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Work retention and nonspecific low back pain.

STUDY DESIGN: A cohort study of patients with nonspecific low back pain (LBP) participated in a 4-week multidisciplinary rehabilitation program. OBJECTIVE: To identify factors that predict work retention 24 months after treatment in patients with nonspecific LBP. SUMMARY OF BACKGROUND DATA: There is evidence that select physical, psychologic, and psychosocial factors are related to positive outcome for work-related nonspecific LBP. However, there is very little information related to work retention following an episode of nonspecific LBP. This is an exploratory study to identify select physical and psychosocial factors related to work retention. METHODS: Patients who returned to work after treatment (n = 67) were followed for 2 years. Physical baseline measures included tests of flexibility, strength, and functional capacity. Psychosocial baseline measures were The Symptoms Checklist 90-R, The Pain Beliefs and Perceptions Inventory, The Oswestry Scale of perceived disability, The Work Stress Inventory, and The Quality of Life Scale. All physical parameters, perceived disability, and quality of life were tested before and after treatment. The dependent variable, work retention, was defined as the number of days that the subject worked during the 2-year follow-up period. Survival analysis was used to establish the predictive model. RESULT: The average time out of work before treatment was 9 months (standard deviation 12.8) for 67 subjects (mean age 40 years [standard deviation 9.6]), including 18 females and 49 males. There were 18 participants (25%) that had interruption of work retention at follow-up. Average work retention was 362 days (range 47-682). Variables that reached a P value of <0.10 in the bivariate analysis were included in the multivariate analysis. They were trunk flexion (hazard ratio [HR = 2.4], 95% confidence interval [CI] 1.24-4.38; P = 0.01), trunk extension (HR = 2.1, 95% CI 1.02-4.16; P = 0.04), the somatization scale from the Symptom Checklist 90 revised (HR = 2.0, 95% CI 1.03-4.05; P = 0.04), and the obsessive-compulsiveness scale from the Symptom Checklist 90 revised (HR = 0.4, 95% CI 0.12-1.15; P = 0.09). Results showed that post-test trunk flexion, somatization, and obsessive compulsiveness predicted work retention (final trunk flexion HR = 2.5 [95% CI 1.26-4.79; P = 0.01], somatization scale HR = 2.5 [95% CI 1.25-4.93; P = 0.01], and obsessive compulsion HR = 0.2 [95% CI 0.07-0.77; P = 0.02]). CONCLUSION: Psychosocial and physical factors are associated with work retention for patients with nonspecific LBP. The predictive value of certain constructs may vary with the time when they are assessed and how outcome is operationalized. Further studies are needed to confirm these findings.

Absenteeism↗

A theoretical model of job retention for home health care nurses.

BACKGROUND: Predicted severe nursing shortages and an increasing demand for home health care services have made the retention of experienced, qualified nursing staff a priority for health care organizations. AIMS: The purpose of this paper is to describe a theoretical model of job retention for home health care nurses. METHODS: The theoretical model is an integration of the findings of empirical research related to intent to stay and retention, components of Neal's theory of home health care nursing practice and findings from earlier work to develop an instrument to measure home health care nurses' job satisfaction. DISCUSSION: The theoretical model identifies antecedents to job satisfaction of home health care nurses. The antecedents are intrinsic and extrinsic job characteristics. The model also proposes that job satisfaction is directly related to retention and indirectly related to retention though intent to stay. Individual nurse characteristics are indirectly related to retention through intent to stay. The individual characteristic of tenure is indirectly related to retention through autonomy, as an intrinsic characteristic of job satisfaction, and intent to stay. CONCLUSIONS: The proposed model can be used to guide research that explores gaps in knowledge about intent to stay and retention among home health care nurses.

Community Health Nursing↗

To stay or not to stay: issues in rural primary care physician retention in eastern Kentucky.

An important aspect of primary care physician availability is the retention of physicians once they have located. While retention has been under-researched compared to recruitment, it is especially important in rural areas where physician shortages already exist. This study reports the results of a retention survey completed by 132 primary care physicians in rural eastern Kentucky. The survey sets up an objective, hypothetical retention scenario and asks physicians to respond to structured questions and to an open-ended question about factors not appearing in the survey. In response to the structured portion of the survey, physicians indicate that relief coverage is the most important factor in rural physician retention. A content analysis of 75 open-ended responses reveals that besides the other factors in the survey, "sociocultural integration" is the pre-eminent retention issue for rural practitioners. This article concludes that the role of the local rural community may be more important in retention than in recruitment. Finally, it is suggested that additional in-depth qualitative research be conducted within the local contexts to enhance the understanding of rural physician retention processes.

Attitude of Health Personnel↗

Retention of platelets by glass bead filters.

Whole blood was passed through glass bead filters and the retention of platelets studied under various experimental conditions. Platelet retention was similar over a wide range of blood flow rates; however, it was decreased at fast rates of flow. Platelet retention was not influenced by the haematocrit value of the blood over a wide range. Retention in filters containing siliconized beads was similar to that in filters with untreated beads. Platelet retention was inhibited by the addition of citrate or adenosine to the blood before passage through the filter and was also less when the blood was cooled. Heparin and phenylindandione therapy did not affect the results. There was a wide range of results of platelet retention tests with normal blood samples and considerable variability between the results of duplicate samples from the same donor. Repeated testing of normal donors over a three-month period gave results which varied widely within the normal range. Twenty-two of 40 uraemic blood samples showed decreased platelet retention. The mechanism of platelet retention from whole blood by glass bead filters is not clear but may be related to platelet aggregation induced by adenosine diphosphate or other aggregating agents.

Adenine Nucleotides↗

Nitric oxide does not contribute to sodium retention and peripheral vasodilation induced by partial portal vein ligation in rats.

The role of nitric oxide (NO) synthesis in the peripheral vasodilation and sodium retention that occurs after partial portal vein ligation (PVL) was investigated. Hemodynamic studies in PVL rats with sodium retention and in sham-operated controls were conducted on the day when PVL rats developed transient and maximal sodium retention. Measurements were obtained before and during two consecutive periods after NO synthesis inhibition with NG-monomethyl-L-arginine (L-NMMA). Under baseline conditions, PVL rats with sodium retention were hypotensive, with equivalent decreases in total peripheral resistance and glomerular filtration rate in comparison to the control group. After L-NMMA, peripheral resistance and arterial pressure increased by similar extent in both groups. As compared with controls, PVL rats with sodium retention remained hypotensive and vasodilated. Furthermore, L-NMMA-induced natriuresis was attenuated in the PVL group. Additionally, serum and urinary levels of nitrate and nitrite did not vary before surgery and at the time of sodium retention. These results suggest that in PVL rats (1) vasodilation is not NO mediated; (2) vasodilation is not a sufficient explanation for sodium retention, and (3) a sodium-retaining factor acting on the renal tubules is responsible for sodium retention.

Animals↗

Effect of 50-Hz electromagnetic field on the retention of toxic radionuclides in rat tissues.

The effect of electromagnetic field (EMF) 50 Hz, 10 mT, on the tissue retention of radiotoxic polonium-210 and thorium-234 was studied in a rat model. Regarding 210Po in the ionic state, small but significant effects were obtained by exposure of rats to EMF either before the intravenous injection of 210Po (pre-exposure) or after the rats had already been injected with 210Po (post-exposure). When compared with control values, pre-exposure to EMF caused a significant 28% decrease in the retention of 210Po in the skin and a 10% decrease in total 210Po retention in the investigated tissues. Relative to controls, post-exposure resulted in a 131% increase in 210Po retention only in the thymus. Regarding carrier-free 234Th in the ionic state, both types of EMF exposure caused a substantial increase in 234Th retention in the liver and spleen and a decrease of 234Th in the bones. A different effect of EMF on the retention of 234Th in the body was obtained when the mass of thorium was increased by adding as carrier 232Th (50 micrograms kg-1 body mass). With pre-exposure, a significant 10% decrease in the high retention of 234Th in the liver (77% of injected radioactivity) was observed. On the other hand, with post-exposure no significant changes in retention of 234Th were found in the tissues.

Animals↗

Nitrogen retention by lambs fed oscillating dietary protein concentrations.

Nitrogen excreted by beef cattle can be retained in manure or lost by volatilization to the atmosphere or by runoff and percolation into surface or ground water. Increasing the retention of dietary N should decrease environmental losses. To this end, the effects of oscillating concentrations of dietary CP on nutrient retention were determined using lambs fed a 90% concentrate diet. Ten St. Croix lambs (average BW = 27 kg) were used in two 5x5 Latin square experiments. Dietary treatments were as follows: 1) 10% CP, 2) 12.5% CP, 3) 15% CP, 4) 10% and 15% CP diets oscillated at 24-h intervals, and 5) 10% and 15% CP diets oscillated at 48-h intervals. Supplemental N was provided by cottonseed meal in Trial 1 and by a 50:50 (N basis) blend of cottonseed meal and urea in Trial 2. Each period of the Latin square lasted 35 d, with excreta collection the final 8 d. Nitrogen retention increased linearly (P<.01) with increasing N intake in both trials (.77, 1.33, and 1.89 g/d for 10, 12.5, and 15% CP, respectively, in Trial 1; .94, 1.78, and 2.19 g/d for 10, 12.5, and 15% CP, respectively, in Trial 2). Compared with continuously feeding the 12.5% CP diet, oscillating the 10 and 15% CP diets on a 24-h basis did not affect N retention (P>.10) in either trial (1.62 and 1.56 g/d for Trials 1 and 2, respectively). Oscillating dietary CP at 48-h intervals did not affect N retention in Trial 2 (1.82 g/d) but increased (P<.05) N retention by 38% in Trial 1 (1.87 g/d). Phosphorus, K, and Na retention and excretion were not affected by dietary treatments in Trial 1. In Trial 2, P retention increased (linear, P<.05) with increasing dietary CP and was greater (P<.05) in lambs on the 48-h oscillation treatment than in lambs fed the 12.5% CP diet. These results suggest that oscillating the dietary CP concentrations might potentially increase the utilization of N by ruminants fed high-concentrate diets.

Animal Feed↗

Retention of different sizes of electronic identification boluses in the forestomachs of sheep.

Twelve types of electronic identification ruminal boluses of different dimensions were used to obtain a model for predicting their retention in the forestomachs of sheep. Boluses (n = 1,662) were made of ceramic materials, and their dimensions varied in o.d. (9 to 21 mm), length (37 to 68 mm), volume (2.5 to 21.0 mL), and specific gravity (0.85 to 3.91). Each bolus contained a half-duplex, standardized, glass-encapsulated transponder (32 x 3.8 mm). Boluses were administered to sheep (n = 1,497) of different ages by using the appropriate balling guns, and their retention under semiintensive conditions was recorded for at least 2 yr. When a bolus was lost, the sheep was rebolused with a heavier bolus. All sheep wore 2 plastic ear tags: one for the official control of health programs and the other for farm use. To determine the anatomical limit for a bolus passing through the gastrointestinal tract, the size of the reticulo-omasal orifice was measured in 46 adult sheep (male, n = 14; female, n = 32) that died by causes not related to bolus administration during the experiment. No signs of disease or growth alteration were detected in the bolused sheep. Total ear tag losses during the experiment period were 7.5% on average. Bolus retention (5 to 100%) varied according to bolus features and age of the sheep, but it showed a plateau after 18 mo. Inadequately dimensioned boluses were regurgitated or passed through the gastrointestinal tract and were excreted with the feces. The diameter of the reticulo-omasal orifice in adult sheep differed between male and female (23.1 and 21.8 mm, respectively; P < 0.01) and was greater than the o.d. of the retained boluses. Retention rate was predicted from bolus weight and volume by a logistic regression (R2 = 0.997; P < 0.001). When retention data from the literature (59.0 to 100%) were included in the model, the adjustment was slightly lower (R2 = 0.967). As a result, the minimum bolus weight estimated to reach a 99.5% retention rate in sheep varied between 16 and 45 g when volume varied between 3 and 22 mL, for boluses with a specific gravity between 2.0 and 5.2. In conclusion, bolus retention rate in sheep varied dramatically according to their features. For safe and efficient retention of electronic identification boluses in sheep, boluses of small volume and diameter (e.g., < 15 mm) with specific gravity and weight greater than 3.0 and 20 g, respectively, are recommended.

Animal Identification Systems↗

Therapeutic communities: what are the retention rates?

The present research is the first in a systematic investigation of retention in therapeutic communities (TCs). Findings are reported from an interrelated set of analyses clarifying retention rates and the temporal pattern of dropout. Retention information was obtained on all admissions to a nonrandom sample of seven traditional (long-term) TCs during February 1-August 15, 1979. Results showed that: (a) Across the seven programs, the 12-month retention rates ranged from 4 to 21%. Program differences were generally nonsignificant. (b) Less than 17% of admissions were readmissions. Among these, however, the number of days before initial dropout was a significant predictor of long-term retention. (c) The temporal pattern of dropout was uniform across programs. Dropout was highest within the first 14 d and declined thereafter, indicating that practically all dropouts leave within 3 months. (d) Based upon rates adjusted for those who had left treatment ("survivor rates"), estimates indicated that the likelihood of continued retention increased significantly with longer stay in treatment. (e) The temporal pattern of dropout was remarkably stable, evident in both replicational and comparative analyses; the latter involved the entire residential drug-free modality in several data systems. The present findings establish that the temporal pattern of retention is orderly, predictable, and has utility for program management and treatment planning, although the phenomenon of retention itself remains to be explained.

Adult↗

Retention of cocaine abusers in outpatient psychotherapy.

Retention in outpatient psychotherapy of 148 crack and cocaine abusers was examined. The clients were predominantly Black (63%) and Hispanic (21%), predominantly male (87%), and the majority (66%) had completed no more than 12 years of high school. Clients entered treatment in a low-cost treatment center in New York City between June 1987 and November 1988. Forty-two percent (62) of the subjects were seen for one or two research interviews only, and did not return to begin therapy. Of the 86 persons who came to at least one therapy session, 30% (26) dropped out before the third session, 28% (24) dropped out between the third and fifth sessions, and 42% (36) were retained for six or more sessions. Short-term and longer-term retentions were analyzed separately, using a battery including sociodemographic variables, treatment history, psychiatric symptomatology, number of arrests, and drug use variables. None of the variables considered was significantly related to short-term retention. There were large although not significant differences in longer term retention by therapist. Longer-term retention was associated significantly with being White (contrasted with being Black) and being young. Nonsignificant but large associations were found between longer-term retention and having few arrests, being Hispanic (contrasted with being Black), and having low SCL-90 scores. Results are compared with previous findings about retention in drug and alcohol treatment. It is suggested that future research on retention in treatment focus less on client variables and more on therapist and program variables.

Adult↗

Growth of lactic acid bacteria in highly concentrated ultrafiltered skim milk retentates.

Buffer capacity of ultrafiltered skim milk retentates at various protein concentrations and growth of direct set, frozen concentrated lactic starter cultures in such retentates were studied. Maximum buffering occurred at approximately pH 5.1 to 5.3. An average .48% lactic acid concentration was required to reduce the pH of plain skim milk to 4.6 compared with 1.01% for skim milk retentates concentrated 2.3:1 and 1.14% for skim milk retentate concentrated 2.6:1. Skim milk retentates concentrated 4.3:1 and 5.8:1 were unable to attain pH 4.6 even when titratable acid was greater than 1.8%. Lactic acid required to reduce pH to 4.6 for the two lower concentrated retentates (2.3:1 and 2.6:1) were 1.85 and 2.45%. Time to attain pH 4.6 was a function of the bacterial cell concentration of the cultures and the total protein level of retentates. Starter organism growth was unaffected by high total solids or ash of retentates. Growth rate and lactose metabolism decreased markedly below pH 5.2 at which point bacterial population was 10(9) cfu/ml.

Animals↗

Effect of topical fluoride on retention of pit and fissure sealants.

PURPOSE: The purpose of this study was to evaluate the clinical effect of topical fluoride on retention of light-cured (CLC) and self-cured (CSC) pit and fissure sealants. METHODS: CLC and CSC sealants were placed in vivo on opposite sides of the arch before and after fluoride treatment. A total of 122 sealants were placed on virgin permanent molars and premolars of 16 dental hygiene students enrolled in a two-year program. Sealant retention in both fluoridated and non-fluoridated teeth was evaluated at 6, 12, and 18 month intervals. RESULTS: Overall sealant retention for both fluoridated and non-fluoridated teeth at 6, 12 and 18 months was 68%, 48%, and 49%, respectively. There was a significant difference (p < 0.001) when fluoridated vs. non-fluoridated teeth were compared. Retention was greater on the fluoridated teeth, with respect to the sealant material (CLC-fluoride). Significant differences (p < 0.001) were found when CLC-fluoride and CLC-no fluoride treatment groups were compared. However, no significant differences were found in retention when CSC-fluoride and CSC-no fluoride groups were compared, or when CLC was compared to CSC irrespective of fluoridation. Significant differences (p < 0.0001) were found when sealant retention on molars was compared to premolars--retention of sealants was greater on premolars. CONCLUSION: This study suggests that sealant retention may not be adversely affected by a topical fluoride treatment applied immediately prior to placement.

Acidulated Phosphate Fluoride↗

Urinary retention in sexually abused women.

Urinary retention is generally believed to be the result of neurogenic or non-neurogenic problems. In men, it is often caused by benign prostatic hypertrophy which can be treated by transurethral surgery.1 In women, however, studies have shown that urinary retention is usually caused by detrusor dysfunction rather than obstruction. Surgery on the urethra or bladder neck is, therefore, inappropriate and ineffective. Once the cause of retention has been determined (i.e whether neurogenic or non-neurogenic in origin), appropriate treatment can be decided upon. The most common neurogenic problems are diabetes mellitus, multiple sclerosis and spinal cord pathologies.(1) Patients with non-neurogenic etiology associated with urinary retention are often found to have psychosocial problems that inhibit detrusor activity causing psychogenic retention.1-4 Studies have found that woman with a history of psychosis, depression and stress/anxiety have a higher incidence of urinary retention than woman with no history of such conditions. Psychological problems involving the loss of loved one, recent marriage break-up, abortion, pelvic surgery, etc. have been found to contribute to the incidence of urinary retention. There is another group of women who may or may not exhibit psychological problems associated with psychogenic urinary retention, but who may develop the same physical manifestations. These women have been sexually abused and have not fully resolved or realized the trauma of the assault. This paper looks at four cases or urinary retention in sexually abused woman, the treatments used and the results and conclusions obtained.

Journal Article↗

Client retention in the British Columbia Methadone Program, 1996-1999.

BACKGROUND: Methadone treatment for heroin addiction has been available for 40 years, but there is relatively little research on the effectiveness of Canadian programs. This paper describes one-year retention among the client cohorts entering the British Columbia Methadone Program during expansion between 1996 and 1999, and examines some factors previously shown to influence retention. METHODS: All methadone maintenance prescriptions dispensed to 1996-1999 program entrants were extracted from records of the BC Triplicate Prescription Program. Retention status and covariates were evaluated one year post-entry using logistic regression. Effects of retention status misclassification on time in the program were assessed with a Cox model for clients who received continuous daily dosing or short carries. RESULTS: Fifty-two percent of program entrants were still receiving methadone one year after entry; 24% had left the program at one year but later returned. Age at program entry and average daily dose of methadone were important predictors of continuation. In the logistic regression, only the 1999 year-of-entry cohort appeared to have a different retention trajectory. Year of entry is not a significant predictor of time in the program for those receiving daily or short carry doses only, and other results are consistent between models. INTERPRETATION: Retention rates in the BC Methadone Program are favourable and consistent with published rates. Program expansion does not reduce retention, once the effects of client age and dose are accounted for. Adequate daily dosing appears crucial to both initial retention and return to treatment.

Adolescent↗

Indium-111 whole-body retention: a method for quantification of disease activity in inflammatory bowel disease.

Quantification of disease activity in inflammatory bowel disease (IBD) has been by measurement of fecal excretion of 111In-granulocytes. The difficulties of this method prompted us to evaluate quantification of whole-body 111In retention, expressed as a percentage of whole-body activity at 3 hr following injection, as an alternative method. The patient stood in front of the uncollimated gamma camera at a distance of 4 m and counts were collected over 2 min. The geometric mean was taken of posterior and anterior counts and compared with a 111In standard. The lower limit of the 95% confidence interval for whole-body retention in normals was 90%. Forty-five studies were performed on 33 patients with IBD. They were assessed in two groups, one to whom routine instructions for the collection of feces were given (Group A) but who did not always comply. The other group received oral and written instructions and were also monitored during the collection period (Group B) and reported full fecal collection. Although in Group A the correlation between fecal excretion and whole-body retention was good (r = 0.7, n = 32; p less than 0.001), in Group B the relationship between fecal excretion and whole-body retention was significantly better (r = 0.95, n = 18; p less than 0.001). On average, 111In whole-body retention was consistent with findings obtained during imaging: 111In excretion (100-whole-body retention) was 7.8% +/- 4.9% in 5 normal scans, 10% +/- 5.9% in 17 (+) scans, 22.3% +/- 8% in 20 (++) scans and 57% +/- 16% in 8 ( ) scans. We conclude that imaging is more sensitive than whole-body retention and fecal excretion in the detection of disease, but for quantification, whole-body retention is an accurate reliable alternative to fecal excretion.

Adult↗

[The study of relation of the retention indices of n-alkenes with their molecular structure].

When the difference values between the retention indices of homologous series of n-alkenes and that of n-alkanes with the same carbon number were plotted with the number of carbon atoms in the molecule, it can be seen that the curve is nearly an exponential curve. We proposed an accurate formula to predict the retention indices of homologous series of n-alkenes. The retention indices of a total of 99 C12-C16 n-alkenes on capillary columns with stationary phase of Squalane, PFE and PEG-4000 were calculated. The standard deviations of the retention indices were +/-0.9-+/-1.5 index units. When the retention indices of n-alkenes with the same carbon numbers and the same geometric structure were plotted with the positions of the double bond in the molecule, it can be seen that the curve is also approximately an exponential curve. Therefore, we put forward an exact formula to predict the retention indices of the n-alkenes. The universality of the formula is demonstrated by predicting a total of 178 retention indices of C15-C18 n-alkenes on capillary columns with stationary phases of C87 hydrocarbon, Apiezonl L, CW-20M. The standard deviations of retention indices were +/-0.9-+/-1.2 index units.

English Abstract↗

On salivary film formation and bacterial retention to solids. A methodological and experimental in vitro study.

A parallel-plate flow cell system was developed to assess individual and combined parameters relevant to oral microbial retention. In this system, internal reflection germanium prisms represented oral solid surfaces including tooth surfaces. The system used, allowed adsorbed protein films to be analyzed in situ by multiple non-destructive surface analytical techniques, without provoking surface associated biofilms. Using a range of biochemical and biophysical techniques, germanium prisms of medium critical surface tension were noted to accurately model film formation at tooth-saliva interfaces. A range of clinically relevant temperatures (22 and 37 degrees C), rinse shear rates (1 and 32 ml/min) and critical surface tensions (high, medium and low) were systematically tested in the flow-cell system for their influence, if any, on salivary microbial retention from whole human saliva. Comparisons of the interfacial organization of adsorbed material were made between human parotid (HPS) and submandibular-sublingual (HSMSL) salivas. The influence of these salivary secretions was also tested on the retention capacities of Streptococcus sanguis and Streptococcus salivarius. Microbial retention was found to be significantly dependent on initial critical surface tensions and rinse flow rates, but not to be affected by tested temperatures. When compared to prisms of low and high critical surface tension, medium critical surface tension prisms retained the highest numbers of microorganisms. No statistically verified morphological selectivity was observed in the retained microbial populations. When the interfacial organizations of HPS and HSMSL were evaluated at low- and medium energy surfaces in the absence and presence the streptococci, comparatively thinner and denser films with pronounced bacterial retention was noted for HPS on prisms of low critical surface tension. In the presence of saliva or salivary fractions, no difference in retention capacities was observed between the tested bacterial strains. The data suggest that in the presence of saliva, physico-chemical and mechanical factors have a major influence on the short term microbial retention to solid surfaces. The amount of salivary proteins being initially retained to a material also seems to be more directly related to the critical surface tension quality of the solid than to the type of bacterial strain present in suspension. The empirical critical surface tension of a material is thus a useful predictor of both microbial retention capacities and primary interactions between saliva and solid surfaces.

Bacterial Adhesion↗

Reversal of signal-mediated cellular retention by subunit assembly of human acetylcholinesterase.

The interrelationship between signal-mediated endoplasmic reticulum retention and control of subunit assembly in secreted complex proteins was examined in recombinant 293 cells expressing human acetylcholinesterase (HuAChE). This was achieved by analyzing the mutual effects of co-residing retention and dimerization signals on enzyme secretion by transfected cells. The function of putative signals within the COOH-terminal tetrapeptide CSDL of HuAChE was examined by site-directed mutagenesis. The CSDL tetrapeptide carries the free cysteine (Cys-580) involved in subunit assembly, yet it fails to function as a KDEL-type retention signal. This was demonstrated by mutations that increase similarity to the canonical retention signal (substitution of CSDL by KSDL) or those that deviate from it (substitution to CSAL). Cells expressing both types of mutants exhibited cell-associated HuAChE levels identical to that of wild type enzyme. Appendage of an engineered KDEL retention signal to a dimerization-impaired HuA-ChE subunit (the C580A mutant) resulted in intracellular retention of large amounts of fully active enzyme not prone to proteolytic degradation. On the other hand, attachment of KDEL to a native, dimerization-competent HuAChE polypeptide did not lead to intracellular retention and allowed efficient secretion of enzyme to the cell growth medium. Yet, appendage of KDEL to the native HuAChE led to some retardation in the transport of enzyme molecules through the Golgi apparatus, as manifested by increase in cellular population of endo H-resistant dimers, when compared with wild type enzyme. Taken together, these results indicate (alpha) that sub-unit dimerization mediated by the COOH-terminal cysteine of HuAChE can reverse the signal-mediated retention by masking recognition of KDEL by its cognate receptor and (b) that the native sequences of the acetylcholinesterase subunit polypeptide do not appear to function as a coupled retention/dimerization signal in the control of secretion of assembled enzyme molecules.

Acetylcholinesterase↗