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Biomedical subjects

A W Kung

Publications and source records attributed to A W Kung.

At least 19 recordsLinked to original sources
PubMed2000

PvuII polymorphisms of the estrogen receptor alpha and bone mineral density in healthy southern Chinese women.

The association between PvuII polymorphisms of the estrogen receptor alpha (ERalpha) gene and total as well as regional bone mineral density (BMD) in healthy Chinese women (n = 182) was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), where P indicated the absence and p the presence of PvuII restriction sites. Subjects with PP genotype had significantly higher BMD at the thoracic spine and ribs (both P < 0.05) when compared with those with Pp and pp genotypes. Although PP genotype had slightly higher BMD values at the lumbar spine L2-L4 region and hip by 8% and 7%, respectively, the results failed to reach statistical significance. After adjusting for age, height, weight, and years since menopause, PP genotype had higher BMD at the left (P < 0.02) and right (P < 0.05) rib region but not at the thoracic spine (P = 0.056). Analyzing the premenopausal subjects alone (n = 64) revealed that subjects with PP genotype had higher adjusted BMD at the right rib region (P < 0.05). When only the postmenopausal women (n = 118) were analyzed, the adjusted BMD of the PP genotype at the thoracic spine was significantly higher (P < 0.05) than the other two groups. In conclusion, estrogen receptor gene has a role in determining bone mass but the clinical impact on its own is probably small.

Asian People↗
PubMed2000

The efficacy and tolerability of alendronate in postmenopausal osteoporotic Chinese women: a randomized placebo-controlled study.

Osteoporosis is a growing health problem in Asian women and it is expected that half of the world's hip fractures will occur in Asia in 50 years' time. As the use of hormonal replacement therapy (HRT) is extremely low in postmenopausal Asian women, nonhormonal agents will be more acceptable for the treatment and prevention of osteoporosis. The efficacy, tolerability, and acceptability of alendronate, an amino-bisphosphonate, for Asian women was evaluated in 70 osteoporotic southern Chinese women in a prospective, randomized, double-blind study. The subjects were randomized to receive either alendronate 10 mg daily or placebo, plus calcium supplementation 500 mg daily. The baseline L 1-4 and hip bone mineral density (BMD) were similar between both groups. At the end of 1 year, there was an increase of 5.8% in the lumbar spine BMD and 3.4% at the total hip with alendronate treatment when compared with baseline values (P < 0.001). Alendronate treatment for 1 year resulted in significant improvement in BMD at all sites measured when compared with placebo. There was also marked reduction in serum alkaline phosphatase (ALP) and urinary n-telopeptide (NTx) in the alendronate group when compared with the placebo group (ALP 25% versus 2%, NTx 75% versus 14%, both P < 0.005). The changes in ALP and NTx at 6 and 12 months correlated with the change in BMD at all sites measured at 1 year (P all <0.05). Alendronate was well tolerated and accepted, although two cases of gastric ulcer were reported. We conclude that alendronate is an effective and well-accepted agent for the treatment of osteoporosis in Asian women.

Absorptiometry, Photon↗
PubMed2000

Effect of calcitriol on bone mineral density in premenopausal Chinese women taking chronic steroid therapy. A randomized, double blind, placebo controlled study.

OBJECTIVE: To study the effect of chronic steroid therapy on bone mineral density (BMD) in premenopausal women with normal menstrual cycles and its treatment. METHODS: A double blind placebo controlled study to evaluate 81 premenopausal women with systemic lupus erythematosus (SLE), aged 31.1 +/- 6 years, taking chronic steroid therapy, with a mean cumulative prednisone dose of 28 +/- 16.2 g. They were randomly allocated to 3 groups: Group 1: 0.5 microg calcitriol and 1200 mg calcium daily; Group 2: 1,200 mg calcium and placebo calcitriol; and Group 3: both placebo calcitriol and placebo calcium. RESULTS: Baseline T score at the lumbar spine was > -1 in 56.8% and < -2.5 in 3.7% of the patients. At the end of 2 years, patients in the calcitriol group exhibited a significant increase of 2.1 +/- 2.4% in BMD at the lumbar spine compared to baseline value (p < 0.05). This change was not significantly different from the respective change in either calcium or placebo group (0.4 +/- 2.9% and 0.3 +/- 3.5%, respectively). No significant changes were observed in any treatment group in BMD at the hip or radius. Alkaline phosphatase increased both in the placebo (baseline: 57.5 +/- 17.5 IU/I; year 2: 60.9 +/- 15.3 IU/A) and the calcium group (baseline: 53.6 +/- 16.6 IU/I; year 2: 59.0 +/- 22.8 IU/1), but this increase reached statistical significance only in the calcium group, while the same variable remained stable in the calcitriol group (baseline: 53.9 +/- 14.1 IU/I; year 2: 54.6 +/- 12.3 IU/I). CONCLUSION: Premenopausal women with SLE taking prolonged steroid therapy had lower BMD but showed no significant bone loss over the 2 year study period. The beneficial effect of calcitriol treatment in these premenopausal women was small, at least when it was instituted late in the course of steroid therapy.

Adrenal Cortex Hormones↗
PubMed1999

Evaluation of a new calcaneal quantitative ultrasound system and determination of normative ultrasound values in southern Chinese women.

Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. The present study aimed at evaluating the precision of the Sahara bone ultrasound densitometer and to determine the normative QUS data in healthy southern Chinese women. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and qualitative ultrasound index (QUI) were determined. The long-term in vitro precision of the Sahara machine over 6 months was 4.6% for BUA and 0.39% for SOS. The short-term in vivo precision was 3.2 +/- 1.3% for BUA, 0.3 +/- 0.2% for SOS and 1.8 +/- 1.0% for QUI. The standardized precision for BUA, SOS and QUI was 4.4, 3.8 and 2.2 respectively. The normative data were determined in 1086 healthy subjects. Postmenopausal women had significantly lower BUA, SOS and QUI levels than the premenopausal women. Significant negative correlations were observed between QUS indices and age. Bone mineral density (BMD) assessments was performed on 349 of these subjects. BUA correlated significantly with lumbar spine BMD (r = 0.326) and femoral neck BMD (r = 0.395). Similar correlations were observed between SOS, QUI and BMD, with r values ranging between 0.446 to 0.522. Despite the fact that Chinese women have significantly lower BMD values than Caucasian women, the mean BUA values for pre- and postmenopausal Chinese women (73 +/- 18 and 59 +/- 18 dB/MHz respectively) were almost the same as those reported for Caucasian women. These normative data will be useful in the assessment of southern Chinese women with fracture risk.

Absorptiometry, Photon↗
PubMed1999

Quantitative ultrasound and symptomatic vertebral fracture risk in Chinese women.

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n = 53), normal postmenopausal women (group II, n = 198), and osteoporotic women without (group III, n = 141) and with vertebral fractures (group IV, n = 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <-2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was -2.87 +/- 1.02 for BUA, -2.54 +/- 0.79 for SOS, -3.17 +/- 0.70 for QUI, -2.65 +/- 0.86 for L2-4 BMD and -2.53 +/- 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2-2.6) for each 1 SD reduction in BUA, 2.72 (1.3-5.3) for SOS, 2.58 (1.4-4.6) for QUI, 2.33 (1.6-3.3) for L2-4 BMD, 2.09 (1. 37-3.20) for femoral neck BMD and 1.88 (1.34-2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0. 92, for SOS, QUI, L2-4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91.

Absorptiometry, Photon↗
PubMed1999

Dual-energy X-ray absorptiometry for body composition estimation in Chinese women.

OBJECTIVE: To determine whether dual-energy X-ray absorptiometry (DXA) is a valid method for body composition assessment of obese and non-obese subjects. DESIGN: Cross-sectional study. SUBJECTS: Chinese women living in Hong Kong; 66 of 91 subjects had body mass index (BMI) of >25 kg/m2. MEASUREMENTS: Anthropometrics, including body weight, body height, waist and hip girth. Percentage body fat (%BF) and fat-free mass (FFM) from DXA (Hologic 2000 plus, Enhanced Array Whole Body Version 5.63) were compared with that based on a tracer dose of deuterium oxide for the determination of total body water (TBW). RESULTS: In both obese and non-obese subjects, FFMDXA was similar to FFMTBW. The Bland and Altman-type analysis indicated that comparable between-methods differences (mean bias) and limits of agreement were obtained in obese and non-obese subjects for FFM (0.4, between -4.4 and 5.2 kg vs 0.5, between -3.1 and 4.1 kg) and %BF (-0.6, between -7.6 and 6.4% vs -1.2, between -8.6 and 6.2%). The %BF bias was independent of age, BMI, hip circumference, and waist-to-hip ratio, but correlated with waist girth (r=0.24, P=0. 021). CONCLUSION: The sources of bias are methodological and anthropometric in nature. The between-methods differences, however, are small and clinically insignificant. DXA is a valid method for assessing the body composition of obese patients. SPONSORSHIP: This study was supported by a HKU-CRCG grant.

Absorptiometry, Photon↗
PubMed1999

Alterations in hepatic lipase and lipoprotein subfractions with transdermal testosterone replacement therapy.

OBJECTIVES: The effect of sex hormone replacement therapy on lipoprotein metabolism is thought to be less marked with the transdermal route because of the lack of hepatic first-pass effect. The aim of this study was to evaluate the effects of testosterone replacement therapy given transdermally via a permeation-enhanced system on plasma lipolytic enzymes (hepatic and lipoprotein lipase), LDL and HDL subfraction concentrations. MEASUREMENTS: Ten patients with primary testicular failure were started on transdermal testosterone (Testoderm(R)). Plasma lipids, lipoproteins and post-heparin plasma lipolytic enzymes were evaluated before and after 3 months of treatment. LDL and HDL subfractions were measured by density gradient ultracentrifugation and hepatic and lipoprotein lipase activities by radio-enzymatic method. RESULTS: Serum testosterone level increased to within the normal range in all subjects whereas serum dihydrotestosterone (DHT) increased to supra-normal values. Plasma hepatic lipase (HL) activity increased after testosterone replacement (24.7 +/- 7.5 vs. 29.2 +/- 8.3 micromol free fatty acid released per hour, P < 0.05) and the increase in HL correlated with the increase in DHT (r = 0.64, P < 0. 05). Small changes were observed in LDL subfraction pattern with an increase in the concentration of small dense LDL-III (80.1 +/- 30.3 vs. 93.0 +/- 27.8 mg/l, P < 0.05). No significant change was seen in the HDL2 subfraction but HDL3 decreased after treatment (0.93 +/- 0. 17 vs. 0.79 +/- 0.14 mmol/l, P < 0.01). CONCLUSIONS: Testosterone replacement, given via a permeation-enhanced transdermal system, is associated with changes in hepatic lipase activity and in LDL and HDL subfractions. Whether these changes adversely influence the cardiovascular risk in the longterm remains to be determined.

Administration, Cutaneous↗
PubMed1999

Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy.

OBJECTIVE: To evaluate the efficacy of calcitriol and hormonal replacement therapy (HRT) in the treatment of steroid-induced osteoporosis in hypogonadal women. METHODS: We studied 28 young patients (aged 37 +/- 6 yr) with systemic lupus erythematosus (SLE) on chronic steroid therapy for 130 +/- 22 months and requiring more than 10 mg/day prednisone. They were amenorrhoeic for more than 2 yr with proven ovarian failure. All had osteopenia with a T score at L2-4 of less than -1. They were randomized to receive HRT (conjugated oestrogen 0.625 mg daily from day 1 to day 21 plus medroxyprogesterone acetate 5 mg daily days 10-21) or calcitriol 0.5 microg daily. All received calcium carbonate 1 g/day. RESULTS: There were no differences in the baseline demographic, bone mineral density (BMD) and biochemical data between the two groups. Lumbar spine BMD increased by 2.0 +/- 0.4% after 2 yr with HRT (P<0.05), but reduced by 1.74 +/- 0.4% (P<0.05) with calcitriol treatment. No change was seen at the distal one-third radius with HRT treatment but significant bone loss (2.3 +/- 1.4%, P<0.02) was observed with calcitriol therapy. BMD at the hip did not change in both groups. Comparing both treatment groups, significant differences in the BMD at the spine (P<0.03) and radius (P<0.05) were seen at the end of 2 yr. The changes in urinary n-telopeptide excretion but not serum osteocalcin at 6 months and 12 months were inversely correlated with the changes in lumbar spine BMD at 24 months. HRT did not cause an adverse effect on SLE disease activity. CONCLUSION: HRT but not calcitriol could prevent bone loss in young hypogonadal women on chronic steroid therapy.

Adult↗
PubMed1999

7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men.

The synthetic steroid 7alpha-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5alpha-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted s.c. into the upper arm and removed after 6 weeks and two injections of TE (200 mg, i.m.) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 +/- 0.1 nmol/L after 3 weeks and 1.3 +/- 0.1 nmol/L after 6 weeks (mean +/- SEM; all men). Nadir testosterone concentrations were 3.6 +/- 0.6 nmol/L at the end of the wash-out phase and 9.4 +/- 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential androgen replacement therapy.

Adult↗
PubMed1999

Effect of radioactive iodine therapy on cytokine production in Graves' disease: transient increases in interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor-alpha, with longer term increases in interferon-gamma production.

Spontaneous and mitogen-stimulated production of interleukin-4 (IL-4), IL-6, IL-10, IL-12, interferon-gamma (IFNgamma), and tumor necrosis factor-alpha were evaluated by enzyme-linked immunospot assay of peripheral blood mononuclear cells from patients with Graves' disease immediately before and at 4, 17, and 59 days after treatment with radioactive iodine. Patients had significantly reduced IL-4 and IFNgamma production before treatment compared with healthy controls. Both cytokines were increased to normal levels by day 17 after treatment, and IFNgamma remained at normal levels on day 59, whereas IL-4 returned to subnormal levels at this time. IL-12 production was initially normal and was not significantly altered by therapy. IL-6, IL-10, and tumor necrosis factor-alpha were also normal before radiotherapy, but increased significantly on day 17, returning to pretreatment levels by day 59. Thus, radioiodine treatment induced a transient increase in both proinflammatory and antiinflammatory cytokines and a more prolonged increase in IFNgamma production, the latter representing a definite shift toward a type 1 cytokine profile.

Adult↗
PubMed1998

Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women.

Controversial results were reported on the association of vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD). We studied allelic frequencies of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms (RFLPs) in 144 normal healthy southern Chinese premenopausal women aged between 30 and 40 years, and correlated their peak bone mass with the VDR genotypes. In comparison to Western populations, the B allele of the BsmI site is only found in 5% of the Chinese population. The BBAAtt genotype is virtually nonexistent in Chinese people. Except for the slightly higher BMD values at the midlateral L-3 vertebra (13.8%, p = 0.045) and at the Ward's triangle (13.3%, p = 0.08) in the bb subjects, no difference could be detected at other sites between the Bb and bb subjects. The same findings were observed when comparing the Tt to tt subjects. Analysis of the VDR genotype revealed that subjects with BbAaTt and BbAATt haplotypes had the lowest peak bone mass. Their L2-4 lumbar spine, midlateral L-3 vertebra, and Ward's triangle BMD was 1.04, 0.90, and 0.75 standard deviation (SD), respectively, lower than the bbAATT counterparts, but none of the comparisons were statistically significant. However, with the low frequency of the B allele, our study had limited power to detect a small difference in the BMD of the various genotypes. In conclusion, although VDR polymorphism is believed to affect calcium absorption, this study failed to confirm a strong relationship between the VDR genotype and peak bone mass in our population with low dietary calcium intake.

Adult↗
PubMed1998

Age-related osteoporosis in Chinese: an evaluation of the response of intestinal calcium absorption and calcitropic hormones to dietary calcium deprivation.

BACKGROUND: Age-related osteoporosis may be associated with inefficient intestinal calcium absorption and bone remodeling. OBJECTIVE: We investigated the pathogenesis of age-related osteoporosis in Chinese women with habitual low calcium intakes. DESIGN: We studied the response of intestinal calcium absorption, calcitropic hormones, and biochemical bone markers to graded dietary calcium deprivation. RESULTS: The osteoporotic subjects (n = 25) had higher urinary calcium excretion (P < 0.05) and lower plasma 1,25-dihydroxyvitamin D concentrations (P < 0.02) than did age-matched control women (n = 25). Parathyroid hormone was not significantly different from that in age-matched control women but was significantly higher than in young women (n = 15, P < 0.05). Fractional 45Ca absorption was approximately 61% in all 3 groups when the diet was unmodified and increased to 71%, 69%, and 68% in the osteoporotic subjects, age-matched control women, and young women, respectively, when dietary calcium was reduced to 300 mg/d. When the osteoporotic women were calcium deprived, serum 1,25-dihydroxyvitamin D failed to increase but urinary calcium excretion persisted. In contrast, supplementation with 1200 mg Ca resulted in a lowering of parathyroid hormone (P < 0.005 compared with the unmodified diet) and 1,25-dihydroxyvitamin D (P < 0.01) and decreased fractional 45Ca absorption (P < 0.01), suggesting that the increased calcium intake was associated with a potent compensatory ability of the intestine and calcitropic hormones to adapt. Calcium supplementation lowered osteocalcin (P < 0.05) but not alkaline phosphatase, which remained elevated in the osteoporotic subjects at all stages. CONCLUSIONS: Elderly osteoporotic women had reduced 1,25-dihydroxyvitamin D production, excessive urinary calcium loss, and high bone turnover. The Chinese women had exceptionally potent intestinal calcium absorption.

Adult↗
PubMed1998

Plasma cholesteryl ester transfer protein activity in hyper- and hypothyroidism.

Thyroid dysfunction is associated with multiple changes in lipoprotein metabolism, and we have determined the effects of thyroid dysfunction on plasma cholesteryl ester transfer protein (CETP) activity. CETP is a plasma protein that mediates the exchange of cholesteryl ester and triglyceride between plasma lipoproteins and plays an important role in high-density lipoprotein metabolism and in the reverse cholesterol transport pathway. Plasma CETP activity was assayed in 18 hyperthyroid and in 17 hypothyroid patients, before and after treatment, by measuring the transfer of cholesteryl esters from exogenous radiolabeled high-density lipoprotein to apolipoprotein B-containing lipoproteins. Plasma CETP activity was increased in hyperthyroid patients, compared with their matched controls (22.11 +/- 8.92% transferred/5 microL.4 h vs. 16.75 +/- 6.48, P < 0.05), whereas in hypothyroid patients, plasma CETP activity was decreased (11.14 +/- 4.84% transferred/5 microL.4 h vs. 17.26 +/- 7.13, P < 0.01). Plasma CETP activity decreased after treatment of thyrotoxicosis, although a significant change was observed, mainly in the severely thyrotoxic patients with free T4 > 100 pmol/L (n = 11, 25.61 +/- 8.12% transferred/5 microL.4 h vs. 21.71 +/- 7.84, P < 0.05). In the hypothyroid patients, there was a significant increase in plasma CETP activity after thyroxine replacement (11.14 +/- 4.84% transferred/5 microL.4 h vs. 15.46 +/- 6.71, P < 0.01). There was a strong positive correlation between log(free T4) and plasma CETP activity (r = 0.51, P < 0.001). In summary, both hyper- and hypothyroidism are associated with significant changes in plasma CETP activity, and these changes are corrected when the patients have been rendered euthyroid.

Adult↗
PubMed1998

A change from stimulatory to blocking antibody activity in Graves' disease during pregnancy.

Remission of Graves' disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry. Median TSAb (determined by cAMP release) decreased from 280% (96-3200) to 130% (range, 35-350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 +/- 9% to 43 +/- 16% (mean +/- SD; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T4 levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy. The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5+ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.

Antibodies, Blocking↗
PubMed1998

Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein.

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL [namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

Adult↗
PubMed1998

Gamma-interferon activates a nuclear protein that binds to the gamma-interferon activation site of the thyroglobulin gene.

The release of interferon-gamma (IFNgamma) has been demonstrated from the infiltrating T lymphocytes of the thyroid gland from patients with autoimmune thyroid disease (AITD). We have shown previously that IFNgamma inhibited thyroglobulin (Tg) gene transcription, and that its action was mediated by an increase in intracellular calcium and inositol phosphates. In the present study, we tried to determine the specific site of action of IFNgamma on the Tg gene. A 565 bp fragment (position -530 to +34) spanning the transcriptional start site of the human Tg promoter was ligated to the luciferase plasmid and transiently transfected into human thyrocytes. Stimulation with TSH (10 mIU/l) and IFNgamma (500 IU/l) resulted in a twofold increase and a 60% reduction in the luciferase activity respectively, similar to the effect observed with the endogenous Tg gene. Deletion studies revealed that the region with the strongest suppression by IFNgamma lay between 5' -388 to -258. Mobility gel shift experiments and DNA footprinting experiments demonstrated that the action of IFNgamma was mediated through a trans-acting protein which complexed to position -282 to -262 TTGAGCCTGTTCCCTC CAAA. Position -272 to -261 TTCCCTCCAA corresponded to the gamma-interferon activation site (GAS) consensus sequence TTNC(C)T NNNA. The turnover time of the nuclear protein lasted for only 4 h although the suppressive effect of IFNgamma on Tg gene transcription lasted for 48 h. The effect of IFNgamma was lost when the thyrocytes were co-treated with genistein, a specific tyrosine kinase inhibitor. The presence of the GAS in the promoter sequence of the Tg gene confirms the specific action of IFNgamma in thyroid hormone metabolism. In conclusion, apart from its regulatory role in T cell development and perpetuation of the immune response in AITD, IFNgamma may also play a role in altering cellular function of the thyrocytes by its action on the Tg gene promoter.

Base Sequence↗
PubMed1998

Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins.

OBJECTIVES: Gonadal steroids are important regulators of lipoprotein metabolism. The aims of this study were to determine the effects of a minimum effective dose of testosterone replacement on high density lipoprotein (HDL) subfractions and apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with primary testicular failure and to investigate the underlying mechanisms of these changes. MEASUREMENTS: Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL. RESULTS: The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05). CONCLUSIONS: Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

Adult↗