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PubMedDate not supplied

Development of Ga-67 labeled DFO-DAS-fibrinogen conjugate as a thrombus imaging agent.

A cluster method developed for labeling large molecular proteins with radioactive metal was applied for 67Ga-labeled fibrinogen. A large number of deferoxamine (DFO) was introduced to human fibrinogen using dialdehyde strarch (DAS) as a spacer-functional polymer. The synthesized DFO-DAS-fibrinogen mentioned above was easily labeled with GaCl3 (67Ga) solution (2 mCi/5 mg). The basic investigations found that 67Ga-DFO-DAS-fibrinogen was applicable to the diagnosis of thrombus, and clinical trials were carried out under the physician-sponsored IND. In our further investigation, improvement of the 67Ga-DFO-DAS-fibrinogen reagent was attempted to obtain high specific radioactivity. This was accomplished with the more familiar 67Ga citrate. From the results of a series of experiments, 67Ga-DFO-DAS-fibrinogen of a new composition labeled using 67Ga citrate with high specific radioactivity (2 mCi/3 mg) was prepared, and both reagents were evaluated as thrombus imaging agents from the chemical and biological aspects. The labeling efficiency and clottability of both 67Ga-DFO-DAS-fibrinogen conjugates were satisfactorily high, more than 95% and 80%, respectively. The biodistribution in rats showed that both 67Ga-DFO-DAS-fibrinogen conjugates were essentially the same. These results suggest that there are no significant differences between reagents. At present, the improved reagents are being supplied for the second clinical trials under physician-sponsored IND.

Animals↗

PubMed1985

Radiological health implications of lead-210 and polonium-210 accumulations in LPG refineries.

Radon-222, a naturally occurring radioactive noble gas, is often a contaminant in natural gas. During fractionation at processing plants, Radon tends to be concentrated in the Liquified Petroleum Gas (LPG) product stream. Radon-222 decays into a number of radioactive metallic daughters which can plate out on the interior surfaces of plant machinery. The hazards associated with gamma-emitting short-lived radon daughters have been investigated previously. The present work reports an analysis of the hazards associated with the long-lived daughters; Pb-210, Bi-210, and Po-210. These nuclides do not emit appreciable penetrating radiation, and hence do not represent a hazard as long as they remain on the inside surfaces of equipment. However, when equipment that has had prolonged exposure to an LPG stream is disassembled for repair or routine maintenance, opportunities for exposure to radioactive materials can occur. This paper reports a series of measurements made on an impeller taken from a pump in an LPG facility. Alpha spectroscopy revealed the presence of Po-210, and further measurements showed that the amount on the impeller surface was well above the exempt quantity. Breathing zone measurements made in the course of cleaning the impeller showed that an inhalation exposure equivalent to breathing Po-210 at the Maximum Permissible Concentration (MPC) for 60 hours could be delivered in less than half an hour. It was concluded that maintenance and repair work on LPG and derivitive product stream equipment must be carried out with the realization that a potential radiological health problem exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution, Radioactive↗

PubMed2004

Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type 1: synthesis and characterization.

Previously reported results suggest that the analogue of the somatostatin des-AA1,2,5[D-Trp8,IAmp9]-somatostatin (CH-275) peptide bearing chelating agents able to coordinate radioactive metals could be used for scintigraphic imaging of tumor lesions overexpressing sstr1. An efficient synthetic procedure for the preparation of the somatostatin analogue CH-275 and its conjugate DTPAGlu-Gly-CH-275, bearing the chelating agent DTPAGlu (DTPAGlu=N,N-bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic acid) on the N-terminus, by solid-phase peptide synthesis and 9-fluorenylmethoxycarbonyl (Fmoc) chemistry, is here reported. Rapid and efficient labeling of DTPAGlu-Gly-CH-275 was achieved by addition of 111In(III) to the compound. Typical yields were greater than 97% as determined by reversed phase high performance liquid chromatography (HPLC) at specific activities in the range 4-9 GBq/micromol (100-250 Ci/mmol). A preliminary biological assay of the binding ability of 111In-DTPAGlu-Gly-CH-275 indicates, however, that the labeled compound does not display any specific interaction with somatostatin sstr1 receptors in the tested cell lines. To confirm this unexpected negative result, competition binding experiments were carried out, in which fixed tracer amounts of the 125I-labeled somatostatin-14 were incubated with the receptor-expressing cells in the presence of DTPAGlu-Gly-CH-275 or CH-275 at concentrations ranging from 10(-10) to 10(-3) M. While CH-275 shows a IC50 of 80 nM similar to that already found in displacement experiments on CHO-K1 sstr1-transfected cells, DTPAGlu-Gly-CH-275 displays instead very low or negligible affinity towards this receptor. The NMR solution characterization indicates that the presence of DTPAGlu does not influence the conformational and chemical features of the peptide moiety, thus suggesting that the loss in binding activity should be due to steric hindrance of either the chelating agent DTPAGlu or its indium complex.

Amino Acid Sequence↗

PubMed1983

Whole body and liver distribution of inhaled mercury vapor in the mouse: influence of ethanol and aminotriazole pretreatment.

Inhalation of radioactive metallic mercury vapor (203Hg0) in the mouse resulted in an accumulation of mercury in several organs where no specific uptake was observed after i.v. injection of inorganic mercury (203Hg2+). This was true for the whole respiratory epithelium (including the lung parenchyma), myocardium, brain, retina of the eye, adrenal cortex, corpora lutea of the ovary, epididymis, brown fat and thyroid gland. It is assumed that these organs have a high capacity for oxidizing Hg0 to Hg2+, which will then be retained in the tissues. Ethanol and aminotriazole (catalase inhibitors) decreased the concentration in several of these organs, although not in an exactly similar pattern. In the livers of non-treated animals, most of the inhaled mercury accumulated in the hepatocytes in the periphery of the lobuli (periportal region), close to where the blood vessels enter the liver parenchyma. Treatment with ethanol or aminotriazole increased the liver mercury content, with more or less all the hepatocytes apparently engaged in the oxidation of Hg0.

Amitrole↗

PubMed1993

Imaging and dosimetry determinations using radiolabeled antibodies.

Numerous studies using radiolabeled antibodies for imaging and therapy of lymphoma have been reported (Table 4). The targeting of lymphoma associated antigens with MoAb appears to be more favorable than the targeting of antigens on epithelial tumor. Antigen abundance may not be the overriding factor in this favorable targeting, since the number of antigenic sites per cell are often in the same range or lower than those targeted in epithelial tumors. This improved targeting is likely related to the greater access of antibody to the target antigen in lymph nodes, bone marrow, circulation, and other sites. With certain antibodies, trafficking of the cells targeted with the radiolabeled antibody may also result in favorable localization [19]. While the most frequently used isotope for imaging and therapy has been 131I, certain limitations have been observed, including its high-energy gamma rays and resulting lower resolution, and the frequent occurrence of dehalogenation [21,25,98]. Many of the antigens expressed by lymphomas undergo antigenic modulation. Antigens that undergo modulation may be targeted successfully, but once modulation occurs the antibody is broken down and the iodine is rapidly excreted from the cells. While this rapid release from normal organs is an advantage, it is an undesirable event at the tumor site. In contrast to the case of 131I MoAb, modulation may be an advantage for targeting with 111In labeled antibodies, since the radioactive metals are retained for longer periods at the tumor sites; even if the antibody is broken down, the 111In is not easily excreted from the cells [52]. Among the most consistent and favorable targeting observed to date is that seen with 111In T101 in CTCL. These studies have shown concentration of 111In in tumor of 10-100 times that seen in other tumor systems using iodinated antibodies. Unfortunately no studies have followed this lead and performed the necessary comparisons between 111In and 131I MoAb to determine if this is a consistent finding. The use of 99mTc labeled MoAb for imaging lymphomas is in its infancy, although preliminary reports appear promising [71]. While in epithelial tumors preferential tumor targeting may take more than 48 hours in lymphomas, targeting is usually seen within the first 24 hours, which is within the window of imaging time for 99mTc. Therefore, further evaluation of 99mTc antibodies should be performed. Determination of the optimum dose of antibody for imaging has been attempted. Studies using various anti-lymphoma directed antibodies have shown widely varying biodistribution and variable dose-response curves.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1975

Molybdenum and iron as functional consitituents of the enzymes of the nitrate-reducing system of Azotobacter chroococcum.

The roles of molybdenum and iron in the enzymes of the assimilatory nitrate-reducing system from Azotobacter chroococcum have been investigated. 1. By adding 99 Mo-molybdate to a cell culture of A. chrocococcum with nitrate as the nitrogen source, it has been possible to incroporate the radioactive metal into a purified preparation of the enzyme nitrate reductase. 2. When 185 W-tungstate was supplied to a culture medium lacking added molybdate, a 185 W-labelled nitrate reductase preparation with negligible activity could be obtained. This in vivo incorporation of tungsten was competitively hindered by molybdenum. 3. The cellular level of nitrite reductase activity gradually increased in response to the addition of increasing amounts of iron to the culture medium. Under the same conditions, of the level of nitrate reductase activity was not affected.

Azotobacter↗

PubMed1990

Preparation, 252Cf-plasma-desorption mass spectrometry and radiometal exchange of the Pb2+ and Bi3+ complexes of a hexalactam macrocycle.

A macrocyclic tricatechol hexalactam ligand readily forms complexes with Pb2+ and Bi3+ ions. Solid samples were isolated and characterized by 252Cf-plasma-desorption mass spectroscopy (252Cf-PDMS). Radioactive metal exchange studies employing 210Pb and 210Bi showed the compounds to be kinetically inert to exchange. The feasibility of using an available source of 203Pb, a potential imaging agent, with this class of compound was shown by synthesis of the labelled hexalactam complex.

Bismuth↗

PubMed1991

Antibody fragments labeled with fluorine-18 and gallium-68: in vivo comparison with indium-111 and iodine-125-labeled fragments.

Although monoclonal antibodies have been radiolabeled with many different radionuclides, the application of positron emission tomography (PET) to the imaging of radiolabeled antibodies has been limited to the investigation of a small number of long-lived radionuclides. In this study, we labeled F(ab')2 fragments of a mouse monoclonal antibody (BB5-G1) specific for a human parathyroid surface antigen with the positron emitting radionuclides, gallium-68 and fluorine-18. The biodistribution of the fragments was evaluated in a nude mice model and the results were compared to those obtained with fragments labeled with iodine-125 and indium-111 using conventional labeling techniques. All labeled fragments bound to human parathyroid tissue implanted in nude mice, with parathyroid-to-muscle ratios reaching as high as 10:1, 4 h after administration. A major difference was observed in the uptake and clearance of the various labeled fragments through the kidney. The halogen activity cleared, but the metal radioactivity was retained in the kidney. The results indicate that the fluorine-18 or gallium-68 labeled fragment may be useful for parathyroid imaging with positron emission tomography.

Albumins↗

PubMed2006

Chelation of UO(2)(2+) by vitamin B6 complex derivatives: synthesis and characterization of [UO2(beta-pyracinide)2(H2O)] and [UO2(Pyr2en)DMSO]Cl2{Pyr2en=N,N'-ethylenebis(pyridoxylideneiminato)}. A useful modeling of assimilation of uranium by living beings.

The vitamin B(6) derivatives 4-pyridoxic acid (anionic) and the Schiff base N,N'-ethylenebis(pyridoxylideneiminato) react with UO(2)(NO(3))(2) * 6H(2)O to give [UO(2)(beta-pyracinide)(2)(H(2)O)] (beta-pyracin=4-pyridoxic acid) and [UO(2)(Pyr(2)en)DMSO]Cl(2)(Pyr(2)en=N,N'-ethylenebis(pyridoxylideneiminato); DMSO=dimethyl sulfoxide). In both compounds the two uranyl oxo ligands set the axis of distorted pentagonal bipyramides. The ability of vitamin B(6) derivatives to react with UO(2)(2+) allowing the chelation of one uranium atom represents a very specific model of assimilation of uranium by living beings. It could also explain the serious damages caused by heavy or radioactive metals like uranium since their complexation "in vivo" by enzymatic systems like pyridoxal phosphate-containing enzymes would lead to a modification of the prosthetic groups of the metalloenzymes with loss of their catalytic activities.

Chelating Agents↗

PubMed2005

A new method for measuring blood-brain barrier permeability demonstrated with Europium-bound albumin during experimental lipopolysaccharide (LPS) induced meningitis in the rat.

The blood-brain barrier (BBB) is a critical extrameningeal site of injury during bacterial meningitis, manifested by enhanced BBB permeability (BBBP). Previous methods to measure altered BBBP during meningitis involve radioactive materials, or are poorly quantified. Europium (EU) is a fluorescent, non-radioactive metal that is a sensitive and stable marker. Europium fluorescence can be measured with a spectrophotometer capable of time-resolved fluorescence (TRF). We used EU-albumin (EU-A) to examine BBBP in experimental lipopolysaccharide (LPS) induced meningitis. The results presented here introduce a simple and accurate method for measuring BBB permeability.

Albumins↗

PubMed2005

New directions in the coordination chemistry of 99mTc: a reflection on technetium core structures and a strategy for new chelate design.

Bifunctional chelates offer a general approach for the linking of radioactive metal cations to macromolecules. In the specific case of 99mTc, a variety of technologies have been developed for assembling a metal-chelate-biomolecule complex. An evaluation of these methodologies requires an appreciation of the coordination characteristics and preferences of the technetium core structures and oxidation states, which serve as platforms for the development of the imaging agent. Three technologies, namely, the MAG3-based bifunctional chelates, the N-oxysuccinimidylhydrazino-nicotinamide system and the recently described single amino acid chelates for the {Tc(CO)3}1+ core, are discussed in terms of the fundamental coordination chemistry of the technetium core structures. In assessing the advantages and disadvantages of these technologies, we conclude that the single amino acid analogue chelates (SAAC), which are readily conjugated to small peptides by solid-phase synthesis methods and which form robust complexes with the {Tc(CO)3}1+ core, offer an effective alternative to the previously described methods.

Chelating Agents↗

PubMed2002

Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies.

Bisphosphonates (BPs) are characterized by a P-C-P backbone structure and two phosphonic acid groups bonded to the same carbon, and are established as osteoclast-mediated bone resorption inhibitors. The nature of the groups attached to the central carbon atom are responsible in determining the potency of bisphosphonates as anti-resorption drugs. However, it is not yet clear the exact relationship between their molecular structure and pharmacologic activities. In this study, molecular geometries of pamidronate, alendronate and neridronate, differing only in the length of the aliphatic chains, were predicted by molecular mechanics and their interactions with hydroxyapatite, the main bone mineral component, were examined. We report the synthesis and radiochemical characterization of 153Sm complexes with pamidronate, alendronate and neridronate. Hydroxyapatite binding and biodistribution studies of these complexes have shown a good correlation with the theoretical molecular modeling interaction studies. So, it is possible to conclude that computational chemistry techniques are a good approach to evaluate specific interactions and may play a relevant role in determining the relative ability of BPs to mineral bone, and open new perspectives to the design of new BPs with increased pharmacological activity. These techniques could be extended to BPs as ligands to carrier radioactive metals, aiming for new bone therapeutic radiopharmaceuticals.

Alendronate↗

PubMedDate not supplied

Novel Tat-peptide chelates for direct transduction of technetium-99m and rhenium into human cells for imaging and radiotherapy.

Rapid and efficient delivery of radioactive metal complexes to the cell interior would enable novel applications in medical imaging and radiotherapy. Membrane permeant peptide conjugates incorporating HIV-1 Tat transactivation protein sequences (GRKKRRQRRR) and an appropriate peptide-based motif (epsilon-KGC) that provides an N(3)S donor core for chelating technetium and rhenium were synthesized. Oxotechnetium(V) and oxorhenium(V) Tat-peptide complexes were prepared by facile transchelation reactions with permetalates, tin(II) chloride and sodium glucoheptonate. RP-HPLC showed two major [(99m)Tc]Tat-peptide species (4) that differed in retention time by approximately 2 min corresponding to two [Re]Tat-peptide species (7) shown to have identical mass, consistent with formation of two isomers, likely the oxo-metal diastereomers. [(99m)Tc]Tat-peptides were stable to transchelation in vitro. In human Jurkat cells, [(99m)Tc]Tat-peptide 4 showed concentrative cell accumulation (30-fold greater than extracellular concentration) and rapid uptake kinetics (t(1/2) < 2 min) in a diastereomeric-comparable manner. Paradoxically, uptake was enhanced in 4 degrees C buffer compared to 37 degrees C, while depolarization of membrane potential as well as inhibition of microtubule function and vesicular trafficking showed no inhibitory effect. Cells preloaded with 4 showed rapid washout kinetics into peptide-free solution. Modification of [(99m)Tc]Tat-peptide by deletion of the N-terminus Gly with or without biotinylation minimally impacted net cell uptake. In addition, the C-terminus thiol of the prototypic Tat-peptide was labeled with fluorescein-5-maleimide to yield conjugate 8. Fluorescence microscopy directly localized conjugate 8 to the cytosol and nuclei (possibly nucleolus) of human Jurkat, KB 3-1 and KB 8-5 tumor cells. Preliminary imaging studies in mice following intravenous administration of prototypic [(99m)Tc]Tat-peptide 4 showed an initial whole body distribution and rapid clearance by both renal and hepatobiliary excretion. Analysis of murine blood in vivo and human serum ex vivo revealed >95% intact complex, while murine urine in vivo showed 65% parent complex. Thus, these novel Tat-peptide chelate conjugates, capable of forming stable [Tc/Re(V)]complexes, rapidly translocate across cell membranes into intracellular compartments and can be readily derivatized for further targeted applications in molecular imaging and radiotherapy.

Amino Acid Sequence↗

PubMedDate not supplied

Synthesis, characterization, and labeling with 99mTc/188Re of peptide conjugates containing a dithia-bisphosphine chelating agent.

Radiolabeling of small receptor-avid peptides at specific predetermined chelation sites with radioactive metals has been an effective approach for production of target-specific radiopharmaceuticals for diagnosis and therapy of diseases. Among various electron-donating groups found on chelator frameworks, phosphines are unique because they display versatile coordination chemistry with a wide range of transition metals. We have recently reported the utility of a dithia-bis(hydroxymethyl)phosphine-based (P2S2) bifunctional chelating agent (BFCA) containing air-stable primary phosphine groups to form 99mTc-labeled receptor-avid peptides by the preconjugation approach. Here we report a novel strategy for labeling small peptides with both 99mTc and 188Re using the P2S2-COOH (6,8-bis[3-(bis(hydroxymethyl)phosphanyl)propylsulfanyl]octanoic acid) BFCA by a postconjugation radiolabeling approach. The first step in this approach involves the coupling of the corresponding (PH2)2S2-COOH intermediate to the N-terminus of the peptide(s). Formylation of P-H bonds with aqueous formaldehyde in the presence of HCl in ethanol affords the corresponding (hydroxymethyl)phosphine-P2S2-peptide conjugates in the form of an oxidatively stable phosphonium salt. The P2S2-peptide conjugates are generated (where the PH2 groups are converted to P(CH2OH)2 groups) by treatment of the P2S2-peptide phosphonium salt(s) with 1 M sodium bicarbonate solution at pH 8.5. Complexation of BFCA conjugates with 99mTc is achieved by direct reduction with Sn(II) tartarate to yield the 99mTc-P2S2-peptide conjugate in near quantitative yields. Complexation of the BFCA conjugates with 188Re is achieved by transchelation with 188Re citrate in yields of >/=90%. In this study, (PH2)2S2-COOH BFCA was conjugated to model peptides. The glycineglycine ethyl ester (GlyGlyOEt)-(PH2)2S2-COOH BFCA conjugate was converted to the hydroxymethylene phosphine form and complexed with 99mTc to produce the 99mTcO2-P2S2-GlyGlyOEt conjugate 8 in RCPs of >/=95%. This singular 99mTc product is stable over 24 h in aqueous solution as confirmed by HPLC. Identical retention times of the 99mTcO2-P2S2-GlyGlyOEt complex and its cold rhenium analogue (ReO2-P2S2-GlyGlyOEt) on HPLC indicates similarity in structures at the macroscopic and the tracer levels. The utility of this postconjugation strategy was further demonstrated by synthesizing a P2S2-D-Lys6-LHRH conjugate and producing its corresponding 99mTc complex in RCPs of >/=88%. Finally, the P2S2-5-Ava-BBN[7-14]NH2 bombesin (BBN) analogue was synthesized, the PH2 groups converted to P(CH2OH)2 groups and subsequently labeled with 188Re to yield a 188Re-labeled bombesin analogue with a RCP of >/=90%. The biological integrity of this conjugate was demonstrated in both in vitro and in vivo. The results of this investigation demonstrate that the (PH2)2S2-COOH BFCA can be conveniently used as a precursor for labeling small receptor-avid peptides with diagnostic (99mTc) and therapeutic (188Re) radionuclides via the postconjugation approach in high yields.

3T3 Cells↗

PubMed2001

Single-photon emission computed tomography and positron-emission tomography assays for tissue oxygenation.

Radiotherapy prescription can now be customized to target the major mechanism(s) of resistance of individual tumors. In that regard, functional imaging techniques should be exploited to identify the dominant mechanism(s). Tumor biology research has identified several mechanisms of tumor resistance that may be unique to radiation treatments. These fall into 3 broad areas associated with (1) tumor hypoxic fraction, (2) tumor growth rate, (3) and the intrinsic radiosensitivity of tumor clonogens. Imaging research has markers in various stages of development for quantifying relevant information about each of these mechanisms, and those that measure tumor oxygenation and predict for radioresistance are the most advanced. Positron-emission tomography (PET) measurement of oxygen 15 has yielded important information, particularly about brain tissue perfusion, metabolism, and function. Indirect markers of tumor hypoxia have exploited the covalent binding of bioreductive intermediates of azomycin-containing compounds whose uptakes are inversely proportional to intracellular oxygen concentrations. Pilot clinical studies with single-photon emission computed tomography (SPECT) and PET detection of radiolabeled markers to tumor hypoxia have been reported. Recently, other studies have attempted to exploit the reduction properties of both technetium and copper chelates for the selective deposition of radioactive metals in hypoxic tissues. A growing number of potentially useful isotopes are now available for labeling several novel chemicals that could have the appropriate specificity and sensitivity. Preclinical studies with "microSPECT" and "microPET" will be important to define the optimal radiodiagnostic(s) for measuring tissue oxygenation and for determining the time after their administration for optimal hypoxic signal acquisition. Radiolabeled markers of growth kinetics and intrinsic radiosensitivity of cells in solid tumors are also being developed. We conclude that radiation oncology is uniquely positioned to benefit from functional imaging markers that identify important mechanisms of tumor radioresistance, since several strategies for overcoming these individual mechanisms have already been identified.

Animals↗

PubMed2005

Tumor-targeting peptide-PNA-peptide chimeras for imaging overexpressed oncogene mRNAs.

We have optimized a method involving continuous solid phase synthesis of chelator-peptide-PNA-peptide probes in order to noninvasively image oncogene mRNAs overexpressed in tumors. The PNA (peptide nucleic acid) probes carry cyclized peptide ligand analogs specific for receptors overexpressed on malignant breast or colorectal cancer cells, and chelators to bind radioactive metal ions, or a fluorophore. In vivo scintigraphic imaging of MCF7 xenografts in immunocompromised mice indicated that CCND1 and MYC [99sTc] chelator-PNA-D (CSKC) probes concentrated in MCF7 cells up to 7 times more than the corresponding mismatch controls.

Breast Neoplasms↗

PubMed2006

Salt stress in Desulfovibrio vulgaris Hildenborough: an integrated genomics approach.

The ability of Desulfovibrio vulgaris Hildenborough to reduce, and therefore contain, toxic and radioactive metal waste has made all factors that affect the physiology of this organism of great interest. Increased salinity is an important and frequent fluctuation faced by D. vulgaris in its natural habitat. In liquid culture, exposure to excess salt resulted in striking elongation of D. vulgaris cells. Using data from transcriptomics, proteomics, metabolite assays, phospholipid fatty acid profiling, and electron microscopy, we used a systems approach to explore the effects of excess NaCl on D. vulgaris. In this study we demonstrated that import of osmoprotectants, such as glycine betaine and ectoine, is the primary mechanism used by D. vulgaris to counter hyperionic stress. Several efflux systems were also highly up-regulated, as was the ATP synthesis pathway. Increases in the levels of both RNA and DNA helicases suggested that salt stress affected the stability of nucleic acid base pairing. An overall increase in the level of branched fatty acids indicated that there were changes in cell wall fluidity. The immediate response to salt stress included up-regulation of chemotaxis genes, although flagellar biosynthesis was down-regulated. Other down-regulated systems included lactate uptake permeases and ABC transport systems. The results of an extensive NaCl stress analysis were compared with microarray data from a KCl stress analysis, and unlike many other bacteria, D. vulgaris responded similarly to the two stresses. Integration of data from multiple methods allowed us to develop a conceptual model for the salt stress response in D. vulgaris that can be compared to those in other microorganisms.

Bacterial Proteins↗

PubMed1967

Tracer studies to locate the site of platinum ions within filamentous and inhibited cells of Escherichia coli.

The distribution of platinum ions within Escherichia coli after the induction of filaments with cis-Pt(NH(3))(2)Cl(4), and after growth inhibition by PtCl(6) (2-), has been determined with radioactive metal compounds ((191)Pt, with a half-life of approximately 3 days) by the simple chemical procedure of Roberts et al. In the filamentous cells, the platinum metal is associated with metabolic intermediates, nucleic acids, and cytoplasmic proteins; whereas, in inhibited cells, the platinum is combined only with the cytoplasmic protein. Similar experiments with gram-positive cells of Bacillus cereus and Staphyloccus aureus, which show no filamentous growth in the presence of cis-Pt(NH(3))(2)Cl(4), reveal that the metal complex does penetrate the cell wall and subsequently becomes bound predominantly by metabolic intermediates.

Bacillus cereus↗