Search PubMed⌕ Search

Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 343 records · Page 19Linked to original sources
PubMed2000

Immunophenotypic and genotypic markers of follicular center cell neoplasia in diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCL) are a biologically and clinically heterogeneous entity. Although some DLBCL represent transformation of follicular lymphomas (FL), the proportion that is of follicular center cell (FCC) origin remains uncertain. Immunophenotypic and genotypic markers used to suggest a FCC origin for a lymphoma (bcl-6 and CD10 expression, lack of CD138 expression, bcl-2 rearrangements [R]) or to subdivide DLBCL (bcl-2 expression, bcl-6 R) were therefore investigated in 22 FL and 44 DLBCL using paraffin section immunostains and Southern blot/polymerase chain reaction analysis. All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 and CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD10+ (grade II or III). Bcl-2R was identified in 4/5 FL-GrI, 3/6 FL-GrII, and 1/3 FL-GrIII. Bcl-6R was found in 0/5, 2/4, and 0/3 FL, respectively. All but 3/41 DLBCL were bcl-6+ with 17/37 also bcl-2+ and CD10+. Three of these cases were also CD138+. Twelve bcl-6+ cases were bcl-2+, CD10-, six bcl-2-, CD10+, and two bcl-2-, CD10-. The three bcl-6- cases were bcl-2+, CD138- and two were CD10+. Bcl-2R was identified in 5/27 DLBCL with 4/5 bcl-2+, 3/4 tested CD10+ and 4/4 bcl-6+. Bcl-6R was identified in 7/26 including three with a classic FL phenotype. The vast majority of DLBCL in this study have an immunophenotype that supports a FCC origin. Although the proportion of DLBCL that co-expressed bcl-6, CD10 and bcl-2 was lower than for the FL, absence of bcl-2 or CD10 may be associated with higher grade FL It is also possible that bcl-6 expression is not completely specific for a FCC origin. Only a minority of cases suggested postfollicular differentiation. Only a minority of DLBCL show bcl-2R, suggesting that many have a different molecular pathogenesis than most low-grade FL. Bcl-6R did not exclude a FCC origin.

B-Lymphocytes↗
PubMed2000

Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies.

Epipodophyllotoxin-associated secondary myeloid leukemia is a devastating complication of acute lymphoblastic leukemia (ALL) therapy. The risk factors for treatment-related myeloid leukemia remain incompletely defined. Genetic deficiencies in glutathione S-transferase (GST) activities have been linked to higher frequencies of a number of human malignancies. Our objective was to determine whether the null genotype for GSTM1, GSTT1, or both, was more frequent in children with ALL who developed treatment-related myeloid malignancies as compared to those who did not. A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome. Among children with ALL who did not develop treatment-related myeloid malignancies, the frequencies of GSTM1 and GSTT1 wild-type, GSTM1 null-GSTT1 wild-type, GSTM1 wild-type-GSTT1 null, and GSTM1 and GSTT1 null genotypes were 40%, 42%, 9% and 9%, respectively. The corresponding frequencies for patients who developed acute myeloid malignancies were 42%, 32%, 11% and 16%, respectively (P = 0.26). A statistically significant increase in the frequency of the GST null genotype was observed in male patients who developed myeloid malignancies as compared to male ALL control patients (P = 0.036), but was not observed in female patients (P = 0.51). Moreover, a logistic regression analysis of possible predictors for myeloid malignancies, controlling for gender and race, did not reveal an association of GSTM1 or GSTT1 null genotypes (P = 0.62 and 0.11, respectively) with treatment-related malignancies. Our data suggest that GSTM1 and GSTT1 null genotypes may not predispose to epipodophyllotoxin-associated myeloid malignancies.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children.

AIMS: This analysis was performed to validate a previously developed population pharmacokinetic model for lamotrigine in order to establish a basis for dosage recommendations for children. METHODS: (a) The importance of the covariates in the final model was confirmed using the model validation dataset. Population and individual (Bayesian estimate) pharmacokinetic parameters were estimated using both the initial model, which included none of the covariates, and the final model. Accuracy and precision of parameter estimation and of concentration prediction were compared between the two models. (b) The performance in predicting the validation concentrations by the final model parameters obtained previously from the model development dataset was assessed. (c) The parameters of the final model were refined using a dataset combining both the development and validation data. RESULTS: Prediction performance of the final pharmacostatistical model was superior to that of the initial model. The results of the validation confirmed that concomitant antiepileptic drugs that increased or reduced lamotrigine clearance in adults had similar effects in children. The validation also verified the linear relationship between weight and clearance. The previously seen small sex effect on clearance was found statistically insignificant. CONCLUSIONS: The current analysis confirmed the previous findings. To achieve the same concentrations, children receiving enzyme-inducing antiepileptic drugs without valproate require higher doses than those receiving valproate; and heavier children require higher doses.

Adolescent↗
PubMed2000

The effects of lamotrigine on the pharmacokinetics of lithium.

AIMS: The treatment of bipolar disorder often includes use of multiple drug therapies. Lithium is one of the most commonly used treatments, but has a narrow therapeutic window. Lamotrigine, an established antiepileptic drug, is emerging as a potentially important new therapy in the treatment of bipolar disorder. The objective of this two-treatment crossover study was to determine whether lamotrigine affects lithium pharmacokinetics. METHODS: Twenty healthy adult men completed the study. Subjects took 2 g lithium gluconate anhydrous every 12 h in the morning and evening for 5 days and in the morning of day 6, with or without 100 mg lamotrigine once daily in the morning for 6 days. Blood and urine samples were collected on day 6 of both treatments to characterize the pharmacokinetics of lithium using noncompartmental methods. RESULTS: The geometric least-square mean ratio for renal clearance of lithium between the combination treatment and lithium alone treatment was 0.93 (95% confidence interval 0.85-1.02). Both treatments were well tolerated. CONCLUSIONS: Lamotrigine does not cause significant change in the pharmacokinetics of lithium.

Adult↗
PubMed2000

Changes in major components of tea fungus metabolites during prolonged fermentation.

Changes in major components and microbes in tea fungus broth (or kombucha; teakwass) prepared from nine different sources during a prolonged fermentation of up to 60 days were investigated. Cell concentrations of both yeasts and acetic acid bacteria in broth were generally higher than those in the cellulosic pellicles. The residual sucrose concentration decreased linearly with time, although the rate fell after the first month. Metabolic fates of glucose and fructose produced as a result of the hydrolysis of sucrose were different. Glucose was not produced in parallel with fructose (0.085 g 100 ml(-1) d(-1)) but was produced with a lower initial rate (0.041 g 100 ml(-1) d(-1)). Both titratable acidity and gluconic acid increased steadily with time for all samples, although gluconic acid was not generated for 6 days until the fermentation had begun. Acetic acid increased slowly to a maximum value of 1.1 g 100 ml(-1) after 30 days; thereafter, it decreased gradually. Gluconic acid contributed to the titratable acidity and thus, the taste of tea fungus broth, during the final stage of fermentation. It is concluded that the desired quality or composition of kombucha can be obtained through the proper control of fermentation time.

Acetic Acid↗
PubMed2000

Growth hormone-releasing hormone decreases voltage-gated potassium currents in GH4C1 cells.

The electrophysiological properties of anterior pituitary somatotropes integrally involve the function of voltage-gated K+ currents. In this study, we have used GH4C1 cell lines to investigate the effect of human GHRH on voltage-gated K+ currents. Because of a clear 'rundown' of the K+ current with classic whole cell recording (WCR) without ATP in pipette solution, nystatin-perforated WCR was the major recording configuration used. Using a low Ca2+ (0.5 mM) bath solution containing Co2+ (1 mM) and TTX (1 microM), GH4 cells predominantly exhibited an outward delayed rectifier K+ current (IK). Local application of growth hormone releasing hormone (GHRH) (100 nM) reversibly reduced the amplitude of the K+ currents (to 83% of control). There was no effect of GHRH on the activation curve of the K+ current and no difference observed using 2.5 mM Ca2+ or low Ca2+ (0.5 mM Ca2++1 mM Co2+) bath solutions. Under the condition of low Ca2+ bath solution, the application of apamin (1 microM) or charybdotoxin (1 microM), two specific blockers of the Ca2+-activated K+ current, did not alter the K+ current or the response to GHRH. This reduction in the K+ current by GHRH was also observed with classic WCR with a pipette solution containing ATP (2 mM). The GHRH-induced reduction in the K+ current was completely abolished by the presence of GDP-beta-s (500 microM) in the pipette solution or by addition of PKC inhibitors, calphostin C (100 nM) and chelerythrine (1 microM), in bath solution. Inhibitor for cAMP-PKA system (Rp-cAMP and H89) did not affect the K+ current response to GHRH. These results suggest that GHRH reduces the voltage-gated K+ current in GH4C1 cells, a response that is mediated by G-proteins and PKC system but not by cAMP-PKA system. The reduction in the K+ current may partially contribute to the GHRH-stimulated growth hormone (GH) secretion.

Apamin↗
PubMed2000

A randomized controlled trial of kurorinone versus interferon-alpha2a treatment in patients with chronic hepatitis B.

It has recently been shown that a Chinese traditional medicine, kurorinone, extracted from Sophora Flavescens Ait, possesses antiviral properties. We evaluated the efficacy and safety of kurorinone treatment in patients with chronic hepatitis B. Ninety-four patients with abnormal alanine transaminase (ALT) levels and hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV) DNA-positivity were randomly assigned to receive either kurorinone 400 mg daily (45 patients) or 3 million units (MU) of interferon-alpha (IFN-alpha) (49 patients, daily for 1 month, every other day for 2 months) for 3 months. Patients were followed-up for 12 months. At baseline, both groups were comparable regarding age, gender and serological parameters. At the end of treatment, complete response (defined as ALT normalization and HBeAg and/or HBV DNA loss) occurred in 50% of the kurorinone group and in 61.3% of the IFN-alpha-treated group (P > NS). At the end of the 12-month follow-up period, a complete response (sustained response) occurred in 26.7-36.7% of kurorinone-treated patients with moderate or mild liver damage and in 44.4-46.7% of IFN-alpha-treated patients with similar liver injury. In kurorinone- as well as in IFN-alpha-treated patients, there was no statistical significant difference with respect to complete response rates between HBeAg-positive and hepatitis B e antibody-positive subgroups. Kurorinone had no untoward side-effects except for local pain at injection sites. The results of this trial suggest that kurorinone is able to inhibit HBV replication and improve disease remission in patients with chronic hepatitis B.

Adolescent↗
PubMed2000

Diverse intracellular signalling systems used by growth hormone-releasing hormone in regulating voltage-gated Ca2+ or K channels in pituitary somatotropes.

Influx of Ca2+ via Ca2+ channels is the major step triggering exocytosis of pituitary somatotropes to release growth hormone (GH). Voltage-gated Ca2+ and K+ channels, the primary determinants of the influx of Ca2+, are regulated by GH-releasing hormone (GHRH) through G-protein-coupled intracellular signalling systems. Using whole-cell patch-clamp techniques, the changes of the Ca2+ and K+ currents in primary cultured ovine and human somatotropes were recorded. Growth hormone-releasing hormone (10 nmol/L) increased both L- and T-type voltage-gated Ca2+ currents. Inhibition of the cAMP/protein kinase A (PKA) pathway by either Rp-cAMP or H89 blocked this increase in both L- and T-type Ca2+ currents. Growth hormone-releasing hormone also decreased voltage-gated transient (IA) and delayed rectified (IK) K+ currents. Protein kinase C (PKC) inhibitors, such as calphostin C, chelerythrine or downregulation of PKC, blocked the effect of GHRH on K+ currents, whereas an acute activation of PKC by phorbol 12, 13-dibutyrate (1 micromol/L) mimicked the effect of GHRH. Intracellular dialysis of a specific PKC inhibitor (PKC19-36) also prevented the reduction in K+ currents by GHRH. It is therefore concluded that GHRH increases voltage-gated Ca2+ currents via cAMP/PKA, but decreases voltage-gated K+ currents via the PKC signalling system. The GHRH-induced alteration of Ca2+ and K+ currents augments the influx of Ca2+, leading to an increase in [Ca2+]i and the GH secretion.

Alkaloids↗
PubMed2000

A preliminary study of sonographic grading of fetal intracardiac echogenic foci: feasibility, reliability and association with aneuploidy.

OBJECTIVES: To prospectively and quantitatively grade intracardiac echogenic focus/foci (ICEF) using sonographic gain reduction and to determine the association of ICEF by grade with fetal aneuploidy. METHODS: Women referred for raised maternal age (> or = 35 years), or > 18 years of age and with a Down syndrome risk > or = 1/270, increased trisomy 18 risk by second trimester serum screen or a prior aneuploid offspring were included in this institutionally approved protocol. Only pregnancies of gestational age between 14 and 24 weeks were included. All women had a targeted ultrasound and were offered fetal chromosome analysis. The classification of ICEF was made from a four-chamber view of the fetal heart. The echo amplitude of the ICEF was compared to that of the thoracic spine and categorized according to the comparative gain setting at which the image of the relevant structure disappeared: Grade O = no ICEF present, Grade 1 = ICEF image lost before thoracic spine when gain was reduced, Grade 2 = ICEF image lost at same gain setting as thoracic spine, Grade 3 = thoracic spine image lost before ICEF. The primary outcome was a prenatally or post-natally detected chromosomal abnormality. RESULTS: A total of 885 eligible women were examined during the 21-month study period. ICEF were seen in 29 (3.3%) fetuses: 24(83%) in the left ventricle and five (17%) in the right ventricle. A chromosome abnormality was identified in 13/671 (1.9%) fetuses without ICEF (Grade 0) and 0/21 (0%) fetuses with Grade 1 ICEF. In contrast, two of five (40%) fetuses with Grade 2 ICEF were aneuploid (P = 0.005). No Grade 3 ICEF were observed. Additional sonographic abnormalities were seen in both aneuploid fetuses with Grade 2 ICEF. Interobserver agreement on ICEF grading was noted in 50/50 (100%) examinations (kappa = 1.0). CONCLUSIONS: Sonographic grading of ICEF is feasible and highly reliable. Grade 2 ICEF, especially when accompanied by additional sonographic markers of a chromosomal abnormality, are associated with aneuploidy significantly more frequently than Grade 1 ICEF.

Adult↗
PubMed2000

Dialysis solution containing hyaluronan: effect on peritoneal permeability and inflammation in rats.

BACKGROUND: Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. METHODS: Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. RESULTS: After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.003; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 +/- 22.8 +/- 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-alpha (11.2 +/- 14.7 vs. 42.3 +/- 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 +/- 86.5 vs. 402.4 +/- 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals. CONCLUSIONS: The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

Animals↗
PubMed2000

Bovine FcgammaRIII with a single extracellular domain.

The full length of gene encoding Fc receptor types III for bovine immunoglobulin G (boFcgammaRIII, CD16) was obtained with PCR from the c DNA library of bovine alveolar macrophages. Through molecular cloning and sequencing it is shown that the coding gene has 507 bp and codes for 168 amino acids. There are signal peptide, transmembrane spanning domain and three potential N-linked glycosylation sites in the sequence. Compared with the boFcgammaRIII cDNA sequence cloned by Collins et al, it deletes 82 amino acids and has only one extracellular domain. It is suggested that this cDNA fragment is a special form of the gene structure of bovine FcgammaRIIIA (CD16-II).

Amino Acid Sequence↗
PubMed2000

Arthritis care: comparison of physicians' and patients' views.

OBJECTIVES: To understand the expressed needs of physicians and their patients with respect to arthritis care, identify areas of agreement and disagreement in doctor and patient views of arthritis care, and to determine the types of educational programs needed. METHODS: Focus group interviews were conducted with 14 physicians of varied specialties and 12 patients with arthritis from Oxford Health Plans. Interviews were audiotaped and transcribed. Analyses were performed by using text processing programs from the Unix computer operating system. Common themes were identified and summarized. RESULTS: Physicians and patients agreed that pain and loss of functioning were the most important problems patients with arthritis faced and that arthritis was incurable. Both agreed that doctors need more time to discuss individual concerns with their patients. More information about diet and exercise and strategies for reducing social isolation were needed. Doctors and patients disagreed about the value of nutritional supplements, joint replacement, and referrals to specialists. Disagreement also existed regarding the belief that pain was an inevitable part of the aging process, and with respect to the use of drug and surgical therapy. CONCLUSIONS: Areas of agreement and disagreement were discussed. Collaboration and negotiation were identified as constructive responses to conflicts between physicians and patients. Patients need to be taught self-care strategies to minimize the impact of arthritis on their daily lives. The specific continuing education needs of physicians involved training in exercise, nutrition, occupational and physical therapy, prescriptions, and alternative medicine.

Aged↗
PubMed2000

Effects of clofibrate and indocyanine green on the hepatobiliary disposition of acetaminophen and its metabolites in male CD-1 mice.

1. The effects of clofibrate (CFB) and indocyanine green (ICG) on the biliary excretion of acetaminophen (APAP) and its metabolites were investigated. 2. Male CD-1 mice were pretreated with 500 mg CFB/kg, i.p. for 10 days. Controls received corn oil vehicle only. After overnight fasting, common bile duct-cannulated mice were challenged with a non-toxic dose of APAP (1 mmol/kg, i.v.). 3. CFB pretreatment did not affect bile flow rate, nor did it affect the cumulative biliary excretion of APAP and its conjugated metabolites. 4. Additional CFB or corn oil pretreated mice were given 30 mumol indocyanine green (ICG)/kg, i.v., immediately before APAP dosing. ICG is a non-metabolizable organic anion that is completely excreted into the bile through a canalicular transport process for organic anions. 5. ICG significantly decreased the bile flow rate and biliary concentration of APAP-glutathione, APAP-glucuronide and APAP-mercapturate within the first hour after dosing without affecting the biliary concentration of APAP. 6. The results indicate that CFB pretreatment does not affect the total amount of APAP and its metabolites excreted in bile. They also suggest that the biliary excretion of several conjugated metabolites of APAP share the same excretory pathway with the organic anion ICG.

Acetaminophen↗
PubMed2000

A study of the association between daily mortality and ambient air pollutant concentrations in Pittsburgh, Pennsylvania.

We have studied the possible association of daily mortality with ambient pollutant concentrations (PM10, CO, O3, SO2, NO2, and fine [PM2.5] and coarse PM) and weather variables (temperature and dew point) in the Pittsburgh, PA, area for two age groups--less than 75, and 75 and over--for the 3-year period of 1989-1991. Correlation functions among pollutant concentrations show important seasonal dependence, and this fact necessitates the use of seasonal models to better identify the link between ambient pollutant concentrations and daily mortality. An analysis of the seasonal model results for the younger-age group reveals significant multicollinearity problems among the highly correlated concentrations of PM10, CO, and NO2 (and O3 in spring and summer), and calls into question the rather consistent results of the single- and multi-pollutant non-seasonal models that show a significant positive association between PM10 and daily mortality. For the older-age group, dew point consistently shows a significant association with daily mortality in all models. Collinearity problems appear in the multi-pollutant seasonal and non-seasonal models such that a significant, positive PM10 coefficient is accompanied by a significant, negative coefficient of another ambient pollutant, and the identity of this other pollutant changes with season. The PM2.5 data set is half that of PM10. Identical-model runs for both data sets reveal instability in the pollutant coefficients, especially for the younger age group. The concern for the instability of the pollutant coefficients due to a small signal-to-noise ratio makes it impossible to ascertain credibly the relative associations of the fine- and coarse-particle modes with daily mortality. In this connection, we call for caution in the interpretation of model results for causal inference when the models use fully or partially estimated PM values to fill large data gaps.

Adolescent↗
PubMed2000

The role of intrarenal nitric oxide in the natriuretic response to dopamine-receptor activation.

Dopamine and dopamine-1 receptor agonists produce diuresis and natriuresis by causing changes in renal hemodynamics and by the activation of dopamine-1 receptors located within the various regions of the nephron. Nitric oxide plays an important role in the maintenance of systemic and regional hemodynamics. The present study was undertaken to investigate the effect of locally generated nitric oxide on renal function and its potential influence on the renal responses to dopamine-1 receptor agonists. The intrarenal infusion of a nitric oxide synthase inhibitor, L-NAME, (50 microg/kg min for 90 min) in anesthetized rats produced significant decreases in urine volume, urinary sodium excretion, glomerular filtration rate and fractional sodium excretion. These changes in renal function were associated with a concomitant decrease in urinary nitrate excretion, an indicator of nitric oxide release. However, L-NAME at this dose did not produce any significant changes in mean arterial pressure or heart rate. Intravenous infusion of fenoldopam (1 microg/kg min for 30 min), a selective dopamine-1 receptor agonist, produced diuresis and natriuresis without causing any changes in mean arterial pressure and heart rate. These renal effects of fenoldopam were significantly attenuated in animals that received the simultaneous infusion of L-NAME (intrarenal). Similar results were obtained with dopamine in that the natriuretic and diuretic response to dopamine was also attenuated during simultaneous infusion of dopamine with L-NAME. In addition, the diuresis and natriuresis produced by fenoldopam and dopamine was associated with increases in urinary nitrate excretion. Interestingly, these increases in the nitrate levels seen with fenoldopam and dopamine were also significantly reduced in the presence of L-NAME. These results indicate that intrarenal nitric oxide plays an important role in regulating renal sodium excretion and that an intact renal nitric oxide system is required for the full expression of diuretic and natriuretic response seen during dopamine-1 receptor activation.

Animals↗
PubMed2000

Minimal structural and glycosylation requirements for ST6Gal I activity and trafficking.

The influence of N-linked glycosylation on the activity and trafficking of membrane associated and soluble forms of the STtyr isoform of the ST6Gal I has been evaluated. We have demonstrated that the enzyme is glycosylated on Asn 146 and Asn 158 and that glycosylation is not required for the endoplasmic reticulum to Golgi transport of the membrane-associated form of the STtyr isoform. In addition, N-linked glycosylation may stabilize the protein but is not absolutely required for catalytic activity in vivo. In contrast, soluble forms of the protein consisting of amino acids 64-403, 89-403, and 97-403 are efficiently secreted and active in their fully glycosylated forms, but retained in the endoplasmic reticulum and inactive in their unglycosylated forms. These results suggest that membrane associated and soluble forms of the STtyr protein have different requirements for N-linked glycosylation. Elimination of the oligosaccharide attached to Asn 158 in the full length STtyr single and double glycosylation mutants generates proteins that are not cleaved and secreted but stably localized in the Golgi, like the STcys isoform of the ST6Gal I. This stable Golgi localization is correlated with the observation that these two mutants are active in in vivo assays but inactive in in vitro assays of membrane lysates. We predict that removal of N-linked oligosaccharides leads to an increased ability of the STtyr protein to self-associate or oligomerize which subsequently allows more stable retention in the Golgi and increased aggregation and inactivity when membranes are lysed in the in vitro activity assays.

Amidohydrolases↗
PubMed2000

Nicotine dependence and its familial aggregation in Chinese.

BACKGROUND: Nicotine dependence is a significant public health problem. This study attempted to characterize the prevalence and familial aggregation of nicotine dependence in China. METHODS: In 1998, we initiated a community-based cross-sectional study among residents of the Yuexi County in Anqing, China. A total of 991 current smokers from 488 randomly selected nuclear families were recruited and surveyed by use of the standardized Fagerstrom Test of Nicotine Dependence (FTND) questionnaire and the Revised Tolerance Questionnaire (RTQ). All study subjects were offspring in their respective nuclear families, and 478 male-male pairs (aged 41.7 +/- 12.1 years) were finally used for data analyses, because the number of female current smokers (n = 5) was too small. RESULTS: The correlation coefficient of the FTND and the RTQ scores was as high as 0.84 (P < 0.0001). Nicotine dependence, defined as an FTND score > or =8 or an RTQ score > or =28, had a prevalence of 12.7% and 11.1%, respectively. The respective sibling recurrent risk was 1.7 and 2.4, according to the FTND or the RTQ criteria. The adjusted odds ratios and 95% CI of nicotine dependence of second siblings in families in which the first sibling was nicotine dependent were 2.13 (95% CI: 1.02-4.43) and 3.50 (95% CI: 1.65-7.36) respectively, according to the FTND and RTQ criteria. CONCLUSIONS: The prevalence of nicotine dependence in male current smokers in China was comparable to that reported in previous US and European studies. Our findings suggest that genetic influences may play an important role in vulnerability to nicotine addiction.

Adult↗