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PubMed1998

Improvement in resource utilization after development of a clinical pathway for patients with pressure ulcers.

Clinical pathways are interdisciplinary patient care plans intended to reduce variance and improve quality of care while lowering health care cost. This study was undertaken to determine whether the development of a clinical pathway for care of patients with pressure ulcers can indeed decrease health care costs while preserving quality of care. A clinical pathway for surgical reconstruction of pressure ulcers was developed by standardizing the current practices of our plastic surgeon group. The pathway provided direction in optimal scheduling of physician interventions along with nursing, physical and occupational therapies, and spinal cord rehabilitation interventions. It covered all potential elements of patient care, including laboratory, radiology, dietary services, intravenous fluids, and use of specialty beds. It defined patient outcomes and outlined discharge planning. Pathways were distributed throughout all services caring for patients with pressure ulcers. Patient charts and billing data were reviewed for the 16-month periods before and after initiation of the pathway. No other significant changes in treatment occurred during this time frame. Ninety-seven patient charts were examined (54 before pathway and 43 after pathway implementation). Parameters evaluated included length of stay and total charges (including bed use, medications, laboratory tests, and radiology). Patient readmission rate was also examined. A significant reduction in patient length of stay and total charges was achieved after implementation of the clinical pathway. Reduction was seen not only for patients treated with flaps by plastic surgery but also for patients with pressure ulcers who were not specifically targeted such as those from other services. The readmission rate decreased slightly, although not significantly, after the pathway inception. Total cost saving was almost $11,000 per patient (23 percent). In conclusion, implementation of a clinical pathway, because it standardizes care and reduces variations and duplication of care, can reduce health care cost without impairing quality of care in the treatment of decubitus ulcer patients.

Costs and Cost Analysis↗

PubMed1991

Limitedly selective action of a delta-agonistic leu-enkephalin on the transmission in spinal motor reflex pathways in cats.

1. The influence of the delta-opioid receptor agonist (D-Ser2)-leu-enkephalin (Thr6) (DSLET) on different spinal reflex pathways was investigated in anaemically decapitated, high spinal cats. Monosynaptic reflexes were tested to analyse excitatory and inhibitory flexor reflex afferent (FRA) pathways from nociceptive (from the skin of the central pad) and non-nociceptive (from skin, joint or group II muscle) afferents, as well as an excitatory nociceptive non-FRA pathway from the central pad to plantaris and intrinsic foot extensors and the inhibitory pathway from Ib muscle afferents. 2. DSLET suffused over the spinal cord (concentration 10(-3)-10(-6) M) caused a concentration-dependent depression of transmission in nociceptive and non-nociceptive FRA pathways. The excitatory FRA pathways including those from group II muscle afferents were more sensitive than the inhibitory ones. The nociceptive non-FRA pathway from the central pad to plantaris and intrinsic foot extensors was less affected than the FRA pathways. The inhibitory pathway from Ib muscle afferents remained almost unaffected. 3. Intravenous injection of DSLET (0.5-3.6 mg/kg) induced dose-dependent effects similar to those from local spinal application. The main difference was that I.V. injection more readily caused depression of the inhibitory FRA pathways to extensors. 4. The effects of local spinal application and of I.V. injection of DSLET were antagonized by I.V. injection of naloxone (0.1-1 mg/kg). 5. The effects of DSLET on spinal reflex pathways in many respects resemble that of monoamines. Possibly there is an interaction and a co-operation of enkephalins and monoamines in motor control.

Afferent Pathways↗

PubMed1993

Magnocellular pathway for rotation invariant Neocognitron.

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

Algorithms↗

PubMed2002

Properties of the pathways from the lateral amygdal nucleus to basolateral nucleus and amygdalostriatal transition area.

Studies have revealed that the amygdala formation is involved in emotional learning, attention, and autonomic functions. Although intra-amygdala connections have been described anatomically, the functional characteristics of these connections are not well understood. We used a rat brain slice preparation with a voltage-sensitive imaging system to compare the electrophysiological characteristics of intra-amygdala pathways. Electrical stimuli delivered to the lateral nucleus (La) caused the optical signal to propagate to basolateral nucleus (BL) and amygdalostriatal transition area (AStr), but not the central nucleus (Ce), consistent with previous anatomical studies, including the recently characterized projections from La to AStr. The velocity of propagation of the evoked potential along the La-AStr pathway was significantly faster than that along the La-BL pathway. In addition, the efficiency of the signal transmission (determined by the rate of decay) along the La-AStr pathway was higher than that along the La-BL pathway. Also, AStr possessed a distinct property of temporal summation of La signals. On the other hand, the La-BL pathway possessed a significantly higher sensitivity to bicuculline/picrotoxin and a stronger paired-pulse inhibition than the La-AStr pathway. Furthermore, the La-BL pathway expressed a higher D-2-amino-5-phosphonovaleric acid (a NMDA blocker) sensitivity than the La-AStr pathway. These results suggest that the La-AStr pathway, which conducts signals with high velocity and less attenuation, may be involved in rapid reflexive responses during fear-induced behavior, whereas the La-BL pathway facilitates signal integration and learning.

2-Amino-5-phosphonovalerate↗

PubMed2003

Laparoscopy-assisted vaginal hysterectomy clinical pathway. A multivariate analysis of impact on costs and quality of care.

Numerous studies have demonstrated that a well-designed clinical pathway is an effective means of sustaining quality while controlling costs in the management of certain disease entities. We evaluated the impact that cost and medical quality have on the implementation of a clinical pathway for laparoscopy-assisted vaginal hysterectomy (LAVH). This retrospective study involved a sample of 124 patients who underwent LAVH in a medical center in central Taiwan. Patients were divided into two groups on the basis of whether they received treatment before or after implementation of the LAVH clinical pathway. The preclinical pathway group was comprised of 40 patients who underwent LAVH before clinical pathway implementation (May-December 1997). The clinical pathway group included 84 patients who underwent LAVH after implementation of the clinical pathway (January 1998-March 1999). In order to study the impact of the LAVH clinical pathway, patient characteristics were controlled by multiple linear regression. The results showed a significant reduction in cost, average length of hospital stay, and average duration of surgery and anesthesia (p < 0.01). Dependent nominal variables for clinical indicators like postoperative intravenous fluid and injection of antibiotics 48 h after surgery, and complications were analyzed by a logistic regression model. The results noted better control of antibiotic intravenous injection 48 h after surgery in the clinical pathway group (p = 0.03). The other indicators included delay of operation day, blood transfusion, patient mortality, and patients readmitted within 2 weeks. There was one operation day delay and one readmission within 2 weeks of discharge in the preclinical pathway group. Based on our results, the implementation of a clinical pathway for LAVH contains cost while maintaining quality of care, especially when the medical fees are paid under the case payment system.

Adult↗

PubMed2006

Effectiveness of a clinical pathway for acute stroke care in a district general hospital: an audit.

BACKGROUND: Organised stroke care saves lives and reduces disability. A clinical pathway might be a form of organised stroke care, but the evidence for the effectiveness of this model of care is limited. METHODS: This study was a retrospective audit study of consecutive stroke admissions in the setting of an acute general medical unit in a district general hospital. The case-notes of patients admitted with stroke for a 6-month period before and after introduction of the pathway, were reviewed to determine data on length of stay, outcome, functional status, (Barthel Index, BI and Modified Rankin Scale, MRS), Oxfordshire Community Stroke Project (OCSP) sub-type, use of investigations, specific management issues and secondary prevention strategies. Logistic regression was used to adjust for differences in case-mix. RESULTS: N = 77 (prior to the pathway) and 76 (following the pathway). The median (interquartile range, IQR) age was 78 years (67.75-84.25), 88% were European NZ and 37% were male. The median (IQR) BI at admission for the pre-pathway group was less than the post-pathway group: 6 (0-13.5) vs. 10 (4-15.5), p = 0.018 but other baseline variables were statistically similar. There were no significant differences between any of the outcome or process of care variables, except that echocardiograms were done less frequently after the pathway was introduced. A good outcome (MRS < 4) was obtained in 66.2% prior to the pathway and 67.1% after the pathway. In-hospital mortality was 20.8% and 23.1%. However, using logistic regression to adjust for the differences in admission BI, it appeared that admission after the pathway was introduced had a significant negative effect on the probability of good outcome (OR 0.29, 95%CI 0.09-0.99). CONCLUSION: A clinical pathway for acute stroke management appeared to have no benefit for the outcome or processes of care and may even have been associated with worse outcomes. These data support the conclusions of a recent Cochrane review.

Aged↗

PubMedDate not supplied

Pathways for continence care: an audit to assess how they are used.

This is a follow-up article to three articles that were published between 2000 and 2001 in the British Journal of Nursing about the development of template pathways for continence care (Bayliss et al, 2000a,b, 2001). It reports on what has happened since the development of these templates. One hundred and forty-four healthcare professionals working in the field of continence care were asked to complete a questionnaire about whether the pathways are being used and what changes have been made to them. The audit found nearly half of the respondents are currently using the pathways and find them an effective method of assessing incontinence and providing equitable quality of care for patients. Many respondents have made changes to the pathways, making them easier to use and adapting them to local practice and the availability of local resources. This was what was anticipated, although the authors noted that variance tracking, which should be the driver for change, had not significantly influenced local pathways. Of those healthcare professionals not using pathways, all said they were still interested in using them, which is particularly encouraging as pathways are promoted in 'Guidelines for Continence Care' (Department of Health, 2000). To provide support to these individuals and encourage the efforts of those already using the pathways, a support group is to be established following a further conference on pathways for continence care later this year. It will be the role of this group to facilitate information sharing on pathway development. As a first step in the dissemination of information, a pack is being produced comprising consolidated versions of the changes to the pathways used in practice all over the country.

Clinical Nursing Research↗

PubMed2004

Convergence and segregation of the multiple rod pathways in mammalian retina.

Using a multidisciplinary approach, we demonstrate that three different pathways are responsible for the transmission of rod signals across the mouse retina. Each pathway serves a primarily nonoverlapping range of stimulus intensities, with ganglion cells receiving either segregated or convergent inputs. For both on-center (ON) and off-center (OFF) ganglion cells, the primary rod pathway carries signals with the lowest threshold, whereas the secondary rod pathway is less sensitive by approximately 1 log unit. In addition, OFF signaling uses a tertiary rod pathway that is approximately 1 log unit less sensitive than the secondary. Although some ganglion cells received rod inputs exclusively from one of the pathways, others showed convergent inputs. Using pharmacological and genetic approaches, we defined classes of ON and OFF ganglion cells for which the scotopic inputs derive only from the primary pathway or from both primary and secondary pathways. In addition, we observed a class of OFF ganglion cell receiving mixed input from primary and tertiary pathways. Interestingly, OFF ganglion cells receiving convergent inputs from all three rod pathways or from the secondary and tertiary pathways together were never observed. Overall, our data show a complex arrangement of convergence and segregation of rod inputs to ganglion cells in the mammalian retina.

Action Potentials↗

PubMed2006

Multiple circuits relaying primate parallel visual pathways to the middle temporal area.

Parallel pathways in the primate visual system parse the sensory signal into magnocellular (M), parvocellular (P), and koniocellular (K) streams. These pathways remain anatomically separate and distinct from their origination in different retinal ganglion cell types, through distinct layers of the lateral geniculate nucleus, and into primary visual cortex (V1), with the M pathway terminating primarily in layer 4Calpha, the P pathway in layer 4Cbeta, and the K pathway in the cytochrome oxidase blobs of layer 2/3. Recent studies indicate that outputs from V1 are less compartmental than previously thought, making it difficult to assess the contributions of M and P pathways to areas beyond V1 in the dorsal and ventral streams. Here we use rabies virus as a retrograde transsynaptic tracer to study the contributions of M and P pathways to areas middle temporal (MT), V3, and V2 of macaque monkey. We find that, although disynaptic inputs through layer 4C of V1 to dorsal stream area MT are dominated by the M pathway, within an additional three synapses MT receives a substantial P input. This P input is unlikely to reach MT via V3, which we show also receives disynaptic inputs dominated by the M pathway. We find that disynaptic inputs to V2, however, can be more balanced and may carry convergent M and P input to MT. Our observations provide evidence for multiple pathways from V1 to MT, with varying degrees of M and P convergence. Each pathway likely provides functionally specialized information to MT and dorsal stream visual processing.

Animals↗

PubMed2000

Mortality and morbidity after hip fracture: can evidence based clinical pathways make a difference?

OBJECTIVE: To evaluate whether evidence based clinical pathways for acute management of hip fracture have an effect on patient care, short term mortality, or residential status. METHODS: Observational cohort study comparing management, as determined by medical record review, and outcomes, as determined by telephone followup 4 months post-fracture, before (n = 455) and after (n = 481) clinical pathway implementation within pathway hospitals as well as between patients admitted to hospitals with (n = 2) and without (n = 4) pathways. RESULTS: Mean age was 82 years, 80% were women and 30% were admitted from nursing homes. Significant improvement in best practice as recommended by evidence based clinical guidelines was evident in pathway hospitals for most components of care. However, compliance was variable and nonpathway hospitals performed better for some (use of spinal anesthesia, avoidance of urinary catheters). After adjusting for potential confounders, no difference was found in 4 month mortality between the pathway (17.6%) and non-pathway (16.8%) patients (OR 0.8, 95% CI 0.5-1.5). There was a nonsignificant reduction in median acute care hospital length of stay of 1 day (p = 0.200) for non-nursing home patients and a significant reduction of 1 day (p = 0.038) for nursing home patients in the pathway hospitals. There was a nonsignificant decrease in admission rates for new patients to nursing homes in pathway hospitals (18.5%) compared to non-pathway hospitals (24.3%) (OR 0.5, 95% CI 0.3-1.1). CONCLUSION: Clinical pathways were associated with increased use of evidence based best practice, some reduction in acute hospital length of stay, but no significant effect on 4 month mortality or residential status. Their development and maintenance were resource intensive and further work on the implementation of evidence based guidelines is needed to determine whether they can influence patient outcomes.

Aged↗

PubMed2002

Effect of a clinical pathway on selected clinical outcomes of pulmonary lobectomy.

BACKGROUND: North American hospitals use clinical care pathways to reduce length of stay, readmissions, and resource utilization and also to increase patient satisfaction. This study examined the effects of clinical pathways after pulmonary lobectomy in Taiwanese patients. METHODS: During 1997, a multidisciplinary team developed a lobectomy clinical pathway. The Program Evaluation Review Technique was used to analyze variances from the clinical pathway. Based on these findings, a standardized clinical pathway was implemented in late 1997. Forty patients participated. The variables of the study are length of hospital stay, readmission rates, spirometry usage, patient education and costs benefited from clinical care pathway use. RESULTS: Fourteen lobectomy patients following the clinical pathway had a mean length of stay of 17.9+/-4.18 days (p < 0.001) and 0% readmission (p < 0.001). Without a pathway, 26 lobectomy patients had a mean length of stay of 37.5+/-6.18 days and 18% were readmitted. Factors affecting clinical pathway success were preoperative days(p < 0.001), postoperative days (p = 0.033), spirometry usage (p = 0.043) and patient education (p = 0.02). Clinical pathway use reduced mean hospital costs by 16% for lobectomy. CONCLUSIONS: Length of hospital stay, readmission rates, spirometry usage, patient education and costs benefitted from clinical care pathway use. Factors critical to success appear to be multidisciplinary teamwork and communication.

Critical Pathways↗

PubMedDate not supplied

Use and evaluation of critical pathways in hospitals.

CONTEXT: Although hospitals have devoted substantial resources to critical pathways, it is not known whether they routinely evaluate the clinical or economic effects of these pathways. OBJECTIVE: To determine how use and evaluation of critical pathways differ between academic and community hospitals. DESIGN: Cross-sectional survey. PARTICIPANTS: Hospitals participating in consortia for improving quality of care associated with the Institute of Health Care Improvement and the VHA, Inc. (formerly known as the Voluntary Hospitals of America, Inc.). Hospital administrators at 41 hospitals completed the survey (71% response rate), representing 13 academic medical centers, 13 community teaching hospitals, and 15 community hospitals. MEASURES: Use of critical pathways and measurement of clinical and economic outcomes of pathways. RESULTS: The median number of adult critical pathways used by academic hospitals, community teaching hospitals, and community hospitals was 25, 18, and 3, respectively. The most common pathways were community-acquired pneumonia, total hip or knee replacement, and stroke or transient ischemic attack. The percentage of hospitals with pathways dedicating staff to manage them was 78% for academic hospitals, 22% for community teaching hospitals, and 14% for community hospitals (P = 0.02). Evaluation practices varied widely among hospitals with pathways. Measures assessed included monitoring length of stay (85%), total hospital costs (74%), in-hospital mortality (62%), infectious complications (53%), readmission rates (47%), functional status (18%), and adverse drug events (15%). CONCLUSION: The use of critical pathways varies substantially among hospitals participating in quality improvement consortia. Use was highest in academic centers and lowest in community hospitals. Many hospitals with pathways do not track important clinical outcomes as part of their evaluation practices.

Academic Medical Centers↗

PubMed2000

High variability of retrograde fast pathway sensitivity to adenosine.

BACKGROUND: Adenosine is widely used as a tool to assess the effectiveness of radiofrequency ablation of concealed accessory pathways. HYPOTHESIS: The goal of this study was to determine the reliability of this test by studying the retrograde fast pathway sensibility in a large patient population with typical atrioventricular (AV) nodal reentry tachycardias. We sought also to determine whether AV nodal properties were predictive of a retrograde fast pathway sensitivity to adenosine. METHODS: In all, 124 patients with inducible AV nodal reentrant tachycardia were included in this study. All patients received a clinically used standard dose of 12 mg adenosine during ventricular pacing, with 500 ms and a constant ventriculoatrial (VA) conduction via the fast pathway. Electrophysiologic parameters of the AV node were determined in all patients in order to correlate them with the adenosine sensitivity of the retrograde pathway. RESULTS: In 74 patients, the injection of 12 mg adenosine resulted in a transient VA block, whereas no VA block occurred in the remaining 50 patients. In two patients, concealed accessory pathways were unmasked after the injection of adenosine. The adenosine sensitivity of the retrograde fast pathway was associated with longer retrograde conduction times and cycle lengths during AV nodal reentrant tachycardias. CONCLUSION: This study shows a high variability of retrograde fast pathway sensitivity to adenosine. Thus, in 40% of patients the lack of VA block after adenosine injection is not specific for persistent accessory pathway function after radiofrequency ablation. Electrophysiologic properties of patients with AV nodal reentrant tachycardias were different in patients with and without adenosine-sensitive retrograde fast pathways, possibly indicating differential patterns of penetration of the retrograde fast pathway into the compact AV node.

Adenosine↗

PubMed2005

Genome wide analysis of transcript levels after perturbation of the EGFR pathway in the Drosophila ovary.

Defects in the epidermal growth factor receptor (EGFR) pathway can lead to aggressive tumor formation. Activation of this pathway during normal development produces multiple outcomes at the cellular level, leading to cellular differentiation and cell cycle activation. To elucidate the downstream events induced by this pathway, we used genome-wide cDNA microarray technology to identify potential EGFR targets in Drosophila oogenesis. We focused on genes for which the transcriptional responses due to EGFR pathway activation and inactivation were in opposite directions, as this is expected for genes that are directly regulated by the pathway in this tissue type. We perturbed the EGFR pathway in epithelial follicle cells using seven different genetic backgrounds. To activate the pathway, we overexpressed an activated form of the EGFR (UAS-caEGFR), and an activated form of the signal transducer Raf (UAS-caRaf); we also over- or ectopically expressed the downstream homeobox transcription factor Mirror (UAS-mirr) and the ligand-activating serine protease Rhomboid (UAS-rho). To reduce pathway activity we used loss-of-function mutations in the ligand (gurken) and receptor (torpedo). From microarrays containing 6,255 genes, we found 454 genes that responded in an opposite manner in gain-of-function and loss-of-function conditions among which are many Wingless signaling pathway components. Further analysis of two such components, sugarless and pangolin, revealed a function for these genes in late follicle cell patterning. Of interest, components of other signaling pathways were also enriched in the EGFR target group, suggesting that one reason for the pleiotropic effects seen with EGFR activity in cancer progression and development may be its ability to regulate many other signaling pathways.

Animals↗

PubMed2001

Evolutionary optimization of metabolic pathways. Theoretical reconstruction of the stoichiometry of ATP and NADH producing systems.

The structural design of ATP and NADH producing systems, such as glycolysis and the citric acid cycle (TCA), is analysed using optimization principles. It is assumed that these pathways combined with oxidative phosphorylation have reached, during their evolution, a high efficiency with respect to ATP production rates. On the basis of kinetic and thermodynamic principles, conclusions are derived concerning the optimal stoichiometry of such pathways. Extending previous investigations, both the concentrations of adenine nucleotides as well as nicotinamide adenine dinucleotides are considered variable quantities. This implies the consideration of the interaction of an ATP and NADH producing system, an ATP consuming system, a system coupling NADH consumption with ATP production and a system consuming NADH decoupled from ATP production. It is examined in what respect real metabolic pathways can be considered optimal by studying a large number of alternative pathways. The kinetics of the individual reactions are described by linear or bilinear functions of reactant concentrations. In this manner, the steady-state ATP production rate can be calculated for any possible ATP and NADH producing pathway. It is shown that most of the possible pathways result in a very low ATP production rate and that the very efficient pathways share common structural properties. Optimization with respect to the ATP production rate is performed by an evolutionary algorithm. The following results of our analysis are in close correspondence to the real design of glycolysis and the TCA cycle. (1) In all efficient pathways the ATP consuming reactions are located near the beginning. (2) In all efficient pathways NADH producing reactions as well as ATP producing reactions are located near the end. (3) The number of NADH molecules produced by the consumption of one energy-rich molecule (glucose) amounts to four in all efficient pathways. A distance measure and a measure for the internal ordering of reactions are introduced to study differences and similarities in the stoichiometries of metabolic pathways.

Adenosine Triphosphate↗

PubMed2001

The evolution and structural anatomy of the small molecule metabolic pathways in Escherichia coli.

The 106 small molecule metabolic (SMM) pathways in Escherichia coli are formed by the protein products of 581 genes. We can define 722 domains, nearly all of which are homologous to proteins of known structure, that form all or part of 510 of these proteins. This information allows us to answer general questions on the structural anatomy of the SMM pathway proteins and to trace family relationships and recruitment events within and across pathways. Half the gene products contain a single domain and half are formed by combinations of between two and six domains. The 722 domains belong to one of 213 families that have between one and 51 members. Family members usually conserve their catalytic or cofactor binding properties; substrate recognition is rarely conserved. Of the 213 families, members of only a quarter occur in isolation, i.e. they form single-domain proteins. Most members of the other families combine with domains from just one or two other families and a few more versatile families can combine with several different partners. Excluding isoenzymes, more than twice as many homologues are distributed across pathways as within pathways. However, serial recruitment, with two consecutive enzymes both being recruited to another pathway, is rare and recruitment of three consecutive enzymes is not observed. Only eight of the 106 pathways have a high number of homologues. Homology between consecutive pairs of enzymes with conservation of the main substrate-binding site but change in catalytic mechanism (which would support a simple model of retrograde pathway evolution) occurs only six times in the whole set of enzymes. Most of the domains that form SMM pathways have homologues in non-SMM pathways. Taken together, these results imply a pervasive "mosaic" model for the formation of protein repertoires and pathways.

Bacterial Proteins↗

PubMed1979

Mechanisms of recombination by the RecBC and the RecF pathways following conjugation in Escherichia coli K12.

The recombinational processes directed by the RecBC and the RecF pathways following conjugation in E. coli have been compared. The viable recombinant products of the RecF pathway show a higher incidence of mismatch correction, higher percentage of heterogeneous clones produced by single ex-conjugants and a much slower rate of integration and segregation compared to the RecBC pathway. There are reasons to suspect that the product of recB and recC genes may be necessary for conversion of the single stranded donor DNA in the zygote to double stranded DNA. Theoretical considerations suggest that an exchange involving only one strand of DNA may be a much slower process, with more stringent homology requirement for the entire exchanged segment, than a double strand exchange of a comparable length; the latter should be much faster, with stringent homology requirements for only the terminal regions of the exchanged segments. It is suggested that the RecF pathway mainly mediates replacement of relatively long stretches of single strands of recipient DNA by the corresponding strands of donor DNA while the RecBC pathway mediates exchange of mostly double stranded DNA between the donor and the recipient; in addition, the RecBC pathway may also catalyze the integration of very small segments of single strands of the donor DNA. A model based on the above basic hypothesis is described. It is further suggested that the enzymes exonucleaseV and exonucleaseI Control the relative yields of the recombinants produced by the two pathways by regulating the supply of the donor substrates required by these pathways; the former diverts the potential substrate of the RecF pathway (single stranded DNA) to the duplex substrates of the RecBC pathway while the latter destroys the substrates of the RecF pathway, especially in absence of exonucleaseV.

Conjugation, Genetic↗

PubMed2004

cDNA microarray-based identification of genes and pathways associated with oxaliplatin resistance.

In order to identify genes whose expression is associated with resistance to the chemotherapeutic agent oxaliplatin, transcripts differentially expressed between an oxaliplatin sensitive and a stably resistant subline were compared in six independent replicates using Stanford cDNA microarrays for five cell lines. "Significance analysis of microarrays" (SAM) was used to identify genes whose expression was statistically significantly different in the sensitive versus resistant members of each cell line pair. The biochemical pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were searched to identify those pathways in which the number of SAM-identified genes exceeded the number expected. This identified four pathways in which upregulated genes were significantly associated with resistance in two of the cell line pairs, and two pathways in which the association was found in three cell line pairs. The search also identified 12 pathways in which downregulated genes were associated with resistance in two cell line pairs and one pathway in which the association reached statistical significance in three cell line pairs. Pathways identified included the ribosome pathway, the Huntington's disease pathway that includes caspase 8, and the ATP synthesis pathways. Determination of the chromosomal location of each SAM-identified gene revealed several locales within which genes lay in close proximity, including three genes (APACD, IF-2, and REV1L) located on chromosome 2 that lie immediately adjacent to each other and were significantly upregulated in three of five cell line pairs. Biochemical pathway and chromosomal mapping of genes identified by SAM as differentially expressed in related cell line pairs points to mechanisms and chromosomal sites not previously suspected of association with the oxaliplatin-resistant phenotype.

Adenosine Triphosphate↗