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Biomedical subjects

F T Lee

Publications and source records attributed to F T Lee.

At least 91 records · Page 5Linked to original sources
PubMed1990

Legg-Calve-Perthes disease: clinical analysis of 57 cases.

The rarity of the Legg-Calve-Perthes disease (LCPD) in Chinese children in Hong Kong has been reported. However, this hip disorder is not uncommon among children in Taiwan between the ages of 3 and 9. Fifty-seven patients with LCPD were observed during a 4-year period. Of these, 47 hips in 43 patients were followed up through a significant course of the disease, with an average period of 38.8 months. The mean age at onset of symptoms was 6.6 years for boys and 7.1 years for girls. Over half of the patients (67%) were older than 6 years of age at onset of the disease. The male: female ratio was 5:1, and the incidence of bilateral involvement was 10%. The majority (85%) belonged to Catterall's group 3 or 4. The skeletal maturity of 17 (68%) these children was delayed an average of 31.8 months. Fifty-three percent of the patients were from families of low socioeconomic status. Delay in diagnosis and presentation with painless limp and stiffness were common. Orthotic management was employed in 15 hips. Surgical containment, either by varus-rotation femoral osteotomy or innominate osteotomy, was achieved in 16 hips. The remaining 16 hips received no treatment. The overall results showed an increase in improvement from 19% to 47% after active treatment of the disease. The chance of satisfactory treatment was reduced considerably when the disease started after the age of 6 years, this was especially obvious in untreated hips. No significant differenced in the healing time between the nonsurgical group and the surgical group was observed.

Age Factors↗
PubMed1988

Hormone-sensitive lipase is involved in the hydrolysis of lipoidal derivatives of estrogens and other steroid hormones.

Long-chain fatty acid esters of 17 beta-estradiol and other steroid hormones, which are formed in hormone-sensitive tissues, can be regenerated to the free hormone by the action of an esterase present in the cytosol. This esterase has now been examined in bovine placenta cotyledons. Activity towards steroid fatty acid esters was accompanied by activity towards a diacylglycerol analogue and cholesteryl oleate. During purification procedures, the ratio of activities towards the diacylglycerol analogue and estradiol 17 beta-oleate remained approximately constant. Activity towards these two substrates was inhibited by increasing concentrations of HgCl2 and phenylmethanesulfonyl fluoride in a parallel manner. Upon treatment with [3H]diisopropyl fluorophosphate, a major labelled species of Mr approx. 84,000 was formed. Activation by ATP and the catalytic subunit of cAMP-dependent protein kinase occurred. These properties were very similar to those of the hormone-sensitive lipase of bovine adipose tissue previously reported and run in parallel in this study. A highly purified preparation of this latter enzyme was found to hydrolyse steroid fatty acid esters and relative activities towards such substrates, diacylglycerol analogue and cholesteryl oleate, were similar to the placenta esterase. When the two esterases were phosphorylated with [gamma-32P]ATP, a labelled species of Mr 84,000 was isolated in both cases by use of an antibody raised against purified hormone-sensitive lipase of bovine adipose tissue. It is concluded that hormone-sensitive lipase is very likely the enzyme responsible for hydrolysis of steroid fatty acid esters in bovine placenta and possibly steroid hormone target tissues in general.

Androgens↗
PubMed1987

Multiple phosphorylation of mouse muscle glycogen synthase.

Glycogen synthase was isolated from extracts of mouse diaphragm muscle by immunoprecipitation with specific antibodies raised against the rabbit muscle enzyme. A procedure was developed which permitted phosphorylation of the immunoprecipitated enzyme by several purified protein kinases. Peptide mapping techniques (including reverse-phase HPLC and thin-layer electrophoresis and chromatography) were used to compare tryptic phosphopeptides of the rabbit and mouse muscle enzymes. The results demonstrated a high degree of similarity in the chemical properties of these peptides, suggesting significant homology around the phosphorylation sites in these proteins. Thus, mouse peptides corresponding to the rabbit muscle peptides containing sites 1a, 1b, 2, 3, and 5 were identified, with protein kinase recognition specificities identical to those of the rabbit enzyme. The study indicates significant conservation in the muscle isozymes of glycogen synthase between mouse and rabbit as well as a similar distribution of phosphorylation sites throughout the enzyme subunit.

Animals↗
PubMed1987

Solubilisation and reconstitution of acylcoenzyme A:estradiol-17 beta acyltransferase.

Acylcoenzyme A:estradiol-17 beta acyltransferase in microsomes of bovine placenta cotyledons was strongly membrane bound. The enzyme was solubilised from microsomes by sodium cholate and was reconstituted into phospholipid vesicles. The apparent Km for estradiol-17 beta was 11 microM which was close to the value of 8 microM previously found with the membrane-bound enzyme. Testosterone was also a substrate for the reconstituted enzyme (apparent Km 62 microM) and was a competitive inhibitor (Ki 74 microM) of the acylation of estradiol-17 beta. Although various long-chained fatty acyl CoAs acted as acyl donors, these proved to have widely differing apparent Km values with palmitoleoyl CoA having the highest affinity (Km 24 microM) and arachidonoyl CoA the lowest affinity (Km 330 microM).

Acyltransferases↗
PubMed1986

Heparin-activated protein kinase from rabbit muscle: relationship to enzymes of the glycogen synthase kinase-3 category.

A heparin-activated protein kinase has been previously identified in rabbit skeletal muscle extracts (Z. Ahmad et al. (1985) FEBS Lett. 179, 96-100). Further study has indicated that this enzyme phosphorylates rabbit muscle glycogen synthase in the same tryptic peptide(s) as the protein kinase FA/GSK-3 (glycogen synthase kinase-3) and is able to activate the ATP-Mg2+-dependent protein phosphatase. These results indicate similarities in properties between the two protein kinases. Exposure of the heparin-activated enzyme to trypsin resulted in loss of heparin activation, from 3-fold to 1.3-fold. One hypothesis suggested by this result is that the enzyme FA/GSK-3 could be a derivative of the heparin-activated enzyme that has lost heparin sensitivity. The conceptual importance of this hypothesis is that it may provide a clue to the mode of regulation of this important class of protein kinases.

Animals↗
PubMed1986

Multiple phosphorylation sites of rat liver glycogen synthase.

Rat liver glycogen synthase was purified to homogeneity by an improved procedure that yielded enzyme almost exclusively as a polypeptide of Mr 85,000. The phosphorylation of this enzyme by eight protein kinases was analyzed by cleavage of the enzyme subunit followed by mapping of the phosphopeptides using polyacrylamide gel electrophoresis in the presence of SDS, reverse-phase high-performance liquid chromatography and thin-layer electrophoresis. Cyclic AMP-dependent protein kinase, phosphorylase kinase, protein kinase C and the calmodulin-dependent protein kinase all phosphorylated the same small peptide (approx. 20 amino acids) located in a 14 kDa CNBr-fragment (CB-1). Calmodulin-dependent protein kinase and protein kinase C also modified second sites in CB-1. A larger CNBr-fragment (CB-2) of approx. 28 kDa was the dominant site of action for casein kinases I and II, FA/GSK-3 and the heparin-activated protein kinase. The sites modified were all localized in a 14 kDa species generated by trypsin digestion. Further proteolysis with V8 proteinase indicated that FA/GSK-3 and the heparin-activated enzyme recognized the same smaller peptide within CB-2, which may also be phosphorylated by casein kinase 1. Casein kinase 1 also modified a distinct peptide, as did casein kinase II. The results lead us to suggest homology to the muscle enzyme with regard to CB-1 phosphorylation and the region recognized by FA/GSK-3, which in rabbit muscle is characterized by a high density of proline and serine residues. A striking difference with the muscle isozyme is the apparent lack of phosphorylations corresponding to the muscle sites 1a and 1b. These results provide further evidence for the presence of liver- and muscle-specific glycogen synthase isozymes in the rat. That the isozymes differ subtly as to phosphorylation sites may provide a clue to the functional differences between the isozymes.

Animals↗
PubMed1986

Screening for congenital hypothyroidism in Hong Kong.

A pilot cord blood TSH screening program for congenital hypothyroidism was commenced in Hong Kong in April 1982. By April 1984, 14 411 neonates born in two hospitals were screened for this disorder. Five cases of primary hypothyroidism and two cases of transient hypothyroidism were detected. The detection of cases of congenital hypothyroidism with only moderately elevated cord blood TSH values means that the recall rate will remain high.

Congenital Hypothyroidism↗
PubMed1986

Modification of a screening technique to evaluate systemic lupus erythematosus in a Chinese population in Taiwan.

Several recent reports have suggested that systemic lupus erythematosus (SLE) may be more common in Chinese than in other populations. We have revised a validated questionnaire devised by Liang, et al, for use in Chinese and surveyed 1,836 people in a community survey and 2,000 students at a girls college in Taipei, Taiwan. This constitutes the largest population yet surveyed with this technique. Only 1 case of probable SLE was identified. Since many apparent normals gave the 3 positive responses suggested to require ANA screening, continued effort should be directed toward increasing survey specificity before the massive population surveys needed to calculate accurate prevalence.

Antibodies, Antinuclear↗
PubMed1985

Phosphoprotein phosphatase inhibitor-2 is phosphorylated at both serine and threonine residues in mouse diaphragm.

Phosphoprotein phosphatase inhibitor-2 (i-2) was rapidly isolated from mouse diaphragm extracts by the use of specific antibodies. The i-2 so obtained was associated with ATP-Mg and FA/GSK-3 dependent phosphatase activity, supporting the idea that i-2 is in fact a component of this form of phosphatase. Inhibitor-2 isolated from diaphragms incubated with [32P]phosphate contained both phosphoserine (approximately 90%) and phosphothreonine (approximately 10%). Therefore, i-2 is multiply phosphorylated in mouse diaphragm and the potential exists for control of the ATP-Mg-dependent phosphatase via multiple phosphorylation sites in vivo.

Adenosine Triphosphate↗
PubMed1985

Hormone-sensitive lipase from swine adipose tissue: identification and some properties.

Swine adipose tissue hormone-sensitive lipase, purified 475-fold to 10% protein purity, has been identified as a polypeptide of Mr = 84,000. The enzyme has high specific activity against tri-, di- and monoacylglycerols, as well as cholesterol esters, and is inhibited by millimolar NaF, and micromolar HgCl2 and DFP. The enzyme polypeptide serves as a substrate for cyclic AMP-dependent protein kinase. The characteristics of the hormone-sensitive lipase from swine adipose tissue are similar to those reported previously for the enzyme from rat. They differ from those reported for the lipase from chicken adipose tissue, and possible reasons for these differences are discussed.

Adipose Tissue↗
PubMed1984

Phosphorylation of glycogen synthase by the Ca2+- and phospholipid-activated protein kinase (protein kinase C).

The Ca2+- and phospholipid-dependent protein kinase (protein kinase C) has been found to phosphorylate and inactivate glycogen synthase. With muscle glycogen synthase as a substrate, the reaction was stimulated by Ca2+ and by phosphatidylserine. The tumor-promoting phorbol esters 12-O-tetradecanoyl phorbol 13-acetate was also a positive effector, half-maximal activation occurring at 6 nM. Phosphorylation of glycogen synthase, but not histone, was partially inhibited by glycogen, half-maximally at 0.05 mg/ml, probably via a substrate-directed mechanism. The rate of glycogen synthase phosphorylation was approximately half that for histone; the apparent Km for glycogen synthase was 0.25 mg/ml. Protein kinase C also phosphorylated casein, the preferred substrate among the individual caseins being alpha s1-casein. Glycogen synthase was phosphorylated to greater than 1 phosphate/subunit with an accompanying reduction in the -glucose-6-P/+glucose-6-P activity ratio from 0.9 to 0.5. Phosphate was introduced into serine residues in both the NH2-terminal and COOH-terminal CNBr fragments of the enzyme subunit. The two main tryptic phosphopeptides mapped in correspondence with the peptides that contain site 1a and site 2. Lesser phosphorylation in an unidentified peptide was also observed. Rabbit liver and muscle glycogen synthases were phosphorylated at similar rates by protein kinase C. The above results are compatible with a role for protein kinase C in the regulation of glycogen synthase as was suggested by a recent study of intact hepatocytes.

Animals↗
PubMed1982

The screening of Chinese cord blood for haemoglobinopathies.

The frequency of haemoglobinopathies among the Hong Kong Chinese newborn was examined by screening 932 consecutive cord blood samples by electrophoresis. The findings indicate that 49 (5.2%) had electrophoretic abnormalities, of which 39 (4.2%) demonstrated the presence of Hb Bart's. 14 of these 39 babies were re-investigated after 1 year and all were proven to carry the alpha-thalassaemia gene. This is the first study in which Chinese babies with Hb Bart's in cord blood had the diagnosis of alpha-thalassaemia trait confirmed in later life. 3 out of 4 other babies had different haemoglobin variants, namely Hb alpha Q, Hb J and Hb New York. 1 out of the 6 babies who had elevated A2 levels at birth was found to carry the beta-thalassaemia trait. None had a serious haemoglobinopathy.

China↗
PubMed1975

Primary treatment of advanced ovarian adenocarcinoma, stages III and IV.

In an attempt to improve the response rate and hopefully the survival rate in women with advanced ovarian adenocarcinoma, three new modalities of therapy for ovarian adenocarcinoma were undertaken in 97 women. Sequential therapy consisted of surgery followed by chemotherapy, second-look laparotomy, and subsequent whole abdominal radiation. Eight women exhibiting a complete clinical response to chemotherapy were subjected to this treatment. However, only one woman (12%) is surviving without evidence of tumor recurrence. Concomitant therapy consisted of external radiation and single alkylating agent chemotherapy in 23 women. Again, the survival was poor: a 5-year survival of 8% without tumor recurrence. The third treatment modality consisted of a randomized study of 66 patients in whom single agent therapy with melphalan was compared with multiple agent therapy consisting of cyclophosphamide, dactinomycin, and 5-fluorouracil. In those women with stage III and IV serous adenocarcinoma of the ovary, a 63% response rate was obtained in patients receiving triple chemotherapy as compared to a 45% response rate in those receiving melphalan. Moreover, 40% of the group given triple chemotherapy exhibited a complete response as compared to only 18% in the group given melphalan.

Adenocarcinoma↗