Anion transport in dog, cat, and human red cells. Effects of varying cell volume and Donnan ratio.

Membrane potential and the rate constants for anion self-exchange in dog, cat, and human red blood cells have been shown to vary with cell volume. For dog and cat red cells, the outward rate constants for SO4 and Cl increase while the inward rate constant for SO4 decreases as cells swell or shrink. These changes coincide with the membrane potential becoming more negative as a result of changes in cell volume. Human red cells exhibit a similar change in the rate constants for SO4 and Cl efflux in response to cell swelling, but shrunken cells exhibit a decreased rate constant for SO4 efflux and a more positive membrane potential. Hyperpolarization of shrunken dog and cat red cells is due to a volume-dependent rate constant for SO4 efflux and a more positive membrane potential. Hyperpolarization of shrunken dog and cat red cells is due to a volume-dependent increase in PNa. If this increase in PNa is prevented by ATP depletion or if the outward Na gradient is removed, the response to shrinking is identical to human red cells. These results suggest that the volume dependence of anion permeability may be secondary to changes in the anion equilibrium ratio which in red cells is reflected by the membrane potential. When the membrane potential and cell volume of human red cells were varied independently by a method involving pretreatment with nystatin, it was found that the rate of anion transport (for SO4 and Cl) does not vary with cell volume but rather with membrane potential (anion equilibrium ratio); that is, the rate constant for anion efflux is decreased and that for influx is increased as the membrane potential becomes more positive (internal anion concentration increases) while the opposite is true with membrane hyperpolarization (a fall in internal anion concentration).


Ouabain binding and coupled sodium, potassium, and chloride transport in isolated transverse tubules of skeletal muscle.

The affinity and number of binding sites of [3H]ouabain to isolated transverse (T) tubules were determined in the absence and presence of deoxycholate. In both conditions the KD was approximately 53 nM while deoxycholate increased the number of binding sites from 3.5 to 37 pmol/mg protein. We concluded that the ouabain binding sites were located primarily on the inside of the isolated vesicle and that the vesicles were impermeable to ouabain. ATP induced a highly active Na+ accumulation by the T tubules which increased Na+ in the T tubular lumen by almost 200 nmol/mg protein. The accumulation had an initial fast phase lasting 2-3 min and a subsequent slow phase which continued for at least 40 min. The rate of the initial fast phase indicated a turnover number of 20 Na+/s. The Na+ accumulation was prevented by monensin but was unaffected by valinomycin. Ouabain did not influence Na+ uptake, but digitoxin inhibited it. At low K+ the accumulation of Na+ was reduced 3.7-fold below the value at 50 mM K+. 86Rb, employed as a tracer to detect K+, showed a first phase of K+ release while Na+ was accumulated. After 2-3 min, K+ was reaccumulated while Na+ continued to increase in the lumen. T tubules accumulated Cl- on addition of ATP. This suggested that ATP initiated an exchange of Na+ for K+ followed by uptake of Na+ and K+ accompanied by Cl-.


Asymmetry in the mechanism for anion exchange in human red blood cell membranes. Evidence for reciprocating sites that react with one transported anion at a time.

The kinetics of chloride and bromide transport were examined in intact human red blood cells and resealed ghosts. Because the influx and efflux of halide ions are almost equal (less than 0.01% difference), the stimulation of the exchange flux by external halides could be determined by measuring 36Cl or 82Br efflux. When the external halide concentration was increased by replacement of isoionic, isotonic solutions of sucrose and the nontransported anion citrate, the stimulation of the exchange flux was hyperbolic and was maximum at 20 mM halide externally. The K 1/2-out, the external concentration of chloride or bromide which stimulated the efflux to half of its maximum value, was 3 and 1 mM respectively, 15-fold smaller than K 1/2-in which we found to be about equal to the K 1/2 of halide self-exchange with nearly equal internal and external concentrations. Thus, the transport mechanism behaves asymmetrically with respect to these transported halides. Bromide flux was two-fold greater in bromide-chloride heteroexchange than in bromide-bromide self-exchange but it was still much smaller than the chloride self-exchange flux. The maximum influx and efflux of bromide in exchange for chloride were roughly eqal. Thus, since the maximum transport rates in the two directions are nearly equal, the kinetics of bromide equilibrium exchange with equal concentrations on the two sides are controlled on the inside where K 1/2 is greatest. The K 1/2-out Cl was a hyperbolic function of internal chloride concentration and was proportional to the maximum flux at each internal chloride concentration. These results are evaluated in terms of two broad categories of models. We conclude that, in contrast to other ion transport systems which have been shown to have kinetics of a sequential mechanism, anion exchange is compatible with a ping-pong mechanism in which a single site reciprocates between inside- and outside-facing orientations with asymmetric K 1/2 values.


Binding of scorpion toxin to receptor sites associated with sodium channels in frog muscle. Correlation of voltage-dependent binding with activation.

Purified scorpion toxin (Leiurus quinquestriatus) slows inactivation of sodium channels in frog muscle at concentrations in the range of 17-170 nM. Mono[125I]iodo scorpion toxin binds to a single class of sites in frog sartorius muscle with a dissociation constant of 14 nM and a binding capacity of 13 fmol/mg wet weight. Specific binding is inhibited more than 90% by 3 microM sea anemone toxin II and by depolarization with 165 mM K+. Half-maximal inhibition of binding is observed on depolarization to -41 mV. The voltage dependence of scorpion toxin binding is correlated with the voltage dependence of activation of sodium channels. Removal of calcium from the bathing medium shifts both activation and inhibition of scorpion toxin binding to more negative membrane potentials. The results are considered in terms of the hypothesis that activation of sodium channels causes a conformational change in the scorpion toxin receptor site resulting in reduced affinity for scorpion toxin.


Calcium measurement in the periphery of an axon.

Aequorin was microinjected into squid giant axons, the axons were stimulated, and the change in light emission was followed. This response was compared with that found when the axon, in addition to being microinjected with aequorin, is also injected with the dye phenol red. Large concentrations of phenol red injected into axons result in a high probability that photons emitted by aequorin, when it reacts with Ca in the core of the axoplasm, will be absorbed before they escape from the axon; photons produced by the aequorin reaction at the periphery of the axoplasm are much less likely to be absorbed. This technique thus favors observing changes in Cai taking place in the periphery of the axon. Stimulation in 50 mM Ca seawater of an aequorin-phenol red-injected axon at 180 s-1 for 1 min produces a scarcely detectable change in Cai; the addition of 2 mM cyanide (CN) to the seawater produces an easily measureable increase in Cai, suggesting that mitochondrial buffering in the periphery is substantial. Making the pH of the axoplasm of a normal axon alkaline with 30 mM NH4+ -50 mM Ca seawater, reduces the resting glow of the axon but results in an even more rapid increase in Cai with stimulation. In a phenol red-injected axon, this treatment results in a measureable response to stimulation in the absence of CN.


Comparison of proteins from Mycobacterium fortuitum, Mycobacterium nonchromogenicum and Mycobacterium terrae using flat bed electrophoresis.

Polyacrylamide gel electrophoresis of bacterial lysates in a flat bed gives a linear relationship between 1n mol. wt of the proteins and the square root of their migration distances, thereby allowing standardization of different electrophoresis runs and precise comparison between homologous bands. The results obtained with Mycobacterium fortuitum, M. terrae and M. nonchromogenicum strains were used in numerical analysis. Mycobacterium fortuitum and M. nonchromogenicum showed a greater internal similarity than M. terrae, while two strains of the latter clustered with M. nonchromogenicum. The method described allows the comparison of mycobacteria with different generation times and provides a large number of good characters for numerical taxonomy.


Antigenic cross-reactivity of major outer membrane proteins in enterobacteriaceae species.

The protein constituents in the outer membrane (OM) of several serotypes of Escherichia coli and some other Enterobacteriaceae cross-reacted antigenically. Solubilized OM preparations of these bacteria were applied in interfacial precipitin tests to antisera elicited in rabbits against whole bacterial cells, absorbed with their appropriate lipopolysaccharide before testing. The resulting immunecomplexes were analysed on polyacrylamide gels. Protein profiles of the immunoprecipitates showed a considerable antigenic cross-reactivity of outer membrane proteins between most E. coli serotypes. Cross-reactivity, though substantially lower, was also found with OM from three other Enterobacteriaceae species, but was not detectable with Pseudomonas aeruginosa OM. When OM preparations were solubilized at room temperature, the peptidoglycan-bound proteins in the molecular weight range 37,000 to 41,000 predominated in the protein profiles of the immunecomplexes. In profiles of immunecomplexes obtained with boiled OM preparations, a heat-modifiable protein (mol. wt 33,000) predominated. The major OM proteins of the Gram-negative bacterium may therefore play a role as common surface antigens of the family of Enterobacteriaceae.


Autoradiographic study of the localization and evolution of growth zones in bacterial colonies.

Incorporation of [3H]leucine in the bacteria of 18 to 48 h-old colonies of Pseudomonas aeruginosa, Pseudomonas putida, Bacillus thuringiensis, Staphylococcus aureus and Escherichia coli enabled the localization of bacterial multiplication sites by means of autoradiography of sagittal sections. In colonies where fast diameter expansion occurred, all the bacteria from the peripheral corona contributed to peripheral growth; in colonies where the expansion was slower, the growth rate of the bacteria in this region was heterogeneous. Besides this peripheral growth, a central region of bacterial multiplication was always found, but with variable localization and extension. In aerobic species, such as P. aeruginosa and P. putida, the central growth site was limited to the zone of oxygen penetration into the bacterial mass. However, in facultatively anaerobic species, bacterial multiplication dependend on nutrient supply. For 48 h-old colonies of S. aureus, a more complex localization of growth seemed to be affected simultaneously by nutrient penetration and accumulation of toxic substances.


Characteristics of a lipolytic and fatty acid-requiring Butyrivibrio sp. isolated from the ovine rumen.

A naturally occurring fatty acid-requiring Butyrivibrio sp. (strain S2), isolated from the ovine rumen, deacylates plant galactolipids, phospholipids and sulpholipids to obtain sufficient fatty acid for growth. Growth in vitro was promoted by adding to the growth medium a single straight-chain saturated fatty acid (C13 to C18) or vaccenic acid. Palmitoleic and oleic acids also supported growth but gave lengthy lag phases probably due to their toxicity. Linolenic and linoleic acids supported good growth but they were completely hydrogenated to trans-11-octadecenoic acid which was incorporated into the bacterial complex lipids. No chain elongation, chain shortening or desaturation of the added fatty acids occurred and all were substantially incorporated into bacterial lipids of the plasmalogen type, partially as a new type of hydrophobic grouping derived from two molecules of fatty acid. The absence of fatty acid unsaturation poses the question of the maintenance of membrane fluidity within this bacterium.


Glucan-binding proteins of Streptococcus mutans serotype c.

Three glucan-binding proteins have been isolated from the extracellular fluid cultures of Streptococcus mutans serotype c. These proteins were adsorbed to glucans containing 1,3-alpha or 1,6-alpha bonds and linked to various chromatographic supports: they were eluted from columns by a dextran solution. Glucosyltransferase activity was associated with two of the glucan-binding proteins.


Numerical taxonomy of Actinomadura and related actinomycetes.

One hundred and fifty-six Actinomadura strains, marker strains of related taxa, and related isolates from bagasse and fodder were the subject of numerical phenetic analyses using 90 unit characters. The data were examined using the simple matching (SSM), Jaccard (SJ) and pattern (DP) coefficients and clustering was achieved using both single and average linkage algorithms. Cluster composition was not markedly affected either by the coefficient or clustering algorithms used or by test error, estimated at 4.5%. Actinomadura dassonvillei, Actinomadura madurae and Streptomyces somaliensis formed good taxospecies, but the separation of Actinomadura pelletieri strains into two clusters by SJ and SSM analysis requires further study. The single representatives of Actinomadura helvata, Actinomadura pusilla, Actinomadura roseoviolacea, Actinomadura spadix and Actinomadura verrucosopora seemed to form new centres of variation while Actinomadura citrea and Actinomadura malachitica showed much similarity with Actinomadura madurae. Most of the isolates form bagasse and fodder were recovered in two well-defined phena, provisionally labelled clusters 'A' and 'B' which showed little similarity to either Actinomadura or Nocardia strains. The effect of the different coefficients on the aggregation of clusters is discussed.


Trimethylamine oxide: a terminal electron acceptor in anaerobic respiration of bacteria.

Trimethylamine oxide (TMAO) stimulated both the anaerobic growth rate and the growth yield of Proteus NTHC 153. The molar growth yield from glucose and pyruvate in tryptone/yeast extract medium doubled in the presence of TMAO, and the organism grew anaerobically on the non-fermentable substrates L-lactate and formate when TMAO was added to the medium. We conclude that TMAO stimulated growth by serving as a terminal electron acceptor in an oxidative phosphorylation process.


The control of the synthesis of isocitrate lyase in a thermophilic bacillus.

From a strain of Bacillus stearothermophilus, devoid of active pyruvate carboxylase, a mutant (NG-15) was selected that grew on acetate in the presence of glucose. This mutant differed from its parent organism in possessing high activities of isocitrate lyase when grown on all carbon sources tested except nutrient broth, in possessing unusually low activities of NADP+-dependent isocitrate dehydrogenase and in containing increased amounts of isocitrate. Revertants of mutant NG-15 which regained the ability to synthesize active pyruvate carboxylase also synthesized isocitrate lyase and isocitrate dehydrogenase to the same extent as the wild-type strain. These results suggest that the regulatory mechanism for the synthesis of isocitrate lyase in the thermophile may be different from that in mesophilic bacilli.


Influence of oxygen tension on nitrate reduction by a Klebsiella sp. growing in chemostat culture.

At dissolved oxygen tensions of 15 mmHg (2 kPa) and below, nitrate-limited continuous cultures of Klebsiella K312 synthesized nitrate reductase (NR) and nitrite reductase (NiR) and excreted ammonia. Under anaerobic conditions over 60% of the nitrate-nitrogen utilized was excreted as ammonia. In contrast, carbon-limited cultures excreted nitrite at dissolved oxygen tensions of 15 mmHg or below and synthesized NR but not NiR. Ammonia repressed neither NR nor NiR synthesis. These observations indicate that below a critical oxygen tension of 15 mmHg Klebsiella K312 utilizes oxygen and nitrate as electron acceptors. This oxygen tension correlates well with the critical oxygen tension observed for a change from oxidative to fermentative metabolism in cultures of Klebsiella aerogenes. The product of dissimilatory nitrate reduction is ammonia in nitrate-limited cultures but principally nitrite in carbon-limited (nitrate excess) cultures.


The components of Mycoplasma salivarium and its growth medium that are responsible for film formation.

Studies on film production by mycoplasmas revealed that film was produced by completely disintegrated mycoplasma cells on Noble agar in the presence of horse serum. Film production was due to an enzymic reaction between mycoplasma lipase, possibly phospholipase A, and phospholipid in serum.


Description of strains of Peptostreptococcus anaerobius isolated from subcutaneous abscesses in cats.

Strains of Peptostreptococcus, Streptococcus and of a Gram-positive coccus, which was initially isolated as an anaerobe but grew subsequently as a facultative organism, were isolated from subcutaneous abscesses in cats. The cat strains of Peptostreptococcus gave metabolic fermentation products in combinations described for P. anaerobius. The Streptococcus strains conformed to the group S. intermedius. The facultative organism described had the metabolic products of P. anaerobius but the distinctly different biochemical characteristics of S. intermedius and fits neither of the genera strictly.


Investigation of recombinants of human influenza and fowl plague viruses.

Recombinants of human influenza type A viruses, A/Krasnodar/101/1959 (H2N2) or A/Habarovsk/15/1976 (H3N2), and fowl plague virus (FPV), strain Weybridge (Hav1Neq1) were obtained. The genome of the recombinant obtained by recombination of influenza A/Habarovsk/15/1976 virus and FPV contained the genes 4 (HA) and 6 (NA) derived from the influenza A/Habarovsk virus and all the other genes [1, 2, 3, 5 (NP), 7 (M), 8 (NS)] from FPV. The genome of the recombinant of A/Krasnodar/101/1959 virus and FPV contained the genes 2, 4 (HA) and 6 (NA) derived from influenza A/Krasnodar virus and all the other genes [1, 3, 5, (NP), 7 (M), 8 (NS)] from FPV. The recombinants, like FPV, gave high virus yields in chick embryos and could multiply at high temperatures (40 and 42 degrees C), but, like human influenza viruses, were non-pathogenic for chickens and did not replicate in chick embryo fibroblast culture, but did replicate in a human conjunctiva cell line, clone 1-5C-4. The virion transcriptase of the recombinants, in a number of properties determined in vitro, was similar to FPV transcriptase but not to the human influenza virus enzyme.


High molecular weight virus DNA in KB cells infected with ts mutants of adenovirus type 2 under permissive and non-permissive conditions.

Temperature-sensitive (ts) mutants of adenovirus type 2 (Ad2), which are deficient in virus DNA synthesis at the non-permissive temperature, have been used to investigate whether virus DNA replication is required for the occurrence of high mol. wt. Ad2 DNA (greater than 100S, 50 to 90S) in human cells productively infected with Ad2. The high mol. wt. virus DNA has been previously shown to consist of virus and cellular DNA molecules covalently linked. The present data indicate that after infection with DNA-ts mutants, the production of high mol.wt. virus DNA is much less sensitive to restrictive conditions than the synthesis of unit length (34S) Ad2 DNA. This finding lends further support to the idea that the occurrence of high mol. wt. virus DNA is independent of the synthesis of unit length virus DNA.


Studies on the mechanism of influenza virus entry into cells.

Inhibitors of glycolysis, oxidative phosphorylation, protein synthesis, membrane Na&-K& transport and microfilament and microtubule function have been employed to elucidate the mechanism of influenza virus uptake by CAM and CEF cells. Electron microscopy demonstrated uptake of virus by viropexis in the presence of all these inhibitors. Utilizing a pulse labelling technique, virus entering CEF cells in the presence of inhibitors was shown to initiate specific virus polypeptide synthesis after neutralization of remaining extracellular virus and removal of the inhibitors. As a consequence of these findings an energy independent mechanism of viropexis has been proposed.


Proteins specified by togaviruses in infected Aedes albopictus (Singh) mosquito cells.

Yields of greater than 10(7) p.f.u./ml at 28 or 37 degrees C of the alphavirus Sindbis and the flavivirus Kunjin were obtained in the Aedes Albopictus (Singh) cell line, the latent periods being 4 to 6 and 10 to 12 h, respectively. Despite a high background of host protein synthesis, virtually all the virus-specified proteins of the flaviviruses Kunjin, Dengue-2 and Japanese encephalitis were labelled and resolved by slab gel electrophoresis of infected and uninfected cell proteins. In contrast, only one induced protein, of mol. wt. 30 000, was identified in cells labelled during Sindbis virus infection. The envelope glycoprotein V3 of Kunjin virus was resolved as a double band in samples of infected cytoplasm labelled with 3H-glucosamine, similar to that of carbohydrate-labelled V3 in vertebrate (Vero) cells. Attempts to reduce host protein synthesis selectively during labelling periods were unsuccessful using either a hypertonic inhibition block or treatment with 0.1 mu g actinomycin D per ml. The most efficient labelling of Kunjin virus-specified proteins was achieved at 37 degrees C in the presence of actinomycin D. The largest non-structural flavivirus protein NV5 migrated slightly faster than NV5 from infected vertebrate (Vero) cells. The small non-structural proteins NV1, NV1 1/2 and NV2 from infected mosquito cells were successively trimmed during post translational periods exceeding 70 min, compared to much shorter periods reported previously for post translational modifications of these proteins in vertebrate cells.


Study of a new strain of paramyxoviruses isolated from wild ducks: structural polypeptides.

By polyacrylamide gel electrophoresis, Duck/Mississippi/75 virus was shown to contain five different types of polypeptides of mol. wt. ranging from 76 X 1O(3) to 43 X 10(3), two of which were glycosylated (mol. wt. 76 X 10(3) and 57 X 10(3). A comparison of this data with similar results obtained using Yucaipa and Newcastle disease virus (NDV) revealed a similarity with NDV, concerning the number, position and mol. wt. of the polypeptides. Haemagglutinating and neuraminidase properties are associated with surface glycoproteins which represent at least 40% of the virus protein. After KCl and Triton X-100 treatment and centrifugation on linear sucrose density gradients (10 to 25%, w/w) it was possible to isolate glycoprotein VP1 of mol. wt 76 X 10(3) with which haemagglutinating and neuraminidase activities were associated.


The effect of inhibitors of glycosylation on interferon production in human lymphoblastoid cells.

Interferon production was inhibited in the Namalwa line of human lymphoblastoid cells by treatment with 2-deoxy-D-glucose or D-glucosamine. D-Glucosamine also inhibited protein synthesis and the cells were no longer viable, whereas 2-deoxy-D-glucose allowed protein and RNA synthesis to continue at control rates, and the cells remained fully viable. It is concluded that a glycosylation step is essential for production of lymphoblastoid interferon.


Molecular species of interferon induced in mouse L cells by Newcastle disease virus and polyriboinosinic-polyribocytidylic acid.

Interferons were stimulated in mouse L cells by Newcastle disease virus (NDV) or by polyriboinosinic-polyribocytidylic acid poly(rI).poly(rC). These were fractionated by sequential affinity chromatography on bovine plasma albumin (BPA)-Sepharose and on omega-carboxypentyl (CH)-Sepharose. Based on their interaction with CH-Sepharose, interferon induced by NDV was resolved into three major bands of activity (L/NDV-1,2,3) and poly(rI).poly(rC)-interferon into two (L/rI:rC-1,2). These interferon components were purified to a specific activity of 3 X 10(7) to 4 X 10(7) units/mg protein by antibody affinity chromatography and examined by electrophoresis in SDS-polyacrylamide gels. A total of five molecular species was thus identified for NDV-induced interferon and three for poly(rI).poly(rC) induced interferon, as summarized in Table 1. We conclude from our observations that mouse interferons can be produced by L cells in multiple forms with specific physiochemical properties and in proportions determined by the type of agent employed for induction.


Characterization of two temperature-sensitive mutants of adenovirus type 5.

The properties of two temperature-sensitive mutants ts 18 and ts 19 of adenovirus type 5 were studied. It was demonstrated that they had a defect such that they failed to assemble virus and showed defective processing of infected cell polypeptides at the restrictive temperature. Analysis, after protease digestion, of the virions produced at the permissive temperature by SDS PAGE, and of the substrate availability of the mutants to the virus protein kinase suggested that polypeptide VI was defective in these mutants.


The toxic effect of double-stranded RNA for interferon-treated cells: evidence for a heterogeneous cellular response and the role of the cell nucleus.

When L929 cells were treated with interferon and subsequently with poly(rI).poly(rC), there was a pronounced toxic effect. Most of the cells lysed, but some survived and grew at the same rate as control cells to yield cells which were as sensitive to the effects of interferon and poly(rI).poly(rC) as the original population. The proportion of surviving cells did not vary with either the cell cycle or the cell density. The treated cells produced interferon and some of the interferon was produced by the resistant cells. Cells which had been X-irradiated before treatment with interferon and poly(rI).poly(rC) behaved similarly so cell division was not necessary for the development of toxicity. The toxic effect also developed when cells were enucleated with the aid of cytochalas in B after treatment with interferon, but not if they were enucleated before treatment. It is concluded that the nucleus is essential for interferon to exert its effect on the cells, but not for the development of cytotoxicity after the addition of poly(rI).poly(rC).


The toxic effect of double-stranded RNA for interferon-treated L cells: studies on membrane transport and with cell-free systems.

We have tested two possible explanations for the toxic effects observed in L cells treated with interferon followed by poly(rI).poly(rC), namely (1) that the toxicity was preceded by and due to a change in membrane permeability which could be monitored by measurement of ion fluxes, or (2) that the toxicity was due to the action of the inhibitors of protein synthesis which are known to be formed when extracts from interferon-treated cells are treated with poly(rI).poly(rC) in vitro. Neither explanation was found to be correct.


Copper chelate affinity chromatography of human fibroblast and leucocyte interferons.

Human fibroblast and human leucocyte interferons display a strong affinity for the copper chelate of bis-carboxymethyl amino agarose, binding tenaciously over a wide pH range (7.4 to 4.0). Their binding is apparently irreversible on a sorbent saturated with copper (24.8 mumol of Cu2+/ml of column bed). However, both interferons can be partially recovered from sorbents of lower copper content, prepared by leaching the columns with sodium citrate at pH 9.0. The recovery of fibroblast interferon from a leached sorbent (5.8 mumol of Cu2+/ml of column bed) is about 30% and that of leucocyte interferon about 60%. Moreover, the strength of binding of leucocyte interferon can be modulated by leaching copper chelate-agarose with citrate of varying concentration.


Stimulation of recombination in phage T4 by nitrous acid-induced lesions.

Recombination of phage T4 can be stimulated more than sixfold above the spontaneous level by treatment with nitrous acid, indicating that the lesions induced by this agent are strongly recombinogenic. Two temperature sensitive mutants defective in exonuclease functions showed less than the wild-type spontaneous level of recombination even after nitrous acid treatment and a ligase mutant showed a highly elevated frequency of recombination after treatment. Since these same mutants have analogous effects on spontaneous recombination, the results imply that nitrous acid-induced lesions in DNA stimulate a recombinational repair process similar in some of its enzymic steps to spontaneous recombination.


[Do male germ cells begin meiosis during fetal life?].

The existence of a preleptotene chromosome condensation and decondensation stage occuring between the last premeiotic interphase and the leptotene stage was described in numberous plants. This stage was also reported in the human fetal oocyte and in various animals (rabbit, sheep, mouse). A similar process of chromosome condensation was described in the human foetal testis, but in this latter, the decondensation phase leading to leptotene was never observed. According to this observation and to various experimental results from the literature, the preleptotene condensation stage could be related to the processes of meiotic initiation. It could represent a phase of transition between mitotic and meiotic behaviour during which the germinal cell could be sensitive to meiosis-inducing factors. It is suggested that the male germinal cell 46,XY could enter meiosis. This hypothesis is confirmed by the observation of the capacity of the XY germ cell in the mouse to become an oocyte. This capacity is normally not expressed, due to the repressive control of the adjacent Sertoli cells. Thus, stimulation of the germinal cell to enter meiosis could result from environmental factors rather than from a genetic programmation.


[Structural abnormalities of the Y chromosome. Observations in ten cases].

The authors report ten cases of structural anomalies involving the Y chromosome: five cases of a dicentric Y chromosome, one ring Y chromosome, one case of a Y isochromosome containing the long arms, one deletion of the long arms (Yq-), one case of an abnormally long Y chromosome (Yq+) and one Y-autosome translocation. Analysis of clinical and chromosomal correlations, especially with respect to sexual differentiation, led to discussing the role of the Y chromosome.


[Congenital cataract linked to the Y chromosome].

A possible Y linked form of congenital cataract is reported, but an autosomal dominant mode of inheritance cannot be ruled out.


Attenuated influenza produced by experimental intranasal inoculation.

To assess the relative effect of natural versus experimental influenza illness on pulmonary function, we compared 43 normal adults with documented nonpneumonic influenza A infection during three outbreaks, 1974 (A/Port Chalmers/74), 1975 (A/Port Chalmers/74), and 1976 (A/Victoria/75) to 24 normal volunteers following nasal inoculation with wild-type influenza A/England/42/72, A/Scotland/74 or A/Victoria/75. In naturally acquired illness, abnormalities in small airway functiion and transiently increase airway reactivity were observed. In contrast, no such dysfunction was observed in experimentally induced illness. This group manifested milder illness and significantly shorter duration of cough.


The absence of differences in cellular immunity in elderly individuals with and without delayed local cutaneous reactions to influenza vaccine.

Two groups of elderly subjects who received bivalent influenza virus vaccine were identified. Those in Group I manifested marked local reactions, suggestive of delayed hypersensitivity reactions, whereas those in Group II, matched with Group I for vaccine preparation, had no cutaneous reactions. In vitro assays of immune function were performed on pairs of subjects from the two groups and included serum immunoglobulin and complement levels, antibody response to vaccine, lymphocyte transformation to mitogens (phytohemagglutinin, pokeweed mitogen and concanavalin A) and antigens (streptokinase-streptodornase, influenza virus vaccine antigens and multiple mixed lymphocytes), and polymorphonuclear leukocyte chemotactic responsiveness. There was no demonstrable correlation between delayed local cutaneous reaction and preservation of in vitro cell-mediated immune function in these elderly individuals.


Clinical evaluation of a rubella passive hemagglutination test system.

A recently marketed passive hemagglutination (PHA) test (Rubacell, Abbott Laboratories) was compared to the hemagglutination inhibition (HI) test for the detection of antibody to rubella virus. The performance of the PHA system in determining immunity to rubella was evaluated by comparing the PHA results and HI results on 1, 086 randomly selected sera submitted for routine premarital and prenatal testing. Of the 1, 079 specimens assayable by both procedures, 1, 053 of the results (97.6%) were in agreement on initial testing. When the 26 initially discrepant specimens were retested for clarification, there was final agreement in 1, 067 of the specimens (98.9%). Twelve specimens were classified as persistently discrepant (five were not retested by PHA) and seven were unassayable by HI. Seven of the specimens with discrepant results were PHA positive and HI negative, and five were PHA negative and HI positive. Discussion of the two tests with respect to technical difficulty, cost, and controls is also included.


HBeAg and anti-HBe detection by radioimmunoassay: correlation with vertical transmission of hepatitis B virus in Taiwan.

A sensitive radioimmunoassay technique was used to detect hepatitis B e antigen (HBeAg). A strong correlation was found between HBeAg positivity of the serum of hepatitis B surface antigen (HBsAg) carrier women in Taiwan and the subsequent development of surface antigenemia in their babies. All babies who became chronic HBsAg carriers were born to HBeAg positive women, maternal HBeAg positivity being a better prior indication of chronic antigenemia developing in the baby than the HBsAg titer in the mother's serum.


Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis.

Non-A, non-B viral hepatitis was transmitted to four colony-born chimpanzees by infusion of three lots of antihemophilic factor (factor VIII) implicated in the transmission of non-A, non-B hepatitis to two human recipients. All four inoculated animals showed histopathological evidence of viral hepatitis, and all demonstrated significant ALT elevations between seven and one-half weeks after inoculation. Acute-phase plasma from one of the infected chimpanzees (no. 771) was shown to induce non-A, non-B hepatitis in two other chimpanzees approximately three weeks after their inoculation. In addition, an acute-phase open liver wedge biopsy obtained from animal no. 771 was processed and examined by immune electron microscopy (IEM) for virus-like particles with convalescent serum from a serologically confirmed case of non-A, non-B hepatitis. Twenty-five to 30 nm (mean = 27 nm) diameter virus-like particles that were either "full" or "empty" were identified in this liver preparation by IEM. Two additional chimpanzees inoculated with a cesium chloride gradient fraction of an isopycnically banded liver homogenate (animal no. 771) also developed elevated ALT activity two to two and one-half weeks later. Our findings have experimentally verified that commercially produced factor VIII materials can induce non-A, non-B hepatitis in champanzees and that the disease can be subpassaged in these animals by inoculation of either acute-phase plasma or liver. These results also provide evidence for the association of 27 nm-diameter virus-like particles with non-A, non-B viral hepatitis.


ECHOvirus 33 replication in human peripheral white blood cells.

ECHOvirus 33 isolated from the cerebrospinal fluid of a patient with agammaglobulinemia was shown to replicate in vitro in peripheral leukocyte suspensions from a normal antibody negative donor. Replication was demonstrated by use of sequential dilution experiments. Washed glass adherent mononuclear cell cultures from a normal antibody negative donor were also capable of supporting ECHOvirus 33 replication in vitro. Leukocyte suspensions from the infected agammaglobulinemic patient extinguished detectable infectious virus in vitro.


Evaluation of Aedes albopictus tissue culture for use in association with arbovirus isolation.

The susceptibility and sensitivity of Aedes albopictus cell cultures to five different primary and four different low-passage arboviruses were tested. Yellow fever, West Nile, Ilesha, eastern equine encephalitis, and Flanders viruses replicated in A albopictus tissue cultures. Replication was determined by the ability of selected tissue culture fluids to infect suckling mice, and by recovery from tissue culture fluid of progressively increasing amounts of complement-fixing (CF) antigen with time. Virus persistence was demonstrated with Nodamura, western equine encephalitis, and Mayaro viruses, but multiplication was not proven; neither persistence nor multiplication was demonstrated with a Kemerovo group virus. When yellow fever and Ilesha viruses were simultaneously inoculated into A albopictus culture, CF antigen for each was consistently detected. In a more detailed comparative study of field specimens, 12 unpassaged strains of yellow fever virus were tested for infectivity in A albopictus tissue culture, Vero cells, and baby mice. Higher titers of virus were detected (0.8--2.3 log ID50 per ml) in Vero cell culture than in A albopictus tissue culture or baby mouse systems. These results suggest the feasibility of using A albopictus cells in association with the primary isolation of arboviruses.


Role loss and working-class manic depression.

This first part of a multiphase longitudinal study looks at life events implicated in manic depression among an American working class, bipolar sample. Three turning points are identified. a) Stressful life events occurred that resulted in loss of significant social roles. b) Attempts to regain or replace the roles or otherwise "fight back" proved ineffective. c) Retreat via depression, and rebellion via mania, ensued. These turning points were well verified for 75 per cent of the subjects prior to first onset, and for 56 per cent prior to most recent onset. Special methodological issues are raised, and the need for a biopsychosocial etiology of manic depression is suggested.


The Minnesota Multiphasic Personality Inventory in predicting response to pharmacotherapy of neurotic outpatients.

The utility of the Minnesota Multiphasic Personality Inventory (MMPI) in predicting treatment response to pharmacotherapy for a group of 54 anxious and 43 depressed outpatients was examined. Discriminant function analyses using the MMPI scales were conducted on groups of improved and unimproved patients. Several significant function, as well as zero-order, differences were found. In general, improved patients scored significantly lower on scales reflecting depression and obsessive-compulsive or schizoid tendencies. They also obtained lower scores on scales measuring interpersonal sensitivity and suggestive of character traits such as low frustration tolerance, impulsivity, and resentment toward authority figures. Additional analyses in which several different profile types were compared for treatment outcome revealed few differences among groups.


Status epilepticus. An uncommon hysterical conversion syndrome.

The distinction between hysterical and organically determined epileptic seizures may be more difficult than is sometimes supposed, and misdiagnosis can have dire consequences. Hysterical seizures may on occasions present as life-threatening crises requiring urgent and intensive treatment. Three such cases, each of which received the diagnosis of status epilepticus, are reported, and their management is discussed.


The interrelationship between self-image disparity and social competence, defensive style, and adjustment status.

Groups of 40 psychiatric and 40 nonpsychiatric male patients were subdivided into equal groups of high and low social competence. Each patient completed a task battery which included three measures of self-image disparity and the Byrne repression-sensitization scale. High competence patients of both types were found to have higher self-image disparities than low competence patients. Psychiatric patients were found to have higher disparity scores than nonpsychiatric patients, although some evidence indicated that this was true only for the low competence groups. Higher scores on the Byrne scale (indicating sensitization) were found for high as compared to low competence patients, and for the psychiatric as compared to nonpsychiatric groups. Defensive style correlated significantly with each of the self-image measures. The results were discussed in the context of both developmental and Rogerian formulations. It was concluded that an individual's maturational level influences both self-image and defensive style, even when the individual is judged psychologically maladjusted.


And if that doesn't work, what next ...? A study of treatment failures in schizophrenia.

A systematic study of schizophrenic patients who did not respond satisfactorily to one of five different forms of treatment given under controlled conditions showed that almost all of them responded satisfactorily to subsequent treatment with the combination of ataraxic drugs and group psychotherapy. Whatever the original form of treatment, and despite subsequent retreatment with drugs and group psychotherapy, there was a treatment-resistant core--a few patients who either responded very slowly or who improved relatively little.


Postpartum mania in bipolar manic-depressive patients withdrawn from lithium carbonate.

Three women, previously diagnosed as bipolar I manic-depressive, were withdrawn from lithium carbonate prophylaxis immediately prior to their pregnancies. The patients had been euthymic while on lithium carbonate for at least 3 1/2 years prior to their pregnancies. Two of the three patients developed a manic syndrome within 2 weeks postpartum. The use of lithium carbonate during pregnancy, and particularly in the postpartum period, requires reassessment. We advocate an ongoing clinical relationship and the reinstitution of lithium in the third trimester in most cases.


Opposite effects of naloxone on substance P-induced changes in brain DOPA synthesis and in locomotor activity in rats.

Intracerebroventricular injection of substance P (SP) enhanced the synthesis of dopamine and noradrenaline (measured as increase in DOPA formation after inhibition of the aromatic L-amino-acid decarboxylase) in rat brain. These biochemical effects were blocked in most brain regions by pretreatment with naloxone. SP also induced vasodilation, salivation and increased locomotor activity. These effects were not antagonized, but, in the case of locomotor activity, potentiated by naloxone. The data suggest the existence of specific SP-containing neuronal pathways for behavior, which pathways are not related to those regulating the synthesis of brain catecholamines.


Dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) levels of individual brain nuclei, effects of haloperidol and pargyline.

Noradrenaline (NA), dopamine (DA) and DOPAC were determined with a newly developed radioenzymatic method simultaneously in the striatum, limbic system, hypothalamus and in catecholamine-containing cell groups of the rat brain. Only a loose relationship could be established between DOPAC and DA contents in the various brain areas. The lowest relative DOPAC level (DOPAC/DA ratio) was found in the median emience, while it was the highest in the periventricular nucleus of the hypothalamus. Haloperidol increased the DOPAC level in only part of the nuclei examined (striatum, olfactory tubercle, central amygdaloid nucleus), while in other limbic regions as well as in the hypothalamic dorsomedial, arcuate and paraventricular nuclei it proved to be ineffective. The DOPAC level in the locus coeruleus was decreased by haloperidol. Pargyline caused an appr. 50% decrease of DOPAC content of most of the nuclei in 10 min; the effectivity of the drug did not show parallelism with that of haloperidol. The monoamine oxidase inhibition caused no change in the DOPAC level in the hypothalamic periventricular and paraventricular nuclei. Results are discussed as a consequence of different reactivity of various DA-ergic terminals and catecholamine cell bodies to haloperidol and pargyline.


A highly sensitive and precise radioenzymatic assay for plasma epinephrine and norepinephrine.

A modification of the procedures for simultaneous radiometric determinations of plasma epinephrine (E) and norepinephrine (NE) was developed. High performance liquid chromatography (HPLC) is excellently suited to separate the radioactive products of the enzymatic methylation of catecholamines. The time-saving procedure shows significant advantages as against the conventional method of isolating normetanephrine and metanephrine by thin layer chromatography. The high sensitivity (detection limit = 1 pg), specifity, and good precision (cv = 6%) of this assay are demonstrated.


An in situ study of the hypothalamo-neurohypophysial complex of the freshwater teleost Ompok bimaculatus (Bloch) with a note on the tetrapodan features of its vascularization.

In Ompok bimaculatus the neurosecretory axons of both the pars magnocellularis and pars parvocellularis component of the nucleus preopticus contribute to the formation of the left and right main tracts. At rostral levels, one third of the tracts are loosely built forming a king of curtain, while they become more compact at caudal levels. The caudal two thirds of the main tracts give off several pairs of lateral tracts which join at the midline to form the paired median tracts. The median and the main tract jointly enter the pituitary as a common tract which, on entering the proximal pars distalis, separates into two and enters the pars intermedia. The hypothalamic and the hypophysial arteries take their origin from the internal carotid artery. The former contribute to the formation of the primary capillary plexus of the median eminence, whereas the latter enter the pituitary directly and ramify in the neuroadeno-interface. The primary capillary plexus is in close topographical contact with the neurosecretory axonal complex where the median and common tracts are formed. At this site at least some axons might have their endings on the capillary plexus. Thus, this region my be comparable in structure to the median eminence of the tetrapods. The neurons of the nucleus lateralis tuberis of O. bimaculatus are AF-positive. The infundibular cavity extends into the main neurohypophysial trunk and is lined by ependymal cells like the third ventricle.


Influence of fluoride on the uptake of 51Cr-chromate by human erythrocytes.

Uptake of 51Cr-chromate by freshly collected human erythrocytes was inhibited by 90 mM sodium fluoride only in cells preincubated with fluoride. In vitro storage also increased the sensitivity of the cells: 90 mM NaF clearly inhibited the uptake of chromate in cells stored in vitro for 5 weeks. Gel chromatography revealed two forms of 51Cr within the cells, one of small molecular weight, which thin layer chromatography indicated was unchanged chromate; the other form was apparently bound to macromolecules such as hemoglobin.


Reactions of molybdenum-sulphur compounds with cyanide: chemical evolution and deactivation of molybdoenzymes.

Reactions of molybdenum-sulphur compounds with cyanide are reported which may be relevant to (1) the chemical evolution of molybdoenzymes and (2) deactivation of molybdoenzymes by cyanide. (1) With aqueous cyanide MoS2 gave thio-bridged complex anions [(Mo(CN)6)2(mu-S)]6- and [(Mo(CN)4(mu-S))2]6-. Under prebiotic conditions such complexes could have been formed similarly from molybdenite and may have been precursors of molybdoenzymes. (2) Only those compounds which contained terminal sulphur bound to molybdenum (i.e., Mo = S groups), viz. oxothiomolybdates and the complex [(Mo(mu-S)(S)(Et2NCS2))2], reacted with cyanide; thiocyanate was formed and the molybdenum underwent two-electron reduction. That the cyanolysable sulphur of xanthine oxidase reacts in the same way with cyanide suggests the presence of a Mo = S group which could be a structural feature of the enzyme or could have been formed by initial cyanolysis of a bound persulphide or cysteine residue.


Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat.

A study has been made of the mechanism of the mutual antagonism between copper and zinc in rats. Dietary zinc concentrations of up to 450 mg/kg had no effect on intestinal 64Cu absorption but 900 mg/kg caused a 40% reduction. This was associated with an increase in the mucosal uptake of 64Cu in the small intestine. This occurred mainly in the form of metallothionein and it appeared that copper displaced zinc from the protein after its synthesis had been induced by zinc. Ths intestinal absorption of 65Zn was decreased by 20% when the dietary copper intake was increased from 3 to 24 mg/kg. Further increases in copper intake to 300 mg/kg did not cause any additional decrease in 65Zn absorption or any change in the association of intestinal 65Zn with metallothionein. Concentrations of this protein in the intestinal mucosa were not influenced by dietary copper intake.


Quadruple sectoranopia and sectorial optic atrophy: a syndrome of the distal anterior choroidal artery.

Loss of upper and lower homonymous sectors in the visual field, and wasting of corresponding sectors in the retinal nerve fibre layer, followed ligation of the distal part of the anterior choroidal artery in a patient with a meningioma of the velum interpositum. Clinical and radiological evidence indicated that the visual pathway was damaged within that part of the lateral geniculate body that is served by the anterior choroidal artery.


Immune complexes in myasthenia gravis.

Complement components were measured and immune complexes were sought in 75 patients with myasthenia gravis. Thirty-four per cent had decreased concentrations of complement component C4, and 29% had circulating immune complexes. The greatest immunological abnormalities were found in patients with mild disease which supports recent immunoelectronmicroscopic findings.


Haemophilic neuromyopathy.

Twenty haemophilic patients were examined neurologically and found to have varying degrees of muscle atrophy. The pathogenesis of the atrophy was investigated by electromyography, serum muscle enzyme levels, and muscle biopsies. In most cases the EMG showed such abnormalities as reduced numbers of functioning motor units and "myopathic" motor unit potentials. Serum enzyme levels were frequently raised, and type 2 fibre atrophy was found in the three patients who underwent muscle biopsy. These findings suggest the presence of neuromyopathic involvement in haemophilic patients.


Pathophysiological mechanisms in cerebral palsy.

To investigate some of the pathophysiological mechanisms in cerebral palsy, surface electromyograms (EMG) were recorded from pairs of flexor/extensor muscles during both voluntary and passive flexion/extension of upper and lower limbs of 20 patients. Elbow, knee, or ankle joint angles were measured simultaneously, as well as the force required to flex/extend the limbs passively at frequencies of 0.1--1.0 Hz. In addition, single motor units were recorded from the first dorsal interosseous muscles of six of the patients. Almost all patients showed resistance to passive movements (hypertonia). This hypertonia did not necessarily impair voluntary flexion/extension movements if alternating EMG activity was maintained in at least one of the pairs of flexor/extensor muscles involved in the movement. In six severly involved patients, there was a complete breakdown in the reciprocal relationship between reciprocally acting pairs of flexor/extensor motoneurones, which resulted in synchronous activation (co-contractions) of flexor/extensor muscles during both voluntary and passive movements. In these patients the hyperactive segmental reflex added to the disabling effects of co-contractions during voluntary movements. Single motor units recorded from patients with dystonic movements were recruited with variable delays (2--10 s) and usually discharged intermittently at high frequencies (60--120/s). This abnormla motor unit discharge pattern may relate to pathology of the basal ganglia.


Alexander's disease: case report including histopathological and electron microscopic features.

We report a case of Alexander's disease in a black South African boy of 9 years. The child presented with a grossly abnormal stooped posture, generalised weakness, and slurred nasal speech. Computerised tomography revealed diffuse low radio-density confined to the white matter, and enlarged ventricles. Cerebral biopsy confirmed the diagnosis. The histopathological and electron microscopic features are essentially the same as those described in previous reports. We note the presence of dense clumps of material within some of the Rosenthal fibres, and can find no reference in the literature describing this. Sural nerve biopsy was normal.


Relationship between presence of vasoconstrictor activity in cerebrospinal fluid and time after subarachnoid haemorrhage from rupture of cerebral arterial aneurysms.

The relationship between clinical condition and vasoconstrictor factors in cerebrospinal fluid was studied in 19 patients for up to six weeks after subarachnoid haemorrhage. Vasoconstrictor activity was assayed biologically. Sixteen of 19 patients improved as vasoconstrictor activity declined; this pattern was not significantly influenced by surgery. Serial angiography was performed on three patients and a qualitative relationship was shown between arterial dilatation, clinical improvement, and reduced pharmacological activity.


Plasma and cerebrospinal fluid tryptophan in multiple sclerosis and degenerative diseases.

Tryptophan and competing neutral amino acid levels were found to be diminished in the plasma of patients with multiple sclerosis and degenerative diseases, the greatest decrease being of tryptophan. Cerebrospinal fluid tryptophan was decreased in multiple sclerosis and motor neurone disease, while leucine and valine were increased. These changes might lead to decreased synthesis of brain serotonin and brain proteins. The ratio between neutral amino acids and tryptophan might be used as an ancillary test in the screening of degenerative diseases.


Spinal cord regeneration in rats made immunologically unresponsive to CNS antigens.

Seventy days after complete spinal cord transection, both treated and untreated rats showed evidence that some corticospinal axons had regenerated. Rats made immunologically unresponsive to CNS tissue showed no increase in corticospinal regeneration as measured by orthograde axoplasmic flow of tritated proline or retrograde axoplasmic labelling with horeseradish peroxidase. However, treated rats did demonstrate electrophysiological evidence of regeneration of long ascending sensory pathways. Tolerant animals additionally treated with cyclophosphamide showed corticospinal axonal regeneration by tritated proline transport and electrophysiological techniques and also showed electrophysiological evidence of ascending sensory tract regeneration.


Involvement of peripheral vasomotor fibres in carpal tunnel syndrome.

It is often assumed that large diameter nerve fibres are affected selectively in patients with compressive peripheral nerve lesions. However, in five of 13 patients with the carpal tunnel syndrome, plethysmography revealed that the normal digital vasoconstrictor response to inspiration was abolished in the index finger but preserved in the little finger of the affected hand. This indicates that the function of sympathetic efferent fibres destined for a median-innervated digit is sometimes disturbed also in patients with median nerve entrapment at the wrist.


Cutaneous sensory function in diabetes mellitus.

That disorders of cutaneous sensation are common in diabetes mellitus can be substantiated by quantitative cutaneous sensory testing. Cutaneous sensory disturbances are not clearly related to clinical factors such as the type, treatment, or duration of diabetes, or ocular complications. Diabetics can be distinguished from nondiabetics on quantitative examination of skin sensation. Juvenile diabetics appear to have fewer cutaneous abnormalities than adults who develop the disease, but the juvenile diabetic is not spared. Disorders of cutaneous sensation may represent a fundamental abnormality of the nervous system in diabetes mellitus. While altered peripheral sensory mechanisms are likely, abnormality of central sensory processing is not excluded by the results of this study.


Single fibre electromyography in central core disease.

Single fibre electromyography in the extensor digitorum communis muscle was studied in five patients with central core disease. The average number of muscle fibre action potentials belonging to the same motor unit was higher in patients than in healthy subjects of the same age. The increase in motor unit fibre density is consistent with increased terminal innervation ratio described in other papers about central core disease.


Cluster headache: trial of a combined histamine H1 and H2 antagonist treatment.

Fifteen patients with symptomatic cluster headache participated in a double-blind crossover trial of a combined histamine H1 and H2 antagonist treatment. The trial lasted six weeks. There was no significant improvement on active treatment as regards mean number of headache attacks per week, intensity, or duration of attacks. These results suggest that histamine does not play a significant role in the pathogenesis of cluster headache.


Clonic hemifacial spasm from posterior fossa arteriovenous malformation.

A 21 year old woman presented with a two year history of right sided clonic hemifacial spasm. Investigations showed a large arteriovenous malformation on the right side of the posterior fossa and surgical exploration was undertaken. Early follow-up at six months showed a complete cure.


The significance of cerebral atrophy for the symptomatology of Parkinson's disease.

Hitherto published results on the impact of brain atrophy on the neurological and psychopathological sympion of this problem without risk of complications. We investigated 173 parkinsonian patients (89 men, 84 women) aged 37--83 years. Besides CT in all patients a standardized neurological and psychopathological investigation was carried out, including psychological tests, intelligence, personality structure, fine motor performance and visual reaction times. The investigations revealed pronounced correlations between CT-findings and more severe clinical symptomatology and a corresponding impairment in daily activities in the levodopa-treated and particularly in the untreated group, above all when there was a combination of cortical atrophy and ventricular enlargement. The same was true for fine motor performance and simple and complex reaction times. These functions were more impaired in patients with brain atrophy, irrespective of its localisation, whether cortical atrophy or ventricular enlargement. In contrast, no statistically significant relationship between the different parameters of brain atrophy and intelligence could be found. Considering cortical atrophy as a specific sign in Parkinson's disease -- our results are in favour of this assumption -- and ventricular enlargement more related to increasing age, parkinsonism is influenced by extranigral lesions inherent in the disease and dependent on increasing age.


Blood selenium in chronic spinal muscular atrophy.

The spinal muscular atrophies (SMA) of childhood comprise the second most common fatal recessive disease after cystic fibrosis, yet the nature of the biochemical defect causing the anterior horn cell degeneration is totally unknown. Recent reports of a cluster of adult motor neurone disease cases from a high seleniferous area in South Dakota have prompted the study of blood selenium in children with SMA in Australia. Eight children with chronic SMA were tested, in addition to 9 obligate heterozygote carriers of the gene. Blood selenium levels of patients and carriers did not differ significantly from that observed in controls. The mammalian effects of selenium toxicity are discussed.


Clinical and electrophysiological studies of diphtheritic neuritis in Jordan.

Eleven patients with acute diphtheritic neuritis were studied clinically and electrophysiologically. Decreased conduction velocity and increased distal motor latency were present in most patients within two weeks of the onset of neurological symptoms. Velocities later fell to approximately 45% of mean normal values. Wasting with electrophysiological evidence of denervation was present in 3 patients. Nerve conduction studies had returned to normal within 3 months in 8 patients. There was a striking dissociation between the time course of the clinical and the neurophysiological abnormalities: early in the illness, peripheral nerve conduction was normal in some patients despite the presence of severe weakness, and later, the maximum electrophysiological abnormalities were sometimes found after clinical recovery had commenced. The nature and sequence of the clinical and electrophysiological changes are in accord with the known pattern and distribution of the pathological changes in the disease.


Lack of correlation between spontaneous fasciculations and double discharges of voluntarily activated motor units.

We have studied the possible correlation between spontaneous fasciculations and double discharges or voluntarily activated motor units in myelopathies and other proximal neuropathies. Though both these phenomena are common in these diseases, they seem to have no correlation in individual muscles. It is concluded that spontaneous fasciculations and doubling of voluntarily activated motor unit potentials have different sites of origin or different mechanism. For example, if doubling reflects a disturbance of firing in the axon hillock, spontaneous fasciculations may originate in a more peripheral part of the motor axon.


Observations on the effect of injection of lymphocytes from multiple sclerosis and Guillain-Barré syndrome in the rabbit eye model.

The effect of 10 X 10(5) peripheral blood lymphocytes (PBL) obtained from patients with multiple sclerosis (MS), Guillain-Barré syndrome (GBS) and healthy controls was studied after injection into the rabbit eye. Infiltration of inflammatory cells, strikingly localized to myelinated strips, was obtained with PBL from some of the MS patients and controls, indicating the non-specificity of the phenomenon. PBL from 2 GBS patients gave the strongest infiltration. No effect was obtained with 10 X 10(4) PBL or CSF lymphocytes from MS patients, indicating that the number of lymphocytes is an essential factor in the induction of lesions.


Distal slowing of motor nerve conduction velocity in diabetic polyneuropathy.

Using the latencies of M response and F wave, motor nerve conduction was assessed along the entire course of the nerve from the spinal cord to the muscle in 102 diabetics and 74 control patients. In diabetics, latencies were increased and conduction velocity decreased over both proximal and distal segments. However, the latency ratio of the proximal to distal segment (F ratio) was slightly but significantly smaller in diabetics (mean +/- SD:0.93 +/- 0.14, 1.35 +/- 0.20, 1.09 +/- 0.19 and 1.02 +/- 0.19 for median, ulnar, tibial and peroneal nerves, respectively) than in control patients (1.05 +/- 0.09, 1.41 +/- 0.12, 1.17 +/- 0.13 and 1.08 +/- 0.12). These findings suggest that motor conduction abnormalities in diabetic polyneuropathy are diffuse over the total length of the nerve, but more intense in the distal than proximal segment. An additional finding in diabetics was that both proximal and distal segments were more frequently affected in the lower than in the upper extremities.


Studies of nuclear proteins in the skeletal muscle of the cardiomyopathic Syrian hamster.

Nonhistone nuclear proteins (NHNP) were isolated from the skeletal muscle of dystrophic hamsters and their respective paired controls. These proteins were extracted with phenol and fractionated by polyacrylamide gel electrophoresis. One-dimensional gel electrophoresis using either sodium-dodecylsulfate or isoelectrofocusing revealed quantitative changes between the two groups. An improved resolution using a two-dimensional system showed both quantitative and very limited qualitative differences. There are differences in proteins focusing at pH 5.0, molecular weight 55,000, in the dystrophic tissue. In addition proteins from dystrophic muscle focusing between pH 5.0 and 7.0, molecular weight 45,000, and proteins focusing between pH 7.0 and 9.0, molecular weights 35,000--45,000 and 60,000--70,000 were reduced as compared to the controls. There were no detectable differences in the electrophoretic patterns between the two groups of proteins derived from skeletal muscle homogenates. The differences in NHNP appear to be reflections of alterations in the nuclear composition of the dystrophic muscle cell. Some of these differences may represent changes secondary to the muscle disease. However, if NHNP interacting with DNA play a major role in the control of genetic expression, some of the manifestations of hamster dystrophy could be due to a different constitution of NHNP in the skeletal muscle.


Isolation and characterization of slow, depolarizing responses of cardiac ganglion neurons in the crab, Portunus sanguinolentus.

1. Tetrodotoxin-resistant, active responses to depolarization of the large cardiac ganglion cells were studied in semi-isolated preparations from the crab, Portunus sanguinolentus. Impulse activity was monitored with extracellular electrodes, simultaneous recordings from two or three large cells were made with intracellular electrodes, and current was passed via a bridge or second intracellular electrode. Preparations were continuously perfused with saline containing 3 x 10(-7) M tetrodotoxin (TTX). 2. About 20 min after introduction of TTX, small-cell impulses and resultant EPSPs in large cells cease, while rhythmic, spontaneous bursting of large cells continues. A pacemaker depolarization between bursts and slow depolarizations underlying the impulse bursts are prominent at this time. Shortly after, spontaneous burst rate slows, and at ca. 25 min, the ganglion becomes electrically quiescent. 3. In the quiescent, TTX-perfused ganglion, injection of depolarizing current into any one of the large cells results in active responses. At current strengths of sufficient intensity and duration (e.g., 20 nA, 20 ms; 5 nA, 500 ms) to depolarize a large cell by ca. 10 mV from resting potential (-53 mV, avg), the graded responses become regenerative and of constant form, provided the stimulation rate is less thna 0.15/s. Such responses have been termed "driver potentials." At more rapid rates, thresholds are increased and responses reduced. 4. Driver potentials of anterior large cells reach peak amplitudes of ca. 20 mV (to -32 mV), have maximum rates of rise of 0.45 V/s and of fall of 0.2 V/s, and a duration of ca. 250 ms. They are followed by hyperpolarizing afterpotentials, a rapidly decaying one (1 s) to -58 mV, followed by a slowly decaying one (7.5 s), -55 mV. Responses of posterior large cells are smaller (16 mV) and slower; the site of active response may be at a distance from the soma. 5. The ability of elicit near-synchronous responses and the identity of amplitude and form of responses among anterior cells and of posterior cells, regardless of which cell receives depolarizing current, indicates that all cells undergo active responses and are stimulated by electrotonic spread of depolarization. 6. The responses involve a conductance increase since memses during a driver potential are much reduced. 7. Depolarization by steady current increases the absolute threshold, decreases the maximum depolarization of the peak, and slows rates of rise and fall. Hyperpolarization increases rates of rise and fall; the absolute value reached by the peak depolarization is unchanged. Hyperpolarization reduces the amplitude of the rapid after-potential relative to the displaced resting potential. 8. Hyperpolarizing current pulses imposed during the rise and peak of driver-potential responses are followed by redevelopment of a complete response. Sufficiently strong hyperpolarization can terminate a response. The current strength needed to terminate a response decreases the later during the response the pulse is given...


Cutaneous masking. II. Geometry of excitatory andinhibitory receptive fields of single units in somatosensory cortex of the cat.

1. The responses of single neurons in the primary somatosensory cortex of the cat to brief air-pulse stimuli were quantitatively examined. These controlled natural stimuli activated almost exclusively rapidly adapting hair units which, on systematic movement of the stimulus through the receptive field, gave unit-response profiles that showed the classical unimodal tent-shaped distribution. 2. Conditioning stimulus-induced inhibition of a response evoked by a fixed test stimulus was measured by systematically moving the conditioning stimulus through the receptive field. The spatial distribution of in-field inhibitory activity was unimodal and highly covariant with that of the conditioning excitation, the peak inhibition corresponding to the functional center of the excitatory receptive field. 3. Nearly one-half of the units studied evidenced inhibition extending beyond the excitatory receptive field, forming a "surround" inhibitory region; but these were usually restricted areas with rather weak inhibitory effects. 4. Time-course measuring revealed, on the average, inhibition effects measureable from 10 ms before to some 70 ms following conditioning stimulation, with peak inhibition delayed some 10--15 ms from the conditioning stimulus onset. We showed the backward inhibition, occurring with the test stimulus delivered before the onset of the conditioning stimulus, to be a property of the test response duration. Inhibition measured in the surround areas had essentially the same time course as the inhibition calculated from measurements made within the receptive fields. 5. The spatial and temporal profiles of the excitatory and inhibitory cortical unitary activity are thus very similar to the parametric features of psychophysical enhancement and masking. These findings suggest that the excitatory and inhibitory activities related to individual stimuli interact in multipoint stimulus paradigms so that simple unimodal composite profiles are synthesized.


Forward masking of auditory nerve fiber responses.

1. Responses of single fibers were obtained from the auditory nerve of chinchillas. Tone-burst stimuli consisted of a masking stimulus followed by a probe stimulus. Forward masking of a fiber's response is defined as a reduction in the magnitude of the probe-evoked response caused by the addition of the masking stimulus. 2. The recovery of probe response magnitude as a function of the time interval between masker offset and probe onset (delta T) follows an exponential time course. A relationship between the time course or magnitude of poststimulus recovery and the characteristic frequency (CF) of a fiber was not detected. 3. The iso-forward masking contour near the threshold of the masking effect across masker frequencies approximates a fiber's frequency threshold curve (FTC). In other words, forward masking tuning curves are essentially the same as frequency threshold curves. 4. The frequency dependence of forward masking is compared to that of two-tone suppression. Tonal stimuli outside the boundaries of a fiber's FTC that produce two-tone suppression are ineffective forward maskers. Certain frequency/intensity combinations within the FTC may produce both suppression and forward masking and tones within the remaining area of the FTC produce no suppression but are effective forward maskers. 5. Both the time course and the magnitude of the forward masking effect are dependent on the discharge rate evoked by the masker regardless of the masker's absolute level or spectral content. An increase in masker-evoked excitation causes an increase in time constant and a greater reduction in probe response magnitude, rd. The function relating rd to masker level parallels the firing rate/masker level function up to 40 dB above response threshold. 6. A decrease in masker duration from 100 ms leads to a decrease in both rd and the time constant of recovery. There is no significant difference between the 100 and 200 ms duration conditions. 7. Forward masking in single fibers is related to the period of poststimulus recovery of spontaneous activity, a component of a fiber's response pattern to the masker, and this component is tentatively identified as a period of recovery from short-term adaptation.


Studies on sensory neurons of the mouse with intracellular-recording and horseradish peroxidase-injection techniques.

1. Dorsal root ganglion (DRG) cells were dissected from the adult mouse with their peripheral nerves, and electrophysiological and morphological studies were performed. 2. The peripheral nerves were stimulateradish peroxidase (HRP) was injected into the cell body, and the size of stained cell body and axon, together with the state of myelination, were examined. 4. F-neurons, whose somatic spike is a tetrodotoxin (TTX)-sensitive Na spike, had a large or medium-sized cell body with a myelinated axon, and shoed a fast conduction velocity (A fibers). 5. A-neurons, whose somatic spike is a  TTX-resistant Na spike, had a small cell body with an unmyelinated axon, and showed a slow conduction velocity (C fibers). 6. Most H-neurons, whose somatic spike is a TTX-resistant combined Na-Ca spike, proved to have conduction velocity and morphological features similar to A-neurons, whereas the rest of them had features similar to F-neurons. 7. A roughly linear correlation was exhibited between each pair of cell body size, axon diameter, and conduction velcoity. 8. Spike conduction along axons to cell bodies were blocked in all neurons either by an elimination of Na ions from the medium or by an application of TTX. 9. The possibility of transmission of different information by different DRG cells and the developmental differentiation of sensory neurons are discussed.


Different species of alpha motoneurons in same pool: further evidence from effects of inhibition on their firing rates.

1. Single units of the plantaris pool were isolated in ventral root filaments of decerebrate cats and their critical firing levels (CFLs) were determined. Motoneurons of similar size were compared in firing rate (FR) during repetitive stimulation of the plantaris nerve to establish control values and also during added stimulation of various inhibitory nerves (sural, hamstrings, or peroneal). 2. Criteria, based on maximal firing rate, were developed whereby certain pairs of units of similar size could be reliably classified into different types. 3. A second, independent set of criteria was formulated by which the same pair of units could be classified according to their responses to added inhibitory inputs. 4. The ability to distinguish motoneurons consistently by more than one set of criteria reinforces the evidence that different physiological types of units exist within a single motoneuron pool. 5. The findings indicate that different types of cells either receive different densities of input from certain inhibitory sources or that they react differentially to the same amounts of these inputs.


Stumbling corrective reaction: a phase-dependent compensatory reaction during locomotion.

1. Tactile stimuli to the paw consisting of a stick making contact or an air puff aimed at the dorsum were used to study the phasic influence of locomotor activity on the reflex pattern elicited in extensor and flexor muscles and on the induced compensatory movements in intact cats. The resulting movements and reflex pattern are called "stumbling corrective reactions." 2. The basic reflex pattern and movements of the stumbling corrective reaction are: a) if the stimulus occurs during the swing phase, a short-latency activation of the flexor muscles, which induces an additional flexion of the limb lifting the paw over the obstacle; b) if the stimulus occurs during the support phase, an inhibition followed by an excitation of the extensor muscles, which neither increase nor decrease the extension. However, the stimulus evokes an increased flexor activity in the succeeding swing phase, which induces a brisker flexion. 3. Tactile stimuli to the proximal part of the limb or to the belly in front of the knee evoked the same type of phase-dependent compensatory reactions. Such reactions would presumably be beneficial for the animal to avoid high obstacles that impede movement. 4. A nonnoxious electrical stimulus (typically 2 mA; 1 ms) applied to the dorsum of the paw was used to study systematically the reflex pattern of the stumbling corrective reaction. Two pathways were defined to the knee flexor (semitendinosus). One early burst was evoked at about 10 ms and one later at about 25 ms after the stimulus. Short inhibitory pathways and longer excitatory pathways (20-50 ms) projected to the extensor nuclei. A short-latency (10 ms) excitatory pathway to the ankle extensor (lateral gastrocnemius) was also activated. 5. A painful electrical stimulus applied to the dorsum of the paw evoked large flexor responses during the whole step cycle. During the support phase the locomotion was disrupted as the supporting limb was withdrawn. 6. The results demonstrate that intact cats are able to compensate rapidly for unpredicted perturbations and that the reflex pattern and the induced corrective movements are adapted to the locomotor activity so that functionally meaningful movements are evoked in each phase of the step cycle. 7. The evoked reflexes and their modulation are consistent with those previously found in chronic spinal cats during walking and in paralyzed spinal cats performing "fictive locomotion." It is suggested that the same spinal pathways are used, and that they are controlled by the spinal "locomotor generator."


Intraspinal tumors in children. A review of 81 cases.

The authors have presented 81 children with intraspinal tumors, all less than 16 years of age. The clinical features indicated that gait disturbance, pain, and sphincter disturbance are the most prominent complaints. Reflex changes, paralysis, and sensory impairment are the most frequent physical findings. Cerebrospinal fluid protein was recorded in 47 patients and was abnormal in 34. Spine radiography was abnormal in 58% of the patients. Seventy of the patients had myelography, and it was diagnostic in 67. Surgery was performed on 79 patients, with a 2.5% operative mortality (30 days postsurgery). Of the 49 patients who are alive, 91.5% are able to walk. Mean follow-up period was 8.5 years. The authors document the benign course of the intramedullary astrocytomas and suggest an approach to their treatment. They encourage an aggressive approach to metastatic intraspinal tumors. The latrogenic origin of some epidermoid tumors is noted. The importance of early diagnosis and treatment of the intraspinal tumors in children is emphasized.


Microsurgical treatment of intracranial vascular malformations.

In the period 1968 to 1978, 83 vascular malformations (AVM's) were treated by operation: 65 were excised and 18 were managed by interruption of afferent arteries. Three cryptic AVM's (two in the thalamus and one in the caudate nucleus) were discovered during exploration of hematomas in normotensive young women. All three of these small malformations were detected on computerized tomographic scans; none was apparent on preoperative angiograms. Two of the four deaths in this series occurred after excision of large, high-flow fistulas; the proposed cause was restoration of normal perfusion pressure in a chronically ischemic hemisphere rendered incapable of autoregulation. The addition of operative adjuncts, in particular, bipolar coagulation and operative microscopy, has extended traditional indications for operation to include favorably situated AVM's that have not bled and certain AVM's situated in critical regions of the brain.


Superficial temporal-middle cerebral artery bypass. A detailed analysis of multiple pre- and postoperative angiograms in 40 consecutive patients.

Pre- and postoperative angiograms on 40 patients undergoing superficial temporal-middle cerebral artery (STA-MCA) bypass surgery have been examined in detail. Multiple postoperative angiograms have been obtained to evaluate the change in both the bypass circuit and the intracranial circulation over time. A reproducible system for evaluating the degree of intracranial vascular filling via the bypass is introduced. The study shows that the STA and its anastomotic branch increase in size over time, measured in months, in the majority of patients. This is paralleled by a progressive increase in the degree of intracranial vascular filling. These changes are proportional to the severity of the vascular disease before surgery. The pattern of preoperative collateral circulation may change over time following the addition of the bypass circuit. The progressive change over time suggests that a static analysis at one time may belie the true effect of the surgery. The change of collateral circulation with augmentation of blood supply to areas of the brain other than those affected by the recent ischemic event, means that a total cerebral evaluation including neuropsychological testing may be necessary for adequate evaluation of the effect of the bypass surgery.


Vasospasm assessed by angiography and computerized tomography.

In 44 consecutive cases of ruptured cerebral aneurysm, vasospasm was demonstrated pre- or postoperatively. These cases were examined by bilateral carotid angiography and computerized tomography (CT), and the relationship between the angiographically visualized distribution of vasospasm, the neurological symptoms, and infarction seen on CT was evaluated. Vasospasm occurred in only some intracranial portions of the cerbral arteries that were immersed in blood-stained cerebrospinal fluid. Angiographically, diffuse vasospasm extensively involving bilateral carotid systems indicated the gravest prognosis for patients. Vasospasm affecting one carotid system and the anterior cerebral arteries on the opposite side often produced permanent neurological deficits. On the contrary, when vasospasm was restricted to one carotid system or to bilateral anterior cerebral arteries, it was usually associated with temporary neurological symptoms; however, it always produced residual neurological symptoms if it extended to the ascending branches (M3) of the middle cerebral arteries. Computerized tomography definitely demonstrated a low-density area or infarction in the territory of the spastic arteries in 25 (71%) of 35 cases with vasospasm. A low-density area was always detected when vasospasm occurred in M3 segments.


Localization in somatic sensory and motor areas of human cerebral cortex as determined by direct recording of evoked potentials and electrical stimulation.

This paper reports and illustrates in figurine style results obtained by electrical stimulation of the cortex in 20 patients and by recording of cortical evoked potentials (EPs) in 13 of these patients, whose surgery required wide exposure of the Rolandic or paracentral regions of the cortex. This study is unique in that cutaneous receptive fields related to specific cortical sites were defined by mechanical stimulation, as is done in animals, in contrast to electrical stimulation of peripheral nerves at fixed sites, as in scalp EP recordings. Observations were made on pre- and postcentral gyri, on the second somatic sensory-motor area, on the supplementary motor area, and on the supplementary sensory area. In two patients with phantom limb pain, the pain was elicited in one on stimulation of the postcentral arm area, and in the other on stimulation of the supplementary sensory leg area. Surgical removal of these areas had the immediate effect of abolishing the phantoms and the pain. Long-term follow-up review was not possible. In one patient with severe Parkinson's disease, stimulating currents subthreshold for the elicitation of movement resulted in disappearance of tremor and rigidity for short periods after stimulation of the precentral gyrus. The possible patterns of organization of the human pre- and postcentral areas are considered and compared with those of the chimpanzee and other primates. In patients in whom data from pre- and postcentral gyri were adequate, it appeared that the precentral face-arm boundary is situated 1 to 2 cm higher than the corresponding postcentral boundary.


Cerebrospinal fluid conductance and compliance of the craniospinal space in normal-pressure hydrocephalus. A comparison between two methods for measuring conductance to outflow.

Conductance to outflow of cerebrospinal fluid (CSF) has been measured by both a lumboventricular perfusion and a bolus injection method in 24 patients with normal-pressure hydrocephalus. One purpose was to investigate whether the less time-consuming technique of bolus, injection gave results comparable to the results obtained by the lumboventricular perfusion technique. There was a poor correlation between the results obtained by the two measurements of conductance to outflow of CSF. It is concluded that the bolus-injection technique cannot substitute for the lumboventricular perfusion test. Compliance of the CSF space was measured by the bolus injection. The presence of B-waves, recorded from long-term intraventricular pressure monitoring, could be correlated to the sum of conductance to outflow and compliance. The correlation offers a possible explanation of the nature of B-waves.


Effect of impounder contact area on experimental spinal cord injury.

The spinal cords of two groups of dogs were subjected to 500 gm-cm impacts using two different configurations of impounders. The impounders varied only in area of contact with the dural surface. All other parameters were kept constant. With one impounder all of the dogs injured were totally paraplegic. The impounder consistently producing total paraplegia straddled the entire width of the dorsal surface of the spinal cord in a manner corresponding to the posterior arch of a vertebra. The injury produced with this impounder is not only consistently reproducible but bears a closer resemblance to clinical injury such as anterior vertebral dislocation than that produced with a smaller impounder.


Iatrogenic carotid-cavernous fistula following Fogarty catheter thromboendarterectomy. Case report.

A case of iatrogenic carotid-cavernous fistula secondary to a Fogarty catheter thrombectomy is presented. The literature and seven previously reported cases are reviewed.


Detection of cryptic vascular malformations by computerized tomography. Report of two cases.

Two cases of cryptic vascular malformation that were not demonstrated by cerebral angiography were detected by computerized tomography. One of these patients had a cavernous angioma in the fourth ventricle with recurrent subarachnoid hemorrhages, and the other harbored a small arteriovenous malformation and intracerebral hematoma. The usefulness and limitations of computerized tomography in the identification of cryptic vascular malformations are discussed.


Internuclear ophthalmoplegia following head injury. Case report.

The most common causes of internuclear ophthalmoplegia (INO) are multiple sclerosis and vascular disease of the brain stem. Rarer causes are tumor, Arnold-Chiari malformation, and syphilis. Myasthenia gravis has, on occasion, presented with ocular abnormalities indistinguishable from INO. A case is described of bilateral INO of brief duration following head trauma. There were no other brain-stem abnormalities. This brings to 11 the number of reported patients in whom head trauma precipitated this abnormality.


High cervical spinal cord compression by an enterogenous cyst. Case report.

A case of enterogenous cyst causing compression of the spinal cord at C-1 is presented. The clinical course and radiological and histological findings are discussed.


Cerebellar ganglioglioma. Case report.

This report presents clinicopathological documentation of a nerve-cell tumor in the right cerebellar hemisphere in a young woman. The nomenclature and some other aspects of tumors containing neuronal cells are discussed.


Xanthogranuloma of the third ventricle. Case report.

The case history of a patient with a xanthogranuloma of the third ventricle is presented. This type of lesion formed by desquamation of epithelium is usually noted as an incidental autopsy finding in the choroid plexus of the lateral ventricles. Total removal via a transcortical transventricular route led to complete recovery. These tumors should be suspected in the geriatric population. The computerized tomography findings and a review of the literature are included.


Abnormal origin of the posterior inferior cerebellar artery. Case report.

Posterior inferior cerebellar arteries originating from the vertebral arteries between the axis and the atlas were demonstrated angiographically in a 12-year-old boy. The patient presented with tetraparesis of sudden onset after a gymnastic exercise. There was no recognizable trauma.


Blood phosphorus levels of laying hens at various time intervals after dosing with phosphoric acid.

Two experiments were conducted to study the pattern of change in serum inorganic phosphorus level in laying hens fed a diet containing 0.30% total phosphorus after dosing with a known amount of phosphorus. Serum phosphorus level of undosed hens was 2.5 mg/100 ml at oviposition in both experiments. After dosing with 100 mg of phosphorus in 10 ml of a phosphoric acid solution, serum phosphorus level increased sharply and reached a peak of about 7.0 mg/100 ml between 30 and 60 minutes in experiment 2. After the peak the elevated level of serum phosphorus decreased logarithmically until 5 to 6 hours after dosing and eventually decreased to 2.5 mg/100 ml which was the serum phosphorus level of undosed hens in experiment 1. The half-life of the elevated portion of serum phosphorus due to the dosing was about 100 minutes.


Determination of a copper requirement to support gestation and lactation for the female albino rat.

Confirmed pregnant female albino rats were fed a purified diet containing 3, 6, 9 or 12 ppm copper throughout gestation and lactation in order to determine a copper requirement for one generation. A diet containing 6 ppm copper was found to meet the biochemical needs for rats during gestation, but the combined stress of gestation plus lactation raised the dietary requirement to 9 ppm copper. Evidence to support these conclusions included measurements of serum copper concentration, serum ceruloplasmin activity, liver iron concentration, milk copper concentration and pup liver copper concentration. The results of these studies suggests that the current National Research Council recommendation of 5 ppm does not maximize the copper status of first generation off-spring in rats.


Transport and metabolism of pyridoxamine and pyridoxamine phosphate in the small intestine of the rat.

The vascularly perfused small intestine of the rat was utilized to study the absorption and metabolism of pyridoxamine (PM) and pyridoxamine-5'-phosphate (PMP), independent of other tissues including erythrocytes. [3H]PM or [3H]PMP was administered intralumenally with or without the addition of unlabeled PM, or PMP or inorganic phosphate. The percentage absorption of PM was 17.1 to 19.7% in 10 minutes and was unaffected by dosages from 0.02 to 200 mumole. The isotope from [3H]PMP at a physiological level (0.02 mumole) was absorbed at the same rate as that from [3H]PM, and the distribution of the 3H remaining in the lumen and in the intestinal tissue and perfusate indicated that hydrolytic removal of the phosphate was occurring extensively in the gut. The spectrum of labeled compounds isolated from the lumen, the perfusate and the mucosa clearly indicated that PMP, unhydrolyzed, can be absorbed slowly and converted to a number of vitamin B-6 forms in the intestinal mucosa. However, the results support the view that under normal physiological conditions the majority of dietary PMP is hydrolyzed to PM which seems to be absorbed by passive diffusion and transported to other organs and tissues via the blood stream.


Effects of fetal and early postnatal thiamin deficiency on avoidance learning in rats.

Thiamin deficiency was induced in two groups of young rats during two stages of growth: deficiency 1, from 8 days prepartum to 10 days postpartum or deficiency 2, from 1 to 18 days postpartum. The deficiency was reversed by thiamin injections for 5 days and return to a normal diet following which animals were tested at 35 days of age. Body weights at 21 and 36 days of age were not significantly reduced by the deficiency nor was brain weight affected. Activity levels were not significantly reduced by deficiency 1 but were reduced in deficiency 2. Both active and passive avoidance learning were significantly impaired in both deficiency 1 and 2, a finding which could not be attributed to alterations in pain sensitivity, motor ability or reduced activity levels. The results indicate that the developing brain is vulnerable to reduced thiamin intake and that the period of vulnerability may be different for activity and avoidance learning.


Long term pancreatic response to feeding heat damaged casein in rats.

Rats were fed a heat damaged casein (autoclaved 24 hours, 121 degrees, 2 atm) diet to determine the effect of poorly digested protein on pancreatic enzyme levels and response to a meal. After 10 days of feeding, the pancreas showed no signs of atrophy, however, chymotrypsin and amylase activities were lower in proportion to body weight. An estimation of secretion during the meal was similar or slightly lower in rats fed heated casein (HC) as compared to the casein diet (C), but a greater levels of enzyme activity was found in the intestinal contents of rats fed HC relative to control rats. These results suggest that the turnover of enzymes in the gut is reduced when a less digestible protein is fed, and that the endogenous pancreatic secretions and the dietary protein are not digested and absorbed as well.


Iron deficiency and its role in cadmium-induced fetal growth retardation.

The aim of this investigation was to establish the relationship of cadmium-induced fetal growth retardation in the mouse to iron deficiency. Pregnant mice were either fed a low iron diet or given 40 ppm cadmium in their drinking water. The effects of these factors on fetal weight and hematological values of the fetuses and dams were established and compared, both with each other and with appropriate controls. Both treatments caused maternal and fetal anemia, the fetuses being more severely affected. The anemic fetuses were also severely growth retarded. These changes, when caused by the iron deficient diet, could be completely prevented by either parenterally or orally administered iron supplements. When the changes were caused by cadmium in the drinking water they were only partially prevented by oral supplements. From these results it was concluded that iron deficiency in pregnancy causes not only anemia but also fetal growth retardation. Cadmium exposure in pregnancy, presumably by blocking intestinal absorption of iron, also causes anemia and hence fetal growth retardation.


Cadmium-induced fetal growth retardation in mice and the effects of dietary supplements of zinc, copper, iron and selenium.

Many of the toxic effects of cadmium can be prevented by prior or simultaneous administration of either zinc, copper, iron or selenium. The aim of this investigation was to determine whether cadmium-induced fetal growth retardation in the mouse could be prevented, or reduced, by dietary supplementation with salts of these elements. Pregnant mice, receiving either distilled water to drink or distilled water containing 40 ppm cadmium, were fed, throughout pregnancy, a normal stock mouse diet supplemented with either zinc (200, 400 or 800 ppm), copper (30, 100 or 400 ppm), iron (200 or 1,000 ppm) or selenium (0.05, 2, 20 or 200 ppm). Also included was a control group which did not receive cadmium or dietary supplements. The animals were killed on the 19th day of pregnancy and the fetuses removed and weighed. The results showed that the iron supplemented diets gave partial protection against the cadmium-induced growth retardation; the other diets were ineffective.


Effects of restricted diet and intestinal flora on the life span of small intestine epithelial cells in mice.

Previous data have shown that the life span of small intestine epithelial cells in germ-free (GF) mice was 4.3 days, while that in conventional (CV) mice was 2.1 days, under ad libitum feeding. On the other hand, in the author's laboratory, it was also found that feeding conditions affected the cells' life span. That is, in CV mice the life span of the cells lengthened under restricted feeding (2.6 days), compared with under and libitum feeding (1.8 days). In the present experiment the life span of small intestine epithelial cells was investigated using radioautography, under controlled feeding (setting it equal to ad libitum feeding) and restricted feeding, in both CV and GF mice. Small intestine samples were taken from the middle part of duodenum, jejunum and ileum. Body weight changes, organ wet weights and intestine were also measured. In the lower part of the small intestine the effects of a restricted diet on epithelial cell life span prolongation appeared clearly in CV mice, but this effect was reduced in GF mice. This may be partly because the restricted group had slightly shorter villi in the case of GF mice.