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Biomedical subjects

C C Lee

Publications and source records attributed to C C Lee.

At least 307 records · Page 17Linked to original sources
PubMed1995

Characteristics of youth suicide in Hong Kong.

This paper explores the intrapersonal and sociocultural factors behind youth suicide in Hong Kong. The coroner's court reports of consecutive population-based youth suicide (below age of 25 years, n = 303) cases from 1986 to 1992 were reviewed. Compared with other countries, Hong Kong had low male but high female youth suicide rates. The number of undetermined deaths did not significantly affect the estimated suicide rates. Cross-cultural differences in youth suicide rates may be understood from a differential distribution of risk factors and cultural attitudes towards role behaviours and suicide. Youth suicides in Hong Kong were characterised by a high prevalence of psychiatric disturbances and age-normative precipitants; both findings bear great resemblances to samples studied elsewhere. The results were evaluated in light of studies in different sociocultural backgrounds and highlighted the universality and specificity of youth suicide in Hong Kong.

Adolescent↗
PubMed1995

Pharmacokinetics of tacrolimus in liver transplant patients.

OBJECTIVE: To characterize the pharmacokinetics of the immunosuppressive agent tacrolimus (FK 506) in liver transplant patients. METHODS: Patients (n = 16) were assessed during and after 1- to 3-day intravenous infusions followed by a 2-week course of oral dose therapy. Plasma and whole blood data were fitted simultaneously with equations accounting for nonlinear drug binding by red blood cells to generate clearance (CL) and volume of distribution (V). RESULTS: The maximum blood/plasma ratio of tacrolimus was 55.5 +/- 26.8 (SD) and half-life averaged 12.1 +/- 4.7 hours. The CL and V were relatively high based on plasma concentrations (CL, 1.7 L/hr/kg; V, 30 L/kg) and low based on whole blood (CL, 54 ml/hr/kg; V, 0.9 L/kg), with moderate variability (coefficient of variation, 34% to 49%) among the patients. Correlations of plasma CL and V with maximum blood/plasma ratios (ranging from 13 to 114) were strong (r = 0.65 and r = 0.73). Blood binding affects the disposition of tacrolimus, and plasma concentrations are indirectly and inversely related to red cell binding. The oral dose data for tacrolimus yielded a brief absorption lag time (tlag, 0.39 hour), a variable first-order absorption rate constant (ka, 4.5 +/- 3.0 hr-1), and consistent bioavailability (F, 25% +/- 10%). The area under the concentration-time curve versus 12-hour minimum concentration relationships for both whole blood and plasma were nearly linear, confirming the utility of trough values for monitoring drug exposure. CONCLUSION: This study provides pharmacokinetic guidelines for the use of tacrolimus in patients undergoing hepatic transplantation. Nonlinear blood binding is a major source of interpatient variation in the disposition of tacrolimus.

Administration, Oral↗
PubMed1995

The gene for a human microfibril-associated glycoprotein is commonly deleted in Smith-Magenis syndrome patients.

Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly/mental retardation syndrome associated with deletion of chromosome 17p11.2. Here we report the identification of a novel gene encoding a human microfibril-associated glycoprotein (MFAP4), which has been mapped to the SMS region. A full-length cDNA corresponding to this gene has been sequenced, and reveals a coding region of 255 amino acids. MFAP4 has a fibrinogen-like domain and shares a high level of sequence homology to a fragment of a bovine 36 kDa microfibril-associated glycoprotein. The N-terminus of the protein bears an Arg-Gly-Asp sequence that serves as the ligand motif for cell surface receptor integrin. These structural features of MFAP4 suggest that it is an extracellular matrix protein involved in cell adhesion or intercellular interactions. Deletion analysis has been conducted on 31 SMS patients by polymerase chain reaction and Southern analysis of somatic cell hybrids retaining the del(17)(p11.2) chromosome or by fluorescence in situ hybridization. The MFAP4 locus is deleted in 30 of 31 SMS patients. Thus, the function of this gene must be considered in the pathogenesis of SMS. Given our previous hypothesis that SMS is a contiguous gene syndrome, complete and exhaustive definition of the critical deletion interval and a thorough phenotype-genotype correlation is required to demonstrate the role and importance of the MFAP4 gene in SMS.

Abnormalities, Multiple↗
PubMed1995

Isolation of chromosome-specific genes by reciprocal probing of arrayed cDNA and cosmid libraries.

We have identified and mapped 61 novel and previously described chromosome 17 and X genes, using a human placental cDNA library. These genes were isolated using a gene identification and mapping strategy based on reciprocal probing of arrayed chromosome specific cosmid and cDNA libraries. This strategy scans gridded cosmids for nuclear genes and isolates the expressed sequence by a cosmid to cDNA filter hybridization. Inherent to this approach is the advantage of identifying the corresponding genomic cosmid clone of a particular cDNA. The genomic and cDNA reagents can be used for fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) based mapping to resolve map positions of cDNAs belonging to gene families and those associated with multiple chromosomes. The downstream utility of reagents generated by the reciprocal probing methods is demonstrated in our studies.

Base Sequence↗
PubMed1995

A new mutagenicity assay method for frameshift mutagens based on deleting or inserting a guanosine nucleotide in the beta-lactamase gene.

The conventional method of site-directed mutagenesis was used to develop two Salmonella strains, JK-1 and JK-2, for detecting frameshift mutagens. The JK-1 strain was derived from Salmonella typhimurium TA1537 strain transformed by a mutant construct. A guanosine nucleotide was inserted between nucleotide residues 312 and 313 of the beta-lactamase gene. The JK-2 strain was obtained by the same procedure, but a guanosine nucleotide in position 315 of the beta-lactamase gene was deleted. The strains were tested with ten frameshift mutagens and the revertants were selected by ampicillin resistance. Representative mutagens including 2-nitrofluorene (2-NF), 2-acetylaminofluorene (AAF), 9-aminoacridine (9-AA), 2,7-diaminofluorene (2,7-DAF) and 2-methoxy-6-chloro-9-(3-(ethyl-2-chloro-ethyl)-aminopropylamino)acridine (ICR-170) were more potent in the JK-1 strain than the JK-2 strain, and the number of revertant colonies were dose related. Under the same conditions, the ampicillin test was more sensitive than the Ames test. Other types of compounds such as 2-methoxy-6-chloro-9-(2-chloroethylaminopropylamino)acridine (ICR-191), benzo[a]pyrene (BP), 4-nitroquinoline N-oxide (4-NQNO), hycanthone and aflatoxin B1 (AFB1) were not as mutagenic to these new strains. The method is quite promising for studying certain specific frameshift mutagens, but more chemical mutagens should be tested to validate its applicability and reproducibility in general use.

Amino Acid Sequence↗
PubMed1995

Genetic diagnosis of haemophilia A of Chinese origin.

Genetic diagnosis of haemophilia A has been studied in two aspects. One is to directly identify the mutations in the factor VIII genes of the affected probands, and the other is to examine the usefulness of several intragenic factor VIII markers for gene tracking. Direct mutational analysis by PCR-SSCP (polymerase chain reaction--single-strand conformation polymorphism) has been accomplished previously in 87 haemophilia A patients, accounting for nearly 10% of cases in Taiwan. Of the 87 cases, 46% were with point mutations, short deletions or insertions, and most of the remaining were with gene inversion readily identified by Southern blotting. Further examination of 112 patients has estimated a 33% incidence for gene inversion in all the patients with haemophilia A, or 37% in severe cases. Since the direct mutational detection described above cannot be used in all Chinese families with haemophilia A, genetic markers were also investigated. The two CA repeat markers located at intron 13 (CA-13) and intron 22 (CA-22), respectively, were amplified and analysed simultaneously. Seven different alleles with 18-24 CAs have been identified for CA-13. Alleles of 20 and 21 CAs are the most common and their population frequency was 0.68 and 0.24, respectively. The CA-22 marker contained a repetition of (GT)n(AG)n as was identified in the white European but not in the Canadian population. Alleles with 25 and 26 GT/AGs account for 18% and 75% of this group of samples, respectively. The expected rate of heterozygosity for either CA markers was 68%, although a value of 57% was observed by haplotype analysis, indicating an association of the two repeat markers. Nevertheless, the study of 62 females showed that with the combined use of CA-13 and CA-22 with BclI, approximately 71% would be informative for these markers. This number may increase to 81% if XbaI polymorphism is added. We propose that a better genetic diagnosis procedure for Chinese individuals would be first to look for the inversion mutation, secondly for one of the intragenic markers, and then at the PCR-SSCP analysis.

Blotting, Southern↗
PubMed1995

Excision of papillary fibroelastoma arising from the septal leaflet of the tricuspid valve.

A case of a papillary fibroelastoma (PFE) arising from the tricuspid valve was reported. It was incidentally detected by two-dimensional transthoracic echocardiography. Prior to 1977, these tumors were exclusively found at postmortem examination. This is only the fourth reported case of a tricuspid valve PFE found by echocardiography, treated by excision, and with tricuspid valvuloplasty preserving the native valve.

Adult↗
PubMed1995

Effect of inhibition of prostaglandin synthesis on breathing movements and pulmonary blood flow in fetal sheep.

During transition from fetal to extrauterine life, respiration increases in incidence and magnitude as pulmonary blood flow dramatically increases. To determine whether alterations in pulmonary blood flow in utero are directly related to alterations in fetal breathing movements (FBM), we studied six chronically instrumented fetal sheep late in gestation to assess the effects of continuous FBM caused by a 4-h infusion of meclofenamate, a prostaglandin synthase inhibitor, on mean pulmonary blood flow to the fetus. We found a striking increase in FBM from 46 +/- 15% (SD) of the time during control to > 85% of the time by 1 h (P < 0.001), with the fetuses exhibiting continuous FBM by the last 1 h of infusion. The mean pulmonary blood flow also increased significantly during the first 90 min of the infusion as the incidences of FBM were increasing (26 +/- 14 and 56 +/- 23 ml.min-1.kg-1 for control and infusion, respectively; P < 0.01). Despite the simultaneous initial increase in FBM and mean pulmonary blood flow, the increase in left pulmonary artery blood flow was not sustained and decreased back to baseline by 2 h, even though the incidence of FBM continued to increase at this time. During the infusion, the mean pulmonary blood flow was not different between the presence or absence of FBM. There were no changes in fetal heart rate or pulmonary or systemic blood pressures during the infusion nor in arterial pH or blood gas tensions. We conclude that this increase in mean pulmonary blood flow in utero was not solely related to the increase in breathing movements.

Animals↗
PubMed1995

Prostaglandin E2 decreases fetal breathing movements, but not pulmonary blood flow, in fetal sheep.

Fetal breathing movements are vital for normal fetal lung growth. Inhibition of these fetal breathing movements is associated with pulmonary hypoplasia. Pulmonary hypoplasia also occurs subsequent to alterations in other factors, such as a significant decrease in pulmonary blood flow. The prostaglandin system is known to have profound effects on both fetal breathing movements and on the pulmonary vascular system. We studied six late-gestation chronically instrumented fetal sheep by using an electromagnetic flow transducer around the left pulmonary artery to determine whether a decrease in fetal breathing movements, subsequent to a continuous infusion of prostaglandin E2 (PGE2), is associated with a decrease in pulmonary blood flow. A continuous PGE2 infusion of 0.88 +/- 0.11 microgram.kg-1.min-1 over 120 min led to a significant decrease in fetal breathing movements (control 40.5 +/- 3.6%, infusion 3.3 +/- 1.6%; P < 0.001). In contrast, the PGE2 infusion had no effect on mean left pulmonary artery blood flow (control 27.7 +/- 9.3 ml.min-1.kg-1, infusion 23.8 +/- 7.0 ml.min-1.kg-1. The PGE2 infusion demonstrated central effects in the percentage of time the fetus was in high-voltage electrocortical activity (control 41.9 +/- 2.5%, infusion 56.5 +/- 5.4%; P < 0.05) and in the amount of time spent in low-voltage electrocortical activity without fetal breathing movements (control 17.5 +/- 2.7%, infusion 40.2 +/- 4.8%; P < 0.05). A significant decrease in the fetal heart rate during the infusion was seen with no effect on either the systemic or pulmonary blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Assessment of interlaboratory performance on the measurement of blood lead levels in Taiwanese adults.

The purpose of this proficiency study was to assess the accuracy and consistency of blood lead level (BLLs) measurements in a study of Taiwanese adults. Three methods, including a certified blood accuracy test, an interlaboratory precision test and an intertime repeated measurement test, were applied to the six participating laboratories. Accuracy tests showed that most of the blood lead measurements were within the acceptable criteria proposed by United States Center for Disease Control and Prevention (U.S. CDC). However, an average of 11% underestimation was found at BLLs below 15 micrograms/dl. Coefficients of variation (CVs) were high in the first 3 months. After technical improvements, the CVs were reduced to acceptable limits of around 15% at low target lead values and 7% at high lead values. Interlaboratory variations of measurements in blood from ten normal healthy donors showed that the standard deviations were less than 2 micrograms/dl, which is within the acceptable criteria of +/- 4 micrograms/dl, in 8 out of 10 samples. Repeated measurements of BLLs in 54 blood samples over two months showed that most of the differences were within the acceptable range with a few exceptions. The mean BLLs measured in the baseline (pre-test) and two months later (post-test) were nearly identical. This proficiency test provides comparable and reliable results of BLL estimations in this multilaboratory study. However, the accuracy and consistency at low BLLs need to be improved.

Adult↗
PubMed1995

Hemiballism-hemichorea: clinical study in 23 Chinese patients.

BACKGROUND: Hemiballism-hemichorea, a well documented movement disorder, is not uncommon in the clinic. However, systematic analysis of the condition in ethnic Chinese on clinical grounds, is still inexplicably lacking. METHODS: This study focused on 23 Chinese patients with hemiballism-hemichorea in Taiwan. The general data, clinical pictures, blood biochemistries, past histories of systemic disease, neuroradiological imaging, methods of treatment, and prognoses of these patients were analyzed retrospectively. RESULTS: The study revealed that ischemic stroke (44%) is the leading cause of this movement disorder, and the metabolic disorder (22%) is also one of the common etiologies of dyskinesia in Chinese patients. In addition to those patients whose condition was caused by non-ketotic hyperglycemia, blood sugar had also obviously increased in patients where the cause was infarction. Pathological lesions contributed to hyperkinesia were found not only in the contralateral basal ganglion but also in the thalamus and subcortical areas. The characteristics of those patients where the cause was infarction and non-ketotic hyperglycemia were: age at onset greater than 60 years, and predominantly in women. Etiologies contributing to this movement disorder in younger patients differ from those in the older. Prognosis of the movement disorder in this study was favorable. CONCLUSIONS: Hemiballism-hemichorea is predisposed to occur in older Chinese women, and metabolic disorder is an important etiology of the movement disorder. When the dyskinesia is encountered in the clinic, the metabolic disorders must be first ruled out as the problem may be rapidly resolved by achieving metabolic control.

Adolescent↗
PubMed1995

Hypereosinophilia in hemodialysis patients.

Hypereosinophilia (EO) is frequently observed in hemodialysis patients without apparent etiology. We prospectively studied hemodialysis (HD) patients during the period between May 1989 and December 1992, and divided the patients into 3 groups: non-eosinophilic control (EOC), intermittent EO (EOI), and persistent EO (EOP), according to the longterm measurements of their blood eosinophil counts. There were 91 patients enrolled in the study which were followed up for 24 months with 23 patients (25.3%) in the EOC group, 53 patients (58.2%) in EOI group, and 15 patients (16.5%) in the EOP group. There were no significant contribution of the type or reuse of the hemodialyzer to the development of EO, neither were age, serum albumin, KT/V, protein catabolic rate (PCR), or the duration of HD. The functional studies of eosinophils showed no significant difference in hypodense eosinophil distribution or eosinophilic cationic protein (ECP) levels between EOP group and EOC group. The distribution of hypodense eosinophils and serum ECP levels before and after dialysis procedure were not uniform, increasing in some but decreasing in the others. Thus the cause of EO is not merely due to the uremic state or dialysis procedures.

Adult↗
PubMed1995

Vacuolar changes in neuromuscular disorders: a morphometric study.

BACKGROUND: Vacuoles in muscle represent a nonspecific alternation and are found in a variety of neuromuscular disorders. To understand their significance, a morphometric study of the vacuolar formation in muscle biopsies from 340 patients was reviewed. METHODS: Vacuolar changes in muscles were found in 24 out of 340 patients with muscle biopsies. The specimens were prepared for histopathological, histochemical and electron microscopic examinations. The location, size, shape, number and content of the vacuoles were recorded. The number of fibers containing vacuoles was also assessed. RESULTS: Observed after modified Gomori trichrome stain, there were rimmed and non-rimmed vacuoles. Rimmed vacuoles were found in limb-girdle myopathy with rimmed vacuoles (5), oculopharyngeal muscular dystrophy (1). inclusion body myositis (2) and neurogenic disorder (1). These vacuoles were usually cleft-like in shape in 5-16% of muscle fibers with a diameter of 3-20 microns. An elevation of acid phosphatase activities and the presence of cytoplasmic debris suggested an autophagic process. In 15 patients with non-rimmed vacuoles, round and oval shapes with variable sizes and numbers were noted. Four with acid maltase deficiency (AMD) had numerous vacuoles containing glycogen, while three with lipid storage disease contained lipid. Interestingly, in AMD the size of the vacuoles was usually more than 10 microns in diameter, but less than 5 microns in lipid storage disease. In other diseases including polymyositis (5), Duchenne muscular dystrophy (2) and hypokalemic periodic paralysis (1), the numbers of vacuoles were usually fewer than three in each fiber. CONCLUSIONS: Vacuolar changes were not specific, but morphometric analysis of the vacuoles may provide some clues in differential diagnosis. The vacuoles were usually numerous in glycogen and lipid storage diseases, while rimmed vacuoles may be found in limb-girdle myopathy with rimmed vacuoles, oculopharyngeal muscular dystrophy, and inclusion body myositis.

Biopsy↗
PubMed1994

Flexion-extension rhythm in the lumbosacral spine.

STUDY DESIGN AND OBJECTIVES: This study was conducted to depict the qualitative and quantitative changes of intervertebral rotation and translation from L1-L2 to L5-S1 during flexion, standing, and extension using dynamic lumbosacral radiographs. METHODS: A radiopaque ruler was placed on the back of each subject for the normalization of translational value. Eighty-nine volunteers were examined. RESULTS: From extension to flexion, all of the intervertebral rotations approached 0 degree from the lordotic position; the translations changed from slightly retro-listhetic to zero displacement. Using L3-L4 as a baseline for calculating the intervertebral differences in flexion, all of the rotational differences were less than 1.5 degrees, except at L5-S1, which remained 5 degrees. The mean translational difference was less than 0.6 mm, except at L5-S1, where it remained 1.5 mm. CONCLUSIONS: The amount of total flexibility was level-dependent and its frequency distribution is important. Qualitative rhythmic changes from extension to flexion and quantitative values of intervertebral difference in flexion help define the normal flexibility more accurately.

Biomechanical Phenomena↗
PubMed1994

Identification of a novel type of alternative splicing of a tyrosine kinase receptor. Juxtamembrane deletion of the c-met protein kinase C serine phosphorylation regulatory site.

We have detected a novel type of structural variant of the tyrosine kinase receptor for c-met, also known as the hepatocyte growth factor receptor, in mouse tissues. The cDNA of the variant transcript of c-met lacks 141 base pairs, which predicts an in-frame deletion of 47 amino acids in the juxtamembrane region of the cytoplasmic domain. Sequence analysis of genomic DNA containing the c-met locus revealed that the absence of a discrete exon is responsible for this 141-base pair deletion and that alternative splicing leads to production of two forms of transcript. These two forms of transcript are designated as c-metsm (for small) and c-metlg (for large) to distinguish the absence or presence of the 141-base pair segment, respectively. The c-metsm variant is present in adult mouse tissues including kidney, liver, and brain as well as in 9-10-day-old embryos. In all cases, expression of c-metsm was lower than that of the normal transcript, c-metlg. An antiserum against mouse c-Met protein immunoprecipitated corresponding protein forms of approximately 152 and approximately 145 kDa from whole kidney lysate under reducing conditions. The size difference of approximately 7 kDa between these isoforms corresponds to the predicted difference of 47 amino acids. The presence of this shorter variant transcript and its corresponding protein isoform in a variety of normal tissues suggests a physiological role. The deleted region in the cytoplasmic domain of c-metsm contains a sequence motif (S985ARS) for protein kinase C phosphorylation that has recently been shown to play a key role in the down-regulation of hepatocyte growth factor receptor kinase activity. The identification of this novel isoform, c-metsm, demonstrates that a tyrosine kinase receptor can achieve additional diversity by alternative splicing at a key regulatory site in its cytoplasmic domain.

Alternative Splicing↗
PubMed1994

Analysis of thymidine kinase gene expression in preimplantation mouse embryos.

Thymidine kinase (TK) activity was examined during the development of preimplantation mouse embryos. TK activity was increased approximately 20-fold from day 2 embryos (2-cell) to day 5 embryos (late blastocyst). TK activity did not change along with the progression into S-phase of the first and the second cell cycles but increased sharply at S-phase of the third cell cycle. Analysis of TK mRNA with a reverse transcription-polymerase chain reaction (RT-PCR) method showed that the level of TK mRNA was low in ovulated eggs and 1-cell embryos and was hardly detectable in day 2 embryos (2-cell), but sharply increased in day 3 embryos (mixture of 5- to 8-cell and morula). The functional role of 5'-flanking sequence of TK gene was also investigated in preimplantation embryos after microinjection with the DNA construct of 5'-flanking sequence of TK (2.4 kb) linked to bacterial lacZ gene (TK2.5lacZ) into the pronucleus of 1-cell and subsequently by histochemical staining with X-gal. beta-Galactosidase activity was first detected in day 3 embryos (8-cell), and 30% of embryos were stained with X-gal in day 4 and day 5 embryos, respectively. These results show that an increase in TK activity occurred after 2-cell stage, and this increase was primarily due to the embryonic activation of TK gene expression. Also, it appears that the 5'-flanking sequence of TK may directly regulate the TK gene expression at the transcriptional level during preimplantation murine development.

Animals↗
PubMed1994

Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNA(Lys) gene.

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.

Adult↗