bluuebunny/crossref_metadata_2025 huggingface dataset:
A Characterization and Targeting of the Infarct Border Zone in a Swine Model of Myocardial Infarction
Authors: Duran Jason M. , Taghavi Sharven , Berretta Remus M. , Makarewich Catherine A. , Sharp III Thomas , Starosta Tim , Udeshi Foram , George Jon C. , Kubo Hajime , Houser Steven R.
Published: June 2012

Introduction: Novel therapies for myocardial infarction (MI) involving stem cells, gene therapy, biomaterials, or revascularization strategies have shown promise in animal studies and clinical trials, but results have been limited partially due to the injection of therapeutics into ischemic myocardium that cannot support their mechanism of action. Accurate targeting of therapeutics precisely to the infarct border zone (BZ) may be essential for effective repair of the ischemic heart.

Methods: Ischemia‐reperfusion MI was induced in Yorkshire swine by inflation of an angioplasty balloon in the left anterior descending coronary artery. Fluorescent microspheres were injected into the BZ under NOGA catheter guidance, and this location was identified grossly then examined by immunohistochemistry and Western analysis.

Results: Analysis of the infarct zone two hours post‐MI revealed a frankly necrotic region devoid of contractile proteins with marked activation of caspase‐3. The NOGA‐defined BZ closely approximates the grossly‐defined BZ and contains intact myocytes and vasculature. Western analysis detected Akt expression and levels of Ca2+ handling proteins equivalent to that of viable tissues.

Conclusions: Histological and Western analysis revealed that NOGA mapping precisely identifies grossly and molecularly defined infarct BZ at a location where there are still viable cells and vessels capable of supporting novel therapeutic strategies. Clin Trans Sci 2012; Volume 5: 416–421
Modeling the Material Microstructure Effects on the Surface Generation Process in Microendmilling of Dual-Phase Materials
Authors: Abdelrahman Elkaseer A. M. , Dimov S. S. , Popov K. B. , Negm M. , Minev R.
Published: June 2012

The anisotropic behavior of the material microstructure when processing multiphase materials at microscale becomes an important factor that has to be considered throughout the machining process. This is especially the case when chip-loads and machined features are comparable in size to the cutting edge radius of the tool, and also similar in scale to the grain sizes of the phases present within the material microstructure. Therefore, there is a real need for reliable models, which can be used to simulate the surface generation process during microendmilling of multiphase materials.This paper presents a model to simulate the surface generation process during microendmilling of multiphase materials. The proposed model considers the effects of the following factors: the geometry of the cutting tool, the feed rate, and the workpiece material microstructure. Especially, variations of the minimum chip thickness at phase boundaries are considered by feeding maps of the material microstructure into the model. Thus, the model takes into account these variations that alter the machining mechanism from a proper cutting to ploughing and vice versa, and are the main cause of microburr formation. By applying the proposed model, it is possible to estimate more accurately the resulting roughness because the microburr formation dominates the surface generation process during microendmilling of multiphase materials. The proposed model was experimentally validated by machining two different samples of dual-phase steel under a range of chip-loads. The roughness of the resulting surfaces was measured and compared to the predictions of the proposed model under the same cutting conditions. The results show that the proposed model accurately predicts the roughness of the machined surfaces by taking into account the effects of material multiphase microstructure. Also, the developed model successfully elucidates the mechanism of microburr formation at the phase boundaries, and quantitatively describes its contributions to the resulting surface roughness after microendmilling.
Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Components of the Cell Cycle and Inhibit T Cell Proliferation
Authors: Patsoukis Nikolaos , Brown Julia , Petkova Victoria , Liu Fang , Li Lequn , Boussiotis Vassiliki A.
Published: June 2012

The inhibitory receptor PD-1 blocks T cell proliferation by preventing cells from leaving the G
1
phase of the cell cycle.
Pan-β-Lactam Resistance Development in Pseudomonas aeruginosa Clinical Strains: Molecular Mechanisms, Penicillin-Binding Protein Profiles, and Binding Affinities
Authors: Moyá Bartolomé , Beceiro Alejandro , Cabot Gabriel , Juan Carlos , Zamorano Laura , Alberti Sebastián , Oliver Antonio
Published: June 2012

We investigated the mechanisms leading to
Pseudomonas aeruginosa
pan-β-lactam resistance (PBLR) development during the treatment of nosocomial infections, with a particular focus on the modification of penicillin-binding protein (PBP) profiles and imipenem, ceftazidime, and ceftolozane (former CXA-101) PBP binding affinities. For this purpose, six clonally related pairs of sequential susceptible-PBLR isolates were studied. The presence of
oprD
,
ampD
, and
dacB
mutations was explored by PCR followed by sequencing and the expression of
ampC
and efflux pump genes by real-time reverse transcription-PCR. The fluorescent penicillin Bocillin FL was used to determine PBP profiles in membrane preparations from all pairs, and 50% inhibitory concentrations (IC
50
s) of ceftolozane, ceftazidime, and imipenem were analyzed in 3 of them. Although a certain increase was noted (0 to 5 2-fold dilutions), the MICs of ceftolozane were ≤4 μg/ml in all PBLR isolates. All 6 PBLR isolates lacked OprD and overexpressed
ampC
and one or several efflux pumps, particularly
mexB
and/or
mexY
. Additionally, 5 of them showed modified PBP profiles, including a modified pattern (
n
= 1) or diminished expression (
n
= 1) of PBP1a and a lack of PBP4 expression (
n
= 4), which correlated with AmpC overexpression driven by
dacB
mutation. Analysis of the essential PBP IC
50
s revealed significant variation of PBP1a/b binding affinities, both within each susceptible-PBLR pair and across the different pairs. Moreover, despite the absence of significant differences in gene expression or sequence, a clear tendency toward increased PBP2 (imipenem) and PBP3 (ceftazidime, ceftolozane, imipenem) IC
50
s was noted in PBLR isolates. Thus, our results suggest that in addition to AmpC, efflux pumps, and OprD, the modification of PBP patterns appears to play a role in the
in vivo
emergence of PBLR strains, which still conserve certain susceptibility to the new antipseudomonal cephalosporin ceftolozane.
Severe Acute Respiratory Syndrome Coronavirus Replication Inhibitor That Interferes with the Nucleic Acid Unwinding of the Viral Helicase
Authors: Adedeji Adeyemi O. , Singh Kamalendra , Calcaterra Nicholas E. , DeDiego Marta L. , Enjuanes Luis , Weiss Susan , Sarafianos Stefan G.
Published: June 2012

Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC
50
s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC
50
] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC
50
] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.
7-[α-(1-Methyl-4-Pyridinothio)-Acetamido] Cephalosporanic Acid
Authors: Buck R. E. , Leitner F. , Price K. E.
Published: June 2012

7-[α-(1-Methyl-4-pyridiniothio)-acetamido] cephalosporanic acid, referred to herein as BL-S 217, is a new broad-spectrum semisynthetic cephalosporin that offers several advantages over cephalothin. A comparison of the activity in vitro of these antibiotics indicates that BL-S 217 is about eightfold more effective against
Streptococcus pyogenes
and
Diplococcus pneumoniae
. Against gram-negative bacteria, BL-S 217 possesses a broader antibacterial spectrum than cephalothin, particularly against members of the
Enterobacteriaceae
family; e.g., BL-S 217 inhibited over 20% more strains of both
Escherichia coli
and
Klebsiella
than cephalothin and also showed some advantage in tests against
Salmonella
and
Enterobacter
. Overall, of 208 strains of
Enterobacteriaceae
tested, 172 were susceptible to BL-S 217 compared to 149 for cephalothin. BL-S 217 was less bound to human serum proteins than cephalothin and gave higher peak blood levels in mice after intramuscular administration. The LD
50
of BL-S 217 in mice after subcutaneous administration was in excess of 4,000 mg/kg. When administered by the same route to mice experimentally infected with cephalothin-sensitive bacterial strains, this new cephalosporin was 20 times more effective than cephalothin in
S. pyogenes
and
D. pneumoniae
infections and 3 to 4 times more efficacious in an
E. coli
infection. Its therapeutic efficacy was comparable to that of cephalothin in infections produced by strains of
Staphylococcus aureus, Klebsiella pneumoniae
, and
Proteus mirabilis
.
Effect of Antibacterial Therapy on Renal Lysozyme Levels in Rats Developing Bacterial Pyelonephritis
Authors: Eudy W. W. , Burrous S. E.
Published: June 2012

In animals developing unilateral
Proteus mirabilis
-induced pyelonephritis, the total soluble renal lysozyme (SRL) of both kidneys undergoes a biphasic elevation. The second phase of elevated SRL is associated with the onset of chronicity in the infected kidney. To discover whether effective antibacterial therapy altered the second elevation of SRL, levels of SRL were determined in rats developing unilateral chronic pyelonephritis with and without effective regimens of antibacterial agents. Therapeutic doses of ampicillin and nitrofurantoin caused elevations of SRL in both kidneys of infected animals, but these differences were not statistically significant (
P
> 0.05). Both agents produce elevations of SRL in uninfected animals which were significant (
P
< 0.05) when compared with normal animals. Kanamycin sulfate at a therapeutic dose induced great elevations of SRL in kidneys of both infected and uninfected animals. It is concluded that infection per se is not the cause of the elevated SRL.
Microiodometric Determination of β-Lactamase Activity
Authors: Sykes R. B. , Nordström K.
Published: June 2012

The product of β-lactamase activity (a penicilloic acid in the case of a penicillin) is stoichiometrically oxidized by iodine. Hence, the β-lactamase activity can be measured as decolorization of the blue starch-iodine complex. Since the decolorization is a slow process, the rate of decolorization gave an underestimate of the rate of penicillin hydrolysis until a steady state was obtained after 15 to 20 min. If the reaction mixture (3 ml) contained no more than 0.001 unit of enzyme, a correct determination of β-lactamase activity was obtained from the microiodometric method described. The method is sensitive and some applications are mentioned.
Polysome Metabolism in
Escherichia coli:
Amicetin, an Antibiotic That Stabilizes Polysomes
Authors: Ennis Herbert L.
Published: June 2012

Amicetin, an aminohexosepyrimidine nucleoside antibiotic, inhibited protein synthesis in intact bacterial cells and in cell-free extracts derived from these cells. At concentrations of antibiotic which rapidly and completely inhibited protein synthesis, the polysomes in the cell were stabilized. Amicetin also inhibited the breakdown of polysomes induced by the streptogramin A antibiotics, rifampin, or puromycin, antibiotics that require peptide bond formation for expression of their action on polysomes. Thus, amicetin is another addition to the list of drugs which may be useful in studying polysome and messenger ribonucleic acid metabolism in vivo. An in vitro system is described which may be generally useful in studying polysome metabolism when antibiotic-sensitive strains are not available.
Biological Properties of Three 3-Heterocyclic-Thiomethyl Cephalosporin Antibiotics
Authors: Wick Warren E. , Preston David A.
Published: June 2012

Three new cephalosporin antibiotics, prepared by substitution of heterocyclic groups on 7-aminocephalosporanic acid, possess certain desirable chemical or biological properties. All three compounds are active in vitro against a variety of gram-positive and gram-negative bacteria. Minimal inhibitory concentrations (MIC) of these bactericidal antibiotics were not significantly affected by changes in
p
H or NaCl content of nutrient broth, or by the use of different inoculum sizes. However, agar-dilution MIC values were generally two- to fourfold lower than the MIC values in comparable broth-dilution tests. Stability to cephalosporinase by two of the compounds extended their antibacterial spectra over cephalothin and cephaloridine to include strains of
Enterobacter
sp. and indole-positive
Proteus
sp. Binding to serum proteins of the new cephalosporins was intermediate between cephalothin and cephaloridine. Excellent concentrations of the antibiotics were attained in mouse blood, after subcutaneous administration of 20 mg per kg. In vitro biological characteristics of the antibiotics were verified by successful therapy of experimental mouse infections. Regression lines were calculated to show the correlation of agar-dilution MIC values with zones of inhibition by the disc testing procedure. Because each of the three new cephalosporins has certain advantageous properties over cephalothin and cephaloridine, additional toxicological and pharmacological data should be obtained for all three compounds.
Inhibition of Experimental Dental Caries by Antibiotics
Authors: Fitzgerald Robert J.
Published: June 2012

A variety of antibiotic and chemotherapeutic agents were tested for their ability to inhibit the development of dental caries in Sprague-Dawley rats receiving the drugs in a coarse-particle sucrose-containing diet. Drugs which inhibit gram-positive microorganisms were effective inhibitors of caries, whereas agents which are active solely against gram-negative bacteria did not inhibit caries development. In vivo efficacy of the agents tested generally, but not invariably, paralleled in vitro inhibition of the growth of
Streptococcus mutans
strain FA-1, an organism which was isolated from carious Sprague-Dawley rats and which is known to induce caries in gnotobiotic Sprague-Dawley rats. Caries was significantly inhibited when 1-ephenamine penicillin (20 units/mg) was administered intermittently in the diet, 1 day per week or 1 week of every 4 weeks, but protection against caries was greatest when the same amount of the drug was fed continuously.
Evaluation of an Experimental Animal Model for Testing Antifungal Substances
Authors: Huppert M. , Sun S. H. , Gross A. J.
Published: June 2012

Accumulated evidence indicates that infection by fungi capable of causing systemic disease usually results in a relatively strong acquired resistance. The working hypothesis for this study was that an antifungal substance, even one with only slight fungistatic activity, could be an effective chemotherapeutic agent by arresting progression of the infection until acquired resistance became effective. The present study involved establishing and evaluating an experimental animal model (coccidioidomycosis in mice) which could be used to test this hypothesis. This model was reasonably similar to the natural disease. Results with infected nontreated animals indicated that the plot of mortality frequency against survival time did not follow a normal distribution curve. Thus, nonparametric procedures were used for evaluation. Use of this model with an established antibiotic (amphotericin B), with a crude preparation of a new antibiotic (CB-310), and with synthetic organoselenium compounds demonstrated that even low levels of antifungal activity could be detected. The model should be useful not only to test the original hypothesis but also to screen antifungal substances for their potential as chemotherapeutic agents.
Antifungal Activity of 5-, 7-, and 5,7-Substituted 2-Methyl-8-Quinolinols
Authors: Gershon Herman , Parmegiani Raulo , Godfrey Patricia K.
Published: June 2012

2-Methyl-8-quinolinol and sixteen 5-, 7-, and 5,7-substituted derivatives with fluoro, chloro, bromo, iodo, nitro, and amino substituents were tested for in vitro antifungal activity against five fungi,
Aspergillus niger, A. oryzae, Trichoderma viride, Myrothecium verrucaria
, and
Trichophyton mentagrophytes
. The 5,7-dichloro and 5,7-dibromo derivatives were the most fungitoxic of the compounds tested. With the exception of these two compounds and 5-iodo-2-methyl-8-quinolinol, the 2-methyl analogues were less active than the corresponding 8-quinolinols.
Antimycobacterial Activity of Some Quinolyl Aryl Sulfides, Sulfones, and Ethers, In Vitro
Authors: Akerkar A. S. , Naftchi N. E.
Published: June 2012

A series of 61 compounds of six different categories (nitrosulfides, nitrosulfones, aminosulfides, aminosulfones, nitroethers, and aminoethers), all heterocyclic analogues of diaminodiphenyl sulfone (DADS), were synthesized by replacing one of the benzene rings of DADS by a 5-nitro-quinoline ring and the other benzene ring by various heterocyclic nuclei. Among these compounds, 51 were found to inhibit the growth of
Mycobacterium tuberculosis
at a concentration of 40 μg or less per ml; 8 compounds were effective at a concentration of 1 μg/ml and 9 were effective at a concentration of 0.1 μg/ml. 5-Amino-8-quinolyl-2,4-dichlorophenyl sulfide was found to be 20 times more effective than isonicotinic acid hydrazide and 80 times more effective than streptomycin.
Transduction of Tetracycline Resistance in
Staphylococcus epidermidis
Authors: Minshew Barbara H. , Rosenblum E. D.
Published: June 2012

Fourteen
Staphylococcus epidermidis
strains were biotyped according to the scheme of Baird-Parker and tested for their sensitivities to
S. epidermidis
typing phages. Tetracycline-susceptible strains were tested for the capacity to be transduced to resistance. Five strains, all of biotype 1, were lysed by one or more phages. Five of eight biotype 1 strains were transduced to tetracycline resistance with rates of 10
−8
to 10
−5
. Three strains of other biotypes were not transduced, nor was PS 73, an unusual coagulase-negative strain. The transducing phage φ367 was isolated from the lysogenic tetracycline-resistant donor strain. The phage morphologically resembles serological group B
S. aureus
phages. Restriction and modification were indicated from the efficiency of plating on phage-sensitive strains.
Beta-Lactamase Activity in Anaerobic Bacteria
Authors: Weinrich A. Elise , Bene Victor E. Del
Published: June 2012

A diverse group of anaerobic bacteria representing a spectrum of resistance to β-lactam antibiotics was studied to characterize their β-lactamase activity and relate it to resistance. The
Bacteroides fragilis
organisms had moderate resistance and produced a cephalosporinase with low activity. The
Clostridium ramosum
was intermediate in resistance and had intermediate, inducible β-lactamase activity. The
B. clostridiiformis
organism was highly resistant, produced a potent inducible penicillinase, and had a barrier to the penicillin substrates. Only the β-lactamase of
C. ramosum
fit Richmond's classification (class IV). Although there was a rough correlation between β-lactamase activity and antibiotic resistance, other mechanisms are undoubtedly involved in determining resistance levels.
Laboratory Evaluation of 3-(5-Tetrazolyl)Penam, a New Semisynthetic Beta-Lactam Antibacterial Agent with Extended Broad-Spectrum Activity
Authors: English Arthur R. , Retsema James A. , Lynch John E.
Published: June 2012

In the new agent 3-(5-tetrazolyl)penam, hereafter referred to as CP-35,587, the carboxyl function at C3 in the penicillin nucleus has been replaced with the 5-tetrazolyl moiety. Marked changes in spectrum and resistance to gram-negative β-lactamases, particularly with regard to
Klebsiella pneumoniae
isolates, were conferred by this modification. The anti-
Klebsiella
activity clearly distinguishes the antibacterial spectrum of CP-35,587 from any known broad-spectrum penicillin. Compared to orally active cephalosporins, the spectrum advantage of CP-35,587 encompasses
Enterobacter, Serratia marcescens, Citrobacter, Providencia, Haemophilus influenzae
, and
Streptococcus faecalis
, both in vitro and in murine infections produced by many of the above-named microorganisms. Thus, CP-35,587 combines and extends the antibacterial activity of broad-spectrum penicillins and orally active cephalosporins.
Inhibition of L5178Y Cells in Culture by Methotrexate and Antibiotics
Authors: Chello P. L. , Bruckner H. W.
Published: June 2012

Methotrexate, tetracycline, gentamicin, streptomycin, and penicillin inhibited the growth of L5178Y murine leukemia cells in culture with I
50
(concentration of drug that caused a 50% inhibition of growth at 72 h) values of 0.0028 μg/ml (6.2 × 10
−9
M), 7.9 μg/ml, 200 μg/ml, 1,700 μg/ml, and 3,000 μg/ml (5,000 U/ml), respectively. At concentrations achieved clinically or utilized in the laboratory, the antibiotics did not alter the I
50
of methotrexate.
Short-Term Storage of Six Penicillins and Cephalothin in Microdilution Trays for Antimicrobial Susceptibility Tests
Authors: Barry A. L. , Effinger L. J. , Badal R. E.
Published: June 2012

To perform microdilution antimicrobial susceptibility tests efficiently, broth dilutions of the antimicrobial drugs should be prepared in large batches and stored frozen until needed. Studies were carried out to document the stability of ampicillin, benzylpenicillin, carbenicillin, methicillin, oxacillin, nafcillin, and cephalothin in microdilution trays during storage at −20 and −60 C. No significant deterioration was noted after 21 days of storage, as detected by bioassay and by replicate minimal inhibitory concentration determinations with control organisms. No significant differences were noted moreover between trays stored for three weeks at −20 C and those stored at −60 C. The microdilution technique was found to be a highly reproducible method for quantitative determination of antimicrobial susceptibility.
Influence of Subtherapeutic Levels of a Combination of Neomycin and Oxytetracycline on
Salmonella typhimurium
in Swine, Calves, and Chickens
Authors: Girard A. E. , English A. R. , Evangelisti D. G. , Lynch J. E. , Solomons I. A.
Published: June 2012

Subtherapeutic levels of oxytetracycline plus neomycin in animal feeds did not bring about increases in the quantity, prevalence, or shedding of
Salmonella typhimurium
in swine, calves, or chickens. In fact, the medication generally reduced the proportion of animals carrying
S. typhimurium
. The medicated groups were fed rations containing oxytetracycline plus neomycin commencing 5 days prior to oral inoculation with
S. typhimurium
and continuing through a 28-day postinoculation period. Colonization of
S. typhimurium
occurred in all three animal species, as evidenced by clinical signs of infection and/or colony counts in feces. Only from swine and on only one occasion was a single resistant colony isolated. It is concluded that no evidence has been obtained which would implicate the continuous low-level feeding of oxytetracycline and neomycin for a 4-week period to a potential increased incidence of disease in animals or as a hazard to humans.
Amikacin in Newborn Infants: Comparative Pharmacology with Kanamycin and Clinical Efficacy in 45 Neonates with Bacterial Diseases
Authors: Howard Jorge B. , McCracken George H. , Trujillo Hugo , Mohs Edgar
Published: June 2012

The pharmacokinetic properties of amikacin (BBK8) were similar to those of kanamycin in newborn infants. Peak serum concentrations of both drugs were in the range of 15 to 25 μg/ml with the exception of kanamycin in babies weighing greater than 2,000 g at birth where peak levels were 12.5 to 15 μg/ml. Volumes of distribution, plasma clearances, and serum half-life values were comparable for the two drugs. The clinical and bacteriological responses to amikacin therapy were assessed in 45 neonates with bacterial diseases. A case fatality rate of 26% was observed in infants with septicemia and/or meningitis, whereas no deaths occurred among 22 infants with urinary tract and mucocutaneous infections. Cultures from infected sites were sterile within 72 h of initiating amikacin therapy in 47% of the infants, continued positive for greater than 72 h in 31%, and were not reevaluated during therapy in 22%. The clinical response was judged to be satisfactory in 92% of the surviving infants. The efficacy of amikacin was comparable to that of kanamycin or gentamicin in neonatal bacterial diseases.
Susceptibility of
Streptococcus mutans
to Antimicrobial Agents
Authors: Ferretti Joseph J. , Ward Margie
Published: June 2012

Fifty strains of
Streptococcus mutans
, including defined strains and clinical isolates, were tested for susceptibility to 20 different antimicrobial agents. Minimal inhibitory concentrations were determined by a liquid microtiter procedure. Antibiotics that were most effective in concentrations below 0.1 μg/ml included penicillin, ampicillin, erythromycin, cephalothin, and methicillin. Antibiotics effective in concentrations between 0.1 μg and 10 μg/ml included rifampin, lincomycin, thiostrepton, spiromycin, vancomycin, streptolydigan, novobiocin, tetracycline, chloramphenicol, spectinomycin, and gentamicin. Antibiotics effective at higher concentrations ranging from 10 μg/ml to 400 μg/ml included the aminoglycosides kanamycin, neomycin, streptomycin, and kasugamycin. Although most antibiotics exhibited inhibitory effects in a narrow range of concentrations, antibiotics such as tetracycline, thiostrepton, and spiromycin had a 1,000-fold range from the lowest to highest concentrations required for growth inhibition.
Mode of Action of a Purified Antitumor Protein from the Proteinaceous Crystal of
Bacillus thuringiensis
subsp.
thuringiensis
on Yoshida Ascites Sarcoma Cells
Authors: Prasad S. S. S. V. , Shethna Y. I.
Published: June 2012

A purified antitumor protein from the proteinaceous crystal of
Bacillus thuringiensis
subsp.
thuringiensis
inhibits the growth of Yoshida ascites sarcoma both in vivo and in vitro. Exogenous respiration of the tumor cells was unaffected by the protein at a concentration as high as 500 μg/ml. The antitumor protein inhibits the uptake and incorporation of labeled precursors into macromolecules. However, the ratio of incorporation over uptake is not affected by the protein. Further, the protein brings about the leakage of 260-nm-absorbing material, proteins, and
32
P-labeled cellular constituents from the Yoshida ascites sarcoma cells. The results show that the action of the antitumor protein appears to alter the cellular permeability of the tumor cells.
Reproducibility of Control Strains for Antibiotic Susceptibility Testing
Authors: Coyle Marie B. , Lampe Mary F. , Aitken Connie L. , Feigl Polly , Sherris John C.
Published: June 2012

Inter- and intralaboratory reproducibility of susceptibility testing requires stable control strains. The Food and Drug Administration diffusion procedure recommends the Seattle strains of
Staphylococcus aureus
(ATCC 25923) and
Escherichia coli
(ATCC 25922) for this purpose. It was of interest to determine the present reproducibility of control cultures maintained in various laboratories over several years. Fifteen cultures each of
S. aureus
and
E. coli
were obtained from laboratories in different parts of the country. Their performance was compared with strains directly derived from ATCC. Diffusion susceptibility tests using a modified overlay technique were made with four replicates. Seven of the eight statistically significant differences in responses of the staphylococci were to penicillin, methicillin, or cephalothin. One culture was a penicillinase producer with a zone 15 mm less than the standard strain. Eleven of the 15 cultures showed no significant deviations or differences greater than 2 mm from the results with the strain derived directly from ATCC. All except the penicillinase producer were of identical phage type. Among 150 organism-antibiotic combinations tested with
E. coli
, all but one reading were within 2 mm of the standard. Four of the six statistically significant differences were in a culture from one laboratory. The stability of the cultures appears to have been influenced by the method of storage. Cultures that were kept frozen during extended storage were remarkably stable. Significant differences were found in cultures from four of five laboratories that maintained cultures in refrigerators or at ambient temperature.
Nosocomial Infection with Gentamicin-Carbenicillin-Resistant
Pseudomonas aeruginosa
Authors: Baird Ian M. , Slepack Jerry M. , Kauffman Carol A. , Phair John P.
Published: June 2012

Pseudomonas aeruginosa
resistant to both gentamicin and carbenicillin was isolated with increasing frequency at the Cincinnati Veterans Administration Hospital during the period 1971 to 1974. A comparison of patients from whom
P. aeruginosa
was isolated during this period failed to reveal any significant clinical differences between the patients colonized or infected with resistant organisms and those colonized or infected with susceptible organisms. Overt clinical infection attributable to either organism was rare. The antibiotic-resistant organisms were isolated most frequently from urine. Isolation of the antibiotic-resistant organisms was more frequent from patients who had previously received gentamicin.
Radioimmunoassay of Iodinated Tobramycin
Authors: Broughton Alan , Strong James E. , Pickering Larry K. , Bodey Gerald P.
Published: June 2012

A radioimmunoassay for tobramycin was developed using antisera from rabbits injected with a tobramycin-bovine serum albumin conjugate. The antibody had a relatively high affinity for
125
I-labeled tobramycin (1.6 × 10
9
liters/mol), thus indicating little interference in immunoreactivity by iodination. The radioimmunoassay was highly specific, and only minor cross-reaction occurred with other aminoglycoside antibiotics. The radioimmunoassay was also more sensitive than previously published tobramycin assays (minimum sensitivity, 280 pg), and there was a significant correlation (
P
< 0.05) with both the radioenzymatic and microbiological assays.
Effect of Treatment with Exogenous Interferon, Polyinosinic Acid-Polycytidylic Acid, or Polyinosinic Acid-Polycytidylic Acid-Poly-
l
-Lysine Complex on Encephalomyocarditis Virus Infections in Mice
Authors: Olsen Gregg A. , Kern Earl R. , Glasgow Lowell A. , Overall James C.
Published: June 2012

The effect of treatment with exogenous interferon was compared with two interferon inducers, polyinosinic acid-polycytidylic acid [poly(I:C)] and [poly(I:C)]-poly-
l
-lysine complex (P-L-L complex), in two model encephalomyocarditis virus infections of mice. Although both inducers stimulated the production of interferon, the peak serum levels induced by P-L-L complex were five- to eightfold greater than those induced with poly(I:C). When encephalomyocarditis virus was inoculated by either the intraperitoneal or the intranasal route, interferon and both of the inducers protected mice against mortality and prolonged the mean day of death when the compounds were given prior to or immediately after viral challenge. In general, treatment with interferon was not as successful as treatment with poly(I:C) or P-L-L complex. In these infections, P-L-L complex appeared to be the most effective agent in that successful treatment resulted when drug therapy was initiated as late as 48 h after virus inoculation. An examination of the effect of treatment on the pathogenesis of the infection indicated that protection was associated with the prevention of viremia and subsequent seeding of target organs, particularly the central nervous system.
Inhibition of Conjugal Transfer of R Plasmids by Pipemidic Acid and Related Compounds
Authors: Nakamura Shinichi , Inoue Satoru , Shimizu Masanao , Iyobe Shizuko , Mitsuhashi Susumu
Published: June 2012

It was found that pipemidic acid and related compounds have the common property of inhibiting the conjugal transfer of R plasmids carried by
Escherichia coli
and
Pseudomonas aeruginosa
. This inhibition was not due to bactericidal activity of the compounds against donors, recipients, or R
+
transconjugants. However, it was correlated inversely with their minimal inhibitory concentrations, depending especially upon sensitivity of donors to the compounds. The inhibition was generally observed in mating systems using various combinations of 14 R plasmids and 9 bacterial strains. The pretreatment of a donor or a recipient strain with pipemidic acid showed only a small inhibitory effect on the transfer of an R plasmid, whereas the presence of the compound during an active mating caused a marked inhibitory effect.
Stability of Gentamicin in Serum
Authors: Jones Sue M. , Blazevic Donna J. , Balfour Henry H.
Published: June 2012

Patients' sera were divided into three portions when the initial gentamicin level was determined and were stored at −20, 4, and 25°C in plastic or glass tubes. Gentamicin levels were repeated after 1 and 2 days of storage at the respective temperatures. There was no significant difference in gentamicin levels among portions, except those from a patient in renal failure with high serum concentrations of carbenicillin.
Procedure for Expediting Determinations of Antibiotic Susceptibility of Gram-Negative, Urinary Tract Pathogens
Authors: Wegner Dennis L. , Neblett Thomas R.
Published: June 2012

Standardized direct disk diffusion antibiotic susceptibility testing on monomicrobial urine specimens is compared with the Food and Drug Administration method. The direct procedure yields acceptable data and may conserve 24 h in reporting results.
Comparative In Vitro Activity of Pirbenicillin, Ticarcillin, and Carbenicillin Against
Pseudomonas aeruginosa
Authors: Murakawa Takeo , Sabath L. D.
Published: June 2012

Pirbenicillin, a semisynthetic penicillin, showed greater in vitro activity against 68 recent isolates of
Pseudomonas aeruginosa
than did ticarcillin or carbenicillin. The median minimum inhibitory concentration of each of these three compounds, respectively, was 3.1, 12.5, and 25 μg/ml when a 10
−4
dilution of an overnight culture (about 10
5
colony-forming units [CFU]/ml) was used as inoculum, but these differences were less striking when larger inocula were used: at 10
7
CFU/ml these values were 6.25, 12.5, and 50 μg/ml, and at 10
8
to 10
9
CFU/ml these values were 50, 50, and 100 μg/ml. All three compounds showed greater inhibitory activity at pH 6 than at pH 8. This pH effect was greatest with pirbenicillin, for 6.25 μg of pirbenicillin per ml inhibited 7, 11, and 57% of the strains at pH 6, 7, and 8, respectively; these values were 4, 4, and 11% with ticarcillin and 0, 0, and 7% with carbenicillin. At sufficient inhibitory concentrations, the rates of bacterial killing of the three compounds were similar. The observed differences in anti-pseudomonad activity were not due to differences in stability to pseudomonad β-lactamases, but all three compounds were more stable than were cefazolin, cephaloridine, and benzylpenicillin.
In Vitro Activity of Netilmicin, Gentamicin, and Amikacin
Authors: Kantor Robert J. , Norden Carl W.
Published: June 2012

The in vitro activity of netilmicin (Sch 20569), a new semisynthetic derivative of gentamicin, was compared with that of gentamicin and amikacin. One hundred and ninety-two clinical isolates of
Enterobacteriaceae, Pseudomonas aeruginosa
, and
Staphylococcus aureus
were tested using both agar and broth dilution techniques. Netilmicin was comparable to gentamicin, with the following exceptions: (i) for
Serratia marcescens
and
P. aeruginosa
, gentamicin was more active than netilmicin; (ii) all strains of
Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis
, and
Citrobacter freundii
, which were resistant to gentamicin, were susceptible to netilmicin; (iii) some strains of
S. marcescens
, indole-positive
Proteus
, and
Providencia
, which were resistant to gentamicin, were susceptible to netilmicin. Netilmicin was more active than amikacin for all
Enterobacteriaceae
and
S. aureus
and equal to amikacin in activity against gentamicin-susceptible strains of
P. aeruginosa
. All strains of
P. aeruginosa
, resistant to gentamicin, were also resistant to netilmicin but were susceptible to amikacin. Minimal inhibitory concentrations (MICs) obtained with broth and agar showed no significant differences except for
P. mirabilis
, where broth MICs were twofold greater than agar MICs, and for
P. aeruginosa
, where agar MICs were twofold higher than broth MICs. The minimal bactericidal concentration (MBC) was either identical to or within one twofold dilution of the MIC for the strains tested. A 100-fold increase in inoculum size produced less increase in MIC and MBC with netilmicin than with gentamicin or amikacin.
Mezlocillin: In Vitro Studies of a New Broad-Spectrum Penicillin
Authors: Bodey Gerald P. , Pan Theresa
Published: June 2012

Mezlocillin is a new semisynthetic penicillin that inhibited 71% of the isolates of
Serratia marcescens
, 67% of
Escherichia coli
, 50% of
Enterobacter
spp., and 49% of
Klebsiella
spp. at a concentration of 12.5 μg/ml. It is also active against both indole-positive and -negative
Proteus
spp. and gram-positive cocci, except penicillin G-resistant
Staphylococcus aureus
. At a concentration of 100 μg/ml, it inhibited 94% of the isolates of
Pseudomonas aeruginosa
. It is more active than ampicillin, carbenicillin, and cephalothin against some gram-negative bacilli.
Amphotericin B Susceptibility Testing of Yeasts with a Bactec Radiometric System
Authors: Hopfer Roy L. , Gröschel Dieter
Published: June 2012

The effect of amphotericin B on CO
2
production was studied using a Bactec 225. A radiometric procedure for yeast susceptibility testing that requires 3 h of incubation was developed. A total of 48 yeast isolates was tested in this system and the results were correlated to tube dilution studies. The drug concentration causing at least a 44% decrease in CO
2
production correlated to the tube dilution minimal inhibitory concentration in 85% of isolates tested and was within one tube dilution of the minimal inhibitory concentration in over 95% of yeasts tested.
Antimicrobial Activity of Cefamandole Against
Salmonella typhi
Authors: Hirschman Shalom Z. , Meyers Burt R. , Miller Albert
Published: June 2012

A patient with
Salmonella typhi
bacteremia was sucessfully treated with cefamandole, a new cephalosporin derivative. Infection has not recurred during 6 months of follow-up observation. Minimum inhibitory concentrations and minimum bactericidal concentrations of cefamandole, cephalothin, ampicillin, and chloramphenicol were compared against 26 strains of
S. typhi
. All the strains were susceptible to cefamandole in vitro. Seven of the strains were resistant to chloramphenicol, and another seven were resistant to both chloramphenicol and ampicillin. Cefamandole appears to warrant further clinical trial for the treatment of typhoid fever.
Cefoxitin: Clinical Evaluation in Thirty-Eight Patients
Authors: Heseltine Peter N. R. , Busch David F. , Meyer Richard D. , Finegold Sydney M.
Published: June 2012

Clinical and bacteriological efficacy, patient tolerance, and toxicity of cefoxitin, a beta-lactamase-resistant cephamycin, were evaluated in 38 patients; 13 had soft tissue infection, 12 had pneumonia, 3 had urinary tract infection, 2 had peritonitis, and 4 had miscellaneous infections. In five patients, infection was clinically evident, though not bacteriologically proven. The latter patients were evaluated with regard to tolerance and toxicity only. Among the 34 infections in 33 patients, 71% were considered clinically cured; 86% of those patients who could be recultured were bacteriologically cured. Phlebitis was noted in 32% of the total group, and eosinophilia was observed in 16%. Unexplained deterioration in renal function occurred in two patients. Mean peak cefoxitin levels in serum were 72 μg/ml 30 min after a 2-g infusion and 32 μg/ml 30 min after a 1-g infusion. Cefoxitin was more active against facultatively and obligately anaerobic gram-negative organisms isolated from these patients than was cephalothin.
Chemotherapy of an Experimental
Bacteroides fragilis
Infection in Mice
Authors: Walker Clay B. , Nitzan Dorrit , Wilkins Tracy D.
Published: June 2012

The efficacies of five common antimicrobial agents were determined for a pure
Bacteroides fragilis
infection in mice. Therapy was begun 4 h after bacterial injection and given every 8 h thereafter for 5 days. Blood levels were determined over an 8-h period for each concentration of antibiotic tested. Clindamycin and tetracycline were the most effective in preventing the formation of abscesses. Chloramphenicol, penicillin G, and cephalothin were not effective in protecting the mice from infection.
Effects of 2-Deoxy-
d
-Glucose and 3-Deazauridine Individually and in Combination on the Replication of Japanese B Encephalitis Virus
Authors: Woodman Daniel R. , Williams Jimmy C.
Published: June 2012

We have tested the potencies of the competitors of glucose, 2-deoxy-
d
-glucose, and of uridine, 3-deazauridine, on the inhibition of Japanese B encephalitis virus multiplication in BHK-21 cell cultures. The relative effectiveness of the viral inhibitors were evaluated individually and in combination in relation to cytotoxicity as a measure of the selectivity of inhibition. When the drugs were administered individually, the antiviral activity was masked by the cytotoxic effect on the host. By combining the two drugs, it was possible to inhibit Japanese encephalitis virus production at noncytotoxic concentrations. The effects of 2-deoxy-
d
-glucose and 3-deazauridine on the growth inhibition of BHK-21 cells in cultures were only additive, while they were clearly synergistic on the inhibition of Japanese encephalitis virus production. Thus, it was possible to achieve an increased antiviral effect without a significant increase in cytotoxicity. Although the precise biochemical mechanism of the antiviral activity of these antimetabolites in combination is not known, our results indicate the potential value of this approach in viral chemotherapy.
Characterization of an R-Plasmid Associated with Ampicillin Resistance in
Shigella dysenteriae
Type 1 Isolated from Epidemics
Authors: Crosa Jorge H. , Olarte Jorge , Mata Leonardo J. , Luttropp Linda K. , Peñaranda Maria E.
Published: June 2012

Ampicillin-resistant strains of
Shigella dysenteriae
type 1 isolated in epidemics in Mexico, Central America, and Bangla Desh were examined for the presence of plasmid deoxyribonucleic acid (DNA) by gel electrophoresis. All strains contained a heterogeneous population of plasmids. Transfer experiments to
Escherichia coli
K-12 indicated that the ampicillin resistance determinant (Ap
r
) was located on a 5.5-megadalton (Mdal) plasmid identical in all Shiga strains examined, as judged by DNA hybridization and by its molecular properties. This 5.5-Mdal plasmid contained the ampicillin transposon (TnA) sequences. There was not a high degree of homology between the Shiga Ap
r
plasmid DNA and DNA obtained from Ap
r
Salmonella typhi
strains isolated from typhoid epidemics in Mexico, previous to the dysentery outbreaks. Although low, the degree of reassociation observed indicated that probably part of the TnA sequence was present in
S. typhi
DNA. The DNA hybridization experiments showed, in addition, that there was a high degree of homology among Ap
r
plasmids isolated from different enterobacteria, and this identity was confirmed by restriction endonuclease activity. These results together with their similarities in molecular and replicative properties indicate that the Ap
r
plasmids, as was suggested for the Sm
r
Su
r
plasmids, possibly evolved once and then epidemiologically spread in the
Enterobacteriaceae
.
Action of the
N
-Trifluoroacetyl Analogue of
d
-Chloramphenicol
Authors: Freeman K. B.
Published: June 2012

The
N
-trifluoroacetyl analogue of chloramphenicol was found to inhibit the growth of
Escherichia coli
less than chloramphenicol, rather than more as previously reported by others. It also inhibits protein synthesis by
E. coli
and rat liver mitochondria less.
Macrolide Resistance in
Staphylococcus aureus
: Induction of Macrolide-Resistant Protein Synthesis
Authors: Allen Norris E.
Published: June 2012

Induction of resistance to macrolide-, lincosamide-, and streptogramin B-type antibiotics in
Staphylococcus aureus
was studied by monitoring the appearance of erythromycin A (EM)-resistant [
14
C]leucine incorporation. Examination of the induction process revealed saturation kinetics and a time course much like that reported for penicillinase in gram-positive bacteria. Induction kinetics in exponentially growing cells were sigmoidal and appeared to reach a maximum and constant rate when growth reached stationary phase. Since the induction of EM-resistant colony-forming ability was complete within 60 min, ribosome modification cannot be limited to a fraction of the population and must occur in essentially every cell. However, EM-resistant growth was expressed in cells where less than half the [
14
C]leucine-incorporating activity was resistant to EM. This suggests that resistance requires that only a threshold level of ribosome modification be exceeded and that, once exceeded, resistance is dominant to sensitivity.
Mutagenicity and Antibacterial Activity of Hydroxamic Acids
Authors: Wang Ching Yung , Lee Lanfong H.
Published: June 2012

Hydroxamic acids demonstrated mutagenic and antibacterial activities. These activities appear to be dependent on the hydroxamic acid function and are probably due to the interaction with deoxyribonucleic acid.
Beta-Lactamases Produced by a
Pseudomonas aeruginosa
Strain Highly Resistant to Carbenicillin
Authors: Labia Roger , Guionie Marlène , Masson Jean-Michel , Philippon Alain , Barthelemy Michel
Published: June 2012

A
Pseudomonas aeruginosa
strain isolated at Besançon Hospital, France, proved to be highly resistant to carbenicillin and showed a high hydrolytic activity toward this antibiotic. We clearly demonstrated that two β-lactamases were synthetized: one of them, constitutive, has its enzymatic activity directed mainly toward penicillins, and carbenicillin appears to be its best substrate (higher

V
max

); thus, this β-lactamase is a “carbenicillinase” that differs from the well-known “TEM-like” enzymes. The isoelectric point of this carbenicillinase is 5.30 ± 0.03. The other one is an inducible cephalosporinase, very similar to the cephalosporinases usually found in these organisms. Its isoelectric point is 8.66 ± 0.04. These two enzymes have been separated by affinity chromatography and isoelectric focusing. The kinetic constants were measured by computerized microacidimetry.