Proton-dependent inhibition of yeast and brain hexokinases by aluminum in ATP preparations. The aluminum present as a contaminant in ATP preparations can cause strong inhibition of yeast hexokinase P-II activity at pH 7.0 or below but has little or no inhibitory effect at a pH of 7.5 or greater. The inhibition is reversed by citrate, 3-phosphoglycerate, malate, phosphate, and catecholamines, all of which have previously been described as activators of hexokinase at low pH. We suggest that these agents activate the enzyme only by virtue of their ability to coordinate with aluminum present in the assay system. The presence of aluminum is also responsible for the "negative cooperativity" observed at low pH with respect to Mg . ATP concentration--i.e., the inhibition by aluminum is uncompetitive at low Mg . ATP concentrations but becomes competitive at high Mg . ATP concentrations. The inhibition is thought to be due to formation of a complex of Al . ATP with the enzyme, with a dissociation constant (Ki) of 0.1 microM. Yeast hexokinase P-I is somewhat less sensitive to A1 than is hexokinase P-II, and yeast glucokinase is not detectably affected. The hexokinase in rat brain (type I) shows a pH-dependent inhibition by Al similar to that observed with the yeast hexokinases, whereas the rat muscle (type II) enzyme is less sensitive, suggesting a possible relationship to aluminum encephalopathy in man.


Organization of the multiple genes for the 70,000-dalton heat-shock protein in Drosophila melanogaster. The organization and number of 70,000-dalton heat-shock protein genes of Drosophila melanogaster has been investigated in a wild-type Oregon R fly stock and in a KC cell line. Six copies were found in the KC cells, and slightly more were found in the Oregon R population examined. In both cases, the basic gene element consisting of the mRNA coding region plus a short 5' "noncoding" sequence element was conserved. Two gene variants distinguished by specific restriction sites were found in both genomic DNAs. Restriction maps of the six genes in KC cells showed that these two gene variants are arranged differently. Restriction analysis of Oregon R embryonic DNA revealed polymorphism in the organization of the genes, which is not observed in KC cells. The data suggest that the arrangement as well as the number of genes for the 70,000-dalton heat-shock protein in D. melanogaster is subject to variations at both the 87A and 87C cytogenetic loci.


Involvement of gangliosides in lymphocyte stimulation. N4-Dinitrophenyl-L-2,4-diaminobutyric acid hydrazide was attached covalently to the aldehyde groups produced by periodate oxidate of bovine brain gangliosides and it was incorporated into mature thymocytes. High concentrations of antibodies to dinitrophenyl (DNP) or lower concentrations followed by protein A agglutinated the cells and stimulated DNA synthesis. Incubation of the thymocytes containing DNP-modified ganglioside with rabbit anti-DNP and fluorescein-labeled anti-rabbit IgG resulted in the formation of uniform rings on the cell surface, which subsequently developed into patches and caps. These results indicate that gangliosides may play a primary role in the lymphocyte activation process.


Effective tumor immunization induced by cells of elevated membrane-lipid microviscosity. The immunogenicity of a series of mouse tumor lines propagated in vivo (T and B lymphomas and mammary adenocarcinoma) was tested after alteration of the cell membrane-lipid microviscosity. Tumor cells used for immunization were first treated to alter the lipid content, then irradiated and injected intraperitoneally into syngeneic mice. A second identical immunization was performed 14 days later. The degree of immunization in the treated mice was assessed by survival time after challenge with untreated viable tumor cells of the same origin as the immunizing cells. For all tumors tested, enrichment of the immunizing cells with cholesterol or cholesteryl hemisuccinate, which increased the membrane-lipid microviscosity significantly, afforded a marked increase in immunization, compared to that obtained with cells that were only irradiated. Furthermore, in over 90% of the mice that were pretreated with cholesteryl hemisuccinate-enriched cells, tumor growth after the challenge was not detectable. Because the lipid-modifying treatments of the immunizing cells involve no toxic substances, these results may provide the basis for a potent approach to immunotherapy of human cancer.


Photoelectric properties and detection of the aromatic carcinogens benza[a]pyrene and dimethylbenzanthracene. The absolute photoelectron quantum yield spectra for benzo[a]pyrene and dimethylbenzanthracene are presented in the wavelength range 180--230 nm. These polycyclic aromatic carcinogens have photoelectron quantum yields of approximately 2 x 10(-3) electrons per incident photon at 180 nm. The quantum yields fall off quickly and monotonically at wavelengths longer than 210 nm (5.9 eV). Threshold values for benzo[a]pyrene and dimethylbenzanthracene are 5.25 +/- 0.06 cV and 5.27 +/- 0.04 eV, respectively. The photoelectron quantum yields of benzo[a]pyrene and dimethylbenzanthracene are several orders of magnitude greater than typical components of biological membranes (amino acids, phospholipids, and polysaccharides). Preliminary micrographs of benzo[a]pyrene and dimethylbenzanthracene sublimed onto poly(L-lysine) and onto dimyristoyl phosphatidylcholine demonstrate the high contrast of small crystallites of carcinogens against a background of membrane components. These results and calculations involving relative contrast factors suggest that the distribution of these carcinogens in biological membranes can be determined by using photoelectron microscopy.


Identification of mannose 6-phosphate in glycoproteins that inhibit the assimilation of beta-galactosidase by fibroblasts. Bovine testicular beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) is rapidly and selectively assimilated by human skin fibroblasts. The assimilation of the enzyme is strongly inhibited by mannose 6-phosphate and by a glycoprotein fraction isolated from bovine testes (glycoprotein inhibitors). These results suggest that beta-galactosidase and the glycoprotein inhibitors have a common recognition marker that contains mannose 6-phosphate. The presence of mannose phosphate in the glycoprotein inhibitors was demonstrated by acid hydrolysis of the glycoproteins to liberate mannose phosphate followed by reduction with NaB(3)H(4) to give [(3)H]mannitol phosphate. The (3)H-labeled compound was identified by paper electrophoresis and by the release of [(3)H]mannitol on treatment with phosphatase. The [(3)H]mannitol phosphate was oxidized with periodate and the resulting phosphorylated fragment, on reduction with NaB(3)H(4), yielded [(3)H]ethylene glycol phosphate, indicating substitution of phosphate on carbon 6 of mannitol. Mannose 6-phosphate was also found in a major carbohydrate-containing fraction of peptides produced from the glycoprotein inhibitors by tryspin digestion. It was estimated that about 2% of the mannose residues were present as mannose 6-phosphate. Phosphorylated oligosaccharides were also identified in hydrolysates of the glycoprotein inhibitors. One, a disaccharide, was identified as alpha-(mannosyl-6-phosphate)-(1 --> 2)-mannose. These observations suggest that the recognition marker of beta-galactosidase contains alpha1,2-linked mannose 6-phosphate; terminal alpha1,2-linked mannose residues are known to occur in the high-mannose type oligosaccharides present on beta-galactosidase.


Cloning immunoglobulin gamma 2b chain gene of mouse: characterization and partial sequence determination. DNA from newborn mice was digested with restriction endonuclease EcoRI, and a 6.6-kilobase fragment encoding immunoglobulin gamma 2b chain mRNA derived from MPC 11 myeloma was enriched about 100-fold by RPC-5 column chromatography and agarose gell electrophoresis. The 6.6-kilobase fragment was cloned with lambda gt WES.lambda B as EK2 vector. The cloned phage (lambda WES.IgH22) contained the constant region gene of the gamma 2b chain but not the variable region gene of MPC 11 mRNA. The constant region genes of the other gamma chains (i.e., gamma 1, gamma 2a, and gamma 3) were not present in lambda gt WES.IgH22 DNA. R-loop mapping indicates that the gamma 2b chain structural gene is divided into two parts (330 +/- 60 SD base pairs and 930 +/- 110 SD base pairs) by an intervening sequence (360 +/- 100 SD base pairs). The nucleotide sequence around the junction of the hinge region and CH2 domain was determined and shown to match the amino acid sequence of the initial part of the CH2 domain of the gamma 2b chain. The base sequence upstream from the junction, however, is unrelated to the amino acid sequence of the CH1 domain and the hinge region of all the gamma chains whose sequences have been determined. These results indicate that the gamma 2b chain gene is interrupted at the junction of the hinge region and CH2 domain by an intervening sequence. The existence of two more intervening sequences, one between the CH1 domain and the hinge region and the other between the CH2 and CH3 domains, is discussed.


Promoter mutations in the transfer RNA gene tyrT of Escherichia coli. The DNA sequences for nine independent promoter mutants of a tyrosine tRNA gene, tyrT of Escherichia coli, are reported. The nine mutations involve six transitions, two transversions, and one deletion. They are located at four different sites in the first 30 base pairs preceding the start point of transcription. The changes found are: a T.A to A.T transversion at position -8 (two mutants); a T.A to C.G transition at position -8 (three mutants); a T.A to C.G transition at position -13 (two mutants); a T.A to C.G transition at position -16 (one mutant); and a deletion of a G.C base pair at position -26/27 (one mutant). Four of the five different mutant tyrT promoters have alterations at positions that might have been expected from DNA sequence studies with other prokaryote promoters. One of these mutants (a G.C deletion at position -26/27) occurs in a stretch of eight consecutive G.C base pairs which may be characteristic of stable RNA promoters.


Passive modulation of blood-group antigens. Rh-positive erythrocytes were enriched and depleted of membrane cholesterol, and the mediated change in the degree of exposure of the D antigens was determined by fluorescence-activated cell sorting, using indirect fluorescent antibody labeling. The results are compatible with a model in which the expression of the D antigens can be modulated significantly by the lipid microviscosity (eta). At a high cholesterol-to-phospholipid ratio (C/PL) of 1.55, which corresponds to eta (25 degrees C) = 7.5 poise (1 poise = 0.1 Pa.sec), the relative detectable number of D antigens was about double than that at C/PL = 0.65, eta (25 degrees C) = 4.1 poise. In analogous experiments similar fluidity changes resulted in only about 20% modulation of expression of the A1 antigen, suggesting that in the native state this antigen is already well exposed on the erythrocyte surface. This type of antigenic modulation may also operate in vivo, and may thus bear some fundamental implications on tumor immunology and autoimmune diseases.


Immunoglobulin differentiation is dictated by repeated recombination sequences within the V region prototype gene: a hypothesis. Analysis of the available DNA sequences of immunoglobulin light chain genes reveals a unique structural pattern. A stretch of about 15 nucleotides repeats five times within the variable (V) region gene, with few base changes. Identification of these homologous sequences is apparent in the embryonic V(lambda) gene and might also be recognized in V(kappa) genes isolated from a myeloma. Although different from each other, the V(lambda) and V(kappa) hyperhomologous sequences display a remarkable resemblance to different prokaryote sequences associated with recombinational events. The homologous sequences appear at all three sites where hypervariable regions of the mature peptide are encoded. In addition, they are located at the site where V/constant (C) recombination is supposed to take place. Consequently, a general model is proposed for immunoglobulin differentiation. The hyperhomologous loci are postulated to be comprised of recombination sequences which makes them available for a mechanism of single-stranded DNA exposure. B cell maturation begins with V/C recombination, a step that is rate limiting. The fidelity of the process is ensured by extensive DNA homology between the two embryonic subgenes of V and C. Next, an error-prone repair system is activated and thereby introduces changes into the content of the immunoglobulin gene at the exposed loci. The process ends when mutations make the recombination sequence unrecognizable as such. The model is consistent with large amounts of data and is compatible with the view that immunoglobulin diversity is being generated somatically.


Some sequence similarities among cloned mouse DNA segments that code for lambda and kappa light chains of immunoglobulins. A comparison between the cloned mouse DNA segments that were found to code for the lambda and kappa light chains of immunoglobulins established that there were seven short nucleotide sequences, two of which matched 6 out of 7, two 7 out of 8, two 8 out of 9, and one 9 out of 10 bases; these sequences were located either at homologous amino acid positions or at positions displaced by four amino acids or less. They all occurred in the framework regions (FRs), five next to the complementarity-determining regions (CDRs). Three of these were unique and did not occur elsewhere in the immunoglobulin nucleotides sequenced thus far or in DNA's of phage phi X174, phage G4, or simian virus 40. Five could serve as sites of joining by recombination or insertion of CDR to FR segments, and the invariant tryptophan that is the first residue of the second FR might serve as a sixth. These sites are consistent with the mini-gene or insertional hypotheses for the generation of antibody diversity but could also serve as points of recognition for a mutator enzyme or could serve to limit somatic mutation to the CDRs.


Cloned pairs of variable region genes for immunoglobulin heavy chains isolated from a clone library of the entire mouse genome. To investigate the organization of immunoglobulin genes, we have constructed a clone library containing 10(6) randomly generated fragments of mouse embryo DNA, corresponding to eight equivalents of the genome. The cloning method involved methylation of embryo DNA at EcoRI recognition sites, partial digestion by EcoRI* endonclease activity, and direct ligation of the resulting large fragments to the lambda phage vector Charon 4A. The library was searched for sequences homologous to a cloned complementary DNA copy of a mu heavy chain mRNA. Nine clones bearing variable heavy chain (VH) sequences were isolated, representing at least eight distinct VH genes. Thus, multiple related VH genes are available in the genome to contribute to immunoglobulin diversity. Each of the two clones carries a pair of VH genes, one pair separated by 15 +/- 1 kilobase pairs of mouse DNA and the other by 14 +/- 2 kilobase pairs. This indicates that related VH genes are clustered and may occur in a tandem array having a repeating unit of 14--16 kilobase pairs. The large spacer sequences between VH genes cannot, however, be highly conserved.


The effects of methamphetamine on fine motor control in rhesus monkeys. Six rhesus monkeys were trained to extend their arms through a tube to press a lever with between 25 and 40 g of force for 3 or 5 sec. Responding was maintained by the delivery of 1.5 cc of water. Stimulus lights indicated whether the exerted force was below 25 g. between 25 and 40 g (i.e., correct) or above 40 g. Sessions were terminated after 50 water deliveries or 30 min had elapsed. Performance was well-maintained in all monkeys. Allowing the animals access to water prior to the session had no effect on performance. Discontinuing sessions for two weeks disrupted some aspects of performance but responding improved within 5 sessions. Single injections of methamphetamine (0.06-0.5 mg/kg) were given IM 20 min prior to the session. The highest dose of 0.5 mg/kg totally eliminated responding. Lower doses decreased rate of responding somewhat and increased phasic activity (i.e., tremors) in a dose-dependent manner. The procedure seems ideally suited for investigating the effects of psychotropic drugs on fine motor control in rhesus monkeys.


Effects of an enkephalin analog on complex learning in the rhesus monkey. Facilitation of the learning of a discrimination reversal task for a reward of food was found in rhesus monkeys after subcutaneous administration of a potent pentafluorinated enkephalin analog. (D-Ala2)-F5-Phe4-enkephalin-NH2. General activity, short-term memory, startle, and analgesia, however, were not significantly affected. In a within-subject design, each of 6 monkeys (3 males and 3 females) received each of 5 doses of the enkephalin analog (0.1, 1, 10, 100, and 1,000 microgram/kg). One daily injection was made for 7 consecutive days, including pre- and posttests on the first and last days with the diluent control. The enkephalin doses, with the exception of the 0.1 microgram/kg level, produced significantly faster learning than the diluent. Some sex differences were suggested by the data, but these effects are difficult to interpret. The results suggest that relatively small amounts of this analog given systematically can exert a reliable effect on a complex behavior such as reversal learning at doses devoid of opiate effects, due perhaps to enhanced cognitive flexibility rather than improvement in short-term memory or association formation.


Effects of zimelidine, a selective 5-HT uptake inhibitor, on serum prolactin levels in man. The levels of serum prolactin were studied both after an acute intake of zimelidine and during a treatment period of 3--7 weeks. No significant changes in basal serum prolactin levels were seen after single oral doses of zimelidine (100 mg) in healthy volunteers during an investigation period of 12 h. Serum prolactin concentrations remained well within the pretreatment levels also during a continuous treatment of depressive patients with zimelidine up to 150 mg orally b.i.d. It is concluded that clinical doses of the selective 5-HT uptake inhibitor zimelidine does not exert any significant effect on serum prolactin levels.


Maturational changes related to dopamine in the effects of d-amphetamine, cocaine, nicotine, and strychnine on seizure susceptibility. The effects of four neural excitants (damphetamine, cocaine, nicotine, and strychnine) on myoclonic and clonic seizure susceptibility were investigated in two age groups (30 and 120 days) of short-sleep mice. Amphetamine and cocaine decreased susceptibility to myoclonus in young mice and increased susceptibility in mature mice. These effects were attenuated by pretreatment with haloperidol, indicating mediation by a dopaminergic system. Amphetamine did not alter clonic susceptibility in either age group of mice, whereas cocaine affected clonic susceptibility and myoclonus. These effects were not attenuated by haloperidol, indicating mediation by systems other than dopamine. Nicotine decreased susceptibility to myoclonus and increased susceptibility to clonus, whereas strychnine increased susceptibility to both types of seizure. Haloperidol, however, failed to alter any of these effects. These results are consistent with our previous work which suggests that a dopaminergic mechanism in these mice undergoes marked developmental changes between 30 and 120 days of age.


Cocaine, d-amphetamine, and pentobarbital effects on responding maintained by food or cocaine in rhesus monkeys. The effects of IM injections of cocaine, d-amphetamine, and pentobarbital were studied in rhesus monkeys whose lever-press responding was maintained under a second-order fixed-interval, fixed ratio schedule of reinforcement. Within each session, fixed-interval components, ending with the IV injection of 30 microgram/kg cocaine (one group of monkeys) or the delivery of a 300 mg food pellet (second group of monkeys), alternated with fixed-interval components ending without an injection of cocaine or the delivery of food (extinction). Drug pretreatments generally caused comparable dose-related decreases in the overall rates of responding reinforced either by cocaine or by food. Response rates during extinction usually increased and then decreased as the dose of each drug increased. An analysis of the drug effects on response rates in different temporal segments of the fixed intervals showed that in both the reinforcement and extinction components, the normally low control rates of responding which occurred earlier in the intervals were usually increased, while higher control rates which occurred later in the intervals were increased less or decreased. Thus, the effects of these drugs were relatively independent of the reinforcing event (food or cocaine) and tended to depend more on the ongoing rate of responding under these conditions.


Social isolation and other behavioral changes in groups of adult vervet monkeys (Cercopithecus aethiops) produced by low, nonchronic doses of d-amphetamine. Doses (0.1--0.7 mg/kg body weight) d-amphetamine were administered to three independent groups of green vervet monkeys (Cerecopithecus aethiops). Each group formed a triad with one male and two females. Amphetamine changed both the individual and the social behavior patterns significantly. Stereotypy and social isolation (withdrawal) were characteristic features of the amphetaminized animals. Also stereotyped social grooming was observed. The results are discussed in relation to behavior changes seen in amphetamine psychoses and in naturally occurring endogenous psychoses. It is emphasized that the study of patterns of behavior is an important object of research and relevant line in future investigations on psychopathology.


Effect of drugs influencing central serotonergic mechanisms on methamphetamine-induced stereotyped behavior in the rat. Pretreatment with L-tryptophan, a precursor of serotonin, was found to decrease the intensity of stereotyped behavior induced by methamphetamine, while methysergide, a serotonin antagonist, was found to increase the intensity of methamphetamine-induced stereotyped behavior. These results suggest that the intensity of methamphetamine-induced stereotypy depends on the balance between central dopaminergic and serotonergic systems and that the central serotonergic system may have an opposing, tonic effect upon central dopaminergic systems involved in the mediation of stereotypy. In contrast to L-tryptophan, however, pretreatment with quipazine, a serotonin agonist, and clomipramine, a selective, serotonin neuronal uptake blocker, was found to potentiate the stereotyped behavior induced by methamphetamine. The probable mechanisms by which quipazine and clomipramine might have potentiated the methamphetamine-induced stereotypy are discussed.


Scopolamine state-dependent memory processes in man. Scopolamine state-dependent learning was investigated in man using four learning and recall tasks. Twenty-eight subjects performed the four tasks on the first day of the 2 day experiment under either the influence of the drug (5 microgram/kg of scopolamine administered IV) or a placebo and tried to recall the material on the second day in either the same or altered drug state. State-dependent learning theory predicts that those subjects in the same drug state on both days should recall more material than those who had their drug condition changed. Results confirmed this prediction for the two recall tasks which did not involve recall cues or prompts but not for the tasks involving memory acids. This implies that the drug state has memory cueing properties of its own and that recall can be enhanced either by restoring the drug state which existed at the time of learning or by providing external prompts.external prompts.


Cannabinols and feeding in sheep.

Cannabinols and feeding in sheep. Marijuana, long used for the euphoria which results, recently has been found to stimulate hunger in humans but in several laboratory animals cannabinoids decrease food intake. Sheep, relatively more sensitive to chemicals that affect food intake, were injected IV with the d-and l-isomers of tetrahydrocannabinol and with a 9-aza-cannabinol) 9-AC) (8-(1,2-dimethylheptyl)-5,5-dimethyl-5H-[1]benzopyranol[3,4]pyridin-10-01, HCL) and feeding behavior was monitored. In the first 30 min, food intake was increased by the l-isomer and by 9-AC but not affected by d-delta 9-THC. After 24 h, feed intake was decreased by at least one dose of d-and l-delta 9-THC and 9-AC. The l-but not d-isomer was active at very low doses compared with doses used in many laboratory animals.


Increased tolerance in mice following prenatal exposure to barbiturate. HS/Ibg (heterogeneous stock) mice dams were fed milled mouse food containing 3 g/kg phenobarbital (PhB) in acid form and water as their only nutritional source from gestation days 9--19. Control females received milled food and water. Blood PhB levels of treated females and fetuses were 40--200 micrograms/ml blood. At the age of 50 days, male offspring were injected with C14 -sodium pentobarbital (PenB) (50 mg/kg). Sleep time and temperature loss were monitored and, in randomly selected individuals, brain PenB levels were determined upon awakening. The experiment was repeated on the same animals for 3 consecutive days. All offspring developed functional (central nervous system) tolerance during the 3 testing days as evidenced by the daily decrease in sleep time while brain levels of PenB upon awakening increased (P less than 0.001). Offspring who received PhB prenatally had generally shorter sleep times, less temperature loss, and higher brain PenB levels upon awakening than controls. The differences were most pronounced on the second day (sleep time reduced 27%, P less than 0.001; temperature loss 47%, P less than 0.001; brain PhB levels increased 23%, P less than 0.01).


A new motility meter based on the Doppler principle. A new motility meter for recording the locomotor activity of small laboratory animals is described in detail. The equipment is designed to record simultaneously, but independently, the motility of eight animals (or groups of animals) in separate cages. The functional mechanism is an application of the well known Doppler principle. The use of electromagnetic waves presents the important advantages of contactless detection and freedom from interference of external stimuli with spontaneous activity; both horizontal and vertical components of movement are registered. To test the equipment, motility was studied in rats treated with saline, haloperidol, d,l-amphetamine, and the combination of haloperidol and d,l-amphetamine. Motility, as measured with the Doppler motility meter, proved to be very sensitive to drug-effects.


Central cholinergic receptor supersensitivity after long-term atropine administration. Rats were treated with a single dose of atropine (AT) at 5 mg/kg, or every day for 14 or 31 days with the same dose of AT, 3 h after the single dose and 24 h after the last dose of chronically administered AT, 10 micrograms of ACh was injected intracerebroventricularly, and two tests were used to examine the behavior of the animals. The tremorigenic effect of oxotremorine was also measured in mice treated with 10 mg/kg of AT for 1 month. It was shown that a single dose of AT antagonized ACh-induced behavior. The long-term treatment with AT enhanced the depressive-behavior of ACh in rats and the tremorigenic effect of oxotremorine in mice. The results suggest that long-term blockade of central cholinergic receptors induces their hypersensitivity.


Some effects of piracetam (UCB 6215, Nootropyl) on chronic schizophrenia. A study is described of effects of a nootropic drug on chronic schizophrenia. The nootropic drugs act on the central nervous system with the cerebral cortex as their target. Chronic schizophrenic patients on the drug showed improvement in object naming and in tests where the patient was required to indicate the number of times he had been tapped. Improvements were also noted in learning and memory tasks. In dichotic listening the patients showed a reduction in the amount of incorrect verbal responses produced. There were no improvements in symptom rating or social behaviour rating. These results suggest some cognitive improvement but little if any change in the disease state of the patient.


Electrophysiological correlates of the behavioral effects of tubocurarine in conscious cats. The effects of tubocurarine on behavior, electrical activity, and auditory evoked potentials were studied in restrained conscious cats. Tubocurarine hydrochloride (doses of 0.05--1 micrograms intraventricularly) produced various central stimulatory effects characterized by EEG desynchronization, decrease in both low (7--9 Hz) and high (10--14 Hz) alpha waves, and decrease in the amplitude and area of the surface positive (P1) wave of auditory evoked potentials. Concomitant with the alterations in brain electrical activity tubocurarine hydrochloride produced generalized behavioral arousal phenomena and the cats became restless and exhibited miaowing and increased movement of the head and ears. Almost all parameters except behavior showed a distinct dose-response relationship. A correlation between the behavioral effects and the EEG analog was thus demonstrated.


Effects of d-amphetamine, maprotiline, L-dopa, and haloperidol on the components of the predatory behavior of the ferret, Putorius furo L. Ferret predation on rats was examined in an arena. One hour before the test one of the following drugs was administered. d-Amphetamine (0.8 and 1.4 mg/kg IM), MAPROTILINE (10 AND 40 Mg/kg orally), L-dopa (30 and 60 mg/kg orally), or haloperidol (0.14 and 0.6 mg/kg IM). Provided that capture was successful, the sequence of the behavioral components was not changed by these drugs. With the exceptions of paw movements and rolling over, which were not affected by the drugs, the components of predatory behavior were influenced differently. This leads to the assumption that a drug affects different mechanisms which control behavior. It is assumed that dopamine is involved in the control of capture elicitation as well as in the control of pursuit and biting. Capture elicitation was inhibited by d-amphetamine and L-dopa, but not by maprotiline, and was even facilitated by haloperidol. The orientation of pursuit movements and biting was impaired by L-dopa and improved by haloperidol, whereas maprotiline did not influence these components.


Stimulation of human prolactin secretion by mescaline. Prolactin (PRL) and Growth Hormone (GH) secretions were studied in human serum after the oral administration of 5 mg/kg mescaline (3,4,5-trimethoxy-beta-phenylethylamine) or 2,3,4-trimethoxy-beta-phenylethylamine (2,3,4-TMPEA) respectively. Mescaline stimulated the secretion of PRL more than four-fold above base-line levels. Peak concentrations were found 90--120 min after drug intake. Five hours later serum PRL was still markedly increased. Mescaline also triggered GH secretion. There was no alteration of serum PRL and GH concentrations after intake of the non-hallucinogenic 2,3,4-TMPEA.


The effect of high dose oxprenolol on stress-induced physical and psychophysiological variables. The effects of oral oxprenolol (480 mg) and lorazepam (2 mg) on skin conductance, reaction time, critical flicker frequency and self-rating visual analogue scales for anxiety, sedation and concentration were investigated in 6 healthy male volunteers. Oxprenolol exerted a central action similar to lorazepam as shown by a significant lowering of skin conductance and decrease in the number of spontaneous fluctuations during stress, impaired critical flicker frequency and decrease in alertness with reduced concentration.


Effect of naloxone on the behaviour of rats exposed to a novel environment. It has recently been suggested that endogenous opiates may play a general role in stress responding. To test this hypothesis, naloxone hydrochloride (0.5-4.0 mg/kg SC) was administered to rats exposed to an open field situation. Naloxone treatment produced a decrease in locomotor activity and rearing, and an increase in defaecation. A simple dose-response relationship was not observed, with the most potent effects exerted by the 1 mg/kg dose. Nvertheless, these results indicate that naloxone increases emotionality in the rat and suggest that opioid peptides may be released under conditions of nonpainful stress.


Piracetam as an aid to learning in dyslexia. Preliminary report. Sixteen male dyslexic children were seen again when adults and matched with 14 student volunteers for a 21-day trial of piracetam. It was found, using a double-blind cross-over technique, that dyslexics significantly increased their verbal learning by 15.0% and students by 8.6% (over and above their placebo increase).


Methadone effects on brain functioning and type A and B CNV shapes. Twelve male outpatients participating in a methadone maintenance treatment program were evaluated for the effects of acute administration of methadone on brain functioning (contingent negative variation or CNV), attention performance (reaction time and continuous performance test), and psychophysiological activity (heart rate and eye blink rate). Individual differences in response to methadone were assessed by classifying patients into two groups on the basis of basal CNV shapes: Type A (quick rise time) and type B (slow rise time). Methadone produced a pattern of increased electrical brain activity (CNV) and enhanced attention performance in type B patients and elevated heart rate and lowered eye blink rate in type A subjects. Results are interpreted in terms of the distraction-arousal and the eye blink-hedonia hypotheses.


A characteristic effect of hallucinogens on investigatory responding in rats. The disruption of the temporal distribution of investigatory responses by rats in a novel hole-board following lysergic acid diethylamide-25 (LSD), as described in a companion paper (Geyer and Light, 1979), was found to be a characteristic effect of a variety of hallucinogens. Similar effects were produced by indoleamine hallucinogens, such as LSD, N,N-dimethyltryptamine, and psilocin, and by phenylethylamine hallucinogens, such as mescaline or 2,5-dimethoxy-4-methylamphetamine (DOM). Congeners of DOM that are inactive in humans had no significant effects. Furthermore, of a variety of other psychoactive drugs tested, only apomorphine produced an effect similar to that of the hallucinogens. These results suggest that a simple behavioral measure of exploration in a hole-board may provide a useful animal model with which to examine the common effects of hallucinogens.


Modification of spontaneous ECoG and behavior in cat by monoamine precursors. The effects of increasing the brain monoamine content on the three types of localized rhythms identified in somatic area I ("mu-type rhythms") were studied in freely moving cats. Increases in brain monoamines (catecholamines and serotonin) were produced by injecting L-Dopa and 5-HTP, L-tyrosine, L-tryptophan and tryptamine were also tested. It is concluded that the two subsets of rhythms, one accompanying high levels of alertness and vigilance and the other appearing during quiet wakefulness, are related to the catecholaminergic systems, while those characterizing drowsiness seem to be controlled by a serotoninergic system. The latter, however, is distinct from that controlling slow sleep.


Effects of meperidine on operant behavioral thermoregulation in mice under conditions of symmetrical thermal drive. The effects of meperidine on operant behavioral thermoregulation were investigated using a convective thermal controller and mice trained to alternate at will the thermal-drive condition, changing it from an air flow of 15 degrees C to one of 45 degrees C, and vice versa. Administration of 15 mg/kg meperidine resulted in significantly lower response rates, a significantly larger fraction of time spent in one (mostly cold) drive condition, and significantly lower body temperatures than administration of saline. In a second experiment the animal was automatically returned to the hot-drive condition every 3 min unless it had been exposed to this condition in the previous 0.4 min although otherwise it remained free to alternative drive conditions at will. Under these conditions, meperidine-treated animals also spent significantly more time in cold drive and had significantly lower body temperatures than control animals, in spite of lower response rates. Pretreatment with 4.5 mg/kg tranylcypromine (4 h prior) did not significantly alter the effects of meperidine administration in either experiment.


Facilitation of opiate- and enkephalin-induced motor activity in the mouse by phenytoin sodium and carbamazepine. In the first experiment, adult male Swiss-Webster mice were systemically injected with a standard dose of morphine. Compared to the influence of vehicle, the motor activity of morphine-injected mice was increased. Neither phenytoin sodium nor carbamazepine alone facilitated motor activity, but pretreatment with both drugs further facilitated the increased motor activity produced by morphine. In a second experiment, mice were injected centrally with a long-acting analog of leu-enkephalin. It also increased motor activity in comparison with vehicle. Again, both phenytoin sodium and carbamazepine further facilitated this response. Both experiments suggest a facilitatory interaction between some aspects of these anticonvulsants and opiate-induced motor activity.


Comparison of serum levels after intramuscular injections of 2% and 10% cis(Z)-flupentixol decanoate in Viscoleo to schizophrenic patients. The serum concentrations of cis(Z)-flupentixol after injection of 2% and 10% cis(Z)-flupentixol decanoate in Viscoleo (Depixol injection, Fluanxol Depot) have been investigated in a crossover study with eight schizophrenic patients. No statistically significant difference was found between the two preparations when the data from individual days or areas under the serum concentration curves were considered. For the individual patients a difference was found between the two treatments in six cases; one preparation gave the higher serum concentration in four cases and the other preparation in two cases. Thus, the difference found within individual patients reflects the intraindividual variation rather than a difference between preparations. The maximum serum concentration was seen at 4 or 7 days after injection. The maximum/minimum fluctuation ratio indicates that dosage intervals longer than 2 weeks seem reasonable for most of the patients. The similarity in the serum concentrations, no matter which concentration of flupentixol decanoate solution was given, indicates that a dispersal and possibly a metabolic breakdown of the oil depot takes place in the muscle.


Amphetamine psychosis and psychotic symptoms. Amphetamine psychosis has been considered to be a pharmacologic model of schizophrenia. Fifteen previously reported cases were reviewed in which experimental induction of amphetamine psychosis occurred in nonschizophrenic drug abusers. Seven (possibly ten) cases manifested Schneider's first rank symptoms and all had World Health Organization Present-State Exam symptoms which discriminated schizophrenia. This observation draws further parallels between the phenomenology of amphetamine psychosis and schizophrenic symptoms.


Reduction of swimming time in mice through interaction of infrasound and alcohol. The effects of noise, alcohol, and the combination of the two were studied on muscular fatigue in several mouse strains to investigate a possible interaction between the two stresses. Muscular fatigue was measured by latency to submersion during a forced-swimming test. Animals were exposed to acoustic stimuli of fixed frequency and intensity for 2h preceding the test. Ethanol was administered orally from 30 min to 3h 30 min prior to testing. Alcohol doses and sound intensities were subliminal when administered separately. While no significant interaction occurred between alcohol and audible sound, the interaction between alcohol and infrasound was highly significant indicating that their joint effects are more than merely additive. Blood alcohol measurements indicate that these interactive effects are prolonged for more than 2h after elimination of alcohol from the blood. Effects are similar in genetically deaf and hearing mice, implicating involvement of nonauditory pathways.


Urinary dicarboxylic acids in patients receiving lithium or rubidium salts. Lithium salts administered in therapeutic doses to four subjects who were kept on controlled diets increased up to fivefold the urinary output of some dicarboxylic acids. Some of the acids affected are intermediates in the tricarboxylic acid cycle, others are chemically similar but not directly related in metabolic terms. This is probably a direct effect on renal transport. Rubidium salts increased urinary 2-oxoglutarate output and blood 2-oxoglutarate levels, probably by some action on intermediary metabolism.


Food-choice in a food-preference test: comparison of two mouse strains and the effects of chlordiazepoxide treatment. In male mice of the C57 strain, chlordiazepoxide (CDP) (2.5, 5.0 and 10.0 mg/kg) reduced the latency to begin eating and prolonged the total time devoted to eating in a food-preference test. The increase in feeding duration arose from an increase in the mean duration of individual eating episodes and not from a change in the number of episodes that were initiated. In contrast, in male mice of the A2G strain CDP (at the same dose levels) did not reduce the latency to begin eating and only prolonged the total time devoted to eating at a single dose level (5.0 mg/kg). The two strains differed in their choice between novel and familiar foods that were concurrently available in the test. The A2G mice virtually ignored the palatable novel foods and devoted all their feeding to the familiar food. The C57 strain, however, spent more time eating the novel foods than the familiar food. CDP at all doses increased the duration of feeding devoted to familiar food in the C57 animals, but did not increase feeding duration in the A2G mice. However, CDP (10.0 mg/kg) increased the time spent eating novel foods in both strains to the same degree. Possible mechanisms underlying the effect of CDP on food-preference behaviour in mice and accounting for the strain difference in response to CDP are considered.


Naloxone effects on serum growth hormone and prolactin in man. Endogenous and exogenous opiate-like compounds have been found to cause increased serum growth hormone and prolactin levels in animals, and, in some cases, humans. Naloxone, a relatively specific narcotic antagonist, decreases serum prolactin and growth hormone levels in animals. Naloxone (20 mg IV) did not significantly alter serum prolactin levels and, minimally but not significantly, increased growth hormone levels in humans to whom it was administered.


Food and water intake in the non-deprived pigeon after chlordiazepoxide administration. Food and water intake were measured in non-deprived pigeons over a 4h period during daytime. Under control conditions, the ratio of food to water intake was approximately 1:1, and both intakes were a simple linear function of time. Chlordiazepoxide (10 mg/kg, i.m.) doubled the mean amount of food intake, whilst leaving water intake unchanged. This is a first indication that chlordiazepoxide can selectively stimulate appetite for food in an avian species. Some birds showed sedation following a first acute injection; its duration was shortened after repeated injections, and the hyperphagic response to the drug was revealed.


Neonatal death in babies with rhesus isoimmunization. In the 27 years, 1951--1977, 4315 babies weighing over 1 kg were born alive in Newcastle suffering from haemolytic disease of the newborn due to Rhesus isoimmunization; 197 (4.5 per cent) died within four weeks of delivery. Many babies with severe anaemia (cord Hb less than or equal to 8 g/dl) died of cerebral and/or pulmonary haemorrhage as a result of coagulation failure; others with hydrops had a chance of recovery with intensive care as long as there was no associated pulmonary hypoplasia. Hyaline membrane disease was no more common in babies with haemolytic disease than in other preterm babies of comparable birthweight, but incorrect assessment of gestational age prior to the induction of labour increased the risk of death from hyaline membrane disease. The introduction of closed chest cardiac massage virtually eliminated the risk of sudden unexpected death during exchange transfusion but there was still a 1.5 per cent chance of sudden circulatory collapse during exchange transfusion. Affected babies of less than 36 weeks gestation with respiratory problems face a substantial risk of kernicterus when the indirect serum bilirubin level exceeds 270 mumol/l (15 mg/100 ml). The establishment of a single referral centre for Rhesus isoimmunization reduced neonatal mortality in the area to half the national average in the early 1950's and this superiority was maintained throughout the next decade.


Studies on some possible biochemical treatments of primary hyperoxaluria. The effects of some putative inhibitors of oxalate production or urinary oxalate excretion have been investigated in the Cynamolgus monkey and in patients with Type I primary hyperoxaluria (hyperoxaluria with glycollic aciduria). Sodium-1-hydroxybutan-sulphonate, D,L-phenyllactate, succinimide and isocarboxazide did not reduce the urinary oxalate excretion in the monkeys. Pyridoxine reduced the excretion of oxalate and glycollate in some patients, and its therapeutic use has been documented over a five-year period. Succinimide, which has been used by other workers for the treatment of non-hyperoxaluric stone formers, did not decrease the excretion of either oxalate or glycollate in three patients in whom it was tried. It did not change the inhibitory activity of the urine with respect to the growth and aggregation of calcium oxalate crystals in any of the three patients, and it did not have any consistent effect on the excretion of calcium oxalate crystals in the one patient who had detectable crystaluria before treatment. We have identified several metabolites of succinimide in the urine of patients taking the drug. These include 2,3-dehydrosuccinamic, 2-hydroxysuccinamic and 3-hydroxysuccinamic acids. Isocarboxazide, cholestyramine and thiamine did not affect the urinary oxalate excretion in the patients. The significance of these observations from the viewpoint of the treatment of primary hyperoxaluria is discussed.


The suitability of negative pions for radiotherapy: 4 years preclinical research with the biomedical PiE3-beam at SIN. The radiobiological experiences over 4 years research with the biomedical pion channel of the 590 MeV proton-accelerator of the Swiss Institute for Nuclear Research (SIN) have been summarized. Mainly sensitive biological systems have been chosen (limiting factor: dose-rate not more than 10 rad/min, exceptionally till 30 rad/min). The RBE values in the peak region vary between 0.7-3.3 and in the plateau region between 0.4-1. The gain factors for pion radiotherapy of cancer are, beside the excellent physical dose distribution, irradiation in the same treatment with two types of radiation: sparsely ionizing (low LET) radiation in plateau (healthy tissue) region and densely ionizing (high LET) radiation in peak (tumor) region. The biological effectiveness ratio in peak and plateau as the clinically most important relation vary between 1.4-4.2. This is valid also for clinically limiting factors such as reaction of skin, of small intestine, vascular damage, dominant lethals in hypoxic cells, tumor induction. For peak pions the RBE in hypoxic cells (tumor cells) can be much higher than in euoxic cells (healthy tissue). This preclinical work supports the hope in a highly effective cancer therapy with negative pions.


Pre-clinical studies of the negative pi-meson beam at TRIUMF. The pi- flux from the biomedical channel at TRIUMF increases with increasing channel momentum, while the contaminating electron flux decreases. Since the electrons appear to result from conversion of the high energy gamma-rays produced by pi0 decay in the production target, the electron contamination can be reduced further by target configurations which minimize gamma conversion. The attenuation of pi- beams by in-flight interactions was found to decrease from an initial value of 1.67 +/- 0.02% per g/cm2 at zero depth to 1.48 +/- 0.02% per g/cm2 near the stopping peak. The inactivation of cultured CHO cells by an extended-peak pi- dose distribution has been measured using the gel technique. The survival data have been fitted by a model which characterizes the physical quality of the dose profile by means of measured star densities. This model provides a convenient method of analysis for large sets of survival data and may be useful for prediction of the biological effect of new pi- dose distributions. The RBE value for 50% survival measured at the centre of a 7 cm extended peak was found to be approximately 1.4, in reasonable agreement with recent values obtained at LAMPF and SIN.


Therapy planning and dosimetry for the pion applicator at the Swiss Institute for Nuclear Research (SIN). At the Swiss Institute for Nuclear Research a 60 beam pion applicator for radiotherapy is under construction. The methods to produce homogeneous dose distributions in arbitrarily shaped volumes is presented, together with details on the activities in therapy planning and dosimetry in view of the use of the use of the applicator for patients.


Measurements at the piE3 single beam correlated to dosimetry and therapy-planning for the pion applicator at SIN. Using ionization chambers, aluminium activation, TLD and scintillation counters 3-dimensional total dose-distributions, stardose-distributions and pion stop-distributions have been measured in a single pion beam for various momenta and momentum spreads. It is demonstrated how these data will be used as an input into the therapy-planning program. The techniques developed are suited to check dynamical treatment with 60 pion beams.


Application of the thermoluminescent dosimetry to a pion beam. The thermoluminescent dosimetry is currently applied to radiation therapy in order to measure dose distributions on phantoms or to control the dose in vivo for special procedures or critical organs. The application of this method to the SIN's (Switzerland) pion beam has been studied. Measurements have been made on the following thermoluminescent materials: 7LiF, 6LiF, Li(nat)F, Li2B4O7, CaF2 : Mn, and CaF2 : Dy. Except for the last one a reduction (10%) of the sensitivity of the phosphors has been observed in the peak relative to the plateau region. An increase of the 6LiF sensitivity relative to that of 7LiF has been pointed out due to the neutron background through the (n, alpha) reaction on 6Li. Glow curves of the LiF phosphors have been measured. A reduction (5%) of the intensities of peak 3 and 4 relative to peak 5 has been observed for irradiation in the peak region. This effect however can't be used in order to localize the dosimeter in the beam because the intensity of the thermoluminescence peaks shows a larger variability in a batch of dosimeters.


Visualization of pi- and pi+ stopping density distributions in one and two dimensions. A technique suitable for mapping pi+/- stopping density distributions in patients or phantoms is described. As a position sensitive detector a multiwire proportional chamber with a slit or a hole collimator in front was applied. Results using a water and a Rando phantom are presented for various momenta and momentum band widths of the pi+/- beam. To our knowledge the two-dimensional visualization of a pi- stopping density distribution was realized for the first time.


Energy deposition spectra of negative pions and their application to radiation therapy. Treatment planning for pion radiation therapy must take into account changes in radiation quality within the patient. At the biomedical channel piE3 of SIN (Swiss Institute for Nuclear Research) microdosimetric measurements have been performed to investigate radiation quality within pion irradiated phantoms. Results are presented in terms of microdosimetric spectra and derived quantities. As expected marked differences are observed between dose peak and plateau for "narrow" pion beams. The influence of simulated site diameter on measured spectra has been found to be more pronounced in the plateau region than in the peak. Investigation of the influence of peak width on radiation quality revealed a dilution of the high-LET dose fraction for broader peaks.


Radiobiological data for clinical dosimetry in pion tumour therapy. Ehrlich ascites tumour cells were irradiated with negative pions at different positions in the plateau and the peak of the depth absorbed dose curve. Dose-survival curves for immediate testing of the viability of the cells are given and are compared with other types of radiations in use for therapy. From the data obtained after repair of potentially lethal damage effective survival curves for fractionated irradiation are evaluated.


[Periosteal reactions in bone tumors (author's transl)]. Morphology of solid, lamellar and spicular periosteal reactions of benign and malignant primary and metastatic bone tumors in x-ray-pictures with regard to common and specific characteristics of different bone tumors is presented. The specific behaviour of the periosteum itself and of the subperiosteal region as an expression of the reactive biodynamics in skeletal neoplasia is demonstrated; and the diagnostic value of the radiograph is explained. The possibilities but also the limitations of sophisticated radiologic image analysis in establishing a differential diagnosis and a diagnosis of bone tumors and other bone lesions are discussed.


The value of B-scan ultrasound following intrauterine fetal transfusion. B-scan ultrasound performed in 6 patients for a total of 15 intrauterine fetal transfusions provided quick, easy, and reliable confirmation of the fetal intra-abdominal placement of transfused blood.


Infective endocarditis in the narcotic addict. As long as the illicit use of heroin and other drugs continues in our society, infective endocarditis will remain a significant medical problem in the drug-using population. The majority of infections are produced by S. aureus, and the tricuspid valve is most commonly involved. Addicts, unlike the general population, may also develop endocarditis with a variety of gram-negative bacilli and have a higher incidence of fungal infection. The outcome of each individual infection is dependent on the prompt recognition of the underlying valvular infection and the institution of antimicrobial therapy. Infection of the tricuspid valve has a much more favorable prognosis than does infection of the aortic or mitral valves. Fungal endocarditis, and frequently gram-negative bacillary endocarditis, require valvular surgery to effect a cure.


[Immunodiffusion tests in gel media with the addition of polyethyleneglycol 6000 for the serodiagnosis of mycoses]. Different immunodiffusion techniques with and without the addition of polyetilenglycol 6000 (PEG), were studied to determine its effect on the sensitivity of these reactions. One hundred thirteen sera from patients who suffered or had suffered deep mycoses (paracoccidioidomycosis: 49, histoplasmosis: 25, aspergillosis: 25, candidiasis: 8 and coccidioidomycosis: 6) were examined by the quantitative Ouchterlony's immunodiffusion procedure. Regular medium and media with 2% and 4% PEG were used. Eighty two out of the one hundred thirteen sera were positive for the regular medium and 91 for the medium containing 2% of PEG; furthermore, an increase of 1 or 2 two fold dilutions in the titers was observed in 40% of the sera, for the later media. Twenty one sera from aspergillosis cases were examined by agarose gel immunoelectrophoresis, 80% had more precipitin bands in the medium with 2% of PEG. Thirty four serum samples of patients suffering aspergillosis, paracoccidioidomycosis and histoplasmosis were studied using the agarose electroosmophoresis with the secondary immunodiffusion test. An increase in the number of the anodic bands were observed in 55% while 64% presented more catodic bands, when the PEG medium was used. This results would indicate that the addition of 2% PEG 6000 to the regular medium improves the sensitivity of the immunodiffusion tests for mycoses.


[Isolation of Ancylostoma duodenale antigens and production of immune sera]. Rabbits were immunized using intact larvae or homogenates from Ancylostoma duodenale. Antisera were tested by immunodiffusion. The homogenates promote the formation of antibodies but the intact worms were not able to induce them. The antisera were partially purified by precipitation with amonium sulphate 40% saturation and filtration through Sephadex G-200. The purified material was attached to Sepharose 6B and used as immunoabsorbent for the isolation of the antigens from the soluble extracts of parasites. The isolated antigens were used in order to obtain new antisera. These antisera were used for the preparation of more efficient immunoabsorbent which allow to isolate new antigens that gave three precipitation lines by immunodiffusion. The polyacrylamide gel electrophoresis of crude homogenate discriminate 12 components, and the electrophoresis of the isolated antigens gave only 3 bands.


Comparison of the effects of 11-palmitoyloxy-delta 9-tetrahydrocannabinol with delta 9-tetrahydrocannabinol and 11-hydroxy-delta 9-tetrahydrocannabinol on the hepatic microsomal drug-metabolizing enzyme system. Delta 9-THC and 11-OH-delta 9-THC appear to in vivo affect the metabolism of both Type I and Type II substrates involving cytochrome P-450 as well as to affect the metabolism of a substrate requiring cytochrome P-448. These effects could not be observed significantly in in vitro experiments at the concentrations used. 11-Palmitoyloxy-delta 9-THC does not appear to affect the metabolism of either Type I or Type II substrates but does appear to affect those substrates requiring P-448. From these studies it appears that long-retained delta 9-THC metabolite 11-palmitoyloxy-delta 9-THC, as well as delta 9-THC and 11-OH-delta 9-THC, could alter in vivo the metabolism and activity of certain drugs and other foreign compounds.


[Immunochemical characterization of rabies virus: determination of precipitable antigens]. Immunodiffusion and immuno-electrophoresis techniques were used to detect rabies precipitable antigens. The passive haemagglutination test with group "O" human red cells treated with tannic acid, was used as control test. The study was done with brain suspensions of rabies virus infected mice (CVS strain). Mouse and horse rabies antisera were used. The analysis of the results of both immunochemical assays showed the presence of two specific antigenic fractions of rabies virus. The same two fractions were detected when the antigens were heated. Experiments with brain extracts centrifuged at high speed, suggested that the antigenic fractions are of the "soluble" type.


Biochemical basis of aroclor 1254 and pesticide toxicity in vitro. 1. Effects on intracellular ATP concentration. Aroclor 1254 and op'-DDT inhibit lymphocyte mitogenic response to PHA. We use petri dish purified lymphocytes for studying the biochemical basis of chemical toxicity. Aroclor 1254 and DDT decrease lymphocyte intracellular ATP concentration. The inhibitory effect on ATP production is due to the suppression of mitochondrial respiration as judged by decreased oxygen consumption. Lymphocyte glycolysis measured by lactate production is not inhibited by Aroclor 1254 to any significant extent. ATP is required for various biosynthetic reactions following mitogenic stimulation. The inhibition of mitochondrial respiration which leads to decreased ATP concentration may be responsible for Aroclor inhibition of lymphocyte mitogenic response to PHA.


Histological and immunological studies on the fowl lacrimal gland following surgical excision of Harder's gland. Surgical removal of the Harderian gland of the domestic fowl resulted in increased secretory activity in the lacrimal gland and also in an increase in goblet cell numbers along the length of the lacrimal gland duct. Plasma cells were more numerous in the lacrimal glands of operated birds and they were capable of antibody responses to both systemically and topically applied bovine serum albumin (BSA). Gel diffusion studies showed the presence of anti-BSA activity in the tears and serum of fowls stimulated after surgical removal of the Harderian gland.


[Central von Recklinghausen disease: report of a clinical case with multifocal symptoms and hydrocephalus due to stenosis of the aqueduct (author's transl)]. A case of von Recklinghausen disease is described in a boy aged 9 years, whose major manifestation was a severe progressive hydrocephalus due to aqueductal stenosis. Family history revealed an autosomal dominant mode of inheritance of the neurofibromatosis. Like other reports in the literature, our case suggests secundary aqueductal stenosis to gliosis typical of "central" forms of von Recklinghausen disease. It seems probable that aqueductal stenosis is dependent on periaqueductal gliosis.


[The hypocalcemia test, using human and salmon synthetic calcitonins. Paradoxical hypercalcemic responses. Responses in patients with Paget's disease treated with EHDP]. The hypercalcemia observed during the acute calcitonin test reflects the size and the activity of the osteoclastic population throughout the entire skeleton. Several calcitonins of animal origin (pork, salmon) have already been used for this test in human pathology, but the results can be flawed by the presence of anti-calcitonin antibodies. The authors demonstrate that human synthetic anti-calcitonin in man has a hypocalcemia effect identical to salmon synthetic calcitonin, with an equipotential dose for the rat. The systematic study of acute salmon calcitonin in various osteopathies makes it possible to note a certain number of paradoxical responses with prolonged hypercalcemia in the hours following injection. This is observed especially in the "hyperosteoidosis states" and the authors attempt to give it a physiopathological explanation. Finally, the acute salmon calcitonin test can be used as a mean of surveillance of the anti-osteoclastic activity of the disphosphonates in the treatment of Paget's disease.


Immunochemical determination of serum transferrin. Reference values, correlation with serum total iron-binding capacity and value in the diagnosis of iron deficiency anaemia and anaemia of chronic disorders. Immunologically determined reference values of serum transferrin are presented for adults and children. A good correlation between serum transferrin and total iron-binding capacity values was found. In 2 groups of anaemic patients - 51 patients with iron deficiency anaemia and 45 patients with anaemia of chronic disorders - serum transferrin determination distinguishes the two groups of anaemic patients from normals somewhat better than TIBC determination.


Torulopsis glabrata pneumonia in a malnourished woman. A middle-aged woman developed malabsorption and severe protein-calorie malnutrition after a near-total gastrectomy for a perforated gastric ulcer. A transbronchial lung biopsy showed pulmonary infection with Torulopsis glabrata. Improvement in the patient's nutritional status was followed by clearing of the pneumonia without the need for antifungal chemotherapy.


Deafness and Waldenström's macroglobulinemia. Neurologic abnormalities are known to occur in a significant number of patients with Waldenström's macroglobulinemia. We have described such a patient whose initial presenting symptom was sudden hearing loss. She had no progression of the hearing deficit with long-term anticoagulant therapy.


Childhood convulsions.

Childhood convulsions. An outline is given of the incidence and aetiology of childhood convulsions. Aspects of diagnosis and drug therapy are discussed.


Determination of the caloric requirement of patients with cancer. The weight change of 16 adult patients with cancer receiving total parenteral nutrition for an average period of 12 days was evaluated. The nitrogen to calorie ratio of the hyperalimentation fluid ranged from 1:144 to 1:235. The amount of nonprotein calories delivered was expressed as a multiple of the resting metabolic expenditure, and patients were divided according to the following different rates of calories delivered/resting metabolic expenditure into three groups: group 1, 1.11 to 1.48, mean 1.33; group 2, 1.55 to 1.76, mean 1.67, and group 3, 1.78 to 2.10, mean 1.87. The weight change in group 2 patients, +0.32 kilograms per day, was statistically different from that of group 1 patients, p less than 0.01, but not from that of group 3 patients. We conclude that the optimal hyperalimentation infusion rate to achieve weight gain in patients with cancer includes 50 nonprotein calories per kilogram per day as well as 1.5 grams of amino acids per kilogram per day with a nitrogen to calorie ratio of 1:208.


Successful treatment with cefaclor of gonococcal urethritis in men. Cefaclor, a new orally administered cephalosporin, was evaluated by a randomized trial for effectiveness in the treatment of uncomplicated urethritis due to Neisseria gonorrhoeae in men. Regimens included 2,3, and 4 g of cefaclor, with or without 1 g of orally administered probenecid, as single daily doses for three days. The diagnoses were confirmed by isolation of N. gonorrhoeae; cures or therapeutic failures were determined by follow-up cultures on day 7 after completion of therapy. Sixty-six (73%) of 90 treated patients were evaluable for efficacy. The bacteriologic cure rate was 98% (65/66); one patient treated with 2 g of cefaclor plus probenecid had a positive culture for N. gonorrhoeae on follow-up examination. Adverse reactions consisted of mild nausea in five patients (7%) and vomiting in one patient (1%) who received 3- or 4-g doses. No treatment was discontinued, and no abnormality of screening hematologic tests or enzymes was observed. Thus, cefaclor, given in multiple doses, was highly efficacious for treatment of uncomplicated gonococcal urethritis in men.


Right atrial catheter insertion through the external jugular vein. The external jugular vein may be used to place a right atrial catheter if the cephalic veins are not suitable for cannulation. Atrophy or sclerosis of the cephalic vein is seen in some patients with malnutrition or a malignant lesion. Some women patients also have cephalic veins of rather small caliber. In these patients, the insertion of the right atrial catheter, using the external jugular vein, may be warranted. The external jugular vein approach is recommended because of its easy accessibility and the lower risk involved than with the internal jugular or cephalic vein approach.


Evaluation of five serologic tests for antibody to Neisseria gonorrhoeae. Sera from 1,167 individuals were tested for antibody to Neisseria gonorrhoeae by use of five different serologic tests. These were complement fixation, the indirect fluorescent antibody test, Gonosticon Dri-Dot, fluorescent gonorrhea test-heated, and gonorrhea screen test. Parallel cultures of material from the throat, urethra, cervix, and rectum were also done. The results were analyzed by a technique intended to separate test effects from population effects. Test specificities ranged from 81.3% for the Dri-Dot test to 96.1% for the indirect fluorescent antibody test. Sensitivities ranged from 55.6% for the Dri-Dot test to 81.5% for the fluorescent gonorrhea test-heated.


Granulocyte adherence assay in acute infection as a reflection of the host resistance. The in vitro granulocyte adherence assay was used in six healthy individuals and 14 patients who had acute gram-negative infection to determine whether or not the assay is altered with acute infection and whether or not it adequately reflects the host resistance. The granulocyte adherence values for all patients were significantly lower than those for healthy individuals. In eight patients who recovered, the initial mean value did not differ from that of six patients who died, 7.2 +/- 5.9 and 7.0 +/- 10.9 per cent, respectively, with 50 milligram nylon fiber columns and 53.9 +/- 3.2 and 54.5 +/- 7.2 per cent with 80 milligram nylon fiber columns. However, it was significantly different, p less than 0.001, in both groups of patients from that in the group of healthy individuals, 24.2 +/- 2.5 per cent with 50 milligram columns and 85.7 +/- 4.6 per cent with 80 milligram columns. Subsequently, a significant change in granulocyte adherence, p less than 0.002, occurred in the patients who recovered. Values rose in all of these patients, while they remained low or further declined in those who died. These observations indicate that the in vitro granulocyte adherence capability is reduced in severe acute gram-negative infection and that if reflects the ability of the host to overcome the infection.


Bronchorrhoea--separation of mucus and serum components in sol and gel phases. Bronchorrhoea sputum separates into two phases--sol and gel--at low speed centrifugation (5000 g), although higher speed (160 000 g) is required to obtain complete separation. Markers of mucus glycoprotein and serum transudate have been estimated in sputum, sol, and gel in five cases of bronchorrhoea associated with chronic bronchitis, asthma, or alveolar cell carcinoma. In all samples markers of both mucus glycoprotein and serum component were present in each phase. The concentration of serum markers was similar in both phases suggesting that it is to the serum that mucus glycoprotein is added. Since the volume of sol is greater, the total of serum components is higher in the sol than in the gel although, in total, a considerable amount was present in the gel. The fucose/sulphate ratio suggests that the glycoprotein in the sol is relatively more sulphated than is that of the gel, indicating that they may represent secretion from different cell types. The pattern of separation of two serum markers, IgA and transferrin, is different from that of albumin. Whether this is because they are locally produced or because they are selectively bound to mucus glycoprotein in the gel is not clear.


Platelet aggregation evoked in vitro and in vivo by phosphatidic acids and lysoderivatives: identity with substances in aged serum (DAS). In serum incubated at 36 degrees C for 18-24 hours a factor (DAS) develops which on intravenous injection into cats evokes platelet aggregation followed by an increase in pulmonary vascular resistance (PVR). This change in PVR is mediated via the platelets since it significantly correlates with the preinjection platelet count. There is evidence that phosphatidic acids (PA) and lysophosphatidic acids (LPA) are the active components of DAS. Investigations performed on platelet-rich plasma from man, cat, pig, dog, rabbit, guinea pig, and rat demonstrate that only human and feline platelets exposed to PA or to LPA are aggregated. Feline platelets are more sensitive to either compound than are the platelets from men; however, human platelets exhibit two exceptional properties, a) the sensitivity rapidly declines with time, b) pretreatment with subthreshold concentrations of LPA or PA induces a specific tachyphylaxis.


A simple enzyme-immunoassay (EIA) test for factor VIII-related antigen (VIIIAGN). An enzyme immunoassay (EIA) system has been developed to measure factor VIII-related antigen (VIIIAGN). This assay gives similar results to the commonly used Laurell electroimmunodiffusion (EID) assay for VIIIAGN as shown by comparison of both techniques with samples from healthy controls, patients with hemophilia A, and patients with von Willebrand's disease. The assay also has a greater precision than the EID technique as demonstrated by multiple assays of aliquots of a single sample. The use of this EIA test for VIIIAGN is simple and employs inexpensive reagents and equipment. The use of expensive antisera is minimized. EIA for VIIIAGN has the advantage of increased sensitivity compared to Laurell EIA.


[Ultrahard longitudinal pendulum irradiation of tumors in the region of the visceral cranium (author's transl)]. An analysis of 71 patients with malignant, mostly extended tumors in the region of the visceral cranium is made, and the irradiation technique as well as the results of a longitudinal pendulum irradiation with high-energy ultrahard X-rays are reported. The advantages in comparison with rays of another quality and with other techniques of irradiation consist in a very small radiation exposure of the skin and in a homogeneous distribution of the dose in the target volume as well as a sparing of the contralateral eye. The adjustment is simple and easy to reproduce, the acute side-effects are small and reversible, the cosmetic result is very good.


Effect of phenoxybenzamine on cerebral blood flow and metabolism in the baboon during hemorrhagic shock. Experiments were performed on 2 groups of baboons anesthetized with Sernylan. One group served as control and the other was premedicated with 5 mg/kg phenoxybenzamine (PBZ). A 2-step hypovolemic shock model was used followed by retransfusion of the shed blood. Cerebral blood flow was measured by the 133Xe clearance method. Arterial and cerebral venous samples were taken and analyzed for blood gases as well as glucose and lactate content. The cerebral metabolic rates of oxygen, glucose, and lactate were calculated. In addition, the effect of CO2 inhalation was studied before shock was induced. PBZ produced no effect on either CBF or the flow response to CO2 prior to bleeding. PBZ pretreatment prevented the fall in cerebral blood flow and CMRO2 produced by systemic hypotension due to bleeding. Lactic acid showed no evidence of change either in production or uptake by the brain during the experimental procedure. The cerebral metabolic pathway of glucose, however, seemed to be affected by PBZ both before and during shock.


Deterimental effect of prolonged hypothermia in cats and monkeys with and without regional cerebral ischemia. In a previous study occlusion of a middle cerebral artery (MCA) followed by 48 h of hypothermia (29 degrees) was lethal in 5 of 5 monkeys as compared to only 3 of 9 normothermic animals. The present study extended these observations in monkeys and cats with or without MCA occlusion. In monkeys MCA occlusion plus 48 h of hypothermia was consistently lethal. Without MCA occlusion of 2 of 3 monkeys survived, but were comatose the first 12 h post-hypothermia. In normothermic cats, MCA occlusion was lethal in only one of 5 animals whereas hypothermia was lethal in 20 of 21 cats with or without MCA occlusion. The detrimental effects of hypothermia were not favorably influenced either by hemodilution or by deliberate alterations in PaCO2. The effect of 48 h of hypothermia and rewarming on cerebral blood flow (CBF) and cerebral metabolites was evaluated in 6 normal monkeys. CBF was reduced 60 to 70 percent at 29 degrees C and returned to only a maximum of 50 percent of control with re-warming. Prior to re-warming distribution of CBF was inhomogeneous. Cerebral metabolites were borderline normal prior to re-warming but energy stores decreased while lactate increased with re-warming.


Manufacture of antithymocyte globulin (ATGAM) for clinical trials. Methods are described for preparing large amounts of horse anti-human thymocyte globulin (ATG, ATGAM; The Upjohn Company) for clinical use. These methods have been used since 1968 to provide material for clinical trials. Characteristics of 40 lots of ATG are summarized.


Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys. We measured total and regional cerebral blood flow (CBF, rCBF) and cerebral metabolic rate (CMR) of oxygen (O2), glucose (G), and lactate (L) levels for 4 h after 16 min global brain ischemia in rhesus monkeys with and without post-insult thiopental therapy. Eleven monkeys weighing 4-5 kg anesthetized with 1 percent halothane, 66 percent nitrous oxide and 33 percent oxygen, were subjected to 16 min global brain ischemia by a combination of trimethaphan hypotension (to a mean arterial pressure of 50 torr) and a high pressure (1500 torr) neck tourniquet. Post-ischemia, 7 monkeys were untreated (controls) and 4 received thiopental 90 mg/kg infused intravenously over 60 min, beginning at 5 min post-ischemia. Total CBF and rCBF were measured by continuous monitoring of cerebral venous (torcula) and parietal-occipital (external scintillation) 133Xe activity, respectively, after intra-innominate artery injection of 500 micronCi 133Xe in saline. In control monkeys, hyperemia in rCBF, but not in total CBF was observed at 6-7 min post-ischemia, whereas both total CBF and rCBF increased in thiopental treated monkeys. The hyperemia in thiopental treated monkeys coincided with an increase in CMRG without a proportional increase in CMRO2 or lactate levels. Indeed, CMRO2 was depressed in the first 30 min post-ischemia. At 30 min post-ischemia, CMRO2 rose to twofold greater than pre-ischemia in control monkeys, but only to pre-ischemic levels in thiopental treated monkeys. The data suggest that thiopental therapy improves distribution of brain blood flow and brain glucose uptake early post-ischemia and depresses CMRO2 later post-ischemia.


Cardiac allograft survival in rhesus primates treated with combined total lymphoid irradiation and rabbit antithymocyte globulin. Eighteen abdominal heterotopic cardiac allografts were performed in outbred rhesus primates. For immunosuppression seven animals received six 100-rad/day total lymphoid irradiation (TLI) doses the week preceding transplant and three 3-mg/kg i.m. rabbit antithymocyte globulin (RATG) doses on postoperative days -1, 0, and +1; five animals were given this RATG dose but no irradiation; three were given TLI alone; and three were given no immunosuppressive therapy. Circulating T lymphocyte counts were monitored in all animals (rosettes). Graft survival in the combined TLI-RATG therapy group (169 +/- 15 days) was significantly greater than in untreated (11 +/- 1 days), RATG alone (22 +/- 12 days), or TLI alone (38 +/- 6 days) treated animals (P less than 0.001, 0.0001, and 0.001, respectively). The animals receiving combined TLI-RATG therapy also achieved significantly greater and more prolonged T lymphopenia than that obtained in the other three groups. Six of seven cardiac allografts placed in animals receiving TLI-RATG therapy were removed electively before cessation of electrical activity; however, in four of these rejection pathology was noted. Thus, it seems that combined TLI-RATG therapy may be of benefit in the management of transplant recipients, but its use will probably not abolish these patients' requirements for immunosuppressive maintenance measures.


Augmentation of hemagglutination by low ionic conditions. Short incubation at 37 C, 80 per cent reduction in ionic concentration and removal of liquid phases after each reaction step, provided the basis for the construction of four new serologic tests for alloantibodies to human erythrocytes. In the first, the incubation fluid was replaced with protamine sulfate to aggregate intensely the evaluated red blood cells. After dispersal by phosphate buffer, residual antibody mediated agglutination could be discerned. As a second method, this low ionic polycation (LIP) test was followed by a normal ionic IgG antiglobulin test (LIP-AGT). A third method employed low ionic washing of erythrocytes and low ionic antiglobulin serum (LIAGT). Finally, a modified LIP test was conducted entirely under low ionic conditions and followed by a low ionic antiglobulin test (modified LIP-AGT). LIP, LIP-AGT and LIAGT were successfully employed for all routine blood bank serology tests. Their sensitivity and impact on blood bank performance are described.


A strong antibody reacting with enzyme modified E positive red blood cells. A high titer antibody was discovered in a healthy young man of blood group A1 R2r. The antibody strongly agglutinated all E positive red blood cells including his own, which had been modified by papain, ficin and bromelin, but only very weakly when modified by trypsin. The antibody was shown to be an IgM antibody. It did not react with unmodified red blood cells.


Fatal delayed hemolytic transfusion reaction due to anti-c + E. A 72-year-old man with a peptic ulcer received seven units of apparently compatible red blood cells. Six days after the last unit, he had a hemolytic transfusion reaction manifested by high fever, marked fall in hematocrit, hemoglobinemia, hemoglobinuria, severe bilirubinemia and oliguria. He went on to become uremic, hyperkalemic, anuric and died five days later. Serologic studies showed that the donor and recipient bloods were completely compatible prior to the transfusions and that unexpected antibodies were not detected. The anamnestic response from donor antigens was precipitous even after a latent period of six days.


The production of nymphs of Hyalomma anatolicum anatolicum for experimental infection with Theileria annulata. Methods are described for the production of nymphs of Hyalomma anatolicum anatolicum for later use in transmission experiments with Theileria annulata where the timing of the application of nymphs to infected cattle needs to be accurately controlled. Larvae are fed on the torsos of rabbits where approximately 98% undergo a two-host feeding cycle. This cycle is interrupted 2 days after the first larvae moult into nymphs by killing the rabbits and the nymphs are then collected with a suction pump. Nymphs produced by the interrupted larval feeding method feed well on cattle, in regard to timing of detachment and weight, compared with nymphs produced by interrupted feeding on rabbits.


Renal handling of urate and oxalate: possible implications for urolithiasis. Both urate and oxalate are organic acids of considerable clinical interest, owing to their limited solubility. Calcium oxalate is the most frequent constituent of renal calculi and occasionally precipitates in body fluids. Urate precipitations are common in the kidney and in various other tissues. In this paper, a short outline of the present knowledge of renal handling of these substances will be followed by some conclusions as to the possible relevance of this knowledge for the understanding of urolithiasis and intrarenal precipitation. Direct (micropuncture) data are available for urate in the rat (1, 6, 7, 10, 21, 23, 28, 36, 42), rabbit (35), dog (34) and cebus monkey (33) and in the rat only for oxalate (11, 15, 20).


Intraperitoneal rupture of pseudodiverticulum of bladder. A case is presented of a pseudodiverticulum of the bladder which developed after a bladder rupture nine years previously. In this case, rupture of the pseudodiverticulum occurred intraperitoneally. The pseudodiverticulum communicated with the bladder via a small fish-mouthed opening surrounded by attenuated fibrotic bladder wall.


Surgical management of gastric torsion.

Surgical management of gastric torsion. Considerable investigation has been devoted to the gastric dilatation-torsion complex. An adequate explanation of its cause has yet to be made, or a means of prevention described. We do know of its highly lethal nature, especially if not aggressively treated, of the high incidence of recurrence, and of the associated pathophysiology. As surgeons, we must approach the patient in an aggressive systematic manner. Decompression and patient stabilization must be achieved prior to definitive surgical management. The surgery planned must correct the obvious pathologic state and include procedures designed to prevent recurrence of this condition. The tube gastrostomy technique promotes gastric fixation by dense adhesion bands exceeding that attainable by gastropexy alone. The procedure is easy to perform, requires little surgical time, and does not appear to be discomforting to the patient. In addition, the tube gastrostomy acts as a convenient decompressive pathway during the postoperative period, circumventing gastric intubation or pharyngostomy tube placement should distention occur.


The gangliosidoses: comparative features and research applications. Ganglioside storage diseases are inherited defects of lysosomal hydrolases that result in intralysosomal accumulation of gangliosides and other complex metabolites. Gangliosidoses occur in man, cats, cattle, dogs and swine. In all species, these diseases are characterized clinically by relentlessly progressive neurological deterioration. Lysosomal hypertrophy with characteristic ultrastructural inclusions occur in neurons, endothelial and other cells. Definitive diagnosis requires biochemical identification of the storage product and enzyme deficiency. Gangliosidoses in animals are important models of human lysosomal diseases and may be a significant complication in the maintenance of certain purebred stocks of domestic animals.


Cardiopulmonary resuscitation in a university hospital. An analysis of survival and cost. A cost analysis and study were done of patient survival after inhospital cardiopulmonary resuscitation during one year at a university hospital. The immediate survival rate in 128 patients was 52 percent. Survival to discharge and six-month survival rates were 19 percent and 15.6 percent, respectively. In all, 23 patients (18 percent) had multiple arrests (two to four per patient) during the same hospital stay. Immediate and six-month survival rates in this group were 52 percent (12 patients) and 9 percent (two patients), respectively. Gender or location where cardiopulmonary arrests occurred in the hospital did not influence survival. The cost of a Code Blue (direct expenses only) was $366. We conclude that the outcome following resuscitation at this university hospital compares favorably with the experience of others, and that the direct cost is modest in relation to the results obtained.


[Acute renal failure following general and vascular surgery (author's transl)]. From 1967 to 1976 after 25851 operations for abdominal and vascular diseases acute renal failure was found in 123 cases. In 1353 patients with gastric surgery we observed acute renal failure in 33 (2,5%), after 1499 operations on the gallbladder and bileduct in 12 (0,8%) and after 725 oprations on the colon and rectum in 40 (5,5%) cases. In almost 80% renal failure was caused by septic shock, which is the reason of the high mortality rate of 88% in our patients. It should be emphasized that only prophylaxis and immediate therapy of septic complications can lower the rate of postoperative renal failure and its letal event.


Surveys of simian malaria in Japan.

Surveys of simian malaria in Japan. The survey of simian malaria in Japan which had been conducted since 1965 showed that no Japanese monkeys (Macaca fuscata fuscata and Macaca fuscata yakui) were infected with malaria parasites. Most interestingly, however, Babesia sp. was found in 4 (4.3%) of 93 Macaca fuscata yakui which had been reared in a monkey park. As for the monkeys imported from abroad, Plasmodium was only found in Macaca irus from Southeast Asia, namely, P. inui (14.1-25.0%), P. cynomologi (0.6, 3.2%) and P. coatneyi (4.3%) from various countries. On the other hand, Hepatocystis kochi was found in high proportion in Cercopithecus aethiops from Uganda. Two other blood sporozoa identified as H. semnopitheci and Entopolypoides macai were also seen in Macaca irus imported from Southeast Asia.


The bacillus cereus toxin: isolation of permeability factor. The Bacillus cereus protein has been obtained from culture fluid in homogenic form as indicated by SDS-disc electrophoresis and immunodiffusion not described before. The protein has a molecular weight of 100000 daltons. Purification was accomplished by the following steps: (1) removal of ballast nitrous components with DE-32 cellulose at pH 7.2; (2) removal of the proteins from the culture filtrate (deluted four times by water) with DE-32 cellulose at pH 8.6; (3) elution by 0.005 M tris-HCl buffer at pH 7.0 containing 0.5 M NaCl; (4) column rechromatography on DE-32 cellulose at pH 8.6. The isolated protein was identified as a vascular permeability factor acording to the bluing zone in rabbit skin tests or to the bluing lung tissue in mice.


Light and electron microscopic studies on gamogony and sporogony of 5 sarcocystis species in vivo and in tissue cultures. The gamogony and sporogony of 2 Sarcocystis species was investigated in their natural final hosts and those of 5 species in various cultured cells with identical features concerning timing and ultrasturcture.


A collaborative study on a new quantitative suspension test, the in vitro test, for the evaluation of the bactericidal activity of chemical disinfectants. In a collaborative study on a new quantitative suspension test for the evaluation of the bactericidal activity of chemical disinfectants, three laboratories performed the in vitro test on a phenol and an aldehyde standard in the critical use dilutions using Staphylococcus aureus and Pseudomonas aeruginosa as test organisms. The most striking finding was that the means of the germidical effect of one laboratory were significant lower than those of both others. Nevertheless the dispersion of the results did not differ among the laboratories. The differences could not be attributed to the subculture technique followed, nor to the daily inconstancy of the bacterial suspension resistance. The only feature that could explain the difference was the assessment of the microbiological work in itself. It should be stated, however, that the variance of the germicidal-effect values were rather low for this kind of microbiological work, so that differences between laboratories were significant even if the absolute values differed less than 1 unit.


Efficacy of inactivators against 14 disinfectant substances. More than 24 inactivators were tested for their suitability against 14 disinfectant substances by a quantitative suspension test. Even simple inactivators were found to be efficace: 0.1% cysteine and 0.5% sodium thiosulfate for mercuric chloride and the iodophor; 0.1% sodium sulfite for these two substances and for the QAC in the lower concentration; 1.0% polysorbate 80 for hexylresorcinol, o-phenylphenol and the QAC in the lower concentration; 0.5% sodium thioglycolate for mercuric chloride, the iodophor and chloramine-T. The inactivator active against most disinfectants was the combination LPHT or 0.3% lecithin / 3.0% polysorbate 80 /0.1% histidine / 0.5% sodium thiosulfate. Also active were: LPWT (0.5% lecithin / 1.0% polysorbate 80 /1.0% Lubrol W / 1.0% sodium thiosulfate), LPT (2.0% lecithin / 2.0% polysorbate 80 / 0.5% sodium thiosulfate) and PS (3.0% polysorbate 80 / 3.0% saponin).


[Examinations on the behaviour of grampositive and gramnegative bacteria on aluminium foil (author's transl)]. The survival times of Staph. aureus, Strept. faecalis, E. coli, Klebs. pneumoniae, Ser. marcescens and P. aeruginosa were found out on aluminium foil. It was examined whether there exists a dependence on the initial colony count and in mixed cultures a mutual influence of the several species of bacteria. The longest survival times were found among the grampositive cocci. Ser. marcescens and Klebs. pneumoniae could no more be indicated after 19 days in case of initial colony count of log 7.0/cm2; E. coli could no more be shown after 14 days. P. aeruginosa had the shortest survival time. The dependence on the initial colony count was ascertained in 3 different concentrations of bacteria. The highest concentrations showed the smallest reduction of cocci and the longest survival times of Enterobacteriaceae respectively. The middle and lowest initial colony counts showed quicker reduction or shorter survival times. Ser. marcescens was more resistant to drying than Klebs. pneumoniae. The quickest dying rates showed P. aeruginosa without any dependence on initial colony count. In mixed cultures with Staph. aureus or Strept. faecalis survival times of Enterobacteriaceae were longer; the same result gave Klebs. pneumoniae in culture together with Ser. marcescens. The following explanation might be possible: because of the drying resistance of grampositive cocci the total bacteria number in these mixed cultures after several days is higher than in monocultures of E. coli, Klebs. pneumoniae or Ser. marcescens. This protects the Enterobacteriaceae against external influences for a longer time. Therefore it is understandable that the effect increases with the length of duration. The same interpretation could apply to the mixed cultures of Klebs. pneumoniae/Ser. marcescens.


[Disinfectant testing with Bacillus spores (author's transl)]. This paper deals with special conditions for testing the sporocidal effect of disinfectants. A method for the production of spore suspensions (Fig. 1) and the negative influence of heating to its resistance against disinfectants was described (Fig. 2). It was shown that spores of a non-virulent strain of Bac. anthracis could be used for this procedure (Fig. 3). In performing the suspension--and the germ-carrier test it was necessary to watch the effect of postinhibition and of inactivators. The application of 10 microliter disposible loops in the suspension-test was recommended. Since the test for the evaluation of the influence of organic matter on the results of disinfection was unreliable (Fig. 4), it was proposed to replace it by invention of a safety-factor. The germ-carrier test should be done with constant amounts of spores, dried to the surface under defined conditions. Exposition of germ-carriers to disinfectants should be done in a chamber with constant temperature and rel. humidity, since the results are strongly influenced by these factors (Fig. 5).


[Immunological study of the cellular components of Pseudomonas aeruginosa. VI. The toxicity and protective properties of its mucus and its fractions]. Capsule-like mucus was obtained from two newly isolated mucoid strains of P. aeruginosa and then treated with ethanol. The mucus was fractionated by the method of differential centrifugation (at 15, 000 g for 1 h, at 105, 000 or 170, 000 g for 3 h) and gel chromatography in columns packed with Sepharose 4B. The sediment fractions contained 30--80% of high molecular polysaccharide protein (peptide) mucus components which were toxic for mice and protected 25--77% of rats against experimental P. aeruginosa infection. The supernatant fluid fractions contained 60--80% of predominantly protein components with molecular mass between 20,000 and 60,000 daltons. These mucus components were slightly toxic for mice and rats and protected 80--100% of rats against P. aeruginosa infection.


[Experimental protective of fraction I of the plague microbe]. The immunogenic properties of the freeze-dried preparation of fraction I tisolated from the culture of avirulent Pasteurella pestis strain were studied in experiments on hamadryas baboons, guinea-pigs and white mice. The preparation was found to have a pronounced protective effect in hamadryas baboons and white mice, especially when the preparation was used in mixture with incomplete Freund adjuvant. In hamadryas baboons resistance to infection was shown to correlate with hemagglutionation antibody titres.


[Dynamics of the accumulation of the basic immunoglobulin classes in the intestinal contents in food toxinfections]. The work presents the data on the dynamics of accululation of the main classes of immunoglobulins (A, G and M) in coprofiltrates obtained from patients with alimentary toxicoinfections (bacteriologically confirmed salmonellosis and diseases of unknown etiology). The levels of immunoglobulins of all classes (mainly IgA and IgG) were shown to be elevated in the process of the disease. The dynamics of the increase in the level of IgA (both general and secretory) was supposed to indicate the formation of local immunity in the intestinal wall. The presence of serum IgA and the characteristic IgG dynamics seemed to be indicative of destructive processes occurring in the intestinal wall. Thus, the dynamics of accumulation of immunoglobulins in coprofiltrates obtained from patients with alimentary toxicoinfections reflects the main local pathological and immunological processes.


[Immunological characteristics of the protein antigens of the family Neisseriaceae. II. The importance of an immunochemical analysis of the protein complexes for a study of taxonomy problems]. The study of antigenic interrelations in the family Neisseriaceae resulted in the isolation of 2 main immunologically separated variants of protein complexes: the first variant was characteristic of nonpathogenic and pathogenic species of the genus Neisseria as well as of 7 taxonomically undefined Neisseria species (N. lactamicus, N. cuniculi, N. ellongata, N. ovis, N. animalis, N. cinerea, N. canis) and Gemella haemolysans; the second variant was represented by the genera Branhamella and Acinetobacter. N. caviae and 3 out of 14 Neisseria strains of undefined species had no common antigens with the genera Neisseria and Branhamella. The importance of the immunotyping of protein complexes for studying the problems connected with the taxonomy of the family Neisseriaceae was considered.


[Analysis of the structural features of the sperm chromatin of amphibia]. Deoxyribonucleoproteid (DNP) organisation of the sperm from amphibian species (Rana temporaria, Triturus vulgaris, Bufo bufo) with different sperm chromosomal basic proteins has been analysed by nuclease fragmentation. Electrophoretic distribution of chromatin fragments reveals regular organisation of DNP in the sperm of the species investigated. In spermal DNP of the frog Rana temporaria, 3 sub-fractions of histone H1 were found. In the sperm of the newt Triturus vulgaris and the toad Bufo bufo, abundant arginin-rich histones H3 and H4 as well as the presence of low molecular weight protamine-like proteins were noted. Spermal chromatin of all the species studied exhibits high content of chromosomal RNA which is resistant to the effect of exogenous RNAse.