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Biomedical subjects

P K Cheung

Publications and source records attributed to P K Cheung.

18 recordsLinked to original sources
PubMed2006

Increasing prevalence of HIV-1 protease inhibitor-associated mutations correlates with long-term non-suppressive protease inhibitor treatment.

Treatment of human immunodeficiency virus type 1 with protease inhibitors (PIs) is associated with the emergence of resistance-associated mutations. Treatment-characterized datasets have been used to identify novel treatment-associated protease mutations. In this study, we utilized two large reference laboratory databases (>115,000 viral sequences) to identify non-established resistance-associated protease mutations. We found 20 non-established protease mutations occurring in 82% of viruses with a PI resistance score of 4-7, 62% of viruses with a resistance score of 1-3, and 35% of viruses with no predicted PI resistance. We correlated mutational prevalence to treatment duration in a treatment-characterized dataset of 2161 patients undergoing non-suppressive PI therapy. In the non-suppressed dataset, 24 mutations became more prevalent and three mutations became less prevalent after more than 48 months of non-suppressive PI-therapy. Longer durations of non-suppressive treatment correlated with higher PI resistance scores. Mutations at eight non-established positions that were more common in viruses with the longest duration of non-suppressive therapy were also more common in viruses with the highest PI resistance score. Covariation analysis of 3036 protease amino acid substitutions identified 75 positive and nine negative correlations between resistance associated positions. Our findings support the utility of reference laboratory datasets for surveillance of mutation prevalence and covariation.

Amino Acid Sequence↗
PubMed2001

Etiological point mutations in the hereditary multiple exostoses gene EXT1: a functional analysis of heparan sulfate polymerase activity.

Hereditary multiple exostoses (HME), a dominantly inherited genetic disorder characterized by multiple cartilaginous tumors, is caused by mutations in members of the EXT gene family, EXT1 or EXT2. The corresponding gene products, exostosin-1 (EXT1) and exostosin-2 (EXT2), are type II transmembrane glycoproteins which form a Golgi-localized heterooligomeric complex that catalyzes the polymerization of heparan sulfate (HS). Although the majority of the etiological mutations in EXT are splice-site, frameshift, or nonsense mutations that result in premature termination, 12 missense mutations have also been identified. Furthermore, two of the reported etiological missense mutations (G339D and R340C) have been previously shown to abrogate HS biosynthesis (McCormick et al. 1998). Here, a functional assay that detects HS expression on the cell surface of an EXT1-deficient cell line was used to test the remaining missense mutant exostosin proteins for their ability to rescue HS biosynthesis in vivo. Our results show that EXT1 mutants bearing six of these missense mutations (D164H, R280G/S, and R340S/H/L) are also defective in HS expression, but surprisingly, four (Q27K, N316S, A486V, and P496L) are phenotypically indistinguishable from wild-type EXT1. Three of these four "active" mutations affect amino acids that are not conserved among vertebrates and invertebrates, whereas all of the HS-biosynthesis null mutations affect only conserved amino acids. Further, substitution or deletion of each of these four residues does not abrogate HS biosynthesis. Taken together, these results indicate that several of the reported etiological mutant EXT forms retain the ability to synthesize and express HS on the cell surface. The corresponding missense mutations may therefore represent rare genetic polymorphisms in the EXT1 gene or may interfere with as yet undefined functions of EXT1 that are involved in HME pathogenesis.

Amino Acid Sequence↗
PubMed2001

Specific inhibition of coxsackievirus B3 translation and replication by phosphorothioate antisense oligodeoxynucleotides.

The 5' and 3' untranslated regions (UTRs) of coxsackievirus B3 (CVB3) RNA form highly ordered secondary structures that have been confirmed to play important regulatory roles in viral cap-independent internal translation initiation and RNA replication. We previously demonstrated that deletions in different regions of the 5' UTR significantly reduced viral RNA translation and infectivity. Such observations suggested strongly that viral RNA translation and replication could be blocked if highly specific antisense oligodeoxynucleotides (AS-ODNs) were applied to target crucial sites within the 5' and 3' UTRs. In this study, seven phosphorothioate AS-ODNs were synthesized, and the antiviral activity was evaluated by Lipofectin transfection of HeLa cells with AS-ODNs followed by infection of CVB3. Analysis by Western blotting, reverse transcription-PCR, and viral plaque assay demonstrated that viral protein synthesis, genome replication, and infectivity of CVB3 were strongly inhibited by the AS-ODNs complementary to different regions of the 5' and 3' UTRs. The most effective sites are located at the proximate terminus of the 5' UTR (AS-1), the proximate terminus of the 3' UTR (AS-7), the core sequence of the internal ribosome entry site (AS-2), and the translation initiation codon region (AS-4). These AS-ODNs showed highly sequence-specific and dose-dependent inhibitory effects on both viral protein synthesis and RNA replication. It is noteworthy that the highest inhibitory activities were obtained with AS-1 and AS-7 targeting the termini of the 5' and 3' UTRs. The percent inhibition values of AS-1 and AS-7 for CVB3 protein VP1 synthesis and RNA replication were 70.6 and 79.6 for AS-1 and 73.7 and 79.7 for AS-7, respectively. These data suggest that CVB3 infectivity can be inhibited effectively by AS-ODNs.

Enterovirus B, Human↗
PubMed2000

Induction of experimental proteinuria in vivo following infusion of human plasma hemopexin.

BACKGROUND: The human plasma constituent hemopexin (Hx), following incubation with renal tissue, is able to induce glomerular alterations in vitro that are similar to those seen in minimal change disease (MCD). Whether this acute phase reactant is also able to induce proteinuria and minimal change-like alterations in vivo is questioned. METHODS: In the first set of experiments, Hx (4.0 mg in 5.0 mL saline) or equal amounts of control fraction, that is, heat-inactivated Hx (HI-Hx), were infused into conscious rats (N = 6) that had been surgically equipped with a cannula inserted into the suprarenal artery (SRA), enabling direct contact of the infusate and the renal microvasculature. Each animal received HI-Hx at day 1 for 15 minutes (flow rate 20.0 mL/h), subsequently followed by saline for seven hours (Flow rate 5.0 mL/h), after which the cannula was disconnected. At day 2, identical infusions in the same rat were carried out, using native Hx. Urine samples collected every 30 minutes during the experiments were monitored for protein content using standard methods. In the second set of experiments, unilateral perfusion was done ex vivo in anesthetized rats with Hx (N = 5) or HI-Hx (N = 3; 1.5 mg/mL; 4.0 mL during 6 min). After reconnection of the circulation, urine samples of both kidneys were collected every 30 minutes during five hours via ureter cannulation. Urinary protein (expressed as the difference in excretion between perfused and nonperfused kidney) was calculated in mg/24 h. In additional experiments, rats were sacrificed two hours after perfusion of Hx or heat-inactivated (control) Hx (first set of experiments) or after five hours (second set of experiments), and kidneys were processed for immunohistochemical and ultrastructural examination. RESULTS: The results of experiment 1 show a significant increase of proteinuria after Hx infusion versus HI-Hx (means +/- SD, 41.91 +/- 16.01 mg/24 h vs. control, 21.22 +/- 5.69 mg/24 h; P </= 0.03). Histochemical and electron microscopical examination of kidney tissue fragments taken at the time of proteinuria showed diminished expression of glomerular ecto-ATPase and enhanced effacement of epithelial foot processes at the ultrastructural level. In the second set of experiments, the results show significant urinary protein excretion peaking one hour after perfusion (6.63 +/- 7.06 mg/24 h), exclusively in Hx-perfused animals (analysis of variance, P < or = 0.001). CONCLUSION: It is concluded that Hx is able to induce proteinuria associated with MCD-like alterations in rat kidney in vivo.

Adenosine Triphosphatases↗
PubMed1999

Angiotensin II receptor antagonists prevent neointimal proliferation in a porcine coronary artery organ culture model.

OBJECTIVES: Angiotensin II (AngII) generation in response to vascular injury has long been assumed to influence neointimal proliferation contributing to restenosis. This concept has been supported by evidence that ACE inhibition and AT1 receptor blockade effectively limits restenosis in the rat. On the other hand, ACE inhibition has proven ineffective in clinical trails. The present study examines the response of the porcine coronary artery after angioplasty in vitro and compares the actions of an ACE inhibitor to AngII receptor antagonists. METHODS AND RESULTS: Captopril, an ACE inhibitor, and the AngII receptor antagonists, losartan and PD123319, were evaluated for their ability to attenuate neointimal proliferation in a porcine organ culture model of coronary restenosis. The neointima was significantly increased by 300% after angioplasty compared to non-angioplasty controls. The AT1 receptor antagonist, losartan, produced a significant reduction in neointimal index at 10(-5) mol/l, while its in vivo metabolite, EXP3174, reduced neointimal proliferation at 10(-6) mol/l. PD123319, a selective antagonist of the AT2 receptor, also restricted neointimal proliferation at 10(-5) mol/l. Treatment with captopril (10(-6) mol/l) increased the neointimal proliferation by approximately 200% after angioplasty. CONCLUSIONS: Direct blockade of AngII receptors effectively inhibits cell proliferation and restenosis post-angioplasty in vitro. ACE inhibition, exclusive of flow, does not attenuate proliferative restenosis. These data suggest that AngII contributes to neointimal proliferation and validates the concept that receptor antagonists could contribute to the therapeutic management of restenosis.

Analysis of Variance↗
PubMed1999

Is 100KF an isoform of hemopexin? Immunochemical characterization of the vasoactive plasma factor 100KF.

The human vasoactive plasma factor 100KF has been proposed to play a role in minimal change disease in relapse. Since preliminary data suggested similarity between 100KF and the human plasma glycoprotein hemopexin (Hx), this study was conducted to compare 100KF with purified Hx for sequence homology, immunostaining properties in Western and dot-blot assays, ability to affect glomerular ecto-ATPase and glomerular polyanions in vitro, as well as their glomerular permeability increasing effect following alternate perfusion into the rat kidney ex vivo. 100KF was purified from normal pooled plasma according to standard chromatographic techniques, and from the same batch Hx was prepared using affinity chromatography. A second batch of Hx was prepared directly from human serum according to a standard protocol. (For comparison, additional Hx samples obtained from other centers were also included in the study.) The results show: (1) 100% homology of 100KF with plasma Hx after internal sequence analysis; (2) positive staining of the eluate with both monoclonal and polyclonal anti-Hx IgG as well as anti-100KF IgG in dot-blot assays, and similar bands on Western blotting using the same antibodies; (3) affection of glomerular polyanions and glomerular ecto-ATPase after incubation of kidney tissue with either 100KF or Hx (1.5 respectively 1.0 mg/ml; 1.0 h, 37 degrees C), as detected by computerized histochemical quantification; and (4) significant enhancement of urinary protein leakage after Hx perfusion followed by diluted rat serum into the rat kidney ex vivo (Hx: 210.65+/-49.79 microg protein leakage per min versus heat-inactivated Hx control: 112.2+/-49.18 microg per min [both n = 6]). From these data and from the observation that both Hx and 100KF activity can be inhibited by serine protease inhibitors but not by broad spectrum collagenase inhibitors, it is concluded that Hx may be closely related or identical to the active moiety of 100KF.

Amino Acid Sequence↗
PubMed1998

Oxygen-dependent injury by a human plasma factor associated with minimal change disease.

The mechanism by which a human plasma factor associated with proteinuria is able to cause experimental glomerular albumin leakage is unknown. This factor (called 100KF) is able to induce glomerular alterations in the rat kidney, similar to those seen in minimal change disease, including loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase. It was previously shown that 100KF is able to stimulate release of reactive oxygen species in inflammatory cells in vitro. This prompted us to test whether 100KF-induced injury is oxygen dependent. The expression of glomerular sialoglycoproteins and ecto-ATPase was evaluated by standard histochemistry and computerized image analysis and expressed in arbitrary units. Rat kidney sections were incubated with or without 100KF under normal or oxygen-poor, i.e., nitrogen, conditions, or with supplementation of superoxide dismutase (SOD, 100 U/ml). The effect of 100KF on glomerular ecto-ATPase was oxygen dependent (32.98+/-2.14 under air vs. 65.20+/-5.53 under nitrogen, P< or =0.01), in contrast to the 100KF-induced loss of glomerular sialoglycoproteins that was not significantly altered under nitrogen (62.67+/-10.08 under air vs. 61.74+/-26.05 under nitrogen). Supplementation of SOD to 100KF solution under normal incubation conditions also suggested oxygen-dependent impairment of glomerular ecto-ATPase. Alternate perfusion ex vivo of the rat kidney with 100KF followed by diluted plasma showed that enhanced leakage of plasma proteins could be inhibited with SOD, indicating oxygen dependency of this 100KF-induced enhanced permeability (60.25+/-19.32 microg urinary albumin/ml after 100KF perfusion vs. 25.23+/-12.05 microg/ml after 100KF plus SOD, P< or =0.01). We conclude that the action of 100KF upon specific glomerular matrix molecules is oxygen dependent, as is the albumin leakage induced by 100KF in the present ex vivo model.

Adenosine Triphosphatases↗
PubMed1997

Homopolymer mutational hot spots mediate herpes simplex virus resistance to acyclovir.

In the majority of cases, the mechanism underlying the resistance to acyclovir (ACV) of herpes simplex viruses (HSVs) is thymidine kinase (TK) deficiency. Plaque isolates from eight ACV-resistant (ACVr) clinical isolates from AIDS patients, of which five reactivated, were sequenced to determine the genetic lesion within the tk gene conferring resistance and whether this may have correlated with reactivation potential. Mutations were clustered within two homopolymer nucleotide stretches. Three plaque isolates (1737-14, 90-150-3, and 89-650-5) had insertion mutations within a stretch of 7 guanosines, while two isolates (89-063-1 and 89-353-1) had frameshift mutations within a stretch of 6 cytosines (a deletion and an insertion, respectively). Mutations resulted in premature termination codons, and the predicted 28- and 32-kDa truncated TK products were detected by Western blot analysis of virus-infected cell extracts. The repair of one homopolymer frameshift mutation (in isolate 1737-14) restored TK activity, demonstrating that this mutation is the basis of TK deficiency. Of the five reactivated isolates, four were TK deficient and contained frameshift mutations while the fifth retained TK activity because of its altered-TK or Pol- phenotype. These data demonstrate that the majority of ACVr clinical isolates contain frameshift mutations within two long homopolymer nucleotide stretches which function as hot spots within the HSV tk gene and produce nonfunctional, truncated TK proteins.

Acyclovir↗
PubMed1996

Impairment of endothelial and subendothelial sites by a circulating plasma factor associated with minimal change disease.

BACKGROUND: The pathogenesis of albuminuria in minimal change disease (MCD) is unknown. A human plasma factor (denoted as 100KF) is able to induce minimal change-like glomerular alterations, i.e. loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase, following in vitro incubation with kidney tissue. In addition, increased (selective) permeability for plasma proteins occurs after perfusion of 100KF into the rat kidney ex vivo. As in kidney tissue from subjects with minimal change disease, subendothelial injury has also been observed, i.e. reduced anionic sites in the lamina rara interna, the question was raised whether injury induced by the plasma factor 100KF involves vascular endothelium or subendothelial matrix of the glomerular capillary wall. METHODS: Permeability studies were carried out by using confluent endothelial monolayers (HUVEC) cultured on a standard two-compartment system. The permeability for a macromolecular marker (horse radish peroxidase) was tested following incubation of the monolayers with either the native plasma factor 100KF or the control factor (heat-inactivated 100KF), in combination with histochemical evaluation of the cells for ecto-ATPase expression. Also quantification of glomerular anionic sites at the ultrastructural level was carried out, after ex vivo perfusion of 100KF or control factor into rat kidneys. RESULTS: The plasma factor 100KF is able to increase the permeability of human endothelial monolayers for macromolecules in a dose-dependent manner (relative increase 122.4 +/- 24, 178.4 +/- 34 and 236.1 +/- 58% after preincubation with 0.05; 0.5 and 1.5 mg/ml 100KF respectively), concomitant with induction of minimal change-like histochemical alterations such as reduced expression of ecto-ATPase. The number of anionic sites in the lamina rara interna of the glomerular capillary wall is significantly diminished following perfusion with the plasma factor 100KF versus control factor (7.58 +/- 1.60 versus 12.57 +/- 2.05 per 1000 nm; P < or = 0.02); in contrast to the lamina rara externa (22.71 +/- 3.15 versus 22.27 +/- 2.92 per 1000 nm; statistically not significant). CONCLUSIONS: Endothelial cells and subendothelial matrix along the glomerular filtration barrier may be considered as target structures for the plasma factor 100KF, leading to initial minimal change-like alterations associated with glomerular albumin leakage.

Animals↗
PubMed1996

Minimal change-like glomerular alterations induced by a human plasma factor.

Circulating factors, including the plasma protease (100 KF) described previously, have been suspected to play a role in the pathogenesis of minimal change disease (MCD) for several decades. This factor was able to induce MCD-like alterations in kidney tissue in vitro, i.e. impairment of glomerular polyanion (GPA), as well as glomerular ecto-ATPase. We conducted permeability studies using alternate perfusion of the rat kidney ex vivo according to standard techniques. Either native 100 KF (n = 7) or control factor (n = 7) perfusion, followed by perfusion with diluted rat serum was carried out, while urine samples were collected by ureter cannulation. Total urinary protein (by spectrophotometry) as well as IgG (by ELISA) and albumin (by rocket electrophoresis) were measured. Sections of perfused kidneys were stained (immuno-) histochemically for GPA and glomerular ecto-ATPase, and the stainability was quantified using image analysis and expressed as arbitrary units. The results show significantly increased protein leakage after perfusion of 100 KF versus control factor (150.0 +/- 48.9 vs. 33.2 +/- 7.7 micrograms/min, p < or = 0.01), while the IgG/albumin ratio has decreased (12.0 +/- 9.4 vs 26.9 +/- 14.4%, p < or = 0.01). Plasma protein leakage after 100KF perfusion is associated with a significant loss of GPA (57.3 +/- 27.5 vs. 98.4 +/-12.0, p < or = 0.01) and significant decrease of glomerular ecto-ATPase expression (28.7 +/- 11.5 vs. 79.5 +/- 15.0, p < or = 0.001). The capability of 100KF to induce MCD-like glomerular lesions, in association with selectively increased permeability for plasma proteins, suggests that this human plasma constituent may be important in the pathogenesis of MCD.

Adenosine Triphosphatases↗
PubMed1994

Upregulation of antithrombotic ectonucleotidases by aspirin in human endothelial cells in-vitro.

Ecto ATP-diphosphohydrolase (apyrase) activity of human endothelial cells following aspirin treatment has been studied in-vitro. It was shown by HPLC analysis of supernatant samples that pre-incubation of the cultures with aspirin resulted in a significantly increased turnover of supplemented ATP into its degradation products (ADP and AMP). Enhanced expression of ectoenzyme after aspirin treatment could be observed as demonstrated by immunofluorescence-staining with monoclonal anti-apyrase antibodies. This suggests enhancement of endothelial ATP-diphosphohydrolase activity induced by aspirin. The present data obtained in human vascular cells in-vitro are in line with results from previous animal studies in-vivo, suggesting a novel cyclooxygenase-independent antithrombotic activity of aspirin.

Adenosine Diphosphate↗
PubMed1994

Systematic bias in the reporting of angioplasty outcomes: accuracy of visual estimates of absolute lumen diameters.

To examine physician bias in reporting percutaneous transluminal coronary angioplasty (PTCA) results and analyze this potential source of errors, and to examine the ability to estimate absolute lumen diameters visually, the authors reviewed 56 successful PTCAs from their institution. Pre- and postprocedural cineangiograms were blindly reviewed by an experienced consensus panel (three members) and compared with the interventional cardiologist's reported outcome (percentage diameter stenosis) and quantitative coronary angiography (QCA) using the Cardiac Measurement System. Staff cardiologists significantly overestimated pre-PTCA stenosis severity (staff 83.7 versus panel 75.2%, P < 0.05) while underestimating residual narrowing (staff 18.4 versus panel 22.8%, P < 0.05), thus exaggerating overall angioplasty benefit (staff -65.3 versus panel -52.4%, P < 0.05). The cumulative error varied greatly among individual staff members (3.4 to 18.0%). Despite these findings, the consensus panel accurately identified pre-PTCA minimum lumen diameter, as measured by quantitative angiography (panel 0.66 versus QCA 0.67 mm, not significant), although they tended to overestimate absolute postprocedural luminal dimensions (panel 2.28 versus QCA 2.00 mm, P < 0.05) and thereby ultimate changes in minimum lumen diameter (panel 1.62 versus QCA 1.33 mm, P < 0.05). Therefore, substantial bias exists in the reporting of PTCA outcomes, which tends to magnify the perceived benefits of the procedure. Well-trained observers can accurately estimate pre-PTCA absolute lumen diameters, although difficulties occur in evaluating residual dimensions.

Adult↗
PubMed1993

Metabolic adaptations to endurance training in older individuals.

The purpose of this study was to describe the effects of moderate intensity exercise training on the muscle energy utilization, blood flow, and exercise performance of four sedentary older individuals (58 +/- 4 yrs). Subjects trained the dominant forearm each day for 12 weeks. The nondominant arm was not trained and served as a within-subject control. 31P nuclear magnetic resonance spectroscopy (31P NMRS) was used to identify the power output in watts (W) at the onset, or threshold, of intracellular acidosis (IT) in the exercising muscle during progressive exercise tests to fatigue. After 6 weeks of training, power output at the IT increased by 14% (p < 0.05) in the dominant arm; however, an additional 6 weeks of the same exercise program failed to produce a further increase in IT power. IT power of the nondominant forearm was not changed. In the dominant forearm, endurance time for a submaximal wrist flexion test was increased 34% and 58% at 6 and 12 weeks, respectively. Maximal voluntary strength was not affected by training, nor was resting or exercising blood flow. The training program delayed the onset of intracellular acidosis during progressive exercise and increased the capacity for submaximal work. These effects did not appear to depend on an increase in muscle blood flow.

Acidosis↗
PubMed1991

Incidence of bacteremia in transesophageal echocardiography: a prospective study of 140 consecutive patients.

The incidence of bacteremia related to transesophageal echocardiography was studied in 140 consecutive patients (71 women and 69 men with a mean age of 53.7 +/- 15 years). Thirty-four patients had one or more prosthetic heart valves. Blood cultures were obtained from each patient through separate venipuncture sites immediately before and after transesophageal echocardiography. An additional late blood culture was obtained in 114 patients 1 h later. The skin was cleaned with povidone-iodine and venipunctures were performed with separate butterfly needles with use of sterile gloves and drapes. Blood samples were drawn into separate syringes, transferred to aerobic and anaerobic culture bottles and processed with use of a semiautomated system. The overall incidence of blood cultures positive for bacteremia was 2% (8 of 394 bottles) and all positive cultures grew in a single blood culture bottle. Positive cultures occurred in 4 (1.4%) of 280 bottles before the procedure, in 2 (0.7%) of 280 bottles immediately after the procedure and in 2 (0.9%) of 228 late (1-h) blood culture bottles. Bacterial isolates were coagulase-negative staphylococci (n = 5), Propionibacterium (n = 2) and Moraxella (n = 1). All were considered contaminants. Mean endoscopic time in these patients was not significantly different from that in the other patients. Follow-up of patients with a blood culture positive for bacteremia revealed no clinical evidence of systemic infection. It is concluded that 1) the incidence of bacteremia related to transesophageal echocardiography is very low, and 2) the incidence of blood cultures positive for bacteremia after transesophageal echocardiography is indistinguishable from the anticipated contamination rate.

Adult↗
PubMed1990

Splenic hemorrhage: a complication of tissue plasminogen activator treatment.

Thrombolytic therapy with tissue plasminogen activator (tPA) for acute myocardial infarction may result in major bleeding complications such as gastrointestinal or intracranial bleeding. A case is described of severe splenic hemorrhage and rupture which developed 3 h after completion of tPA infusion for suspected acute myocardial infarction. The patient developed hypovolemic shock with abdominal pain and distension and further evidence of myocardial necrosis. A computed tomography scan of the abdomen was helpful in elucidating the diagnosis, and surgical splenectomy resulted in a good patient outcome, though the period of hypotension had increased the extent of myocardial necrosis.

Aged↗
PubMed1982

Thymine inhibits suppression by an Escherichia coli nonsense and frameshift suppressor.

A mutant strain of Escherichia coli suppressed a frameshift and some UAG, UAA, and UGA mutants of bacteriophage T4 at 37 degrees C but not at 31 degrees C. This suppression was inhibited by the addition of thymine or thymidine to the medium used to test phage growth. Furthermore, the suppressor strain required thymine or thymidine for growth on minimal medium at 43 degrees C and if this auxotrophy was removed by reversion or recombination the strain no longer suppressed. These results suggest a link between thymidine nucleotide biosynthesis and suppression.

Escherichia coli↗