate solutions and enterosorption occurred at higher concentrations. The modification of intraluminal bicarbonate by the proximal duodenal mucosa is important in the regulation of intraduodenal pH and abnormal function of this mechanism may play a role in the pathogenesis of duodenal ulceration because of incomplete hydrochloric acid neutralization.


Necrotizing vasculitis of the gallbladder and the appendix. Similarity in the morphology of rheumatoid arteritis and Polyarteritis nodosa. Two patients with rheumatoid arthritis (RA) and polyarteritis nodosa (PN) presented with abdominal pain. Both revealed necrotizing vasculitis of the gallbladder and the appendix respectively. The controversial role of corticosteroids in the pathogenesis of rheumatoid arteritis, the rarity of rheumatoid arteritis of the gallbladder and the morphologic similarity of the vascular lesion in the gallbladder and appendix are discussed.


The effect of ethanol and bile on electrolyte movement across canine proximal duodenal mucosa. The existence of a gastric mucosal barrier, controlling H+ N+ flux has been well established. The disruption of this barrier by ethanol and bile has also been confirmed. This study was designed to investigate the effect of ethanol and bile on the duodenal mucosa, which, as we have shown, is similar to gastric mucosa in that there is H+, Na+ flux. In 10 dogs, duodenal explants with an intact blood supply were placed within lucite chambers. Under basal conditions there was H+ insorption and Na+ exsorption. Neither bile nor ethanol caused increased H+ Na+ flux. Acute erosions did not develop in the proximal duodenum, as has been shown to occur when bile or ethanol is instilled into the stomach. These studies, therefore, demonstrate that although H+ Na+ occurs across the duodenal mucosa, bile or ethanol do not cause changes in ionic flux and acute erosions do not develop.


Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis. N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.


Blockade of myocardial slow inward current at low pH. The effect of low pH on the slow cationic inward current was studied in isolated perfused embryonic chick ventricles (16-21 days old). In order to study the slow current, the fast Na+ current was inactivated by partial depolarization to about -40 mV by elevation of K+ (25 mM). Subsequent exposure of the tissue to catecholamines or methylxanthines allowed slowly rising overshooting electrical responses (the "slow response") with with accompanying contractions to be elicited by electrical stimulation. These slow responses are insensitive to tetrodotoxin and are Na+- and Ca2+-dependent. It was found that the isoproterenol- and caffeine-induced slow responses were abolished at about pH 6.1; 50% inhibition occurred at about pH 6.5. The rate of rise of the normal action potential, which is dependent on a fast Na+ current, was only slightly affected at these same pH levels; however, electromechanical uncoupling occurred, as expected from inhibition of the slow current. Therefore, the slow current was blocked at an acid pH that did not block the fast Na+ current.


Rio Grande--a new phlebotomus fever group virus from south Texas. Three strains of a new Phlebotomus fever group virus were isolated from pack rats (Neotoma micropus) collected in south Texas during 1973--1974; the name Rio Grande was proposed for this virus. The virus is pH 3.0 labile, sensitive to the action of sodium deoxycholate and heat (56 degrees C) labile. The results of a serosurvey indicated that pack rats are probably the principal vertebrate host for Rio Grande virus and that year-round transmission of the virus may occur. Because no isolations of this virus were made from hematophagous insects, the vector, if any, remains undetermined.


Multiple endocrine adenomatosis type IIB. Report of two cases and review of the literature. The combination of bilateral medullary thyroid cancer, bilateral pheochromocytoma, Marfanoid body habitus with arachnodactyly, pectus excavatum, mucosal neuromas, and hyperplastic corneal nerves has become recognized as a definite entity, multiple endocrine adenomatosis (MEA) Type IIB. Two cases of MEA Type IIB are described, along with diagnosis, treatment, pitfalls in management, and related syndromes. When this syndrome is suspected, a careful search for other hyperfunctioning endocrine glands, particularly pheochromocytoma, must be made. Failure to recognize pheochromocytoma may prove a serious hazard if thyroidectomy is the initial procedure. The value of thyrocalcitonin as an indicator of the presence of medullary thyroid cancer and its value as a familial screening test are discussed.


[Continuity of life situation and "successful" aging (author's transl)]. The determinants of "successful" aging have been a main concern in social gerontological research. The Continuity Hypothesis suggests that there is a relationship between an older person's life satisfaction and the similarity of his social life situation in middle adulthood and in old age. The old person is the more likely to score low in life satisfaction the less similar his old age situation to his life situation in middle adulthood. This hypothesis has been tested in summer 1973 in Cologne with a sample of 406 people aged 65 and over. Findings indicate that continuity of life situation may be an important variable accounting for life satisfaction in old age. Moreover, it could be shown that the various negatively experienced life changes since adulthoood formed a complex of interacting variables, thereby increasing the negative effect on the old person's life satisfaction. Health proved to be one of the most important variables. The continuity hypothesis as stated here represents a modified version of activity theory.


[Psychic help for aged people of day-care-centers by attending person-centered encounter groups (author's transl)]. 45 old people (Average age 72 years) took part in 9 person-centered encounter groups together with younger people (Average age 32 years). Psychological changes of the old people were collected by questionaires and compared to a control group of 38 old people who subsequently took part in 4 encounter groups without younger people. Excerpts from the encounter talks were rated in certain variables. delta The old people of the mixed aged encounter groups showed constructive psychological changes after participation, for example reduced feelings of loneliness, reduced stress with emotional problems, and they see ageing less resignative. The mixed aged encounter groups were more helpful for the old people than the groups without younger people. The old people of the mixed group were more emotionally occupied by their own person, they showed more self-exploration and self-acceptance, they talked with more emotional engagement about their experiences and were more genuine; 3 months later their self-disclosure in an interview with a stranger was higher.


[Poverty in old age (author's transl)].

[Poverty in old age (author's transl)]. The legitimate claim on social assistance riveted in the Federal Legislation on Social Welfare and deduced from the welfare-state-postulate of the Constitution is only partially valid (obligatory assistance only). Applying this claim substantially is legally tied to discretionary decisions of the administration. Handling such estimates in a restrictive way makes the legitimate claim invalide. Social values are significantly determined by equivalent-maxims. Claims on social assistance, however, are not being deduced from preperformances (in a judical sense in regard of pensions) but are being derived from a diffuse claim on a social state incured with the odium of statutory relief for the necessitous. It is empirically provable that the causes for need of social assistance are of a social kind. Therefore, the claim on social assistance can only be a claim to "reparation". This understanding could be seen as an adequate basis for a progressive administration of social welfare.


[Causes and outward forms of poverty in old age (author's transl)]. In the Federal Rupublic nearly 20% of the elderly people live on the edge of below the property-line, which is well-marked by public assistance. In spite of legal claims 75% of the needy elderly do not explore all possible avenues. The ascertainment of this high percentage which had been never estimated exactly-about which, hitherto, impressionistic or opportunistic declarations have been made rather than reliable assertions-is a result of a representative empirical research. The authors have conducted structured interviews, analysis of official files and explorative interviews with old people and with those who are, in a broad sense, competent regarding their need. The analysis of the old peoples' social biographies significantly showed the invariance regarding the class the necessitous belong to; generally workers or people of the farming section either become or remain poor. Deficient vocational education is the beginning of a lifelong outstanding external determination. Their non-problematical replaceability at work surrenders them to the enterpreneur's calculation. When growing older they often endure professional depreciation and financial reduction. After they have retired, need encreases. Individual failure is not the cause for poverty, however the belonging to the working-classes; all those belonging to these classes are potentially poor, due to their replaceability and exchangeability at work. At the lower end of the class-hierarchy potential poverty changes into actual poverty. Causative regarding formation of these classes is the fact, that the material possibilities of the social production cannot be used by the actual producers. The causes for poverty which reproduces itself always within the same classes can't be removed by legal means which can only relief poverty.


[Significance of environmental hygiene for aging individuals (author's transl)]. Problems in the field of modern hygiene have changed in parallel with the current shift of morbidity and mortality in the direction of non-infections diseases such as vascular and circulatory disturbances and malignant tumors. As a consequence, hygienic care for the aged is becoming increasingly more important, and with it the close association between Hygiene and the sciences of Gerontology and Geriatrics. Because of long-term, chronic exposure via air, food, and drinking-water, environmental carcinogens such as the P.A.H. and nitrosamines constitute serious health hazards especially in advanced old age. Also, the accumulation in human body fat of biocides of the class of chlorinated hydrocarbons (e.G. DDT) must be considered an alarming finding, since toxic effects may be expected as a result of fat resorption in elderly subjects. Thus, there is a need for the further development and broadening of the field of Gerohygiene as an essential part of General Gerontology.


[Education: a theme in gerontology (author's transl)]. The paper presents a review of the history of educational gerontology ("andragogy" or "gerontagogy") which has a special role within the field of gerontology. Whereas gerontological sciences such as biology, medicine, psychology, and sociology in (frequently interdisciplinary) approaches study the process of aging, educational gerontology makes use of the findings of these research areas, intending to influence the process of aging. There is a need for education in old age - provided this is not restricted to the acquisition of knowledge and skills or the extension of academic training into old age. It is stressed that an offer of "education for the aged" or even of "help for the life in age" very ofter is rejected by old people as they are induced to feel incompetent when invited to school and training courses of that kind. Future "gerontagogy" will have to notice and to respect resistance of that kind and will have to endeavour to increase the motivation to learn in old age in adequate ways. A first goal of educational gerontology should be to develop programs going beyond those developed for children and realized in traditional institutions of pedagogy. Referring to results of differential gerontology programs for "educating" and "stimulating" aged persons will have to be rather variable to fit individual goals and motivations of the old. The differential approach necessary to meet individual and rather specific demands will require a more thorough "training of trainers" than is realized today in the Federal Republic of Germany.


[Interrelationship of motivation and barriers in the learning process in old age (author's transl)]. Started from the concept of lifelong learning it is discussed that the relation between motivation and barriers or obstructions has important influence on learning in old age. Even if differential view has been regarded, in general we may suppose that motivation will have a decreasing tendency and barriers an increasing tendency in old age. This concept is seen together with Welford's Cost- and Benefit-Theory (1976), discussed for Motivation, Capacity, Learning and Age. Consequences would be to look for measures to increase the motivation and decrease the barriers as far as possible.


[Consistency and variability of intellectual and psychomotor abilities in aged people (author's transl)]. Several methods of statistical analyses, featuring as well group specific changes and intra-individual changes, in an investigation of intelligence, psychomotor abilities of 121 aged men and women over a period of 7 years, lead to results that there are many different aspects of consistancy and change. An attempt is made to discuss these results in the framework of differential and developmental psychological aspects.


[Evaluating programs for preparation to old age: some theoretical thoughts and a practical example (author's transl)]. In the first part methodically satisfactory experimental designs for evaluating programs for preparation to old age on the basis of Cambell & Stanely (1963) are sketched including conditions which hinder the realization of the ideal notions. In the second part an experiment for comparing two preparatory courses to old age using different methods of instruction is described. It was observed that the more demanding teaching method resulted in more anxiety for old age. This led to the conclusion, that programs for preparation to old age should be planned as a sequence of several units in which the mastering of the new ideas may be learned and in which this learning process may be supervised.


[Academic learn in old age (author's transl)]. To test the capacity of the elderly to sustain prolonged intellectual activity, 80 volunteers from 60 to 90 years of age received instruction in reading German, previously not studied by them. Special methods of instruction were employed to stimulate interest and self confidence. Independent tests after three and six months showed that average progress was several times more rapid than that observed in high school children under normal conditions. Extremely beneficial effects on the personal attitudes of the participants resulted from the social contact involved. A later experiment involving learning to play the recorder produced similar results.