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PubMed1979

Maintenance energy requirements, energy retention and heat production of young obese (ob/ob) and lean mice fed a high-fat or a high-carbohydrate diet.

Female obese (ob/ob) and lean mice were weaned at 21 days of age, placed in wire-mesh cages maintained at 25 to 30 degrees, and fed a high-fat or a high-carbohydrate diet for 21 days. The body energy balance procedure was utilized to determine the maintenance energy requirements, and the efficiency of dietary energy utilization, above maintenance, in these mice. Heat production of each mouse was measured weekly in a gradient-layer calorimeter. Regressions of changes in body energy per kg3/4 on metabolizable energy intake per kg3/4 indicated that the maintenance energy requirement averaged 72 kcal/kg3/4/day for obese mice and 124 kcal/kg3/4/day for lean mice. Diet composition did not influence the maintenance energy requirements, but utilization of energy, above maintenance, in obese mice fed the high-fat diet was 41% more efficient than observed in obese mice fed the high-carbohydrate diet and 38 to 71% more efficient than observed in lean mice. Heat production, per unit body weight was lower in obese mice than in lean mice. The lowest heat production was observed in obese mice fed the high-fat diet. The 40% lower maintenance energy requirement of the obese mice is a major factor contributing to the high efficiency of energy retention in these mice. Consumption of a high-fat diet further improved the ability of the obese mice to retain dietary energy.

Animals↗
PubMed1987

Maintenance nitrogen requirements and intestinal microorganisms in rats.

Nitrogen (N) balance trials with young growing rats fed diets with and without nonabsorbable antibiotics and with various concentrations of crude protein (CP) were conducted to measure maintenance N requirements. In addition, cecal contents were analyzed for ammonia (NH3), urea (U) and free amino acids (AA) to study the reduction in maintenance N requirements due to the action of antibiotics. Results of the N-balance trials verified the reduction in maintenance N requirements with antibiotics as described in the literature. The reduction, however, was not as large as previously demonstrated, possibly because of severe diarrhea and greater liquid accumulation in the cecum of rats fed antibiotics. The concentration of free AA and U in the postabsorptive region of the intestine (cecum) of rats consuming antibiotics was greater than when antibiotics were not consumed. Cecal N concentrations supported the concept that the mode of action of antibiotics in reducing maintenance N requirements was via reduced destruction of AA of body origin in the lower intestine. Cecal levels of NH3 were similar in both antibiotic and nonantibiotic groups. The amount of N needed for body maintenance when conditions favored minimum destruction of body AA by lower intestine microorganisms was small, less than 1% dietary CP. Maintenance N may be limited to the needs for tissues on the exterior of the body, such as hair, which are poorly recycled through the digestive tract.

Amino Acids↗
PubMed2005

Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer.

BACKGROUND: Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC). METHODS: Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided. RESULTS: A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32). CONCLUSION: Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.

Adult↗
PubMed1994

Combined-modality treatment of small-cell lung cancer: randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with small-cell lung cancer with the objective of improving the results of induction chemotherapy and defining the role of consolidating chest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamycin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide and cisplatin given for two cycles). All patients received prophylactic cranial irradiation with 30 Gy, and after four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall response rate of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response rate was achieved with the AVP-induction chemotherapy with an 80% response rate and 32% complete remissions. Similar results were achieved with the alternating regimen of MOC/AVP. In contrast, patients treated with the EVA induction regimen had significantly lower overall remission (56%) and complete remission rates (7%). The role of consolidating chest irradiation could not be clarified in limited-disease patients due to the small number of them who were randomised to the maintenance part of the study. However, in patients with extensive disease in partial remission after induction treatment, combined maintenance therapy had a more significant adverse effect on survival than maintenance chemotherapy alone (median survival in the maintenance phase of 148 days versus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide and cisplatin is an active induction treatment. Consolidating chest irradiation is contraindicated in patients with extensive disease in partial remission after induction when given in a sequential manner, as in our trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy.

Fifty-five episodes of central nervous system (CNS) toxoplasmosis developing in 43 of the 329 AIDS cases seen at our institution were diagnosed during a 34-month period and were prospectively studied. Acute episodes were treated with a pyrimethamine/sulfadiazine (P/S) combination for a mean of 21 days. Because of a previously known major allergy to sulfonamides, three episodes were treated with clindamycin instead of sulphadiazine. In those patients who accepted maintenance therapy, a combination of P/S or pyrimethamine and clindamycin (P/C) was administered 2 days per week. Thirty-six patients (83.7%) survived the first episode. Four of these 36 were lost to further study. Six of the 12 (50%) who decided not to undergo maintenance therapy relapsed (mean follow-up: 12 months). Fourteen patients were given P/S and none relapsed while they were on maintenance therapy (mean follow-up: 10.3 months). Six patients received an intermittent maintenance treatment with P/C and one relapsed 2 months after starting the maintenance therapy (mean follow-up: 13.7 months). We conclude that an intermittent (2 days per week) maintenance treatment for CNS toxoplasmosis with P/S was effective in preventing relapses, although prospective randomized studies remain to be done.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effect of maintenance hemodialysis on male sexual performance.

Prior studies have suggested that male patients with uremia suffer from sexual dysfunction that worsens when they are placed on maintenance hemodialysis. The authors report a prospective study of the effect of maintenance hemodialysis on male sexual functioning using nocturnal penile tumescence (NPT) measures and detailed sexual histories. Twenty men already on maintenance hemodialysis and 23 men with advanced renal failure who began maintenance hemodialysis within 4 months of entering the study were followed at 4-month intervals for 1-year and 6-month intervals for the following 18 months. Sexual performance as assessed by NPT, frequency of intercourse, and complaints of erectile failure remained remarkably stable over time for both groups. When renal failure patients moved to maintenance hemodialysis, their frequency of intercourse increased significantly despite stability of NPT. These results suggest not only that maintenance hemodialysis does not worsen sexual functioning, but that adaptation to a sexual deficit is possible after starting hemodialysis.

Adult↗
PubMed1975

A comparison of maintenance and nonmaintenance outpatient prescription directions, durations of coverage, and costs per day.

The purpose of this paper is to present the results of a study on maintenance and nonmaintenance drugs written for outpatients not covered by prescription insurance. The average cost to the patient for a day's supply of drugs, as well as the average dosage, frequency of administration, and length of duration for maintenance and nonmaintenance drugs were examined. The objective of the study was to present the economics and prescribing patterns for the two groups of drugs in order to provide data on the costs involved and the prescribing patterns of physicians. The results of comparing the various components of maintenance and nonmaintenance drugs revealed that significant differences exist in the dosage direction, frequency of administration, units prescribed per day, lengths of duration, costs per day, prescription prices, and quantities prescribed and dispensed. Maintenance drug prescriptions tend to have lower dosage directions, costs per day, and frequencies of administration and higher quantities prescribed and dispensed, prescription prices, and lengths of duration. Two variables, frequency of administration and quantity prescribed, were found to have the greatest influence on the cost per day and length of duration for maintenance drug prescriptions. It is the conclusion of this study that further examination into the factors which influence the physician when he specifies the frequency of administration and quantity to prescribe on maintenance drug prescriptions be conducted.

Analysis of Variance↗
PubMed2000

Prediction of fluindione maintenance dosage hampered by large intraindividual variability.

In a previous study, the authors proposed a method to individualize fluindione dosage regimen, based on a pharmacokinetic/pharmacodynamic model describing the evolution of the International Normalized Ratio (INR). In this method, daily maintenance dosage for a target INR depends on the product of individual Cl and C50. The present work shows the results of a follow-up study in 50 patients for whom target INR was 2.5. INR measurements and dosage regimens were recorded both during hospital stay and during the 1st month of treatment. Patients were defined as equilibrated after 1 month if the last two INRs were in the range 1.5-3.5 under a stable dosage regimen. Actual maintenance dose was compared with the dose predicted using the three first INRs measured in the hospital. Intraindividual variability of Cl*C50 between hospital stay and after 1 month was evaluated. After 1 month, only 27 patients (54%) were equilibrated. Actual maintenance dose varied from 5 to 30 mg daily. There was no bias between predicted and actual maintenance dose (1.4 mg), but a large root mean squared error (8 mg) was found. The intraindividual variability in Cl*C50 between hospital and maintenance regimen was high (93%), which may explain the dispersion in the predicted maintenance dose.

Anticoagulants↗
PubMed2004

Long-term exercise maintenance, physical activity, and health-related quality of life after cardiac rehabilitation.

OBJECTIVE: The purpose of this study was to determine exercise maintenance rate, leisure-time objective physical activity level, and health-related quality of life in relation to exercise maintenance over the 6-mo period after a supervised 5-mo recovery-phase cardiac rehabilitation program in acute myocardial infarction patients. The study also investigated whether exercise maintenance resulted in reproducible health-related quality-of-life outcomes comparable with those of the Japanese normal population. DESIGN: This observational study comprised 109 acute myocardial infarction patients (89 men, 20 women; mean age, 63.5 +/- 10.1 yrs). Physiologic outcomes (peak oxygen uptake, handgrip, and knee-extension strength) measured at 1 and 6 mos after acute myocardial infarction onset were compared. Completed exercise maintenance and health-related quality-of-life questionnaires and results of electronic pedometer recordings to evaluate leisure-time objective physical activity level were assessed 6 mos after cardiac rehabilitation. RESULTS: The mean period from acute myocardial infarction to evaluation of outcomes was 18.8 +/- 3.4 mos. Ninety of 109 patients (82.6%) continued exercise for >6 mos after cardiac rehabilitation (exercise group); 19 patients (17.4%) quit exercise after cardiac rehabilitation (nonexercise group). Improvement in physiologic outcomes was noted at 6 mos vs. those at 1 mo, but outcomes were not significantly different between groups. The exercise group performed significantly better than the nonexercise group for leisure-time objective physical activity level and scored significantly higher than the nonexercise group for seven of eight health-related quality of life measures, attaining scores similar to those of the Japanese normal population. CONCLUSIONS: At >18 mos after acute myocardial infarction, the exercise maintenance rate in our patients remains high, and exercise maintenance may be one of the factors contributing to improvement of health-related quality of life and leisure-time objective physical activity level.

Aged↗
PubMed2006

Innovations in agonist maintenance treatment of opioid-dependent patients.

PURPOSE OF REVIEW: To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. RECENT FINDINGS: The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings show not only efficacy with respect to improvement of health, reduction of illicit drug use, reduction of criminality and stabilization of social conditions, but also cost effectiveness in the treatment of chronic treatment-resistant heroin addicts. SUMMARY: Agonist maintenance treatment has become the first-line treatment for chronic opioid dependence. High-quality studies demonstrate the effectiveness of a growing number of different agonist maintenance treatments for opioid dependence such as methadone and buprenorphine. In addition, there is new evidence for the effectiveness of other agonists, mainly slow-release morphine, intravenous and inhalable diamorphine and possibly oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine should be implemented into the healthcare system to treat a group of severely dependent treatment-resistant patients. Furthermore, the opioid-dependent patients not under treatment need to be engaged in maintenance treatments through other harm reduction measures. Agonist maintenance treatment is very effective in stabilizing the health condition and social situation, while also reducing harm, thereby increasing life expectancy and quality of life.

Buprenorphine↗
PubMed1995

Weight maintenance after a very low calorie diet (VLCD) weight reduction period and the effects of VLCD supplementation. A prospective, randomized, comparative, controlled long-term trial.

OBJECTIVES: To evaluate the efficacy of a structured very low calorie diet (VLCD) weight reduction/weight maintenance behaviour programme on weight maintenance in obese patients (BMI > or = 30 kg/m2). DESIGN: Prospective, randomized, controlled intervention trial. SETTING: University out-patient obesity clinic. SUBJECTS: A total of 114 obese patients from the waiting list were invited to participate in the structured weight reduction/weight maintenance programme lasting for 64 weeks. Sixty patients agreed to participate. INTERVENTION: All 60 patients were placed on a Cambridge 330 kcal day-1 diet during the first 12 weeks. Fifty-two were subsequently randomized to either a well balanced hypocaloric diet (1600 kcal day-1), of which 220 kcal were provided by two sachets of Cambridge diet (group 1), or the same energy provided by the same principal diet (group 2) during the following 52-week weight maintenance period. MAIN OUTCOME MEASURES: During the VLCD period, the mean body weight decreased significantly from 112.4 +/- 19.8 to 91.6 +/- 17.7 kg (P < 0.0001). Seventy-one per cent of the weight loss was fat. During the weight maintenance period the average body weight increased significantly in group 1: 8.0 +/- 8.2 vs. 12.3 +/- 9.7 kg in group 2 (P < 0.0001). After the 64-week treatment period the mean body weight in group 1 was 93.7 +/- 18.1 kg and significantly lower compared to 109.9 +/- 23.8 kg in group 2 (P = 0.008). Compliance was high: 87% completed the VLCD period and 75% completed the whole 64-week treatment programme. CONCLUSION: Very low calorie diet as part of the dietary allowance during the weight maintenance programme partly prevents weight regain. This finding can be translated into practical treatment recommendations.

Adult↗
PubMed2006

Adjusting the frequency of continuation and maintenance electroconvulsive therapy to prevent relapse of catatonic schizophrenia in middle-aged and elderly patients who are relapse-prone.

The purpose of the present paper was to study the effect of continuation electroconvulsive therapy (ECT) on the prevention of relapse in middle-aged and elderly patients with intractable catatonic schizophrenia. It was found that continuation ECT is efficacious to sustain remission for patients who suffer relapse after response to acute ECT despite continuation neuroleptics. However, three patients suffered relapse during continuation ECT, therefore the effect of adjusting the frequency of continuation ECT and maintenance ECT was investigated in these patients with catatonic schizophrenia who relapsed during continuation ECT. These patients with DSM-IV catatonic schizophrenia who relapsed during continuation ECT were treated with more frequent continuation ECT and subsequent maintenance ECT after response to acute ECT. The patients' Brief Psychiatric Rating Scale (BPRS) scores were prospectively evaluated until relapse. Patients were considered to be relapsers if they had a BPRS score >or=37 for 3 consecutive days. The three patients with catatonic schizophrenia who relapsed during continuation ECT were treated successfully with more frequent continuation ECT and subsequent maintenance ECT. No patient experienced a severe adverse effect from continuation or maintenance ECT. More frequent continuation ECT and maintenance ECT deserves consideration in middle-aged and elderly patients with intractable catatonic schizophrenia who suffer relapse during continuation ECT. Large-scale systematic studies are warranted to investigate the optimum use of continuation and maintenance ECT in patients with catatonic schizophrenia.

Aged↗
PubMed2004

Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome.

BACKGROUND: Mild hypoandrogenism in men, usually defined by low levels of testosterone, is a peculiar feature of abdominal obesity that independently predicts the development of insulin resistance and diabetes mellitus. Little is known about the short- and long-term effects of weight loss on sex steroids in abdominally obese men, however. OBJECTIVES: We assessed the effect of rapid weight loss and sustained weight maintenance on the plasma concentrations of testosterone and other sex hormones in 58 abdominally obese men (age, 46.3 +/- 7.5 years; body mass index, 36.1 +/- 3.8 kg/m(2); waist girth, 121 +/- 10 cm) with the metabolic syndrome. RESULTS: The men lost on average 16.3 +/- 4.5 kg during a 9-week very low-calorie diet (VLCD) and maintained 14.3 +/- 9.1 kg weight loss after a 12-month maintenance period (vs. baseline, p < 0.001). Sex hormone-binding globulin (SHBG) increased from 27.6 +/- 11.9 to 48.1 +/- 23.5 nmol/l during the VLCD but decreased to 32.6 +/- 12.9 nmol/l during weight maintenance, which was still higher than at baseline (p < 0.001). Free testosterone (fT) increased from 185 +/- 66 to 208 +/- 70 pmol/l (p = 0.002) during the VLCD and remained high after 1 year of weight maintenance (212 +/- 84 pmol/l, p = 0.002). Total testosterone levels followed a pattern intermediate between fT and SHBG. Plasma estradiol and dehydroepiandrosterone sulphate concentrations changed only transiently or not at all. CONCLUSIONS: Rapid weight loss with successful weight maintenance in abdominally obese men with the metabolic syndrome brings about a sustained increase in fT levels. The dramatic increase in SHBG attenuated initially during weight maintenance but remained elevated. These findings may be important with regard to prevention of progressive metabolic decompensation and cardiovascular disease associated with obesity and the metabolic syndrome.

Adipose Tissue↗
PubMed2005

Maintenance tocolysis.

BACKGROUND: Women who are undelivered after 48 hours of tocolysis remain at increased risk of preterm labour, but it is not clear whether prolonged treatment is effective. OBJECTIVE: To review the current evidence for the effectiveness of maintenance tocolysis. METHODS: The results of published systematic reviews were summarised. RESULTS: Four systematic reviews and two trials published too recently for inclusion were identified. Maintenance tocolysis with beta-agonists and magnesium sulphate was ineffective in prolonging gestation or reducing any adverse fetal outcomes. One trial of maintenance tocolysis with nifedipine was underpowered to rule out an effect on prolonging gestation. One trial using the oxytocin receptor blocker, atosiban, showed that this drug used as maintenance tocolysis does prolong gestation, but the trial was too small to demonstrate any reduction in substantive fetal outcomes. CONCLUSIONS: There is insufficient evidence to justify the routine use of maintenance tocolysis in preterm labour. It remains plausible that prolongation of gestation might be beneficial in selected cases of very preterm labour where fetal compromise and infection have been ruled out. The only tocolytic that has been shown to prolong gestation when used as maintenance therapy is atosiban.

Adrenergic beta-Antagonists↗
PubMed1989

Maintenance of grip on life and goals of life: a valuable criterion for evaluating outcome in schizophrenia.

This article describes the evaluation of schizophrenia patients' maintenance of grip as a comprehensive assessment of the total psychosocial status of these patients. This evaluation was tested with new schizophrenic patients (DSM-III) who took part in a standardized interview at entry and after a 2-year follow-up. The interviews and examinations were conducted by the psychiatric teams responsible for the treatment of the patients. There was a clear positive correlation between the evaluation of maintenance of grip and interpersonal interaction, heterosexual development, hobbies, level of activity and productivity (working) of the patients, and a negative correlation with negative symptoms. The psychodynamically interpreted evaluation of the degree of regression correlated positively with maintenance of grip, but only after the 2-year follow-up. At entry the other variables describing the psychosocial status of the patient explained 22% of the variation in maintenance of grip, but 41% at the follow-up stage. The evaluation of maintenance of grip presented at baseline also predicted the coping of the patients during the follow-up stage. The authors recommend that the evaluation of maintenance of grip be used as an auxiliary tool in the assessment and treatment of schizophrenia patients.

Adolescent↗
PubMed1984

Long-term maintenance of patients treated for advanced periodontal disease.

The aim of the present investigation was to evaluate the periodontal conditions of a group of patients who, following active treatment of extremely advanced periodontal disease, had been maintained for 14 years in a well-supervised maintenance care program. The present sample included 61 subjects out of an initial group of 75 individuals who in 1969 were referred to and treated by the authors. Following an initial examination, the patients were given detailed instructions in proper plaque control measures and were subjected to scaling and root planning and surgical elimination of pathologically deepened pockets. After the termination of the active treatment phase, the patients were placed in a maintenance care program including recall appointments every 3-6 months. At the initial examination, immediately after the completion of the active treatment phase and then once a year, all patients were examined regarding oral hygiene, gingival conditions, probing depths and clinical attachment levels. In addition, the interproximal alveolar bone height was determined from full mouth radiographs obtained before active treatment, at the completion of active therapy and 1, 3, 5, 8, 10, 12 and 14 years after treatment. The results from the repeated examinations demonstrated that treatment of advanced forms of periodontal disease resulted in clinically healthy periodontal conditions and that this state of "periodontal health" could be maintained in most patients and sites over a period of 14 years. It was also demonstrated that the treatment and maintenance programs described were equally effective in young and older patients. The individual mean values describing probing depths, attachment levels, and bone heights did not vary significantly over the 14 years of observation. A more detailed analysis of the data revealed, however, that a small number of sites in a few patients lost a substantial amount of attachment. This attachment loss occurred at different time intervals during the course of the maintenance period. Thus, 43 surfaces in 15 different patients were exposed to recurrent periodontal disease of a significant magnitude. This recurrent inflammatory periodontal disease caused the loss of 16 teeth in 7 different patients during the maintenance period. The data reported question the validity of using individual mean values to describe alterations of the periodontal conditions during maintenance following active periodontal therapy.

Adult↗
PubMed1987

Relationship between malocclusion and maintenance of teeth.

The relationship between the presence of malocclusion and maintenance of teeth in adulthood was studied in a randomly drawn sample of 499 35-44-yr-old Danes. Maintenance of teeth in the past was expressed through the number of teeth present, attachment level and information of regularity of dental visits. Maintenance at present was expressed as caries present, plaque and gingivitis. The relationship of these parameters to the presence of a malocclusion symptom was analyzed directly and the indirect influence was studied through the influence of a subjectively perceived malocclusion and its impact on satisfaction. It appeared that satisfaction was significantly related to maintenance of teeth and to a positive dental behavior. A perceived malocclusion was shown to have a negative influence on satisfaction and thus indirectly on maintenance. If a public orthodontic service is aiming at lifetime maintenance of teeth, malocclusions leading to dissatisfaction with teeth and a subjectively perceived need should be taken into consideration when ranking children with regard to treatment priority.

Adult↗
PubMed1997

Contribution of different segments of the par region to stable maintenance of the broad-host-range plasmid RK2.

A 3.2-kb region of the broad-host-range plasmid RK2 has been shown to encode a highly efficient plasmid maintenance system that functions in a vector-independent manner. This region, designated par, consists of two divergently arranged operons: parCBA and parDE. The 0.7-kb parDE operon promotes plasmid stability by a postsegregational killing mechanism that ensures that plasmid-free daughter cells do not survive after cell division. The 2.3-kb parCBA operon encodes a site-specific resolvase protein (ParA) and its multimer resolution site (res) and two proteins (ParB and ParC) whose functions are as yet unknown. It has been proposed that the parCBA operon encodes a plasmid partitioning system (M. Gerlitz, O. Hrabak, and H. Schwabb, J. Bacteriol. 172:6194-6203, 1990; R. C. Roberts, R. Burioni, and D. R. Helinski, J. Bacteriol. 172:6204-6216, 1990). To further define the role of this region in promoting the stable maintenance of plasmid RK2, the parCBA and parDE operons separately and the intact (parCBA/DE) par region (3.2 kb) were reintroduced into an RK2 plasmid deleted for par and assayed for plasmid stability in two Escherichia coli strains (MC1061K and MV10delta lac). The intact 3.2-kb region provided the highest degree of stability in the two strains tested. The ability of the parCBA or parDE region alone to promote stable maintenance in the E. coli strains was dependent on the particular strain and the growth temperature. Furthermore, the insertion of the ColE1 cer site into the RK2 plasmid deleted for the par region failed to stabilize the plasmid in the MC1061K strain, indicating that the multimer resolution activity encoded by parCBA is not by itself responsible for the stabilization activity observed for this operon. To examine the relative contributions of postsegregational cell killing and a possible partitioning function encoded by the intact 3.2-kb par region, stability assays were carried out with ParD provided in trans by a compatible (R6K) minireplicon to prevent postsegregational killing. In E. coli MV10delta lac, postsegregational killing appeared to be the predominant mechanism for stabilization since the presence of ParD substantially reduced the stability of plasmids carrying either the 3.2- or 0.7-kb region. However, in the case of E. coli MC1061K, the presence of ParD in trans did not result in a significant loss of stabilization by the 3.2-kb region, indicating that the putative partitioning function was largely responsible for RK2 maintenance. To examine the basis for the apparent differences in postsegregational killing between the two E. coli strains, transformation assays were carried out to determine the relative sensitivities of the strains to the ParE toxin protein. Consistent with the relatively small contribution of the postsegregational killing to plasmid stabilization in MC1061K, we found that this strain was substantially more resistant to killing by ParE in comparison to E. coli MV10delta lac. A transfer-deficient mutant of thepar-deleted plasmid was constructed for the stable maintenance studies. This plasmid was found to be lost from E. coli MV10delta lac at a rate three times greater than the rate for the transfer-proficient plasmid, suggesting that conjugation can also play a significant role in the maintenance of plasmid RK2.

Bacterial Proteins↗