Tissue-reacting antibodies (EVI antibodies) in nifurtimox-treated patients with Chagas's disease. Antibodies reacting against endothelial cells, vascular structures, and heart and skeletal muscle cells (EVI antibodies) were studied in 10 patients (one to 14 years of age) treated with Nifurtimox. The patients were observed for several months to two years after the onset of symptoms of acute infection with Trypanosoma cruzi. Although these 10 patients were selected because after treatment their sera became negative for antibodies to T. cruzi as detected by the immunofluorescence test, sera from six patients remained positive for EVI antibodies. It is suggested that EVI antibodies may be self-perpetuated in the absence of infection. Further studies are needed to determine the pathogenic significance of EVI antibodies.


Genetic control of cytolytic T-lymphocyte responses. I. Ir gene control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. The ability of cytotoxic T lymphocytes (CTL) induced in vitro to trinitrophenyl (TNP)-modified syngeneic cells to cross-reactively lyse a TNP allogeneic spleen target varies among inbred mouse strains. The cross-reactive CTL phenotype was found to be histocompatibility 2 (H-2) linked and to be dominant in F1 hybrid mice. All strains investigated demonstrated cross-reactivity except for some strains bearing portions of the H-2k haplotype. The gene(s) controlling this response maps to the K and/or I-A region of the H-2 complex. We have termed the immune response (Ir) gene responsible for controlling the specificity of CTL induced to TNP-modified syngeneic cells Ir-X-TNP.


Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. Bone marrow cells from C3H (H-2k) mice, a strain that does not exhibit cross-reactive lysis of trinitrophenyl (TNP)-modified allogeneic targets, were allowed to mature in heavily irradiated (B6 times C3H)F1 (H-2b/k) recipients, an F1 hybrid that does demonstrate cross-reactive lysis. Spleen cells from these chimeric mice were removed after 3-4 mo and by H-2 typing shown to be of C3H origin. These cells were found to be tolerant to B6 alloantigens by mixed lymphocyte reaction and cell-mediated cytotoxicity and, when stimulated in vitro with TNP-modified syngeneic cells, now cross-reactively lysed TNP-modified allogeneic targets. These studies demonstrate that the host environment where T cells differentiate influences the specificity of the primary cytolytic T-lymphocyte (CTL) response to TNP-modified syngeneic antigens.


Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype. Secondary effector T-cell populations generated by cross-priming with heterologous influenza A viruses operate only in H-2K or H-2D compatible situations, when assayed on SV40-transformed target cells infected with a range of influenza A viruses. The H2-Kb allele is associated with a total failure in the generation of influenza-immune cytotoxic T cells, though this is not seen for the primary response to vaccinia virus. In both influenza and vaccinia development of effector T cells operating at H-2Db is greatly depressed in B10.A(2R) (kkkddb) and B10.A(4R) (kkbbbb), but not in B10 (bbbbbb), mice. However, there is no defect in viral antigen expression at either H-2Kk or H-2Db in B10.A(2R) target cells. This apparently reflects some inadequacy in the stimulator environment, as (A/J X B6) F1 T cells can be induced to respond at H-2Db when exposed to vaccinia virus in an irradiated B6 but not in a B10.A(4R) recipient. The present report, together with the accompanying paper by Zinkernagel and colleagues, records the first rigorous demonstration of both a nonresponder situation and a probable Ir-gene effect for conventional infectious viruses. Possible implications for the evolution of H-2 polymorphism and mechanisms of Ir gene function are discussed.


In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells. The H-2 haplotype of the chimeric host determines the responder phenotype of maturing T cells. Spleen cells of chimeric mice formed when (K(k) nonresponder to D(b) x K(b) responder to D(b) plus vaccinia)F(1) bone marrow cells were used to reconstitute K(b)D(b) (C57BL/6 D(b) responder) irradiated recipients generated high levels of D(b) plus vaccinia virus-specific cytotoxic T cells. The same stem cells used to reconstitute K(k)D(b) (B10.A (2R) D(b) nonresponder) irradiated recipients resulted in spleen cells that responded well to K plus vaccinia, but responsiveness to D(b) was low. A generally low response to D(k) plus vaccinia, which seems to be regulated by D(k), was confirmed in chimeras. Thus, K(d)D(d) (D(d) plus vaccinia responder) stem cells differentiating in a K(d)D(k) chimeric host failed to generate a measurable response to D(k) plus vaccinia. In contrast, stem cells from K(d)D(k) (D(k) plus vaccinia low responders) differentiating in a K(d)D(d) (K(d) and D(d) high responders to vaccinia) host do generate responsiveness to D(d) plus vaccinia. These results indicate that in chimeras, the Ir phenotype is independent of the donor T cell's Ir genotype, and that thymic selection of a T cell's restriction specificity for a particular H-2 allele of the chimeric host also defines that T cell's/r phenotype.


Alternative pathways of T lymphocyte activation. Data presented in this paper suggest that there may be two alternative pathways which T lymphocytes can use in generating a cytotoxic response to alloantigens in vitro. First, there is the pathway taken when stimulator and responder cells differ by an entire H-2 complex where Ly1+2- helper T lymphocytes respond to I region encoded lymphocyte defined differences and provide help to the Ly1-2+ cytotoxic T lymphocytes responsive primarily to K/D region encoded cytotoxicity defined determinants. Second, there is the pathway taken when stimulator and responder cells differ by only K or D region differences without an I region encoded difference; under these conditions, an Ly1+2+ cell, which does not appear to play a significant role in the development of a cytotoxic response to an entire H-2 difference, appears to play a pivotal role.


Two-gene control of the expression of a murine Ia antigen. Two dimensional polyacrylamide  gel electrophoresis of Non-Idet P-40 extracts and of specific Ia immunoprecipitates from [35S]methionine-labeled mouse spleen lymphocytes has revealed that the cell surface expression of some Ia antigens appears to be controlled by two genes. One locus, which maps in the I-A subregion, is probably the structural gene for an Ia polypeptide chain. The second locus, which maps between the I-J and H-2D regions, controls whether this I-A encoded molecule (Ae) remains in the cytoplasm or is modified and expressed on the cell surface. Complementation between these two loci allowing surface expression of Ae can occur in the cis or trans chromosomal position. Both the I-A molecule and a polypeptide chain coded for by a locus in I-E are coprecipitated by anti-I-E antibodies, suggesting that these two chains are associated with each other as a multisubunit complex in the cell. Because the ability to complement I-A for Ae expression is a property only of those strains which synthesize an I-E-encoded protein, it is likely that the I-E product itself is regulating the expression of Ae. These observations suggest several mechanisms by which interaction between two I region loci can generate new cell surface molecules. As a result, they may have important implications for understanding the molecular basis of two gene control of immune responsiveness and immune suppression.


In vitro sensitization of thymocytes. Role of H-21 I region determinants and cell-free mixed leukocyte culture supernates in generation of cytotoxic responses. Stimulation of thymocytes in vitro by spleen cells differing for the entire H-2 complex leads to a significant proliferative response without a significant cell-mediated lympholysis (CML) response. Addition of soluble cell-free supernates (SF), (taken from a 7-day mixed leukocyte culture) enables these cultures to develop CML response. For optimal CML response, the SF has to be added within 48 h of onset of cultures. Although with spleen cells as responding cells, SF could quantitatively replace I-region different stimulating cells for generation of CML responses, with thymocytes as responding cells, stimulation with I-region cells appeared obligatory for the generation of CML responses. The implications of these findings are discussed.


Induction of human immunoglobulin synthesis and secretion in somatic cell hybrids of mouse myeloma and human B lymphocytes from patients with agammaglobulinemia. Somatic cell hybrid clones were isolated from the fusion of RPC 5,4 mouse myeloma cells and B lymphocytes from three patients with agammaglobulinemia. One patient had X-linked agammaglobulinemia; the remaining two patients had common varied agammaglobulinemia. All three patients had B lymphocytes which fail to secrete immunoglobulin. The hybrid nature of the clones was established by examination of metaphase chromosome spreads. Most of the clones from all three patients expressed surface immunoglobulin of mouse and human parental origin. Clones from two of the patients had fewer cells with surface Ig than hybrids from normal persons, while clones from the third patient had large numbers of surface Ig fluorescent cells. Most of the clones from all three patients synthesized and secreted human and mouse immunoglobulin. As determined by sodium dodecyl sulfate acrylamide gel electrophoresis of radioactively labeled proteins, clones from each of the patients produced human gamma, alpha, and mu-heavy chains. These studies demonstrate the presence of functional structural genes coding for human immunoglobulin heavy chains in B lymphocytes of patients with agammaglobulinemia. Further, they represent induction in the somatic cell hybrids of a gene product not expressed in the parental B lymphocytes.


Differences in the time course of regional cerebral hemo-dynamics of gray and white matter during experimental hypertension. Investigations concerned with the pathogenesis of hypertensive encephalopathy have reported two opposing changes in cerebral hemodynamics during induced hypertension: (1) vasospasm or vasoconstriction of the leptomeningeal arteries and (2) increase of cerebral blood flow which has been termed "breakthrough" of the cerebral autoregulation. To resolve this apparent conflict, continuous measurements of focal cerebral flow and oxygen availability were made in 17 baboons by the use of implanted platinum electrodes placed in both gray and white matter during induced hypertension. Autoregulation was initially well maintained in gray matter followed by "breakthrough" but the autoregulatory response was poorly maintained in the cerebral white matter. The vasoconstriction of the leptomeningeal arteries reported in earlier investigations from observations made through a skull window appears to be due to a marked autoregulatory response to hypertension rather than vasospasm. The autoregulatory response appears to be efficient in gray matter but relatively deficient in white matter.


Teichoic acid serology in staphylococcal infections of infants and children. Counterimmunoelectrophoresis and gel diffusion were utilized for the detection and titration of antibodies to staphylococcal teichoic acids in various disease states caused by coagulase-positive staphylococcus in infants and children. Serum samples were obtained on admission and serially for 2 to 12 weeks during illness. Teichoic acid antibodies were found by CIE in 12 of 21 patients (57%) with invasive CPS disease with bacteremia (Group A), in two of 17 patients (12%) with CPS infection without bacteremia (Group B), in none of 27 patients with bacteremia and/or invasive infections caused by organisms other than CPS (Group C), and in none of 24 noninfected, hospitalized patients or healthy children (Group D). Gel diffusion was useful for titrating antibodies in seropositive sera. Teichoic acid serology is a useful adjunct in the diagnosis of invasive CPS infections. The presence of these antibodies by CIE and gel diffusion may help to identify patients with endothelial or metastatic infections associated with staphylococcal bacteremia.


Biliary excretion of diethylstilbestrol in the rhesus monkey. The biliary excretion of diethylstilbestrol in the bile fistula rhesus monkey was investigated during exogenous taurocholate- and taurodehydrocholate-induced choleresis. Following intravenous administration, 36% of the dose was excreted into the bile (as diethylstilbestrol monoglucuronide) and 53% in the urine (as diethylstilbestrol monoglucuronide plus more polar unidentified metabolites). During the steady-state infusion of diethylstilbestrol, with taurocholate-induced choleresis, a bile flow dependent transport for the biliary excretion of diethylstilbestrol monoglucuronide was observed. Evidence for carrier-mediated transport of this metabolite was a bile-to-blood concentration ratio which ranged from 228 to 279 during steady-state experiments. In vitro experiments indicated that diethylstilbestrol monoglucuronide forms an association with taurocholate, as well as the micellar structures of bile, resulting in a severalfold enhancement of solubility above that in aqueous buffer alone. Taurodehydrocholate, a non-micelle-forming bile salt, did not interact with this metabolite and had no effect on its solubility. Substitution of taurodehydrocholate for taurocholate during the steady-state infusion of diethylstilbestrol produced no significant changes in the transport of diethylstilbestrol monoglucuronide from blood to bile.


Nitroglycerin stability in polyethylene glycol 400 and povidone solutions. The stability of solutions of nitroglycerin in several common pharmaceutical solvents and compounds used as tablet excipients was investigated using a UV spectrophoto metric assay. Included in the study were povidone (I), polyethylene glycol 400 (II), and solvents such as absolute alcohol, propylene glycol, and glycerol. At the elevatted temperatures of the accelerated stability studies, only II demonstrated a considerable adverse effect on the stability of the nitroglycerin solution. It is postulated that a "reaction compound" was formed between nitroglycerin and II which regenerated nitroglycerin depending on hydrolysis conditions. Based on the Arrhenius equation and with initial rates of up to 6 hr of degradation, the predicted stability for a II solution of nitroglycerin in terms of its 10% decomposition at 25 degrees was approximately 7 days.


Interaction of cromolyn sodium in aqueous solution with magnesium ions. The interaction of the antiasthmatic drug cromolyn sodium with Mg2+ ions in solution was studied. Selective ion electrode and torsion viscometer measurements were used to establish the degree of interaction. At the concentrations studied, the cromolyn ion had no more affinity for Mg2+ than SO42-. However, thixotropic gels were formed between 4 X 10(-2) M cromolyn sodium and 4 X 10(-4) Mg2+. At lower concentrations of Mg2+, viscosity still increased significantly. However, when the cromolyn concentration was lowered, the increase in viscosity was much less marked.


Radioimmunoassay for danazol in human and monkey plasma. A sensitive method is described for the radioimmunoassay of danazol in monkey and human plasma. Antiserum was developed in rabbits, and a second antibody was used to separate bound from free danazol. The radioimmunoassay was specific for danazol, and the limit of detection ranged from 1.4 to 2.8 ng/ml. Exogeneous danazol could be quantitated accurately in both monkey and human plasma. The radioimmunoassay results agreed with values obtained by inverse isotope dilution after intravenous administration of 14C-danazol to monkeys. The assay was used successfully to measure danazol in plasma from human volunteers receiving 200 mg of danazol.


Identification of endogenous gamma-hydroxybutyrate in human and bovine brain and its regional distribution in human, guinea pig and rhesus monkey brain. Gamma-Hydroxybutyric acid (GHB), a compound that has interesting neuropharmacological actions when administered systemically, was shown by means of gas chromatography-mass spectrometry to be present in postmortem samples of human brain in concentrations ranging from 2 to 20 nmol/g. Tissue samples from the basal ganglia contained 2 to 3 times as much GHB as tissue samples from cortical regions. The regional brain distribution of GHB was examined in the guinea pig and rhesus monkey and found to parallel the distribution observed in human brain. The levels of GHB found in the regional areas of human and monkey brain investigated were higher than the levels found in similar regions of guinea-pig brain. Additional studies demonstrated that there is a slow postmortem increase (about 2-fold) in the endogenous levels of GHB in bovine caudate and guinea-pig brain which is maximal about 6 hr postmortem. This postmortem increase could in part explain the higher levels of GHB found in human brain. However, postmortem changes could not account for the large differences observed in the levels of GHB found in bovine caudate and those found in guinea-pig, monkey and human caudate. Only traces of GHB could be detected in human blood and cerebrospinal fluid.


Changes in the effects of d-amphetamine on escape responding by its prior effects on punished responding. Responses of squirrel monkeys adjusted the intensity of a continuous electric shock under two different schedules. In one schedule, responses decreased a shock intensity which otherwise was increased at a fixed rate (escape). In the other schedule, responses produced food pellets but also increased a shock intensity which otherwise decreased at a fixed rate (punishment). When animals were first studied under the escape schedule, d-amphetamine increased responding. Similarly, when animals had an intervening experience under the punishment schedule with no drugs administered, or when the drug was given but shock increments were tempoerarily eliminated during those drug sessions, d-amphetamine still increased subsequent escape responding. However, when animals under the punishment schedule were given d-amphetamine and shock increments occurred as usual during the drug session, the drug no longer increased either punished or subsequent escape responding. The effects of d-amphetamine on escape responding were completely different depending on the individual's prior drug experience.


Viscoelastic properties of the periodontal ligament and mucous membrane. Load deformation studies were carried out on the maxillary arches of three adult Macaca irus monkeys using tooth-borne and tissue-borne plates. By means of an electronically controlled dynamometer, forces with different loading rates, creep, and simulated chewing loads were applied to the plates. The displacement was measured electronically relative to posterior teeth using a linear variable displacement transducer. The six main viscoelastic features noted by other workers for individual teeth under load have been confirmed for the test plates and can be attributed to the connective tissues in the periodontium and in the mucosa. The magnitude of displacement of the tissue-borne plate, however, was appreciably greater than for the tooth-borne plate, and the recovery was far slower. Reducing the part of the plate in contact with mucosa produced greater intrusion, and reducing the number of teeth supporting the tooth-borne plate produced greater displacement.


Does acetylcholine change the electrical resistance of the basal membrane of secretory cells in eccrine sweat glands? The present experiment was intended to study whether or not acetylcholine decreases the electrical resistance of the basal membrane of secretory cells in stimulating eccrine secretion of fluid and electrolytes. An isolated segment of the secretory coil of the monkey palm eccrine sweat gland was dissected out in vitro and immobilized in the tip of a constriction pipette. Using a bridge-balanced single glass microelectrode, input impedance of the secretory cell was compared before and after local superfusion of acetylcholine in each cell. The mean input impedance was 27 Momega, which did not significantly change after application of acetylcholine. Between 15 and 30 sec after cessation of acetylcholine superfusion, input impedance increased by 42% and then returned to normal within 60 sec. The current-induced voltage deflection due to intraluminally injected current pulse was measured across both the basal membrane (deltaVb) and the epithelial wall (deltaVt) as qualitative measures of the respective membrane resistances. Both deltaVb and deltaVt increased by about 10%, but their ratio remained unchanged after stimulation with acetylcholine. A Ca++ ionophore, A23187, which is as potent a stimulant of eccrine sweat secretion as acetylcholine in vitro, also failed to change the above two parameters. It was concluded that the decrease in the electrical resistance of the basal membrane of the secretory cells could not be detected in the sweat gland after stimulation with acetylcholine or A23187. The possibility was discussed that the action of acetylcholine at the basal membrane is one of enhancing the activity of the nonconductive pathway rather than the conductive pathway in this exocrine gland.


DNA repair synthesis in rat retinal ganglion cells treated with chemical carcinogens or ultraviolet light in vitro, with special reference to aging and repair level. A system in which the retinal tissues of noninbred Wistar rats were used in combination with autoradiography was developed for measurement of DNA repair synthesis in ganglion cells of the central nervous system. Retinal tissues in short-term organ culture were treated with various carcinogens plus tritiated thymidine ([methyl-3H]dThd) or were irradiated with UV light and then treated with [methyl-3H]dThd. Preliminary study with retinal tissues from rats at various ages revealed no age-associated changes in the levels of unscheduled DNA synthesis in ganglion cells.


Comparison of the effects of beeswax: trioctanoin and trioctanoin vehicles on 3-methylcholanthrene, benzo[a]pyrene, and 7,12-dimethylbenz[a]anthracene subcutaneous carcinogenesis in three strains of mice and one hybrid. Subcutaneous tumor induction with three dose levels of 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), and 7,12-dimethylbenz[a]anthracene (DMBA) in two vehicles was studied in C3H/Anf Cum, C57BL/6 Cum, DBA/2J, and (C57BLXC3H/Anf)F1 (BC3F1/Cum) mice. Median tumor dose levels were significantly lower when the three carcinogens were suspended in trioctanoin. When beeswax: trioctanoin (B:T) was used as a vehicle, the three carcinogens differed in their abilities to be absorbed or solubilized from the vehicle by the three strains of mice and the hybrid. In C3H/Anf mice, BP in B:T failed to produce tumors. In BC3F1 mice, no tumors were produced by MCA, BP, or DMBA in B:T. In C57BL/6 mice, no tumors were produced with DMBA or MCA in B:T. In DBA/2 mice, no tumors were produced by BP or MCA in B:T. These results indicated that the interpretation of tumor induction results obtained with B:T vehicle may be related to the conditions of bioassay rather than to the carcinogenic potential of a compound.


Mechanism of genetic resistance to Friend virus leukemia in mice. V. Relevance of Fv-3 gene in the regulation of in vivo immunosuppression. Infection with the Friend murine leukemia virus complex (F-MuLV) suppressed humoral antibody synthesis in vivo and lymphocyte mitogenesis in vitro. Both these effects of F-MuLV were under host genetic control. In vitro suppression of lymphocyte mitogenesis was regulated by a single autosomal gene called Fv-3 that is dominant for susceptibility. Genetic analyses, with the use of the susceptible DBA/2 and resistant B10.D2/n parents, their F1, intercross, and backcross progeny, indicated that a single autosomal gene dominant for susceptibility regulated the in vivo susceptibility to immunosuppression by F-MuLV. Individual [(DBA/2xB10.D2)F1xB10.D2] mice were typed both for susceptibility to F-MuLV-induced suppression of lymphocyte mitogenesis in vitro (an Fv-3 function) and susceptibility to immunosuppression by F-MuLV in vivo. Such an analysis indicated that the same mice that were susceptible or resistant to immunosuppression in vivo were susceptible or resistant to suppression of lymphocyte mitogenesis in vitro. Spearman's rank analysis of the data also indicated that the in vivo and in vitro immunosuppressive effects of F-MuLV were correlated with and not independent of each other. Thus Fv-3, which regulates the effect of F-MuLV on lymphocytes in vitro, also appears to regulate the effect of F-MuLV on antibody-forming cells in vivo.


Effect of chemical carcinogen treatment on the immunogenicity of mouse mammary tumors arising from hyperplastic alveolar nodule outgrowth lines. The experiments reported herein examined the effects of chemical carcinogen treatment of precursor hyperplastic alveolar nodules on the immunogenicity of subsequent mammary tumors in mice. The results of in vitro immunogenicity assays were compared with those of in vivo transplantation resistance tests. This comparison demonstrated that the in vitro assays predicted qualitatively and quantitatively the results from the in vivo test. In addition, the data suggested that the immunogenicity of a tumor depends on events occurring during the development of precursor hyperplastic alveolar nodules rather than during the development of subsequent mammary tumors.


Bacteriophage SPO1 development: defects in a gene 31 mutant. SPO1 temperature-sensitive mutant ts14-1, located in cistron 31, has a DD (DNA synthesis-delayed) phenotype at 37 degrees C and produces progeny in a stretched program. At 44 degrees C it behaves as a DO (DNA synthesis-defective) mutant and shuts off the viral RNA synthesis about 10 min after infection. The thermal sensitivity of this mutant is due to the inactivity of gp-31 (the product of gene 31) at 44 degrees C. However, gp-31 is synthesized at that temperature and partly recovers its activity at 37 degrees C. Only 5 min at the permissive temperature is enough to trigger the continuation of the phage program and to produce progeny. The partial defect at 37 degrees C and the expansion of the middle program together with the pleiotropic defects at the nonpermissive temperature could be suitable for the study of the controls involved in bacteriophage development.


Bacillus subtilis bacteriophages SP82, SPO1, and phie: a comparison of DNAs and of peptides synthesized during infection. The genomes of Bacillus subtilis phages phie, SPO1, and SP82 were compared by DNA-DNA hybridization, analysis of DNA fragments produced by digestion with restriction endonucleases, comparison of the arrays of peptides synthesized during infection, and phage neutralization. DNA-DNA hybridization experiments indicated that about 78% of the SP82 DNA was homologous with SPO1 DNA, whereas 40% of the phie DNA was homologous to either SPO1 or SP82 DNA. Agarose gel electrophoresis was used to compare the molecular weights of DNA fragments produced by cleavage of SP82, SPO1, and phie DNAs with the restriction endonucleases Hae III, Sal I, Hpa II, and Hha I. Digestion of the DNAs with Hae III and Sal I produced only a few fragments, whereas digestion with Hpa II and Hha I yielded 29 to 40 fragments, depending on the DNA and the enzyme. Comparing the Hpa II fragments, 51% of the SP82 fragments had mobilities which matched those of SPO1 fragments, 32% of the SP82 fragments matched the phie fragments, and 34% of the SPO1 fragments matched the phie fragments. Comparing the Hha I digestion products, 62% of the SP82 fragments had mobilities matching the SPO1 fragments, 24% of the SP82 fragments matched the phie fragments, and 22% of the SPO1 fragments matched the phie fragments. Analysis of peptides by electrophoresis on one-dimensional sodium dodecyl sulfate-polyacrylamide slab gels showed that approximately 70 phage-specific peptides were synthesized in the first 24 min of each infection. With mobility and the intervals of synthesis as criteria, 66% of the different SP82 peptides matched the SPO1 peptides, 34% of the SP82 peptides matched the phie peptides, and 37% of the SPO1 peptides matched the phie peptides. Phage neutralization assays using antiserum to SP82 yielded K values of 510 for SP82, 240 for SPO1, and 120 for phie.


Genome-linked protein associated with the 5' termini of bacteriophage phi29 DNA. A DNA-protein complex was isolated from Bacillus subtilis bacteriophage phi29 by sucrose gradient sedimentation or gel filtration in the presence of agents known to break noncovalent bonds. A 28,000-dalton protein was released from this complex by subsequent hydrolysis of the DNA. The DNA-protein complex was examined for its susceptibility to enzymes which act upon the 5' and 3' termini of DNA molecules. It was susceptible to exonucleolytic degradation from the 3' termini by exonuclease III but not from the 5' termini by lambda exonuclease. Attempts to label radioactively the 5' termini by phosphorylation with T4 polynucleotide kinase were unsuccessful despite prior treatment with alkaline phosphatase or phosphatase treatment of denatured DNA. Removal of the majority of the bound protein by proteolytic digestion did not increase susceptibility. These results suggest that the linked protein is covalently attached to the 5' termini of phi29 DNA.


Evidence that the neck appendages are adsorption organelles in Bacillus subtilis bacteriophage phi29. A mutant of Bacillus subtilis unable to adsorb phage phi29 efficiently has been isolated. This mutant can be infected by host range mutants of the phage. Since the host range mutations map in cistron 12, which codes for neck appendage protein, this would tend to confirm that these organelles are involved in viral adsorption.


Control of corynebacteriophage reproduction by heteroimmune repression. Corynebacteriophages beta and gamma are closely related but heteroimmune; hence, gamma reproduces in C7(beta). A series of gamma mutants, designated gamma-bin (beta-inhibited), has been isolated. They reproduce in only 2 to 14% of infected C7(beta) cells, and, as a result, plaque with an efficiency of 10(-4) to 10(-5) on this strain. The proportion of C7(beta) cells in which gamma-bin phage can replicate is increased to 30 to 80% when immunity is lifted by UV induction of C7(beta) or by heat induction of C7(beta-tsr3). The gamma-bin mutants carry out a normal vegetative or lysogenic cycle in strain C7 and thus do not appear to be defective in any essential phage function. Infection of C7(beta) by gamma-bin results in cell killing whether the infection is productive or nonproductive. The data support the hypothesis that inhibition of gamma-bin is due to the direct or indirect action of a beta prophage gene. The simplest hypothesis is that gamma-bin phages have sustained mutations in an operator site and that beta repressor now combines with the mutated operator to inhibit normal replication in a significant proportion of infected cells.


Evidence for an adenovirus type 2-coded early glycoprotein. We have identified an adenovirus type 2 (Ad2)-induced early glycopolypeptide with an apparent molecular weight of 20,000 to 21,000 (20/21K), as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 20/21K polypeptide could be labeled in vivo with [(3)H]glucosamine. [(35)S]methionine- and [(3)H]-glucosamine-labeled 20/21K polypeptides bound to concanavalin A-Sepharose columns and were eluted with 0.2 M methyl-alpha-d-mannoside. The pulse-labeled polypeptide appeared as a sharp band with an apparent molecular weight of 21K, but after a chase it converted to multiple bands with an average molecular weight of 20K. This variability in electrophoretic mobility is consistent with glycosylation or deglycosylation of the 20/21K polypeptide. Analysis of the pulse and pulse-chase-labeled forms by using partial proteolysis indicated that the polypeptides were highly related chemically, but not identical. Most of the 20/21K polypeptide is localized in the cytoplasm fraction of infected cells lysed by Nonidet P-40. The 20/21K polypeptide and a 44K polypeptide, labeled with [(35)S]methionine or [(3)H]glucosamine in Ad2-infected human cells, were precipitated by a rat antiserum against an Ad2-transformed rat cell line (T2C4), but not by antisera against three other Ad2-transformed rat cell lines, or by serum from nonimmune rats. The partial proteolysis patterns of the 20/21K and the 44K polypeptides were indistinguishable, indicating that the two polypeptides are highly related, and suggesting that the 44K polypeptide might be a dimer of the 20/21K polypeptide. The 20/21K polypeptide was also induced in Ad2-early infected monkey and hamster cells. These results imply that the 20/21K polypeptide is synthesized in Ad2-infected human, monkey, and hamster cells, and in one but not all Ad2-transformed rat cells. Thus, the 20/21K polypeptide is probably viral coded rather than cell coded and viral induced.


Correlated genetic and EcoRI cleavage map of Bacillus subtilis bacteriophage phi105 DNA. The seven previously identified EcoRI cleavage fragments of phi 105 DNA were ordered with respect to their sites of origin on the phage genome by marker rescue. One fragment, H, did not carry any determinants essential for replication. This fragment was totally missing in a deletion mutant which exhibited a lysogenization-defective phenotype. There is a nonessential region on the phi 105 genome which begins in fragment B, spans fragment H, and ends in fragment F. The size of the nonessential region, as estimated by alterations observed in the fragmentation patterns of deletion mutant DNAs, is approximately 2.7 X 10(6) daltons. Two new EcoRI cleavage fragments with molecular weights of approximately 0.2 X 10(6) were detected by autoradiography of 32P-labeled DNA. These small fragments were not located on the cleavage map.


Restriction endonuclease mapping of bacteriophage phi105 and closely related temperate Bacillus subtilis bacteriophages rho10 and rho14. Cleavage maps of the three similar Bacillus subtilis temperate bacteriophages, phi105, rho10, and rho14, were constructed by partial digestion analysis utilizing the restriction endonuclease EcoRI. Comparison of the topography of these maps indicates that all phage DNAs posses cohesive ends and a number of EcoRI restriction sites; the fragments are conserved, and the estimated base substitution/nucleotide divergence between these phages is 0.03 to 0.07 based on conserved fragments or between 0.03 and 0.11 based on conserved cleavage sites. These lines of evidence indicate that phi105, rho10, and rho14 are closely related. Double-enzyme digestion analysis reveals that rho14 DNA has unique SalGI and BglII restriction sites and phi105 DNA has a unique SalGI restriction site, making these phages possible cloning vectors for B. subtilis.


Restriction fragment analysis of bacteriophage SPP1 in vitro transcription by host RNA polymerase. In vitro transcription of SPP1 DNA occurred on only one of the two strands, the same which is predominantly transcribed in SPP1-infected cells. Transcripts were distributed in several size classes. Analysis of elongation kinetics and of size distribution, coupled with hybridization to DNA restriction fragments, showed that some regions of the template have more initiation sites than others; some have none. Some regions were transcribed directly, some were transcribed from initiation sites located in other regions, and one was never transcribed. Several transcription initiation sites on SPP1 DNA are located on EcoRI fragment 1; four to five others are distributed among other fragments. Cutting the DNA with EcoRI did not introduce artifactual initiation sites. In vitro transcription units can be localized and oriented with respect to the EcoRI restriction map of SPP1 DNA.


Intravesical thio-tepa in the immediate postoperative period in patients with recurrent transitional cell carcinoma of the bladder. Recurrent transitional cell carcinoma was treated with prophylactic intravesical thio-tepa in 22 cases. Group 1 patients were treated with 30 mg. twice daily for the first 3 days postoperatively. Group 2 patients were given additional treatment at increasing intervals indefinitely. Before therapy control patients averaged 1 recurrence every 9.5 months. Group 1 patients averaged 1 recurrence per 33 mpnths. Group 2 patients averaged 1 recurrence per 41 months. Leukopenia occurred in only 2 patients. Thio-tepa can be given safely in the immediate postoperative period and is effective in decreasing the recurrence rate of superficial bladder tumors.


The controversy of single versus multistaged urethroplasty. Experience with various 1 stage repairs for urethral strictures (patch graft, and excision and reanastomosis techniques) gained by ourselves and others is compared to reports on multistaged urethroplasties (Johanson, Leadbetter-Johanson and Turner-Warwick). Increased hospitalization, absence from employment and the morbidity of multiple anesthetics and operations are features of the multistaged approaches compared to the 1 stage operations. Furthermore, no advantage was seen when initial or final success rates were compared.


Un-cross-matched blood for emergency transfusion. One year's experience in a civilian setting. One year's experience (56 cases) in the use of un-cross-matched blood for emergency transfusion in a large civilian teaching hospital showed that 49 transfusions were given as un-cross-matched, group-specific (ABO and Rh) blood in emergencies. Seventy-seven percent (43) of blood requests were for patients with trauma, unexpected massive intraoperative hemorrhage, or ruptured aneurysm. The indications for emergency transfusion were questionable in ten cases. There were no adverse effects noted even though complete serologic testing had not been done. While the use of un-cross-matched blood is usually safe, the potential for serious reaction exists. Overuse should be discouraged.


Gray-scale ultrasonic cholecystography. A primary screeing procedure. The accuracy of ultrasonic cholecystography is well established. However, oral cholecystography remains the primary screening examination. Ultrasonic and oral cholecystograms were performed in 100 consecutive patients to determine if ultrasound could be used as a primary screening procedure, particularly in patients with acute right-upper-quadrant pain, suggestive of acute cholecystitis. Ultrasound compared favorably with oral cholecystography in accuracy and specificity. It was also cost-effective, saving one to two days of hospitalization.


Idiopathic chronic intestinal pseudo-obstruction. Use of central venous nutrition. Patients with idiopathic chronic intestinal pseudo-obstruction suffer from malnutrition because of inability to maintain adequate oral intake without the development of obstructive symptoms. We have successfully used central venous nutrition in two patients with this syndrome, both on a short-term and long-term home-maintenance basis. Hyperalimentation can provide adequate nutrition in patients with intestinal pseudo-obstruction until normal bowel function returns or until definitive therapy for this chronic disease is found.


Valproic acid (Depakene). A new anticonvulsant agent. Valproic acid, a new anticonvulsant, is most effective in absence seizures (simple and complex), but it has produced improvement in tonicclonic seizures, mixed absence with tonic-clonic seizures, and myoclonic epilepsy. It is useful alone or as an adjunct to other anticonvulsants and may allow the dosage of the latter to be reduced. Some patients who are refractory to other anticonvulsants may respond to valproic acid. Adverse reactions occur in about 20% of patients. Gastrointestinal disturbances and drowsiness (usually noted when valproic acid is given with other anticonvulsants) are the most common reactions; hair loss is observed less frequently. Untoward effects are usually transient and do not require discontinuation of use of the drug.


Therapy of gonorrhea. Comparison of trimethoprim-sulfamethoxazole and ampicillin. Eighty-nine men with gonococcal urethritis were randomly treated with trimethoprim-sulfamethoxazole, four tablets (trimethoprin, 320 mg, and sulfamethoxazole, 1,600 mg) twice daily for two days, or ampicillin, 3.5 g, plus probenecid, 1 g, in a single dose. Forty-one (95.3%) of 43 patients who received trimethoprin-sulfamethosazole and 41 (97.6%) of 42 given ampicillin were cured. Neither drug caused major side effects. All isolates of Neisseria gonorrhoeae were susceptible in vitro to trimethoprim-sulfame-thoxazole, and all but one were inhibited by ampicillin. The ampicillin-resistant strain (minimum inhibitory concentration, 4 micrograms/ml) produced penicillinase and was reovered from a patient who responded to treatment with trimethoprim-sulfamethoxazole. There was no significant correlation between the minimum inhibitory concentrations of trimethoprim-sulfamethoxazole and ampicillin. It is concluded that trimethoprim-sulfamethoxazole is as efficacious and safe as ampicillin in the therapy of gonococcal urethritis.


Comparison of effects of acetaminophen on liver microsomal drug metabolism and lipid peroxidation in rats and mice. Studies were conducted to determine the in vivo effect of acetaminophen (AAP) on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver. AAP was found to inhibit ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase, however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 hours after this administration to rats and mice. On the other hand, AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 observed among the components of the liver microsomal electron transfer system of rats and mice.


[Effect of nitroglycerin, digoxin and inderal of myocardial asynergy in ischemic heart disease]. The effect of nitroglycerin, digoxin and inderal on myocardial asynergy was studied in 108 patients with ischemic heart disease by means of echocardiography. The effect of nitroglycerin was studied in 32 patients; myocardial contractions were restored in the areas of asynergy in 15 patients, in 17 the character of myocardial asynergy did not change. The effect of digoxin was studied in 42 patients; intensification of myocardial contractions in the asynergic areas was noted in 18 patients in 16 the character of asynergy of the myocardium did not change, and in 8 paradoxical protrusion of the cardiac wall increased. Prescription of inderal for 34 patients did not lead to the development of additional areas of myocardial asynergy; proportionate decrease of the amplitude of the systolic myocardial movement in healthy areas and in areas with hypo-and dyskinesia was noted in such cases. The study showed changeability of the character of myocardial asynergy under the effect of the drugs investigated, which should be taken into account when these drugs are given to patients with ischemic heart disease.


The effect of dietary crude fiber levels on rhesus monkeys during quarantine. A study was conducted to determine the effect of dietary crude fiber level on intestinal disorders in the feral rheusus monkey (Macaca mulatta) during the first 60 days of the quarantine period. Three experimental baked diets containing 2.4%, 7.0%, and 9.8% crude fiber and a commercially extruded diet containing 2.2% crude fiber were fed during the study. The morbidity rate of intestinal disorders at the 7% crude fiber level was 1.4%, which was significantly less (p less than 0.05) than the 11.1%, 12.5%, and 20.8% morbidity for the monkeys fed the diets containing 2.4%, 9.8%, and 2.2% crude fiber, respectively. Monkeys fed the 7% crude fiber diet had a mean number of treatment days for intestinal disorders per monkey of 0.014, which was significantly lower (p less than 0.05) than the 0.9, 0.5, and 1.4 days for those fed the 2.4%, 9.8%, and 2.2% fiber diets, respectively.


Prevalence of metazoan parasite infections in five species of Asian macaques. Necropsy examination was performed on a total of 697 wild-caught macaques of five species. Helminthic parasites were found to be prevalent among these macaques, with species of Strongyloides, Oesophagostomum, Anatrichosoma, Trichostrongylus, and Gongylonema being the most common patent infections. Some of the larval stages of nematodes (ascarids, spirurids), cestodes (hydatid, Sparganum), and pentastomids grew into adults in appropriate definitive hosts upon experimental feeding, enabling species identification.


Social and reproductive behaviors in surrogate-reared squirrel monkeys (Saimiri sciureus). A colony of 16 surrogate-reared squirrel monkeys was observed for the adequacy of social and reproductive behaviors at maturity. Aside from some self-directed abnormalities centering around nonnutritive orality, this group was behaviorally normal in spite of having no contacts with mother-reared, older conspecifics. Half (N=5) of the females gave birth, with four infants viable. One infant has remained with the colony and is thriving. The other three remained with the group for as long as 42 days before death or removal. Maternal care appeared adequate. Mean estimated conception age for females was 35 months, and the mean impregnation age for males was estimated to be 42 months.


Antigenic relationship of two strains of simian hemorrhagic fever virus. Serological comparison of the prototype and an epizootic (Corbell) strain of simian hemorrhagic fever virus revealed that the two viruses were serologically similar. The prototype strain differs from the Corbell strain in that the latter cannot be cultivated in vitro. Serological comparison of the prototype virus grown in tissue culture and its homologous antibody and the prototype and Corbell viruses recovered from rhesus monkey serum and their homologous antibodies showed differences and suggest that a complex relationship exists which has not yet been defined.


Animal models of human cholesterol gallstone disease: a review. Human cholesterol gallstone disease has been a frequent and serious problem. A number of animal models have been reviewed for comparative study of cholesterol lithogenesis. These models in general have involved (1) decreasing bile salt excretion, (2) increasing dietary cholesterol, or (3) inducing gallbladder infection or stasis.


Suspected ascorbic acid deficiency in a colony of squirrel monkeys (Saimiri sciureus). Subperiosteal cranial hematomas were observed in five female squirrel monkeys. The absence of trauma in the clinical history, the characteristic clinical changes, and the pathological lesions suggested that the animals were scorbutic. Analysis of feed which was soaked in water, or left on the ground for varying time periods at different temperatures, indicated that there was loss of ascorbic acid. During the manufacture of monkey feed, ascorbic acid is dusted on as a final process. The practice of soaking feed resulted in the "washing off" or the destruction of ascorbic acid. This disease outbreak emphasized the important of management practices in a primate colony.


Aortic total glycosaminoglycan and dermatan sulfate changes in atherosclerotic rhesus monkeys. The composition and content of aortic glycosaminoglycans were studied in groups of rhesus monkeys fed control or atherogenic diets for 9 or 19 months. Aortic uronic acid content was significantly increased in both groups of monkeys with atherosclerosis. The major glycosaminoglycan in both control and atherosclerotic aortas was chondroitin sulfate with lesser amounts of heparan sulfate, dermatan sulfate, and hyaluronic acid. Dermatan sulfate was the only glycosaminoglycan to show a statistically significant elevation (65 to 87 per cent) in animals fed the atherogenic diet. This increase was positively correlated with the increased accumulation of aortic cholesterol (r = 0.4709, p less than 0.05). The results indicate that dermatan sulfate may be the major glycosaminoglycan involved during the early events of atherogenesis perhaps through retention of lipoprotein in the atherosclerotic artery.


Effects of cerebellar lesions on monkey jaw-force control: implications for understanding ataxic dysarthria. Eight macaques were trained on one of two isometric force regulation tasks. Six animals were trained to maintain a static force for a 2-sec period, and two animals were trained to make a rapid series of bites on a force transducer four times in succession. Electromyographic (EMG) electrodes were chronically implanted into temporalis and masseter muscles. Lesions were made in the cerebellum in seven monkeys and a control surgery with no neural damage was performed on one monkey. Following cerebellar lesions, the abilities of the monkeys to maintain a static isometric force for 2 sec were impaired. Animals overshot the correct force band and force tremors increased in amplitude following the lesions. Cerebellar lesions were followed also by a reduction in biting frequency from about 3 Hz to 2 Hz. Measurements of the temporalis EMG indicated that the reduced biting rate was associated primarily with a prolongation of the inter-EMG interval and secondarily with a prolongation of the EMG duration. Changes in jaw-force regulation following the lesions appear to be similar to the types of changes observed in arm control in monkeys, and in the speech of persons with ataxic dysarthria.


E.N.T. manifestations of Von Recklinghausen's disease. Von Recklinghausen's Disease (VRD) is a neurocutaneous, systemic disease characterized by CNS tumors and disorders, cafe-au-lait spots, generalized cutaneous neurofibromata, skeletal deformities, and somatic and endocrine abnormalities. It is an autosomal dominant, hereditary disorder found in approximately 1:2500 to 3300 births. There are many manifestations of this disease in the head and neck region of interest to the otolaryngologist. Case reports of three patients with multiple ENT involvements are detailed. A review of the literature is presented with a brief discussion of diagnosis and treatment. The most common intracranial tumor in the adult is the acoustic neuroma, usually bilateral, while in the child it is the astrocytoma. A defect in the sphenoid bone is common and may produce temporal lobe herniation into the orbit causing pulsatile exophthalmos. Involvement of the facial bones usually causes radiolucent defects secondary to neurofibromata within nerve pathways, and a variety of asymmetrical changes, especially within the mandible. "Elephantiasis" of the face is a hypertrophy of the soft tissues overlying a neurofibroma, often quite extensive and disfiguring. Laryngeal and neck involvement may compromise the airway and early and repeated surgical intervention is required. The over-all malignancy rate approaches 30%, indicating that the patient with VRD may be predisposed to developing a malignancy. There appears to be an increased surgical risk in these patients, with some demonstrating abnormal responses to neuromuscular blockade.


Intramural diverticulosis of the esophagus. A description is given of the etiology and pathology of intramural esophageal diverticulosis as so far discussed in the literature. In view of the course and the clinical findings in two young patients in whom this diagnosis was established, it is suggested that intramural diverticulosis develops as a result of a devolopmental disorder in the autonomic nervous system.


Degradation of missense mutant beta-galactosidase proteins in Escherichia coli K-12. Ten out of 43 missense mutations in the lacZ gene of Escherchia coli gave rise to polypeptide chains that were degraded in vivo. While many of the mutants appeared to be fully or partially CRM-, there appeared to be no obvious correlation between degradation, map position, altered subunit association and the half-life of the mutant proteins.


The genome of B. subtilis phage SPP1: assignment of 5'--3'-polarity to the complementary strands of SPP1 DNA. The left part of the SPP1 chromosome can be defined by the presence of dispensable DNA.  With this definition, the polarities of the separable H and L strands of SPP1 DNA ar 5'--3' and 3'--5', respectively, from left to right.


[Amino acid makeup characteristics of bacteria utilizing nonnatural compounds]. A peculiarity of the amino acid pool has been discovered for the first time in bacteria utilizing such synthetic compounds as gamma butyrolactam, epsilon-caprolactam and zeta-aminoenanthic acid. The main components of the amino acid pool are omega-aminoacids (including synthetic ones) as well as glutamic acid. The total amino acid content increases upon utilization of the compounds being tested three times (Pseudomonas fluorescens), five times (Pseudomonas dacunchae) and seven times (Pseudomonas perolens) as compared to the control variants. These data suggest that hydrolysis and transamination of synthetic omega-amino acids play an important role in the constructive and energy metabolism of the bacteria under study.


[Electron microscopic study of Bacillus subtilis mutants differing in the serine proteinase activity and spectrum]. Vegetative cells and spores of the colonial morphological mutants of Bacillus subtilis A-50 were studied by electron microscopy. The ultrastructure of vegetative cells from both asporogenic colonial-morphological mutants and those which were capable of forming spores in the presence of high concentrations of nitrogen and carbon sources with a decreased activity and a modified spectrum of serine proteases differed from the parent strain by the presence of a microcapsule, the uneven thickness of a cell wall, and the absence of a distinct periplasmic space. Crystalline inclusions of a regular shape were detected in the sporeforming mutant in those cells which were devoid of spores. Spores of the mutant had additional layers.


Mapping by interspecies transformation experiments of several ribosomal protein genes near the replication origin of Bacillus subtilis chromosome. Bacillus subtilis 168 was transformed with DNAs from B. amyloliquefaciens K or B. licheniformis IAM 11054. These two species show a considerable difference in ribosomal proteins from B. subtilis. Analyses of the transformants indicated that the genes for 16 proteins, S3, S5, S8, S12, S17, S19, BL1, BL5, BL6, BL8, BL14, BL16, BL17, BL22, BL23 and BL25 are located in the cysA-str-spc region on B. subtilis chromosome. The genes for 10 proteins, S4, S6, S13, S16, S20, BL15, BL18, BL20, BL24 and BL28 could not be found in this region in the present experiments.


[Drug therapy of osteoarthrosis of the hip (author's transl)]. Experience in therapy with sulindac and S-adenosyl-L-methionine (SAMe) is reported. Sulindac is an indene derivative which is particularly indicated in degenerative skeletal diseases and is essentially free from the well-known side-effects of traditional analgesics. The results of therapy were good in 75%. SAMe is the most important methyl group donor and is consequently responsible for the methylation (inactivation) of histamine, upon which its antiphlogistic action is based. SAMe is also particularly involved in the transfer of sulfate groups in the body. Sulfur compounds are esentially involved in the synthesis of cartilage. The short-term trials with SAMe were altogether more favorable than the longterm trials, yet there was a longterm effect in about half the cases.


[Surgical treatment of osteoarthritis of the hip (author's transl)]. Surgery can improve function for one or more decades for patients with osteoarthritis of the hip, even though the operations may not be very invasive. The indications must be made by surgeons in collaboration with rheumatologists. There is no patent recipe, no 'common' intervention which gives a reliable result in all cases. The patient must be studied in all stages of development of his disease: his joint structure in the radiogram, the morphology of the bones, the functional requirements and his general state of health influence the decision regarding the possibility and modality of a surgical intervention. The patient's return to an active life which would not have been possible for him under medicinal treatment supports the importance of surgical treatment.


[Pathophysiology of lung resections (author's transl)]. Changes of adaptation and complications which may appear after extended lung operations must be known both to the surgeon and to the doctor responsible for the after-treatment. They are divided into pulmonary, cardiac, and intestinal early and late sequelae. Pathophysiology, clinical aspects and therapy of the most frequent changes are briefly demonstrated in this paper, sometimes with the aid of our own illustrations and experimental results.


[Pathophysiology, clinical aspects and course of bullous emphysema (author's transl)]. Bullous emphysema (progressive lung dystrophy) is a disease of advanced age and over 90% of the patients are men. The bullous changes in the l-ng perferentially affect the apical fields and the left lower area. Bronchographic visualization is in this case not possible. The disease runs a progressive course. Valvular stenoses of the bronchi and especially of the bronchioles in various types of primary pulmonary disease are of considerable importance etiologically.


[The effect of pyritinol on the human cerebrovascular circulation (author's transl)]. The change in global and regional cerebral circulation after intravenous administration of pyritinol was investigated in 14 patients with acute or subchronic cerebral ischemia. The measurement of the cerebral circulation was performed by intraarterial isotope clearance with 133xenon using a multidetector apparatus. With a single administration of pyritinol (400 mg) there was a statistically significant increase in the cerebral circulation in the gray matter by 6.7 ml/100 g/min corresponding to 9.7% (p less than 0.01) 10 minutes after the end of the drug injection. In the areas of all portions of the brain with defective circulation there was a significant increase in blood flow by 8.9, 0.8 and 3.2 ml/100 g/min (gray matter, white matter, total substance), corresponding to 12.3%, 4.4% and 8.1%. In areas with a normal initial status, the increase in blood flow attained statistical significance in the gray matter only (p less than 0.05).


[Prophylaxis of immediate and delayed reactions in exogenic allergic bronchial asthma (author's transl)]. In 14 antigen provocation tests in 12 patients with allergic bronchial asthma, an immediate bronchoconstriction could be demonstrated by whole body plethysmography and a delayed reaction in 6 other cases. The examinations were repeated after a single prophylactic application of 40 mg disodium cromoglicate. By this means, 10 of the 14 immediate reactions and 4 of the 6 delayed reactions could be completely or largely prevented; in 4 and 2 patients respectively the protective effect was unsatisfactory. In longterm experiments over 4--6 months an improvement in the findings was recorded in 9 of the 12 patients. A rare side-effect of disodium cromologlicate therapy is irritation of the respiratory tract, in some cases with not inconsiderable respiratory obstruction.


[The cost of pacemaker therapy from 1970 to 1975 with particular reference to the new hospital legislation (author's transl)]. The changes introduced by the new legislation on hospital allowances are discussed with reference to the costs (1970 to 1975) for inpatient treatment of patients with pacemakers. As a result of the new legislation, centralizing pacemaker therapy must cause a great strain on the regional statutory insurance authorities if the area served by the pacemaker center is greater than that of the health insurance authority.


[Diagnosis and treatment of infantile cardiac insufficiency (author's transl)]. Congenital vitium cordis and myocardial diseases, rare arrhythmias and other factors are the causes of heart failure which imposes a life-threatening clinical condition in infancy and childhood with a sometimes characteristic, but often also unspecific symptomatology. An intensive program of general and medicinal measures is required of which digitalis therapy is the central feature. In addition, diuretics, catecholamines and buffer substances are essential among other things. The success and duration of treatment depends on the primary disease.


[Gastroenterological endoscopy--fascination and obligation (author's transl)]. The development of fiber endoscopy has made possible routine endoscopic bioptic examination of the upper (including the duodenum) and lower digestive tract (with the terminal ileum). Biopsy material can be obtained in the necessary quantities with forceps or a loop. In many centers endoscopy is already the basic method for the diagnosis of diseases of the upper digestive tract. A similar tendency is also becoming apparent in colo-ileoscopy. The increase in the frequency of endoscopic investigations is accompanied by a decrease in the number of complications. The increasing importance and dissemination of gastrointestinal fiber endoscopy demands greater and better training facilities and adequate control of qualifications together with an integrated cooperation with the pathologists.


[Echographic or radiographic cholecystography? (author's transl)]. In a prospective echographic and radiographic investigation of 281 patients and in a retrospective evaluation of 86 operated patients, echography and radiography gave approximately equally accurate diagnoses. By using both methods no pathological finding will be overlooked. For reasons of radiation protection, echographic examinations should be carried out first. If the echographic results agree with the clinical findings the radiological cholecystography can be dispensed with. Radiological investigation should be carried out if the echographic findings are at variance with the clinical findings. Consequently echographic cholecystography certainly cannot replace radiography, but it does contribute in that radiographic examination can be used selectively.


[The enzyme-linked immunosorbent assay (ELISA)--a new serodiagnostic method for the detection of parasitic infections (author's transl)]. The enzyme-linked immunosorbent assay (ELISA) is a new serodiagnostic aid for the indirect demonstration of parasites. Examples of the application of ELISA are given in a review of the literature. Antibodies against Babesia and Besnoitia could be detected in various domestic and laboratory animals. The application of ELISA for the detection of toxoplasma antibodies also under the influence of hammondia infections is discussed. Larva migrans visceralis could be demonstrated using ELISA in mono-infected mice and dogs, cross reactions with other helminth antibodies in human sera do not, however, permit a reliable diagnosis of larva migrans visceralis. The enzyme-linked immunosorbent assay may be recommended as a screening test for contamination investigations.


Epidemiology and health services administration: future relationships in practice and education. Florence Nightingale's mid-nineteenth century proposals for standard classification of diseases were a model for assessing quality of hospital care. A century later, health planning, management, and evaluation are still in pursuit of her unrealized--and imperfect--objectives. Historical, statistical, and epidemiological limitations to linking the cost and outcome of treating patients and populations are examined; an integrated model is offered for operational rapprochement between medical and administrative services.


Successes of prevention.

Successes of prevention. Despite the intuitive--and historically persistent--appeal of preventive medical measures, latter-day skeptics find less cause for continued optimism. The failure of expectations is only partly a confusion of definitions. An examination of what is prevented, and by whom, suggests new professional as well as political strategies, and anticipates new dilemmas.


Kindling: the first decade.

Kindling: the first decade. The kindling phenomenon is a progressive increase in the strength of epileptiform activity evoked by spaced (in time) and repeated electrical stimulation of certain brain structures. The work that has been done on the kindling phenomenon is reviewed, with an emphasis on those studies that deal with underlying mechanisms. Based on the work that has been done thus far, it is clear that the kindling effect is not due to any type of gross tissue damage. It is also clear that at least some of the effects are due to changes at the synapse and that these changes are widely distributed in the brain. The changes might be due to an increasing efficacy at excitatory synapses or a decreased effectiveness at inhibitory synapses, or both. The long term post-tetanic potentiation data and some preliminary electron microscopic studies support the former mechanism, whereas the depletions of catecholamines in kindled tissue support the latter. In addition to these transynaptic changes, there may be other changes that occur at the site of the stimulating electrode, and these changes may be based on a different mechanism. These ideas and the relevant data are discussed.


Decision theory in medicine: a review and critique. Decision theory's role in medicine will lie between the extremes of naive optimism ("a Rosetta stone") and unmitigated pessimism ("a computerized Ouija board"). Its application to public health policy, research, and administrative problem-solving is established; experience offers some guidelines for more limited use in clinical practice.


Maternal syndrome associated with hydrops fetalis: case report. A case of maternal fluid retention syndrome associated with fetal hydrops due to rhesus isoimmunisation is reported. The aetiology and clinical features are discussed. Prophylactic anti-Rh immunoglobin should reduce the incidence of such cases in the future.


[Comparative study of the bactericidal action of the body of Ornithodoros papillipes ticks]. Experiments in vivo have shown that the ticks of Ornithodoros papillipes inhibit both Gram-positive and Gram-negative bacteria. On Gram-positive microorganisms most sensitive to bactericidal effect of ticks have turned to be micrococci, staphylococci, streptococci and bacteria of diphtheria, of Gram-negative ones--Bacillus coli. Of Gram-positive microorganisms less sensitive were Listeria, of Gram-negative ones--salmonellae, agents of tularemia and pseudotuberculosis. At the infection with bacteria the organism of the tick produces a bactericidal substance which causes the dying off of the microbal population. The ability of the bactericidal substance to lyse the inhibited cells of Micrococcus lysodeiktickus as well as the coincidence of data on sensibility to the tick bactericidal substance obtained experimentally in vitro and in vivo have shown that lysozyme is an active antibacterial substance in the tick's organism.


Dieldrin, DDT, PCBs, and mercury levels in freshwater mullet from the upper Great Lakes, 1975-76. Freshwater mullet harvested commercially during various seasons of 1975-76 from the upper Great Lakes were analyzed for organochlorine pesticides, PCBs, and mercury. Species analyzed were Catostomus commersoni, C. catostomus, and Moxostoma erythruran. Whole ground fish, mechanically deboned flesh, head, middle, and tail steaks, and various muscles were analyzed for pesticides and PCBs; only edible flesh was analyzed for mercury. Dieldrin ranged from none detected to 0.23 ppm in deboned and whole ground samples, the DDT range was a trace to 0.30 ppm, and PCBs ranged from 0.06 ppm to 0.79 ppm. Levels were also higher in head sections and in high fat-containing medial muscle and belly flap. Mercury levels ranged from 0.03 ppm to 0.28 ppm in the flesh of mullet from Lake Michigan.


[Joint parasitism of Microsporidia (Nosematidae) and Mermithidae (Nematoda) in the larvae of blood-sucking mosquitoes (Diptera, Culicidae)]. A double infection of the larvae of Aedes flavescens and A. cantans with Thelohania opacita and larvae of Mermithidae was established. The double infection is not accompanied by the rise of pathogenic effect of the parasites on the hosts. Mermithids parasitizing mosquitoes infected with microsporidians inhibit the development of Protozoa. The inhibition degree depends on the duration of contacts of coparasites as well as on the developmental phase of microsporidians at the moment of penetration of nematodes.


Circadian activity rhythms of the pig-tailed macaque, Macaca nemestrina, under constant illumination. Locomotor activity was recorded in singly caged pig-tailed macaques Macaca nemestrina in constant conditions with intensities of illumination varying between 0.003 lux and 100 lux. Each animal was kept in at least 5 different conditions for 2-3 weeks each. Three quantities of the circadian rhythm: the period, the duration of activity as opposed to rest, and the amount of activity per period, could be shown to be positively correlated with light intensity. As in 6 other diurnal primate species, these findings contradict the so-called circadian rule according to which opposite correlations should exist between the circadian parameters and light intensity in diurnal and in nocturnal species of animals.


Characterization of an immunoglobin cDNA clone containing the variable and constant regions for the MOPC 21 kappa light chain. Nucleotide sequence analysis and restriction endonuclease mapping have been used to characterize a cDNA copy of immunoglobulin MOPC 21 Kappa mRNA clones in the bacterial plasmid pMB9. Three regions of the inserted cDNA of plasmid pL21-1 have been sequenced and match the known protein sequence at amino acid residues 1-24, 128-138 and 171-179. With these sequences to provide absolute correlations between the restriction map and the structural gene sequence it has been possible to exactly deduce the positions of all 11 of the insert restriction sites mapped within the structural gene. The pL21-1 insert contains the complete variable and constant regions as well as parts of the 3' untranslated and polypeptide leader coding sequences.


Recombinant DNA clones constructed from immunoglobulin kappa light chain messenger RNA. Recombinant DNA clones have been generated from mouse myeloma MOPC 21 immunoglobulin kappa light chain mRNA. Complementary DNA (cDNA) synthesized on kappa light chain mRNA by reverse transcriptase was made double stranded and inserted into the bacterial plasmid vector, pMB9. Approximately 70 tetracycline-resistant transformed colonies containing kappa light chain mRNA sequences were identified by colony hybridization. Five of these recombinant clones were selected and characterized. Three clones contain both kappa light chain constant and variable region sequences. Two of these three recombinant clones have been shown to include all of the kappa light chain constant and variable region coding sequences. Another of the five selected recombinant clones contain kappa light chain constant region sequences. The remaining characterized clone appears to be derived from sequences at the 5'-end of kappa light chain mRNA, possibly extending to the terminal cap structure.


Computer method for predicting the secondary structure of single-stranded RNA. We present a computer method utilizing published values for base pairing energies to compute the most energetically favorable secondary structure of an RNA from its primary nucleotide sequence. After listing all possible double-helical regions, every pair of mutally incompatible regions (whose nucleotides overlap) is examined to determine whether parts of those two regions can be combined by branch migration to form a pair of compatible new subregions which together are more stable than either of the original regions separately. These subregions are added to the list of base pairing regions which will compete to form the best overall structure. Then, a 'hyperstructure matrix' is generated, containing the unique topological relationship between every pair of regions. We have shown that the best structure can be chosen directly from this matrix, without the necessity of creating and examing every possible secondary structure. We have included the results from our solution of the 5S rRNA of the cyanobacterium Anacystis nidulans as an example of our program's capabilities.


Meeting exceptional nutritional needs. 2. Elemental enteral alimentation. Elemental enteral alimentation (EEA) is an alternative to parenteral nutrition in patients with a functioning gastrointestinal tract and increased caloric requirements or in whom regular oral feeding is impossible or impractical. EEA is given by nasogastric, jejunostomy, or gastrostomy tube. It is useful in cases of short-gut syndrome, pancreatic disease, partial intestinal obstruction, colitis, neuropsychiatric cachexia, trauma, fistula, vascular insult, and renal and liver disease, as well as in patients being prepared for surgery or requiring hyperalimentation after surgery or abdominal irradiation. Strict attention must be paid to fluid and electrolyte status and to blood and urine glucose levels in patients receiving EEA. With use of a nasogastric tube, infection of the middle ear is a possible but uncommon complication.


RNA metabolism, manganese, and RNA polymerases of zinc-sufficient and zinc-deficient Euglena gracilis. The three major RNA classes from zinc-sufficient [(+Zn)] and zinc-deficient [(=Zn)] Euglena gracilis have been separated by affinity chromatography on oligo(dT)- and N-[N'-[m-(dihydroxyboryl)phenyl]succinamoyl]aminoethyl (DBAE)-celluloses. The total RNA content and the ribosomal and transfer RNA fractions are the same in (+Zn) and (=Zn) cells. IN (-Zn) cells, the messenger RNA fraction increases, and its altered base composition reveals additional bases and a 2-fold increase in the (G+C)/(A+U) ratio. Since the intracellular content of manganese increases in (-Zn) cells, we have examined its role in determining these changes in RNA composition. An increase in the Mn2+ content from 1 to 10 mM in assays with RNA polymerases I and II from (+Zn) cells and those with the single RNA polymerase from (-Zn) cells decreases the ratio of UMP to CMP incorporated from 1.7 to 1.0, 2.1 to 0.8 and 3.5 to 0.4, respectively. Thus, Mn2+ concentration can significantly alter the products of the enzymatic action of RNA polymerases from both (+Zn) and (-Zn) E. gracilis cells.


High concentration of thyrotropin-releasing hormone in pancreatic islets. The concentration of thyrotropin-releasing hormone (TRH, thyroliberin) in rat islets of Langerhans is 30-fold higher than in whole rat pancreas, indicating that the islets are the main source of pancreatic TRH. The TRH extracted from islets is indistinguishable from synthetic TRH in its immunological and biological properties and in its inactivation by human serum. The physiologic function of islet TRH is unknown. However, because TRH is antagonistic to somatostatin in other systems, and somatostatin also is concentrated in islets in high concentrations, it is possible that islet TRH may serve a similar antagonistic function in the regulation of islet cell secretory activity.


Genetic regulation of tissue-specific expression of amylase structural genes in Drosophila melanogaster. Laboratory strains of Drosophila melanogaster were screened for spatial variations in adult midgut alpha-amylase (1,4-alpha-D-glucan glucanohydrolase, EC 3.2.1.1) expression. No strain-specific differences were found anteriorly, but three patterns of activity were discerned in the posterior midgut: A, activity throughout most of the region; B, activity in the anterior part of the region; and C, little or no activity. Alleles of a control gene, map, are responsible for this tissue-specific regulation of activity; e.g., mapA homozygotes produce the A pattern and mapC homozygotes the C pattern. The map locus was placed at 2--80 +/- on the genetic map of chromosome 2R, about two crossover units distal to the Amy structural gene region for alpha-amylase. Electrophoretic studies showed that mapA is trans acting in mapA/mapC flies, allowing expression of amylase isozymes coded for by genes on the opposite chromosome. The map gene behaves as a temporal gene that is clearly separable from the tightly linked, duplicated Amy structural genes.


Assignment of genes for immunoglobulin kappa and heavy chains to chromosomes 6 and 12 in mouse. Using somatic cell hybrids from fusions of lymphocytes of two different mouse stocks with the myeloma cell line X63-Ag8, we have assigned genes for the immunoglobulin heavy and kappa-type light chains to chromosomes 12 and 6, respectively. The two mouse stocks exhibit karyotypes consisting of nine pairs of metacentric chromosomes as a result of centric fusions of acrocentric chromosomes in different combinations. In the hybrid cells these metacentric chromosomes can be distinguished from the acrocentric chromosomes of myeloma origin, permitting correlation of Ig chain expression with mitotic loss of individual metacentric chromosomes.


Somatostatin inhibits release of thyrotropin releasing factor from organ cultures of rat hypothalamus. Somatostatin in concentrations of 10(-6) to 10(-8) M inhibited basal release of thyrotropin releasing factor in organ culture of rat hypothalamus. Norepinephrine in doses of 10(-4)--10(-6) M induced release of thyrotropin releasing factor which increased progressively with time and was temperature and dose dependent. This enhanced thyrotropin-releasing-factor release was inhibited by somatostatin at 10(-6)--10(-8) M.


Azo dyes prevent hydrocarbon-induced leukemia in the rat. A set of intraveous injections of 7,8,12-trimethylbenz[a]anthracene consistently elicited leukemia in more than 75% of young adult Long-Evans female rats. There was a profound reduction in the incidence of leukemia in companion groups of rats fed small amounts (1--10 mg) of Sudan III or Sudan IV prior to each injection of the carcinogenic hydrocarbon. Repeated feedings of 1 mg of Sudan III induced cumulative increases in the concentration of menadione reductase (EC 1.6.99.2) in liver, whereas protein concentration was unchanged. A single feeding of 1 mg of Sudan III prevented fatal toxicity in all members of large groups of rats injected with massive doses of 7,12-dimethylbenz[a]anthracene, but 50% of the survivors developed leukemia; unprotected rats succumbed in 1--3 days. Sudan III was not carcinogenic under the experimental conditions.


Synapses involving auditory nerve fibers in primate cochlea. The anatomical mechanisms for processing auditory signals are extremely complex and incompletely understood, despite major advances already made with the use of electron microscopy. A major enigma, for example, is the presence in the mammalian cochlea of a double hair cell receptor system. A renewed attempt to discover evidence of synaptic coupling between the two systems in the primate cochlea, postulated from physiological studies, has failed. However, in the outer spiral bundle the narrow and rigid clefts seen between pairs of presumptive afferent fibers suggest the possibility of dendro-dendritic interaction confined to the outer hair cell system. The clustering of afferent processes within folds of supporting cells subjacent to outer hair cells is in contrast to the lack of such close associations in the inner hair cell region. The difference reinforces the suggestion of functional interaction of some sort between the outer hair cell afferent nerve processes.


Energetics of sodium transport in toad urinary bladder. The ratio of the rate of transepithelial sodium transport, JNa, across the isolated toad urinary bladder to the simultaneously measured rate of transport-dependent metabolism, JsbCO2, has been measured as a function of the transepithelial electrical voltage, deltapsi. The ratio remains constant with a mean value of 18 to 20 over the range of imposed voltages of 0 to +70 mV. With increasing hyperpolarization of the bladder, JNa decreases and the calculated electromotive force or apparent "ENa" of the sodium pump increases. From thermodynamic and kinetic arguments it is shown that the apparent "ENa" approaches the maximal electrochemical potential gradient, ENa, against which sodium can be transported by this tissue only when JNa approximately 0. At this unique condition F ENa (in which F is the Faraday constant) is the maximal free energy of the chemical reaction driving sodium transport and thus equal to the maximal extramitochondrial phosphorylation potential and the maximal free energy of the mitochondrial respiratory chain within the transporting cells.


Brief communication. Comparative pharmacology of norcocaine in M. mulatta and M. fascicularis. Norcocaine was administered intravenously (0.05, 0.5, 5.0 mg/kg) to three chaired unanesthetized male rhesus monkeys and to three chaired male cynomolgus monkeys. Respiration rate, heart rate and rectal temperature were monitored. In the rhesus monkeys tachycardia and hyperventilation resulted. However, similar qualitative and quantitative changes were not observed in the cynomolgus species. There was a statistically significant difference in the response to norcocaine across species. These results indicate that cynomolgus monkeys are either less sensitive or respond differently than rhesus monkeys to some of the pharmacological effects of norcocaine. Furthermore, these data confirm that norcocaine is an active derivative of cocaine in both rhesus and cynomolgus monkeys.


Correlation of PCB body burden with behavioral toxicology in monkeys. Eight monkeys fed 2.5 ppm PCB in their daily diet conceived, delivered and nursed five infants, three of which survived past weaning at four months of age. PCB residues in fat in the surviving infants at 8, 10 1/2, and 23 months of age declined linearly when plotted as log concentration versus time (first order clearance), and these functions extrapolated to presumed peak PCB levels of 21, 114, and 123 microgram/g fat (ppm) at 4 months of age. Behavioral tests on these three infants and four normal controls revealed hyperlocomotor activity at 6 and 12 months of age correlated with peak PCB body burdens. Higher peak PCB body burdens also were correlated with increased errors in five of nine learning tasks conducted between 8 and 24 months of age. Point estimates of zero-effect levels of PCB body burdens ranged around 21 ppm, although it was clear that even the monkey carrying only 21 ppm PCBs at four months of age exhibited some behavioral deficits persisting through the final testing at 24 months of age.


The use of 10B to enhance the tumour dose in fast-neutron therapy. Incorporation of 10B in tumours treated by fast-neutron therapy would increase the tumour dose via the reaction 10B(n, alpha)7Li which occurs with partially thermalised neutrons. The extent of the dose enhancement was measured for neutron beams with median energies of 2.4, 3.3, 7.0 and 9.0 MeV by two techniques: with a BF3 proportional counter in three beams and activation of 23Na in the fourth. The results obtained with the two techniques are in good agreement. The magnitude of the dose enhancement depends upon the depth, field size and neutron beam energy. The dose enhancement at a depth of 8 cm varied from 0.32% with the lowest-energy beam to 0.07% with the highest-energy beam for each microgram of 10B uptake per gram of tissue. The products of the reaction in 10B would, however, have an RBE about twice that of the fast-neutron dose in the absence of boron. The method may be useful if drugs providing adequate uptake of 10B can be synthesised.


Pion radiotherapy: studies with nuclear emulsions. Nuclear emulsions were used to provide information on (1) the pion star distribution for a therapy beam; (2) star production as a function of pion energy and residual range in nuclear emulsion; (3) the distribution of nuclear framgent ranges in emulsion; and (4) the neutron energy spectrum and fluence produced by negative pion capture in tissue, during treatment of a patient. This last item is important for determining the whole-body dose delivered to a patient undergoing pion radiotherapy.


[Pattern-sensitive epilepsy with an unusual triggering mechanism]. A case of pattern-sensitive epilepsy is reported which is characterized in that the pattern is formed from images of human faces with clearly recognizable eyes. Similarities to previously reported cases of pattern-sensitive epilepsy as well as dissimilarities from those cases are discussed.


[Clinical significance of serum phenytoin level]. Phenytoin serum concentrations in 115 epileptics treated on an inpatient basis showed, in two groups, only relatively weak correlation with the dosage used. The range of variation was assigned a factor of 16. For individual patients there was observed a correlation between the dosage in mg/kg and the corresponding phenytoin serum concentration. The level of phenytoin serum concentration was not found to be related to the frequency of attacks. The effective phenytoin serum level showed interindividual differences and can be low as well as relatively high. Resulting from this is the need for determining, from the determination of serum concentrations, the effective serum concentration for each individual patient.


[Lymphadenopathy in phenytoin treatment]. The authors report on a 20-year-old patient who developed hydantoin lymphadenopathy during treatment with diphenylhydantoin. The problems associated with clinical and histological delimination from malignant lymphomata are described by reference to the literature. Hydantoin lymphadenopathy is regarded as a drug-induced allergic and toxic process.


Dependency of different types in schoolchildren with epilepsy. By means of the Self-Administered Dependency Questionnaire (SADQ), 4 types of dependency on mother were measured in 65 children with epilepsy attending ordinary school, sub-grouped according to sex, level of schooling, electrographic type of epilepsy, and drug treatment. The various dependency scores of each subgroup were compared with the appropriate norms available for the SADQ. Compared with normal boys, epileptic boys of primary school age (N = 16) were generally found to be more in need of close physical emotional contact with their mother and her physical proximity when away from home, although they were less ready to talk to her about their practical problems and ask for her help. The needs of epileptic boys of secondary-school age (N = 18) were expressed more in terms of their mother's help with practical matters at home. In contrast, no significant differences were apparent between epileptic and normal girls at either level of schooling. In comparisons between epileptic children who consistently produced only generalized seizure activity in their EEG (N = 31), a right temporal spike discharge (N = 16) or a similar discharge on the left (N = 18), both boys and girls with a left temporal spike discharge tended to show significantly higher need for close physical emotional contact with their mother than children in the other electrographic groups. No clear relationship was seen between dependency scores and type of anti-epileptic drug treatment.


Continuation therapy in endogenous depression controlled by changes in the TRH stimulation test. Thyrotropin response to thyrotropin-releasing hormone is impaired during endogenous depression and normalized between the depressive periods. Changes in the thyrotropin response to thyrotropin-releasing hormone were shown to be of predictive value and might be useful in the control of continuation therapy with antidepressants in patients with endogenous depression.


High-affinity 3H-serotonin binding to caudate: inhibition by hallucinogens and serotoninergic drugs. The specific binding of 3H-serotonin to calf caudate homogenate was studied. The dissociation constant was 2nM and the number of specific sites was 14fmoles/mg protein. Of many drugs tested, inhibition of specific 3H-serotonin binding occurred almost exclusively with serotonin agonists and antagonists. The concentrations for 50% inhibition of 3H-serotonin binding by serotonergic agonists follow: bufotenin, 6nM; 5-methoxytryptamine, 12 nM; psilocin, 35nM; dimethyltryptamine, 220 nM; and tryptamine, 270 nM. The concentrations for the antagonists were: LSD 9.5 nM; methysergide 16nM and metergoline 25nM.


Combined effects of ethanol and diazepam on performance and acquisition of serial position sequences by pigeons. The effects of diazepam and ethanol, alone and in combination, were studied in pigeons responding under acquisition and performance chain schedules. Both diazepam and ethanol increased the number of pecks on the incorrect key (errors). Under the acquisition schedule both diazepam and ethanol increased errors at doses lower than those under the performance schedule. Under both schedules effects of combinations of ethanol and diazepam were usually greater than the sum of the effects of the individual drugs.


Methamphetamine and diphenhydramine effects on the rate of cognitive processing. Three cognitive tasks in which performance depends primarily on the rate of cognitive processing were given to 24 male subjects before and after oral doses of methamphetamine (10 mg), diphenhydramine hydrochloride (100 mg), and placebo. Each subject was tested on Monday, Wednesday, and Friday of one week with drug orders balanced across subjects. Compared with placebo and diphenhydramine, methamphetamine increased the rate at which a visual display was scanned for a target stimulus. Methamphetamine affected neither a time-production task nor a divided attention task that required the subject to perform two cognitive tasks in a limited amount of time. This suggests that methamphetamine can increase cognitive processing speed on tasks involving familiar cognitive operations but that an increase is not likely in tasks involving more complicated decision processes. Compared with placebo and methamphetamine, diphenhydramine caused subjects no experience geophysical time as passing more slowly, but the drug had no significant effects on the visual search or divided-attention tasks. This suggests that time perception is more likely to be altered by diphenhydramine than is performance on tasks requiring short periods of rapid cognitive processing.


Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine. (--)-Nuciferine and its Hofmann degradation product atherosperminine showed divergent psychopharmacological effects. Because nuciferine has been reported to be a neuroleptic and atherosperminine has some chemical resemblance to dopamine, they were investigated for their dopamine-receptor activities. Nuciferine had a pharmacologic profile of action associated with dopamine-receptor blockade; i.e., it induced catalepsy, inhibited spontaneous motor activity, conditioned avoidance response, amphetamine toxicity and stereotypy. On the other hand, atherosperminine produced effects associated with dopamine receptor stimulation, i.e., stereotypy, increase in spontaneous motor activity and amphetamine toxicity, reversal of haloperidol-induced catalepsy and inhibition of conditioned avoidance response, inhibition of morphine analgesia, and potentiation of the anticonvulsant action of diphenylhydantoin. The results are discussed on the basis of the chemical configuration of the two compounds.


The practical significance of nortriptyline plasma control. A prospective evaluation under routine conditions in endogenous depression. The problem of the advantage of using nortriptyline (NT) plasma level during treatment for endogenous depression has been approached. In an ordinary psychiatric department, 34 patients had their NT level checked the second week of treatment and their dosage subsequently adjusted, if it was outside the recommended therapeutic plasma range (50--150 ng/ml). A cautious dose policy led to low plasma levels followed by dose increase in about 40% of the patients. Only in a few patients was the plasma level above the upper limit. The general outcome, about 20% failures, was compatible with the best in literature. These and other results suggest that controlling the NT plasma concentration, aiming at a level of around 100 ng/ml, might offer a therapeutic advantage, but only if the department has established a therapeutic strategy that involves such a monitoring system. The therapeutic outcome was the same as or even better in the old-age group than that in patients under 65 years of age.


The effect of lithium on amphetamine-induced locomotor stimulation. A behavioural study was performed to investigate how lithium interacts with monoamine mechanisms. Acute lithium pretreatment partially antagonized amphetamine-induced locomotor stimulation in mice. A rather small dose of L-dopa, which had no stimulant effect on locomotor activity of its own, caused a dose-dependent antagonism of the lithium-induced suppression of the amphetamine-induced locomotor stimulation. Additionally, acute lithium pretreatment had no effect on the apomorphine-clonidine-induced locomotor stimulation after elimination of presynaptic activity by means of pretreatment with reserpine and alpha-MT. Our interpretation of these results is that the inhibitory effect on amphetamine-induced locomotor stimulation is likely to be mediated via presynaptic mechanisms (i.e., decreased release of catecholamines or inhibition of catecholamine synthesis or a combination of both mechanisms) and, further, lithium seems to have no effect at or beyond the catecholamine receptors. However, the possibility that lithium may increase the activity in neuronal systems antagonizing the catecholamine neurons cannot be excluded.


Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid). The anticonvulsant potency and neurological toxicity of two new catalytic inhibitors of GABA-transaminase have been assessed in acute experiments in baboons with a natural syndrome of photic epilepsy. gamma-Acetylenic GABA, 160--200 mg/kg, or gamma-vinyl GABA, 450--950 mg/kg, intravenously, gave complete protection against generalised myoclonus or seizure responses induced by photic stimulation (in baboons without or with priming with subconvulsant doses of allylglycine). The protection became maximal 1--3 h after injection, and continued for 7--24 h. Signs characteristic of the acute toxicity of anticonvulsant drugs (nystagmus and ataxia) were not seen. The potential use of these compounds in human epilepsy deserves investigation.


Enhanced choice of familiar food in a food preference test after chlordiazepoxide administration. Chlordiazepoxide (5.0 and 10.0 mg/kg) increased the time spent eating familiar laboratory chow, in a food-choice test in which both familiar and novel food objects were available. Chlordiazepoxide did not affect the feeding response to the novel food. Prior handling of the rats and repeat testing affected feeding responses in the test, although in ways which were different from and independent of the effect of chlordiazepoxide. Chlordiazepoxide may facilitate feeding responses by a direct enhancement of feeding motivation, and not necessarily secondarily by either a release of suppression of feeding or as attenuation of anxiety evoked by unfamiliarity.


The effects of chlordiazepoxide on a delayed pair comparison task in pigeons. Five pigeons were successfully taught a variation of the Konorski delayed pair comparison task, using a red and a green stimulus. The bird was required to respond to the left or right hand key, depending on whether the 2 successively presented centre key stimuli were the same (left) or different (right). The delay intervals ranged from zero to 9 s, and stable performance decrements (with increasing delay) were obtained. Chlordiazepoxide which, it has been argued, produces behavioural changes similar to those observed after hippocampal lesions was found to disrupt performance at doses greater than 4 mg/kg (i.m.). All delays (including zero) were affected. Some interpretations of this result in terms of encoding and attention are discussed, and some reference made to the possible neuropharmacological basis of this drug action.


The production of morphine tolerance and physical dependence by the oral route in the rat. A comparative study. A method for the chronical administration of morphine by the oral route is discussed and compared with the production of physical dependence to morphine by injection. The method recommends the administration of Morphine HCl dissolved in a 45% sucrose syrup and given orally for 4 weeks. The initial concentration of morphine in the syrup was 1 mg/ml and was increased weekly up to 4 mg/ml at the end of the experiment. This procedure rendered the animals physically dependent on morphine as observed by drug withdrawal, when abstinence symptoms were easily identified.