bluuebunny/crossref_metadata_2025 huggingface dataset:
A Decade of Imaging Cellular Motility and Interaction Dynamics in the Immune System
Authors: Germain Ronald N. , Robey Ellen A. , Cahalan Michael D.
Published: June 2012

The Immune System in Three Dimensions

Immune cells must traffic within the tissues in which they reside and also through the bloodstream and lymphatic system in order to defend the host against infection. Until 10 years ago, immunologists had very little idea about how the immune response was coordinated in three dimensions. This all changed with the application of two-photon microscopy, applied intravitally or on tissue explants, to the immune system.

Germain
et al.

(p.
1676
) review how studies using this technology have informed our knowledge of immune system dynamics and discuss how to apply this technology in the future to gather further insights.
Synthesis of Self-Pillared Zeolite Nanosheets by Repetitive Branching
Authors: Zhang Xueyi , Liu Dongxia , Xu Dandan , Asahina Shunsuke , Cychosz Katie A. , Agrawal Kumar Varoon , Al Wahedi Yasser , Bhan Aditya , Al Hashimi Saleh , Terasaki Osamu , Thommes Matthias , Tsapatsis Michael
Published: June 2012

Go with the Flow

Effective absorption or filtration can be achieved by having a material with multiple levels of porosity, so that the main flow can occur in the larger channels, while smaller passageways can be used to sequester a secondary material. It can be difficult to make these materials because the pores need to be different sizes, but still fully connected to each other.

Zhang
et al.

(p.
1684
) show that a hierarchical zeolite can be made through a simple process using a single structure-directing agent that causes repetitive branching. This leads to a material with improved transport and catalytic properties.
Penicillin-binding proteins of Streptomyces cacaoi, Streptomyces olivaceus, and Streptomyces clavuligerus
Authors: Ogawara H , Horikawa S
Published: June 2012

Penicillin-binding proteins of three Streptomyces strains, S. cacaoi, S. olivaceus, and S. clavuligerus, were examined by gel electrophoresis and fluorography. In a beta-lactamase producer, S. cacaoi, at least five membrane-bound penicillin-binding proteins were detected, but in two beta-lactam producers, S. olivaceus and S. clavuligerus, fewer penicillin-binding proteins were detected. Mecillinam and methicillin bound selectively to some penicillin-binding proteins in S. cacaoi, whereas they did not bind at all to those in S. olivaceus and S. clavuligerus. Clavulanic acid bound to penicillin-binding proteins only at a very high concentration in S. cacoi. This compound did not bind to those of S. olivaceus and S. clavuligerus. Penicillin-binding proteins in culture supernatant and cytoplasm and minimum inhibitory concentrations of these strains against benzylpenicillin were also examined.
Activity of the cefotaxime (HR756) desacetyl metabolite compared with those of cefotaxime and other cephalosporins
Authors: Wise R , Wills P J , Andrews J M , Bedford K A
Published: June 2012

The desacetyl metabolite (DES) of cefotaxime (HR756) is formed in vivo to a significant extent. The in vitro activities of DES, the parent compound, and cefazolin, cefoxitin, and cefuroxime were compared against 70 bacterial isolates. DES was found to possess approximately 1/10th the activity of the parent compound against the common Enterobacteriaceae, but was somewhat more active than the other three compounds tested. DES had no useful activity against Pseudomonas aeruginosa and was less active than cefotaxime or cefoxitin against Staphylococcus aureus or Bacteroides fragilis. Because DES may accumulate in renal failure or be concentrated in the biliary tract, its antimicrobial activity may have considerable clinical significance.
In Vitro Antibacterial Activity of AM-715, a New Nalidixic Acid Analog
Authors: Ito Akira , Hirai Keiji , Inoue Matsuhisa , Koga Hiroshi , Suzue Seigo , Irikura Tsutomu , Mitsuhashi Susumu
Published: June 2012

AM-715 [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid] is a new nalidixic acid analog. AM-715 has a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. The antibacterial activity of AM-715 was greater than those of pipemidic acid and nalidixic acid. AM-715 had higher antibacterial activity against
Pseudomonas aeruginosa
than did gentamicin. Most nalidixic acid-resistant bacteria were susceptible to AM-715, and cross-resistance was not observed between AM-715 and various antibiotics. The minimal concentration of AM-715 required to inhibit the growth of 75% of the total number of clinical isolates was as follows:
Escherichia coli
, 0.04 μg/ml;
Klebsiella pneumoniae
, 0.1 μg/ml;
Serratia marcescens
, 0.88 μg/ml;
Enterobacter
spp., 0.076 μg/ml;
Staphylococcus aureus
, 1.10 μg/ml;
P. aeruginosa
, 0.38 μg/ml; and nalidixic acid-resistant strains of gram-negative bacteria, 0.62 μg/ml. AM-715 at minimal inhibitory concentrations or at slightly higher concentrations had bactericidal activity against various species of bacteria. The effect of inoculum sizes on minimal inhibitory concentrations and minimal bactericidal concentrations of AM-715 against gram-negative bacteria was smaller than on those of pipemidic acid and nalidixic acid. The dose-response curve of AM-715 indicated a steep gradient, and the 50% inhibited doses of AM-715 were 0.014 μg/ml against
E. coli
ML4707 and 0.21 μg/ml against
P. aeruginosa
NC-5.
Evaluation of slow infusions of co-trimoxazole by using predictive pharmacokinetics
Authors: Morgan D J , Raymond K
Published: June 2012

Digital computer simulations of plasma concentration-time profiles of single intravenous infusions of trimethoprim (160 mg)/sulfamethoxazole (800 mg) based on data from other workers showed that increasing the infusion period from the hitherto generally recommended 1 to 1.5 h to 6 h did not significantly affect the interval (approximately 10 h and 8.5 h, respectively) during which trimethoprim and sulfamethoxazole plasma concentrations were maintained above their minimum effective plasma concentrations (selected as 0.6 microgram/ml and 25 microgram/ml, respectively). For the 6-h infusion, the simulated peak plasma concentration of trimethoprim was only approximately 27% less than for the 1-h infusion, and that for sulfamethoxazole was approximately 30% less. The validity of these predictions was confirmed by plasma concentration measurements of trimethoprim and sulfamethoxazole in six patients undergoing gynecological surgery, who received co-trimoxazole (160 mg of trimethoprim, 800 mg of sulfamethoxazole) postoperatively by constant-rate intravenous infusion over a 4-h period. It is concluded that infusions of the dose of intravenous co-trimoxazole over periods from 1 to at least 6 h are therapeutically equivalent.
In vitro and in vivo resistance of herpes simplex virus to 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine)
Authors: Smith K O , Kennell W L , Poirier R H , Lynd F T
Published: June 2012

In vitro passage of the Patton strain of herpes simplex virus type 1 (HSV-1-P) in the presence of acycloguanosine (ACG) led to the emergence of a highly drug-resistant strain (HSV-1-P-ACG-R). Over 1% of virions in 6 of 15 HSV strains tested were able to form plaques in the presence of 10 mumol of ACG on first exposure to the drug. Therefore, there exists among HSV strains a broad range of susceptibilities to ACG, and some strains contain particles which are partially resistant to ACG before ever contacting the drug. HSV-1-P-ACG-R was partially resistant to iododeoxyuridine; conversely, iododeoxyuridine-resistant virus was highly resistant to ACG. ACG-resistant virus (HSV-1-P-ACG-R) was equal to its parent strain (HSV-1-P) in susceptibility to adenine arabinoside. The HSV-1-P-ACG-R strain produced corneal lesions in rabbits which were completely refractory to topical treatment with 1% unguent ACG, but responsive to 3% ACG. Partially resistant HSV could be isolated from the eyes of rabbits infected with ACG-susceptible virus and treated topically with either 1 or 3% ACG for 6 days.
Activity of cephalosporins against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci: minimal effect of beta-lactamase
Authors: John J F , McNeill W F
Published: June 2012

Eight cephalosporins were tested for their activity against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci and for their resistance to beta-lactamase from methicillin-resistant, coagulase-negative staphylococci. Susceptibility testing by the agar plate method was evaluated for the effect of inoculum size and duration of incubation. Methicillin-susceptible, coagulase-negative staphylococci were highly susceptible to the cephalosporins, with cephapirin and cepahlothin showing the greatest activity, followed by cefazolin and cefamandole. Methicillin-resistant, coagulase-negative staphylococci displayed nearly total cross-resistance to the cephalosporins. Resistance increased with increasing inoculum size. Beta-Lactamases produced by methicillin-resistant, coagulase-negative staphylococci had a minimal hydrolytic effect on cepahlothin, cephapirin, cefazolin, and cefamandole and no measurable effect on cefoxitin. There was no correlation between the anti-staphylococcal activity and resistance to beta-lactamases.
Vaspar broth-disk procedure for antibiotic susceptibility testing of anaerobic bacteria
Authors: West S E , Wilkins T D
Published: June 2012

A modification of the Wilkins-Thiel broth-disk procedure for antibiotic susceptibility testing of anaerobic bacteria is described. This method utilizes an aerobically prepared medium overlaid with molten vaspar. Specialized anaerobic techniques or prereduced media are not required.
Effects of sulfamethoxazole and trimethoprim on human neutrophil and lymphocyte functions in vitro: in vivo effects of co-trimoxazole
Authors: Anderson R , Grabow G , Oosthuizen R , Theron A , Van Rensburg A J
Published: June 2012

The effects of sulfamethoxazole and trimethoprim individually and in combination on in vitro neutrophil random migration, chemotaxis to autologous endotoxin-activated serum and the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, phagocytosis and postphagocytic Nitro Blue Tetrazolium reduction, glycolysis, hexose monophosphate shunt activity, myeloperoxidase-mediated protein iodination, hydrogen peroxide production, and degranulation were assessed. The effects on lymphocyte mitogen-induced transformation were also evaluated. It was found that the test agents individually and in combination at high concentrations (> 100 microgram/ml) caused the inhibition of neutrophil postphagocytic myeloperoxidase-mediated protein iodination, which was related to the interference with H2O2 formation as the enzyme per se was unaffected. Both agents caused the inhibition of lymphocyte transformation at high concentrations (> 100 microgram/ml). In vivo studies before and after the ingestion of co-trimoxazole by three individuals showed no inhibition of any of the neutrophil functions tested. The inhibition of lymphocyte transformation was observed in one individual after the ingestion of the chemotherapeutic agent. These findings indicate that the concentrations which inhibit neutrophil H2O2 production and lymphocyte transformation in vitro are not attainable in vivo.
Evaluation of the Sensititre system for quantitative antimicrobial drug susceptibility testing: a collaborative study
Authors: Gavan T L , Jones R N , Barry A L
Published: June 2012

This three-center collaborative study was conducted to evaluate samples of Sensititre antimicrobial microdilution panels (GIBCO/INVENEX). Sensititre minimum inhibitory concentrations of 27 bacterial isolates were compared with those obtained by a reference microdilution method. The Sensititre and microdilution minimum inhibitory concentrations were equivalent within +/- 1 dilution in 87.6% of the comparable test results. Intralaboratory reproducibilities of the Sensititre and microdilution endpoints were equivalent with 80.4 and 82.4%, respetively, of on-scale endpoints in absolute agreement. Sensititre was more reproducible among laboratories, with nearly a 10% greater agreement of triplicate results. The Sensititre microdilution test as evaluated gave results which were essentially equivalent to those obtained with a standardized microdilution method.
R-factor carriage in a group F vibrio isolated from Bangladesh
Authors: McNicol L A , Kaper J B , Lockman H A , Remmers E F , Spira W M , Colwell R R
Published: June 2012

Two group F vibrio organisms have been identified among a collection of vibrio strains isolated from the aquatic environment in Bangladesh. Neither group F strain produced a cholera-like enterotoxin. One of the isolates, BV12, contained an R plasmid conferring resistance to streptomycin and chloramphenicol.
Inhibition of Peptidoglycan, Ribonucleic Acid, and Protein Synthesis in Tolerant Strains of
Streptococcus mutans
Authors: Mychajlonka Myron , McDowell Thomas D. , Shockman Gerald D.
Published: June 2012

Exposure of exponentially growing cultures of
Streptococcus mutans
strains FA-1 and GS-5 to various concentrations of benzylpenicillin (Pen G) resulted in inhibition of turbidity increases at low concentrations (0.02 to 0.04 μg/ml). However, in contrast to some other streptococcal species, growth inhibition was not accompanied by cellular lysis or by a rapid loss of viability. In both strains, synthesis of insoluble cell wall peptidoglycan was very sensitive to Pen G inhibition and responded in a dose-dependent manner to concentrations of about 0.2 and 0.5 μg/ml for strains GS-5 and FA-1, respectively. Higher Pen G concentrations failed to inhibit further either growth or insoluble peptidoglycan assembly. Somewhat surprisingly, Pen G also inhibited both ribonucleic acid (RNA) and protein syntheses, each in a dose-dependent manner. Compared with inhibition of peptidoglycan synthesis, inhibition of RNA and protein syntheses by Pen G was less rapid and less extensive. Maximum amounts of radiolabeled Pen G were specifically bound to intact cells upon exposure to about 0.2 and 0.5 μg/ml of Pen G for strains GS-5 and FA-1, respectively, concentrations consistent with those that resulted in maximum or near-maximum inhibitions of the synthesis of cellular peptidoglycan, RNA, and protein. Five polypeptide bands that had a very high affinity for [
14
C]Pen G were detected in a crude cell envelope preparation of strain FA-1. After exposure of cultures of strain FA-1 to the effects of saturating concentrations of the drug for up to 3 h, addition of penicillinase was followed by recovery of growth after a lag. The length of the lag before regrowth depended on both Pen G concentration and time of exposure. On the basis of these and other observations, it is proposed that the secondary inhibitions of cellular RNA or protein synthesis, or both, are involved in the tolerance of these organisms to lysis and killing by Pen G and other inhibitors of insoluble peptidoglycan assembly.
Identification of a nicotinamide adenine dinucleotide glycohydrolase and an associated inhibitor in isoniazid-susceptible and -resistant Mycobacterium phlei
Authors: Davis W B
Published: June 2012

Nicotinamide adenine dinucleotide glycohydrolase (NADase) activity was demonstrated in the catalases fraction of Sephadex G-200-chromatographed sonic extracts of isoniazid (INH)-susceptible (Inhs) and -resistant (Inhr) Mycobacterium phlei. Since crude extracts had no demonstrable activity even after heating, active fractions of the NADase were purified chromatographically by removing the inhibitor with Sephadex G-200. Assays for oxidized nicotinamide adenine dinucleotide (NAD+) hydrolytic activity were done by following the disappearance of NAD+ by the methods of alcohol dehydrogenase or cyanide addition. The NADase activity was linear with respect to time as well as concentration of enzyme and was inhibited in the presence of 0.04 M NADP, benzoic acid hydrazide, or nicotinamide. Crude extracts or pooled concentrated Sephadex G-200 fractions eluting after the catalase inhibited NADase activity by at least 70%. Inhibitor activity was present in both the Inhs and Inhr strains of M. phlei. The activity of the partially purified inhibitors was reversible by INH or nicotinic acid hydrazide at levels between 10 and 100 mM. These findings indicate that an NADase inhibitor system which is sensitive to reversal by INH functions in both the Inhs and Inhr strains; however, unlike previous studies with other mycobacterial species, the enzyme is sensitive to inhibition by nicotinamide. Furthermore, the inhibitors are heat stable and sensitive to reversal by nicotinic acid hydrazide as well as INH.
Pharmacokinetics of nafcillin in infants with low birth weights
Authors: Banner W , Gooch W M , Burckart G , Korones S B
Published: June 2012

The pharmacokinetics of nafcillin were studied in 13 premature neonates with suspected sepsis. The mean weight of the infants studied was 1.19 kg (range, 0.73 to 2.21 kg). Infants less than 7 days of age were given 100 mg of nafcillin per kg per 24 h (every 12 h), and infants more than 7 days of age were given 100 mg of nafcillin per kg per 24 h (every 8 h). Blood samples were obtained before the first dose on day 3 of therapy and at 0.5, 1.5, 3, and 6 h thereafter. Nafcillin concentrations were measured by a microbiological assay. A mean volume of distribution of 326 ml/kg and an elimination rate constant of 0.2040 h-1 were obtained in 10 patients less than 21 days of age. Three patients from 24 to 68 days of age had a mean volume of distribution of 303 ml/min and a mean elimination rate constant of 0.3944 h-1 (P less than 0.05). These data suggest that doses of nafcillin lower than those currently recommended may be adequate to achieve desired peak plasma levels of approximately 75 microgram/ml in infants with low birth weights.
In vitro activities of moxalactam and cefotaxime against aerobic gram-negative bacilli
Authors: Jorgensen J H , Crawford S A , Alexander G A
Published: June 2012

The in vitro activities of two new beta-lactam antibiotics, moxalactam disodium (LY 127935) and cefotaxime (HR-756), were compared with cefoxitin, cefamandole, cefuroxime, cephalothin, and, in some instances, carbenicillin, gentamicin, and amikacin against aerobic gram-negative bacilli. Test isolates included normally cephalosporin-resistant members of the Enterobacteriaceae and Pseudomonas spp. and a variety of nonfermentative or oxidase-positive bacteria. Both moxalactam and cefotaxime demonstrated impressive in vitro activities against both groups of microorganisms. The two new drugs were clearly more active than any of the other beta-lactam antibiotics against species of Escherichia, Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, and Serratia. An additive or synergistic effect could also be demonstrated with the majority of Pseudomonas and Serratia isolates when either moxalactam or defotaxime was combined with amikacin.
Effect of acyclovir on the proliferation of human fibroblasts and peripheral blood mononuclear cells
Authors: Levin M J , Leary P L , Arbeit R D
Published: June 2012

The effect of acyclovir on human cells was measured. A concentration of 50 to 100 microM inhibited the division of fibroblasts to a variable extent, depending on the experimental design and the confluency of the monolayer. The magnitude of this effect was less than that caused by human leukocyte interferon when these antiviral agents were compared at clinically relevant concentrations. Acyclovir also inhibited thymidine incorporation by peripheral blood mononuclear cells stimulated by either phytohemagglutinin or three different herpesvirus antigens. A linear dose-response curve was observed with these cells, and their proliferation was inhibited 50% by 100 microM acyclovir. Inhibition was exerted on T-cell proliferation without apparent effect on the release of lymphokines or on monocyte function.
Pharmacokinetics of alafosfalin, alone and in combination with cephalexin, in humans
Authors: Allen J G , Lees L J
Published: June 2012

Alafosfalin is a phosphonodipeptide with significant activity as an antibacterial agent and as a potentiator of beta-lactam antibiotics. Studies in humans showed that oral doses of 50 to 2,500 mg were well absorbed, but some metabolic hydrolysis occurred before the drug reached the general circulation. Oral bioavailability was approximately 50% and was largely independent of dose. Alafosfalin has an elimination half-life of about 60 min and does not accumulate during chronic administration. Healthy volunteers excreted intact phosphonodipeptide in the urine. The recovery was dose dependent and increase from 6 +/- 1% after 50-mg doses to 17 +/- 1% after 2,500-mg doses. This change with dose occurred because the human kidney has a small, saturable capacity for reabsorbing the phosphonopeptide. Less alafosfalin was excreted in the urine of subjects with impaired glomerular function. When alafosfalin was coadministered with cephalexin, both compounds wer absorbed, distributed, and eliminated at virtually identical rates. Oral administration of 500 mg of the phosphonodipeptide plus 250 mg of the beta-lactam antibiotic gave approximately equal concentrations of the drugs in plasma, with a fourfold excess of cephalexin in the urine. This 2:1 combination is being tested in the clinic.
Clinical trial of piperacillin with acquisition of resistance by Pseudomonas and clinical relapse
Authors: Simon G L , Snydman D R , Tally F P , Gorbach S L
Published: June 2012

A total of 20 serious infections were treated with piperacillin. These infections included bacteremias (5), pneumonias (5), urinary tract infections (5), soft tissue infections (3), septic arthritis (1), and osteomyelitis (1). The most common bacterial pathogen was Pseudomonas aeruginosa, accounting for eight infections. The clinical and bacteriological response rates were 75 and 70%, respectively. Four of the five patients who failed to respond to piperacillin therapy were infected with Pseudomonas. In two patients with Pseudomonas infections clinical relapse was accompanied by the development of piperacillin-resistant P. aeruginosa. The findings suggest that the use of piperacillin as a single agent for the treatment of serious gram-negative infections may be ill-advised, especially if P. aeruginosa is the offending pathogen.
Comparative low-dose nephrotoxicities of gentamicin, tobramycin, and amikacin
Authors: Hottendorf G H , Gordon L L
Published: June 2012

Most investigations of the comparative nephrotoxicities of aminoglycosides in animals have utilized large multiples of the human dose. Furthermore, many of these assessments have used only one or two dose levels and have not described a dose-response comparison among antibiotics. Because of this lack of comparative dose-response data over a range of low multiples of the human dose, the nephrotoxicities of gentamicin, tobramycin, and amikacin were investigated in 180 rats, utilizing doses ranging from one to seven times the equivalent human clinical doses. Histopathological evaluations of both kidneys from each rat were scored without knowledge of the treatment, and statistical analyses of the results indicated that a linear and parallel dose-response relationship existed for each drug, the relative nephrotoxicity over the range of doses analyzed was gentamicin > tobramycin > amikacin (P = 0.0001), and, unlike amikacin, the human dose equivalents (milligrams per kilogram) of gentamicin and tobramycin were significantly nephrotoxic in rats (P < 0.05).
Inhibition of clinically significant bacterial organisms in vitro by 2-acetylpyridine thiosemicarbazones
Authors: Dobek A S , Klayman D L , Dickson E T , Scovill J P , Tramont E C
Published: June 2012

Antibacterial activity of 65 2-acetylpyridine thiosemicarbazones and related compounds was determined by using clinical isolates of nine bacterial genera. Minimal inhibitory concentrations (MICs) of 0.002 to 0.062 micrograms/ml were obtained with 23% of the compounds for Neisseria gonorrhoeae and 0.016 to 0.062 micrograms/ml with 17% of the compounds for N. meningitidis. Staphylococcus aureus was inhibited in the MIC range of 0.125 to 0.5 micrograms/ml by 18% of the thiosemicarbazones, whereas 26% inhibited group D enterococcus with an MIC of 0.25 to 2.0 micrograms/ml. Poor antibacterial activity was shown toward the gram-negative bacilli, i.e., Pseudomonas, Klebsiella-Enterobacter, Shigella, Escherichia coli, and Proteus.
Penicillin-binding components of penicillin-susceptible and -resistant strains of Streptococcus pneumoniae
Authors: Percheson P B , Bryan L E
Published: June 2012

Three strains of Streptococcus pneumoniae with low-level resistance to penicillin, one strain with resistance to penicillin, and three strains susceptible to penicillin were compared. The three susceptible strains had very similar patterns of penicillin-binding components (PBCs) as detected by fluorography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels of these strains showed four major bands and a single minor band. All of the resistant strains showed different PBC patterns from those obtained for susceptible strains. The most marked changes were observed with the most resistant strain SPR110, which showed markedly reduced intensity of PBC 3 and a reduction in intensity of PBCs 1 and 2, as well as additional bands in the region of band 2. Low-level resistant strains had band densities different from the susceptible strains principally for PBC 3. No beta-lactamase activity or plasmid was detected in the resistant strains. An apparent difference in affinity for cloxacillin was also demonstrated between some of the PBCs of susceptible strain S. pneumoniae SPS101 and resistant strain S. pneumoniae SPR110. Penicillin resistance in the low-level resistant and the resistant strains was associated with PBCs possessing different properties from those seen in the three susceptible strains. Reduction in affinity for penicillin or a reduction in the amount of a PBC protein, or both, are the probable explanations of penicillin resistance in these strains.
Pyocin inhibition of Neisseria gonorrhoeae: mechanism of action
Authors: Morse S A , Jones B V , Lysko P G
Published: June 2012

Purified R-type pyocins (611 131) from Pseudomonas aeruginosa PA103 exhibited bactericidal activity against Neisseria gonorrhoeae. Killing of gonococci was a single-hit process requiring as few as 1 pyocin per colony-forming unit. Deoxyriboinucleic acid, ribonucleic acid, protein, and lipid syntheses were rapidly and completely inhibited. Oxygen uptake was also inhibited, but occurred after the inhibition of macromolecular synthesis. The cell lysis which occurred after pyocin inhibition of gonococcal growth was the result of endogenous gonococcal autolysin activity.
Effects of potassium and sodium ions on the killing action of a Pichia kluyveri toxin in cells of Saccharomyces cerevisiae
Authors: Middelbeek E J , Crützen Q H , Vogels G D
Published: June 2012

Loss of viability of toxin-treated cells of Saccharomyces cerevisiae SCF 1717 could be prevented in the period before they altered physiologically if cells were incubated in media with a suitable concentration of potassium (0.08 to 0.13 M) and hydrogen ions (pH 6.2 to 6.7). Incorporation of higher amounts of potassium chloride in the media had a pronounced negative effect on cell survival, particularly when the pH of the medium was lowered. Replacement of KCl by NaCl in the plate media was even more deleterious to toxin-treated cells and, in contrast with potassium, low concentrations of sodium ions could not sustain recovery of cells. Complete recovery of a toxin-treated cell suspension required an incubation of 3 h in a suitable medium. The recovery process was blocked by cycloheximide.
Characterization of chloramphenicol-resistant Haemophilus influenzae
Authors: Roberts M C , Swenson C D , Owens L M , Smith A L
Published: June 2012

We examined nine chloramphenicol-resistant (minimal inhibitory concentration, greater than or equal to 15 micrograms/ml) Haemophilus influenzae strains isolated in various parts of the world to characterize the genetic and biochemical bases of the resistance; four were type b. All nine contained conjugative plasmids, ranging in molecular weight from 34 x 10(6) to 46 x 10(6), which encoded for resistance to chloramphenicol and tetracycline or chloramphenicol, tetracycline, and ampicillin. Deoxyribonucleic acid homology studies showed that these plasmids were closely related to a previously described ampicillin-resistant plasmid, RSF007, and to each other. All nine isolates and their chloramphenicol-resistant transconjugants produced chloramphenicol acetyltransferase. We conclude that chloramphenicol resistance in these strains of H. influenzae is via plasmid-mediated production of chloramphenicol acetyltransferase.
Inhibition of cellular alpha and virally induced deoxyribonucleic acid polymerases by the triphosphate of acyclovir
Authors: St Clair M H , Furman P A , Lubbers C M , Elion G B
Published: June 2012

The effect of the triphosphate of 9-(2-hydroxyethoxymethyl)guanine (acyclovir, acycloguanosine) on cellular alpha deoxyribonucleic acid (DNA) polymerases (DNA nucleotidyltransferases), DNA polymerases of several members of the herpes group, vaccinia virus DNA polymerase, and Friend leukemia virus ribonucleic acid-dependent DNA polymerase was examined. Several viruses, which were found to be susceptible to acyclovir, were found to induce DNA polymerases which were sensitive to acyclovir triphosphate (acyclo-GTP). Human cytomegalovirus and the H29R strain of herpes simplex virus type 1, however, were found to be relatively insusceptible to acyclovir, even though their induced DNA polymerases were inhibited by low concentrations of acyclo-GTP. The amount of acyclovir anabolized to acyclo-GTP was significantly lower for human cytomegalovirus and H29R than for the more susceptible viruses. Vaccinia virus and Friend leukemia virus induced DNA polymerases which were insensitive to inhibition by low concentrations of acyclo-GTP, anabolized little acyclovir to acyclo-GTP, and were found to be insensitive to inhibition by acyclovir. Uninfected WI-38 cells were not susceptible to inhibition by acyclovir, anabolized little acyclovir to acyclo-GTP, and had an alpha DNA polymerase which was insensitive to inhibition by low concentrations of acyclo-GTP.
Binding of cycloheximide to ribosomes from wild-type and mutant strains of Saccharomyces cerevisiae
Authors: Stöcklein W , Piepersberg W
Published: June 2012

Cycloheximide bound to cytoplasmic (80S) ribosomes of the yeast Saccharomyces cerevisiae with an association constant (Ka) of 2.0 (+/- 0.5) x 10(7) M-1. The number of binding sites found per ribosome was between 0.4 and 0.6; it was reduced by high-salt treatment of ribosomes 60S particles prepared in the presence of high salt had a lower affinity (Ka: 5.5 [+/- 0.5] x 10(6) M-1) than did 80S ribosomes, but a greater proportion of particles (0.8) were able to bind. No specific binding to 40S subunits was observed. The addition of supernatant fractions (S100, high-salt wash fraction) increased the number of binding sites found per 80S ribosome up to 0.8, leaving the association constant unchanged. In contrast, the affinity of 60S subunits was enhanced to a Ka value of 3.5 x 10(-7) M-1 by the addition of supernatant fractions, whereas the number of binding sites stayed constant. A model to explain these facts is proposed. 80S ribosomes, as well as 60S subunits of strain cy32, which is highly resistant to cycloheximide and altered in ribosomal protein L29 (18), showed a drastically reduced affinity for the drug (Ka values of 2.0 x 10(6) M-1).
Synergy of penicillin and decreasing concentration of aminoglycosides against enterococci from patients with infective endocarditis
Authors: Matsumoto J Y , Wilson W R , Wright A J , Geraci J E , Washington J A
Published: June 2012

To determine whether low concentrations of aminoglycosides in combination with penicillin could effectively kill enterococci in vitro, we tested penicillin (20 micrograms/ml) in combination with decreasing concentrations of either streptomycin (20, 10, 5, and 1 micrograms/ml) or gentamicin (5, 3, 1, and 0.5 micrograms/ml) against 13 strains of streptomycin-susceptible and 7 strains of streptomycin-resistant enterococci isolated from patients with infective endocarditis. At 24 h, penicillin plus each increment in streptomycin concentration resulted in a statistically significant increase in killing of streptomycin-susceptible enterococci, compared with the next lower streptomycin concentration (P less than 0.01). At 24 h, against streptomycin-susceptible and streptomycin-resistant enterococci, there were no statistically significant differences in killing between combinations containing 5 micrograms of gentamicin per ml and those containing 3 micrograms/ml. Against streptomycin-susceptible enterococci, there were statistically significant differences in killing between combinations containing 3 micrograms of gentamicin per ml and those containing 1 micrograms/ml. Against streptomycin-resistant enterococci, statistically significant differences in killing were detected with combinations containing 5 micrograms of gentamicin per ml and those containing 1 microgram/ml.
Anti-herpes simplex virus and anti-human cell growth activity of E-5-propenyl-2'-deoxyuridine and the concept of selective protection in antivirus chemotherapy
Authors: Cheng Y C , Grill S , Ruth J , Bergstrom D E
Published: June 2012

E-5-Propenyl-2'-deoxyuridine (E-5-propenyl-dUrd) inhibited the growth of herpes simplex virus (HSV) types 1 (HSV-1) and 2 in culture. The concentration of drug required to give a 2-log reduction in virus titer was 5 microM for HSV-1 and 23 microM for HSV-2. The anti-HSV-1 activity of this agent was more potent than 5-propyl-dUrd, equivalent to E-5(3,3,3-trifluoropropenyl)-dUrd, and less potent than E-5-bromovinyl-dUrd. The HSV-1 mutant (B2006) lacking the ability to induce virus-specific thymidine kinase could not be inhibited by E-5-propenyl-dUrd. The binding constants of E-5-propenyl-dUrd to HSV-1, HSV-2, varicella-zoster virus, and human mitochondrial thymidine kinases were established to be 0.2, 6.2, 0.3, and 0.8 microM, respectively. Thymidine phosphorylation catalyzed by human cytosol thymidine kinase could not be inhibited by E-5-propenyl-dUrd at a concentration 10-fold higher than the thymidine in the assay. When thymidine and E-5-propenyl-dUrd were added concomitantly at equal concentrations to virus-infected cells, the antiviral activity was not reversed in HSV-1 and only partially reversed in HSV-2. E-5-Propenyl-dUrd also inhibited the growth of human cells in culture with 50% inhibitory dose of 50 microM. Since this inhibition could be readily reversed by a lower concentration of thymidine, the idea of selective protection is proposed. This approach could avoid the cytotoxic effect of an antiviral agent with properties similar to E-5-propenyl-dUrd without sacrificing antiviral activity.
Liquid chromatographic assay of ketoconazole
Authors: Andrews F A , Peterson L R , Beggs W H , Crankshaw D , Sarosi G A
Published: June 2012

A reverse-phase, high-pressure liquid chromatographic method for the rapid and quantitative determination of ketoconazole has been developed. Drug levels from 0.5 to 10 microgram/ml can be determined in either yeast nitrogen base medium or human serum by using an octadecylsilane column. A retention time of 4.9 +/- 0.1 min resulted when the drug was eluted from a column with 75% methanol-25% 0.02 M (pH 7.5) phosphate buffer at a flow rate of 2 ml/min. Optimum sensitivity was obtained at a wavelength of 231 nm.
Experimental intraabdominal candidiasis in rabbits: therapy with low-total-dose intravenous amphotericin B
Authors: Bayer A S , Edwards J E , Guze L B
Published: June 2012

By using a recently developed rabbit model, we examined the efficacy of relatively low-total-dose intravenous amphotericin B (Am-B; 7 to 14 mg/kg) in the treatment of intraabdominal candidiasis due to Candida albicans. Forty-eight percent of the rabbits developed evidence of hematogenously disseminated infection (Candida endophthalmitis) before therapy. By day 7 of therapy, there was a significant decrease in the mean log10 colony-forming units per gram of peritoneal abscess in comparison with both pretherapy cultures and concomitantly sacrificed controls (no Am-B treatment; P less than 0.25). By day 11 of therapy, peritoneal abscesses were sterilized by Am-B, whereas control rabbit cultures remained positive. In contrast, low-dose Am-B therapy produced no significant decrease in colony-forming units per gram of renal or chorioretinal abscess in rabbits which developed hematogenously disseminated candidiasis. Serum Am-B levels approached or exceeded the minimal fungistatic concentrations for this C. albicans strain in most animals tested. Low-dose Am-B was effective in eradicating intraabdominal candidiasis, but was not curative when extraperitoneal dissemination occurred.
In vitro susceptibility of Mycobacterium fortuitum to cefoxitin
Authors: Cynamon M H , Patapow A
Published: June 2012

The in vitro susceptibility of Mycobacterium fortuitum to cefoxitin was studied by agar dilution, broth dilution, and disk diffusion methods. Of 13 isolates, 11 were found to be susceptible by disk diffusion. At a concentration of 25 microgram/ml or lower, all 13 isolates were inhibited when tested by broth dilution, but only 12 of 13 isolates were inhibited when tested by agar dilution.
In vitro susceptibility of Salmonella to various antimicrobial agents, including a new cephalosporin, Ro 13-9904
Authors: Chau P Y , Ng W S , Ling J , Arnold K
Published: June 2012

The in vitro susceptibility of 363 strains of Salmonella isolated in Honk Kong to various antimicrobial drugs was tested, and the minimum inhibitory concentrations of ampicillin, mecillinam, and six cephalosporins (cephalexin, cephradine, cefamandole, cefoxitin, cefuroxime, and Ro 13-9904) for these strains were determined by an agar dilution method. Although strains of the typhoid and paratyphoid group remained susceptible to most antibiotics tested, many strains of the gastroenteric group of salmonellae were found to be resistant to multiple antibiotics, including ampicillin, chloramphenicol, and, occasionally, trimethoprim. Mecillinam and cefamandole, although active against most of the Salmonella strains tested, were shown to be less active against ampicillin-resistant strains. By contrast, Ro 13-9904 exhibited remarkably uniform and high activity against all the Salmonella strains tested, irrespective of their ampicillin resistance.
R plasmid with carbadox resistance from Escherichia coli of porcine origin
Authors: Ohmae K , Yonezawa S , Terakado N
Published: June 2012

Escherichia coli isolates of porcine fecal origin from a farm where the antibacterial agent carbadox was used were examined for resistance to carbadox (Cdxr). Of 72 strains examined, 24 showed resistance to this drug. All 24 Cdxr strains, except one, were also resistant to tetracycline (Tcr), streptomycin (Smr), spectinomycin (Spcr), sulfadimethoxine (Sur), kanamycin (Kmr), ampicillin (Apcr), or a combination of tetracycline, streptomycin, spectinomycin, sulfadimethoxine, and ampicillin. The Cdxr character was invariably transmissible by conjugation to E. coli K-12 jointly with other drug resistance, with the resistance patterns present in transconjugants being Cdxr Smr Spcr Apcr or Cdxr Smr Spcr Sur Apcr. About 25% of these transconjugants simultaneously lost the resistance to carbadox, streptomycin, spectinomycin, and ampicillin or carbadox, streptomycin, spectinomycin, sulfadimethoxine, and ampicillin or carbadox, streptomycin, spectinomycin, sulfadimethoxine, and ampicillin in the presence of acriflavine. Agarose gel electrophoretic analysis of deoxyribonucleic acid from a transconjugant showed a single plasmid deoxyribonucleic acid molecule with a molecular weight of about 28 x 10(6), which was capable of transforming E. coli C to Cdxr Smr Spcr Apcr. This resistance was transmissible by conjugation as a unit to other K-12 strains. These results confirmed the presence of an R plasmid specifying the Cdxr character in the host strain.
Repair of membrane alterations induced in baby hamster kidney cells by polyene macrolide antibiotics
Authors: Malewicz B , Jenkin H M , Borowski E
Published: June 2012

We studied the correlation between chemical characteristics of 13 polyene macrolide antibiotics and the ability to repair the membrane permeability changes induced by polyenes in BHK-21 cells grown in shaker culture. It had been demonstrated that large-macrolide-ring polyenes with rigid molecules (heptaenes) induced specific membrane permeability pathways which were repaired by the eucaryotic cells under the proper conditions. The influence of environmental conditions on the repair process was examined. Aureofacin trimethylammonium methyl ester derivative was used as a selected representative of polyene macrolides inducing specific pathways. The factors influencing the repair process, monitored by measuring the ability of BHK-21 cells to control K+ membrane transport, were examined during and after cell contact with the antibiotic. We found that the repair process was dependent upon the temperature, the concentration of the antibiotic, time of its contact with cells, potassium concentration in the medium, and availability of an energy source. The repair process occurred in the presence of cycloheximide, which inhibited protein synthesis in BHK-21 cells. Results showed that the repair process plays an important role in mammalian cell recovery from the toxic effects of polyenes.
In vitro activity of N-formimidoyl thienamycin, moxalactam, and other new beta-lactam agents against Bacteroides fragilis: contribution of beta-lactamase to resistance
Authors: Brown J E , Del Bene V E , Collins C D
Published: June 2012

N-Formimidoyl thienamycin (N-F-thienamycin) and moxalactam were compared with other currently available and investigational antibiotics against 100 clinical isolates of Bacteroides fragilis by an agar dilution method. N-F-thienamycin was the most active among the beta-lactam agents tested, with a minimal inhibitory concentration for 90% of isolates (MIC90) of 0.25 micrograms/ml. Moxalactam was next in activity, with an MIC90 of 4 micrograms/ml. N-F-thienamycin was somewhat more active, and moxalactam was slightly less active, than metronidazole and clindamycin. An increase in inoculum size caused an increase in the MIC of N-F-thienamycin, cefoperazone, and cefotaxime. This inoculum effect could influence the usefulness of these drugs in certain clinical conditions. The minimal bactericidal concentration was less than two times the MIC for most agents and less than four times the MIC for all beta-lactam agents at each inoculum size tested. Investigation of the mechanism of resistance to beta-lactam agents demonstrated a correlation between the level of resistance and beta-lactamase activity in each strain tested. N-F-thienamycin and cefoxitin were not hydrolyzed, and moxalactam was less susceptible to hydrolysis than the other beta-lactam antibiotics. Moxalactam and N-F-thienamycin may prove to be useful against infections with B. fragilis.
Effects of vancomycin on renal function in rats
Authors: Aronoff G R , Sloan R S , Dinwiddie C B , Glant M D , Fineberg N S , Luft F C
Published: June 2012

To assess the effects of vancomycin on the kidney, we gave rats doses of 10, 50, 100, 200, and 400 mg/kg per day. Creatinine clearance and urine protein excretion did not differ significantly from the control values. Urine osmolality was unchanged. Mild histological changes occurred in rats given the highest dose. We conclude that although histopathological changes occurred at high doses, vancomycin does not alter renal function in rats.
Isolation and identification of gamma-aminobutyric acid in Streptomyces lincolnensis
Authors: Haak W J , Reineke L M
Published: June 2012

Gamma-aminobutyric acid was isolated from ruptured cells of Streptomyces lincolnensis. Its isolation and purification by preparative liquid-solid chromatography and subsequent identification by gas chromatography-mass spectroscopy are reported.
In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy
Authors: Anderson R , Gatner E M , van Rensburg C E , Grabow G , Imkamp F M , Kok S K , van Rensburg A J
Published: June 2012

The effects of dapsone on polymorphonuclear leukocyte functions and lymphocyte mitogen-induced transformation were assessed in vitro and in vivo in normal individuals and in newly diagnosed untreated patients with lepromatous leprosy. The effects of dapsone on the cell-free generation of superoxide by the xanthine: xanthine oxidase system and iodination of bovine serum albumin by horseradish peroxidase were also investigated. In normal individuals dapsone mediated stimulation of polymorphonuclear leukocyte migration in vitro and vivo. Dapsone had no effect on postphagocytic hexose monophosphate shunt activity in vivo. Similar effects were found in patients with lepromatous leprosy. Dapsone also decreased the inhibitory activity of serum from patients with lepromatous leprosy on normal polymorphonuclear leukocyte migration in vitro. Progressive loss of serum-mediated inhibition of migration was observed after ingestion of dapsone by the patients. Further experiments showed that stimulation of polymorphonuclear leukocyte motility was related to inhibition of lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo.
Myxothiazol, a new antibiotic interfering with respiration
Authors: Thierbach G , Reichenbach H
Published: June 2012

Myxothiazol, a new antibiotic from the myxobacterium Myxococcus fulvus, inhibited the growth of many yeasts and fungi at concentrations between 0.01 and 3 micrograms/ml. It was generally inactive against bacteria. The inhibitory effect was cytostatic. With Candida albicans, Saccharomyces cerevisiae, and Mucor hiemalis, the growth inhibition was neutralized by glucose. Soon after being added to a cell suspension, the compound almost completely blocked oxygen consumption.
Pharmacology of cefotaxime and its desacetyl metabolite in renal and hepatic disease
Authors: Wise R , Wright N , Wills P J
Published: June 2012

The pharmacology of cefotaxime and the metabolite desacetyl cefotaxime was studied in 40 patients with various degrees of renal and hepatic failure who received 0.5 or 1 g of cefotaxime intravenously. Patients with severe renal impairment (creatinine clearance, 3 to 10 ml/min) had a cefotaxime serum half-life of 2.6 h and desacetyl cefotaxime serum half-life of 10.0 h. The equivalent figures were 1.0 and 1.5 h, respectively, in subjects with normal renal function. The presence of an acute coexisting illness together with severe renal impairment was associated with a further prolongation of the serum half-lives. Hepatic dysfunction was accompanied by a reduction in desacetyl metabolite formation. A reduction of cefotaxime dosing to 0.5 g twice a day would appear prudent when the creatinine clearance is 5 ml/min or less to avoid accumulation of the parent compound and the metabolite.