Mobile health technologies for the management of systemic lupus erythematosus: a systematic review.

OBJECTIVE: We aimed to perform a standardized review of available mobile health (mHealth) applications (apps) for systemic lupus erythematosus (SLE) and to conduct a systematic review of the literature on mHealth technologies in SLE. METHODS: Google Play and AppStore in the United States of America were queried and the quality of eligible mHealth apps was assessed using the Mobile App Rating Scale (MARS). Web of Science, EMBASE, Medline, and Cochrane databases were systematically searched from inception through June 2019. RESULTS: Of 324 mHealth apps found, 20 were eligible for inclusion; 10 focused on education, 7 offered tools to track patient-reported symptoms, 5 included interactive online communities, and 1 enabled emoji sharing. The reviewed apps scored poorly on the MARS quality scale with a mean score 2.3 (0.6) out of 5. Of 1147 studies identified in the literature review, 21 were eligible for inclusion; 11 studies (52.4%) focused on the development and use of mHealth for providing patient information, while only 2 (9.5%) were randomized trials of mHealth interventions. CONCLUSIONS: Although there is growing interest in the development of mHealth technologies to support SLE patients, currently available tools are of poor quality and limited functionality, and the literature examining this area is sparse.

Non-pharmacologic therapies for systemic lupus erythematosus.

BACKGROUND: Non-pharmacologic therapies have been deemed as potentially beneficial for patients with systemic lupus erythematosus. We conducted an updated review to determine the effects of these therapies to inform practice. METHODS: A literature search was performed using PubMed (MEDLINE), EMBASE, Cochrane, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Google Scholar from inception until August 2018. We included randomized controlled trials of non-pharmacologic therapies in systemic lupus erythematosus patients with sample size ≥10. Systemic lupus erythematosus was defined by 1982 or 1997 American College of Rheumatology criteria. Studies were synthesized separately by patient-reported outcomes and disease activity. Due to the heterogeneity of interventions and comparisons, a meta-analysis was not performed. RESULTS: A total of 15 randomized controlled trials involving 846 participants met the inclusion criteria. Of the 15 trials, eight used exercise interventions, six used psychological interventions (one group psychotherapy, three cognitive behavioral therapies, one psychoeducation, one mindfulness-based cognitive therapy) and one used electro-acupuncture. Five of 15 studies utilized control groups consisting of usual medical care. Other studies included control interventions of relaxation, attention placebo, symptom monitoring support, education, minimal needling, isotonic and resistance exercise. Compared with the control conditions, non-pharmacological interventions were associated with a significant improvement in fatigue in three out of six studies. Three out of eight studies reported improved anxiety and depression, and one study reported improved pain after interventions. Seven out of 11 studies reported improvement in overall quality of life in at least one domain of the Short-Form Health Survey. Of note, no studies demonstrated an improvement in disease activity after 5-52 weeks of non-pharmacological therapies. CONCLUSION: This review showed promising results for physical exercise and psychological interventions as adjuncts to traditional medical therapy for improvement in fatigue, depression, pain and quality of life for systemic lupus erythematosus. Further high-quality randomized controlled trials with longer follow-up periods are warranted.

Feasibility of Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests in systemic lupus erythematosus outpatients.

Objective The aims of this study were to assess the feasibility of administering Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests (CATs) to outpatients with systemic lupus erythematosus (SLE). Methods Adults with SLE were recruited during routine outpatient visits at an SLE Center of Excellence. Participants completed 14 PROMIS CATs and provided feedback on their experience. Differences in socio-demographic and clinical characteristics between participants and non-participants were evaluated. Results A total of 204 (86%) of 238 socioeconomically and racially diverse SLE patients completed PROMIS CATs. There were no significant differences between participants and non-participants. Time constraints were cited most frequently as reasons for non-participation. More than 75% of individuals submitted positive comments, including approval of the content and format of questions, and the survey's promotion of self-reflection. A minority of participants cited challenges, most often related to question phrasing (8%) and technical difficulties (6%). Conclusions The administration of PROMIS CATs was feasible and positively received in a diverse cohort of SLE outpatients. Neither socio-demographic nor disease characteristics were significant barriers to successful completion of PROMIS CATs. PROMIS CATs have great potential for efficiently measuring important patient-centered outcomes in routine clinical care of a wide range of SLE patients.

Alcohol consumption, hazardous drinking, and alcohol dependency among the population of Andaman and Nicobar Islands, India.

BACKGROUND: Harmful use of alcohol is one of the globally recognized causes of health hazards. There are no data on alcohol consumption from Andaman and Nicobar Islands. OBJECTIVE: The objective of the study was to assess the prevalence and pattern of alcohol use among the population of Andaman and Nicobar Islands, India. METHODS: A representative sample of 18,018 individuals aged ≥14 years were chosen by multistage random sampling and administered a structured instrument, a modified version of the Gender, Alcohol, and Culture: An International Study (GENACIS) which included sociodemographic details and Alcohol Use Disorders Identification Test (AUDIT). RESULTS: The overall prevalence of alcohol consumption was 35% among males and over 6.0% in females, aged 14 and above. Two out of every five alcohol users fit into a category of hazardous drinkers. One-fourth of the total users (23%) are alcohol dependents. Both the hazardous drinking and dependent use are high among males compared to females. Almost 18.0% of male drinkers and 12.0% of female drinkers reported heavy drinking on typical drinking occasions. The predominant beverages consumed were in the category of homebrews such as toddy and handia. CONCLUSION: The present study highlights the magnitude of hazardous drinking and alcohol dependence in Andaman and Nicobar Islands, India and the complex sociocultural differences in the pattern of alcohol use. Based on the AUDIT data, among the population of Andaman and Nicobar Islands (aged 14 and above), one out of ten requires active interventions to manage the harmful impact of alcohol misuse.

Synthesis and photoluminescence properties of red emitting phosphor La2-x Eux Li0.5 Al0.5 O4 [x = 0.2-2] with K2 NiF4 structure.

Europium (Eu)3+ -substituted La2 Li0.5 Al0.5 O4 red emitting phosphors were prepared by a conventional high-temperature solid-state reaction method. Powder X-ray diffraction, diffuse reflectance spectra and spectrofluorometry were used as vital characterizing tools for the phosphors. The Eu concentration dependence luminescence properties and Judd-Ofelt intensity parameters were investigated and calculated, respectively. All compositions showed an orange red emission (due to the magnetic and electric dipole transitions of the Eu3+ ion) with the appropriate Commission Internationale de l'Eclairage (CIE) colour gamut under near ultraviolet or blue ray light excitation. The calculated critical distance showed that the energy transfer occured between Eu to Eu via an exchange mechanism. The Eu1.4 La0.6 Li0.5 Al0.5 O4 composition showed the highest red emission intensity with CIE colour saturation compared with that of the commercial Eu-activated yttrium oxysulfide red phosphor.

Synthesis and photoluminescence of EuII in barium zinc orthosilicate: a novel green color emitting phosphor for white-LEDs.

A series of Eu2+ -activated barium orthosilicates (BaZnSiO4 ) were synthesized using a high-temperature solid-state reaction. A photoluminescence excitation study of Eu2+ shows a broad absorption band in the range of 270-450 nm, with multiple absorption peak maxima (310, 350 and 400 nm) due to 4f-5d electronic transition. The emission spectra of all the compositions show green color emission (in the spectral region 450-550 nm with a peak maximum at 502 nm and a shoulder at ~ 490 nm) with appropriate Comission Internationale de l'Eclairage (CIE) color coordinates. The two emission peaks are due to the presence of Eu2+ in two different Ba sites in the BaZnSiO4 host lattice. The energy transfers between the Eu2+ ions in BaZnSiO4 host are elucidated from the critical concentration quenching data based on the electronic multipolar interaction. All Eu2+ -activated BaZnSiO4 phosphor materials can be efficiently excited in the ultraviolet (UV) to near UV-region (270-420 nm), making them attractive candidate as a green phosphor for solid state lighting-white light-emitting diodes.

Effect of hypertension at presentation on prognosis in patients with dilated cardiomyopathy presenting with normal renal angiogram.

BACKGROUND & OBJECTIVES: Dilated cardiomyopathy (DCM) is a progressive disease of heart with systolic and diastolic dysfunction carrying a poor long-term prognosis. The prognostic index and predictors of mortality are considered to be useful in guiding the treatment. This study was undertaken to evaluate the effects of hypertension at presentation on prognosis in patients with DCM presenting with normal renal and coronary angiogram. METHODS: An observational, analytical, non-interventional and a combination of retrospective and prospective study was conducted in patients between 15 and 75 yr of age with DCM having on and off symptoms while receiving treatment in a cardiology outpatient department for more than a year. Sixty patients who fulfilled the inclusion criteria were enrolled in the study. Left ventricular systolic and diastolic functions were assessed by echocardiography along with New York Heart Association (NYHA) functional class prospectively and at baseline retrospectively. Patients were grouped into two categories: DCM with hypertension at presentation (HTNAP, Category 1) and DCM without hypertension at presentation (NHTNAP, Category 2). The primary end-points were the number and dose of parenteral drugs at hospitalization, duration of hospital stay and change in the left ventricular (LV) systolic function expressed as LV ejection fraction, and the secondary end-points included overall mortality, change in LV and right ventricular systolic and diastolic functions and change in the NYHA functional class between baseline and three month follow up in patients. RESULTS: Thirty five and 25 patients presented with HTNAP and NHTNAP, respectively (total 60). The overall mortality was 10 per cent (6/60). The number of hospitalizations was less in HTNAP category and of days of hospital stay was 6.3 in HTNAP and 9.8 in NHTNAP, the difference being significant (P < 0.001). The HTNAP category required less parenteral diuretics and inotropes compared with the NHTNAP category. The echocardiographic parameters showed better improvements in the HTNAP group as compared to the NHTNAP group. Overall, the patients in the <35 yr of age showed the best prognosis (P < 0.001). INTERPRETATION & CONCLUSIONS: Normal or high blood pressure response at acute presentation of DCM leads to better prognosis which may be due to an intact renovascular and an active sympathetic system and can depict the stage of DCM.

Long Term Results of Esophageal Bypass for Corrosive Strictures without Esophageal Resection Using a Modified Left Colon Esophagocoloplasty--A Report of 105 Consecutive Patients from a Single Unit Over 30 Years.

BACKGROUND/AIMS: Esophageal stricture due to corrosive ingestion is a common cause of benign esophageal obstruction in developing countries. The immediate and long-term results of surgical bypass using a modification of the left colon conduit, will be reviewed. METHODOLOGY: From 1977 to 2008, 105 patients underwent esophageal bypass for corrosive esophageal strictures using this procedure which has several modifications, detailed in the text, from the conventional left colon conduit. RESULTS: Acids were the most common corrosive implicated (70.5%). Eighty nine patients underwent a bypass based on the left colic vessel through the substernal route. The subcutaneous route was used in the rest for varying reasons. Postoperatively three patients died. Conduit necrosis was seen in only one patient. Postoperative morbidity included pneumothorax in 15, cervical anastomotic stenosis in one, cervical anastomotic leak in 13 (less than 3% the last 75 cases) and recurrent laryngeal nerve palsy in 6 (5.7%). 72 patients had normal swallowing and 33 had only occasional minor difficulty with solid food on follow-up. CONCLUSIONS: Surgical bypass using a modification of the left colon esophagocoloplasty remains a reliable procedure with acceptable morbidity and good relief of dysphagia.

Tobacco use and nicotine dependency in a cross-sectional representative sample of 18,018 individuals in Andaman and Nicobar Islands, India.

BACKGROUND: Data on prevalence, pattern of tobacco use, proportion of population dependent on nicotine and their determinants are important for developing and implementing tobacco control strategies. The aim of the study was to estimate the prevalence and determinants of tobacco use and nicotine dependency. METHODS: A cross-sectional survey among a representative sample of 18,018 individuals in the age group of >=14 years was conducted in the Union Territory of Andaman and Nicobar Islands during 2007-09. A structured questionnaire, a modified version of an instrument which was used successfully in several multi-country epidemiological studies of the World Health Organisation, was used to survey individual socio-demographic details, known co-morbid conditions, tobacco use and alcohol use. Fagerström Test for Nicotine Dependence (FTND) was used to estimate nicotine dependence. RESULTS: The response rate of our survey was 97% (18,018/18,554). Females (n = 8,888) were significantly younger than males (34.3 + 14.6 Vs 36.2 + 15.4 years). The prevalence of current tobacco use in any form was 48.9% (95% CI: 48.2-49.6). Tobacco chewing alone was prevalent in 40.9% (95% CI: 40.1-41.6) of the population. While one tenth of males (9.7%, 95% CI: 9.1-10.4) were nicotine dependent, it was only 3% (95% CI: 2.7-3.4) in females. Three fourth of the tobacco users initiated use of tobacco before reaching 21 years of age. Age, current use of alcohol, poor educational status, marital status, social groups, and co-morbidities were the main determinants of tobacco use and nicotine dependence in the population. CONCLUSION: The high prevalence of tobacco use especially the chewing form of tobacco in the Union Territory of Andaman and Nicobar Islands and the differences in prevalence and pattern of tobacco use and nicotine dependency observed across subgroups warrants implementation of culturally specific tobacco control activities in this population.

Association of hypertension with risk factors & hypertension related behaviour among the aboriginal Nicobarese tribe living in Car Nicobar Island, India.

BACKGROUND & OBJECTIVES: There are no composite estimates on prevalence of hypertension among indigenous tribes in India. The present study was carried out to estimate the prevalence of hypertension, its association with determinants, and to assess the hypertension related behaviour of the Nicobarese aborigines. METHODS: This cross-sectional survey was carried during 2007 and 2009. Subjects were chosen by two stage design. Total 975 subjects of 1270 (response rate of 76.8%) were investigated (M: 43.5%; F: 56.5%). The data were collected by history, clinical examination (blood pressure), and examination (weight and height). The association of hypertension with age, education, tobacco, alcohol consumption and their dependency status (KF score, QF value, and AUDIT score) and nutritional status was estimated by bivariate regression analysis; the increasing trend in the prevalence of hypertension with increasing age and decreasing educational status was analysed by χ2 for linear trend. Significant variables in bivariate regression analysis (age, education, alcohol consumption status, and nutritional status) were subjected to multiple logistic regression analysis (MLR). RESULTS: The prevalence of hypertension was 50.5 per cent [95% CI 46.1-54.9 (M: 50.7%; F: 50.3%)]. The prevalence of tobacco, alcohol consumption, and overweight/obesity was 88, 54, and 37 per cent respectively. The bivariate analysis has shown association between hypertension and age, education subcategories, alcohol consumption, and overweight/obesity (P<0.05). The increasing trend in the prevalence of hypertension with increasing age (χ2 for linear trend=95.88, P< 0.001) and decreasing educational status (χ2 for linear trend=25.55, P< 0.001) was statistically significant. MLR analysis revealed a significant association between hypertension and various age categories and overweight/obesity. INTERPRETATION & CONCLUSIONS: The findings of the present study highlight high prevalence of hypertension among Nicobarese aborigenes.

Unanticipated complication of a malpositioned central venous catheter.

We report an unusual complication that occurred late in the postoperative period, due to a damaged and malpositioned peripherally inserted central catheter (PICC) used for central venous pressure monitoring during esophagocoloplasty and for postoperative parenteral nutrition. On the seventh postoperative day, the development of a leak from the neck wound coincided with the administration of intravenous fluids via the PICC. The leak had occurred as a result of slow erosion of the left internal jugular vein (IJV) by the damaged edges of the catheter.

Transventricular mitral commissurotomy in critical mitral stenosis during pregnancy.

The management of a pregnant patient with mitral stenosis is a subject of debate with regards to the optimal type of treatment and the time of intervention. We performed trans-ventricular mitral commissurotomy (TVMC) either as an isolated procedure in the second trimester, or in combination with Cesarian section at term. We retrospectively analyzed our experience with TVMC during pregnancy and formulated a protocol for its management. Between January 1987 and April 2002, fifty one patients underwent TVMC for critical mitral stenosis during pregnancy. In 38 patients, elective TVMC was performed during the second trimester, while in 12, it was performed as an initial procedure along with Cesarian section at term. One patient had an emergency TVMC in the second trimester when she presented with intractable acute pulmonary edema. There were no maternal mortalities. Three patients who developed post-operative mitral regurgitation were managed conservatively. Another two patients who developed cerebral embolism with hemiplegia recovered completely without any neurological deficit. There was only one fetal death in a patient where TVMC was performed as an emergency procedure for acute pulmonary edema. We conclude that TVMC in pregnancy is a safe, cost effective alternative in critical mitral stenosis complicating pregnancy.

Effect of urea denaturation on tryptophan fluorescence and nucleotide binding on tubulin studied by fluorescence and NMR spectroscopic methods.

Tubulin, the major protein of microtubules, has been shown to be an example of protein undergoing multistep unfolding. Local unfolding and stepwise loss of a number of characteristic functions were demonstrated. In order to understand urea induced effects on tryptophan fluorescence and nucleotide binding on tubulin, both fluorescence and NMR techniques were used. Tubulin was denatured by different urea concentrations. The present experiments were carried out at concentrations of tubulin (to approximately 10 microM) at which most of the protein will be in the dimeric state. Quenching studies in the presence of KI suggest that all the tryptophans are fairly solvent exposed. Similar studies using acrylamide as quencher, suggest unfolding of tubulin at these protein concentrations to be an apparent two state process between the native and the completely unfolded states unlike at low concentrations where a partially folded intermediate was observed. No observable effects of the nucleotide or the metal ion on tryptophan fluorescence were observed. An attempt was made using NMR to monitor the changes in the nucleotide interaction with tubulin as the protein is unfolded by urea denaturation. No significant effects were observed in the binding of the nucleotide to tubulin by urea denaturation.

Gene transfer of type 1 interleukin-1 receptor extracellular-domain complementary DNA into rabbit synovial cell line HIG-82 results in cellular blockade of interleukin-1 signal transduction.

OBJECTIVE: To produce, by means of expression cloning, a soluble type 1 interleukin-1 receptor (sIL-1R), and to assess its inhibitory properties on the IL-1 pathway. METHODS: High-affinity IL-1R sites were identified in a human chondrosarcoma cell line by means of 125I-IL-1beta binding. A 1-kilobase complementary DNA (cDNA) encoding the ligand-binding domain of the type 1 IL-1R was cloned by using polymerase chain reaction, and the cDNA was inserted into a mammalian expression vector pRc/CMV. The sIL-1R expression vector was transfected into a rabbit synovial cell line (HIG-82) and a stably transfected cell population was selected. The production of sIL-1R was confirmed in the medium of transfected cells using 125I-IL-1beta binding. 35S labeling of transfected cultures, followed by immunoprecipitation and gel electrophoresis, was used to characterize the size of the recombinant sIL-1R. Stromelysin and IL-1alpha steady-state messenger RNA (mRNA) levels were assessed by Northern blotting. Prostaglandin E2 (PGE2) release was measured by enzyme-linked immunosorbent assay. RESULTS: IL-1R on the surface of HIG-82 cells bound 125I-IL-1beta with an equilibrium dissociation constant (Kd) of 67.3 +/- 7.8 pM (mean +/- SD). Transfection of the sIL-1R expression vector into a synovial cell line in vitro resulted in the appearance of an sIL-1R protein that bound 125I-IL-1beta with high affinity in the medium (Kd = 108 +/- 5 pM). Two protein bands (Mr 42 kd and 47 kd) were immunoprecipitated with an antibody against type 1 T cell-derived sIL-1R. Expression of sIL-1R was accompanied by a marked decrease in both stromelysin and IL-1alpha steady-state mRNA levels. In conjunction, there was a significant inhibition of basal and IL-1-stimulated PGE2 released by sIL-1R-producing cells. CONCLUSION: The data suggest that gene transfer of type 1 sIL-1R into the synovium may be an effective means of inhibiting IL-1-induced metalloproteinase expression and inflammatory responses.

Interaction of bis(1-anilino-8-naphthalenesulfonate) with yeast hexokinase: a steady-state fluorescence study.

Bis(1-analino-8-naphthalenesulfonate) (bis-ANS) is a useful probe for hydrophobic areas on protein molecules and it has been proposed that it has a general affinity for the nucleotide binding site(s). There appear to be two different classes of binding sites for bis-ANS on hexokinase and these can be tentatively assigned as primary and secondary binding sites. The rate of binding of bis-ANS at the primary binding site is fast, whereas binding at secondary site(s) is slow. The slow increase in the fluorescence intensity on binding with bis-ANS is not due to conformational change in the enzyme, which may lead to the increase in the quantum yield of the bound dye. Circular dichroism measurements indicate that there is no significant change in the secondary structure on binding with this probe. In the presence of saturating amounts of glucose, the increase in fluorescence intensity due to binding at the secondary binding site(s) is significantly lowered. This indicates that glucose-induced conformational change has been sensed by this probe. From kinetic studies, it has been observed that bis-ANS is an effective competitive inhibitor of yeast hexokinase with respect to ATP. The stoichiometry of binding of this fluorescent probe is about one per subunit at the primary site both in the presence and absence of glucose, and the dissociation constant of bis-ANS is unaffected by glucose. It is possible to decrease significantly the amount of fluorescence intensity at the primary site by nucleotides. These results indicate that bis-ANS interacts at the site where nucleotide interacts. Energy transfer experiments indicate the proximity of some tryptophan(s) and bound bis-ANS molecule(s).

Metalloprotease-mediated cleavage secretion of pulmonary ACE by vascular endothelial and kidney epithelial cells.

The pulmonary isozyme of angiotensin-converting enzyme (ACEP) is present in the body both as a cell-associated protein in endothelial, epithelial, and monocytic cells and as a soluble protein in various body fluids including serum. The mechanism by which soluble ACEP is produced in vivo is unknown. Using in vitro transfected cell culture systems, we previously demonstrated that the rabbit testicular isozyme of ACE (ACET), which shares extensive homology with ACEP, is first synthesized as a plasma membrane-anchored ectoprotein and then secreted to the culture medium by cleavage removal of its COOH-terminal membrane-anchored tail. Here, using in vitro cultures of arterial endothelial cells and acutely isolated renal epithelial cells, we demonstrate that ACEP is also cleavage secreted from their natural producer cells. Biochemical and immunological characterization of the in vitro secreted ACEP protein revealed that it is missing the COOH-terminal membrane-anchored region of the cell-associated ACEP. Similar analysis of ACEP proteins present in rabbit serum, lung, and kidney established that ACEP secretion in vivo is also caused by the cleavage removal of the COOH-terminal region of the cell-associated protein. To characterize the proteolytic enzyme responsible for ACEP secretion, we employed rabbit renal proximal tubular epithelial cells and demonstrated significant inhibition of secretion by compound 3, a hydroxamic acid-based inhibitor of specific metalloproteases. In contrast, the inhibitors of chymotrypsin, trypsin, serine, aspartate, and cysteine proteases were ineffective. These results indicate that soluble ACEP production by vascular endothelial and renal epithelial cells, both in vitro and in vivo, is achieved by cleavage removal of its membrane-anchoring COOH-terminal tail by a metalloprotease.

Nucleotide binding to tubulin-investigations by nuclear magnetic resonance spectroscopy.

In an attempt to distinguish between the interaction of GTP and ATP with tubulin dimer, high-resolution 1H- and 31P-NMR experiments have been carried out on the nucleotides in the presence of tubulin. The location of the ATP binding sites on the protein in relation to the GTP sites is still not clear. Using NMR spectroscopy, we have tried to address this question. Evidence for the existence of a site labelled as X-site and another site (labelled as L-site) for both the nucleotides on tubulin has been obtained. It is suggested that this X-site is possibly the putative E-site. In order to gain further insight into the nature of these sites, the Mg(II) at the N-site has been replaced by Mn(II) and the paramagnetic effect of Mn(II) on the linewidth of the proton resonances of tubulin-bound ATP and GTP has been studied. The results show that the L-site nucleotide is closer to the N-site metal ion compared to the X-site nucleotide. On the basis of these results, it is suggested that the L-site of ATP is distinct from the L-site of GTP while the X-site of both the nucleotides seems to be same. By using the paramagnetic effect of the metal ion, Mn(II), at the N-site on the relaxation rates of tubulin-bound ATP at L-site, distances of the protons of the base, sugar and phosphorous nuclei of the phosphorous moiety of ATP, from the N-site metal ion have been mapped. The base protons are approximately equal to 0.8-1 nm from this metal ion site. On the other hand, the phosphorous nuclei of the phosphate groups are somewhat nearer (approximately equal to 0.4-0.5 nm) from the N-site metal ion.

Role of glycosylation in the biosynthesis and activity of rabbit testicular angiotensin-converting enzyme.

Angiotensin-converting enzyme (ACE) is a type I glycoprotein anchored in the plasma membrane by a hydrophobic domain near its carboxyl terminus. The enzymatically active extracellular domain of ACE is slowly released from the cell by cleavage-removal of its membrane-anchoring carboxyl-terminal region. In the present study, we investigated the role of N- and O-glycosylation in intracellular transport and extracellular cleavage-secretion of rabbit testicular ACE. For ACE expression, we used an in vitro translation system, a permanently transfected mouse cell line, and human and Chinese hamster cells transiently transfected with vaccinia virus-T7 RNA polymerase-driven expression vectors. Sugar modifications of ACE were analyzed by testing its sensitivity to specific glycosidases. Cellular protein glycosylation was inhibited by using chemical inhibitors and a mutant cell line defective in protein glycosylation. Our experiments demonstrated that newly synthesized ACE acquires both N- and O-linked sugars before its cleavage-secretion and complete blockage of glycosylation results in rapid intracellular turnover of underglycosylated ACE. However, ACE synthesized without N-linked complex sugars and O-linked sugars can undergo normal transport and cleavage-secretion, and the underglycosylated protein is enzymatically active.