The isolation of strains of rickettsiae of the spotted fever group in Israel and their differentiation from other members of the group by immunofluorescence methods.


Candida albicans antibodies in candidiasis.


Concentration of penicillin and tetracycline in maxillary sinus secretion after a single dose.


Trimethoprim in the treatment and long-term control of urinary tract infection.


Orthopaedic infections treated at an infectious disease hospital.


An evaluation of the genetic structure of a Drosophila melanogaster population with respect to the characteristic radius incompletus. I. Change in characteristic caused by selection.


The effect of boron on the nucleolus, chromocenter, and chromosomes of Drosophila melanogaster salivary gland cells.


Investigation of the operon of riboflavin biosynthesis in Bacillus subtilis. 3. Production and properties of mutants with a complex regulator genotype.


Ectopic atrial rhythms in the primate.

Ectopic atrial rhythms in the primate.


Effect of hemorrhagic shock on capillary transport in dog skeletal muscle.


Studies on the antithrombotic effect of dextran effect on platelet 5-hydroxytryptamine and adenine nucleotides.


Study on the acute effects of O-(beta-hydroxyethyl)-rutoside (HR) on the increased muscle capillary permeability in long-term diabetics.


Betahistine HCL antagonism upon neural influence on microcirculation.


Effects of O-(beta-hydroxyethyl)-rutosides (HR) and indomethacin on transcapillary macromolecular transport and prostaglandins following scalding injury.


Vascular and extravascular spaces in two transplantable tumors of the rat.


Characterization of rat liver lysosomal cathepsin A1.


Purification and properties of cathepsin D from human erythrocytes.


Studies on the lipase of Chromobacterium viscosum. 3. Purification of a low molecular weight lipase and its enzymatic properties.


Purification and properties of a nitrate reductase-inactivating enzyme.


Interaction of bovine carbonic anhydrase with acetate ions.


The molecular basis of contractility. I.


NMR studies of the two binding sites of acetate ions to manganese(II) carbonic anhydrase.


The identification of the forms of folate found in the liver, kidney and intestine of the monkey and their biosynthesis from exogenous pteroylglutamate (folic acid).


Antibodies to indolealkylamines: serotonin and melatonin.


The transfer of glucose to steroids by sheep liver microsomes.


The 4.5 Angstrom resolution structure of a bacterial serine protease from Streptomyces griseus.


Biosynthesis of the diguanosine nucleotides. I. Purification and properties of an enzyme from yolk platelets of brine shrimp embryos.


A rapid quantitative microtitration of Pseudomonas aeruginosa antibody.


The effect of the amount of nucleic acid load on hydroxylapatite chromatography.


Serological survey of Pseudomonas aeruginosa strains isolated from patients in Canadian hospitals.


Glycerol ester hydrolase, lipase, of Myxococcus xanthus FB.


New data on the taxonomy of the Brazilian marmosets of the genus Callithrix Erxleben, 1777.


Heart rate (radiotelemetrical registration) in macaques and baboons according to dominant-submissive rank in a group.


Maternal-fetal weight relationships in primates.


The effect of corpora allata on the plasma membrane of the symbiotic bacteria of the oocyte surface of Periplaneta americana L.


Influence of growth conditions on the composition of some streptococcal amino acid pools.


Spinal cord blood flow in the rhesus monkey by the hydrogen clearance method.


Studies on dentin. I. Mantle dentin.

Studies on dentin. I. Mantle dentin.


Studies on plasma somatomedin activity in different animal species.


Parathyroid hormone secretion in disorders of calcium metabolism studied by means of EDTA.


The changing scene in public health: Delta Omega Lecture.


Cross-resistance and collateral susceptibility to antifolic antimalarial compounds. Series of strains of Streptococcus faecium ATCC 8043, Lactobacillus casei ATCC 7469, and Pediococcus cerevisiae ATCC 8081 with increasing resistance to the active antifolate antimalarial drugs chlorguanide triazine (CGT), pyrimethamine (PM), and trimethoprim (TMP) were isolated. These mutant strains, stable for at least 3 to 5 years, were examined for cross-resistance and collateral susceptibility to the above compounds and to methotrexate (MTX). Generally, they exhibited cross-resistance to all four compounds, but resistance of a strain to one compound did not predict accurately its resistance to another drug. Unexpectedly, L. casei resistant to CGT exhibited collateral susceptibility to MTX, TMP, and PM varying from 5- to 20-fold. P. cerevisiae developed resistance to CGT readily but maintained its susceptibility to PM and TMP after prolonged exposure to these compounds. Resistance to these antimalarial antifolates was accompanied by only low-grade cross-resistance to MTX, a representative antileukemic antifolate agent.


Mechanisms and spectrum of streptomycin resistance in a natural population of Pseudomonas aeruginosa. A survey of 200 strains of Pseudomonas aeruginosa isolated from clinical specimens was made in an attempt to correlate the spectrum of their streptomycin resistance and the mechanism of resistance. The strains can be classified into three groups, according to their level of resistance to streptomycin: susceptible, low-level resistant, and high-level resistant strains. The mechanism of resistance of high-level resistant strains is either an R factor-mediated inactivation of streptomycin by phosphorylation or streptomycin-resistant ribosomes. However, such high-level resistant strains comprised less than 10% of the total strains isolated; the majority of the strains resistant to streptomycin were of low-level resistance. The latter are associated with a diminished uptake of streptomycin, and no evidence of streptomycin inactivation, resistant ribosomes, or R factors could be detected. The most probable explanation of low-level resistance is reduced permeability to streptomycin. Modification of the growth medium used in uptake studies simultaneously affected strongly both streptomycin incorporation and the minimal inhibitory concentration of streptomycin.


Comparison of tobramycin, gentamicin, colistin, and carbenicillin in Pseudomonas sepsis in monkeys. Intravenous inoculation of 3.4 x 10(10) to 7.4 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in eight of nine monkeys. After intramuscular administration, in two equal doses, of 5 mg of tobramycin, gentamicin, and colistin per kg per day beginning 16 hr after challenge, 4 of 11, 4 of 11, and 3 of 10 monkeys died, respectively. Administration of daily doses of 100 to 400 mg of carbenicillin per kg was followed by death in 5 of 12. Duration of illness in the surviving monkeys in each therapy group was similar. Under the conditions of this study, prior administration of vincristine sulfate resulted in a decrease in leukocytes and enhanced susceptibility to Pseudomonas infection. Using this model for studies of comparative efficacy of antibiotics, we observed comparable results after treatment with tobramycin, gentamicin, colistin, and carbenicillin.


Inhibition of chlorination in Streptomyces aureofaciens by nitriles and related compounds. A number of nitriles and cyano compounds inhibited chlorination by Streptomyces aureofaciens. In most cases, this inhibition was enhanced by bromide. Methylene blue and p-amino-propiophenone reversed the inhibition to some extent.


Comparison of colistin-carbenicillin, colistin, and carbenicillin in Pseudomonas sepsis in monkeys. Intravenous inoculation of 6.2 x 10(10) to 6.7 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 5 days after intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in 8 of 10 untreated monkeys. When similarly infected monkeys were treated intramuscularly with 2.5 mg of colistin or 50 mg of carbenicillin per kg per day, all three monkeys in each treatment group survived; one of three monkeys receiving both antibiotics at the above doses died. Six of seven monkeys treated with 1.25 mg of colistin per kg per day and three of seven treated with 25 mg of carbenicillin per kg per day died; four of nine monkeys receiving both antibiotics at these doses died. A combination of the data obtained at both dose levels tested shows that 6 of 10, 3 of 10, and 5 of 12 monkeys, respectively, died after treatment with colistin, carbenicillin, and the colistin-carbenicillin combination. Antibacterial activity of serum from both infected and normal monkeys was not appreciably different when the two antibiotics were given singly or in combination. Under the conditions of this study and with the doses employed, the response of monkeys treated with the antibiotic combination did not differ significantly from that of monkeys treated with a single agent.


Biliary excretion of a new semisynthetic cephalosporin, cephacetrile. The biliary excretion of a new derivative of cephalosporin, cephacetrile (CIBA 36 278 Ba), was studied (i) in the isolated perfused rabbit liver, (ii) in humans with a duodenal tube, and (iii) in patients after cholecystectomy with a Kehr's drain in the common bile duct. The biliary excretion of the antibiotic was very low in the perfused liver, and no antibiotic activity was found in liver tissue at the end of the experiment. This observation, together with the finding of a rapid decline of the antibiotic concentration in the circulating blood serum, favors the assumption that a metabolic transformation of CIBA 36 278 Ba in liver tissue takes place. In humans, the antibiotic concentration was found to be low both in the duodenal juice and in the bile obtained by external drainage. The biliary concentrations found in these subjects seem to be inferior to those required for the inhibition of the common bacteria of biliary infections. In renal failure, however, the biliary excretion of CIBA 36 278 Ba increased considerably.


A9145, a new adenine-containing antifungal antibiotic: fermentation. A9145 is a basic, water-soluble, antifungal antibiotic which is produced in a complex organic medium by Streptomyces griseolus. The metabolite has a molecular weight of 510, and contains adenine as well as sugar hydroxyl and amino groups. Although glucose, fructose, glucose polymers, and some long-chain fatty acid methyl esters supported biosynthesis, oils were superior, with cottonseed oil being preferred. Several ions and salts, especially Co(2+), PO(4) (3-), and CaCO(3), were stimulatory. Adenine, nucleosides, and some amino acids increased the accumulation of A9145 in shaken-flask fermentors. Enrichment of the culture medium with tyrosine afforded maximal enhancement of antibiotic production in both flask and tank fermentors. Control of the dissolved O(2) level was also critical, the optimal concentration being 3 x 10(-2) to 4.5 x 10(-2) mumole of O(2)/ml. Optimization of various fermentation parameters increased antibiotic titers approximately 135-fold in shaken flask fermentors and 225-fold in stirred vessels.


Cation reversal of inhibition of growth by valinomycin in Streptococcus pyogenes and Clostridium sporogenes. Study of the antimicrobial spectrum of valinomycin revealed that, in addition to the gram-positive bacteria reported in literature, Streptococcus pyogenes and Clostridium sporogenes are also susceptible to this antibiotic. The minimal inhibitory concentrations (MIC) of the antibiotic for S. pyogenes grown aerobically and anaerobically did not differ markedly, negating the hypothesis that oxidative phosphorylation is involved in the mechanism of action of this antibiotic. This conclusion is further strengthened by the inhibition of growth of C. sporogenes, an obligate anaerobe. In a medium with a low K(+) concentration, the MIC for S. pyogenes was 0.02 mug/ml, the lowest ever recorded for this antibiotic. The inhibition of growth of S. pyogenes and C. sporogenes was readily reversed by addition of K(+) to the medium, indicating a compensation for net efflux of K(+) from the cells when the transmembrane potential reached equilibrium. In contrast to these bacteria, Bacillus subtilis was less susceptible to the antibiotic when the potassium concentration of the medium was low. The addition of potassium in the presence of valinomycin increased the inhibition of growth, which appears to result from dissipation of metabolic energy as in the mitochondrial system.


Amoxicillin, a new penicillin antibiotic. Amoxicillin (alpha-amino-p-hydroxybenzyl penicillin, BRL 2333) is a new semisynthetic penicillin which is structurally similar to ampicillin, but which is better absorbed and yields higher concentrations in serum and urine. The in vitro susceptibility of 145 strains of Enterobacteriaceae and 30 isolates of Pseudomonas aeruginosa was determined against various concentrations of amoxicillin and ampicillin in agar. In addition, inhibitory zones around discs containing 10 mug of amoxicillin were measured and compared with results of agar dilution studies. The drug also was evaluated in the treatment of 38 patients with bacteriuria, who received doses of either 750 mg or 1 g/day for 10 days. In vitro, amoxicillin was comparable in activity to ampicillin; most isolates of Escherichia coli and Proteus mirabilis were inhibited by 10 mug or less/ml, whereas the majority of strains of Enterobacter, Klebsiella, indole-positive Proteus species, and Pseudomonas grew in concentrations greater than 50 mug/ml. Clinically, amoxicillin was effective in eradicating bacteriuria due to susceptible organisms and was very well tolerated. For practical purposes, however, amoxicillin performed no better than a host of other drugs presently available for the treatment of acute, uncomplicated bacteriuria.


In vitro effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses. Virazole (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a highly soluble new synthetic nucleoside having significant, reproducible activity against a broad spectrum of deoxyribonucleic acid and ribonucleic acid viruses in vitro. The drug inhibited viral cytopathogenic effects in monolayers of cells infected for 3 days with type 3 adeno, types 1 and 2 herpes, myxoma, cytomegalo, vaccinia, infectious bovine rhinotracheitis, types 1A, 2, 8, 13, and 56 rhino, types 1 and 3 parainfluenza, vesicular stomatitis, subacute sclerosing panencephalitis, Semliki Forest, Newcastle disease, and measles viruses. Hemagglutinin production by influenza A(2), influenza B, and type 1 parainfluenza viruses in chicken embryo cells was reduced by Virazole treatment. Recoverable intra- and extracellular virus titers were reduced by the drug in experiments with type 1 herpes, vaccinia, type 3 parainfluenza, and vesicular stomatitis viruses. Plaque formation by type 1 herpesvirus was also inhibited by exposure of the infected cells to Virazole. Pretreatment of cells with the compound, followed by its removal before addition of type 1 herpesvirus, severely lessened the antiviral activity; the compound was still moderately effective in reducing the viral effects on the cells when added as long as 22 hr after the virus. Parallel experiments, in which the antiviral activity of a number of known active drugs was compared, indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials. The CCED(50) of Virazole to chicken embryo cells was approximately 1,000 mug/ml, although concentrations as low as 10 mug/ml caused slight (15%) inhibition in total cellular protein after 72 hr of incubation.


Comparison of gentamicin, carbenicillin and gentamicin, and carbenicillin in Pseudomonas sepsis in monkeys. Intravenous inoculation of 6.0 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intratracheal inoculation of 2.5 mg of vincristine sulfate resulted in fatal sepsis in all of three untreated control monkeys. After intramuscular administration of either 2.5 mg of gentamicin or 50 mg of carbenicillin per kg per day, three of four monkeys in each group survived. When both antibiotics were given at the same dose but in separate sites, six of eight monkeys survived. Antibacterial activity of serum from infected monkeys or normal monkeys was not appreciably different when the two antibiotics were combined. Under the conditions of this study, there was no apparent difference in response of monkeys treated either with gentamicin or carbenicillin alone or with the combination of the two antibiotics.


Molecular characterization of the R factors implicated in the carbenicillin resistance of a sequence of Pseudomonas aeruginosa strains isolated from burns. An outbreak of R-factor-mediated carbenicillin resistance in Pseudomonas aeruginosa in burned patients in March 1969 was followed by a second outbreak 6 months later. No R-factor-carrying P. aeruginosa strains were detected in the intervening period but R-factor-determined lactamase was commonly encountered, particularly in Klebsiella aerogenes strains. A comparison of the molecular properties of the R factors in pseudomonads from the first and second phases with those in the Klebsiella strains from the intervening period showed them to be very closely related. A single R-factor type therefore may have been maintained in the Burns Unit between the two Pseudomonas outbreaks as a plasmid conferring resistance to ampicillin in K. aerogenes.


Discrepancy between carbenicillin and ampicillin activities against enterococci and Listeria. For infections of the newborn, carbenicillin has theoretical advantages over ampicillin, when given with an aminoglycoside, because of its activity against Pseudomonas and many indole-positive Proteus strains. Agar and broth dilution susceptibility studies demonstrated comparable activities of carbenicillin and ampicillin against coliform organisms but greater resistance of enterococci and Listeria to carbenicillin. However, the significance of the higher inhibitory concentrations is questionable because many serum specimens containing concentrations of carbenicillin lower than the minimal bactericidal values for Listeria and enterococcus strains had demonstrable in vitro bactericidal activity. Carbenicillin and gentamicin combinations had greater antibacterial activities than either drug alone against all enterococci tested and against 50% of Listeria strains. The questions of efficacy raised by contradictory in vitro data may be answered by clinical studies of carbenicillin and gentamicin in infections of the newborn.


Mode of action illudin S.

Mode of action illudin S. The effect of the antitumor antibiotic illudin S on bacterial macromolecular synthesis was investigated. Illudin S was found to be inhibitory to in vivo deoxyribonucleic acid (DNA) synthesis from thymidine. Ribonucleic acid (RNA) synthesis was inhibited only at a concentration of illudin S 10 times that which inhibited DNA synthesis. The rate of protein synthesis remained the same except for a brief initial inhibition. When thymidine triphosphate was used for in vitro DNA synthesis, inhibition by illudin S did not occur, as tested with partially purified DNA polymerase II from Escherichia coli pol A(1) (-), with E. coli DNA-dependent RNA polymerase, with E. coli pol A(1) (-) spheroplasts, and with frozen and thawed Bacillus subtilis cells. A protein fraction isolated from B. subtilis capable of forming thymidine mono-, di-, and triphosphates from thymidine was not inhibited by illudin S. Furthermore, (14)C-illudin S taken up by B. subtilis cells was reisolated unchanged, making an intracellular activation of illudin S unlikely. Therefore, an attractive hypothesis is that illudin S inhibits DNA synthesis from thymidine which does not proceed through deoxyribonucleoside triphosphates, the generally accepted substrates for DNA synthesis.


Interaction between deoxyribonucliec acid and distamycin A studied by transformation in Bacillus subtilis. Distamycin A inhibits deoxyribonucleic acid (DNA)-mediated transformation and transfection in Bacillus subtilis at doses with little or no antibacterial effect. The inhibition of transformation parallels the inhibition of DNA uptake; further-more, during the transformation process, donor DNA molecules become distamycin and deoxyribonuclease resistant at the same time. This demonstrates that the drug acts by inhibiting DNA uptake. Although the drug is known to bind DNA, the inhibition is not related to affinity of the drug for DNA. This is shown by the lack of dependence of the extent of inhibition on DNA concentration, whereas the degree of inhibition depends upon cell concentration. Supporting this view is the fact that transformation by single-stranded DNA was also inhibited, even though the drug does not bind to denatured DNA. Distamycin A probably interferes with transformation by competing with DNA for some unknown bacterial component involved in transport of DNA into the cell.


Susceptibility of whole cells and spheroplasts of Pseudomonas aeruginosa to actinomycin D. Cells of Pseudomonas aeruginosa suspended in 0.2 M Mg(2+), 20% sucrose, 0.01 M tris(hydroxymethyl)aminomethane, or water partially release lipopolysaccharide. The release of alkaline phosphatase from the periplasmic space and the ability to form spheroplasts on lysozyme treatment is directly related to the lipopolysaccharide released during treatment with 0.2 M Mg(2+), 20% sucrose, or other agents. The synthesis of ribonucleic acid (RNA) by intact cells, magnesium-lysozyme spheroplasts, or 20% sucrose-lysozyme spheroplasts is not sensitive to actinomycin D, whereas RNA synthesis by intact cells or spheroplasts in the presence of ethylene-diaminetetraacetic acid (EDTA) is sensitive to actinomycin D. EDTA alone has an inhibitory effect on RNA synthesis by whole cell, by magnesium-lysozyme spheroplasts, and by 20% sucrose-lysozyme spheroplasts. The experimental data indicate that, although the cell wall is damaged by 0.2 M Mg(2+) or 20% sucrose treatment in the presence of lysozyme, the treated cells or spheroplasts are still resistant to actinomycin D. These results suggest that the cytoplasmic membrane should be considered as the final and determinative barrier to this antibiotic in this organism.


Pharmacokinetic studies of tobramycin and gentamicin. Broth dilution susceptibility tests of 100 isolates of Pseudomonas aeruginosa and 101 isolates of Staphylococcus aureus against tobramycin (formerly nebramycin factor 6) and gentamicin showed that tobramycin was more effective against P. aeruginosa and less effective against S. aureus. The minimal inhibitory concentration of tobramycin against the Pseudomonas sp. isolates that required 5 mug of gentamicin per ml for inhibition ranged from 0.63 to 0.31 mug/ml. Peak concentrations in the blood of 10 healthy adults after intramuscular injection of 80 and 40 mg of tobramycin averaged 3.7 +/- 0.62 and 2.4 +/- 0.27 mug/ml, and declined to 0.56 +/- 0.05 and 0.26 +/- 0.02 mug/ml, respectively, after 6 h. The urine recovery averaged 60%. The half-life was 1.6 h. During continuous intravenous infusion of tobramycin and gentamicin (infusion rate 6.6 mg per h), blood levels at steady state were 0.94 +/- 0.10 and 1.04 +/- 0.06 mug/ml, respectively. For both antibiotics, the calculated distribution volume ranged from 15 to 17 liters. The renal clearance to tobramycin averaged 76% and that of gentamicin averaged 85% of the total clearance, indicating that the drugs are primarily eliminated by the kidneys. The present results suggest that tobramycin may be more successful in the treatment of Pseudomonas infections than gentamicin at the same dosage (80 mg intramuscularly three to four times daily).


Pharmacokinetics of the aminoglycoside antibiotic tobramycin in humans. The pharmacokinetics, distribution, and plasma and renal clearance of a new aminoglycoside antibiotic, tobramycin, was studied in the treatment of 18 elderly male patients (average age, 69 years) with urinary tract infections. Ten of these patients had normal renal function and eight had impaired renal function of various degrees. After administration of 1 mg of tobramycin/kg of body weight every 6 to 8 h (two to three times the half-life), urine concentrations were found to be sufficient in the treatment of urinary tract infections caused by susceptible organisms. The renal clearance of tobramycin during constant intravenous infusion was also studied in eight patients. Good correlation was found between the patients serum creatinine and the half-life of tobramycin. The half-life of tobramycin in patients with normal renal function (serum creatine [Formula: see text] to 1.5 mg/100) was on the average 3 h. For practical purposes, therefore, the dosage of tobramycin in the treatment of urinary tract infections should be 1 mg/kg of body weight every 6 to 8 h in patients with normal renal function. For patients with impaired renal function, the dosage interval is calculated by multiplying the patients' serum creatinine by six. If the dosage intervals are kept unchanged, the dosage must be divided by the patients' serum creatinine. The initial loading dose should always be 1 mg/kg. The total renal clearance of tobramycin (92% of the glomerular filtration rate) was not influenced by the administration of probenecid, which indicates that tobramycin is excreted only by glomerular filtration.


Increased susceptibility of Neisseria gonorrhoea from a rural area. The in vitro susceptibility of 18 to 24 isolates of Neisseria gonorrhoea were tested against 12 different antimicrobial agents. These isolates represent all of the gonococcal organisms which had been isolated by the bacteriology laboratory of the Vermont State Department of Health from 1 March to 31 July 1972 and originated from patients cultured in Vermont. These isolates were considerably more susceptible to penicillin G and tetracycline than are current isolates from elsewhere in the United States and Canada. Possible explanations for this difference are discussed.


Penicillin-tobramycin synergism against enterococci: a comparison with penicillin and gentamicin. Combinations of penicillin plus tobramycin have been compared with penicillin plus gentamicin against 27 strains of enterococci isolated from blood cultures. Penicillin plus gentamicin was synergistic against all strains. The combination of penicillin plus tobramycin was equally effective against strains of Streptococcus facalis, but was ineffective against all four strains of S. faecium tested.


Chloroquine-resistant Plasmodium falciparum: difference in the handling of 14C-amodiaquin and 14C-chloroquine. (14)C-amodiaquin and (14)C-chloroquine were used to study drug binding by preparations of owl monkey erythrocytes infected either with a chloroquine-susceptible (CS) or with a chloroquine-resistant (CR) strain of P. falciparum. Both of these drugs are derivatives of 4-aminoquinoline, but they differ in their side chains, and there are differences in the way they are handled by preparations of erythrocytes infected with malaria parasites. Although the apparent association constant for the binding of either drug is approximately 10(7) mol(-1), two to three times more radioactivity was bound from (14)C-amodiaquin than from (14)C-chloroquine. Furthermore, there was no apparent difference between CS and CR parasites with respect to (14)C-amodiaquin binding, whereas erythrocytes infected with CR parasites have a deficiency of (14)C-chloroquine binding. This difference in the handling of amodiaquin probably accounts for its superiority in the treatment of the owl monkey and of humans infected with CR P. falciparum.


Silver sulfadiazine: effect on the ultrastructure of Pseudomonas aeruginosa. Pseudomonas aeruginosa exposed to silver sulfadiazine (AgSu) were examined in an electron microscope. The treated cells were distorted in shape, and structures (blebs) protruded from the cell surface. These "blebs" appeared to arise from the cell wall. A strain of P. aeruginosa resistant to AgSu did not display these changes. Upon exposure of P. aeruginosa to silver nitrate, none of these changes was seen; rather, such cells are characterized by large, central aggregations of nuclear material. The results are consistent with previous findings which suggested that AgSu acted at the cell surface.


Mechanisms of R factor R931 and chromosomal tetracycline resistance in Pseudomonas aeruginosa. The mechanism of tetracycline resistance mediated by R931 (a Pseudomonas aeruginosa R factor not yet successfully transferred to Escherichia coli recipients) was examined. In strain 931 (R931) (minimal inhibitory concentration [MIC] 200 mug/ml) significant tetracycline uptake did not occur until 100 mug of tetracycline per ml was included in uptake studies. The introduction of R931 into strain 280 resulted in a significant decline in (3)H-tetracycline uptake. In both strains 931 (R931) and 280 (R931), a further reduction in tetracycline uptake resulted from pre-incubation with 1 mug of tetracycline per ml. Tetracycline resistance in R(-)P. aeruginosa strains 1731, 1885, and 494, considered to be of chromosomal origin, was associated with a lack of tetracycline uptake until the MIC of the strain was obtained. No evidence of tetracycline inactivation or ribosomal resistance was detected in R(-) or R(+) strains. The MIC for R(-) strains was generally about 25 mug/ml and that for R(+) strains was 75 to 200 mug/ml.


Characteristics of R931 and other Pseudomonas aeruginosa R factors. R factors were detected in 3.3% of 233 hospital isolates of Pseudomonas aeruginosa using P. aeruginosa recipients in conjugations. Transferred markers included streptomycin, tetracycline, and sulfonamide resistance. Gentamicin resistance was transferred from two strains previously shown to acetylate gentamicin. A group of R factors exemplified by R931 were characterized by failure to transfer to Escherichia coli recipients. Such R factors formed a single compatibility group when examined in a P. aeruginosa recipient. Other P. aeruginosa R factors, including RP4, showed stable coexistence with the R931 group. It is proposed that RP4 and similar R factors be members of the P-1 compatibility group and that R931, R3108, R209, and R130 be members of a group termed P-2. The buoyant densities of all R factors examined were similar, about 1.716 to 1.719 g/cm(3). The content of R-factor deoxyribonucleic acid (DNA) relative to the total DNA varied among the different R factors, ranging from about 18 +/- 2% in log-phase cells of 931 (R931) to undetectable for 679 (R679). However, R679, which transferred from strain 679 at extremely low and irregular frequencies to an E. coli host, was shown to represent about 4% R-factor DNA in that host. The relative DNA content of R931 appeared to decline in the stationary growth phase of 931 (R931) or 280 (R931). R931 covalently closed circular DNA was isolated by ethidium bromide-CsCl gradient centrifugation and examined by electron microscopy. Two major molecular distributions existed, having contour lengths of 0.5 and 12.4 mum. The molecular weights were estimated to be 10(6) and 25 x 10(6). Both molecules were under relaxed replication control. R factor R931 exists as a naturally occurring high-frequency transfer system in P. aeruginosa strains 931 and 1310. However, in strain 280 it acts as if subject to fertility repression. Other members of the P-2 compatibility group also are high-frequency transfer systems in the natural host and in strain 1310. RP4 is restricted from recipient strain 1310. Some additional recipient effects were noted in that strains 1310 or 280 sometimes differed in recipient effectiveness with a given donor. Agglutination reactions with absorbed antiserum were able to distinguish between two members of the same R-factor compatibility group, R931 and R3108.


Pharmacokinetic studies in animals and humans of a new cephalosporin, the sodium salt of 7-cyanacetamidocephalosporanic acid. The sodium salt of 7-cyanacetamidocephalosporanic acid (CAA) had a relatively short serum half-life in rabbits (21 min by intravenous and 30 min by intramuscular administration) and in humans (33 min by intravenous injection). The drug was not extensively bound (about 35%) to serum in either species. Even after large doses (500 mg/kg), CAA was not well absorbed from the gastrointestinal tract of rabbits. Urinary excretion of antibacterial activity was rapid after intravenous and intramuscular administration in rabbits and after intravenous administration in men. Expressed as unchanged CAA, antibacterial activity appeared in the urine to the extent of 84% for humans, 35% for rabbits and 32% for rats. Excretion proceeded partly by active renal tubular secretion in rabbits. In this latter species, low concentrations of the active drug were detected in cerebrospinal fluid and bile after an intravenous dose of 25 mg/kg. CAA was well tolerated after intravenous administration of a single dose in both rabbits and humans.


Transfection in B. subtilis.

Transfection in B. subtilis.


Immunological recognition of polynucleotide structure.


Recent advances in molecular pathology. Regression of atherosclerosis--a perspective.


Effects of elevated temperature on the mycetome and symbiotes of the bed bug Cimex lectularius (Heteroptera).


Proceedings: Effect of growth hormone release inhibiting hormone on the release of growth hormone and other pituitary hormones in man.


Effect of prolonged storage of spores on field applications of Nosema locustae (Microsporida: Nosematidae) against grasshoppers.


Pathological effects of Urosporidium (Haplosporida) infection in microphallid metacercariae.


Total-body potassium and lean body mass in males with an abnormal sex chromosome complement.


The effect of sex hormones on rat liver carbonic anhydrase.


The phylogeny of human globin genes investigated by the maximum parsimony method.


Some dynamic properties of linear, hyperbolic and sigmoidal multi-enzyme systems with feedback control.


Pentane production by peanut lipoxygenase.


Studies of complement levels in normal human pregnancy.


The integrative approach in medicine--implications of neuroendocrine mechanisms.


Sex differences in passion and play.

Sex differences in passion and play.


Sexuality and reproduction.

Sexuality and reproduction. The relationship between coital rates, a quantitative index of sexuality, and the quality and quantity of reproduction is discussed in terms of sex ratio, delayed fertilization, frequency of intercourse, intercourse distribution within the  menstrual cycle, acceleration of ovulation, and the quality of intercourse.  Frequency of intercourse affects chances of conception, but its effect on twinning and sex ratio are unclear.  Current research on reproduction offers little evidence of the effect of intercourse quality on reproduction in fully fecund individuals; research into the possible effect on reduced fecundity would be desirable.


Observations on the development of antibodies to thiamine tetrahydrofurfuryl disulfide in rabbits.


Structural organization of developing chloroplasts in Euglena.


The effect of ethylenediaminetetraacetic acid on yeast cell membranes.


Pyrazapon (CI-683): a new antianxiety agent.


Childhood asthma in Finland. A survey of 559 patients.


Histochemical localization of acetylcholinesterase enzyme in the 'limbic system' of the brain of the squirrel monkey (Saimiri sciureus).


Serine neutral proteinase from Bacillus pumilus as metalloenzyme.


Organon thalamo-chorioidalis in the taenia thalami of the cat and other mammals.


Capacity of group A, B, C, D, and G streptococci to agglutinate sensitized sheep red cells.


Association of capsid protein with Semliki Forest virus messenger RNAs.


"Pitting" and "corrosion" of the surface of agar cultures by colonies of some bacteria from the respiratory tract.


Search for thymidine phosphorylase, nucleoside deoxyribosyltransferase and thymidine kinase in genus Neisseria.


Bacteriophage typing of Mycobacterium ranae (Fortuitum). The use of unadapted and adapted phages in the development of a typing system.


Patient compliance with antibiotic regimens.


Encephalogenic cardiomyopathy after stimulation of the brain stem in monkeys.


Problems of treatment of anorexia nervosa.


The treatment of advanced prostatic carcinoma with medroxyprogesterone.


A comparison of propranolol and prindolol in the treatment of essential hypertension.


Clinical evaluation of SE 1520 in the treatment of hypertension.


A double-blind comparison of two oral contraceptives containing 50 mu g. and 30 mu g. ethinyl estradiol. 150 women participated in a double-blind clinical trial comparing 2 dosages of an oral contraceptive agent: 250 mcg d-norgestrel + 50 mcg ethinyl estradiol and 150 mcg d-norgestrel + 30 mcg ethinyl estradiol.  The 150/30 combination resulted in shorter cycles, longer menses (p.001), shorter latent period (p.001), and a higher instance of breakthrough bleeding and spotting (p.05 and p.001).  The 250/50 dose caused a significantly higher incidence of breast discomfort (p.001), leg cramps (.02), and nausea (.001).  More 250/50 dose women dropped out for more than 1 reason than in the lower dose group.


A double-blind clinical evaluation of the safety and efficacy of phentermine hydrochloride (Fastin) in the treatment of exogenous obesity.


Doxycycline treatment in gonorrhea.

Doxycycline treatment in gonorrhea.


The rapidity of the effect of different types of topical corticosteroids: a double-blind comparison between Diproderm ointment 0.05 percent and Calmuril-Hydrocortisone 1 percent.


Osteomyelitis associated with vascular insufficiency.


Clinical observations on the use of a long-acting phenothiazine (fluphenazine enanthate) in chronic schizophrenics.


The use of mesoridazine in geriatrics.

The use of mesoridazine in geriatrics.


Structure-activity relationships within the class of 1,4-benzodiazepines: presence of chlorine and central nervous system activities.


Bioavailability and activity of betamethasone 17-benzoate in gel and cream formulations: comparison with proprietary topical corticosteroid preparations in the vasoconstrictor assay.


Characteristic actions of CDP-choline on the central nervous system.


A comparison of three laboratory tests for pregnancy diagnosis in the mare.


The neutral proteases of human granulocytes. Isolation and partial characterization of granulocyte elastases.


Secondary isotope effect in the phosphorylase reaction.


Purification and some properties of an endocellular sucrase from a constitutive mutant of Bacillus subtilis Marburg 168.


Fluorescent products from aging Drosophila melanogaster: an indicator of free radical lipid peroxidation damage.


Are there major degenerative changes in the flight muscle of ageing diptera?


Perfusion fixation of the kidney of the domestic fowl.


Cellular distribution of beta-trace protein in CNS and brain tumours. The low-molecular weight beta-trace protein constitutes about seven per cent of the total protein content in human cerebrospinal fluid. Within the central nervous system the protein is found predominantly in white matter and fractions enriched in glial cells. Immunofluorescence studies on sections of monkey brains show that beta-trace protein is particularly localized to cells such as astrocytes and oligodendrocytes. Significantly higher amounts of beta-trace protein are found in brain tumours derived from glial cells than in other tumours.


Orally administered betahistine and regional cerebral blood flow in cerebrovascular disease.


Combined intrathecal and intramuscular gentamicin for gram-negative meningitis. Pharmacologic study of 21 patients.


Acquired phagocyte dysfunction. A complication of the hypophosphatemia of parenteral hyperalimentation.


Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-1974.


Inhibition of clofibrate-induced antidiuresis by glybenclamide in patients with pituitary diabetes insipidus.


Editorial: Hypoalimentation during hyperalimentation.


Letter: Contamination of fluid for parenteral nutrition.


Editorial: Vasodilator therapy of myocardial infarction.


Administrative problems and solutions in screening for gonorrhea.


Organochlorine residues in woodcock wings, 11 states--1970-71.


Residues of mirex and certain other chlorinated hydrocarbon insecticides in beef fat--1971.


Residues of PCB's and PCT's in Canadian and imported European cheeses, Canada--1972.


Long-term treatment of endogenous depression with nortriptyline with control of plasma levels.


Psychiatric inpatients in 1982: how many beds?


Medical Research Council Unit on the Development and Integration of Behaviour.


Inter-laboratory discrepancies in serum immunoglobulin estimations.


The natural history of bacterial colonization of the newborn in a maternity hospital. I.


Methamphetamine effects on responding under a multiple schedule of shock presentation.


Editorial: Oral therapy in diabetes mellitus.


Bilateral symmetrical periarticular trauma in epileptics.


Failure of chemotherapy in treatment of giant condyloma acuminata (Buschke-Loewenstein tumor).


Factor VIII, a series of homologous oligomers and a complex of two proteins.


Suppression of cocaine self-administration by extinction and punishment.


Shwartzman reaction in an HL-A-identical renal allograft.


Chronogenetics. Its foundations, scope, and impact.


Tympanoplasty for bony ossicular fixation.


Staphylococcal endocarditis following septorhinoplasty.


Letter: Gold nephropathy and glucocorticoids.


Immunological enhancement of atherogenesis in rabbits. Persistent susceptibility to atherogenic diet following experimentally induced serum sickness.


Alveolar macrophage function in immunized, burned rats.


A comparative study of the distribution of soluble and particulate glycyl-L-leucine hydrolase in the small intestine.


Increased glucuronidation of bilirubin in man and rat by administration of antipyrine (phenazone).


The ventilatory response in diabetic ketoacidosis.


Effect of nicotinic acid on cholesterol metabolism in monkeys.


Hypothalamic control of anterior pituitary hormone secretion--characterized hypothalamic-hypophysiotropic peptides.


Establishment of multiple lymphoblastoid lines from single lymph nodes and study of their immunoglobulin synthesis.


The underdevelopment of health or the health of underdevelopment: an analysis of the distribution of human health resources in Latin America.


Experimental middle ear effusions: an immunofluorescent study.


Percent charging of transfer ribonucleic acid and levels of ppGpp and pppGpp in dormant and germinated spores of Bacillus megaterium. The levels of transfer ribonucleic acids (tRNAs) specific for 14 amino acids were almost identical in dormant spores and in spores germinated from 6 to 75 min. Germinated spore tRNAs specific for all amino acids tested were between 63 and 93% charged, and there was no significant change in this value from 6 to 75 min of germination. In contrast, tRNAs isolated from dormant spores specific for nine different amino acids were almost completely(>93%) uncharged. However, some dormant spore tRNAs, i.e., those for arginine, histidine, isoleucine, and valine, showed significant (21 to 72%) levels of aminoacylation. Dormant spores contained no detectable guanosine penta- (pppGpp), tetra- (ppGpp), or triphosphate (GTP). However, these nucleotides appeared in the first minutes of germination, and thereafter all increased in parallel with a ratio of pppGpp plus ppGpp to GTP of 0.07 to 0.11, which is characteristic of unstarved vegetative cells.


Physiological influences on cell division patterns in the div IV-B1 MINIcell-producing mutant of Bacillus subtilis. The proportion of abnormal divisions resulting in minicells is influenced by growth stage and medium composition.


Acceleration of dextransucrase activity of Streptococcus mutans by secretory immunoglobulin A. The effect of immunoglobulins on the activity of dextransucrase purified from Streptococcus mutans strain HS-6 is described. When human salivary immunoglobulin A (IgA) or colostral IgA, either natured or denatured, was incubated with dextransucrase, the rate of the dextran synthesis was markedly accelerated, whereas human serum IgA or IgG neither accelerated nor inhibited the enzyme activity. The results suggest that a portion unique for secretory IgA, the secretory component, might be related to the enzyme acceleration. On the other hand, specific rabbit antiserum against the dextransucrase inhibited completely dextran synthesis by the enzyme.


Specificity and induction of undecyl acetate esterase from Pseudomonas cepacia grown on 2-tridecanone. Undecyl acetate esterase from Pseudomonas cepacia grown on 2-tridecanone was strongly inhibited by organophosphates and other esterase inhibitors. Also, p-chloromercuribenzoate at 1 x 10(-4) M showed a 70% inhibition of esterase activity. The enzyme hydrolyzed both aliphatic and aromatic acetate esters at substrate concentrations of 0.25 M. Under these conditions the highest reaction rate was toward undecyl acetate. No lipase or proteolytic activity was demonstrated. Undecyl acetate esterase was classified as a carboxylesterase (B-esterase). Cell-free activity studies on the production of undecyl acetate esterase grown on different carbon sources plus zymogram studies demonstrated that the enzyme was inducible when 2-tridecanone, 2-tridecanol, undecyl acetate and, to a lesser extent, 1-undecanol were growth substrates. Induction of undecyl acetate esterase during oxidation of 2-tridecanone supports the view that undecyl acetate is an intermediate in the degradation of the methyl ketone.


Tests for deoxyribonucleic acid synthesis in toluenized Bacillus subtilis cells. Several tests were devised to further characterize deoxyribonucleic acid (DNA) synthesis in toluenized Bacillus subtilis cells. Vigorous agitation of toluenized cells (localization test) demonstrated that the DNA replication is exclusively a cell-associated process. A DNA "repair" condition was also applied to toluenized cells and shown to be distinct from DNA replication in its DNA polymerase I dependency and its ability to synthesize DNA on template which is either cell associated or free, outside the cell. This repair condition was used in conjunction with the localization test to demonstrate the penetration of deoxyribonuclease I and possibly DNA polymerase I into toluenized cells. Therefore, we suggest that the localization test can be used to test the penetration of proteins into toluenized cells for both the DNA repair and replication processes.


Pyruvate carboxylase deficiency in pleiotropic carbohydrate-negative mutant strains of Pseudomonas aeruginosa. Cell extracts of Pseudomonas aeruginosa strain PAO were found to contain pyruvate carboxylase activity. Specific activities were minimal when cells were grown on Casamino Acids, acetate, or succinate, but were three- to fourfold higher when cells were grown in glucose, gluconate, glycerol, lactate, or pyruvate minimal media. The reaction in crude cell extracts and in partially purified preparations was dependent on pyruvate, adenosine 5'-triphosphate, and Mg(2+), but was not affected by either the presence or absence of acetyl coenzyme A. Activity was nearly totally inhibited by avidin and this inhibition was substantially blocked by free biotin in incubation mixtures. Cell extracts were shown to fix (14)CO(2) in a reaction that had these same characteristics. Eight pleiotropic, carbohydrate-negative mutant strains of the organism were isolated after nitrosoguanidine mutagenesis. Each mutant strain grew normally in acetate, succinate, and citrate minimal media but failed to utilize glucose, gluconate, 2-ketogluconate, mannitol, glycerol, lactate, and pyruvate as sole sources of carbon and energy. These strains were found by quantitative transductional analysis with phage F116 to form a single linkage group. Cell extracts of each mutant strain were either lacking or severely deficient in pyruvate carboxylase activity. Spontaneous revertants of five of the eight strains were isolated and found to recover simultaneously both pyruvate carboxylase activity and the ability to utilize each of the C(6) and C(3) compounds. A second linkage group of similar mutant strains that grew on the C(3) compounds was found to contain normal levels of pyruvate carboxylase activity, but each strain was deficient in an enzyme of the Entner-Doudoroff pathway.


Induction of partial immunologic tolerance in rats and progressive loss of cellular antigenicity in Gross virus lymphoma. Gross virus-induced lymphoma cells express strong virus-associated (Gross murine leukemia virus [G-MuLV]) antigens and are consistently rejected when grafted in normal adult syngeneic rats. By contrast, similar grafts are tolerated and allowed to grow progressively by rats that have been injected at birth with deaggregated G-MuLV antigens. However, the tolerance induced by this procedure is only partial as the grafted lymphoma cells lose their G-MuLV membrane antigens. These cells showing an antigenic disjunction, with negative membrane and positive cytoplasmic G-MuLV antigenic expression, become transplantable in normal-nonconditioned adult recipients. By further grafting, the expression of cytoplasmic G-MuLV antigens is similarly lost while the lymphoma cells substantially increase their transplantability, rate of growth, and capacity for metastasis.


The nicotinic cholinergic receptor protein: improved purification method, preliminary amino acid composition and observed auto-immuno response.


Nuclear localization of S-100 protein.

Nuclear localization of S-100 protein.


The mediator of cellular immunity. VII. Localization of sensitized lymphocytes in inflammatory exudates. Peritoneal exudates induced in rats infected with Listeria monocytogenes contain sensitized lymphocytes which can protect normal recipients against a Listeria challenge. The protective cells arise in lymphoid tissue remote from the peritoneal cavity. Those formed in the caudal lymph nodes of subcutaneously infected rats are delivered to the thoracic duct and hence to the blood from where they are drawn into exudates. Immunoblasts are the most immature members of this protective cell population and they alone among the cells in central lymph localize in exudates induced by killed bacteria. They do so in substantial numbers, but only during the early postinduction period. The "homing" of immunoblasts to inflammatory foci seems to be determined by a general property of the cells rather than their immunological commitment; however, the intense inflammation induced by organisms to which an animal has been specifically sensitized is accompanied by an exuberant influx of immunoblasts into lesions. Sensitized lymphocytes that extravasate in the inflamed peritoneal may generate more of their own kind, but some give rise to small lymphocytes. The latter also have protective properties and, with time, comprise an increasing portion of the protective cell population. The results imply that the tissue disposition of sensitized lymphocytes in the body is determined by a complementary relationship between blood-borne immunoblasts and vascular endothelium in inflamed tissue. The results also provide a plausible explanation for the concentration of sensitized lymphocytes at sites of microbial implantation where they alone would be expected to collaborate with monocyte-derived macrophages in the control of infection.


Immunological approach to the characterization of cholinergic vesicular protein.


Immunochemical studies on cholinergic synaptic vesicles.


Electrophoretic profiles of aqueous-soluble proteins of human cerebral cortex: population and developmental characteristics.


Increased concentrations of acidic metabolites of dopamine in the superior cervical ganglion following preganglionic stimulation in vivo.


Antibacterial efficiency of mercurials.

Antibacterial efficiency of mercurials.


Brain sphingolipids in I cell disease (mucolipidosis II).


Intestinal motor effects of a unique analgesic agent.


Letter: Relationship between pH and antibacterial activity of glutaraldehyde.


Intracellular J chain in mouse plasmacytomas secreting IgA, IgM and IgG.


Complement-mediated mixed aggregation of murine spleen cells.


Lipopolysaccharides inhibit lymphosarcoma cells of bone marrow orgin.


Bacteroids in the ovaries of a tsetse fly.


Infectious particles in a marine ciliate.


Deposition of DDE and polychlorinated biphenyls in dated sediments of the Santa Barbara basin. Analysis of dated oceanic sediments from the Santa Barbara Basin of the Southern California Bight has shown that deposition of polychlorinated biphenyls (PCB) began about 1945 and that DDE [1,1-dichloro-2-2-bis(p-chloro-phenyl)ethylene] first appeared in sediments deposited about 1952. Concentrations of both show a progressive increase through 1967; estimated deposition rates (in grams per square meter per year) in 1967 of DDE and PCB were 1.9 x 10(-4) and 1.2 x 10(-4), respectively.


Addison's disease--serological studies.

Addison's disease--serological studies.


The effect of thyrotrophin releasing hormone on the release of thyrotrophin and other pituitary hormones in man under basal conditions and following adrenergic blocking agents.


Thyrotrophin releasing factor (TRF) in cerebrospinal fluid of the 3rd ventricle of rat.


Iodoproteins in congenital goitre with elevated levels of serum TSH and T3.


Para-articular ossifications after total hip replacement.


Inborn errors of lipid metabolism.

Inborn errors of lipid metabolism.


On the transferrin concentration in serum of sows and growing pigs and in sow colostrum.


Liver injury in protein-calorie malnutrition: an electron microscopic study.


Stature and lean body mass.

Stature and lean body mass.


Impaired cellular immunity in marasmic infants.


Serum levels of immunoglobulins, cell-mediated immunity, and phagocytosis in protein-calorie malnutrition.


Some effects of malnutrition on the immune response in man.


Effects of protein insufficiency on immune responsiveness.


Something old, something new in the visual act of the patient with strabismus.


An evaluation of factors associated with the depression of immunity in malnutrition and in measles.


Bacterial microflora of the upper gastrointestinal tract in infants without diarrhoea.


Iodine balance studies in protein-calorie malnutrition.


On the increased precursor incorporation into the DNA of rat liver mitochondria irradiated in vitro.


The use of immunoadsorbent columns for the isolation of antibodies specific for antigens associated with human bronchogenic carcinoma. An immunoadsorbent technique is described whereby tumour-specific antibodies may be isolated. Extracts from normal human lung tissue were pooled and bound to cyanogen bromide activated Sepharose 4B. Antisera raised in rabbits to a variety of extracts from human bronchogenic carcinoma were passed through these immunoadsorbent columns to yield antisera specific for tumour-associated antigens as demonstrated by immunodiffusion and immunoelectrophoresis.


Reinterpretation of hyperamylasemia in diabetic coma.


Immunochemical measurement of lipoprotein-X.


Effects of hypoglycemic sulfonamides on glucagon and insulin secretion in ducks and dogs.


Metabolic effects of sodium bicarbonate in management of diabetic ketoacidosis.


Metabolism of trehalose in Euglena gracilis. Beta glucose 1,6-bisphosphate, activation factor of phosphoglucomutase for beta glucose 1-phosphate.


If all the sea were PCB.

If all the sea were PCB.


Effects of anti-human neutrophil antibodies in vitro. Quantitative studies. Opsonic, antiphagocytic, cytotoxic, and metabolic effects of homologous and heterologous antibodies against human neutrophils were analyzed by means of quantitative assays to facilitate detection of antibody activity, and to probe membrane function of these cells. Normal human neutrophils were purified by gradient centrifugation, sensitized with heat-inactivated antineutrophil antisera, and incubated with rabbit alveolar macrophages in balanced salt solution containing nitroblue tetrazolium. The macrophages engulfed sensitized neutrophils and reduced nitroblue tetrazolium to formazan in phagocytic vacuoles. The initial rate of nitroblue tetrazolium reduction by macrophages ingesting the neutrophils was measured spectrophotometrically. Neutrophils treated with rabbit anti-human leukocyte antiserum or IgG, with sera from mothers of infants with neonatal isoimmune neutropenia, and with 27% of sera from frequently transfused patients promoted rapid rates of nitroblue tetrazolium reduction by alveolar macrophages. This indicates that antineutrophil antibodies without added complement opsonized neutrophils for ingestion by the macrophages. Some sera from frequently transfused patients with opsonic activity for certain donors' neutrophils did not agglutinate these neutrophils (44%), did not lyse them in the presence of fresh plasma (47%), and did not inhibit phagocytosis of particles by the neutrophils (26%). The reverse was not observed. The opsonic activity of antineutrophil antiserum appears to be the most sensitive and a quantitative means of detecting antibody activity in vitro.Low concentrations of rabbit anti-human leukocyte antisera or IgG stimulated the ingestion rate of unopsonized or opsonized particles by human neutrophils, and, as previously reported by others, enhanced rates of oxidation of [1-(14)C]glucose by the cells. High concentrations of the antisera or IgG inhibited ingestion. All concentrations of homologous antineutrophil antisera tested only inhibited ingestion of particles by neutrophils and none altered rates of resting glucose oxidation by the cells. The findings suggest that heterologous antibodies disturb membrane antigens that trigger oxidative metabolism and enhance as well as inhibit ingestion, and that these antigens are common to all human neutrophils. In contrast to other studies with antimacrophage antibodies, antineutrophil antibodies altered phagocytic rates of both unopsonized and opsonized particles although there were differences in dose-response curves depending on the type of particle tested. Thus, antineutrophil antibodies do not merely cover selected receptor sites.


The effects of the natriuretic factor from uremic urine on sodium transport, water and electrolyte content, and pyruvate oxidation by the isolated toad bladder. The urine of patients with chronic uremia contains a gel filtration fraction that is natriuretic in the rat. The effects of this fraction on the isolated urinary bladder of the toad were examined in the present studies. When added to the serosal surface of the bladder, a significant and substantial fall in short-circuit current and potential difference was observed. The changes began after a lag period of at least 10 min and continued over a period of 60 min. The decrease in short-circuit current at the end of 1 h averaged 44%. The same fraction from the urine of normal subjects produced no significant change in either short-circuit current or potential difference. When the isolated epithelial cells from the toad bladder were incubated in the presence of the inhibitor, intracellular sodium content increased significantly. There was no change in intracellular water content; hence the intracellular concentration of sodium increased by a mean of 7 meq/liter. The changes in intracellular potassium content and concentration were not satistically significant. When the isolated epithelia were incubated with the uremic factor, there was also a significant decrease in pyruvate utilization in relation to cells from paired hemibladders incubated in the absence of the fraction. The fraction from normal subjects produced no change in either intracellular sodium content or pyruvate oxidation. The results suggest that the inhibitor acts from the serosal surface, inhibits sodium transport across the serosal barrier, and produces a decrease in substrate utilization in association with the change in transepithelial sodium transport.


The mechanism of uridine diphosphate-sugar-4-epimerase reactions. Isotope discrimination with 4-tritiated substrates.


Hypothalamic-pituitary function in diverse hyperprolactinemic states. Prolactin secretion in normal adults is characterized by periods of episodic secretion which increase in magnitude during sleep. In this study, we report the 24-h mean prolactin concentrations, prolactin secretory patterns, and associated pituitary hormone function in nine patients (seven women and two men) with hyperprolactinemia of diverse etiologies. Four of the women and one of the men had clinically demonstrable pituitary tumors, one boy had a hypothalamic tumor, and the three other women had "functional" hyperprolactinemia. The 24-h mean prolactin concentrations derived from averaging the 20-min interval samples for 24 h ranged from 28.6 to 1,220 ng/ml. The plasma prolactin patterns in these patients showed persistence of episodic secretion in all and loss of the normal sleep-wake difference in plasma prolactin in seven of nine. Three of the patients with galactorrhea and comparable 24-h mean prolactin concentrations (58.3, 59.7, and 64.3 ng/ml) showed similar prolactin secretory patterns despite different etiologic mechanisms. Evaluation of the secretory patterns of luteinizing hormone (LH) in these patients showed loss of normal pulsatile LH release and a low 24-h mean LH concentration in the patient with the pituitary tumor, while the two patients without clinically demonstrable pituitary tumors ("post-pill" galactorrhea and "idiopathic" galactorrhea) showed normal LH secretory patterns and 24-h mean LH concentrations. The 24-h mean cortisol concentrations and secretory patterns were normal in five of the seven patients who had these parameters measured. The patient with the hypothalamic tumor had a low 24-h mean cortisol concentration and production rate and absent response to metyrapone. The patient with "idiopathic" galactorrhea had an elevated 24-h mean cortisol concentration but normal cortisol production rate and urinary 17-hydroxycorticoid excretion. Growth hormone secretion was abnormal in four of the patients (one with the hypothalamic tumor and three with pituitary tumors). Thyrotropin-releasing hormone (TRH) administration in four patients resulted in normal TSH release in two patients (one of whom developed galactorrhea after the test), an absent response in the patient with the hypothalamic tumor, and a blunted response in one of the women with a pituitary tumor. The two men had low 24-h mean plasma testosterone concentrations (69 and 30 ng/100 ml) and symptoms of impotence and loss of libido. Five of the women (four with pituitary tumors and one with Chiari-Frommel syndrome) had either low 24-h mean LH concentrations, abnormal LH secretory patterns, or both. These data indicate that patients with hyperprolactinemia encompassing a varied etiological range frequently show loss of the normal sleep-associated increase in prolactin secretion as well as abnormalities in the regulation of the other hypothalamic pituitary-regulated hormones. The finding that the abnormalities in LH, growth hormone, thyrotropin, and cortisol (adrenocorticotrophic) secretion were almost uniformly confined to the patients with the clinically demonstrable hypothalamic or pituitary tumors suggests that the size of the lesion is the critical factor.


Deoxyribonucleic acid polymerase from Tetrahymena pyriformis. Purification and properties of the major activity in exponentially growing cells.


On the specificity of phospho-N-acetylmuramyl-pentapeptide translocase. The peptide subunit of uridine diphosphate-N-actylmuramyl-pentapeptide.


A proteolytically activated tyrosinase from frog epidermis.


How to handle secondary impression trays.


Subunit I of G beta replicase and 30 S ribosomal protein S1 of Escherichia coli. Evidence for the identity of the two proteins.


Cytoplasmic type 80 S ribosomes associated with yeast mitochondria. 3. Changes in the amount of bound ribosomes in response to changes in metabolic state.


Analysis of lung culture of Rickettsia prowazedi E strain with regard to its capacity of increasing virulence in passages on the lungs of white mice.


The longterm care of the patient suffering from cerebral palsy. II.


Synthesis and antifolate activity of 10-deazaminopterin.


Synthesis of 1-deaza-N10-methylfolic acid and related compounds.


Ethambutol. Synthesis of an unsaturated analog.


The induction of tumour immunity in mice using glutaraldehyde-treated tumor cells.


Immunological detection of antigen(s) associated with rat colon carcinoma.


Riboflavin and adrenal cortex.

Riboflavin and adrenal cortex.


The yellow baby.

The yellow baby.


Present status of radium.

Present status of radium.


Pulp structure in bilateral and opposing pairs of teeth.


Biologic tests of a methyl methacrylate composite material.


Selective destruction of the pigmented epithelium in the ciliary body of the eye. Perfusion of the internal carotid artery with hypertonic solution selectively destroys most of the pigmented epithelium of the ciliary body of the monkey eye, converts fenestrated endothelium of capillaries to continuous endothelium, and transiently breaks down the blood-aqueous barrier. The nonpigmented epithelium regenerates and the intraocular pressure returns to normal even though the pigmented epithelium is permanently destroyed.


Effect of TRH, and short-term exposure to experimental stress or cold on the serum immunoassayable TSH concentration in the rat.


In vitro procedure for measuring phagocytosis of blood neutrophils.


Brucella ovis as a cause of abortion in ewes.


Diagnosis of Mycobacterium bovis and Mycobacterium paratuberculosis infections in cattle by in vitro lymphocyte immunostimulation.


Comparative in vitro activity of three aminoglycosidic antibiotics: BB-K8, kanamycin, and gentamicin. Kanamycin, BB-K8, and gentamicin were tested in parallel against 1,037 bacterial strains isolated from clinical material. The activity of BB-K8 at 20 mug/ml was comparable to that of gentamicin at 8 mug/ml against Pseudomonas aeruginosa and against Enterobacteriaceae, with the exception of gentamicin-resistant strains of Proteus rettgeri and Providencia stuartii, in which case the activities of BB-K8 and kanamycin were the same. BB-K8 exhibited little or no activity against streptococci. The activity of BB-K8 was affected by pH and inoculum size. A regression graph for inhibition data with a 10-mug disk of BB-K8 was developed, and synergistic activity of penicillin and BB-K8 against Streptococcus faecalis was tested.


Antiprotozoal activity of rubratoxin B.

Antiprotozoal activity of rubratoxin B. Growth of Tetrahymena pyriformis HSM was inhibited by a concentration of 25 mug of rubratoxin B per ml of growth medium. The inhibitory effect of aflatoxin B(1)-rubratoxin B mixtures on growth of T. pyriformis was induced by rubratoxin B only. Total cellular deoxyribonucleic acid increased in the presence of 5 mug of rubratoxin B per ml of growth medium, whereas higher concentrations (25 mug/ml of growth medium) were required before a decrease in total protein was observed.


Enumeration of tubercle bacilli in sputum of patients with pulmonary tuberculosis. A method for precise microscopic enumeration of acid-fast bacilli in the sputum of patients with pulmonary tuberculosis is described. The total number of acid-fast bacilli and the number of culturable cell units of tubercle bacilli per milliliter of sputum were determined in 269 specimens from 28 patients collected prior to and/or during chemotherapy, to establish the usefulness of the procedure for evaluation of the effects of chemotherapy. Prior to or very early in the course of therapy, there was good agreement between microscopically and culturally measurable bacilli in 27 of 28 patients. Thereafter, there were systematic divergences in five patients and occasional divergences in most others. Yet, in general, in 20 of the 28 patients, the microscopically determined population provided a useful measure of the number of culturable tubercle bacilli present. Although the microscopic procedure does not allow species identification of mycobacteria or differentiation between viable and nonviable cells, it often provided, within hours rather than days or weeks, useful information on the residual burden of acid-fast bacilli in sputum during chemotherapy. The nature of the disease in those patients in whom microscopy failed to provide useful information is discussed.


Inactivation of dried bacteria and bacterial spores by means of gamma irradiation at high temperatures. Dried preparations with Streptococcus faecium, strain A(2)1, and spores of Bacillus sphaericus, strain C(I)A, normally used for control of the microbiological efficiency of radiation sterilization plants and preparations with spores of Bacillus subtilis, normally used for control of sterilization by dry heat, formalin, and ethylene oxide, as well as similar preparations with Micrococcus radiodurans, strain R(1), and spores of Bacillus globigii (B. subtilis, var. niger) were gamma irradiated with dose rates from 16 to 70 krad/h at temperatures from 60 to 100 C. At 80 C the radiation response of the spore preparations was the same as at room temperature, whereas the radiation resistance of the preparations with the two vegetative strains was reduced. At 100 C the radiation response of preparations with spores of B. subtilis was unaffected by the high temperature, whereas at 16 and and 25 krad/h the radiation resistance of the radiation-resistant sporeformer B. sphaericus, strain C(I)A, was reduced to the level of radiation resistance of preparations with spores of B. subtilis. It is concluded that combinations of heat and gamma irradiation at the temperatures and dose rates tested may have very few practical applications in sterilization of medical equipment.


Effect of heat on the antimicrobial activity of brillant green dye. Antimicrobial activity of brilliant green dye in Trypticase soy broth (BBL) is reduced and ultimately destroyed by prolonged autoclaving at 121 C. Loss of antimicrobial activity is accompanied by decolorization of the dye. This is consistent with other evidence that antimicrobial activity of brilliant green resides in the colored dye ion. The dye is not decolorized when heated in distilled water or peptone, but is decolorized by heating in glucose, glycine, or sodium dodecyl sulfate, showing that decolorization results from reaction with components of the medium. To ensure optimal results, it is recommended that bacteriological media be sterilized by heat prior to addition of brilliant green dye.


Salmonellae in the environment around a chicken processing plant. Studies have been conducted over a 2-year period to determine the extent to which a poultry processing plant served as a reservoir of salmonellae reaching the external environment, to examine the question of the importance of salmonellae in the environment, and to consider how best to control the spread of the organisms. The studies have been undertaken at a chicken processing plant handling between 75,000 and 80,000 birds per day. Populations of salmonellae and indicator bacteria were estimated in the raw wastes, through the waste treatment plant, and in the receiving stream waters. The results demonstrate that salmonellae are present in poultry processing wastes in a surprisingly constant relation to fecal coliforms (in excess of 1 Salmonella per 500 fecal coliforms), that serotypes in the environment are constantly changing, and that they may reflect unusual conditions in the processing plant, or a possible source of infection among human and animal residents of the environment. Disinfection of poultry processing wastes is recommended.


Immobilized aspartase-containing microbial cells: preparation and enzymatic properties. The immobilization of asparatase-containing Escherichia coli was investigated by various methods, and the most active immobilized cells were obtained by entrapment in a polyacrylamide gel lattice. Other asparatase-containing bacteria were also entrapped by the same method, and the enzymatically active immobilized cells were obtained. The aspartase activity of the immobilized E. coli cells was increased nine- to tenfold by autolysis of the cells entrapped in the gel lattice. Enzymatic properties of the immobilized E. coli cells were investigated and compared with those of the intact cells. The optimal pH was 8.5 for the immobilized cells and 10.5 for the intact cells. The aspartase activities of immobilized and intact cells were not activated by Mn(2+), which can activate the immobilized and native aspartases. The heat stability of the immobilized cells was somewhat higher than that of the intact cells. Bivalent metal ions such as Mn(2+), Mg(2+), Ca(2+) protected against thermal inactivation of the aspartase activity of the immobilized and intact cells.


Proteinase activity in slow lactic acid-producing variants of Streptococcus lactis. Variants of Streptococcus lactis that produce lactic acid slowly in milk were isolated by inducing plasmid loss in the wild type at 39 to 40 C. Such strains had lost most of their surface-bound proteinase activity and were designated prt(-). The specific proteinase activities of S. lactis C10 prt(+) whole cells and solubilized cell walls were 7 and 18 times, respectively, those of the prt(-) strain, but spheroplast lysates of prt(+) and prt(-) strains contained similar proteinase activity. S. lactis H1 showed a similar relative distribution of activity between prt(+) and prt(-) cellular fractions, although the overall level was lower. The limited growth in milk, characteristic of prt(-) strains, can be explained in terms of their low surface-bound proteinase activity.


Membrane filter method for the isolation and enumeration of Pseudomonas aeruginosa from swimming pools. A membrane filter technique using black membrane filters, MacConkey agar and fluorescence under ultraviolet (UV) light was investigated for the quantitative isolation of Pseudomonas aeruginosa from swimming pools. Three thousand four hundred forty-five samples were collected from public swimming pools and enumerated by this method over a 6-month period. Fluorescent cultures were isolated from 222 specimens. Seventy-seven of these fluorescent cultures were selected for biochemical screening, with 75 (97%) being verified as P. aeruginosa. To further assess the specificity and sensitivity of this UV screening technique, a comparative study was made of some morphological and biochemical characteristics of fluorescent pseudomonads obtained from different sources. The sensitivity of the method was unimpaired by either colony types or biochemical variations of P. aeruginosa. The failure of the other two fluorescent species, P. fluorescens and P. putida, to grow and/or fluoresce on MacConkey agar at 37 C illustrates the specificity of this technique. Further studies are needed to compare the viability of P. aeruginosa on MacConkey agar to that of efficacious nonselective media.


Evaluation of fetal risk resulting from cord-entanglements during parturition.


Sialic acid content of cortical bone.

Sialic acid content of cortical bone.


Preparation of immobilized lactase. Continued studies on the enzymatic hydrolysis of lactose.


AMP-aminohydrolase of human skeletal muscle: partial purification and properties.


Distribution and biochemical effects of pentylenetetrazol in brains of swine treated with a polychlorinated biphenyl.


Partial characterization of aerolysin, a lytic exotoxin from Aeromonas hydrophila. Conditions are defined for the production, in high titers, of an extracellular hemolytic toxin of Aeromonas hydrophila, here termed "aerolysin." Substantial purification of the toxin was accomplished by means of salt fractionation, dialysis, and gel filtration, with a yield of 24% of the starting activity. Analysis of the product by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed a single, heavy protein band and a number of faint protein bands. The estimated molecular weight of the heavy band (50,000) was in close agreement with that (53,000) of the substance responsible for hemolytic activity as determined by gel filtration. Purified aerolysin is a labile substance, apparently protein. It is not inactivated by any of several proteases under the conditions employed nor is it inhibited by any of several lipids tested. About 0.1 mug administered to mice intravenously is lethal. The physical properties of aerolysin show considerable resemblance to those described for the exotoxin of Pseudomonas aeruginosa.


Characterization and evaluation of a soluble antigen complex prepared from the yeast phase of Histoplasma capsulatum. Soluble yeast-phase (YPS) antigen preparations (Reeves et al., 1972) were obtained from three strains of Histoplasma capsulatum. These were analyzed by agar-gel diffusion and complement fixation tests with human sera from known cases of histoplasmosis. Two of the preparations contained the H and M antigens normally found in histoplasmin, whereas the third preparation contained the H but not the M antigen. In addition, a group of unknown antigens, designated as the Y (yeast) antigens, were demonstrated in all three YPS preparations. On the basis of Sephadex gel filtration data, the molecular weight of the YPS M antigen was estimated to range from 117,000 to greater than 200,000; that of the YPS H antigen was estimated to range from about 60,000 to greater than 200,000; and that of the Y antigens was estimated to range from less than 10,000 to 100,000. Complement fixation tests with human homologous and heterologous sera showed that the Y antigens were specific for H. capsulatum; Y antigens were not detected in the single lot of histoplasmin used in this study. When 60 human histoplasmosis sera and serum samples from nine animals experimentally infected with H. capsulatum were analyzed, it was found that antibodies to the Y antigens occurred with about the same frequency as antibodies to the H antigen but with less frequency than that of antibodies to the M antigen. When used in rabbits as immunogens for the preparation of specific antisera to H. capsulatum, the components of the YPS preparations caused the formation of numerous cross-reacting antibodies. The data from this study show that the value of the YPS preparations for the serological diagnosis of histoplasmosis rests on the specificity of the H, M, and Y antigens and on the fact that the primary production of antibodies is restricted to these antigens in the course of natural infections. The YPS preparations were found to be stable for a period of at least 11 months under a variety of storage conditions and temperatures. Data obtained with various killing agents and metabolic inhibitors suggest an improved method for preparing the YPS antigens by using a suitable strain and killing the cells with iodoacetate.


Isolation of substances responsible for lymphokine activity from sensitized mouse spleen cells. Cultures of brucella-sensitized mouse spleen cells exposed to Brucella abortus antigens in vitro release macrophage migration inhibition factor (MIF) and macrophage spreading factor. Subjecting the supernatants from such cultures to preparative scale electrophoresis in acrylamide gel yields several fractions, one of which contains both MIF and macrophage spreading factor. This material has properties attributable to guinea pig MIF: it is nondialyzable, heat stable, nontoxic to macrophages from heterologous murine donors, and has a greater anodal electrophoretic mobility than guinea pig serum albumin. Another fraction from the gel column inhibits macrophage spreading; its electrophoretic mobility is similar to that of guinea pig gamma globulin. Neither brucella antigen nor skin reactive substances were detectable in any acrylamide gel column fraction when tested by the mouse footpad induration assay technique.


New streptococcal serotypes causing pyoderma and acute glomerulonephritis types 59,60, and 61. Three new streptococcal M serotypes, types 59, 60, and 61; have been described. They were first isolated from patients with pyoderma and acute glomerulonephritis (AGN), seen during epidemiological studies in Alabama. A possible antigenic relationship between types 59 and 61 was suggested by their T-agglutination reactions; a more specific T antiserum prepared for type 59 was useful in separating these two types, as well as other strains known to share T antigens 11, 12, and 5/27/44. On the basis of precipitin tests, a common antigenic determinant among types 59, 61, and 49 was suggested. This is of interest in view of the relation between these types and AGN. Type 59 has been relatively more widespread in distribution than type 61, but neither have been related to epidemic AGN. Type 60, first identified as "T-4," thus being related to previously described M types which share this antigen, is of great interest in terms of the epidemiology of AGN. Most strains in our collection were recovered from patients with pyoderma and AGN or from their infected siblings. Recently, the type was found to be prevalent among patients with pyoderma and AGN seen in Trinidad. Data reported in relation to these new types further illustrate the dichotomy in M serotypes common to pyoderma and AGN on the one hand and those types found in collections of patients with pharyngitis on the other hand. The high rate of non-M-typable streptococci among pyoderma collections, encountered earlier, is best explained by lack of suitable reference antisera available for prevalent pyoderma serotypes.


Bacterial clearance and endocarditis in American opossums. The American opossum is the only experimental animal that regularly develops bacterial endocarditis spontaneously. There was no relation between the ability of opossums to clear bacteria from the bloodstream and the subsequent development of endocarditis.


Suppression of growth of Ehrlich ascites tumor cells in mice by trehalose-6,6'-dimycolate (cord factor) and BCG. Growth of Ehrlich ascites tumor cells in mice pretreated with cord factor was compared to growth of the tumor cells after pretreatment with Calmette-Guérin bacilli. Growth of Ehrlich ascites cells was strongly inhibited in the peritoneal cavities of mice pretreated with 80 mug of cord factor. The median survival time of the animals was prolonged (70 versus 17 days), and 40% of the mice survived more than 90 days. Tumor suppression was still detectable 36 days after administration of cord factor. The effect of cord factor was local. Comparable results were obtained with living or killed Calmette-Guérin bacilli. The results are discussed.


Activity of carbenicillin and ticarcillin against Pseudomonas aeruginosa compared by paired in vitro tests.


Experience with low temperature storage of bacteria and fungi.


Prevention of hemolysis induced by ellipticine (NSC-71795) in rhesus monkeys.


Total synthesis of bisnorpenicillin V.

Total synthesis of bisnorpenicillin V.


Antimicrobial activity of 8-deazafolic acid.


Tetrathionate broth as a medium for simultaneous demonstration of Salmonella and Pseudomonas aeruginosa.


Polychlorinated biphenyl toxicity to Japanese quail as related to degree of chlorination.


Differences in response of caged White Leghorn layers to various polychlorinated biphenyls (PCBs) in the diet.


Surface changes in the epicardium of chickens fed polychlorinated biphenyls.


Selection for body weight at eight weeks of age. 13. Fecundity.


Transplantation of posterior polar plasm in Drosophila. Induction of germ cells at the anterior pole of the egg. In Drosophila melanogaster the primordial germ cells are normally formed at the posterior tip of the egg during the preblastoderm stage. In order to determine whether the posterior polar plasm is capable of inducing the formation of primordial germ cells in another region of the embryo, portions of this cytoplasm were transferred from wild-type embryos of the early cleavage stage to the anterior tip of mwh e embryos of the same age. At various times after the injection (15-200 min), embryos were fixed for histological analysis. Alternating thick and thin sections were examined for the presence of experimentally induced pole cells. In more than half of the embryos analyzed in this way, one to six cells were found containing the polar granules as well as round nuclear structures, both of which are characteristic of normal pole cells and are not present in blastoderm cells. In order to determine whether these "pole cells" function normally, i.e., develop further into germ cells, the cells induced at the anterior tip of mwh e blastoderm embryos were introduced into the posterior region of y w sn(3) hosts of the same age. The flies resulting from these embryos were mated to y w sn(3) partners. In addition to the expected y w sn(3) progeny, wild-type flies heterozygous for mwh e and, therefore, descended from the experimentally induced pole cells were found in 4% of the crosses. Such flies did not appear in the control experiments after transfer of normal anterior cells from noninjected blastoderm embryos. These results demonstrate that the posterior polar plasm can be transferred to the anterior tip of the embryo and that in this presumptive somatic region it still retains its capacity to determine the formation of the primordial germ cells.


A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Dialyzed serum from clotted monkey blood ("blood serum") promotes the proliferation of monkey arterial smooth muscle cells in culture, but dialyzed serum prepared from recalcified platelet-poor plasma ("plasma serum") is much less effective. Addition of platelets and calcium to platelet-poor plasma increases the activity of plasma serum to the same level achieved with blood serum. Furthermore, addition to plasma serum of a platelet-free supernatant prepared by exposing purified platelets to thrombin also stimulates the proliferation of smooth muscle cells. Thus, much of the growth-promoting activity of dialyzed serum is directly or indirectly derived from platelets. This finding has important implications for the response of arteries to localized injury and provides a key to further understanding of the role of factors derived from blood serum in promoting cell proliferation in vitro.


Unequal mitotic sister chromatin exchange as the mechanism of ribosomal RNA gene magnification. It is hypothesized that magnification of the gene coding for ribosomal RNA occurs by unequal mitotic sister chromatid exchange on the basis of five different lines of evidence. These are: (1) rDNA magnification occurs in mitotically active germ cells; (2) decreases in rDNA redundancy can be genetically produced, a phenomenon termed reduction; (3) magnification and reduction events are reversible and reciprocal; (4) it is possible to generate bb(+) and bb somatic bristle mosaics (bb mutants are partially deficient for rRNA genes); and (5) magnification of bb in a ring X chromosome is reduced. Implications of these results and the unequal sister exchange (USE) hypothesis are discussed.


Genetic control of imaginal disc development in Drosophila. Many of the functions required for formation of the imaginal discs of Drosophila melanogaster larvae, from which adult structures are derived, are disc-specific and not required for formation of other larval tissues. Mutants blocked in disc-specific functions can produce mature viable larvae, indicating that larval development is not dependent on concomitant disc development. Some of the mutant larvae have no detectable discs (discless mutants), and other have small discs that cannot differentiate into adult structures (small disc mutants). From the results of genetic complementation and mapping experiments with such mutants, it was estimated that the genome of D. melanogaster contains around a thousand complementation groups, or about a fifth of all complementation groups in the genome, that are essential specifically for the development of all the discs. The developmental defects in some of the disc mutants appear to involve autonomous functions of the imaginal cells, and in other mutants functions provided by the larval environment to support disc development. This distinction was made on the basis of two functional tests. The purpose of one of the tests was to detect the presence in young embryos of determined imaginal cells capable of differentiating after transplantation to a wild-type host; the other test measured the capacity of early third-instar larvae to act as hosts for the further development of immature discs transplanted from a wild-type donor. Three discless mutants that were tested in this way appeared to be defective in autonomous functions of the imaginal cells, since the embryos contained no imaginal cells that could be detected in the first test, whereas the larvae, although devoid of discs, showed a normal capacity to support disc development in the second test. One of the small disc mutants tested was defective in a larval rather than an imaginal cell function, since the embryos had a normal complement of functional imaginal cells, whereas the larvae were incapable of supporting disc development. Thus, both types of disc-specific functions are essential for normal disc development.


Kinetic evidence for the presence of two prostaglandin receptor sites regulating the activity of intestinal adenylate cyclase sensitive to Escherichia coli enterotoxin. Kinetic behavior most consistent with the presence of two independent, but simultaneously acting, regulatory effector sites for prostaglandins has been presented for adenylate cyclase (EC 4.6.1.1) of rabbit intestinal epithelial cells. One site regulates activation of the catalytic site, while the other site regulates inhibition. A synthetic prostaglandin analogue, 7-oxa-13-prostynoic acid, is recognized at both sites in a concentration-dependent manner. At concentrations of 7-oxa-13-prostynoic acid less than 45 mug/ml, activation is seen, while at higher concentrations, inhibition is seen. Different naturally occurring prostaglandins appear to be site-specific. Prostaglandin E(1) gives only activation of the cyclase, while prostaglandin A(1) gives only inhibition of the activated cyclase. When saturating concentrations of prostaglandin E(1) are used to activate adenylate cyclase, no further activation by 7-oxa-13-prostynoic acid can be elicited, indicating that both molecules activate at the same site. The similarity of inhibition constants for both 7-oxa-13-prostynoic acid and prostaglandin A(1) suggests that the mode of binding is the same for both compounds and that they probably inhibit by acting at the same site. The inhibition by 7-oxa-13-prostynoic acid and by prostaglandin A(1) overrides enzyme activation produced by either Escherichia coli enterotoxin, prostaglandin E(1), or sodium fluoride, suggesting that in intestinal adenylate cyclase this site is the primary regulatory site (i.e., primary allosteric effector site) for enzyme activity. These data suggest that sites exist on adenylate cyclase which would allow prostaglandins to serve as the intracellular messengers by which the cell controls its adenylate-cyclase-mediated response to extracellular stimulation, as with hormones.


Evidence for the presence of the toxin-binding protein on the plasma membrane of sugarcane cells. Helminthosporoside is a host-specific toxin produced by Helminthosporium sacchari, both in culture and in infected sugarcane tissue. The susceptibility of any given clone of sugarcane to disease is invariably associated with the presence of a toxin-binding protein. This report presents evidence for the presence of the toxin-binding protein on the plasma membrane of the plant cell. This evidence includes, among others: (1) The protection of susceptible plant tissues by prior treatment with antiserum to the binding protein, (2) the successful pyridoxylation and reduction of the binding protein in vivo followed by its isolation, (3) the reaction of sugarcane cells and free protoplasts with [(3)H]antiserum prepared against the binding protein, and (4) the agglutination of sugarcane protoplast preparations with antiserum to the binding protein.


Partial purification of detergent-soluble HL-A antigen and its cleavage by papain. HL-A antigen solubilized with the non-ionic detergent, Brij 99, has been purified to about 50% of homogeneity from a cultured human lymphoblast line. It consists of two nonidentical subunits of 44,000 and 12,000 molecular weight (MW). Upon papain proteolysis the 44,000 MW peptide is converted by at least two cleavages to a 34,000 MW peptide, but the 12,000 MW peptide appears to be unchanged. Concomitantly, the apparent molecular weight in gel filtration chromatography under nondenaturing conditions in the presence of Brij 99 is reduced from 460,000 to 45,000. HL-A molecules produced by direct papain proteolysis of membranes and by papain treatment of purified detergent-soluble HL-A are identical.


Epileptic fits in cysticercosis.

Epileptic fits in cysticercosis.


Tuberculosis survey in East Central State, Nigeria: implications for tuberculosis programme development.


Use of sulfadiazine in the prophylaxis of group A meningococcal carriers in Egypt.


Pediatric urinary tract infection. Significance of vaginal bacteria.


A simplified and rapid direct method for the determination of triiodothyronine in human serum.


Scanning electron microscopy on the distribution of the minute blood vessels in the thyroiod gland of the dog, rat and rhesus monkey.


Effect of isoniazid on the in vivo mycolic acid synthesis, cell growth, and viability of Mycobacterium tuberculosis. When an actively growing culture of the H37Ra strain of Mycobacterium tuberculosis was exposed to isoniazid at a concentration of 0.5 mug/ml, the cells began to lose their ability to synthesize mycolic acids immediately. After 60 min, the cells had completely lost this ability. The synthesis of the three mycolate components-alpha-mycolate, methoxymycolate, and beta-mycolate-was inhibited. The viability of the isoniazid-treated cells was unaffected up to about 60 min of exposure, after which time there was a gradual decline in the viability to about 18% after 180 min. Correspondingly, growth of the drug-treated cells slowed down and stopped after 24 hr. The inhibition of the synthesis of mycolic acids was reversible if the drug was removed before the loss of viability set in. Incubation of the viable cells in the absence of the drug for 24 hr restored the mycolate synthesis. These results strongly suggest that the inhibition of the synthesis of the mycolic acids is closely associated with the primary mechanism of action of isoniazid on the tubercle bacilli. The sequence of events which leads to the loss of viability of cells exposed to isoniazid is described.


Activation of prephenoloxidase. 3. Release of a peptide from prephenoloxidase by the activating enzyme.


Dissociation of tetanus neurotoxin into two polypeptide fragments.


Enzymatic breakdown of tetanus toxin.

Enzymatic breakdown of tetanus toxin.


Chemical modification of the tryptophan residue in toxin B from the venom of the Indian cobra.


The pathology of experimental lead encephalopathy in the baboon (Papio anubis).


Quantitative aspects of ribosomal RNA synthesis during ovarian development in two mutants of Drosophila melanogaster.


Delta-aminolevulinic acid synthetase activity in normal human bone marrow and in patients with idiopathic sideroblastic anemia.


Regulatory link between lactate dehydrogenase and biosynthesis of porphyrin and heme in microorganisms.


Effect of oxygen on heme and cytochrome content in some facultative bacteria.


Role of oxygen in the late steps of heme synthesis in pseudomonads and Escherichia coli.


Comparison of porphyrin and heme biosynthesis in various heterotrophic bacteria.


Peptic digestion of pig IgM.

Peptic digestion of pig IgM.


Equine anti-hapten antibody. 8. Isoelectric fractions of IgM and 7S anti-lactose antibody.


Does J chain mediate the combination of 19S IgM and dimeric IgA with the secretory component rather than being necessary for their polymerization?


The membranes of the basal labyrinth in kidney cells of the stickleback, Gasterosteus aculeatus, studied in ultrathin sections and freeze-etch replicas.


Spermatogenesis in pharate adult testes of Drosophila in tissue cultures without ecdysones.


Differentiation in breast cancer.

Differentiation in breast cancer.


Clinical value of tumour-associated antigens.


Palindromes in chromosomes.

Palindromes in chromosomes.


The structure of psi DNA.

The structure of psi DNA.


Vaginal flap incision for urethral diverticulectomy.


Nocardiosis of the testis.

Nocardiosis of the testis.


Serum folic acid levels and pregnancy in South Australia. A study of the factors associated with low serum folic acid levels with particular reference to racial groups and lactation.


Letter: The use of nebulized intal in asthma.


Rapid grouping of streptococci by immunoelectroosmophoresis.


The establishment of rumen ciliate protozoa in sheep fed on whole barley to appetite.


Autoradiographic evidence for the occurrence of cell fusion cultures of Theileria-infected bovine lymphoid cells.


An investigation of the association between circulating antibody levels and systemic anaphylactic sensitivity in cattle.


Capsular and somatic antigens of Pasteurella multocida, types B and E.


Factor XII-induced fibrinolysis: studies on the separation of prekallikrein, plasminogen proactivator, and factor XI in human plasma.


Uses of epidemiology in housing programmes and in planning human settlements. Report of a WHO Expert Committee on Housing and Health.


Histochemistry of enzymes involved in the synthesis and breakdown of glycogen in the junctional zone of the rat's placenta.


Retinal effects of a multiple-pulse laser.


Metabolism of two valence states of inhaled antimony in hamsters.