[Effect of the inoculum on beta-fructofuranosidase synthesis by Aspergillus awamori].

The influence of the age and amount of the inoculum on the beta-fructofuranosidase synthesis by Aspergillus awamori 16 was studied during submerged cultivation. The level of the synthesis increased significantly when the 36-hour mycelial inoculum was used.


[Lipid synthesis by Micrococcus freudenreichii in media containing unsaturated hydrocarbon's].

The growth and synthesis of lipids by thermotolerant bacteria Micrococcus freudenreichii K-219 were investigated in the mineral medium containing a mixture of unsaturated (I-) and saturated hydrocarbons. The bacteria utilized primarily I-alkenes. In lipids the predominant fractions were phospholipids (57%) and free fatty acids (20%). The content of waxes which were in significant quantities in n-alkane containing media (9%) was not higher than 0.3% dry matter upon utilization of I-alkenes. There was a certain correlation between carbon atoms of synthesized fatty acids and unsaturated hydrocarbons used. Bacteria utilizing I-alkenes showed no elevated unsaturation of cell lipids as compared to those assimilating n-alkanes. These data give evidence for different pathways of oxidation of alkenes and alkanes by the above microbial strain.


[The effect of iron concentration on pectin decomposition by Aspergillus niger and Aspergillus awamori].

The effect of cations Fe2+ and Fe3+ on the decomposition of apple pectin by the enzymic preparations of Asp. niger and Asp. awamori has been examined. Fe ions have delayed the process of enzymic decomposition of the pectin molecule. In the presence of Fe3+ far less amounts of monogalacturonic acid are formed. The presence of Fe ions makes the pectin molecule more stable to the effect of pectolytic enzymes.


[Preparation and kinetic properties of immobilized benzyl penicillin acylase].

An active insoluble preparation of immobilized benzyl penicillin acylase (IBA) EC 3.5.1.11 has been obtained by its entrapping into polyacrylamide gel lattice. Due to immobilization the preparation maintains up to 87% of its initial activity. The kinetics of IBA at low substrate concentrations obeys the Michaelis-Menten law; however, the apparent KM value decreases and the temperature optimum elevates. The inhibition by the reaction products--6-aminopenicillanic acid and phenylacetic acid--has been found to be 4.3 mM. The resultant IBA preparation proves to be suitable for hydrolysis of 5% benzyl penicillin solutions.


[The structure of caseins from cow milk].

The paper presents a review of up-to-date data on the primary structure of alphas1-, beta- and kappa-casein of cow milk, gives amino acid substitutes in the genetic forms, arrangement of bitter peptides resulting from enzymic degradation and discusses the possible mechanism of phosphorylation. With respect to the primary structure alimentary specificity of caseins is discussed.


[Formation of alcohols during sucrose heating with amino acids].

The formation of alcohols during sucrose heating with amino acids was investigated. The sucrose heating to 180-190 degrees C resulted in the formation of methanol and ethanol and its heating with alanine--propanol and isobutanol. The sucrose heating with phenylalanine led to the formation of beta-phenylethanol as well. Alcohols were identified as benzoates by paper chromatography. They were also identified by infrared spectra.


[Photoisomerization of provitamins D under influence of various ultraviolet radiation].

The influence of various sources of ultraviolet radiation on the photoisomerization of provitamins D--ergosterol and 7-dehydrocholesterol--was studied under industry-like conditions. The yield of previtamins and, consequently, vitamins D was higher with the use of erythemic lamps with luminophore E-2 and luminophore E-3 than with the use of lamps PRK-2.


[Effect of mineral fertilizers on the microflora of corn roots].

The paper describes studies of the density of microorganisms grown on meat-peptone agar, fungi, nitrifiers, cellulose degraders, actinomycetes and azotobacter in the soil of the radical area of corn grown in field experiments with various doses and ratios of mineral fertilizers. In the forest-steppe zone (leached chernozem) of the Krasnoyarsk region mineral fertilizers activated proliferation of radical microorganisms grown on meat-peptone agar, fungi, nitrifiers and cellulose degraders. The effect of the tested fertilizers was dissimilar during plant vegetation. Under the influence of fertilizers proliferation of actinomycetes increased at the phase of 3--4 leaves. At later phases of the plant development a similar tendency was manifest upon soil application of N120P60K60, N60P120K60 and N120P120K120. The azotobacter density increased only after application of N60P120K60, N60P60K120 and N30P60K30.


[Isolation of alkaloid-like substances from penicillium fungi].

Alkaloid-like substances have been obtained from the cultivation of fungi Penicillium granulatum and Penicillin corylophillum. The procedure for their preparative isolation has been developed. They do not have physico-chemical characteristics typical of alkaloids viridicatine and cyclopenine, previously isolated from Penicillium fungi. The presence of nitrogen in the structure has been shown in the product synthesized by Penicillium granulatum. Ultraviolet, infrared, nuclear magnetic resonance and mass spectra have been recorded for the product.


[Kinetic sorption of nicotinic acid by anionites].

Studies of the kinetic sorption of nicotinic acid have demonstrated that the ionites AH-22, AH-31 and IR-45 absorb it quantitatively from water solutions. The static exchange capacity of nicotinic acid makes 3.5 mmole/g for AH-22 and IR-45 and 2.0 mmole/g for AH-31 and remains unchanged after ionite sterilization. Ionite AH-22 absorbs also quantitatively nicotinic acid from reaction mixtures used in its microbiological synthesis from 3-methyl pyridine. Formic acid (2n) desorbs entirely nicotinic acid from the above ionites. The sorption of nicotinic acid on AH-22 and IR-45 ionites is associated with diffusion processes; there is no chemical interaction between nicotinic acid and the ionites tested.


[High voltage electrophoresis in starch gel of sarcoplasmatic and myofibrillar proteins of animal skeletal muscles].

The procedure for cooling starch gel during high voltage electrophoresis (voltage gradient 30-35 v/cm) of proteins of skeletal muscles of animals has been developed. In cooling the gel cuvette by ethanol of 15 divided by -20 degrees and -35 divided by -40 degrees C during electrophoresis in interrupted buffer systems of sarcoplasmatic and myofibrillar proteins the temperature of the gel plate does not exceed 26 degrees C in the most important sites. This allows heat denaturation of proteins during their separation.


[Composition of lipids of Actinomyces olivaceus--synthesis of vitamin B 12].

Total cellular lipids of the synthetic of vitamin B12 Act. olivaceus involve predominantly phospholipids (about 70%). Lipid phosphates consist of phosphatidyl ethanol amine and phosphatidyl-2,3-butandiol (over 40 and 30%, respectively) and lower quantities of phosphatidyl inositol olmonomanoside and cardiolipin. The neutral fraction includes the predominating fraction of triglycerides (over 20%) as well as mono- and diglycerides, free fatty acids, hydrocarbons and three fractions similar to waxes, sterines and sterine esters in their Rf values.


[Growth-inhibitory substances in barley grain during postharvest ripening].

The investigation studied the occurrence of growth-inhibitory substances in barley grain during postharvest ripening cultivated in different climatic zones. It was shown that the amount of inhibitory substances accumulated in grain was higher under unfavourable ripening conditions. Heat treatment of freshly harvested barley accelerated their disintegration. The disappearance of growth-inhibitory substances coincided with the termination of postharvest ripening of barley grain.


[Effect of urea and amino acids of the ornithine cycle on the biomass accumulation and amino acids synthesis by Candida guilliermondii].

When assimilating urea, arginine, ornithine and citrulline as the sole source of nitrogen, C. guilliermondii shows a higher economic coefficient of biomass accumulation (54.2, 59.7, 40.6% respectively) as compared with ammonium sulphate whose coefficient is 35.6%. Nitrogen sources exert a significant influence on the content of essential amino acids in the alcohol soluble fraction of cell biomass. For instance, urea and arginine are responsible for the accumulation of ornithine (220 and 480 mug/100 mg abs. dry weight), arginine (470 and 587 mug), aspartic acid (220 mug), glutamic acid (520 and 444 mug), alanine (460 and 500 mug), whereas ammonium sulphate provides an accumulation of serine--52 mug, glycine--57 mug, gamma-aminobutyric acid--480 mug, phenyl alanine--96 mug and leucine--96 mug.


[Double substrate-oxygen limitation of the growth of methanol oxidizing yeasts].

The influence of the double substrate-oxygen limitation on the specific rate of growth of two strains of methanol oxidizing yeast Candida boidinii was studied in a chemostat. On the basis of the bottle-neck theory in the metabolic chain of biochemical reactions, relations between the specific rate of yeast growth and limiting concentrations of methanol and oxygen are suggested. They agree with a certain mechanism of enzymic bisubstrate reactions.


[Regulation of lysine biosynthesis in the leucine-dependent mutant of Micrococcus glutamicus].

The role of leucine in metabolism of Micrococcus glutamicus was examined in relation to the lysis synthesis by the homoserine- and leucine-dependent strains of M. glutamicus 106 and the homoserine-dependent strain of M. glutamicus 95. In addition to the growth function, leucine produced a controlling effect on the yield of the end product. In the presence of leucine the inhibitory effect of isoleucine on the lysine yield was reduced or reversed. The end effect depended on the leucine: isoleucine ratio. The mechanism of interaction of amino acid metabolites with respect to the lysine biosynthesis in both strains is discussed.


[Effect of oleic acid and Tween-80 on lysine synthesis by the culture Corynebacterium glutamicum].

The effect of oxidized and unoxidized oleic acid and Tween-80 on the growth and lysine synthesis by the producers C. glutamicum strains 95, 8, 28 was investigated. Surface active substances like oxidized and unoxidized oleic acid and Tween-80 during cultivation of the lysine producers on the glucose medium (the synthetic medium) and the medium with molasses and corn extract either inhibited the culture growth, thus reducing lysine yield, or accelerated the culture growth, thus increasing lysine yield. Oxidized and unoxidized oleic acid produced the greatest effect when added to the nutrient medium on the 48th cultivation hour. The increment of synthesized lysine was 120-150% of the control. Tween-80 proved to be very effective when added at early stages of fermentation (20 hours).


[Metabolism of monocarbon compounds during biological purification of sewage waters].

Pathways and rates of metabolism of three 14C1-compounds (methanol, formaldehyde, and formic acid) were investigated by means of the heterogeneous population of activated sludge microorganisms. For the above microbial population formaldehyde was the primary or preferential substrate. During an hour aeration it was processed by activated sludge 6 times faster than by sodium formiate and 2 times faster than by methanol. The basic pathways of its transformation were oxidation via formiate to CO2 with its partial reutilization and direct incorporation into the sludge biomass via the primary formation of serine. An addition of methanol increased the incorporation of 14C-formadehyde into biomass and decreased the formation of free 14CO2. The main mechanism of the transformation of 14C-formiate in activated sludge was its oxidation to CO2. An addition of methanol and formaldehyde induced no essential changes in the rate or pattern of their metabolism.


[Cytochrome f from Chlorella pyrenoidosa Pringsheim 82 T].

Cytochrome of the f type was isolated from the thermophilous autotrophic strain Chlorella pyrenoidosa Pringsheim 82T and purified on Sephadex G-75. The isolation procedure allowed a simultaneous production of glutamate dehydrogenase isoenzymes. From 100 g of Chlorella wet paste 100 to 120 nM of electrophoretically unicomponent protein with a molecular weight of 12,000 to 13,000 were isolated. The Chlorella cytochrome had an absorption spectrum in the visible light that was typical of the f type cytochromes.


[Study of ultrafiltration of trypsin solutions].

The dependence of the rate of trypsin ultrafiltration on the concentration, pressure and structure of membranes was studied. During ultrafiltration of diluted trypsin (0.3 mg/ml), water and sodium chloride the flow rate increased linearly with a pressure increase in the range of 0.4-4.2 kg/cm2. During ultrafiltration of trypsin solutions of a concentration of 1 mg/ml and over at a pressure of 2-3 kg/cm2 deviations from linear proportionality occurred which enhanced with an increase in the protein concentration and a decrease in membrane permeability.


[Separate measurement of fluoroanalogues of desmosterol, cholesterol, 7-dehydrocholesterol by thin-layer and gas-liquid chromatography].

An attempt was made to develop a new method for separate measurement of sterols of similar chemical structure--desmosterol, cholesterol, 7-dehydrocholesterol--by means of thin-layer and gas-liquid chromatography. Fluoroanalogues of the sterols were well separated in the adsorbent thin layer. This facilitated their further identification, quantitation and accumulation. Similar results were obtained with the aid of gas liquid chromatography.


[Free amino acids in milk containing different amounts of dry substances after its fermentation by lactic acid Streptococci].

The content of free amino acids in milk containing different amounts of dry substances (11.2, 16, 18%) was measured. An increase in the content of dry substances reduced the capacity of lactic acid streptococci to accumulate threonine, proline, alanine, tyrosine and elevated their capacity to accumulate serine, cystine, norleucine, phenylalanine. The content of free amino acids was much higher during continuous cultivation than at the end of the stationary phase.


[Volatile oil of Anethum Graveolens L. as an inhibitor of yeast and lactic acid bacteria].

The antimicrobial activity of 25 volatile oils from aerial parts and seeds of dill (Anethum graveolens L.) of different geographical origin towards yeast Saccharomyces vini and lactic acid bacteria Lactobacterium buchneri was measured by serial dilutions. Volatile oils from mature seeds and green parts of the plants harvested at late vegetation phases showed the highest activity. The geographical origin of plants influenced insignificantly the antimicrobial activity of volatile oil.


[Cytochromes of paraffin oxidizing yeast Candida guillermondii K-5].

The cytochrome group of the enzymes-electron carriers in the terminal site of the respiratory chain of paraffin-oxidizing yeast C. guilliermondii K-5 has been identified. Spectral peaks of their reduced form correspond to the following wave lengths: c-412, a1-510 and a2-546nm. Variations in the content of cytochrome C of the accumulative culture have been studied. Reduced forms are predominant in the lag-phase and in the phase of exponential growth. This predominance disappears in the phase with negative acceleration and the dying culturt contains a greater number of oxidized forms.


[Influence of products of thermophilous methane fermentation on the mixed lactic acid bacterial culture].

The effect of products resulting from thermophilous methane fermentation on the accumulation and ratio of different lactic acid bacteria (Str. lactis, Str. cremoris, Str. diacetilactis, Str. diacetil. var. acetoinicus, Leuc. citrovorum8 L. plantarum) was investigated upon their combined cultivation in milk and serum. In combined cultivation of the streptococcal culture the rate of growth of a single strain differed from that in separate cultivation. Str. cremoris was accumulated with the highest rate during its separate cultivation and with the lowest rate during its combined cultivation. An addition of products of thermophilous methane fermentation to the combined culture of streptococci of different strains increased the growth rate and accumulation of each strain. At the same time the products influenced differently the quantitative ratios of various strains in the resulting biomass. For instance, the relative content of Str. cremoris and Leuc. citrovorum decreased insignificantly and that of Str. lactis and Str. diacetil. var. acetoin.increased. The combined cultivation of the five streptococcal strains with L. plantarum in the medium containing no additions of thermophilous methane fermentation products increased the relative content of L. plantarum from the beginning of fermentation. In the medium containing the additions of this parameter varied sinusoidally with a minimum of 6 to 9 hours. Possible mechanisms of these changes are discussed.


[Effect of the growth phase and nutrient medium on the survival of lyophilized cells of Pseudomonas denitrificans].

The influence of the growth phase and cultivation condition of Pseudomonas denitrificans on the survival of the culture after lyophilization was examined. The culture removed for drying in the stationary phase showed the highest resistance to lyophilization. The cells dried at the beginning of exponential phase displayed enhanced sensitivity to lyophilization. Addition to the cultivation medium (meat-peptone broth) of Tween-80 (0.25%) caused an increase of proteins, lipids and polysaccharides in cells and an enhancement of their telerance to lyophilization.


[Effect of low temperature treatment of liquid nutrient media on the reproduction of microorganisms].

The development of bacterial cultures of 37 microbial strains was studied after their 4-5 and 24 hour cultivation in liquid thawed and normal nutrient media. The cultivation of gram-positive aerobic bacteria, facultative anaerobic bacteria, actinomycetes and moulds in pre-frozen nutrient media increased 2-4 fold their reproduction as compared to that in the media that were not prefrozen. An insigificant acceleration of growth was found in six strains of gram-negative aerobic bacteria.


[Study of catalase and proteolytic activities of different variants of Bacillus mesentericus].

Catalase and proteolytic activity of the culures and morphological variants of Bacillus mesentericus fuscus, Bac. mesentericus vulgatus were studied. The variants were obtained as a result of prolonged cultivation of the stock strains in the potato mash under the layer of vaseline oil. The level of catalase activity varies in different morphological variants of the same culture, changes with age and depends on the storage conditions. The catalase activity in the rough, smooth and papillar variants that were freshly isolated from the potato mash was 1.5=2.5 times lower than that in the variants long kept on the agar medium. The quantitative indexes of the proteolytic activity of different variants also varied.


[Use of enzymic preparations during diosgenine isolation from Dioscorea caucasica Lipsky].

The use of enzymic preparations of the cellulolytic and macerating effect was studied as applied to the isolation of diosgenine from rhizomes of Dioscorea caucasica Lypsky. The enzymic treatment of the steroid containing raw material prior to acid hydrolysis increased the yield of diosgenine by 30-48%. It is suggested that additional extraction of diosgenine takes place due to: 1) enzymic hydrolysis of structural polysaccharide components of the plant tissue and intercellular binding materials and 2) disintegration of glycoside bonds of saponins.


[Variability of the protein and amino acid content in the rice grain].

The amino acid composition of raw protein of ten regional varieties of rice harvested in 1972 and 1973 was investigated. The amino acid composition was measured in the Hd-1200e analyzer. Coefficients of variations in the content of protein and invididual amino acids were determined in relation to the rice variety. Consistent correlation between the lysine concentration in the protein and the protein content in the grain was established. The influence of climatic conditions on the protein accumulation in the rice grain was noted.


[Phytoalexin activity in apples as an indication of their resistance to phytopathogenic microorganisms].

Phytoalexin activity of various apple varieties was measured during their storage at subcryoscopic (-2.3 degrees C) and supracryoscopic (-1.3 degrees C) temperatures. More resistant late winter apple varieties Renet Simitrenko and Renet Champagne showed higher phyto-alexin activity than the autumn-winter strain Calville Snowy. By the end of storage the phytoalexin activity decreased independently on the storage conditions. However, the apples that were kepat at supracryoscopic temperature retained a hight phytoalexin activity. The apples which were kept at -2.3 degrees C showed no phytoalexin activity.


[Disintegration of cells of methane oxidizing bacteria by gas decompression].

The efficacy of disrupting cells of methane oxidizing bacteria M. trichosporium strain 20 by air decompression was measured. The efficacy increased with a rise of the gas pressure, density of the bacterial suspension and the ratio of the air and suspension volumes. The relationship between the efficacy of disruption of the microorganisms and the rate of pressure reduction showed a distinct maximum. The efficacy of the bacterial disruption did not change with an increase of the time of saturation of the bacterial suspension by air from 30 sec. to 60 min.


[Study of thermostable proteins in potatoes by isoelectric focusing].

With the aid of the method of isoelectric focusing eight thermostable proteins with isoelectric points of 3.6, 3.9, 4.u, 5.1, 5.8, 6.6, 7.2 and 10.0 were found in the extract from potato tubers of the Lyubimets variety. All the proteins had inhibitory activity in relation to alpha-chymotrypsin and trypsin.


[Polarographic assay of nicotinic acid in the culture liquid].

The method of potarographic assay of nicotinic acid in the culure liquid has been developed. The effect of all the constituents of the culture liquid on the accuracy of measurements has been tested. The analytic scheme which provides elimination of interfering components has been devised. As the polarographic medium 0.1 n HCl was used. The quantity of nicotinic acid was measured with respect to the wave of E1/2 = - 1.18 v. The described method makes it possible to identify nicotinic acid at concentrations of 3.3 X 10(-4) M to 3.3 X 10(-3) M in the culture liquid with an error of not more than +/-5%.


[Comparative characterization of polysaccharide fractions in grapes].

Different methods of isolating polysaccharides from grapes were evaluated with respect to the three indictrial grape varieties Traminer pink, Rkatsiteli, Cabernet-Sovinjon. Hot water extration was shown to be the best method in the isolation of water-soluble polysaccharides in primary wine-making. The qualitative and quantitative composition of the isolated polysaccharides was found to depend on the method of isolating polysaccharide fractions. The polysaccharides of grapes were heterogeneous in their molecular weight. The results of periodate oxidation of high molecular weight carbohydrates suggest a branched structure of polymers of water-soluble polysaccharides of grapes.


[Enzynatic method of disrupting yeast cell walls].

The influence of the preparation of mucolytic enzymes obtained from the culture liquid filtrate of Actinomyces griseinus on the yeast Candida guilliermondii was investigated. Lipids, hydrocarbons and proteins were extracted and free amino acids were separated from the biomass made of disrupted yeast cells. The extract contained 73% of cytoplasmic substances whereas normal yeast (enzymically untreated) contain on the average 13.7%. Lipids and hydrocarbons were measured.


[Trypsin concentration by ultrafiltration].

Criteria for the selection of membranes and optimal conditions for the trypsin concentration by ultrafiltration through acetylcellulose membranes have been developed. The possibility of a repeated concentration of trypsin by means of these membrances has been shown.


[Effect of amino acids on the hemicellulase synthesis by the fungus Aspergillus awamori 16-4E].

The effect of different amino acids on the hemicellulase synthesis by the fungus Aspergillus awamori 16-4E was investigated. The favorable influence of beta-alanine on the enzyme synthesis was demonstrated. Quantitative changes of beta-alanine and glutamic acid in the cell of Asp. awamori 16-4E were followed during the fungal development.


[Changes in the intracellular pool of free amino acids of Streptococcus lactis under different cultivation conditions].

The intracellular pool of free amino of Streptococcus lactis--lysine producer contains a good number of amino acids when cultivated on the corn medium. Glutamic acid, proline, alanine, lysine, leucine, histidine and arginine are in predominance. An almost complete amino acid pool develops at an early exponential phase of Str. lactis growth under stationary cultivation conditions. The content of free amino acids increases 4-fold during the transition from the early exponential phase to the stationary phases under submerged cultivation conditions. This can be attributed to a more intensive amino acid exchange during the medium stirring than during stationary cultivation.


[Comparative study of moderate and virulent phages of mesophilous lactic acid streptococci].

A method has been developed to identify phage containing mesophilous lactic acid streptococci. The method is based on the chloroform treatment of young cultures. The isolated moderate phages P4St and P6St are morphologically identical and serologically related to one another and to virulent phages P1Sv, P2Sv, P3Sv, P12Sv, P13Sv that can be isolated in industrial phagolysis.


[Proteolytic preparation from the culture of Bacillus polymyxa str. 13-13].

A proteolytic preparation has been isolated from the culture fluid filtrate Bacillus polymyxa str. 13-13 by salting out with (NH4)2SO4 (0.7 of complete saturation). The data characterizing the amino acid composition and the enzymic system of the resultant preparation are given. It has been shown that the proteolytic activity depends on the enzyme containing metal ion, i. e. metal enzyme.


[Multiple forms of acid phosphatase of the mould Aspergillus awamori str. 22].

By isoelectric focusing and DEAE-cellulose and Sephadex G-150 chromatography it has been shown that extracellular acid phosphatase produced by Aspergillus awamori str. 22 exists as a mixture of oligomers of molecular weights ranging from 30,000 to 140,000. With an increase of aggregation of molecules of acid phosphatase the isoelectric point increases from 4.6 to 5.4.


[Effect of products of thermophilous methane fermentation on the fermentation of fruit must by Saccharomyces vini].

Experiments were carried out to study the effect of extracts from products of thermophilous methane fermentation at a dose of 0.7+2.0 ml/100 ml on the proliferation and fermentation activity of yeast Saccharomyces vini of the Yablochnaya-7 and Vishnevaya-33 race during their cultivation in the Hansen medium and in the apple and cranberry must with a normal and elevated content of sugar and acid. In some experiments the must was enriched in (NH4)2HPO4 at a dose of 0.3 g/l. Additions of small amounts of products of thermophilous methane fermentation accelerated fermentation of fruit musts with a normal sugar content and to a greater extent musts with an increased sugar content (27%). In the must enriched in (NH4)2HPO4 an almost complete (over 98%) fermentation of sugar developed for 27 days. In the must with an increased acidity (due to citric acid added to bring titrable acidity to 25 g/l) additions of the preparation also accerlerated the begining of the fermentation and increased its intensity.


[Effect of cultivation conditions on the activity of respiration of Saccharomyces bayanus].

The effect of sugar and ammonium nitrogen content in the initial nutrient medium as well as the cultivation temperature on the respiration activity and respiratory quotient of yeast used in the champagne manufacture was studied. An addition of ammonium nitrogen stimulated respiratory processes in the yeast cell. The respiration activity increased with an increase of pH to 4.0. With an elevation of the sugar content of the substrate the respiratory quotient increased resulting in an uneconomic utilization of sugar. The maximum respiration activity and minimum respiratory quotient occurred at a temperature of 20 degrees.


[Effect of magnesium concentration in the culture medium on the trace element requirement of yeasts].

The effect of different magnesium concentrations in the culture liquid (ranging from 2=6 to 220 mg/l) on the accumulation of Mg and Mn ions in the yeast Candida guilliermondii was studied during their continuous cultivation on purified liquid paraffins. A reverse correlation between the accumulation of magnesium and manganese in the yeast biomass was established. The magnesium content in the biomass increased with an increase of its concentration in the nutrient medium. The biomass yield was optimal at a concentration of magnesium ions in the nutrient medium of 10=25 mg/l. Under these conditions the content of magnesium ions was 0.4 mg % and that of manganese ions (upon their concentration in the nutrient medium of 1=2 mg/l) was 20 mg%.


[Vitamin biosynthesis by germinating seeds at low temperature and in overmoistened soil].

The distribution of farnesene and farnesene hydroperoxide in apples of different varieties was studied. The relationship between the content of these compounds and the pathological browning of the apple surface, scald was followed. It was shown that 1) farnesene and farnesene hydroperoxide were concentrated in the cuticle; 2) there was no distinct correlation between farnesene concentration and scald, 3) there was a direct correlation between the concentration of farnese hydroperoxide and scald development; 4) the factors that inhibited farnesene oxidation (antioxidants, low oxygen concentration, mineral oils--farnesene absorbers) slowed down the scald development during apple storage.


[Method of electrophoretic determination of S-methyl methionine in plants].

A method to determine S-methyl methionine (vitamin U) in plants has been devised. The method includes S-methyl methionine extraction extract purification on cationite KU-2 in the NH4+-form, S-methyl methionine eluation with 2n water solution of NH4OH from the cation exchange resin, eluate evaporation in vacuo, dissolution of the residue in a minimal amount of water acidified with hydrochloric acid, electrophoretic separation of S-methyl methionine from basic amino acids, ninhydrine development of the electrophoregram, methanol eluation of the spot corresponding to S-methyl methionine, and colorimetry of the solution at 506 mmu. Relative error is +/-2.5%.


[Use of colour reactions to identify lipid classes, including tocopherols, by thin-layer chromatography].

Colour reactions of different classes and individual lipids of plant origin with organic and inorganic compounds (used as reagents) were studied to identify them in thin-layer silica gel. Some of the reagents (p-dimethyl phenylene diamine, chromotropic acid in H2SO4, Ti(SO4)2 in H2SO4) helped to detect main lipid classes and to identify selectively individual compounds (alpha- and gamma-tocopherols). Hydrochloric p-nitrophenyl diazonium, p-dimethyl aminobenzaldehyde are of interest mainly as group reagents to lipid classes with common properties. The reaction sensitivity is measured in micrograms.


[Preparation of cell walls of group A Streptococcus. Methods of disintegration, isolation and control].

A method for disintegration of cells of group A streptococcus on the Edebeau extrusion press was developed. The level of disintegration was controlled by cell count in stained preparations, Coultier electronic counter and electron microscope. The streptococcus cell disintegration in the Edebeau extrusion press at a temperature of --40 degrees, a pressure of 3200 kg/cm2 and two cycles of the process was completed by 96-98%.


[The effect physical factors and proteolytic enzymes on actinomycete mycelium and spores].

The influence of enzymes (lyzozyme, trypsin, papain) and physical factors (hydrostatic pressure, mechanical sand grinding, extrusion in the frozen state, ultrasonic treatment) on the spores and mycelium of actinomycetes Actinomyces streptomycini B-6 and Thiobacillus vulgaris 2681 was studied. Actinomycete spores proved to be stable to trypsin and papain. Lyzozyme induced an almost complete disruption of the mycelium. The influence of hydrostatic pressure and lyzozyme on spores was the least effective. The best disruption of spores was produced by ultrasonic treatment and extrusion in the frozen state. The intensity of coloration of pigmented supernatants was the highest during ultrasonic disruption of spores.


A preliminary investigation of the effects of salinity on the bacterial flora of the Tay estuary.

Two features of the effects of salinity on the bacterial flora of the Tay estuary are considered. First the effect of salinity on the size and species composition of the resident microflora at various sites within the estuary. The second part is concerned with data obtained from laboratory experiments designed to study the effects of subjecting marine and freshwater bacteria, isolated from the Tay, to salt stress.


Quality control in diagnostic virology.

Quality control in diagnostic virology is in its infancy and some preliminary investigations are reported. Simulated specimens containing viruses have been prepared and distributed so that they could be included in the routine work of virus isolation in participating laboratories. Sera containing antibodies to rubella and influenza virus have also been sent to laboratories for testing. Laboratories were able to check their results immediately after the closing date, and could compare their performance with that of other laboratories when the analysis of each distribution was circulated. The results so far show considerable variation in performance and indicate that there is room for improvement in some laboratories. There is no evidence to show whether the exercise has had any effect on the practice of virology in participating laboratories but some baselines have been produced for comparison with the results of investigations in the future.


Effect of cholesterol feeding on circadian rhythm of hepatic and intestinal cholesterol biosynthesis in hamsters.

Forty-eight adult hamsters were divided equally into two groups fed a control diet and a 2% cholesterol diet, respectively, under a rigid lighting (6 PM-6 AM) and feeding (6 PM-8 AM) schedule for three weeks. The cholesterol synthetic activity of the liver, stomach, small intestine, cecum, colon and kidney was measured by in vivo conversion of acetate-1-14C to cholesterol in four animals each time at 4 hour intervals. A remarkable circadian rhythm with the peak at midnight and the nadir at noon was found in the liver of the control hamsters, but was completely abolished in the cholesterol-fed animals since the activity was nearly totally suppressed at all times. The small intestine exhibited a similar rhythm with the peak at midnight but maintained a high baseline activity from 8 AM to 6 PM. Cholesterol feeding did not alter the baseline activity but reduced 17% of the peak activity. Other organs failed to show such a circadian rhythm.


Tartrazine: solid-phase radioimmunoassay studies of an azo dye implicated in allergic reactions (azo dyes and allergy).

A solid-phase radioimmunoassay procedure was adapted for the haptenic study of tartrazine, an azo dye implicated in various forms of allergy. Further, the haptenic relationship of tartrazine and aspirin was investigated, since sensitivity of individuals to the two substances is often clinically associated. The specificity of antibody to tartrazine was directed strongly toward a pyrazolone intermediate of the molecule, 1-(4-sulfophenyl)-3-carboxy-5-hydroxy-pyrazole. Aspirin did not cross-react with anti-tartrazine, suggesting that the clinical association of aspirin and tartrazine sensitivity in patients is a nonimmunological phenomenon.


Arginine deficiency and orotic aciduria in mammals.

Dietary arginine deficiency in rats causes significant increases in urinary excretion of urea, citric acid and orotic acid independently of feed intake. Urea excretion during arginine deficiency depends upon the diet, sex, age, and species. Thus urea excretion has limitations as an indicator of arginine availability. Although elevated urinary citric acid during arginine deficiency is more consistently observed, it may be influenced by citric acid in natural dietary ingredients. Orotic acid excretion, however, appears to be a reliable indicator of available dietary arginine based upon studies in rats, mice, hamsters, guinea pigs, rabbits, and dogs.


Urine concentration and dilution: effect on red cell survival.

Survival time of 51Cr-labeled red cells was determined in dogs subjected to water restriction excreting concentrated urine and again following a 6-week period of ad lib. water intake. During water restriction, RBC survival was reduced to one-seventh of normal. In rats with untreated diabetes insipidus, 51Cr RBC survival was reduced 30% as compared to the pitressin-treated state. It appears that RBC survival may be influenced by osmotic stress associated with the state of urine concentration and dilution.


Uptake of mercury and mercury-amino acid complexes by rat renal cortex slices.

This study was undertaken in order to assess the effects of metabolism and complexations with amino acids on the renal uptake of mercury using rat renal cortex slices as the experimental system. Mercury levels attained in the slices after 60 min of incubation were 50% higher with mercuric cysteine than with mercuric chloride. This enhancement of uptake with mercuric cysteine was reduced in the presence of a tenfold molar excess of histidine or lysine, but not by serine. Excess cysteine markedly increased mercury uptake. Incubation at 25 degrees significantly reduced uptake of mercuric cysteine, but not mercuric chloride. Anaerobic conditions and incubation in the presence of DNP each reduced mercuric cysteine uptake to the control level of mercuric chloride without affecting uptake of mercuric chloride. The differential aspects of metabolism on the uptake of mercuric cysteine and mercuric chloride and the competitive effects obtained with amino acids known to compete with cysteine in renal reabsorption support the hypothesis that a portion of the renal uptake of mercury operates through amino acid transport mechanisms acting on mercury-amino acid complexes.


Characterization of acetylcholine-induced insulin secretion in the isolated perfused dog pancreas.

In the presence of a nonstimulatory concentration of glucose, a 60-min perfusion with 50 muM acetylcholine was shown to elicit a monophasic release of insulin in the isolated dog pancreas preparation. A decline in secretory response, which may be due to desensitization of the beta-cell to acetylcholine, was noted during the latter part of the perfusion interval. The potent insulin secretory response elicited by acetylcholine during the 60-min period was abolished 0y 25 muM atropine. Inhibition of the insulinotropic action of acetylcholine was also noted with administration of the mitotic spindle inhibitor, colchicine. When compared to 20-min control perfusions, addition of 1 mM colchicine resulted in a 50% reduction in acetylcholine-induced insulin release. These results suggest that insulin secretion stimulated by acetylcholine can be considered to be due to a muscarinic action of this agent which is dependent, at least in part, upon the microtubular system of the beta-cell.


The matrix of rat calvarium as transformant of fibroblasts.

Allogeneic transplantation of coarse powders of the rat calvarial matrix to subcutaneous spaces resulted in transformation of fibroblasts to chondroblasts and osteoblasts. The emergence of new phenotypes was quantitated by determination of alkaline phosphatase activity and 45Ca incorporation. A comparison of the matrices from rat calvarium and diaphyseal bone revealed that matrix of the shaft of long bones is more potent as transformant than matrix of the vault of the skull.


Intrarenal blood flow distribution: effect of carotid occlusion.

In this study we have examined the influence of bilateral carotid occlusion on intrarenal blood flow distribution. Using labeled microspheres to determine intrarenal hemodynamics, bilateral carotid ligation in mannitol or saline expanded dogs resulted in an increase in outer cortical blood flow and a decrease in inner cortical flow. Total renal blood flow and glomerular filtration rate did not change significantly during carotid occlusion whereas the average mean arterial blood pressure rose from 130 to 166 mmHg. Inner cortical flow resistance increased substantially after carotid occlusion; outer cortical resistance was unchanged. These results suggest that bilateral carotid occlusion selectively activates inner cortical renal sympathetic fibers.


Vascular responses to plasma hypoosmolality in man.

To study limb vascular responses to plasma hypoosmolality in man, we infused test solutions of hypoosmolar NaCl (145 mOsm/kg) and control solutions of isosmolar NaCl (290 mOsm/kg) into the brachial arteries of 14 mornotensive and 13 essential hypertensive patients. Limb blood pressures were monitored, limb blood flow was measured by indicator-dilution, and limb vascular resistance was calculated as mmHg/ml flow/min/100 cm3 limb volume. The infusions did not significantly change systemic plasma osmolality, sodium concentration, or blood pressure. Compared to control infusions, the hypoosmolar infusions decreased limb venous plasma osmolality and serum sodium concentrations by an average of 12 mOsm/kg and 7 mEq/1, respectively. Compared to control infusions, limb venous serum concentrations of potassium, calcium, magnesium, or blood hematocrit were not altered by the hypoosmolar infusions. In response to the hypoosmolar infusions, limb resistance increased by 28% in normotensives and by 26% in hypertensives. We conclude that the acute local vascular response to a small reduction in plasma osmolality in the limb of man is a large increase in vascular resistance. We found no evidence for abnormal responses to plasma hypoosmolality in essential hypertensives.


Absence of detectable interferon in jejunal biopsies, jejunal aspirates, and sera in experimentally induced viral gastroenteritis in man.

Seven of thirteen normal volunteers inoculated with either the Norwalk of Hawaii agent of viral gastroenteritis demonstrated clinical illness, with typical rapid onset, short duration, and rapid recovery. Examination of sera, jejunal aspirates, and jejunal biopsy specimens obtained 48-96 hr after inoculation, failed to reveal the presence of interferon in samples from either ill or well subjects.


Changes in the daily rhythm of plasma corticosterone concentration related to seasonal conditions in the white-throated sparrow, Zonotrichia albicollis.

Circadian variations in concentrations of plasma corticosterone were investigated in the white-throated sparrow maintained on short (10-hr) or long (16-hr) daily photoperiods. In addition, the plasma concentrations of corticosterone were determined throughout a day in birds that were in the reproductively photosensitive spring migratory condition, the reproductively photorefractory post nuptial molt condition, and the fall migratory condition. Distinct unimodal rhythms were found in photosensitive birds. The daily rise occurred 12 hr after the offset of light in birds kept on both the short and the long photoperiodic regimens. There was no discernible daily variation in photorefractory birds kept on a 16 hr daily photoperiod and there was a bimodal rhythm in the birds that were in the fall migratory condition. The results are consistent with an hypothesis that assigns an important role to the circadian rhythm of corticosteroid concentration in the photoperiodic mechanism controlling seasonal reproductive and migratory conditions in the white-throated sparrow.


Influence of dietary safflower oil and tallow on growth, plasma lipids and lipogenesis in rats, pigs and chicks.

Rats, chicks and pigs were fed diets containing safflower oil or tallow. Plasma triglyceride levels were elevated when tallow, rather than safflower oil was added to the diet of rats, unchanged in chicks and lowered when tallow, rather than safflower oil was fed to pigs. The rate of fatty acid synthesis in rat and chick liver was higher, whereas the rate of lipogenesis in adipose tissue preparations from rats and pigs was lower when tallow, rather than safflower oil was fed. These results indicate that there are species-specific, as well as organ-specific, metabolic responses to various dietary fats.


Effect of oral contraceptives and pregnancy on erythrocyte deformability and surface charge.

Erythrocyte deformability and surface charge were studied in normal premenopausal women, oral contraceptive users, and pregnant women. The increased incidence of thrombosis in women taking oral contraceptives could not be explained by decreased erythrocyte deformability or surface charge. However, the decreased erythrocyte deformability of late pregnancy may relate to thrombosis during this period and to increased hemolysis in patients with certain hemoglobinopathies.


Influence of quinidine and propranolol on the intracellular distribution of 45Ca in rat heart.

The intracellular distribution of 45Ca in the rat heart was studied following separate and combined administration of quinidine and propranolol. Both drugs caused an increased uptake of 45Ca in the nuclear-cell membrane fraction but quinidine suppressed the uptake in mitochondrial and microsomal fractions whereas propranolol did not affect the uptake of 45Ca in these fractions. In addition, there was an increase in serum radioactivity noted with quinidine which was not observed with propranolol. Combined treatment resulted in restoration of normal values for blood and mitochondrial fractions and an increased uptake of 45Ca in the microsomal fraction.


Lack of effect of portacaval shunt on ornithine decarboxylase activity in regenerating rat liver.

The influence of the end to side portacaval shunt on the level of activity of the enzyme ornithine decarboxylase following partial hepatectomy was investigated. A sharp rise in the enzyme level was found in both the shunted animals and in the normal controls. The chronology of the increase in enzymic activity was somewhat altered in the portacaval shunted animals, but both groups had similar peak values. The rate of cell division was also found to be unaffected. This report finds no evidence of support for the reported inhibition by the portacaval shunt of the increase in ornithine decarboxylase following partial hepatectomy.


The toxicity of thioxanthene neuroleptics to isolated rat liver cells.

A series of thioxanthenes was tested for cytotoxicity to isolated rat hepatocytes, as measured by the loss of an intracellular enzyme (GOT) to the surrounding medium. The relative order of potency was found to be: SKF 10812 greater than cis- = trans-chlorprothixene = N-756A greater than cis- = trans-flupenthixol greater than xanthiol greater than methixene = cis- = trans-clopenthixol = N-716 greater than N-710. The presence of an unsaturated exocyclic bond increased the apparent toxicity as did the presence of a substituent (trifluoromethyl, chlorine, bromine) at the two position of the tricyclic nucleus. The trifluoromethyl substituted thioxanthenes were three to four times more potent than their halogenated analogs, but there were no differences in potency among the halogenated (chlorine or bromine) thioxanthenes. Compounds which had a dimethylaminopropylidene side chain were five to six times stronger in causing enzyme leakage than were their analog which had a hydroxyethylpiperazinylpropylidene side chain. Although only the cis-isomers of each compound are highly active neuroleptics, both isomers were equipotent at causing the efflux of GOT from rat hepatocytes.


Immune responses of inbred guinea pigs against random terpolymers containing L glutamic acid and L alanine.

The immune responses of the inbred guinea pig strains 2 and 13 have been determined against random terpolymers of L glutamic acid and L alanine and a third amino acid. Strain 2 guinea pigs responded against GAT10, GAT20(LLD), GAT10(NO2)15, GAT4, and GAL10. However, strain 13 guinea pigs responded only against GAT10. The explanation offered is that strain 2 guinea pigs, which have the Ir-GA gene, recognize the polymers via random GA determinants present in sufficient concentration in all of the above polymers. However, strain 13 guinea pigs recognize the GAT10 via the Ir-GT gene, and reduction in the concentration of tyrosyl residues below 10 mole % by various procedures alters the concentration of available random GT determinants necessary for interaction with the gene product of the Ir-GT gene.


Inhibition of cyclocytidine-induced enlargement of parotid and heart by propranolol or sympathectomy.

Enlargement of salivary glands and heart of mouse as well as rat is caused by chronic administration of the antitumor agent cyclocytidine. In rat, the effects are maximal within 3 days, and are reversible, but with heart, not readily so. The organ enlargement, in both species, is the result of an action of the cyclocytidine involving beta adrenergic receptors since administration of propranolol 20 min prior to injection of cyclocytidine prevented the enlargement as well as the increases in nucleic acids associated with the enlargement. These beta adrenergic effects appear mediated through indirect actions of cyclocytidine that probably involve release of norepinephrine from postganglionic nerve fibers. This conclusion is based on the findings that parotid sympathectomized for 5 days does not exhibit the same secretory responses and glandular enlargement with cyclocytidine administration that are observed in the innervated mate. For example, amylase activity of the innervated gland was reduced from 525 mg/mg of gland (unstimulated parotid) to approximately 190 two hr after administration of 500 mg/kg of cyclocytidine, whereas that of the sympathectomized gland was unchanged (510 mg/mg). In addition, cyclocytidine caused only a small increase in weight and nucleic acid content of the sympathectomized parotid, whereas the innervated mate exhibited the usual marked increases in all parameters (weight and RNA were twice as great as those of untreated rats). Guanethidine and bretylium were used in conjunction with cyclocytidine to provide additional evidence for the indirect beta adrenergic action of cyclocytidine on heart and parotid gland.


Actions of prostaglandins E1 and F2alpha on isolated intrapulmonary vascular smooth muscle.

The effects of PGE1 and PGF2alpha were studied on isolated strips of intrapulmonary arteries and veins from dog, sheep, swine and man. PGF2alpha contracted human arterial strips in a dose-dependent fashion, relaxed slightly sheep arteries and had no effect on dog arteries. Canine, sheep and human venous strips were contracted by PGF2alpha. PGE1 relaxed slightly both veins and arteries from dog and sheep. Human arteries usually contracted slightly and human veins usually relaxed slightly to PGE1. In a limited number of experiments, swine arteries and veins failed to respond to PGF2alpha or PGE1. All the vascular strips contracted well when exposed to NE. These results suggest that the responses of intrapulmonary vessels to PGF2alpha and PGE1 are species-dependent. PGF2alpha generally exhibits a contractile action, especially on veins. PGE1 usually relaxes intrapulmonary vessels. With regard to vessels from man, PGF2alpha is a powerful stimulant while PGE1 produces only small, variable effects.


Effect of treatment on longevity in spontaneously hypertensive rats.

Continuous control of the pressure of spontaneously hypertensive rats at systolic levels of 90-100 mm Hg with antihypertensive agents significantly prolonged their life span. The mean survival time in control animals was 73 weeks as compared to 96 weeks in treated SHR (P less than .0005) with 11% of the latter surviving to approximately 3 yr of age. Cardiovascular lesions were limited almost exclusively to the control rats. The general health, body weight and reproductive functions of the experimental animals remained normal throughout the drug treatment. These results indicate that by preventing the rise in blood pressure and consequent cardiovascular complications the life span of the SHR may be prolonged to that of the normal albino rat.


Toxic effects of a new boron containing heterocycle: 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro 3a,4a,4-diazabora-S-indacene.

LD50 values in mice for 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro-3a,4a,4-diazabora-S-indacene (Myborin) were determined by the ip, po, and sc routes. The LD50 value for ip was 69.5 mg/kg found by the method of Litchfield and Wilcoxon, with upper and lower confidence limits of 77.8 and 62.1 mg/kg. Oral and sc LD50's were approximated after the method of Deichmann and LeBlanc and were found to be 180 mg/kg (po) and 420 mg/kg (sc). Each of these values has a confidence range of +/- 30%. Myborin induced convulsions, hyperreflexia, and death accompanied by tetany when given by either the ip or oral routes. Moreover, Myborin induced porphyria in animals surviving for 24 hr after these routes of administration and in virtually all animals dosed sc. Death by the sc route is probably a result of acute porphyria. Hepatomegaly and skin photosensitivity were demonstrated to be profound. Boron levels in the livers of mice were determined colorimetrically 24 hr after ip injections of Myborin and in untreated control mice. The quantity of boron found in the experimental group was 15.46 mug/g wet liver as compared to 8.11 mug/g wet liver for controls (P less than 0.01). The difference corresponds to 23% of the injected quantity of boron.


Distribution and disappearance rate of submaxillary renin.

Highly purified submaxillary renin (SR) labeled with 125I was injected intravascularly into adult male mice following removal of submaxillary glands and kidneys, and the disappearance of this labeled SR from the circulating vascular volume was studied on the basis of a two compartment system. There was a fast and a slow component to the disappearance curves. Mean half-times of the fast and slow component were 12.4 +/- 0.4 min and 86 +/- 3 min in sialoadenectomized mice, while in mice whose submaxillary glands and kidneys were removed the half-times were 14.7 +/- 0.4 min and 108 +/- 7 min, respectively. The uptake of radioactivity by various organs of the mouse was also measured. Accumulation of radioactivity occurred in the kidneys and liver. Only trace amounts of radioactivity were found in the other organs. The findings suggest that the fast component of the disappearance curve was probably due to equilibration of the injected labeled SR in the circulation. However, the fast component may be related to some extent to the rapid uptake of labeled SR by the kidneys. The half-time of the slow component may represent the true halflife of SR in mice, since a significant reciprocal relationship between the half-times of the slow component and metabolic rate constant k10 was observed both in sialoadenectomized mice and in nephrectomized-sialoadenectomized mice.


Serum prolactin levels in fetal and neonatal hamsters and the relationship to maternal levels.

Immunoreactive prolactin was measured by RIA in 13.5-15.5 day gestation fetal and 0.5-3.5 day neonatal hamster serum and found to significantly reflect rises and falls in maternal levels. On the average, fetal and neonatal levels were 37% of maternal prolactin serum levels. 125I-PRL injected into 13.5-15.5 day pregnant hamsters was demonstrated to cross the placenta and enter fetal circulation. Ten min after injection, fetal serum levels were calculated to be an average of 3.9% of the radioactivity recorded in maternal serum. There is a strong possibility that fetal prolactin serum levels may be, at least in part, attributed to a maternal source.


Changes in blood hormone levels during the immune response.

Injection of three different antigens into rats or mice led in the course of several days to about a threefold increase in serum corticosterone levels and concommitantly to a decrease in thyroxine (rats). In view of the known immuno-suppressive effect of the glucocorticoids the possibility is considered that the endocrine changes induced during the immune response could significantly modulate the subsequent character of the immune response, e.i. magnitude, duration and lymphoid cell proliferation, however, a more complete pattern of hormonal variations and their cause needs to be established. These findings while admittedly preliminary, suffice to provide an indication of a temporal pattern of hormonal change during the immune response which could be important in immunoregulation.


Ecteinascidia turbinata extracts inhibit DNA synthesis in lymphocytes after mitogenic stimulation by lectins.

Aqueous ethanol extract of a tunicate which was previously found to exert antitumor and immunosuppressive activities in vivo was tested for its effect on normal human lymphocytes in vitro. The extract suppressed the uptake of tritiated thymidine by lymphocytes stimulated with mitogen. This suppressive effect did not require continuous presence of the extract. Treatment of lymphocytes prior to mitogenic stimulation resulted in suppressive effect. The fact that suppression by the extract could also be achieved 24 hr after exposure to mitogen, an interval which was found to suffice for the attainment of maximal commitment for blastogenic transformation indicates that Ete can act at a stage subsequent to the binding of the lectin and elicitation of a mitogenic signal(s).


Disposition of dapsone and monoacetyldapsone in rats.

Female Buffalo and Lewis rats receiving 1.0 mg DDS/kg ip exhibited higher plasma levels of DDS and its monoacetylated metabolite, MADDS, than did male rats of each strain receiving the same dose. The fraction of the total measured drug in plasma as MADDS at 8 hr in female rats of both strains ranged from 43 to 62% compared with a range of 28-31% in male rats. Plasma half times of disappearance (T1/2) of DDS ranged from 5.0 to 6.8 hr and were not different among sexes and strains. Deacetylation of MADDS to DDS occurred when equimolar doses of MADDS were administered. An approach to a steady state of acetylation-deacetylation was indicated by comparing the percentage MADDS of the total drug in plasma in the respective sexes and strains receiving both drugs. T1/2 values of MADDS were significantly lower than values for DDS in Lewis rats. They were not different in Buffalo rats. Protein binding studies in plasma from rats receiving 5.0 mg DDS or 5.8 mg MADDS/kg showed 67-72% binding of DDS and 91% binding of MADDS. These in vivo observations were confirmed by in vitro binding studies. Comparison of these results with those of earlier studies in mice and man indicates that the rat is a better model of man than is the mouse for studies on the disposition of DDS.


Virulence of Streptococcus mutans: biochemical and pathogenic characteristics of mutant isolates.

The in vitro dextran-sucrase activities and adherence to glass of S. mutans 6715 and PS14 wild types and mutants were quantitated and compared with their in vivo cariogenicity in young, gnotobiotic rats. In general, S. mutans PS14 mutants B414 and B421 and 6715 mutant C4 demonstrated less dextran-sucrase activity and adherence than parental strains and caused fewer carious lesions in gnotobiotic rats. Rats monoinfected with either PS14 mutants B414 or B421 had less plaque and viable S. mutans in plaque than rats infected with parental strain. Both S. mutans 6715 mutants C211 and C229, demonstrated greater enzyme activity and adherence than the parental strain and produced more carious lesions.


Effect of propranolol on plasma renin activity, renal cortex renin, and adrenal and brain isorenins in rats.

Propranolol administration to rats was studied for its effects on plasma renin activity, renal renin content, and adrenal and brain isorenins. Propranolol was given intraperitoneally at 6 and 30 mg/kg/day for a 15-day period. Pulse rate was significantly decreased. There were no effects on the isorenin content of adrenal or brain tissue or on renal renin content. Rats responded in two completely different ways with respect to plasma renin activity. Two-fifths had a total suppression of plasma renin activity; the rest had concentrations similar to those in controls. These observations are consistent with those seen during chronic administration of propranolol to hypertensive patients and suggest that its antihypertensive effect may in some patients be through the suppression of renin release. Its mechanism of action in most patients remains at present unclear.


Brain cholesterol XVIII: EFFECt of methylphenidate (Ritalin) on [U-14C] glucose and [2-3H] acetate incorporation.

The effect of a single injection of methylphenidate (Ritalin, 4 mg/kg) on precursor ([2-3H]acetate and [U-14C]glucose) incorporation into brain cholesterol was studied. The drug caused a steady decrease in the concentration of brain cholesterol during the 24-hr period examined. Incorporation studies during this time with [U-14C]glucose indicated higher than normal incorporation for all time periods studied. The most significant incorporation increases took place 2 and 4 hr after drug injection. Experiments using [2-3H]acetate as the sterol precursor gave incorporation values which tended (not significantly) to be lower than control values at 2 and 4 h. The values after 12 hr were less than normal, while the 24-hr group indicated an increase to or slightly higher than normal values. These data suggest that the pharmacological effect of methylphenidate may be due to lowering of brain cholesterol levels directly or on some more basic metabolic process leading to a decreased level of membrane sterols.


Effects of high but nontoxic dietary zinc on zinc metabolism and adaptations in rats.

The effects of feeding a high but nontoxic zinc level to young rats for varied time periods on zinc metabolism and adaptations were investigated. Adding 600 ppm supplemental zinc to a "corn-soy" diet for periods from 7 to 42 days did not materially affect stable zinc level in any tissue studied. However, in every tissue, 65Zn retention from a single oral dose declined sharply with duration of added zinc feeding to 21 days, indicating a continuing adaptation in zinc metabolism for at least this period of time. Likewise, fecal 65Zn excretion increased with length of feeding time on high zinc, indicating a continuing reduction in net absorption for most of the 42-day period. When the data are compared with similar previous cattle studies, it is evident that there are major qualitative differences in zinc metabolism and homeostatic control between rats and cattle.


Prolactin and growth hormone synthesis: effects of perphenazine, alpha-methyltyrosine and estrogen in different thyroid states.

The effects of thyroid hormones on prolactin (PRL) and growth hormone (GH) synthesis by the rat anterior pituitary gland were assessed in vitro. A marked reduction (84-87%) in the rate of H3-leucine incorporation into GH was evident 2-4 weeks after thyroidectomy, while incorporation into PRL was 52-71% less than that measured in glands from intact rats. A single injection of T4 (200 mug/kg) administered to thyroidectomized (THX) rats 48 hr before sacrifice significantly increased incorporation into both pituitary hormones, although the stimulation of GH synthesis was much more dramatic. Perphenazine, alpha-methyltyrosine and estrogen enhanced the rate of PRL synthesis in intact rats. Thyroid ablation did not affect the response to perphenazine, but significantly increased the response to alpha-methyltyrosine and estrogen. On the other hand, administration of T4 to THX rats receiving perphenazine, alpha-methyltyrosine or estrogen diminished the stimulatory influence of these treatments on PRL synthesis. Perphenazine, alpha-methyltyrosine and estrogen had no effect on the rate of GH synthesis in THX rats, nor did they alter the ability of T4 to restore GH synthesis in these animals. These results indicate that GH synthesis in the rat is dependent upon thyroid hormones and support the concept that these hormones exert their stimulatory effect directly on pituitary somatotrophs. Pituitary lactotrophs, however, appear to retain much of their capacity to synthesize PRL under conditions of thyroid deficiency. The changes in pituitary PRL levels and synthesis rate induced by thyroid ablation might reflect differences in the number rather than the activity of these cells.


Glucose tolerance, plasma and pancreatic insulin levels in zinc deficient rats.

Two experiments were conducted to examine the effect of zinc deficiency on glucose tolerance, and on blood and pancreatic insulin concentrations. In the first study, no significant differences in blood glucose or plasma insulin levels were noted between pair-weighted zinc deficient and zinc sufficient rats after an oral glucose load. In the second experiment, the concentration of pancreatic insulin in pair-fed zinc sufficient rats did not differ significantly from that of zinc deficient rats. However, a zinc deficient group fed ad libitum had significantly lower pancreatic insulin levels, suggesting that food restriction may cause increased pancreatic insulin. Thus, zinc deficiency per se had no apparent effect on oral glucose tolerance or pancreatic insulin concentrations.


Glucagon stimulation of hepatic gluconeogenesis in neonatal pigs.

The effect of an infusion of glucagon on gluconeogenesis was studied in 5-day-old piglets. Glucagon stimulated hepatic new glucose formation from lactate, but did not significantly change blood glucose or plasma free fatty acid levels. The data suggest that glucagon enhances substrate flow in the gluconeogenic pathway in neonatal animals.


Influence of altitude and age on pulmonary arterial pressure in cattle.

Pulmonary arterial pressures in native cattle ranging in age from 3 months to 10 yr were found to be increased with increasing altitudes of residence from sea level to 3048 m. At altitudes of 2590 and 3048 m, but not at sea level or 1524 m, the pressures were higher in older than in younger cattle. The magnitude of the pulmonary arterial pressure, and probably the rate of progression of pulmonary hypertension at high altitude, were much less in native cattle than in cattle that were newcomers from low altitude. Natural and artificial selection are believed to have minimized the level of pulmonary hypertension in native high altitude cattle, thus protecting them from high mountain or brisket disease.


Congenital abnormality of pituitary-thyroid axis in spontaneously hypertensive rats (SHR) and stroke-prone rats (SPR).

In an attempt to study whether TSH abnormality was genetically determined in SHR and SPR, plasma T4, T3, TSH and prolactin concentrations were measured in the animals with intervals of 1 to 3 months. Hypertension was found in 6-month-old SHR and SPR, but it was not found in younger animals. In contrast, a decrease of plasma T3 and an increase of plasma TSH were found in 15-day-old SHR. Also, an increase of TSH was found in 1-month-old SPR in spite of normal plasma T3 concentration. These abnormalities in SHR and SPR increased progressively with age. It is suggested that thyroid-pituitary abnormality was genetically determined in SHR and SPR.


Viscosity and gelation studies in deer hunting hemoglobins.

Sickling, viscosity and gelling properties of the red cells and the hemoglobins of three Virginia white-tailed deer homozygous for types II and III (the sickling types) and V (the nonsickling type), respectively, have been analyzed. The sickling of erythrocytes of deer with type II or III is inhibited by urea and cyanate at concentrations which are comparable to those used in in vitro studies of red cells from patients with sickle cell anemia. No differences were observed between the viscosities of the three deer hemoglobin types at temperatures of 12 degrees C or above. High concentrations of deer hemoglobin types II and III gelled at 1 degree C and at pH values of 7.4-7.7; the minimum gelling concentration of type II was 33.5 g% and of type III was 38 g%. Gel formation was not observed at pH values between 6.7-7.1. Hemoglobin type V did not gel and prevented the formation of gels of type II and III in mixtures at pH 7.6-7.7.


A rapid method for establishing short-term primary cultures of human tumor cells from fresh tumor biopsies.

A rapid method for the establishment of short-term primary cultures of human tumor cells obtained from fresh surgical biopsies is described. The method consists of the separation of the viable fraction of tumor cells by differential flotation on ficoll-hypaque density solution and its subsequent seeding into culture flasks. Tumor cell growth is established within 2-3 days. The incidence of overgrowth with fibroblasts is apparently reduced and usually delayed for 4-5 weeks, but cannot be prevented by this method.


Antigenic properties of subcellular fractions from canine pancreas: development of a zymogen membrane specific antibody.

Immunization of rabbits with a membrane preparation from dog pancreas produced precipitating antibody against an antigen present in the pancreas of several mammals. This antigen appears to be organ-specific but not species-specific and is localized in the pancreatic zymogen granule membrane fraction. It is thought to represent glycoproteins of mol wt 70,000-90,000 as well as a smaller species of mol wt less than 10,000.


Lipid composition in postnatal methylazoxymethanol-treated swiss albino mouse cerebellum.

Postnatal Swiss albino mice were treated with with methylazoxymethanol acetate (MAM) or saline and sacrificed at 25 days of age. Granule cell depletion resulted. Significant reduction in the cerebellar weight, protein, ganglioside sialic acid , cerebrosides, sulfatides, and phospholipids were documented. There was not, however, selective reduction of any component known to be associated with the synaptic structures. Specific association of cerebellar ganglioside with its granule cell population was not substantiated. Cerebroside/sulfatide ratios were not different in the two groups, indicating that significant alterations previously observed in spinal cord were not present in the cerebellum. It was concluded that the bulk of cerebellar granule cells and their synaptic connections could be deleted without affecting total ganglioside and phospholipid concentrations.


The use of radioactive microspheres to quantitate hyperemia in dermal inflammatory sites.

A variety of dermal lesions produced by PGE1, tuberculin, and allogeneic lymphocytes were induced in rabbits, guinea pigs, and sheep, respectively. Microspheres labeled with 85Sr were injected into the ascending aorta, and the distribution of radioactivity in the lesions, saline control sites, and various major organs was assessed. It was concluded that the trapping of the microspheres was related to the degree of hyperemia induced, and that this technique enabled a quantitative measure of the blood flow. PGE1 was found to be a potent mediator of hyperemia and to have a significant effect on the blood flow at a dose of 1 ng. The blood flow to cellular hypersensitivity reactions was measured and the capacity of the skin to accomodate a large increase in flow during the inflammatory response was established.


Renin substrate in plasma of various mammalian species: electrophoresis on polyacrylamide gel.

The plasma of eight different species was subjected to electrophoresis on polyacrylamide gel, and the position of renin substrate was determined. There are considerable differences in the electrophoretic mobility of the renin substrates tested. Sheep substrate shows the slowest migration and mouse substrate the most rapid. The species tested appear to fall into two groups: slow-moving substrates occuring in the plasmas of sheep, cow, pig, and rabbit and fast moving substrates in man, dog, rat, and mouse. In most species only a single peak of renin substrate appeared, but in man and dog a minor peak was often observed in addition to the prominent major one. The classification of human renin substrate as an alpha-2-globulin is questioned.


Arterial-venous magnesium gradients in hypovolemic shock: an indication of the irreversible state.

Arterial-venous magnesium differences were examined in mongrel dogs stressed with reversible and lethal hypovolemia. Increases in serum Mg with hemorrhage have long been known to occur in both humans and animals, yet, increased blood Mg levels have not been viewed as an indicator of the irreversible shock state. The magnesium gradient was shown to be a good indicator of cell destruction which is consistent with lethal shock.


Hematologic changes in chronic arthritis of mice induced by Mycoplasma arthritidis.

The arthritis caused by iv injection of M. arthritidis in mice was found to be associated with neutrophilia and lymphopenia without a change in the total WBC concentration. A mild anemia developed which was characterized by hypoferremia and plentiful RE iron but with an increased plasma total iron-binding capacity. This anemia therefore differs from the anemia of chronic disorders and indeed from any anemia which occurs in man.


Renal function in the choline deficient rat.

Abnormalties in renal concentrating ability and free water reabsorption, and a diminished sodium excretion, glomerular filtration rate, and effective renal plasma flow were observed in adolescent rats which ingested a lipotrope deficient diet for 10 months.


The role of potassium ion in muscle glycogenolysis and glycolysis.

We have presented evidence that in an in vitro system, glycogenolysis and glycolysis function normally at potassium levels far below those observed in muscle cell water of severely deficient dogs. We suggest that a functional impairment of glycogenolysis or glycolysis is unlikely to be a mechanism by which potassium deficiency leads to rhabdomyolysis.


Influence of dietary carbohydrate on copper, iron, and zinc status of the rat.

Rats were fed diets containing starch, sucrose, glucose, or fructose as the carbohydrate source, and the influence of these carbohydrates on copper, iron, and zinc status was determined. It was found that copper absorption was reduced in animals receiving glucose. This reduction was exaggerated when a high level of iron was present in the diet, indicating a possible antagonism between iron and copper at the site of absorption. Iron and zinc status of the animals also appeared to be influenced to some extent by dietary carbohydrate.


Local regulation of the uterine blood flow by the umbilical circulation.

Observations were made of the responses of the uterine blood flow in the near-term pregnancy to occlusion of the umbilical circulation to a few cotyledons of the near-term sheep placenta and in one placenta of the multiparous rabbit pregnancy. It was found that the uterine blood flow declined to 67% of its predicted value 1 day after umbilical ligation in the sheep placenta and to 61% of its predicted value 1 day after the death of one of the fetuses of the rabbit pregnancy. The change in the uterine blood flow in response to the occlusion of the umbilical blood supply to the adjacent area is a local response and is similar in its time course and magnitude to the response of the whole placenta which has been previously observed by Raye et al. (9). This local response of the uterine blood flow is considered to be evidence that the uterine blood flow is in part determined and controlled by the structural or chemical nature of the adjacent fetal compartment.


Adenylate cyclase stimulation by trypsin.

Adenylate cyclase activity of a rat embryo fibroblast cell line (F111) is markedly increased by brief treatment with 1:300 trypsin. The degree of stimulation depends upon the length of time the cells are treated and the concentration of trypsin. Crystalline trypsin produced a stimulation similar to that obtained with 1:300 trypsin. Further, the addition of soybean trypsin inhibitor blocked the stimulation of adenylate cyclase by 1:300 trypsin. Trypsin-treated adenylate cyclase responds to PGE1, but there is no increase over that of untreated enzyme. This result and the increase in fluoride-stimulated levels of activity suggest that the trypsin is acting upon the catalytic unit of the enzyme.


Effect of calcitonin on DNA synthesis in experimental wounds.

3H-thymidine incorporation and intracellular distribution in epidermal cells and fibroblasts of scar tissue from wounded rabbits were studied following synthetic salmon calcitonin administration. Both scintillation counting and electron microscopic autoradiography revealed a marked increase in 3H-thymidine incorporation within nuclear dense chromatin of epidermal and fibroblasts cells, mainly in 2-day wounded rabbits and at 2.5 hr. Then, 3H-thymidine uptake decreased moderately. These findings demonstrate an important role of calcitonin on DNA synthesis.


Simian hemorrhagic fever virus: a new togavirus.

Using the prototype strain of SHF virus, we have confirmed the nature of the genome (RNA), the presence of an envelope (derived from an internal membrane), the virion size (45-50 nm), and probable cubic symmetry. We have also described four viral structural proteins and determined the phospholipid content of the virions. The known properties of SHF virus suggest that it should be classified in the Togavirus family, and possibly in the Flavivirus group.


Serum prolactin levels in rats following isoproterenol-induced myocardial infarction.

Circulating prolactin levels were monitored in nonarteriosclerotic, arteriosclerotic, and hormonally sterilized male and female Sprague-Dawley rats during the acute necrosis and repair phases of myocardial infarction induced by isoproterenol. Male rats are particularly prone to succumb to acute myocardial ischemia but reduction of androgen levels by neonatal sterilization improved survival considerably. Circulating prolactin levels are greatly increased, particularly in females, during acute myocardial ischemia. Since androgens suppress the hypothalamic center for prolactin release, prolactin levels were delayed and transitory in males. It is suggested that the superior survival of female rats may be related to their greater production of prolactin during acute stages of myocardial ischemia, which would dampen the tachycardia-inducing effects of the potent beta-adrenergic stimulating agent, isoproterenol.


The relationship between sodium excretion and renin secretion by the perfused kidney.

The effect of altered tubular sodium reabsorption on renin secretion (RSR) was examined under conditions in which other factors influencing renin release could be controlled or excluded. To do this, isolated canine kidneys were perfused at constant pressure with blood circulating from donor animals. Volume expansion or hemorrhage of the donor dogs produced large changes in the animal's blood pressure, renal function, sodium excretion (UNaV), and RSR, but were without effect on renal hemodynamics, UNaV, or RSR in the perfused kidney. Hemodilution without volume expansion, resulted in hypotension, decreased UNaV and increased RSR in the donor dogs, and increased UNaV and suppressed RSR in the perfused kidney. These effects of hemodilution in the perfused kidney were partially reversed when plasma protein concentration was restored to control levels with hyperoncotic albumin, and, overall, there was a significant inverse relationship between electrolyte excretion and RSR. These results provide new evidence for the hypothesis that the rate at which sodium is delivered to the macula densa is an important determinant of the rate of renin secretion.


Prevention of hypertension in the SH rat: effects of differential central catecholamine depletion.

Six-hydroxydopamine (6-OHDA) was administered intraventricularly to 6-week-old male spontaneously hypertensive (SH) rats of the Okomoto strain and to normotensive rats of the Kyoto-Wistar strain. In addition, bilateral lateral tegmental lesions were placed in 35-40-day-old SH rats to interrupt ascending noradrenergic pathways. SH rats treated with 6-OHDA did not develop hypertension and had lower heart rates than control rats. Blood pressure and heart rate of Kyoto-Wistar animals were unaffected by the drug treatment. 6-OHDA produced widespread depletion of norepinephrine throughout the CNS of both SH and Kyoto-Wistar rats. Bilateral lateral tegmental lesions interrupted the dorsal noradrenergic bundle and depleted forebrain norepinephrine. These lesions did not prevent the development of hypertension and led to an increased heart rate. It is concluded that 6-OHDA does not produce its effect through a nonspecific lowering of blood pressure, but rather, that it interferes with the expression of the hypertensive syndrome. The lack of effect seen following depletion of forebrain norepinephrine as the result of interruption of the dorsal noradrenergic bundle indicates that the fibers destroyed by this lesion are not essential for the development of genetically determined hypertension.


Effects of cholestyramine on 1,2-dimethylhydrazine-induced enteric carcinoma in germfree rats.

Oral administration of 1,2-dimethylhydrazine (DMH) induced intestinal neoplasms in germfree rats. A supplement of 2% cholestyramine resin in the diet increased the frequency of DMH-induced intestinal tumors and accelerated malignant transformation. Bile acids in the cecal content were determined with and without cholestyramine in order to obtain a correlation between the bile acid metabolism and the enteric carcinogenesis.


Studies on gluconeogenesis and ketogenesis in isolated hepatocytes from alloxan diabetic rats.

Gluconeogenesis and ketogenesis were studied in isolated hepatocytes obtained from normal and alloxan diabetic rats. Insulin treatment maintained near-normal blood glucose levels and caused an increase in glycogen deposition. The third day after insulin withdrawal the rats displayed a diabetic syndrome marked by progressive hyperglycemia and glycogen depletion. Net glucose production in liver cells isolated from alloxan diabetic rats progressively increased with time up to 72 hr after the last in vivo insulin injection. Maximal glucose production was observed at 72 hr with 10 mM alanine, lactate, pyruvate, or fructose. Glucose production decreased at 96 hr. The same pattern was observed with the incorporation of labeled bicarbonate into glucose. Ketogenesis in liver cells and hepatic lipid content also peaked at 72 hr.


The urea requirement and urease production of some human species of T-mycoplasmas.

Seven species of human T-mycoplasmas that grow in Fraction A and 20 mug urea/ml died when the urea was omitted. Two species would not grow in Fraction A broth containing 10 mug/urea/ml. The other five strains grew in broth containing 10 mug  urea/ml and were adapted by serial passage in broth containing decreasing concentrations of urea to grow in broth containing 2.5 mug/ml urea, but not in broth containing 1.25 mug/ml. Therefore the minimal urea requirement is not the same for the growth of all strains of T-mycoplasmas. In exponential phase broth cultures, urease was detected only intracellularly, none being found in the medium.


Effects of pretreatment with anti-inflammatory drugs on ozone-induced lung damage in rats.

The effects of pretreatment with acetylsalicylic acid (aspirin), hydrocortisone, indomethacin, and heparin administered ip against the pulmonary edema produced by O3-exposure (4 ppm for 4 hr) were studied in rats. These anti-inflammatory drugs were found to alter the injurious effect of O3 on lung differently. First, aspirin at the high dose (125 mg/kg) accentuated O3-induced lung injury, and had no effect at the low dose (10 mg/kg); second, hydrocortisone (50 mg/kg) failed to have any effect; third, indomethacin at a high dose (20 mg/kg) offered a significant degree of protection, but had no effect at the low dose (2.5 mg/kg); and fourth, heparin (1000 units/kg) also offered a significant degree of protection against the lung damage normally induced by O3-exposure. Several mechanisms for the favorable and unfavorable interactions of anti-inflammatory drugs with O3-exposure are discussed.


Scopolamine induced changes in activity and reactions to novelty.

The behavior of hooded rats was observed in an exploration box comprising novel and familiar halves following IP injections of 0.1, 0.25, 0.5, 0.75 or 1.00 mg/kg scopolamine or isotonic saline. Drug administration occurred after, rather than before, exposure to one of the alternative halves. All doses decreased reactions to the previously inaccessible novel half but decreases were greater for the 2 lowest doses. Rearing behavior was also suppressed by each dose whereas the number of apparatus cells entered (locomotion) was decreased by low doses but increased by high. The 3 behavioral measures showed declines in frequency during the course of each experimental session. However, low doses of the drug enhanced and high doses retarded these declines for rearing and cells entered. The study illustrated the difficulty in explaining data by unitary processes (such as attenuated habituation) when several behavioral indices and drug doses are employed within a single investigation.


Protection by nicotine from behavioral disruption caused by reticular formation stimulation in the rat.

Male Sprague-Dawley rats prepared with chronic electrodes in the mesencephalic reticular formation were trained to perform on a visual attention task. Short trains of electric current delivered to the reticular formation effectively blocked performance in a reversible and reproducible fashion. Subcutaneous administration of 100 mug/kg nicotine (as the base) served to attenuate the behavioral disruption caused by reticular stimulation. The suggestion that it is a nicotine-induced limbic system activation which antagonizes the behavioral disruption caused by electrically-induced reticular over-activation, is discussed.


Effects of haloperidol, methyltyrosine and morphine on recovery from lesions of lateral hypothalamus.

In rats loss of body weight and lethality were measured after bilateral electrolytic lesions of the lateral hypothalamus. The rats with incomplete lesions initially lost body weight but recovered spontaneously. Treatment with haloperidourgery facilitated the recovery in those rats. The rats with more complete lesions lost body weight which resulted in eventual death. Treatment with haloperidol (4 mg/kg/day) or morphine (60 mg/kg/day) given daily for six days before surgery promoted recovery and reduced the incidence of death. The drugs used in this study inhibit activity of brain dopamine receptors to result in the supersensitivity and/or promotion of regenerative processes. These effects are considered to be related to the facilitation of recovery from nerve injury.


Gamma-butyrolactone sleep: A 24-hour rhythm paralleling normal sleep in the rat and CNS amine changes.

The duration of sleep induced by a fixed dose of gamma-butyrolactone (GBL) (350 mg/kg, IP) FOllows the normal circadian sleep pattern of rats. GBL sleep duration is maximal at 1800 hr and minimal at 0600 hr. CNS amine changes are not extensive, but when normal sleep is anticipated, GBL treatment increases dopamine and serotonin levels and decreases norepinephrine levels.


Delta 9-tetrahydrocannabinol produced discrimination in pigeons.

In an operant situation pigeons learned to peck one response key 90 min after an injection of 0.25mg/kg delta9-tetrahydrocannabinol (delta9-THC) and another key when trained nondrugged. When tested with doses of delta9-THC lwer than the training dose the birds disciminated 0.20 mg/kg of the drug from the nondrugged state but not 0.15 mg/kg or lower doses. The animals were able to discriminate the drug state from the nondrugged 180 min but not 360 min after the injection At a shorter interval (45 min) both drug and nondrug responding appeared. Cannabinol and cannabidiol (4.0 - 8.0 mg/kg) did not elicit any drug responses, nor did pentobarbital, ditran or amphetamine. Tests with LSD resulted in both drug and nondrug responding. When administering noncannabinoid drugs in combination with delta9-THC 0.15 mg/kg the birds responded at the key associated with the drug state, suggesting interactional effects.


Changes in developing behavior following prenatal administration of imipramine.

Female rats were given oral doses of Imipramine (5mg/kg) from 14-21 days prior to mating to conception or Day 19 or gestation and the physical maturation and behavioral development of their offspring was compared with that of controls. There were significant differences between the weights of the Imipramine and control animals at 21 days and the appearance of some reflexes was delayed. Behavior in an open field was observed when the rats were 9, 13, 17 and 21 days of age and it was found that exploratory responses were less frequent in the drug exposed offspring. In contrast there were no obvious physical anomalies and the adult behavior of the Imipramine animals on a spontaneous alternation task and a swimming maze did not differ from that of controls.


Differential effects of scopolamine and D-amphetamine on avoidance: Strain interactions.

In a discriminated Y-maze avoidance task it was observed that mice of the A/J strain were superior to mice of the DBA/2J strain, which in turn made more avoidance responses than C57BL/6J mice. Moreover, the A strain was also observed to acquire a discrimination problem more readily than either of the other strains. Administration of scopolamine enhanced active avoidance performance in A, but not DBA/2 or C57BL/6 mice. D-Amphetamine improved performance in both A and DBA/2 mice but had negligible effects on the performance of the C57BL/6 strain. Neither drug affected discrimination performance irrespective of strain. In an inhibitory avoidance task the C57BL/6 strain was found to perform more poorly than the A strain which was inferior to DBA/2 mice. Scopolamine disrupted performance in all three strains, while d-amphetamine was found to disrupt the performance of the A and DBA/2 strains only. The results were interpreted in terms of the role of associative and nonassociative effects of shock in modulating avoidance behavior.


Effects of d-amphetamine and scopolamine on activity before and after shock in three mouse strains.

In three experiments the following results were obtained: (a) Activity was greater both prior to and following exposure to shock among C57BL/6J mice than in DBA/2J mice, which in turn was greater than that of A/J mice. (b) Scopolamine hydrobromide increased general activity in DBA/2 and A mice, but had either no effect or decreased activity in the C57BL/6 strain. Following exposure to shock, however, the disinhibitory effects of scopolamine were apparent in all three strains. (c) d-amphetamine increased activity in all three strains. Moreover, following the single shock d-amphetamine had excitatory effects among both A and DBA/2 mice such that activity exceeded the level observed with d-amphetamine alone. Following several shock presentations a small but significant excitation was observed in C57BL/6 mice as well. Data were interpreted in terms of disinhibitory and excitatory effects of scopolamine and d-amphetamine, respectively, as well as possible interactions between the catecholaminergic and cholinergic systems. In addition, implications for sources of strain differences in avoidance behavior are discussed.


Effects of manipulating cholinergic tone upon the activity-stress ulcer.

Eighty rats were housed in standard activity wheel cages and fed for only 1 hr per day. The animals were divided into 10-animal drug groups that received either 0.25, 050, 1.0 mg/kg of scopolamine methylbromide, or 0.06, 0.125, 0.250 mg/kg of carbachol, 3 times a day. Two separate 10-animal saline control groups accompaned each drug series. All animals died within 6 days and most demonstrated significant gastric lesions in the glandular fundus of the stomach. All dosages of scopolamine methylbromide significantly reduced the number and severity of gastric lesions and in some cases abolished all signs of stomach pathology. None of the dosages of carbachol significantly affected either the number of degree of gastric ulceration noted in the body of the stomach. These results were interpreted to suggest that the secretion of gastric acid may be an important contributing factor in the formation of gastric ulcers in animals subjected to the activity-stress procedure.


Norepinephrine uptake by hypothalamic tissue from the rat related to feeding.

Norepinephrine (NE) uptake by rat hypothalamus in vitro was studied in relation to food intake. Significant daily variations in NE uptake were observed in caudal hypothalamus from freely feeding rats. A maximal elevation occurred at the beginning of the night when food intake is also increasing to a maximum. NE uptake by caudal hypothalamus from relatively hungry rats previously adjusted to restricted feeding during the daytime was enhanced in afternoon and evening when compared with uptake by tissue from ad lib feeding animals. Determination of NE uptake by caudal hypothalamus from freely feeding individual rats and registration of individual meals taken by these rats revealed a relation between hypothalamic neuronal activity and the feeding pattern of the rat. A positive correlation was observed between NE uptake in vitro and feeding rate during a 2- to 4-hr interval. It also appeared that NE uptake by caudal hypothalamus is dependent on the time elapsed after the last meal. The data were evaluated in view of physiological studies concerning the onset of feeding and the hypothesis of hypothalamic adrenergic control of food intake.


Profile of drug effects on temporally spaced responding in rats.

A differential reinforcement of low rate schedule was used with rats to test 15 psychotropic drugs. The computer analysis was based on interresponse time (IRT). Mean IRT, IRT standard deviation, median IRT, IRT midrange, modal IRT, frequency of modal IRT, and an efficiency index, in addition to numbers of responses and reinforcements and the IRT histogram were obtained for each rat in each drug test. An increase in number of responses and a peak shift to shorter IRTs in the histograms were observed with amphetamine, methamphetamine, priradrol and nicotine, as reported by many other investigators. Decrease in IRT midrange and less change in number of responses were observed with diazepam and chlordiazepoxide. Long pauses were found with LSD-25, 2,5-dimethoxy-4-methylamphetamine (DOM) and mescaline. In a factor analysis, the following main factors were obtained. High values in factor loading a1 were observed with chlorpromazine, chlordiazepoxide, pentobarbital, imipramine, nialamide, LSD-25, DOM and mescaline. With these drugs, mean IRT and IRT standard deviation were also high. Values for a2, were high with amphetamine, methamphetamine, pipradrol and nicotine. High a3 values were observed in some rats with chlorpromazine, diazepam, chlordiazepoxide, pentobarbital, pipradrol and caffeine. The changes in a3 values were correlated with changes in the IRT midrange. These results may be valuable in classifying new compounds in drug screening programs as being of the amphetamine type, nicotine type, diazepam type of LSD-25 type.


Effects of lysergic acid diethylamide (LSD) on temporal recovery (pre-pulse inhibition) of the acoustic startle response in the rat.

In a series of 6 experiments 40 mug/kg d-lysergic acid diethylamide (LSD) augmented acoustic startle amplitude in rats when long intertone intervals (4, 8, 16, or 32 sec) were used but not when short interstimulus intervals were used (0.02, 0.1, 0.5, 1, or 2 sec). In contrast, 8 mg/kg d-amphetamine augmented startle when either long or short interstimulus intervals were used. The results suggest that LSD augments startle by accelerating the decay of pre-pulse inhibition (temporal recovery process) which may be one mechanism by which LSD can alter sensory processing.


Marihuana-like activity of new synthetic tetrahydrocannabinols.

11-Methy-delta8-, 9-nor-delta8, and 9-nor-delta9-tetrahydrocannabinol (THC), newly synthesized cannabinoids which are not 11-hydroxyated in vivo, were tested for cannabinoid activity. Delta8-, delta9-THC and each synthetic analog produced static ataxia in unanesthetized dogs, hypotension and bradycardia in anesthetized dogs, and decreased spontaneous activity in mice. All synthetic analogs tested produced a greater degree of tolerance to the behavioral effect in dogs than did delta8-THC. 11-Methyl-delta8-THC was more effective than delta8-THC in decreasing spontaneous activity in mice, but was less active in producing the behavioral and cardiovascular effects in dogs. 9-nor-delta9-THC was less active than delta9-TCH, but 9-nor-delta8-THC was as active as delta8-THC in all observations. These results suggest that the 11-hydroxy metabolites of delta8- and delta 9-THC are not solely responsible for the biological activity of tetrahydrocannabinol.


6-Hydroxydopamine and avoidance: Possible role of response suppression.

The intraventricular administration of 6-HD to rats pretreated with pargyline resulted in severe, long-lasting decreases in avoidance responding with little or no effect on escape responding. Despite the fact that the rats failed to avoid, they appeared to be able to discriminate the CS, as was evident from freezing behavior and other symptoms of an apparent fear reaction during the CS. The increase in freezing, a response that was incompatible with avoidance was seen during the first few test sessions after 6-HD treatment and seemed to be largely responsible for a gradual decline in avoidance responding during this same period. The role of CA depletion in the animal's response to aversive stimuli thus appears to be a significant aspect of the avoidance decrement that follows 6-HD administration.