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Biomedical subjects

K K Ho

Publications and source records attributed to K K Ho.

At least 55 records · Page 3Linked to original sources
PubMed2000

Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation.

Insulin modulates the biological actions of GH, but little is known about its effect on human hepatic GH receptors (GHRs). Using the human hepatoma cell line HuH7 as a model, we investigated insulin regulation of total, intracellular, and cell surface GHRs and receptor biosynthesis and turnover. Insulin up-regulated total and intracellular GHRs in a concentration-dependent manner. It increased surface GHRs in a biphasic manner, with a peak response at 10 nmol/L, and modulated GH-induced Janus kinase-2 phosphorylation in parallel with expression of surface GHRs. The abundance of GHR messenger ribonucleic acid and protein, as assessed by RT-PCR and Western analysis, respectively, markedly increased with insulin treatment. To examine whether insulin regulates GHRs at the posttranslational level, its effects on receptor surface translocation and internalization were investigated. Insulin suppressed surface translocation in a concentration-dependent manner, whereas internalization was unaffected. Moreover, insulin actions on total GHRs and surface translocation were inhibited by PD98059 and wortmannin, respectively. In conclusion, insulin regulates hepatic GHR biosynthesis and surface translocation in a reciprocal manner, with surface receptor availability the net result of the divergent effects. The divergent actions of insulin appear to be mediated by the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways, respectively.

Androstadienes↗
PubMed2000

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth.

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases ofnoninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-3 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGH at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P < .001), free PGH and total PGH correlated very closely (r = 0.98). The results are consistent with an inhibitory function for GHBP in vivo and support a critical role for placental GH and IGF-I in driving normal fetal growth.

Adult↗
PubMed2000

Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex.

We have previously shown that exogenous estrogens exert route-dependent effects on serum GH and insulin-like growth factor I (IGF-I) levels. IGF-I circulates as a ternary complex with IGF-binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). It is not known whether IGFBP-3 and ALS in blood are regulated by estrogen and, if so, whether this is also route dependent. In the present study we investigate the effects on IGFBP-3 and ALS of oral and transdermal estrogens (study 1), of different oral estrogen formulations (ethinyl estradiol, conjugated estrogen, and estradiol valerate; study 2), of different estrogen dosages (study 3) in normal postmenopausal women, and of oral estrogen in hypogonadal GH-deficient women (study 4). Administration of oral, but not transdermal, estrogen in normal postmenopausal women significantly decreased serum levels of IGFBP-3 and ALS (P < or = 0.005). The suppressive effects were similar with different oral estrogen formulations, and the degree of suppression increased with estrogen dosage. In hypogonadal GH-deficient women, oral estrogen treatment also significantly reduced IGFBP-3 and ALS (P = 0.02). The changes in IGF-I in each of the four studies paralleled the changes in both IGFBP-3 and ALS. In conclusion, exogenous estrogens suppress serum IGFBP-3 and ALS in a route- and dose-dependent manner, which are in parallel with the effects on serum IGF-I. These actions of oral estrogen are independent of endogenous GH status.

Administration, Cutaneous↗
PubMed2000

Distribution and abundance of messenger ribonucleic acid for growth hormone receptor isoforms in human tissues.

Two alternatively spliced exon 9 variants of human GH receptor (GHR) messenger ribonucleic acid (mRNA), GHR-(1-279) and GHR(1-277), were recently identified in liver. They encode receptor proteins lacking most of the intracellular domain and inhibit GH action in a dominant negative manner. Little is known about tissue distribution and abundance of these GHR isoforms. We have developed quantitative RT-PCR assays specific for the full-length and truncated GHRs and investigated their expression in various human tissues and cell lines. The mRNA of full-length GHR and GHR-(1-279) were readily detectable in all tissues investigated, with liver, fat, muscle, and kidney showing high levels of expression. These two receptor isoforms were also detected in a range of human cell lines, with strongest expression in IM9, a lymphoblastoid cell line. In contrast, GHR-(1277) message was expressed at low levels in liver, fat, muscle, kidney, and prostate and in trace amount in IM9 cells. Full-length GHR was the most abundant isoform, accounting for over 90% of total receptor transcripts in liver, fat, and muscle for quantitative RT-PCR. However, liver had 2- to 4-fold more full-length receptor mRNA and 16- to 40-fold more GHR-(1-277) mRNA than fat and muscle, whereas the mRNA levels of GHR-(1-279) were similar in the three tissues. GHR-(1-279) constituted less than 4% in liver and 7-10% in fat and muscle. GHR-(1-277) accounted for 0.5% of total GHR transcripts in liver and less than 0.1% in the other two tissues. These data suggest that the absolute and relative abundance of mRNA of the three GHR isoforms may be tissue specific. The regulation of expression of exon 9 alternatively spliced GHR variants may provide a potential mechanism for modulation of GH sensitivity at the tissue level.

Adipose Tissue↗
PubMed2000

Route-dependent endocrine and metabolic effects of estrogen replacement therapy.

The route of estrogen replacement therapy has a major impact on the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Estrogen administration by the oral, but not the transdermal, route reduces IGF-I and increases GH levels in postmenopausal women. This perturbation of the GH-IGF-I axis occurs with different forms of estrogen treatment, indicating that the dissociation of the somatotropic axis and concomitant increase in GH-binding protein levels are intrinsic effects of the oral route of estrogen administration. In clinical studies, oral estrogen reduced postprandial lipid oxidation, compared with transdermal estrogen. Oral estrogen was also associated with a reduction in lean body mass and an increase in fat mass, compared with transdermal estrogen. In contrast, the route of estrogen therapy had no impact on carbohydrate metabolism or the estrogen-induced increase in bone mineral density. The findings of route-dependent changes in body composition add a new dimension to health considerations concerning estrogen therapy in postmenopausal women and may have significant implications for estrogen replacement therapy in young hypogonadal females.

Administration, Cutaneous↗
PubMed2000

Spaced dentition--open, close or redistribute?

A spaced dentition can be due to various reasons such as hypodontia, tooth size discrepancy and impeded eruption. The dilemma for clinicians is whether to close, open or redistribute space. Closing space by orthodontics eliminates the need for prosthetic rehabilitation but it might compromise aesthetics and function. On the other hand, opening space is more complex and requires long-term maintenance. Based on these drawbacks, a careful occlusal analysis and an individualized treatment plan are mandatory for achieving the best result. The prognosis for closing space and substituting congenitally missing maxillary laterals with canines depends on factors such as overjet, lip support, crown colour, shape and root position. If these are unfavourable, opening space for prosthetic replacement is then preferred. Discrepancy between tooth and jaw size results either in spacing or crowding. The location of the spacing and the amount of overjet are important factors guiding the direction of treatment.

Adolescent↗
PubMed1999

Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery.

BACKGROUND: Cardiac complications are important causes of morbidity after noncardiac surgery. The purpose of this prospective cohort study was to develop and validate an index for risk of cardiac complications. METHODS AND RESULTS: We studied 4315 patients aged > or = 50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. The main outcome measures were major cardiac complications. Major cardiac complications occurred in 56 (2%) of 2893 patients assigned to the derivation cohort. Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index: high-risk type of surgery, history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative serum creatinine >2.0 mg/dL. Rates of major cardiac complication with 0, 1, 2, or > or = 3 of these factors were 0.5%, 1.3%, 4%, and 9%, respectively, in the derivation cohort and 0.4%, 0.9%, 7%, and 11%, respectively, among 1422 patients in the validation cohort. Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes. CONCLUSIONS: In stable patients undergoing nonurgent major noncardiac surgery, this index can identify patients at higher risk for complications. This index may be useful for identification of candidates for further risk stratification with noninvasive technologies or other management strategies, as well as low-risk patients in whom additional evaluation is unlikely to be helpful.

Aged↗
PubMed1999

Comparative analysis of early and late angiographic outcomes using two quantitative algorithms in the Balloon versus Optimal Atherectomy Trial (BOAT).

Although substantial intersystem variability has been shown among several commercially available quantitative angiographic (QA) analysis algorithms, no previous study has compared the angiographic findings using 2 different QA systems performed at the same central angiographic laboratory. The purpose of this study was to compare the early and late QA results obtained with the CMS (MEDIS) and ARTREK (ImageComm) QA systems in the Balloon versus Optimal Atherectomy Trial. Directional atherectomy (n = 496) or balloon angioplasty (n = 490) was performed in 986 patients; late QA follow-up was available in 767 patients (77.7%). QA analysis was performed by 2 independent observers using the CMS and ARTREK systems. Correlation between the 2 QA systems for baseline measurements was good (Pearson's R = 0.78), although the CMS system resulted in larger baseline reference diameter (RD) (3.22 +/- 0.45 vs 3.07 +/- 0.40 mm; p <0.0001) and baseline minimal lumen diameters (MLD) (1.05 +/- 0.35 vs 0.92 +/- 0.32; mm p <0.0001) than the ARTREK system. The final and follow-up RD (+0.17 and +0.11 mm, respectively) were also larger using the CMS system. In contrast, the final and follow-up measurements of MLD and percent diameter stenosis were not significantly different using the 2 QA systems. The QA system did not affect the ability to detect a difference in restenosis rates (>50% follow-up diameter stenosis) between the 2 treatment groups (CMS, directional atherectomy [31.8%]; balloon angioplasty [40.5%]; p = 0.013 and ARTREK, directional atherectomy [33.9%], balloon angioplasty [41.3%]; p = 0.036). Only lesion irregularity contributed to the difference in baseline measurements of MLD and percent diameter stenosis. We conclude that important differences in measurements of RD, baseline MLD, and percent diameter stenosis were noted using the CMS and ARTREK systems. Both systems, however, were able to detect a treatment benefit associated with directional atherectomy in BOAT. The comparability of other angiographic systems will require similar evaluation in other studies.

Algorithms↗
PubMed1999

Acute and nine-month clinical outcomes after "suboptimal" coronary stenting: results from the STent Anti-thrombotic Regimen Study (STARS) registry.

OBJECTIVES: This registry collected the 30-day and 9-month clinical outcomes of patients whose coronary stent implantation was suboptimal, and compared them with the cohort of patients with "optimal" stenting in the randomized portion of the STent Anti-thrombotic Regimen Study (STARS) trial. BACKGROUND: Although "optimal" stenting combined with an aspirin and ticlopidine regimen carries a low (0.5%) incidence of subacute stent thrombosis, only limited data are available for patients in whom stents are deployed suboptimally. METHODS: In the STARS, 312 (15.9%) of 1,965 patients enrolled were excluded from participation in the randomized trial based on a perceived "suboptimal" result of coronary stenting. Of these, 265 patients met prespecified criteria for suboptimal stenting, and were followed in a parallel registry, which was compared with the randomized STARS optimal stenting cohort. The primary end point was a 30-day composite of death, emergent target lesion revascularization, angiographic thrombosis of the target vessel without revascularization and nonfatal myocardial infarction (MI) unrelated to direct procedural complications. RESULTS: Registry patients had a similar frequency of the primary end point compared with the overall randomized cohort (3.0% vs. 2.2%), with this end point correlating to use of multiple stents, smaller final lumen diameter and absence of ticlopidine from the poststent regimen. Overall 30-day mortality (1.1% vs. 0.06%, p = 0.009) and periprocedural non-Q wave MI (8.7% vs. 4.2%, p = 0.003) were more frequent in registry patients, and appeared to be related to acute procedural complications. Clinical restenosis was significantly higher for registry patients (26.8% vs. 16.0%, p = 0.001), relating to greater prevalence of independent predictors such as smaller final lumen diameter and multiple stent use. CONCLUSIONS: In the STARS registry, the inability to perform optimal stenting correlated with smaller final lumen diameter and longer stent length. With ticlopidine-containing regimens, the acute clinical results of "suboptimal" stent deployment are clinically acceptable, although they are not quite as good as those of optimal stenting using similar drug therapy.

Acute Disease↗
PubMed1999

Initial characterization of the GH-IGF axis and nutritional status of the Ati Negritos of the Philippines.

BACKGROUND AND OBJECTIVE: The Ati Negritos are a Pygmy-like aboriginal population from the Philippines with physical characteristics of short stature, dark skin and woolly, kinked hair. Their final height, components of their GH-IGF axis and various nutritional markers are described. SUBJECTS, DESIGN AND MEASUREMENTS: Auxological data and sera for the components of the GH-IGF axis and nutritional parameters were collected from 9 adult Ati Negritos in their native environment and 10 Filipinos in Sydney. RESULTS: The height SDS (- 3.66 +/- 1.1 vs. - 1.01 +/- 1.2), weight SDS (- 2.30 +/- 1.6 vs. 0.10 +/- 0.7), and BMI SDS (- 1.4 +/- 1.8 vs. - 0.2 +/- 0.5) between the two groups were significantly different (P < 0.01). The mean height of the 6 male Ati Negritos was 149 +/- 7 and 144 +/- 3 cm for the females and are comparable with the African Pygmies and the Mountain Ok people of Papua New Guinea. The Ati Negritos showed lower growth hormone binding protein (GHBP), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), acid labile subunit (ALS), zinc, albumin, ferritin, iron, iron saturation and much higher insulin-like growth factor binding protein 2 (IGFBP-2) and plasma transferrin concentrations. No differences were noted in random growth hormone (GH), plasma insulin-like growth factor II (IGF-II), nor in their plasma concentrations of prealbumin, thyroid stimulating hormone (TSH) and free thyroxine (T4). CONCLUSION: Perturbations of both the GH-IGF-I axis and nutritional markers exist in the Ati Negritos. These findings may be determinants of their stature; however, the aetiology of these changes remains to be fully elucidated.

Adult↗
PubMed1999

Helical computed tomography angiography in the evaluation of Chinese living renal donors.

OBJECTIVE: To determine the suitability of helical computed tomography angiography (CTA), recently used in the anatomical evaluation of potential living renal donors (LRDs) in the Caucasian population, for Chinese LRDs. SUBJECTS AND METHODS: Eighteen consecutive potential LRD candidates underwent both CTA and conventional renal angiography (CRA). Results from each were interpreted while unaware of the results from the other. Renal function was monitored after each radiological procedure. RESULTS: Both procedures were able to identify all four accessory renal arteries present. One prehilar branch of < 1 mm in diameter was not recognized on CTA. Renal artery ostial stenosis in one subject with normal blood pressure was identified on CTA, but not on CRA. CTA better delineated the renal venous and parenchymal anatomy and cost 60% less than CRA. There was no change in renal function after either procedure. CONCLUSION: Despite there being few subjects. CTA has potential value as an alternative to CRA for the anatomical assessment of potential LRDs in Hong Kong. Advantages include a short examination time, non-invasiveness and lower cost. CTA may provide an opportunity to living-related and unrelated renal donor transplantation in this conservative Chinese culture.

Adult↗
PubMed1999

Rubisco small subunit gene family in cassava.

Cassava leaves of two different cultivars, Brazil and Buloh, were used to isolate mRNA. The mRNA isolated was successfully used in the construction of cDNA libraries for each of the cultivars. The cDNA libraries were screened for members of ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit gene family and positive clones were sequenced. A total of seven different SSU genes, of which five were from cultivar Brazil and two were from cultivar Buloh, were isolated. Comparison results show that even though all the sequences are highly similar, they can be classified into three subfamilies. Homology between members of the same subfamily is higher than homology between members from the same cultivar.

Amino Acid Sequence↗
PubMed1999

Impairment of hand function and loss of earning capacity after occupational hand injury: prospective cohort study.

OBJECTIVE: To examine the loss of earning capacity and permanent impairment of a cohort of male patients who had experienced finger amputation due to occupational injury. DESIGN: Prospective cohort study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Twenty-eight male patients aged 26 to 55 years who presented with work-related finger amputations in their dominant right hand from 1990 through 1991. MAIN OUTCOME MEASURES: Type and extent of amputation, and hand function before and after (mean, 11 months; range, 8-6 months) the patients' return to work. Assessment results were compared with patients' percentage loss of earning capacity as calculated using the scale described in the Employees' Compensation Ordinance of Hong Kong. RESULTS: Patients with injuries that corresponded to a loss of earning capacity of 12% or greater had a significant impairment in their hand function (P<0.05); the hand function of this group after their return to work significantly improved (P<0.05). There were no significant differences between the loss of earning capacity scores as calculated by the Hong Kong, American Medical Association, or Indian Medical Association scales. CONCLUSION: Patients whose loss of earning capacity of 12% or greater are likely to have significant long-term impairments of hand function. Thus, a more intensive rehabilitation programme should be provided to this group.

Journal Article↗
PubMed1998

A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators.

BACKGROUND: Antithrombotic drugs are used after coronary-artery stenting to prevent stent thrombosis. We compared the efficacy and safety of three antithrombotic-drug regimens - aspirin alone, aspirin and warfarin, and aspirin and ticlopidine - after coronary stenting. METHODS: Of 1965 patients who underwent coronary stenting at 50 centers, 1653 (84.1 percent) met angiographic criteria for successful placement of the stent and were randomly assigned to one of three regimens: aspirin alone (557 patients), aspirin and warfarin (550 patients), or aspirin and ticlopidine (546 patients). All clinical events reflecting stent thrombosis were included in the prespecified primary end point: death, revascularization of the target lesion, angiographically evident thrombosis, or myocardial infarction within 30 days. RESULTS: The primary end point was observed in 38 patients: 20 (3.6 percent) assigned to receive aspirin alone, 15 (2.7 percent) assigned to receive aspirin and warfarin, and 3 (0.5 percent) assigned to receive aspirin and ticlopidine (P=0.001 for the comparison of all three groups). Hemorrhagic complications occurred in 10 patients (1.8 percent) who received aspirin alone, 34 (6.2 percent) who received aspirin and warfarin, and 30 (5.5 percent) who received aspirin and ticlopidine (P<0.001 for the comparison of all three groups); the incidence of vascular surgical complications was 0.4 percent (2 patients), 2.0 percent (11 patients), and 2.0 percent (11 patients), respectively (P=0.01). There were no significant differences in the incidence of neutropenia or thrombocytopenia (overall incidence, 0.3 percent) among the three treatment groups. CONCLUSIONS: As compared with aspirin alone and a combination of aspirin and warfarin, treatment with aspirin and ticlopidine resulted in a lower rate of stent thrombosis, although there were more hemorrhagic complications than with aspirin alone. After coronary stenting, aspirin and ticlopidine should be considered for the prevention of the serious complication of stent thrombosis.

Aged↗
PubMed1998

The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women.

The route of estrogen replacement therapy has a major impact on the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. Estrogen administration by the oral, but not the transdermal route, reduces IGF-I and increases GH levels in postmenopausal women. To investigate whether these perturbations have metabolic consequences, we compared the effects of 24 wk each of oral (Premarin 1.25 mg) and transdermal (Estraderm 100TTS) estrogen on energy metabolism and body composition in 18 postmenopausal women in an open-label randomized crossover study. Energy expenditure, lipid oxidation (lipid(ox)), and carbohydrate oxidation (CHOox) were measured by indirect calorimetry in the fasted and fed state before and after 2 and 6 mon treatment. Lean body mass, fat mass, and total body bone mineral density were measured by dual X-ray absorptiometry before and after 6 mon treatment. Mean (+/-SE) Luteinizing hormone levels fell to comparable levels during oral and transdermal estrogen, and bone mineral density was significantly increased by both treatments. Mean IGF-I was significantly lower during oral estrogen (77+/-7 versus 97+/-7 microg/liter, P < 0.05) treatment. Lipid(ox) 30-60 min after a standardized meal was significantly lower (36+/-5 versus 54+/-5 mg/min, P < 0.01) and CHOox higher (147+/-13 versus 109+/-12 mg/min, P < 0.05) with oral compared with transdermal estrogen. Oral estrogen resulted in a 1.2+/-0.5 kg (P < 0.05) increase in fat mass and a 1.2+/-0.4 kg (P < 0.01) decrease in lean mass compared with transdermal estrogen. Lean body mass (0.4+/-0.2 kg) and fat mass (0. 1+/-0.4 kg) did not change significantly during transdermal estrogen. In summary, when compared with the transdermal route, oral estrogen reduces lipid(ox), increases fat mass, and reduces lean body mass. The route of estrogen therapy confers distinct and divergent effects on substrate oxidation and body composition. The suppression of lipidox during oral estrogen therapy may increase fat mass although the fall in IGF-I may lead to a loss of lean body mass. The route-dependent changes in body composition observed during estrogen replacement therapy may have important implications for postmenopausal health.

Administration, Cutaneous↗