The generalized convulsive seizure state induced by daily electrical stimulation of the amygdala in split brain cats. Daily unilateral electrical stimulation of amygdala in forebrain bisected cats provoked the development of the final stage of the kindled convulsion with remarkable rapidity regardless of presence or absence of anterior commissure. The chronological and spatial pattern of propagation of afterdischarge, interictal spike discharge, and clinical manifestations strongly suggest the significant role played by the midbrain reticular formation and possibly other brainstem structures in the progressive electroclinical seizure development. This assumption was supported by the results of a lesion study in which placement of a destructive lesion in the ipsilateral midbrain reticular formation markedly increased the generalized seizure triggering threshold, lateralized the afterdischarge to the stimulated hemisphere when induced with increased intensity stimulation, fragmented clinical seizure manifestations, and failed to produce progression of clinical and electrographic events with prolonged daily stimulation. This is in contrast to the insignificant effect produced by a peduncular lesion. Our findings suggest that vertical (limbic-brainstem), but not horizontal (transhemispheric interlimbic) connection is critically involved in the amygdaloid seizure development while the forebrain commissures may play a role in the development of bisynchronous and bisymmetrical ictal and interictal electrographic and clinical manifestations. Finally, possible differential effect of forebrain bisection depending on developing in contrast with a established (cerebral) hemispheric epileptogenic process is postulated to explain the "facilitatory" effect observed in our series in contrast to the beneficial effects reported on some intractable seizure patients.


Kinetic properties of hexokinase in resected temporal lobes of patients with drug-resistant epilepsy. Properties of the cerebral glycolytic enzyme, hexokinase, were studied in biopsy samples of human temporal lobe, obtained during lobectomy for drug-resistant epilepsy and compared "blind" with contol biopsy samples of human cerebral cortex. No significant changes in the total activity or subcellular distribution of the enzyme were observed but the Km value for glucose was altered. The 17 control samples gave a normal mean value for Km (glucose) of 0.05 mM and the 14 epileptic samples gave a significantly higher mean value of 0.09 mM. The drugs used in previous treatment of the epilepsies were "scored" with respect to type and dose; analysis of these in relation to the kinetic results eliminated the possibility that the increase in Km value was an artifact due to the drugs. The observed change in enzyme kinetic properties is discussed in terms of potential interactions of small molecules with the isoenzymes of cerebral hexokinase.


Relative frequency of different types of epilepsy: a study employing the classification of the International League Against Epilepsy. Approximately three-quarters of epileptic patients seen in consultation by specialists can easily be assigned to one of the diagnostic categories of the International League against Epilepsy. When patient age is taken into account, such a distribution shows that partial epilepsy is more common than generalized epilepsy (62% versus 38%) in patients of all ages, especially in those over 15 years of age (78% versus 22%). In contrast, generalized epilepsy is more frequent in subjects under 15 than partial epilepsy (55% versus 45%). In this younger age group the rarity of partial epilepsy is primarily due to the infrequency of temporal lobe epilepsy (21% of cases, as opposed to 56% in subjects over 15), whereas both primary and secondary generalized epilepsy contribute to the frequency of generalized epilepsy in this group.


Serum pyridoxal, folate, and vitamin B12 levels in institutionalized epileptics. Serum pyridoxal, folate, and vitamin B12 concentrations were measured in 68 institutionalized patients with severe epilepsy. Twenty-five patients had a reduced level of pyridoxal and thirty-three a reduced level of folate. There was no instance of a low serum vitamin B12 although in three patients the levels were found to be abnormally high. Fifteen patients had both a low serum pyridoxal and a low serum folate but there was no significant correlation. All patients had a normal hemoglobin concentration and a normal mean corpuscular volume. There was no close relationship between reduced serum vitamin levels and single or groups of anticonvulsant agents, although the size of the groups was too small to permit a detailed study.


Neuroexcitatory and depressant effects of penicillin at the cat soleus neuromuscular junction. Penicillin administered intraarterially in a dose of 200 units per kg produced high frequency (ca 300 Hz) repetitive discharges originating in motor nerve endings in response to single stimuli applies to the cat soleus nerve. The high frequency repetitive discharges were antidromically conducted and recorded on ventral root filaments. Simultaneously each repetitive burst was transmitted to the muscle, producing an increase in contractile strength by converting a twitch into a brief tetanic contraction. Posttetanic potentiation in this system, which is mediated by repetitive discharges originating in nerve terminals after high frequency stimulation, is augmented by penicillin; larger doses depressed posttetanic potentiation, and still larger doses produced varying degrees of neuromuscular block. Events similar to those observed after intraarterial injections were recorded when penicillin was administered intravenously in larger doses. These data suggest that in the presence of penicillin the motor nerve terminals remain depolarized for a prolonged period after excitation by the stimulus, thus providing a current sink for the parent axon. Under the influence of this constant cathodal focus the axon fires repetitively at the high frequency.


Biofeedback in epileptics: equivocal relationship of reinforced EEG frequency to seizure reduction. It has been reported that biofeedback training of 12- to 14-Hz activity recorded over Rolandic cortex was accompanied by a reduction in seizure incidence in four human epileptics (Sterman et al., 1974). Biofeedback training of 12- to 14-Hz activity was provided for two epileptics and had no effect on clinical EEGs, seizure incidence, or proportion of EEG spectral power in the frequency range being trained. Subsequently, biofeedback training of 6- to 12-Hz Rolandic activity was provided for three epileptics. Two patients experienced reductions in seizure not accompanied by medication changes. Since no learning of 6- to 12-Hz activity was detected, the changes in seizure incidence are not attributed to EEG biofeedback. It is suggested that the experience in the feedback setting provided these two patients with new techniques of relaxation. In view of the lack of statistical evidence of EEG changes following EEG biofeedback and the small number of patients trained to date, it appears wise to maintain a cautious attitude until the issue of causality is clear.


EEG of a nocturnal seizure in a patient with "benign epilepsy of childhood with Rolandic spikes". The first EEG recording is reported of a child with "benign epilepsy of childhood with Rolandic spikes" during a partial motor (facial) seizure, which occurred during Phase II of natural sleep.


Antiepileptic and prophylactic effects of tetrahydrocannabinols in amygdaloid kindled cats. Acute administration of delta8-tetrahydrocannabinol (delta8-THC) or delta9-THC failed to affect partially developed or fully developed kindled amygdaloid seizures in cats. However, delta9-THC was quite effective in suppressing focal AD in the stimulated amygdala when administered very early in kindling, before the development of any clinical manifestations. This finding suggested that chronic administration of delta9-THC during kindling might block the process of seizure development, which was supported by the observation that three of four cats failed to kindle when treated with the drug. The cat that failed to be protected by delta9-THC was also insensitive to the general electroclinical effects of moderately high doses of delta9-THC. The prophylactic activity of delta9-THC is in contrast to the ineffectiveness of diphenylhydantoin, a drug whose anticonvulsant activity is often compared with that of THC.


Epileptogenic properties of folic acid and N5 methyltetrahydrofolate in cat. The epileptogenic properties of folic acid and N5-methyltetrahydrofolate applied locally on the cortex were compared in cats. Neither substance was epileptogenic except in very high concentration, on the order of 10(-3) M. N5-Methyltetrahydrofolate, the folate derivative most widely distributed in the central nervous system and CSF of mammals, was not more epileptogenic than folic acid. Because the level of N5-methyltetrahydrofolate is only slightly diminished in patients treated with anticonvulsants, the change cannot account for the therapeutic effect of the drugs.


Amino-acid sequence of toxin III of Naja haje. The complete amino acid sequence of toxin III of Naja haje (72 residues) has been established mainly by use of a protein sequenator (identification of 70 residues). The two C-terminal residues have been determined by digestion with carboxypeptidases A and B. Addition of succinylated protein or peptide greatly improved the performance of the sequenator for the Edman degradation of peptides: on one peptide (39 residues) degradation went to step 34 with a protein program and on two peptides (10 and 13 residues) degradation reached the last amino acid with a peptide program (use of dimethylbenzylamine). Amino acid analysis of tryptic peptides obtained by digestion of the C-terminal cyanogen bromide peptide are in full agreement with the sequence established by automatic degradation. The sequence of toxin III of Naja haje is unique and is very similar to that of Naja nivea alpha (although there are 9 differences), of Naja melanoleuca b (11 differences) and also to that of Naja naja A (18 differences).


Identity and activities of lysosomal enzymes in parenchymal and non-parenchymal cells from rat liver. 1. Intact parenchymal and non-parenchymal cells were isolated from rat liver. The parenchymal cells were purified by differential centrifugation, while non-parenchymal cells were obtained free of parenchymal cell contamination by preferentially destroying the parenchymal cells with the aid of pronase (0.25%). 2. The ability to isolate pure intact parenchymal and non-parenchymal cells permitted the characterization and measurement of specific activities of various lysosomal enzymes, representing the main functional hydrolytic activities of the lysosomes in these distinct cell types. 3. Lysosomal enzymes catalysing the hydrolysis of the terminal carbohydrate moiety of glycoproteins and glycolipids were not particularly enriched in the non-parenchymal cells as compared to parenchymal cells. The ratio of the specific activities of non-parenchymal cells over parenchymal cells varied between 0.7 for N-acetyl-beta-D-hexoseaminidase to 2.1 for alpha-glucosidase. This suggests no specific role of the non-parenchymal cells in the hydrolysis of terminal carbohydrate moieties of glycoproteins and glycolipids. 4. The enzymes acid phosphatase and aryl sulphatase, representing the phosphate and sulphate hydrolyzing activities, were enriched in the non-paranchymal cells as compared to the parenchymal cells by a factor of 2.5. 5. The most important peptidase cathepsin D, representing protein breakdown capacity, is enriched in the non-parenchymal cells as compared to parenchymal cells by a factor 6.0, suggesting a possible specific function of non-parenchymal cells in protein breakdown. 6. The most enriched lysosomal enzyme, representing lipid hydrolysis, is acid lipase, which is enriched in the non-parenchymal cells with a factor of 10. 7. The distribution of lysosomal enzymes between parenchymal and non-parenchymal cells suggests different functional roles of the lysosomes in these cell types. It can be concluded that the non-parenchymal cells possess a set of lysosomal enzymes which makes them extremely suitable for a phagocytic and antimicrobial function in the liver.


Studies on plasma free-fatty-acid metabolism and triglyceride synthesis of brown adipose tissue in vivo during cold-induced thermogenesis of the newborn rabbit. Parameters of plasma free fatty acid metabolism (pool size, half time, disappearance rate, turnover time and absolute turnover rate), the influx of plasma free fatty acids into the glycerides of brown adipose tissue and the pathway of triglyceride synthesis in brown adipose tissue (glycerol-1-phosphate versus monoglyceride pathway) were examined after intravenous injection of [1-14C]palmitate in newborn rabbits. In the thermoneutral environment of 35 degrees C the turnover rate of plasma free fatty acids was 10.20 mumol/min per 100 g body weight and its flux into the glycerides of brown adipose tissue 0.367 mumol/min per 100 g body weight. Cold exposure at an ambient temperature of 20 degrees C caused a decrease to 5.84 mumol/min and 0.207 mumol/min per 100 g body weight, respectively. Both under basal conditions at an ambient temperature of 35 degrees C and under cold-induced thermogenesis at an ambient temperature of 20 degrees C triglyceride synthesis in brown adipose tissue ran through the glycerol 1-phosphate pathway.


The initial binding of Cu(II) to some amino acids and dipeptides: a 13C nuclear-magnetic-resonance study. The initial binding of Cu2+ ot L-lysine, L-histidine, glycyl-histidine and histidyl-glycine in aqueous solutions was examined by 13C nuclear magnetic resonance spectroscopy. The measurements were carried out in a substantially improved way employing the pulse Fourier transform technique. Spectra of both high quality and resolution were obtained. Cu2+ complex formation with L-lysine occurred with the alpha-amino and carboxyl group attributable to the well expressed broadening effect of the 13C signals of the alpha-carbon atom and the carboxyl atom. The epsilon-amino group was not involved. Measurements of the Cu chelates using L-histidine and glycyl-histidine and histidyl-glycine confirmed the ambidentate nature of the histidine residue. It was concluded that an equilibrium exists between two Cu-complex species designated as histamine-like and histamine-like/glycine-like species. In the homogeneous histamine-like Cu complex, the Cu2+ is exclusively bound with 4 nitrogens, while in the other species one oxygen of the glycyl carboxyl group is involved in the Cu2+ binding. Blocking of this carboxyl groups by peptide bonding as found in histidyl-glycine favoured the formation of a Cu complex where the imidazole carbons of the histidyl residue were the most influenced species.


Kinetic investigation of the alpha-chymotrypsin-catalyzed hydrolysis of peptide-ester substrates. The relationship between the structure of the peptide moiety and reactivity. A number of peptide-ester substrates of the general structure Ac-Lxn-...-Lx2-Lx1-OMe have been synthesized and their alpha-chymotrypsin-catalyzed hydrolysis studied. The kinetic analysis involved varying the concentration of substrate and methanol product, and measuring rates along the entire progression curve. For the dipeptide esters Ac-Lx2-Lx1-OMe and the amino-acid derivatives Ac-Lx1-OMe the following constants could be determined: the dissociation constant of the enzyme-substrate complex, KEA, both rate constants of the acylation step, k23 and k32, and the forward rate constant of the deacylation step, k31. For the tripeptide ester Ac-Ala-Ala-Tyr-OMe it appears that the rate constant for the dissociation of the enzyme-substrate complex, k21, is smaller than the rate constant for acylation, k23. Thus, for this substrate only the association and dissociation rate constants k12 and k21 could be determined and the values of k23, k32 and k31 only indirectly estimated. The influence of structural changes in the peptide moiety of the substrates on reactivity has been established by comparing the rate constants of appropriate pairs of substrates. It was found that the substrate reactivity, as measured by k23/KEA, increase with the number and strength of the secondary interactions in a manner consistent with the binding scheme which has been proposed on the basis of crystallographic studies. The effect of a particular interaction on k23 and on KEA is dependent on the nature of the other interactions. However, the effect of k23/KEA appears to be independent of the presence of the other interactions and therefore characteristic of that particular interaction. The results for these substrates are compared with those found previously for a series of peptide substrates of the structure Ac-Lxn-... Lx2-...-Lx1-Gly-NH2 which have the same acyl moiety as the peptide esters studied in this work.


Polyadenylation of RNA in vitro in isolated chromatin and nuclei. Poly(A) is added post-transcriptionally to RNA transcribed in vitro by endogenous form B DNA-dependent RNA polymerase bound to the template in isolated nuclei or chromatin. It is also added to processed fragments of the products from alpha-amanitin-resistant RNA polymerases A and/or C. The poly(A) segments are of similar size to those found in nuclear RNA pulse-labelled in vivo and are added onto the 3' terminus of RNA chains (whether pre-existing, completed during the incubation in vitro or created by fragmentation of larger RNA transcripts). That poly(A) addition is not directly mediated by any of the nuclear DNA-dependent RNA polymerases is shown by the differential sensitivities of RNA and poly(A) syntheses to increasing ionic strength and transcriptional inhibitors such as the exotoxin from Bacillus thuringiensis.


Molecular changes associated with proteolysis of bovine factor V by thrombin. Native factor V contains two major polypeptide chains, h and 1. The molecular weights determined by gel electrophoresis in the presence of sodium dodecylsulfate and dithiothreitol (125 000 and 73 000) are in reasonable agreement with those obtained by gel filtration in 5 M guanidine-HC1 (125000 and 64000). Exposure of factor V to thrombin results in cleavage of the heavier chain to an altered form with a molecular weight of 87000. The other fragment of this proteolytic reaction appears to be a carbohydrate-rich piece, which migrates abnormally slowly on gel electrophoresis conducted under denaturing and reducing conditions. Both proteolytic cleavage products remain associated with the light chain during the purification of factor V. The 87000-Mr fragment is present in samples of factor V which are isolated by immunoprecipitation of blood obtained from a single animal by venous catheter. This finding suggests that some proteolysis may occur in vivo. In contrast, the molecular weight of the light chain is unaltered after thrombin proteolysis of either purified factor V or thrombin-treated plasma.


Heart hexokinase: quaternary structure changes accompanying the binding of regulatory molecules. Heart hexokinase monomer has a molecular weight of 97000 and so20,w 5.2 S. It exists in equilibrium with dimer of 194000 molecular weight and so20,w 8.1 S. The proportions of monomer and dimer presence of added ligands are 91% and 9% respectively. The existence of these forms may be demonstrated by separation on electrophoresis or chromatography. In the presence of the regulatory molecule glucose 6-phosphate, the dimer form of the enzyme is favoured. The glucose 6-phosphate mediated dimerisation is abolished in the presence of phosphate or ATP-Mg and less effectively by free ATP. Glucose has no effect on the manomer-dimer equilibrium. On prolonged storage of hexokinase in glucose 6-phosphate polymers are also formed and polymerisation is further enhanced by removal of the ligand.


Animal DNA-dependent RNA polymerases. Partial purification and properties of three classes of RNA polymerases from uninfected and adenovirus-infected HeLa cells. DNA-dependent RNA polymerase was solubilized from normal and adenovirus-2 infected HeLa cells. Multiple peaks of enzyme activity were separated by DEAE-Sephadex chromatography. In addition to class A and B enzyme activities (respectively insensitive and sensitive to inhibition by 10 nM alpha-amanitin), three peaks of class C enzyme activity were found which are sensitive to inhibition by alpha-amanitin only at much higher concentrations (0.1 mM). Rechromatography of these class C peaks indicates that they are not chromatographic artifacts. Class C enzymes differ from class A and B enzymes by several criteria including inhibition by alpha-amanitin, immunological properties, and the ability to transcribe native calf thymus DNA at high ionic strength. However, the ionic strength optimum and the divalent cation requirements of class C enzymes are not invariant characteristics of the enzymes and are markedly dependent on the nature and the amount of template in the reaction. No differences, either qualitative or quantitative, were found between the multiple enzymes isolated from normal or adenovirus-2 infected cells. All of the partially purified HeLa cell RNA polymerases were able to transcribe an intact double-stranded adenovirus-2 DNA under conditions where no transcription occurred with purified calf thymus AI and B RNA polymerases. Since the multiple enzymes were devoid of endonuclease and exonuclease activities, the ability of the partially purified enzymes to transcribe adenovirus-2 DNA cannot be ascribed to initiation of RNA synthesis at nicks of single-stranded regions of the DNA. No differences in transcriptional ability between corresponding enzyme classes from normal or infected cells, but a comparison of the ability of the various enzyme classes to transcribe intact viral DNA revealed large differences. Although partially purified HeLa class A and B enzymes were able to initiate on the intact viral DNA to a limited extent only, it appears that the class C enzymes transcribe intact duplex DNA much more efficiently than any other class of eukaryotic polymerase yet reported.


Adenine nucleosides in solution: circular dichroism studies and base conformation. Adenosine, AMP, S-adenosylhomocysteine, S-adenosylmethionine, aristeromycin and 25 other synthetic adenosine analogs modified in the 4' or 5' positions show certain groups of different circular dichroism (CD) spectra. Both positive and negative Cotton effects can occur in the long-wavelength part (250-270 nm) of the spectra. Molar ellipticities [theta] range from -6000 (in adenosine 5'-carboxylate) to +4000 deg. cm2 dmol-1 (in 5'-deoxy-5'iodoadenosine), including some compounds with small, polar 5'-substituents in which low-intensity bands are found in signed pairs. Most of these adenosine derivatives that have the same adenine chromophore and a ribofuranose moiety unsubstituted in the 2' and 3' positions prefer an anti-conformation of the adenine base, as evidenced by proton magnetic resonance spectroscopy. In the majority of cases, electronic perturbations of the chromophore or major alterations of the assymmetric sugar residue can be excluded as sources of the CD variations. Therefore a correlation of the long-wavelength CD bands with the glycosyl torsion angle phiCN is suggested, where the gauche, gauche/anti combination which is typical of AMP in the crystal and in solution (phiCN approximately -40degrees, [theta] negative) is one reference point and a region for phiCN = 0degrees ([theta] positive) is assigned to compounds with space-filling substituents such as S-adenosylmethionine. Both negative and positive Cotton effects can be associated with the anti conformation range. Within this series, the base conformation of novel nucleoside structures could be predicted from CD measurements. The CD spectrum gives no indication, however, of whether a certain torsion angle is the result of a rigid structure (as in AMP) or the average value of a molecule with high rotational freedom (as in 5'-deoxyadenosine). The conformations of aristeromycin and 4'-thioadenosine are discussed in relation to adenosine, and a structure-determining effect of the 4' bridge atom is noted.


Biochemical research on oogenesis. Comparison between transfer RNAs from somatic cells and from oocytes in Xenopus laevis. The properties of tRNA from oocytes of Xenopus laevis were compared with those of tRNA from somatic cells of the same species. Both types of tRNAs were found to have the same average length and to contain an equal variety of modified nucleotides. However, tRNA from small oocytes differed from somatic tRNA by its chromatographic behavior on methylated-albumin kieselguhr columns. The elution profiles from reversed-phase chromatography 5 columns of several aminoacyl tRNAs were compared after charging somatic and oocyte tRNSs with 3H or 14C-labelled amino acids. Striking differences in peak position were observed when tRNA from small oocytes was mixed and co-chromatographed with somatic tRNA. The differences were less important when tRNAs from large oocytes and from somatic cells were compared. Mixtures of egg and somatic tRNAs gave completely or almost completely coincident elution profiles. Only one isoacceptor, tNRA1Met (initiator tRNA) had the same position in all reversed-phase chromatography 5 chromatograms. The results are discussed in terms of possible post-transcriptional modifications of tRNA in the course of oogenesis. An alternative explanation resorting to changes in the tRNA population of the growing oocyte is also envisaged.


Characterization of yeast ribosomal DNA. High-molecular-weight yeast ribosomal DNA, purified by preparative Hg2+/Cs2SO4 gradient centrifugation, was characterized using RNA-DNA hybridization, CsC1 gradient analysis and denaturation-renaturation experiments. The following conclusions are drawn from the results of these studies. 1. 55--60% of the total yeast rDNA is made up of sequences coding for 42-S ribosomal precursor RNA. 2. The mean length of the 42-S precursor cistrons corresponds to a molecular weight of 6.2 X 10(6). 3. The overall G + C content fo yeast rDNA is 42%. On the hand, both the segments coding for the nonribosomal excess RNA of the 42-S precursor and those specifying 26-S and 17-S rRNA have a higher G + C content of 46.9--47.5%. 4. The 42-S precursor cistrons are closely bound up with sequences rather low in G + C content (34--35%), which account for 40--45% of the total yeast rDNA. In contrast to the multiple 42-S precurosr cistrons which show very little or no base sequence divergence these intervening (A + T)-rich sequences display a considerable heterogeneity in base sequence.


Transcription of the genome of adenovirus type 12. Viral mRNA in productively infected KB cells. In human KB cells productively infected with adenovirus type 12, viral DNA replication starts between 12 and 14h postinfection. Virus-specific, polysome-associated mRNA was investigated early (6-8h) and late (26-28h) after infection. Most of the viral mRNA was polyadenylated and accounted for 0.46% and 24.1% of the mRNA synthesized early and late postinfection, respectively. The viral-specific mRNA isolated both early and late after infection falls into several distinct size-classes, ranging in molecular weights between 0.3X10(6) and 1.5X10(6) for the early RNA and between 0.6X10(6) and 2.3X10(6) for the RNA synthesized late in the infection.


Interaction between the synthesis of alpha and beta globin. We have examined the relationship between alpha and beta globin chain syntheses by utilizing the distribution of isoleucyl residues in rabbit hemoglobin. The alpha globin chain contains three isoleucyl residues while the beta chain of certain rabbits contains no isoleucine. O-Methyl-L-threonine, an isoleucine isostere, inhibits incorporation of radiolabeled amino acids into alpha chains in rabbit reticulocytes. When alpha chain synthesis is inhibited by 50-85%, beta synthesis is stimulated by 15-50%. The excess labeled beta chains are not distinguishable from authentic beta chains by any of the following criteria: (a) carboxymethyl cellulose chromatography in sodium phosphate-urea buffers, (b) electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate, and (c) electrophoresis of methionine-containing tryptic peptides. The stimulation of beta synthesis continues after the pool of excess alpha chains has been exhausted by preincubation with O-methyl-L-threonine. The stimulation does not occur, however, when 1 mM 2-mercaptoethanol is added to the incubation medium or when the cells are excessively diluted in the incubation mixture. The rates of beta chain initiation and elongation during stimulation have been compared to the rates during normal synthesis. Although both rates are increased, the rate of elongation increases more than initiation, suggesting that initiation is the rate-limiting step in increased beta chain production. The stimulation of beta synthesis when alpha synthesis is inhibited is interpreted as resulting from relief of competition between alpha and beta mRNAs for limiting components of the protein synthetic apparatus.


Studies on norepinephrine-induced efflux of free fatty acid from hamster brown-adipose-tissue cells. Cells were isolated from brown adipose tissue of warm-adapted hamsters and the fate of free fatty acids released during norepinephrine-induced lipolysis was investigated. The isolated resting cells contain between 100-400 nmoles cell-associated free fatty acids per 10(6) cells; most preparations contained about 200 nmoles/10(6) cells. During norepinephrine-stimulated lipolysis, the level of cell-associated free fatty acids remains constant or decreases gradually, but does not increase, while the concentration of extracellular fatty acids increases linearly. The rate of norepinephrine-stimulated efflux of free fatty acids was 40 +/- 20 nmol X min-1 X 10(6) cells-1 (n = 11) at 37 degrees C. The data strongly indicate that brown adipose tissue can supply free fatty acids to the circulatory system in hamster.


Requirement for ribosome-releasing factor for the release of ribosomes at the termination codon. With the use of 3H-labeled R 17 amB2 phage RNA having an UAG codon at the seventh triplet of the coat cistron, release of the RNA from ribosomes at the termination codon was studied. The ribosome-releasing factor previously described was shown to stimulate the process of mRNA release at the termination factor (RF-1). GTP was required for this process and guanosine 5'-(beta,gamma-methylene)triphosphate could not replace GTP. No apparent change of size of R 17 RNA was observed during the release of the R 17 RNA from the ribosomes. The ribosome-releasing factor is distinct from the known termination codon-specific factor such as RF-1.


Precursor mRNA from erythroid-enriched bone-marrow cells of the rabbit. Electron microscope investigation of precursor mRNA molecules, molecular weight about 1.7 X 10(7), containing mRNA-like structures at one end. Precursor mRNA (pre-mRNA) molecules, sedimenting at greater than 45 S, from erythroid-enriched bone marrow cells of the rabbit and hemoglobin mRNA molecules from rabbit reticulocytes were investigated by electron microscopy. Four of 98 measured pre-mRNA molecules had a length between 15 and 17.1 mum. In some of the pre-mRNA molecules a characteristic condensed structure was observed at one end, strikingly resembling the structure of the mRNA molecules.


The amino-acid sequence of isoinhibitor K form snails (Helix pomatia). A sequence determination by automated Edman degradation and mass-spectral identification of the phenylthiohydantoins. Performic-acid-oxidized isoinhibitor K of snails (Helix pomatia) was subjected to arginine-directed tryptic proteolysis. Six peptide fragments including one overlap peptide from limited cleavage of the Arg-3-Pro-4 bond were purified to homogeneity. Four arginine peptides and the C-terminal peptide were sequenced by automatic Edman degradation using a special peptide program. The phenylthiohydantoins were all identified by chemical ionization mass spectrometry, except four cysteic acid residues that were identified on an amino acid analyzer after acid hydrolysis. Quantitative evaluation of the phenylthiohydantoins by chemical ionization mass spectrometry using total molecular-ion beam integration greatly facilitated sequencing. The mass spectrum of the dipeptide less than Glu-Gly revealed that the N-terminus was blocked by pyroglutamic acid. The complete amino acid sequence of isoinhibitor K was determined. An almost 50% homology between the sequences of the snail inhibitor and the bovine trypsin-kallikrein inhibitor (Kunitz) became obvious. A comparison of all homologous sequences of this particular class of proteins known to date is presented.


Regulation of rat-liver glycoprotein: N-acetylneuraminic acid transferase activity by pyrimidine nucleotides. CMP-N-acetylneuraminic acid: glycoprotein sialyltransferase activities were assayed in rat liver microsomal fractions using desialylated fetuin as the substrate acceptors for N-acetylneuraminic acid. It was found that cytidine nucleotides specifically depressed enzyme activities. CMP was shown to act as a competitive inhibitor with an apparent Ki of 0.62 mM. N-Acetylneuraminic acid at 1.15 mM had no effect on enzyme activities. Uridine nucleotides at 1.15 mM, especially UDP, increased enzyme activities. UDP may act as an allosteric activating agent increasing the apparent V. Other nucleotides, sugars and nucleotide-sugars at similar concentrations affected sialyltransferase activities only slightly. A general mechanism is proposed for the regulation of glycosyltransferase activities by free nucleotides.


Identification by gas chromatography and mass spectrometry of 1-monoglycerides in European hamster brown adipose tissue and plasma. 1. In organ culture, brown adipose tissue of the hibernator, the European hamster, synthezises from [14C]acetate a compound which is secreted into the culture medium. 2. Gas chromatographic-mass spectrometric analysis of samples, extracted from brown adipose tissue and corresponding to that unknown radioactive compound, used as a marker, lead to the identification of the two major components as 1-monoglycerides: 1-monopalmitin and 1-monoolein. 3. The two 1-monoglycerides are also present in the blood plasma and are not of alimentary origin. 4. The problem of the significance of 1-monoglycerides in brown adipose tissue and plasma is discussed in connexion with the postulated indirect role of brown adipose tissue in thermogenic processes.


Interactions of colipase with bile salt micelles. 1. Ultracentrifugation studies. A detailed investigation by ultracentrifugation of the colipase-taurodeoxycholate system showed the formation of well-defined mixed associations with a sedimentation coefficient of about 2.2S. The fact that these associations were only detectable above the critical micelle concentration of the salt indicated that micelles rather than monomers were bound to the cofactor. Two technical difficulties must be overcome before the weight of the associations could be measured with a reasonable accuracy. Firstly, the partial specific volume of the associations was determined using a digital microdensimeter and the interferometric system of the ultracentrifuge for concentration determinations. Secondly, due to the fact that micelle concentrations could not be equilibrated by dialysis, even after an extended period of time, an appropriate dilution of the ligand in the buffer compartment was necessary in order to compensate for its fixation by colipase in the solution. Then, the ionic strength dependence of the weight of the associations was found to vary in parallel with that of the micelles and to be in each case equal to the sum of the weights of one colipase molecule and one micelle. Therefore, colipase can be expected to contain a single high affinity site for bile salt micelle binding.


Interactions of colipase with bile salt micelles. 2. Study by dialysis and spectrophotometry. The finding reported in the preceding paper that colipase is able to bind one sodium taurodeoxycholate micelle per molecule was confirmed by dialysis and spectrophotometry. Dialysis in the presence of labelled sodium taurodeoxycholate provided a direct qualitative proof of taurodeoxycholate binding to colipase. This binding was found to occur only above the critical micelle concentration. But, dialysis did not give any information about the composition of the associations, because equilibrium was not attained at the end of the assays. Addition of sodium taurodeoxycholate above the critical micelle concentration was also observed to induce a strong perturbation of the ultraviolet spectrum of one or several of the three tyrosines of colipase. The variation of the perturbation as a function of sodium taurodeoxycholate concentration was consistent with the binding of a single micelle to colipase. The dissociation constant calculated in "micelle molarity" was approximately 1 X 10(-4) M. The colipase-bile salt micelle association can fix one molecule of lipase to form a ternary complex which represents an interesting model of a protein-protein interaction mediated by an organized lipid structure. The ternary complex is probably also a model for lipase-substrate interactions in the presence of an amphipath.


Two-dimensional gel electrophoresis of ribosomal proteins from streptomycin-sensitive and streptomycin-resistant mutants of Chlamydomonas reinhardi. Ribosomal proteins from three mutant strains of Chlamydomonas reinhardi were analysed and compared by one-dimensional and two-dimensional gel electrophoresis. One mutant was streptomycin-sensitive the other two were streptomycin-resistant, one with a Mendelian the other with a non-Mendelian pattern of inheritance. In the 30-S subunits of chloroplast ribosomes approximately 25 proteins are found and in the 50-S subunits 34 proteins. The 40-S subunits of cytoplasmic ribosomes contain about 31 proteins and the 60-S subunits 44 proteins. The molecular weights of most proteins in all subunits are in the range of 10 000 to 35 000. However, the 60-S subunits contain in addition a protein of molecular weight 50 000 and the 30-S subunits show 6-7 bands of molecular weights from 50 000 to 83 000. The proteins of the cytoplasmic 80-S ribosomes or of their subunits from all three mutants are electrophoretically identical. The proteins of the 70-S organellar ribosomes and both of their subunits show distinct differences between the three strains. Our results indicate that organellar ribosomal proteins are in part controlled by nuclear DNA and in part by organellar DNA.


Reliability of human and machine measurements in patient monitoring. In a study on 29 patients for 152 hours a continuous monitoring system has been shown to have a reliability of 90.53% for pulse rate and 82.20% for arterial blood pressure, but for approximately half of the period of unreliable monitoring a not obviously artifactual reading was being displayed. The relevance of this to possible incorrect diagnosis and management is discussed. The monitor and a nurse using traditional chart keeping methods gave equivalent charts with respect to average levels and trends, but the monitor assisted chart showed a much greater variability. The latter tended to obscure underlying trends and render clinical diagnosis from the chart more difficult.


Biochemical quantification of blunt injuries. During eight post-traumatic days, the blood loss and severity of trauma were correlated with the blood levels of lactate, creatinine and catecholamines in 45 patients with multiple blunt injuries. During two days these biochemical indicators correlated with the extent of thoracoabdominal, pelvic and cerebral injuries. In the critically injured patients all three parameters were elevated throughout the observation period. No correlations were observed between plasma catecholamines and lower limb injuries, which seems to make the importance of catecholamines for predicting the onset of fat embolism syndrome less useful.


Haemodynamic study of prolonged deep accidental hypothermia. Right heart catheterisation was undertaken in six patients with accidental deep hypothermia. Studies were carried out before and after rapid blood volume expansion, with and without Isoproterenol infusion, and were repeated at normal body temperatures. The initial haemodynamic pattern indicated a marked hypovolemia with a simultaneous decrease of both cardiac output and ventricular filling pressures, and a decreased measured total blood volume. Rapid correction of the hypovolemia revealed cardiac insufficiency, in part due to the persisting bradycardia. Left ventricular function was depressed in patients with prolonged cold exposure and normal in patients with short exposure. These abnormalities disappeared after Isoproterenol infusion during hypothermia, and spontaneously after return to normothermia. No imbalance existed between the decreased cardiac output and oxygen uptake in hypothermia, arterio-venous oxygen difference being within normal limits.


Epidural analgesia for the treatment of multiple ribfractures. Epidural analgesia can be the choice of therapy for all patients with ribfractures and only minor coexisting injuries who are conscious and able to cooperate. In these cases we believe that EA is equivalent or even better than artificial ventilation with all its problems. Generally these patients are far easier to handle and one needs less nursing staff. The dignity of the patients can be maintained and the convalescent time in the intensive care unit is shorter. The criteria for the treatment and for measuring the progress of the patients with multiple ribfractures are discussed.


Active immunization against tetanus in man. III. Antibody response to vaccine injections in the presence of therapeutic doses of human tetanus immune globulin. a record of five cases. The tetanus antitoxin titres of five tetanus cases treated with 6,000-45,000 IU of human immune globulin and 2-4 doses of adsorbed tetanus toxoid were followed during 1 year. A typical response to the second injection of toxoid might be masked by the passively administered antibodies. The rise in titre after the third injection of toxoid was of the same magnitude as in patients receiving only active immunization. Hence the possible impediment by large doses of human immune globulin does not seem to play any practical role in complete immunization with three doses of tetanus toxoid.


Plasma volume after dextran infusion in rats sensitive and non-sensitive to dextran. Plasma volume determinations were done with RIHSA under normal conditions and after intravenous infusion of dextran solutions. The plasma volume of normal rats in millilitre was found to be 0.026 X body weight + 0.92. Infusion of dextran into dextran-sensitive Sprague-Dawley rats was followed by a marked plasma volume reduction and haemoconcentration as consequence of an anaphylactoid reaction. This reaction could be partially inhibited by pretreatment with cyproheptadine chloride. Plasma volume determination with the method used in this study can be used to evaluate the dextran-anaphylactoid reaction. In dextran non-sensitive Wistar rats, infusion of dextran had a strong plasma volume-expanding effect comparable to the plasma volume-expanding effect of dextran in humans. No signs of abnormal leakage of fluid out into the extravascular space were evident, which indicated that the Wistar rats really were non-sensitive to dextran.


Dextrans and the formation of pulmonary metastases after intravenous tumour cell injection in rats non-sensitive to dextran. This study showed, that in a syngeneic tumour-host system in rats non-sensitive to dextran, dextran 40 and dextran 100 did not stimulate metastasis formation after intravenous tumour cell injection, neither when given as intravenous pretreatment nor when given in the tumour cell suspension. Dextran 1000 stimulated the formation of metastases in both these situations. Disturbed microcirculation, intravascular coagulation and effects upon the tumour cell membrane appear to be the main resons, why dextran 1000 stimulated metastasis formation under the experimental conditions used.


Transport and conjugation of 14C-bilirubin during acute and chronic cholestasis in the cholecystectomized dog. The role of the lymphatics in the regurgitation of bilirubin during acute and chronic extrahepatic cholestasis in the dog was studied after intravenous injection of 14C-bilirubin. In acute cholestasis the injected labelled bilirubin was rapidly removed from plasma and reappeared in thoracic duct lymph as labelled bilirubin conjugates. No labelled conjugates were at any time demonstrated in plasma. This is most easily explained as a result of a bilio-lymphatic regurgitation. In chronic cholestasis the labelled bilirubin conjugates were delivered back into the blood, and no specific transport function of the lymph was found. Our results indicate a change in liver cell secretory direction in long-standing cholestasis.


Hemodynamics, compartments and the renin-aldosterone system in chronic heart failure. In 12 patients with chronic mitral or aortic disease plasma renin activity (PRA) and aldosterone secretion rate (ASR) were correlated to hemodynamics, kidney function, plasma and interstitial fluid volume, and plasma sodium concentration, both in the congestive state (I) and after sodium depletion (II). PRA (I) and ASR (I) were normal or slightly elevated and increased normally after sodium depletion. A significant inverse correlation between plasma concentration (I + II) and PRA (I + II) was found. Further an abnormal inverse correlation between increments in PRA and cumulative sodium loss was demonstrated. By contrast, no correlations were found between PRA and ASR on one hand and pressures, kidney function or compartments on the other, neither in I - elevated pressures in the atria, low renal plasma flow, large compartments, nor in II - reduced pressures and compartments, almost unchanged kidney function. It is concluded that PRA hardly plays any primary role in the maintenance of sodium and fluid retention in human chronic congestive heart failure.


Prolongation of the tachycardia zone: a possible mechanism for medical failure in paroxysmal supraventricular tachycardia. Paroxysmal supraventricular tachycardia in man has been considered to be due to either development of reentry utilizing AV junctional tissue or the presence of an ectopic pacemaker located within the atrium. Most contemporary information suggests that AV junctional reentry is the dominant mechanism for this arrhythmia in man. This present study identifies that the frequence of tachycardia episodes may be correlated with the width of a tachycardia zone as determined by the atrial extrastimulus technique. Moreover, pharmacological therapy directed toward the elimination of this arrhythmia can be assessed utilizing this atrial stimulation technique. Findings in this present study identify that, in patients with widened tachycardia zones, propranolol therapy may not be efficacious. This latter finding is no contrast to the previous observations suggesting that propranolol therapy is the drug of choice for reentrant arrhythmias in man.


Cardiac rupture following myocardial infarction. The 38 months incidence of cardiac rupture in a coronary care unit was found to be 10/460 or 2.1%. The patients at high risk were elderly people with a first transmural infarct, digitalized, experiencing recurring pain without a pericardial friction rub. 7/10 heart ruptures occurred within 36 hours after the first symptoms of infarction. Decreasing left ventricular work may be an effective method for preventing rupture of infarcted myocardium.


Fatal dislodgment of ball from aortic Starr--Edwards valve prosthesis. A case is reported of fatal dislodgment of the ball from an aortic Starr-Edwards valve prosthesis 48 mth after its implantation. A description is given of the typical clinical picture of this catastrophe. The most noticeable finding in our patient was the 8-hr interval between onset of symptoms and death.


Double outlet right ventricle with l-malposition and uncommitted ventricular septal defect. A case is described which exhibited Double Outlet Right Ventricle (DORV) with l-malposition of the aorta in association with a ventricular septal defect of the noncommitted, atrioventricular canal variety. When the ventriculoarterial relationship of DORV is encountered, it is more usual to find the aorta to the right of the pulmonary artery. Review of the literature shows that examples of DORV and l-malposition have been described with subaortic, subpulmonary and doubly committed defects, but we are unaware of any previous example reported with a noncommitted defect. These findings indicate that DORV with l-malposition should be anticipated in association with the same accompanying defects as those described in DORV with d-malposition, and emphasize the necessity for adopting a segmental approach to nomenclature. They also have morphogenetic significance, suggesting that DORV with l-malposition is closely linked with the anomalies for anatomically corrected malposition and concordant (complete) l-transposition. The present case exhibited an electrocardiographic superior axis, which is probably related to the presence of the atrioventricular canal deformity. The coexistence of hypoplasia of the aortic isthmus is speculatively related to the presence of conal and valvar factors, which can be considered to have reduced aortic blood flow.


Anterograde block in accessory pathways with retrograde conduction in reciprocating tachycardia. 3 patients with reciprocating tachycardia are described. In all 3, tachycardia was due to a reentrant mechanism. Anterograde conduction was via the AV node while retrograde conduction was over an accessory (Kent) pathway. In none of the 3 patients did this pathway sustain anterograde conduction despite pacing the atrium close to its location. With the advent of surgical modes of therapy, it is important to recognize such 'silent' bypasses. The observations which allow this diagnosis of unidirectional anterograde block in an accessory pathway and the exclusion of AV nodal reentry, the main differential diagnostic possibility, are discussed.


Double ectopic accelerated ventricular and nonaccelerated ventricular or supraventricular rhythms. Three patients with acute inferior wall myocardial infarction has accelerated idioventricular rhythms alternating and (or) coexisting with: (a) AV junctional (or low atrial) rhythm (Case 2); (b) paroxysmal ventricular tachycardia and another accelerated idioventricular rhythm (Case 3); and (c) AV junctional rhythm, paroxysmal ventricular tachycardia and accelerated idioventricular rhythm from another center (Case 4). The tracings from a fourth patient (Case 1) served to focus attention on one of the most pertinent features of accelerated idioventricular rhythms, namely the gradual decrease in rate to values below that of the preexisting basic rhythm. Cardioacceleration with atropine and cardiosuppression with lidocaine failed to abolish the arrhythmias or relieve the symptoms in cases  3 and 4. Atrial stimulation proved the most effective mode of therapy in these two patients.


Sinoatrial block during lithium treatment. Lithium is known to produce T wave changes in the ECG, whereas effect upon the conducting system of the heart has not been described. In our patient lithium produced sinoauricular block and possibly tachycardia. The correlation between lithium treatment and tachyarrhythmias is discussed. When during lithium treatment block is found, the treatment should preferably be stopped, but if this is not possible it is important to realize that digitalis should not be used as a prophylactic drug against tachycardia, as it worsens the block and therefore increases the frequency of arrhythmia, even leading to Adams-Stokes attacks.


Assessment of left ventricular function and hemodynamic reserve by volume loading in acute myocardial infarction. Volume manipulations in 27 patients (volume loading n = 22; phlebotomy n = 5) with acute myocardial infarction (AMI) and 7 normal subjects has been performed in order to evaluate left ventricular performance in terms of cardiac index (CI) and pulmonary artery enddiastolic pressure (EDPAP). An EDPAP in the range of 18-22 mm Hg was in general associated with maximal cardiac output. In patients with AMI maximal cardiac performance was significantly lower compared to normal subjects (p less than 0.01). Volume loading that increased the EDPAP beyond the level of 18-22 mm Hg usually deteriorated cardiac performance in AMI. A phlebotomy in 5 subjects with severe pulmonary congestion decreased EDPAP significantly from 32 to 24 mm Hg (p less than 0.1) without a change of cardiac index (2.2 - 2.5 1/min/m2;NS). In 11 patients left ventricular performance was assessed during the acute and convalescent period. 4-6 weeks after AMI resting EDPAP decreased from initially 16 to 11 mm Hg (p less than 0.02), whereas cardiac index did not change significantly (3.1-3.3. 1/min/m2;NS) and even did not rise markedly after volume loading (3.3-3.4 1/min/m2;NS). By plotting the relative change of cardiac index after volume loading against the individual infarct size (n = 16), left ventricular hemodynamic reserve was assessed and revealed a significant depression compared to normal subjects (n = 7). A rough reverse relationship (r = -0.69) between left ventricular hemodynamic reserve and infarct size was observed.


T-wave alternans associated with heart failure and hypomagnesemia in alcoholic cardiomyopathy. Marked T wave abnormality developed in a patient with alcoholic cardiomyopathy. The T negativity was  of giant size and occurred in an alternating sequence in the presence of sinus rhythm. This change was rapidly transient, disappearing in 3 days. The complete electrocardiographic recovery was temporally related to successful treatment of severe heart failure, normalization of initially low serum magnesium level, and abolition of recurrent ventricular fibrillation.


Prediction of sudden death in patients discharged after acute myocardial infarction. A follow-up was made of 475 patients discharged after an acute myocardial infarction. Sudden death, i.e. death within 2 hours after the onset of the final attack, was more common in patients below 60 years on admission than in the older age groups. Patients succumbing suddenly often had a history of an earlier myocardial infarction. They also had a higher incidence of inferior infarcts and more frequently showed ventricular tachycardia during the early hospital period than those dying more than 24 hours after the onset of the final episode. When comparisons were made with all patients dying after more than 2 hours' duration of the terminal attack no significant differences were noted for these or other parameters. Prediction of sudden death in immediate survivors of acute myocardial infarction thus seems elusive. Further studies of the relations between the incidence of ventricular ectopic activity during the early and late hospital phase of acute myocardial infarction and sudden death after discharge from hospital are implicated.


Late banding operation in children with ventricular septal defect and pulmonary arterial hypertension. Since 1960 31 children, 2-10 years old, with large ventricular septal defects and pulmonary arterial hypertension, underwent pulmonary artery banding in Munich. 22 of these children were recatheterized 3-5 years after the operation. Only 8 of these children were shown to have a definite decrease in pressure distal to the band, and in only 2 of these children a reduction of pulmonary vascular resistance to values at the upper limit of normal could be shown. In the remaining children either little or no alteration and rarely even a definite increase of pulmonary vascular resistance was found. There was only a poor correlation between pressure changes and resistance changes. During preoperative catheterization oxygen breathing was shown to produce a more than 50% reduction in the pulmonary arterial pressure in 8 cases. Of these, only 5 showed a decrease of pulmonary vascular resistance after pulmonary artery banding. This decrease, however, was relatively small.


Ruptured sinus of Valsalva aneurysm with aortic-left atrial fistula. We report the case of a previously healthy 56-year-old male who suddenly developed severe chest pain and pulmonary edema. Cardiac catheterization and angiography revealed an aneurysm of the noncoronary sinus of Valsalva which had ruptured into the left atrium. This was confirmed at operation and it was noted that there were no signs of bacterial infection or rheumatic valve disease. We therefore concluded that the aneurysm was of congential origin. A successful repair of the defect was carried out and the patient made a satisfactory recovery. There are only 3 other reported cases of rupture of a congenital sinus of Valsalva aneurysm into the left atrium, and in only one case did the aneurysm originate from the noncoronary sinus and this patient had associated rheumatic aortic and mitral valve disease. We have received the classification of sinus of Valsalva aneurysms, the associated congenital and acquired defects and the presenting features of unruptured and ruptured aneurysms.


The effect of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction. Intracardiac conduction studies using His bundle electrography (HBE) were performed in 14 patients admitted to hospital following an overdosage of one of the tricyclic antidepressant drugs and in another 12 patients before and during administration of therapeutic doses of nortriptylline. Amongst the former group, 7 of 8 patients showed impaired distal intracardiac conduction (H-V interval) following overdosages of nortriptyline, imipramine or amitriptyline but none of the 6 patients with doxepin overdosage. The prolonged H-V interval had returned to normal at a repeat study 7 days later. In the therapeutic dose study, 5 of 12 patients showed an increase in the H-V interval by more than 10 msec during treatment with nortriptyline. Four of these 5 patients had plasma nortriptyline levels of over 200 ng/ml. Tricyclic antidepressant drugs show a quinidine-like effect in toxic, and in some patients, in therapeutic doses. This finding may having a bearing on the treatment of cardiac arrhythmias in patients following overdosage with these drugs and may provide a clue to the reported increase in the incidence of sudden deaths in 'cardiac patients' following therapeutic doses of such agents.


Decreased haem synthetase activity in blood cells of patients with erythropoietic protoporphyria. A constant finding in erythropoietic protoporphyria (E.P.P.) is a raised protoporphyrin content of the erythrocytes. It has been shown before that the biosynthesis of this protoporphyrin takes place in the erythroid cell. In circulating blood cells of patients with E.P.P. the haem synthetase activity is significantly decreased. This observation and the increased protoporphyrin concentration in the cells can be explained by assuming a decreased stability of haem synthetase in the red blood cells of E.P.P. patients.


Mechanisms of albumin loss during peritoneal dialysis in man. Albumin loss in the dialysate was evaluated during a total of 5 peritoneal dialyses carried out on 3 uraemic patients. The measurements were made by two different methods, the first based on the evaluation in the dialysate of intravenously injected radioiodinated albumin, the second one based on a radioimmunoassay of the protein in the dialysate. The results obtained showed three main mechanisms of protein loss during peritoneal dialysis: 1) albumin shift from extravascular sites adjacent to the peritoneum, 2) direct passage of albumin from blood stream to peritoneal cavity, and 3) tendency of the inter-dialysis peritoneal fluid to equilibrate with plasma proteins. Furthermore, the observations made on a patient with evident peritonitis proved the importance of the intrinsic biological properties of the peritoneum in determining the amplitude of protein wasting by the dialysate.


The effects of metiamide on gastric secretion and stress ulceration in rats. The effects of metiamide, a histamine H2 blocker, on gastric secretion and ulcer formation in stressed pylorus-occluded rats were investigated. Metiamide, like atropine, significantly reduced the volume of gastric secretion and total acid output in unrestrained pylorus-occluded rats. Both drugs produced greater decreases in the volumes of gastric secretion in stressed rats than in their corresponding unrestrained groups. Stress itself reduced both parameters. Metiamide, like atropine, significantly reduced the incidence of gastric stress ulcers. When given together these two drugs did not provide greater protection. The results obtained with metiamide indicate that histamine plays a role in basal gastric secretion and in the pathogenesis of stress ulcers. As no correlation between gastric acid secretion and ulcer formation was demonstrated in this study, it is suggested that H2 receptors may also be involved in gastric motility. However, the possibility that metiamide could exert its ulcer-protecting effects through other mechanisms cannot yet be excluded.


Structural aspects of the effect of ethyl benzoates on caffeine contracture. The effect of ethyl benzoate, ethyl o- and p-fluorobenzoate and ethyl o- and p-toluate on the caffeine-induced contracture of frog sartorius muscle was investigated. All drugs with the exception of ethyl o-toluate depressed caffeine-induced contractures. It is proposed that the methyl group in ethyl o-toluate sterically blocks the ester carbonyl group from exerting its inhibitory action. It is further proposed that ethyl o-aminobenzoate exerts its potentiating effect through the lone pair of electrons on the nitrogen atom.


Decrease in rat striatal acetylcholine levels by some direct- and indirect-acting dopaminergic antagonists. Several direct- or indirect-acting dopamine receptor antagonists were found to decrease rat striatal acetylcholine levels. The maximum decrease of about 50% was produced by pimozide (0.5 mg/kg), by haloperidol (0.5 mg/kg) and by reserpine (2.5 mg/kg). The decreases in acetylcholine produced by pimozide and by haloperidol were found to be specific for the striatum and did not alter diencephalonic, mesencephalonic, cerebellar or hemispheric acetylcholine levels. Furthermore, these two drugs completely blocked the increase in striatal acetylcholine produced by the dopamine receptor agonist, apomorphine, and had no effect on striatal choline acetyltransferase and cholinesterase. These data suggest that haloperidol and pimozide act on the striatal cholinergic neurons through strong blockade of dopamine receptors. Reserpine presumably decreased striatal acetylcholine levels indirectly by depleting biogenic amines. Clozapine and 1-fenfluramine were unable to block the action of apomorphine, as was shown previously for chlorpromazine. It is thus suggested that these drugs are reversible dopamine receptor antagonists. Their weaker action in decreasing striatal acetylcholine may depend upon this property.


Suppression of ventricular automaticity by antidysrhythmic agents. In view of the potentially important role of automaticity in the genesis of ventricular dysrhythmias, the effects of four widely used antidysrhythmic agents on ventricular automaticity were examined in anesthetized dogs at doses previously shown to antagonize experiments induced rhythm disturbances. Quinidine, and particularly procainamide, lidocaine and propranolol slowed ventricular rate in A-V blocked dogs. Quinidine and procainamide but particularly the last two agents also markedly prolonged overdrive suppression. Thus, all four substances depressed automaticity. However, propranolol was effective at doses substantially lower than those required to antagonize several experimental dysrhythmias.


Deleterious effects of taurine in cats with digitalis-induced arrhythmias. An established model of digitalis toxicity was used to investigate the antiarrhythmic properties of taurine. I.v. doses of taurine ranging from 0.01 to 4.0 mmole/kg were ineffective in converting a deslanoside-induced arrhythmia to sinus rhythm. Indeed, taurine was found to aggravate the arrhythmia and in three experiments precipitated ventricular fibrillation. In addition, pretreatment with 5 mmole/kg taurine i.v. had no significant effect on the doses of deslanoside to produce ventricular arrhythmia and fibrillation.


Increased susceptibility to seizures and decreased catecholamine turnover in spontaneously hypertensive rats. Spontaneously hypertensive rats (SHR) were compared with normotensive Wistar rats for their sensitivity to tonic extensor seizures. SHR were more sensitive to seizures and did not respond to the anticonvulsant effects of L-DOPA. SHR had a slower turnover rate of norepinephrine in brain stem and cortex and of dopamine in striatum. Steady-state levels of catecholamines were similar in both groups. These findings are consistent with earlier ones that reported an inverse relationship between central catecholamine activity and sensitivity to electroconvulsive seizures.


Effect of bretylium on cardiovascular changes induced by coronary occlusion in the cat. The influence of bretylium pretreatment on the heart rate, blood pressure, contractile force and cardiac rhythm changes produced by occlusion of the anterior descending coronary artery was evaluated in chloralose-anesthetized cats. Bretylium pretreatment shortened the duration of the ventricular arrhythmia. This drug however had no effect on the other cardiovascular changes evoked by coronary occlusion. These results suggest that the sympathetic nervous system has a role in maintaining electrical instability after experimentally induced myocardial infarction.


Prostaglandin 15-hydroxydehydrogenase activity during pregnancy in rabbits and rats. Prostaglandin 15-hydroxydehydrogenase (PGDH) activity in the rabbit lung increased strikingly during pregnancy. This change did not occur in the kidney, or spleen. In the corresponding organs from the rat, PGDH activity was essentially the same in pregnant and non-pregnant animals. These results are discussed in relation to the hypothesis that the increased PGDH activity in the pregnant rabbit lung is secondary to an elevated concentration of prostaglandins in the venous blood.


A centrally acting antihypertensive agent (R28935) not mediated via central alpha-adrenoreceptors. Intraventricular administration (i.c.v.) of R28935 (25 mug) produced a marked fall in blood pressure without any bradycardia in conscious renal hypertensive cats. This hypotensive effect was not antagonised by central administration of tolazoline (200 mug i.c.v.) or phentolamine (200 mug). However, these doses of alpha-adrenoreceptor blocking agents did antagonise the centrally mediated hypotensive actions of clonidine (20 mug i.c.v.) or alpha-methyl-dopa (1 mg i.c.v.). Infusions of R28935 in the perfused artery preparation did not modify the basal perfusion pressures or modify the vasoconstrictor actions of noradrenaline or 5-hydroxytryptamine. The results suggest that R28935, an analogue of pimozide, exerts a central hypotensive effect not mediated via central alpha-adrenoreceptors, and does not have any peripheral sympathomimetic action.


The effect of pretreatment with 6-hydroxydopamine on the norepinephrine concentration and sensitivity of the rat vas deferens. Injection of 6-hydroxydopamine via the dorsal vein of the penis results in a marked depletion of the endogenous norepinephrine of the vas deferens. Seven days after pretreatment with 6-hydroxydopamine there is a shift to the left and increase in maxima of the dose-response curves for norepinephrine and methoxamine. The results indicate that pretreatment with 6-hydroxydopamine produces denervation of the vas deferens and that the in vitro tissue exhibits both prejunctional and postjunctional supersensitivity.


Receptive field mechanisms of sustained and transient retinal ganglion cells in the cat. Receptive field organization of 135 sustained and 45 transient retinal ganglion cells was investigated in lightly pentobarbitone-anaesthetised cats. Stimuli were concentric annuli presented alone or simultaneously with a small spot centred on the receptive field, against photopic, mesopic or scotopic backgrounds. The addition of the test spot led to reduction in diameter of the centre-surround boundary of receptive fields of sustained retinal ganglion cells (assessed with annuli), and a decrease in diameter of the annulus which was most effective on the surround. In transient cells there was only marginal reduction in diameter of the centre-surround boundary, measured with annuli, and little or no decrease in diameter of the most effective annulus. Reducing background intensity from photopic to scotopic induced changes in response patterns and receptive field organization of sustained and transient retinal ganglion cells which were independent of stimulus intensity. Against photopic backgrounds, large annuli evoked surround-type responses from the majority of transient ganglion cells and from all sustained cells. In the scotopic range, surround-type responses could still be evoked from sustained cells, whereas predominantly centre-type responses were obtained throughout the receptive fields of transient cells. With transition from cone to rod vision, receptive field surrounds of sustained and transient cells became progressively less responsive than centres; in consequence the diameter of the centre-surround boundary increased. The initial, high frequency burst of impulses in discharges at annulus onset or offset became less evident and response latency increased substantially. The results are consistent with a model in which the centre and surround receptive field mechanisms are spatially co-extensive in transient retinal ganglion cells, albeit of different shape, but only partially overlapping in sustained retinal ganglion cells. It is suggested that the surround mechanism in sustained cells is spatially more extensive than the centre mechanism but does not extend entirely through the centre of the field.


Optokinetic nystagmus during selective retinal stimulation. Nystagmic eye movements in response to selective optokinetic stimulation of different parts of the retina were studied in normal human subjects by two methods: 1. a digital computer controlled by the eye movement signal was used to generate an optokinetic display which stimulated only the peripheral retina, simulating a central scotoma, and 2. a single dot of 0.6 degrees in diameter was used as the stimulus during maintained forward gaze. The results show that stimulation of the central or peripheral retina alone can produce optokinetic nystagmus in man, and that essentially the same type of nystagmus is produced in both cases. The slow phase velocity of nystagmus evoked from the peripheral retina falls off rapidly with distance from the fovea but can be facilitated by attention. Results are compared with other findings and a possible explanation is offered for the observed variation in slow phase speed which occurs during constant velocity optokinetic stimulation.


Effects of visual cortex lesions following recovery from monocular deprivation in the cat. Six monocularly deprived (MD) and four normal cats were trained monocularly on two-choice form and pattern discriminations. MD cats trained through the initially deprived eye were able to learn the discriminations; however, they required many more trials than normals. Retention tests showed that MD cats have nearly perfect retention of the discriminations over periods of up to 4 months. With retention intervals of 6 months or longer, there is a tendency for the MD cats to show an initial drop in performance, particularly on more difficult discriminations. However, criterion performance typically was attained with considerable savings, indicating good retention even over these extended intervals. Following the preoperative training and retention testing, the cats received one of the three types of visual cortex lesions. Two MD cats received total visual cortex removal (areas 17, 18, and 19). This produced a complete postoperative loss of the discriminations with continued chance performance over 800--1000 trials. Two MD cats and two normal cats received removal of the monocular segment of area 17, with the central visual field projection region of area 17 and all of areas 18 and 19 remaining intact. This produced no loss of the discriminations in either normal or MD cats beyond what is expected on the basis of normal forgetting. Two MD cats and two normal cats received removal of areas 18, 19, and the central 5--10 deg. of the visual field projection in area 17. Postoperative retention was somewhat variable for both normal and MD cats. However, subsequent acquisition of the discriminations by both normal and MD cats was in sharp contrast to the prolonged deficits produced by total visual cortex lesions. These results indicate that one or more of visual cortical areas 17, 18, and 19 are involved in the recovery of visual discrimination capacities in MD cats. However, the monocular segment of striate cortex does not appear to be specially involved in this ability, as has been suggested by previous investigations. Possible mechanisms for the recovered visual capacities in MD cats are considered.


Responses of striate cortical cells to moving edges of different curvatures. The responses of twenty cells to stimuli of varying curvature were measured in cat's striate cortex. All the investigated cells were sensitive to the orientation of lines and not hypercomplex. Fourteen cells showed a systematic change of response with curvature. The optimal curvatures of the cells were distributed over the whole range investigated. Six cells were insensitive to curvature. The responses from all the typical simple cells (8) varied with curvature, whereas all the complex cells (5) were insensitive to curvature changes. The curvature tuning curves were broad and the variability to individual stimuli was high, independent on whether the cell responded best to straight or to curved edges. The findings do not support the view that individual cells of area 17 could detect curvature.


Nuclear magnetic resonance studies in normal and edematous brain tissue. The nmr relaxation rate results show unequivocally that there are at least two fractions of tissue water in both normal and edematous white matter which do not exchange on an nmr time scale (i.e. at times of the order of milli-seconds to fraction of a second). In conjunction with the electron microscopic determination of the extracellular volumes of normal and edematous white matter, the relaxation results can be interpreted in terms of the following model. The two slowly-exchanging water components giving rise to the non-exponential relaxation correspond to cellular and extracellular water; edema changes the relaxation rate of the extracellular component much more than that of the cellular component (the extracellular component becoming more "liquid-like" in its relaxation). Such behavior is consistent with the properties of the extracellular water being due to rapid exchange between motionally restricted water adsorbed at the surface of myelin sheaths, and relatively unrestricted, bulk water. Edema presumably increases the relative amount of the "bulk" water between the axons.


The effect of area and intensity on the response of cat retinal ganglion cells to brief light flashes. 1. The action potentials of single optic tract axons were recorded in cats anaesthetized by pentobarbital. The receptive fields were stimulated with brief light flashes (20 or 25 msec) of variable area (0.18 less than or equal to A less than or equal to 11.8 degrees) and stimulus intensity (0.36 less than or equal to I less than or equal to 360 cd-m-2). 2. Retinal on-center and off-center neurons responded in one of two ways to brief light flashes: oscillatory responses (O-response) to certain stimulus combinations or non-oscillatory responses (N-response) for all stimulus combinations. 3. The O-respnse of on-center neurons was characterized in its PST-histogram by up to five peaks. Neurons exhibiting an O-response at medium and/or strong stimulus intensities responded at low AxI-values with an N-response. Other neurons, however, exhibited for all stimulus combinations an N-response, in which the instantaneous neuronal impulse rate decreased after an initial peak approximately expronentially with time. 4. The O-response of off-center neurons exhibited with medium AxI-values up to four peaks in the PST-histograms. N-type off-center neurons had at low and medium AxI-values a short primary inhibition period which was followed by a fast rising and slowly decaying activity period. 5. Ricco's law was only valid for small AxI-values not more than one 10log unit above threshold. For higher stimulus values (especially in the O-response) an increment of the stimulus intensity was usually more effective than an equal increment of the stimulus area. 6. On-center and off-center neurons located in about the same region of the retina had a strong tendency to discharge alternately with each other. 7. A superposition model is proposed as an explanation of the experimental data. 8. Possible correlations between the neurophysiological findings and the fast oscillatory after-images seen in corresponding psychophysical experiments are discussed.


The tendon organs of cat soleus: static sensitivity to active force. The static force sensitivity of soleus tendon organ (Ib) afferents has been studied by noting their responses to graded force development produced by isometric contractions of either the whole muscle or single motor units. Data included responses of 23 Ib afferents to contraction of 8 whole muscles (8 experiments) and 16 Ib afferents to contraction of 30 motor units (5 experiments). Tendon organ responses of varying magnitude to contraction of the whole muscle or several of its individual motor units could be explained by differences in the number of muscle fibers that insert into each receptor's capsule and by differences in the contraction strength of these fibers. This finding suggests that soleus tendon organs have similar absolute sensitivities to static force development. An estimate was made of this absolute sensitivity and the value obtained (314 pps/g of force actually coupled to the receptor) is 2 orders of magnitude greater than those previously reported indices that simply relate Ib firing rate to force as measured at the tendon. The relationship between force exerted on a tendon organ's capsule and Ib firing rate is whown to be curvilinear and in keeping with a possible saturation effect that reduces the receptor's responsiveness to active contractions at relatively long muscle lengths.


Sensitivity of Purkinje cell dendrites to glutamic acid. The distribution of glutamate sensitive site was studied in vitro in thin cerebellar sections from guinea-pigs, in which Purkinje cell bodies and some of the principal dendrites were identified microscopically. Glutamate administered near the cell body induced firing. Stronger excitation, however, was produced when glutamate was administered to the molecular layer along a strip of tissue extending from the soma of the cell under study towards the pial surface of the slice. Excitation induced by glutamate slowly declined in some cells during prolonged administration. D-Glutamate was a weaker excitant than the L-isomer. These results suggest that the dendrite of the Purkinje cell is more sensitive to glutamate that the cell soma.


The motor units of cat medial gastrocnemius: problem of their categorisation on the basis of mechanical properties. The mechanical properties of 126 motor units from medial gastrocnemius muscle have been studied in 12 adult cats. Units with long contraction times (greater than 45 msec) were non fatigable (24 out of 26 units) and small (25 out of 26 units with less than or equal to 0.3% of the parent whole muscle tetanic tension) thus forming a very homogeneous population. In contrast, fast twitch units (contraction time less than or equal to 45 msec) exhibited a very broad range of tetanic tensions and fatigability. Significant correlations were found, however, within the fast contracting population which indicate a tendency for the more fatigable units to develop more tetanic tension and to be faster contracting. These findings are discussed in relation to the problems associated with using the interrelationships between twitch contraction time, tetanic tension and fatigue resistance to classify motor units into subpopulations sharing similar mechanical properties.


Effects of serial lesions of somatosensory cortex and further neodecortication on tactile retention in rats. Four groups of rats with bilateral lesions of somatosensory cortex and one of animals sustaining only sham operations were tested for retention of a difficult tactile discrimination. Two of the lesion groups had serial ablations, in one case with interoperative testing, and two had one-stage lesions. Bilateral ablations of somatosensory cortex severely retarded retention in all lesion groups relative to the control group and serial and one-stage groups did not differ from each other. The sham operated rats then experienced lesions of cortex anterior and posterior to the somatosensory areas. These lesions only marginally affected retention. Somatosensory cortex then was ablated and severe performance decrements were seen. Removal of additional neocortex in animals that previously had relearned the discrimination after somatosensory cortex lesions also resulted in very poor retention. These data demonstrate the importance of the somatosensory cortex in mediating tactile discriminations and suggest that non-somatosensory cortex may play a role in recovery after somatosensory cortical lesions.


Patterns of projection and braching of reticulospinal neurons. Extracellular microelectrodes were used to record the activity of reticulospinal neurons within the medial ponto-medullary reticular formation in the cat. In one series of experiments reticulospinal neurons were activated from electrodes in the ventro-medial reticulospinal tract (RSTm) and in the ipsi- and contralateral lateral reticulospinal tracts (RSTi, RSTc) at spinal levels C1--2, C4, Th1 and L1. RSTm neurons were found primarily in n.r. pontis caudalis and the rostro-dorsal part of n.r. gigantocellularis. 71% of these neurons projected as far as the lumbar spinal cord. RSTi neurons projecting to C4 and beyond were clustered in the caudo-ventral part of n.r. gigantocellularis, but those RSTi neurons projecting to the first three cervical segments were located more rostro-dorsally. In all, 63% of the RSTi neurons projected to the lumbar spinal cord. RSTc neurons, which comprised only 5% of the reticulospinal population, were found throughout n.r. gigantocellularis. RSTm neurons had a median conduction velocity of 101 m/sec whereas RSTi and RSTc had median conduction velocities on the order of 70 m/sec. In a second series of experiments microstimulation was used to activate branches of reticulospinal neurons within the gray matter of the cervical enlargement. Twenty-two of thirty-three neurons found to project to the cerivcal ventral horn were branching neurons that also sent axons to the lumbar spinal cord. Thus much of the teticulospinal activity reaching the cervical enlargement also acts at one or more other spinal levels. Detailed investigation of the course of reticulospinal axons within the cervical gray matter indicated that a single axon may traverse wide areas of the ventral horn including regions on both sides of the spinal cord.


Spectral and temporal characteristics of activation and suppression of units in the cochlear nuclei of the anaesthetized cat. 1. The responses are described of cochlear nucleus neurons of anaesthetized cats as a function of time in dependence on intensity and frequency of tonal stimuli. Depending on spectral properties three types are distinguished in the group of spontaneously active units: A type (activation only) AS type (activation and suppression) and S type (suppression only). The A(S) neurons have insufficient spontaneous activity to judge presence or absence of suppression. 2. Four temporal patterns of response are distinguished: transient, sustained, build up and complex. Units of the A type display a sustained time course of activation and have properties similar to those of auditory nerve fibres. S type units show sustained suppression. Temporal patterns of activation other than sustained were found only in the AS and A(S) units. 3. The recordings indicate that on suppression and off suppression are present more frequently in VCN neurons than previously found. The suppression phenomena in the DCN are, however, still more wide spread and more dramatic in appearance. 4. In contrast to earlier findings, off suppression was always observed and never seen to extent beyond the on activation band in A neurons. Data from AS neurons indicate that off suppression is neither simply an affect of high firing rates nor simply a continuation of on suppresion. 5. The relations between off suppression and spectral and temporal characteristics of on activation and suppression can be matched with a model featuring overlapping antagonistic inputs and postexcitatory inhibition.


Neurons in the cochlear nucleus investigated with tone and noise stimuli. 1. Responses of cochlear nucleus neurons to stationary and amplitude modulated noise stimulation are investigated and compared with responses to tonal stimuli. 2. Cross-correlation functions, computed from responses to stationary noise stimulation, showing a clear oscillation could be most easily obtained from low CF fibres presumed to be auditory nerve fibres and low CF cochlear nucleus neurons showing only activation response and a primarylike temporal pattern of response to tone bursts. This reflects good quality of phase locking in these neurons. 3. The CCF reflects strongly the frequency selectivity of the neuron as revealed in its response area but not the temporal pattern of response to tone bursts. 4. Responses to noise bursts are correlated with the responses to tone bursts of many different frequencies in both their sign (i.e. activation or suppression) and their temporal pattern. 5. The concept of two independently operating mechanisms, one depending on the fine time structure of the stimulus (the carrier) and the other on its amplitude, and determining respectively the fine time structure of the response pattern and its magnitude, is introduced. Experimental data are presented which lend support to the adequacy of the description in the majority of cases and reveal its shortcomings in others.


Statistical analysis and interpretation of the initial response of cochlear nucleus neurons to tone bursts. 1. Subject of investigation is the initial response of cochlear nucleus neurons and units presumed to be auditory nerve fibres to CF tone burst stimulation. 2. The initial response is characterized by computing the distribution of the latency of the first spike and of the duration of the first interval in the ensemble of responses to a large number of stimuli. 3. In many of the neurons the properties of both distributions appear to be related. The presumed auditory nerve fibres and spontaneously active cochlear nucleus neurons showing only activation responses to tonal stimuli (A type) exhibit irregularity in both response onset and intervals. Minimum latency and minimum first intervals are short. On the other hand, spontaneously active neurons with both activation and suppression in the response area (AS type) and silent neurons showing only activation (A(S) type) often show a more precisely timed onset of response and narrow interval distributions. In many neurons this leads to oscillations in the PSTH (chopping). In these neurons minimum latency and minimum first interval have higher values. The longer minimum latency cannot be attribute-d to longer pure time delays in these neurons. 4. The results are interpreted as speaking in favour of temporal integration as an important mechanism in many of the AS and A(S) neurons, particularly those in the DCN. The firing patterns of A neurons are thought to indicate virtual absence of this mechanism. 5. Using pure time delay estimates derived from cross-correlation functions, computed from the responses to stationary noise, an attempt is made to estimate the integration time in the cochlear and in the cochlear nucleus neurons.


Development of vestibulo-ocular responses in visually deprived kittens. The vestibular system contributes to the stabilisation of visual images on the retina by means of vestibulo-ocular compensatory reactions. The development of vestibular control of eye movements has been studied in twelve week old kittens, reared in total darkness, which have been compared with a control group of kittens reared in normal conditions. Postrotatory nystagmus, nystagmus during sinusoidal oscillations, visual suppression of vestibular nystagmus by fixation and pathological mystagmus following hemilabyrinthectomy, have been used as indicators of the functional state of the vestibulo-ocular control system. The results shown that most of the essential features of this control are present in dark-reared kittens. However, differences have been noted which possibly concern precise regulation of compensatory movements and head-eye coordination. The frequency of vestibular nystagmus is much smaller and the initial deviation of post-rotatory nystagmus in the direction of the change of movement is weak or absent in dark-reared kittens. Habituation also seems to operate differently in the two groups of kittens. Visual suppression of vestibular nystagmus is present, however, showing that an important part of the neuronal basis for visual-vestibular interaction has developed.


[Study of the mechanism of action of the new antidepressant pyrazidol]. The biochemical mechanism of action produced by a new antidepressant pyrazidol (1,10-trimethylene-8-methyl-1, 2, 3, 4-tetrahydropyrazino[1,2-a] indole hydrochloride) includes the inhibitory influence on the neuronal uptake of norepinephrine and a reversible comparatively short-lived inhibitory effect on the MAO activity.


[Effect of psychotropic substances on the uptake of [H3]-gamma-aminobutyric acid by rat brain synaptosomes]. The in vitro effects of some neuroleptics and antidepressants on the accumulation of [3H]/-GABA by the synaprosomes of the rat brain cortex were studied. Chloropromazine, trifluoperazine, fluphenazine, perphenazine, thioproperazine, haloperidol, trifluperidol,  droperidol, imipramine, haloanison and phthoracyzine were found (in order of a decreasing activity) to inhibit the [3H]/-GABA uptake of synaptosomes. Neuroleptics, except for a new drug carbidine, proved to be more potent inhibitors than antidepressants are. The tranquilized diazepan failed to have any effect on the [3H]/-GABA uptake. The rats synaptosomes treated with chlorpromazine and imipramine were found to display a decreased ability to accumulate [3H]/-GABA. The suppressive effect of psychotropic agents on the [3H]/-GABA uptake by synaptosomes is suggested to be due, at least partly, to their known inhibitory influence on the Na+, K+-dependent ATPase.


[Pain-alleviating action of fentanyl and pentazocine in combination with droperdol and carbidine]. Tests staged on rabbits showd that analgesic (phentanyl and pentasocine), neuroleptics (droperidol and carbidine) and their combinations produce a more pronounced and analgesic action with an electric irritation of the dental tissues than with that of the rabbit's paw. Neuroleptanalgesic mixtures containing pentasocine display a somewhat weaker analgesic activity, but their effect lasts longer and they have a less marked influence on the respiration. Mixtures containing cabidine in lieu of droperidol produce a somewhat greater analgesic effect and relax and skeletal muscles less.


[Effect of tranquilizers and analgesics on the permeability of the histohematic barriers for sulfacyl in inflammation]. The effect of neurotropics (analgetics and tranquilizers) on the permeability of histo-blood barriers in normalcy and pathology was wound to be dissimilar. In tests conducted on intact rats the studied neurotropic agents used in pharmacological doses did not affect the permeability of the histological-blood barriers of the brain and spleen with respect to the indicator--sodium sulfacyl. In rats with an inflammation focus the same drugs produced changes of the said factor, not always similar in their orientation (rise of fall).


[Study of the changes in the membrane permeability of smooth muscle cells for Ca45 and Na22 isotopes under the action of catecholamines]. Relaxation of smooth muscles of the stomachal band, but not of the portal vein of rats, induced with isadrine, is accompanied by a reduced entrance of Ca45 into the cells, this process, however, being barred by propranol. Contraction of smooth muscles of the seminal duct, aortic band and that of the portal vein of the rats, induced by norepinephrine is attended by an intensified incorporation of Ca45 in the cells, which diminishes in the presence of phentolamine. Norepinephrine stimulates an insignificant increase of the Na22 entrance into the cells of the portal vein and does not produce any regular changes in the movement of this isotope in the cells of the seminal duct of the rats.


[Prophylactic and therapeutic action of etimizol on the change in myocardial tissue metabolism in a neurogenic lesion]. The effect of aethimizol, introduced to rabbits before and after inflicting a 3-hours long extraordinary stimulation applied to the reflexogenic zone of the aortic arch, was studied. Investigations covered some aspects of energy metabolism and the level of the norepinephrine mediator in the muscle of the heart and also the functional state of the latter. Aethimizol was found to prevent shifts of the studied metabolic factors, induced by electric stimulation, and also to avert depletion of norepinephrine in the tissue of the myocardium and normalize its function.


[Effect of prostaglandins F2alpha and E1 on systemic and regional hemodynamics]. In experiments with anesthetized female-rats the influence of intravenous prostaglandins F2alpha (40 mg/kg) and Ei (10 mg/kg) on the cardiac output (by the method of dye dilution) and on the blood flow distribution among organs and tissues (by the method of Rb86 distribution) was studied. Prostaglandin F2alpha increased the arterial pressure, cardiac output along with the volume of the circulating plasma and reduced the total peripheral resistance. The hypertensive effect of prostaglandin F 2alpha is, under the circumstances, conditioned by the increased cardiac output and this substance is also instrumental in augmenting the proportion of the blood flow going to the digestive tract, skeletal muscles and, at the same time, in reducing its share flowing to the liver, spleen, skin and the uterus. Prostaglandin E1 reduced the blood pressure and total peripheral resistance and raised the cardiac output. The hypotensive effec of prostaglandin Ei is due to the fall of the total peripheral resistance. This compound tends to increase the part of the cardiac output that goes to supply the intesine, liver, lungs, myocardium and skeletal muscles and cuts down that part which caters for the stomach and kidneys.


[Action of ornid and papavperine on the biopotential and electrolytic balance of the vascular wall]. The influence of ornidium (bretylan) and papaverine on the biopotential and electrolytes metabolism in the vascular wall was studied in tests with cats. With their single administration ornidium (30 mg/kg) and papaverine (10 mg/kg) were found to increase the electrongegative biopotential and the potassium content in the vasculr wall. Ornidum causes the amount of magnesium to augment in the wall of venous vessels and of calcium--in the abdominal aorta. When used course-wise papaverine dose not produce any changes in the biopotential, but increases the potassium content in the venous vessels and decreases the amount of magnesium in the abdominal aorta.


[Effect of ether-oxygen anesthesia and of the premedication agents on the toxicity and cardiotonic effect of strophanthin]. Experiments conducted with mice, rats and cats demonstrated ether-oxygen anesthesia to reduce the tolerance of the animals to strophanthin in the LD50 and MDL tests. The premedication agents (atropine, promedol, diprazine) increased, according to observations on mice and rats, the resistance of the animals to strophanthin. In tests on dogs involving determination of the cardiac ejection by thermodilution strophanthin in a dose of 44 gamma/kg and under ether-oxygen anesthesia with premedication produced a statistically significant increase of the systolic cardiac index and well-marked bradycardia. Exclusion of thepremedicationagents drastically lowered the effect of strophanthin.


[Effect of aminazine on the lymphocyte blast transformation]. Chlorpromazine used in low concentrations during in vivo experiments stimulates the lymphocytes blast transformation reaction (LBR) in the blood of donors and in that of rabbits, while in large doses it suppresses this reaction. When LBR is stimulated with phitohemagglutinin (PHA), chlorpromazine weakens the reaction. Follwing a single intravenous injection of chlorpromazine to a rabbit the spontaneous LBR rises, while the stimulating effect of PHA declines. After a repeated introduction there of there are on the rise: spontaneous LBR, the reactions developing in response to PHA, the phenomenon of inhibition with chlorpromazine of the blast reaction stimulation, caused by PHA.


[Anti-inflammatory properties of some immunodepressants]. As evidenced from experiments conducted on rats immunodepressants-antimetabolites 6-mercaptopurine, methotrexate and 5-fluoruracil exert an antiexudative action and inhibit inflammation in its proliferative phase, as well as significantly change the count of leucocytes and their formula in the peripheral blood. It was established that the anti-exudate properties of these compounds may not be related to their immunodepressive action, while inhibition of proliferation is occasioned by their specific cytostatic effect.