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Biomedical subjects

C H Huang

Publications and source records attributed to C H Huang.

At least 19 recordsLinked to original sources
PubMed2003

Generation of monoclonal antibodies against Blo t 3 using DNA immunization with in vivo electroporation.

BACKGROUND: House dust mite allergy is closely associated with allergic diseases. Blomia tropicalis mite species is an important clinical species in the tropics. The cDNA clone encoding Blo t 3, a group 3 allergen from B. tropicalis, has been isolated in our laboratory. OBJECTIVE: This study was designed to generate Blo t 3-specific monoclonal antibodies (mAbs) for the detection, characterization and purification of this allergen. METHODS: Mice were immunized intramuscularly with naked plasmid DNA encoding Blo t 3 gene with in vivo electroporation. Hybridomas were generated by the fusion of the splenocytes to X63-Ag8.653 myeloma cells. Purified native Blo t 3 was obtained by mAb immuno-affinity purification and the allergenicity of native Blo t 3 was determined by human IgE enzyme-linked immunosorbent assay (ELISA). RESULTS: A panel of class-switched and high-affinity mAb recognizing a wide spectrum of Blo t 3 epitopes have been generated. These mAbs are useful for western immunoblot assay, sandwich ELISA and affinity purification of native Blo t 3. Allergenicity of native Blo t 3 protein was examined with 44 mite-allergic sera and approximately 57% of the tested sera had positive serum IgE reactivity to the native Blo t 3. CONCLUSIONS: These results demonstrated that intramuscular injection of naked DNA encoding Blo t 3 gene combined with in vivo electroporation is an effective and simple method to raise monoclonal antibodies that can be used for characterization and purification of Blo t 3.

Adult↗
PubMed2001

The application of intramolecular radical cyclizations of acylsilanes in the regiospecific formation of cyclic silyl enol ethers.

Acylsilanes with terminal alpha-stannyl bromide or xanthate functionalities are prepared. Alpha-stannyl radicals generated from these acylsilanes undergo intramolecular cyclizations to give cyclic silyl enol ethers regiospecifically. The radical processes involve radical cyclization, Brook rearrangement, and beta-fragmentation in sequence. A tributylstannyl group serves as the radical leaving group. The newly formed sigma-bond and pi-bond are located between the same two carbon atoms. This approach is limited to the formation of five-membered rings. In another route, omega-bromo-alpha-phenylsulfonylacylsilanes are synthesized. The radical cyclizations of these alpha-sulfonylacylsilanes also give cyclic silyl enol ethers. The phenylsulfonyl moiety is the radical leaving group in this system. Furthermore, the newly formed sigma-bond and pi-bond are located at adjacent positions sharing a single carbon atom. The latter approach is effective for both five- and six-membered ring formation.

Journal Article↗
PubMed2001

Rottlerin stimulates metallothionein gene expression but inhibits metal transport in Chinese hamster ovary cells.

Metallothionein (MT) can be induced by various metals. We have shown previously that H7, a protein kinase C (PKC) inhibitor, inactivates metal-induced MT gene expression. To investigate whether a specific PKC isoform is involved in the induction process, inhibitors for various PKC isoforms were administered to cadmium-resistant Chinese hamster ovary (Cd(R)) cells. None of the inhibitors used can reduce metal-induced MT gene expression. However, a PKCdelta inhibitor, rottlerin, induced MT mRNA expression in Cd(R) cells in the presence or absence of Cd. Notably, the induction occurs through the activation of the MT transcriptional factor (MTF-1) and is not related to an increase of metal influx. Furthermore, metal accumulation is reduced in the presence of rottlerin. Pulse-labeling analysis indicated that MT protein synthesis increased in Cd(R) cells upon rottlerin treatment. These results suggest that rottlerin blocks metal transport but stimulates MT synthesis in Cd(R) cells. Since rottlerin is capable of reducing the cellular accumulation of Cd, it was expected that the cytotoxic effect of Cd would decrease in the presence of rottlerin. Treating the parental cell of Cd(R) with Cd and rottlerin together indeed showed a decline of cytotoxicity compared to cells treated with Cd alone. We further examined how MTF-1 was activated by rottlerin. Rottlerin-induced MTF-1 activity was not affected in Cd(R) cells by the addition of EDTA. It was, however, diminished by administering an intracellular Zn chelator, TPEN. The result implies a mobilization of intracellular Zn ions after rottlerin treatment in Cd(R) cells. To investigate whether the described results occur in all types of cells, another cell line (GH(3)) was used to study the effect of rottlerin on MT gene expression. The result revealed that rottlerin did not increase the amount of MT mRNA in GH(3) cells. This differential effect between cell lines may be useful for investigating the regulatory mechanism of MT gene expression.

Acetophenones↗
PubMed2001

Induction of disabled-2 gene during megakaryocyte differentiation of k562 cells.

Megakaryocyte differentiation is often accompanied by the changes of gene expression pattern. Here we reported that the expression of DAB2, a putative adaptor protein in cell signaling, was induced at the protein and mRNA levels upon 12-O-tetradecanoylphorbol-13-acetate-mediated megakaryocyte differentiation of human chronic myeloid leukemic K562 cells. On the other hand, the differentiation agents DMSO and retinoic acid had no effect on DAB2 expression. Analysis of promoter activity with the human DAB2 luciferase reporter constructs suggested that the regulation is partially at the transcriptional level. The responsive sequences located within an 80-bp DAB2 promoter region. To determine the involvement of MEK1-p42/p44 MAPK pathway in mediating DAB2 gene expression, we have performed the following experiments and found that (i) there was sustained activation of p42/p44 MAPK, but not p38 MAPK, upon K562 cells differentiation; (ii) application of MEK1 inhibitor U0126 reduced the expression of DAB2 protein, mRNA and promoter activity, as well as cell differentiation; (iii) constitutively active MEK1 increased DAB2 promoter activity; and (iv) dominant negative ERK2 abolished constitutively active MEK1-induced DAB2 promoter activity. Taken together, our results indicate that DAB2 gene is induced upon megakaryocyte differentiation by the MEK1-p42/p44 MAPK pathway and may define a new role of DAB2 in hematopoietic cell differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Collection efficiency and capacity of three samplers for acidic and basic gases.

This paper compares the collection efficiency and capacity of a coated porous metal disk with those of a silica gel tube and an impinger at the acid or basic aerosol concentration of two times the permissible exposure limitation (Taiwan IOSH, Institute of Occupational Safety and Health), relative humidity of 80 +/- 5%, and temperature of 30 +/- 3 degrees C in the laboratory. Using 5% sodium carbonate/glycerin coating, the collection efficiencies of the porous metal disk for nitric acid, hydrogen chloride, and hydrogen fluoride are found to be higher than those of the silica gel tube and the impinger when the sampling time is less than 3.0 h. The gas collection capacity of the porous metal disk coated with 5% sodium carbonate is calculated to be 3.9, 5.8, and >2.5 mg for nitric acid, hydrogen chloride, and hydrogen fluoride, respectively. For ammonia, the porous metal disk coated using 4% citric acid performs slightly better than the impinger, and the corresponding capacity is slightly greater than 33.6 mg.

Aerosols↗
PubMed2001

Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice.

Band 3 and glycophorin A (GPA) are the 2 most abundant integral proteins in the human erythrocyte membrane. Earlier studies suggested that the 2 proteins may associate not only in the mature erythrocyte membrane, but also during their posttranslational processing and intracellular trafficking. The purpose of this study was to directly examine the GPA-band 3 interaction in vivo and determine the nature of this association during erythroid membrane biogenesis. Transgenic mice were generated expressing the human glycophorin A gene and were used to examine how the induction of human GPA expression affected the levels of murine GPA and band 3 expression in the red cell membrane. Murine GPA expression was reduced in erythrocytes expressing human GPA, whereas the level of band 3 expression remained constant, implying a tight coupling of band 3 and GPA expression in the membrane of mature red cells. In vivo GPA dimerization was not modulated solely by the GPA transmembrane motif, but the distance between this motif and the basic residues on the cytoplasmic side of the transmembrane domain may also be important. In addition, GPA monomers with varying degrees of glycosylation dimerized, providing clear evidence that carbohydrate structures on the extracellular domain do not affect dimerization. The association between the multiple transmembrane-spanning protein, band 3, and the single transmembrane-spanning sialoglycoprotein, GPA, may serve as a model for interactions of other multi-pass and single-pass polypeptides during membrane biogenesis.

Animals↗
PubMed2001

The intrinsic stability of the noble gas-coordinated transition-metal complex ions.

Density-functional-theory and high-level ab initio calculations have been performed on the [AuXe4]2+ ion and some other hypothetical xenon-, krypton-, and argon-coordinated transition-metal complex cations in the gas phase. Geometry optimization at the QCISD(T) level using a (6s7p4d2f1g) basis set for Au and a (4s4p2d1f) set for Xe predicted Au-Xe bond lengths in good agreement with the AuXe4(2+)(Sb2F11-)2 crystal structure. The ligand-binding energies of the [AuXe4]2+, [AuXe4]3+, and [PtXe4]2+ ions were predicted to be 229, 565, and 233 kcal/mol, respectively, at the CCSD(T) level. It is found that higher-level correlation effects are important to obtain accurate geometry parameters. The calculated results also indicated that various trivalent, tetravalent, and hexavalent transition-metal complexes of xenon or krypton might also be intrinsically stable.

Drug Stability↗
PubMed2001

Rh type B glycoprotein is a new member of the Rh superfamily and a putative ammonia transporter in mammals.

Ammonium transporters play a key functional role in nitrogen uptake and assimilation in microorganisms and plants; however, little is known about their structural counterpart in mammals. Here, we report the molecular cloning and biochemical characterization of Rh type B glycoproteins, human RhBG and mouse Rhbg, two new members of the Rh family with distinct tissue specificities. The RhBG orthologues possess a conserved 12-transmembrane topology and most resemble bacterial and archaeal ammonium transporters. Human RHBG resides at chromosome 1q21.3, which harbors candidate genes for medullary cystic kidney disease, whereas mouse Rhbg is syntenic on chromosome 3. Northern blot and in situ hybridization revealed that RHBG and Rhbg are predominantly expressed in liver, kidney, and skin, the specialized organs involving ammonia genesis, excretion, or secretion. Confocal microscopy showed that RhBG is located in the plasma membrane and in some intracellular granules. Western blots of membrane proteins from stable HEK293 cells and from mouse kidney and liver confirmed this distribution. N-Glycanase digestion showed that RhBG/Rhbg has a carbohydrate moiety probably attached at the NHS motif on exoloop 1. Phylogenetic clustering, tissue-specific expression, and plasma membrane location suggest that RhBG homologous proteins are the long sought major ammonium transporters in mammalians.

Amino Acid Sequence↗
PubMed2001

Molecular mechanics and calorimetric studies of phosphatidylethanols.

Phosphatidylethanols (PEths) are negatively charged diacyl phospholipids that are ubiquitously present in humans under the condition of alcohol intoxication. These lipids, derived in vivo from other naturally occurring phospholipids such as phosphatidylcholines (PC) via transphosphatidylation reaction as catalyzed by phospholipase D in the presence of ethanol, are well known to affect many biochemical properties of the cell membranes in humans. In this communication, we applied the combined approach of molecular mechanics (MM) simulations and high-sensitivity differential scanning calorimetry (DSC) to investigate the structure and phase transition behavior of PEth. We first determined the energy-minimized structures of tetrameric C(15):C(15)PEth arranged in two types of packing motif by the MM approach. An inwardly bent orientation of the lipid headgroup was observed; specifically, the methyl terminus of PEth's headgroup was juxtaposed intramolecularly to the C(2) atom of the sn-2 acyl chain. Clearly, this headgroup conformation was rather unique among all naturally occurring phospholipids. Subsequently, the phase transition behavior of the fully hydrated lipid bilayers prepared individually from 11 species of saturated C(X):C(Y)PEth with the same MW was studied by DSC, and the resulting Tm values were codified in terms of the normalized acyl chain asymmetry (deltaC/CL). A V-shaped Tm profile was observed in the plot of Tm versus deltaC/CL for each subclass of these lipids, suggesting two types of packing motif for C(X):C(Y)PEth at T < Tm. Moreover, it was observed that within each packing motif these Tm values were, on average, 2.0 +/- 0.9 degrees C smaller than the Tm values of the corresponding saturated PC. However, based on the unique headgroup conformation of PEth, we were able to predict that monounsaturated PEth with a cis double bond near the H2O/hydrocarbon interface would exhibit a higher Tm than the corresponding PC. Most interestingly, this prediction was indeed borne out by DSC results obtained with C(18):C(20:1delta5)PC and C(18):C(20:1delta5)PEth.

Brassica↗
PubMed2001

Mixed-chain phospholipids: structures and chain-melting behavior.

It has long been established that diacyl phospholipids isolated from animal cell membranes are predominantly of a mixed-chain variety, meaning that the sn-1 and sn-2 acyl chains are saturated and unsaturated acyl chains, respectively. In general, monoenoic and dienoic acids are found in the sn-2 acyl chain of phosphatidylcholine (PtdCho), whereas polyenoic acids are in phosphatidylethanolamine (PtdEth). These unsaturated chains contain only cis-double bonds, which are always methylene-interrupted. In recent years, the structures and the chain-melting behavior of mixed-chain PtdCho and PtdEth have been systematically studied in this laboratory. Specifically, we have examined the effects of chain unsaturation of the sn-2 acyl chain on the phase transition temperature (Tm) of many PtdCho and PtdEth by high-resolution differential scanning calorimetry (DSC). The Tm values, for instance, obtained from all-unsaturated mixed-chain PtdEth derived from a common precursor can be grouped together according to their chemical formula to form a Tm-diagram. Hence, all the Tm values can be compared simply, systematically, and simultaneously using the Tm-diagram. In addition, the energy-minimized structures of mixed-chain phospholipids containing different numbers/positions of methylene-interrupted cis-double bonds have been simulated by molecular mechanics calculations (MM). In this review, the results of our MM and DSC studies carried out with various mixed-chain phospholipids are summarized. In addition, we emphasize that the combined approach of MM and DSC yields unique information that can correlate the various Tm-profiles seen in the Tm-diagram with the structural variation of mixed-chain lipids as caused by the introduction of different numbers/positions of methylene-interrupted cis-double bonds.

Chemical Phenomena↗
PubMed2001

Morphometric identification of luminal narrowing of myocardial capillaries after cardioplegic arrest.

BACKGROUND: Because there is no smooth muscle cell surrounding the capillary endothelial cells, the effect of coronary microcirculation at the capillary level following cardioplegic arrest and reperfusion would be much different from that of resistant arterioles. We therefore studied the effect of hypothermic blood cardioplegic arrest and subsequent reperfusion on the myocardial capillaries in cardiac operation patients. METHODS: Twenty-seven patients who underwent cardiac operations were included in this study. Three sequential biopsies (preischemia, ischemia, and reperfusion) were obtained from the right atrium. This study was restricted to blood vessels with a diameter of less than 8 microns. Ten randomly selected capillaries from each biopsy were measured for luminal surface area, endothelial cytoplasmic surface area, and total cross-sectional surface area of capillaries. RESULTS: From stereologic morphometric studies, the serial changes in total cross-sectional surface area were not statistically significant (p = 0.152). However, there was a significant swelling of endothelial cytoplasm following ischemia and reperfusion (p = 0.0007). Meanwhile, changes in luminal surface area of capillaries following ischemia and reperfusion were also remarkable (p = 0.0008). CONCLUSIONS: The most striking finding of this study was the progressive decrease in capillary lumen during ischemia and after reperfusion. The swelling of endothelial cells is a major determinant of luminal narrowing of capillaries in patients receiving cardioplegic arrest.

Adolescent↗
PubMed2001

Real-time PCR for rapid genotyping of angiotensin-converting enzyme insertion/deletion polymorphism.

OBJECTIVE: To develop a real-time PCR technique for detection of the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene. DESIGN AND METHODS: Three primers were designed for performing real-time PCR in the presence of SYBR Green I as flurochrome followed by melting curve analysis. Forty human genomic DNA that have been genotyped by two-rounds of conventional PCR were used for evaluation of this technique. RESULTS: Melting curve analysis indicated the melting peak at 73.9 degrees C and 76.2 degrees C corresponding to the presence of I and D alleles, respectively. Comparable genotyping results were obtained by both conventional and real-time PCR. Besides, the mistyping of ID allele individuals by the first run of conventional PCR were accurately genotyped by single-tube real time PCR. CONCLUSIONS: The real-time PCR method presented in this study provides a rapid and sensitive way for genotyping of ACE gene that may be suitable for large-scale clinical and epidemiologic study.

Alleles↗
PubMed2001

The influence of inserting a Fuji pressure sensitive film between the tibiofemoral joint of knee prosthesis on actual contact characteristics.

OBJECTIVE: To investigate the influence of inserting a Fuji pressure sensitive film between the tibiofemoral joint of knee prosthesis on actual contact characteristics. DESIGN: A finite element analysis was used to investigate the alteration of contact characteristics of the tibiofemoral joint due to inserting a pressure sensitive film between the contacting surfaces. BACKGROUND: The discrepancy between actual contact behaviors of tibiofemoral joint of knee prosthesis and the measurement using Fuji pressure sensitive film was not discussed extensively. The change of direct contact circumstance of the tibiofemoral joint due to inserting a pressure sensitive film was not well reported. METHOD: A two-dimensional finite element model of the tibiofemoral joint of knee prosthesis in the sagittal plane was constructed. Four different radii of the femoral component were used to investigate the conformity effect. Two-layers of plane strain element were used to model the pressure sensitive film. The influence of inserting a pressure sensitive film on the actual contact characteristics was analyzed by comparing the results of the change in contact radius. RESULTS: Inserting a pressure sensitive film between contacting surfaces would disturb the original contact behaviors, especially in the lowest conformity design. The maximum difference of contact radius between the model simulating actual contact circumstance and the model with inserting a pressure sensitive film between contacting surface was 77% in the lowest conformity condition at the smallest load. CONCLUSIONS: This study proposes a quantitative analysis of contact characteristics in the tibiofemoral joint of knee prosthesis between the models with and without inserting a pressure sensitive film into the contact surface. The measurement of contact area in artificial tibiofemoral joints by using Fuji pressure sensitive film is always overestimated its true contact area by 14-77%. RELEVANCE: This study revealed the measurement of contact characteristics of artificial tibiofemoral joints by using Fuji pressure sensitive film which depends on not only the applied load, but also the conformity and material properties of the contact surface. Therefore, the information of the conformity and material properties of the contact surface should be provided as well as the applied load wherever a measurement of contact characteristics using Fuji pressure sensitive film is analyzed and interpreted.

Biomechanical Phenomena↗
PubMed2001

The investigation of three-dimensional vibration for piezoelectric rectangular parallelepipeds using the AF-ESPI method.

Electronic speckle pattern interferometry (ESPI) is a powerful tool for the full-field measurement of a deformed body. In this paper, a three-dimensional vibrating block that couples the out-of-plane and in-plane motions is investigated using the amplitude-fluctuation ESPI (AF-ESPI). This method demonstrates the advantages of combining high processing speed, such as in the subtraction method, with high fringe sensitivity, such as in the time-averaged method. The optical system for AF-ESPI is then employed to analyze the volume vibration of piezoelectric material for a rectangular parallelepiped configuration. Based on the fact that fringe patterns measured by the AF-ESPI method appear as a clear picture only at the resonant frequency, both the natural frequencies and the out-of-plane and in-plane vibration mode shapes are successfully obtained in this study. Finally, the impedance analysis as well as the finite element method (FEM) with three-dimensional model are also conducted to compare with the result obtained by AF-ESPI. It is shown that the numerical calculation and the experimental result agree fairly well for both the resonant frequency and the mode shape in three-dimensional configurations.

Journal Article↗
PubMed2001

Vibration characteristics of composite piezoceramic plates at resonant frequencies: experiments and numerical calculations.

The experimental measurement of the resonant frequencies for the piezoceramic material is generally performed by impedance analysis. In this paper, we employ an optical interferometry method called the amplitude-fluctuation electronic speckle pattern interferometry (AF-ESPI) to investigate the vibration characteristics of piezoceramic/aluminum laminated plates. The AF-ESPI is a powerful tool for the full-field, noncontact, and real-time measurement method of surface displacement for vibrating bodies. As compared with the conventional film recording and optical reconstruction procedures used for holographic interferometry, the interferometric fringes of AF-ESPI are produced instantly by a video recording system. Because the clear fringe patterns measured by the AF-ESPI method will be shown only at resonant frequencies, both the resonant frequencies and corresponding vibration mode shapes are obtained experimentally at the same time. Excellent quality of the interferometric fringe patterns for both the in-plane and out-of-plane vibration mode shapes are demonstrated. Two different configurations of piezoceramic/aluminum laminated plates, which exhibit different vibration characteristics because of the polarization direction, are investigated in detail. From experimental results, we find that some of the out-of-plane vibration modes (Type A) with lower resonant frequencies cannot be measured by the impedance analysis; however, all of the vibration modes of piezoceramic/aluminum laminated plates can be obtained by the AF-ESPI method. Finally, the numerical finite element calculations are also performed, and the results are compared with the experimental measurements. Excellent agreements of the resonant frequencies and mode shapes are obtained for both results.

Letter↗
PubMed2001

Experimental and numerical investigations of resonant vibration characteristics for piezoceramic plates.

Electronic speckle pattern interferometry (ESPI) is a full field, non-contact technique for measuring the surface displacement of a structure subjected to static loading or, especially, to dynamic vibration. In this article we employ an optical system called the amplitude-fluctuation ESPI with out-of-plane and in-plane measurements to investigate the vibration characteristics of piezoceramic plates. Two different configurations of piezoceramic plates, namely the rectangular and the circular plates, are discussed in detail. As compared with the film recording and optical reconstruction procedures used for holographic interferometry, the interferometric fringes of AF-ESPI are produced instantly by a video recording system. Because the clear fringe patterns will be shown only at resonant frequencies, both the resonant frequencies and the corresponding mode shapes are obtained experimentally at the same time by the proposed AF-ESPI method. Excellent quality of the interferometric fringe patterns for both the in-plane and out-of-plane vibration mode shapes is demonstrated. The resonant frequencies of the piezoceramic plates are also measured by the conventional impedance analysis. From experimental results, we find that the out-of-plane vibration modes (type A) with lower resonant frequencies cannot be measured by the impedance analysis and only the in-plane vibration modes (type B) will be shown. However, both the out-of-plane (bending) and in-plane (extensional) vibration modes of piezoceramic plates are obtained by the AF-ESPI method. Finally, the numerical finite element calculations are also performed, and the results are compared with the experimental measurements. It is shown that the numerical calculations and the experimental results agree fairly well for both the resonant frequencies and the mode shapes.

Journal Article↗
PubMed2001

Emergence of reduced susceptibility and resistance to fluoroquinolones in Escherichia coli in Taiwan and contributions of distinct selective pressures.

A survey of 1,203 Escherichia coli isolates from 44 hospitals in Taiwan revealed that 136 (11.3%) isolates were resistant to fluoroquinolones and that another 261 (21.7%) isolates had reduced susceptibility. Resistance was more common in isolates responsible for hospital-acquired (mostly in intensive care units) infections (17.5%) than in other adult inpatient (11.4%; P = 0.08) and outpatient isolates (11.9%; P > 0.1). Similarly, reduced susceptibility was more common in isolates responsible for hospital-acquired infections (30.9%) than in other adult inpatient (21.0%; P = 0.04) and outpatient (21.4%; P = 0.06) isolates. Isolates from pediatric patients were less likely to be resistant (1.3 versus 12.0%; P < 0.01) but were nearly as likely to have reduced susceptibility (17.7 versus 21.9%; P > 0.1) as nonpediatric isolates. There was an inverse relationship in the proportion of isolates that were resistant versus the proportion that had reduced susceptibility among isolates from individual hospitals (R = 0.031; P < 0.05). In an analysis of isolates from two hospitals, all 9 resistant strains possessed double point mutations in gyrA and all 19 strains with reduced susceptibility strains had single point mutations; no mutations were found among fully susceptible strains. Risk factors for resistance included underlying cancer (odds ratio [OR], 83; 95% confidence interval [CI(95)], 7.3 to 2,241; P < 0.001), exposure to a quinolone (OR, undefined; P = 0.02), and exposure to a nonquinolone antibiotic (OR, 20; CI(95), 2.2 to 482; P < 0.001); underlying cancer was the only independent risk factor (OR, 83; CI(95), 8.6 to 807; P < 0.001). There were no significant associations between any of these factors and reduced susceptibility. Whereas acute and chronic quinolone use in cancer patients is a major selective pressure for resistance, other undetermined but distinct selective pressures appear to be more responsible for reduced susceptibility to fluoroquinolones in E. coli.

Adolescent↗